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

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.

Electrophysiological Effects of Purinergic Receptor Agonists on Atrial Muscle Fiber under Normal and Ischemic Conditions

BACKGROUND: The electrophysiological effects of purinergic receptor agonists, adenosine triphosphate(ATP) and adenosine were examined using conventional microelectrode technique in rat atrial muscle fibers under superfused with a normal or a simulated ischemic(hypoxic, hyperkalemic and acidotic) physiologic salt solution(PSS) in vitro. METHODS: Action potential parameters, such as maximal diastolic potential(MDP), action potential amplitude(APA), rate of phase 0 depolarization(dv/dtmax) and action potential duration(APD90) were measured in electrically paced, physiologic salt solution(Tyrode's) superfused left rat atrium. In the experiment of ischemic simulation in vitro, normal physiologic salt solutions(NPSS0 were modified(MPSS) and superfused in substitute for normal Tyrode's solution. To investigate the effects of purinergic receptor agonists, ATP or adenosine was added to the superfused tyrode's solutions(NPSS or MPSS) in molar concentration. RESULTS: Under superfused with normal PSS, ATP(10(-3), 10(-4)M) elicited slight hyperpolarization in MDP, and both ATP(10(-6)-10(-3)M) and adenosine(10(-6)-10(-3)M) shortened the duration of normal action potential in a dose-dependent manner. The other paramaters were not affected by the drugs. Superfusion with ischemic PSS caused reductions in MDP as well as APA, dv/dtmax and, especially, APD90. The effects produced by the initial 10 minutes of superfusion with ischemic PSS almost completely disappeared during a subsequent period of continued superfusion with normal PSS, but, those by the initial 20 min lasted in some degree. Both ATP(10(-4)M) and adenosine(10(-4)M) attenuated the reduction in the rate of phase 0 depolarization and the amplitude of the action potential amplitude produced by the ischemic PSS. CONCLUSION: Purinergic receptor agonists, ATP and adensoine, caused a concentration-dependent shortening of the action potential duration in rat atrial muscle fibers and they attenuated the reductions in the rate of phase 0 depolarization and action potential amplitude in fibers superfused with ischemic PSS.