Alterations in endocardial activation of the canine papillary muscle early and late after myocardial infarction.

Abstract

Permanent coronary occlusion produces time-dependent changes in surviving subendocardial cellular properties. We compared the functional alterations in Purkinje (P) and ventricular muscle (VM) activation early (24 hr) and late (4 weeks or greater) after permanent coronary occlusion in an in vitro preparation of canine papillary muscle. High-density extracellular (1 to 2 mm resolution) and selected intracellular recordings were made in five animals early and seven animals late during stimulation of a free-running P strand. Activation patterns of P and VM layers from ischemic and unaffected papillary muscles were compared in the same animal. Average P layer conduction velocity was determined in normal and ischemic regions with the use of a linear array of recording and stimulating electrodes. Purkinje activation was altered little in the early phase of infarction, while healing was associated with a generalized 25% reduction in P layer conduction velocity and localized block and fragmentation of P waveforms. Intracellular recordings at sites of nonsynchronous P activation revealed electrotonic interaction between cell groups. At 24 hr, small groups of VM were present but with abnormal activation patterns in regions of necrosis with fragmented and delayed extracellular waveforms produced by partially uncoupled groups of cells. Local delay and block could be modulated by rate and site of stimulation. After healing, VM activation abruptly stopped at the visual infarct border, marked by a characteristic "end potential." These studies demonstrate important differences in the functional attributes of the P and VM layers studied early and late after coronary occlusion. Alterations in cell-to-cell relationships are likely very important in determining abnormalities of activation in both settings.

Role of Purkinje Fibers in Post-Infarction Ventricular Tachycardia

“…However, in this as well as another study (13), slow conduction was demonstrated in Purkinje fibers that were present within regions of scar. It is unclear whether the conduction delay was present only in the Purkinje fibers or also at the Purkinje-myocardial tissue interface.…”

Effects of anisotropy on the development of cardiac arrhythmias associated with focal activity

“…The values of coupling conductance we used are at least one order of magnitude smaller than the values of gap junctional conductance required for normal conduction in ventricular tissue [14,31]. Under conditions of myocardial ischemia, discrete groups of surviving cells are separated from other groups of cells by connective tissue [10,18,37]. The slow conduction and fractionated waveforms that are characteristic of conduction in ischemic tissue are indications of the successive activation of groups of cells for which the intergroup conductance is limiting the conduction.…”

“…Our use of a model of elements of variable sizes can be scaled to represent the conduction between groups of cells under the conditions that, within each group, the cells of the group are themselves well coupled to each other and essentially isopotential. That this condition is met under certain ischemic conditions is indicated by the brief duration of each compo- nent of the fractionated signals and also from direct microelectrode recordings from cells within the groups [18]. Thus, the conduction between groups of 100 cells ("size 100 elements") connected by a conductance of 5 µS would have the same characteristics of electrical loading and also the success or failure of conduction as one would observe between single cells ("size 1 elements") connected by a conductance of 50 nS.…”

“…Cellular electrophysiological dysfunction may lead to conduction slowing and/or block which may facilitate reentrant arrhythmias, or, alternatively, to localized areas of ectopic activity which may generate non-reentrant arrhythmias. Numerous studies of healed infarctions in ventricular tissue have shown fractionated electrical activity indicative of the partial electrical uncoupling of groups of cells [10,18,37]. Direct evidence for reduced coupling between cells comes from immunohistochemical studies showing that there are smaller and fewer gap junctions in peri-infarction zones [24,32].…”

Effects of Ischemia on Discontinuous Action Potential Conduction in Hybrid Pairs of Ventricular Cells

“…3 Action potentials in these regions have prepotentials and notches due to electrotonic interactions with nearby cells. 4 During acute ischemia, excessive concentrations of catecholamines are observed within the unperfused myocardium. 5 Depletion of catecholamines or treatment with ␤-blockers decreases the incidence of ischemia-induced arrhythmias.…”