Biomedical subjects

C L Kerrigan

Publications and source records attributed to C L Kerrigan.

At least 37 records · Page 2Linked to original sources

PubMed1994

Arterial ischemia in skin flaps: microcirculatory intravascular thrombosis.

Although endothelial cell injury and microcirculatory intravascular thrombosis have been implicated in the pathophysiology of skin-flap failure, the basic underlying pathophysiology has not been documented previously. This study focuses on the morphologic changes and the alteration in platelet, fibrinogen, antithrombin III, and von Willebrand factor levels in flaps injured by arterial ischemia and reperfusion. A thrombogenic arterial anastomosis model is compared with simple arterial clamping as methods to achieve flap ischemia. Bilateral buttock skin flaps and latissimus dorsi island flaps were elevated in 12 pigs. All flaps had a primary ischemic insult of 2 hours' duration by simple clamp application. During this interval, a thrombus-generating, microvascular anastomosis was prepared, and during a 2-hour period of reperfusion, laser Doppler and transiluminator monitoring of the vascular pedicle allowed documentation of embolic events from the thrombus-generating anastomosis. In group 1 (n = 6), the flaps were then subjected to 7 (buttock skin) and 5 (latissimus dorsi) hours of complete arterial ischemia by clamping. During the secondary ischemic period, the poor microanastomosis was resected and repaired. Radioactively labeled autologous platelets (111In) and human fibrinogen (125I) were injected intravenously half an hour before secondary reperfusion. After 4 hours of reperfusion, flap biopsies and venous effluent were collected and prepared for electron microscopic analysis. The flaps and control tissue were harvested and the radioactivity was counted. In group 2 (n = 6), flaps were subjected to 6 hours of secondary ischemia by using the same technique as in group 1. Central venous and flap venous blood was sampled at baseline as well as upon immediate secondary reperfusion and after 4 and 8 hours of reperfusion. The hematocrit, platelet count, fibrinogen, antithrombin III, and von Willebrand factor levels were determined for these intervals. Platelets and fibrinogen accumulated significantly in buttock skin flaps and in the latissimus dorsi skin and muscle components as compared with similar control tissue (p < 0.05). There was no significant difference in platelet or fibrinogen accumulation after comparing the two ischemic models. Electron microscopic studies showed occluded capillaries with activated platelets in the flaps. Control tissue showed very little capillary occlusion. Platelet count was significantly decreased both in central venous (p < 0.05) and in adventitial infolding flap venous blood (p < 0.025) during immediate reperfusion as compared with baseline. These findings confirm that microcirculatory intravascular thrombosis is implicated in skin-flap ischemia-reperfusion injury. This study provides physiologic support for treatment modalities aimed at counteracting the various components in the coagulation pathways responsible for thrombus formation.

Anastomosis, Surgical↗

PubMed1994

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.

Animals↗

PubMed1993

Ischemia reperfusion injury: a review.

Ischemia reperfusion injury is reviewed in the context of the evolution of flap research over the past decade. A description of the clinical relevance of this field is presented and the possible etiologies are reviewed. The pathophysiology of this injury is then explored in some detail. Both skin and myocutaneous flaps, in a variety of animal models, are discussed. Research performed in vitro, as well as in other organ systems similarly affected by ischemia and reperfusion, is also examined. Particular attention is placed on the function of several newly described inflammatory mediators where it appears relevant to future research and treatment in the field of reconstructive microsurgery.

Animals↗

PubMed1993

Biodegradation of the polyurethane foam covering of breast implants.

Although it is generally accepted that polyurethane-covered breast implants have decreased the incidence of clinical capsular contracture, there remain many unanswered questions regarding the physical and chemical degradation of the polyurethane foam covering itself. We have systematically studied the fibrous capsule and polyurethane foam recovered from human breast "explants" in an effort to characterize more precisely the biodegradation of polyurethane foam in the human body. Seventy-five freshly retrieved polyurethane-covered implants and surrounding capsule from 47 patients have been analyzed. Capsular tissue from several sampling sites around the surface of the implants was digested in a collagenase solution until foam was recovered or all tissue was digested. Additional samples were fixed in 10% formalin. Scanning electron microscopy was used to look for structural changes in the recovered intact foam and to determine the foam strut widths. Fourier transform IR spectroscopy and x-ray photoelectron spectroscopy were used to analyze the chemical composition of the polyurethane. The formalin-preserved capsule samples were examined histologically for further evidence of foam degradation. Of the 75 prostheses analyzed, 36 (48 percent) were removed because of capsular contracture and 10 (13 percent) because of infection or exposure of the prosthesis. The remaining 29 (39 percent) implants were removed for various other reasons. Visibly intact foam was recovered from 36 (48 percent) prostheses after enzymatic digestion of capsule tissue. There was a progressive decline in the ability to recover intact foam as the total implantation time increased. Scanning electron microscopy revealed fractures and fissures in the foam structure and thinning of the polyurethane struts. The mean strut width of control, unimplanted foam was 49 +/- 1.5 microns (+/- SEM). Retrieved foam from implants which developed capsular contracture and the infected implants had strut widths of 30 +/- 3.1 and 32 +/- 3.1 microns, respectively. In implants removed for other reasons, the polyurethane foam strut width was 41.2 +/- 2.3 microns. Despite an inability to recover visibly intact foam from 39 specimens, standard light microscopy of 37 of these same specimens showed residual polyurethane still present in the capsule. Various degrees of scalloping and fracturing of the foam were seen in the histologic sections. There is convincing evidence by scanning electron microscopy and histology that polyurethane is degrading. It was not possible to quantitate accurately the rate of degradation, but factors such as capsular contracture, infection, and time appear to have a role in the biodegradation of polyurethane in the human body. These relationships require further study.

Biodegradation, Environmental↗

PubMed1992

Leeches: controlled trial in venous compromised rat epigastric flaps.

Leeches were studied for their efficacy to improve survival of venous compromised rat skin flaps. In 22 rats, bilateral epigastric island flaps were created and subjected to 6 h of venous occlusion. One flap in each animal was randomised to leech treatment, while the contralateral flap served as its own control. Flap survival, leech feeding time, weight gained by the leech and bleeding time from leech bites were measured. The area of flap survival was significantly increased in leech treated flaps compared to contralateral controls (n = 22 pairs, p = 0.03; Wilcoxon signed rank test). Weight gained in the feeding leech averaged 1.3 +/- 0.2 g (n = 18). Leech feeding time was 107 +/- 13 min (n = 18). Bleeding time from each leech bite averaged 79 +/- 12 min (n = 18). Hence, the extent of flap necrosis resulting from venous impairment can be partly diminished by leech treatment until definitive surgical venous revascularisation.

Animals↗

PubMed1992

Neutrophil localization following reperfusion of ischemic skin flaps.

A swine model of island latissimus dorsi myocutaneous and buttock cutaneous flaps was used to examine neutrophil localization and flap survival after 6 hours of global ischemia followed by 24 hours of reperfusion. Radioactivity from autotransfused neutrophils labeled with indium-111 enabled their localization. Radioactivity in ischemic latissimus dorsi flaps was increased by 101 +/- 30 percent over contralateral control latissimus dorsi flaps (n = 6, p = 0.01). Radioactivity in ischemic buttock flaps was increased by 142 +/- 40 percent over contralateral control buttock flaps (n = 6, p = 0.008). Despite increased neutrophil localization to ischemic flaps, the magnitude of tissue radioactivity failed to provide sufficient information to predict ischemic injury as measured by flap survival and tissue water content.

Analysis of Variance↗

PubMed1992

Altered neutrophil function following reperfusion of an ischemic myocutaneous flap.

The neutrophil has been implicated as a source of oxygen free radicals provoking the reperfusion injury in various ischemic organs. This provided the motivation to explore the pathophysiologic role of the neutrophil in a swine model of postischemic latissimus dorsi myocutaneous flaps. Neutrophil function, neutrophil sequestration, and the anatomic distribution of muscle injury were estimated following a 6- to 8-hour global ischemic insult. Neutrophil function as measured by phorbol myristate acetate-stimulated superoxide production was found to be enhanced on reperfusion of ischemic flaps (n = 17). Neutrophil sequestration estimated from the arterial-venous difference of flap blood (n = 12) demonstrated that postischemic flaps more avidly sequester neutrophils than nonischemic flaps. The anatomic distribution of muscle injury (n = 7) was predominantly localized to the proximal portion of the ischemic flap. The enhanced functional response exhibited by neutrophils reperfusing an ischemic myocutaneous flap supports an active neutrophil role in the mediation of reperfusion injury.

Analysis of Variance↗

PubMed1992

Effect of allopurinol on the survival of experimental pig flaps.

Allopurinol has been reported to improve cell survival in a variety of conditions, including the ischemia-reperfusion injury occurring in skin flaps. It has been suggested that the beneficial effect of allopurinol on rat skin flaps is through blockage of xanthine oxidase-generated oxygen-derived free radicals. We have previously reported on the lack of xanthine oxidase activity in the skin of humans and pigs as compared with that of rats. This current study attempts to improve skin and myocutaneous flap survival in pigs in two separate experiments using allopurinol. In the first experiment, a suspension of 50 mg/kg (N = 12) allopurinol resulted in no significant difference in the survival of control and treated flaps. Because of the negative results in the first experiment, a second experiment was designed making several changes. The length of the global ischemic insult was reduced from 8 to 6 hours, and allopurinol was administered as a solution of 300 mg/kg (N = 14). This higher dose is expected to produce complete inhibition of xanthine oxidase in this animal model. These changes resulted in three operative deaths, no improvement in skin-flap survival, and a decrease in myocutaneous flap survival. Allopurinol's therapeutic effectiveness and its mechanism of action in an ischemia-reperfusion injury model lacking xanthine oxidase activity are discussed.

Allopurinol↗

PubMed1992

Cyclophosphamide-induced neutropenia: effect on postischemic skin-flap survival.

In a blinded study, 24 pigs were randomized to a 5-day preoperative treatment regimen of cyclophosphamide (n = 12) or placebo (n = 12). At operation, buttock cutaneous and latissimus dorsi myocutaneous flaps were created and then subjected to 6 hours of global ischemia. After 24 hours of reperfusion, flap skin and muscle survivals were determined. All cyclophosphamide-treated animals were rendered neutropenic (less than 500 neutrophils/mm3 of peripheral blood). The results show that neutropenia had no effect on postischemic buttock cutaneous flap survival. In contrast, cyclophosphamide-induced neutropenia demonstrated a significant protective effect on postischemic latissimus dorsi myocutaneous flap survival. This study further implicates the neutrophil as a significant factor in the mediation of ischemia/reperfusion injury of myocutaneous flaps.

Analysis of Variance↗

PubMed1991

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.

Analysis of Variance↗

PubMed1991

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.

Animals↗

PubMed1991

Pathophysiology of ischemic skin flaps: differences in xanthine oxidase levels among rats, pigs, and humans.

Oxygen-derived free radicals have been implicated in a variety of diseases and pathologic processes, including ischemia reperfusion injury (IRI). Based on experimental work with rat skin-flap models, the enzyme xanthine oxidase (XO) has been proposed as a major source of free radicals responsible for tissue injury and flap necrosis. The presence of this enzyme is variable within different tissues of a specific species and between species. Xanthine oxidase levels in pig and human skin have not previously been reported. The activity of xanthine oxidase in the skin of rats (N = 16), pigs (N = 7), and humans (N = 8) was measured after varying intervals of ischemia and in the rat also following reperfusion. Control pig and human skin were found to contain minimal enzyme activity, almost 40 times less than that of the rat. In the rat, xanthine oxidase activity was stable throughout a prolonged period of ischemia, and a significant decrease in activity was found after 12 hours of reperfusion (p less than 0.05). In humans, xanthine oxidase activity was unaffected by ischemia time, and in the pig, it did not increase until 24 hours of ischemia (p less than 0.05). The potential sources of free radicals and the mechanism of action of xanthine oxidase and its inhibitor allopurinol in improving flap survival in different species are reviewed.

Analysis of Variance↗

PubMed1990

Critical ischemia times and survival patterns of experimental pig flaps.

Previous work on critical ischemia time suggested (1) a greater susceptibility of myocutaneous flaps over skin flaps to the ischemia reperfusion injury and (2) that duration of ischemia may affect the survival area of a flap. Using a pig model, 55 animals were operated on and the critical ischemia times and survival patterns of the buttock skin (n = 85) and latissimus dorsi myocutaneous (n = 88) island flaps were determined after being submitted to 0, 2, 4, 6, 8, 10, 12, 14, and 16 hours of normothermic ischemia. The average critical ischemia times (CIT50) were determined to be 9 and 10 hours for the buttock skin and latissimus dorsi myocutaneous flaps, respectively. Percentage of total area surviving (%TAS) in those flaps which did survive was adversely affected by increases in the ischemic interval in both flap models. A statistically significant decrease in percentage of total area surviving was found after 6 and 8 hours of ischemia for the buttock skin and latissimus dorsi myocutaneous flaps, respectively.

Animals↗

PubMed1989

Experimental reconstruction of cutaneous defects with microvascular jejunal transplants.

In a rat model, island and free flap transfers of jejunal segments were performed to provide a vascularised base in surgically created wounds. These thin, pliable flaps were subsequently stripped of mucosa and skin-grafted to provide a durable cutaneous cover. Histological evaluation of the flaps was performed. Advantages and disadvantages of the procedure are discussed.

Animals↗

PubMed1989

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.

Animals↗

PubMed1989

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).

Animals↗

PubMed1986

Primary and secondary critical ischemia times of myocutaneous flaps.

The primary critical ischemia time of the latissimus dorsi myocutaneous flap model was determined in the pig. Latissimus dorsi flaps were subjected to a primary ischemic insult of 2 hours (mimicking the ischemic event of free-tissue transfer). Following 12 hours of normal flow, the flaps were subjected to a second ischemic insult ranging from 0 to 12 hours. The secondary critical ischemia time (11.3 hours) was found to be statistically comparable to the primary critical ischemia time (9.1 hours). Questions are raised concerning the mechanism of action of this phenomenon and its clinical relevance.

Animals↗

PubMed1986

Free tissue transfers to the upper extremity.

With the expanded surgical options provided by free tissue transfers, upper extremity reconstruction has progressed to a level of greater finesse. Recognizing the ideal tissue for restoration of function and aesthetics, thin skin dorsally and sensate glabrous skin volarly, is the first step to effective application of microsurgery in the hand. With complex deformities, all missing components must be considered and the patient's goals realistically defined. An in-depth understanding of hand function is combined with an exhaustive knowledge of free tissue donor sites and a reconstructive plan is formulated. Staged reconstruction may be necessary, depending on the complexity of the problem. Ideal donor tissues are not always available, but it is expected that advances in immunology will soon make "spare part surgery" a viable alternative.

Adult↗