Holly R. Middlekauff
David Geffen School of Medicine at UCLA
United States of America
Professor, MedicineFaculty, Cardiology
The focus of my research is to understand the mechanisms of exercise dysfunction in patients with heart failure. I work exclusively with patients, that is, humans with heart failure, as well as healthy control subjects, - not animal models; my research in conducted in the Human Physiology Laboratory in the UCLA Clinical & Translational Research Center. In this work, we have found that reflex control of the neurovascular system during exercise is different in patients with heart failure compared to healthy controls. Heart failure patients have exaggerated increases in sympathetic nerve activity and renal artery vasoconstriction during exercise. The exaggerated reflex sympathetic activation appears to be mediated by exaggerated sensitivity of muscle mechanoreceptors' nerve endings present in skeletal muscle which are sensitive to mechanical deformation during exercise. Additionally, we are studying abnormalities of excitation-contraction coupling in the skeletal muscle in humans with heart failure. We have found that the expression of several critical calcium handling proteins is reduced in patients with heart failure. We are now collaboration with Dr. Julio Vergara and Dr. Marino DiFranco to determine if these abnormalities in protien content are associated with functional abnormalities in excitation contraction coupling in the skeletal muscle in humans with heart failure.