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M M Gebhard

Publications and source records attributed to M M Gebhard.

At least 19 recordsLinked to original sources

Development and evaluation of a training module for the clinical introduction of the da Vinci robotic system in visceral and vascular surgery.

BACKGROUND: With the increasing use of the surgical robotic system in the clinical arena, appropriate training programs and assessment systems need to be established for mastery of this new technology. The authors aimed to design and evaluate a clinic-like training program for the clinical introduction of the da Vinci robotic system in visceral and vascular surgery. METHODS: Four trainees with different surgical levels of experience participated in this study using the da Vinci telemanipulator. Each participant started with an initial evaluation stage composed of standardized visceral and vascular operations (cholecystectomy, gastrotomy, anastomosis of the small intestine, and anastomosis of the aorta) in a porcine model. Then the participants went on to the training stage with the rat model, performing standardized visceral and vascular operations (gastrotomy, anastomosis of the large and small intestines, and anastomosis of the aorta) four times in four rats. The final evaluation stage was again identical to the initial stage. The operative times, the number of complications, and the performance quality of the participants were compared between the two evaluation stages to assess the impact of the training stage on the results. RESULTS: The operative times in the final evaluation stage were considerably shorter than in the initial evaluation stage and, except for cholecystectomies, all the differences reached statistical significance. Also, significantly fewer complications and improved quality for each operation in the final evaluation stage were documented, as compared with their counterparts in the initial evaluation stage. These improvements were recorded at each level of experience. CONCLUSIONS: The presented experimental small and large animal model is a standardized and reproducible training method for robotic surgery that allows evaluation of the surgical performance while shortening and optimizing the learning-curve.

Animals↗

Intravital microscopy of pulmonary microcirculation after single lung transplantation in pigs.

BACKGROUND: Pulmonary reperfusion injury is a significant risk factor following lung transplantation (LTx). Unfortunately, in vivo observations and quantitative analyses of the pulmonary microcirculation following LTx are technically demanding. METHODS: Pigs, weighing 18 to 22 kg, served as the laboratory animals. The left lung was harvested and preserved using donor aortic vessel segments, the pulmonary artery, and the cuff of the lung veins were extended. After 4 hours of ischemia, the lungs were transplanted by direct connection of the conduits to the left atrial appendage and the left pulmonary artery of the recipient. The lungs were placed extrathoracically and ventilated. The recipient left lung was excluded. With this procedure, mechanical trauma to the lung and moving artefacts were avoided. Intravital microscopic observation became feasible. RESULTS: Following reperfusion, oxygenation of pulmonary venous blood was excellent. However, blood flow distribution was significantly reduced to the transplanted lung compared with the native right recipient lung. Pulmonary vascular resistance was significantly increased, dropping from 3500 to 1000 dynes x s x cm(-5) during reperfusion compared to a value of 500 for the native right lung. The pulmonary microcirculation showed a significant number of no-reflow areas with extremely reduced red blood cell velocities. Greater than 90% of microvessels (<30 microm) showed velocities below 0.1 mm/sec. In conclusion, microvascular injury seems to be a major pathogenic factor for the development reperfusion failure. Quantification of alterations within the microvasculature may shed light on various treatment modalities that reduce perfusion failure.

Animals↗

Evaluation of microperfusion disturbances in the transplanted liver after Kupffer cell destruction using GdCl3: an experimental porcine study.

BACKGROUND: Organ function after liver transplantation is determined by ischemia-reperfusion injury. Destruction of Kupffer cells with gadolinium chloride (GdCl3) has been shown to have a possible preventive effect on the extent of this injury, which can be extrapolated by analyzing the distribution of hepatic microperfusion. The aim of this study was to evaluate the protective effect of GdCl3 on disturbances of microperfusion in the transplanted liver. METHODS: Landrace pigs were randomly divided into three groups. In the control group (CG; n=6) a mapping of the native liver was conducted. For mapping, the four hepatic liver lobes were named from right to left with A to D and every lobe was divided into three vertical segments (cranial, medial, and caudal). In each of these 12 areas, microperfusion was quantified using a thermodiffusion probe (TD [mL/100 g/min]). The other two groups were considered as transplanted treated group (TTG; n=10) and transplanted nontreated group (TnTG; n=10). The TTG received an infusion of 20 mg/kg GdCl3 intravenously 24 hours before organ harvesting. Then standardized orthotopic liver transplantation was performed. In TnTG, standardized orthotopic liver transplantation was carried out without prior GdCl3 injection. In the recipients, the microperfusion of transplanted livers were mapped in both TnTG and TTG, in two different time points (1 hour [n=5] and 24 hours (n=5]) after reperfusion. RESULTS: A significant reduction of macrophages in the TTG livers in comparison to the CG and TnTG livers was observed (P<.05). However, the number of macrophages in CG and TnTG livers showed no significant difference (P>.05). Regarding liver microperfusion, in TnTG, a marked heterogeneity was detected in the livers after reperfusion. Significant differences between liver lobes (horizontal planes; P=.032) and vertical layers of intralobar liver parenchyma (P=.029) were observed. The same pattern was seen in TTG livers after reperfusion and a significant difference between horizontal (P=.024) and vertical layers (P=.018) of liver tissue were observed. Comparing intralobar regional flow data between vertical planes 24 hours after reperfusion still showed a prominent variation of hepatic tissue perfusion in TnTG livers (P=.028). Within the same horizontal layers, no significant differences between lobes were measured anymore (P=.16). Contrary to TnTG, in TTG, a homogenous pattern of regional liver tissue perfusion was recorded 24 hours after reperfusion. Comparison of TD data on the liver regions showed no significant microperfusion differences in either horizontal (P=.888) or vertical (P=.841) layers. CONCLUSIONS: Application of GdCl3 resulted in a significant reduction of Kupffer cells. Twenty four hours after transplantation microperfusion showed a homogeneous pattern, which constituted an earlier and better recovery of the transplanted liver. Therefore, destruction of Kupffer cells reduced ischemia-reperfusion injury and seemed to be responsible for the early recovery of microperfusion disturbances and thus for an improvement of graft function.

Animals↗

Surface contact measurement of electrical cell uncoupling in the mouse heart during ischemia.

Electrical cell uncoupling via gap junction closure is assumed to cause characteristic changes of the passive dielectric spectrum of ischemic heart tissue. In order to find an independent evidence for this assumption, we analysed heart tissue during ischemia, measured the open state of gap junctions by means of dye transfer and correlated this parameter with the time course of the dielectric permittivity. The hearts were pre-ischemically arrested by perfusion with Ringer solution containing 20 mmol/L of potassium (group KCL, n=10). This solution was also used with the addition of two gap junction blockers, either 3 mmol/L heptanol (group HEP, n=4) or 20 micromol/L palmitoleic acid (group PA, n=7). During subsequent ischemia at 21.0+/-0.5 degrees C, we monitored the passive dielectric permittivity spectrum and the spread of dye. After a sigmoidal increase the dielectric permittivity reached an upper plateau at 61+/-22 min of ischemia in KCL, at 45+/-7 min in PA, and already during perfusion at 2+/-1 min in group HEP. At the beginning of ischemia, dye migrated to neighbouring cells in groups KCL and PA but not in HEP. In KCL and PA, the intercellular diffusion of dye stopped after 64+/-26 and 40+/-11 min of ischemia, respectively. Our results suggest that the sigmoidal increase in dielectric permittivity and the reduction of dye diffusion depend on a common mechanism, namely gap junction closure.

Animals↗

Platelet function in acute experimental pancreatitis induced by ischaemia-reperfusion.

BACKGROUND: Ischaemia-reperfusion (IR)-associated microcirculatory changes play a major role in acute post-transplantation pancreatitis. The pathophysiological role of platelets in these events is unknown. The aim of this study was to examine platelet adhesion and function during early reperfusion after pancreatic ischaemia. METHODS: Rats were subjected to warm pancreatic ischaemia by cross-clamping of the pancreatic vessels for 1 h. After 1 h of reperfusion, platelet-endothelium interaction was evaluated after platelet separation and staining by fluorescence microscopy. Amylase levels and pancreatic histology were evaluated 24 h after reperfusion. Animals treated according to an identical protocol, but without ischaemia, served as controls. RESULTS: Mild pancreatitis had developed by 24 h after IR; serum amylase levels were significantly higher than those in control animals. The numbers of adherent platelets in capillaries and venules were significantly increased, and platelet velocity in capillaries was significantly decreased, in the IR group compared with controls. There was significantly more oedema and inflammation in pancreatic tissue after IR. CONCLUSION: Warm ischaemia for 1 h followed by reperfusion for 24 h caused mild pancreatitis in this experimental model. The pancreatic microcirculation was characterized by pronounced platelet-endothelium interaction in capillaries and venules. These results suggest that platelet activation may play an important role in acute post-transplantation pancreatitis.

Acute Disease↗

Laparoscopic organ retrieval for living donor liver transplantation does not prevent graft injury.

The cause of transplant failure may be difficult to define. However, organ retrieval before preservation and transplantation is an important factor. Organ manipulation during harvesting, which is inevitable with most techniques, leads to injury upon reperfusion including microcirculatory disturbances. Recently, laparoscopic organ retrieval has been successfully performed for human living donor liver transplantation (LDLT). Pneumoperitoneum for laparoscopy changes the pattern of hepatic blood flow. To study the effects of pneumoperitoneum on the graft prior to cold storage, livers from Sprague-Dawley rats underwent pneumoperitoneum with an intra-abdominal pressure of 8 mm Hg for 90 minutes. Subsequently, intravital microscopy was performed to assess intrahepatic microcirculation and transaminases were measured. Serum transaminases increased 1.5-fold compared with sham controls (P < .05). Intrahepatic microcirculation was significantly disturbed immediately after pneumoperitoneum. If this is confirmed in humans, laparoscopic organ retrieval for LDLT would be expected to decrease graft quality and not be beneficial in liver transplantation.

Animals↗

A novel model for the investigation of orthotopically growing primary and secondary bone tumours using intravital microscopy.

Here is reported the development of an experimental model using intravital microscopy as a tool to orthotopically investigate malignant bone tumours. Although up to 85% of the most frequently occurring malignant solid tumours, such as lung and prostate carcinomas, metastasize into the bone, and despite the knowledge that a tumour's course may be altered by its surrounding tissue, there is no adequate experimental model available enabling the investigation of orthotopically grown bone tumours in vivo. Intravital microscopy is an internationally accepted experimental method, used in various acute and chronic animal models, that enables qualitative and quantitative analysis of the angiogenesis, microcirculation, growth behaviour, etc. of various benign and malignant tissues. Non-invasive investigations of up to several weeks are possible. Additionally, tissue samples can be taken after termination of the in vivo experiments for further ex vivo investigation (histology, immunohistochemistry, molecular biology, etc.), elucidating the mechanisms that underlie the in vivo observations. Severe combined immunodeficient mice were fitted with a cranial window preparation where the calvaria served as the site for orthotopic implantation of the solid human tumours Saos-2 osteosarcoma (primary) and A 549 lung carcinoma and PC-3 prostate carcinoma (secondary). In all preparations, the take rate was 100%. Histological assessment confirmed the data obtained in vivo, showing typical tumour growth with infiltration of the surrounding osseous and soft tissues. This novel model serves as a valuable tool in understanding the biology of primary and secondary bone tumours in physiological and pathophysiological situations, with implications for the most areas of tumour therapy such as chemotherapy, radiation and antiangiogenesis.

Animals↗

Monitoring water content of rat lung tissue in vivo using microwave reflectometry.

Measurement of lung water is an important diagnostic means of assessing pulmonary oedema. Water content affects the dielectric spectrum at microwave frequencies, but quantification is still a problem. A new lung tissue model is presented that allows the calculation of water content from dielectric permittivity. The dielectric permittivity of lung tissue was measured by microwave reflectometry using a non-invasive surface probe. During perfusion of rat lungs (n = 22) with blood, injury was induced by interruption of the blood supply for a duration between 0 (control) and 2 h. Water content was assessed from dielectric permittivity using a new mixture formula and was also determined by drying and weighing. The mixture formula allows for the dielectric polarisation of water, dry matter and air in the tissue. A linear correlation was found between total water content determined from dielectric permittivity and that from drying and weighing (y= 1.001x, R2 = 0.8). Lung injury showed an increase in total water content from 80.9 +/- 1.2% (control) to 84.1 +/- 0.9% (p < 0.01). The analysis of dielectric permittivity data at microwave frequencies with the new tissue model is sensitive enough to detect water accumulation produced by lung injury and it can be used to monitor total water content without tissue destruction.

Animals↗

Monitoring of water content and water distribution in ischemic hearts.

We determined water content and water distribution by fitting dielectric spectra of ischemic canine hearts between 5 MHz and 3 GHz with a newly developed model which describes heart cells and subcellular organelles as rotational ellipsoids filled with electrolyte enclosed by an isolating membrane. The fraction of dry material is modelled by spherical particles with a small dielectric permittivity. Free model parameters were water content, cell volume fraction, and the conductivity of the electrolytes. Resulting model parameters were compared to data from tissue desiccation and to conductivity changes produced by protons and lactate ions. We investigated hearts in two states: during ischemia after interruption of blood flow (pure ischemia, PI, n=5) and during ischemia after resuscitation with Tyrode's solution (IAR, n=14). The difference between water content determined by tissue desiccation and by dielectric spectroscopy was less than 0.5%. During 360 min of ischemia, water content in IAR decreased from 85+/-1.6% to 83+/-2.2% and in PI from 80+/-0.8% to 78+/-1.5%. Cellular volume fraction in IAR increased from 0.47+/-0.045 to 0.63+/-0.031 and in PI from 0.62+/-0.014 to 0.73+/-0.013, which is consistent with published morphometric data. After 180 min of ischemia, the increase of the cytosolic conductivity was 0.14+/-0.02 S/m as calculated from the dielectric spectrum and was similar to the conductivity increase which was roughly estimated on the basis of tissue lactate concentration. In conclusion, dielectric spectroscopy combined with our model analysis facilitates the monitoring of water content and distribution by means of nondestructive surface probes.

Animals↗

Characterization of hepatic parenchymous perfusion heterogeneity and regional flow kinetics after porcine liver transplantation.

BACKGROUND: In clinical practice, a heterogeneous hepatic tissue microperfusion (MC) is often observed after liver resection or transplantation (LTx). Nevertheless this hepatic perfusion phenomenon has never been really quantified with respect to its anatomic distribution and time course in detail. The aim of the study was to characterize liver perfusion heterogeneity and local flow kinetics both in the physiological situation and after standardized ischemia and reperfusion using an established model of porcine LTx. METHODS: Regional distribution of hepatic MC in healthy native porcine livers (control group; n = 8) was analyzed in comparison with data derived 60 min, 24 h, and 72 h after porcine LTx (transplantation group; n = 8 each subgroup; cold ischemia time: 5.7 +/- 1.2 h). MC was measured with implanted thermal diffusion electrodes (TD). Flow in hepatic artery and portal vein was continuously detected by ultrasonic probes. For standardization of measurement localizations, porcine liver lobes were divided anatomically into three horizontal layers (cranial, medial, caudal), defining 12 distinct hepatic measurement regions. RESULTS: In the control group, a homogenous liver MC with a mean flow of 81.6 +/- 13.9 ml/100 g/min was detected in all regions. After LTx, a marked MC heterogeneity was noted 60 min after reperfusion. MC rehomogenization was first documented within horizontal liver planes 24 h later. Comparison of MC between planes showed persisting heterogeneity with a significant intralober drop of mean MC in the cranio-caudal direction. Complete MC rehomogenization (both between horizontal and vertical liver planes) was detected 72 h after reperfusion. Still, an overall reduction of mean liver perfusion by about 15% was existent. CONCLUSIONS: A homogenous tissue perfusion was observed in healthy porcine livers. In contrast, marked heterogeneity of hepatic MC was detected after LTx. Heterogeneity presents as a very dynamic and temporary phenomenon. Early horizontal flow rehomogenization and reconstitution of normal blood flow, particularly primarily in the cranial liver layers, appear to be characteristic features during early flow reconstitution after postischemic reperfusion. Due to heterogeneity and time-dependent flow dynamics, measurement of MC volumes at single hepatic regions may not always allow a valid characterization of liver perfusion quality during the first 24 h after postischemic reperfusion.

Animals↗

In vivo assessment of angioarchitecture and microcirculation in experimental liver cancer: a new model in rats.

The rising incidence of unresectable hepatocellular malignancies remains a therapeutic challenge. Little is known about the mechanisms of angiogenesis and immunological aspects of liver tumor vessels. The aim of this study was to investigate hepatic and tumor microcirculation and leukocyte-endothelium interaction by means of intravital microscopy in a rat model of hepatocellular carcinoma. Off-line analysis showed that the angioarchitecture as well as blood flow velocity in liver cancer is heterogeneous. The leukocyte-endothelium interaction is significantly reduced compared to normal liver tissue. The data suggest that the main mechanism is a reduced expression of adhesion molecules demonstrating an effective immune escape mechanism of this tumor. The model represents a useful experimental tool to explore angiogenesis inhibition or immunological therapeutic strategies in experimental liver cancer.

Animals↗

Angiogenesis inhibition with TNP-470, 2-methoxyestradiol, and paclitaxel in experimental pancreatic carcinoma.

INTRODUCTION: Inhibition of tumor angiogenesis is a novel therapeutic modality for various malignancies. AIM: To investigate the effect of different antiangiogenic agents (TNP-470, 2-methoxyestradiol, and paclitaxel) on growth and neovascularization of experimental pancreatic cancer. METHODOLOGY: In 25 male Lewis rats, tumor induction was achieved by orthotopic and subcutaneous tumor fragment implantation of ductlike pancreatic cancer DSL6A. Four weeks after tumor implantation, the animals were randomly treated with TNP-470, 2-methoxyestradiol, or paclitaxel. After 2 weeks of antiangiogenic therapy, total tumor volume, vital tumor surface, vascular density, and apoptosis were measured. RESULTS: Total tumor volume and vital tumor surface were not significantly different in any of the treatment groups. Similarly, vascular density and apoptosis were not altered by treatment with the various angiogenesis inhibitors at the specific doses used. CONCLUSION: We conclude that in contrast to many earlier studies, angiogenesis inhibition by a single-drug application and by the doses used in the present model did not reveal a favorable therapeutic effect on pancreatic cancer DSL6A. The combination of different angiogenesis inhibitors or higher doses might be more effective.

2-Methoxyestradiol↗

Experimental monitoring of hepatic glucose, lactate, and glutamate metabolism by microdialysis during surgical preparation of the liver hilus.

Mechanical liver manipulation can lead to hepatic microcirculation (MC) impairment. The pathobiochemical relevance of this phenomenon is not fully understood. Microdialysis (MD) allows a quantification of metabolic products in interstitial fluid, thus enabling analysis of the hepatic metabolic state during changes of liver perfusion. The aim of the study was to quantify the functional effects of standardized surgical liver preparation both on liver metabolism and microperfusion. Two groups of animals (pigs, n = 25) were formed: In the trial group (TG; n = 13) the liver was mobilized, followed by hilar preparation. In the control group (CG; n = 12) mobilization of the liver without hilar dissection was performed. Surgical manipulation was followed by an observation in both groups. Hepatic interstitial glucose, lactate, and glutamate concentrations were detected by MD and liver MC by thermodiffusion. During liver mobilization MC decreased significantly in both groups (TG; 86.7 +/- 2.0 to 73.4 +/- 2.3 ml/100 g min; and CG; 88.3 +/- 3.1 to 71.9 +/- 2.2 ml/100 g/min). In the trial group levels decreased further during hilar preparation reaching minimal values of 65.6 +/- 2.8. After preparation MC recovered to baseline. Glucose, lactate, and glutamate concentrations increased significantly during liver mobilization in the trial (glucose; 0.52 +/- 0.13 to 0.88 +/- 0.19 mmol/L; lactate; 0.34 +/- 0.07 to 0.54 +/- 0.07 mmol/L; glutamate; 34.5 +/- 3.6 to 52.6 +/- 8.0 micromol/L) and control group (glucose; 0.58 +/- 0.06 to 0.95 +/- 0.13 mmol/L; lactate; 0.30 +/- 0.06 to 0.49 +/- 0.07 mmol/L; glutamate; 32.9 +/- 2.36 to 56.1 +/- 5.12 micromol/L). Throughout hilus preparation maximum values could be measured in TG (glucose; 1.69 +/- 0.34; lactate; 0.90 +/- 0.18; glutamate; 63.5 +/- 7.2). After termination of mobilization or preparation baseline concentrations were reached again. MD allows monitoring of metabolic changes in hepatic parenchyma. Surgical liver preparation leads to changes of intrahepatic glucose, lactate, and glutamate levels (without alterations of parameters in systemic plasma) along with hepatic MC impairment. Reconstitution of hepatic MC was accompanied by rapid normalization of metabolic parameters. By measuring specific parameters, MD could prove to be of use for functional assessment of metabolic effects due to MC disturbances.

Animals↗

The complex dielectric spectrum of heart tissue during ischemia.

INTRODUCTION: Because of the variety of tissue structures, the interpretation of the passive complex dielectric permittivity spectrum epsilon (omega) of the heart is still a problem. The aim of this work was to correlate epsilon (omega) of heart tissue with physical processes on cellular level. METHODS: epsilon (omega) of canine hearts was continuously measured in the range from 10 Hz to 400 MHz during cardioplegic perfusion and during following ischemia. Cardioplegic perfusion was performed with HTK (Custodiol) without or with heptanol, in order to produce electrical cell uncoupling via the closure of gap junctions. To analyse epsilon (omega), we present two heart models which consider cell shape, electrical cell coupling, and dielectric polarisation of cell membranes and membranes of intracellular structures. RESULTS: epsilon (omega) of heart tissue shows an alpha-, beta-, and gamma-dispersion. epsilon (omega) remains unchanged during cardioplegic perfusion with HTK, but if heptanol is added, there is an immediate decrease in the region of alpha-dispersion and an increase in the low frequency part of beta-dispersion. Similar changes are observed during ischemia following HTK perfusion without heptanol; additionally, the beta-dispersion shifts to higher frequencies. Using our models, we obtain analogue changes of epsilon (omega) by fitting model parameters which describe water content, water distribution, extra- and intracellular conductivity, and gap junction resistance. DISCUSSION: Changes of these tissue properties as calculated by our models based on the measurement of epsilon (omega) are consistent with intraischemic changes of heart tissue known from immunohistochemical, biochemical, and histological investigations. The next step will be to use our models for the prognosis of irreversible tissue damage.

Animals↗

Glutathione depletion with L-buthionine-(S,R)-sulfoximine demonstrates deleterious effects in acute pancreatitis of the rat.

A common pathway in the pathogenesis of acute pancreatitis is the generation of free oxygen radicals. The most important defense mechanisms are free radical scavengers, especially glutathione. This study evaluates the influence of the inhibition of glutathione synthesis with L-buthionine-(S,R)-sulfoximine (BSO) on the course of experimentally induced acute pancreatitis in rats and the effects on isolated pancreatic acini and their secretion pattern. Thus acute necrotizing pancreatitis was induced with intraductal infusion of low-dose glycodeoxycholic acid and subsequent hyperstimulation with cerulein with and without pretreatment with BSO. In vitro pancreatic acini were isolated and stimulated with different concentrations of cerulein with and without BSO. The BSO-treated group showed a significantly reduced survival, more necrosis, and a decreased secretion of amylase in vivo. No effect on secretion pattern in either groups was seen in vitro and BSO did not exert toxic effects. Based on the data presented, this study demonstrates deleterious effects of scavenger depletion on the course of experimental pancreatitis. This is due to the systemic effects of free oxygen radicals rather than to local effects.

Acute Disease↗

The role of pre-ischaemic application of the nitric oxide donor spermine/nitric oxide complex in enhancing flap survival in a rat model.

Spermine/nitric oxide complex (Sper/NO) is a new nitric oxide (NO) donor with a long half-life providing controlled biological release of NO in vivo. The purpose of this study was to determine whether flap survival could be improved by pre-ischaemic or post-ischaemic intravenous administration of Sper/NO. We divided 37 male Wistar rats into four experimental groups. An extended epigastric adipocutaneous flap was raised in each animal. The mean area of flap necrosis was assessed for all groups on the fifth postoperative day, using planimetry software. The average area of flap necrosis was mean +/- s.d. = 68.2%+/-18.1% in the control group, and 29.7% +/- 13.3% in the non-ischaemic controls. The group with pre-ischaemic application of Sper/NO demonstrated an average flap necrosis of mean+/-s.d. = 11.2%+/-5.9%, whereas this increased to 59.2%+/-14.4% in the group receiving Sper/NO 5 min prior to reperfusion. The group with pre-ischaemic application of Sper/NO showed a significantly lower area of flap necrosis than either of the control groups or the group receiving Sper/NO just prior to reperfusion (P < 0.05). The group receiving Sper/NO just prior to reperfusion demonstrated a significantly higher mean area of flap necrosis than the non-ischaemic controls (P < 0.05), but did not differ significantly from the control group. Our data show that pharmacological preconditioning and enhancement of flap survival can be achieved by intravenous administration of Sper/NO. The application of Sper/NO at the end of the ischaemia period or in the early reperfusion period provides no protection against ischaemia-reperfusion injury.

Animals↗