Effect of oxygen withdrawal on active and passive electrical properties of arterially perfused rabbit ventricular muscle.

Abstract

Oxygen withdrawal from myocardial cells leads to changes of the transmembrane action potential (mainly action potential shortening), to cellular uncoupling, and to changes of vascular permeability. This study was aimed at the simultaneous measurement of electrical activity and passive electrical properties (extracellular and intracellular longitudinal resistance) in arterially perfused rabbit papillary muscles under different conditions of changed oxygen supply. These included 1) complete anoxia (erythrocyte-free perfusate), 2) hypoxia (Po 2 between 23-28 mm Hg, erythrocytes present) in the presence and absence of glucose, and 3) normoxia with erythrocyte-free perfusate. Similarly to myocardial ischemia, rapid cellular uncoupling occurred only after an initial stable period of approximately 17 minutes, and it required complete anoxia. The marked shortening of the action potential developed before cellular uncoupling. In six out of eight experiments, the fibers were inexcitable when uncoupling started. In severe hypoxia, no significant change of internal longitudinal resistance was observed over 35-40 minutes. The time course of the extracellular longitudinal resistance was different from the change in intracellular resistance: A marked decrease occurred almost immediately after the onset of oxygen withdrawal. This decrease was followed by a small increase in conduction velocity, which was most likely due to a change in the interstitial compartment (edema). It was observed during anoxic as well as during hypoxic perfusion. We conclude that 1) cellular uncoupling in arterially perfused tissue requires almost complete oxygen lack and occurs with a delay of more than 10 minutes, 2) marked action potential shortening precedes uncoupling, and therefore can not simply be attributed to an increase in free, intracellular calcium, and 3) vascular endothelial function is more sensitive to oxygen withdrawal than the myocyte. (Circulation Research 1989;64:532-541) R emoval of the oxygen supply from ventricular myocardium leads to rapid changes of electrical activity 1 and to the early development of malignant ventricular arrhythmias.2 Two experimental models are widely used for investigation of metabolic and electrical changes associated with inadequate myocardial oxygen supply. These include the production of 1) myocardial anoxia or hypoxia by decreasing the oxygen content of the coronary perfusate, or 2) myocardial ischemia by the arrest of coronary flow. The essential difference between these two conditions is the complete absence of extracellular washout in the case of myocardial ischemia. This causes products of ischFrom the Department of Physiology, University of Berne, Beme, Switzerland.Supported by the Swiss National Science Foundation (Grant 3.903.0-85 to A.G.K.) and the Swiss Foundation of Cardiology.Address for correspondence: Andrt G. Kteber, MD, Department of Physiology, University of Beme, Bflhlplatz 5, CH-3012, Berne, Switzerland.Received March 31, 1988; accepted August 18, 1988. emic metabolism (e.g., lact...

Electrical Properties and Conduction in Reperfused Papillary Muscle

“…During reperfusion, r o decreases beyond values measured before ischemia, and probably relates to interstitial edema caused by an ischemia/reperfusion-induced microvascular injury or endothelial dysfunction, analogous to that observed with hypoxia. 13 In contrast to rapid changes in r o , r i recovers more slowly. The difference in the rates of recovery of r o and r i in reperfused tissue leads to a change in the ratio, r o /r i , that is lower than that measured in the muscle before ischemia.…”

Protective effect of gap junction uncouplers given during hypoxia against reoxygenation injury in isolated rat hearts

“…5, B and C). Moreover, the onset of the marked changes in electrical impedance, which some authors have related to the onset of cell-to-cell electrical uncoupling based on an associated increase in intracellular but not extracellular resistance (18), was also significantly delayed when compared with control hearts (for tissue resistivity: 7.75 Ϯ 1.84 min of hypoxia in heptanol-treated vs. 4.02 Ϯ 0.29 min in control hearts, P ϭ 0.016; for phase angle: 8.56 Ϯ 1.81 vs. 4.71 Ϯ 0.40 min, P ϭ 0.015; Fig. 4, C and D).…”

“…This complex nature makes the use of changes in electrical impedance as an index of changes in gap junction-mediated cell coupling difficult, particularly when measured at a single frequency. However, changes in electrical resistivity during hypoxia, measured at a single frequency, have been well characterized in isolated rabbit papillary muscles (18), a model that allows discrimination between extracellular and intracellular resistivities. In this model, after an initial small decrease in total resistivity, because of changes in the extracellular compartment, there is a marked increase in total myocardial resistance because of a rise in the resistivity of the intracellular compartment (gap junctional and/or cytoplasmic resistances).…”

“…In this model, after an initial small decrease in total resistivity, because of changes in the extracellular compartment, there is a marked increase in total myocardial resistance because of a rise in the resistivity of the intracellular compartment (gap junctional and/or cytoplasmic resistances). Based on the observed increase in intracellular but not extracellular resistance, Riegger et al (18) related the onset of the marked increase in total resistivity to the onset of cell-to-cell electrical uncoupling. The fact that, in contrast to the isolated rabbit papillary muscle preparation, our model is characterized by a complex cellular structure and fiber orientation resulting in different anisotropy in the different myocardial layers from endocardium to epicardium may complicate the interpretation of our results.…”

Gap junction-mediated spread of cell injury and death during myocardial ischemia–reperfusion

“…First, the slow progression of electrical abnormalities could reflect, in part, a progressive decrease of GJ conductivity and the persistence of residual electrical coupling in severely ischemic cells over prolonged periods of time. Moreover, the complete blockade of impulse propagation may occur before GJ conductivity reaches zero [53,57,65,70] due to depressed excitability [71,72]. The dissociation between GJ conductance and conduction blockade is well illustrated by the fact that under certain circumstances, such as current-to-load mismatch, conduction block may occur in the presence of normal GJ conductance [71 -73].…”