Experimental myocardial infarction with left ventricular failure in the isolated perfused rat heart. Effects of isoproterenol and pacing

Abstract

Within one minute of acute coronary artery occlusion in the isolated rat heart performing external mechanical work, cardiac output and left ventricular peak systolic pressure fell by one-third to onequarter and there were decreases in the contents of ATP and phosphocreatine (CP) in the ischaemic tissue. Left ventricular and diastolic pressure rose, and dp dt max fell. Cardiac output was steady for 60 min post-ligation. The size of infarction was quantified by the use of radioactive microspheres; over one-half of the left ventricle was rendered ischaemic. There was a biphasic response to dl-isoprenaline HCl (10 −6 m) added to the perfusate. A temporary increase in cardiac output was followed by a rapid decrease as the heart rate exceeded about 350/min, although dp dt max increased throughout. When the heart rate was fixed by pacing, isoproterenol was able to double stroke volume and dp dt max , coronary flow rose by about one-third. Thus in this model the positive inotropic effect of isoproterenol on the ischaemic myocardium became masked as a negative contribution associated with a concomitant chronotropic effect developed. There was also a negative effect of pacing on the cardiac output of non-ligated hearts, but the magnitude was less. It is proposed that a fixed coronary flow rate limited the oxygen delivery to the myocardium as the heart rate rose.