Tag: cardiovascular disease

High Burden of Uncontrolled Disease in KwaZulu-Natal

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A comprehensive health-screening program has found a high burden of poorly controlled or uncontrolled disease KwaZulu-Natal, along with a high incidence of undiagnosed diseases.

The study, published in The Lancet Global Health, found that four out of five women over 30 had a chronic health condition, and that the HIV-negative population and older people had the highest burden of undiagnosed or poorly controlled non-communicable diseases such as diabetes and hypertension. The study was conducted at the Africa Health Research Institute (AHRI).

Study co-leader Emily Wong, MD, at AHRI in Durban, said: “The data will give AHRI researchers and the Department of Health critical indicators for where the most urgent interventions are needed,” Dr Wong said. “The research was done before COVID, but it has highlighted the urgency of diagnosing and treating people with non-communicable diseases — given that people with uncontrolled diabetes and hypertension are at higher risk of getting very ill with COVID.” 

HIV-associated tuberculosis infections are particularly prevalent in Durban. Dr Wong of the University of Alabama works there to understand the impact of HIV infection on tuberculosis pathogenesis, immunity and epidemiology. In sub-Saharan Africa, 15 years of intense public health efforts that increased access to antiretroviral therapy has resulted in decreased AIDS mortality and raised life expectancy. As a result, there is an increasing priority to address other causes of disease, including tuberculosis and non-communicable diseases.

Over 18 months, health workers screened 17 118 people aged 15 years and older via mobile camps within 1 kilometre of each participant’s home in the uMkhanyakude district. They found high and overlapping burdens of HIV, tuberculosis, diabetes and hypertension among men and women.

While the HIV cases were largely well diagnosed and treated, some demographic groups  still had high rates of undiagnosed and untreated HIV, such as men in their 20s and 30s. In contrast, the majority of people with tuberculosis, diabetes or hypertension were either undiagnosed or not well controlled. Of particular concern was the high rates of undiagnosed and asymptomatic tuberculosis discovered, as it remains one of the leading causes of death in South Africa.

“Our findings suggest that the massive efforts of the past 15 years to test and treat for HIV have done very well for that one disease,” Dr Wong said. “But in that process, we may have neglected some of the other important diseases that are highly prevalent.”

The mobile camps screened for diabetes, high blood pressure, nutritional status (obesity and malnutrition), and tobacco and alcohol use, as well as HIV and tuberculosis. The tuberculosis screening component included high-quality digital chest X-rays and sputum tests for people who reported symptoms or had abnormal X-rays. Clinical information was combined with 20 years of population data from AHRI’s health and demographic surveillance research. Using a sophisticated data system combined with artificial intelligence to interpret the chest X-rays, AHRI’s clinical team examined the information in real time, referring people to the public health system as needed.

The study found that: 

  • Half of the participants had at least one active disease, and 12 percent had two or more diseases. Diabetes and hypertension incidences were 8.5 percent and 23 percent, respectively.
  • One-third of the people were living with HIV, but this was mostly well diagnosed and treated. A particularly high burden of HIV, high blood pressure and diabetes was seen in women.
  • For tuberculosis, 1.4 percent of the people had active disease, and 22 percent had lifetime disease. About 80 percent of the undiagnosed tuberculosis was asymptomatic, with higher rates of active tuberculosis seen in men.
  • Several disease patterns varied by geographical location — eg, the highest HIV burden was seen near main roads, while higher rates of tuberculosis and non-communicable diseases were seen in more remote areas.

Source: University of Alabama at Birmingham

Journal information: Wong, E. B., et al. (2021) Convergence of infectious and non-communicable disease epidemics in rural South Africa: a cross-sectional, population-based multimorbidity study. The Lancet Global Health. doi.org/10.1016/S2214-109X(21)00176-5.

Drop in Heart Attacks Linked to COVID Pandemic

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A sharp drop in heart attacks in Finland last year seems to be a result of the COVID pandemic, doctors believe.

Cardiologist Mika Laine noticed a roughly 30 per cent reduction in the number of patients suffering myocardial infarction at Helsinki University Central Hospital in April and May 2020. But what was even more surprising was that this was not an isolated occurrence.

“When we started to study this further, we noticed that exactly the same phenomenon happened everywhere else in Finland and also in other countries in Europe and in the United States. So it was a kind of global phenomenon that happened during the COVID pandemic,” he told Euronews.

What was behind the drop?

Dr Laine is of the opinion that the fall in heart attack patient numbers results from changes made in response to the COVID outbreak.

“We have the exact same genes that we had a year ago, two years ago. So it has to be something in the environment that has changed,” he said. One major factor could be the massive global shift to remote working for many people, as a result of the lockdowns.

“People are at home, they are less stressed because they don’t need to go through morning traffic, hurry to work and so forth,” Dr Laine added.

EU Science Hub data shows that even before the pandemic, Finns worked remotely more than almost any other EU country. Last May, EU labour research body Eurofound revealed that Finnish workers made the fastest switch to teleworking in the EU, with nearly 60 per cent switching over.

“We also see this decrease in those people who are retired, who don’t go to work, so it cannot be just because you’re commuting,” said Dr Laine.
He however cautioned that there could be other factors behind the fall in heart attack patients.

Was there a real fall in heart attacks in 2020?

“We know that many people stopped smoking because smoking was associated with severe COVID mortality,” he said.

Better air quality in urban areas as a result of the lockdown could be another cause, Laine said, since airborne particles are known to be a risk factor for heart disease.

However not all are convinced that the pandemic had a positive impact on patients with all types of heart conditions.

Research published in the Journal of the American College of Cardiology in January found that, during the early phase of the pandemic, deaths due to ischaemic heart disease and hypertensive diseases increased in some parts of the US. Some patients may have died as a result of avoiding hospital visits due to infection fears, the researchers noted. 

A temporary or permanent effect?

With Finland, however,Dr Laine believes that was not the case.

“We haven’t seen any increase in mortality in cardiac diseases and so currently we think that it’s a true decrease in the number of cases and not because patients are not seeking help,” he said. “People were not dying at home to myocardial infarction”.

According to Dr Laine, the number of heart attack patients in Finland remains about 5 per cent lower than average, despite the easing of COVID restrictions.

“I think this is a typical example that environmental factors can have profound effects on myocardial infarction. And I think it’s motivating us to change our lifestyle healthier,” Dr Laine said.

Source: EuroNews

Angioplasty Needed by Smokers 10 years Before Non-smokers

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Smokers needed their blocked arteries fixed nearly 10 years earlier than non-smokers, and patients with obesity underwent these procedures four years earlier than non-obese patients, according to a new US study.

Angioplasty is a nonsurgical procedure that opens clogged or narrow coronary arteries. The procedure involves inserting an inflatable balloon-tipped catheter through the skin in extremities and then inflating the balloon once it reaches the stenosed arterial site. The balloon pushes the atherosclerotic intraluminal plaque against the arterial wall and restores the luminal diameter, and so restores blood flow to the heart muscle.

The study included patients with no heart attack history, treated at hospitals across Michigan. The patients had all undergone angioplasty and/or stenting to widen or unblock their coronary arteries and restore blood flow. Nearly all of them had at least one traditional risk factor, including smoking, obesity, high blood pressure, high cholesterol and diabetes. Most patients had three or more.

Furthermore, compared to men, women generally had their first procedure at a later age. Over the past ten years, among patients undergoing their first angioplasty or stent procedure, obesity and diabetes rates have increased, while smoking and high cholesterol have decreased.

“Smoking is a completely preventable risk factor,” said senior author Devraj Sukul, MD, MSc, an interventional cardiologist and a clinical lecturer at the University of Michigan Health Frankel Cardiovascular Center. “If we direct additional efforts at preventing smoking and obesity we could significantly delay the onset of heart disease and the need for angioplasty and stenting.”

“In Michigan, we will work to help every smoker quit at the time of cardiac care because it is an unmatched teachable moment for patients,” said Michael Englesbe, M.D., a surgeon and professor at Michigan Medicine who serves as portfolio medical director for the Collaborative Quality Initiatives.

Source: Medical Xpress

Journal information: Zoya Gurm et al, Prevalence of coronary risk factors in contemporary practice among patients undergoing their first percutaneous coronary intervention: Implications for primary prevention, PLOS ONE (2021). DOI: 10.1371/journal.pone.0250801

New Measurement of Heart Function Could Benefit High-risk Heart Patients

A new measurement of heart function developed at UVA Health could improve survival for people with heart failure by identifying high-risk patients who require tailored treatments, according to a new study.

The study is the first to show a survival benefit from wireless pressure monitoring sensors implanted in the pulmonary arteries. Pulmonary artery proportional pulse pressure, or PAPP, is a new measure of heart function that can identify patients at very high risk of hospitalisation or death from systolic heart failure or pulmonary hypertension (high blood pressure in the heart and lungs).

Previous work showed that patients with low PAPPs were at much higher risk than those with higher PAPPs, so the researchers tested whether these benefits were maintained in patients undergoing implantation of pressure sensors that continuously monitor pressure in the pulmonary artery.

“We found that PAPP is a very good measure of how stiff or compliant the pulmonary arteries are. The stiffness of the pulmonary arteries determines how much resistance the right side of the heart has overcome to pump blood effectively to the lungs,” said Sula Mazimba, MD, MPH, a heart failure expert at UVA Health and the School of Medicine. “The importance of this simple measure is that it can identify patients that are at greatest risk of dying or being hospitalised. This allows us to tailor more aggressive treatments.”

Heart failure causes more than 1 million hospital admissions each year, and approximately half of patients die within five years of diagnosis.

The new study evaluated the benefits of PAPP monitoring in patients with systolic heart failure, where the left ventricle is weak, as well as those with pulmonary hypertension.

To find out if PAPP monitoring could predict outcomes in these patients, Dr Mazimba and colleagues analysed data from 550 participants in the CHAMPION clinical trial, whose participants were randomised to receive an implantable, wireless heart monitor called the CardioMEMS HF System.

They found that participants with a below-average PAPP had a significantly higher risk of hospitalisation or death compared with those with higher PAPPs. Furthermore, the monitoring  reduced the risk of death for those with low PAPPs by 46% annually during two to three years of follow-up.

“The implications of this study are highly significant,” said co-investigator Kenneth Bilchick, MD, MS, a cardiologist at UVA Health. “We now have identified a specific group of patients who appear to have a marked improvement in survival with implantation of these pulmonary artery wireless monitors. As a result, the findings of the study could maximise the impact of this technology for a large number of potential candidate patients. This is an excellent example of how secondary analyses of clinical databases maintained by the National Institutes of Health can result in novel and personalised approaches to patient care.”

The researchers say further study is necessary to gauge the full potential of PAPP monitoring to improve care for patients with heart failure, but early results were encouraging.

“In the past, the function of the right chamber of the heart was often ignored and considered to be inconsequential to the overall performance of the heart, but we are now learning that this is not the case,” Dr Mazimba said. “Having tools that signal when the right side of the heart is under strain may aid clinicians to adopt timely tailored treatments for heart-failure patients.”

Source: UVA Health

Ventricular Assist Device Pulled from Market due to Failures

Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

The HeartWare system, a left ventricular assist device (LVAD) for advanced heart failure patients, is being discontinued immediately, according to the Food and Drug Administration.

The manufacturer, Medtronic, is halting global distribution and sale of its HeartWare system in the wake of observational evidence of increased neurological adverse events and mortality for its LVAD compared with similar mechanical circulatory support (MCS) devices.

Last December, some HeartWare LVADs were recalled because of complaints that the pump may delay or fail to start. So far 100 of these complaints have been received, including 14 patient deaths and 13 cases where an explant was necessary, the FDA noted.

“We have been carefully monitoring the adverse events associated with this device and support its removal from the marketplace,” said Bram Zuckerman, MD, director of the Office of Cardiovascular Devices at the FDA’s Center for Devices and Radiological Health, in a statement.

Medtronic now advises physicians to immediately stop new implants of the HeartWare device, but does not recommend explants.

The company is working on a plan for ongoing support of the some 4000 patients around the world who currently have this LVAD. It received commercial approval for use in the US in November 2012.

The FDA named Abbott’s HeartMate 3 as one alternative LVAD for patients with end-stage heart failure. This device features a magnetic levitation system that keeps the rotor separate without mechanical contact.

“The FDA is working closely with both Medtronic and Abbott to ensure patient care is optimised during this transition period and that there is an adequate supply of devices available to provide this patient population with options for end-stage heart failure treatment,” said Dr Zuckerman.

In a separate press release, Abbott reassured the public that it has the ability to meet increased demand for MCS devices as a result of HeartWare withdrawal from clinical use.

Source: MedPage Today

Heart Risk in Transgender Men Receiving Hormones

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A study of transgender people receiving gender-affirming hormone therapy found that certain hormones increased certain cardiometabolic risk factors. 

Gender-affirming or cross-sex hormone therapy is integral to the management of transgender individuals, but there is only limited understanding of the effects of such hormones on cardiovascular health. Research is limited by the absence of large cohort studies, lack of appropriate control populations, and inadequate data acquisition from gender identity services. Existing epidemiological data suggest that the use of oestrogens in transgender females increases the risk of myocardial infarction and ischaemic stroke. Conversely, testosterone use in transgender males is currently lacking any consistent or convincing evidence of increased risk of cardiovascular or cerebrovascular disease.

This retrospective study included 129 transgender individuals receiving gender-affirming hormone therapy. In transgender males receiving testosterone, there was an average 2.5% drop in HDL cholesterol levels seen each year of using gender-affirming hormone therapy (P=0.03). However, researchers did not see this change in transgender females on estradiol during the average 48-month follow-up period. Additionally, the researchers found no significant changes in LDL cholesterol, triglycerides, HbA1c, or 25-hydroxyvitamin D levels in transgender males or transgender females.

About 53% of the participants in the study identified as transgender males, and more than 60% of the cohort was white. The median age of the total cohort was 26 with a BMI of 25.5. The majority of transgender males were on intramuscular injectable preparations of testosterone cypionate.

Similar to prior studies, a significant decrease in HDL was noted in TM on testosterone therapy. The researchers noted that further study is needed on the correlation of this finding with changes in diet and exercise while on testosterone therapy and impact on cardiovascular events. Reassuringly, no other changes noted in cardiovascular parameters.

“Further long-term data is needed for patients receiving this hormone therapy to assure that their long-term cardiovascular risk is optimised,” concluded Samihah Ahmed, MD, MBA, of Northwell Health Lenox Hill Hospital in New York City, who presented the findings.

Source: MedPage Today

Presentation information: Ahmed S, et al “Cardiometabolic risk factors in transgender individuals taking gender-affirming hormone therapy through four years” AACE 2021. 

Averting Heart Failure by Shutting Down a Heart Protein

Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

Shutting down a protein found in cardiac muscle could be a new mechanism to treat post-heart attack heart failure, according to research led by the University of Cambridge.

New drugs are needed to improve the heart’s pumping ability after damage from a heart attack. Drugs that strengthen the contraction of failing heart muscle have been deemed unsafe, leaving a gap in the heart attack and heart failure armamentarium.

Researchers now believe that they might have identified a new drug target—a protein called MARK4.

In research funded by the British Heart Foundation (BHF), Cambridge scientists found levels of MARK4 were elevated in mouse hearts after a heart attack. When they compared mice with and without MARK4 in the heart, they found hearts lacking the protein pumped blood 57% more efficiently. This protective effect was seen 24 hours after a heart attack and persisted over the entire follow-up period of four weeks.

The team was first in identifying that MARK4 fine-tunes a structural network within the heart muscle cell—called the microtubule network—that attaches to the machinery governing heart muscle cells contraction and relaxation. When MARK4 levels were increased after a heart attack, microtubules were tightly anchored onto the contractile machinery in the heart, increasing resistance and hindering normal function. When MARK4 levels were reduced, microtubules were loosely anchored, making contraction and relaxation easier.

Following a heart attack the speed of contraction in MARK4-lacking muscle cells increased by 42 percent and the speed of relaxation increased by 47 percent, compared to muscle cells from mice that had the MARK4 protein. They were also almost on par with healthy heart muscle performance, attesting to the power of reducing MARK4.

Based on these findings, the researchers suggested that drugs to switch off MARK4 could be a new way to improve recovery and help the heart to pump blood more efficiently in people with failing hearts.

Dr Xuan Li, BHF Intermediate Research Fellow at University of Cambridge BHF Centre of Research Excellence, said: “After years of research we’ve revealed an entirely new and promising way that could help the recovery of failing hearts.

“It’s early days, and we now need to test the longer-term effects of switching off MARK4. But if drugs to do that prove successful, the life-changing benefits could be seen in people with other types of heart disease as well as those who’ve had a heart attack and developed heart failure.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said: “Heart attacks are a major cause of disability worldwide—people who’ve had a major heart attack are at much greater risk of developing chronic heart failure. There are around 920 000 people living with heart failure in the UK, and we desperately need drugs to drastically improve the heart’s function in these patients.

“These findings are a positive step forward. Further research is needed to refine and test drugs that can target MARK4 before we’ll see them given to people who’ve had a heart attack and develop heart failure.”

Source: University of Cambridge

Study Links OCD to Increased Risk of Stroke

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Adults with obsessive-compulsive disorder (OCD) were more than three times as likely to have an ischaemic stroke later in life compared to adults who do not have OCD, according to new research.

OCD involves intrusive thoughts which may be accompanied by actions to alleviate the stress brought on by these thoughts; these are called obsessions and compulsions, respectively. Potentially debilitating, OCD typically manifests in adolescence and is under-reported and under-treated. The World Health Organization ranks OCD as one of the ten most disabling conditions worldwide, with a lifetime prevalence of 1% to 3%.

Clinical research has shown that patients with OCD often have stroke-related metabolic disorders, such as obesity and diabetes. 

While a growing body of evidence suggests an association between OCD and stroke risk, with some patients developing OCD after a stroke, OCD may also influence stroke risk. OCD raises the risk for ischaemic stroke more than 3-fold, especially among older adults
Drawing on health records from 2001-2010 from the Taiwan National Health Insurance Research Database, researchers compared stroke risk between 28 064 adults diagnosed with OCD and 28 064 adults without an OCD diagnosis. The average age at diagnosis was 37 years old, with equal representation of men and women, with a maximum data coverage of 11 years.

Analysis showed that even after controlling for factors known to increase stroke risk such obesity and high blood pressure, OCD remained an independent risk factor for ischaemic stroke. However, no differences were found when considering hemorrhagic strokes, and medications to treat OCD were linked to increased risk of stroke.
Ya-Mei Bai, MD, PhD, Professor, Department of Psychiatry, Taipei Veterans General Hospital, said: “The results of our study should encourage people with OCD to maintain a healthy lifestyle, such as quitting or not smoking, getting regular physical activity and managing a healthy weight to avoid stroke-related risk factors.”

Worldwide, stroke is the second-leading cause of death after heart disease. Cerebrovascular diseases often present complex cases, and this study was the first to consider how OCD and strokes may be associated on a longer time scale. 

Limitations include the observational nature of the study being unable to establish cause and effect, as well as the inclusion in the data of only stroke patients who sought health care. Additionally, information on disease severity and outcome was not included along with family medical history or environmental influences, which can further affect both the extent of OCD and severity of strokes.

“For decades, studies have found a relationship between stroke first and OCD later,” said Prof Bai. “Our findings remind clinicians to closely monitor blood pressure and lipid proles, which are known to be related to stroke in patients with OCD. More research is needed to understand how the mental processes connected to OCD may increase the risk of ischaemic stroke.”

Source: News-Medical.Net

Journal information: Chen, M-H., et al. (2021) Increased Risk of Stroke in Patients With Obsessive-Compulsive Disorder: A Nationwide Longitudinal Study. Stroke: Journal of the American Heart Association. doi.org/10.1161/STROKEAHA.120.032995.

Familial High Cholesterol Often Eludes Genetic Testing

Image source: National Cancer Institute/Unsplash

Most familial hypercholesterolemia (FH) cases would go undetected if people were to rely on array-based genetic tests alone, a new study suggests.

FH predisposes people to elevated levels of LDL cholesterol, which can lead to premature coronary artery disease and early death.  

For example, the 23andMe test, which has a limited screen for only 24 known FH variants, would have missed over 60% of individuals with the autosomal dominant disorder. This figure was even worse for non-European ancestry individuals.

“Limited-variant screens may falsely reassure the majority of individuals at risk for FH that they do not carry a disease-causing variant, especially individuals of self-reported Black/African American and Hispanic ancestry,” according to Amy Sturm, of the Geisinger Genomic Medicine Institute in Danville, Pennsylvania, and colleagues.

In their study, limited-variant screening would miss nearly 94% and 85% of Black and Hispanic individuals with confirmed FH pathogenic variants. However this would be true for only a third of Ashkenazi Jewish people.

“The reduced yield of limited-variant screening could result in a major health care disparity for groups already affected by social and medical disenfranchisement that beget serious health disparities including a significantly higher rate of cardiovascular death among Black/African American individuals,” the investigators said.

“When FH is strongly clinical suspected, even if array-based FH reporting has negative results, a clinical genetic test should still be considered,” according to an accompanying note by JAMA Cardiology editors Pradeep Natarajan, MD, MMSc, of Massachusetts General Hospital and Harvard Medical School in Boston, and Elizabeth McNally, MD, PhD, of Northwestern University Feinberg School of Medicine in Chicago.

“Genetic databases overrepresent European ancestry populations and therefore make interpretation of genetic variation more accurate in these cohorts. However, even 64% of the FH mutations in European American individuals would have been missed by the 24-variant [test],” noted Drs Natarajan and McNally.

“Unfortunately, genetic testing for FH is underused, with 90% of affected individuals worldwide remaining undiagnosed and only 3.9% of patients with FH in the U.S. having a record of genetic testing,” noted Dr Sturm and colleagues.

“Recent expert statements recommend that patients suspected of having FH be offered genetic testing and that first-degree relatives of genetically positive individuals be screened for FH by lipid profile or genetic testing,” according to them.

Comprehensive genetic testing with next-generation sequencing (NGS) detects over 2000 potentially pathogenic variants within full genomes. Assay-based screens such as 23andMe only test for a small subset of known variants, and not the number present.

Both types of genetic tests for FH are available either in clinical settings or as a direct service to consumers.

“Whether testing is obtained directly by a consumer or through a clinical setting, those tested should consult with a genetic counselor or other qualified health care professional to fully understand the benefits and limitations of the different types of genetic testing for FH,” Sturm’s group urged.

For the study, the authors took deidentified NGS results, sourced from a single clinical laboratory, for gene panels of individuals receiving comprehensive genetic testing either for an FH indication (4563 participants) or as proactive health screening (6482 participants).

The researchers had tested both cohorts for more than 2000 possible variants in four FH-associated genes: LDLR, APOB, PCSK9, and LDLRAP1.

With the limited screening tests, only 8.4% of people with FH indication had a positive detection, compared to 27.0% for comprehensive NGS genotyping. In the proactive cohort of people with no clinical suspicion of FH, clinically significant FH variant prevalence was about one in 191 according to the comprehensive test.

A limitation was the researchers’ inability to confirm genetic testing results with medical and family histories.

Source: MedPage Today

Journal information: Sturm AC, et al “Limited-variant screening vs comprehensive genetic testing for familial hypercholesterolemia diagnosis” JAMA Cardiol 2021; DOI: 10.1001/jamacardio.2021.1301.

Unexpected Discovery Opens Up Stroke and Cardiac Arrest Treatments

Image source: Pixabay

In a surprising discovery, researchers at Massachusetts General Hospital (MGH) identified a mechanism that protects the brain from the effects of hypoxia. This serendipitous finding, which they report in Nature Communications, could help develop therapies for strokes, as well as brain injury resulting from cardiac arrest.

However, this study began with a very different objective, explained senior author Fumito Ichinose, MD, PhD, an attending physician in the Department of Anesthesia, Critical Care and Pain Medicine at MGH, and principal investigator in the Anesthesia Center for Critical Care Research. Ichinose and his team are developing techniques for inducing suspended animation, a state similar to hibernation where a human’s body functions are temporarily slowed or halted for later revival. 

Ichinose believes that the ability to safely induce suspended animation could have valuable medical applications, such as pausing the life processes of a patient with an incurable disease until an effective therapy is found. Often seen in science fiction, and currently studied by NASA, it could also allow humans to travel long distances in space.

A 2005 study found that inhaling a gas called hydrogen sulfide caused mice to enter a state of suspended animation. Hydrogen sulfide, which smells like rotten eggs, is sometimes called ‘sewer gas.’ Oxygen deprivation in a mammal’s brain leads to increased production of hydrogen sulfide. As this gas accumulates in the tissue, hydrogen sulfide can halt energy metabolism in neurons, causing them to die. Oxygen deprivation is a hallmark of ischaemic stroke, the most common type of stroke, and other injuries to the brain.

At first, Dr Ichinose and his team set out to study the effects of exposing mice to hydrogen sulfide repeatedly, over an extended period. At first, the mice entered a suspended-animation-like state—their body temperatures dropped and they were immobile. “But, to our surprise, the mice very quickly became tolerant to the effects of inhaling hydrogen sulfide,” said Dr Ichinose. “By the fifth day, they acted normally and were no longer affected by hydrogen sulfide.”

Interestingly, the mice that became tolerant to hydrogen sulfide were also able to tolerate severe hypoxia. Ichinose’s group suspected that enzymes in the brain that metabolise sulfide might be responsible for this. They discovered that levels of one particular enzyme, called sulfide:quinone oxidoreductase (SQOR), rose in the brains of mice when they breathed hydrogen sulfide for several days. They thus hypothesised that SQOR plays a role in resistance to hypoxia.

Nature has strong evidence for this; for example, female mammals resist hypoxia better than males—and the former have higher levels of SQOR. When SQOR levels are artificially reduced in females, their hypoxia resistance drops. (Oestrogen may be responsible for the observed increase in SQOR, as the hypoxia protection is lost when a female mammal’s estrogen-producing ovaries are removed.) Additionally, some hibernating animals, such as the thirteen-lined ground squirrel, are highly tolerant of hypoxia, which allows them to survive as their bodies’ metabolism slows down during the winter. The brain of a typical ground squirrel has 100 times more SQOR than that of a similar-sized rat. However, when the researchers ‘switched off’ expression of SQOR in the squirrels’ brains, they lost their protection against the effects of hypoxia.

Meanwhile, when the researchers artificially increased SQOR levels in the brains of mice, “they developed a robust defense against hypoxia,” explained Dr Ichinose. His team increased the level of SQOR using gene therapy, currently a technically complex, impractical approach. On the other hand, the team demonstrated that ‘scavenging’ sulfide, using an experimental drug called SS-20, reduced levels of the gas, thereby sparing the brains of mice when hypoxic.

Human brains have very low levels of SQOR, meaning that even a modest accumulation of hydrogen sulfide can be harmful, said Dr Ichinose. “We hope that someday we’ll have drugs that could work like SQOR in the body,” he says, noting that his lab is studying SS-20 and several other candidates. Such medications could be used to treat ischemic strokes, as well as patients who have suffered cardiac arrest, which can lead to hypoxia. Dr Ichinose’s lab is also investigating how hydrogen sulfide affects other parts of the body. For example, hydrogen sulfide is known to accumulate in other conditions, such as certain types of Leigh syndrome, a rare but severe neurological disorder usually leading to early death. “For some patients,” said Dr Ichinose, “treatment with a sulfide scavenger might be lifesaving.”

Source: Medical Xpress

Journal information: Eizo Marutani et al, Sulfide catabolism ameliorates hypoxic brain injury, Nature Communications (2021). DOI: 10.1038/s41467-021-23363-x