Protection of the ischaemic dog heart by oxfenicine

Myocardial ischaemia was produced in closed-chest anaesthetised dogs by coronary embolisation with Sephadex microspheres. Myocardial enzyme release and lactate production were used to quantitate the severity of ischaemia. In dogs pretreated with oxfenicine (S-4-hydroxyphenylglycine; 0.1mmol.kg^?1) 1h prior to embolisation, peak lactate production (extraction ratio ?25±13%) was significantly less than in control dogs (?72±5%; p < 0.01), and the time post-embolisation at which nett lactate uptake became re-established was reduced from 1.4h to 0.4h. Myocardial release of lactate dehydrogenase isoenzyme 1 (HBDH) up to 5h post-embolisation was reduced by 40% in oxfenicine pretreated dogs and there was a similar reduction in the HBDH arterio-coronary sinus difference. Since oxfenicine pretreatment did not modify the major haemodynamic determinants of myocardial oxygen consumption, we conclude that these beneficial effects result from the ability of oxfenicine to divert myocardial metabolism from fatty acid to carbohydrate oxidation, with a consequent reduction in oxygen demand.