Myocardial infarction with and without reperfusion in sheep: early cardiacand neurohumoral changes

There are few stable and reproducible large-animal models of chronic heart failure produced by ischaemic damage to the myocardium. Here we characteriz e a novel method of inducing myocardial damage in closed-chest sheep by cat heter delivery of thrombogenic coils, and compare this with a newly describ ed open-artery model of card iac injury in sheep. Sham controls were compar ed with animals subjected to (a) 90 min of coronary artery occlusion/reperf usion by PTCA (percutaneous transluminal coronary angioplasty) balloon, and (b) permanent coronary artery occlusion induced by catheter delivery of th rombogenic coils (seven sheep/group). Both balloon occlusion/reperfusion an d permanent coil occlusion resulted in well-defined anteroapical infarcts, as documented by ECG changes. significant rises in creatine kinase (both gr oups P < 0.001) and troponin-T (both groups P < 0.05), and post-mortem exam ination. Washout of enzymes was much more rapid in the reperfused group (P < 0.01). Infarction resulted in significant reductions in left ventricular (LV) ejection fraction (both groups P < 0.01) and regional wall abnormaliti es. Ejection fraction 7 days post-coil (21.3+/-4.2%) was significantly lowe r (P < 0.01) than that 7 days post-balloon (38.8+/-4.5%). Coil-induced infa rction was associated with acutely reduced arterial pressure (P < 0.05), an d increases in heart rate (P < 0.05), atrial pressures (P < 0.05), plasma b rain natriuretic peptide levels(P < 0.05) and adrenaline levels (P < 0.05). Rises seen in plasma endothelin levels in sham controls were blunted in th e coil group (P < 0.001). Haemodynamic changes were less marked in the ball oon group. in conclusion, restriction of coronary artery occlusion to 90 mi n results in infarction, but less LV dysfunction with reduced early remodel ling, compared with permanent occlusion. Acute changes in biochemical marke rs, haemodynamics, neurohormones and LV function confirm that these are exc ellent models of open- and closed-artery myocardial infarction leading to a symptomatic LV dysfunction.