First description of the effect of a non-sulfonylurea compound, tetramethylpyrazine, on coronary response to desoxyglucose-induced ischemia.

The compound 2,3,5,6-Tetramethylpyrazine (TMP; Ligustrazine), a flavouring component and sweetness enhancer for beverages constitutes a commonly used food additive. Now we studied the effect of TMP on coronary artery dilation during ischemia: In our experiments we used isolated, Langendorff-perfused guinea pig hearts, arrested with K(+)-rich Normal Tyrode solution (in mM: NaCl 129.5, KCl 15, MgCl2 0.8, CaCl2 1.0, glucose 10), buffered with 10 mM HEPES to pH 7.4 at 37 degrees C, equilibrated with 100% O2. Ischemia was simulated by equimolar replacement of glucose by 2-deoxyglucose (DOG), an inhibitor of oxydative phosphorylation. We found that coronary perfusion pressure (CPP) decreased by 20 +/- 1.2 cm H2O (from initially 90 cm H2O; n = 6, +/- SEM) within 15 min from the onset of DOG. In the presence of 1 mM TMP the decrease in CPP was largely attenuated and CPP declined by 1.4 +/- 1.0 cm H2O (n = 6, +/- SEM; p < 0.01). In 2 out of the 6 TMP experiments even as light increase in CPP (< 2 cm H2O) could be seen. We conclude that TMP, a blocker of ATP-dependent K(+)-channels in pancreatic beta-cells and possibly in arterial smooth muscle cells, prevents coronary dilation in response to ischemia. The possible suppression of this vital mobilization of coronary reserve during ischemia in patients with coronary artery disease certainly merits further attention and may question the use of this compound as a food additive.