Biomaterial Database

Differences in the electrophysiological response of canine ventricular epicardium and endocardium to ischemia. Role of the transient outward current. 1993

A Lukas, and C Antzelevitch

Masonic Medical Research Laboratory, Utica, NY 13501-1787.

BACKGROUND Acute ischemia is known to produce more severe electrophysiological disturbances in canine ventricular epicardium than endocardium, although the mechanism for the differential sensitivity is still unresolved. Recent studies have demonstrated the presence of a prominent transient outward current (Ito) in ventricular epicardium but not endocardium. The present study was designed to test the hypothesis that the differential sensitivity of these two tissues to ischemia results, at least in part, from a more prominent Ito in epicardium than in endocardium. RESULTS Isolated canine ventricular epicardial and endocardial tissues and myocytes were studied by standard microelectrode techniques. Simulated ischemia (hyperkalemia, hypoxia, and acidosis) abolished the action potential plateau and caused a 50% to 60% shortening of action potential duration in epicardium but only a 10% to 20% shortening in endocardium. 4-Aminopyridine, an Ito inhibitor, restored the plateau in epicardium and reduced the dispersion of action potential duration between epicardium and endocardium. Stimulation protocols that minimized the contribution of Ito, such as acceleration of the stimulation rate or introduction of early premature beats, produced a paradoxical prolongation of the epicardial response caused by restoration of the action potential dome. Thus, ischemia-induced dispersion of repolarization was greatly diminished at rapid rates and after premature beats. Similar results were obtained in tissues and myocytes obtained from the same myocardial layers, suggesting that the differential sensitivities of epicardium and endocardium to ischemia are largely a result of inherent differences in cellular properties. CONCLUSIONS Our data suggest that the presence of a prominent Ito in epicardium but not endocardium contributes importantly to the selective electrical depression of epicardium by simulated ischemia. The repolarizing influence of Ito serves to amplify the ischemia-induced changes in inward (ICa and INa) and outward (calcium-activated) currents. By facilitating loss of the dome in epicardium, Ito contributes to the development of a marked dispersion of repolarization between normal and ischemic epicardium and between epicardium and endocardium, thereby providing the electrophysiological substrate for the genesis of reentrant arrhythmias.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010496	Pericardium	A conical fibro-serous sac surrounding the HEART and the roots of the great vessels (AORTA; VENAE CAVAE; PULMONARY ARTERY). Pericardium consists of two sacs: the outer fibrous pericardium and the inner serous pericardium. The latter consists of an outer parietal layer facing the fibrous pericardium, and an inner visceral layer (epicardium) resting next to the heart, and a pericardial cavity between these two layers.	Epicardium,Fibrous Pericardium,Parietal Pericardium,Pericardial Cavity,Pericardial Space,Serous Pericardium,Visceral Pericardium,Cavities, Pericardial,Cavity, Pericardial,Pericardial Cavities,Pericardial Spaces,Pericardium, Fibrous,Pericardium, Parietal,Pericardium, Serous,Pericardium, Visceral,Pericardiums, Fibrous,Pericardiums, Serous,Serous Pericardiums,Space, Pericardial,Spaces, Pericardial
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D004558	Electric Stimulation	Use of electric potential or currents to elicit biological responses.	Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D004699	Endocardium	The innermost layer of the heart, comprised of endothelial cells.	Endocardiums
D006352	Heart Ventricles	The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.	Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000255	Adenosine Triphosphate	An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.	ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2