Oxygen Hyperbaric Pressure Therapy (OHPT) for Decubitus Ulcers

Aim:  This study aims to establish a pressure ulcers model that visualizes the microcirculation, and to examine the participation of ischemia‐reperfusion injury in the pathophysiology of pressure ulcers.
Methods:  An original system composed of a new skinfold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia‐reperfusion injury, animals were divided into two groups: the compression‐release group in which the animals received four cycles of compression‐release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day1 (35 hours) after the first evaluation.
Results and Conclusions:  The cyclic compression‐release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia‐reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. The finding supports the significant contribution of ischemia‐reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.     

AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

In vivo analysis of microcirculation following closed soft-tissue injury.

Major loss of tissue is an almost invariable consequence of severe closed soft-tissue injury. Clinically, the extent of soft-tissue trauma determines the outcome of complex injuries and significantly influences bone healing. With use of a new animal model, this study quantitatively analyzed microcirculation, i.e., nutritive perfusion and leukocyte-endothelial cell interaction, in skeletal muscle after standardized closed soft-tissue injury. By means of a computer-assisted controlled-impact technique, a severe standardized closed soft-tissue injury was induced in the left hindlimb of 28 rats. The rats were assigned to four experimental groups (n = 7 per group) that differed by time of analysis (1.5, 24, 72, and 120 hours after injury); rats that were not injured served as controls (n = 7). Intramuscular pressure was measured, and microcirculation in the rat extensor digitorum longus muscle was analyzed by in vivo fluorescence microscopy, which allowed assessment of microvascular diameters, functional capillary density, number of rolling and adherent leukocytes in venules, and microvascular permeability. Edema weight gain was quantified by the ratio of wet to dry weight of the extensor digitorum longus muscle. Microvascular perfusion of the skeletal muscle was characterized by a significant reduction in functional capillary density, which was paralleled by an increase in capillary diameter throughout the 120 hours of observation when compared with the controls. Trauma-induced inflammatory response was reflected by a markedly increased rolling and adherence of leukocytes, primarily restricted to the endothelium of postcapillary venules; this was accompanied by increased microvascular permeability, indicative of a substantial loss of endothelial integrity. The microcirculation surrounding the core of the damaged tissue area resembled that of ischemia-reperfusion injury in skeletal muscle, i.e., heterogeneous capillary perfusion, pronounced microvascular leakage, and adherence of leukocytes. Enhanced vascular leakage and leukocyte adherence (24-72 hours after injury) coincided with the maximum intramuscular pressure (which was not indicative of compartment syndrome) and edema formation. These results demonstrate that initial changes, leading to ultimate tissue death, after closed soft-tissue injury are caused on the microcirculatory level. This standardized model provides further insight into microvascular pathophysiology and cellular interactions following closed soft-tissue injury. Thus, it is an adequate tool for testing novel therapeutic interventions.     

Development of a simple, noninvasive, clinically relevant model of pressure ulcers in the mouse.

The formation of pressure ulcers and other skin wounds is considered to be a multifactorial process. Cycles of ischemia-reperfusion have been considered to be significant contributing factors in the pathogenesis of pressure ulcers. This study reports the development of a reproducible murine model of ischemia-reperfusion injury by the external application of magnets. Mice were sedated with 50% CO2:50% O2 for 50-60 s. Dorsal hair was shaved and the area cleaned. The skin was gently pulled and placed between two round ceramic magnetic plates (5 x 12 mm diameter, 2.4 g weight, 1000 G magnetic force). The resultant "pinch" procedure was designed to leave a 5-mm skin bridge between the magnets, creating 50 mm Hg pressure between the plates. Three 12-h ischemia-reperfusion cycles were employed to cause pressure ulcer formation. Animals tolerated the procedure well. They returned to normal activity a few minutes after magnet placement. The lesions reached their maximum at 10 days postinjury. Full-thickness skin loss with damage and necrosis of subcutaneous tissue (ulcer stage 3) was observed in all cases, reaching a mean stage score of 3.6 +/- 0.6 of based on a 0-5 scale for extent of injury by visual assessment. Thus, an inexpensive, reproducible murine pressure ulcer model was developed, which results in graded injury without long-term immobilization of the animals. This method will facilitate the development of new prevention and management strategies.     

TNF-α、IL-1在I期压疮中的作用及表达

目的探讨促炎细胞因子TNF-α、IL-1在I期压疮中的作用及表达,为临床早期预防提供依据。方法将40只雄性SD大鼠按随机数字表法分为对照组和实验A、B、C、D组各8只。对照组不予压力,实验结束时施行安乐死;实验A、B、C、D组于大鼠双后肢建立压疮模型,均施加22.47kPa压力,形成缺血再灌注循环(施压2h后移开施压柱,让局部血流恢复0.5h后再施压,即为1个I/R),分别予以2个、3个、4个、5个I/R后再施行安乐死。光镜下观察皮肤肌肉组织病理变化,测定肌肉组织中TNF-α及IL-1含量、髓过氧化物酶(MPO)。结果实验A、B、C、D组皮肤、肌肉光镜下观察均出现炎性细胞浸润、水肿,且随着循环数的增加损伤逐渐加重;各实验组与对照组比较,差异有统计学意义(均P<0.01);实验组间TNF-α、ILV-1、MPO含量比较,差异有统计学意义(均P<0.01)。结论压疮形成过程中缺血再灌注损伤引起的炎性反应可加重组织细胞损伤,促炎细胞因子起着重要作用。     

A new chamber technique for intravital microscopic observations in the different soft tissue layers of mouse hindleg

BACKGROUND: A newly developed observation chamber has been designed for comfortable limb immobilization during intravital microscopic analysis, which permits direct, repeated, long-lasting observations of the microcirculation in the various hindleg soft tissues. METHODS: Experiments were performed under inhalation isoflurane/nitrous oxide anesthesia. Intravenously injected fluorescein isothiocyanate (FITC)-dextran (M, 150,000) and Rhodamine 6G (Sigma, St. Louis, MO) allowed for visualization of both microcirculatory phenomena in arterioles, capillaries, and venules and macrocirculatory structures as superficial saphenous artery and vein. Skin microcirculation analysis was performed from the epidermal side (group A, n = 7), whereas observation of deeper situated tissues was performed after oval skin excision on the medial surface of the tibial area (group B, n = 7). FITC-dextran (M, 150,000; group C, n = 8) injected into the foot pad permitted visualization of venous, arterial, and accompanying lymphatic vessels. With the aid of a computer-assisted microcirculation analysis system, functional capillary density, vessel diameter, edema formation, and leukocyte-endothelial cell interactions were evaluated. The ratio of rolling leukocytes, given as percentage of all leukocytes passing the vessel segment during a 30-second observation interval, and the number of sticking leukocytes per square millimeter of endothelial surface were determined. RESULTS: This new model allows the analysis of the complex in vivo changes of macro- and microcirculatory parameters in the different (venous, arterial, lymphatic) vessels of the covering tissues (skin and muscle) of the mouse hindleg. CONCLUSION: The potential applications of this technique include the study of mechanical trauma, ischemia-reperfusion injury, and tissue compression mimicking both acute and prolonged venous stasis on both the microcirculatory and macrocirculatory levels in the different tissue compartments.     

A chronic pressure ulcer model in the nude mouse

The pathophysiology of pressure ulcers is not yet fully understood. Widely used experimental models lead to pressure ulcers in the skin and the subcutaneous tissue only. The aim of the present study was to develop a clinically relevant deep pressure ulcer model in nude mice involving all relevant tissue layers. Balb/c nude mice were anesthetized and a steel disk was implanted under the great gluteus muscle. Full recovery was allowed for 10 days. Pressure was then periodically applied (2 hours compression, 1 hour recovery) using a Neodymium magnet in conjunction with the disk in the unanesthetized mouse. Cycles were repeated for 1, 4, 6, 8, or 10 times. Controls underwent the same procedure without placement of the magnet. The pressure ulcer grade was found to be cycle dependent,with the highest degree after 10 cycles. Histological evaluations revealed signs of necrosis in the skin and subcutaneous fat after four, and in the muscle after eight and 10 cycles of compression. Polymorphnuclear granulocyte infiltration in certain layers was found to be dependent on the number of cycles. We conclude that this clinically relevant nude mouse model can be used to investigate the mechanism of pressure ulcer development and to study new therapeutic approaches.     

Ischemia-reperfusion injury in chronic pressure ulcer formation: a skin model in the rat.

Most animal models of chronic pressure ulcers were designed to study only the role of ischemic injury in wound formation, often using single applications of constant pressure. The purpose of this study was to develop and characterize a reproducible model of cyclic ischemia-reperfusion injury in the skin of small un-anesthetized animals using clinically relevant pressures and durations. Ischemia-reperfusion injury was created in a 9 cm2 region of dorsal skin in male rats by periodically compressing skin under a pressure of 50 mm Hg using an implanted metal plate and an overlying magnet. We varied the total number of ischemia-reperfusion cycles, examined the effect of varying the frequency and duration of ischemic insult, and compared ischemia-induced injury to ischemia-reperfusion-induced injury with this model. Tissue injury increased with an increasing number of total ischemia-reperfusion cycles, duration of ischemia, and frequency of ischemia-reperfusion cycles. This model generates reproducible ischemia-reperfusion skin injury as characterized by tissue necrosis, wound thickness, leukocyte infiltration, transcutaneous oxygen tension, and wound blood flow. Using this model, the biological markers of ischemia-reperfusion-induced wound development can be studied and therapeutic interventions can be evaluated in a cost-effective manner.     

Effects of hypothermia and rewarming on the mucosal villus microcirculation and survival after rat intestinal ischemia-reperfusion injury

OBJECTIVE: To determine the effects of hypothermia and rewarming on changes in the villus microcirculation induced by intestinal ischemia-reperfusion (I/R). SUMMARY BACKGROUND DATA: The small intestine is extremely sensitive to I/R injury, and although hypothermia can reduce cellular injury, its capacity to influence the villous microcirculation after intestinal I/R is unclear, especially after the return to normothermic conditions. METHODS: Core body temperature of PVG rats was maintained at either 36 degrees to 38 degrees C (n = 12) or 30 degrees to 32 degrees C (n = 24) and then subjected to 30 minutes of intestinal ischemia. A subgroup of hypothermic animals (n = 12) were returned to normothermic conditions 120 minutes after clamp removal. The mucosal surface was visualized in an exteriorized ileal segment and macromolecular leak (MML) and leukocyte adhesion were monitored using in vivo microscopy (n = 6 in each group). MML from individual villi and numbers of adherent leukocytes within villi were determined for 2 to 4 hours after clamp removal. Heart rate and mean blood pressure were monitored in all animals. Control animals underwent sham surgery (n = 12). RESULTS: Ten of 12 normothermic animals failed to survive the reperfusion period, whereas all hypothermic animals and 11 of 12 of the hypothermic animals that were returned to normothermic conditions survived. MML was significantly increased in all animals subjected to I/R, although leakage was more marked in animals subjected to continuous normothermia. Enhanced leukocyte adhesion and decreased blood flow were observed only in normothermic animals. CONCLUSIONS: Hypothermia might prove to be an effective strategy for preventing adverse side effects in clinical settings in which intestinal I/R can be predicted.     

Effect of age, impaction types and operative time on inflammatory tissue reactions following lower third molar surgery

Objective

It is widely known that stress conditioning can protect microcirculation and induce the release of vasoactive factors for a period of several hours. Little, however, is known about the long-term effects of stress conditioning on microcirculation, especially on the microcirculation of the periosteum of the calvaria. For this reason, we used intravital fluorescence microscopy to investigate the effects of heat shock priming on the microcirculation of the periosteum over a period of several days.

Methods

Fifty-two Lewis rats were randomized into eight groups. Six groups underwent heat shock priming of the periosteum of the calvaria at 42.5°C, two of them (n = 8) for 15 minutes, two (n = 8) for 25 minutes and two (n = 8) for 35 minutes. After 24 hours, a periosteal chamber was implanted into the heads of the animals of one of each of the two groups mentioned above. Microcirculation and inflammatory responses were studied repeatedly over a period of 14 days using intravital fluorescence microscopy. The expression of heat shock protein (HSP) 70 was examined by immunohistochemistry in three further groups 24 hours after a 15-minute (n = 5), a 25-minute (n = 5) or a 35-minute (n = 5) heat shock treatment. Two groups that did not undergo priming were used as controls. One control group (n = 8) was investigated by intravital microscopy and the other (n = 5) by immunohistochemistry.

Results

During the entire observation period of 14 days, the periosteal chambers revealed physiological microcirculation of the periosteum of the calvaria without perfusion failures. A significant (p < 0.05) and continuous increase in functional capillary density was noted from day 5 to day 14 after 25-minute heat shock priming. Whereas a 15-minute exposure did not lead to an increase in functional capillary density, 35-minute priming caused a significant but reversible perfusion failure in capillaries. Non-perfused capillaries in the 35-minute treatment group were reperfused by day 10. Immunohistochemistry demonstrated an increase in cytoprotective HSP70 expression in the periosteum after a 15-minute and a 35-minute heat shock pretreatment when compared with the control group. The level of HSP70 expression that was measured in the periosteum after 25 minutes of treatment was significantly higher than the levels observed after 15 or 35 minutes of heat shock exposure.

Conclusion

A few days after heat shock priming over an appropriate period of time, a continuous increase in functional capillary density is seen in the periosteum of the calvaria. This increase in perfusion appears to be the result of the induction of angiogenesis.     

Perfluorocarbon in microcirculation during ischemia reperfusion

BACKGROUND: The effects of perfluorocarbon (PFC) emulsions administered at a nonhemodiluting dose were studied in the hamster window chamber model to determine the difference in ischemia-reperfusion injury associated with PFC delivery before and after an ischemic episode. STUDY DESIGN: Ischemia was induced by compressing the periphery of the window chamber for 1 hour. Vessel diameter, red blood cell velocity, rolling and adherent leukocytes, and functional capillary density (FCD) were assessed by intravital microscopy. The animals received an infusion (10% blood volume) of PFC emulsion or equivalent volumes of saline, before or after ischemia. Two groups were studied in each experimental protocol: A, infusion after ischemia; and B, infusion before ischemia, where a fraction of the infused material stagnated in the ischemic zone during the occlusion time. Measurements were made before induced ischemia and at 0.5, 2, and 24 hours of reperfusion. RESULTS: Animals treated with PFC after ischemia had substantially decreased leukocytes rolling and sticking in postcapillary venules and recovered functional capillary density and blood flow when compared with saline-treated controls. Conversely, administration of PFC before ischemia considerably reduced functional capillary density and increased leukocyte activation after reperfusion. CONCLUSIONS: Results indicate that PFC without stagnation within an ischemic zone attenuates postischemic reperfusion injury of striated skin muscle, presumably through the reduction of leukocyte-endothelial cell interactions. Accordingly, PFC effects on ischemia-reperfusion injury are determined mainly by the time of administration relative to the ischemic episodes.     

Attenuation of renal ischemia-reperfusion injury with selectin inhibition in a rabbit model

BACKGROUND: The selectin glycoproteins are involved in the pathogenesis of renal ischemia-reperfusion injury. We investigated the ability of glycyrrhizin, a known selectin inhibitor, to attenuate renal ischemia-reperfusion injury. METHODS: Eighteen New Zealand white rabbits underwent midline laparotomy with renal artery cross-clamping. After 30 minutes of reperfusion, group 1 (control, n = 10) animals received a saline infusion, while group 2 (GLY, n = 8) animals received a glycyrrhizin infusion. Renal function was compared between the two groups after 72 hours of reperfusion. A t test was utilized, with alpha set at P<0.05. RESULTS: Group 1 and group 2 animals had similar baseline renal function. However, after 72 hours of reperfusion, group 1 animals had a significantly higher mean blood urea nitrogen creatinine ratio than group 2 animals (P<0.01), indicating preserved renal function in rabbits treated with glycyrrhizin. CONCLUSIONS: Selectin blockade using glycyrrhizin attenuates renal ischemia-reperfusion injury when given 30 minutes after the onset of reperfusion in a rabbit model.     

左旋精氨酸对再灌注期大鼠提睾肌微循环的作用

目的 探讨再灌注期肌瓣微循环的变化及其与NO的关系。方法 以体重180－220g雄性SD大鼠,制成大鼠提睾肌缺血再灌注模型（热缺血5h,再灌注2h）,应用电视显微影像系统,观察缺血再灌注期肌瓣微循环的变化。结果 ①再灌注期左旋精氨酸（L－arg)治疗组微动脉复流率较对照组明显增高（P＜0．01）,对照组于再灌注30min微动脉复流率最低,仅为53％。②再灌注期L－arg能使复流之微动脉A1、A2的血管收缩幅度明显减小（P＜0．05）,血管流速明显加快,毛细血管的灌流密度显著增加。③再灌注期微静脉内皮细胞受损,静脉回流障碍,局部形成一种“只灌不流”的病理现象,使肌瓣组织出现大片明显的漏出性出血。结论 NO生成剂能够扩张微动脉,疏通肌瓣的微循环,改善组织的灌 流;再灌注期微静脉回流障碍可能是造成组织损伤的重要因素。     

Pharmacological preconditioning of rat liver by up-regulation of heme oxygenase 1

PURPOSE: We investigated whether pharmacologically induced up-regulation of heme oxygenase 1 by pyrrolidine dithiocarbamate (PDTC) conferred protection against subsequent ischemia-reperfusion injury (IRI) to the rat liver after temporary vascular occlusion of 70% of the organ. METHODS: Female Wistar rats (200 to 250 g body weight) anesthetized with pentobarbitone were cannulated in the carotid artery and jugular vein. After laparotomy, a rubber band was applied around the entire vascular supply to the median and left lateral lobes, enabling vascular occlusion of 70% of the liver. A laser Doppler miniprobe was placed on the left lateral lobe to monitor peripheral liver blood flow (PLBF). Immediately upon completion of the surgery, the rats were administered either PDTC (50 mg/kg intravenously; n = 8) or its solvent (isotonic NaCl; n = 8). After 60 minutes, regional ischemia was induced for 30 minutes. The animals were then monitored for 2 hours of reperfusion. Blood samples for alanine transferase (ALT) estimation (as a measure of parenchymal injury) were drawn immediately prior to ischemia and reperfusion, as well as 60 and 120 minutes after reperfusion; PLBF was calculated at these times. RESULTS: ALT increased in the course of the experiments but there was no difference between the groups. The reduction in PBLF due to ischemia-reperfusion was significantly lower in the PDTC group: about 16% versus 40%, after 2 hours of reperfusion. CONCLUSION: Pretreatment with PDTC attenuated the disturbance of hepatic microcirculation, but not parenchymal injury, in the early phase of IRI.     

Microcirculation in mixed arterial/venous ulcers and the surrounding skin: Clinical study using a laser Doppler perfusion imager and capillary microscopy

To treat mixed skin ulcers effectively, it is important to investigate skin microcirculation in greater detail. Therefore, we used laser Doppler perfusion imaging and capillary microscopy for assessing both subpapillary and nutritive microcirculation in four defined regions of the skin in 17 patients with mixed ulcers caused by a combination of peripheral arterial occlusive disease and chronic venous insufficiency. Laser Doppler area flux was significantly higher in the ulcer areas than in the areas without granulation tissue and those in intact skin. The flux in the scars was higher than that in the intact skin or in the ulcer areas without granulation tissue. Capillary density in the intact skin was higher than the densities in nongranulation tissue areas, granulation areas, and scar areas ( p <0.001 for all comparisons). To conclude, the ulcer areas without granulation tissue did not show a healing tendency due to poor subpapillary and nutritive perfusion; the granulation tissue exhibited high subpapillary perfusion as a sign of healing. In the scars, sufficient blood supply could be detected in both layers as a sign of an almost complete healing process. Blood supply in the intact skin is, however, already affected by distorted microcirculation in the ulcers.     

Transplantation of preconditioned intestinal grafts is associated with lower inflammatory activation and remote organ injury in rats

Reperfused grafts--particularly the intestine--release free radicals and cytokines into the systemic circulation. The type of discharge, which is greatly dependent on the local injury, may also induce inflammatory activation in distant organs and leading to multiple system and organ failure. It has been suggested that intestinal grafts from tacrolimus (TRL)-pretreated donors show improved morphology and microcirculation. We studied whether transplantation of intestines from TRL-pretreated donors influenced inflammatory response and remote organ injury posttransplantation. Donor Sprague Dawley rats received TRL or saline (controls) intravenously at 6 hours prior to graft harvest. The intestinal grafts were preserved in saline for 3 hours before transplantation. At 6 and 12 hours postreperfusion hepatic and renal cortical microcirculation were assessed using laser-Doppler flowmetry (n = 8-12 per group). Blood pressure was measured; liver, kidney, and serum samples were obtained. We analyzed hepatic and renal ICAM-1 expression and caspase-3-like activity as well as plasma content of tumor necrosis factor-alpha and interleukin-6. Pretreated graft recipients had higher mean arterial pressure (82 +/- 10 vs 51 +/- 17 mm Hg, P < .05) and renal perfusion at 6 hours whereas liver perfusion was similar at both 6 and 12 hours. Liver and renal functions were also superior among recipients of pretreated grafts. Both caspase-3-like activity and ICAM-1 expression in liver and kidney were lower in pretreated graft recipients. Plasma IL-6 levels were lower in animals receiving pretreated grafts. Transplantation of intestines from TRL-pretreated donors was followed by a lower systemic inflammatory response, improved organ function and decreased remote injury early posttransplantation compared with animals receiving grafts from untreated donors.     

Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates

BACKGROUND: We previously demonstrated that therapy with a new endothelin A receptor antagonist (ET-RA) significantly reduced mortality rates in severe acute pancreatitis (AP) in the rat without attenuating local signs of disease severity (intrapancreatic protease activation, acinar cell necrosis). This raised the question as to why ET-RA was so effective. The purpose of this study was to assess the effect of ET-RA on microcirculation (particularly capillary permeability) within and outside of the pancreas on intravascular fluid loss and extravascular fluid sequestration and on distant organ function. METHODS: Severe AP was induced in rats by standardized intraductal bile acid infusion and cerulein hyper-stimulation. Starting 6 hours (n = 24 rats) and 12 hours (n = 30 rats) after the onset of AP, animals randomly received either the ET-RA (LU-135252) or saline solution with fluid resuscitation (6 mL/kg/h Ringer's lactate). At 24 hours, animals were relaparotomized for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Further monitoring included cardiorespiratory and renal parameters, hematocrit levels and quantification of ascites and pleural effusions, and acinar cell necrosis at autopsy. Groups of sham-operated healthy animals (n = 6 animals each) that had been treated according to the same protocol served as control animals. RESULTS: ET-RA treatment that was started 6 hours after AP-induction significantly decreased hematocrit levels (38% +/- 1% vs 45% +/- 2% with saline solution treatment), reduced ascites and pleural effusions (6.7 +/- 1.3 mL vs 11.9 +/- 1.3 mL), and improved urine production (4.8 +/- 0.5 mL vs 2.9 +/- 0.6 mL) and respiratory parameters. Moreover, all microcirculatory parameters were improved; in particular, capillary permeability was stabilized (158% +/- 9% vs 248% +/- 8% in the colon). These beneficial effects were also seen when therapy was delayed until 12 hours after AP induction. Pancreatic necrosis was not significantly reduced. The overall mortality rate was 12% in ET-RA-treated animals and 42% in saline solution-treated control animals (P <.05). In healthy animals ET-RA did not significantly alter the target parameters, except for a reduction of capillary permeability in the pancreas. CONCLUSIONS: Improved microcirculation and stabilized capillary permeability in ET-RA-treated animals together with reduced intravascular fluid loss and extravascular fluid sequestration and improved renal and pulmonary function (1) may explain improved survival in this model, (2) support the hypothesis that systemic disease sequelae significantly contribute to outcome in AP, and (3) suggest that ET-RA may be a promising therapeutic tool in AP because it counteracts microcirculatory disorders that contribute to pancreatitis-associated organ dysfunction even when therapy is delayed to a point at which pancreatic injury may no longer be influenced.     

Changes of microcirculation dynamics in the formation of edema following spinal compression injury in rabbits

The changes in microcirculation dynamics were investigated, after giving acute compression to the spinal cord in rabbits. When the 8th thoracic cord was compressed for one minute with a plummet weighing 50g, paraparesis occurred, from which the animals could recovered within two weeks. The blood flow at the compressed region, determined by the hydrogen clearance method, one hour after the injury was increased to 154% of the pre-injury level, while the flow was reduced by 22% six hours later. The vascular permeability, estimated by the fluorescein method, was found to be 3.3 times greater in the injured animals than that in controls only at one hour after compression. The water contents of the spinal cord, determined by the dry weight method, were gradually increased up to six hours. These results suggest that vasogenic edema due to the primary damage to the vascular system in the spinal cord may occur within one hour of the compression and cytotoxic edema may appear six hours later.     

银杏叶提取物对体外肺缺血再灌注损伤保护作用的实验观察

目的:探讨银杏叶提取物对体外肺缺血再灌注损伤的保护作用.方法:按肺移植供肺获取和保存方法,对30只家兔的肺进行获取、保存,然后采用体外循环装置,建立体外肺缺血再灌注损伤模型.分3组,分别在手术前30 min从耳背静脉注入生理盐水、PGE1、银杏叶提取物.结果:银杏叶提取物和PGE1均可使肺组织中超氧化物歧化酶(SOD)含量升高,丙二醛(MDA)含量降低;使肺动脉压(PAP)降低,肺组织湿干重比降低;降低肺组织中的凋亡细胞数和改善肺组织病理变化.银杏叶提取物组的上述指标均优于对照组和PGE1组.结论:银杏叶提取物对肺缺血再灌注损伤有显著的保护作用.