Unanticipated Lessening of the Rise in Extracellular Potassium During Ischemia by Pinacidil

Abstract

Our results indicate that the rise in [K+]e during ischemia is due to multiple factors, including K conductance across membrane channels, K driving force as reflected by the time that the action potential is at its plateau voltage, and the metabolic effects of ischemia. The unanticipated lessening of the rise in [K+]e by pinacidil reflects the balance of its effects on these several parameters.

Mechanistic investigation of extracellular K+accumulation during acute myocardial ischemia: a simulation study

“…Our results show that only the simultaneous activation of the three mechanisms leads to the experimentally observed pattern of [K ϩ ] o : an initial fast rise, followed by a plateau phase. Furthermore, the plateau level and the time to onset of the plateau phase in our simulations were in the range of experimental data obtained during acute myocardial ischemia (21,22,46,48). It is important to note that even if the alteration of ischemic mechanisms continued during the whole ischemic period, [K ϩ ] o remained constant during the plateau phase.…”

“…3 provides a more precise comparison between the increase of [K ϩ ] o observed in simulation A and the experimental results obtained in different preparations after 6, 8, 10, and 11 min of ischemia under a similar heart rate. The first of each group of bars represents the data of simulation A, whereas the following bars correspond to the measures obtained in ischemic cardiac tissues of rabbit, pig, and guinea pig (21,44,46,48,58). The rate of stimulation (in beats/ min) applied in each case is specified on the top of the bars.…”

“…Subsequently, the increase of Rn INaK reflects the en- (21,44,46,48,58). The rate of stimulation applied in each case is specified at the top of the bars (in beats/min).…”

Continuous Coronary Venous K<SUP>+</SUP> Monitoring During Myocardial Ischemia in Swine Hearts

“…38) We also showed that ATP-sensitive K + c h a n n e l o p e n e r, p i n a c i d i l d e c r e a s e s t h e rise in [K + ] e during no-flow ischemia. 39) However, β-adrenergic-blocking agent propranolol does not affect the rise in [K + ] e , or the fall in pH e during noflow and low-flow ischemia when the heart rate is held constant. 25,40) We showed that midmyocardial [K + ] e , pH e , and TQ-ST change were the most sensitive marker of myocardial ischemia than other electrical and mechanical indexes of ischemia, but these parameters were impossible to measure clinically.…”

Effects of Propranolol and Verapamil on Changes in TQ and ST Segment Potentials During Graded Coronary Flow Reduction in a Porcine Myocardial Ischemia Model

“…14,21,22,23) We demonstrated that the ATP-sensitive K + channel opener pinacidil lessened the rise in extracellular K + during acute myocardial ischemia mainly by a marked decrease of the action potential duration of the ischemic myocardium. 24) Recently, intracoronary administration of verapamil and nicorandil, an ATP-sensitive K + channel opener, has been shown to be effective for the treatment of slow/no flow phenomenon in the acute coronary syndrome. 25,26) Therefore, intracoronary administration of verapamil and ATP-sensitive K + channel opener before balloon occlusion of the coronary artery or in the presence of acute myocardial ischemia may aggravate ST segment elevation of the AC-coupled ECG in spite of the anti-ischemic effects of these drugs.…”