Pharmacodynamic Research Of Brain Natriuretic Peptide In Treatment Of Pulmonary Hypertension After Mitral Valve Replacement

Background and Objectives:For rheumatic heart disease patients with pulmonary hypertension, the valve replacement surgery can improve their hemodynamics. However, because of the release of vasoactive substance and the inflammatory medium release, and the break of blood cells and endothelial cells that all caused by the extracorporeal circulation, the patients’pulmonary hypertension still exists after operation or even aggravates. The pulmonary hypertension can increase the right ventricular afterload, leading to the heart failure or low cardiac output syndrome. The rhBNP, which was stored in the ventricular diaphragm particles, is a very important plasma marker for the diagnosis of heart failure, that has been recognized internationally. The physiological function of rhBNP is to dilate the blood vessels, the natriuretic diuresis, to maintain the balance of cardiac vascular and other systems, and to prevent the volume overload. Now the rhBNP has gotten the approval of FDA and can be used in the treatment of decompensated congestive heart failure. But until now, there is rare report about the effect of rhBNP in the treatment of pulmonary hypertension.The objective of the research is to investigate the pharmacodynamics of rhBNP in the treatment of pulmonary hypertension in patients after mitral valve replacement surgery, and to its molecular mechnics. Because the similarity of rhBNP and PGE1in pharmacodynamics, we use the later as control to make sure the clinical value of rhBNP.Methods:60MVR patients with a mean post-operative pulmonary arterial pressure≥25mmHg were randomly divided into3groups,20patients in each group. The patients were sent to ICU after operation; those in the control group received infusion of saline at2ml/h for24hours; those in the PGE1group received continuous infusion of PGE1at30ng/kg/min for24hours; those in the rhBNP group first received intravenous injection of rhBNP at2μg/kg and then received continuous infusion at0.01μg/kg/min for24hours. The mean radial arterial pressure (MAP), central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PAWP), cardiac output index (CI), and pulmonary vascular resistance index (PVRI) were monitored via Swan-Ganz catheter before treatment, at1h,3h,6h,12h,18h, and24h after treatment, and2h after discontinuation; the duration of ventilator-assisted breathing was also statistically counted. The pulmonary arterial pressure (PAP), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), and Tei index [Tei index=(isovolumetric contraction time+isovolumetric relaxation time)/ejection time] were tested via ultrasonic cardiogram (UCG) before operation,1week and3months after operation; the levels of thromboxane-A2(TXA2) and cyclic guanosine monophosphate (cGMP) in the peripheral venous blood were detected with ELISA methods before operation, at pre-treatment,24hours after treatment,1week and3months after operation.Results:①For all the patients enrolled, the post-operative MAP, CVP, CI, and PAWP had no significant difference compared with the preoperative values; while MPAP and PRVI were lower. For patients in the control group, the post-treatment hemodynamic changes had no significant trends; for patients in the PGE1group, MAP, MPAP, PRVI, and PAWP were decreased one hour after treatment, then remained unchanged at this level, and rebounded after treatment discontinuation; PGE1had no significant effect on CI or CVP; for patients in the rhBNP group, MPAP, PRVI and PAWP were decreased3hours after treatment, of which MPAP and PRVI were decreased less than the PGE1group, and then maintained at this level, without obvious hemodynamic rebound after treatment discontinuation; rhBNP had no significant effect on MAP, CVP, or CI. The ventilator-assisted breathing duration was shorter in the PGE1group than in the rhBNP and control group; although no statistically significant difference was observed between rhBNP group and control group, the mean ventilator-assisted breathing duration in the rhBNP group was shorter compared with the control group.②The PAP and Tei index was significantly decreased for all patients one week after operation from pre-operation, while LVEF was increased; no significant difference was observed in PAP and LEVF3months after operation compared with those observed one week after operation. There was no significant difference among the three groups at any observation time point. The Tei index is correlated with PAP (r=0.674,P<0.05),but has no significant correlation with LVEF or LVEDD.③In the control group, the immediate post-operative TXA2was increased compared with the preoperative values, while cGMP was decreased, continuously until24hours after operation, and both returned to the preoperative levels one week after operation, continuously until3months after operation; in the PGE1group, TXA2was decreased while cGMP was increased after treatment, and both returned to the preoperative levels one week after operation; the re-examination was performed3months after operation and showed no significant difference. In the rhBNP group, cGMP was increased and TXA2had no obvious change after treatment; cGMP returned to the preoperative level one week after operation; the re-examination was performed3months after operation and showed no significant difference. Both PGE1and rhBNP could cause cGMP increase after treatment, but the increase level in the rhBNP group was higher than that in the PGEI group.Conclusion:Both rhBNP and prostaglandin E1can effectively reduce pulmonary arterial pressure after treatment, but prostaglandin E1has faster and more significant efficacy; the effects of these two drugs on reducing pulmonary arterial pressure may be mediated by different pathways; the short-term postoperative medication with PGE1and rhBNP has no significant effect on long-term cardiac remodeling and heart function.