Protective Action of Purinergic and Cholinergic Agonists on the Ischemic Myocardium in the Rat

Kim, Jae Ha; Park, Sang Duck; Ju, Jeong Min; Kook, Hyun; Cho, Jeong Gwan; Park, Ok Kyu

Abstract

BACKGROUND
Purinergic and cholinergic agonists elicit negative-inotropic and chronotropic effects, anticip-ating their protective action from the damage of overloaded myocardium. However, the actions of the agents during the ischemic insults are not yet clearly informed. The aim of this study was to investigate the role of the purinergic and cholinergic agonists on the simulated ischemic myocardium of the rat atrial fiber preparations. METHOD: Various action potential parameters (maximum diastolic potential MDP;action potential amplitude APA;velocity of phase 0 depolarization dV/dtmax;action potential duration APD90) were measured and compared in electrically paced, normal (NPSS) and modified physiological salt solution (MPSS) superfused rat atrial fibers in vitro, using conventional 3M-KCl microelectrode technique. Ischemia-simulated modified physiologic solutions were prepared by changing the solution's composition.
RESULTS
Hypoxic-and/or hyperkalemic-MPSS decreased all the action potential (AP) variables. However, no significant changes of the AP variables were developed by the acidic-or glucose-free MPSS. Adenosine (Ado) and cyclopentyladenosine (CPA) only decreased the APD90 in a dose-dependent manner. Acetylcholine (Ach) and carbachol (Cch) hyperpolarized the MDP, increased the dV/dtmax with certain doses, and decreased the APD90 dose-depen-dently. The potency for APD90-decrease was greater in order, CPA>Cch>Ach>Ado. Ado and CPA did not affect the hypoxic, hypokalemic MPSS-induced dV/dtmax-decrease. On the other hand, Ach and Cch sig-nificantly inhibited the dV/dtmax-decrease by the hypoxic hypokalemic-MPSS. Ado, CPA, Ach and Cch sig-nificantly augmented the hypoxic, hypokalemic MPSS-induced APD90-decrease. The inhibition by the Ach and Cch on the MPSS-induced dV/dtmax-decrease was not affected by DPCPX, but atropine significantly attenuated the inhibition by the cholinergic agonists. DPCPX inhibited the augmentation by the Ado and CPA on the MPSS induced APD90-decrease, and atropine inhibited the effect of the cholinergic agonists.
CONCLUSION
Both purinergic and cholinergic agonists not only shorten the AP duration by themselves but also enhance the AP-shortening effect elicited by the ischemia, and therefore, it is inferred that both agonists prevent further tissue damage from the ischemic insults.