Cerebral effects of resuscitation with either epinephrine or vasopressin in an animal model of hemorrhagic shock.

PURPOSE: The use of epinephrine (EN) or vasopressin (VP) in hemorrhagic shock is well established. Due to its specific neurovascular effects, VP might be superior in concern to brain tissue integrity. The aim of this study was to evaluate cerebral effects of either EN or VP resuscitation after hemorrhagic shock. METHODS: After shock induction fourteen pigs were randomly assigned to two treatment groups. After 60 min of shock, resuscitation with either EN or VP was performed. Hemodynamics, arterial blood gases as well as cerebral perfusion pressure (CPP) and brain tissue oxygenation (PtiO2) were recorded. Interstitial lactate, pyruvate, glycerol and glutamate were assessed by cerebral and subcutaneous microdialysis. Treatment-related effects were compared using one-way ANOVA with post hoc Bonferroni adjustment (p < 0.05) for repeated measures. RESULTS: Induction of hemorrhagic shock led to a significant (p < 0.05) decrease of mean arterial pressure (MAP), cardiac output (CO) and CPP. Administration of both VP and EN sufficiently restored MAP and CPP and maintained physiological PtiO2 levels. Brain tissue metabolism was not altered significantly during shock and subsequent treatment with VP or EN. Concerning the excess of glycerol and glutamate, we found a significant EN-related release in the subcutaneous tissue, while brain tissue values remained stable during EN treatment. VP treatment resulted in a non-significant increase of cerebral glycerol and glutamate. CONCLUSIONS: Both vasopressors were effective in restoring hemodynamics and CPP and in maintaining brain oxygenation. With regards to the cerebral metabolism, we cannot support beneficial effects of VP in this model of hemorrhagic shock.

Microdialysis as a Part of Invasive Cerebral Monitoring During Porcine Septic Shock.

BACKGROUND: Metabolic changes in critically ill patients with endotoxin-induced septic shock are measured primarily by techniques that afford organ-specific metabolic monitoring based on interstitial fluid samples. The present study was designed to evaluate the role of cerebral microdialysis (MD) as a part of invasive neuromonitoring during endotoxemia in a porcine model. MATERIALS AND METHODS: Continuous endotoxin infusion was administered to 7 female pigs and, in addition to hemodynamic monitoring and blood chemistry, interstitial lactate, pyruvate, glucose and glycerol concentrations in muscle, liver, and cerebral tissue were measured via in vivo MD for an observation period of 180 minutes. RESULTS: The cerebral concentrations of lactate and glycerol showed no significant increases, whereas the hepatic and muscular levels rose dramatically under endotoxemia. However, the lactate/pyruvate ratio and especially the lactate/glucose ratio showed a profound and significant increase in brain tissue as well. Cerebral perfusion pressure decreased from 77 to 50 mm Hg without reaching pathologic values. CONCLUSIONS: Although our results confirm the special protection of the brain during endotoxemia compared with other organs, early metabolic changes become evident by increasing lactate/pyruvate ratio and lactate/glucose ratio. MD appears to be a suitable additional technique in invasive neuromonitoring for obtaining early information about metabolic deterioration in the brain during septic shock.

Cerebral metabolism during experimental endotoxin shock and after preconditioning with monophosphoryl lipid A.

PURPOSE: Preconditioning with low doses of monophosphoryl lipid A (MPL) has been shown to induce endotoxin tolerance and to reduce the metabolic and hemodynamic consequences of endotoxin shock. However, no data are available about the effects of endotoxin preconditioning on cerebral metabolism during endotoxemia. The study was designed to determine the effects of endotoxin preconditioning with MPL on cerebral metabolism via microdialysis compared to muscle tissue metabolism during experimental endotoxemia. METHODS: In a controlled animal study, continuous endotoxin infusion (1µg/kg b.w. per h) was administrated to 7 female mixed-breed pigs after pretreatment with MPL in incremental doses of endotoxin during days 5-2 before the experiments. In the control group, 7 animals received a saline pretreatment. In addition to hemodynamic monitoring and blood gas analyses, interstitial lactate, pyruvate, glucose and glycerol concentrations in muscle and cerebral tissue were measured using in vivo microdialysis. RESULTS: There were no significant differences between the two groups with respect to hemodynamic parameters, while mixed venous oxygen saturation (SvO2), arterial blood pH and mean pulmonary arterial pressure (MPAP) were significantly higher in the preconditioned group. Cerebral perfusion pressure (CPP) and brain tissue oxygen pressure (ptiO2) values stayed stable throughout the experiment with no inter-group differences. While interstitial concentrations of lactate and glycerol as well as the lactate/pyruvate (LP) and the lactate/glucose (LG) ratio in muscle tissues were significantly increased in control animals compared to those who had been pretreated with MPL; the results of cerebral microdialysis showed no significant changes in interstitial lactate or glycerol levels in both groups. However, the lactate/glucose (LG) ratio in the control group showed a significantly higher increase than in the preconditioned group. CONCLUSIONS: Preconditioning with low doses of MPL ameliorates the negative metabolic effects of endotoxin shock in muscle tissue. With regard to cerebral metabolism, the present study suggests that MLP preconditioning provides moderate advantages, at least in an experimental model of endotoxin shock.

Significant [C3a] increase in free flaps after prolonged ischemia.

BACKGROUND: Free tissue transfer (FTT) represents a clinical model to measure ischemia-reperfusion injury (IRI). This study was conducted to detect substances relevant for IRI after FTT. METHODS: Eighteen patients underwent lower leg reconstruction with free myocutaneous latissimus dorsi muscles and were monitored clinically and by microdialysis technique. Patients were retrospectively classified as group A (n = 12) (no prolonged IRI) or group B (n = 6) (prolonged IRI). One catheter was placed into the flap and one into the reference tissue. Samples were collected during ischemia and in 90 min steps after reperfusion. Biochemical substances (glucose, pyruvate, lactate, and glycerol) and immunological substances (interleukin 8 [IL-8], complement 3a [C3a], and regulated on activation normal T cell expressed and secreted [RANTES]) were then analyzed. RESULTS: All free myocutaneous latissimus dorsi flaps healed primarily. Minor complications included revisions of the microvascular anastomoses due to hematoma or thrombus formation and increased total flap ischemia time in group B significantly when compared to group A (P < 0.001). No significant differences of biochemical substance concentrations were detected during reperfusion in target and control tissue of both groups. IL-8 and C3a were at detectable levels, whereas the results for RANTES were inconsistent. Either for group A and group B, we found higher concentrations of C3a in target tissue compared with control tissue. Furthermore, during the first 90 min of reperfusion, we found a highly significant increase of C3a (P < 0.001) in the target tissue of patients with increased ischemia time. CONCLUSIONS: Given our results, C3a is a highly sensitive early indicator of ischemia-reperfusion damage. Our results give further insight into development of IRI after complicated FTT.

Functional recovery of chronic ischemic myocardium after surgical revascularization correlates with magnitude of oxidative metabolism.

BACKGROUND: The purpose of this study was to validate myocardial microdialysis measurements in patients after myocardial infarction with or without associated postoperative functional recovery in order to develop a highly sensitive tool for real-time in vivo detection of microcellular disorder during cardiac operations. METHODS: In 20 patients undergoing coronary artery bypass grafting, microdialysis catheters were implanted into scar or hibernating segments detected by means of magnetic resonance imaging, and into a vital area of the right ventricle (control). Myocardial glucose, lactate and pyruvate were analyzed perioperatively. Myocardial ethanol washout was measured as a sign of recovered local blood flow. RESULTS: After surgical revascularization, improvement of wall motion was found in all hibernating segments compared to the scar segments paralleling an increased glucose delivery to the tissue and increased myocardial tissue flow. The myocardial glucose/lactate ratio and pyruvate also showed significantly higher values. Microdialytic measurements of the viable segments were comparable with those of the right ventricle. CONCLUSIONS: Our results indicate that microdialysis measurements parallel magnetic resonance imaging findings in patients with revascularization of chronic ischemic myocardium with dyskinetic segments. The metabolism of those segments is characterized by a significantly increased tissue flow, an increased utilization of glucose and a better oxidative nutrition.

A single prophylactic dose of pentoxifylline reduces high dependency unit time in cardiac surgery - a prospective randomized and controlled study.

BACKGROUND: The pathogenesis of the post cardiopulmonary bypass (CPB) organ dysfunction syndrome is complex, with inflammation being an important component. The purpose of this prospective, randomized and controlled study was to evaluate the effect of a single dose of pentoxifylline (PTX) prior to CPB on high dependency unit time. MATERIALS AND METHODS: We studied 39 patients undergoing aorto-coronary bypass surgery with CPB. Patients received either 5 mg kg(-1) PTX after induction of anaesthesia or saline as placebo. Haemodynamics, parameters of pulmonary function and plasma levels of tumour necrosis factor alpha (TNFalpha) and C-reactive protein (CRP) were measured after the induction of anaesthesia (pre-CPB) and after weaning from CPB (post-CPB), 1 h after the admission to the intensive care unit (ICU) and on the morning of the first postoperative day (1 POD), respectively. In addition, ventilation time and the high dependency unit time, i.e. the time till transferral to a peripheral ward, were documented. RESULTS: Patients in the PTX group had lower TNFalpha values (6.3 ng ml(-1) (4/8.2) vs 9.1 ng ml(-1) (6.5/13.7)) (median (25%/75%), p=0.021), lower systolic (28+/-7 mm Hg vs 35 +/- 9 mm Hg, mean+/-SD, p=0.011) and mean pulmonary artery pressures (21+/-5 vs 26+/-6 mm Hg, p=0.017) after admission to the ICU than control patients. Haemodynamics and pulmonary function parameters did not differ. There was a trend towards earlier weaning from the respirator in the PTX group (10.0+/-3.5 h) (min/max: 4/16; confidence interval (ConF): 1.8 h) than the control group (12.3+/-4.2 h) (min/max: 5-24; ConI: 2.4 h) (p=0.077). Patients treated with PTX could be transferred to a peripheral ward about 24 h earlier than control patients (95+/-35 h, min/max: 32/190 h; ConI: 17 h; 119+/-29 h, min/max: 66/165 h; ConI: 16 h) respectively; p=0.037). CONCLUSION(S): A single dose of PTX prior to CPB was able to reduce plasma levels of TNFalpha. In this descriptive study, there was a trend towards reduced duration of ventilation and the high dependency unit time, i.e. the time till transferral to a peripheral ward was shortened.

The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting.

INTRODUCTION: Myocardial dysfunction necessitating inotropic support is a typical complication after on-pump cardiac surgery. This prospective, randomized pilot study analyzes the metabolic and renal effects of the inotropes adrenaline and milrinone in patients needing inotropic support after coronary artery bypass grafting (CABG). METHODS: During an 18-month period, 251 patients were screened for low cardiac output upon intensive care unit (ICU) admission after elective, isolated CABG surgery. Patients presenting with a cardiac index (CI) of less than 2.2 liters/minute per square meter upon ICU admission - despite adequate mean arterial (titrated with noradrenaline or sodium nitroprusside) and filling pressures - were randomly assigned to 14-hour treatment with adrenaline (n = 7) or milrinone (n = 11) to achieve a CI of greater than 3.0 liters/minute per square meter. Twenty patients not needing inotropes served as controls. Hemodynamics, plasma lactate, pyruvate, glucose, acid-base status, insulin requirements, the urinary excretion of alpha-1-microglobuline, and creatinine clearance were determined during the treatment period, and cystatin-C levels were determined up to 48 hours after surgery (follow-up period). RESULTS: After two to four hours after ICU admission, the target CI was achieved in both intervention groups and maintained during the observation period. Plasma lactate, pyruvate, the lactate/pyruvate ratio, plasma glucose, and insulin doses were higher (p < 0.05) in the adrenaline-treated patients than during milrinone or control conditions. The urinary excretion of alpha-1-microglobuline was higher in the adrenaline than in the control group 6 to 14 hours after admission (p < 0.05). No between-group differences were observed in creatinine clearance, whereas plasma cystatin-C levels were significantly higher in the adrenaline than in the milrinone or the control group after 48 hours (p < 0.05). CONCLUSION: This suggests that the use of adrenaline for the treatment of postoperative myocardial dysfunction - in contrast to treatment with the PDE-III inhibitor milrinone - is associated with unwarranted metabolic and renal effects.

Analysis of the myocardial metabolism by microdialysis during open beating heart surgery.

OBJECTIVES: Microdialysis allows the in vivo biochemical analysis of interstitial fluids. Our aim was to reveal in vivo reliable data of the myocardium during open beating heart surgery. DESIGN: In ten patients undergoing routine beating coronary artery bypass grafting a microdialysis catheter was inserted into the left ventricle. Measurements were performed up to 45 min after anastomosis. Data were retrospectively compared with standard on-pump procedures. RESULTS: The myocardial lactate remained stable during anastomosis, followed by a significant decrease of lactate after revascularisation. Myocardial glucose levels showed a slight decrease, followed by a significant increase after revascularisation. Myocardial purines showed a slight increase during anastomosis, followed by a sharp decrease during reperfusion period. CONCLUSIONS: In contrast to on-pump procedures myocardial lactate and purines showed less increasing trend during the ischemic period, while myocardial glucose remained stable as a sign of preserved tissue blood flow. Myocardial microdialysis showed different values compared to the elective on-pump CABG and previous animal studies. This technique allows bedside monitoring of biochemical changes, suggesting its possible role as a clinical monitoring tool.

The effects of angiotensin-converting enzyme inhibition on the urinary excretion of NTproBNP in male volunteers.

AIMS: This study was designed to test if the renal excretion of the N-terminal prohormone of the B-type natriuretic peptide (NTproBNP) is modulated by angiotensin-converting enzyme inhibition (ACE-I). METHODS: Following 7 days on a sodium-enriched diet and an induction period of 4 days with incremental dosages of enalapril (2.5, 5, 7.5, 10 mg) or placebo, 10 healthy subjects underwent crossover and double-blind treatment with 20 mg enalapril sodium or placebo at 8:00 h. After 4 h (at 12:00 h), 20 ml.kg(-1) NaCl 0.9% was infused over 60 min. Hemodynamics were determined and blood and urine were sampled at 8:00, 12:00, 13:00, 14:00, 16:00, and 18:00 h. Angiotensin II (AII), NTproANP, and NTproBNP were determined by radio- and electrochemiluminescence immunoassays. RESULTS: In the whole group, ACE-I led to a lower arterial blood pressure during the fourth day of induction and during the time from 8:00 to 16:00 h, a decrease in AII levels from 8:00 to 14:00 h (p < 0.05), and to a higher cumulative urine output (p < 0.05) in comparison with control. Neither cumulative sodium nor urinary NTproBNP/creatinine excretion were significantly increased after ACE-I. However, a subgroup of 6 volunteers - showing an increase in sodium excretion after ACE-I - also demonstrated lower AII levels at 13:00 h, a higher cumulative urine flow, and a higher urinary NTproBNP/creatinine excretion in comparison with control (all: p < 0.05). CONCLUSIONS: This suggests that the renal excretion of NTproBNP is modified by enalapril. However, it remains to be determined if this is a direct effect of ACE-I, the decrease in arterial blood pressure, or other potentially confounding variables like bradykinin or endopeptidase activity.

Evaluation of myocardial metabolism with microdialysis during bypass surgery with cold blood- or Calafiore cardioplegia.

BACKGROUND: For the first time, microdialysis was used to investigate in vivo and online the myocardial metabolism during and after cardiac surgery in patients treated with two different methods of myocardial protection. METHODS: Thirty patients underwent standard CABG with one of two different methods of myocardial protection. The patients were randomised to receive either cold blood (COLD group) or warm modified Calafiore cardioplegia (WARM group). Microdialysis probes were implanted into the myocardium of left ventricular apical region of the heart. Cardioplegia was given antegrade only. Microdialysis measurements were performed at time intervals before, during and 24 h after cardiopulmonary bypass and analysed for glucose, lactate, pyruvate and glycerol. RESULTS: Myocardial lactate concentrations were significantly higher in the WARM group compared with that of the COLD group, while serum lactate was comparable. Glycerol was significantly higher at the end of the clamping time in the WARM group. At the same time the glucose-lactate ratio as a marker of nutritional disorder had significantly lower levels in the WARM group. The cumulative CK-MB release over 24 h was significantly higher in those hearts protected with warm blood. CONCLUSIONS: The oxidative stress measured was significantly higher in patients undergoing CABG using modified Calafiore cardioplegia, whereas the cold cardioplegia minimised the effects of aortic clamping. The results indicate that cold cardioplegia offers superior protection of the heart, in terms of more rapid normalisation of myocardial metabolism. In elective myocardial revascularisation, intermittent antegrade warm blood cardioplegia is a comparable safe method of myocardial protection. However, in patients referring to a long clamping time, advantages of cold cardioplegia for myocardial revascularisation may be magnified.

[Treatment anxiety in oral and maxillofacial surgery]. / Behandlungsangst in der Mund-, Kiefer- und Gesichtschirurgie.

BACKGROUND: Oral and maxillofacial operations are stressful treatment situations for patients. Specific data on this phenomenon were acquired through a multicenter study. MATERIAL AND METHODS: A 10-page questionnaire was answered by 600 oral and maxillofacial patients before individual treatment. Control groups consisted of 800 surgical, dental, internal medicine and general practitioner patients. 26 practices and hospital departments in 11 German cities were involved in the study. RESULTS: Both subjective anxiety assessment by patients and objective measurement (State Trait Anxiety Inventory; STAI) indicated a high level of treatment anxiety for oral and maxillofacial treatment. STAI scores for OMFS patients were significantly higher than in control groups. Especially female patients, patients treated under local anaesthesia and out-department patients showed high anxiety scores. Treatment experience in oral and maxillofacial surgery does not modify anxiety in case of recurrent treatment. CONCLUSION: Managing perioperative anxiety today is still a major challenge in oral and maxillofacial surgery. Irrespective of technical and pharmacological advances further studies on this topic and the development and establishing of stress-reducing and anxiolytic perioperative techniques are of considerable importance.

C3a levels and occurrence of subdermal vascular thrombosis are age-related in deep second-degree burn wounds.

BACKGROUND: After second-degree burns, thrombosis of the subdermal vascular plexus may occur, necessitating epifascial necrectomy instead of tangential excision to ensure split skin graft healing. Until now, no parameter has been obtained to explain this phenomenon. METHODS: Thirty-four patients with deep second-degree burn wounds were divided into 2 groups. In group 1, patients' age was < 60 years, in group 2, > 60 years. In each patient, 2 microdialysis catheters were introduced into subdermal tissue of deep second-degree thermal wounds immediately after admission. Another 2 catheters were introduced in control tissue. We measured biochemical parameters (lactate, glycerol and glucose) and complement 3a (C3a) until surgery was performed. The surgically removed tissue was examined histologically. RESULTS: In thermal wounds of both groups, glucose levels fell, but lactate and glycerol levels rose compared to healthy tissue. Within the first 24 hours after trauma, C3a levels were significant higher in both groups, compared with controls (P < .01). After 24 hours the levels in group 1 had fallen to nonsignificant values, while in group 2 these levels remained high until surgery was performed (P < .001). We found significantly more thrombotic blood vessels in deep dermal tissue of group 2 (P < .005). Abbreviated burn severity index score was comparable in both groups. CONCLUSIONS: C3a is continuously elevated in deep second-degree burned wounds in patients > 60 years. This finding may be related to the occurrence of significantly more thrombotic blood vessels in deep dermal tissue of elderly patients. Microdialysis therapy is a useful tool to measure metabolic and immunologic parameters in thermally damaged tissue.

Bench-to-bedside review: microdialysis in intensive care medicine.

Microdialysis is a technique used to measure the concentrations of various compounds in the extracellular fluid of an organ or in a body fluid. It is a form of metabolic monitoring that provides real-time, continuous information on pathophysiological processes in target organs. It was introduced in the early 1970s, mainly to measure concentrations of neurotransmitters in animal experiments and clinical settings. Using commercial equipment it is now possible to conduct analyses at the bedside by collecting interstitial fluid for measurement of carbohydrate and lipid metabolites. Important research has been reported in the field of neurosurgery in recent decades, but use of metabolic monitoring in critical care medicine is not yet routine. The present review provides an overview of findings from clinical studies using microdialysis in critical care medicine, focusing on possible indications for clinical biochemical monitoring. An important message from the review is that sequential and tissue-specific metabolic monitoring, in vivo, is now available.

The relationship between urotensin II plasma immunoreactivity and left ventricular filling pressures in coronary artery disease.

The role of urotensin II (U-II)--a vasoactive, mitogenic, and inotropic, peptide--in the pathophysiology of heart failure is controversial. The present study explores the relationship between plasma U-II immunoreactivity (U-IIIR) and hemodynamics in patients with coronary artery disease (CAD). Thirty-six patients with CAD-3 undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) and 36 medical patients (MED group) with CAD-1 to CAD-3 during right heart catheterization were studied. Significant correlations were observed between pulmonary capillary wedge pressure (PCWP) and U-IIIR--determined by enzyme immunoassay (EIA)--before (rho = 0.83) and after (rho = 0.6) cardiopulmonary bypass in the CABG group. With the exception of the CPB period, CABG patients with increased PCWP before CPB had higher U-II(IR) concentrations throughout the procedure. Significant correlations were observed between U-IIIR, proANP, proBNP, and mean right ventricular pressure (RVPM) in MED patients. No correlation was detectable between U-IIIR and PCWP. However, MED patients with CAD-3 (n = 13) had higher levels of U-IIIR, NTproANPIR (RIA), NTproBNPIR (EIA) and higher cardiac filling pressures than patients with CAD-1 (n = 13). These findings support an association between plasma U-IIIR levels and diastolic myocardial dysfunction in ischemic heart failure. The discrepancies regarding left and right cardiac filling pressures and U-IIIR levels in CABG and MED patients require further evaluation.

Effects of tilting and volume loading on plasma levels and urinary excretion of relaxin, NT-pro-ANP, and NT-pro-BNP in male volunteers.

The polypeptide relaxin (RLX) has been suggested to play a role in cardiorenal integration and to be related to the natriuretic peptide system. We hence examined the effects of variations in thoracic blood volume and intravenous volume loading on plasma and urinary RLX levels and associated changes in natriuretic peptide levels in healthy men. Two groups of eight subjects were randomly tilted into a 15 degrees feet-down or a 15 degrees head-down position. Ten volunteers were crossover subjected to an infusion of 15 ml/kg of 0.9% NaCl (over 60 min) or control during an observation period of 10 h. Blood and urine were sampled at timed intervals. RLX, NH(2)-terminal prohormones of atrial natriuretic peptide (NT-pro-ANP), and NH(2)-terminal prohormones of brain natriuretic peptide (NT-pro-BNP) were determined by enzyme, radio-, and electrochemoluminescence immunoassays, respectively. NT-pro-ANP levels (in percentage of baseline levels) were higher (P < 0.05) during the head-down (124 +/- 13%) than during the feet-down position (82 +/- 6%). NT-pro-BNP and RLX were not affected by tilting. Volume loading induced a short-lasting increase in plasma NT-pro-ANP, a delayed increase in plasma NT-pro-BNP, had no effect on plasma RLX, and induced a parallel increase in urine flow, renal excretion of sodium, RLX, and NT-pro-BNP. It is concluded that variations in thoracic blood volume in healthy men are not associated with variations in plasma RLX. Increased urinary RLX and NT-pro-BNP excretion during volume loading suggest renal production and a possible role of kidney-derived RLX and brain natriuretic peptide in sodium homeostasis in men.

Myocardial redox state during coronary artery bypass grafting assessed with microdialysis.

PURPOSE: Microdialysis allows the biochemical analysis of interstitial fluids of nearly every organ as a bedside procedure. This technique could be useful to reveal data about the myocardial metabolism during cardiopulmonary bypass in human coronary artery bypass graft (CABG) surgery. METHODS: In 17 patients undergoing CABG a myocardial microdialysis catheter (CMA 70, CMA/Microdialysis AB, Sweden) was inserted in the apical region of the beating heart. Microdialysis measurements were performed at timed intervals before, during, and after cardiopulmonary bypass (CPB). The concentrations of lactate and pyruvate were analyzed semi-continuously. RESULTS: During CPB the myocardial lactate-pyruvate-ratio (LPR) rose from an initial 11 (8-15) to 33 (29-41) ( P<0.01). After CPB the LPR decreased to 4 (3-7) at the end of observation ( P<0.05). The pyruvate concentration showed an immediate increase from 34 (30-42) microM at the end of CPB to 181 (147-234) microM after removal of the cross-clamp with subsequent increase during reperfusion ( P<0.01). Plasma lactate and pyruvate showed no essential changes during the study. CONCLUSION: Using the microdialysis technique it was possible to analyze myocardial metabolic changes during CABG. The course of myocardial LPR as a sensitive indicator of the myocardial redox state showed profound changes during and after CPB. We propose the microdialysis technique as an additional monitoring tool in CABG.

Altered pulmonary vascular reactivity in mice with excessive erythrocytosis.

Pulmonary vascular remodeling during chronic hypoxia may be the result of either oxygen deprivation or erythrocytosis. To separate experimentally the effects of hypoxia and erythrocytosis, we analyzed transgenic mice that constitutively overexpress the human erythropoietin gene in an oxygen-independent manner. These mice are characterized by polycythemia but have normal blood pressure, heart rate, and cardiac output. In transgenic mice, pulmonary artery pressure (PAP) was increased in vivo but was reduced in blood-free perfused lungs. The thromboxane receptor agonist U46619 caused a smaller rise in PAP in isolated transgenic lungs than in lungs from wild-type mice. The transgenic pulmonary vasculature was characterized by elevated prostacyclin production, stronger endothelial nitric oxide synthase expression, and reduced pulmonary vascular smooth muscle thickness. The fact that transgenic polycythemic mice have marked pulmonary hypertension in vivo but not in vitro suggests that their pulmonary hypertension is due to the increased blood viscosity, thus supporting an independent role of polycythemia in the development of pulmonary hypertension. In addition, our findings indicate that the lungs of transgenic animals adapt to the high PAP by elevated synthesis of vasodilators and reduced vascular smooth muscle thickness that tend to reduce vascular tone and vascular responsiveness.

Interstitial glycerol increase in microdialysis after glycerol enema.

Microdialysis allows the measurement of extracellular concentrations of various endogenous substances, such as excitotoxic amino acids or metabolic end products. Recent advances in microdialysis techniques have led to widespread use in patients with brain disorders. Microdialysis has proved to be a useful tool for monitoring cerebral biochemical metabolism and secondary brain damage in severe head injury, subarachnoid haemorrhage, stroke, and epilepsy. In our neurosurgical intensive care unit, microdialysis was performed on 42 patients. Four patients received a glycerol enema for therapy of a paralytic ileus. A glycerol peak was observed in both intracerebral and subcutaneous microdialysis occurring three to four hours after the glycerol enema in all four patients. The highest glycerol value was 1187micromol/l cerebral and 2997micromol/l in the subcutaneous tissue. Our study indicates that besides the measurement of serum osmolality and serum glycerol level, microdialysis may be an additional valuable tool to control glycerol therapy in patients with cerebral oedema and elevated intracranial pressure.