Inhibition of poly(adp-ribose) polymerase reduces cardiomyocytic apoptosis after global cardiac arrest under cardiopulmonary bypass.

Abstract

Cardiomyocytic apoptosis occurs after cardiopulmonary bypass (CPB) despite the use of perfusion techniques and cardioplegic solutions. Reactive oxygen species (ROS) cause single-strand DNA breaks and activate nuclear poly(ADP-ribose) polymerase (PARP), which leads to cellular damage. Therefore, the inhibition of PARP might protect cardiomyocytes from oxidative injuries. In this study, experiments were designed to determine whether a PARP inhibitor could decrease the myocardial ischemia/reperfusion injury after cardioplegia-induced global cardiac arrest under CPB, attenuate the appearance of cardiomyocytic apoptosis, and decrease damage from ROS. New Zealand white rabbits (10 in each group) were subjected to total CPB. Rabbits were weaned from CPB and reperfused for 4 h before the hearts were harvested. 3-Aminobenzamide and/or 3-aminobenzoic acid was added to the cardioplegic solution. The ascending aorta was cross-clamped for 60 min while intermittent cold crystalloid cardioplegic solution was infused into the aortic root every 20 min. The reperfused hearts were harvested and studied for evidence of apoptosis using the TUNEL method and Western blot analyses. The oxidative insults were checked using ELISA to detect plasma isoprostane and cytokines levels. The occurrence of cardiomyocytic apoptosis was significantly less in PARP inhibitor recipients than in PARP-inhibitor-naive controls. Plasma isoprostane and various cytokines were significantly elevated in PARP-inhibitor-naive controls but significantly reduced in PARP inhibitor recipients. Western blot analysis revealed similar patterns. PARP inhibitor-supplemented crystalloid cardioplegic solution diminished postischemic cardiomyocytic apoptosis and ROS-mediated injuries after global cardiac arrest under CPB, possibly via inhibiting both caspase-dependent and -independent apoptotic pathways, which also preserved postischemic myocardial contractility.

• Authors: Chi-Hsiao Yeh, Tzu-Ping Chen, Chieh-Hung Lee, Yi-Chen Wu, Yu-Min Lin, Pyng Jing Lin
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 25 Issue 2 Pg. 168-75 (Feb 2006) ISSN: 1073-2322 [Print] United States
• PMID: 16525356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminobenzoates
• Benzamides
• Cardioplegic Solutions
• Enzyme Inhibitors
• Poly(ADP-ribose) Polymerase Inhibitors
• meta-Aminobenzoates
• 3-aminobenzamide
• Poly(ADP-ribose) Polymerases
• 3-aminobenzoic acid

Topics

• Aminobenzoates (administration & dosage)
• Animals
• Apoptosis (drug effects)
• Benzamides (administration & dosage)
• Cardioplegic Solutions (administration & dosage)
• Cardiopulmonary Bypass
• Enzyme Inhibitors (administration & dosage)
• Heart Arrest (drug therapy, enzymology, pathology)
• Male
• Myocytes, Cardiac (enzymology, pathology)
• Poly(ADP-ribose) Polymerase Inhibitors
• Poly(ADP-ribose) Polymerases (metabolism)
• Rabbits
• Reperfusion Injury (drug therapy, enzymology, pathology)
• meta-Aminobenzoates