Ischemic stroke increases heart vulnerability to ischemia-reperfusion and alters myocardial cardioprotective pathways

Alexandre Meloux (1) , Eve Rigal (1) , Luc Rochette (1) , Yves Cottin (1) , Yannick Bejot (1) , Catherine Vergely (1)

1 PEC2 - Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon]

Background and Purpose-For years, the relationship between cardiac and neurological ischemic events has been limited to overlapping pathophysiological mechanisms and common risk factors. However, acute stroke may induce dramatic changes in cardiovascular function. The aim of this study was to evaluate how prior cerebrovascular lesions affect myocardial function and signaling in vivo and ex vivo, and how they influence cardiac vulnerability to ischemia-reperfusion (IR) injury. Methods-Cerebral embolization was performed in adult Wistar male rats through the injection of microspheres into the left or right internal carotid artery. Stroke lesions were evaluated by microsphere counting, tissue staining and assessment of neurological deficit 2h, 24h and 7 days after surgery. Cardiac function was evaluated in vivo by echocardiography and ex vivo in isolated perfused hearts. Heart vulnerability to IR injury was investigated ex vivo at different times post-embolization and with varying degrees of myocardial ischemia. Left ventricles (LV) were analyzed with western blotting and quantitative RT-PCR. Results-Our stroke model produced large cerebral infarcts with severe neurological deficit. Cardiac contractile dysfunction was observed with an early but persistent reduction of LV fractional shortening in vivo and of LV developed pressure (LVDevP) ex vivo. Moreover, after 20 or 30 minutes of global cardiac ischemia, recovery of contractile function was poorer with impaired LVDevP and relaxation during reperfusion in both stroke groups. Following stroke, circulating levels of catecholamines and GDF15 increased. Cerebral embolization altered nitro-oxidative stress signaling and impaired the myocardial expression of ADRB1 and cardioprotective SAFE signaling pathways. Conclusions-Our findings indicate that stroke not only impairs cardiac contractility and also worsens myocardial vulnerability to ischemia. The underlying molecular mechanisms of

Mots clés: Brain; Heart; Stroke; Myocardial ischemia; Nitro-oxidative stress; Autonomic nervous system Subject terms: Ischemia; Myocardial Infarction; Ischemic Stroke

Domaines: Cardiologie et système cardiovasculaire

Alexandre Meloux, Eve Rigal, Luc Rochette, Yves Cottin, Yannick Bejot, et al.. Ischemic stroke increases heart vulnerability to ischemia-reperfusion and alters myocardial cardioprotective pathways. Stroke, 2018, 49 (11), pp.2752-2760. ⟨10.1161/STROKEAHA.118.022207⟩. ⟨hal-03431603⟩