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Biomedical subjects

B C Cooley

Publications and source records attributed to B C Cooley.

52 records · Page 3Linked to original sources

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↗

Experimental study of the influence of arterial trauma on dependent distal tissue survival.

An experimental model was developed combining arterial trauma with island flap creation using the rat groin flap system. Flap arteries were subjected to crush/avulsion injuries with subsequent microvascular repair. A second series involved resection 4 hr after thrombosis of injured flap arteries and interpositional vein grafting to reestablish circulation. A single bolus of systemic heparin was administered to half of the animals from each series on a blinded, randomized basis. Arterial patency at 7 days correlated with flap survival. There was no case of partial flap loss. Patencies improved in the first series from 31% to 71% with heparin administration (P less than 0.05) and from 58% to 90% in the second (not significantly different). A third series involving immediate resection of traumatized vessel and vein graft replacement achieved a patency of 92% (without heparinization). These results support the value of replacement of all traumatized arterial tissue with vein grafts and indicate the efficacy of systemic heparin (in single bolus) for enhancing the likelihood of maintaining patency. Furthermore, it is suggested that the occurrence of a thrombogenic site in the arterial inflow to a region of dependent tissue does not lead to partial tissue loss, and thus thromboembolic events may not be responsible for this clinical phenomenon.

Anastomosis, Surgical↗

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↗

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↗

Perfusion of free flaps with heparinized whole blood during ischemic storage.

This study was designed to investigate the use of heparinized whole blood as a perfusate for extending the tolerable ischemic interval of free flaps. Unilateral free groin flaps stored at 20 degrees for 30 hr were used in four groups of 12 rats each. One group served as a control while a second involved systemic heparinization immediately prior to raising the flap for storage. The third and fourth groups underwent a brief perfusion (10-30 min) with anticoagulated whole blood midway through the ischemic interval (15 hr); one of these groups involved temporary revascularization to the arterial system of a donor heparinized rat. The fourth group received hand-perfused anticoagulated (with heparin and citrate) whole blood administered through a cannula placed in the flap artery. After the 30-hr interval, flaps were replanted to the original groin site with standard microvascular technique. Percentages of the numbers of surviving flaps were: 8 percent for controls, 58 percent for both preheparinized and donor-perfused flaps, and 92 percent for the hand-perfused group. The authors conclude that anticoagulated blood within the flap vasculature during ischemic storage can improve the chance for viable reperfusion after replantation, and may offer a safeguard against the no-reflow phenomenon after extended ischemia.

Animals↗

Thrombosis of microvascular anastomoses in traumatized vessels: fibrin versus platelets.

Thrombosis is the end result of two closely interrelated processes: the coagulation cascade and the platelet aggregation process. To determine their relative contribution, we used pharmacologic agents that selectively block each process. The specific effect of each pharmacologic agent on either fibrin deposition or platelet activity was confirmed morphologically by scanning electron microscopy and was substantiated with ADP-induced platelet aggregation and blood clotting time determinations. Forty-two rats had both femoral arteries subjected to a standardized crush-avulsion injury. A total of 84 femoral microvascular anastomoses were subsequently performed. None of the 24 control anastomoses treated with saline remained patent, whereas 6 of 24 of the anastomoses treated with dazmagrel (a selective thromboxane synthetase and platelet aggregation inhibitor), 2.5 mg/kg IV, remained patent and 18 of 24 of those treated with a single dose of heparin, 200 U/kg IV, remained patent. All 12 anastomoses treated with both drugs remained patent but developed a 33 percent hematoma rate. We conclude that in this microvascular model, fibrin mesh deposition is a more significant factor than platelet aggregation in the pathogenesis of occlusional thrombosis within traumatized arteries. Its temporary inhibition with a single dose of heparin yielded a 75 percent improvement in patency rate.

Anastomosis, Surgical↗

Scanning electron microscopy of crush/avulsion arterial trauma:effect of heparin and aspirin administration.

A model of vascular trauma and subsequent reanastomosis with poor postoperative likelihood of patency was developed in the rat femoral artery. Patency rates were significantly improved with intravenous heparin, intragastric aspirin, and both agents together. Heparin yielded higher patency than aspirin. Intimal surfaces of the vessels at various postoperative intervals were observed with the scanning electron microscope. More fibrin accumulation was seen in the aspirin-treated animals, while more platelet aggregation was found in the heparin-treated group. Both platelet aggregation and fibrin strand development appeared retarded with both agents administered. All groups demonstrated good healing of the ruptured intimal surfaces, beginning at 2 days postoperatively. It is concluded that fibrin strand development is a more significant factor in microvascular occlusion than platelet aggregation.

Animals↗

Experimental models for evaluating antithrombotic therapies in replantation microsurgery.

A variety of anticoagulation and antiplatelet aggregation agents are in use clinically, and in applications to microvascular surgery, a clear choice for the most effective therapy has not been determined. Models of vascular trauma combined with microvascular anastomosis have been developed for comparing the efficacy of these agents in maintaining vascular patency. In a rat model of microvascular thrombosis, heparin effectively prevents occlusion in both arteries and veins, at clinical levels of administration. Aspirin helps prevent thrombosis, but not as well as heparin. These results support the beneficial effect of antithrombotic drug therapies, and suggest a more potent role of the heparin-inhibited fibrin clot over platelet aggregation in creating thrombotic occlusion of small vessels.

Animals↗

A rat uterine horn model of genital tract wound healing.

A rat uterine horn model of genital tract wound healing is described. Healing was reflected by acquisition of strength and elasticity, measured by burst strength (BS) and extensibility (EX), respectively. A tensiometer (Instron Corp., Canton, MA) was used to assess these characteristics in castrated and estrogen-supplemented or nonsupplemented animals. While the horn weights (HW), BS, and EX of contralateral horns were not significantly different, the intra-animal variation of HW was 7.2%, BS was 17.7% and EX was 38.2%. In a second experiment, one uterine horn was divided and anastomosed, and the animal given estrogen supplementation or a placebo pellet. Estrogen administration was found to increase BS and EX of anastomosed horns prior to 14 days, but had no beneficial effect at 21 or 42 days. The data suggest that estrogen may be required for optimal early healing of genital tract wounds.

Animals↗

Laser-assisted vasal anastomosis in the rat and man.

In order to study the efficacy of laser-assisted vasal anastomosis (LAVA), a microscopic carbon dioxide surgical laser (Xanar) was utilized in the anastomoses of human vas deferens in vitro and the Sprague-Dawley rat vas deferens in vivo. The longitudinal tensile and internal hydrostatic pressure strengths of laser-assisted vasal anastomoses were compared to conventional microsurgical suture anastomoses in the human vas deferens. The LAVA group had a greater mean internal hydrostatic pressure strength (p less than 0.001) and a lesser mean longitudinal tensile strength (p less than 0.001) than the conventional microsurgical group. Further evaluation was performed in the Sprague-Dawley rat model, comparing post-operative fertility, patency, healing and sperm granuloma occurrence among four surgically treated groups and a control group: LAVA, conventional suture anastomosis, sham operated, and vasectomized. Light and scanning electron microscopic examination revealed equivalent healing in both the LAVA and conventional groups. Fertility was not statistically different in the LAVA, conventional, control, and sham operated groups. However, the incidence of gross sperm granulomas observed in the LAVA group (80%) was much higher than in the conventional suture anastomosis group (0%). In conclusion, laser-assisted vasal anastomosis is a fast and simple technique for vasal reanastomosis and was as successful (in pregnancies) as conventional suture anastomosis in producing fertility in rats undergoing vasal reanastomosis, but the incidence of sperm granuloma is higher.

Animals↗

Microvascular repair following local crush and avulsion vascular injury.

A model has been developed demonstrating intimal damage resulting from a combined crush and avulsion injury to the femoral artery of the rat. Revascularization after traumatization is accomplished with microvascular anastomosis of the severed ends. Vascular patency rates at 2 and 7 days postoperatively are low (0-25%) in comparison with control groups (90-100%). A high correlation is found between patency tests performed at 20 minutes and at 2 days after blood flow re-establishment. Systemically administered heparin improves traumatized-vessel patency dramatically.

Animals↗

Lysis of venous clots by local intraarterial Thrombolysin injection in the rat.

Intravascular coagulation is the final common pathway of failure in replanted digits and "free" tissue transfers. To address this clinical problem, a model based upon intimal damage and stasis in the rat femoral vein was developed. The ability of local, intraarterially administered Thrombolysin to achieve "local" clot lysis was investigated. "Systemic anticoagulation" was measured by standard hematologic monitoring and "systemic thrombolysis" by lysis of a contralateral standard femoral vein clot. The mean drug volume required for local clot lysis was proportional to the clots' duration time; 7.8 ml required for the 30-minute, and 17.0 ml required for the 60-minute clot (p less than 0.05). Lysis was achieved by local intraarterial Thrombolysin in 87% of the clots of 30 minutes' duration and in 94% of the clots of 60 minutes' duration. Overall, just 3.6% of contralateral clots lysed (p less than 0.001). Systemic anticoagulation did not occur.

Animals↗

Alcohol-induced alterations in hippocampal afterdischarges and afterdischarge thresholds: dose-reponse studies.

The hippocampal afterdischarge (AD) has been suggested as an index of toxicant-induced CNS change [1]. The present experiments report raised AD thresholds, decreased AD durations, shorter post-stimulation latencies to AD onset, decreased numbers of AD spike complexes and increased numbers of spikes/complex following alcohol administration. Results are discussed in light of single-unit data concerning alcohol effects upon hippocampal cells, and the biphasic effects of alcohol upon behavior.

Animals↗