(Press-News.org) A research team with the Faculty of Medicine & Dentistry at the University of Alberta reported findings that significantly improve understanding of how widely used drugs in Pulmonary Arterial Hypertension (PAH) affect the heart health of treated patients.
The research shows that medications often prescribed for PAH could block the function of an important hormone in the heart, decreasing the strength of contraction of the right heart chambers, a potentially important and yet unrecognized adverse effect.
PAH is a disease that affects the blood vessels of the lungs, causing a progressive narrowing and restriction of the blood flow through the lungs. This narrowing puts a significant strain in the right chamber (right ventricle) of the heart that pushes the blood through the lungs. Eventually the right ventricle fails, causing heart failure and death.
One of the causes of the narrowing of the lung blood vessels is the increased levels of endothelin in the lungs, a hormone that constricts blood vessels throughout the body. Commonly used and very expensive drugs that block the actions of endothelin, which are called endothelin receptor antagonists, or ERAs, are now used throughout the world to treat PAH patients. However, the effects of these drugs in the right ventricle had not previously been studied, until now.
Led by cardiologist Evangelos Michelakis and cardiac surgeon Jayan Nagendran's in a laboratory setting, a multidisciplinary team of cardiologists, cardiac surgeons, pathologists and scientists at the U of A studied human hearts from 50 PAH patients and laboratory models. The team showed that, while in the normal hearts, ERAs do not have significant effects because the endothelin levels are quite low, this is not the case in the diseased hearts of PAH patients. In the thickened right ventricles from PAH patients, the levels of endothelin are significantly increased.
This new finding suggests that this increase may be beneficial for hearts impacted by PAH, since endothelin is known to increase the strength of contraction of the heart muscle. In other words, as the right ventricle has to work harder pushing blood through the narrowed blood vessels, endothelin may help it function better, but this may be blocked by ERAs. The research team also showed that, as expected, ERAs decrease the strength of contraction of the diseased right ventricles.
"These new findings—that ERAs have direct effects on the right chambers of the heart—have important implications for treated patients" said Nagendran. "For example, PAH patients treated with ERAs can develop fluid retention (swelling), which is currently treated with diuretics. As fluid retention can be a result of decreased right ventricle function, the new findings suggest that this could be a previously unrecognized important adverse effect of these drugs."
In other words, while ERAs may have a beneficial effect on the lung blood vessels, they may also have unwanted effects on the heart.
"While this does not mean that PAH patients should stop using these drugs, this new research sheds more light on the overall mechanism of action of these drugs in PAH patients," said Michelakis. "It may also help physicians to better approach the treatment of PAH patients and design clinical studies to validate these new findings in large populations."
PAH tends to mostly affect younger women, although both sexes of all ages can be affected. The survival of PAH patients is similar to that of patients with metastatic breast cancer, but the yearly cost of treatment can be more than double compared to that of metastatic breast cancer, and can exceed $200,000 per patient.
### The study is published in the Jan. 18 issue of Circulation Research, a journal of the American Heart Association, and was funded by a grant from the University Hospital Foundation – Mazankowski Alberta Heart Institute, by the Alberta Innovates Health Solutions and by the Canada Research Chairs Program.
Michelakis and Nagendran are available for interviews Friday, January 18 between 9:00 a.m. and 12:30 p.m. MST
For more information, please contact:
Quinn Phillips, communications associate
780-248-2048, cell: 780-399-7505, quinn.phillips@ualberta.ca
New UAlberta research shows commonly prescribed medications could have adverse effects
2013-01-17
ELSE PRESS RELEASES FROM THIS DATE:
Novel technique reveals dynamics of telomere DNA structure
2013-01-17
Biomedical researchers studying aging and cancer are intensely interested in telomeres, the protective caps on the ends of chromosomes. In a new study, scientists at UC Santa Cruz used a novel technique to reveal structural and mechanical properties of telomeres that could help guide the development of new anti-cancer drugs.
Telomeres are long, repetitive DNA sequences at the ends of chromosomes that serve a protective function analogous to that of the plastic tips on shoelaces. As cells divide, their telomeres get progressively shorter, until eventually the cells stop ...
Diabetic fruit flies support buzz about dietary sugar dangers
2013-01-17
LA JOLLA, Calif., January 15, 2013 – Regularly consuming sucrose—the type of sugar found in many sweetened beverages—increases a person's risk of heart disease. In a study published January 10 in the journal PLOS Genetics, researchers at Sanford-Burnham Medical Research Institute and Mount Sinai School of Medicine used fruit flies, a well-established model for human health and disease, to determine exactly how sucrose affects heart function. In addition, the researchers discovered that blocking this cellular mechanism prevents sucrose-related heart problems.
"Our study ...
NFL players may be at higher risk for depression as they age
2013-01-17
SAN DIEGO – National Football League (NFL) players may be at increased risk of depression as they age due to brain damage resulting from concussions, according to two studies released today that will be presented at the American Academy of Neurology's 65th Annual Meeting in San Diego, March 16 to 23, 2013.
"The Centers for Disease Control and Prevention estimates that about 1.6 to 3.8 million sports concussions occur each year. While it is known that sports concussions can cause immediate disturbances in mood and thinking, few studies have investigated the long-term ...
Shorter woman, taller man: Preferences for partner height translate into actual partner choices
2013-01-17
Finding Mr. or Ms. Right is a complicated process, and choosing a mate may involve compromising on less important factors like their height. However, research published January 16 in the open access journal PLOS ONE by Gert Stulp and colleagues from the University of Groningen, Netherlands suggests that despite the many other factors involved, people's preferences for a partner's height are reflected in real couples in the UK.
Given the average heights of men and women in typical Western populations, two out of every hundred couples should comprise a woman who is taller ...
Warmest spring on record causes earliest flowering ever observed in eastern U.S.
2013-01-17
Exceptionally warm spring weather in 2010 and 2012 resulted in the earliest flowering times known in 161 years of recorded history at two sites in the eastern US, according to research published January 16 in the open access journal PLOS ONE by Elizabeth Ellwood of Boston University and colleagues.
Many plants need a long winter break to undergo physiological changes that make them bloom in the spring. According to several previous studies, this blooming is occurring earlier than before due to warmer springs caused by climate change. The consequences of such early flowering ...
Earliest sea cow ancestors originated in Africa, lived in fresh water
2013-01-17
A new fossil discovered in Tunisia represents the oldest known ancestor of modern-day sea cows, supporting the African origins of these marine mammals. The find is described in research published January 16 in the open access journal PLOS ONE by Julien Benoit and colleagues from the University of Science and Technology in Montpellier, France.
Some fossils of sea cow ancestors have been found in Jamaica, but the Tunisian fossil is more primitive and pre-dates these, revealing an older ancestor for sea cows that emerged at the same time as other modern mammals. Unlike ...
'Shell-shocked' crabs can feel pain
2013-01-17
The latest study by Professor Bob Elwood and Barry Magee from Queen's School of Biological Sciences looked at the reactions of common shore crabs to small electrical shocks, and their behaviour after experiencing those shocks. The research has been published in the Journal of Experimental Biology.
Professor Elwood's previous research showed that prawns and hermit crabs respond in a way consistent with pain. This latest study provides further evidence of this.
Professor Elwood said: "The experiment was carefully designed to distinguish between pain and a reflex phenomenon ...
New study sheds light on the origin of the European Jewish population
2013-01-17
Despite being one of the most genetically analysed groups, the origin of European Jews has remained obscure. However, a new study published online today (Thursday) in the journal Genome Biology and Evolution by Dr Eran Elhaik, a geneticist at the Johns Hopkins School of Public Health, argues that the European Jewish genome is a mosaic of Caucasus, European, and Semitic ancestries, setting to rest previous contradictory reports of Jewish ancestry. Elhaik's findings strongly support the Khazarian Hypothesis, as opposed to the Rhineland Hypothesis, of European Jewish origins. ...
Seeing beyond cameras: Predicting where people move in CCTV blind spots
2013-01-17
A new model from Queen Mary, University of London could be a useful security tool in tracking people in large, busy venues such as airport terminals and shopping centres.
The research fuses information gathered from multiple Close-Circuit Television (CCTV) network cameras and geographical maps for the first time, and could be useful in locating people in blind-spots where the CCTV cannot see, known as invisible areas.
Co-author Professor Andrea Cavallaro and director of Queen Mary's Centre for Intelligent Sensing, based in the School of Electronic Engineering and ...
Study suggests lung cancer mortality highest in black persons living in most segregated counties
2013-01-17
CHICAGO – Lung cancer mortality appears to be higher in black persons and highest in blacks living in the most segregated counties in the United States, regardless of socioeconomic status, according to a report published in the January issue of JAMA Surgery, a JAMA Network publication.
Lung cancer is the leading cause of cancer death in the United States and blacks are disproportionately affected with the highest incidence and mortality rates.
Awori J. Hayanga, M.D., M.P.H., of the University of Washington, Seattle, and colleagues examined the relationship between race ...