The Role of Zofenopril in Myocardial Protection During Cardioplegia Arrest: An Isolated Rat Heart Model

Abstract Background: Zofenopril has beneficial effects in acute myocardial infarction, and improves the functional recovery after ischemia and reperfusion. Aim of the study: The aim of this study was to investigate the cardioprotective effects of zofenopril, when added to a standard cardioplegic solution or when orally administered as pretreatment. Methods: A Langendorff model for isolated rat hearts was employed: three groups of eight hearts each were used, respectively, with plain St. Thomas cardioplegia as control (group A and C), and the same solution added with 12.5 mg of zofenopril (group B). The third group (C) was pretreated for 7days with oral administration of zofenopril (6.5 mg/day). The hearts had a baseline perfusion for 30 minutes with Krebs-Henseleit solution at 37°C, cardioplegia administration for 3 minutes, then 30 minutes of ischemia without any perfusion, and finally 30 minutes of reperfusion with Krebs-Henseleit solution at 37°C. Results: Left ventricle developed pressure was significantly higher in the reperfusion period only in the pretreated group (group C) with respect to groups A and B (p = 0.016). Similar results were obtained regarding dP/dt curves (p = 0.020). No differences were demonstrated between groups for cellular viability expressed as creatine phospho-kinase (p = ns) and lactate dehydrogenase release (p = ns). Conclusions: Zofenopril as oral pretreatment showed protective effects in an isolated model of cardioplegic arrest, although improvements in myocardial viability (enzymatic release) could not be demonstrated. Further experimental and clinical evaluations are necessary to assess the direct cardioprotective effect of zofenopril, modifying the length of treatment and the dosage of the drug.