Dr. Holly Middlekauff
Professor  of Medicine and Physiology
310-206-6672
hmiddlekauff@mednet.ucla.edu

Research Interests:

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 General Clinical 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. In the near future, we will begin studies to assess the mechanisms underlying the skeletal muscle myopathy in heart failure. Specifically, we will test the hypothesis that sympathetic activation directed to skeletal muscle is the instigator of the skeletal myopathy of heart failure.

Representative Publications:

Middlekauff HR, Chiu J, Hamilton MA, Fonarow GC, MacLellan R, Hage T, Moriguchi J, Patel J. Muscle mechanosensitivity in heart failure. Am J Physiol Heart Circ Physiol 2004; 287:H1937-43.

Middlekauff HR, Chiu J. Cyclooxygenase products sensitize muscle mechanoreceptors in healthy humans. Am J Physiol Heart Circ Physiol 2004; 287:H1944-49.

Middlekauff HR. How does cardiac resynchronization therapy improve exercise capacity in chronic heart failure? J Cardiac Failure 200511:534-541.

Middlekauff HR and Sinoway L. Point/Counterpoint: Increased mechanoreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure. J Appl Physiol, 2006

Representative Publications:

Chen, B.M. and Grinnell, A.D. (1997) Kinetics, Ca++ dependence, and biophysical properties of integrin-mediated mechanical modulation of transmitter release from frog motor neerve terminals. J. Neurosci.  17:904-916

Yazejian, B.M., Sun, X.-P., and Grinnell, A.D. (2000) Tracking presynaptic Ca++ dynamics during neurotransmitter release with Ca++-activated K+ channels. Nature Neurosci. 3:566-571.

Sun, V.-P., Yazejian, B, and Grinnell, A.D. (2004) Electrophysiological properties of BK channels in Xenopus motor nerve terminals. J. Physiol. 557:207-228

Synapse in Xenopus 
Nerve-muscle cell culture

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