Captopril-induced glutamate release at the start of reperfusion after cold cardioplegic storage of pig hearts

Byline: Flemming Randsbaek, Hans-Henrik Kimose, Thomas Bjerre, Ulla MA[cedilla]ldrup, Hans Erik BA[cedilla]tker, Torsten Toftegaard Nielsen Abstract: Objective: We sought to evaluate the effects of captopril on glucose-related metabolism during hypothermic cardioplegic storage and subsequent reperfusion. Methods: 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. Results: 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. Conclusions: 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. (J Thorac Cardiovasc Surg 2000;119:1030-8) Author Affiliation: Department of Cardiology and Institute of Experimental Clinical Research, Skejby Hospital, Aarhus University Hospitals, University of Aarhus, Denmark Article History: Received 30 June 1999; Revised 16 September 1999; Revised 8 November 1999; Accepted 6 December 1999 Article Note: (footnote) [star] Supported by the Danish Health Research Council, grant No. 9600822 (Aarhus University, Novo Nordisk Centre for Research in Growth and Regeneration)., [star][star] Address for reprints: Flemming RandsbA[bar]k, MD, Department of Cardiology, Skejby Hospital, Aarhus University Hospitals, Brendstrupgaardvej, 8200 Aarhus N, Denmark.