Research in Professor Matthew Kay’s laboratory is focused on studying cardiac electrical activity and mitochondrial function during normal and disease conditions. Work is primarily focused on understanding how hypoxia, ischemia, and heart failure alter myocardial energy supply and demand and identifying how that may motivate deadly arrhythmias. Professor Kay and his research team have specific expertise in high-speed optical assessments of cardiac physiology, including optical mapping and absorbance spectroscopy, and have developed powerful algorithms to analyze time varying optical signals.
Recent projects address hypotheses related to metabolism and electrophysiology during hypoxia, ischemia, and heart failure using fluorescence imaging of mitochondrial NADH, sarcolemma membrane potential, intracellular calcium, and, recently, myocardial absorbance assessments of mitochondrial ETC chromophore redox state. Results from bi-ventricular working rabbit hearts have revealed a critical balance between oxygen supply and demand during high work load, particularly when capillary oxygen reserve is absent. Other projects investigate mitochondrial damage and ROS production during ischemia/reperfusion injury and the toxic effects of plasticizers on cardiac electrical activity and metabolism. Optogenetic approaches are used to selectively modulate the activity of cardiac autonomic nerves to study how sympathetic and parasympathetic tone influences electromechanical function. Recent work with GWU neuroscientist David Mendelowitz, PhD is focused on examining how chronic selective activation of hypothalamic oxytocin neurons improves cardiac function and favorably alters indices of cardiac ischemia and damage that occurs in heart failure animals.
The Kay Lab at The George Washington University performs general methods in experimental cardiovascular and cardiac research that include ex-vivo Langendorff and working heart perfusion (mice, rats, guinea pigs, and rabbits), in-vivo echocardiography of small animals, trans-ascending aortic constriction model of heart failure, ECG acquisition and signal analysis, optical mapping of isolated perfused hearts, dose-response drug studies using isolated hearts, neurocardiac optogenetics, glass micropipette electrode measurements of cardiac action potentials, perflourocarbon emulsion production for organ perfusion, CUBIC clearing of tissue, 2D and 3D confocal microscopy, and general biochemical assessments that include western blotting, immunohistochemistry, and general absorbance assays.
Publications
- Asfour H, Wengrowski AM, Jaimes III R, Swift LM & Kay MW (2012). NADH Fluorescence Imaging of Isolated Biventricular Working Rabbit Hearts. J Vis Exp Jul 24, 1–7.
- Cauley E, Wang X, Dyavanapalli J, Sun K, Garrott K, Kuzmiak-Glancy S, Kay MW & Mendelowitz D (2015). Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure. Am J Physiol Heart Circ Physiol 309, H1281-7.
- Garrott K, Dyavanapalli J, Cauley E, Dwyer MK, Kuzmiak-Glancy S, Wang X, Mendelowitz D & Kay MW (2017a). Chronic activation of hypothalamic oxytocin neurons improves cardiac function during left ventricular hypertrophy-induced heart failure. Cardiovasc Res 18, 32–39.
- Garrott K, Kuzmiak-Glancy S, Wengrowski A, Zhang H, Rogers J & Kay MW (2017b). KATP channel inhibition blunts electromechanical decline during hypoxia in left ventricular working rabbit hearts. J Physiol 595, 3799–3813.
- Jaimes R, Kuzmiak-Glancy S, Brooks DM, Swift LM, Posnack NG & Kay MW (2016). Functional response of the isolated, perfused normoxic heart to pyruvate dehydrogenase activation by dichloroacetate and pyruvate. Pflügers Arch - Eur J Physiol 468, 131–142.
- Jaimes III R, Kuzmiak-Glancy S, Brooks D & Kay MW (2014). Short Term Functional Effects of Pyruvate Dehydrogenase Complex Activation in the Normoxic Heart. Am J Physiol Hear Circ Physiol.
- Jaimes III R, Walton RD, Pasdois PLC, Bernus O, Efimov IR & Kay MW (2016). A Technical Review of Optical Mapping of Intracellular Calcium within Myocardial Tissue. Am J Physiol Heart Circ Physiol 310, H1388–H1401.
- Kuzmiak-Glancy S, Jaimes R, Wengrowski AM & Kay MW (2015). Oxygen demand of perfused heart preparations: how electromechanical function and inadequate oxygenation affect physiology and optical measurements. Exp Physiol 100, 603–616.
- Kuzmiak S, Jaimes III R & Kay M (2012). The effect of dichloroacetate on NADH fluorescence in isolated perfused rat hearts. In Arizona Physiological Society Conference, Glendale, AZ.
- Moreno A, Kuzmiak-Glancy S, Jaimes R & Kay MW (2017). Enzyme-dependent fluorescence recovery of NADH after photobleaching to assess dehydrogenase activity of isolated perfused hearts. Sci Rep 7, 45744.
- Wengrowski AM, Kuzmiak-Glancy S, Jaimes R & Kay MW (2014). NADH changes during hypoxia, ischemia, and increased work differ between isolated heart preparations. Am J Physiol Heart Circ Physiol 306, H529-37.
- Wengrowski AM, Wang X, Tapa S, Posnack NG, Mendelowitz D & Kay MW (2015). Optogenetic release of norepinephrine from cardiac sympathetic neurons alters mechanical and electrical function. Cardiovasc Res 105, 143–150.
