Depressed contractile function in reperfused canine myocardium: metabolism and response to pharmacological agents.
Regional myocardial function was measured with miniature ultrasonic crystals before, during, and after 10 min of coronary occlusion in anaesthetised open-chest dogs. In normal myocardium, intracoronary isoprenaline (0.1 micrograms . min-1) increased contraction velocity during the first third of systole (early systolic velocity) from 13.8 +/- 2.5 to 19.4 +/- 3.9 mm . s-1 . cm-1, (P < 0.01), and blood flow (microspheres) from 0.55 +/- 0.04 to 0.80 +/- 0.12 cm3 . min-1 . g-1 (P < 0.05); lactate extraction was unchanged. Coronary occlusion induced dyskinesia with a fall in early systolic velocity to -10.0 +/- 2.4 mm . s . -1 . cm-1 (P < 0.01). Abrupt reperfusion after 10 min of ischaemia permitted recovery towards normal, but regional function then deteriorated over 15 min. After a second infusion of isoprenaline, early systolic velocity increased from 0.8 +/- 2.2 to 14.2 +/- 2.5 mm . s-1 . cm-1 (P < 0.01), blood flow 0.44 +/- 0.03 to 0.73 +/- 0.14 cm3 . min-1 . g-1 (P < 0.01) and oxygen consumption 50 +/- 5 to 58 +/- 5 mm3 . min-1 . g-1 (P < 0.05). Lactate extraction was unchanged. In a further series of experiments, administration of nitroglycerin and methoxamine accelerated recovery from dyskinesia induced by coronary occlusion, but did not modify late deterioration during reperfusion. Similarly, neither propranolol nor hypertonic mannitol were found to modify reperfusion damage. Four agents which affect calcium ion movement were studied. Verapamil and isoprenaline, drugs which respectively diminish and enhance calcium slow current, had no effect on reperfusion damage. By contrast, ruthenium red, a non-specific calcium inhibitor reduced deterioration and calcium ionophore (A23187; Lilly) increased it. muDepressed function in reperfused myocardium is not the result of residual ischaemia per se, gut is consistent with calcium overload during the period of reperfusion.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D007773:Lactates; D012430:Ruthenium Red; D000001:Calcimycin; D008353:Mannitol; D011433:Propranolol; D014700:Verapamil; D005996:Nitroglycerin; D007545:Isoproterenol