Neurohormones in an ovine model of compensated postinfarction left ventricular dysfunction

Clinical heart failure, often the result of myocardial infarction, may be p receded by a period of compensated left ventricular impairment. There is su bstantial need for an experimental model that reflects this human condition . In sheep, coronary artery ligation produced consistent left ventricular a nteroapical myocardial infarctions resulting in chronic (5 wk), stable hemo dynamic changes compared with sham controls, including reductions in ejecti on fraction (51 +/- 2 vs. 30 +/- 5%, P < 0.001), cardiac output (6.3 +/- 0. 2 vs. 5.1 +/- 0.2 l/min, P < 0.01), and arterial pressure (93 +/- 2 vs. 79 +/- 3 mmHg, P < 0.001), and increases in cardiac preload (left atrial press ure, 3.3 +/- 0.1 vs. 8.3 +/- 1.3 mmHg, P < 0.001). These changes were assoc iated with acute and sustained increases in plasma concentrations of atrial natriuretic peptide (ANP; 5 wk, 11 +/- 2 vs. 27 +/- 5 pmol/l, P < 0.001), brain natriuretic peptide (BNP; 3 +/- 0.2 vs. 11 +/- 2 pmol/l, P < 0.001), and amino-terminal pro-brain natriuretic peptide (NT-BNP; 17 +/- 3 vs. 42 /- 12 pmol/l, P < 0.001). Significant correlations were observed between pl asma levels of the natriuretic peptides (ANP, day 7 to week 5 samples; BNP and NT-BNP, day 1 to week 5 samples) and changes in left ventricular volume s and ejection fraction. In contrast, renin activity, aldosterone, catechol amines, and endothelin were not chronically elevated postinfarction and wer e not related to indexes of ventricular function. Coronary artery ligation in sheep produces the pathological, hemodynamic, and neurohormonal characte ristics of compensated left ventricular impairment secondary to myocardial infarction. Plasma concentrations of the cardiac natriuretic peptides are s ensitive markers of left ventricular dysfunction. This is a reproducible mo del that reflects the clinical condition and should prove suitable for inve stigating the pathophysiology of, and experimental therapies in, early left ventricular dysfunction.