Beneficial effect of hyperbaric oxygen therapy on liver regeneration after 90% hepatectomy in rats

BACKGROUND/AIMS: Hyperbaric oxygen therapy (HBOT) has been reported to augment oxygen delivery to ischemic tissues and improve the liver dysfunction in clinical cases. HBOT was performed after 90% hepatectomy in rats to determine its effect on the regeneration of remnant liver. METHODS: After 90% hepatectomy was performed in 8-week-old male Wistar rats, the animals were subdivided into an HBOT (2 atm abs., 80% O2, 1 h/day, 3 days) group and a non-HBOT group. Members of both groups were sacrificed, usually every 4 h until a maximum of 50 h after hepatectomy, and the liver regeneration rate, the proportion of PCNA-positive cells and the ATP volume in the remnant tissues were examined. RESULTS: In the HBOT group, the liver regeneration rate at 36 h and 50 h after operation and the proportion of PCNA positive cells at 8 h was significantly increased compared with the non-HBOT group. The ATP volume in the remnant livers in the HBOT group was also significantly increased at 12 h. CONCLUSION: HBOT augmented liver regeneration after hepatectomy by stabilization of energy metabolism induced by oxygen delivery in rats.     

Beneficial effects of hyperbaric oxygen therapy on islet transplantation

We envisage that hyperbaric oxygen (HBO) would ameliorate islet anoxia, preventing early graft failure. Thus, treatment of HBO to diabetic recipients should improve the outcome of islet transplantation. We tested this hypothesis by syngeneically transplanting insufficient number of islets (150 islets) into streptozotocin-diabetic C57BL/6 mice, each followed by HBO (2.4 ATA, 100% O2) therapy for 1.5 h from day 0 to 28, once daily (group A) or twice daily (group B), or from day 5 to 28, once daily (group C) or twice daily (group D), 6 days/week. Recipients without HBO treatment served as controls. At day 28 after transplantation, groups B, C, and D gained weight and had lower blood glucose compared with their baseline values. In addition, groups B and D had higher insulin content of the graft than the controls. To determine the optimal timing of HBO therapy, groups B and D were compared with recipients treated with HBO twice daily, 6 days/week, from day -14 to 0 (group E) and from day -14 to 28 (group F). At day 28 after transplantation, groups B, D, E, and F had significantly lower blood glucose than their individual baseline values and higher insulin content of the graft than controls. But only group F had more beta-cell mass of the graft than controls. These findings lend credence to the expectation that peritransplant application of adequate frequency of HBO to diabetic recipients would enhance the performance and growth of the islet graft, resulting in an improvement of the outcome of the transplantation.     

Beneficial effects of pentoxifylline pretreatment in non-heart-beating donors in rats

BACKGROUND: Pentoxifylline (PTX) pretreatment of recipients was shown to protect against liver graft failure from ischemia-reperfusion injury after orthotopic rat liver transplantation. It has also been shown that PTX protects against normothermic ischemia-reperfusion injury to the liver in lobar ischemia model in the rat. Whether PTX can benefit the liver procured from non-heart-beating donors (NHBDs) with up to 9 hr of cold ischemia is unknown. METHODS: Donor and recipient rats were pretreated with intraperitoneal PTX (50 mg/kg) 1 hr before cardiac arrest and transplantation, respectively. Grafts were transplanted 0, 30, and 60 min after cardiac arrest with additional 1 and 9 hr of cold ischemia in both PTX-pretreated or untreated (control) groups (10 rats per group). PTX (25 mg/kg/day) was continuously given to the surviving rats for 5 days postoperatively. Recipient survival rates, serum enzyme levels, and histopathological examination of postreperfusion liver biopsies were all analyzed. RESULTS: The survival rates, serum enzyme levels, and postreperfusion histology were significantly improved in groups pretreated with PTX compared to the controls. CONCLUSION: Donor and recipient PTX pretreatment significantly improves the viability of the liver grafts procured from NHBDs.     

The effects of hyperbaric oxygen on free flaps in rats

The effects of hyperbaric oxygen on survival were investigated in free flaps and island flaps. Skin flaps transplanted following 18, 21, and 24 hours of preservation at 24 degrees C demonstrated survival rates of 20%, 10%, and 0%, respectively. Treatment with hyperbaric 100% oxygen improved the survival rates to 66%, 67%, and 40%. A preservation time of 21 to 24 hours at room temperature appears to be the threshold of irreversible ischemic damage. In acute island flaps, flap survival was improved significantly from 35% to 53% and 64% of the random flap area by preoperative or postoperative treatment, respectively. Prolonged preoperative and postoperative treatment improved survival to 66%.     

Beneficial effects of administering intraportal prostaglandin E1 postoperatively to hepatectomy patients with massive intraoperative blood loss

Massive intraoperative blood loss is a major cause of complications following hepatectomy. To evaluate the efficacy of intraportal prostaglandin E₁ (PGE₁) for preventing liver deterioration in hepatectomy patients with an intraoperative blood loss of over 2000 ml, a retrospective analysis was conducted on 10 patients given intraportal PGE₁ (portal group), 6 given intravenous PGE₁ (venous group), and 10 given no treatment (control group). PGE₁ was infused at 250 or 500 g/day in the portal group and at 720 g/day in the venous group, and continued for 3 days postoperatively. Alanine aminotransferase (ALT) and total bilirubin (T.Bil) were measured on postoperative days (PODs) 1, 3, 5, and 7. ALT was lower in the portal group than in the other two groups on each POD, and significantly lower than in the control group on POD 3 (P<0.05). T.Bil was significantly lower in the portal group than in the control group on PODs 5 and 7 (P<0.05). T.Bil on POD 7 was under 1.5 mg/dl in 1 (10.0%), 6 (60.0%), and 2 (33.3%) of the control, portal, and venous group patients, respectively, with a significant difference between the control and portal groups (P<0.05). These results confirmed that intraportal PGE₁ was beneficial for improving hepatic function and preventing cholestasis in patients with a blood loss of over 2000 ml at risk of developing postoperative liver deterioration.     

高压氧后处理对大鼠神经病理性痛及脊髓小胶质细胞活化的影响

目的 探讨高压氧(hyperbaric oxygen,HBO)后处理对大鼠神经病理性疼痛(neuropathic pain,NP)镇痛效果及脊髓小胶质细胞活化的影响. 方法 雄性SD大鼠24只,采用随机数字表法将大鼠分成4组(每组6只):假手术组(S组)、坐骨神经慢性压迫组(C组)、HBO后处理2.0组(H2.0组)与HBO后处理2.5组(H2.5组).采用坐骨神经慢性压迫损伤法建立NP模型,H2.0和H2.5组于术后1d开始给予相应压力的HBO后处理,1次/d连续7次,每天出HBO舱后1h测定各组大鼠机械缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足反射潜伏期(thermal withdrawal latency,TWL),术后7d测定MWT和TWL后处死,用免疫组化法测定大鼠脊髓小胶质细胞的活化情况. 结果 与S组比较,C组MWT降低及TWL缩短,脊髓内小胶质细胞数量与活化率上升为(156±9)个和44.9％(P＜0.05);与C组比较,H2.0组和H2.5组MWT升高及TWL延长,H2.0组和小胶质细胞数量与活化率分别为(64±7)个和5.7％(P＜0.05),H2.5组小胶质细胞数量与活化率分别为(62±5)个和6.1％(P＜0.05);H2.0组与H2.5组小胶质细胞数量与活化率差异无统计学意义(P＞0.05). 结论 HBO后处理可减轻大鼠NP,其机制与抑制脊髓内小胶质细胞活化有关.     

Beneficial effect of hyperbaric oxygen on island flaps subjected to secondary venous ischemia

The potential for hyperbaric oxygen therapy (HBO) to decrease the untoward effects of a secondary ischemic event was studied in the rat superficial epigastric flap model. The secondary venous ischemic flap was created by cross-clamping the vascular pedicles for 2 h. Twenty-four hours later, the flap was reelevated and the venous pedicle was occluded for 5 h. Thirty-two rats were divided into three groups. In experimental group 1, animals received HBO treatment immediately prior to the initial flap elevation and ischemia at 2 atmosphere pressures for 90 min. In experimental group 2, the rats underwent a similar course except for a second 90-min HBO course immediately prior to the secondary venous occlusion. The rats without HBO therapy were used as controls. The results showed that all control flaps were nonviable at 1 week by clinical inspection and fluorescein injection. Complete flap survival occurred in 20% of group 1 flaps and 30.8% of group 2 flaps. Partial flap survival occurred in the rest of the flaps in these two groups, with mean survival areas of 48% and 55%, respectively. In conclusion, HBO treatments significantly increase the survival of flaps subjected to a secondary ischemia, even if administered before the primary ischemia. Administering HBO prior to secondary venous ischemia was marginal, which may be due to the effect of O(2) given by HBO not lasting longer than 5 h.     

Beneficial effects of arterialization of the portal vein on extended hepatectomy

BACKGROUND: Extended hepatectomy may result in postoperative liver failure. The aim of this study was to evaluate the effects of arterialization of the portal vein on oxygen supply, hepatic energy metabolism and liver regeneration after extended hepatectomy. METHODS: Portal haemodynamics were evaluated 0 or 10 days after arterialization of the portal vein in three experimental groups: 85 per cent partial hepatectomy, 85 per cent partial hepatectomy 10 days after arterialization of the portal vein and 85 per cent partial hepatectomy 10 days after ligation of the hepatic artery. Survival rates, weight of the regenerating liver, levels of adenine nucleotides and hepatic energy charge were assessed. RESULTS: Arterialization of the portal vein caused a significant increase in partial pressure of oxygen and oxygen saturation. Portal blood flow 10 days after arterialization was significantly increased. Survival rate and weight of the regenerating liver in the group with arterialization of the portal vein were significantly higher than those in the other two groups. The group with arterialization of the portal vein showed the highest levels of adenosine 5'-triphosphate. CONCLUSION: The increase in portal blood flow and oxygen supply produced by arterialization of the portal vein has beneficial effects on hepatic energy metabolism and liver regeneration, and leads to improved survival after experimental extended hepatectomy.     

Ultrastructural changes in the hepatocytes following massive hepatectomy in rats

This study was carried out to investigate the ultrastructural changes of the hepatocytes of the remnant liver after 70% hepatectomy in rats. The remnant liver regained the preoperative weight one week after hepatectomy. During this early posthepatectomy period, the volume of the each hepatocytes increased to a peak 48 hours after hepatectomy, then returned to normal within one week. Electronmicroscopically mitochondria of the hepatocytes became swollen and the cristae were shortened until 3 hours after hepatectomy. Dividing mitochondria were also observed in the initial 2 hours. The volume density of the mitochondria measured as a percentage of the mitochondrial volume per the cytoplasmic volume of hepatocytes. It increased and reached a peak 3 hours after hepatectomy (p less than 0.05) and thereafter returned to the same value as the control within 6 hours. Then it gradually decreased until 7th day (p less than 0.001). The volume density of lipid droplets increased to a peak 48 hours after hepatectomy (p less than 0.01). These significant ultrastructural changes of the hepatocytes indicate an important roles of mitochondria especially in the energy metabolism in the early posthepatectomy period.     

Effect of hyperbaric oxygen on the ligament healing process in rats

Animal experiments were done to investigate whether administration of hyperbaric oxygen promotes scar tissue formation, increases expression of the Type I procollagen gene, and improves the tensile properties of healing ligament. In 76 Sprague-Dawley rats, a 2-mm segment of the medial collateral ligament was removed. Thirty-eight rats were exposed to hyperbaric oxygen at 2.5 atmospheres absolute for 2 hours 5 days per week (Group H), whereas the remaining rats were exposed to room air (Group C). The animals were sacrificed at 3, 7, 14, and 28 days postoperatively. In situ hybridization histochemistry was done to examine the Type I procollagen gene expression in healing ligaments in 40 rats, whereas a tensile failure test was done in the remaining rats. The amount of scar tissue was greater in Group H than in Group C. Type I procollagen gene expression at 7 or 14 days was significantly greater in Group H than in Group C. The ultimate load and stiffness in Group H were significantly greater than in Group C at 14 days. Administration of hyperbaric oxygen promotes scar tissue formation and increases Type I procollagen gene expression in healing ligaments. These effects are associated with the improvement of their tensile properties.     

The effects of zoledronic acid and hyperbaric oxygen on posterior lumbar fusion in a rabbit model

We studied the effects of hyperbaric oxygen (HBO) and zoledronic acid (ZA) on posterior lumbar fusion using a validated animal model. A total of 40 New Zealand white rabbits underwent posterior lumbar fusion at L5-6 with autogenous iliac bone grafting. They were divided randomly into four groups as follows: group 1, control; group 2, HBO (2.4 atm for two hours daily); group 3, local ZA (20 μg of ZA mixed with bone graft); and group 4, combined HBO and local ZA. All the animals were killed six weeks after surgery and the fusion segments were subjected to radiological analysis, manual palpation, biomechanical testing and histological examination. Five rabbits died within two weeks of operation. Thus, 35 rabbits (eight in group 1 and nine in groups 2, 3 and 4) completed the study. The rates of fusion in groups 3 and 4 (p = 0.015) were higher than in group 1 (p < 0.001) in terms of radiological analysis and in group 4 was higher than in group 1 with regard to manual palpation (p = 0.015). We found a statistically significant difference in the biomechanical analysis between groups 1 and 4 (p = 0.024). Histological examination also showed a statistically significant difference between groups 1 and 4 (p = 0.036). Our results suggest that local ZA combined with HBO may improve the success rate in posterior lumbar spinal fusion.     

Effects of hyperbaric oxygen therapy on caustic esophageal injury in rats

Background/purpose

Caustic esophageal burn is a serious problem in pediatric surgery. Even though many clinical and experimental studies had been performed, the complication rate could not be reduced to a satisfying level. In this study, the authors evaluated the effects of hyperbaric oxygen (HBO) therapy in caustic esophageal burn in rats.

Methods

Rats were divided into 4 groups, and caustic burn at the distal esophagus was created by applying 50% NaOH for 3 minutes in all groups. The first and third groups did not receive HBO therapy. HBO therapy was applied to the second group for 2 days and to the fourth group for 28 days. To evaluate the effects of short-term HBO therapy, the first 2 groups were compared for ulceration, inflammation, and submucosal vascular thrombosis after 2 days. The third and fourth groups were compared for the long-term effects of HBO therapy. Rats in these groups were killed after 28 days and compared for the collagen content, weight, and mortality rate.

Results

In the second group, which received 2 days of HBO therapy, ulcer depth and vascular thrombosis were significantly lower than these in the first group (P = .022 and P = .020, respectively). The fourth group, which received 4 weeks of HBO therapy, had a significantly reduced mortality rate, weight loss, and collagen score and hydroxyproline level if compared with the third group (P = .035; P = .016; P = .028; and P = .033, respectively).

Conclusions

These results indicate that HBO therapy is useful in caustic esophageal burn both in short-term and long-term use.     

Effects of supplemental oxygen and hyperbaric oxygen on tendon healing in a rat model

Systemic supplemental oxygen therapy (SOT) and hyperbaric oxygen therapy (HBOT) have been shown to positively impact wound healing. The purpose of this study was to evaluate the effects of SOT and HBOT on tendon healing in a rat tendon model. The right patellar tendon of 90 male Sprague-Dawley rats was completely sectioned. Animals were randomized to receive HBOT, SOT, or room air therapy. Animals were sacrificed at 3- and 6-weeks postoperatively. The ultimate tensile strength in axial extension was compared between groups. Statistical significance was calculated using the Student's t-test. The SOT group exhibited the highest tensile strength at both time-points, although HBOT was the only treatment that exhibited a statistically significant increase in tensile strength between time-periods (p = 0.006). There was no statistical difference in ultimate tensile strength when the three groups were compared at the 3- or 6-week time-points. Results presented here cannot support the premise that intermittent HBOT or SOT significantly increases the healing of tendon repairs.     

Potential effects of hyperbaric oxygen therapy in acute pancreatitis

BACKGROUND: To extract from the biomedical published reports, the effects of hyperbaric oxygen (HBO) on inflammatory disease, in particular acute pancreatitis. METHODS: This review will explain these effects and evaluate potential mechanisms of action of HBO in acute pancreatitis. A Medline/PubMed search (January 1966 to July 2004) with manual cross-referencing was conducted, including all relevant articles investigating the molecular and systemic effects of HBO on inflammatory diseases, particularly focusing on the studies of acute pancreatitis. All publication types, languages and subsets were searched. RESULTS: Original and review articles and short communications were extracted. The selected original articles covered the molecular and systemic effects of HBO and the effects in inflammatory disease states. The major findings are that HBO can act as an anti-inflammatory agent and as an antimicrobial agent. Many of the effects of HBO would be beneficial in the treatment of acute severe pancreatitis. Work carried out to date in animal models of acute pancreatitis shows promising improvements in severity but studies are limited to date. CONCLUSION: Acute pancreatitis impairs the pancreatic and systemic microcirculation and causes acute inflammation. These processes are potentially improved by HBO therapy.     

Effect of hyperbaric oxygen on liver regeneration in a rat model

Hyperbaric oxygen therapy is a treatment that has been gradually implemented for the treatment of several pathologic conditions. The present study evaluated the effect of hyperbaric oxygen therapy for hepatic regeneration and its relationship to mitochondrial function. Male Wistar rats underwent partial hepatectomy (70%) and subsequently underwent two sessions of hyperbaric oxygen (90 minutes each, at a pressure of 2 ATA). The animals were sacrificed at 24 and 48 hours after surgery. Hepatic regeneration was evaluated by the dry weight of the remaining liver, the hepatic regeneration rate, the hepatic DNA content, and the hepatocyte proliferation rate using the "proliferating cell nuclear antigen" (PCNA) content. Function of the mitochondria was evaluated by its oxygen consumption during respiratory states 3 and 4, its respiratory control ratio (RCR), its membrane potential, as well as its osmotic swelling. We also measured serum levels of aminotransferases. The results revealed an increased dry weight of the remaining liver, regeneration rate, and DNA content at 24 and 48 hours after hepatectomy. The hepatocyte proliferation rate was significantly higher among animals treated with hyperbaric oxygen therapy at 48 hours after surgery. There was no significant difference in aminotransferase levels. Mitochondrial respiration revealed reduced oxygen consumption in state 3 after 48 hours. These results demonstrated that hyperbaric oxygen stimulates hepatic regeneration at 24 and 48 hours after 70% hepatectomy. The effect of hyperbaric oxygen on hepatic tissue occurs without tissue damage and protects mitochondria after 48 hours.     

Effect of hyperbaric oxygen on survival of composite grafts in rats.

Most treatment with hyperbaric oxygen (HBO) in plastic surgery is for wounds, burns, crush injuries, and infections. We aimed to find out if HBO increases the survival of composite grafts in rats. Twenty Sprague-Dawley rats were randomly assigned to two equal groups (treatment and control). A template 30 x 30 mm was placed on the skin and a composite graft taken from the upper back was harvested and then resutured to the fascia in situ. The treated group was placed in a hyperbaric chamber set at 202 kPa and 100% oxygen for 90 minutes daily for two weeks. Control animals were given no treatment. After death the mean surviving internal surface area of the graft was 372.5 (117.9) mm2 in the control group and 561.3 (85.7) mm2 in the experimental group (p=0.001). Treatment with HBO improved the surviving area of composite grafts in rats, and the beneficial effect was prominent only on the inner surface of the graft.     

高压氧对大白鼠颈动脉吻合口愈合的影响

目的　观察高压氧对大白鼠颈动脉吻合口愈合的影响。方法　 3 6只SD大白鼠 ,建立切断颈动脉后再吻合的模型。实验组 :术后高压氧治疗共 2 4只大鼠。对照组 :术后不作处理共 12只大鼠。术后 1、3、5、7d 4个时间组处死动物 ,取颈动脉样本 ,行光镜和免疫组化观察。用计算机图像分析系统比较血管各层的厚度。结果　术后 1、3d两组颈动脉内膜、中膜和外膜的厚度 ,无明显差别 (P >0 .0 5 )。术后7d ,对照组颈动脉中膜、外膜的厚度均大于实验组 (P <0 .0 5、P <0 .0 1)。免疫组化结果证实对照组的外膜有明显的炎症反应及纤维母细胞增生。结论　高压氧可减少炎症和纤维母细胞的增生 ,有促进动脉吻合口的愈合作用。