Biomedical subjects
Publications and source records attributed to H L Bush.
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A sustained increase in muscle compartment pressures can cause tissue necrosis. When compartment pressures exceed recumbent tibial vein pressures, blood flow in tibial veins may be impaired. These changes can be detected by Doppler venous flow evaluation. In 26 patients at risk for compartment syndrome, serial examinations, Doppler venous flow, and measurements of compartment pressures were performed. All patients with abnormal Doppler venous flow results had or developed neuromuscular deficits. Patients with normal Doppler venous flow either initially or after fasciotomy did not develop the compartment syndrome. This syndrome can be evaluated and followed up sequentially by measuring Doppler venous flow in tibial veins.
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Platelet aggregation and release phenomena are central to most postulated mechanisms of thrombosis and neointimal hyperplasia after carotid endarterectomy. Therefore high-dose aspirin (HDA) has been advocated to minimize these sources of endarterectomy failure. We have defined low-dose aspirin (LDA) that selectively blocks platelet cyclooxygenase but preserves arterial wall cyclooxygenase in the nonhuman primate, Macaca fascicularis. We compared this theoretically optimal aspirin dose with HDA and no treatment (control) in a model of carotid endarterectomy. The aspirin was started before operation and continued for 6 weeks after operation, at which time the endarterectomized vessels were excised. The patency and morphologic findings of the arteries were measured. Platelet function was monitored by bleeding time and serum thromboxane A2 determinations. LDA and HDA were associated with 100% patency, whereas the control group had 50% patency. However, HDA did not protect the vessel from developing neointimal hyperplasia, which was seen in the control group and was associated with platelet adherence to the flow surface at 6 weeks. At 6 weeks, LDA significantly decreased but did not totally prevent neointimal hyperplasia and the flow surface was healed. Therefore the genesis of neointimal hyperplasia after endarterectomy may be more complex than simply a function of platelet-vessel wall interaction.
We undertook a prospective randomized trial to examine whether an intravenous cytomegalovirus (CMV) immune globulin would prevent primary CMV disease in renal-transplant recipients. Fifty-nine CMV-seronegative patients who received kidneys from donors who had antibodies against CMV were assigned to receive either intravenous CMV immune globulin or no treatment. The immune globulin was administered in multiple doses over the first four months after transplantation. The incidence of virologically confirmed CMV-associated syndromes was reduced from 60 percent in controls to 21 percent in recipients of CMV immune globulin (P less than 0.01). Fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20 percent of controls (P = 0.05). Only 4 percent of globulin recipients had marked leukopenia (reflecting serious CMV disease), as compared with 37 percent of the controls (P less than 0.01). There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17 percent of controls as compared with 4 percent of globulin recipients). A significant reduction in serious CMV-associated disease was observed even when patients were stratified according to therapy for transplant rejection (P = 0.04). We observed no effect of immune globulin on rates of viral isolation or seroconversion, suggesting that treated patients often harbored the virus but that clinically evident disease was much less likely to develop in them. We conclude that CMV immune globulin provides effective prophylaxis in renal-transplant recipients at risk for primary CMV disease.
To determine the causes and optimum management of early in situ bypass occlusions, we reviewed our experience of 13 thromboses occurring within the first 30 postoperative days in 148 in situ saphenous vein reconstructions. All early thrombosed bypasses were performed for limb salvage, with 31% of bypasses to the popliteal level and 69% to infrapopliteal vessels. The median time to occlusion was 24 hours. All patients underwent reoperation. Graft failure was due to retained venous valves in 31% of the procedures, other technical problems in 38%, and inadequate outflow in 31%. Reoperative surgery was individualized. In grafts explored for thrombosis, the one-year graft patency rate was 46%, and the limb salvage rate was 54%. Graft patency did not appear to correlate with the presumed cause of initial graft occlusion. Our results indicate that an aggressive surgical approach is appropriate in early in situ graft thrombosis.
Neointimal hyperplasia of the arterial wall may occur after carotid endarterectomy. This proliferative lesion is a pathologic response of the injured arterial wall and may lead to progressive stenosis. We investigated the effect of endothelial cell seeding (ECS) or antiplatelet therapy with aspirin (ASA) on inhibition of this lesion in a canine model. Endarterectomies were performed in 160 carotid arteries; 46 endarterectomies were treated perioperatively with aspirin (325 mg per day), 34 were seeded with a high density (3 X 10(6)) of autogenous endothelial cells, and 80 were untreated control arteries. At selected time intervals, the patent arteries were perfusion-fixed and the cross-sectional area (measured in square millimeters) of neointimal hyperplasia was measured by means of digital planimetry. At 6 weeks, patency of the endarterectomized carotid artery was 88% in the ASA and ECS groups, in contrast to 35% in the control group (p less than 0.01). The cross-sectional area of neointimal hyperplasia was not significantly different in the ASA and the control groups at 6 weeks. However, the ECS group showed a marked reduction in neointimal hyperplasia at 6 weeks (p less than 0.01). This inhibition of neointimal hyperplasia after carotid endarterectomy by ECS may reflect accelerated luminal healing or a direct inhibition of smooth muscle cell proliferation in the injured arterial wall.
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During a 14-month period we used a left-flank, retroperitoneal, retrorenal approach in 23 high-risk patients with abdominal aortic aneurysm (AAA). Fourteen patients underwent suprarenal/celiac cross clamp for juxtarenal/suprarenal AAA and/or associated occlusive disease. Other indications for this approach included diminished cardiac and/or pulmonary reserve, previous extensive abdominal surgery, obesity, and inflammatory AAA. There was only one death (4%) in this high-risk group and minimal operative morbidity. The flexibility afforded by this approach for high aortic exposure allowed expeditious proximal anastomoses with minimal postoperative renal dysfunction. Pulmonary complications, ileus, and pain were reduced and patient mobilization was rapid despite the complex nature of the operative procedures. We believe that this approach offers significant advantages for all cases of AAA but particularly for anatomically complex lesions and medically high-risk patients.
Tissue plasminogen activator and urokinase were evaluated in a model of prosthetic graft thrombosis. In addition, the effects of thrombus age on lysability and the effect of thrombolytic agents on endothelium were examined. Polytef (polytetrafluoroethylene [PTFE]) grafts (3 mm X 3.5 cm) were placed in femoral arteries of dogs and graft thrombosis was induced. Grafts were treated with a local infusion of either urokinase or tissue plasminogen activator (4000 units/min) and the times for initial flow, complete thrombolysis, and anastomotic bleeding were noted. The luminal surfaces of the grafts and the proximal arterial segments were assayed for the production of thromboxane A2 and prostacyclin and examined with scanning electron microscopy. No difference in the ease of graft lysis was observed, but 50% of tissue plasminogen activator-treated vs 0% of urokinase treated grafts had extravasation of blood through the wall. Grafts treated with tissue plasminogen activator produced less thromboxane A2 and had less thrombus than those treated with urokinase. No differences between arteries exposed to either agent and control arteries were seen. Grafts treated 1,3,5, and 7 days after thrombosis were progressively more difficult to lyse. We conclude that tissue plasminogen activator is an effective thrombolytic agent, but has a potential for local bleeding complications. Grafts of PTFE are thrombogenic after lysis, but may be less so with tissue plasminogen activator than with urokinase. No effect on arterial endothelium was seen, and our studies confirm the clinical impression that older thrombi are more difficult to lyse.
Optimal infrainguinal revascularization should provide limb salvage for the longest duration of time. It is not known whether limb salvage is longer with an initial below-knee popliteal or tibial in situ saphenous vein graft or with staged bypasses; that is, an initial above-knee popliteal prosthetic bypass if feasible, followed by a more distal vein graft should the above-knee prosthetic graft fail. A retrospective review of 197 lower extremity vascular reconstructions performed since 1976 utilizing polytetrafluoroethylene (PTFE), umbilical vein, or in situ saphenous vein was completed. The data were analyzed for differences in limb salvage and prevention of limb threatening ischemia among three subgroups: above-knee prosthetic bypass, below-knee or tibial in situ saphenous vein bypass, and staged reconstructions (above-knee prosthetic bypass with subsequent in situ bypass). The groups were similar with respect to severity of limb threatening ischemia as indicated by mean preoperative ankle-brachial indices. Cumulative secondary limb salvage at 36 months was 73 percent for prosthetic grafts in the above-knee position, 78 percent for in situ saphenous vein grafts in the below-knee or tibial position, and 87 percent for staged reconstruction with an initial prosthetic graft to the above-knee position followed by a distal in situ vein bypass when the prosthetic graft fails.
When the saphenous vein is used in the in situ position for arterial bypass surgery, it is associated with more optimal preservation of the endothelial lining and with improved graft patency compared with reversed vein grafts. However, it is not clear whether preservation of endothelial integrity persists after arterialization. The goal of this study was to establish whether preservation of the endothelium before arterialization is a critical factor in the development of late functional and morphologic abnormalities of autogenous vein grafts. Paired reversed and in situ vein grafts were created in 75 mongrel dogs. Veins to be used in the reversed position were excised and stored in either heparinized whole blood at 37 degrees C or saline solution at 4 degrees C. Veins were studied before and after arterialization. The veins were arterialized by anastomosis to the carotid artery and excised at intervals of 1 day to 12 weeks for studies of the luminal production of prostacyclin and thromboxane A2 in addition to luminal morphology. Before arterialization, normothermic whole blood preserved biochemical function of the endothelium significantly better than hypothermic saline solution, but not as well as the in situ vein procedure. Soon after arterialization, all three vein grafts showed significant functional and morphologic abnormalities consistent with injury of the vein graft. Morphologic healing of the endothelial monolayer progressed slowly back to normal; however, the biochemical capacity of the vein graft never matched that of the prearterialized vein, nor that of normal host arteries. Regardless of surgical technique, all vein grafts exhibited a period of abnormal structure and function, which exposed them to the risk of thrombogenesis. This period of potential leukocyte or platelet interaction with the vein wall could lead to release phenomena as well as proliferative changes in the vessel wall.
Despite successful thrombolysis of occluded prosthetic grafts, rethrombosis remains a problem. We investigated the efficacy of aspirin in maintaining patency of polytetrafluoroethylene grafts (3 mm X 3.5 cm) in canine femoral arteries after thrombolytic therapy. After induction of thrombosis, either tissue-type plasminogen activator (t-PA) or urokinase (UK) was infused just proximal to the thrombus (4000 U/min) until complete thrombolysis was achieved. Five of the 10 UK-treated dogs and five of the 10 t-PA-treated dogs received aspirin immediately after recanalization, and aspirin was continued (325 mg/day) for 4 weeks or until occlusion occurred. A systemic aspirin effect was confirmed by marked depression of serum thromboxane B2 and absent platelet aggregation. Only two of the 10 grafts in the aspirin-free group remained patent for 4 weeks. The remaining eight grafts had all reoccluded by 2 weeks. None of the 10 grafts in the aspirin-treated group reoccluded during the 4 weeks. This significantly improved patency (p less than .001) in the aspirin-treated group was observed equally in grafts treated with t-PA or UK. Thus aspirin is a potent agent in preventing rethrombosis after thrombolytic recanalization of prosthetic grafts.
The purpose of the present study was to examine the effects of surgery on plasma beta-endorphin dynamics. Plasma beta-endorphin levels were measured by liquid chromatography/radioimmunoassay in seven patients undergoing elective surgery. Blood samples were obtained every 4 hr for two 24-hr periods: one beginning 48 hr before surgery and the other beginning 48 hr after surgery. Computer analysis of beta-endorphin levels as a function of clock time demonstrated a true circadian rhythm preoperatively with a mean of 28.0 +/- 5.9 pg/ml. In the postoperative period mean beta-endorphin levels were significantly elevated (85.6 +/- 20.7 pg/ml, P less than 0.005). Surgical procedures caused significant phase shifting in the grouped mean circadian rhythm of plasma beta-endorphin (mean = 2.4 hr). When the data was analyzed individually, plasma circadian rhythms were found to be totally abolished in the three patients with the longest operative times (mean = 3.8 hr) and significantly displaced in time in the remaining four patients. These prolonged alterations in plasma endogenous opioid peptide levels following surgery have not been previously reported, and should be considered in the management of the postsurgical patient.
A transient delirium, including hallucinations and disorientation, occurred at some time during a 48 to 72 hr postoperative period in patients recovering from elective surgery in an intensive care unit. The occurrence of delirium in these patients was associated with a significant and unusually prolonged postoperative increase in circulating levels of beta-endorphin (B-endorphin) and cortisol, and a total disruption of normal plasma circadian rhythms of B-endorphin and cortisol. Postoperative mean 24-hr plasma levels of B-endorphin and cortisol were not significantly different from preoperative baseline levels in those patients who did not exhibit post-surgical delirium. Circadian rhythms of B-endorphin and cortisol in the non-delirious patients also remained normal following surgery, although peak plasma concentrations were significantly phase-shifted to later in the day. A disruption in circadian rhythms of the endogenous opiate/hypothalamic-pituitary-adrenal axis may represent an important component of post-operative psychological changes that are frequently observed in the intensive care unit setting.
Revascularization of the lower extremity using the in situ saphenous vein bypass graft has resurfaced as a clinical alternative to reversal of the saphenous vein. Early patency rates have been excellent, however, concern has been raised about the durability of the in situ technique. Our total experience with this technique has been reviewed to evaluate its effectiveness on a teaching vascular service. Seventy-six limbs in 71 patients were revascularized using the in situ technique. The distal anastomosis was created at the below-the-knee popliteal level in 26 limbs and at the infrapopliteal level in 50 limbs. Operative assessment of the vein quality showed 42 percent to be phlebitic or less than 4 mm in diameter. Hospital mortality was 0 and late mortality was 8 percent. Cumulative life table analysis showed the graft patency rate to be 89 percent 1 month postoperatively, 82 percent at 1 year, 77 percent at 2 years, and 72 percent up to 4 year postoperatively. Patency was independent of runoff to the pedal arch and the level of the distal anastomosis. Limb salvage at 4 years was 83 percent for distal popliteal grafts and 79 percent for infrapopliteal reconstructions. Our results indicate that the long-term durability of the in situ saphenous vein graft is excellent despite suboptimal veins and poor runoff. When performed properly, it is the preferred technique for arterial reconstruction below the knee joint.
The cause of endothelial injury during vein harvesting and preservation is complex. Hypothermia is thought necessary to preserve cell viability but has been implicated in morphologic injury to the endothelium. This study explored the effect of temperature on preserving endothelial function using prostacyclin production as a metabolic marker. Canine veins were atraumatically excised and matched segments were stored at three temperatures using either nutrient medium or heparinized saline. After storage, endogenous production of prostacyclin by the luminal surface of each vein was collected in a closed perfusion system at 37 degrees C and assayed by radioimmunoassay. Optimal prostacyclin production was observed in veins stored in tissue culture medium at normothermia. Preservation of normal endothelial function may require revision of traditional vein graft-harvesting techniques.
Graft thrombosis soon after reconstruction remains a major obstacle to the use of reversed vein grafts in infrapopliteal reconstruction. Our clinical experience with in situ vein grafts corroborates Leather's results by demonstrating an overall graft patency of 95% below the knee at 1 year and 94% in the infrapopliteal group. It has been postulated that this improved early patency rate of in situ vein grafts is the result of more optimal preservation of the endothelium of the vein graft. To investigate this hypothesis, human saphenous veins were handled by an in situ and a reversed technique. The intact vein segments were then tested for luminal production of prostacyclin and thromboxane A2 and fixed for scanning electron microscopic analysis of the surface morphology. This study demonstrated that endothelial cell prostacyclin release is enhanced in human in situ vein segments but not in reversed vein segments. In addition, luminal production of thromboxane A2 is significantly greater in the reversed than in the in situ vein segments. These findings are associated with marked endothelial structural damage in the reversed veins and minimal endothelial disruption in the in situ veins. Therefore the ratio of the antiaggregatory vasodilator prostacyclin to the proaggregatory vasoconstrictor thromboxane A2 is significantly more favorable for the in situ vein segment than for the reversed vein segment. The observed excellent early patency of the in situ vein grafts in our poor-risk patient population may in part be the result of this favorable balance of prostacyclin and thromboxane A2 and the more optimally preserved endothelial morphology.