Recovery from heart failure: structural and functional analysis in a canine model

Abstract

Chronic, rapid ventricular pacing produces congestive heart failure in the dog. Using echocardiography, the features of developing heart failure were analysed and the capacity of this model for recovery was assessed once pacing had been discontinued. Fifteen dogs were studied; nine were paced at 250 beats/min (bpm) to severe heart failure (5.0 ± 1.8 weeks) and six served as sham controls. In the paced animals at severe heart failure, two-dimensional echocardiography demonstrated a significant increase in diastolic cross-sectional cardiac area (from 11 ± 3 to16 ± 2 cm2, p < 0.05), associated with a marked fall in area ejection fraction (54 ± 8 to 21 ± 8%, p < 0.05), and significant left ventricular wall thinning (from 6.0 ± 0.7to4.7 ± 0.9 mm, p < 0.05). In addition, significant increases in heart rate (77 ± 7 to 126 ± 13 bpm, sinus rhythm; p < 0.05), respiratory rate (41 ± 13 to 80 ± 20 cycles/min, p < 0.05), and body weight (21 ± 1 to 24 ± 3 kg, p < 0.05) were noted. Serum sodium fell (146 ± 3 to 140 ± 8 mmol/L, p < 0.05), while blood urea nitrogen (6 ± 2 to 10 ± 2 mmol/L, p < 0.05) and creatinine (86 ± 12 to 101 ± 15 mmol/d, p < 0.05) increased. Recovery was characterized by rapid improvement such that all measured parameters normalized by 1 week, except for cross-sectional cardiac area which remained dilated up to 4 weeks (14 ± 3 cm2, p < 0.05 versus control). Necropsy data obtained from paced dogs after 4 weeks of recovery demonstrated cardiac hypertrophy when compared with sham controls (9.4 ± 1.2 versus 7.7 ± 0.9 g/kg, p < 0.05), but no histologic abnormality was revealed under light microscopy. Left ventricular norepinephrine levels were similar to those of sham controls (617 ± 323 versus 676 ± 177 ng/g wet weight, not significant). The rapid recovery of ventricular systolic performance demonstrated in this heart failure model suggests that reversible substrate depletion is the mechanism responsible. Despite this recovery, there is persistent diastolic enlargement of the left ventricle indicating that structural remodeling has taken place.