A procedure for some hypertension; a new vaccine; mitochondria and heart disease: Upstate Medical University's HealthLink on Air for Sunday, June 9, 2024

Host Amber Smith: Coming up next on Upstate's "HealthLink on Air," a surgeon tells about a procedure for people whose medications are not effective in treating their high blood pressure.

Wei Li, MD: We use ultrasound as the energy to basically ablate, or kind of block, the nerve surrounding the renal artery, because the nerves surrounding the renal artery are the ones to mediate blood pressure change.

Host Amber Smith: A county health commissioner discusses new protections against a virus carried by mosquitoes.

Katie Anderson, MD, PhD: We think that there are many regions of the world where chikungunya continues to circulate, but probably at relatively low levels.

Host Amber Smith: And a graduate student explains heart disease research at a cellular level.

Gargi Mishra: The way in which mitochondria have been targeted has overemphasized their bioenergetic function.

Host Amber Smith: All that, and a visit from The Healing Muse, coming up after the news.

This is Upstate Medical University's "HealthLink on Air," your chance to explore health, science and medicine with the experts from Central New York's only academic medical center. I'm your host, Amber Smith.

On this week's show, chikungunya virus has a new vaccine. Then we'll learn about the mitochondria that generate energy for living cells. But first, how renal denervation can help people with resistant hypertension.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

High blood pressure can lead to stroke, heart attack, kidney damage and other problems. Many people struggle to control their high blood pressure with lifestyle modifications and medications. They have what's known as resistant hypertension. An endovascular surgeon at Upstate now offers a procedure to help lower high blood pressure. Dr. Wei Li is an associate professor of surgery at Upstate, and he's here to tell us about ultrasound renal denervation.

Welcome back to "HealthLink on Air," Dr. Li.

Wei Li, MD: Thank you Amber. Thank you for the nice introduction.

Host Amber Smith: Well, let's start with a description of what blood pressure is and why it's an important measure of our health. What is a healthy blood pressure number?

Wei Li, MD: The healthy blood pressure numbers in the United States, according to the national guidelines, are anything above 130 over 80 are considered hypertension. And according to many studies in the nation, one in two Americans suffer hypertension in our lifetime.

Host Amber Smith: So the blood pressure reading, does this kind of tell us how well our arteries are working? Is that what we use it for?

Wei Li, MD: That's correct. Not only tell us how well our arteries system is working, also tell us how much blood flow and if there's any potential damage to our end organs -- meaning brain, heart, kidneys -- can benefit or can be harmed by the blood flow perfusion. If the blood pressure is too high, will damage our heart and the brain, kidney and even more. With hypertension, certain patients unfortunately cause mortality as a result of heart failure or stroke. Some of them are related to hypertension.

Host Amber Smith: So why do some people get high blood pressure or hypertension? What causes that?

Wei Li, MD: It's a long story. Hypertension can be causedwith many, many reasons. And there are two different categories. One is primary hypertension, which I think majority of hypertension patients belong to that category. The second one we call secondary hypertension. Very few people statistically belong to that category.

I think this today's topic, we mainly talk about primary hypertension that could be potentially treated with renal denervation, which is a new technology the U.S. FDA (Food and Drug Administration) approved recently in November last year.

Host Amber Smith: So that is for people whose hypertension is uncontrolled with multiple medications and with multiple lifestyle modifications.

Wei Li, MD: Mm-hmm.

Host Amber Smith: They still have high blood pressure. And so now the FDA has approved this new procedure. What can you tell us about it? What's it called, and how does it work?

Wei Li, MD: This new procedure actually started around eight, seven years ago. And the current device are second generations, and their two manufacturers make this device. The current generation, according to the FDA clinical trial, both devices can, on average, lower the blood pressure, systolic blood pressure, we call SBP, by 10 millimeters of mercury. As background information in a big journal, notable to any medical professionals, published in 2016, a reduction of 10 millimeters of mercury in systolic blood pressure is associated with substantial or significant risk reductions. For example, 28% reduction in heart failure, 27% reduction for stroke, 17% for coronary disease, meaning heart vessel disease, and 5% reduction for chronic kidney failure. And the most important thing is the 13% reduction for mortality by even as little as 10 millimeters of mercury, 10 point of blood pressure drop in SBP, we call systolic blood pressure. So that's the benefit, and the very significant benefit, that could potentially offer by these two newer generation renal innovation devices.

Host Amber Smith: Those numbers do sound significant. How safe is the procedure? And, are there any risks?

Wei Li, MD: Like any other newer minimally invasive procedure, they all have a risk. However, the benefit at the current time, based on the clinical trial and also my personal experience, the benefit outweighs the risks. However, we always consider risk for any procedure, even for a small procedure like hernia repair, gallbladder removal, they all have a risk.

But I think for this particular procedure, is generally speaking, considered low-risk procedure, can be done with local anesthesia, moderate sedation without going to the operating room. And we can do what we call in the "cath lab," (catheterization lab) and patient comes in the same day in the morning and then finish the procedure and then to be discharged on the same day.

Host Amber Smith: So, Dr. Li, I understand you're the principal investigator of studies for Recor Medical, the maker of this renal denervation device. What does that role involve?

Wei Li, MD: That role involves actually a post-market study. The study is considered to get the real world experience after the FDA approved the devices, and I was selected as a PI (principal investigator) for this study. And actually for this year, the study organizer only picked about 30 PIs or institutions to be part of the study. And I was honored to be selected as the only vascular surgeon PI among this 30 PIs in this study. And of course, Upstate is one of the 30 sites, first batch of the 30 sites.

And to be in this study, that means what? Meaning we are able to offer the, not only the commercial use of the device to treat non-controlled hypertension or resistant hypertension. Also as an institution, as my study group, we'll be able to contribute the real world experience in terms of this study. This is significantly important compared to the pre-approval study population because this is a real world experience on the general public.

Host Amber Smith: So can you walk us through what patients will experience? How would a person be determined to be a candidate for this procedure?

Wei Li, MD: There are three different indications or criteria for patient to be selected, to be indicated, for this procedure. And the first one will be patient on three blood pressure medications with maximum dose they can tolerate and still cannot meet the goal of blood pressure of 130 over 80.

And the second group of patients who are indicated (for the) procedure are the ones, the patient, for whatever reason, they cannot have a good compliance with the medication they were given. For example, maybe because of the side effects, maybe because the patient's personal reasons. For example, frequent travelers cannot take the water pills every day, for example, because if that's the case, they have to go to the bathroom frequently, right? Then some of them in the second group, a lot of them are working group, working age group patients. They cannot tolerate the side effects. And then at the end of the day, between the work and life, they end up with uncontrolled hypertension.

The third one the group for the patients who have non-controlled hypertension above 130 over 80. And those group patients already suffer the complications from their hypertension. For example, they already had stroke, they already had heart attack, already have kidney issues. But luckily they still can survive at this time.

But I think the renal denervation offers a good adjunct treatment for all three groups, in addition to the blood pressure medications. I want to make it clear, the renal denervation procedure is not designed as a sole treatment for hypertension. They are designed as adjunct treatment, which is the first ever minimally invasive treatment for hypertension, in addition to conventional, traditional medication. Most of them are pills.

Host Amber Smith: So the patient may still require some medications, is what you're saying, after the procedure.

Wei Li, MD: Yes, that's exactly correct. For example, my first patient was on four medications, still couldn't get control, and my first time I saw him, I remember his blood pressure was 190 over 89. The second time I saw him, the blood pressure was 180 over 86. That was about four months apart. And he was very actively involved with his cardiologist, general cardiologist, to get pressure control, but was not able to over four months. And then at the same time, he had another aortic pathology, which gave him additional risk factor in terms if the blood pressure not controlled.

So after procedure, he was normotensive, blood pressure about 120 over 70. As a result, I actively reached out with his cardiologist, even from day zero, on the same day of the surgery, to coordinate the care. And at the current time he not only reduced the from four to two medications, but even the two medication he has right now, I was told by him and the family and his cardiologist, those two medications, now he's taking with reduced dose.

We all know the less medication, the less side effect; and the lower dose, the better in terms of not only side effect and also overall given the magnitude of hypertension. And if you take the population as a whole, that procedure itself will offset some of the health care expenditures for the long run.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith. I'm talking with Dr. Wei Li. He's an associate professor of surgery at Upstate, and he's the first vascular surgeon, not just in Upstate New York, but globally, to perform the ultrasound renal denervation on a patient after the FDA approval.

So patients who have uncontrolled high blood pressure, they may be referred to you by their primary care doctor or their nephrologist or a cardiologist. And then they come to you, and once you determine that they're a good candidate for this procedure, and they decide they want to do it, can you walk us through how it's actually done?

Wei Li, MD: We give the patient the material about the procedure. We have a very detailed, we call in medicine or surgery we call "informed consent," with heavy involvement of the patient, not only patient, but also family because they need to understand what the procedure is. Because this group of patients, a lot of them are relatively healthy. We make sure they understand the risk/benefit.

And once the patient understand the procedure, once we determine the patient's a good fit for the procedure, then we start planning.

Host Amber Smith: So the procedure takes about an hour. It takes place in the hospital. Is the patient awake for this, or are they under anesthesia?

Wei Li, MD: Patient is awake, and I can have the conversation with the patient because sometime ask the patient: hold breathing, breathe in and out, and then relaxing. In the procedure, of course we give local anesthesia just like we go to the dental office, right? We can inject local anesthesia to make a patient more comfortable. We give something called moderate sedation, meaning patient is not asleep, but we give some medicine to make patient comfortable as much as possible remove their anxiety, for example.

At the same time, they are alert. They can have a conversation with the providers.

It's considered outpatient procedure. The patient is admitted in the morning and discharged after the procedure, in this case early in the afternoon.

Host Amber Smith: Now you said it's minimally invasive. It's a single incision that you make, is that right?

Wei Li, MD: I would say you can call it single incision, but it's mostly a needle hole. It's about 1.5 millimeters on the skin and then requires no, or almost no, stitches.And the patient walks out the hospital on the same day, walking around at the same day.

Host Amber Smith: So you need that so that you can access the artery.

Wei Li, MD: Yes.

Host Amber Smith: And then you insert something that goes, how far? How far down the artery do you go before you -- because that's how you apply the ultrasound through this, this probe or something, right?

Wei Li, MD: Actually we use ultrasound for different means. At first we use ultrasound guidance to access the arteries, so we make sure it's minimally invasive. We use a needle at the groin area, only one groin, not two. How far it goes: the catheter wire system goes up, from the groin to the kidney level to the aorta and around the renal artery. And then we put the catheter system into the renal artery with a careful maneuver.

We advance the catheter with a balloon into the renal artery, and we utilize ultrasound as energy. And the energy, this is what they call renal ultrasound based renal denervation. We use ultrasound as the energy to basically ablate, or kind of block, the nerve surrounding the renal artery, because the nerves surrounding the renal artery are the ones to mediate blood pressure change. Because a patient with uncontrolled hypertension, somehow the activity of those nerves surrounding renal artery have a higher than average activity so we try to decrease the activity of those nerves to block the pathway of hypertension, the circuit.

So this was done through energy from the ultrasound. And then of course we use the balloon filled with the water because ultrasound transfuses or travels better through the water. The nerve around the renal artery can be treated, and as a result, lower the blood pressure.

Host Amber Smith: So even though the patient has some conscious sedation, can they feel when you're doing this? Can they tell that you're near their kidney when you're doing the work?

Wei Li, MD: Most people don't feel too much. I think small proportion, and my patients, did not feel at all. But according to the pre FDA approval study, some patients feel some pain in the back. That's why we need good coordination, as a team, with our nurses, at the bedside and during the procedure, to give the medication in advance before we trigger the ultrasound energy to treat the nerve. It's individually different. It varies from patient to patient, but overall it should be tolerable. It should not require major medication for pain.

I alert the patient before I start the treatment, because it requires three activations of ultrasound energy deliveries for each artery. So totally together is about six treatments, less than 10 seconds for each treatment and total together 60 seconds or less.

With the trained individual practitioners, and I think this is a good adjunct treatment with minimally invasive technology to treat uncontrolled hypertension, which is a disease that over 100 years was treated with pills only.

Host Amber Smith: So how soon after this procedure does the blood pressure lower?

Wei Li, MD: It varies from individual to individual. For this particular patient, the pressure drop on the table, to normal pressure from 170 over 80, all the way down to 120 over 70. Individual response is different from patient to patient. So that's why that requires a lot of coordination among care providers. Depending the level of responsiveness on the patient, we address medication accordingly.

For the long term, most patients can maintain more than 10 points of blood pressure decrease over long term. After procedure, the pressure as a human body because the body try to repair and try to reset back to their status from before the operation, before the procedure. We may expect some of this patient blood pressure may slowly back up a little bit, right? But I think based on the study we have, prior to FDA approval, the study still suggested that the long-term blood pressure reduction is still there. And as a result, we'll significantly reduce the complications from the hypertension.

Host Amber Smith: Do we know how long the denervation will last? Will those nerves kind of re-nervate?

Wei Li, MD: So at this time, based on the study, the FDA indication and suggestions are we only do one time per patient lifetime for renal denervation.

Then that means based on all the study published from the clinical trial prior to FDA approval for both devices, actually, the FDA does not suggest doing a second time renal denervation with either device. That's based on the study we have so far. Because it's a new device, less than half years old, long term, I think rely on physicians, rely on the post-market study, which I'm one PI in the nation to confirm or to revise the indication if there is a change in terms of long-term result.

Host Amber Smith: I know that you said, Dr. Li, the patient may end up needing to still take their blood pressure medicine, but different dosages or fewer meds maybe. Are there other restrictions after the procedure for patients? Does this impact what they can and can't do?

Wei Li, MD: For the short term, immediately after the procedure, of course, like any other procedure like hernia repair, or gallbladder removal, I always tell the patient activity as tolerated, and return to work if they're not heavy labor. If they're office worker or even moving around their house, I do not have much restrictions.

Of course, whenever a patient adjusts medications, patient needs to closely watch their blood pressure, because whenever there's change on the medications, the blood pressure, the body responds differently from patient to patient. And even if the medication decreased by half, I would suggest the patient monitor their blood pressure closer than before. Maybe check the blood pressure at least once a day and then talk to the providers who gave them medication frequently in case the patient finds their blood pressure fluctuation, or decreasing or increasing.

Host Amber Smith: I appreciate you making time for this interview, Dr. Li.

Wei Li, MD: Thank you.

Host Amber Smith: My guest has been Dr. Wei Li, an associate professor of surgery at Upstate who offers a renal denervation procedure for people with resistant hypertension. I'm Amber Smith for Upstate's "HealthLink on Air."

This tropical, mosquito-borne virus has a new vaccine -- next on Upstate's "HealthLink on Air."

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

A new vaccine is available for a virus called chikungunya. We'll learn who needs to consider this vaccine and what chikungunya is with my guest, Dr. Katie Anderson. She's the health Commissioner for Onondaga County and a faculty member in microbiology and immunology at Upstate. Welcome back to "HealthLink on Air," Dr. Anderson.

Katie Anderson, MD, PhD: Thanks for having me.

Host Amber Smith: Chikungunya is another virus that's spread by the bite of an infected mosquito. What else can you tell us about chikungunya?

Katie Anderson, MD, PhD: Chikungunya is yet another of new viruses that are emerging in recent years. It's been known for several decades, and previously was isolated to areas of Africa and Asia, but there was a big epidemic of it. It swept through Central and South America in 2013, 2014, and caused a lot of disease. It's a mosquito-borne virus, similar to other ones we've had emerging -- West Nile, dengue, Zika -- but it's in a different family. It's an alpha virus. And the name is of particular significance to note. It has nothing to do with chickens. It relates to an (African) Makonde (language) word from where it was identified in Africa and refers to the severe joint pain that you get with chikungunya, and it translates to "that which bends up," meaning you're so stooped over when you get chikungunya, it earned this name. But it can be a quite significant, painful acute illness.

Host Amber Smith: So do all mosquitoes potentially carry this virus?

Katie Anderson, MD, PhD: It's important to note that it's spread by the same mosquito, the same pesky mosquito, that spreads yellow fever, Zika, dengue, and chikungunya now as well, and who knows what other viruses to come: Aedes aegypti, which is a major public health pest.

It's also spread by another vector called Aedes albopictus, which is why you can sometimes see these viruses spreading into areas that are more temperate, so parts of Europe, for example. The percentage of mosquitoes who may have chikungunya is generally quite low. But during epidemics where there have been these massive explosive epidemics of chikungunya -- for example, in Latin America, 10 years ago or so -- the percentage of mosquitoes carrying the virus could be much higher, on the order of 10 to 20%. But typically now we believe it's relatively low.

Host Amber Smith: Now, how does the mosquito get infected? Are they born already infected, or do they have to, do they get this from another animal?

Katie Anderson, MD, PhD: That's a great question. So we believe that there is some, what's called vertical transmission, where it can be passed down within mosquito generations. But most of it is picked up when the mosquito feeds on an infected person. And Aedes aegypti is a particularly significant health threat because it only feeds on humans, by and large.

So you have an infected human who infects the mosquito. And then it takes about one week for the mosquito to be able to infect someone else. It has to go through their gut to their saliva, and then it'll infect new people.

Host Amber Smith: Does it spread from person to person? If someone is infected with chikungunya, do they spread it to their family members?

Katie Anderson, MD, PhD: No. We don't believe so, and we haven't seen that. It's a blood-borne virus. There have been a few rare instances of laboratory workers becoming infected with chikungunya when they're working with it in the lab, as well as rare healthcare workers who maybe had a needle stick. But it requires blood transfer or infection within a mosquito.

Host Amber Smith: Where are the problem areas or the countries that have had the outbreaks that we need to be concerned about today?

Katie Anderson, MD, PhD: So before 2013, which is when we had the huge epidemic in the Americas, it would've been just a handful of countries that we knew had a chikungunya case here, a chikungunya case there. It's very similar to Zika in that regard.

But in 2013, there was the arrival in the Caribbean and then explosive spread throughout Central and South America. And now over a hundred countries and territories have experienced chikungunya transmission. And that includes, again, it followed the same distribution of the Aedes aegypti mosquito, which is most of the tropical and subtropical regions of the globe.

But one of the biggest challenges with chikungunya is that the areas that are problem areas, so where you need to be particularly concerned for travel, it can be very unpredictable. And it can be very hard to counsel people on how to avoid chikungunya exposure. So we think that there are many regions of the world where chikungunya continues to circulate, but probably at relatively low levels.

In contrast, there are places like Paraguay last year where they had a massive explosive epidemic where the risk would've been much higher. But it's very unpredictable, this virus.

Host Amber Smith: Is ther a transmission in the United States to be concerned with, or is this mostly people traveling to more tropical areas?

Katie Anderson, MD, PhD: The risk of chikungunya -- and the same would follow with dengue and Zika -- is largely within travelers. And that's not to say we don't have the mosquitoes here in the United States, because large parts of the US have Aedes aegypti, large parts have Aedes albopictus, but we think that we have a couple things going for us in our favor in that the structure of our housing, the fact that we by and large have screens on our windows, that we have air conditioning units, for example, often, are protective factors. So even though we have the vectors here, we don't tend to see widespread distribution or circulation of any of these viruses.

But that said, when chikungunya was blasting through the Americas in 2013 and 14, we did have limited transmission in Florida, of just maybe a dozen cases, suggesting it's possible, but we don't think we have the right conditions for massive epidemics just yet.

Host Amber Smith: This is Upstate's "HealthLink on Air" with your host Amber Smith. I'm talking with Onondaga County Health Commissioner Dr. Katie Anderson about the chikungunya vaccine that's available.

Now, let's go over the symptoms of chikungunya in a human. How soon after infection would someone start noticing symptoms, perhaps?

Katie Anderson, MD, PhD: It's typical to know when you've been exposed because it typically comes through the bite of an infected mosquito, which in many places of the world is a very common occurrence. But about four to seven days after you're exposed, you'll start to develop symptoms which can be very similar to many other viral illnesses.

So the individual may have a high fever that comes on quickly. The joint pain is most likely the most significant and debilitating aspect of this infection, typically in the hands and feet, and individuals may also have muscle pain, headache, nausea, fatigue and rash. Typically, this acute phase, at least the fever, will resolve within the matter of days, two to three days. The problem with chikungunya is that we think that it doesn't become a chronic illness, but the joint pain symptoms in particular can be profound and can continue for weeks to months, to years.

Host Amber Smith: How difficult is it to get a diagnosis?

Katie Anderson, MD, PhD: I would say quite, quite difficult. And the reason for that is that the symptoms that we're describing overlap a lot with dengue. They overlap with a lot of other common tropical infections. And these are occurring in areas that don't have a lot of laboratory capacity. So there are tests for chikungunya. For example, you could do what's called a PCR (polymerase chain reaction) where you look for the virus in the blood, or you could look for chikungunya antibodies.

But that's not commonly done in most of the places where people would get this virus. So it's typically a clinical diagnosis, which would mean a physician would say, this looks like chikungunya, so I'm calling it chikungunya. But again, it overlaps a lot with other viruses and other diseases.

Host Amber Smith: How is it likely treated?

Katie Anderson, MD, PhD: Well, the treatment is limited to supportive care. There's no specific antiviral for chikungunya, just like there isn't one for dengue or for Zika. Treatment is supportive, so you treat the joint pain, you treat the fever and try to support the person's symptoms as they recover from this acute phase.

For certain individuals -- and it's a minority, but it can be a significant proportion -- maybe 30% of people who will go on to have extended, prolonged, debilitating joint pain. And those folks may benefit from seeing a rheumatologist and going on more specific treatment for the arthritis.

Host Amber Smith: Let's talk about this vaccine. What do we need to know about it? What's it called?

Katie Anderson, MD, PhD: It's called Ixchiq.

Host Amber Smith: Ixchiq. Is it for adults or children, or both?

Katie Anderson, MD, PhD: So this vaccine was just approved by the FDA in recent months and then recently got its designation from the ACIP. So to go over the pathways for vaccines again: so the FDA (Food and Drug Administration) will review, for the United States, the safety records, the immunogenicity, how well it seems to work, the efficacy, so in terms of how much disease it prevents, and then it will give a regulatory approval. The ACIP (Advisory Committee on Immunization Practices), which is the next meeting that happened somewhat recently, is when the CDC's (Centers for Disease Control and Prevention) advisory board will review how they recommend this vaccine be used in the United States.

So the recommendations are specific for our context. And the recommendation for Ixchiq from ACIP was that it's for adults, and it should be considered for individuals who are traveling, and traveling to a place either with an outbreak, so that would be like Paraguay last year, where the risk is really high, or if they're going to a place where there was chikungunya transmission in the last five years, and who are particularly high risk to be exposed to mosquitoes or have a bad outcome. So it's a very specific and somewhat intentionally vague description for who should get this, really just prompting a discussion with a travel medicine physician.

Host Amber Smith: How long does it offer protection for a person?

Katie Anderson, MD, PhD: The goal of the vaccine is long-term protection. But I think in the context of this vaccine, and this relates back to the somewhat unique epidemiology of chikungunya, it had a somewhat unique pathway where there are still things that we're learning about it in terms of how long the protection may be.

So typically when you're evaluating a vaccine, first you check for safety. In small trials, it passed that. You look for immunogenicity, which means that it makes an immune response to what you're trying to protect. It did that, in the period after vaccination occurred. And then the next step would typically be to look and see how well does it prevent disease when given to large numbers of people, on the order of thousands.

We can think back to COVID, again, an atypical example, but there's certainly were efficacy trials to prove how well it worked. For chikungunya, it is near impossible to try to identify where the next epidemic may be and how you would find enough people to be able to say it's efficacious, or that it works very well.

So based upon the antibody response that the vaccine generates, and the safety, the fact that at two-year follow-up, the level of the immune response is still quite high, at 95%, there's a presumption that it will work well to prevent chikungunya. I think that's a fairly reasonable assumption, but what comes next is the trials for all of these, this Valneva Austria vaccine, Ixchiq and others that are in development. They can be licensed without these efficacy data, but that needs to come and be proven next. So I think there's more to come in terms of how long it protects and what exactly we know.

Host Amber Smith: At this point, are there any precautions, or can this be given to anyone safely, or are there any conditions that a person might think twice before they get the vaccine?

Katie Anderson, MD, PhD: This one is a live attenuated vaccine. So there's a wide variety of different vaccine types we get. The fact that it's live attenuated means that it's similar, for example, to measles, mumps and rubella. So there's certain people who should not get this, people who have a compromised immune system, for example, or people who take medications that suppress their immune system. Because it is a live vaccine that should replicate in your body and cause an infection, really a low-level infection, to be protective. So they would be contraindicated.

And then it should be noted that as with all vaccines, there are some minimal side effects that are noted with this, like some mild joint pain, some headache and some occasional fevers.

Host Amber Smith: Well, if someone thinks that they qualify for this, and they've got travel coming up to an area that might be problematic, where do they get the vaccine?

Katie Anderson, MD, PhD: The vaccine will most likely be available through travel clinics. And my understanding is in our area here in Central New York, they're not available yet, but maybe coming to travel clinics in the coming weeks or months.

And I'll say that, if I was a travel medicine physician, and I've done some of this in the past, I would be most likely to recommend this for people who are traveling to a place, just like the ACIP says, clearly if there's a large epidemic going on, and then the rest would come down to how long are you going for? What is the level of the health care system to the place that you're traveling to? If you got an illness that made you really sick for a couple of days, how would that impact that trip that you're taking? And have kind of a discussion, hand in hand, with an assessment of how well insurance will cover this because this vaccine may be on the order of $300-plus dollars.

Host Amber Smith: So it's a lot for someone to consider, kind of pluses and minuses, whether they get it or not?

Katie Anderson, MD, PhD: And there are, analogous, there are similar discussions that happen for other travel vaccines -- for Japanese encephalitis, for rabies. These can also be expensive vaccines. But for certain scenarios, they may be very appropriate for a person to consider receiving, but not likely for everyone.

Host Amber Smith: Well, that makes sense. Thank you so much for making time for this interview, Dr. Anderson.

Katie Anderson, MD, PhD: Nice talking with you. Thank you.

Host Amber Smith: My guest has been Dr. Katie Anderson. She's the health commissioner for Onondaga County and a faculty member in microbiology and immunology at Upstate. I'm Amber Smith for Upstate's "HealthLink on Air."

Next on Upstate's "HealthLink on Air" -- heart disease research at the cellular level.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

The campus of an academic medical center, such as Upstate Medical University, contains a multitude of researchers. And today we'll meet one of them who's studying the quality control of mitochondria for a healthier heart. Ms. Gargi Mishra is a graduate student in biochemistry and molecular biology at Upstate, in the laboratory of Dr. Xin Jie Chen, working toward her MD and PhD degrees.

Welcome to "HealthLink on Air," Ms. Mishra.

Gargi Mishra: Thank you so much for having me.

Host Amber Smith: Let's start with some basic definitions. What are mitochondria?

Gargi Mishra: Mitochondria are organelles within our cells.

So if we can think of our cell as having a plasma membrane and various different things within it that help that cell make energy, help translate DNA, help divide, mitochondria perform the job of helping produce energy.

And if we were to go a step back, mitochondria weren't always in our cells, and our cells weren't always modern, the way they are (now).

Many, many, many, many, many years ago, a precursor to our cell, a eukaryotic cell, engulfed a very ancient bacterium. And rather than just eating at that bacterium and digesting it, that bacterium took a place up in the cell and became what is called an endosymbiont and began to provide energy for the cell.

And that, in modern times, became the mitochondrion within our cell, or, like, multiple mitochondria within our cell.

Host Amber Smith: So our cells have evolved over centuries to have mitochondria. And this is in all the cells of our body, right?

Gargi Mishra: Yes. This is in all the cells of our body because we're a eukaryotic organism, all our cells, and eukaryotic cell essentially means that it has its DNA packaged into a nucleus, which is again, membrane bound, whereas bacteria are prokaryotes, so sure, they have DNA, but it's just not membrane bound into a nucleus.

Host Amber Smith: Now, are mitochondria important because of their energy function? Is that the big thing about them?

Gargi Mishra: That is what they are known for the most. If you think about textbooks and what students learn in middle school or high school, you know the phrase is: Mitochondria are the powerhouses of the cell. So there's certainly those energy hubs that help generate energy for the cell, but they are extremely important for other functions that are just lesser known.

So they're important for generating various metabolites that the cell uses. They're essential for immune signaling. They are important for signaling associated with cell death and cell proliferation, the balance of calcium within our cells, and that's especially relevant for different types of cells, such as heart muscle or skeleton muscle.

The way those types of cells contract and relax, to a huge degree, depends on the calcium levels within them. So, yes, mitochondria perform many other functions besides producing energy, but that is what they're known for the most.

Host Amber Smith: You used the term "metabolite." Can you explain what that is?

Gargi Mishra: Metabolites are basically molecules that enzymes will act on to either synthesize into, like, a larger metabolite or break it down into energy. So an example of a metabolite could be glucose, or it could be acetyl-CoA, or various other molecules that can be used for energy purposes.

Or it can be shuttled off to outperform another function in a different pathway.

Host Amber Smith: So what are the functions that relate to the heart?

Gargi Mishra: I think the most salient functions that mitochondria perform in the context of the heart, first and foremost, for sure, is energy production. The heart is an organ that is working 24/7, nonstop, even before our parent gave birth to us.

And until we take our last breath, our hearts are pumping blood, and so they require huge amounts of energy, and our heart especially utilizes fatty acids as the preferred substrate (source) for energy production and that generates ATP (adenosine triphosphate), which is the energy currency of the cell.

And so mitochondria are relevant for that, first and foremost. And then again, as I mentioned, they're important for metabolite synthesis. So various types of cholesterols, such as cardiolipin, acetate and various other metabolites, are generated with the help of pathways that occur within and surrounding mitochondria.

Mitochondria are important for calcium homeostasis, which, again, is relevant for heart function and the way the heart cell is able to contract so that the organ is able to pump blood.

And then, if you were to think about slightly lesser-known functions, mitochondria are important for what is called this "redox balance." Taking a step back, while mitochondria are helping produce energy, that process generates what are called these free radicals or, reactive oxygen species. And, because these can be generated by huge amounts. these can lead to a lot of what is called oxidative stress within the cell. And so, you would think that mitochondria are the ones producing it, that they're causing the trouble. But they also have the enzymes that can help to disperse and reduce some of these reactive oxygen species, or ROS, as they're called.

And then finally the even more lesser two known functions. One would be what is called mitochondrial dynamics. So mitochondria can undergo fission and fusion. Fusion refers to multiple different tiny mitochondria fusing into one large mitochondrion, or they can undergo fission, where that larger mitochondrion can break up into tinier mitochondria, and that can help redistribute energy and metabolites within that heart cell.

And then finally, the least studied or understood function in the context of the heart is just the production of mitochondria in timely fashion as the heart cells are doing what they're supposed to do, and also the clearance of damaged mitochondria or of proteins that may accumulate outside of those mitochondria. And that we refer to as mitochondria biogenesis, which is just the production of mitochondria and mitochondrial quality control, which would be the turnover of mitochondria. And those things are also relevant for heart function.

Host Amber Smith: You used the term "redox." Can you explain what that is?

Gargi Mishra: It's a combined term for reduced versus oxidative, and that redox balance, in the context of mitochondria and what they do, is essentially referring to the amount of reactive oxygen species that are being produced as mitochondria help generate energy.

If you were to get into the nitty-gritty of it, you can have a more reduced state in the cell. It's basically referring to charges in or around the mitochondria. A reduced state would be having more protons, like minus charges, and the oxidative state would be having fewer protons.

Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith.

I'm talking with Gargi Mishra. She's studying at Upstate to obtain her MD degree and her PhD degree, working in biochemistry and molecular biology. So if I understand correctly, mitochondria have already been targeted as treatment areas for diseases of the heart muscles, such as cardiomyopathy; arrhythmias, where the heart's electrical system is malfunctioning; heart attacks; heart failure.

So that's kind of already been studied quite a bit, right?

Gargi Mishra: Yes, for sure. Mitochondria have been targeted in these things, and it makes sense why. Various genetic mutations in mitochondria can directly lead to cardiomyopathies or various forms of arrhythmias and also other types of insults, whether it be lifestyle induced based on someone's diet or the toxins they're exposed to, or various different drug treatments can induce cardiomyopathies that also indirectly cause these various diseases, via causing mitochondrial dysfunction.

But the way in which mitochondria have been targeted has overemphasized their bioenergetic function. So supplementation of various metabolites, such as, let's say, acetyl-CoA or NAD (nicotinamide adenine dinucleotide) or various antioxidants that have been used, are all kind of overemphasizing the energy production function of mitochondria. Or calcium homeostasis function of mitochondria or the redox balance or, to a lesser degree, targeting mitochondrial dynamics function of those organelles.

But what remains understudied or underutilized as an approach for targeting mitochondria is simply mitochondrial production and mitochondrial quality control.

Host Amber Smith: That's what you're looking at, right?

Gargi Mishra: Yes. That is something that our lab collectively has been interested in for a very long time, and I would like to quickly give a shout-out to an older graduate student, Liam Coyne, MD, PhD, who's currently in his intern year at Johns Hopkins, pursuing a physician-scientist training program there. And Liam's PhD focused on, first and foremost, establishing how defects in mitochondrial production, simply from mitochondrial protein import not occurring, can lead to this phenomenon called protein import clogging on the mitochondrial surface, and how that can be used as a way to explain the mechanism for various diseases.

And then if we were to go even a step back, my PI (principal investigator), Dr. Xin Jie Chen, his work, I would say in around 2015, helped establish this form of protein-induced stress, which he termed "mitochondrial precursor overaccumulation stress," or mPOS, which, again, is caused when proteins that are supposed to end up in mitochondria because they help form mitochondria are not able to get in. They cause this traffic jam on the surface of those mitochondrial import channels, and then the accumulation of these proteins in the cytoplasm can lead to stress within the cell and eventually lead to cell death.

And so, based off of what Dr. Chen found and what Liam found as, like, a new form of mitochondrial dysfunction, my project is focused on finding ways in which we can reverse mPOS, or ways in which we can reverse clogging, which we refer to as trying to identify novel anti-clogging pathways.

Host Amber Smith: So you've identified some problems, and now you're trying to figure out a way to solve those issues.

Gargi Mishra: Yes, that's exactly right.

Host Amber Smith: Commonly, we think of stress as being a negative. Is mitochondrial protein import stress always bad for the heart?

Gargi Mishra: No. That, again, is a very excellent question. The type of mutant protein that I use as a model for studying protein import clogging in yeast, it translates to a mutant protein that does in fact cause cardiomyopathy in humans.

And again, our hypothesis for how this happens is because this mutant protein is getting stuck on protein import channels and preventing the import of other mitochondrial proteins from getting in.

That being said, we have a mouse model in our lab where we're just over-expressing the healthy version of this protein (not mutated, as it would be in a disease) by about twofold, and in that mouse model, which is something that my colleague Arnav Rana is working on -- he's also an AHA (American Heart Association) funded research fellow in our lab -- what he's actually found is that over-expressing two copies of just the healthy protein that we want to import through the channel, causes extremely mild levels of protein import stress, and this translates to improved heart function.

And this is an extremely paradoxical finding, but it's also not too unsurprising because if we were to think of it from the perspective of doing exercise, so let's say if you're doing cardio, you're going on a long run, you're biking every day, or you're swimming, you're basically pushing your heart to try to keep up with the, let's say, the energy demand or the metabolite demand for it to perform its function. And in those cases, mitochondria production or mitochondrial biogenesis is actually upregulated to some degree. And so you can imagine that if you're trying to produce more mitochondria, you're trying to do more protein import.

And so while all these proteins are trying to be imported in, so new mitochondria can form, at some point, there can be just a mild level of traffic jam. Think about it as, like, rush hour, on I-81, right? It's not necessarily a complete traffic jam because a car crash happened, but it's just a lot of cars trying to get to where they need to go. And so that process of doing exercise translates to what we think, we speculate, it translates to low levels of protein import stress that ultimately, through various signaling pathways, leads to a stronger heart, improved ejection fraction (how much blood the heart pumps), which is the readout that Arnav uses. And so Arnav, in his PhD, is trying to identify what are those signaling pathways downstream of that mild protein import stress that are leading to this healthier phenotype (observable characteristics) in these mice.

Host Amber Smith: Well, very interesting. I want to thank you for making time to tell us about your research.

Gargi Mishra: Thank you so much, Amber.

Host Amber Smith: My guest has been Gargi Mishra, a fellow in biochemistry and molecular biology at Upstate, working on both her MD and PhD degrees. I'm Amber Smith for Upstate's "HealthLink on Air."

And now, Deirdre Neilen, editor of Upstate Medical University's literary and visual arts journal, The Healing Muse, with this week's selection.

Deirdre Neilen, PhD: Gloria Heffernan is the author of the chapbook called "Hail to the Symptom," from Moonstone Press. Her poem "Silence Interrupted" will be especially appreciated by a particular middle-aged generation.

"Silence Interrupted"

I remember the silence

of a shallow pool among the rocks of Sabino Canyon.

Sycamores, saguaros and a stillness so deep

it was shattered by the thrum

of butterfly wings fluttering past my ear.

I remember the silence

of a late-night subway platform,

far below the midnight city streets

just before the A-train roared into view

obliterating the momentary quiet.

I remember the silence

of early morning meditation

before the ceaseless sound of tinnitus arrived

like the flat-line tone of a heart monitor

announcing the death of silence.

Host Amber Smith: This has been Upstate's "HealthLink on Air," brought to you each week by Upstate Medical University in Syracuse, New York.

Next week on HealthLink on Air, a new infusion medication to slow Alzheimer's.

If you missed any of today's show, or for more information on a variety of health, science, and medical topics, visit our website at healthlinkonair.org.

Upstate's "HealthLink on Air" is produced by Jim Howe, with sound engineering by Bill Broeckel.

This is your host, Amber Smith, thanking you for listening.