Heart Matters: Physiology of the Body s Powerhouse 11/28/12. Igor Mitrovic, MD

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1 BIOGRAPHY: Heart Matters: Physiology of the Body s Powerhouse 11/28/12 Igor Mitrovic, MD Igor Mitrovic, MD is Jack D. and DeLoris Lange Endowed Chair in Systems Physiology I, Professor in Department of Physiology University of California San Francisco. Dr. Mitrovic is Director of Professional School Education at his Department and he is responsible for the professional school physiology education at UCSF. He directs and co directs several courses in the Schools of Medicine and Pharmacy. His professional interests are centered around teaching and mentoring as well as development and improvement of the professional school curricula. His research interests include neurobiology of stress and stress resilience as well as neurobiology of addiciton and pain. He is a recepient of numerous teaching awards from all the professional schools at UCSF.Besides University work, he is also a Scientific Director of Institute For Health Solution, a non profit organization that studies and promotes approaches which lead to increased stress resilience and improved emotional well being. Dr. Mitrovic is also a Visiting Professor at University of Kragujevac School of Medicine (Kragujevac, Serbia) as well as recipient of the Honorary Doctorate Degree from the University of Kragujevac. BIBLIOGRAPHY: I. Mitrovic and T.C. Napier: Electrophysiological evidence for mu, delta, and kappa opioid receptors in the ventral pallidum. J. Pharmacol. Exp. Ther., 272: , T.C. Napier, I. Mitrovic, L. Churchill, M.A. Klitenick, and P.W. Kalivas: Substance P in the ventral pallidum: The anatomy, of an accumbal to pallidal projection, and electrophysiological and behavioral consequences of pallidal substance P. Neuroscience, 69:59 70, I. Mitrovic and T.C. Napier: Interaction between microiontophoretically applied mu opioid agonist DAMGO and substance P in regulation of ventral pallidal neuronal activity. Synapse, 23: , I. Mitrovic and T.C. Napier: Substance P attenuates and DAMGO potentiates amygdala glutamatergic neurotransmission within the ventral pallidum. Brain Research, 792: , C. Abbadie, K. Skinner, I. Mitrovic, and A. I. Basbaum: Neurons in the dorsal column white matter of the spinal cord: complex neuropil in an unexpected location. Proceedings of the National Academy of Sciences, 96:260 5, I. Mitrovic*, M. Margeta Mitrovic*, R. C. Riley*, L. Y. Jan, and A. I. Basbaum: Immunohistochemical localization of GABAB receptors in the central nervous system. The Journal of Comparative Neurology, 405: , 1999.

2 N.A. Muma, J.M. Lee, L. Gorman, B.A. Heidenreich, I. Mitrovic, T.C. Napier: 6 hydroxydopamineinduced lesions of dopaminergic neurons alter the function of post synaptic cholinergic neurons without changing cytoskeletal proteins. Experimental Neurology, 168: , Mitrovic I and Napier TC: Mu and kappa opioid agonists modulate ventral tegmental input to the ventral pallidum. European Journal of Neuroscience. 15:257 68, I.Mitrovic, M. Margeta Mitrovic, S.R. Bader, L.Y. Jan, M. Stoffel, A. I. Basbaum: Contribution of GIRK2 channels to sex differences in response to morphine and clonidine antinociception in mice. Proceedings of National Academy of Sciences, 100: , B.A. Heidenreich, I. Mitrovic, G. Battaglia, T.C. Napier: Limbic pallidal adaptations following longterm cessation of dopaminergic transmission: lack of upregulation of dopaminergic receptor function. Experimental Neurology, 186: , Mitrovic, I. Cardiovascular Disorders: Vascular Disease in Pathophysiology of Disease, an introduction to Clinical Medicine, 6th edition, Lange McGraw Hill I. Mitrovic, L. Fish de Peña, L. Frassetto, L Mellin: Rewiring the Stress Response: A New Paradigm for Health Care; Hypothesis, 9: 1 7, 2011.

3 Cardiovascular Physiology Heart Matters: Physiology of Body s Powerhouse Heart Matters: Physiology of Body s Powerhouse Little pump that could Electronic control Generates pressure to force blood flow Two sets of cardiac Electrical Mechanical Heart: the little pump that could Objectives: Describe the origin of the electrical impulses in the excitable (eg. Heart) cells (or, how are cells like batteries) Explain what happens when a heart muscle cell is electrically activated Name the place of origin of the normal electrical impulse in the heart and describe its spread Correlate the signals (waves) recorded in the ECG with the electrical activity in the heart muscle Speculate on the possible consequences of electrical failure in the heart Describe the process of electro-mechanical coupling Explain the mechanism of ventricular pressure generation and its function in cardiovascular system Speculate on the consequences of the mechanical failure of the heart Heart s Electrical Heart s mechanical Fibrilations 1

4 Heart: two pumps for two circulatory systems Systemic circulation and Pulmonary circulation Left heart: Systemic Right heart: Pulmonary 2* 25/2* Alveoli 25/10* Right heart in lungs Airway 5* 120/3* 120/80* Left heart MAP= 95* Elastic arteries Venules and systemic veins in tissues Arteriole Valves *pressure in mmhg 15* Cells in tissues 35* Regulation of blood vessel radius Heart cells are like batteries Specialized proteins called ion pumps and ion channels generate electric potential (inside of a cell is more negative than outside) Na + [145] Na + [10] Cardiac myocyte What happens when one ventricular heart cell (battery) is switched on Membrane potential (mv) +70 E Na K + [4] K + [135] Time E K Ca ++ [0.0001] Ca ++ [2] Heart muscle cells are electrically connected! Specialized proteins called gap junctions allow for current flow between the heart muscle cells Signal that turns on the cardiac cells starts in the atria There is a coordinated spread of electrical current from SA node through ventricles 2

5 Electrical signals (action potentials in different parts of the heart Pacemaker potential is unstable oscillates; origin of electrical impulses Pacemaker Pacemaker SA Node Atrial myocyte AV Node Purkinje fiber Ventricular myocyte Membrane potential (mv) +70 E Na E K Time Atrial cells are turned on before signal arrives to ventricular cells Atrial cells are turned on before signal arrives to ventricular cells +70 E Na Membrane potential (mv) Time E K Atrial cells are turned on before signal arrives to ventricular cells Electrocardiograph (ECG) registers electrical activity of the heart muscle +70 E Na Membrane potential (mv) Time E K 3

6 Coordinated current spread results in coordinated contraction Heart s Electrical Fibrilations Heart s Electrical Fibrilations Heart s Electrical Blocks in conduction between atria and ventricles Heart Matters: Physiology of Body s Powerhouse Little pump that could Heart electrical activity is controlled by specialized pacemaker and conductive cells Electrical activity can be regulated by sympathetic and parasympathetic nervous system Electrical activation of heart muscle generates ECG waves Irregular electrical activity results in heart How does the pump do it? 4

7 Electro-mechanical coupling (aka excitation-contraction coupling) T-tubules enable extracellular fluid to reach deep inside cardiomyocyte Electro-mechanical coupling (aka excitation-contraction coupling) Calcium enters cytoplasm when the muscle cell is turned on (aka activated or depolarized) What makes fluid move through a tube (or a set of connected tubes :-)? Systemic circulation and Pulmonary circulation 2* 25/2* Alveoli 25/10* Airway 5* 120/3* 120/80* Right heart in lungs Left heart MAP= 95* Elastic arteries P1 - P2 = P Venules and systemic veins in tissues Arteriole Q P Valves 15* Cells in tissues 35* Regulation of blood vessel radius *pressure in mmhg Ventricular contraction generates driving pressure Heart s mechanical : failing pump 5

8 Which pump is failing? 2* 25/2* Alveoli 25/10* Right heart Venules and systemic veins in lungs Airway in tissues 5* Left heart 120/3* 120/80* MAP= 95* Elastic arteries Arteriole Heart Matters: Physiology of Body s Powerhouse Little pump that could Electrical activation of heart muscle cells causes calciummediated contraction Ventricular contraction generates driving pressure that pumps blood from veins to arteries Ventricular contraction strength depends on free calcium in the muscle cytoplasm and can be regulated by sympathetic nervous system Failing heart is characterized by the inability to generate sufficient contractile force ( mechanical failure) Valves *pressure in mmhg 15* Cells in tissues 35* Regulation of blood vessel radius 6