Cardiac ischemia/reperfusion injury is inversely affected by thyroid hormones excess or deficiency in male Wistar rats

Abstract

AimThyroid dysfunctions can increase the risk of myocardial ischemia and infarction. However, the repercussions on cardiac ischemia/reperfusion (IR) injury remain unclear so far. We report here the effects of hypothyroidism and thyrotoxicosis in the susceptibility to IR injury in isolated rat hearts compared to euthyroid condition and the potential role of antioxidant enzymes.MethodsHypothyroidism and thyrotoxicosis were induced by administration of methimazole (MMZ, 300 mg/L) and thyroxine (T4, 12 mg/L), respectively in drinking water for 35 days. Isolated hearts were submitted to IR and evaluated for mechanical dysfunctions and infarct size. Superoxide dismutase types 1 and 2 (SOD1 and SOD2), glutathione peroxidase types 1 and 3 (GPX 1 and GPX3) and catalase mRNA levels were assessed by quantitative RT-PCR to investigate the potential role of antioxidant enzymes.ResultsThyrotoxicosis elicited cardiac hypertrophy and increased baseline mechanical performance, including increased left ventricle (LV) systolic pressure, LV developed pressure and derivatives of pressure (dP/dt), whereas in hypothyroid hearts exhibited decreased dP/dt. Post-ischemic recovery of LV end-diastolic pressure (LVEDP), LVDP and dP/dt was impaired in thyrotoxic rat hearts, whereas hypothyroid hearts exhibited improved LVEDP and decreased infarct size. Catalase expression was decreased by thyrotoxicosis.ConclusionThyrotoxicosis was correlated, at least in part, to cardiac remodeling and increased susceptibility to IR injury possibly due to down-regulation of antioxidant enzymes, whereas hypothyroid hearts were less vulnerable to IR injury.

β-Blocker inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

“…Furthermore, we recently demonstrated that hyperthyroidism furthered LV stunning while hypothyroidism was mostly followed by improved post-ischemic recovery of LV hemodynamic properties and decreased infarct size (47). These findings are consistent with our present work, which suggests that cardiac hypothyroidism is an adaptive condition important for guaranteeing an allostatic condition in HF.…”

Octreotide (somatostatin analog) attenuates cardiac ischemia/reperfusion injury via activating nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in rat model of hyperthyroidism

“…Regarding ventricular function, baseline values of LVDP and ±dp/dt were lower in the hyperthyroid rats and revealed a decreased recovery of LVDP and ±dp/dt following I/R with increase in LVEDP (post-ischemic contracture) indicating more susceptibility to I/R injury. These findings are supported by findings of other researchers [11,19] who demonstrated that LVDP recovery was significantly impaired due to persistently increased LVEDP levels throughout the reperfusion period with marked reduction in contractility and relaxation velocities in thyrotoxic rat hearts. In contrast, it was noticed that there was an improvement in the cardiac hemodynamic in the hyperthyroid male mouse heart after I/R injury [25].…”

“…Supporting our results, it was found that catalase, SOD2, and GPX1 mRNA expressions were downregulated in hyperthyroid rat hearts after I/R injury [19]. In addition, clinical studies described diminished antioxidant enzymes expression in hyperthyroid patients that could be reestablished by antithyroid drugs [31].…”

“…Following acclimatization for 1 week, rats were randomly divided into two groups: control (C) euthyroid group (n = 10) and hyperthyroid (HT) (n = 30) groups. Rats in hyperthyroid group received L-thyroxine (synthetic form of T4) (Eltroxin tablet, aspen, Egypt) (12 mg/ L) in drinking water for 35 days [19]. After assessment of hyperthyroidism, the hyperthyroid rats were randomly divided into three equal subgroups (n = 10): hyperthyroid control positive (HTC) group, hyperthyroid octreotide treated (HT+OCT) group, and hyperthyroid octreotide + Nrf2 inhibitor brusatol treated (HT+BRU+ OCT) group.…”

The Wolff–Chaikoff effect ameliorates heat stress in rats

“…This may explain the persistent tachycardia observed even after 3 days of KI stoppage. Association between raised thyroid hormone level and cardiac output (by both enhancing ventricular contractility and increasing HR) is well established [28]. Thyroid hormones bind with β-adrenergic receptors coupled to G-protein and increase intracellular cAMP activity (the pertinent second messenger system) resulting in greater ventricular ejection fraction and, thus, reduced end systolic volume.…”