Insular infarct size but not levosimendan influenced myocardial injury triggered by cerebral ischemia in rats

Abstract

Cerebral injuries can trigger stress-related cardiomyopathy. The extent of cerebral injury and the involvement of the insular cortex influence the incidence and extent of myocardial injury (MI), and drugs with proven neuroprotective and cardioprotective properties such as levosimendan might be beneficial. This hypothesis was addressed in a rat model of transient middle cerebral artery occlusion. Transient brain ischemia was induced for 60 min by intraluminal occlusion of the middle cerebral artery in 40 male Wistar rats. Treatment with levosimendan (24 µg/kg) was started briefly before reperfusion. Hemodynamic parameters were recorded and cerebral and MI quantified after 24 h. Levosimendan treatment significantly reduced cerebral infarct size in the cortex, but not in the striatal and insular regions. However, its effects on survival (28 vs. 45%), incidence of MI (8 vs. 33%) as indicated by a troponin I (sTnI) threshold of 4.8 µg/L and large insular infarcts of ≥10 mm(3) (23 vs. 50%) failed to reach statistical significance. Blood pressure demonstrated significant differences related to insular infarct size during reperfusion. Levosimendan demonstrated no relevant effects on markers of MI (sTnI = 1.5 ± 2.8 vs. 5.3 ± 7.2 µg/L, P = 0.121). Insular infarct size could be identified as the only predictor of MI (odds ratio = 1.86, P = 0.037). In conclusion, the current investigation confirmed insular infarct size as a predictor of MI and source of hemodynamic compromise, but failed to demonstrate an effect of levosimendan on MI trigged by brain ischemia. A hardly protectable insular region might explain this.

Stroke–heart syndrome: current progress and future outlook

“…The mice with cardiac dysfunction had more severe insular cortex damage and increased sympathetic activity [75]. Moreover, larger insular infarct volumes correlate with more severe myocardial injury [87]. Meanwhile, this evidence supports the notion that the lateralization of the insula is closely connected with autonomic responses.…”

Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats

“…Moreover, a recent report showed that levosimendan was beneficial in a model of injury to the immature brain following cardiopulmonary bypass (Namachivayam et al, 2014). Finally, Varvarousi et al (2014) described positive effects of levosimendan in post-cardiac arrest brain injury, and Bleilevens et al (2014) showed that levosimendan treatment significantly reduces cerebral infarct size in the cortex in a rat model.…”

The Heart Is at Risk: Understanding Stroke-Heart-Brain Interactions with Focus on Neurogenic Stress Cardiomyopathy—A Review

“…32 The major pathophysiological aspect of altered function within the brainheart axis in the pathogenesis of stroke-associated NSC is fur-ther supported by experimental and clinical research evidence which indicates a correlation between the development of cardiac dysfunction and ischemic events involving the insular cortex, especially the right insular cortex. [33][34][35] Indeed, current neuroimaging studies using functional magnetic resonance and positron emission tomography have confirmed the insular cortex as a cardinal regulator of the central autonomic nervous system. 36 The latter observation is crucial if taken into account that blood supply of insular cortex comes from the middle cerebral artery making it particularly susceptible to cerebrovascular disease.…”

“…Moreover, supra-physiological levels of epinephrine may have a negative inotropic effect, as they contribute to the switching of β 2 -adrenergic receptors from canonical stimulatory G-protein-activated cardiostimulant to inhibitory G-protein-activated cardiodepressant pathways [ 32 ]. The major pathophysiological aspect of altered function within the brain-heart axis in the pathogenesis of stroke-associated NSC is further supported by experimental and clinical research evidence which indicates a correlation between the development of cardiac dysfunction and ischemic events involving the insular cortex, especially the right insular cortex [ 33 - 35 ]. Indeed, current neuroimaging studies using functional magnetic resonance and positron emission tomography have confirmed the insular cortex as a cardinal regulator of the central autonomic nervous system [ 36 ].…”