The importance of myocardial amino acids during ischemia and reperfusion in dilated left ventricle of patients with degenerative mitral valve disease

Abstract

Taurine, glutamine, glutamate, aspartate, and alanine are the most abundant intracellular free amino acids in human heart. The myocardial concentration of these amino acids changes during ischemia and reperfusion due to alterations in metabolic and ionic homeostasis. We hypothesized that dilated left ventricle secondary to mitral valve disease has different levels of amino acids compared to the right ventricle and that such differences determine the extent of amino acids' changes during ischemia and reperfusion. Myocardial concentration of amino acids was measured in biopsies collected from left and right ventricles before cardioplegic arrest (Custodiol HTK) and 10 min after reperfusion in patients undergoing mitral valve surgery. The dilated left ventricle had markedly higher (P < 0.05) concentrations (nmol/mg wet weight) of taurine (17.0 +/- 1.5 vs. 10.9 +/- 1.5), glutamine (20.5 +/- 2.4 vs. 12.1 +/- 1.2), and glutamate (18.3 +/- 2.2 vs. 11.4 +/- 1.5) when compared to right ventricle. There were no differences in the basal levels of alanine or aspartate. Upon reperfusion, a significant (P < 0.05) fall in taurine and glutamine was seen only in the left ventricle. These changes are likely to be due to transport (taurine) and/or metabolism (glutamine). There was a marked increase in the alanine to glutamate ratio in both ventricles indicative of ischemic stress which was confirmed by global release of lactate during reperfusion. This study shows that in contrast to the right ventricle, the dilated left ventricle had remodeled to accumulate amino acids which are used during ischemia and reperfusion. Whether these changes reflect differences in degree of cardioplegic protection between the two ventricles remain to be investigated.

Fig. 1

Changes in myocardial taurine (a) and glutamine (b) during cardioplegic arrest and reperfusion. The concentrations of taurine and glutamine in biopsies collected from both left and right ventricles before cross-clamping the aorta (pre-ischemia) and after 10 min reperfusion. Data are shown as mean ± SEM (n = 12). *P versus pre-ischemia in corresponding ventricle

Fig. 2

Changes in myocardial glutamate (a) and alanine (b) during cardioplegic arrest and reperfusion. The concentrations of glutamate and alanine in biopsies collected from both left and right ventricles before cross-clamping the aorta (pre-ischemia) and after 10 min reperfusion. Data are shown as mean ± SEM (n = 12). *P versus pre-ischemia in corresponding ventricle

Fig. 3

Ischemic cardioplegic stress (a) and reperfusion injury (b). Lactate release following the release of cross-clamp was used to assess the metabolic ischemic stress early after reperfusion. Reperfusion injury as measured by post-operative release of creatine kinase (CK-MB). Data are shown as mean ± SEM (n = 12). CK-MB values at 1, 6, 12, and 24 h were significantly higher than 48 h. *P versus pre-ischemia in the corresponding ventricle

Fig. 4

Markers of myocardial metabolic stress. The alanine/glutamate (a) and glutamine/glutamate (b) ratios in left and right ventricles calculated before cross-clamping the aorta (pre-ischemia) and after 10 min reperfusion. Data are shown as mean ± SEM (n = 12). *P versus pre-ischemia in the corresponding ventricle. **P versus pre-ischemia in the left ventricle. ^†P versus all other values