The Protective Effect of rhBNP on Postresuscitation Myocardial Dysfunction in a Rat Cardiac Arrest Model

Abstract

Purpose. We investigated the protective effects and the underlying mechanisms through which recombinant human brain natriuretic peptide (rhBNP) acts on postresuscitation myocardial dysfunction (PRMD) in the cardiac arrest (CA) model. Methods. Ventricular fibrillation was induced and untreated for 6 min. And the time of cardiopulmonary resuscitation was 8 min, after which defibrillation was attempted in this rat model. 24 Sprague Dawley rats (450–550g) were randomized into cardiopulmonary resuscitation (CPR) + rhBNP and CPR + placebo groups after restoration of spontaneous circulation (ROSC). rhBNP was infused at PR 30 min (loading dose: 1.5 µg/kg, 3 min; maintenance dose: 0.01 µg/kg/min, 6 h). Vital signs, ejection fraction (EF), cardiac output (CO), myocardial performance index (MPI), and 24 h survival rate were continuously recorded. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and N-terminal probrain natriuretic peptide (NT-proBNP) were detected by ELISA. Heart tissues were evaluated by light microscopy. The protein expression levels of myocardial inflammatory factors (IL-6 and TNF-α), Toll-like receptor 4 (TLR4), nuclear transcription factor-κB (NF-κB) subunit p65 (p65), and phosphor-p65 were analyzed by western blotting. Results. The administration of rhBNP attenuated the severity of PRMD and myocardial tissue injuries, with improvement of MAP (mean arterial blood pressure), ETCO2 (end-tidal CO2), serum level of NT-proBNP, EF, CO, and MPI values. The serum levels and protein expression levels in myocardial tissue of IL-6 and TNF-α after ROSC were reduced by inhibiting the expression of TLR4/NF-κB. Conclusion. Our research demonstrated that the administration of rhBNP attenuated the severity of PRMD and myocardial tissue injuries and increased the 24 h survival rate in this CA model. rhBNP administration also reduced the serum and myocardial tissue levels of IL-6 and TNF-α after ROSC, likely due to the suppression of the TLR4/NF-κB signaling pathway and the regulation of inflammatory mediator secretion.

The protective effect of a short peptide derived from cold-inducible RNA-binding protein in a rat model of cardiac arrest and resuscitation

“…C23 and TLR4 have a strong a nity, thus inhibiting CIRP binding to TLR4/MD2 complex [13]. Toll-like receptors are widely expressed in brain tissues, myocardial tissues, and serum in CA/CPR model [33][34][35][36]. Both the PAMPs and DAMPs can activate TLR4 receptors on the surface of cells.…”

Cardiac Arrest – An interdisciplinary scoping review of preclinical literature from 2020

“…These findings are compelling in that they provide evidence that attenuation of mitochondrial injury and reactive oxygen species generation during cardiac arrest can lead to meaningful outcomes, and encourages further work on this aspect using larger animal models and mechanistic studies [11]. In another preclinical rat model, recombinant human brain natriuretic peptide (rhBNP) was administered following return of spontaneous circulation (ROSC ) in order to regulate expression of nuclear transcription factor kappa B as a way to attenuate injurious cellular injury pathway [12]. The authors found that animals receiving the rhBNP had improved survival rates at 24 hours post-ROSC, reduced myocardial tissue injury and reduced circulating levels of interleukin 6 and tumor necrosis factor alpha over controls, suggesting a protective effect [12].…”

“…In another preclinical rat model, recombinant human brain natriuretic peptide (rhBNP) was administered following return of spontaneous circulation (ROSC ) in order to regulate expression of nuclear transcription factor kappa B as a way to attenuate injurious cellular injury pathway [12]. The authors found that animals receiving the rhBNP had improved survival rates at 24 hours post-ROSC, reduced myocardial tissue injury and reduced circulating levels of interleukin 6 and tumor necrosis factor alpha over controls, suggesting a protective effect [12].…”

The protective effects of phosphodiesterase-5 inhibitor, sildenafil on post-resuscitation cardiac dysfunction of cardiac arrest: by regulating the miR-155-5p and miR-145-5p

“…Postresuscitation myocardiac dysfunction, an important component of the postcardiac arrest syndrome, is caused by ischemia/reperfusion (I/R) injury and includes primary manifestations such as arrhythmias, myocyte apoptosis, and contractile dysfunction [ 3 ]. Furthermore, post-resuscitation myocardial dysfunction is considered the leading cause of death within 72 h after successful CPR [ 4 ]. Therefore, studies of new medications that aim to improve post-resuscitation myocardial dysfunction are of great urgency and importance.…”