D. Obal

Effect of sevoflurane preconditioning on ischaemia/reperfusion injury in the rat kidney in vivo

Background and objective: Whereas the protective effect of anaesthetic and ischaemic preconditioning has been described for several organs, it is uncertain whether this mechanism is also effective in the kidney. We compared the effect of preconditioning with sevoflurane and preconditioning with short episodes of ischaemia on renal ischaemia/reperfusion injury in the rat in vivo. Methods: Fourteen days after right‐sided nephrectomy, anaesthetized male Wistar rats were randomly assigned to a sham‐operated group (no arterial occlusion, n = 5) or underwent 45 min of left renal artery occlusion (control group, n = 9) followed by 3 days of reperfusion. Two further experimental groups of animals were preconditioned prior to ischaemia either by administering 1 MAC sevoflurane for 15 min followed by 10 min of washout (sevoflurane group, n = 10) or by subjecting the animals to three short episodes of renal ischaemia (ischaemia‐preconditioned group, n = 8). Blood creatinine was measured during reperfusion and morphological damage was assessed by histological examination. Results: Baseline creatinine values were similar in all four groups (0.7 ± 0.2 mg dL−1; mean ± SD) and remained unchanged in the sham‐operated animals after 3 days (0.8 ± 0.2 mg dL−1). Creatinine levels increased in the ischaemic preconditioning group (3.3 ± 1.2 mg dL−1) and sevoflurane preconditioning group (4.0 ± 1.1 mg dL−1) compared to the control group (1.6 ± 0.6 mg dL−1). Morphological damage was less severe in the control group, i.e. in animals without preconditioning, than in both preconditioning groups. Conclusion: Neither sevoflurane nor ischaemic preconditioning preserves renal function or attenuates cell damage in the rat in vivo.

The effect of aminophylline on loss of consciousness, bispectral index, propofol requirement, and minimum alveolar concentration of desflurane in volunteers.

BACKGROUND: Adenosine is a soporific neuromodulator; aminophylline, which is clinically used as a bronchodilator, antagonizes the action of adenosine in the central nervous system. Thus, we tested the hypothesis that aminophylline delays loss of consciousness (LOC) and speeds recovery of consciousness (ROC) with propofol anesthesia, and that aminophylline increases the minimum alveolar concentration (MAC) of desflurane. METHODS: In this double-blind crossover study, volunteers were randomized to either aminophylline or saline on different days. Aminophylline 6 mg/kg was given IV, followed by 1.5 mg · kg−1 · h−1 throughout the study day. After 1 h of aminophylline or saline administration, propofol 200 mg was given at a rate of 20 mg/min. The bispectral index was continuously monitored, as were times to LOC and ROC. After recovery from propofol, general anesthesia was induced with sevoflurane and subsequently maintained with desflurane. The Dixon “up-and-down” method was used to determine MAC in each volunteer after repeated tetanic electrical stimulation. RESULTS: Eight volunteers completed both study days. Time to LOC was prolonged by aminophylline compared with saline (mean ± sd) (7.7 ± 2.03 min vs 5.1 ± 0.75 s, respectively, P = 0.011). The total propofol dose at LOC was larger with aminophylline (2.2 ± 0.9 vs 1.4 ± 0.4 mg/kg, P = 0.01), and the time to ROC was shorter (6.18 ± 3.96 vs 12.2 ± 4.73 min, P = 0.035). The minimum bispectral index was greater with aminophylline (51 ± 15 vs 38 ± 9, P = 0.034). There was no difference in MAC. CONCLUSION: Aminophylline decreases the sedative effects of propofol but does not affect MAC of desflurane as determined by tetanic electrical stimulation.

Haemodynamic changes during halothane, sevoflurane and desflurane anaesthesia in dogs before and after the induction of severe heart failure

Background and objective: The effects of desflurane and sevoflurane on the failing myocardium are still uncertain. We investigated the effects of different concentrations of sevoflurane, desflurane and halothane in dogs with pacing induced chronic heart failure. Methods: Global (left ventricular pressure, left ventricular dP/dt, Konigsbergtransducer) and regional myocardial function (systolic segment length shortening, ultrasonic crystals) were measured in chronically instrumented dogs with tachycardia induced severe congestive heart failure. Measurements were performed in healthy dogs and after induction of heart failure in the awake state and during anaesthesia with 0.75, 1.0, 1.25 and 1.75 minimum alveolar concentration (MAC) of halothane, sevoflurane or desflurane. Results: The anaesthetics reduced dP/dtmax in a dose-dependent manner in healthy dogs (dP/dtmax decreased to 43-53% of awake values at 1.75 MAC). Chronic rapid left ventricular pacing increased heart rate and left ventricular end-diastolic pressure and decreased mean arterial pressure, left ventricular systolic pressure and dP/dtmax. The reduction in contractility was similar in the failing myocardium (to 41-50% of awake values at 1.75 MAC). Segmental shortening was reduced during anaesthesia by 50-62% after pacing compared with 22-44% in normal hearts. While there were similar effects of the different anaesthetics on diastolic function in healthy dogs, after induction of heart failure a more pronounced increase of the time constant of isovolumic relaxation and a greater decrease of dP/dtmin was observed with sevoflurane than with desflurane, indicating a stronger depression of diastolic function. Conclusions: While the negative inotropic effects of sevoflurane and desflurane were similar in normal and in the failing myocardium in vivo, desflurane led to a better preservation of diastolic function in the failing myocardium.

Influence of the angiotensin II AT1 receptor antagonist irbesartan on ischemia/reperfusion injury in the dog heart

Abstract The aim of the present study was to investigate whether the non-peptide angiotensin II type 1 (AT1) receptor antagonist irbesartan (SR 47436, BMS 186295, 2-n-butyl-3[2‘-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]-1,3-diaza-spiro[4,4]non-1-en-4-one) has myocardial protective effects during regional myocardial ischemia/reperfusion in vivo. Eighteen anesthetized open-chest dogs were instrumented for measurement of left ventricular and aortic pressure (tip manometer and pressure transducer, respectively), and coronary flow (ultrasonic flowprobes). Regional myocardial function was assessed by Doppler displacement transducers as systolic wall thickening (sWT) in the antero-apical and the postero-basal wall. The animals underwent 1 h of left anterior descending coronary artery (LAD) occlusion and subsequent reperfusion for 3 hours. Irbesartan (10 mg kg−1, n=9) or the vehicle (KOH, control, n=9) was injected intravenously 30 min before LAD occlusion. Regional myocardial blood flow (RMBF) was measured after irbesartan injection and at 30 min LAD occlusion using colored microspheres. Infarct size was determined by triphenyltetrazolium chloride staining after 3 h of reperfusion. There was no recovery of sWT in the LAD perfused area in both groups at the end of the experiments (systolic bulging, −15.1±6.1% of baseline (irbesartan) vs. −12.3±3.0% (control), mean±SEM). Irbesartan led to an increase in RMBF in normal myocardium (2.47±0.40 vs. 1.35±0.28 ml min−1 g−1, P<0.05), and also to an increase in collateral blood flow to the ischemic area (0.27±0.04 vs. 0.17±0.02 ml min−1 g−1, P=<0.05). Infarct size (percent of area at risk) was 24.8±3.2% in the treatment group compared with 26.9±4.8% in the control group (P=0.72). These results indicate that a blockade of angiotensin II AT1 receptors with irbesartan before coronary artery occlusion led to an increase in RMBF, but did not result in a significant reduction of myocardial infarct size.

Hydrochloric acid-induced lung injury: effects of early partial liquid ventilation on survival rate, gas exchange, and pulmonary neutrophil accumulation.

Objective Partial liquid ventilation can improve respiratory functions in acid-induced lung injury. We studied the effects of the interval between induction of injury and initiation of partial liquid ventilation on survival, gas exchange, and pulmonary neutrophil accumulation.Material and methods Anesthetized rats were randomly assigned to one of five groups (n = 6 per group). Group 1 served as the control group, in the other groups an extended lung injury was induced by intratracheal instillation of hydrochloric acid. Whereas lungs of group 2 were gas-ventilated, group 3 received an early partial liquid ventilation (5xa0min after acid instillation) and group 4 a delayed partial liquid ventilation (30xa0min after acid instillation, 5xa0ml/kg perfluorocarbon). Group 5 received an additional continuous perfluorocarbon application of 5xa0ml·kg-1·h-1 (30xa0min after acid instillation). Blood gases were measured with an intravascular blood gas sensor.Results Acid instillation resulted in a marked decrease in PO2-values within 30xa0min (from 481±37xa0mmHg to 128±71xa0mmHg, FiO2 1.0). Survival rate of the study period (12xa0h) was higher with early partial liquid ventilation. We observed no differences between groups in peak PO2-values during treatment. Histopathological examination, however, showed less pulmonary neutrophil accumulation in lungs of the early partial liquid ventilation group when compared to the delayed partial liquid ventilation group.Conclusions Our results suggest that early partial liquid ventilation increases survival after extended acid-induced lung injury. While effects on arterial oxygenation appear not to predict acute survival we observed less intrapulmonary neutrophil accumulation with early partial liquid ventilation.

Partial liquid ventilation in acute salt water-induced lung injury

Background and objectives: Salt‐water aspiration results in pulmonary oedema and hypoxia. We tested the hypothesis that partial liquid ventilation has beneficial effects on gas exchange and rate of survival in acute and extended salt water‐induced lung injury. Methods: Anaesthetized, ventilated rats (tidal volume 6 mL kg−1, PEEP 5 cmH2O) received a tracheal salt‐water instillation (3%, 8 mL kg−1 body weight) and were randomly assigned to three groups (n = 10 per group). While lungs of Group 1 were gas‐ventilated, lungs of Group 2 received a single perfluorocarbon instillation (30 min after the injury, 5 mL kg−1 perfluorocarbon) and lungs of Group 3 received an additional continuous perfluorocarbon application into the treachea (5 mL kg−1 h−1). Arterial blood gases were measured with an intravascular blood gas sensor. Results: Salt‐water instillation resulted in a marked decrease in PaO2 values within 30 min (from 432 ± 65 to 83 ± 40 mmHg, FiO2 = 1.0, P < 0.01). Arterial oxygenation improved in all three groups irrespective of treatment. We observed no significant differences between groups in peak PaO2 and PaCO2 values. Conclusions: Our results suggest that partial liquid ventilation has no additional beneficial effects on gas exchange after life‐threatening salt water‐induced lung injury when compared to conventional gas ventilation with positive end‐expiratory pressure.