Susceptibility to systolic dysfunction in the myocardium from chronically infarcted spontaneously hypertensive rats

Abstract

Norton GR, Veliotes DG, Osadchii O, Woodiwiss AJ, Thomas DP. Susceptibility to systolic dysfunction in the myocardium from chronically infarcted spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 294: H372-H378, 2008. First published November 9, 2007 doi:10.1152/ajpheart.01024.2007.-We explored whether the hypertensive heart is susceptible to myocardial dysfunction in viable noninfarcted tissue post-myocardial infarction (MI), the potential mechanisms thereof, and the impact of these changes on pump function. Six to seven months after the ligation of the left anterior descending coronary artery, left ventricular (LV) myocardial systolic function, as assessed from the percent shortening of the noninfarcted lateral wall segmental length determined over a range of filling pressures (ultrasonic transducers placed in the lateral wall in anaesthetized, openchest, ventilated rats) and the percent thickening of the posterior wall (echocardiography), was reduced in infarcted spontaneous hypertensive rats (SHR-MI) (P Ͻ 0.05) but not in normotensive Wistar-Kyoto (WKY-MI) animals compared with corresponding controls [SHRsham operations (Sham) and WKY-Sham]. This change in the regional myocardial function in SHR-MI, but not in WKY-MI, occurred despite a similar degree of LV dilatation (increased LV end-diastolic dimensions and volume intercept of the LV end-diastolic pressurevolume relation) in SHR-MI and WKY-MI rats and a lack of difference in LV relative wall thinning, LV wall stress, apoptosis [terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL)], or necrosis (pathological score) between SHR-MI and WKY-MI rats. Although the change in regional myocardial function in the SHR-MI group was not associated with a greater reduction in baseline global LV chamber systolic function [end-systolic elastance (LV Ees) and endocardial fractional shortening determined in the absence of an adrenergic stimulus], in the presence of an isoproterenol challenge, noninfarct-zone LV systolic myocardial dysfunction manifested in a significant reduction in LV Ees in SHR-MI compared with WKY-MI and SHR and WKY-Sham rats (P Ͻ 0.04). In conclusion, these data suggest that with chronic MI, the hypertensive heart is susceptible to the development of myocardial dysfunction, a change that cannot be attributed to excessive chamber dilatation, apoptosis, or necrosis, but which in turn contributes toward a reduced cardiac adrenergic inotropic reserve. pressure-overload hypertrophy; remodeling; myocardial systolic function; cardiac reserve THE PRESENCE OF HYPERTENSIVE cardiac hypertrophy is a wellrecognized risk factor for myocardial infarction (MI) and may predispose to a greater reduction in pump function post- MI (6a,7,10,11,23,24). The impact of hypertension and associated cardiac hypertrophy on pump dysfunction post-MI could be attributed in part to an impact of elevated afterload on infarct size (25, 30) or adverse cardiac remodeling in noninfarcted tissue (10 -12, 23). However, what has not been explored is wheth...

Effect of acute exercise on cardiovascular hemodynamic and red blood cell concentrations of purine nucleotides in hypertensive compared with normotensives rats

“…There is also evidence to suggest that ATP turnover and supply of ADP in myocardial tissue is more restricted in SHRs, particularly when energy demand is increased in hard work conditions [Hickey et al 2009]. This could be partly attributed to dysfunctional ATP synthesis in mitochondria in SHRs [Doroshchuk et al 2004], which has also been shown to be more susceptible to systolic dysfunction after myocardial ischemia insult [Norton et al 2008]. These data together suggest that energy and ATP metabolism and the response to exercise are different in SHRs as demonstrated in the current study, and may potentially be used for cardiovascular disease management.…”

“…This could be partly attributed to dysfunctional ATP synthesis in mitochondria in SHRs [Doroshchuk et al . 2004], which has also been shown to be more susceptible to systolic dysfunction after myocardial ischemia insult [Norton et al . 2008].…”

Folic acid mitigated cardiac dysfunction by normalizing the levels of tissue inhibitor of metalloproteinase and homocysteine-metabolizing enzymes postmyocardial infarction in mice

“…The time course of postinfarct LV dilatation can occur in acute, subacute, and later phases (50). Serial echocardiographic studies have shown that LV dilatation can be observed from as early as 2 wk and lasted 30 mo after MI, and the LV dilatation involved both infarcted and noninfarcted heart regions (16,37). In the early phase of MI, infarct expansion and regional dilatation contribute to the ventricular enlargement (19,26).…”

Dietary-Induced Obesity Hastens the Progression From Concentric Cardiac Hypertrophy to Pump Dysfunction in Spontaneously Hypertensive Rats

“…22 The dietary intervention was initiated at an age when SHRs have concentric LVH without pump dysfunction or increases in diastolic chamber stiffness. 27,28 The experimental diet resembles a Western-type diet, 29 the constituents of which are described in an online Data Supplement (available at http://hyper.ahajournals.org). The diet is designed to induce hyperphagia, 29 resulting in a greater energy intake (570Ϯ23 kJ/d) as compared with the control group (371Ϯ18 kJ/d), with similar increments in caloric intake noted in both SHRs and WKY rats.…”