Canine nonischemic left ventricular dysfunction: a model of chronic human cardiomyopathy

J Card Fail. 2005 Oct;11(8):638-44. doi: 10.1016/j.cardfail.2005.05.006.

Abstract

Background: The mechanisms of cardiac remodeling during chronic heart failure remain poorly defined. We sought to advance a chronic canine model of nonischemic cardiomyopathy.

Methods and results: Male dogs (n = 6) received decremental right ventricular apical tachypacing (12 months) to achieve and maintain stable left ventricular (LV) dysfunction. After 10 months of tachypacing, 120 beats/min was sufficient to maintain stable LV dysfunction. Electrocardiography, echocardiography, and tissue Doppler imaging were done to evaluate electrophysiology, LV dimensions and function, and dyssynchrony during normal sinus rhythm. The 6-minute walk test was used to evaluate functional capacity. We observed increases in both QRS duration (P < .0001) and QRS amplitude (P < .0001). LV fractional shortening was reduced from a baseline of 38.0 +/- 1.4% to 11.2 +/- 1.4% (P < .0001). LV end-diastolic dimension increased from 3.8 +/- 0.1 cm at baseline to 5.3 +/- 0.3 cm (P < .0001); LV end-systolic dimension increased from 2.3 +/- 0.1 cm to 4.7 +/- 0.2 cm (P < .0001). LV mass increased from 85.9 +/- 3.5 g at baseline to 179 +/- 13.7 g (P < .0001). There was evidence of LV dyssynchrony (P < .04) during both normal sinus rhythm and right ventricular tachypacing, compared with control dogs. The distance a dog walked in 6 minutes was significantly less at 12 months compared with normal controls (540 +/- 32 m versus 277 +/- 64 m, P < .008).

Conclusion: This nonischemic model of canine cardiomyopathy reproduces many aspects of chronic human heart failure including reduced fractional shortening, dilated ventricular dimensions, increased LV mass, decreased functional capacity, and dyssynchrony.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cardiomyopathies / physiopathology*
  • Chronic Disease
  • Disease Models, Animal
  • Dogs
  • Echocardiography, Doppler
  • Electrocardiography
  • Heart Conduction System / physiopathology*
  • Heart Rate
  • Humans
  • Hypertrophy, Left Ventricular / physiopathology
  • Male
  • Models, Cardiovascular
  • Natriuretic Peptide, Brain / blood
  • Research Design
  • Stroke Volume
  • Time Factors
  • Troponin C / blood
  • Troponin I / blood
  • Ventricular Dysfunction, Left / blood
  • Ventricular Dysfunction, Left / physiopathology*
  • Ventricular Remodeling

Substances

  • Biomarkers
  • Troponin C
  • Troponin I
  • Natriuretic Peptide, Brain
  • C-Reactive Protein