Determining optimal pretreatment in cardiac surgery: an experimental study

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.

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.

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).

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.