Effects of low-dose recombinant human brain natriuretic peptide on anterior myocardial infarction complicated by cardiogenic shock

Abstract INTRODUCTION: The mortality due to cardiogenic shock complicating acute myocardial infarction (AMI) is high even in patients with early revascularization. Infusion of low dose recombinant human brain natriuretic peptide (rhBNP) at the time of AMI is well tolerated and could improve cardiac function. OBJECTIVE: The objective of this study was to evaluate the hemodynamic effects of rhBNP in AMI patients revascularized by emergency percutaneous coronary intervention (PCI) who developed cardiogenic shock. METHODS: A total of 48 patients with acute ST segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock and whose hemodynamic status was improved following emergency PCI were enrolled. Patients were randomly assigned to rhBNP (n=25) and control (n=23) groups. In addition to standard therapy, study group individuals received rhBNP by continuous infusion at 0.005 µg kg−1 min−1 for 72 hours. RESULTS: Baseline characteristics, medications, and peak of cardiac troponin I (cTnI) were similar between both groups. rhBNP treatment resulted in consistently improved pulmonary capillary wedge pressure (PCWP) compared to the control group. Respectively, 7 and 9 patients died in experimental and control groups. No drug-related serious adverse events occurred in either group. CONCLUSION: When added to standard care in stable patients with cardiogenic shock complicating anterior STEMI, low dose rhBNP improves PCWP and is well tolerated.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.