Paul C. Simpson, MD
Staff Physician, Medical Service, SFVAMC
Professor of Medicine, UCSF
Email: paul.simpson@ucsf.edu
New Treatments for Heart Failure
Dr. Simpson is interested in discovering new drugs to treat heart failure, one of the most common causes of hospitalization and death in veterans. In the 1980s, Dr. Simpson developed a new in vitro culture model of heart failure, and used this model to show that a type of receptor for adrenalin had marked anabolic effects in heart muscle cells. He has pursued this finding since, and recently discovered that mice lacking the key receptor develop heart failure. This finding correlates with clinical trials showing that blocking this receptor in human patients causes heart failure. Therefore, this basic research has two key implications for clinical practice. First, use of drugs that block these key receptors - a common practice in prostate disease - needs to be considered carefully. Second and conversely, activating this key receptor might be a new way to treat heart failure. Dr. Simpson is working now to test this novel idea. Early experiments have been very promising in two main ways. First, in mice, a drug that activates the key receptor (an alpha-1-adrenergic receptor) can prevent heart failure caused by a chemotherapy used in breast cancer, and can improve heart failure caused by a heart attack. Second, in humans, the pattern of receptors in the heart is the same as in mice, suggesting that the experiments in mice might well be relevant to human problems, and lead to a new drug to treat heart failure.
Chan T, Dash R, Simpson PC. 2008. An alpha-1A-adrenergic receptor subtype agonist prevents cardiomyopathy without increasing blood pressure. Circulation 118:S533.
Jensen BC, Swigart PM, Laden M-E, DeMarco T, Hoopes C, Simpson PC. 2008. Alpha-1-adrenergic receptor subtypes in human heart failure. J Card Fail 14:S3.
