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The acute myocardial infarction (AMI) and sudden cardiac death (SCD), both associated with acute cardiac ischemia, are one of the leading causes of adult death in economically developed countries. The development of new approaches for the treatment and prevention of AMI and SCD remains the highest priority for medicine. A study on the cardiovascular effects of chronic hypoxia (CH) may contribute to the development of these methods. Chronic hypoxia exerts both positive and adverse effects. The positive effects are the infarct-reducing, vasoprotective, and antiarrhythmic effects, which can lead to the improvement of cardiac contractility in reperfusion. The adverse effects are pulmonary hypertension and right ventricular hypertrophy. This review presents a comprehensive overview of how CH enhances cardiac tolerance to ischemia/reperfusion. It is an indepth analysis of the published data on the underlying mechanisms, which can lead to future development of the cardioprotective effect of CH. A better understanding of the CH-activated protective signaling pathways may contribute to new therapeutic approaches in an increase of cardiac tolerance to ischemia/reperfusion. [ABSTRACT FROM AUTHOR]

Aims Vagal nerve stimulation ( VNS) protects from myocardial and vascular injury following myocardial ischaemia and reperfusion ( IR) via a mechanism involving activation of alpha-7 nicotinic acetylcholine receptor (α7 n AChR) and reduced inflammation. Arginase is involved in development of myocardial IR injury driven by inflammatory mediators. The aim of the study was to clarify whether VNS downregulates myocardial and vascular arginase via a mechanism involving activation of α7 n AChR following myocardial IR. Methods Anaesthetized rats were randomized to (i) sham-operated, (ii) control IR (30-min ischaemia and 2-h reperfusion, (iii) VNS throughout IR, (iv) the arginase inhibitor nor- NOHA+ IR, (v) nor- NOHA+ VNS+ IR, (vi) selective α7 n AChR blockade by methyllycaconitine ( MLA) followed by VNS throughout IR and (vii) MLA+IR. Results Infarct size was reduced by VNS compared to control IR (41 ± 3% vs. 67 ± 2% of the myocardium at risk, P < 0.001). Myocardial IR increased myocardial and aortic arginase activity 1.7- and 3.1-fold respectively ( P < 0.05). VNS attenuated the increase in arginase activity compared to control IR both in the myocardium and aorta ( P < 0.05). MLA partially abolished the cardioprotective effect of VNS and completely abrogated the effect of VNS on arginase activity. Arginase inhibition combined with VNS did not further reduce infarct size. Conclusion Vagal nerve stimulation reduced infarct size and reversed the upregulation of arginase induced by IR both in the myocardium and aorta via a mechanism depending on α7 n AChR activation. The data suggest that the cardioprotective effect of VNS is mediated via reduction in arginase activity. [ABSTRACT FROM AUTHOR]