Abstract
Objective. This study investigated the effects of short-term intermittent hypoxia (IH) preconditioning on cardiac structure and function in rats and the influence of ischemia reperfusion (I/R) injury. Special attention was then paid to the involvement of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF).Methods. Wistar rats were given IH treatment for 1, 7, 14, or 28 days. Some of them were thereafter subject to myocardial infarction surgery. Right ventricle systolic pressure (RVSP), myocardial capillary density (CD), and mRNA/protein expression of HIF-1α, VEGF, and Bcl-2 in rat myocardial tissue were determined. Apoptotic cell number was determined by TUNEL staining, and concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured.Results. IH treatment for 1, 7, 14, and 28 days reduced the myocardial infarction size, whereas IH for 28 days increased the RVSP, ratio of right to left ventricle weight (RV/LV+S), and CD. IH up-regulated the mRNA and protein levels of HIF-1α, VEGF, and Bcl-2 both under normal and I/R conditions. The induced expression of HIF-1α and VEGF by IH reached a peak after 7 days of treatment. Moreover, IH for 28 days induced cardiomyocyte apoptosis, whereas prior treatment with IH for 1, 7, 14, and 28 days all markedly attenuated the apoptosis effected by the subsequent I/R injury. IH also decreased the concentrations of MDA but increased those of SOD in myocardial tissue of both in normal rats and following I/R.Conclusions. The present study demonstrates that short-term IH protects the heart from I/R injury through inhibiting apoptosis and oxidative stress. The up-regulation of HIF-1α and VEGF by short-term IH may participate in the cardioprotective effect of IH.
Highlights
Acute hypoxia is characterized by pronounced and selective redistribution of the blood-flow that ensures adequate O2 supply to vital organs
A slight increase of the Right ventricle systolic pressure (RVSP) was observed after 28 days of intermittent hypoxia (IH) treatment, while there were no changes of RVSP at 1, 7, and 14 days of IH (Table I)
There was a tendency towards an increase in capillary density (CD), a statistically significant change was only observed after 28 days of IH (Table I)
Summary
Acute hypoxia is characterized by pronounced and selective redistribution of the blood-flow that ensures adequate O2 supply to vital organs. Vital organs develop resistance to ischemic stress. Since the first report about beneficial effects of preconditioning on ischemia/reperfusion (I/R) injuries by Murry et al [2], the underlying mechanisms of preconditioning have been studied extensively. This principle has been applied in the development of therapeutic strategies for prevention and treatment of ischemia in brain [3,4], heart [5,6], and other organs [7,8]. There is a need for more effective and simple methods of preconditioning
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
