Effect of Na+ reduction and monensin on ion content and contractile response in normoxic and ischaemic reperfused rat hearts.
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)
van den Ende
R
R
Division of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, The Netherlands.
Guttmann
I
I
Scheufler
E
E
Pfaffendorf
M
M
van Zwieten
P A
PA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
D008985:Monensin; D012964:Sodium; D011188:Potassium; D002118:Calcium