Effects of Hyperosmotic Sodium Chloride Perfusion on Ischemia/Reperfusion Injury in Isolated Hearts of Normal and Stroke-Prone Spontaneously Hypertensive Rats

Abstract

Background: Hyperosmotic solutions have been used successfully in different shock resuscitations with cardioprotection. This study was to examine the effects of hyperosmotic sodium chloride on isolated heart function and heart responses to ischemia/reperfusion in normotensive and hypertensive rats. The roles of hyperosmolarity-induced antioxidants including hyperosmolarity-relevant heat shock proteins as well as vasodilating endothelial nitric oxide synthase (eNOS) and vasoactive catecholamines were investigated.Methods: Hearts of normal rats and stroke-prone spontaneously hypertensive rats were isolated and perfused for 30 min with control Krebs-Henseleit buffer (osmolarity 300 mOsm/L) or hyperosmotic buffer of different sodium chloride concentrations (320, 350 and 400 mOsm/L) before subjected to 40-min global ischemia followed by 10-min hyperosmotic reperfusion and 30-min normal buffer reperfusion. Heart function, creatine phosphokinase leakage and myocardial antioxidants were examined. Myocardial antioxidants after hyperosmotic perfusion with different osmolytes were assayed with Western blotting.Results: Pre-ischemic hyperosmotic sodium chloride perfusion enhanced heart contractility and diastole function and reduced coronary vascular resistance in both normal and hypertensive hearts. Post-ischemic recoveries of heart function were improved in hyperosmotic perfused hearts, associated with lower creatine phosphokinase leakage, higher coronary flow, reduced coronary resistance and lower norepinephrine overflow. At the end of reperfusion, the myocardial activities of total superoxide dismutase and catalase, glutathione content as well as osmosis-relevant heat shock protein 32 and 90 were increased in hyperosmotic hearts. In addition to sodium chloride, in vitro hyperosmotic mannitol, glucose and raffinose also increased protein expressions of antioxidants including superoxide dismutase, catalase, heat shock protein 32 and 90 and vasodilating eNOS. Conclusion:Hyperosmotic perfusion enhanced heart function and preconditioned normal and hypertensive hearts against ischemia/reperfusion injury. The hyperosmolarity-induced up-regulations in myocardial antioxidants including heat shock proteins and eNOS may play an important role in the hyperosmolarity-induced cardioprotection.

Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts

“…In Shen's et al [10] study, prefused with hyperosmolar NaCl gave similar results: increased coronary artery flow and decreased coronary artery resistance, increased left ventricular function, and increased levels of catalase but not SOD. Shen et al [10] also compared the effects of a 2 hour perfusion of rats hearts with solution made hyperosmolar with 4 different osmolytes (NaCl, glucose, mannitol, and raffinose) and found no significant differences in levels of the cellular constituents measured. They did not, however look at left ventricular function.…”

“…They did not, however look at left ventricular function. Our findings and Shen's et al [10], therefore, may be due entirely to the hyperosmolarity.…”

“…A study of diabetic hearts from rats with severe hyperglycaemia also showed an increase in catalase, but not SOD, compared to normal hearts [4]. And a study of hyperosmotic sodium chloride perfusion of normal and stroke-prone spontaneously hypertensive rat hearts also showed increased catalase but not increased SOD, although in this study raising the osmolarity to 400 mOsm/L was able to increase SOD slightly [10]. In our study, levels of catalase were increased 20%, but levels of the marker of myocardial damage, CPK, however, were decreased 60%.…”

Effects of Vasodilation and Arterial Resistance on Cardiac Output

“…Heart collects the deoxygenated blood from the body and pushes it to the lungs where it becomes oxygenated, and then heart pumps the oxygen rich blood to the body. Normal functioning of heart is very important to lead a healthy life [5]. Vasodilation is widening of blood vessels caused by relaxation of smooth muscle cells in the vessel walls particularly in the large arteries, smaller arterioles and large veins thus causing an increase in blood flow [6].…”

High Risk Factors of Cardiovascular Diseases in Type 2 Diabetes

“…Some studies suggested no association between alcohol intakes and type 2 diabetes. Systolic and diastolic heart function, myocardial creatine phosphokinase leakage and myocardial antioxidants after ischemia/ reperfusion were examined [42].…”