Effects of levosimendan on myocardial ischaemia-reperfusion injury.

BACKGROUND AND OBJECTIVE: Levosimendan has a cardioprotective action by inducing coronary vasodilatation and preconditioning by opening KATP channels. The aim of this study was to determine whether levosimendan enhances myocardial damage during hypothermic ischaemia and reperfusion in isolated rat hearts. METHODS: Twenty-one male Wistar rats were divided into three groups. After surgical preparation, coronary circulation was started by retrograde aortic perfusion using Krebs-Henseleit buffer solution and lasted 15 min. After perfusion Group 1 (control; n = 7) received no further treatment. In Group 2 (non-treated; n = 7), hearts were arrested with cold cardioplegic solution after perfusion and subjected to 60 min of hypothermic global ischaemia followed by 30 min reperfusion. In Group 3 (levosimendan treated; n = 7), levosimendan was added to the buffer solution during perfusion and the hearts were arrested with cold cardioplegic solution and subjected to 60 min of hypothermic global ischaemia followed by 30 min reperfusion. At the end of the reperfusion period, the hearts were prepared for biochemical assays and for histological analysis. RESULTS: Tissue malondialdehyde levels were significantly lower in the levosimendan-treated group than in the non-treated group (P = 0.019). The tissue Na+-K+ ATPase activity was significantly decreased in the non-treated group than in the levosimendan-treated group (P = 0.027). Tissue myeloperoxidase (MPO) enzyme activity was significantly higher in the non-treated group than in the levosimendan-treated group (P = 0.004). Electron microscopic examination of the hearts showed cardiomyocytic degeneration at the myofibril, mitochondria and sarcoplasmic reticulum in both non-treated and levosimendan-treated groups. The severity of these findings was more extensive in the non-treated group. CONCLUSIONS: Treatment with levosimendan provided better cardioprotection with cold cardioplegic arrest followed by global hypothermic ischaemia in isolated rat hearts.

Diclofenac and metamizol in postoperative analgesia in plastic surgery.

BACKGROUND: Postoperative pain relief after major surgery cannot be achieved with opioids alone in all patients without respiratory depression or other significant drawbacks. Modern medical practice, therefore, dictates the use of alternative analgesic agents as an adjunct or substitute to minimize the deleterious effects and to facilitate an earlier return to work and daily activities. Diclofenac and metamizol inhibit prostaglandin synthesis, thus attenuate the peripheral nociceptive sensitization caused by the surgical trauma. This investigation was conducted to determine the potency of diclofenac compared with metamizol in the control of postoperative pain after various plastic surgical operations under general anesthesia. METHODS: A multiple-dose, randomized, double-blind clinical trial composed of one hundred and sixty-six patients was conducted. Group M patients received 1 g intramuscular metamizol (every 8 hours) and Group D patients received 75 mg intramuscular diclofenac (every 12 hours). Additional analgesia requirements were recorded and meperidine was used as the complementary analgesic when needed. Pain was assessed by visual analogue scores. Platelet count and bleeding time analyses were performed preoperatively and on the first postoperative day. RESULTS: Metamizol decreased the additional analgesia requirement during the 18 hours following surgery. This was also associated with significantly lower pain scores. There was no significant difference between the patients receiving either metamizol or diclofenac in terms of pain scores, additional request for analgesia and frequency of side effects from the 18th until the 48th hour postoperatively. However, the use of diclofenac was associated with reduced side effects, though a reduction in platelet number and prolongation of bleeding time was noted in the majority of the patients receiving diclofenac. CONCLUSIONS: Metamizol is significantly superior to diclofenac for the reduction of postoperative pain after plastic surgery in the first 18 hours after plastic surgery procedures and reduces the need for additional analgesia.

Could adding magnesium as adjuvant to ropivacaine in caudal anaesthesia improve postoperative pain control?

Recently, most studies reported magnesium as a N-methyl-D-aspartate receptor antagonist and its analgesic and perioperative anaesthetic effects have been discussed with central desensitization pathway. We investigated the effects of caudal ropivacaine plus magnesium and compared with ropivacaine alone on postoperative analgesia requirements. After hospital ethic committee's consent, 60 patients (ASA I-II, 2-10 years old) who had lower abdominal or penoscrotal surgery were enrolled in the study. After general anaesthesia induction, caudal blockage was applied. Patients were randomly assigned in two groups. Ropivacaine 0.25% was administered to Group R (n=37), ropivacaine 0.25% plus 50 mg magnesium to Group RM (n=23) in 0.5 ml kg-1 volume. Postoperative analgesia level was recorded at 15 min and 1, 2, 3, 4, 6 h by using Paediatric Objective Pain Scale (POPS) and The Children's Hospital of Eastern Ontoria Pain Scale (CHEOPS). Postoperative motor blocks were evaluated with Modified Bromage Motor Block Scale. According to demographic characteristics, there were no significant differences between the two groups (P>0.05). POPS, CHEOPS, Bromage Motor Scales, analgesia duration and adverse effects were similar in Group R and Group RM. It has been shown that addition of magnesium as an adjuvant agent to local anaesthetics for caudal analgesia has no effect on postoperative pain and analgesic need.

Inhibition of bacterial growth by lignocaine in propofol emulsion.

Contamination of propofol, in an emulsion formulation, has been associated with infective complications. Local anaesthetics,some of which are known to have antibacterial properties, are frequently added to the solution to reduce pain on injection. We examined the growth rates of E. coli, S. aureus, S. epidermidis and P. aeruginosa in propofol with and without lignocaine 0.1%-2% after incubation for 2, 5 and 24 hours at 37 degrees C. Growth of microorganisms in each solution was compared by counting the number of colony forming units (CFU). Propofol supported the growth of all microorganisms. An increase in the number of CFUs was observed in all drug combinations 2, 5 and 24 hours after inoculation except for S. aureus (P<0.05). No difference was found in CFU numbers between 2 and 5 hours for this microorganism. With E. coli, a significant decline in colony counts was observed in mixtures of 1% and 2% lignocaine (P<0.05). With the other microorganisms only 2% lignocaine showed a significant reduction in the number of CFUs (P<0.05). We conclude that lignocaine in recommended clinical doses (0.05%-0.1%) did not exhibit adequate antibacterial activity to prevent infective complications.

Efficacy of tramadol versus meperidine for pain relief and safe recovery after adenotonsillectomy.

BACKGROUND AND OBJECTIVE: Adequate relief of pain after tonsillectomy is a common problem. We compared meperidine and tramadol when given at induction of anaesthesia with respect to their effects on postoperative pain relief and emergence characteristics after adenotonsillectomy in children. METHODS: Fifty children aged 4-7 yr undergoing tonsillectomy were randomly assigned to receive either tramadol 1 mg kg(-1) (n = 25) or meperidine 1 mg kg(-1) (n = 25) before commencement of the surgical procedure. Anaesthesia was induced with propofol (with cis-atracurium for muscle relaxation) and maintained with sevoflurane in oxygen and nitrous oxide. Postoperative pain was scored by a blinded observer using a facial pain scale in the recovery room at 0 (at arrival of the patient in the postoperative care unit) and at 10, 20 and 45 min thereafter. Agitation scores were also assessed by the same observer at 0 min. Heart rate and mean arterial pressure were recorded at regular intervals. The time to recovery to spontaneous respiration and the incidence of postoperative nausea and vomiting were noted. RESULTS: Facial pain scale scores were increased in the tramadol group at 0, 10 and 20 min (P < 0.05). No difference was observed in scores at the 45th min postoperation. Agitation scores were higher in the tramadol group than in the meperidine group. No statistical difference was found between the two groups. Heart rates and mean arterial pressures were similar in both groups. The time to recovery to spontaneous respiration was delayed with meperidine compared with tramadol (P < 0.05). The incidence of nausea and vomiting was not statistically different between groups. CONCLUSIONS: Meperidine was more effective for pain relief and provides better emergence characteristics than tramadol after tonsillectomy in children.

A possible central antinociceptive effect of dipyrone in mice.

The antinociceptive effect of dipyrone, a nonsteroidal and inflammatory drug, was studied in a series of experiment employing tail-flick and hot-place models and the abdominal constrictor test. The drug was given via intracerebroventricular (i.c.v.), intrathecal (i.t.) or subcutaneous (s.c.) routes. Dipyrone exhibited no analgesic activity in the tail-flick and hotplate tests while it inhibited the number of stretches in a dose-dependent manner. The antinociceptive effect of dipyrone administered by the i.c.v. and i.t. routes was almost complete reversed by naloxone treatment. The same procedure attenuated but not completely inhibited the dipyrone action induced by s.c. administration. Histopathological examination revealed that i.t. dipyrone application produces no significant lesion in the spinal cord. The results suggest that dipyrone may exert a central antinociceptive action reversed by naloxone.

The effect of aprotinin on ischemia-reperfusion injury in the rabbit kidney.

Tissue subjected to a period of ischemia undergoes functional and morphological damage that increases during the reperfusion phase. In this study, the protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit unilateral renal ischemia-reperfusion (I/R) model. New Zealand rabbits, weighing 1.5-2 kg, were randomized to receive either aprotinin 30.000 KIU x kg(-1) and 10.000 KIU x kg(-1) x h(-1) i.v. infusion (group I, n= 7) or equivalent volumes of 0.09% sodium chloride (SF) (group II, control, n= 7) i.v. 15 minutes before a 45 minutes interruption of left renal artery blood flow and then 45 minutes of reperfusion. Blood samples were obtained before and after the ischemia-reperfusion period for measurement of nitric oxide serum (NO) levels with the nitrite/nitrate colorimetric method. Histological changes were evaluated by quantitative measurements using a numerical score (0-4) and immunohistochemical analysis of inducible nitric oxide synthase (iNOS) expression was determined. A Wilcoxon W -test was used for statistical analysis of biochemical measurements and mean values were expressed as +/-sd. Histological examination revealed the distinctive pattern of ischemic renal tissue injury with obvious signs of epithelial necrosis. The intensity of epithelial necrosis was more extensive in the SF group. Immunohistochemical analysis showed that there was severe immunostaining in the tubular epithelium in both cortical and medullary regions and iNOS expression was more intense in SF-only cases. The staining results for aprotinin cases did not differ much from the non-ischemic kidney. Biochemical analysis revealed an increase in serum NO levels in both groups (P< 0.05), but this was more evident in the SF group (mean NO levels were 38.63 +/- 19.03 micromol x L(-1) in group I, 50.63 +/- 24.28 micromol x L(-1) in group II). No statistically important difference was observed between the two groups. These results suggest that aprotinin may be beneficial in the prevention of systemic inflammation after transient renal ischemia.