Ischemic stroke induced myocardial dysfunction associated with nitro-oxidative stress and sympathetic overactivity

Abstract

Complex interactions exist between cerebro- and cardiovascular diseases: while cardiac diseases are risk factors for cerebral ischemia, ischemic stroke may reciprocally induce heart dysfunctions. The aim of this study was to evaluate how prior cerebrovascular lesions may affect myocardial function and which signals are involved in these processes. Cerebral embolization was performed in adult Wistar male rats by the injection of microspheres into the left or right common carotid artery. Two or 24 hours after stroke or sham embolization, hearts were isolated and perfused ex vivo in the Langendorff mode. Two hours after stroke, the baseline left ventricular developed pressure of hearts from both stroke groups was diminished [106.6 ± 4.4 (left), 106.2 ± 4.7 (right) vs. 129.9 ± 2.7 (sham)] and 24 hours after surgery, the same alteration was observed [91.8 ± 3.7 (left), 104.0 ± 5.3 (right) vs. 120.9 ± 5.1 (sham)]. Echocardiographic measurements showed that left ventricular fractional shortening was altered from both stroke groups 2 hours [38.4 ± 0.4 (left), 38.1 ± 0.4 (right) vs. 41.5 ± 0.6 (sham)] and 7 days after surgery [38.2 ± 0.7 (left), 36.0 ± 0.7 (right) vs. 42.0 ± 0.5 (sham)]. Epinephrine, norepinephrine and growth differentiation factor 15 (GDF15) plasma levels were increased, 2 h after surgery, in rats from both stroke groups, as compared with sham operated. 24 h after surgery, catecholamine levels was also increased and GDF15 only for left stroke rats. Additionally, an increased expression of nitric oxide synthase-3 gene and protein was observed in hearts of stroke rats. Glutathione peroxidase-1 gene overexpression was also observed. To conclude, this study highlighted the deleterious consequences of stroke on cardiac function at different stroke time both ex vivo, in the isolated heart, and in vivo. The molecular mechanisms involved in these processes need to be further investigated in so far as they may involve the sympathetic nervous system and nitro-oxidative stress.