monensin and Myocardial-Ischemia

The possibility was explored whether the functional properties of Na+/Ca2+ exchange are altered after ischaemia, thereby contributing to the elevated intracellular (i) Ca2+ levels in ischaemic reperfused hearts. The intracellular Na+, K+ and Ca2+ contents in rat Langendorff heart preparations were determined by atomic absorption spectrometry under normoxic conditions, after ischaemia (30 min) and after ischaemia (30 min) plus reperfusion (30 min). In addition, the influence of modulating the Na+ gradient (Na+o/Na+i) across the sarcolemma was studied with respect to cardiac contractility and intracellular ion content. This was done by either decreasing extracellular (o) Na+ or by increasing Na+i with monensin, both in normoxic and reperfused hearts. Both Na+o reduction and monensin led to an increase in contractility and coronary flow, an effect which was nearly abolished in reperfused hearts. Under normoxic conditions the intracellular ion contents amounted to Na+ = 12.4 +/- 0.4, K+ = 99.0 +/- 3.1 and Ca2+ = 0.64 +/- 0.02 mmol/kg cell (means +/- SEM, n = 7). In normoxic hearts, lowering Na+o reduced and monensin increased Na+i, thereby both leading to a decrease in Na+ gradient; no effect on total Ca2+i content was observed. Na+i increased twofold after ischaemia as compared to the normoxic situation, an effect which was aggravated (4 fold increase) in reperfused hearts. The opposite effects were observed for K+i with a 25% decrease after ischaemia and a 40% decrease in reperfused hearts. Only after ischaemia plus reperfusion was Ca2+i increased (6 fold).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Calcium; Dose-Response Relationship, Drug; Heart; Ion Transport; Male; Monensin; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Potassium; Rats; Rats, Wistar; Sodium

The intracellular cation contents were determined in isolated perfused rat heart using cobaltic EDTA as a marker of the extracellular space. In hearts in which Na+ accumulation was induced with monensin, a Na+ ionophore, during 20 min-ischemia which otherwise did not result in accumulation of Na+, the levels of Na+ and Ca2+ were significantly higher after reperfusion with a significant decrease in K+. While the recovery of the cardiac mechanical function (CMF) was complete after reperfusion in control hearts, the recovery was incomplete in monensin-hearts. Dichlorobenzamil (DCB), the most specific inhibitor of Na(+)-Ca2+ exchanger, infused for 10 min before induction of ischemia in a dose of 10(-5) M, which produced a definite suppression of CMF (over 80%), inhibited the accumulation of Ca2+ and Na+ and the loss of K+ and ATP after 40 min-ischemia and reperfusion. The same dose of DCB given for 3 min before induction of ischemia and after reperfusion, which produced a less than 20% inhibition of CMF, failed to prevent the Ca2+ accumulation after 40 min-ischemia and reperfusion. These findings are at variance with the idea that the accumulation of Na+ during ischemia and the consequent augmented operation of Na(+)-Ca2+ exchange is responsible for accumulation of Ca2+ after reperfusion.

Topics: Adenine Nucleotides; Amiloride; Animals; Calcium; In Vitro Techniques; Ion Transport; Male; Monensin; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Perfusion; Potassium; Rats; Sodium