Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart

Abstract

Chouabe, C., J. Amsellem, L. Espinosa, P. Ribaux, S. Blaineau, P. Mé gas, and R. Bonvallet. Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart. Am J Physiol Heart Circ Physiol 282: H1452-H1460, 2002; 10.1152/ajpheart.00286. 2001.-Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities.hypertrophy; right ventricular myocytes; fibrosis; action potential; ionic currents RECENT EVIDENCE in animal models of left ventricular (LV) hypertrophy (LVH) suggests that LVH regression is associated with normalization of ventricular electrophysiology (18,19,28). Chronic hypoxia is the main pathophysiological factor in severe disturbances of the cardiovascular system, represented by pulmonary, ischemic, and congenital heart disease and in cardiopulmonary changes induced by exposure to a high-altitude environment (17). Development of right ventricular (RV) hypertrophy (RVH) is a common consequence of increased pulmonary vascular resistance in most mammals (including humans) living at high altitudes (25). This phenomenon also occurs in experimental animal models during exposure to either normobaric or hypobaric high-altitude hypoxia simulated under laboratory conditions (21). One of the most typical characteristics of phenotypical adaptations is their reversible nature. It has been shown that even severe chronic hypoxia-induced changes, such as pulmonary hypertension and RVH, are completely reversible after removal of the animals from the hypoxic atmosphere for a sufficiently long period of time (15). Recently, we demonstrated that chronic hypobaric high-altitude hypoxia induced true RV myocyte hypertrophy in rats and that hypertrophied cells showed prolongation of their action potential duration (APD) compared with control cells (4, 5). Moreover, we showed that the decrease of the transient outward current (I to1 ) a...

Effects of aging on the cardiac remodeling induced by chronic high-altitude hypoxia in rat

“…1 in Ref. 11), where only the interstitial endomysial extracellular matrix (see Fig. 4, A and B, in Ref.…”

“…Ventricular wall thickness and interstitial collagenic mass measurements were made as previously described (11). Briefly, after aortic retrograde perfusion of the heart, 2-mm-thick transversal ventricular slices were performed with a vibratome, dehydrated, and resin embedded.…”

Normalisation of hypoxaemia following successful percutaneous closure of a bidirectional shunting secundum atrial septal defect without pulmonary hypertension in a patient with severe non‐ischaemic cardiomyopathy and refractory ventricular tachycardia

“…In animal models, it is well established that chronic hypoxia‐induced cardiac structural, functional and biochemical abnormalities are corrected following replacement of normoxic conditions. Depending on the severity of hypoxic conditions, complete reversibility of haemoglobin, haematocrit, pulmonary hypertension, RV hypertrophy and cardiac electrophysiological abnormalities and energy metabolism is seen within weeks of normoxic recovery . Studies exploring the relative protective effect of preconditioning following chronic hypoxia on myocardial infarction size have shown significantly increased risk of ventricular arrhythmias compared with normoxic counterparts .…”

Evaluation of remodeling in left and right ventricular myocytes from heterozygous (mRen2)27 transgenic rats

“…Ventricular wall thickness was measured as previously described (Chouabe et al 2002). Briefly, after aortic retrograde perfusion of the heart, 2-mm-thick transversal ventricular slices were cut with a vibratome, dehydrated, and embedded in resin.…”