Hemodynamic, left ventricular structural and hormonal changes after discrete myocardial damage in the dog

Transmyocardial direct-current (DC) shock produces localized left ventricular myocardial necrosis without obstruction to coronary blood flow. In 43 dogs sequential measurements of hemodynamic, neuroendocrine and myocardial structural changes were made at baseline and for 16 weeks after DC shock. Six dogs (14%) died in the peri-shock period. By 1 week after shock, left ventricular mass, as measured by nuclear magnetic resonance imaging, had increased from a mean value ± SD of 67.9 ± 10.1 to 82.5 ± 12.9 g (p = 0.0001). Left ventricular end-diastolic volume was unchanged at 1 week but increased at 16 weeks from 56.1 ± 10.3 to 70.3 ± 10.7 ml (p = 0.0003). Left ventricular mass demonstrated a further increase at 12 months (107.8 ± 14.8 g). Rest cardiac output was significantly decreased at 4 months (3.67 ± 1.23 to 3.18 ± 0.81 liters/min, p < 0.01) as was stroke volume (43 ± 9 to 37 ± 7 ml, p ≤ 0.01). Left ventricular ejection fraction decreased progressively from 73% to 38% at 1 year. At 4 months there were increases in mean pulmonary artery pressure (18 ± 4 to 23 ± 4 mm Hg, p < 0.01), pulmonary capillary wedge pressure (9 ± 3 to 15 ± 3 mm Kg, p < 0.01) and right atrial pressure (5 ± 4 to 9 ± 3 mm Hg, p < 0.01). Plasma norepinephrine was increased at 4 months (318 ± 190 to 523 ± 221 pg/ml, p = 0.0003), whereas plasma renin activity was not significantly changed (4.3 ± 2.6 vs. 5.2 ± 3.4 ng/ml per h). Microsphere regional blood flow studies demonstrated a 50% reduction in skeletal muscle blood flow at 4 months (0.06 ± 0.06 ml/min per g compared with 0.12 ± 0.09 in normal dogs, p = 0.05), and a reduction in the endocardial/epicardial blood flow ratio (1.11 ± 0.13 compared with 1.24 ± 0.13 in normal dogs, p = 0.02). Therefore, in this model of acute left ventricular damage, left ventricular hypertrophy precedes progressive left ventricular dilation. The hemodynamic and hormonal changes mimic the pattern observed in patients who develop left ventricular dysfunction after myocardial infarction and the model thus provides a unique opportunity to study physiologic and pharmacologic responses during this period.