Evaluation Of Efficacy And Mechanism Of Recombinant Human Brain Natriuretic Peptide On Congestive Heart Failure

PrefaceCongestive hear failure (CHF) is a significant case of mobility and mortality. Since 1990s' the therapy to CHF emphasis on suppressing the nerohormone activation in order to decrease the adverse effect and delay the development of the ventricular remodeling. The pharamacological management of CHF patient includes diuretics, angiotension—converting enzyme inhibitions (ACEI) and angiotensionⅡ receptor blocks (ARB), β — blocks, aldosterone—blocks, and so on. Many new drugs had been made, brain natriuretic peptide(BNP) is one of them. In 1998 BNP was found from the brain of pig by Japanese scientist Sudon, recombinant human brain natriuretic peptide (rhBNP) is a man—made—peptide through gene engineering. It has the same amino — acid ring structure as BNP. So the patient of CHF may benefit from rhBNP. This experiment obverses the change of index of CHF and the plasma concentration of K~+ , N_a+ , ALD and ET—1 in order to examine the efficacy, safety and the mechanism of rhBNP in patients with CHF.Materials and methodsThe subject were 35 patients who were hospitalized in our ward for CHF from June 2003 to May 2004. This is a randomized ,open and controlled study . After the whole patients receive the standard therapies (including diuretics, ACEI, ARB and so on). rhBNP and nitroglycerin wasadded respectively. The trial groups, at first 1. 5ug/kg of rhBNP was iv , then 0. 0075ug/kg ivdrop continued 24h. The controlled group, at first lOug/min of nitroglycerin was given, then these patient was give 5ug every time until the observer was satisfied with the effort. 20min before receiving the drug and Omin, 15min, 30min, lh, 2h, 4h, 8h, 12h, 24h, after pharmacologic treatment we observe the systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, respiratory rate and the severity of dyspnea of patients and measure the pulmonary capillary wedge pressure (PCWP) , pulmonary artery pressure (PAP) , cardiac index (CI) and right atrial pressure (RAP). 20min before receiving the drug and 24h, 3d after pharmacologic treatment , the plasma concentration of K+ , Na+, aldosterone (ALD) and endothelin (ET—1) were measured. Values are expressed as rneaniSD. The plasma concentration of K+ , Na+ , ALD and ET—1 analysis was performed using unpaired student's t — tests. The efficacy of rhBNP was tested with a chi — square test. SPSS11. 5 software package was adopted to examine all values.Result1. Physical examination: Dyspena and the degrees of SBP were improved in both of the two groups, but rhBNP produced more favorable reduction.2. Index of hemodynamics: In the trial group elevated filling pres-sureconsistenly and rapidly lowers in PCWP and PAP than in controlled group, but not in RAP and CI.3. Plasma concentration of K+ and Na+: In the trial group, after pharmacologic treatment the plasma concentration of K+ and Na+ were different than before receiving the drug. This situation was not found in controlled group.4. Plasma concentration of ALD and ET—1: In the trial group, 24h after pharmacologic treatments , The ALD and ET—1 concentration are more favorable reduction than before receiving the drug, 3d after pharma-cologic treatment , the ALD concentration are more favorable reduction than before, but the ET —1 concentration is not. In the controlled group, neither the concentration of ALD nor the ET—1 concentration decreased. 5. Adverse effect;rhBNP was associated with significant fewer adverse events than nitroglycerin in this trial.DiscussionThe activation of remin—angiotension — aldosterone system (RASS) and sympathetic nervous system (SNS) in heart failure lead to the CHF patient feel discomfortable including dyspnea, the increase of heart rate and respiratory rate. This trial showed that in both of the group dyspnea and the degrees of SBP were improved but the trial group is more significant than the controlled groupThrough the hemodynamics index of 14 patients, we found that the decrease of PCWP and PAP is more remarkable and can take effect in 15min after the receiving the drug. The VAMC trial data supported the same ideal. rhBNP is a drug which can improve not only clinical outcome but aslo the index of hemodynamic.ALD plays an important role during the progress of ventricular remodeling. This trial showed that rhBNP can resist RASS. ET—1 is the strongest systolic factor in body, rhBNP can also stand up to it. The rhBNP agonize the guanylate cyclase—coupled natriuretic peptide receptor A (NPR —A) which lead to the increase of cyclin GMP (cGMP) then CGMP serves as an intracellurar second message. This new drug can improve the symptomatic abnormativas and resist the adverse effort of neu-rohormone as well as its safety make it an attractive drug for CHF patients.Conclusion 1. rhBNP can reduce the systolic blood pressure, heart rate, respira-tory rate and the severity of dyspnea of CHF patients.2. rhBNP can consistently and rapidly lowers elevated filling pressure in PCWP and PAP.3. rhBNP can reduce the Na+ , ALD , and ET — 1 concentration and increase the concentration of K+.