A simple method for producing graded aortic insufficiencies in rats and subsequent development of cardiac hypertrophy

Selective perforation of the right cusp of the aortic valve alone (1V) or in combination with that of the left valve cusp (2V) by a plastic rod inserted from the right common carotid artery was performed to cause aortic insufficiency (AI) in rats. The development of cardiac hypertrophies subsequent to these interventions to cause graded cardiac volume overloads was followed up every week till the end of week 4 after the operations by radiographic measurement of the cardiothoracic ratio (CTR). Rats were killed 2 and 4 weeks after the operations, and the density of beta-adrenoceptors in hypertrophied cardiac muscle membranes was determined by radioligand binding assay and compared with sham-operated (sham) rats. Production of AI resulted in an enlargement of the cardiac shadow in 1VAI and 2VAI rats, with significant graded increases in the CTR at the end of week 3. The occurrence of graded cardiac hypertrophies was well revealed in graded increases of the heart weight/body weight ratio among the sham, 1VAI, and 2VAI rats at the end of both week 2 and week 4. There was a tendency to stepwise increases due to graded AI in the density of binding sites for 3H-dihydroalprenolol, with a significant increase in 2VAI rats at the end of week 2. At the end of week 4, plasma norepinephrine levels of 2VAI rats was raised significantly as compared with the sham rats. Selective perforation of either one or two cusps of the aortic valve can be performed with ease using touch alone and provides us with a simple method for producing graded cardiac hypertrophies in rats due to pure volume overload.