Perioperative changes of serum orphanin in diabetic patients and its relationship with sympathetic nervous system.

The occurrence of cardiovascular events in diabetic patients during the perioperative period is related to the activation of sympathetic nerves. Basic research shows that serum nociceptin/orphanin FQ (N/OFQ) levels in diabetic neuropathy rats increased, and N/OFQ reduces the release of norepinephrine (NE). We hypothesize that N/OFQ will affect the sympathetic nervous system during perioperative myocardium of diabetic patients. 66 patients with unilateral knee arthroplasty were divided into diabetes group (D group) and non-diabetes group (N group). Measured blood glucose, serum NE, N/OFQ concentrations at the 30 min before anesthesia (T0), 1 h after surgery (T1), 24 h after surgery (T2) and the cardiac troponinI (cTnI) concentration at T0 and T2. Compared with N group, the concentration of blood glucose, N/OFQ and cTnI in D group was higher and the NE was lower at T0 (P < 0.05). At T1, the blood glucose, N/OFQ, NE concentrations of D group increased, only the blood glucose increased in N group (P < 0.05). Serum N/OFQ of D group from T0 to T1 was correlated with the change trend of blood glucose, NE concentration from T0 to T1 and cTnI from T0 to T2(r = 0.386, P = 0.027; r = 0.350, P = 0.046; r = 0.363, P = 0.038). The outcomes demonstrated that the preoperative serum N/OFQ concentration in diabetic patients was increased, and the increase in N/OFQ concentration during the operation was related to the increase in NE and cTnI concentrations, perioperative N/OFQ may mediate myocardial injury through sympathetic nervous system.

Non-peptide orphanin receptor antagonist activity in rat myocardial ischemia-induced cardiac arrhythmias.

One of the causes of sudden cardiac death is arrhythmia after acute myocardial ischemia. After ischemia, endogenous orphanin (N/OFQ) plays a role in the development of arrhythmias. It is discussed in this paper how nonpeptide orphanin receptor (ORL1) antagonists such as J-113397, SB-612111 and compound-24 (C-24) affect arrhythmia in rats following acute myocardial ischemia and what the optimal concentrations for these antagonists are. The electrocardiogram of the rat was recorded as part of the experiment. The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the myocardium were measured following euthanasia. Following the use of three antagonists, we found the lowest inflammatory factor concentrations and the smallest number of ischemic arrhythmia episodes. All of them had a small impact on cardiac function. LF/HF values were significantly reduced in all three antagonist groups, suggesting that they are involved in the regulation of sympathetic nerves. In conclusion, pretreatment with the three antagonist groups can effectively reduce the concentration of TNF-α and IL-1ß, and the occurrence of arrhythmias after ischemia can also be significantly reduced. Inflammation and sympathetic activity may be related to the mechanism of action of antagonists.

Antagonism of N/OFQ attenuates externalization of ß1-adrenergic receptor and ventricular arrhythmias in acute myocardial ischemia rat model.

Nociceptin/orphanin FQ (N/OFQ) and adrenergic activations play roles in promoting cardiac arrhythmia in acute myocardial ischemia but whether N/OFQ and ß1-adrenergic activities interact and how they interact in the arrhythmogenesis are still unknown. We designed this study to investigate the potential interaction of N/OFQ and ß1-adrenergic activities and the underlying mechanism in arrhythmogenesis in acute myocardial ischemia. Ventricular arrhythmia was evaluated in anaesthetized rats following permanent coronary artery occlusion (CAO), in presence and absence of UFP-101 (a selective antagonist of N/OFQ receptor). The changes of ß1-adrenergic receptor (ß1-AR) in plasma membrane of cardiomyocytes were quantitatively evaluated and the relations with the alterations of phosphorylated Raf kinase inhibitor protein (p-RKIP) and phosphorylated connexin 43 (p-Cx43) were investigated. The ventricular arrhythmia was 59% less in the animals pre-treated with UFP-101 than the placebo-treated control (difference of means = -2.41; 95% confidence interval (CI) -2.84 to -1.99; P < 0.001). Meanwhile, p-RKIP and membrane ß1-AR in the myocardium were downregulated by 59% and 24%, respectively (p-RKIP: difference of means = -6.91; 95% CI -8.38 to -5.45; P < 0.001; membrane ß1-AR difference of means = -27.06; 95% CI -29.89 to -24.23; P < 0.001). Artificial upregulation of RKIP by didymin significant increased ß1-AR in plasma membrane of the cardiomyocytes in the animals prone to ventricular arrhythmia. The findings may suggest that activation of N/OFQ receptor in acute myocardial ischemia induces upregulation of p-RKIP, externalization of ß1-adrenergic receptor and downregulation of p-Cx43 in the cardiomyocytes, which promotes ventricular arrhythmia.

Time-dependent expression of skeletal muscle troponin I mRNA in the contused skeletal muscle of rats: a possible marker for wound age estimation.

To estimate the age of skeletal muscle contusion, the expression of troponin I mRNA in contused skeletal muscle of rats was detected using real-time polymerase chain reaction (PCR). A total of 51 Sprague-Dawley male rats were divided into control and contusion groups, and another nine rats received contusion injury after death. At 0.5, 1, 6, 12, 18, 24, 30, and 36 h after contusion, the rats were killed with a lethal dose of pentobarbital. Total RNA was isolated from muscle specimens using the SV Total RNA Isolation System and reverse transcribed into first-strand cDNA. Sequence-specific primers were then used to conduct real-time PCR to analyze the expression levels of sTnI mRNA. At 0.5, 1, and 6 h after contusion, the expression levels of sTnI mRNA decreased to 78.17% (P < 0.05), 41.58% (P < 0.05), and 32.13% of that in the control group, respectively. However, there were no significant changes in the expression levels of sTnI mRNA from 6 to 36 h (P > 0.05) after contusion when normalized to RpL32 expression. The expression levels of sTnI mRNA in the normal and contused skeletal muscle of postmortem rats were about 70% of that in the control group (P < 0.05), and no significant changes in the expression levels of sTnI mRNA in the postmortem contusion group were noted among different time points after injury. This result suggests that determination of sTnI mRNA levels by real-time PCR is useful for the estimation of wound age.

Tramadol reduces myocardial infarct size and expression and activation of nuclear factor kappa B in acute myocardial infarction in rats.

BACKGROUND AND OBJECTIVE: Some anaesthetics show cardioprotective properties, but the underlying mechanism remains elusive. The aim of this study was to investigate the cardioprotective effect of tramadol and the association of the effect with the changes in expression and activation of nuclear factor kappa B (NF-kappaB) in acute myocardial infarction in a rodent model. METHODS: Male Sprague-Dawley rats were randomly divided into three groups: the sham group, exposure of anterior parts of the heart was carried out without ligation of the coronary artery; coronary artery occlusion (CAO) group, ligation of the left anterior descending branch of the coronary artery was performed; and the group in which the animals were pretreated with tramadol (12.5 mg kg(-1), intravenously) before the CAO (T + CAO). The infarct size, expression of NF-kappaB subunit p65 mRNA and protein and intercellular adhesion molecule-1 mRNA were examined. Isolated nucleus suspension was analysed by flow cytometry to determine activation of NF-kappaB. RESULTS: The area at risk (percentage of left ventricle) was 46.4 +/- 6.2 and 48.2 +/- 5.9% in the CAO and T + CAO groups, respectively, showing no statistical difference in area at risk/left ventricle between the two groups (P > 0.05). The infarct size (percentage of risk area) was reduced from 44.9 +/- 6.8% in CAO animals to 31.6 +/- 7.7% in T + CAO animals. The reduction of infarct size in the T + CAO group was statistically significant (P < 0.05). Expression of NF-kappaB and its mRNA and intercellular adhesion molecule-1 mRNA was significantly increased in the CAO group compared with the sham group and was significantly decreased in the T + CAO animals. Flow cytometry assay revealed that tramadol attenuated the activation of NF-kappaB by 13.4%. CONCLUSION: Tramadol may protect myocardium against acute myocardial ischaemic injury and could reduce myocardial infarct size, which may be associated with the expression and activation of NF-kappaB.