Effects of an increase in haemoglobin O2 affinity produced by BW12C on myocardial function in the erythrocyte-perfused rabbit heart in vitro and myocardial infarct size in the dog.
The effects of BW12C on myocardial function in the erythrocyte-perfused rabbit heart and on myocardial infarct size in the anaesthetized dog have been evaluated. Perfusion of rabbit hearts with erythrocytes pretreated with BW12C (10(-3) M-4 X 10(-3) M) produced concentration-dependent decreases in left ventricular pressure (LVP), LVP dP/dt and coronary perfusion pressure. A concomitant decrease in PO2 and an increase in lactate production by the myocardium was also observed. Perfusion of rabbit hearts with Krebs Henseleit buffer containing BW12C (10(-5)-10(-4) M) caused no change in measured variables. Although BW12C (10(-3) M) caused a small decrease in LVP, coronary perfusion pressure and heart rate, these changes were not significant. In anaesthetized dogs, an infusion of BW12C (total dose 50 mg kg-1, i.v.) caused small, but significant, changes in haemodynamic status. The oxygen saturation curve was shifted to the left and relative % oxygenation (P20) was shifted to the left throughout the course of the experiment. (P20, control 16.3 +/- 0.4 mmHg; after BW12C 7.9 +/- 1.4 mmHg). Pretreatment with BW12C (total dose 50 mg kg-1) caused no change in area at risk but significantly increased the myocardial infarct size by 410%. These studies with BW12C demonstrate that alteration in haemoglobin-oxygen affinity can induce adaptive physiological changes in tissue function and metabolism and can assume a critical role when oxygen supply may be impaired due to a flow-limiting stenosis.
D000447:Aldehydes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001547:Benzaldehydes; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004912:Erythrocytes / Q000502:physiology; D006321:Heart / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism*; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D009203:Myocardial Infarction / Q000503:physiopathology*; D010101:Oxygen Consumption / Q000187:drug effects*; D011817:Rabbits
D000447:Aldehydes; D001547:Benzaldehydes; D006454:Hemoglobins; C039599:5-(2-formyl-3-hydroxyphenoxy)pentanoic acid