A. Karim Qayumi

Propofol enhances red cell antioxidant capacity in swine and humans

PurposeTo determine the effect of an anaesthetic with antioxidant potential, propofol, on red blood cell (RBC) antioxidant enzyme activities and RBC susceptibility to peroxidative challenge.MethodsPropofol was administered by intravenous bolus (2.5 mg·kg−1) and continuous infusion (36 and 72 ml·hr−1 in nine swine; 216 ml·hr−1 in two swine), to achieve serum concentrations between 5 and 30μg·ml−1 for two hours at each rate. Arterial blood sampling was at 0,10, 30, 60, and 120 min for each rate of infusion, for measurement of plasma propofol concentration, activities of plasma and RBC Superoxide dismutase, glutathione peroxidase, gluthathione reductase, RBC catalase, and RBC malondialdehyde (MDA) formation in response to exvivo oxidative challenge with t-butyl hydrogen peroxide (tBHP; 1.5mM). Antioxidant mechanisms were determined byin vitro study of MDA formation, GSH depletion, and oxidation of haemoglobin to methaemoglobin in human erythrocytes exposed to propofol 0–75 μM. The antioxidant potential of propofol was compared with that of alpha-tocopherol utilising the reaction with 2,4,6-tripyridyl-s-triazine (TPTZ).ResultsPropofol had no effect on plasma or RBC antioxidant enzyme activities. It inhibited RBC MDA production over the range of 0–20 μg·ml−1 (y = −18.683x + 85.431 ; R2 = 0.8174). Effective propofol concentrations for 25% and 50% reductions in MDA levels were 7–12 and 12–20 μg·ml−1, respectively. Propofol has a similar effect on human erythrocytesin vitro (R2 = 0.98).ConclusionPropofol antagonises the effects of forced peroxidation of red cells at anaesthetic and sub-anaesthetic concentrations in swine. Its actions include scavenging of oxygen derived free radicals in a tocopherol-like manner.RésuméObjectifDéterminer l’effet d’un agent anesthésique possédant un potentiel antioxydant, le propofol, sur l’activité d’un enzyme antioxydant des globules rouges (GR) et sur la susceptibilité des GR à une provocation peroxydative.MéthodesLe propofol a été administré en bolus intraveineux (2,5 mg·kg−1) et en infusions continues (36 et 72 ml·h−1 chez 9 porcs; 216 ml·h−1 chez 2 porcs) pour obtenir des concentrations sériques entre 5 et 30 μg·ml−1 durant deux heures à chaque vitesse d’infusion. Des prélèvements sanguins par voie artérielle ont été réalisés à 0, 10, 30, 60 et 120 min. pour chaque vitesse d’infusion; on a mesuré la concentration de propofol, l’activité de la superoxyde dismutase du plasma et des GR, de la peroxydase du glutathion, de la réductase du glutathion, de la catalase du GR, ainsi que de la formation dans le GR de la malondialdehyde (MDA) en réponse à une provocation oxydative exvivo avec le peroxyde d’hydrogène t-butylique (tBHP, 1,5 mM). Les mécanismes antioxydants ont été déterminés par l’étudein vitro de la formation de MDA, de la déplétion de GSH ainsi que de l’oxydation de l’hémoglobine en methémoglobine dans des GR humains exposés au propofol 0–75 μM. Le potentiel antioxydant du propofol a été comparé à celui de l’alpha-tocophérol en utilisant la réaction avec le 2,4,6-tripyridyl-s-triazine (TPTZ).RésultatsLe propofol n’a pas eu d’effet sur l’activité de l’enzyme antioxydant du plasma ou des GR. Il a inhibé la production de MDA par les GR pour tout le spectre de 0–20 μg·ml−1 (y = −18.683x + 85.431 ; R2 = 0,8174). Les concentrations de propofol efficaces pour obtenir une réduction des taux de MDA de 25 et de 50% étaient respectivement de 7–12 et de 12–20 μg·ml−1. Le propofol a un effet analogue sur les globules rouges humainsin vitro (R2 = 0,98).ConclusionLe propofol, à des concentrations anesthésiques et subanesthésiques chez le porc, antagonise les effets d’une peroxydation forcée des globules rouges. Son mode d’action comporte l’épuration des radicaux libres provoqués par l’oxygène comme le fait le tocophérol.

High dose propofol enhances red cell antioxidant capacity during CPB in humans.

PurposeTo compare low vs high dose propofol and isoflurane on red cell RBC antioxidant capacity in patients during aortocoronary bypass surgery (ACBP).MethodsTwenty-one patients, for ACBR were anesthetized with sufentanil 0.5–10 μg·kg−1 and isoflurane 0–2%; ISO = control; n=7), or sufentanil 0.3 μg·kg−1, propofol 1–2.5 μg·kg−1 bolus then 100μg·kg−1 before, and 50 μg·kg−1·min−1 during CPB (LO; n=7), or sufentanil 0.3 μg·kg−1, propofol 2–2.5 μg·kg−1 bolus then 200 μg·kg−1·min−1 (HI; n=7). Venous blood was drawn pre-and post-induction, after 30 min CPB, 5, 10, and 30 min of reperfusion, and 120 min post-CPB to measure red cell antioxidant capacity (malondialdehyde (MDA) production in response to oxidative challenge with t-butyl hydrogen peroxide) and plasma propofol concentration. Preinduction blood samples were analyzed for antioxidant effects of nitrates on red cells. The tBHP concentration response curves for RBC MDA in ISO, LO and HI were determined.ResultsPreoperative nitrate therapy did not effect RBC MDA production. Perioperative RBC MDA production was similar in ISO and LO groups. Sustained intraoperative decrease in RBC MDA was seen with propofol 8.0 ± 2.4 − 11.8 ± 4.5 μg·ml−1 in HI (P < 0.05- 0.0001). MDA production vs log plasma propofol concentration was linear in HI dose.ConclusionsDuring CPB, RBC antioxidant capacity is enhanced and maintained with HI dose propofol. Propofol, at this dose, may prove useful in protecting against cardiopulmonary ischemia-reperfusion injury associated with ACBRRésuméObjectifComparer une faible dose (LO) vs une forte dose (HI) de propofol et d’isoflurane sur la capacité antioxydante des globules rouges (GR) lors d’un pontage aortocoronarien (PAC).MéthodeLors d’un PAC, 21 patients ont reçu une anesthésie avec du sufentanil 0,5–10 μg·ml−1 et de l’isoflurane 0–2 %; (ISO = témoin, n = 7) ou du sufentanil 0,3 μg·kg−1 un bolus de propofol 1–2,5 μg·kg−1 suivi d’une perfusion de 100 μg·kg−1·min−1 avant le PAC et de 50 μg·kg−1·min−1 pendant le PAC (LO, n = 7), ou du sufentanil 0,3 μg·kg−1, un bolus de propofol 2–2,5 μg·kg−1 et une perfusion de 200 μg·kg−1·min−1 (HI, n = 7). Le sang veineux a été prélevé avant et après l’induction, 30 min après le PAC, à 5, 10 et 30 min pendant la reperfusion et 120 min après la CEC afin de mesurer la capacité antioxydante des GR (production de dialdéhyde malonique DAM en réponse à la provocation oxydante avec du peroxyde d’hydrogène t-butyl PHtB) et la concentration plasmatique de propofol. Les échantillons de sang prélevés avant l’induction ont été analysés pour vérifier les effets antioxydants des nitrates sur les GR. Les courbes illustrant la réaction des GR au DAM chez les patients des groupes ISO, LO et HI ont été déterminées.RésultatsLa thérapie préopératoire aux nitrates n’a pas changé la capacité antioxydante des GR, donc la production de DAM a été semblable dans les groupes ISO et LO. Une baisse peropératoire de production de DAM a toutefois été observée avec 8,0 ± 2,4 – 11,8 ± 4.5 μg·ml−1 de propofol dans le groupe HI (P < 0,05 - 0,0001). La production de DAM vs le logarithme de la concentration plasmatique de propofol était linéaire dans le groupe HI.ConclusionPendant la CEC, la capacité antioxydante des GR a été améliorée et maintenue par une forte dose de propofol. Administré selon cette dose, le propofol peut se révéler utile pour protéger des lésions cardio-pulmonaires liées à l’ischémie de reperfusion associée au PAC.

Evaluation of ventricular contractility indexes in the dog with left ventricular dysfunction induced by rapid atrial pacing

Eight dogs were studied by simultaneous invasive hemodynamic and two-dimensional echocardiographic methods to determine whether left ventricular contractility is altered by 2 weeks of rapid atrial pacing. Additionally, this study evaluated the response of three ventricular contractility indexes to both the pacing intervention and acute load alteration. The indexes compared were ejection fraction, peak systolic pressure to end-systolic volume index ratio (SBP/ESVI) and end-systolic wall stress to end-systolic volume index ratio (ESWS/ESVI). After 2 weeks of pacing at 265 +/- 20 min-1 (mean +/- SD), cardiac index and ejection fraction were reduced to 73 +/- 38 ml/kg per min and 22 +/- 6%, respectively, from 161 +/- 22 and 46 +/- 7 before pacing (both p less than 0.001). Concomitantly, SBP/ESVI and ESWS/ESVI were reduced to 34 +/- 10 mm Hg/ml per kg and 54 +/- 19 g/cm2 per ml per kg, respectively, from 84 +/- 29 and 121 +/- 36 before pacing (both p less than 0.005). There were high correlations for the changes in SBP/ESVI and ejection fraction (r = 0.94, p less than 0.001) and ESWS/ESVI and ejection fraction (r = 0.89, p less than 0.003). Acute afterload alteration with phenylephrine depressed ejection fraction but not SBP/ESVI or ESWS/ESVI. Therefore, this study demonstrates 1) that left ventricular contractility is markedly depressed in the dog by 2 weeks of rapid atrial pacing, and 2) that SBP/ESVI and ESWS/ESVI are superior to ejection fraction as ventricular contractility indexes because these ratios accurately measure contractility changes but are influenced less by after-load conditions.

Computer-Assisted Learning: cyberPatientTM - A Step in the Future of Surgical Education

Computer-assisted learning is a hot topic and is evolving parallel with the rapidly growing computer technology. Today, modern computers with sophisticated software are able to create a new dimension in the application of many important pedagogical principles and philosophies. Modern computers with excellent multimedia applications are capable of simulating a realistic situation that enriches the educational environment, improves the learning process, and brings new challenges to the process of learning by doing. The use of computers in medical industry and in medical education lags far behind other applications in the industrial world. Although a great many computer-assisted learning programs have been developed in the last decade and patient simulation has been attempted, there are no computer programs in the market that are capable of simulating the realism of the patient-doctor relationship. cyberActive Technology Ltd. has been able to complete this mission. The computer software cyberPatient developed by cyberActive Technology Ltd. is able to realize this long-term dream of medical students and educators. The discrepancy between theoretical and practical medical knowledge in the classical medical education was greater than in any other aspect of science. In classical medical education, diseases were taught beginning with etiology and pathogenesis to signs and symptoms. In practice, the patient comes to the doctor with complaints, and the doctor has to think backward to find out about the etiology and pathogenesis. This discrepancy created enormous difficulties for interns and young doctors with respect to the application of theoretical medicine to medical practice. This was one of the reasons why medical schools turned to a new problem-based learning curriculum. The new curriculum, however, has brought new challenges and problems of its own. Some of the problems include patient availability, increased demands for teachers, and, in turn, significant increases in the costs of medical education. Intensive use of computers may be a solution for problem-based learning. The aim of this article is to give an overview of computer-based learning and its place in the future of medical education.

The metabolism of 15-p-[123I]-iodophenylpentadecanoic acid in a surgically induced canine model of regional ischemia

The purpose of this study was to examine the longitudinal effect of gradual coronary occlusion on regional myocardial metabolism of 15-p-123I-iodophenyl pentadecanoic acid ([123I]IPPA). Adult dogs were imaged using [123I]IPPA and planar gamma imaging. A thoracotomy was performed and an ameroid constrictor of appropriate size permanently positioned on the left anterior descending coronary artery. The dogs were imaged after injection of 3–5 mCi [123I]IPPA at various times over a 2-week period. With imaging on days 7 and 14, the dogs were paced at a rate of 185. Time-activity curves were generated and t1/2 values calculated using monoexponential curve fitting. Results indicate a significant increase in t1/2 between control and 14 days after surgery in the apical wall (29±7 to 53±18 min;P<0.05). Although there was also an increased t1/2 in the lateral wall, this was not significant (27±8 to 78±99 min;P > 0.05). There was no significant change in t/12 in the septal wall (27±9 to 33±8 min;P>0.05). We conclude that [123I]IPPA is a useful indicator of

Mastering instruments before operating on a patient: the role of simulation training in tool use skills.

Background. We examined the impact of tool complexity on surgeons’ performance and evaluated the value of using a simulation-based program for reducing training cost. Methods. Three pairs of surgical graspers with increasing mechanical complexity, which were designed for open, laparoscopic, and endoscopic procedures, were used in performing a simple object transportation task. Task times and mental workload of 17 surgeons were compared using all 3 variations of the graspers to test the impact of tool complexity on surgical performance. Subsequently, 4 of these surgeons decided to enter a 3-week training phase and practiced with these 3 surgical instruments on a daily basis. Learning curves were plotted to examine the value of using simulation for proficiency training with these tools. Results. Task time was significantly prolonged as tool complexity increased. Practice in a simulated environment shortened the task time significantly and moderately reduced mental workloads. However, the difference in task time varied among the 3 types of tools. Between days 1 and 9, task times for each types of grasper were reduced by 55% (endoscopic), 42% (open), and 22% (laparoscopic). Conclusions. Tool complexity may degrade a surgeon’s performance. Extensive simulation training programs are important for surgeons to gain proficiency in handling a tool before they practice on patients.

Quantifying surgeon’s contribution to team effectiveness on a mixed team with a junior surgeon

BACKGROUNDnA surgical team often consists of an experienced surgeon and surgeons in training. This project quantified the contribution of the experienced surgeon to the teamwork in a team comprised of 1 experienced and 1 novice surgeon (Mixed Team).nnnMETHODSnAn experienced and a novice surgeon in a Mixed Team were required to complete a peg transportation task and an intracorporeal suture task collaboratively. Tasks were evaluated by a summative score (up to 100 points) that was calculated on task speed and accuracy. Performances of 24 Mixed Teams were compared to 24 Novice Teams (each composed of 2 novices) and 8 Expert Teams (each composed of 2 experienced surgeons).nnnRESULTSnThe Mixed Teams performed better (67.6 points) than the Novice Teams (51.3; P < .001) but worse than the Expert Teams (88.3; P < .001). When examining individual performance in the Mixed Teams, we observed that experienced surgeons maintained their superior performance like they did in the Expert Teams (P = .153). Novices in the Mixed Teams, however, showed markedly better performances than they did in the Novice Teams (P = .024).nnnCONCLUSIONnInstant guidance and instruction from experienced surgeons inspire novices performance, providing a foundation for surgical teamwork effectiveness.

Centre of Excellence For Simulation Education and Innovation (CESEI)

Simulation is becoming an integral part of medical education. The American College of Surgeons (ACS) was the first organization to recognize the value of simulation-based learning, and to award accreditation for educational institutions that aim to provide simulation as part of the experiential learning opportunity. Centre of Excellence for Simulation Education and Innovation (CESEI) is a multidisciplinary and interprofessional educational facility that is based at the University of British Columbia (UBC) and Vancouver Costal Health Authority (VCH). Centre of Excellence for Simulation Education and Innovations goal is to provide excellence in education, research, and healthcare delivery by providing a technologically advanced environment and learning opportunity using simulation for various groups of learners including undergraduate, postgraduate, nursing, and allied health professionals. This article is an attempt to describe the infrastructure, services, and uniqueness of the Centre of Excellence for Simulation Education and Innovation.