Effect of thromboxane A2 synthetase inhibitor on metabolism and contractility in ischemic reperfused rabbit heart.

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.
AuthorsH Kawabata, T Ryomoto, R Katori
JournalAngiology (Angiology) Vol. 48 Issue 8 Pg. 689-97 (Aug 1997) ISSN: 0003-3197 [Print] UNITED STATES
PMID9269138 (Publication Type: Journal Article)
Chemical References
  • Blood Substitutes
  • Enzyme Inhibitors
  • Fluorocarbons
  • Methacrylates
  • Phosphates
  • Phosphocreatine
  • perfluorotributylamine
  • Adenosine Triphosphate
  • Thromboxane-A Synthase
  • ozagrel
  • Adenosine Triphosphate (metabolism)
  • Animals
  • Blood Substitutes
  • Coronary Circulation (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Fluorocarbons
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Male
  • Methacrylates (pharmacology)
  • Myocardial Contraction (drug effects)
  • Myocardial Reperfusion
  • Myocardial Reperfusion Injury (metabolism, physiopathology)
  • Myocardium (metabolism)
  • Phosphates (metabolism)
  • Phosphocreatine (metabolism)
  • Rabbits
  • Thromboxane-A Synthase (antagonists & inhibitors)
  • Ventricular Pressure (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: