Previous work with rats has shown that positive results from left ventricular aneurysm repair are short term due to left ventricular remodeling but can be maintained longer with postoperative use of an angiotensin converting enzyme-inhibitor drug. In the current work, postoperative administration of atrial natriuretic peptide (ANP) had beneficial effects at 4 weeks after surgery on left ventricular remodeling, function, and fibrosis. The findings suggest that intravenous infusion of ANP may be helpful clinically during the postoperative period.

Left ventricular aneurysm repair is designed to decrease stress on the ventricular wall and improve left ventricular function. Previous work with rats has shown that positive results from repair procedures are short term due to ventricular remodeling; results can be maintained longer with postoperative use of an angiotensin converting enzyme-inhibitor drug.

In the current work, Dr. Tsuneyoshi's group decided to test postoperative atrial natriuretic peptide (ANP) based on its inhibitory activity against the renin-angiotensin system and against post-myocardial infarction ventricular remodeling, as well as its well-known natriuretic and vasodilatory effects.

The research model uses rats that have developed chronic ischemic cardiomyopathy with LV aneurysm 4 weeks after ligation of the left anterior descending artery. The repair procedure involved plication of the aneurysm.

Afterward, rats (15 rats per group) were randomized to intravenous infusion of ANP (0.5μg/kg/min, Carperitide, recombinant alpha-hANP) or of normal saline. Both infusion treatments were given for 4 weeks via osmotic mini-pump. Cardiac evaluations were done over the 4-week treatment period and at its end for both groups of rats.

There were no significant differences between treatment groups in systolic blood pressure or heart rate.

The anticipated appearance of re-dilatation in the left ventricle was observed. However, ventricular re-dilatation in the ANP group was significantly milder than that seen in the saline group. Moreover, an akinetic segment gradually increased in the saline group but remained unchanged in the ANP group. Overall, rats that received ANP had better left ventricular remodeling and left ventricular function per echocardiography than the rats that received saline.

Catheterization at 4 weeks showed that the rats in the ANP group had significantly lower left ventricular end-diastolic pressure and Tau. End systolic elastance was higher in the ANP rats.

Fibrosis was evaluated with chemical measures and histologically. The mRNA expression of BNP and TGF-beta 1 (inducer of fibrosis) was significantly lower in the rats that received ANP. Interstitial fibrosis at a site away from the repair site was significantly lower in the rats in the ANP group (based on computerized analysis, fibrosis involved 3.8 ±1.6 percent of myocardium in ANP group and 7.9±2.8 percent in saline group).

Dr. Tsuneyoshi summarized by concluding that ANP had clear beneficial effects in the rat model of chronic ischemic cardiomyopathy and surgical repair up to 4 weeks after left ventricular aneurysm repair in terms of left ventricle remodeling, function, and fibrosis. Intravenous ANP may well have a clinical role in management of patients who undergo left ventricular aneurysm repair.