Levosimendan cardioprotection in acutely beta-1 adrenergic receptor blocked open chest pigs.

BACKGROUND: Levosimendan and volatile anesthetics have myocardial pre-conditioning effects. beta-1 adrenergic receptor antagonists may inhibit the protective effect of volatile anesthetics. No information exists as to whether this also applies to the pre-conditioning effect of levosimendan. We therefore investigated whether levosimendan added to metoprolol would demonstrate a cardioprotective effect. METHODS: Three groups of anesthetized open chest pigs underwent 30 min of myocardial ischemia and 90 min of reperfusion by temporary occlusion of the largest side branch from the circumflex artery or the left anterior descending artery. One group (CTRL) served as a control, in another group (BETA), a metoprolol-loading dose was intravenously injected 30 min before ischemia, and in a third group (BETA+L), a levosimendan infusion was added to metoprolol. Myocardial tissue concentrations of glucose, glycerol, and lactate/pyruvate ratio as the primary end-points were investigated with microdialysis in ischemic and non-ischemic tissues. RESULTS: At the end of the ischemic period, statistically significant differences were only found between CTRL and BETA+L in the ischemic myocardium, with a lower lactate/pyruvate ratio, lower glycerol, and higher glucose concentrations in BETA+L as compared with CTRL. There were no differences in non-ischemic myocardium. From 10 to 90 min of reperfusion, no more differences were found between groups. CONCLUSION: The cardioprotective effect of levosimendan on ischemic metabolism with a reduction in the myocardial lactate/pyruvate ratio, less glycerol accumulation, and better preserved glucose concentration does not seem to be prevented by beta-1 adrenergic receptor antagonism with metoprolol.

Levosimendan cardioprotection reduces the metabolic response during temporary regional coronary occlusion in an open chest pig model.

BACKGROUND: Inotropic and myocardial anti-ischemic effects have been demonstrated with levosimendan. The comparison of levosimendan started before an ischemia-reperfusion event as compared with levosimendan started during ischemia has not been studied. METHODS: In anesthetized pigs, a major branch of the circumflex artery was completely occluded for 30 min and then reperfused. The metabolism in the ischemic myocardium and in non-ischemic control myocardium was studied with microdialysis concomitantly with monitoring of global hemodynamics and coronary artery flow in the chosen artery. In the protection group (PRO, n= 6), a levosimendan infusion was started 30 min before coronary artery occlusion, and in the treatment group (TRE, n= 6), a levosimendan infusion was started 10 min after the coronary artery occlusion with a loading dose of 13.3 microg/kg followed by an infusion of 0.67 microg/kg/min. A two-way repeated measures ANOVA completed with Bonferroni's multiple comparison procedure was applied to the data. A P < 0.05 was considered significant. RESULTS: During the ischemic period, the cardiac output and contractility (dp/dt(max)) were higher in the PRO as compared with the TRE and the systemic vascular resistance was lower. The myocardial microdialysate glucose concentration in the ischemic area during ischemia was higher in the PRO as compared with the TRE, and the lactate/pyruvate ratio and the lactate concentration were lower. The differences in the metabolites persisted into the first 10 min of reperfusion. No differences were found for the non-ischemic areas. CONCLUSION: Levosimendan used throughout myocardial ischemia-reperfusion might have a cardioprotective affect on the response to myocardial ischemia as compared with levosimendan started during the ischemia.

Myocardial glycerol release, arrhythmias and hemodynamic instability during regional ischemia-reperfusion in an open chest pig model.

BACKGROUND: To develop cardioprotection against peri-operative myocardial ischemia-reperfusion injury, we need animal models where the local metabolism and blood flow are studied concomitantly with the global circulatory consequences during regional coronary occlusion. METHODS: In six anesthetized domestic pigs, the largest branch of the circumflex artery was occluded for 30 min. Microdialysate was sampled from the ischemic and non-ischemic myocardium along with continuous measurements of local coronary artery flow, global hemodynamics and registration of arrhythmias, from baseline through to 30 min of ischemia and 180 min of reperfusion. RESULTS: During ischemia, the microdialysate glucose concentration decreased, the glycerol concentration increased and the lactate/pyruvate ratio increased significantly. For glycerol, there was a further increase at reperfusion. During ischemia, cardiac output was unchanged; however, during reperfusion there was a significant drop lasting for several minutes, longer than the period in which an increased number of arrhythmias were registered. CONCLUSION: The present study demonstrates deranged circulation and arrhythmias corresponding to ischemic metabolism after regional myocardial ischemia and reperfusion. Reperfusion induced more pronounced circulatory changes than the actual ischemia. A substantial increase in myocardial glycerol release seems to be a marker of ischemic metabolism and may prove to be an indicator of reperfusion injury.

Effect of Iloprost infusion on metabolism in critical limb ischemia, utilizing microdialysis. A pilot study.

AIM: In critical limb ischemia (CLI), the prognosis to keep the leg is poor if revascularisation is not possible. Treatment with prostanoids has proven to be beneficial regarding pain relief, ulcer healing and limb salvage but only in a proportion of patients. Prostanoids exert their effect in different ways e.g. on white blood cells and endothelial cells. No study has so far investigated the effect of prostanoids on the local tissue metabolism. The aim of this study was to investigate if infusion of the prostacyclin analogue, iloprost (PGI2) improves the local metabolism measured by microdialysis technique. METHODS: Eleven patients, 7 men and 4 women, median age 75 years (range 64-89 years), suffering CLI (Fontaine stage III and IV), were included. Patients with insulin dependent diabetes mellitus were excluded. Microdialysis catheters (CMA 60) were inserted subcutaneously in the ischemic leg and in the pectoral region, respectively. An iloprost infusion was given for 6 hours during 3 days preceded by a control day. Registrations of glucose and lactate levels were performed hourly. RESULTS: No significant differences were found in lactate or glucose levels over the treatment period but a trend of increasing glucose and decreasing lactate was observed. Compared to the control day, lactate was significantly lower during (p=0.02) and after (p<0.05) the infusion. This was also true for the reference catheter during the infusion period (p=0.02). CONCLUSIONS: No immediate improvement in glucose or lactate levels in ischemic tissue could be observed after 3 days of iloprost infusion, but a significant lactate decrease was found compared to a previous control day, suggesting a possible metabolic response.

Microdialysate metabolites before, during and after vascular surgery for chronic leg ischaemia.

OBJECTIVE: to investigate peripheral metabolism in the leg during bypass surgery for chronic ischaemia. PATIENTS AND METHODS: in eight patients, microdialysis catheters were placed in the anterior and posterior tibial muscles, subcutaneously in the leg and, for reference, subcutaneously in the pectoral region. Tissue glucose, glycerol and lactate levels were measured between induction of anaesthesia and the first postoperative day. RESULTS: glucose levels increased postoperatively at all four sites. Glycerol levels decreased during the day of surgery. Glycerol was significantly lower in the leg than in the pectoral region. Muscle lactate increased after anaesthesia, but before proximal clamping, and no further significant intra-operative increase was observed. Post-operatively, lactate decreased to baseline levels. Subcutaneous lactate levels followed the changes observed in muscle but did not reach statistical significance. CONCLUSION: bypass surgery for chronic ischaemia temporarily worsens ischaemic metabolism in the leg.

Exotic snake bite: a challenge for the Scandinavian anesthesiologist?

BACKGROUND: Venomous snake bites are uncommon in the Scandinavian countries. Envenomation from exotic snakes do however occur, mostly amongst snake handlers. This case report documents the effects and treatment for envenomation from Hoplocephalus bungaroides, or the Broad-Headed snake, native to eastern and southern Australia. Snakes of the genus Hoplocephalus have previously been described as of 'lesser medical importance' because of their rarity. METHODS: This case report describes the signs, symptoms and management of systemic envenomation in a previously healthy man. RESULTS: The patient developed signs of severe coagulopathy less than an hour after envenomation. There was also biochemical evidence of rhabdomyolysis, and cardiotoxicity. At no time did the patient develop respiratory insufficiency, neurotoxicity or renal failure. The patient was initially managed with i.v. crystalloids, plasma, corticosteroids and antifibrinolytics and by observation in the intensive care unit (ICU). Coagulopathy resolved after causal treatment with monovalent Tiger snake antivenom. CONCLUSION: The patient made good progress and was well on discharge from the ICU 26 h postenvenomation.

Regional tissue metabolism during open or endovascular abdominal aortic aneurysm surgery.

OBJECTIVE: to investigate differences in regional tissue metabolism between open and endovascular aneurysm repair utilising a microdialysis technique. MATERIALS: eight patients receiving endovascular stent grafts (STENT) and six patients undergoing open aortic surgery (OPEN) for abdominal aortic aneurysms were studied prospectively but non-randomised. METHOD: microdialysis catheters placed subcutaneously in the pectoral and calf region, respectively. RESULTS: microdialysate glucose levels increased in the OPEN group on the day of surgery. Microdialysate lactate levels increased transiently in the leg in the STENT group. In the OPEN group lactate increased in the leg after aortic cross-clamping. Glycerol decreased in the pectoral region in the STENT group after surgery, but remained elevated in the OPEN group. CONCLUSION: we found indications that the metabolic impact of the two aortic procedures differ. This may be of clinical importance when selecting patients for either open aortic surgery or endovascular stentgrafting.