Analysis of myocardial action potential in left ventricular hypertrophy of Goldblatt rats

Abstract

Action potentials were measured in hypertropl~ied rat myocardium by means of glass microelectrodes. Left ventricular hypertrophy was induced by experimental chronic coarctation of one renal artery without contralateral nephrectomy. The action potentials of the hypertrophied myocardium exhibit a marked prolongation without any significant changes in the transmembrane resting potential, in the amplitude, or in the maximum upstroke velocity of the action potential. The increase in the half-width of the action potential for the 6-week stage after the surgical procedure is 235%, for the 12-week stage 281%, and for the 24-week stage 314%. The prolongation of the action potentials was more marked when the degree of hypertrophy was more severe.After depression of the fast Na + inward current either by tetrodotoxin, by augmentation of the extracellular K + concentration, or by reduction of the extracellular Na + concentration, action potentials with similar marked broadening were still obtained in hypertrophied myocardium. The results under variation of the extracellular Ca ++ concentration and simultaneous inactivation of the fast Na* channels suggest that the slow transmembrane inward current is primarily carried by Ca ++ ions.The prolongation of the action potentials could be one cause of the significant increase in the time to peak force as well as the augmentation of isometric force found in this model of hypertrophied myocardium.In contrast to numerous available mechanical, biochemical and mor. phological data, few studies on electrical properties of hypertrophied cardiac muscle have been published: Most studies are concerned with electrocardiographic alterations under cardiac hypertrophy and correlate changes in ECG with changes in geometry of the hypertrophied heart without regard for possible alterations in the transmembrane electrical activity of the hypertrophied cardiac cell.

Non-uniform electrophysiological properties and electrotonic interaction in hypertrophied rat myocardium.

“…In cats showing evidence of congestive heart failure, the action potentials showed marked alterations . In contrast to the variable electrophysiological changes observed in cats with right ventricular hypertrophy, we (Aronson, 1980) and others (Gulch et al, 1979) have found substantial and consistent prolongation of action potentials in rats with left ventricular hypertrophy induced by renal hypertension. In addition, it has been reported that spontaneously hypertensive rats (Hayashi and Shibata, 1974;Heller and Stauffer, 1979) and rats made hypertensive with deoxycorticosterone acetate (Heller and Stauffer, 1979) have longer action potentials than do control rats.…”

“…For example, in a morphometric study of hypertrophied left ventricles from rats with renal hypertension, Loud et al (1978) and Anversa et al (1978) reported a greater enlargement of epicardial cells than endocardial cells after 1-4 weeks of hypertension. In the same model, Aronson (1980) recently reported a 50% prolongation of action potential duration in hypertrophied rat papillary muscle driven at a cycle length of 1000 msec (35°C), and Gulch et al (1979) reported a 180% increase in action potential duration in left ventricular trabeculae driven at a cycle length of 5000 msec (25°C). These results suggest that hypertrophy induced by renal hypertension may be a non-uniform process that affects endocardial, papillary muscle, and epicardial fibers to a different degree.…”

“…Endocardial action potentials in general, and HBP action potentials in particular, have a distinctive steep relation between duration and stimulation frequency which may be due to a difference in the rate dependence of a membrane conductance ( RENOVASCULAR hypertension in rats produced by unilateral clipping of one renal artery imposes a gradual and chronic pressure overload on the heart. Left ventricular hypertrophy resulting from such a chronic pressure overload is associated with characteristic contractile Kammereit and Jacob, 1979; Capasso et al, 1980), ultrastructural (Wendt-Gallitelli andLoud et al, 1978;Anversa et al, 1978;Wendt-Gallitelli et al, 1979), and electrophysiological alterations (Gulch et al, 1979; Aronson, 1980).…”

“…Left ventricular hypertrophy resulting from such a chronic pressure overload is associated with characteristic contractile Kammereit and Jacob, 1979;Capasso et al, 1980), ultrastructural (Wendt-Gallitelli andLoud et al, 1978;Anversa et al, 1978;Wendt-Gallitelli et al, 1979), and electrophysiological alterations (Gulch et al, 1979;Aronson, 1980).…”

Renal hypertensive hypertrophy in the rat: a substrate for arrhythmogenicity

“…We (12) and others (29,21,3,35,36) have shown that in the renal hypertensive rat there are considerable alterations in the cell membrane as evidenced by dramatic prolongation of the transmembrane action potential. It has also been shown that people with hypertensive hypertrophy have an increased susceptibility to ventricular arrhythmias and that these arrhythmias might very well cause sudden death in this population.…”