Investigating the Effect of the Poly(Adp-ribose) Polymerase Inhibitor 5-aminoisoquinolinone and the Na⁺-H⁺ Exchanger Inhibitor Zoniporide on Isolated Perfused Rat Hearts during Ischemia-reperfusion Injury

Abstract

The goal of this study was to investigate whether the combination of the Poly(ADP-ribose) polymerase inhibitor 5-aminoisoquinolinone (5-AIQ) and the Na⁺-H⁺ exchanger inhibitor zoniporide (ZN) provides increased protection against ischemia-reperfusion (I/R) injury. Rats were separated into 5 groups (n=8): Group 1: Control group, Group 2: I/R, Group 3: 5-AIQ, Group 4: ZN and Group 5: Mix (5-AIQ+ZN). Isolated rat hearts were subjected to 30 min of global ischemia, followed by 120 min of reperfusion using Langendorff’s apparatus. In groups 3, 4 and 5, 5-AIO (7.5 μM/L) and ZN (50 nM/L) were added to Tyrode Solution after a stabilization period. The level of lactate dehydrogenase (LDH) was determined in the sample perfusate. Myocardial infarct size was determined using the triphenyltetrazolium chloride method. Heart tissues were stored to determine the malondialdehyde (MDA) content, total oxidant status (TOS) and total antioxidant status (TAS). Compared to the 5-AIQ and ZN groups, there was no notable difference in the LDH, MDA, TOS, TAS and hemodynamic parameters of the 5-AIQ+ZN group, but myocardial infarct size decreased significantly, as determined by volume and weight measurements. These results show that the combined use of Zoniporide and 5-Aminoisoquinolinone provides increased protection against I/R injury by reducing myocardial infarct size.

Key words

ischemia-reperfusion injury - langendorff - zoniporide - 5-aminoisoquinolinone - Na⁺-H⁺ exchanger (NHE) inhibitor - poly(ADP-ribose) polymerase (PARP)

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