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

## TL;DR

Adding Angiotensin-(1–9) to Del Nido cardioplegia improves heart protection during surgery by reducing injury from blood flow restoration.

## Contribution

This study shows that Angiotensin-(1–9) enhances the cardioprotective effects of Del Nido cardioplegia during ischemia/reperfusion.

## Key findings

- Angiotensin-(1–9) reduced lactic dehydrogenase release in cardiomyocytes during simulated ischemia/reperfusion.
- Hearts treated with Angiotensin-(1–9) had fewer arrhythmias and faster recovery of ventricular function.
- Reperfusion with Del Nido cardioplegia and Angiotensin-(1–9) improved left ventricular function recovery.

## 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.