Comparison of effects of aprikalim and of hypoxic and ischaemic preconditioning on extracellular potassium accumulation, metabolism, and functional recovery of the globally ischaemic rat heart.
OBJECTIVE
The aim was to compare the effects of a potassium channel opener, aprikalim, and of hypoxic and ischaemic preconditioning on extracellular K+ concentration change, metabolism, and ventricular function in isolated globally ischaemic rat hearts.


METHODS
Isovolumetric rat hearts (37 degrees C) were treated with 1 microM (apri 1) or 30 microM (apri 30) aprikalim, or preconditioned with either 10 min of hypoxia (N2PC) or 5 min of ischaemia followed by 5 min of perfusion (IPC5) or 10 min of ischaemia followed by 3 min of perfusion (IPC10). Control hearts received neither treatment nor preconditioning. All hearts received 30 min of sustained ischaemia followed by 25 min of reperfusion. Extracellular K+ concentration was measured with a potassium sensitive electrode inserted into the extracellular space of the left ventricular wall.


RESULTS
Recovery of left ventricular developed pressure after 25 min of reperfusion was only 19.20(SEM 5.09)% of the preischaemic level in the control group. No recovery was obtained for the apri 1 group. In contrast, a very good recovery was obtained for the apri 30 group [96.69(10.92)%], the N2PC group [104.92(17.40)%], and the IPC10 group [84.96(9.86)%]. The IPC5 group, however, did not have improved recovery of left ventricular pressure [14.15(5.61)%]; this is likely to be related to differences in the stimulation of anaerobic glycolysis. The protection was also markedly attenuated by pretreatment with 50 microM glibenclamide in the apri 30, N2PC, and IPC10 groups [22.76(9.00), 66.06(6.09), and 46.18(7.06)%, respectively]. Hearts treated with aprikalim before inducing ischaemia showed a concentration dependent increase in [K+]e. Hypoxic (N2PC) and ischaemic preconditioning (IPC5 and IPC10) were also associated with an increase in [K+]e over the 5-10 min period preceding the 30 min of sustained ischaemia. During sustained ischaemia all groups showed a nearly triphasic pattern of extracellular K+ changes with an early rising phase, with the exception of the N2PC group for which the early [K+]e rise was barely detectable.


CONCLUSIONS
An increase in [K+]e before sustained ischaemia is one of the mechanisms involved in the conditions affording protection. Although important, this is not sufficient, and further protection may be accomplished by decreased stimulation of anaerobic glycolysis during the sustained ischaemia.
Guo
A C
AC
Laboratoire de Physiologie Cellulaire, URA CNRS 1121, Université Paris XI, Orsay, France.
Diacono
J
J
Feuvray
D
D
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001481:Basal Metabolism / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D010477:Perfusion; D010847:Picolines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D007773:Lactates; D010847:Picolines; D011714:Pyrans; D019344:Lactic Acid; C061043:aprikalim; D011188:Potassium