IKs blockade in border zone arrhythmias from guinea-pig ventricular myocardium submitted to simulated ischemia and reperfusion

The causal relationship between intracellular Ca2+ overloading and reperfusion-induced contracture was examined from changes in intracellular Ca2+ concentration ([Ca2+]i) at rest, changes in the magnitude and time course of intracellular Ca2+ transients, and the development of contracture. Single myocytes isolated from guinea pig hearts were subjected to the conditions mimicking ischemia and reperfusion. Ischemic condition was produced by superfusing myocytes with hypoxic substrate-free solutions containing elevated concentrations of K+, H+, and lactate as described by Ferrier et al. (Circ. Res. 56: 184-194, 1985). Changes in [Ca2+]i were estimated using fura-2 as the Ca2+ indicator. Under these conditions, twitch contractions were suppressed during simulated ischemia associated with an early and gradual rise of [Ca2+]i. The development of contracture, however, was not observed. Upon “reperfusion” of myocytes that had been subjected to 20 min of the above “ischemic” condition, the elevated [Ca2+]i declined rapidly. With the recovery of twitch contractions, contracture developed despite a substantial decrease in [Ca2+]i. These results indicate that reperfusion-induced contracture is not associated with a concomitant increase in [Ca2+]i in isolated myocytes.

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Proarrhythmic and Antiarrhythmic Effects of Bupivacaine in an In Vitro Model of Myocardial Ischemia and Reperfusion

Anesthesiology ◽

10.1097/00000542-199805000-00024 ◽

1998 ◽

Vol 88 (5) ◽

pp. 1318-1329 ◽

Cited By ~ 10

Author(s):

Sandra Picard ◽

Rene Rouet ◽

Frederic Flais ◽

Pierre Ducouret ◽

Gerard Babatasi ◽

...

Keyword(s):

Myocardial Ischemia ◽

Guinea Pig ◽

In Vitro Model ◽

Cardiovascular Effects ◽

Control Group ◽

Ischemia And Reperfusion ◽

Myocardial Ischemia And Reperfusion ◽

Simulated Ischemia ◽

Vitro Model

Background Bupivacaine may have toxic cardiovascular effects when accidentally administered by intravascular injection. However, its electrophysiologic effects in the presence of myocardial ischemia remain unknown. The authors evaluated the electrophysiologic and anti- and proarrhythmic effects of bupivacaine in an in vitro model of the ischemic and reperfused myocardium. Methods In a double-chamber bath, a guinea pig right ventricular muscle strip was subjected partly to normal conditions and partly to simulated ischemia followed by reperfusion. The electrophysiologic effects of bupivacaine were studied at 1, 5, and 10 microM concentrations. Results Bupivacaine (5 and 10 microM) decreased the maximal upstroke velocity of the action potential (Vmax) in normoxic conditions and further decreased (10 microM) the Vmax decrease induced by ischemic conditions. Bupivacaine reduced the mean occurrence time to the onset of myocardial conduction blocks (9 +/- 3 min; mean +/- SD; P < 0.005 with 5 and 10 microM, compared with 17 +/- 6 min during simulated ischemia with no drug or control), and it increased the number of preparations that became inexcitable to pacing (55% of preparations, with 1 microM and 100% with 5 and 10 microM, compared with 17% for the control group). The incidence of spontaneous arrhythmias was reduced by 5 and 10 microM bupivacaine during ischemia and reperfusion and was enhanced by 1 microM bupivacaine during the ischemic phase. Conclusions In guinea pig myocardium under ischemic conditions, bupivacaine induced a loss of excitability at concentrations of 5 and 10 microM. Proarrhythmic effects observed at 1 microM were considered as lower than the cardiotoxic range in normoxic conditions. The incidence of reperfusion arrhythmias was decreased at all concentrations.

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