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D C Michaels

Publications and source records attributed to D C Michaels.

23 records · Page 2Linked to original sources
PubMed1984

A mathematical model of the effects of acetylcholine pulses on sinoatrial pacemaker activity.

A mathematical model of dynamic vagus-sinus interactions was devised based on Hodgkin and Huxley-type equations of time- and voltage-dependent membrane currents. Brief vagal pulses were modeled with a concentration-dependent, acetylcholine-activated, potassium current. Single acetylcholine ("vagal") pulses scanning the sinus cycle induced changes in pacemaker rhythm that depended on pulse magnitude, duration, and time of occurrence during the cycle. Phase-response curves summarizing these effects are strikingly similar to experimental results. Notably, appropriately timed acetylcholine pulses could produce an acceleratory response. With repetitive acetylcholine input, the model produced various patterns of synchronization of the sinus pacemaker. There was stable entrainment at harmonic (i.e., 1:1, 2:1, etc.) relations, as well as more complex arrhythmic patterns that depended on the relationship between the acetylcholine cycle length and the sinus pacemaker period. In some cases, shortening of the acetylcholine input cycle length led to "paradoxical" acceleration of the sinus pacemaker. Simulations suggest that many clinically observed sinus rhythm disturbances can be explained by dynamic vagus-sinus interactions.

Acetylcholine↗
PubMed1983

A model of dynamic vagus-sinoatrial node interactions.

Computer simulations of dynamic vagus-sinoatrial (SA) node interactions were performed using an empirical model. The phasic effects of single vagal trains on pacemaker cycle length obtained experimentally in isolated preparations were summarized in phase response curves (PRCs). These PRCs were used to stimulate the interactions of the sinoatrial pacemaker with single or with repetitive vagal input. For single stimuli, the triphasic inhibitory curve describing the time course of a brief vagal burst (G. Brown and J. Eccles. J. Physiol. London 82: 211-241, 1934; and J. Jalife and G. K. Moe. Circ. Res. 45: 595-607, 1979) was used to predict the PRC at any given spontaneous pacemaker cycle length. In simulations of repetitive vagal input the model predicted the entrainment of the pacemaker. The patterns of interaction were dependent on the shape and amplitude of the PRC as well as on the relationship between the spontaneous pacemaker period and the vagal cycle length. At certain vagal frequencies, stable entrainment of the pacemaker occurred, and the entrained pacemaker period held harmonic relations to the vagal input (i.e., 1:1, 2:1, and so on). At other frequencies, zones of instability were found in which arrhythmic patterns developed. These predictions of the model matched the experimental results very closely. Under some conditions, during simulations with fixed sinovagus coupling intervals, the model generated patterns of sinus activity similar to those occurring experimentally or in patients with apparent sinoatrial block. The model was also capable of generating patterns similar to those obtained in cases of isorhythmic atrioventricular dissociation. The study of these interactions may have important bearing on the understanding of the dynamic control of heart rate by the parasympathetic nervous system and may be used to explain certain cardiac dysrhythmias.

Animals↗
PubMed1983

Dynamic vagal control of pacemaker activity in the mammalian sinoatrial node.

Dynamic heart rate control by parasympathetic nervous input involves feedback mechanisms and reflex bursting of efferent cardiac vagal fibers. Periodic vagal bursting induces phasic changes in sinoatrial cycle length and can entrain the pacemaker to beat at periods that may be identical to those of the vagal burst. We investigated the electrophysiological basis of these phenomena in isolated sinus node preparations (rabbit, cat, and sheep). In the presence of propranolol (3.9 X 10(-6)M), relatively brief (50-150 msec) trains of stimuli, applied onto the endocardial surface of the preparation, activated postganglionic vagal terminals and induced a brief hyperpolarization of sinoatrial pacemaker cells. This vagally mediated hyperpolarization could alter the pacemaker rhythm by an amount that depended on its duration and its position in the cycle, as well as on the duration of the free-running pacemaker period. When the free-running period was sufficiently long and the hyperpolarization was induced sufficiently early in the spontaneous cycle, a "paradoxical" acceleration of the pacemaker rhythm ensued. Phasic changes were plotted on phase-response curves, constructed by scanning systematically the sinoatrial pacemaker period with single or repetitive vagal trains. These phase-response curves enabled us to predict the entrainment characteristics and the levels of synchronization of the pacemaker to the vagal periodicity. The overall data explain the cellular mechanisms involved in the phasic effects of brief vagal discharges on sinoatrial periodicity, and provide conclusive evidence for the prediction that repetitive vagal input is capable of forcing the cardiac pacemaker to beat at rates that can be faster or slower than the intrinsic pacemaker rate. These data should improve our knowledge of the dynamic control of heart rate by neural reflexes and aid in our understanding of rhythm disturbances generated by the interaction of the cardiac pacemaker with vagal activity.

Acetylcholine↗
PubMed1975

Cardiac effects of ethacrynic acid, a Na+, K+-ATPase inhibitor.

To test hypotheses relating positive inotropic effects of cardiac glycosides (CG) to inhibitory effects on Na,K-ATPase, cardiac actions of other inhibitors were examined. Ethacrynic acid was studied using microelectrode recordings of dog Purkinje fibers (DP) and cat papillary muscle (CP), and isometric recordings of CP at Lmax stimulated at 1/sec (36.5 degrees C). Results with all doses (20-200 gamma/ml) were similar, differing only in latency. Actions of ethacrynic acid on electrical activity of DP and CP were, chronologically: increase in duration of the action potential (AP), and decrease in dV/dt, overshoot, and resting potential. In CP an initial increase (2-5 min) in contractility (10-15 percent) was followed by decreased in active tension and dP/dt with parallel increases in resting tension and duration of contraction. ATP levels were unchanged, eliminating the possibility of ethacrynic acid acting as a metabolic poison. Simultaneous recording of contractions and AP in CP showed that the positive inotropic effect was always associated with a lengthening of the AP. In a series of CP, ouabain (2 gamma/ml) always increased contractility when ethacrynic acid had already reduced it by 75 percent. These results suggest that Na,K-ATPase inhibition is not responsible for the inotropic effects of CG.

Action Potentials↗