The effect of
thromboxane A2 synthetase inhibitor (OKY-046) on myocardial metabolism and contractility during
ischemia and reperfusion was examined by the
phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts with use of an
artificial blood substitute, perfluorochemical
emulsion Fluosol-43. After normothermic fifteen-minute global zero-flow
ischemia or fifteen-minute global low-flow
ischemia (coronary perfusion pressure = 20 mmHg), reperfusion of sixty minutes was carried out.
OKY-046 was administered from forty-five minutes prior to the global
ischemia.
Adenosine triphosphate (
ATP),
creatine phosphate (CrP),
inorganic phosphate (Pi), pH, left ventricular systolic developed pressure (LV Dev.P) and coronary flow were continuously measured. Twenty-eight heart were divided into four experimental groups consisting of 7 hearts each; Group I consisted of controls with zero-flow
ischemia; Group II, perfusion with
OKY-046 (10(-6) M) in zero-flow
ischemia; Group III, controls with low-flow
ischemia; and Group IV, perfusion with
OKY-046 in low-flow
ischemia. Group II showed a significant inhibition of the increase in Pi and of the decrease in
ATP, CrP, and pH during global
ischemia compared with Group I, and a suppression of the overshoot of CrP observed after postischemic reperfusion. Group IV also showed a significantly marked improvement of
ATP, CrP, and pH and significant suppression in Pi during low-flow
ischemia compared with Group III. These were no differences in LV Dev.P and coronary flow among any groups. In conclusion,
OKY-046 has a significantly beneficial effect on metabolism during both
myocardial ischemia and reperfusion.