Morphine Enhances Pharmacological Preconditioning by Isoflurane: Role of Mitochondrial KATP Channels and Opioid Receptors

Background: Adenosine triphosphate-regulated potassium channels mediate protection against myocardial infarction produced by volatile anesthetics and opioids. We tested the hypothesis that morphine enhances the protective effect of isoflurane by activating mitochondrial adenosine triphosphate-regulated potassium channels and opioid receptors.

Methods: Barbiturate-anesthetized rats (n = 131) were instrumented for measurement of hemodynamics and subjected to a 30 min coronary artery occlusion followed by 2 h of reperfusion. Myocardial infarct size was determined using triphenyltetrazolium staining. Rats were randomly assigned to receive 0.9% saline, isoflurane (0.5 and 1.0 minimum alveolar concentration [MAC]), morphine (0.1 and 0.3 mg/kg), or morphine (0.3 mg/kg) plus isoflurane (1.0 MAC). Isoflurane was administered for 30 min and discontinued 15 min before coronary occlusion. In eight additional groups of experiments, rats received 5-hydroxydecanoic acid (5-HD; 10 mg/kg) or naloxone (6 mg/kg) in the presence or absence of isoflurane, morphine, and morphine plus isoflurane.

Results: Isoflurane (1.0 MAC) and morphine (0.3 mg/kg) reduced infarct size (41 +/- 3%; n = 13 and 38 +/- 2% of the area at risk; n = 10, respectively) as compared to control experiments (59 +/- 2%; n = 10). Morphine plus isoflurane further decreased infarct size to 26 +/- 3% (n = 11). 5-HD and naloxone alone did not affect infarct size, but abolished cardioprotection produced by isoflurane, morphine, and morphine plus isoflurane.     

The value of intranasal surgery in assuring the success of a conjunctivodacryocystorhinostomy

Conjunctivodacryocystorhinostomy is a much maligned procedure, and there are widely varying opinions about its efficacy and long-term success. We present our modification of the procedure used in 38 eyes of 29 patients over 10 years, with an average follow-up of 2.5 years, which has resulted in a very high rate of success.     

Pharmacokinetics and pharmacodynamics of vecuronium and pancuronium in anesthetized children

The pharmacokinetics and pharmacodynamics of vecuronium and pancuronium were determined in 12 children (3-6 yr) undergoing minor surgery under 60% nitrous oxide, 1 MAC halothane anesthesia. When the level of anesthesia and the electromyograph (EMG) recording of the adductor pollicis were stable, an intravenous bolus of vecuronium (100 micrograms/kg) or pancuronium (100 micrograms/kg) was administered. Plasma concentrations of the two muscle relaxants were determined for 6 hr after the administration by means of a fluorimetric assay followed by a thin layer chromatography. Plasma concentrations of vecuronium and pancuronium declined biexponentially in children and no metabolites could be detected in plasma. The elimination half-lives of vecuronium and pancuronium did not differ significantly. The volume of distribution at steady state (Vdss) was greater (P less than 0.05) after vecuronium (320 +/- 181 ml/kg; mean +/- SD) than after pancuronium (203 +/- 36 ml/kg). Plasma clearance of vecuronium (2.8 +/- 0.9 ml X min-1 X kg-1) was greater than that of pancuronium (1.7 +/- 0.2 ml X min-1 X kg-1; P less than 0.05). Plasma concentrations measured at 10%, 50%, or 90% recovery of the EMG response did not differ significantly for vecuronium and pancuronium. Thus the shorter duration of action of vecuronium is probably due to its greater apparent volume of distribution, as well as to its higher plasma clearance. Thus although the elimination half-lives are comparable, the plasma disappearance of vecuronium is more rapid than that of pancuronium.     

Dexmedetomidine Produces Similar Alterations in the Determinants of Left Ventricular Afterload in Conscious Dogs before and after the Development of Pacing-induced Cardiomyopathy

Background: The authors tested the hypothesis that intravenous dexmedetomidine produces alterations in left ventricular (LV) afterload that are deleterious to cardiac performance in conscious dogs with pacing-induced cardiomyopathy.

Methods: Dogs (n = 8) were fitted with instruments for long-term measurement of LV and aortic blood pressure, aortic blood flow, and subendocardial segment length and received dexmedetomidine (1.25, 2.5, and 5 [micro sign]g/kg) in a cumulative manner before and after 19 +/- 3 (mean +/- SEM) days of rapid LV pacing. LV afterload was measured with aortic input impedance [Zin ([Greek small letter omega]) and quantified with a three-element Windkessel model. Hemodynamics and Zin ([Greek small letter omega]) were assessed under control conditions and 5 and 60 min after administration of each dose.

Results: Dexmedetomidine caused early and late decreases in heart rate, the maximum rate of increase of LV pressure, mean aortic blood flow, and stroke volume in dogs before and after pacing. Dexmedetomidine caused similar early increases in total arterial resistance and decreases in total arterial compliance in dogs before and after pacing. Early dexmedetomidine-induced increases in resistance and decreases in compliance caused similar reductions in mean aortic blood flow in cardiomyopathic compared with healthy dogs. Resistance and compliance returned to control values, and characteristic aortic impedance decreased late after dexmedetomidine in healthy dogs. In contrast, resistance remained elevated late after dexmedetomidine in dogs with dilated cardiomyopathy.     

Behavioural strategies used by the hookworms Necator americanus and Ancylostoma duodenale to find, recognize and invade the human host

The infective third-stage larvae of the hookworms Necator americanus and Ancylostoma duodenale infect their human hosts by active skin invasion, but A. duodenale is in addition capable of oral infection. The behaviour of the larvae when crawling on surfaces has already been described. Here we analyse in various in vitro systems the other behavioural invasion phases: activation, penetration, and orientation within the host. The larvae normally remained in a motionless, energy-saving, resting posture. An activation to sinusoidal locomotion was stimulated in both species by similar cues such as touch, vibration, water currents, heat, light, and chemicals. Human breath in addition stimulated searching and waving (nictating) behaviour, which facilitates a change-over to the host. Activating cues in air streams were warmth and moisture; CO₂ activated only in combination with warmth and/or moisture. Penetration behaviour in both species was stimulated by warmth and skin extracts. The stimulating components of skin extracts were fatty acids, but their stimulating characteristics differed from those inducing schistosome cercarial skin penetration. After penetration into agar substrates, both species showed thermo-orientation, but only A. duodenale followed gradients of serum. The directing serum cues were not amino acids and glucose (the supposed cues for schistosome blood vessel localization), but Ringers solution attracted the larvae. The host-finding and host-invasion behaviour of both hookworm species is well adapted to the invasion of the human skin, and there seems to be no particular adaptation of A. duodenale behaviour to the oral infection mode. Hookworm host-finding behaviour is not as complex as that of schistosome cercariae but seems well adapted to the ecological conditions in the transmission sites.