Changes in left ventricular function and remodeling after myocardial infarction in hypothyroid rats

Abstract

It has been shown that hypothyroidism may lead to delayed wound healing after experimental myocardial infarction (MI) in rats and increased infarct size in dogs. However, the long-term effect of hypothyroidism on left ventricular (LV) remodeling after MI has not been determined. Adult female Sprague-Dawley rats with and without surgical thyroidectomy (TX) were used in the study. Four weeks after TX, MI or sham MI was performed on TX and non-TX rats. Rats from all groups were examined 4 wk later. Four weeks after TX, hypothyroid-induced LV dysfunction was confirmed by echocardiography. In terminal experiments 4 wk after MI, TX sham-MI rats showed smaller hearts and impaired LV function compared with non-TX sham-MI controls. TX ϩ MI rats showed smaller hearts with bigger infarct areas, higher LV end-diastolic pressures, and greater impairment of relaxation (ϪdP/dt) compared with non-TX MI rats. Relative changes after MI between TX and non-TX rats for most other hemodynamic and echocardiographic indexes were similar. These results suggest that preexisting hypothyroidism exaggerates post-MI remodeling and worsens LV function, particularly diastolic function. low thyroid function; cardiac ischemia; heart failure HYPOTHYROIDISM IS A common condition in the general population. The prevalence rate is 4.6% in the United States population (0.3% clinical, 4.3% subclinical), is higher in females than in males, and increases with age (4). Hypothyroidism has been found to be associated with an increased risk of cardiovascular diseases such as atherosclerosis and myocardial infarction (MI) (3,19). Hypothyroidism has also been shown to delay wound healing in experimental MI rats (9) and causes increased MI size in dogs (7). However, the long-term effect of preexisting hypothyroidism on post-MI left ventricular (LV) remodeling is unknown.In this study, thyroidectomized (TX) rats were used to investigate the influence of hypothyroidism on LV remodeling after MI. We found that hypothyroid rats developed cardiac atrophy and had less LV chamber dilatation but more severe LV dysfunction 4 wk after MI. MATERIALS AND METHODSExperimental design. Adult female euthyroid (non-TX) and TX Sprague-Dawley rats weighing between 209 and 257 g were purchased from Charles River Laboratories (Wilmington, MA). MI surgery was performed 4 wk after TX. Animals from non-TX or TX groups were randomly assigned to MI or sham-MI surgery, respectively. MI was produced by a ligation of the left descending coronary artery as described in previous publications; sham MI was produced with a similar procedure, except the ligature was loosely tied (1, 15). Survivors were placed into the following groups: 1) TX ϩ MI (n ϭ 8), 2) TX ϩ sham-MI (n ϭ 10), 3) non-TX ϩ MI (MI, n ϭ 11), and 4) non-TX sham-MI group (S, n ϭ 10). Animals were housed two per cage and kept on a 12-h:12-h light-dark cycle with food and water provided ad libitum. Pre-MI surgery echocardiographic data were collected 4 wk after TX. In terminal experiments 4 wk later, cardiac function was assessed by...

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