Biomedical subjects

M F Angel

Publications and source records attributed to M F Angel.

At least 37 records · Page 2Linked to original sources

PubMed1993

Verapamil enhances the survival of primary ischemic venous obstructed rodent skin flaps.

The effect of verapamil, a calcium channel blocker, on the survival of skin flaps subjected to primary venous obstruction was studied. Skin flaps 9 x 4 cm, which are axial patterns with random extension, were elevated in Sprague-Dawley rats. A microvascular clamp was placed on the vein alone for 8 hours. Group 1 received verapamil (0.3 mg/kg) before flap elevation and before clamp release; group 2 received saline on the same schedule. Group 3 received verapamil (0.3 mg/kg) as above, plus every 8 hours for 5 days postoperatively. Group 4 received saline on the same schedule. There was no difference in survival between groups 1 and 2. Group 3 had 100% improvement in the flap survival compared with group 4 (78% vs 37%). Verapamil, if administered for the duration of the experiment, significantly increased flap survival.

Abdomen↗

PubMed1993

Further clinical use of the interposition arteriovenous loop graft in free tissue transfers.

The use of an arteriovenous fistula (AVF) to afford vascular access for free tissue transfer is described in 11 consecutive patients from a 1 year period. The leg was the site of pathology in six cases, and a reversed saphenous AVF to the femoral vessels was created. In the remaining five cases, those in the head and neck and arm regions, the recipient vessels varied. The mean patient age was 37.7 years, and ten of 11 patients were male. Etiologies of defect were automobile accidents in six cases, neoplasm in three, and gunshot wound and electrical injury in one patient each. Mean ischemia time was 113 +/- 15 min. Mean length of AVF was 27.3 +/- 2.1 cm. All flaps survived. AVF was a useful technique in the current study. Several maneuvers were undertaken to minimize the risk of thrombosis. All patients were given aspirin prior to AVF creation. Patients received dextran 40 in the postanastomosis period for 5 days. Finally, every effort was made to create the AVF between large vessels, especially in the leg, to maximize blood flow.

Adolescent↗

PubMed1993

Amelioration of secondary ischaemic injury by perfusion with University of Wisconsin (UW) solution in rat skin flaps.

This study was designed to observe the effect of perfusion with University of Wisconsin (UW) preservation solution on skin flap survival following secondary ischaemia caused by venous obstruction in rats. An epigastric flap model was used. Saline-perfused flaps exhibited no significant improvement in survival compared to untreated animals (NS). Skin flaps perfused with UW solution, however, had a significant increase in survival to 40% (8/20) (p < 0.01) when perfused before the onset of primary ischaemia and 30% (p < 0.05) when given before the onset of secondary ischaemia. These results show that UW solution improves skin flap survival, presumably through preservation of the microvasculature.

Adenosine↗

PubMed1993

Microanalyses of enzymes and metabolites in ischemia/reperfusion-induced partial-thickness skin wounds.

A transition zone between well-perfused proximal tissue and inadequately perfused distal tissue was evaluated histologically and biochemically in skin flaps. Cranially based pedicle flaps, 3 x 7.5 cm, were made on the backs of female Sprague-Dawley rats. Flap survival was 22% of the original flap area at 7 days and 40% at 14 days after flap elevation (p < 0.001). The transition zone consisted of full-thickness skin survival proximally and partial-thickness wound distally. It is evident that skin wounds induced by ischemia or reperfusion repair continuously between 7 and 14 days after flap elevation. Tissue glucose, lactate, and hypoxanthine levels were measured to assess capillary perfusion in the transition zone on postoperative day 3. The proximal full-thickness skin 5 mm from the wound margin demonstrated no significant changes in glucose and lactate levels compared with normal skin. The partial-thickness wounds exhibited no change in glucose (a 33% decrease was not statistically significant) but a significant increase (319% of normal) in lactate level (p < 0.05). Hypoxanthine levels increased to 453% of normal in full-thickness skin (p < 0.01) and to 787% in partial-thickness wounds (p < 0.001). Metabolic response was evaluated by enzyme assays in the transition zone. Hexokinase activity increased by 251% of normal (p < 0.05), glucose 6-phosphate dehydrogenase by 245% (p < 0.01), and glutathione reductase by 184% (p < 0.05) in the proximal full-thickness skin. Hexokinase activity further increased by 482% of normal (p < 0.01), glucose 6-phosphate dehydrogenase by 379% (p < 0.05), and glutathione reductase by 346% (p < 0.01) in partial-thickness wounds. The results suggest that partial-thickness wounds have less capillary circulation but greater antioxidant enzyme activities than does the survival area with full-thickness skin.

Journal Article↗

PubMed1993

The dorsal skin-flap model in the rat.

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Animals↗

PubMed1993

Effects of sympathetic denervation and oxygen free radicals on neovascularization in skin flaps.

An island skin flap, with its sole blood supply based on the inferior epigastric vessels, in Sprague-Dawley rats (female, 220 to 250 gm) was used as a model for the investigation of neovascularization. Flap survival after pedicle ligation was considered an indicator of neovascularization. Vascular pedicles were ligated on days 2 to 5 after flap elevation, and the time course of neovascularization in the innervated and denervated flaps was determined by measurements of survival on day 7 after pedicle ligation (on days 9 to 12 postoperatively). Neovascularization sufficient to maintain viability was established at 4 and 5 days after flap elevation in the innervated and denervated flaps, respectively. The effects of various scavengers of oxygen free radicals on neovascularization were evaluated in the innervated and denervated flaps. The pedicles were ligated 3 days after flap elevation. Flap survival was assessed on day 7 after pedicle ligation (on day 10 postoperatively). Treatment with a single dose of deferoxamine (50 mg/kg) increased the viability from 48 to 69 percent of flap area in the denervated flaps (p < 0.01) but produced little effect on viability in the innervated flaps. In the denervated flaps, treatments with a single dose of superoxide dismutase, intravenously and intraarterially, also substantially increased the survival rates from 29 to 86 percent (marginally significant) and 100 percent (p < 0.05), respectively. Allopurinol improved the survival from 43 to 88 percent; the difference was not statistically significant. The results suggest that denervation resulted in a delay of neovascularization and that severe sympathetic denervation contributes to the production of oxygen free radicals, which may exert their inhibitory effects on neovascularization.

Allopurinol↗

PubMed1992

Further investigation of secondary venous obstruction.

The first ischemic insult a tissue suffers is primary (1 degree). A second ischemic episode, such as thrombosis after free tissue transfer may be regarded as secondary (2 degrees) ischemia. The current study investigated 2 degrees ischemia in rodent epigastric flaps. Flaps were elevated in 50 Sprague-Dawley rats: group 1 had 5 hours 1 degree venous ischemia induced by placement of microvascular clamps; group 2 was like group 1, except venous continuity was re-established by venous anastomosis after resection of the venous segment previously microclamped; group 3 had 15 minutes of 1 degree ischemia, 24 hr later 5 hr of 2 degrees venous ischemia was induced by placement of microvascular clamps; group 4 was like group 3, except the venous segment was excised. Necrosis was evaluated on postoperative day 7. Both secondary ischemic groups had significantly less flap survival than the corresponding primary ischemic groups (P less than 0.001 for both). Resection of a portion of the vein and subsequent microanastomosis did not reduce flap survival (NS). Secondary venous ischemia of 5-hr duration is poorly tolerated by rodent skin flaps. There was no difference in flap survival in those flaps whose veins were clamped for 5 hr compared to those flaps whose clamped venous segments were resected and re-anastomosed.

Anastomosis, Surgical↗

PubMed1992

Biochemical analysis of the venous flap in the dog.

There has been great interest stimulated by reports on factors influencing the survival of skin flaps which possess only venous inflow and outflow, i.e., venous flaps. The present study serially (Days 1, 2, and 4 postoperatively) observed several biochemical factors which might affect flap survival. ATP levels were measured to assess endogenous energy stores, malonyldialdehyde (MDA) and xanthine oxidase (XO) to estimate free radical production, superoxide dismutase (SOD) to quantify antioxidant defenses, and edema to measure inflammatory changes. Eighteen thighs on nine dogs were assigned randomly to one of three groups: full-thickness skin grafts, flaps based solely on the saphenous artery and vein (AV flaps), or flaps based solely on the saphenous vein (venous flaps). These were regarded as being mostly ischemic, totally perfused, and partially ischemic, respectively. Control skin biopsies were obtained adjacent to surgical sites. AV flaps and control skin were similar in all respects. Venous flaps compared with skin grafts were significantly less edematous (P less than 0.01) had less MDA and XO (P less than 0.05), but no significant differences in SOD and ATP levels. However venous flaps had significantly less ATP than AV flaps (P less than 0.01). Thus venous flaps survive despite depletion of ATP levels. These results suggest that decreased free radical production and lessened edema may be important factors in promoting ultimate survival of venous flaps.

Adenosine Triphosphate↗

PubMed1992

The response of the rabbit rectus femoris muscle to ischemia and reperfusion.

The rectus femoris muscle of the rabbit is perfused by a single artery and vein and is a valuable new model for study of ischemia-reperfusion injury of skeletal muscle. The consequences of increasing duration of ischemia to the rectus femoris have been examined. Postischemic muscle survival (means +/- SEM), as measured by Nitro blue tetrazolium (NBT) staining 24 hr after ischemia, was 90.5 +/- 1.5% after 2 hr normothermic ischemia, 77.1 +/- 7.7% after 3 hr, 41.8 +/- 7.6% after 3 1/2 hr, and 10.7 +/- 8.7% after 4 hr. Histology confirmed the NBT findings at 24 hr and showed considerable regeneration of muscle fibers 1-2 weeks after injury. The injury caused by 3 1/2 hr normothermic ischemia is the most suitable baseline for study of the effects of pharmacological agents in ischemic muscle injury. Further study of the effects of 3 1/2 hr ischemia by a quantitative Evan's blue method revealed a rapid increase in vascular permeability commencing at the start of reperfusion and lasting for 5-6 hr. Vascular labeling with saccharated ferric oxide showed widespread labeling of venules within the injured muscle and electron microscopic examination showed severe injury to both leaking and nonleaking small blood vessels. However, increased vascular permeability accounted for only a small part of the increase in weight of ischemic muscle.

Animals↗

PubMed1992

The biochemical basis of secondary ischemia.

In this study rat epigastric island flaps were used as a model to investigate selected tissue biochemical changes occurring during secondary ischemia. It was hypothesized that free radical damage, depletion of free radical scavengers, depletion of ATP, and increased edema might explain differences in flap survival between partial (venous obstruction) and total (arteriovenous obstruction) ischemia and decreased flap survival with increasing ischemia time. Flaps were given 2 hr or primary ischemia, 8 hr of normal perfusion, then secondary ischemia of 0, 2, 4, 8, or 12 hr with either arteriovenous obstruction or venous obstruction. Biochemical analysis of the skin was performed after 0, 24, or 96 hr reperfusion. Only minor differences were found between arteriovenous and venous ischemia for any of five biochemical parameters, despite a previous finding that venous ischemic flaps are more susceptible to necrosis. Levels of xanthine oxidase and malonyldialdehyde (both indices of free radical generation) increased with ischemia time. Levels of superoxide dismutase (a free radical scavenger) correspondingly decreased. Tissue levels of ATP decreased after ischemia and recovered to normal for shorter but not for longer ischemia times after 96 hr of reperfusion in parallel with flap survival. Edema increased immediately after the ischemic insult but decreased once the tissue became necrotic. These results imply roles for free radicals, ATP, and edema in secondary ischemia, but do not distinguish between arteriovenous and venous secondary ischemia.

Adenosine Triphosphate↗

PubMed1992

Timing relationships for secondary ischemia in rodents: the effect of venous obstruction.

In a previous study, timing relationships were studied for flaps subjected to secondary ischemia by total pedicle interruption. In the current paper, using a rodent epigastric flap, a similar study for flaps subjected to secondary ischemia by venous obstruction was performed. These conditions were designed to mimic a venous thrombosis following flap transfer, as would be performed clinically. In Experiment 1, the time interval between primary and secondary ischemia was varied. When the interval was 72 hr, flaps with secondary ischemia had similar survival to those with primary ischemia. However, when the time interval was 24 hr, flap survival after secondary ischemia was significantly worse than after primary ischemia (p less than 0.01). In Experiment 2, the duration of primary ischemia was varied (15 min, 30 min or 1.5 hr), prior to a fixed interval between primary and secondary ischemia and 5 hr of secondary ischemia. These conditions produced significantly more necrosis than 5 hr of primary ischemia. Thus, even short periods of primary ischemia may have detrimental effects on flap survival after a subsequent period of secondary ischemia. This may have important clinical ramifications.

Animals↗

PubMed1992

The beneficial effect of dextran on anastomotic patency and flap survival in a strongly thrombogenic model.

Dextran lowers the probability of thrombus formation, by reducing platelet aggregation and adhesion and by increasing fibrinolysis. All studies to date using dextran for microvascular reconstruction have examined only short-term (1 to 2 hr) patency in isolated vessels. The current study used an established thrombotic model (inverted sleeve interposition graft), to investigate the effect of dextran on the long-term survival of pedicle flaps. A6- x 3-cm epigastric flap was elevated. A 2-mm inverted sleeve interposition graft was placed on the artery side of the pedicle by microvascular techniques. One group received dextran (17 cc/kg) 2 hr preoperatively and every 6 hr postoperatively for the next 72 hr. A control group received saline on the same schedule. Survival was assessed on postoperative day 7, at which time necrosis was obvious. Several parameters (clotting studies and electron microscopy) were studied to characterize the phenomenon more clearly. Only 25 percent of saline-treated flaps survived (2/8), while all dextran-treated flaps survived (7/7) (p less than 0.02, Fisher exact test). Thus, dextran allowed flaps to survive by preventing thrombus formation, despite a strong thrombogenic focus.

Animals↗

PubMed1992

Deleterious effect of urokinase used to treat experimental intra-arterial thiopental injection injuries.

UNLABELLED: Inadvertent arterial drug injections continue to be an important source of morbidity. Although the clinical picture of thiopental injection has been well defined over the past 50 years, there is still much controversy concerning pathophysiology and treatment regimen. Recently, a case report showed the efficacy of urokinase in treating this problem. The current study used the reliable ear model to study more closely this phenomenon. Rabbits were divided into four groups. Ears in Group 1 rabbits (n = 10) received an intra-arterial thiopental (15 mg/kg) injection. Group 2 rabbits (n = 10) received thiopental followed by a 1-ml saline injection 15 minutes later. Group 3 rabbits (n = 10) received thiopental followed by 50,000 U of urokinase. Finally, Group 4 rabbits (n = 4) received an intra-arterial injection of saline alone. Necrosis was evaluated 2 weeks later and expressed as a percentage. Student's t tests were used to evaluate data significance. RESULTS: Group 1 (thiopental alone) and Group 2 (thiopental and saline) rabbits had significantly more necrosis than Group 4 (saline alone) rabbits, 21.2% and 17.5% versus 0% (p less than 0.001 for both). Group 3 (thiopental and urokinase) rabbits had significantly more necrosis (46.5%) than Groups 1 and 2 rabbits (p less than 0.001 for both). CONCLUSION: From this study, we found that treatment of intra-arterial thiopental injection injuries with urokinase was of no benefit, but more importantly, it increased tissue necrosis by approximately 100%. Clinical use of this treatment is to be discouraged until underlying mechanisms are better defined.

Animals↗

PubMed1992

Hair removal by a depilatory does not affect survival in rodent experimental flaps.

The current study looked at the effect of topically applied hair depilatory agent Nair on flap survival. In a 10 x 3-cm dorsal rat flap model, there were no statistically significant differences in survival noted on postoperative day 7 between control skin and flaps receiving 6 to 24 minutes of Nair preoperatively. Therefore, hair depilation by Nair can be used safely in this model.

Administration, Cutaneous↗

PubMed1992

The serratus anterior free tissue transfer for craniofacial reconstruction.

The serratus anterior muscle was used as a free tissue transfer to reconstruct complex craniofacial defects in 5 patients. Serratus anterior muscle alone and serratus anterior muscle with rib were the transfers made. All flaps survived and scapular winging did not occur. The serratus anterior muscle has several advantages for the reconstruction of medium-sized craniofacial defects. Because of its position, a two-team approach is possible. It has a consistent pedicle anatomy and low donor site morbidity. It has a large caliber vessel and a long pedicle. When compared with the commonly employed rectus abdominis flap for moderate-sized defects, the serratus muscle offers greater versatility in design and has the option of incorporating bone and innervated muscle without increasing significant donor site morbidity.

Adolescent↗

PubMed1991

Secondary ischaemia in rabbit skin flaps: the roles played by thromboxane and free radicals.

1. Biochemical mechanisms of ischaemia were investigated in rabbit skin flaps subjected to 2 h of primary ischaemia then, 24 h later, to 4 h of secondary ischaemia. During secondary ischaemia, flaps underwent either total ischaemia (arterial and venous blood supply occluded) or partial ischaemia (vein only occluded). Some of these flaps were treated at the time of reperfusion with the free-radical scavenger superoxide dismutase (EC 1.15.1.1) and/or the thromboxane synthetase inhibitor UK-38,485. 2. After 30 min of reperfusion, superoxide dismutase treatment significantly reduced blood thromboxane levels, elevated during ischaemia. Superoxide dismutase also reduced tissue levels of malonyldialdehyde and xanthine oxidase, indicators of free-radical damage, and restored the depleted tissue levels of superoxide dismutase. 3. UK-38,485 treatment failed to significantly alter any of these tissue free-radical parameters, although this agent significantly reduced blood thromboxane levels. 4. Combined superoxide dismutase plus UK-38,485 treatment was not significantly better than either treatment alone with respect to any parameter. 5. Partial ischaemia led to consistently higher levels of tissue free radicals and blood thromboxane than did total ischaemia. Thus partial ischaemia appears to result in greater free-radical damage than total ischaemia. 6. These results are consistent with the hypothesis that thromboxane acts as a mediator for free-radical damage in the ischaemic changes within the flap.

Animals↗

PubMed1991

Timing relationships for secondary ischemia in rodents: the effect of arteriovenous obstruction.

The first ischemic insult a tissue suffers is primary (1 degree) ischemia. A second ischemic episode, such as thrombosis after free tissue transfer, may be regarded as secondary (2 degrees) ischemia. Timing relationships were studied in a rodent epigastric-flap model. In a first experiment, the interval between 1 degree ischemia and 2 degrees ischemia was varied. Flaps which had 2 degrees ischemia 12 and 36 hr after the 1 degree episode, had decreased ischemic tolerance, compared with 1 degree ischemic flaps; 2 degrees ischemic flaps, after an interval of 72 hr, had an ischemic tolerance similar to 1 degree ischemic flaps. In a second experiment, the length of the 1 degree ischemia was varied. It was found that as little as 5 min of 1 degree ischemia significantly decreased the subsequent tolerance of 2 degrees ischemia. The possible clinical significance of these results is discussed.

Animals↗

PubMed1991

A biochemical study of acute ischemia in rodent skin free flaps with and without prior elevation.

Elevation of a vascular island flap 24 hours before an ischemic insult (prior elevation) has been shown to significantly increase flap survival, and to decrease blood thromboxane levels, compared with acutely ischemic flaps. The current study considered whether prior elevation causes other biochemical alterations that could be beneficial for flap survival. Tissue levels of adenosine triphosphate (a major tissue energy store), superoxide dismutase (a major defense against free radicals), xanthine oxidase (an enzymatic source of free radicals), and edema were measured. Rat epigastric flaps, with or without prior elevation, had 10 or 12 hours of acute ischemia. Biopsies were taken at 0, 12, or 24 hours after reperfusion. Skin from flaps with no ischemia (control flaps) or control skin was harvested at the same times. Acutely ischemic flaps had significantly lower levels of adenosine triphosphate and less edema than those in prior elevated ischemic flaps after 12 hours of ischemia (both, p less than 0.05). Superoxide dismutase and xanthine oxidase did not vary significantly. It is not clear whether the increased adenosine triphosphate level in prior elevated flaps is the cause or the result of increased tissue viability. Prior elevation did not alter free radical mechanisms. Furthermore, prior elevation was beneficial for flap survival despite increased edema.

Adenosine Triphosphate↗