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Background and objectives: A positive effect of insulin-glucose-potassium infusion in severe bupivacaine-induced cardiovascular collapse has been described in vivo. It has been speculated that an antagonistic influence of insulin on sodium channel inhibition, transient outward potassium current, calcium-dependent adenosine triphosphatase or even improved myocardial energetics may be responsible for this effect. Using an isolated heart model, we therefore sought to further elucidate insulin effects in L-bupivacaine-induced myocardial depression. Methods: An isolated rat heart constant-pressure perfused, non-recirculating Langendorff preparation was used. Hearts were exposed to L-bupivacaine 5 μg mL-1 and insulin 10 mIU mL-1. Heart rate, systolic pressure, the first derivative of left ventricular pressure (+dPldt), coronary flow, double product, PR and QRS intervals were recorded. Hearts were freeze-clamped and high-performance liquid chromatography measurement of the total adenine nucleotide pool was performed. Results: L-Bupivacaine led to a significant decrease in heart rate, +dP/dt, systolic pressure, coronary flow and double product, and to an increase in PR and QRS. Insulin exerted a positive inotropic effect, significantly augmenting +dP/dt and systolic pressure in both L-bupivacaine-treated and control hearts. Heart rate, coronary flow, total adenine nucleotides, PR and QRS were not significantly changed by the insulin intervention. Conclusion: Insulin did not have a significant effect on total adenine nucleotides in controls and in L-bupivacaine-treated hearts. However, it does exert a positive inotropic action in bupivacaine-induced myocardial depression. We conclude that the positive effect of insulin application lies in positive inotropic action and not in changes in total adenine nucleotides. [ABSTRACT FROM AUTHOR]

Background and objective: Tissue depletion of adenosine during endotoxaemia has previously been described in the lung. Therapeutic approaches to prevent adenosine depletion and the role of A1 and A2 receptor agonists, however, have not been investigated until now. Methods: In isolated and ventilated rabbit lungs, it was tested whether pretreatment with adenosine A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 10-7 mol, n = 6) or A2 receptor agonist 5′-(N-cyclopropyl)-carboxyamido adenosine (CPCA; -7 mol, n = 6) prior to injection of lipopolysaccharide (LPS) (500 pg mL 1) influenced pulmonary artery pressure (PAP), pulmonary energy content and oedema formation as compared with controls, solely infused with LPS (n = 6). Release rates of adenosine and uric acid were determined by high-performance liquid chromatography. Pulmonary tissue concentrations of high-energy phosphates were measured and the adenine nucleotide pool, adenosine 5′-triphosphate (ATP)/adenosine 5′-diphosphate (ADP) ratio and adenylate energy charge of the pulmonary tissue were calculated. Results: Administration of LPS induced increases in PAP within 2 h up to 20.8 ± 2.9 mmHg (P <0.01). While pretreatment with the A1 agonist merely decelerated pressure increase (13.8 ± 1.1 mmHg, P <0.05), the A2 agonist completely suppressed the pulmonary pressure reaction (9.6 ± 1.0mmHg, P<0.01). Emergence of lung oedema after exclusive injection of LPS up to 12.0 ± 2.9g was absent after A1 (0.6 ± 0.5 g) and A2 (-0.3 ± 0.2 g) agonists. These observations were paralleled by increased adenosine release rates compared with LPS controls (P < 0.05). Moreover, tissue concentrations of ADP, ATP, guanosine 5′-diphosphate, guanosine 5′-triphosphate, nicotinamide-adenine-dinucleotide and creatine phosphate were significantly reduced after LPS. Consequently, the calculated tissue adenine nucleotide pool and the adenylate energy charge increased after adenosine receptor stimulation (P = 0.001). Conclusions: Adenosine A1- and A2-receptor agonists reduced LPS-induced vasoconstriction and oedema formation by maintenance of tissue energy content. Thus, adenosine receptor stimulation, in particular of the A2 receptor, might be beneficial during acute lung injury. [ABSTRACT FROM AUTHOR]

Background: The local anaesthetic prilocaine has a low systemic toxicity mainly because of a high absorption in the lung and a large volume of distribution and thus is associated with a lower risk of neurological or cardiac side-effects. However, the major disadvantage is the formation of methaemoglobin by its metabolite o-toluidine. This prospective observational study was performed to identify factors that are associated with increased prilocaine-induced methaemoglobinaemia. Patients and methods: One Hundred and sixty two patients undergoing major knee surgery under general anaesthesia combined with peripheral nerve blocks (femoral nerve block, combined femoral/sciatic nerve block or lumbar plexus block) received a single bolus injection of 300 or 400 mg prilocaine about 30 mm before surgery via a catheter. The proper placement was verified using nerve stimulation via a stimulating catheter. Three hours after prilocaine injection, venous blood samples were drawn and methaemoglobin levels were measured by standard photometric technique. Data was subjected to a stepwise multiple regression analysis. Results: The mean methaemoglobin for all patients was 2.7% (range: 0.9-15.4%). A higher dose of prilocaine and younger age were the most important predictive factors for higher methaemoglobin formation. Female sex and to a lesser extent the use of high-concentration/low-volume prilocaine also increased methaemoglobin levels. These four factors of the model explain 36% of the total variance. Other investigated factors, including the patient's height, weight, body mass index, the site of catheter insertion, the anaesthetist's judgement concerning the difficulty of catheter placement, duration of catheter placement or an inadvertent puncture of a venous or arterial vessel, had no significant impact on the concentration of methaemoglobin. Conclusion: The use of prilocaine for regional block is safe, since the older patients who might be more susceptible to suffer from clinical symptoms of methaemoglobinaemia usually form less methaemoglobin. However, since prediction of high methaemoglobin levels is difficult, anaesthesiologists performing regional blocks in patients who might be jeopardized by a decreased oxygen transport capacity should avoid high doses of prilocaine. [ABSTRACT FROM AUTHOR]

SummaryAs elevated endothelin-1 (ET-1) levels have been reported in systemic inflammatory diseases, the role of ET-1 as a promoter of inflammatory reactions is currently under investigation. The purpose of this study was to investigate the potential influence of ET-1 on systemic vascular pressure and immune function in terms of blood clearance and organ distribution of injected Escherichia coli in a rabbit model. To enable quantification of the clearance process, defined numbers of exogenous E. coli (108 cfu) were injected intravenously 60 min after starting the infusion of ET-1 (0.2 μg kg-1 min-1; n=9) or after saline infusion (controls, n=9). Parameters monitored were arterial blood pressure, airway pressure, serum lactate concentrations and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were killed, and tissue samples of liver, kidney, spleen and lung were collected for bacterial counts. ET-1 infusion produced an increase in mean arterial pressure (83.9±3.9 mmHg vs. 50.1±4.1 mmHg at 120 min; P< 0.01) associated with higher serum lactate concentrations (12.6±1.3 vs. 5.4±0.3 mg dL-1; P< 0.001) and a delayed bacterial elimination from the blood compared with controls. Furthermore, there was increased colonization of the lungs (3.6±0.5×103 cfu vs. 745±120 cfu; P<0.01), spleen (142.4±45.4×103 cfu vs. 22.7±5.2×103 cfu; P<0.05) and kidney (758±329 vs. 357±151 cfu; NS), reflecting a reduced bacterial killing function. [ABSTRACT FROM AUTHOR]