| dc.description | The effect of pharmacological agents on changes in electrical and contractile activity were examined in a novel cellular model of simulated ischemia and reperfusion in guinea pig ventricular myocytes. Electrical activity was recorded with both conventional and voltage clamp techniques using intracellular microelectrodes filled with 2.7 M KCl. Contractions were monitored with a video edge detector. In the absence of drug, exposure of myocytes to simulated ischemia caused depolarization of the membrane potential, abbreviation of the action potential duration (APD) and inhibition of contraction. Under voltage clamp, the calcium current (I$\rm\sb{Ca}$) declined gradually in ischemia. Signs of Ca$\sp{++}$ overload, including oscillatory after potentials (OAP), transient inward current (I$\rm\sb{Ti}$) and aftercontractions occurred in 73% of myocytes in reperfusion. Upon reperfusion, APD and I$\rm\sb{Ca}$ recovered slowly; however, contractions recovered quickly and temporarily exceeded control. Amiloride, a Na$\rm\sp+/H\sp+$ exchange inhibitor, during ischemia and reperfusion lowered incidence of I$\rm\sb{Ti}$ in early reperfusion. Nifedipine, a Ca$\sp{++}$ channel blocker, and lidocaine, a Na$\sp+$ channel blocker, had no effect on I$\rm\sb{Ti}.$ Induction of OAP, I$\rm\sb{Ti}$ and aftercontraction in reperfusion was associated with reduced peak I$\rm\sb{Ca}.$ Further analysis of contractions demonstrated that the L-current associated contraction, the Na$\sp+$-Ca$\sp+$ exchange contraction and the contraction initiated by the novel release mechanism were inhibited by simulated ischemia. Reperfusion in the absence of drug caused a transient overshoot in the magnitude of all three contractions. The transient overshoot of the three different contractions could be selectively inhibited by different pharmacological interventions. The effects of the nucleoside adenosine (ADN) on cardiac cellular electrical and contractile activity were determined during ischemia and reperfusion. ADN had no effect under control conditions. When ADN was present during ischemia, abbreviation of APD was greater and recovery was delayed. In ischemia, I$\rm\sb{Ca}$ declined equally, and contractions were abolished in control and ADN-treated myocytes. ADN abolished contractile overshoot and reduced incidence of I$\rm\sb{Ti}$ and aftercontractions to 37.5%. The effects of exogenous ADN were inhibited by both the non-selective ADN antagonist 8-phenyltheophylline and the A$\sb1$-selective antagonist cyclopentyltheophylline, Exogenous ADN in ischemia may protect the myocardium in reperfusion via A$\sb1$ receptors. | en_US |
