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

A heart failure model was developed using conscious pigs subjected to seria l myocardial infarctions followed by intermittent rapid ventricular pacing. Aortic and atrial catheters, left ventricular (LV) pressure gauge, LV dime nsion crystals, ascending aortic flow probe, pacing leads, and two coronary artery occluders were implanted in 15 pigs. The initial distal left. circu mflex coronary artery (LCX) occlusion produced a modest infarct, i.e., 18 /- 3% of LV, and the second proximal LCX occlusion, performed 48 h later, e nlarged the infarct to 33 +/- 2% of the LV with only modest changes in LV f unction. Thereafter, the pigs were subjected to ventricular pacing at 220 b eats/min, which was maintained for 7 days and terminated for 3 days. This p acing cycle was repeated two more times and resulted in significantly impai red LV function and systemic hemodynamics. For example, after the second cy cle of pacing, LV rate of pressure change (dP/dt, -41 +/- 4% from 2,778 +/- 112 mmHg/s), velocity of circumferential fiber shortening (V-cf: -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-diastoli c 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 (LA P) (+21 +/- 1 mmHg from 5 +/- 1 mmHg) were increased significantly. Importa ntly, 3 wk after cessation of the final pacing cycle, LV dP/dt (-40 +/- 5%) , V-cf(-48 +/- 9%), and CI (-30 +/- 4%) remained depressed, whereas LV EDD (+39 +/- 5%), TPR (+43 +/- 9%), and LAP (+13 +/- 4 mmHg) were still increas ed. In contrast, hemodynamic impairment in six conscious pigs subjected to pacing only did not persist when pacing was terminated. Thus this model cou ld provide a unique opportunity to study both the effects of preclinical th erapeutic interventions and the mechanisms involved in the development of h eart failure.