Tadalafil Effect Of Cardiac Hypertrophy And Cx43Against Shunt Pulmonary Hypertension In Rats

Objective:Pulmonary artery hypertension, which is a kind of disease of pulmonary circulation, associated with a variety of factors, is a clinical pathophysiological syndrome characterized by increased pulmonary artery pressure and pulmonary vascular resistance, and finally resulting in right heart failure and death. It is known that connexin43plays an important role in the onset of many diseases such as CAD, CD, tumor and ventricular hypertrophy. Our study is to develop a model of pulmonary artery hypertension by shunts, and discuss the relationship between tadalafil and myocardial hypertrophy and CX43in the rats of this model.Method:Twenty-four male Sprague-Dawley rats weighing250-290g were divided into3groups(A,B and C) randomly:group A was for blank, just using normal sodium four weeks after operation which was clamping the abdominal aorta30s in the abdominal cavity was opened; group B was for control, using normal sodium four weeks after producing an aortocaval fistula; In group C we used tadalafil(10mg/kg/d)four weeks after producing an aortocaval fistula.Animals(B,C) were anaesthetized and exposed inferior vena cava and abdominal aorta by opening the abdominal cavity via a midline incision. The aorta was punctured at the union of segment two thirds caudal to the renal artery and the one third cephalic to the aortic bifurcation with an18G disposable needle. Once the aorta was clamped, the needle was fully withdrawn and a drop of cyanoacrylate glue was to seal the aorta punctured point. The clamp was removed30s later. The shunts could be verified by thickened vena cava, blood color or blood wave. After this, the abdominal cavity was closed. Six weeks later, the animals were anaesthetized and chest was opened by microcatheter which was to measure the value of mPA, mPAP, RVSP and dp/dtmax. The value of NO was measured by artery blood of carotid. Then hearts were obtained and atriums were cut off. We measured the value of RV/H and RV/BW. Degree of heart muscle fibrosis of myocardium of right ventricle and the values of CVF were obtained by Masson dyeing; Information of Cx43was obtained by immunohistochemistry and western-blot.SPSS13.0statistical software was applied to conduct statistical analysis. Data were expressed in means±td. Comparisons between groups were performed by one-way ANOVA and comparisons in groups were made by using repeated measure ANOVA. If the differences between the contrast group was a significant statistical one, we used P<0.05to express the statistical significant differences.Results:1Haemodynamics:Our study showed significant increase in group B compared to group A(P<0.05), and there was no notable difference of dp/dtmax(P>0.05); value of mPAP,RVSP had a significant deduce and dp/dtmax had a notable increase in group C(P<0.05). There was no significant in the value of mPA(P>0.05).2RV hypertrophy:The values of RV/H and RV/BW had a marked increase in the group B(P<0.05) compared to group A, and the value was decreased notably in group C(P<0.05).3NO in the serum:NO in the serum had a significant decrease in the group B(P<0.05) compared to group A, and NO in the serum had a significant increase in group C(P<0.05).4CVF:The CVF of myocardium had a marked increase in the group B(P<0.05) compared to group A, and it had a marked decrease in the group5Cx43in the myocardium:There was no significant difference in the value of Cx43(P>0.05).6Results of light microscopy:6.1Masson dyeing in the myocardium of right ventricle: Group A:myocardium of right ventricle had a line in order, and a little fibroglia fibrils appeared in the spatium intermusculare; group B:there was marked hypertrophy in the myocardial cell and had a disorder in the heart muscle fiber. Some collagen protein dyeing blue could be seen in the spatium intermusculare; group C:diminution, decurtation could be seen in the myocardial cell and collagen protein decreased in the spatium intermusculare.6.2Cx43in the immunohistochemistry:Group A Cx43was mainly situated in the end-to-end point, with an order in line. Group B Cx43was mainly situated in the side-by-side point, with a disorder in line. Group C was between group A and group B.Conclusion:For the rats in this model, tadalafil is able to decrease the PAH pressure, restrain RV hypertrophy and myocardial fibrosis, impact of Cx43distribution. It also exhibit functions of improving RV function and easing preload. Thus myocardium of right ventricle can be protected.