In vivo and ex vivo effects of propofol on myocardial performance in rats with obstructive jaundice

Liu

et al. 2017

Oncotarget

The spinal origin of jaundice-induced altered peripheral nociceptive response poorly understood. In the current study, we aimed to first validate rats with bile duct ligation (BDL) as a jaundice model accompanied by altered peripheral nociceptive response, and then to analyze differential gene and lncRNA expression patterns in the lower thoracic spinal cord on different time courses after BDL operation by using high-throughput RNA sequencing. The differentially expressed genes (DEGs) identified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, followed by clustering analysis, Gene Ontology analysis and pathway analysis. As a result, a total of 2033 lncRNAs were differentially expressed 28d after BDL, in which 1545 probe sets were up-regulated and 488 probe sets were down-regulated, whereas a total of 2800 mRNAs were differentially expressed, in which 1548 probe sets were up-regulated and 1252 probe sets were down-regulated. The RNAseq data of select mRNAs and lncRNAs was validated by RT-qPCR. 28d after BDL, the expressions of lncRNA NONRATT002335 and NONRATT018085 were significantly up-regulated whereas the expression of lncRNA NONRATT025415, NONRATT025388 and NONRATT025409 was significantly down-regulated. 14d after BDL, the expressions of lncRNA NONRATT002335 and NONRATT018085 were significantly up-regulated; the expression of lncRNA NONRATT025415, NONRATT025388 and NONRATT025409 was significantly down-regulated. In conclusion, the present study showed that jaundice accompanied with decreased peripheral nociception involved in the changes of gene and lncRNA expression profiles in spinal cord. These findings extend current understanding of spinal mechanism for obstructive jaundice accompanied by decreased peripheral nociception.

Section: Discussionsupporting

confidence: 93%

Altered expression of differential gene and lncRNA in the lower thoracic spinal cord on different time courses of experimental obstructive jaundice model accompanied with altered peripheral nociception in rats

Liu

et al. 2017

Oncotarget

“…Hyperbilirubinemia is also associated with increased occurrences of postoperative renal failure and hemorrhagic shock 3 4 . Other than extracellular water depletion, defective vascular reactivity, subclinical myocardial dysfunction and systemic endotoxemia, cardiovascular autonomic dysfunction is also involved in cardiovascular instability 5 6 7 8 9 . Our recent study 10 further demonstrated that both sympathetic and vagal components of arterial baroreflex were depressed in jaundiced patients, which may partially explain the increased susceptibility of cardiovascular instability to the above-mentioned perioperative complications.…”

mentioning

confidence: 99%

Bilirubin Modulates Acetylcholine Receptors In Rat Superior Cervical Ganglionic Neurons In a Bidirectional Manner

Zhang

Dong

et al. 2014

Sci Rep

Autonomic dysfunction as a partial contributing factor to cardiovascular instability in jaundiced patients is often associated with increased serum bilirubin levels. Whether increased serum bilirubin levels could directly inhibit sympathetic ganglion transmission by blocking neuronal nicotinic acetylcholine receptors (nAChRs) remains to be elucidated. Conventional patch-clamp recordings were used to study the effect of bilirubin on nAChRs currents from enzymatically dissociated rat superior cervical ganglia (SCG) neurons. The results showed that low concnetrations (0.5 and 2 μM) of bilirubin enhanced the peak ACh-evoked currents, while high concentrations (3 to 5.5 µM) of bilirubin suppressed the currents with an IC50 of 4 ± 0.5 μM. In addition, bilirubin decreased the extent of desensitization of nAChRs in a concentration-dependent manner. This inhibitory effect of bilirubin on nAChRs channel currents was non-competitive and voltage independent. Bilirubin partly improved the inhibitory effect of forskolin on ACh-induced currents without affecting the action of H-89. These data suggest that the dual effects of enhancement and suppression of bilirubin on nAChR function may be ascribed to the action mechanism of positive allosteric modulation and direct blockade. Thus, suppression of sympathetic ganglionic transmission through postganglionic nAChRs inhibition may partially contribute to the adverse cardiovascular effects in jaundiced patients.

“…In OJ patients, the matter turns out completely opposite. Since Green et al described the cardiac injury of OJ firstly in 1986,23 studies afterwards have continuously confirmed that cardiac disfunction is one of the common complications in patients with OJ 24. Experimental studies indicated that effects of bile duct ligation on myocytes including decrease of contraction rates and amplitude leads to cardiac disfunction potentially 25.…”

Section: Discussionmentioning

confidence: 99%

Plasma BNP level combined with surgical Apgar score to predict operative major cardiac adverse events in malignant obstructive jaundice patients

Huang

et al. 2016

Pak J Med Sci

Objective:To investigate the predictive effect of major adverse cardiac events (MACE) in malignant obstructive jaundice (OJ) patients using plasma brain natriuretic peptide (BNP) level and surgical Apgar scoring (SAS) system.Methods:Forty one malignant OJ patients undergoing surgical treatments were studied at a single center. Pre-and postoperative plasma BNP level, total bilirubin (TBil) and data of cardiac function (HR, CVP, CI, LVEF%) were detected, the SAS was calculated during the surgery, the relationship of both plasma BNP level and SAS with MACE after surgery was analyzed.Results:Thirteen patients out of 41 (31.71%) experienced MACE without cardiac death. OJ patients had a higher plasma BNP level than baseline before operation (191.61±105.76 pg/ml VS 175 pg/ml, P<0.05), the cardiac function data was improved (CVP: t=4.761, p=0.000; CI: t=3.539, p=0.001; LVEF%: t=3.632, p=0.001) after the operation. Patients with lower SAS had increasing incidence of MACE after surgery.Conclusion:Malignant OJ patients with higher preoperative BNP level and lower surgical Apgar score were identified at high risk of MACE after surgery.