Comparison of myotoxic effects of levobupivacaine, bupivacaine and ropivacaine: apoptotic activity and acute effect on pro-inflammatory cytokines.

We investigated the myotoxic effects of bupivacaine, ropivacaine and levobupivacaine on rat skeletal muscle and compared its apoptotic activity and acute effects on pro-nflammatory cytokines. We divided 40 Wistar albino rats into four equal groups. Rats were injected intramuscularly with 0.5% bupivacaine (group B), 0.5% ropivacaine (group R), 0.5% levobupivacaine (group L) or 0.9% normal saline (group SF). Animals were sacrificed on the second day after the injection. TNF-α, IL-1 and IL-6 levels were examined in muscle tissue using immunohistochemistry and immunofluorescence. Apoptotic cells were visualized by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. We found that levobupivacaine caused the lowest TNF-α, IL-1 and IL-6 expression levels, while the bupivacaine group caused the highest level compared to the other two agents. The greatest number of apoptotic cells was found in the bupivacaine group. Bupivacaine was more myotoxic than other anesthetic agents and increased apoptosis. The number of TUNEL positive apoptotic cells was lowest in the SF group. The greatest IL-1 immunoreactivity was found in the bupivacaine group. Bupivacaine and ropivacaine produced greater IL-6 expression than the SF group. Bupivacaine and ropivacaine caused greater TNF-α expression than the SF group, whereas the immunoreactivity of TNF-α was similar in the bupivacaine and ropivacaine groups.

The effect of levosimendan combined with 20% lipid emulsion treatment on survival from bupivacaine induced toxicity in experiment.

BACKGROUND: Recent reports demonstrated that levosimendan improved post-resuscitation myocardial function in rat and pig models. MATERIALS AND METHODS: Rabbits were randomized into 4 groups as 12 rabbits in each group. Bupivacaine 10 mg/kg was injected as an intravenous bolus to all groups. Basic life support was performed by mechanical ventilation and manual external chest compressions. After 1 min, animals in the group 1 received 1.5 ml/ kg saline 0.9% solution, and animals in the groups 2 and 4 received 5 ml/kg 20% lipid emulsion for 1 min through the ear vein followed by continuous infusion at 0.25 ml/kg/min. Three additional boluses of 1.5 ml/ kg lipid emulsion were repeated at 5-min intervals. The group 3 received fluid resuscitation plus levosimendan (3 µg/kg/min) 1 min after asystole and the group 4 received both levosimendan and lipid emulsion treatment. Return of spontaneous circulation and hemodynamic metrics were obtained in 20 minutes. RESULTS: The number of rabbits that survived after cardiac resuscitation was lower in the Groups 1 (0%) and 3 (33.3%) than in the Group 4 (91.7%) with a statistically significant difference (p < 0.001). The number of rabbits that survived resuscitation was higher in the Group 4 than in the Group 2 (66.7%), though not with a statistically significant difference (p = 0.317). The median duration of cardiac arrest in the Group 4 was significantly shorter than that in the other three groups (p < 0.001). CONCLUSIONS: In this rabbit model of bupivacaine-induced cardiac arrest, resuscitation with combined iv lipid emulsion and levosimendan was more efficacious than lipid alone (Tab. 3, Ref. 24).

Adding magnesium to levobupivacaine for axillary brachial plexus block in arteriovenous fistule surgery.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare the effect of adding magnesium to levobupivacaine on sensory and motor block onset and duration for axillary brachial plexus block in chronic renal failure (CRF) patients scheduled for arteriovenous fistule surgery (AVFS). METHODS: 80 patients, ASA III, aged 30 to 70 years, randomized and divided into 4 groups: Group I (n = 20) received total 41 ml of levobupivacaine 0.5 % + 1 ml NaCl 0.9 % mixture; Group II (n = 20) received 41 ml of levobupivacaine 0.5 % + 1 ml magnesium sulfate (150 mg) mixture; Group III (n = 20) received total 41 ml of levobupivacaine 0.25 % + 1 ml NaCl 0.9 % mixture; and Group IV (n = 20) received total 41 ml of levobupivacaine 0.25 % + 1 ml magnesium sulfate (150 mg) mixture by perineural axillary brachial plexus block. All patients were evaluated with regard to motor and sensory blocks. Motor and sensory block ending times were recorded. RESULTS: Motor and sensory block onset times were statistically decreased in Group II when compared with Goup I, and also the motor and sensory block durations were increased in Group II when compared with Goup I (p < 0.05). Sensory block onset times were statistically decreased in Group IV when compared with Goup III (p < 0.05). CONCLUSIONS: We conclude that by its decreasing effect on local anesthetic dose, magnesium may reduce the side effects due to high local anesthetic doses in patients with CRF (Tab. 1, Ref. 11).

The effect of different doses of flumazenil on acetaminophen toxicity in rats.

BACKGROUND: Acetaminophen is an analgesic drug that is used safely in therapeutic doses. At high doses, it causes hepatotoxicity, resulting in hepatic necrosis. Some medications and methods are available for treatment of acetaminophen overdose. However, results are inconsistent, and sufficient outcomes cannot always be obtained. OBJECTIVE: The mechanism of action of acetaminophen has not been fully understood. It has been suggested that it exerts its effects on GABA receptors. Flumazenil has been experimentally proven to produce an antagonism on acetaminophen's analgesic effect.The purpose of this study was to determine whether flumazenil antagonized the toxic effects of acetaminophen overdose in rats. METHODS: A total of 49 Wistar albino rats weighing between 250 - 350 g were used in the study. Nine rats were examined for a preliminary study, and the other rats were randomly divided into five groups with eight subjects in each. CONTROL GROUP: Saline; Acetaminophen group: 3 g/kg acetaminophen; Experimental Group F1: 3 g/kg acetaminophen + 0.1 mg/kg flumazenil; Experimental group F2: 3 g/kg acetaminophen + 1 mg/kg flumazenil; Experimental group F3: 3 g/kg acetaminophen + 10 mg/kg flumazenil. Acetaminophen was administered in a 3 ml saline solution by way of gastric catheter. Flumazenil was administered by way of intraperitoneal injections. Serum levels of acetaminophen, AST, ALT, LDH, ALP and bilirubin were recorded over a 24-hour period. RESULTS: Serum acetaminophen levels were similar between the groups. The AST, ALT, ALP, LDH, total bilirubin and direct bilirubin levels of Group A were significantly higher compared with the Group C, Group F1, Group F2 and Group F3. There was not a statistically significant difference in the AST, ALT, ALP, LDH, total bilirubin or direct bilirubin levels of the flumazenil-administered groups. CONCLUSION: Flumazenil's prevention of the acetaminophen-induced increase in liver enzymes is promising. There is some indication that flumazenil could be used in treatment of acetaminophen intoxication (Tab. 2, Ref. 25).

The effects of intraoperative infusion of dexmedetomidine on early renal function after percutaneous nephrolithotomy.

BACKGROUND: Percutaneous nephrolithotomy (PCNL) may interfere with renal function because of continuous fluid irrigation and compression. The aim of this study was to evaluate the effects of an intraoperative infusion of dexmedetomidine on renal function in patients undergoing PCNL. METHODS: This study included 40 patients between the ages of 18 and 65 years who underwent PCNL. After induction of anesthesia, we administered 100 ml of normal saline to the patients in the control group (n=20) and 1 mcg/kg dexmedetomidine in 100 ml of normal saline to the patients in the dexmedetomidine group (n=20) over 10 min. Throughout the surgery, 1 mcg/kg/h dexmedetomidine and 1 ml/kg/h normal saline infusions were given to the dexmedetomidine and control groups, respectively. Renal function, electrolytes, serum levels of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were analyzed after induction and post-operatively at 2, 8 and 24 h. Renin levels and blood gas analyses were performed after induction and before extubation. RESULTS: No statistically significant differences were found between the two groups with regard to renal function, creatinine clearance (CrCl), NGAL, cystatin C and serum electrolyte levels at 0, 2, 8 and 24 h post-operatively. End-surgery renin levels in the dexmedetomidine group were significantly lower than the baseline levels in the control group. CONCLUSION: In PCNL, an intraoperative infusion of dexmedetomidine was not found to have beneficial effects on CrCl, NGAL or cystatin C levels early after the procedure; however, it reduced renin levels.

Characteristics and prognosis of breast cancer in younger women.

PURPOSE: Women under 40 years of age comprise a small proportion of patients with breast cancer. Clinical and pathological features of the disease in these patients are different from those in older patients with this type of cancer. In the present study we investigated the clinicopathological characteristics and prognostic factors in young patients with breast cancer. METHODS: We retrospectively reviewed the medical records of 249 consecutive breast cancer patients who were admitted to our department between August 2001 and December 2005. Clinicopathological features were determined both in patients under and over 40 years of age. RESULTS: 106 (42.5%) patients were under and 143 (57.5%) were over 40 years. The mean age was 35.2 years for those under 40 years and 54 for those older than 40 years. At diagnosis, 10.4% of the patients in the younger age group and 7.0% in the older age group had metastasis (p=0.500). Patients in the younger age group exhibited higher estrogen receptor (ER) negativity (48.1 vs. 37.1%) (p=0.425) and a higher percentage of family history of breast cancer (4.7 vs. 2.8%) (p=0.651). Breast cancer in younger women was more frequently associated with other poor prognostic factors such as perineural and/or lymphovascular invasion. The 5-year overall survival was 6.3% for the younger patients and 22.2% for the older ones (p=0.004). CONCLUSION: This study demonstrates that breast cancer in younger patients has significantly more poor prognostic features compared to older ones.