protective effect of insulin against isoflurane and sevoflurane induced hepatocellular apoptosis

Several studies deducted that inhalational anesthetics induce apoptosis in human cells. Insulin is believed to have an antiapoptotic action so it is widely used as cardioprotective agent against ischemic reperfusion injuries. This study compared the apoptotic effect of inhalational anesthetics and figuring out the antiapoptotic effect of insulin against perioperative induced hepatocellular apoptosis using immune histochemical study of liver biopsy. Eighty [ASA I] patients scheduled for laparoscopic cholecystectomy were randomly allocated into 4 groups [20 patients each]. Two groups were anesthetized using isoflurane and the other two were anesthetized using sevoflurane. The control groups [IC, SC] received normal saline and the insulin groups [II, SI] received glucose, insulin and potassium [GIK] infusion. Infusions were given 2 hours before induction of anesthesia. Liver biopsy was taken before the umbilical port closure. In liver biopsy Caspase 3, 7, 9 and Akt activity were evaluated. Liver function tests were estimated before infusion and one day after surgery. Serum K and blood glucose levels were closely monitored all through the study. The results showed that in the isoflurane groups, the percentage of caspase 3 and 7 positive cases decreased while Akt positive cases increased significantly in II compared to IC respectively [p < 0.05]. In the sevoflurane groups, the percentage of caspase 3 positive cases decreased significantly in SI compared to SC group [p < 0.05]

Role of the endothelial factors: Nitric oxide, substance P and endothelin, in mediating circulatory effects of halothane and isoflurane

Endothelial cells [ECs] contribute to the regulation of blood pressure and blood flow by releasing vasodilators such as nitric oxide [NO], substance P [SP], prostacyclin [PGI [2]] and adrenomedullin, as well as vasoconstrictors including endothelin [ET] and platelet-activating factor [PAF]. Several previous studies have discussed the relation between anaesthetics and the vascular endothelium in vitro only and demonstrated that volatile anaesthetics [halothane and isoflurane] can alter endothelium-dependant vasodilatation in vitro. In vivo studies are scarce in that field. This could be attributed to the radical nature of NO and its very short half-life and involvement of labor-intensive assay and handling of radioactive isotopes. Consequently, determination of the more stable end products of NO, nitrite and nitrate, was used as a measure for NO production. It is the aim of the current study to make use of this technique to ascertain whether NO, as well as SP and ET, is actually involved in the circulatory effects of isoflurane/halothane, in the clinical context. The study was conducted on 40 patients of [ASA classes I and II], scheduled for open abdominal and/or pelvic procedures of minimum 1 hour duration. Reduction of MBP more than 20% of the preoperative level was considered hypotension. Induction in both groups was done by IV fentanyl [2 micro g/ kg], sodium thiopentone [4-7mg/kg] followed by vecuronium [0.1mg/kg] for intubation and long acting muscle relaxation. Anaesthesia was maintaied using 100% oxygen and halothane 0.5-1%, or isoflurane 0.6-1-2%, in groups Land II respectively. Mechanical ventilation was adjusted to maintain normocapnia. Nitrous oxide was omitted and increments of fentanyl and vecuronium were titrated to the patients' needs. Monitoring of arterial blood pressure and heart rate was done every 5 minutes. Reversal was done using prostigmine [0.08mg/kg] and atropine sulphate [0.02mg/kg]. Venous blood samples were collected before induction, 15, 30 and 60 minutes after initiation of anaesthesia [T0, T1, T2, T3], at cessation of anesthesia and fifteen minutes later [T4 and T5]. Plasma endothelin concentration was determined by enzyme immunoassay technique. Plasma substance P was measured by radioimmunoassay. Determination of serum nitrite and nitrate was done by a colorimetric assay. We have succeeded in ascertaining the role of nitric oxide in isoflurane-induced hypotension, but not halothane. The hypotensive effect of isoflurane which is known to be basically related to peripheral vasodilator mechanism may be via its stimulatory effect on vasodilator mediator [NO]. The role of ET and SP could be related to the short-term changes, mediated by the endothelium, in vasomotor tone in response to alterations in shear stress, in face of the significant hypertension that follows cessation of isoflurane anaesthesia

Impact of small dose ephedrine versus priming principle on pharmacodynamics of cistracurium

This study aimed to compare the impact of adding a small dose ephedrine versus priming technique, with a bolus dose, on the onset time, recovery index and clinical duration of cisatracurium. Also, the intubating conditions and hemodynamic changes were evaluated. Forty-five patients were randomly assigned and allocated into three groups of 15 patients each. Induction was achieved in all three groups by fentanyl 1-2 mug/kg and propofol 2 mg/kg. Patients in group A received a bolus dose of 100 mug/kg cisatracurium after induction. Patients in group B were given ephedrine [70 pg/kg] 5 seconds before induction, then 100 mug/kg cisatracurium. Patients in group C were given priming dose 15 mug/kg cisatracurium before induction, followed by 8.5 mug/kg 4 minutes after priming dose. Maintenance was done by NO2/O2, halothane. Neuro-muscular blockade was monitored using TOF- Guard [Organon-Teknika] by recording the acceleration of the thumb resulting from supramaximal stimulation of ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. Anesthesia was induced by fentanyl and propofol and then maintained by 0.870 halothane in fresh gas flow [66% N20 in 33% 02]. In conclusion, both techniques, priming and small dose ephedrine, produced significant reduction in onset time of cisatracurium as compared to using bolus dose. This was more eminent in the priming group, there was a significant prolongation of clinical duration as well and was void of adverse hemodynamic effects