Biomedical subjects

G J Rozanski

Publications and source records attributed to G J Rozanski.

26 records · Page 2Linked to original sources

PubMed1989

Active components of excitability in K+-depolarized ventricular muscle.

The steady-state and dynamic characteristics of excitability were assessed in isolated guinea pig papillary muscles depolarized with elevated [K+]o to resting potentials near -60 mV. Transmembrane potentials were recorded from fibers during application of low-amplitude current pulses used to analyze net changes in active membrane components of excitability in terms of elicited local responses and measure threshold current (Ith). Generated local responses were blocked entirely by tetrodotoxin and lidocaine, which increased steady-state Ith by more than 200%. In the absence of Na+ channel-blocking agents, local responses showed marked but characteristic attenuation in a time- and voltage-dependent manner by preceding subthreshold depolarizations, which concomitantly reduced excitability. However, local responses and excitability were also modulated by small changes in [Ca2+]o (+/- 0.7 mmol) and reduced by exposure to slow channel blockers and to Cs+. Thus these data suggest that while the Na+ channel is the primary active component of excitability in partially depolarized ventricular muscle, Ca2+ -mediated and Cs+ -sensitive conductances may also participate, although to a lesser extent. These findings may help explain the frequency-dependence of excitability and conduction under conditions of ischemia in the intact heart.

Animals↗

PubMed1987

Electrophysiological properties of automatic fibers in rabbit atrioventricular valves.

Subsidiary atrial automaticity generated by cardiac fibers of the rabbit tricuspid valve was studied in vitro with the use of standard microelectrode techniques. The time course of diastolic depolarization of leading pacemaker fibers was characteristically biphasic over a potential range of -80 to -55 mV, with a brief primary phase of relatively steep slope and a longer secondary phase of lesser slope. The regenerative upstroke of pacemaker potentials was suppressed by cobalt ions and varied with changes in extracellular Ca2+ concentration in a manner suggesting a slow channel process. The time course of each diastolic phase, estimated by measuring slope, varied in a reproducible manner with changes in membrane potential elicited with long duration current pulses. Cesium ions reduced the slope of both diastolic phases at all potentials with greater effects on the primary diastolic phase, but spontaneous activity in the absence of current pulses was not significantly altered. Furthermore, pacemaker activity varied with changes in extracellular K+ concentration and in response to barium ions in manners suggesting the presence of a decaying K+ conductance. These experiments demonstrate the utility of valve tissue as a model of subsidiary atrial pacemaker activity and suggest the presence of current systems qualitatively similar to those observed in the sinoatrial node.

Action Potentials↗

PubMed1986

Automaticity in atrioventricular valve leaflets of rabbit heart.

Microelectrode techniques were used to study the electrophysiological properties of pacemaker fibers in isolated atrioventricular valves of the rabbit heart. In spontaneously beating tricuspid and mitral valve preparations superfused with normal Tyrode solution, leading pacemaker activity was generated by fibers located on the valve leaflet. Impulse conduction from the automatic focus to atrial myocardium was slow, and in approximately 50% of preparations, exit block occurred. Valve pacemaker fibers had significantly different action potential characteristics compared with the primary pacemaker cells of the sinoatrial node. However, the activity of both pacemaker types was largely insensitive to tetrodotoxin but readily suppressed by verapamil. Endogenous neurotransmitters, released from postganglionic nerve endings in the vicinity of valve pacemaker fibers, exerted profound chrono- and dromotropic effects. Brief cholinergic stimuli strongly influenced valve pacemaker cycle length in a phase-dependent manner, qualitatively similar to that in the sinoatrial node. During overdrive of valve pacemaker fibers with external bipolar stimuli, locally released neurotransmitters modified automaticity and conduction which, under certain conditions, favored pacemaker escape. These data demonstrate that the atrioventricular valve leaflets contain cardiac fibers capable of generating spontaneous impulses and that intrinsic autonomic nerves may play a role in precipitating premature extrasystoles.

Action Potentials↗

PubMed1985

Electrophysiology of functional subsidiary pacemakers in canine right atrium.

Glass microelectrodes were used to study the electrical activity of the subsidiary atrial pacemaker (SAP) cells that maintain atrial excitation after suppression of the sinoatrial node. Tissues with documented SAP activity were isolated from the canine inferior right atrium and superfused in vitro with Tyrode solution containing norepinephrine (NE, 10(-8)-10(-7) M). SAP action potentials exhibited prominent diastolic depolarization and a significantly lower maximum diastolic potential, take-off potential, overshoot, rate of rise, and amplitude than typical atrial muscle. Withdrawal of NE completely blocked SAP propagation, although SAP automaticity continued at a slower rate. Acetylcholine (ACh, 5 X 10(-8) M) usually produced complete exit block and decreased spontaneous rate. Higher concentrations of ACh (10(-6) M) elicited a prominent hyperpolarization (19.2 +/- 6.6 mV), completely suppressing SAP automaticity. In quiescent preparations exposed to NE greater than or equal to 10(-7) M, external stimuli at short cycle lengths (less than 1,000 ms) elicited action potentials with delayed afterdepolarizations, which frequently caused nondriven repetitive activity. This triggered activity was inhibited by verapamil or withdrawal of NE. These studies identify and characterize the electrical activity of functional subsidiary pacemakers located in a specific region of the inferior right atrium. In addition, fibers within this region display triggered activity. Spontaneous activity generated by fibers within the SAP region may cause atrial dysrhythmias.

Acetylcholine↗

PubMed1984

Alterations in subsidiary pacemaker function after prolonged subsidiary pacemaker dominance in the canine right atrium.

In vivo and in vitro techniques were used to study the functional characteristics of subsidiary atrial pacemaker activity 4 to 11 months after surgical excision of the sinoatrial node region of the dog heart. Characteristics of this long-term subsidiary atrial pacemaker activity were compared with those of sinoatrial node and short-term subsidiary atrial pacemaker activities. Extracellular bipolar electrodes were used to estimate the site of earliest activation and monitor spontaneous rate. Under both in vivo and in vitro conditions, long-term pacemaker activity was located in the same region of the inferior right atrium as was short-term pacemaker activity. Under in vitro conditions, long-term activity was characterized by a reduced sensitivity to acetylcholine and overdrive pacing and by a lack of dependence on beta-adrenergic stimulation compared with short-term activity. Furthermore, long-term pacemaker activity was more sensitive to acetylcholine and less sensitive to norepinephrine (greater than 10(-7) M) compared with sinoatrial node activity. It is concluded that the subsidiary atrial pacemakers that emerge soon after removal of the sinoatrial node are the same as those pacemakers that ultimately assume long-term control of the heart. In addition, after subsidiary atrial pacemakers assume dominant pacemaker function, their dependence on norepinephrine and their response to acetylcholine and overdrive pacing are reduced. These changes facilitate a more stable regulation of atrial pacemaker rhythm and, thereby, make subsidiary atrial pacemaker function more like that of the sinoatrial node.

Acetylcholine↗

PubMed1984

Reflected reentry in nonhomogeneous ventricular muscle as a mechanism of cardiac arrhythmias.

Arrhythmogenesis in ventricular muscle exhibiting nonhomogeneous excitability was studied in isolated tissues from feline and canine hearts. Longitudinal bundles were mounted in a three-chambered bath and simultaneous transmembrane recordings were obtained from fibers in each chamber. Nonhomogeneous excitability was established by depressing only the central segment (1 to 2 mm wide) with high-K+ Tyrode's solution, which induced discontinuity of propagation associated with step delays mediated by electrotonic current flowing through the depressed zone. When transmission delays were long, activity distal to the site of block returned to proximal tissue as one of two forms of reflected reentry, each elicited by a different mechanism. Type I reflection, occurring with antegrade delays of 30 to 60 msec, was characterized by an early secondary depolarization due to electrotonic spread of currents from delayed responses in the depressed segment. Type II reflection evolved with delays greater than 90 msec and was manifest as a closely coupled regenerative action potential that developed independently of a pacemaker mechanism and of slow but continuous conduction. We conclude that delayed activation of excitable elements, which occurs when propagation is discontinuous, may lead to rhythm disturbances of focal origin that are mediated by electrotonic interactions across a zone of depressed tissue.

Action Potentials↗

PubMed1984

Determinants of postrepolarization refractoriness in depressed mammalian ventricular muscle.

Functional determinants of postrepolarization refractoriness were studied with microelectrodes in isolated cat and dog ventricular muscle preparations mounted in a three-chambered bath. Frequency-dependent conduction delay and block were readily manifested when the central segment (1 mm) was superfused with high potassium (20-30 mM) Tyrode's solution. Conduction disorders were attributed to postrepolarization refractoriness involving slow recovery in the amplitude of elicited subthreshold depolarizations in depressed fibers distal to the central blocked zone. Investigations of subthreshold phenomena in homogeneously depressed tissues indicated that a relatively large local response participated in the voltage displacement induced by subthreshold depolarizing currents. The local response was blocked by tetrodotoxin (10 micrograms/ml) or verapamil (2 micrograms/ml) when resting membrane potential was near -70 or -50 mV, respectively. At either level of reduced membrane potential, gradual recovery in diastolic excitability correlated closely with time-dependent recovery of the local response, the rate of which was also proportional to the current intensity applied. Thus, postrepolarization refractoriness in depressed ventricular muscle fibers is a function of the time for recovery of active subthreshold properties (the local response), as well as intensity of excitatory current input. These factors may play a role in the development of delayed conduction and reentry that occur at faster heart rates under ischemic conditions.

Action Potentials↗

PubMed1983

Functional characteristics of sinoatrial and subsidiary pacemaker activity in the canine right atrium.

A canine in vitro right atrial preparation was developed to study the functional characteristics of subsidiary atrial pacemaker (SAP) activity and to compare them with those of sinoatrial node (SAN) activity. Extracellular bipolar electrodes were used to estimate the site of earliest activation and monitor spontaneous rate. Ligation of the SAN artery at the midportion of the sulcus terminalis suppressed SAN activity and usually (73.5%) elicited SAP activity in a well-defined region of the inferior atrium. SAP activity in this region required a "threshold" concentration of norepinephrine (10(-8) M) in the Tyrode's perfusate. In response to all concentrations of norepinephrine tested, SAN activity attained a greater maximum spontaneous rate than SAP activity. Cholinergic stimulation with acetylcholine or eserine elicited a greater negative chronotropic response from SAP than SAN activity. Overdrive pacing suppressed SAP activity to a significantly greater extent than SAN activity. We conclude that this in vitro preparation can be useful for studying the pharmacology and electrophysiology of subsidiary atrial pacemakers that emerge after suppression of SAN activity. In contrast to SAN activity, SAP activity requires norepinephrine and is more sensitive than SAN activity to acetylcholine and overdrive pacing. Consequently, after loss of SAN function, autonomic modulation of SAP activity may result in atrial dysrhythmias and prolonged periods of overdrive suppression.

Acetylcholine↗