[Open educational resources for otorhinolaryngology : A pilot study on needs assessment and implementation]. / Open Educational Resources für die HNO-Heilkunde : Ein Pilotprojekt zur Bedarfsanalyse und Implementierung.

BACKGROUND: Open educational resources (OER) are educational materials licensed openly by authors, permitting usage, redistribution, and in some instances, modification. OER platforms thereby serve as a medium for distributing and advancing teaching materials and innovative educational methodologies. OBJECTIVE: This study aims to determine the present state of OER in otorhinolaryngology and to examine the prerequisites for seamlessly integrating OER into the curricular teaching of medical schools, specifically through the design of two OER blended learning modules. METHODS: OER content in the field of otorhinolaryngology was analyzed on OER platforms, ensuring its relevance to the German medical curriculum. Data protection concerns were addressed with legal counsel. The blended learning modules were developed in collaboration with medical students and subsequently published as OER. RESULTS AND CONCLUSION: This project yielded the first OER from a German ENT department, tailored to the German medical curriculum. One significant barrier to OER use in medicine, more than in other fields, is data protection. This challenge can be navigated by obtaining consent to publish patient data as OER. OER hold the promise to play a pivotal role in fostering cooperation and collaboration among educators, aiding educators in lesson preparation, and simultaneously enhancing didactic quality.

[Educational film on the geriatric basic assessment in primary care-Methods of cinematic authenticity]. / Lehrfilm über das geriatrische Basisassessment in der hausärztlichen Versorgung ­ Methoden filmischer Authentizität.

BACKGROUND: The relevance of care of older persons in general practice requires the conveyance of procedural and conditional knowledge of the geriatric basic assessment (GBA) even during medical studies. There is a need for action with respect to student knowledge on specific problems of older patients. This paper describes how the primary care situation can be made tangible for students based on a film project at the Hannover Medical School (MHH). METHOD: During film production, strategies for creating authenticity were applied using cinematic means. The film is used in the teaching module of family medicine at MHH. Student evaluation investigated whether the educational film provided an emotional experience and whether the presentation mode of the GBA was perceived as authentic. RESULTS: The majority of students were emotionally touched by the film. The educational film was successful in conveying the complexity of care of older people and in presenting the special role of family physicians in geriatric care. DISCUSSION: The students recognized the necessity of the GBA and found the representation predominantly realistic; however, individual cinematic reception and previous experiences also influence the perception of the cinematic form with respect to the representation of reality. This method might improve the conveyance of authenticity in educational videos in medicine.

International multicentre review of perioperative management and outcome for catecholamine-producing tumours.

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.

Infarct size reduction by AT1-receptor blockade through a signal cascade of AT2-receptor activation, bradykinin and prostaglandins in pigs.

OBJECTIVE: We studied the effect of the angiotensin II type 1 (AT1)-receptor antagonist candesartan on infarct size resulting from regional myocardial ischemia in pigs. BACKGROUND: The effects of AT1-receptor blockade on infarct size in different species remain controversial and its potential cardioprotective mechanisms are still unclear. In pigs, infarct development closely resembles that observed in humans. METHODS: A total of 62 enflurane-anesthetized pigs underwent a protocol of 90-min low-flow ischemia and 120-min reperfusion. Systemic hemodynamics (micromanometer), regional myocardial function (sonomicrometry), regional myocardial blood flow (microspheres) and infarct size (TTC [triphenyl tetrazolium chloride]-staining) were determined. RESULTS: Left ventricular peak pressure decreased with candesartan (1 mg/kg i.v.) from 97+/-2 standard error of the mean (SEM) to 86+/-5 mm Hg and was then readjusted by aortic banding. In placebo pigs (n=9), infarct size was 21.8+/-4.8% of the area at risk. Candesartan (n=7) reduced infarct size to 9.7+/-2.5% (p < 0.05). Pretreatment with the AT2-receptor antagonist PD123319 (3 microg/kg/min intracoronarily [i.c.]; n=8), the bradykinin B2-receptor antagonist HOE140 (0.01 microg/kg/min i.c.; n=8) or the cyclooxygenase inhibitor indomethacin (10 mg/kg i.v.; n= 8) per se did not affect infarct size but did abolish the reduction of infarct size achieved by candesartan (PD123319 + candesartan (n=7): 23.2+/-4.7%; HOE140 + candesartan (n=7): 18.2+/-4.0%; indomethacin + candesartan (n=8): 21.1+/-5.2%). Hemodynamics, regional myocardial blood flow during ischemia and the area at risk were comparable among all groups of pigs. CONCLUSIONS: Reduction of infarct size by the AT1-receptor antagonist candesartan in pigs involves angiotensin II type 2 receptor (AT2) activation, bradykinin and prostaglandins.

Enhanced reduction of myocardial infarct size by combined ACE inhibition and AT(1)-receptor antagonism.

The effects of the angiotensin-converting-enzyme inhibitor (ACEI) ramiprilat, the angiotensin II type 1 receptor antagonist (AT(1)A) candesartan, and the combination of both drugs on infarct size (IS) resulting from regional myocardial ischaemia were studied in pigs. Both ACEI and AT(1)A reduce myocardial IS by a bradykinin-mediated process. It is unclear, however, whether the combination of ACEI and AT(1)A produces a more pronounced IS reduction than each of these drugs alone. Forty-six enflurane-anaesthetized pigs underwent 90 min low-flow ischaemia and 120 min reperfusion. Systemic haemodynamics (micromanometer), subendocardial blood flow (ENDO, microspheres) and IS (TTC-staining) were determined. The decreases in left ventricular peak pressure by ACEI (by 9+/-2 (s.e. mean) mmHg), AT(1)A (by 11+/-2 mmHg) or their combination (by 18+/-3 mmHg, P<0.05 vs ACEI and AT(1)A, respectively) were readjusted by aortic constriction prior to ischaemia. With placebo (n=10), IS averaged 20.0+/-3.3% of the area at risk. IS was reduced to 9.8+/-2.6% with ramiprilat (n=10) and 10.6+/-3.1% with candesartan (n=10). Combined ramiprilat and candesartan (n=10) reduced IS to 6.7+/-2.1%. Blockade of the bradykinin-B(2)-receptor with icatibant prior to ACEI and AT(1)A completely abolished the reduction of IS (n=6, 22.8+/-6.1%). The relationship between IS and ischaemic ENDO with placebo was shifted downwards by each ACEI and AT(1)A and further shifted downwards with their combination (P<0.05 vs all groups); icatibant again abolished such downward shift. The combination of ACEI and AT(1)A enhances the reduction of IS following ischaemia/reperfusion compared to a monotherapy by either drug alone; this effect is mediated by bradykinin.

In vitro validation of a metabolic monitor for gas exchange measurements in ventilated neonates.

OBJECTIVE: To evaluate the Datex Deltatrac II for measurements in neonates requiring mechanical ventilation. DESIGN: Prospective laboratory evaluation, using a ventilated lung model and gas injection. During simulation of 79 neonatal respiratory settings, assessment of oxygen consumption (VO2), carbon dioxide production (VCO2) and respiratory quotient (RQ) was compared to a reference method (mass spectrometry, wet gas spirometry) using the statistical method of Bland and Altman. INTERVENTIONS: Respiratory variables, which may influence the accuracy and precision of gas exchange measurements, were varied within the following ranges: inspired oxygen fraction (FIO2): 0.21-0.8, expired carbon dioxide fraction (FECO2) and inspiratory-expiratory oxygen fraction (DFO2): 0.0032-0.0256, expiratory flow rate: 1.0-2.5 l/min, inspiratory pressure: 10-55 mbar, respiratory rate 25-60/min, constant RQ of 1. This resulted in 79 tests with VCO2 and VO2 ranging from 8-64 ml/min. MEASUREMENTS AND RESULTS: The coefficient of repeatability for ten single subsequent Deltatrac measurements was 8.09 ml/min for VO2 and 9.17 ml/min for VCO2 compared to 2.02 ml/min and 0.90 ml/min for VO2 and VCO2 with repeated reference measurements. The coefficient of repeatability of the Deltatrac measurements improved considerably when means of subsequent 5 min intervals were compared: 0.68 ml/min for VO2 and 0.28 ml/ min for VCO2. The difference between the two methods (Deltatrac-reference) was -3.8 % (2 s: 11.4%) for VO2, 13.2% (2s: 7.9%) for VCO2 and 17.6% (2s: 16.7%) for RQ. The agreement between methods deteriorated with smaller (FECO2) or DFO2 and increasing FIO2. CONCLUSIONS: Considering limits of agreement of less than +/- 20% as clinically acceptable, results for VO2 assessment indicate acceptable accuracy and precision whereas VCO2 and RQ assessments exceed this limit. Limited accuracy and precision result from detection of CO2 following dilution of expiratory gases and increased sensitivity to error propagation by Haldane equations due to the small differences between inspiratory and expiratory gas fractions.

Implementation of a web-based, interactive polytrauma tutorial in computed tomography for radiology residents: how we do it.

PURPOSE: Due to the time factor in polytraumatized patients all relevant pathologies in a polytrauma computed tomography (CT) scan have to be read and communicated very quickly. During radiology residency acquisition of effective reading schemes based on typical polytrauma pathologies is very important. Thus, an online tutorial for the structured diagnosis of polytrauma CT was developed. MATERIALS AND METHODS: Based on current multimedia theories like the cognitive load theory a didactic concept was developed. As a web-environment the learning management system ILIAS was chosen. CT data sets were converted into online scrollable QuickTime movies. Audiovisual tutorial movies with guided image analyses by a consultant radiologist were recorded. RESULTS: The polytrauma tutorial consists of chapterized text content and embedded interactive scrollable CT data sets. Selected trauma pathologies are demonstrated to the user by guiding tutor movies. Basic reading schemes are communicated with the help of detailed commented movies of normal data sets. Common and important pathologies could be explored in a self-directed manner. CONCLUSIONS: Ambitious didactic concepts can be supported by a web based application on the basis of cognitive load theory and currently available software tools.

[A web-based e-learning tool in academic teaching of trauma surgery. First experiences and evaluation results]. / Webbasiertes E-Learning-Tool in der unfallchirurgischen Lehre. Erste Erfahrungen und Evaluationsergebnisse.

There are lots of possibilities for universities to offer contents of teaching to students by the Internet. Often the students can download slides or a special lecture note from the intranet of the university. Another way is to make a movie of the lecture and post this lecture movie on the Internet. In the Hanover Medical School we employed an alternative. It was developed by the Trauma Surgery Clinic and the Institute of Medical Informatics at the Hanover Medical School. Our goal was to use just one web-based content resource for the lecture and for the work at home. The Institute of Medical Informatics used a web-based content management system (CMS) Schoolbook to implement this e-learning application.Since October 2005 the Trauma Surgery Schoolbook has been used in the lecture on trauma surgery in all terms, and we evaluated the academic year 2005/2006. The results of the evaluation showed us that the students were very interested in using this e-learning application. The possibility to reinforce the learning material at home is a good chance for the students. Also the organisation of lectures was improved because the materials were all in one place. The lecturer needs to learn several new tasks, but we also got a positive response. Our experiences of the last academic year showed that it was a good way to use one web-based content resource for teaching and learning in the context of a lecture.

Recombinant factor VIIa reduces transfusion requirements in liver transplant patients with high MELD scores.

Patients undergoing orthotopic liver transplantation (OLT) often experience significant coagulopathy and remain at risk for excessive blood loss and massive transfusion. The ability of recombinant factor VIIa (rFVIIa) to reduce transfusion requirements during OLT has not been well established. This retrospective study investigates whether rFVIIa reduces transfusion requirements in liver transplant patients with a significantly prolonged prothrombin time (PT) and a model of end-stage liver disease (MELD) score of > 20. Eleven patients received a single dose of rFVIIa (58 +/- 18 microg kg(-1)) at the time of incision. This group was matched with a selected control group that fulfilled all of the inclusion/exclusion criteria. Patient characteristics, pre-operative PT, HCT, PLT and MELD were identical between groups. Prophylactic application of rFVIIA reduced packed red blood cells (3.9 +/- 2.6 versus 6.9 +/- 2.3 U, P = 0.01) and fresh-frozen plasma (FFP) (12.6 +/- 6 versus 19.8 +/- 7 U, P = 0.018) transfusion requirements when compared with the control group. FFP administration in the first 24 h after surgery was also significantly less in the rVIIa group when compared with the control group (388 +/- 385 versus 1225 +/- 701 mL, P = 0.003). Hospital stay following transplantation tended to be shorter in the rFVIIa group, albeit statistical significance was not achieved (11 +/- 7.3 versus 7.9 +/- 2.7, P = 0.2). All but one patient in the control group survived for 30 days after transplantation. In a selected group of patients with prolonged PT and high MELD score, the prophylactic application of rFVIIa at the start of the OLT may reduce perioperative transfusion requirements.

eLearning in education and advanced training in neuroradiology: introduction of a web-based teaching and learning application.

INTRODUCTION: New information technologies offer the possibility of major improvements in the professional education and advanced training of physicians. The web-based, multimedia teaching and learning application Schoolbook has been created and utilized for neuroradiology. METHODS: Schoolbook is technically based as a content management system and is realized in a LAMP environment. The content is generated with the help of the developed system and stored in a database. The layout is defined by a PHP application, and the webpages are generated from the system. RESULTS: Schoolbook is realized as an authoring tool so that it can be integrated into daily practice. This enables the teacher to autonomously process the content into the web-based application which is used for lectures, seminars and self-study. A multimedia case library is the central building block of Schoolbook for neuroradiology, whereby the learner is provided with original diagnostic and therapeutic data from numerous individual cases. The user can put individual emphasis on key learning points as there are various ways to work with the case histories. Besides the case-based way of teaching and learning, a systematically structured way of dealing with the content is available. CONCLUSION: eLearning offers various opportunities for teaching and learning in academic and scientific as well as in economic contexts. Web-based applications such as Schoolbook may be beneficial not only for basic university education but also for the realization of international educational programmes such as the European Master of Medical Science with a major in neuroradiology.

Minimal protection of the liver by ischemic preconditioning in pigs.

Ischemic preconditioning (IP) protects the rat liver. In pigs, in which hepatic tolerance to ischemia is similar to that in humans, information on IP is lacking. Therefore, in enflurane-anesthetized pigs, hepatic vessels were occluded for 120 min (protocol 1) or 200 min (protocol 2) without (control) and with IP (3 times 10 min ischemia-reperfusion each). In protocol 1, cumulative bile flow (CBF) during reperfusion was greater in IP (47.3 +/- 5.2 ml/8 h) than in control (17.1 +/- 7.8 ml/8 h, P < 0.05). ATP content tended to recover toward normal during reperfusion in IP, whereas it remained at ischemic levels in control. Serum enzyme concentrations increased similarly during reperfusion, and <1% hepatocytes were necrotic or stained terminal deosynucleotidyl transferase-mediated dUTP nick-end labeling-positive in control and IP groups. In protocol 2, no differences in CBF, ATP, or serum enzyme concentrations during reperfusion were measured between control and IP groups, except for a somewhat reduced lactate dehydrogenase in IP. The number of necrotic or terminal deosynucleotidyl transferase-mediated dUTP nick-end labeling-positive hepatocytes tended to be greater in the IP than the control group. Thus IP provides some functional protection against reversible ischemia but no protection during prolonged ischemia in pigs.

No involvement of endogenous nitric oxide in classical ischemic preconditioning in swine.

Endogenous nitric oxide (NO) is involved in the protection by classical ischemic preconditioning (IP) against ischemia-induced arrhythmias in anesthetized dogs. Furthermore, NO triggers and mediates protection against infarction and stunning in delayed IP in conscious rabbits. Up to now it is unclear whether or not endogenous NO is also involved in the protection against infarction by classical IP in vivo. In 45 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 min followed by 2 h of reperfusion resulted in an infarct size (IS, triphenyl tetrazolium chloride-staining) of 20.5+/-5.4% (S.E.M.) of the area at risk. Inhibition of NO synthase by l -nitro arginine (l -NA, 30 mg/kg i.v.) increased left ventricular (LV) peak pressure from 93+/-3 to 120+/-1 mmHg (P<0.05), but did not alter IS (22.4+/-5. 6%). With aortic constriction to match the increase in LV peak pressure with l -NA, IS was unchanged (18.1+/-5.1%). IP by 10 min ischemia and 15 min reperfusion preceding the 90 min target ischemia reduced IS to 2.0+/-0.8% (P<0.05 v. non-preconditioned groups). This reduction of IS by IP was not affected by l -NA (1.3+/-0.9%, P<0.05 v. non-preconditioned groups). Area at risk and myocardial blood flow (microspheres) during ischemia were not different among groups. Relationships between IS and subendocardial blood flow with l -NA or aortic constriction, respectively, were not different from that with placebo, but were significantly shifted downwards by IP with and without l -NA. Thus, endogenous NO does not alter infarct size development per se and is not involved in the protection against infarction by classical IP in pigs in vivo.

Intraperitoneal and retroperitoneal carbon dioxide insufflation evoke different effects on caval vein pressure gradients in humans: evidence for the starling resistor concept of abdominal venous return.

BACKGROUND: The authors hypothesized that intraperitoneal and retroperitoneal carbon dioxide insufflation during surgical procedures evoke markedly different effects on the venous low-pressure system, induce different inferior caval vein pressure gradients at similar insufflation pressures, and may provide evidence for the Starling resistor concept of abdominal venous return. METHODS: Intra- and extrathoracic caval vein pressures were measured using micromanometers during carbon dioxide insufflation at six cavity pressures (baseline and 10, 15, 20, and 24 mmHg and desufflation) in 20 anesthetized patients undergoing laparoscopic (supine, n = 8) or left (n = 6) or right (n = 6) retroperitoneoscopic (prone position) surgery. Intracavital, esophageal, and gastric pressures also were assessed. Data were analyzed for insufflation pressure-dependent and group effects by one-way and two-way analysis of variance for repeated measurements, respectively, followed by the Newman-Keuls post hoc test (P < 0.05). RESULTS: Intraperitoneal, unlike retroperitoneal, insufflation markedly increased, in an insufflation pressure-dependent fashion, the inferior-to-superior caval vein pressure gradient (P < 0.00001) at the level of the diaphragm. In contrast to what was observed with retroperitoneal insufflation, transmural intrathoracic caval vein pressure increased at 10 mmHg insufflation pressure, but the increase flattened with an insufflation pressure of more than 10 mmHg, and pressure decreased with an inflation pressure of 20 mmHg (P = 0.0397). These data are consistent with a zone 2 or 3 abdominal vascular condition during intraperitoneal and a zone 3 abdominal vascular condition during retroperitoneal insufflation. CONCLUSIONS: Intraperitoneal but not retroperitoneal carbon dioxide insufflation evokes a transition of the abdominal venous compartment from a zone 3 to a zone 2 condition, presumably impairing venous return, supporting the Starling resistor concept of abdominal venous return in humans.

Attenuation of myocardial stunning by the AT1 receptor antagonist candesartan.

The effect of AT1 receptor blockade on myocardial stunning is still somewhat ambiguous. In some prior studies, coronary occlusion was of too long duration such that the effects of infarction and stunning on the recovery of contractile function could not be distinguished. In others, blood pressure was decreased such that the improved wall excursion could be the consequence of reduced afterload and/or of attenuated stunning. The present study, therefore, investigated the effect of the AT1 receptor antagonist candesartan in a pure model of myocardial stunning with controlled systemic hemodynamics. Fourteen anesthetized open-chest dogs were subjected to 15 minutes occlusion of the left circumflex coronary artery (LCx) and 4 hours subsequent reperfusion. Systemic hemodynamics (micromanometer), regional myocardial blood flow (colored microspheres), and posterior wall thickening (PWT, sonomicrometry) were measured, and data were compared between 7 placebo controls (group 1) and 7 dogs receiving 1 mg/kg candesartan i.v. before LCx occlusion (group 2). Left ventricular peak pressure was kept constant by an intra-aortic balloon, and heart rate did not change throughout the protocol. Regional myocardial blood flow was not different between the groups under control conditions, increased in response to candesartan in group 2 (posterior subendocardial blood flow from 0.99 +/- 0.18 to 1.57 +/- 0.45; p < 0.05 vs. control conditions), but was not different during myocardial ischemia and at 4 hours of reperfusion between the groups. Under control conditions and during myocardial ischemia, PWT was also not different between the groups. At 4 hours of reperfusion, PWT was still depressed in group 1 (-1.5 +/- 3.4% vs. 17.7 +/- 5.6% during control conditions, p < 0.05), whereas PWT had recovered in group 2 (11.4 +/- 3.7% at 4 hours reperfusion vs. 18.3 +/- 2.7 during control conditions, NS, p < 0.05 vs. group 1). In conclusion, pretreatment with the AT1 receptor antagonist candesartan improved the functional recovery of reperfused myocardium. This attenuation of myocardial stunning was not based on more favorable systemic hemodynamics or regional myocardial blood flow.

No protection of the porcine kidney by ischaemic preconditioning.

One or more episodes of sublethal ischaemia and reperfusion delay infarct development during subsequent, sustained ischaemia in the heart and skeletal muscle. The present study tested whether or not such ischaemic preconditioning (IP) also protects the kidney. Enflurane-anaesthetized pigs underwent 60 min of right renal vessel occlusion (RVO), followed by 8 h of reperfusion without (placebo group, n = 8) or with three preceding cycles of 10 min RVO and 10 min reperfusion (IP group, n = 8). After 8 h of reperfusion, kidneys were oliguric in both groups (placebo group: 23 +/- 21 ml x h(-1), IP group: 24 +/- 27 ml x h(-1)). A transient polyuric phase occurred in the IP group at 2 h reperfusion. The reperfused kidneys did not excrete inulin, creatinine or urea in both groups, although renal blood flow during reperfusion was similar to baseline. Morphological damage ranged in both groups from single cell necrosis to disseminated patchy necrosis; the number of pyknotic cells tended to be higher in the IP group than in the placebo group (27.0 +/- 7.1 vs. 15.6 +/- 5.6%, n.s.). In anaesthetized pigs, IP did not therefore attenuate renal dysfunction and morphological damage resulting from 60 min of renal normothermic ischaemia followed by 8 h of reperfusion.

Inconsistent relation of MAPK activation to infarct size reduction by ischemic preconditioning in pigs.

The importance of the activation of mitogen-activated protein kinases (MAPK) for the cardioprotection achieved by ischemic preconditioning (IP) is still controversial. We therefore measured infarct size and p38, extracellular signal-regulated kinase (ERK), and c-Jun NH(2)-terminal kinase (JNK) MAPK phosphorylation (by biopsies) in enflurane-anesthetized pigs. After 90 min low-flow ischemia and 120 min reperfusion, infarct size averaged 18.3 +/- 12.4 (SD)% (group 1, n = 14). At similar subendocardial blood flows, IP by 10 min ischemia and 15 min reperfusion (group 2, n = 14) reduced infarct size to 6.2 +/- 5.1% (P < 0.05). An inconsistent increase in p38, ERK, and p54 JNK phosphorylation (by Western blot) was found during IP; p46 JNK phosphorylation increased with the subsequent reperfusion. At 8 min of the sustained ischemia, p38, ERK, and p54 JNK phosphorylation were increased with no difference between groups (medians: p38: 207% of baseline in group 1 vs. 153% in group 2; ERK: 142 vs. 144%; p54 JNK: 171 vs. 155%, respectively). MAPK phosphorylation and reduction of infarct size by IP were not correlated, thus not supporting the concept of a causal role of MAPK in mediating cardioprotection by IP.