Randsbaek F, Kimose H H, Bjerre T, Moldrup U, Botker H E, Nielsen T T
Department of Cardiology and Institute of Experimental Clinical Research, Skejby Hospital, Aarhus University Hospitals, University of Aarhus, Denmark.
J Thorac Cardiovasc Surg. 2000 May;119(5):1030-8. doi: 10.1016/S0022-5223(00)70099-7.
We sought to evaluate the effects of captopril on glucose-related metabolism during hypothermic cardioplegic storage and subsequent reperfusion.
We compared hearts from control pigs with hearts from pigs treated with increasing oral doses of captopril for 3 weeks (12.5-150 mg daily), an intravenous bolus (25 mg) before operation, and captopril-containing cardioplegic solution (1 mg/L). The hearts were excised after infusion of cold crystalloid cardioplegic solution and stored in saline solution (4 degrees C-6 degrees C). In one series we studied myocardial blood flow and arteriovenous differences in oxygen, glucose, lactate, glutamate, and alanine during 60 minutes of postcardioplegic blood reperfusion. In this series captopril-treated hearts were reperfused with captopril-containing blood (1 mg/L). In another series we obtained biopsy specimens from the left ventricle throughout 30 hours of hypothermic cardioplegic storage and monitored tissue content of energy-rich phosphates, glycogen, glutamate, and alanine.
Captopril increased glutamate and alanine release 11- to 17-fold at the start of reperfusion (P <.001). Furthermore, captopril increased myocardial oxygen and glucose uptake during reperfusion (P <.001 for both), whereas lactate release and myocardial blood flow were unaffected by captopril. At the start of reperfusion, there was a positive correlation between glutamate release and glucose uptake in captopril-treated hearts (r = 0.66, P =.05). We found no statistically significant differences between captopril and control hearts in tissue content of adenosine triphosphate, glycogen, glutamate, alanine, or lactate during 30 hours of cardioplegic storage.
The metabolic effects of captopril are strictly related to reperfusion, during which oxidative metabolism of glucose is improved. The captopril-induced increase in glutamate and alanine release at the start of reperfusion after cardioplegic storage may reflect a switch in metabolism of glucose-related amino acids.
我们旨在评估卡托普利在低温心脏停搏液保存及随后再灌注期间对糖相关代谢的影响。
我们将对照猪的心脏与经口服递增剂量卡托普利治疗3周（每日12.5 - 150毫克）、术前静脉推注（25毫克）以及含卡托普利心脏停搏液（1毫克/升）处理的猪的心脏进行比较。在输注冷晶体心脏停搏液后切除心脏，并将其保存在盐溶液中（4℃ - 6℃）。在一个系列中，我们研究了心脏停搏后血液再灌注60分钟期间的心肌血流量以及氧、葡萄糖、乳酸、谷氨酸和丙氨酸的动静脉差值。在这个系列中，用含卡托普利的血液（1毫克/升）对经卡托普利处理的心脏进行再灌注。在另一个系列中，我们在低温心脏停搏液保存的30小时内从左心室获取活检标本，并监测富含能量的磷酸盐、糖原、谷氨酸和丙氨酸的组织含量。
在再灌注开始时，卡托普利使谷氨酸和丙氨酸释放增加了11至17倍（P <.001）。此外，卡托普利增加了再灌注期间心肌对氧和葡萄糖的摄取（两者P均 <.001），而乳酸释放和心肌血流量不受卡托普利影响。在再灌注开始时，经卡托普利处理的心脏中谷氨酸释放与葡萄糖摄取之间存在正相关（r = 0.66，P =.05）。在心脏停搏液保存30小时期间，我们发现卡托普利处理组与对照组心脏在三磷酸腺苷、糖原、谷氨酸、丙氨酸或乳酸的组织含量方面无统计学显著差异。
卡托普利的代谢作用与再灌注密切相关，在此期间葡萄糖的氧化代谢得到改善。心脏停搏液保存后再灌注开始时卡托普利诱导的谷氨酸和丙氨酸释放增加可能反映了糖相关氨基酸代谢的转变。
