Stephan Klaus

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.

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

IntroductionMyocardial 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).MethodsDuring 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).ResultsAfter 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).ConclusionThis 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.Clinical trials registration: ClinicalTrials.gov NCT00446017.

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.

Biochemical tissue monitoring during hypoxia and reoxygenation

Oxygen deficiency during critical illness may cause profound changes in cellular metabolism and subsequent tissue and organ dysfunction. Clinical treatment in these cases targets rapid reoxygenation to avoid a prolonged impaired synthesis of cellular high-energy phosphates (ATP). However, the effect of this therapeutic intervention on tissue metabolism has not been determined yet. Thus the present study was designed to determine the effects of hypoxia and reoxygenation with either room air or 100% oxygen on variables of interstitial metabolism in different tissues using in vivo microdialysis. Twenty-seven adult, male CD-rats (407-487 g; Ivanovas, Kisslegg, Germany) were studied during general anesthesia. Following preparation and randomization, rats were normoventilated for 45 min (FiO(2) 0.21), followed by induction of hypoxia (FiO(2) 0.1, 40 min) and reoxygenated for 50 min either with FiO(2) 1.0 (group 1, n=10) or FiO(2) 0.21 (group 2, n=10). Control animals (n=7) were ventilated with 21% oxygen during the observation period. Additional to invasive haemodynamic parameters, biochemical tissue monitoring was performed using CMA 20 microdialysis probes, inserted into muscle, subcutaneous space, liver, and the peritoneal cavity allowing analyses of lactate and pyruvate at short intervals. Hypoxia induced a significant reduction in mean arterial pressure (MAP) in group 1 and 2 compared with the control group (P<0.05) without any significant differences between both treatment groups. This was accompanied by a significant increase in blood lactate (10.5+/-3.1 mM (group 1) and 12.3+/-4.1 mM (group 2) vs. 1.5+/-0.3 mM (control); P<0.05) and severe metabolic acidosis (base excess (BE): -18.3+/-5 mM (1) and -17.3+/-7 mM (2) vs. -2.6+/-1.8 mM (control), P<0.05). During hypoxia, the interstitial lacate/pyruvate ratio in groups 1 and 2 increased to 455+/-199% (muscle), 468+/-148% (intraperitoneal), 770+/-218% (hepatic) and 855+/-432% (subcutaneous) (P<0.05 vs. control, respectively). No significant inter-organ or inter-group differences in interstitial dialysates were observed in the treatment groups, neither during hypoxia nor during reoxygenation. Our data suggest, that hypoxia induces comparable metabolic alterations in various tissues and that reoxygenation with 100% oxygen is not superior to 21% oxygen in restoring tissue metabolism after critical hypoxia.

Assessment of fluid balance by measurement of skin tissue thickness during clinical anaesthesia.

Study objective: To determine if measuring skin tissue thickness by a recently developed 10 MHz ultrasound scan may be used as a valuable parameter to guide fluid therapy and detect fluid shifts to the extravascular space during surgical procedures in addition to central venous pressure (CVP).

Subcutaneous microdialysis for metabolic monitoring in abdominal aortic surgery.

Microdialysis, that is the sampling of interstitial fluid via semi-permeable tubes, has been shown to be suitable for detecting ischemic changes e.g. in brain and heart tissue. The purpose of the present study was to investigate the possibility of monitoring with subcutaneous microdialysis peri-operative metabolic sequelae of elective abdominal aortic surgery. In 22 patients microdialysis catheters were inserted subcutaneously in the lower leg as well as the shoulder serving as a reference topographic region. Lactate, pyruvate and glycerol, which indicate ischemia or reperfusion, were measured. We observed severe metabolic changes within the interstitial fluid of the lower extremity during ischemia followed by normalization during reperfusion. Despite high interstitial concentrations of lactate and glycerol indicating severe ischemia during clamping of the abdominal aorta these parameters returned to pre-operative values within 2 hrs after declamping and all patients recovered completely. Objective.Information about the metabolic state of the lower extremity during and after infrarenal aortic aneurysm repair should modify peri-operative treatment. The aim of the study was to evaluate whether microdialysis of the subcutaneous tissue reflects metabolic changes during ischemia and reperfusion. Lactate, pyruvate and glycerol concentrations were measured in the subcutaneous tissue of the lower extremity and compared to the microdialysis measurements from shoulder subcutaneous tissue. Method.In 22 patients microdialysis catheters were inserted preoperatively in the subcutaneous space of the left shoulder and the left calf. Samples were taken at timed intervals before, during and after clamping of the abdominal aorta. Results.The subcutaneous glycerol concentration of the calf was increased during the clamping period from initially 68 ± 11 µM up to 182 ± 27 µM (p< 0.05); the lactate/pyruvate (L/P) ratio was increased eightfold. After declamping these values normalized to baseline. Microdialysis measurements of the shoulder showed no prominent changes during the entire course of observation. Conclusions.Subcutaneous microdialysis was able to detect metabolic changes due to ischemia during clamping of the abdominal aorta as well as reperfusion there after. It is a suitable technique to monitor the peri-operative course of the dependent tissue after abdominal aortic vascular surgery.

Clinical biochemical tissue monitoring during ischaemia and reperfusion in major vascular surgery

Background: Major vascular surgery with aortic cross-clamping is associated with temporary ischaemia of the lower limb due to lack of tissue blood flow. The present study was designed to determine if the short-term changes in cellular metabolism occurring during this situation can be detected by subcutaneous microdialysis. It was also hoped to ascertain if this new technique is useful in the continuous bedside monitoring of metabolism during aortic surgery. Methods: In a controlled clinical study 20 patients undergoing elective aortic surgery were monitored using microdialysis probes that were inserted in the subcutaneous tissue of the left lower limb and a non-ischaemic region (shoulder). Interstitial fluid was obtained and the concentrations of glucose and lactate during lower limb ischaemia and during reperfusion were measured and compared with concentrations observed in fluid obtained from the non-ischaemic control tissue. Results: Circulatory occlusion caused an immediate and significant decrease in the glucose/lactate ratio from 3·1±1·3 to 0·48±0·5 (P<0·05) that returned to preocclusion values within 2 h of commencing reperfusion. Conclusion: We suggest that microdialysis may be used both to assess acute changes in tissue metabolism during ischaemic periods and also to act as an additional tool for the detection of peri-operative acute variations in limb blood flow.

Tissue metabolism during endotoxin shock after pretreatment with monophosphoryl lipid A

OBJECTIVE Preconditioning pigs with low doses of monophosphoryl lipid A (MPL), a non toxic derivate of lipid A, has been shown to induce endotoxin hyporesponsiveness and to reduce the metabolic and hemodynamic consequences of endotoxin shock. However, the mechanism is presently unclear. This study was designed to elucidate the effects of pretreatment with MPL on tissue metabolism in different organs by in vivo microdialysis of interstitial fluid. METHODS In a controlled animal study at the university research laboratory, seven female mixed-breed pigs were exposed to an endotoxin infusion (1 microg/kg b.w. per h) after pretreatment with MPL in incremental doses of endotoxin during days 5-2 before the experiments. Seven animals receiving a saline pretreatment served as a control group. Hemodynamic variables and blood gas analyses including blood lactate were determined every 30 min until the animals died. Interstitial lactate and glycerol levels were measured in muscle, subcutaneous tissue and liver using in vivo microdialysis. RESULTS Survival time was significantly prolonged after MPL preconditioning (8.95 (7.5-9.1) h vs. 5.35 (5.0-5.6) h, P<0.05). Hemodynamic parameters were not significantly different between the treatment and control groups, while mixed venous saturation (81% (70-93%) vs. 30% (22-48%)) and arterial blood pH (7.39 (7.33-7.44) vs. 7.21 (7.1-7.25)) and pO(2) were significantly higher in the preconditioned group (P<0.05). The interstitial concentrations of lactate and glycerol in all investigated tissues were significantly higher in control animals than the those who had been pretreated with MPL (P<0.05). CONCLUSIONS Preconditioning with low doses of monosphosphoryl lipid A attenuates the negative effects of endotoxemia on tissue metabolism, probably by reducing O(2)-consumption. These changes may be subtle and, hence, only fully detectable by monitoring tissue metabolism.

Na+/H+exchange inhibitor cariporide: effects on respiratory dysfunction after cardiopulmonary bypass:

The purpose of the present study was to evaluate the potential of the Na+/H+ exchange inhibitor cariporide to protect the lung from injury after cardiopulmonary bypass (CPB). In a randomized placebo-controlled study, 16 pigs were subjected to CPB for 75 min. Administration of vehicle or cariporide (bolus 180 mg, 40 mg/hour) began 30 min pre-CPB and was continued throughout the protocol. The alveolo-arterial O2-gradient (AaDO2), the pulmonary shunt (Qs/Qt), the compliance (Cpl), haemo-dynamic variables and glycerol and water content in lung tissue were measured 10 min before and up to 180 min post-CPB. All animals in the control versus 75% in the cariporide group survived the experiment. At 5 and 60 min post-CPB, the mean AaDO2 and at 5, 60 and 180 min post-CPB, the mean pulmonary vascular resistance index were higher in the cariporide group (p < 0.05), respectively. More lung water accumulation was found in the cariporide group (p < 0.05). Mean Cpl decreased; the Qs/Qt and glycerol in lung tissue increased without significant intergroup difference. In this model, the inhibitor of the Na+/H+ antiporter showed no protective effect on lung injury after CPB and might even have harmful effects on pulmonary vascular tone and function.

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.