Effects Of Mechanical Ventilation Combined With Penehyclidine Hydrochloride On Cardiac Function And Cardiac Local Renin-angiotensin System Of Acute Respiratory Distress Syndrome Rats

Objective:To observe the effect of mechanical ventilation combined with penehyclidine hydrochloride on heart function and cardiac renin-angiotensin system (RAS) of the acute stage of acute respiratory distress syndrome (ARDS) in rat, and investigate the protective effect and related mechanisms of PHCD on the heart function of rats and provide a valid scientific basis for clinical treatment.Methods:Ninety healthy male Sprague-Dawley rats with age of12-16weeks, were randomly divided into five groups. Control Group (Sham-operated and normal saline control group, n=18):Group A (only tracheal intubation, the right carotid artery catheterization, and tail vein injection of normal saline0.15ml/kg, n=18); Group B(ARDS without intervention group:building the ARDS model of rats induced by tail vein injection of oleic acid0.15ml/kg, n=18); Group C (ARDS with mechanical ventilation treatment group:tidal volume (VT)=6ml/kg, respiratory rate (RR)=60BPM, inspired oxygen concentration (FiO2)=50%, inspiratory to expiratory ratio (I:E)=1:2, end-expiratory pressure (PEEP)=3cmH2O, n=18); Group D (ARDS with PHCD treatment group: intraperitoneal injection of PHCD0.017mg/kg, n=18); group E (ARDS with mechanical ventilation and PHCD combined treatment group:the ventilator settings in accordance with group C, and the PHCD usage and dosage in accordance with Group D). All groups were randomly divided into3subgroups respectively by1h,2h and4h after the modeling, and there were6rats in each group with effective detection and executed alive for materials. Recording the heart rate (HR), right common carotid artery systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular systolic pressure (LVSP), maximum rising and falling rate of left intraventricular pressure (±LVdp/dtmax), and left ventricular end-diastolic pressure (LVEDP) at each time point after the modeling. The serum concentrations of cardiac troponin T (cTnT) and brain natriuretic peptide (BNP) were determined at the corresponding time points by Enzyme linked immunosorbent assay. Angiotensin Ⅰ (Ang Ⅰ), angiotensin Ⅱ (Ang Ⅱ) content and the renin activity (Renin) were detected in left ventricular myocardial tissue by radioimmunoassay. PASW Statistics V18.0 statistical software was used for data analysis. Statistical significance was assessed by One-way ANOVA and the relationship between the experimental results was calculated with the pearson correlation coefficient.Results:At the same time points, compared with group A, in other groups, LVSP and±LVdp/dt were significantly decreased (P<0.05), LVEDP, Ang I, Ang II content and renin activity were significantly increased (P<0.05) and the levels of serum cTnT and BNP were significantly higher (P<0.05). In each subgroup of group C, compared with group B, the LVSP and±LVdp/dtmax increased, the serum cTnT and BNP levels also decreased and LVEDP, Ang I, Ang II content and renin activity were decreased, while all the indicators with no statistically significance (P>0.05). In group D, LVSP and±LVdp/dtmax was significantly increased (P<0.05), LVEDP was significantly reduced (P<0.05), serum cTnT and BNP levels were significantly reduced (P<0.05). Ang I, Ang II content and Renin activity were reduced, there were not statistically significant(P>0.05)in group E, LVSP and±LVdp/dtmax, was significantly increased (P<0.05), LVEDP was significantly reduced (P<0.05), serum cTnT and BNP levels, Ang I, Ang II content, and the renin activity in myocardial tissue was significantly reduced (P<0.05). The correlation analysis indicated that Ang II content and renin activity of rats’ myocardial tissue were positively correlated with LVEDP, serum cTnT and BNP content, and were negatively correlated with LVSP and±LVdp/dtmax.Conclusion:ARDS could induce myocardial damage, decrease cardiac function and activation of cardiac local RAS in rats; MV combine with PHCD can improve ARDS rat heart function and promote indirect inhibition of myocardial RAS activation level; RAS activation level is positively correlated with the degree of damage of heart function in ARDS rats the myocardial tissue.