The Effect Of Dexmedetomidine On Myocardial Diastolic Function Of Early Sepsis And Its Mechanism

ObjectivesTo explore and discuss the effect of dexmedetomidine hydrochloride on myocardial injury by sepsis and explore its possible mechanism both clinically and experimentally, so as to explore a new treating method for sepsis.MethodsThis study includes clinical study and experimental research.Clinical study:Part one:Only patients with myocardial damage caused by sepsis were adopted in this study. All cases were chosen from ICU patients of Renmin Hospital of Wuhan University, who were admitted from January2010to december2010.All the patients were diagnosed according to the ACCP/SCCM and were divided into control group(n=20), early stage of sepsis group(n=15) and severe sepsis group(n=15).This study is single-blind,randomized trial. All patients received preloading treatment with voluven. Cardiac systolic (EF, FS) and diastolic function(E/A) were detected with ultrasound instrument (American HP5500). ELISA was used to detect the plasma levels of TNF-α, IL-6and IL-1at two time points.Part two:Choose the patients at the early stage of sepsis as the research object. After preloading treatment with voluven, patients were treated with small doses of dexmedetomidine or middle doses of dexmedetomidine. Cardiac function and plasma levels of TNF-a, IL-6and IL-1were detected as described in part one.Experimental study:Cardiomyocytes of adult Spraque-Dawley male rats (SD) were divided and cultured. The whole-cell patch clamp technique was used to observe the effects of different dosages (0.6ng/ml,1.8ng/ml,5.4ng/ml,10ng/ml,200ng/ml) of dexmedetomidine on channel current of L calcium ion (ICa-L) in ventricular myocytes.ResultsClinical study section1.There was no significant difference in left ventricular wall thickness, EF and FS between early stage group (10±0.57,65±3.23,30±5.73)and control group (11±0.15,65±4.13,32±9.73)(P>0.05). Compared with control group(1.42±0.13),the E/A ratio in early stage group was significantly decreased (P<0.05),accompanied with increased plasma levels of TNF-α, IL-1and IL-6levels (28.36±4.36,6.25±0.15,511.3±33.41). Plasma levels of CKMb, MYO and cTnT in Severe sepsis group (183±1.52,153±6.22,5.75±0.79) were significantly higher than those in control and the early phase group (21±4.07,52±6.51,0.13±0.18and18±6.11,63±5.64,0.11±0.26)(P<0.05).2. Heart rate (86±3.37) in small doses of dexmedetomidine group at24h time point was significantly declined,compared with5min point(98±4.24), indicated that small doses of dexmedetomidine can stabilize the heart rate and reduce myocardial oxygen oxygen. Low doses of dexmedetomidine had no significant effect on cardiac systolic function (P>0.05), but can significantly improve the myocardial diastolic function (P<0.05) and reduce the release of inflammatory factors (P<0.05), while there was no significant difference in the level of serum myocardial enzymes between two groups(P>0.05).Experimental studyDexmedetomidine has inhibitory effect on ICa-L, in a dose-dependent manner. High concentrations can make the Ⅰ-Ⅴ curve upward; different concentrations of dexmedetomidine almost has no effect on the activation potential, peak activation potential and reversal potential; low concentration (0.6ng/ml,1.8ng/ml and5.4ng/ml) of the right medetomidine activation curve of ICa-L steady state was not statistically significant, but higher concentrations of dexmedetomidine (lOng/ml and200ng/ml) can make the ICa-L steady-state activation curve shifts to the right, half activation voltage increases, the curve slope increases; different concentrations of dexmedetomidine has no obvious effect on ICa-L inactivation curves; with the increase of medetomidine concentration the recovery curve downward, calcium channel inactivation, channel inactivation recovery time increases gradually; dexmedetomidine inhibitory effect on ICa-L can be weakened by Yu Henbin, suggested the right beauty care medetomidine inhibitory effect on L type calcium channel current may be mediated by a2adrenergic receptorConclusion1. Ventricular diastolic function at early stage of sepsis was impaired,accompanied with increased inflammatory factors release,while there was no significant change in myocardial enzyme levels. It indicated that The impaired diastolic function at early stage of sepsis (cardiac dysfunction)) may be related to the release of inflammatory factors. 2. Dexmedetomidine can effectively improve myocardial diastolic function, and can significantly reduce the release of inflammatory factors.3. Dexmedetomidine has inhibitory effect on ICa-L. Small doses of dexmedetomidine has little effect on the ICa-L, but the decrease of ventricular myocytes platform period of calcium, thereby reducing the calcium overload in myocardial cells, which may be one of the mechanisms about a small dose of dexmedetomidine improvement in sepsis early myocardial diastolic dysfunction.