The health burden of breast hypertrophy.

Women seeking consultation for the surgical relief of symptoms associated with breast hypertrophy have been the focus of many studies. In contrast, little is known about those women with breast hypertrophy who do not seek symptomatic relief. The purpose of this study was to describe the health burden of breast hypertrophy by using a set of validated questionnaires and to compare women with breast hypertrophy who seek surgical treatment with those who do not. In addition, this latter group was compared with a group of control women without breast hypertrophy. Women seeking consultation for surgery were recruited from 14 plastic-surgery practices. Control subjects were recruited by advertisements in primary-care offices and newspapers. Women were asked to complete a self-report questionnaire that included the European Quality of Life (EuroQol) questionnaire, McGill Pain Questionnaire, Multidimensional Body Self Relations Questionnaire (MBSRQ), the Short Form-36 (SF-36) questionnaire, and questions regarding breast-related symptoms, comorbidities, and bra size. Descriptive statistics were compiled for three groups of women: (1) hypertrophy patients seeking surgical care, (2) hypertrophy control subjects (those whose reported bra-cup size was a D or larger), and (3) normal control subjects (those whose reported bra-cup size was an A, B, or C). The multiple linear regression method was used to compare the health burdens across groups while adjusting for other variables. Two hundred ninety-one women seeking surgical care and 195 control subjects were enrolled in the study. The 184 control subjects with bra-cup information available were further separated into 88 hypertrophy control subjects and 96 normal control subjects. In the control group, bra-cup size was correlated with health-burden measures, whereas in the surgical candidates, it was not. When scores were compared across the three groups, significant differences were found in all health-burden measures. The surgical candidates scored more poorly on the EuroQol utility, McGill pain rating index, MBSRQ appearance evaluation, physical component scale of the SF-36, and on breast symptoms than did the two control groups. In addition, the hypertrophy control subjects scored more poorly than the normal control subjects. With multiple linear regression analysis incorporating important potential confounders, the poorer scores in the surgical candidates remained statistically significant. It was concluded that breast hypertrophy in those seeking surgical care and those not seeking surgery has a significant impact on women's quality of life as measured by validated and widely used self-report instruments including the EuroQol, MBSRQ, McGill Pain Questionnaire, and the SF-36. Likewise, a new assessment instrument for breast-related symptoms also demonstrated greater symptomatology in women with breast hypertrophy.

An Internet-based utility assessment of breast hypertrophy.

The Internet has changed the way people shop, do business, and communicate with one another. Even those who try to avoid computers are bombarded with Web advertisements on television and in newspapers and magazines. The Internet also has excellent, but still largely underused, potential for conducting research studies. A Web-based questionnaire essentially combines the power and graphic flexibility of a computer with the freedom of a mail survey. The specific goals of this study were (1) to develop a Web-based utility assessment tool and (2) to use this tool to measure the health burden of breast hypertrophy by using the Internet to sample a population. An open-enrollment, Internet-based survey was developed to assess societal preferences for mild and severe breast hypertrophy using three established assessment techniques: visual analogue scale, time trade-off, and standard gamble. Subjects were recruited from a Web-based clinical trial listing service. Demographics, subjects' utility for their current health, and responses to a comorbidity index were also recorded. Data were recorded from August 1, 1999, to January 31, 2000. There were 480 unique responses, and 356 (74 percent) met the inclusion criteria. The respondents were predominantly female (81 percent), Caucasian (83 percent), and in the middle income brackets. Their mean age was 32.9. The average score for capacity of understanding was 4.99 out of 5 (5 = excellent). The median utility score for severe breast hypertrophy (visual analogue scale, 0.70; time trade-off, 0.85; standard gamble, 0.88) differed significantly from the median utility score for mild breast hypertrophy (visual analogue scale, 0.93; time trade-off, 1.0; standard gamble, 0.98) for each method. The results showed that the construction of a Web-based questionnaire for utility assessment is feasible and can be used to capture the utility of health states. The authors were able to enroll a large number of subjects with excellent capacity to understand the study, resulting in a high rate of usable responses. The applicability of these data to cost-effectiveness studies is limited by the extent to which the sampled population of this study is representative of society in general. The demographics of this study sample also differed from those of the Internet population. The study was piloted by measuring the values for breast hypertrophy, but the procedure could be used to assess the burden on quality of life of any disease and, potentially, the efficacy of surgical interventions. The study method is recommended as an accurate and cost-effective alternative for measuring quality of life.

Measuring health state preferences in women with breast hypertrophy.

The purpose of this article is to introduce the measurement of utilities, or patient preferences, to the plastic surgery community. Specifically, the study demonstrated the development and validation of a utility measure for estimating the health-related quality of life in women with breast hypertrophy. Two self-administered instruments were developed, a Wheel and a Table. All subjects completed the utility assessments for their "current health" and again for "breast-related symptoms." The reliability of the instruments was assessed in repeat (test-retest) interviews of 47 women within 10 to 18 days. Utilities obtained with the new instruments were also compared with the performance of other validated utility assessment instruments, including a visual analogue scale, a computer-based instrument (U-Titer), and a preference classification system (EuroQol). Of the 47 women in the test-retest reliability study, 21 had experienced breast hypertrophy (13 had not had reduction surgery and 8 had undergone reduction mammaplasty). Mean utility values for breast-related symptoms among women with breast hypertrophy (n = 13) were: Table, 0.85; Wheel, 0.90; and U-Titer, 0.66. Current health utility scores were significantly lower for women with breast hypertrophy (n = 13), as measured by all instruments except the Wheel. The Table had good reliability and distinguished women with breast hypertrophy from those without. Although the Table provided higher utility values for the same health state compared with the computer-based interview (U-Titer), it is much less costly to implement. The Table is recommended as a reasonable alternative for use in multicenter studies of women with breast hypertrophy. The reported utility value for breast hypertrophy of 0.86 is much lower than predicted. It is comparable with the reported burden of living with other health conditions, such as moderate angina (0.90) and a kidney transplant (0.84).

Surgeon perspectives on surgical options for early-stage breast cancer.

To evaluate the practice patterns of general and plastic surgeons regarding patients with early-stage breast cancer, all general and plastic surgeons in Quebec and Maryland were mailed self-administered questionnaires evaluating surgeon demographics, practice patterns, treatment preferences, and satisfaction with the results of lumpectomy and radiation therapy or breast reconstruction. Response rates of 38.3 percent and 26.7 percent were obtained for general surgeons in Quebec and Maryland, respectively. The ratio of reported mastectomies to lumpectomies was 1:2 in Maryland and 1:5 in Quebec. All general surgeons considered lumpectomy an important option. Ninety percent of Maryland surgeons versus 44 percent of Quebec surgeons considered mastectomy important. A total of 53.6 percent versus 24.9 percent of general surgeons in Maryland and Quebec, respectively, considered delayed reconstruction an important option. Additionally, 81.3 percent of Maryland surgeons considered immediate reconstruction important, and 79.6 percent discussed it with all stage I or II patients. More than 75 percent of Quebec general surgeons reported discussing immediate or delayed reconstruction with < or =50 percent of these women. Response rates of 53.6 percent and 48.8 percent were obtained for plastic surgeons in Quebec and Maryland, respectively. In one year Quebec plastic surgeons reported that they performed less than half the number of reconstructions performed by Maryland plastic surgeons (7.2 versus 17.3). In Quebec, 82.3 percent of surgeons reported that they frequently discuss delayed reconstruction, 25.1 percent immediate, 62.5 percent pedicled TRAM, and 51.7 percent nonautogenous options. In Maryland, 74.3 percent of plastic surgeons frequently discuss delayed reconstruction, 95.7 percent immediate, 89.9 percent pedicled TRAM, and 85.9 percent nonautogenous options. For women with early-stage breast cancer, regional variations exist in the surgical options discussed and provided.

Surgical options for the early-stage breast cancer: factors associated with patient choice and postoperative quality of life.

Patients with early-stage breast cancer have three surgical options: lumpectomy with radiotherapy, mastectomy alone, and mastectomy with breast reconstruction. Our objective was to compare women in these three groups with respect to demographics, preoperative counseling, postoperative body image, and quality of life. Women having undergone surgery for stage 1 or 2 breast cancer between 1990 and 1995 were selected by random sampling of hospital tumor registries and were mailed a self-administered questionnaire, which included the Medical Outcomes Survey Short Form 36. Patients were stratified into three mutually exclusive groups: lumpectomy with axillary node dissection and radiotherapy, modified radical mastectomy, and modified radical mastectomy with breast reconstruction. In total, 267 of 525 surveys were returned (50.9 percent). Compared with mastectomy patients, breast reconstruction patients were younger (p < 0.001), better educated (p = 0.001), and more likely Caucasian (p = 0.02). Among mastectomy patients, 54.9 percent recalled that lumpectomy had been discussed preoperatively and 39.7 percent recalled discussion of breast reconstruction. Post-operative comfort with appearance was significantly lower for mastectomy patients. The relationship between type of surgery and postoperative quality of life varied with age. Under 55, quality of life was lowest for mastectomy patients on all but two Medical Outcomes Survey Short Form 36 subscales. Over 55, quality of life was lowest for lumpectomy patients on all subscales (p < 0.05 for all subscales except social functioning and role-emotional). Treatment choice may be related to age, race, education, and preoperative counseling. Whereas the effect of breast cancer on a woman's life is complex and individual, the type of surgery performed is a significant variable, whose impact may be related to patient age.

Surgical treatment of early breast cancer: what would surgeons choose for themselves?

CONTEXT: Although breast-conserving surgery (BCS) is less invasive than mastectomy and results in similar survival, many women eligible for BCS continue to undergo mastectomy. Whether the persistent use of mastectomy means that women do not understand their options or reflects an informed preference is unknown. OBJECTIVE: To learn which treatment surgeons would choose when asked to imagine that they themselves had early-stage breast cancer. DESIGN: Cross-sectional survey. SAMPLE: Convenience sample of 40 staff and resident surgeons attending surgical grand rounds at Dartmouth-Hitchcock Medical Center in 1998. MAIN OUTCOME MEASURE: Choice of BCS or mastectomy for the treatment of stage I breast cancer. RESULTS: Twenty-six male and 14 female surgeons participated in the survey. Half chose BCS and half chose mastectomy for treatment of their hypothetical early-stage breast cancer. Results did not differ by the sex of the surgeon. CONCLUSION: Even after being reminded of the equivalent 10-year survival statistics, half of the surgeons surveyed said that they would choose mastectomy over BCS for themselves. The assumption that BCS is the "right" choice for early-stage breast cancer may be unwarranted because many patients may have an informed preference for mastectomy.

Platelet activating factor antagonism in pure skin flaps exposed to ischaemia-reperfusion injury.

Platelet activating factor (PAF) is an inflammatory mediator that participates in neutrophil activation and adhesion to the endothelial cells. The PAF-antagonist (L-659.989) improves survival in myocutaneous flaps after ischaemia-reperfusion injury. To establish whether PAF antagonism improves survival in a pure skin flap, we subjected bilateral porcine buttock skin flaps (n = 14) to eight hours of ischaemia and 18 hours of reperfusion. L-659.989 or saline were given by local intra-arterial bolus infusion five minutes before reperfusion. There was no improvement in flap survival. Neutrophil accumulation as indicated by myeloperoxidase activity was increased in both groups compared with control tissue that had not been operated on (p < 0.01). There was no difference between treatment groups. Although it protected myocutaneous flaps, PAF antagonism did not protect pure skin flaps from ischaemia-reperfusion injury. A possible explanation is differences in flow-patterns that do not allow otherwise effective drugs to enter the area at risk, and so inhibit them from exerting a beneficial effect.

Aprotinin attenuates platelet accumulation in ischaemia-reperfusion-injured porcine skeletal muscle.

This purpose of this study was to evaluate the effect of aprotinin, a serine protease inhibitor, in ischaemia- and reperfusion-injured myocutaneous flaps and skin flaps. Flap survival, microcirculatory platelet accumulation, and regional blood flow were investigated in seventeen pigs which had been subjected to 8 h of ischaemia and 18 h of reperfusion. The pigs were randomly assigned to aprotinin treatment (n = 9) or saline (n = 8). In-vitro studies were performed to investigate the influence of aprotinin on the activated partial thromboplastin time. The survival of skeletal muscle correlated positively with the concentration of aprotinin (P = 0.02) and could not be explained by regional changes in blood flow. Platelet accumulation was decreased in aprotinin-treated muscle (P = 0.04). In-vitro (n = 10), 100 kallikrein inactivator units/ml aprotinin prolonged the activated partial thromboplastin time both in plasma (P = 0.001) and in blood (P = 0.002), suggesting an anticoagulant rather than a procoagulant effect. In conclusion, aprotinin at high concentrations may be beneficial for the survival of skeletal muscle and provides protection from platelet accumulation in the microcirculation of skeletal muscle exposed to ischaemia and reperfusion injury.

E-selectin and L-selectin blockade in pure skin flaps exposed to ischaemia and reperfusion injury.

The inflammatory recruitment of leucocytes is a main cause of tissue damage in ischaemia/reperfusion (I/R) injury. Under appropriate flow conditions, E-selectin and L-selectin participate in the initial deceleration of neutrophils (PMNs) on inflamed endothelial cells before transmigration of PMNs into the surrounding tissue. Previous work from our lab showed increased survival of I/R injured myocutaneous flaps after treatment with anti-E/L-selectin. In this study, we have evaluated a combined antibody to E-selectin and L-selectin (EL-246) in porcine pure skin flaps exposed to I/R injury. Buttock skin flaps were exposed to eight hours of ischaemia and 20 hours of reperfusion. EL-246 or saline was given intra-arterially into the flaps. Estimated surviving area was not improved in the treated group. The lack of effect of EL-246 supports our suspicion that different mechanisms are involved in I/R injury in myocutaneous flaps compared with pure skin flaps. As a certain shear stress must be present for the selectins to exert their effect, a possible explanation for the diverse results in muscle and skin might be different reflow patterns.

Kinetics of E-selectin expression in surgical flaps.

During the ischemia/reperfusion phenomenon, adhesion molecules seem to play a critical role in the recruitment of neutrophils to sites of eventual tissue injury. E-selectin is an endothelium-derived molecule that mediates adhesion of neutrophils to activated endothelial cells. In vitro expression of E-selectin, after exposure to stimuli such as endotoxin, interleukin 1, or tumor necrosis factor alpha is maximal at 4 to 6 h, followed by a decline toward basal levels at 24 to 48 h. Characterizing the temporal expression of E-selectin in an in vivo model of skin flap ischemia-reperfusion would help to determine the optimal approach to eventual pharmacologic blockade. This intervention may prove therapeutically beneficial in attenuating flap injury. This study, using the standard porcine buttock skin flap model, was designed to evaluate immunohistochemically the expression of E-selectin in flaps subjected to (1) arterial ischemia (8 h)-reperfusion (18 h), (2) venous ischemia (8 h)-reperfusion (18 h), and (3) distal ischemia (26 h). Four flaps were examined per group, with 8 biopsies being collected sequentially over the 26-h study period from each flap. Blinded, semi-quantitative histologic scoring revealed the following results: (1) E-selectin is absent in normal porcine skin; (2) with arterial ischemia/reperfusion, E-selectin expression in flaps was maximal at 1 h of reperfusion, declining thereafter; (3) with venous ischemia/reperfusion, E-selectin expression peaked during the first hour of ischemia, with subsequent decline; and (4) within a flap designed to sustain distal ischemia, E-selectin expression is relatively more intense in regions of the flap distant from the vascular pedicle, and maximal at 6 h after flap elevation. Our conclusion, therefore, is that the kinetics of E-selectin expression within the tissues of porcine skin flaps differs depending on the type of ischemic insult sustained. Interpretation of these findings, correlating possible pathophysiologic differences in the different models of ischemia, is offered.

Sedimentation of formed elements in distally ischaemic flaps.

Our aim was to find out whether thrombosis has a key role in distally ischaemic flaps and whether heparin improves flap survival in distally ischaemic myocutaneous and pure skin flaps in pigs. In experiment 1 we measured the concentration of coagulation factors in the venous effluent from both viable flaps and distally ischaemic flaps. In experiment 2 radioactively labelled blood components (red cells, platelets and fibrinogen) were injected intravenously and the distribution of each tracer was measured. In experiment 3 either heparin or saline was given as a local, continuous direct intra-arterial infusion. Fluorescein was used in all experiments to estimate the eventual flap survival. Our results indicate that thrombosis is not an important factor in distal ischaemia, and that heparin did not improve survival. Instead, there seems to be selective pooling of formed elements in the ischaemic portion of the flap.

E- and L-selectin adhesion molecules in musculocutaneous flap reperfusion injury.

Definition of the elements governing leukocyte adhesion to the microvascular endothelium may lead to new forms of treatment for reperfusion injury. The objectives of this study, employing a porcine latissimus dorsi flap reperfusion model, were (1) to characterize the expression of E- and L-selectin adhesion molecules and (2) to test for a possible benefit of E- and L-selectin blockade in the preceding experimental setting. In experiment 1, full-thickness biopsies were collected sequentially over an 8-hour ischemia and subsequent 6-hour reperfusion period. Immunocytochemistry was performed with monoclonal antibody EL-246, an antibody that crossreacts with both E- and L-selectin. In experiment 2, the binding of EL-246 to L-selectin on circulating porcine neutrophils was determined by flow cytometric analysis. In experiment 3, in situ hybridization was performed using complementary RNA probes for detection of endothelial E-selectin mRNA. In experiment 4, bilateral flaps were elevated in six pigs and subjected to 8 hours of arterial ischemia followed by 20 hours of reperfusion. Flaps on each animal were randomly assigned to receive either treatment with a continuous local intraarterial infusion of EL-246 (1 mg per flap) or solvent vehicle. Muscle and skin survivals were assessed by nitroblue tetrazolium and intravenous fluorescein staining techniques, respectively. Computer digitization permitted quantitation of relative tissue survival. In experiment 1, specific immunostaining of microvascular endothelium was achieved using EL-246. Greater-intensity staining was detected in reperfusion than in baseline or ischemic sections. In experiment 2, flow cytometric analysis indicated specific recognition by EL-246 of isolated peripheral porcine neutrophils (> 45 percent staining) as compared with an isotype-matched control antibody (< 3 percent staining). In experiment 3, in situ hybridization studies demonstrated an early ischemic up-regulation and later reperfusion downregulation of E-selectin mRNA during the reperfusion period. In experiment 4, administration of monoclonal antibody EL-246 afforded a significant augmentation in mean percentage survival of muscle (37.6 versus 18.7 percent, p = 0.015) and skin (48.6 versus 29.3 percent, p = 0.046). In conclusion, it was determined that E-selectin is expressed along the microvascular surface and is upregulated and subsequently downregulated during ischemia-reperfusion conditions. The monoclonal antibody EL-246 appears to recognize porcine L-selectin as well as E-selectin. Blockade of E/L-selectin-mediated leukocyte adhesion significantly reduces musculocutaneous flap reperfusion injury.

The role of platelet-activating factor in musculocutaneous flap reperfusion injury.

UNLABELLED: Platelet-activating factor is an extremely potent lipid-inflammatory mediator implicated in the pathophysiologic mechanism of reperfusion injury in a variety of organs. The purpose of this study, employing a porcine latissimus dorsi flap model, was to (1) examine the expression of platelet-activating factor and (2) evaluate the possible benefit and mechanism of action of platelet-activating factor antagonism in musculocutaneous flap reperfusion injury. Experiment 1: In 6 pigs, bilateral flaps underwent 8 hours of arterial ischemia followed by 12 hours of reperfusion. Biopsies were collected sequentially and analyzed immunohistochemically for platelet-activating factor expression. Different processing techniques, however, were unable to detect specific tissue expression of platelet-activating factor. Experiment 2: In 11 pigs, bilateral flaps underwent 8 hours of arterial ischemia followed by 20 hours of reperfusion. A lipophilic platelet-activating factor receptor antagonist (L-659,989) was administered as a single dose to treated flaps by a local intraarterial route prior to reperfusion. This treatment augmented the survival of both muscle (48.3 versus 19.7 percent) and skin (49.8 versus 42.0 percent) components of the flaps in a statistically significant fashion (p = 0.001). Experiment 3: In 3 pigs, a radiolabeled structural analogue of L-659,989 (14C-L-680,573) was administered to flaps in a fashion similar to experiment 2. After 8 hours of ischemia, sequential full-thickness flap biopsies were collected over the initial 6 hours of reperfusion. The radio-labeled platelet-activating factor receptor antagonist was found to be highly concentrated within treated flaps, with gradual decay over the initial 6 hours of reperfusion. Experiment 4: Thirty minutes prior to completion of 8 hours of arterial ischemia, autologous neutrophils labeled with indium-111 were reintroduced into the systemic-circulation of 5 pigs. Prior to reperfusion, treated flaps received L-659,989 as in experiment 2. Over the initial 4 hours of reperfusion, the flaps were imaged in situ by a gamma camera at 3-minute intervals. The platelet-activating factor receptor antagonist was found to significantly attenuate the accumulation of radioactivity within treated flaps. CONCLUSION: Platelet-activating factor expression within musculocutaneous flaps subjected to ischemia and reperfusion was non directly demonstrated in this study. Still, we have shown that (1) the specific platelet-activating factor receptor antagonist L-659,989 is beneficial to the survival of both muscle and skin flap components, (2) a single, prereperfusion local dose of this lipophilic drug remains concentrated within the flap during the early inflammatory phase of reperfusion, and (3) during reperfusion, platelet-activating factor antagonism is able to directly or indirectly diminish the accumulation of acute inflammatory cells in musculocutaneous flaps.

Biodegradation of polyurethane foam, revisited, in the rat model.

In a prospective, randomized, controlled animal study, we systematically analyzed implanted polyurethane foam to determine the rate of degradation in the rat and to compare it to our previous human data. Sixteen 1-cm2 silicone-backed pieces of polyurethane foam were randomly implanted into dorsal subcutaneous pockets in each of 16 Sprague-Dawley rats. Eight animals had polyurethane implants removed at 3 and 6 months and the remaining 8 animals at 9 and 12 months. Specimens were examined either by histology or by scanning electron microscopy of recovered foam after collagenase digestion of the capsule. Histologically, there was evidence of foam degradation and a multinucleated giant cell inflammatory response surrounding the implants. With the scanning electron microscope, the strut width of the polyurethane foam upon implantation measured 51.4 +/- 1.3 microns (mean+SEM). This progressively decreased to 29.1 +/- 1.3 microns at 3 months, 16.6 +/- 0.6 micron at 6 months, 14.9 +/- 0.5 micron at 9 months, and 13.2 +/- 0.3 micron at 12 months (p < 0.0001). Duration of implantation has a significant impact on polyurethane degradation as measured by scanning electron microscopy in the rat animal model. The rate of degradation in the rat is much faster than in our human study, indicating that the rat studies cannot be used to draw conclusions regarding rate of biodegradation in humans.

Global flap ischemia: a comparison of arterial versus venous etiology.

It has been suggested by clinical observations that acute venous thrombosis following free-flap surgery results in more severe tissue injury than postoperative arterial thrombosis. This current study, in the pig model, was designed (1) to determine the rate of survival and the percentage area of flap survival in both cutaneous and myocutaneous flaps following a secondary venous ischemic insult, (2) to compare this with findings following a secondary arterial ischemic insult, and (3) to determine the reliability of laser Doppler flowmetry and dermofluorometry index in the prediction of necrosis outcome following both venous and arterial ischemic insults. A total of 116 flaps were elevated in 29 pigs. Data analysis documented a decrease in the rate of flaps surviving venous ischemia as compared with arterial ischemia or control and of arterial ischemia as compared with control. In contrast to our previous work, a lower rate of buttock flaps survived a secondary ischemic insult (of either arterial or venous etiology) than did the cutaneous component of the myocutaneous flaps. As expected, as the length of ischemia increased, the rate of flaps surviving decreased, as did the percentage area of survival. Although laser Doppler performed slightly better than dermofluorometry index, as measured on immediate reperfusion following secondary venous ischemia, both were relatively poor predictors of eventual survival or necrosis. Under conditions of immediate reperfusion following secondary arterial ischemia, dermofluorometry index proved to be a superior predictor of ultimate necrosis as compared with laser Doppler flowmetry.

Ibuprofen treatment of ischemic musculocutaneous flaps.

The nonsteroidal antiinflammatory drug ibuprofen was tested as a potential agent in the pharmacological management of ischemia and reperfusion injury of swine flaps. After 6 hours of global ischemia, ibuprofen treatment was found to significantly improve the postischemic musculocutaneous flap survival. This was demonstrated by a dramatic 30.4 +/- 9.3% (p < or = 0.005) improvement in ischemic muscle survival, whereas the skin survival of ischemic musculocutaneous flaps was only moderately improved by 6.0 +/- 3.2% (p < or = 0.05). Thus, ibuprofen is potentially a powerful and effective treatment agent in the management of critically ischemic flaps and replants with high skeletal muscle content.

Venous ischemia in skin flaps: microcirculatory intravascular thrombosis.

Although endothelial cell injury and microcirculatory intravascular clotting have been implicated in the pathophysiology of skin-flap failure and various hematologically active drugs have been used to improve flap survival, the basic underlying pathophysiology has not been documented previously. In this study of venous ischemia in pig flaps, we focus on the accumulation and distribution of platelets and fibrinogen in the flap, on the morphologic changes in the flap microcirculation, and on changes in various coagulation factors in the venous effluent from the flap. Bilateral buttock skin flaps and latissimus dorsi myocutaneous flaps were designed and elevated on 12 pigs. All flaps had a primary ischemic insult (clamp application to the vascular pedicle) of 2 hours, followed by 2 hours of reperfusion, and then one side was subjected to a 6-hour period of secondary venous ischemia (clamp application to the dominant flap vein). In six animals, radioactively labeled autologous platelets and human fibrinogen were injected intravenously half an hour before termination of secondary venous ischemia. Flaps were weighed and counted for radioactivity. Flap biopsies and the buffy coat of venous effluent were processed for electron microscopy. In the other six animals, venous effluent was collected before secondary ischemia, upon immediate reperfusion, and at 4 and 8 hours after termination of secondary ischemia. Venous plasma levels of fibrinogen, von Willebrand factor, and antithrombin III were measured. Platelet and fibrinogen accumulation was increased in flaps with venous stasis when compared with control flaps at both time intervals studied; a twofold increase was seen prior to reperfusion, and a threefold increase was seen following 4 hours of reperfusion. Venous effluent could not be collected from buttock skin flaps because of slow reflow and clotting in the collecting system. In comparing the venous effluent of control flaps with that of venous ischemic latissimus dorsi flaps, hematocrit was significantly elevated. Blood samples collected for analysis of fibrinogen, antithrombin III, and von Willebrand factor could not be analyzed because of postcollection clotting. Electron microscopy showed extravasation of red blood cells and activated platelets, fibrin, and red blood cells in distended and partly disrupted capillaries. The venous ischemia reperfusion injury is associated with thrombosis in the microcirculation and alterations in consumption of coagulation factors. This study gives physiologic support for potential beneficial effects of treatment modalities that aim at counteracting the different components of thrombus formation.