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lecture7-heart-rate regulation-arrhythmias-updated.pdf

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BIOL 4510
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Lecture 7 Heart Rate Regulation and Arrhythmias The importance of heart rate The amount of blood pumped by the heart per minute is given by: Cardiac Output (L/min) = CO = Stroke Volume (L/beat) X Heart Rate (beats/min) = SV*HR For a typical human, SV ~ 70 mls and HR ~60 beats/min, therefore CO ~ 4.2Litres/min Heart rate (HR) is the major factor determining the cardiac output. HR can vary by a factor of 3-4 in most people (although the ability to vary HR declines strongly with age). Since the beating in the heart is initiated by the SA node, to understand the regulation of HR we need to understand how the spontaneous firing rate of the SA node is regulated. When there is an increased demand for CO, HR increases. This occurs primarily be altering autonomic nerve inputs to the heart. The autonomic nervous system is comprised of two parts: 1) the sympathetic nerve system and 2) the parasympathetic nerve system. Both nerve outputs originate from the cardiorespiratory centre in the medulla oblongata (brain stem). The sympathetic nerves innervate all the heart (including the SA node) via the cervical paravertebral ganglia which project most axons directly to the heart. The parasympathetic nerves are carried via the cranial nerve X (also called the vagus nerve) and these neurons innervate the ganglia of the heart (which are located in the fat pads of the heart). 1 Since electrical depolarization (= action potential) initiates mechanical events in cardiomyocytes, it is the repetitive depolarizations of the heart that drive the beating rate. Electrical depolarizations (i.e. action potentials) begin in the SA node and then propagate to the other regions of the heart in a well defined temporal and spatial sequence. The figures below, review the order of electrical excitation (and therefore contraction) of the heart. The order of contraction is as follows: SA node atrial muscle (contracts) AV node (slow conduction velocity) Bundle of His (slow conduction) Purkinje fibers (very fast conduction) taking depolarization quickly to the apex of the ventricle ventricular muscle (fast conduction). Atria contract before ventricles How does this ordering come about? The answer is that the s pread of electrical signals through the heart involves propagation of action potentials (i.e. depolarizations) from cell-to-cell by a regenerative process just like in nerve tissue (i.e. local depolarization of membrane causes local curre+ts to flow, which causes depolarization of adjacent regions...reaches threshold for activation of Na channels when the membrane potential reaches about -50 mV, at this time voltage gated Na channels open, leading to full depolarization). The SA node is capable of spontaneously firing (i.e. generating depolarizations). When SA node cells depolarize, positive charge spreads to the adjacent atrial myocytes that are electrically coupled via gap junction. 2 Active Ro Passive Patch Depol. Na ++++ ++++++++++++++++++++++++++ Cm Rm R Gap i Junctions 40 SpatialSpread Chargingtime 20 x/ 0 t/ Vx= 0e (mV) =radimsRi/(2Rt V01e ) 10V) E-40 Em = m m -80 0 0 Distance (mm) 0 time (msec) 10 Repetitive generation of action potentials (AP) in the heart does not require nervous tissue. Specialized myocytes in the heart are capable of spontaneous action potential generation: SA nodal cells, AV nodal cells as well as myocytes in the Bundle of HIS and Purkinje fibers Myocytes in the conducting system are key control points for the regulation of heart rate and dromotropic properties of the heart The orderly depolarization of different regions of the heart is designed to optimize the sequence of mechanical events (i.e. sequence of contraction of the heart); in this manner the utilization of energy for mechanical work is optimized The time- and space-dependent changes in electrical activity in the heart can be detected throughout the body and this is the basis for the electrocardiogram (ECG) The origin of the ECG signal = regional variations in the depolarization or repolarization of cardiomyocytes which sets up charge differences; in other words whenever the cells of the atria or ventricles are not all at the same potential, an electrical signal will be generated in the body (which can be easily detected) P-wave = process of depolarization of atria; QRS is due to ventricular depolarization; T-wave is sequence of repolarization in ventricles. There is no signal when heart is uniformly depolarized or repolarized 3 The orderly sequences of depolarization and repolarization ensure efficient pumping action by heart and reduces the likelihood of arrhythmias (i.e. abnormal rhythms of the heart). Action Potentials in Pacemaker Cells and Their Regulation Figure above shows the differences in APs between atrial/ventricular myocytes compared to myocytes of the SA and AV node. There are two currents that are present in large amounts in SA and AV nodal myocyes that are not present in atrial/ventricular myocytes: I K,ACH and If(more about these later) 4
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