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Determining optimal pretreatment in cardiac surgery: an experimental study
Masahiro Fujii1, Hiromasa Yamashita2, Yasuhiro Kawase2
1Department of Cardiovascular Surgery, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan. m-fujii@nms.ac.jp.
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.
Insights
Esaxerenone and sacubitril/valsartan improved heart function recovery after cardioplegic arrest in rats. Both drugs reduced myocardial injury, suggesting they offer protection against damage from cardiac procedures.
Area of Science:
- Cardiology
- Pharmacology
- Cardiovascular Surgery
Background:
- Current heart failure treatments include four drug classes, improving survival.
- Cardioplegic arrest during surgery can cause myocardial damage.
Purpose of the Study:
- To investigate the myocardial protective effects of esaxerenone and sacubitril/valsartan against cardioplegic arrest.
- To assess if these drugs can counteract harm caused by cardiac arrest procedures.
Main Methods:
- Male Wistar rats were treated with esaxerenone or sacubitril/valsartan for two weeks.
- Isolated rat hearts underwent cardioplegia and global ischemia followed by reperfusion.
- Functional recovery and troponin T levels were measured to assess myocardial injury.
Main Results:
- Esaxerenone and sacubitril/valsartan groups showed significantly improved recovery of left ventricular developed pressure compared to controls.
- Troponin T levels, a marker of myocardial injury, were significantly lower in the drug-treated groups.
Conclusions:
- Pre-treatment with esaxerenone or sacubitril/valsartan enhances myocardial protection during cardioplegic arrest.
- These drugs may attenuate myocardial injury associated with hyperkalemic cardioplegic arrest.
