Myocutaneous flap ischemia: flow dynamics following venous and arterial obstruction.

To further clarify the pathogenesis of the poorer prognosis in skin flaps exposed to venous stasis compared with arterial insufficiency, a microsphere study was conducted in bilateral rectus abdominis island flaps in seven pigs. The relationship between capillary blood flow and arteriovenous (A-V) shunting was studied during progressive 1-hour intervals of arterial insufficiency and venous stasis and during 3 hours of reperfusion. Under controlled conditions, total blood flow was reduced from 100 percent to both 50 and 25 percent by application of an adjustable clamp on the artery supplying one flap and on the vein draining the contralateral flap. The relative distribution between A-V shunt flow and capillary blood flow was different in arterial insufficiency when compared with venous stasis at both the 50 percent and the 25 percent blood flow levels. In the arterial insufficiency flaps, the A-V shunt flow and capillary blood flow shared the total blood flow in the following percentages: 64/36 (at 100 percent total blood flow), 44/56 (at 50 percent total blood flow level), and 22/78 (at 25 percent total blood flow level). In the venous stasis flaps, the A-V shunt flow and the capillary blood flow shared the total blood flow in percentages of 70/30, 66/34, and 55/45, respectively. Hence, in arterial insufficiency flaps, capillary blood flow was spared by a relatively greater decline in A-V shunting compared with venous stasis flaps. Redistribution of capillary blood flow from subcutaneous tissue to muscle was observed, whereas blood flow was equally distributed throughout the length of the flaps at all flow levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fuel metabolism in a pig myocutaneous island flap model

Unilateral denervated myocutaneous island flaps based on the superior epigastric vessels were raised in 24 pigs and the metabolic changes during the first 6 postoperative hours were monitored. Secondary to flap elevation, decreased arteriovenous (A-V) differences in oxygen, glucose, and alanine levels were observed, indicating the opening of A-V shunts and increased arterialization of the venous blood. Venous outflow increased during the first 3 hours, but the A-V differences in all metabolites were constant over the entire 6-hour observation period. Exchange of intermediary metabolites therefore increased within the first 3 hours, after which a steady state was established. The main flap fuels seemed to be fatty acids, muscle proteins, and glycogen, whereas blood-borne carbohydrates and ketone bodies played only a minor role as energy sources. Anaerobic metabolism was increased secondary to flap elevation from 2 to 6 percent as compared with preelevation values. No changes were found in concentrations of plasma catecholamines, which were constantly high. An average weight gain of 3 to 4 percent per hour was equally distributed to skin, subcutis, panniculus carnosus, and muscle. Thus the flap seemed to adapt to the new perfusion pattern within a few hours by a slightly increased anaerobic metabolism, but still with an oxidative metabolism of more than 90 percent.     

Peripheral neovascularization of muscle and musculocutaneous flaps in the pig.

Late loss of free muscle flaps following surgical or accidental trauma to the dominant vascular pedicle has been reported. In this study, time-dependent ligation of the dominant vascular pedicle was undertaken in denervated latissimus dorsi musculocutaneous or muscle-only island flaps in the pig. Muscle flaps were covered with a skin graft, and silicon rubber sheets were inserted between the flaps and their bases to simulate a poorly vascularized bed. Hemodynamic and viability studies were then performed using intravenous fluorescein (skin viability), tetrazolium blue (muscle viability), and radiolabeled 15-micron microspheres (capillary blood flow). Blood flow did not change in acutely raised musculocutaneous flaps (n = 10) but was significantly elevated in acutely raised muscle-only flaps (n = 10), suggesting that the skin paddle may steal blood flow from the underlying muscle in musculocutaneous flaps. Peripheral neovascularization at 1 day to 8 weeks was assessed (n = 30). Viability increased during the first week of revascularization and was not different in musculocutaneous and muscle-only flaps. Revascularization of muscle-only flaps was enhanced compared with musculocutaneous flaps in the 2- to 8-week period.     

Effect of vascular delay on viability, vasculature, and perfusion of muscle flaps in the rabbit

The delay procedure is known to augment pedicled skin or muscle flap survival. In this study, we set out to investigate the effectiveness of vascular delay in two rabbit muscle flap models. In each of the muscle flap models, a delay procedure was carried out on one side of each rabbit (n = 20), and the contralateral muscle was the control. In the latissimus dorsi flap model, two perforators of the posterior intercostal vessels were ligated. In the biceps femoris flap model, a dominant vascular pedicle from the popliteal artery was ligated. After the 7-day delay period, the bilateral latissimus dorsi flaps (based on the thoracodorsal vessels) and the bilateral biceps femoris flaps (based on the sciatic vessels) were elevated. Animals were divided into three groups: part A, assessment of muscle flap viability at 7 days using the tetrazolium dye staining technique (n = 7); part B, assessment of vascular anatomy using lead oxide injection technique (n = 7); and part C, assessment of total and regional capillary blood flow using the radioactive microsphere technique (n = 6). The results in part A show that the average viable area of the latissimus dorsi flap was 96 +/- 0.4 percent (mean +/- SEM) in the delayed group and 84 +/- 0.7 percent (mean +/- SEM) in the control group (p < 0.05, n = 7), and the mean viable area of the biceps femoris flap was 95 +/- 2 percent in the delayed group and 78 +/- 5 percent in the control group (p < 0.05, n = 7). In part B, it was found that the line of necrosis in the latissimus dorsi flap usually appeared at the junction between the second and third vascular territory in the flap. Necrosis of the biceps femoris flap usually occurred in the third territory, and occasionally in both the second and the third territories. In Part C, total capillary blood flow in delayed flaps (both the latissimus dorsi and biceps femoris) was significantly higher than that in the control flaps (p < 0.05). Increased regional capillary blood flow was found in the middle and distal regions, compared with the control (p < 0.05, n = 6). In conclusion, ligation of either the dominant vascular pedicle in the biceps femoris muscle flap or the nondominant pedicle in the latissimus dorsi muscle flap in a delay procedure 1 week before flap elevation improves capillary blood flow and muscle viability. Vascular delay prevents distal flap necrosis in two rabbit muscle flap models.     

Arteriovenous shunting and regional blood flow in myocutaneous island flaps: an experimental study in pigs

In eight pigs, total blood flow, regional capillary blood flow distribution, and arteriovenous (AV) shunting were studied during the first 4 postoperative hours after elevation of a myocutaneous rectus abdominis island flap. Capillary blood flow and AV shunting were measured using radioactive microspheres before flap creation and 1 and 4 hours after surgery. Total blood flow, measured continuously as venous outflow, increased in the first postoperative hour (p less than 0.05). Elevation of the flap caused a slight decrease in skin capillary blood flow (p less than 0.05), whereas muscular capillary blood flow increased (p less than 0.01). AV shunting accounted for 50 percent of the total flap blood flow, whereas it was negligible in the abdominal wall prior to flap elevation. Thus stalk blood flow, skin appearance, and skin temperature may be poor indicators of nutritional capillary perfusion. However, the clinical and nutritional consequences of these findings remain to be established.     

Fasciocutaneous flaps: an experimental model in the pig

No experimental studies have substantiated the claim that fasciocutaneous flaps are superior to skin flaps. Using fasciocutaneous flaps designed in the pig, both flap survival and blood flow were assessed. The forelimb and hindlimb fasciocutaneous flaps survived to 8.2 +/- 0.3 cm and 7.9 +/- 0.3 cm, respectively, compared with 7.3 +/- 0.3 cm and 6.7 +/- 0.3 cm for the comparable cutaneous flaps, a statistically significant finding (p less than 0.01). Random fasciocutaneous flaps survive 12 to 18 percent longer than skin flaps. Using the radioactive microsphere technique, blood flow was measured after flap elevation, and flap survival was estimated using fluorescein. Again, a significant difference in flap survival was found, but there was no significant difference in measured blood flow. This can be explained by the relatively large interval between blood flow measurements (2 cm) compared with the observed difference in survival length (1.0 +/- 0.3 cm).     

Differing flow patterns between ischemically challenged flap skin and flap skeletal muscle: implications for salvage regimens.

In this study, the authors tested the hypothesis that there is a significant difference in spatial patterns of reflow in skin as opposed to skeletal muscle after an ischemic insult. The authors believe that this pathophysiologic difference between the two flap types has significant implications for flap salvage strategies. Bilateral buttock skin flaps (10 x 18 cm) and latissimus dorsi myocutaneous flaps (10 x 20 cm) were elevated in Landrace pigs (n = 7). Flaps on one side of the animal were randomly assigned to 6 hours of arterial occlusion, with the contralateral side acting as control. At 15 minutes, 1 hour, and 4 hours after reflow, radioactive microspheres (15 microm) were injected into the left ventricle. After 18 hours of reperfusion, skin and muscle viability were estimated by intravenous fluorescein and soaking in nitroblue tetrazolium, respectively. Flow rates in the skin with an ischemia-reperfusion injury were significantly reduced (30 to 53 percent), at all time intervals, compared with controls. The flow rate in the fluorescent skin with ischemia-reperfusion injury of the latissimus dorsi flaps (0.037 ml/min/g at 15 min) was greater than in that of the buttock flaps (0.018 ml/min/g). The muscle flaps with ischemia-reperfusion injury had significantly higher flow rates than control muscle flaps at all time intervals studied (at 1 hour, 0.32 ml/min/g compared with 0.16 ml/min/g, respectively). In flap skeletal muscle, an early hyperemic phase during reperfusion maintains a significant blood flow to all regions, including the area of the flap that is destined for necrosis. In flap skin, however, there is a marked decrease in flow rates. These differences have important implications for the intravascular delivery of therapeutic agents to the damaged portions of the flap. Transdermal drug delivery systems should be explored as an alternative to intravascular regimens for the salvage of flap skin with ischemia-reperfusion injury.     

Effect of capsulectomy on the hemodynamics and viability of random-pattern skin flaps raised on expanded skin in the pig

Skin flaps constructed on expanded skin usually include the underlying capsular tissue. It has been hypothesized that capsulectomy may jeopardize the viability of the expanded skin flap. The experiments reported herein were designed to test this hypothesis. Specifically, we studied the hemodynamics and viability of random-pattern skin flaps (8 X 20 cm) raised on delayed bipedicle flaps (group A) and on expanded skin pockets with capsulectomy at the time of flap elevation (group B) or with intact underlying capsular tissue (group C). Each group was randomly assigned to each flank in 16 pigs. Skin pockets were expanded by inflation of subcutaneous silicone tissue expanders with sterile saline (299 +/- 7 ml; X +/- SEM) over a period of 3 weeks. At the end of this period, the bipedicle flaps were constructed. Eight days later, random-pattern skin flaps were raised on bipedicle flaps and skin pockets. The length and area of skin flap viability, judged by the fluorescein dye test performed 1 day postoperatively, were not significantly different (p greater than 0.05) among groups A, B, and C (n = 31 to 32). There also were no significant differences (p greater than 0.05) in total skin capillary blood flow measured 1 day postoperatively (A = 2.6 +/- 0.4, B = 2.4 +/- 0.4, and C = 2.7 +/- 0.6 ml/min per flap; n = 15 to 16) and in skin viability assessed 7 days postoperatively (A = 74 +/- 2, B = 75 +/- 2, and C = 76 +/- 2 percent; n = 16) among delayed skin flaps and skin flaps raised on expanded skin pockets with or without capsulectomy. The results of this flap viability study were confirmed in 5 minipigs in a separate experiment. We conclude that capsulectomy did not have a detrimental effect on the hemodynamics and viability of random-pattern skin flaps raised on expanded skin. Furthermore, we hypothesize that skin flaps raised on expanded skin are similar to delayed skin flaps in that the skin blood flow is optimally augmented; therefore, the capsular tissue does not add significant blood supply to the overlying skin.     

Dermofluorometry: thresholds for predicting flap survival

The dye fluorescence index (DFI) has been cited as an accurate predictor of skin-flap survival. However, two thresholds, one each for flap survival and flap necrosis, have been advocated. A DFI of less than 15 to 20 percent predicts failure, and a DFI greater than 35 to 50 percent predicts survival. Values of 20 to 35 percent indicate an uncertain outcome. The present study was undertaken (1) to determine the optimum threshold for flap survival prediction in pigs, and (2) to compare dermofluorometry with flap blood flow as measured by radioactive microspheres. Dermofluorometry was found to be an accurate (90 percent) and repeatable predictor of skin and fasciocutaneous flap survival in pigs. At 2 and 5 hours after flap elevation, the optimum DFI thresholds are 7 and 27 percent, respectively. This reflects the dynamic nature of circulation in acute skin flaps and the increased dye delivery over time. Using these calculated thresholds, a high degree of correlation was found with survival estimated at 24 hours. Dermofluorometry also was correlated with the blood flow index. Thus not only is it an accurate flap monitor, but a quantitative estimate of flap blood flow can be obtained.     

Hemodynamics and vascular sensitivity to circulating norepinephrine in normal skin and delayed and acute random skin flaps in the pig

Cutaneous circulation in 4 X 10 cm skin samples and delayed and acute random skin flaps constructed on the flanks of castrated Yorkshire pigs (13.3 +/- 0.7 kg; n = 12) were studied during intravenous infusion (0.5 ml per minute) of 5% dextrose solution (vehicle) and 5% dextrose containing norepinephrine (1 microgram/kg per minute). Total and capillary blood flow and A-V shunt flow were measured by the radioactive microsphere technique 6 hours after the raising of 4 X 10 cm single-pedicle acute and delayed random skin flaps using the technique and calculations published previously. Fluorescein dye test was also performed to assess vascular perfusion. It was observed that the capillary blood flow in the single-pedicle delayed skin flaps was similar to that in the normal skin, and the maintenance of this normal skin blood flow was not due to the closing of A-V shunt flow in the delayed skin flaps. Similarly, the significant (p less than 0.01) decrease in capillary blood flow and distal perfusion in the acute skin flaps compared with the delayed skin flaps was not due to the opening of A-V shunts in the acute skin flaps. There was no evidence to indicate that A-V shunt flow per se was the primary factor for the regulation of capillary blood flow in the acute and delayed skin flaps in the pig. Our data seemed to indicate that tissue ischemia in the distal portion of acute skin flaps was likely the result of vasoconstriction of the small random arteries which supplied blood to arterioles and A-V shunts, and locally released neurohumoral substances may play an important role in the pathogenesis of vascular resistance and ischemia in the acute skin flaps.     

Survival and blood flow evaluation of canine venous flaps

Using a canine model, we compared postoperative viability of saphenous venous flaps, cephalic venous flaps, and composite-tissue grafts without vascular connections. Of the saphenous flaps, 14 percent survived. Of the flaps based on the cephalic vein, 75 percent survived. Cephalic composite-tissue grafts were 13 percent successful. The presence of a more intricate venous plexus in a flap seems to increase its chances of success. Arterial injections of radioisotope-labeled microspheres were used to chart revascularization in cephalic flaps. These flaps demonstrated arterial blood flow by day 3, while the composite grafts showed no flow until day 7. Venous injections of microspheres distal to the flap were used to test vein-to-capillary blood flow. No significant entrapment of microspheres within the flaps occurred at any time, suggesting such flow to be inadequate.     

Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: efficacy and mechanism

Distal skin ischemic necrosis is a common complication in skin flap surgery. The pathogenesis of skin flap ischemic necrosis is unclear, and there is no clinical treatment available. Here, we used the 4 x 10 cm rat dorsal skin flap model to test our hypothesis that subcutaneous injection of vascular endothelial growth factor 165 (VEGF165) in skin flaps at the time of surgery is effective in augmentation of skin flap viability, which is associated with an increase in nitric oxide (NO) production, and the mechanism involves 1) an increase in skin flap blood flow in the early stage after surgery and 2) enhanced angiogenesis subsequently to sustain increased skin flap blood flow and viability. We observed that subcutaneous injection of VEGF165 in skin flaps at the time of surgery increased skin flap viability in a dose-dependent manner. Subcutaneous injection of VEGF165 at the dose of 2 microg/flap increased skin flap viability by 28% (P < 0.05; n = 8). Over 80% of this effect was blocked by intramuscular injection of the NO synthase (NOS) inhibitor Nomega-nitro-L-arginine (13 mg/kg) 45 min before surgery (P < 0.05; n = 8). The VEGF165 treatment also increased skin flap blood flow (2.68 +/- 0.63 ml x min(-1) x 100 g(-1)) compared with the control (1.26 +/- 0.10 ml x min(-1) x 100 g(-1); P < 0.05, n = 6) assessed 6 h postoperatively. There was no change in skin flap capillary density at this time point. VEGF165-induced increase in capillary density (32.2 +/- 1.1 capillaries/mm2; P < 0.05, n = 7) compared with control (24.6 +/- 1.4 capillaries/mm2) was seen 7 days postoperatively. There was also evidence to indicate that VEGF165-induced NO production in skin flaps was stimulated by activation of NOS activity followed by upregulation of NOS protein expression. These observations support our hypothesis and for the first time provide an important insight into the mechanism of acute local VEGF165 protein therapy in mitigation of skin flap ischemic necrosis.     

Hydrogen clearance: assessment of technique for measurement of skin-flap blood flow in pigs

The hydrogen clearance technique has been used for many years by investigators to determine brain blood flow and has been partially validated in this setting using other methods of blood flow measurement. The method has been modified to allow blood flow measurements in skin, but the accuracy of H2 clearance for measuring skin blood flow has not been determined. Multiple blood flow measurements were performed using H2 clearance and radioactive microspheres on skin flaps and control skin in pigs. On 12 pigs, a total of 117 flap and 42 control skin measurements were available for analysis. There was no significant difference between the two techniques in measuring mean control skin blood flow. In skin flaps, H2 clearance was significantly correlated to microsphere-measured blood flow, but it consistently gave an overestimate. Sources of error may include injury to the tissues by insertion of electrodes, consumption of H2 by the electrodes, or diffusion of H2 from the relatively ischemic flap to its well-vascularized bed. Further studies are necessary to determine the cause of this error and to measure the technique's accuracy in skeletal muscle and other flaps.     

Monitoring acute skin-flap failure

Reliable and repeatable means for the objective postoperative monitoring of skin flaps is a necessity. If a failing free flap can be recognized early, it can be salvaged by revision of the appropriate anastomoses. For the threatened distal portion of a conventional flap, external factors, such as kinking or hematoma, may be corrected or drug therapy instituted. We have analyzed blood from stab wounds in experimental pig flaps for pO2, pCO2, pH, and hematocrit. The results were compared with fluorescein penetration and flap surface temperature. The most significant finding was hematocrit readings of threatened flaps (54 percent) elevated above those of control flaps (35 percent). pH readings in the jeopardized flaps were 0.4 units below control. These two measures proved to be more reliable than intermittent temperature readings. In contrast to the fluorescein test, which can be used only once, stab wound analysis is repeatable at any time in the postoperative period. It can be effectively used to follow dynamic changes within a skin flap.     

Measurement of carotid body blood flow in cats by use of radioactive microspheres

To resolve the controversy regarding carotid body blood flow, we used the radioactive microsphere technique for determination of tissue blood flow. We also measured the blood flow to several other tissues in the cat. Blood flow experiments were performed on 13 cats that were anesthetized, paralyzed, and mechanically ventilated with air. Different numbers of differently labeled 9-, 15-, and 25-micron microspheres were injected via a catheter into the left atrium. It was determined that one injection of 5 x 10(6) 15-micron microspheres was appropriate for the determination of carotid body blood flow. Flows to the carotid bodies and other organs by use of this protocol were as follows (ml.min-1.100 g-1, means +/- SE): carotid bodies, 1,417 +/- 143; adrenal glands, 406 +/- 89; left kidney, 355 +/- 69; right kidney, 375 +/- 74; heart, 201 +/- 39; liver 81 +/- 14; pancreas, 80 +/- 21; superior cervical ganglia, 62 +/- 9; carotid artery wall, 2.4 +/- 1.1. The blood flow to the carotid bodies was the highest for any organ. This measurement provides new evidence that tissue blood flow to the carotid body is very high. This high flow is consistent with the prompt physiological reflex functions of the carotid body.     

Differential effects of venous stasis and arterial insufficiency on tissue oxygenation in myocutaneous island flaps: an experimental study in pigs.

The supply, consumption, and tissue tension of oxygen were studied in experimental bilateral myocutaneous island flaps in five control pigs and in eight pigs during progressive 1-hour intervals of flap ischemia. Progressive ischemia was obtained by partial to complete clamping of the artery in one flap, producing arterial insufficiency, and simultaneous clamping of the vein in the other flap, producing venous stasis. Blood flow was reduced to 50, 25, and 0 percent of baseline. In the arterial insufficiency flaps, the oxygen tension in subcutaneous tissue, muscle, and venous outflow was significantly reduced once blood flow was reduced to 50 percent of baseline. Oxygen consumption during partial vessel occlusion was lower in the venous stasis flaps than in the arterial insufficiency flaps when blood flow was reduced to 25 percent of baseline, suggesting either that cellular metabolism is reduced in the venous stasis flaps or that the oxygen which is delivered is unavailable for the cells. Increased presence of tissue fluid in the venous stasis flap inhibits the diffusion of oxygen through the interstitial tissue, and this may explain the lower oxygen consumption. During 3 hours of reperfusion, increased blood flow was observed in the arterial insufficiency flaps, whereas blood flow in the venous stasis flaps was sluggish. The arterial insufficiency flaps recovered more rapidly than the venous stasis flaps during the first hour of reperfusion, judged by the rate of increase in oxygen tension and the higher venous oxygen tension. Oxygen tension increased more rapidly in muscle than in subcutaneous tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

A study on the effectiveness of a thromboxane synthetase inhibitor (OKY-046) in increasing the survival length of skin flaps

In an experimental study to test the thromboxane (TX) synthetase inhibitor OKY-046, two random-pattern skin flaps, each measuring 15.5 x 2 cm, and caudally based, were elevated on the backs of rabbits, and the effect of the test drug on their survival length was evaluated. The results indicated that the survival length of the skin flaps was 4.5 +/- 0.2 cm in the control group and 6.8 +/- 0.3 cm in the OKY-046-treated group, hence exceeding the control value by more than 50 percent, which was statistically significant. A laser speckle flow-meter showed that the OKY-046-treated flaps had significantly greater blood flow as compared with the control group both at 1 and 48 hours after operation. Whereas the blood flow values were significantly lower at 48 hours than at 1 hour after operation in the control group, no such reduction was noted in the OKY-046-treated group. On the other hand, while plasma TXB2 was found elevated at 1 hour postoperatively in the control group, such a response to the surgical intervention was blocked and the plasma TXB2/6-keto prostaglandin (PG) F1a ratio was decreased in the OKY-046-treated group. These results clearly indicated that OKY-046 suppressed a plasma thromboxane elevation induced by surgery, it augmented the flap blood flow, and it thereby increased flap survival length, suggesting that the drug might be helpful clinically and that further investigation must be carried out concerning its application.     

Neutrophil retention in model capillaries: deformability, geometry, and hydrodynamic forces

The initial retention of neutrophils within the pulmonary microvascular bed occurs in both physiological and pathological states, yet the factors responsible for this retention are poorly understood. Because the diameter of the neutrophil is approximately 7.03 micron and the mean pulmonary capillary diameter is 5.5 micron, we postulated that geometric constraints imposed by the microvascular bed, the deformability of the neutrophil, and the hydrodynamic characteristics of blood were important determinants of neutrophil retention. We used a filtration system wherein 111In-labeled human neutrophils (111In-N) suspended in a serum-containing buffer were passed through Nuclepore filters of known pore size. Compared with 99mTc-labeled erythrocytes (99mTc-RBC), the passage of 111In-N was delayed and a higher percentage was retained within the filter. Because the neutrophil and RBC are approximately equal in diameter, the deformability of the neutrophil must be less than that of RBC. As the flow rate increased, retention in the filters decreased logarithmically from 72 +/- 5% (flow rate 0.5 ml/min) to 15 +/- 4% (10.0 ml/min). As the number of RBC in the buffer increased, neutrophil retention in 5-micron filters decreased in a linear fashion from 65 +/- 6% at hematocrit of 0 to 33 +/- 2% at hematocrit of 10. The perfusion pressure and shear stress were of critical importance, and there was a logarithmic relationship between retention and perfusion pressure or shear stress (tau), whether the increase in pressure or tau was generated by increasing flow or by increasing the hematocrit of the perfusate. As the pore size of the filter increased, the retention of neutrophils decreased in a logarithmic fashion: from 75 +/- 5% in the 3-micron filter to 4 +/- 1.3% in the 12-micron filter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of sodium pentobarbital anesthesia on blood flow in skin, myocutaneous, and fasciocutaneous flaps in swine.

Drug effect on flap blood flow is most commonly determined in anesthetized animals, yet the effect of the anesthetic is often poorly understood. Halothane and nitrous oxide cause profound changes in skin blood flow and thus provide an unsuitable anesthetic technique for use in measuring drug effects on skin and myocutaneous flaps in swine. The goal of this study was to determine the effects of sodium pentobarbital anesthesia on cardiovascular parameters and blood flow in skin, myocutaneous, and fasciocutaneous flaps in pigs. In seven pigs, 7 forelimb skin flaps, 7 forelimb fasciocutaneous flaps, 14 arterial buttock flaps, and 14 latissimus dorsi flaps were created. Blood flow was measured at 2-cm intervals along each flap while the animal was awake and anesthetized. A cardiac depressant effect of pentobarbital was observed, but no change in blood flow could be demonstrated in control skin or control muscle. However, pentobarbital did significantly increase blood flow in all viable portions of arterial and random skin flaps, fasciocutaneous flaps, and the cutaneous segments of the latissimus dorsi flap. These demonstrated effects of pentobarbital should be taken into consideration in designing and analyzing studies of flap blood flow in the acute postoperative phase.     

Vascular endothelial growth factor expression in pig latissimus dorsi myocutaneous flaps after ischemia reperfusion injury

Exogenous administration of vascular endothelial growth factor (VEGF) improves long-term viability of myocutaneous flaps. However, endogenous expression of this substance in flaps following ischemia-reperfusion injury has not been reported previously. Endogenous production of VEGF was measured in myocutaneous pig latissimus dorsi flaps after ischemia-reperfusion injury. Latissimus dorsi myocutaneous flaps (15 x 10 cm) were simultaneously elevated bilaterally in six Yorkshire-type male pigs (25 kg). Before elevation, three flap zones (5 x 10 cm) were marked according to their distance from the vascular pedicle. After isolation of the vascular pedicle, ischemia-reperfusion injury was induced in one flap by occlusion of the thoracodorsal artery and vein for 4 hours, followed by 2 hours of reperfusion. The contralateral flap served as a control. Perfusion in each zone was monitored by laser Doppler flowmetry at baseline, during ischemia, and during reperfusion. At the end of the protocol, skin and muscle biopsies of each flap zone and adjacent tissues were obtained for later determination of VEGF protein levels. VEGF concentrations were quantified using the Quantikine human VEGF immunoassay. Skin perfusion was similar among all flap zones before surgery. Flow fell in all flaps immediately after flap elevation. After 4 hours of ischemia, blood flow in the ischemic flaps was significantly decreased (p < 0.05) compared with nonischemic control flaps. After 2 hours of reperfusion, flow in ischemic flap skin recovered to levels similar to those in control flaps. VEGF protein concentrations in muscle tissue exceeded concentrations in skin and decreased from zones 2 to 3 in control and ischemic flaps. No significant differences in VEGF concentrations between ischemic and control muscle zones were observed. However, the concentration of VEGF in all muscle zones was significantly higher (p < 0.05) than muscle adjacent to the flap. Concentrations in skin zones 1 and 2 were significantly higher (p < 0.05) in ischemic flaps than in control flaps, but levels in zone 3 (most ischemic flaps) showed no significant difference.