Determining optimal pretreatment in cardiac surgery: an experimental study.

OBJECTIVES: Heart failure patients with reduced ejection fraction are currently treated with four drug combinations: angiotensin receptor/neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors, resulting in improved survival outcomes. Herein, we examined whether myocardial protection by esaxerenone or sacubitril/valsartan may present a counter-effect to the harm caused by cardioplegic arrest.

METHODS: Male Wistar rats fed a normal diet were orally administered esaxerenone (3 mg/kg; Esax) or sacubitril/valsartan (68 mg/kg; SaV) once a day for 2 weeks from 6 weeks of age. Age-matched, untreated male Wistar rats served as controls (Control). Isolated rat hearts were aerobically Langendorff-perfused and subjected to 2 min of St Thomas' Hospital 2 cardioplegia (STH2) infusion and 28 min of normothermic global ischemia followed by 60 min of reperfusion. The recovery of function was measured during 60 min of reperfusion. Additionally, troponin T levels were measured after reperfusion as myocardial injury.

RESULTS: The final recovery of left ventricular developed pressure (presented as the percentage of preischemic value) in the Control, Esax, and SaV groups was 50.7 ± 6.2%, 68.5 ± 7.4%*, and 69.3 ± 14.3%*, respectively (*p < 0.05 vs. Control). Troponin T (ng per gram wet weight) levels in the Control, Esax, and SaV groups were 166.8 ± 78.1, 77.0 ± 14.6*, and 74.2 ± 36.6*, respectively (*p < 0.05 vs. Control).

CONCLUSION: Oral administration of esaxerenone or sacubitril/valsartan to rats 2 weeks prior to surgery enhanced the myocardial protection afforded by STH2 and may attenuate the myocardial injury caused by hyperkalemic cardioplegic arrest.