A novel heart failure model induced by sequential coronary artery occlusions and tachycardiac stress in awake pigs

Abstract

A heart failure model was developed using conscious pigs subjected to serial myocardial infarctions followed by intermittent rapid ventricular pacing. Aortic and atrial catheters, left ventricular (LV) pressure gauge, LV dimension crystals, ascending aortic flow probe, pacing leads, and two coronary artery occluders were implanted in 15 pigs. The initial distal left circumflex coronary artery (LCX) occlusion produced a modest infarct, i.e., 18 ± 3% of LV, and the second proximal LCX occlusion, performed 48 h later, enlarged the infarct to 33 ± 2% of the LV with only modest changes in LV function. Thereafter, the pigs were subjected to ventricular pacing at 220 beats/min, which was maintained for 7 days and terminated for 3 days. This pacing cycle was repeated two more times and resulted in significantly impaired LV function and systemic hemodynamics. For example, after the second cycle of pacing, LV rate of pressure change (dP/d t, −41 ± 4% from 2,778 ± 112 mmHg/s), velocity of circumferential fiber shortening ( Vcf: −53 ± 6% from 1.1 ± 0.1 s−1), and cardiac index (CI: −42 ± 5% from 122 ± 4 ml ⋅ min−1⋅ kg−1) were reduced significantly, whereas LV end-diastolic diameter (EDD: +34 ± 6% from 39 ± 2 mm), total peripheral resistance (TPR: +75 ± 16% from 0.79 ± 0.05 U), and mean left atrial pressure (LAP) (+21 ± 1 mmHg from 5 ± 1 mmHg) were increased significantly. Importantly, 3 wk after cessation of the final pacing cycle, LV dP/d t (−40 ± 5%), Vcf(−48 ± 9%), and CI (−30 ± 4%) remained depressed, whereas LV EDD (+39 ± 5%), TPR (+43 ± 9%), and LAP (+13 ± 4 mmHg) were still increased. In contrast, hemodynamic impairment in six conscious pigs subjected to pacing only did not persist when pacing was terminated. Thus this model could provide a unique opportunity to study both the effects of preclinical therapeutic interventions and the mechanisms involved in the development of heart failure.