Neurological and emotional sequelae of exposure to ethylene oxide

Subjects were 66 traumatic brain-injured (TBI) versus 22 neurotoxic-injured individuals (due to ethylene oxide - ETO). Among significant findings were higher cognitive functioning for the TBI group for FSIQ, VIQ and PIQ; elevated scores on MMPI scales 1, 2, 3 and 8 for both groups, and elevated anxiety scores on the MAACL for the ETO group relative to the TBI group. Results indicate a more severe impact of ETO exposure in the areas of intellectual functioning and anxiety.     

Xenon improves recovery from myocardial stunning in chronically instrumented dogs

In this study we tested the hypothesis that inhalational administration of xenon improves recovery from myocardial stunning. Ten dogs were chronically instrumented for measurement of heart rate; left atrial, aortic, and left ventricular pressure; coronary blood-flow velocity; and myocardial wall-thickening fraction. Regional myocardial blood flow was determined with fluorescent microspheres. Catecholamine plasma levels were measured by high-performance liquid chromatography. An occluder around the left anterior descending artery (LAD) allowed the induction of a reversible LAD ischemia. Animals underwent 2 experimental conditions in a randomized crossover fashion on separate days: (a) 10 min of LAD occlusion under fentanyl (25 microg. kg(-1). h(-1)) and midazolam (0.6 mg. kg(-1). h(-1)) (control) and (b) a second ischemic episode under the same basal anesthesia with concomitant inhalational administration of 75 +/- 1 vol% xenon (intervention). Anesthesia was induced 35 min before LAD occlusion and was discontinued after 20 min of reperfusion. Dogs receiving xenon showed a significantly better recovery of wall-thickening fraction up to 12 h after ischemia. The increase in plasma epinephrine during emergence from anesthesia and in the early reperfusion period was significantly attenuated in the xenon group. There were no differences between groups concerning global hemodynamics, blood-flow velocity, or regional myocardial blood flow. In conclusion, inhalational administration of 75 vol% xenon improves recovery from myocardial stunning in chronically instrumented dogs under fentanyl/midazolam anesthesia.     

Hemin, inducer of heme-oxygenase 1, improves functional recovery from myocardial stunning in conscious dogs

OBJECTIVE: To examine the effects of pretreatment with hemin, an inducer of the potential antioxidative enzyme heme-oxygenase 1 (HO-1) or heat-shock protein 32, on myocardial stunning. DESIGN: Randomized animal study. SETTING: Animal laboratory of a university hospital. PARTICIPANTS: Chronically instrumented mongrel dogs (n = 44). INTERVENTIONS: Dogs underwent chronic instrumentation for measurement of hemodynamics and myocardial wall thickening fraction (WTF). Experiments with 12 dogs were performed on separate days in a crossover fashion: (1) 10 minutes of left anterior descending (LAD) coronary artery occlusion after application of hemin (9 mg/kg/d) for 1 week and (2) 10 minutes of LAD coronary artery occlusion without hemin pretreatment. In control experiments (n = 32), the reversible induction of HO-1, using gel electrophoresis and Western blotting, was determined. MEASUREMENTS AND MAIN RESULTS: WTF was measured as a baseline value before hemin administration and at predetermined time points until complete recovery from stunning. LAD artery occlusion caused a significant reduction in the WTF in the LAD-perfused area with and without hemin, without significant hemodynamic changes. At all time points, after 1 minute of reperfusion, the WTF as percentage of baseline values was significantly higher after hemin pretreatment (p < 0.05). Baseline WTF values were reached after 24 hours with and after >48 hours without hemin pretreatment (p < 0.05). CONCLUSION: Hemin pretreatment attenuates myocardial stunning in conscious dogs.     

Naloxone improves functional recovery of myocardial stunning in conscious dogs through its action on the central nervous system

This study tests the hypothesis that naloxone, but not its quarternarysalt, naloxone methiodide (which does not enter the centralnervous system), improves recovery from myocardial stunningin conscious dogs. Twenty dogs were chronically instrumentedfor measurement of heart rate, left atrial, aortic and leftventricular pressure (LVP), LV dP•dt_max^–1 and myocardialwall thickening fraction (WTF). Regional myocardial blood flowwas determined with coloured microspheres. Occluder around theleft anterior descending artery (LAD) allowed induction of reversibleLAD ischaemia. Each of the 20 dogs underwent two LAD ischaemicchallenges. Experiments (performed on separate days, in crossoverfashion) were: (i) 10 min of LAD occlusion after applicationof naloxone 63 µg kg^–1 or naloxone methiodide 63µg kg^–1 and (ii) occlusion without naloxone or naloxonemethiodide. WTF was measured at baseline and until completerecovery occurred. LAD ischaemia significantly reduced LAD WTFwith (mean (SD) 54 (15)% lower than baseline) and without naloxone(55 (16)% lower than baseline), without significant haemodynamicdifferences. Between 1 to 30 min of reperfusion, WTF was significantlyhigher with naloxone (P<0.05). There was no difference inWTF with or without naloxone methiodide. We conclude that naloxoneimproved recovery from myocardial stunning in conscious dogs,and that this was centrally mediated. Br J Anaesth 2001; 86: 545–9     

Naloxone prevents increased atrial natriuretic peptide release during regional myocardial ischaemia and stunning in awake dogs

Background. Atrial natriuretic peptide (ANP) release is increasedin patients with ischaemic left ventricular dysfunction. A beneficialeffect of naloxone on recovery from myocardial stunning wasshown previously. The aim of this study was to investigate theeffects of naloxone on ANP release during regional myocardialischaemia and stunning in awake dogs. Methods. Ten dogs were chronically instrumented for measurementof heart rate, left atrial, aortic, and left ventricular pressure(LVP), LV dP·dt_max/min^–1, and myocardial wall-thickeningfraction. An occluder around the left anterior descending artery(LAD) allowed induction of reversible ischaemia in the LAD-perfusedmyocardium. Each dog underwent two ischaemic episodes (randomizedcrossover fashion; separate days): 10 min of LAD occlusion (1)after application of naloxone (63 µg kg^–1), and(2) without naloxone. ANP levels were measured at baseline (BL)and at predetermined time points until complete recovery ofmyocardial stunning occurred. Results. LAD ischaemia-induced release of ANP (peak level: 182(30) vs 27 (7) pg ml^–1 BL) only in the control group withoutnaloxone. Between 1 and 180 min of reperfusion, ANP levels weresignificantly higher only in the control group (P<0.05). Conclusion. Pre-ischaemic application of naloxone prevents thisischaemia-induced ANP-release in conscious dogs. Br J Anaesth 2002; 88: 87–93     

Studies on a case of HHH-syndrome (hyperammonemia, hyperornithinemia, homocitrullinuria)

A patient with the hyperornithinemia, hyperammonemia, homocitrullinuria syndrome is described. This patient represents the 12th documented case of this rare, presumably autosomal recessive condition. Increased levels of ammonia, ornithine and homocitrulline were demonstrated in blood and cerebrospinal fluid. The blood ammonia concentration could be lowered by supplementation of the diet with low doses of arginine. High doses of arginine precipitated seizures, although plasma levels of arginine and ornithine were not altered. The uptake of ornithine by the particulate fraction of the patient's fibroblasts was lower than that of controls, but still measurable. It is suggested that HHH patients have a partial impairment of the uptake of ornithine by mitochondria.     

新缩瞳剂包公藤甲素人工合成研究

包公藤甲素是从包公藤(Erycibe obtusifolia Benth.)茎中提得的一个新莨菪烷生物碱,具有强烈的缩瞳作用,临床用于治疗青光眼。本文报道用合成的6β-乙酰氧基托品酮为原料,经卤代、水解、还原和N-去甲基化等反应合成包甲素(8)。经光谱测定证实8与天然包甲素的结构完全一致。合成品系外消旋体,其作用机理与天然品相同,而强度则减半。