PRESSURE OVERLOAD INDUCED CARDIAC-HYPERTROPHY WITH AND WITHOUT DILATION

Objectives. The present study was designed to produce a small animal model showing compensated hypertrophy followed by congestive heart failure within a reasonable time period. Background. Although there are various large animal experimental models of hypertrophy and heart failure, the occurrence of these two stages within a reasonable time period has not been shown very successfully in small animals. Methods. A mildly constricting band was placed around the ascending aorta of very young guinea pigs (mean age 25 +/- 3 days) to impose a gradually increasing pressure overload. The animals were examined at different postoperative intervals up to 20 weeks. Results. At 10 weeks, there was a 56% increase in ventricular weight/body weight ratio, a 33% increase in left ventricular wall thickness and a significant increase in left ventricular systolic pressure. The animals with 20 weeks of banding had developed various clinical symptoms of congestive heart failure including dyspnea, cyanotic appearance of the extremities, hydrothorax and ascites. Although at this stage there was 86% hypertrophy, the increase in wall thickness was only 20%, indicating cardiac dilation. Depressed left ventricular systolic pressure and increased left ventricular end-diastolic pressure and the increase in wet weight/dry weight ratio in the lungs and liver at 20 weeks also indicated the occurrence of heart failure. The collagen content in the heart of animals with banding for 10 and 20 weeks was 160% and 240%, respectively, of that in corresponding sham control animals. Conclusions. The data suggest that the heart was in a stage of compensated hypertrophy for up to 10 weeks, whereas heart failure was seen at 20 weeks. The two functional stages, compensatory hypertrophy followed by prolonged failure, make this model appropriate for studies on the transition of heart hypertrophy to congestive heart failure.