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Biomedical subjects

J S Gould

Publications and source records attributed to J S Gould.

At least 19 recordsLinked to original sources
PubMed1992

The de-endothelialized rat carotid arterial graft: a versatile experimental model for the investigation of arterial thrombosis.

A novel model of arterial thrombosis was developed. A mechanical endothelium-denuding injury was created (using a scalpel blade) on harvested, freezer-stored rat carotid arteries. Vessel length of 5 mm. were grafted into the femoral arteries of recipient Sprague-Dawley rats using microvascular anastomotic technique. Patency rates in untreated animals were compared with those in animals receiving systemic aspirin or heparin. The control group patency after 2 hours of flow was 15%, while grafts in aspirin- and heparin-treated animals achieved 35% and 95% patency rates, respectively. Uninjured non-frozen carotid grafts in untreated animals yielded a 95% patency rate, while frozen grafts achieved an 80% patency. Therapeutic levels of aspirin, heparin, and urokinase were confirmed through tail bleeding and whole blood clotting tests, as well as platelet aggregation studies and scanning electron microscopy of the graft lumenal surfaces. A long-term series using syngeneic grafts placed in recipients (Lewis-to-Lewis) and employing systemic heparinization demonstrated maintenance of patency for 4 weeks. Scanning electron microscopy revealed good re-endothelialization, well advanced by one week. Histology confirmed the regrowth of endothelial cells, but showed sparse cellular repopulation of medial and adventitial layers. The mechanical injury model was compared to enzymatic de-endothelialization (using trypsin or collagenase), for which patency rates were similar (10% and 0%, respectively). Trypsin de-endothelialized vessels were tested in vitro for the amount of active trypsin remaining bound to the lumenal surface; no detectable activity was found when trypsin inhibitor was applied following trypsin treatment. The versatility of allowing both in vitro evaluation and in vivo patency assessment demonstrates the uniqueness and value of this new model, offering an avenue toward more direct investigations of surface-mediated thrombotic processes.

Anastomosis, Surgical↗
PubMed1992

Comparison of the influence of intralumenal irrigation solutions on free flap survival.

Heparin is commonly included in the irrigation solution used during microvascular surgery. Evidence has accumulated to indicate a beneficial effect of heparin on anastomotic patency, implying that its topical use is critical to success even in routine microvascular repairs. This investigation compared heparin and urokinase as additives to the irrigation solution (Ringer's lactate) used during rat groin free flap replantation. A newly trained microsurgeon performed all surgical procedures to lower the possible success rate through microsurgical inexperience and, thus, to create a stronger challenge for the topical irrigant. Solutions were administered on a blinded, randomized basis. Vessel patency and flap survival were followed for 7 days. No statistically significant differences were found between any of the treatment groups: patency and survival rates of 67% for heparin, 57% for urokinase, and 73% for controls (vehicle only). The flap failures that occurred may have been attributable to undetected technical errors due to the microsurgical inexperience of the surgeon. In a separate series, an experienced microsurgeon achieved 93% success using vehicle without additives for irrigation. These results suggest that topical heparin or urokinase is not essential for achieving high levels of success during microvascular surgery.

Administration, Topical↗
PubMed1992

Influence of topical heparin on stasis-induced thrombosis of microvascular anastomoses.

An experiment was done to determine whether topical heparin and the association of anastomoses with dependent tissue (free flaps) exert any influences on stasis-induced microvascular thrombosis. Rat femoral vessel anastomoses with or without free flap construction were used in a total of 50 male Sprague-Dawley rats. Saline either with or without heparin was used for intralumenal irrigation during the anastomosis. Following anastomotic repair, the femoral vessels were reclamped, inducing stasis for either 2 or 4 hr. Our results showed that static blood had little adverse effect on thrombosis at the arterial anastomosis when reclamped for up to 4 hr in both standard and flap-associated anastomoses. Topical heparin significantly reduced the incidence of stasis-induced thrombosis of venous anastomoses. The venous patency rates in standard anastomoses were lower than those in flap-associated anastomoses after both 2 and 4 hr of stasis. From these results, we conclude the following. 1) Arteries may be reclamped for up to 4 hr without detriment despite static blood being in contact with the anastomotic site. 2) Topical heparin may be helpful in increasing the patency rate of venous anastomoses after a period of blood stasis. 3) Free flap construction may play a role in decreasing stasis-induced microvascular thrombosis.

Administration, Topical↗
PubMed1992

The effect of venous flow alterations upon patency of rat femoral vein anastomoses.

The rat femoral vein has become a standard model for laboratory training in microvascular anastomotic technique as well as for research investigations into factors affecting venous patency. This study examined the short-term patency (1 and 7 days) of rat vein anastomoses. The influences upon patency of epigastric flap creation and distal femoral vessel ligation (epigastric flow only) were explored. In a separate experiment, blood flow from the femoral vein was determined through catheter collection of venous efflux; the influences of island epigastric flap creation and distal femoral ligation on flow rates were explored. It was found that 82% of basic femoral vein anastomoses were patent at one day, while 100% of anastomoses associated with an epigastric flap and ligated/transected distal femoral vessel circulation (creating a low-tension anastomosis) were patent (P less than 0.01). With distal femoral vessel ligation and no transection (normal tension at the repair), anastomoses were patent in 90% of the veins when an epigastric flap was also raised, and in 60% when a flap was not created. When a flap was raised without disturbing the distal femoral circulation, vein patency was 75% at one day. When the vein anastomosis was performed with distal femoral vein ligation, the patency rate was 50%. All veins patent at 1 day were also patent at 7 days post-op; 96% of veins clotted at 1 day were found to be patent at 7 days. The venous efflux was not found to vary significantly when an epigastric flap was raised.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1992

Free flap transfer of the cutaneous maximus muscle in the rat: comparison to the latissimus dorsi muscle flap.

A new rat model of free muscle flap transfer is presented. Microvascular transplantation of the cutaneous maximus muscle flap is performed at the groin site, with anastomosis of the axillary vessels to the appropriate femoral vessels. This muscle flap has many useful attributes for experimental manipulation. It has a high success rate following transplantation, the anatomy is consistent, the dissection is straightforward, the length of pedicle is relatively long (10 mm), the vessels for repair are of sufficient size (1.0-1.35 mm diameter), and the microsurgical procedure can be performed in a relatively short period. The donor site deficit causes minimal impairment to animal mobility, and no evidence of limb ischemia is noted after ligation of the axillary vessels. The cutaneous area adjacent to the muscle is perfused by muscular perforators supplied by the flap pedicle; thus a skin island may be used to monitor the flap or to create a composite myocutaneous transfer. The cutaneous maximus muscle has mixed muscle types and anatomic dimensions similar to those of the latissimus dorsi muscle, and it provides ample tissue for pharmacological and biochemical studies, yet it presents easier dissection and microanastomoses than the latissimus flap, with more potential for versatility in application. The advantages of this muscle flap make it a very useful experimental model for flap transfer research.

Animals↗
PubMed1992

Physiologic alteration of fibrinogen levels: influence upon patency of microvenous anastomoses.

High baseline levels of plasma fibrinogen have been correlated with increased risk for cardiovascular disease. Since fibrinogen plays a central role in both coagulation and platelet aggregation and is a primary component of thrombi, this study was designed to assess the relationship of circulating fibrinogen concentration and vein anastomotic patency. Subcutaneously injected turpentine was used to increase, and intravenous ancrod (snake venom) to decrease, plasma fibrinogen levels. Rat femoral vein anastomoses were performed, and patency was assessed after 120 min of flow. Rat tail bleeding times were obtained, and blood samples were drawn to determine fibrinogen and plasma protein concentrations, Lee-White clotting times, and activated partial thromboplastin times (APTT). Increased patency was found in the ancrod group (88%) (P < 0.05 vs. controls); turpentine-treated and control groups were not significantly different (71% and 63%, respectively). The ancrod group also showed significantly prolonged tail bleeding times and APTT. Fibrinogen levels were significantly decreased in the ancrod group (1.73 mg/ml) and elevated in the turpentine group (4.91 mg/ml) vs. controls (2.34 mg/ml; P < 0.005). These results indicate that elevated fibrinogen levels, in particular when triggered by an acute-phase response, do not appear to predispose small vessel repairs toward thrombosis. Furthermore, this study supports the use of ancrod as an anticoagulant for microvascular surgery.

Anastomosis, Surgical↗
PubMed1992

Antithrombotic benefit of subendothelium-bound urokinase: an experimental study.

To improve the outcome of extremity replantation, microsurgeons have administered systemic antithrombotic agents (e.g., heparin, aspirin, dextran). To obviate the risks associated with systemic anticoagulation, we have investigated the use of topically applied urokinase for its binding capacity to arterial subendothelium and for its ability to prevent subsequent thrombosis. An arterial model of thrombosis associated with intimal deendothelialization was developed. Donor rat carotid arteries were everted and mechanically deendothelialized with a scalpel blade. The vessels were next subjected to one of several treatments, which included 30-minute incubation with urokinase, heparin, or vehicle (lactated Ringer's solution). The vessels were then washed, reinverted to normal orientation, sectioned into 5 mm lengths, and grafted into the femoral arteries of recipient rats. Two-hour patency rates were 25% for controls (n = 20), 10% for heparin-treated vessels (n = 10), and 55% for urokinase-treated vessels (n = 20); this last was significantly greater than the other two groups. In vitro investigations revealed that urokinase has a high capacity for binding to subendothelium, with a release half-life of approximately 20 minutes. Surface-bound urokinase was found to have proteolytic activity similar to that of urokinase in solution. These results indicate that urokinase may be a more beneficial irrigating solution additive than heparin for repair of traumatized vessels.

Administration, Topical↗
PubMed1992

Maintenance of patency after vascular trauma by topical irrigation with a peptide homologous to the carboxy-terminus of the fibrinogen gamma chain.

Synthetic peptides with amino acid sequences homologous to the carboxy-terminal sequence of the gamma chain of human fibrinogen were evaluated for their capacity to inhibit thrombus development. A 21-residue peptide effectively inhibited surface-mediated fibrin clot propagation in vitro. Since this effect was localized to the surface, we proceeded with in vivo evaluation, using site-specific topical application only. In a rat model of arterial trauma and microvascular repair, topical application of the 21-residue peptide significantly reduced the rate of thrombosis to 17%, as compared with a control rate of 83%; in comparison, a 12-residue homologue reduced the thrombosis rate only modestly to 61%, which was not significant compared with the control rate. These results indicate the feasibility of antithrombotic therapy with topically applied agents, an approach that may obviate the use of systemic anticoagulation in extremity-replantation surgery.

Administration, Topical↗
PubMed1992

Microvascular salvage procedures with adjuvant antithrombotic therapy for restitution of patency in a rat model.

Thrombosis following microvascular anastomosis requires further surgical intervention, involving anastomotic resection and reanastomosis or interpositional vein grafting. This study was undertaken to investigate different methods of salvaging thrombosed vessels, using a rat-vein model of error-induced thrombosis. Vessels were reconstructed 4 hr after the onset of thrombosis, using one of three methods: Group 1--removal of the erroneously placed stitch; Group 2--anastomotic resection and re-anastomosis; and Group 3--resection and replacement with a vein graft. Adjuvant antithrombotic therapy was simultaneously evaluated, assessing the influence of systemic Iloprost or heparin. Patency rates at one day postoperatively were 0 percent, 12.5 percent and 37.5 percent for Groups 1, 2, and 3, respectively. Following Iloprost infusion, these rates increased to 25 percent, 25 percent, and 56.3 percent, respectively and, following heparin administration, to 50 percent, 68.8 percent, and 81.8 percent, respectively. Significant increases were found for vein grafting (Group 3), and for the heparin-treated subgroups using all three methods. Effective levels of both Iloprost and heparin were confirmed by increases noted in rat-tail bleeding times. Significant rates of recanalization by three days following one-day occlusion were found in Groups 1 and 2. These results support the application of vein-graft replacement for thrombosed veins, concurrently with systemic heparinization. This study further confirms the high rate of recanalization seen in thrombosed rat femoral veins.

Anastomosis, Surgical↗
PubMed1992

The influence of diabetes on free flap transfer: I. Flap survival and microvascular healing.

Although recent clinical case presentations suggest that diabetes does not predispose free tissue transfers to increased risk of failure, this remains an open question. The present study used a syngeneic rat strain (Lewis) for free groin flap transplantations between normal rats and streptozotocin-induced diabetic rats (2 months' duration of symptoms), to investigate the influence of diabetes on flap transfer. Flap survival at 1 week, vascular patency, flap histology and ultrastructure, and scanning electron microscopy of anastomotic sites and of corrosion casts of flap vasculature were used as bases for comparison. No differences were found in comparisons of flap survival between any groups of transfer combinations (normal flap onto normal recipient, diabetic flap onto normal recipient, normal flap onto diabetic recipient, and diabetic flap onto diabetic recipient); 100% success was achieved in each group. No differences were found in histology or corrosion casts. Transmission electron microscopy revealed a thickening of the capillary basement membrane in rat diabetic skin after only 8 weeks of symptoms. This ultrastructural finding is consistent with similar capillary basement membrane thickening seen in many other tissues of short- and long-term diabetic animals and humans. Re-endothelialization across the arterial anastomosis at 2 weeks postoperatively was significantly faster in normal versus diabetic animals (p less than 0.05). The predominantly negative findings of this study support the application of free flap transfers in diabetic patients. It is concluded that reconstructive efforts involving free tissue transfer may not be contraindicated in diabetic patients.

Animals↗
PubMed1992

The influence of diabetes on free flap transfer: II. The effect of ischemia on flap survival.

Insulin-dependent diabetes mellitus causes microangiopathic changes in many tissues, including skin and muscle. It is not known if such changes are detrimental to free flap transfer, particularly after extended ischemia. To address this issue, we used an experimental design by using a syngeneic rat strain (Lewis) for free groin flap and muscle flap transplantations from streptozotocin-induced diabetic rats (2 month's duration of symptoms) to normal rats. Flaps from age-matched normal donors were transplanted to normal recipients for control comparisons. Groin flaps were stored ischemically for 12 or 18 hours at room temperature, or for 48 hours in the cold (4 degrees C) before transplantation. Flap survival and vascular patency were assessed at 7 days. Cutaneous maximus muscle flaps were transplanted to the groins of recipients after 6 hours of room temperature ischemia. Vascular patency, muscle viability, flap weight change (edema), and dehydrogenase activity were assessed after 2 days of reperfusion. Seventy percent, 67%, and 73% of diabetic groin flaps survived after 12, 18, or 48 (cold) hours of ischemia, respectively, in comparison with 90%, 73%, and 87% of normal flaps undergoing the same respective ischemia periods. The differences were not significant, even when the data were pooled (p greater than 0.1). Muscle flaps also showed no significant differences for the parameters studied. These results support the use of microvascular reconstructive surgery in diabetic patients, suggesting that moderate ischemic challenges do not compromise free flap transfer or extremity replantation.

Animals↗
PubMed1992

A simultaneous distal phalanx avulsion fracture with profundus tendon avulsion. A case report and review of the literature.

Avulsion injuries of the flexor digitorum profundus are fairly common injuries, yet simultaneous avulsion fractures of the insertion of this tendon associated with rupture of the tendon from the bony fragment is rarely described and is more complicated. In the 24-year-old athlete, the injury was classified according to the system of Leddy and Packer. The authors' method of treatment is also described. Similar cases presented in the literature are reported, with emphasis on pathomechanism, physical findings, and surgical repair method. In this rare injury, stabilization of the distal interphalangeal joint is necessary even at the expense of early motion.

Adult↗
PubMed1992

Management of acute and chronic vascular injuries to the arm and forearm. Indications and technique.

Acute arterial injuries of the upper extremity account for half of civilian arterial injuries in the United States. The great majority of these injuries are due to penetrating trauma, with stab wounds and gunshot wounds being the most common cause. The history of the injury and a careful physical examination will identify most injuries. Arteriography should be performed when a vascular injury is suspected but not confirmed by physical examination. Reconstruction of critical vascular lesions is essential for restoration of flow distally. Noncritical lesions may be repaired in most cases, with long-term patency rates averaging 50% to 68%. Although amputation is uncommon after upper-extremity vascular injury, long-term disability can be significant in those patients with concomitant nerve injury. Chronic upper-extremity ischemia may be secondary to atherosclerotic occlusive disease, aneurysms, or arteriovenous fistulas. Angiography will delineate the diseased or occluded arterial segment, allowing bypass to be successful in more than 90% of cases. With careful attention to proper diagnosis and treatment, good to excellent long-term relief of symptoms can be obtained.

Acute Disease↗
PubMed1991

Rat femoral vein-to-vein grafts as a microvascular practice model: factors that influence patency.

The rat femoral vein has become a standard model for microvascular anastomosis practice as well as for research investigations into various manipulative influences upon venous patency. Although vein grafts to the rat artery are the focus of many experimental studies, few reports have investigated vein-to-vein grafts. This study examines the short-term patency (1-3 days) of vein grafts interpositioned to the rat femoral vein. Several factors are studied for their ability to alter the patency rate. The results indicate that patency is difficult to achieve following the creation of a second serial anastomosis (construction of a vein-to-vein graft). Systemic heparin consistently improves patency rates, and trends toward increased patency are seen for reduction in longitudinal tension of the repaired vessel. It is also implied that a deeper understanding of venous hemodynamics and thrombotic events may lead to improved methodologies in the clinical applications of microvenous repairs. These results indicate that rat vein-to-vein grafts may provide a challenging microvascular training model, while introducing the novice microsurgeon to some of the complicating factors encountered with microvascular grafting.

Anastomosis, Surgical↗
PubMed1991

Effects of venous hypertension on rabbit free flap survival.

A two-stage project was developed to study the effect of increased venous pressure on blood flow and survival in microvascular free tissue transfers. A rabbit epigastric fasciocutaneous free flap model was used. The blood flow in the rabbit epigastric free flap is 1.07 +/- 0.06 ml/min. The average venous pressure is 8.6 +/- 1.7 cm water. A logarithmic relationship between blood flow and venous pressure was demonstrated, with a statistically significant decrease in blood flow to 20-35% of the control values when the venous pressure rose above 28-30 cm water. This study stands in support of the tolerance by free tissue transfers of pressures below this range. The results further show a positive correlation between increasing venous pressure and free flap failure.

Animals↗
PubMed1991

Topically applied antithrombotic agents offer a new therapeutic approach to the prevention of microvascular thrombosis.

In the quest to develop optimal antithrombotic therapies for reconstructive microsurgery, with concomitant minimization of patient risk for generalized hemorrhage, surgeons have been turning to localized intraarterial delivery of various agents. An extension of this direction is to design agents that bind specifically to the site of thrombogenesis and effectively inhibit or prevent the buildup of thrombotic components. Progress in this direction must make use of the latest developments in the molecular understanding of coagulation, platelet adhesion/aggregation, and fibrinolytic processes. This article reviews pertinent developments in the biochemical understanding of thrombosis and discusses current avenues of investigation in the development of topically applied agents that help prevent microvascular thrombotic occlusion.

Administration, Topical↗
PubMed1991

Evaluation of the effect of pharmacologic agents on crush-avulsion arterial injuries: a scanning electron microscopy study.

This study was designed to investigate the short-term formation and composition of thrombus occurring at sites of arterial intimal injury in rabbits. Anti-coagulants, platelet anti-aggregation agents, and fibrinolytic agents were evaluated for their influence upon the developing thrombus, utilizing scanning electron microscopy to determine thrombus surface composition. These agents included: heparin, aspirin, dextran 40, streptokinase, and prostacyclin. The results are consistent with the known nature of each of these agents. When two agents were given simultaneously, each acting on different aspects of thrombogenesis (platelets vs. fibrin), the outcome appeared synergistic, with substantial reduction in thrombus accumulation; clear inhibition of both platelet aggregation and fibrin polymerization was noted. These findings support the clinical use of two agents used simultaneously, one inhibiting fibrin strand formation and the other inhibiting platelet adherence aggregation, for the prevention of micro-arterial thrombosis.

Animals↗