Sherlock Holmes, move over!
Dr. Keith Brunt, assistant professor in the Department of Pharmacology at 黑料吃瓜网Medical School, 鈥斅燽ased at 黑料吃瓜网Medicine Saint John 鈥斅爃as undertaken a classic example of detective work to determine the cause of air-hunger in heart patients.
Conducted together with a colleague at the University of Guelph (Dr. Jeremy Simpson), the findings, , are set to change textbooks on this disease process.
The mystery begins
This story starts in a bar over a glass of beer, with two research colleagues discussing the finer points of terminology between congestive heart failure and heart failure. One points out that while most heart failure patients experience shortness of breath, or 鈥渁ir-hunger,鈥� they don鈥檛 all have lung congestion. Thus the research question begins to form as to why? The two scientists are Dr. Brunt and Dr. Simpson.
This question led to a study on identifying the first instance in which breathlessness could be identified in an experimental model.The study, which took seven years to complete, examined what happens, when it happens, why it happens and what can treat it using an experimental model of hypertensive heart failure.
The first two years of the study saw everything go well. However, what the researchers initially expected to be a physical explanation for breathlessness was disproven by their own findings. 鈥淐onfirmatory experiments failed and we had to figure out why,鈥� says Dr. Simpson. 鈥淭his led us to look at the brain.鈥�
They brought graduate students on board and co-supervised them at a distance between their two universities as they established themselves as early career scientists in Canada.
Findings and what happens
鈥淲e鈥檝e been treating heart failure and hypertension for 30 years but did not know about the role the kidney鈥檚 hormones have on the brain in creating breathlessness and what that would mean for heart patients,鈥� explains Dr. Brunt. 鈥淲e also didn鈥檛 realize the secondary effect of air-hunger actually occurs much sooner than the physical changes in the lungs.鈥�
It begins with the kidneys sending signals to the brain as the heart develops trouble pumping enough blood. It requests more blood by sending out hormones (angiotensin and norepinephrine) to the brain which makes the heart pump harder and the respiratory muscles to work harder than they should.
The problem occurs when the respiratory muscles don鈥檛 get a break. This leads to atrophy in the muscle tissue, which results in inefficient productivity that in turn would make patients breathless. The question became why some patients get better some of the time and others continue to struggle.
What helps and what this means for heart patients
Dr. Brunt and Dr. Simpson found that only a few drugs that are already on the market for heart failure (like candesartan) cross the blood-brain barrier and cancel out the signals to the brain. This enables the respiratory muscles to relax and recover. Other drugs (like valsartan) do not cross this barrier, so the signals continue and the patient experiences air-hunger.
鈥淏asically these could findings could mean an improved quality of life for patients living with hypertension and developing heart failure,鈥� says Dr. Simpson.
鈥淭he drugs we tested are already on the market, which means they can start being used today,鈥� says Dr. Brunt. 鈥淲e don鈥檛 have to wait for the development and testing of new drugs that could take years or decades to help today鈥檚 patients. Physicians can begin using this information in the art-of-medicine today.鈥�
Looking forward
The two researchers are currently working with cardiologists and respirologists at the New Brunswick Heart Centre to monitor patients with hypertension and heart failure on these medications in a clinical study that focuses on the balance and combination of the medications prescribed.
鈥淚t鈥檚 not just heart patients we are interested in, but we are also looking at how similar mechanisms may be operating in other diseases (like sleep apnea and COPD),鈥� says Dr. Simpson.
This study was funded by the Heart and Stroke Foundation of Canada, the Canadian Lung Association and Natural Sciences and Engineering Research Council (NSERC).