Effects of hyperbaric oxygen on expression of fibrinolytic factors of human endothelium in a simulated ischaemia/reperfusion situation.

BACKGROUND: Treatment with hyperbaric oxygen (HBO2) is controversial when treating disorders other than decompression sickness. Still, HBO2 is a treatment modality that has gained recognition in certain situations of ischaemia reperfusion. However, not much is known about its effect on the endothelial cells. Based on earlier studies, the hypothesis was that HBO2 treatment stimulates the release of fibrinolytic factors. The aim of the study was to investigate the effect of HBO2 treatment on cultured endothelial cells in a simulated ischaemia-reperfusion model. METHODS: To mimic the clinical situation during ischaemia reperfusion, endothelial cells were subjected to anoxia for 8 h, followed by reperfusion with either HBO2 or normobaric air for 1.5 h, and compared with an untreated control that was not exposed to anoxia. Components investigated were the fibrinolytic stimulator tissue plasminogen activator (t-PA), urokinase plasminogen activator (uPA) and the antagonist. plasminogen activator inhibitor type one (PAI-1). RESULTS: Immediately after 8 h of total anoxia and reoxygenation with HBO2 (for 1.5 h), the mean (SEM) concentrations of t-PA, PAI-1 and uPA were significantly increased compared to the other groups. The difference between the normobaric and control groups, measured at 1.5 h, 6 h and 24 h post-anoxia, persisted throughout the experiment. CONCLUSION: In this ischaemia-reperfusion model. HBO2 stimulates the release of fibrinolytic factors. These observations might be relevant in trauma care in preventing thromboses and/or microembolization following ischaemia-reperfusion.

Treatment with hyperbaric oxygen affects endothelial cell fibrinolysis.

OBJECTIVE: To investigate the effect of hyperbaric oxygen treatment (HBO) on the thrombolytic properties of endothelial cells. SETTING: University hospital, Sweden. INTERVENTIONS: Human endothelial cells were derived from saphenous veins, and exposed to oxygen in a compression chamber at 2.5 atmospheres absolute (ATA, =250kPa). Cells exposed to 2.5 ATA with a gas mixture similar to air (HB Air), and unpressurised air-exposed cells served as controls. MAIN OUTCOME MEASURES: Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). RESULTS: Immediately after treatment there was a significant increase in t-PA protein in the medium in cultures treated with HBO compared with HB Air (p = 0.015, n = 6), and untreated controls (p = 0.015, n = 6). The PAI-1 concentration in media was also higher in the HBO-treated group compared with HB Air (p = 0.004, n = 6) and untreated controls (p = 0.004, n = 6). Six hours after treatment there was still a significant increase in PAI-1 in the HBO-treated group compared with untreated controls (p = 0.007, n = 6), but not with the pressure control. t-PA concentrations were similar. Specific mRNA for t-PA and PAI-1 was detectable immediately after treatment and six hours later in all experimental groups as assessed by reverse transcriptase polymerase chain reaction (RT-PCR). HBO increased the gene expression for both t-PA and PAI-1. CONCLUSIONS: HBO affects endothelial cell function and its fibrinolytic response. These findings may have clinical relevance in hyperbaric medicine and trauma care.

Effects of hyperbaric oxygen treatment on neutrophil activation and pulmonary sequestration in intestinal ischemia-reperfusion in rats.

Treatment with hyperbaric oxygen (HBO) has shown promising results in some models of ischemia, the major effect being a reduction in the local ischemic damage. The present study investigated the effects of HBO treatment on neutrophil activation and leukosequestration during reperfusion following intestinal ischemia in a rat model. The superior mesenteric artery was clamped for 2 h and subsequently reperfused for 90 min. One group of male Sprague-Dawley rats (n = 9) was given HBO and another group (n = 9) served as controls. Prior to ischemia, leukocytes and erythrocytes were separated, radiolabelled with 111ln and 51Cr, respectively, and reinfused. Leukocyte transit factor, the ratio between the mean passage time of leukocytes and erythrocytes was used to quantitate leukosequestration and the fraction of circulating, spontaneously nitroblue tetrazolium (NBT)-reducing neutrophils was used to measure the degree of neutrophil preactivation. HBO treatment reduced the level of leukocyte pooling significantly, especially in the lungs but also, to a minor degree, in the systemic vascular bed. The percentage of NBT-positive cells increased in all animals after reperfusion, but the increase was significantly reduced by HBO treatment. In conclusion, HBO treatment reduces leukosequestration and neutrophil preactivation following intestinal ischemia-reperfusion.

Effects of spinal cord stimulation (SCS) in patients with inoperable severe lower limb ischaemia: a prospective randomised controlled study.

OBJECTIVES: This study was designed to test the hypothesis that spinal cord stimulation (SCS) improves limb salvage in patients with inoperable severe leg ischaemia. DESIGN: Prospective randomised controlled study with 18 months follow-up. SETTING: Vascular surgical units in two university hospitals. MATERIALS: Atherosclerotic (n = 41) and diabetic (n = 10) patients having chronic leg ischaemia with rest pain and/or ischaemic ulcerations due to technically inoperable arterial occlusions. CHIEF OUTCOME MEASURES: Limb salvage and amount of tissue loss within 18 months, pain relief. MAIN RESULTS: Twenty-five patients were randomized to SCS and 26 to analgesic (control) treatment. Macrocirculatory parameters were not different in the two groups during follow-up. Long-term pain relief was observed only in the SCS group. At 18 months, limb salvage rates in the SCS and control groups were 62% and 45% (N.S.). Tissue loss was less (p = 0.05) in the SCS group. A subgroup analysis of patients without arterial hypertension showed a significantly lower amputation rate in the SCS vs the control group. CONCLUSIONS: SCS provided long-term pain relief but limb salvage at 18 months was not significantly improved by SCS in this rather small study. The results suggest that SCS may reduce amputation levels in patients with severe inoperable leg ischaemia and be most effective in patients without arterial hypertension.

Ascorbate preserves gastric mucosal metabolism and microcirculation after hemorrhagic shock and retransfusion in rats.

The gastric mucosal microcirculation and purine nucleotide metabolism were studied in rats after hemorrhagic shock and retransfusion. The mucosal surface density of perfused vessels (SDPV) and the mucosal levels of ATP, ADP, AMP, IMP, hypoxanthine and uric acid were measured following 15 min of hemorrhagic shock and 10 and 30 min after retransfusion, and the effects of pretreatment with allopurinol or ascorbate were studied. During shock there was a dephosphorylation of nucleotides and a decline in the SDPV. Retransfusion led to an additional reduction in the SDPV, but a complete restoration of preshock nucleotide levels 30 min after retransfusion. Allopurinol accelerated early rephosphorylation of nucleotides without effects upon SDPV while ascorbate completely preserved the mucosal level of energy-rich nucleotides 15 min after hemorrhagic shock and increased SDPV during early reperfusion. The results showed that there was a renewal of energy stores in gastric mucosa after hemorrhagic shock and retransfusion although parts of the vascular bed were not reperfused. The mucosal energy depletion after 15 min of hemorrhagic shock and part of the mucosal vessel injury after retransfusion were prevented by pretreatment with ascorbate.

Gastric mucosal microcirculation and purine nucleotide metabolism after retransfusion of rats in hemorrhagic shock.

Gastric mucosal microcirculation and purine nucleotide metabolism were studied after hemorrhagic shock and retransfusion in rats. The number of perfused microvessels and the concentration of adenosine triphosphate, adenosine monophosphate, inosine monophosphate, inosine, hypoxanthine, xanthine, and uric acid were investigated in mucosal biopsy specimens after 15 or 45 min of hemorrhagic shock and after 15 min of shock followed by 30 min of retransfusion. During shock a dephosphorylation of nucleotides and a decrease in the number of perfused microvessels occurred, the more the longer the duration of the shock period. Retransfusion led to an additional reduction in the number of perfused microvessels, but there was a partial restoration of high-energy phosphate metabolites in those areas of the mucosa which maintained a blood flow. The results indicate that there is a renewal of energy stores in gastric mucosa after hemorrhagic shock and reperfusion, although parts of the vascular bed are not reperfused.

Diagnosis and treatment of colovesical fistulas.

A review of the symptoms and signs as well as preoperative investigations was made in 12 patients with proved colovesical fistulas. The symptoms were predominantly those of the lower urinary tract. The value of barium enema, cystogram, cystoscopy and sigmoidoscopy was pointed out. Treatment consisted of a combined treatment with colostomy and indwelling bladder catheter, primary closure of the fistula only and various staged procedures with bowel resection. We emphasize the value of the one-stage procedure in the uncomplicated case.