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CARDIOVASCULAR
AND RENAL PHARMACOLOGY
BARRY M. MASSIE, M.D., Professor of Medicine, Cardiology
Our research continues to involve several areas of investigation related to the pathophysiology and management of heart failure, which are summarized below.
Although impaired left ventricular function is responsible for most of the manifestations of heart failure, work from our laboratory and others has demonstrated that in the chronic state, exercise intolerance is a significant part due to abnormalities of the peripheral circulation and skeletal muscle. We have reported changes in muscle function, composition, biochemistry, and metabolism in patients with even mild congestive heart failure. Although we continue investigations in patients, we have begun to use an animal model in order to delineate the mechanism of these abnormalities. The animal studies demonstrate for the first time that the changes in skeletal muscle are a primary response to heart failure, rather than to the resulting limitation inactivity.
Also, our group continues to investigate new therapies for heart failure. I have been the Principal Investigator of several national and international multicenter trials, and am now planning two critical studies: a trial of antithrombotic therapy with aspirin or warfarin in heart failure, and the first randomized, controlled trial of therapy in patients with heart failure and preserved systolic function.
We have also had the opportunity to study new drug treatments for heart failure. Currently we are performing the initial investigations of a novel diuretic which works by blocking adenosine A1 receptors, a dopamine-beta hydroxylase inhibitor, and an endothelin antagonist.
Utilizing the rat coronary artery ligation model to produce heart failure, we have been examining the time dependent changes in gene expression in cardiac myocytes and non-myocyte cells. Two manuscripts have been submitted.
Stimulated by the results of a survey we performed, which demonstrated substantial differences in practice patterns between cardiologists and primary care physicians. We have begun to study guideline adherence, resource utilization, and outcomes in these groups within the Kaiser Permanente Medical Care Group. We are also examining these issues in multicenter trials. In the next year, we expect to commence a pilot randomized study of heart failure management by specialists and generalists.
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