A chronic pressure overload animal model was created in young guinea pigs by surgical constriction of the descending thoracic aorta. Hemodynamics, echocardiography and myocyte size characterization demonstrated compensated pressure overloaded left ventricular (LV) hypertrophy at 4 weeks (4 wk), and congestive left heart failure 6 months (6 mo) after aortic constriction. Compared to age-matched sham-surgery control groups, the cell length and length/width ratio of isolated LV myocytes were significantly increased at 6 mo but not at 4 wk. LV myocyte lengthening was statistically correlated to an increase in LV chamber dimension and diastolic wall stress at 6 mo. These data demonstrate that myocyte lengthening occurs in mechanical overload-induced congestive heart failure, contributes to LV chamber dilatation, and is associated with increased end-diastolic wall stress. Myocytes of the other three chambers remained morphometrically normal at 4 wk. Hypertrophy of left atrial (LA) and right ventricular and atrial myocytes was evident at 6 mo. Increases in both cell length and cross-sectional area contributed significantly to the hypertrophy in the three chambers. More than 85% of LV myocytes were binucleate and the binucleation remained unchanged in the sham-surgery group from the tested 4 wk to 6 mo time point. LV hypertrophy and failure showed no significant effects on the binucleation of LV myocytes. By contrast, over 96% of LA myocytes were mononucleate. The mononucleate percent of LA myocytes was not appreciably altered during either normal growth or hypertrophy induced by secondary hemodynamic overload due to LV failure.
Bibliographical noteFunding Information:
This work was supported in part by grant HL30696 from NIH (AMG). We are grateful to Suleman Said, Kurt Lustig and Tetsutaro Tamura, for their technical assistance. We would like to thank Ms Nancy Ball of the Department of Internal Medicine at the University of Cincinnati, Cincinnati, Ohio for her advice and guidance on the guinea pig surgery. The South Dakota Heart Research Foundation Cardiovascular Research Institute is a partnership between the University of South Dakota School of Medicine and Sioux Valley Hospitals and Health System.
- Chronic pressure overload
- Congestive heart failure
- Guinea pigs
- Myocyte remodeling