Angiotensin-(1–9) Improves the Cardioprotective Effects of Del Nido Cardioplegia Against Ischemia/Reperfusion Injury

Abstract

Del Nido cardioplegia (DNC), a blood-and-crystalloid solution containing high and low concentrations of potassium and calcium, respectively, is used as a single-dose antegrade infusion to induce immediate cardiac arrest in the surgery of patients with cardiovascular diseases requiring extracorporeal circulation. Adding cardioprotective molecules may further reduce the damage-triggered ischemia/reperfusion (I/R) injury. Angiotensin-(1–9) (Ang-(1–9)) and angiotensin-(1–7) (Ang-(1–7)), members of the counter-regulatory renin-angiotensin system, have shown cardioprotective effects in cardiac hypertrophy and I/R models. This study aimed to evaluate the effects of Ang-(1–9) and Ang-(1–7), as adjuvants of the DNC, on cardioprotection and ventricular function in isolated rat hearts subjected to I/R and in cultured neonatal rat ventricular myocytes subjected to simulated I/R (sI/R). The addition of DNC and Ang-(1–9) and Ang-(1–7) decreased lactic dehydrogenase (LDH) release in cultured cardiomyocytes subjected to sI/R in comparison to those cardiomyocytes subjected to sI/R and incubated with DNC alone. Moreover, hearts treated with Ang-(1–9) during reperfusion after DNC + I/R exhibited fewer arrhythmias and required less time to reach left ventricular developed pressure stability. Overall, reperfusion with DNC and Ang-(1–9) improves the recovery of the left ventricular function of the heart.