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

Abstract

SUMMARY We studied the distribution and nature of the electrical changes associated with myocardial hypertrophy induced by renal hypertension in rats. Standard microelectrode techniqueB were used to study transmembrane action potentials recorded from endocardial, papillary muscle, and epicardial fibers from hypertrophied (HBP) and normal (SHAM) hearts. We also determined the effects of stimulation frequency on the action potentials recorded from these preparations. To assess whether altered intercellular electrical connections contribute to the electrophygiological changes associated with hypertrophy, we analyzed the spatial steady state voltage decrement produced by passing intracellular constant current pulses and determined the effective input resistance (R^,) of endocardial HBP and SHAM preparations. Our results show that the action potential prolongation that accompanies hypertrophy is not uniform. Thus, the entire course of repolarization is prolonged in endocardial and papillary muscle fibers, but only the latter half of repolarization is prolonged in epicardial fibers. 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).The most consistent alterations in the myocardium of rats with renal hypertension are enlargement of the myocytes and prolongation of the action potential. However, the degree of alteration in these properties appears to vary according to the region of the left ventricle studied. 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.The purpose of the present study was to characterize further the distribution and nature of the electrical changes associated with myocardial hypertrophy. This was...

Heterogeneity of the action potential in isolated rat ventricular myocytes and tissue.

“…Even though the resting potential and overshoot measured in this study are as large as those found by others in rat ventricular tissue (Payet et al, 1978;Gulch, 1980;Lazarus et al, 1980;Aronson, 1980;Keung and Aronson, 1981), they are on the low side for mammalian ventricular muscle. For example, the ca.…”

“…As expected from Figure 2, the APD25 and APD75 of type III action potentials (14.5 ± 1.9 and 46.0 ± 4.1 msec) were significantly longer ( P < 0.01-0.001) than those of type II (7.4 ± 1.1 and 38.2 ±-6.7 msec) which, in turn, were longer ( P < 0.001) than those of type I (3.1 ± 1.0 and 21.5 ± 3.6 msec). The other significant difference (P < 0.05-0.001) between the three types of action potentials was that the amplitude of type III Gulch (1980), and Keung and Aronson (1981), found that the configuration of the action potential in rat ventricle was not homogeneous. Thus, one explanation for the presence of several populations of action potentials in the isolated myocytes is that there are also several populations in the intact tissue.…”

Transmural distribution of isomyosin in rabbit ventricle during maturation examined by immunofluorescence and staining for calcium-activated adenosine triphosphatase.

“…However, stresses induced in the rat by renal hypertension which produce hypertrophy increase cell size more in the epicardial layers, and resulting transmural gradients become evident in mitochondrial-to-myofibrillar ratio and in the Tsystem surface density (Anversa et al, 1978). Regional regulation of electrical properties in the epicardial myocytes has also been seen in the rat during hypertrophy (Keung and Aronson, 1981).…”

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

“…The electrophysiological changes underlying spontaneous ectopic activity in LVH are not well understood, but hypertrophied myocardium clearly represents a complex substrate for arrhythmic disturbance. Prolongation of the cardiac action potential has been reported in experimental animal models, and abnormalities in individual currents, including I CaL , I Na , and I to , have been described in hypertrophied cardiac myocytes (Keung and Aronson, 1981;Keung, 1989;Ryder et al, 1993;Yokoshiki et al, 1997). Increased interstitial fibrosis, a universal feature of hypertensive LVH (Weber, 2000), may create zones of altered electrical conductance.…”