Fujii Masahiro, Yamashita Hiromasa, Kawase Yasuhiro, Bessho Ryuzo, Ishii Yosuke
Department of Cardiovascular Surgery, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan.
Department of Cardiovascular Surgery, Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo, Tokyo, 113-8603, Japan.
Gen Thorac Cardiovasc Surg. 2024 Nov 14. doi: 10.1007/s11748-024-02102-1.
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.
射血分数降低的心力衰竭患者目前采用四种药物联合治疗：血管紧张素受体/脑啡肽酶抑制剂、β受体阻滞剂、盐皮质激素受体拮抗剂和钠-葡萄糖协同转运蛋白2抑制剂，从而改善了生存结局。在此，我们研究了依沙克瑞诺或沙库巴曲缬沙坦的心肌保护作用是否可能对心脏停搏造成的损害产生抵消作用。
从6周龄开始，给正常饮食的雄性Wistar大鼠每天口服一次依沙克瑞诺（3 mg/kg；Esax）或沙库巴曲缬沙坦（6 mg/kg；SaV），持续2周。年龄匹配的未治疗雄性Wistar大鼠作为对照（Control）。将离体大鼠心脏进行有氧Langendorff灌注，给予2分钟的圣托马斯医院2号心脏停搏液（STH2）灌注以及28分钟的常温全心缺血，随后再灌注60分钟。在再灌注60分钟期间测量功能恢复情况。此外，再灌注后测量肌钙蛋白T水平作为心肌损伤指标。
对照组、依沙克瑞诺组和沙库巴曲缬沙坦组左心室舒张末压的最终恢复情况（以缺血前值的百分比表示）分别为50.7±6.2%、68.5±7.4%和69.3±14.3%（与对照组相比，p<0.05）。对照组、依沙克瑞诺组和沙库巴曲缬沙坦组的肌钙蛋白T（每克湿重纳克数）水平分别为166.8±78.1、77.0±14.6和74.2±36.6*（*与对照组相比，p<0.05）。
在手术前2周给大鼠口服依沙克瑞诺或沙库巴曲缬沙坦可增强STH2提供的心 肌保护作用，并可能减轻高钾性心脏停搏引起的心肌损伤。
