Endoxin-mediated myocardial ischemia reperfusion injury in rats in vitro.

Abstract

Myocardial ischemia reperfusion results in an increase in intracellular sodium concentration, which secondarily increases intracellular calcium via Na(+)-Ca2+ exchange, resulting in cellular injury. Endoxin is an endogenous medium of digitalis receptor and can remarkably inhibit Na+/K(+)-ATPase activity. Although the level of plasma endoxin is significantly higher during myocardial ischemia, its practical significance is unclear. This research is to investigate whether endoxin is one of important factors involved in myocardial ischemia reperfusion injury. Ischemia reperfusion injury was induced by 30 min of global ischemia and 30 min of reperfusion in isolated rat hearts. Heart rate (HR), left ventricular developed pressure (LVDP), and its first derivative (+/-dp/dtmax) were recorded. The endoxin contents, intramitochondrial Ca2+ contents, and the Na+/K(+)-ATPase activity in myocardial tissues were measured. Myocardial damages were evaluated by electron microscopy. The endoxin and intramitochondrial Ca2+ contents in myocardial tissues were remarkably higher, myocardial membrane ATPase activity was remarkably lower, the cardiac function was significantly deteriorated, and myocardial morphological damages were severe in myocardial ischemia reperfusion group vs. control. Anti-digoxin antiserum (10, 30 mg/kg) caused a significant improvement in cardiac function (LVDP and +/-dp/dtmax), Na+/K(+)-ATPase activity, and myocardial morphology, and caused a reduction of endoxin and intramitochondrial Ca2+ contents in myocardial tissues. In the present study, the endoxin antagonist, anti-digoxin antiserum, protected the myocardium against the damages induced by ischemia reperfusion in isolated rat hearts. The results suggest that endoxin might be one of main factors mediating myocardial ischemia reperfusion injury.

• Authors: Yong-Sheng Ke, He-Gui Wang, De-Guo Wang, Gen-Bao Zhang
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 82 Issue 6 Pg. 402-8 (Jun 2004) ISSN: 0008-4212 [Print] Canada
• PMID: 15381964 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardenolides
• Immune Sera
• Saponins
• Sodium-Calcium Exchanger
• digoxin-like factors
• Digoxin
• Sodium-Potassium-Exchanging ATPase
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Cardenolides
• Digoxin
• Female
• Humans
• Immune Sera (biosynthesis)
• In Vitro Techniques
• Male
• Mitochondria, Heart (enzymology, metabolism, ultrastructure)
• Myocardial Reperfusion Injury (enzymology, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Saponins (biosynthesis)
• Sodium-Calcium Exchanger (physiology)
• Sodium-Potassium-Exchanging ATPase (antagonists & inhibitors, metabolism)