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Biomedical subjects

L M Graham

Publications and source records attributed to L M Graham.

At least 55 records · Page 3Linked to original sources
PubMed1988

Utilizing angiogenic agents to expedite the neovascularization process in skin flaps.

The revascularization of a skin flap after flap transposition is an important step in flap survival. This study investigates the efficacy of certain angiogenic agents to expedite the neovascularization process and to increase the viability of skin flaps. Eighty-four island skin flaps were designed on the auricles of 42 New Zealand White rabbits to achieve 90% necrosis over a 7-day period. Thirty-six flaps were treated with Endothelial Cell Growth Supplement (ECGS) or Endothelial Cell Growth Factor (ECGF) at several concentrations topically or immersed in Gelfoam. The remaining flaps were used as normal saline controls. Flap viability and peripheral neovascularization were documented by polar planimetry, angiography, and histological analysis. The flap viability of the ECGS-Gelfoam -treated flaps was 100% greater than their normal saline-Gelfoam controls (p = .021). Flap angiograms demonstrated increased vascular ingrowth among the treated flaps compared to the controls. This study suggests that angiogenic agents can expedite flap neovascularization and have the potential to increase flap viability.

Administration, Topical↗
PubMed1988

Systemic effects of prosthetic vascular graft implantation.

The effect of prosthetic vascular graft implantation on systemic complement activation, as well as leukocyte and platelet counts, was studied in rabbits. Animals underwent aortic clamping and declamping alone (group I) or with implantation of an externally supported PTFE graft (group II) or preclotted knitted Dacron graft (group III). Fifteen minutes after declamping, mild activation of complement reflected as a fall in CH50 to 72% of preoperative baseline values was observed in group I animals. Comparatively greater activation was seen in group II (43% baseline) and group III (28% baseline) animals. The differences between groups I and II (p less than 0.05) and I and III (p less than 0.01) were significant. The drop in platelet count was greater in group II (66% baseline) and group III (53% baseline) animals compared with group I (86% baseline). Neutrophil counts decreased in group I animals (75% baseline), but, again, this fall was more marked in group II (35% baseline) and group III (43% baseline) animals. The difference between groups I and II was significant (p less than 0.05). Similarly, monocyte count decreased in group I animals (80% baseline), which was also more marked in group II (32% baseline) and group III (31% baseline) animals. The differences between group I and groups II and III were significant (p less than 0.05 for each). These trends persisted throughout the first postoperative hour. These results suggest that the blood-surface interactions produced systemic effects in vivo.

Animals↗
PubMed1988

Endothelial cell proliferation in vitro after incubation with anticoagulant and antiplatelet drugs.

An in vitro tissue culture model was used in the evaluation of various anticoagulant and antiplatelet drugs on endothelial cell proliferation and eicosanoid production. Low concentrations, less than normally achieved plasma concentrations of various heparins (beef lung, porcine intestinal and low molecular weight heparin from porcine intestine), increased endothelial cell growth. Higher concentrations showed a decrease for regular heparins, most marked for beef lung heparin -45%, compared to -21% for porcine intestinal heparin, but still an increase, +22%, was noted for low molecular weight heparin. Of the antiplatelet drugs, ibuprofen and dazoxiben reduced plating efficiency and endothelial cell proliferation. Of the antiplatelet drugs, all but dipyridamole reduced prostacyclin metabolite production. The difference in endothelial cell proliferation between heparins is of great interest and warrants further investigation.

Animals↗
PubMed1988

Endothelial cell seeding of expanded polytetrafluoroethylene vena cava conduits: effects on luminal production of prostacyclin, platelet adherence, and fibrinogen accumulation.

The blood-surface interface of 12 mm ID x 5 cm ePTFE vena cava conduits, unseeded (n = 8) and seeded (n = 8) with enzymatically derived autologous endothelial cells, was studied in a canine model at 4 and 12 weeks after graft implantation. Acetylsalicylic acid (325 mg each day) and Coumadin (prothrombin time 1.4 to 1.7 times the control value) were administered preoperatively and continued 4 weeks postoperatively. Platelets labeled with 111In and 125I-labeled fibrinogen were administered 24 hours before graft removal. Luminal platelet adherence, expressed as 10(6) platelets/cm2 of graft surface, was 8.9 +/- 5.6 vs. 56.4 +/- 8.0 (p less than 0.008) and 4.0 +/- 0.9 vs. 12.4 +/- 2.3 (p less than 0.005) in seeded vs. unseeded grafts at 4 and 12 weeks, respectively. Luminal fibrinogen deposition, expressed in micrograms per square centimeter of graft surface, was 11.8 +/- 2.2 vs. 32.0 +/- 2.0 (p less than 0.06) and 6.1 +/- 2.4 vs. 12.4 +/- 6.3 (p less than 0.005) in seeded vs. unseeded grafts at 4 and 12 weeks, respectively. Cumulative 4- and 12-week luminal production of 6-keto-PGF1 alpha from seeded and unseeded grafts represented 11% and 5%, respectively, of that produced from the native iliac vein. Luminal endothelial cell coverage was 71% +/- 22% vs. 33% +/- 9% and 79% +/- 8% vs. 55% +/- 8% (p less than 0.05) in seeded and unseeded grafts at 4 and 12 weeks, respectively. Although endothelialization was not complete in seeded vena cava grafts, it is clear that seeded prostheses exhibited improved thromboresistance compared with unseeded conduits.

Animals↗
PubMed1988

Effect of anticoagulant and antiplatelet drugs on in vitro smooth muscle cell proliferation.

Effects of anticoagulant and antiplatelet drugs on vascular smooth muscle cell plating efficiency and proliferation were assessed using in vitro tissue culture techniques. Canine carotid artery smooth muscle cells were derived, pooled and plated into tissue culture cluster wells to which various drugs were added. Regular beef lung and porcine intestinal and low molecular weight porcine intestinal heparins reduced smooth muscle cell counts. Among antiplatelet drugs, reduced smooth muscle cell counts were seen with dipyridamole and ibuprofen, as well as with the combinations of ASA and dipyridamole, and ASA and dazoxiben. Although in vitro results cannot necessarily be extrapolated to in vivo settings, especially in regard to antiplatelet drugs, results of this study indicate direct effects of certain commonly used clinical agents in reducing smooth muscle cell growth.

Animals↗
PubMed1987

Alternative techniques of seeding cultured endothelial cells to ePTFE grafts of different diameters, porosities, and surfaces.

Attachment of 111Indium-oxine labeled cultured canine venous endothelial cells to expanded polytetrafluorethylene (ePTFE) grafts was evaluated in vitro. Three alternative seeding techniques were studied in grafts having different diameters, porosities, and surfaces, including: (I) manual milking of blood containing endothelial cells within the graft; (II) a two-step procedure of incubating grafts initially with blood and then with an endothelial cell suspension; and (III) mechanical spinning of grafts filled with blood containing endothelium. Method II had significantly higher cell attachment to the graft (11.6%) than did Method I (1.5%) or III (4.7%). A somewhat higher seeding efficiency was noted in 10-mm-I.D. grafts (11.6%) compared to 6-mm-I.D. grafts (6.3%). Different graft porosity, created by altering internodal distances, did not cause significant changes in cell attachment (10 microns, 13.4%; 30 microns, 6.3%; 90 microns, 16.0%). Fibronectin-coated surfaces, which should have enhanced cell adhesion, demonstrated a 6.0% cell attachment, a lower efficiency than the 11.6% observed with a blood coating alone. Acetone-soaked surfaces, which should have predictably exhibited less hydrophobicity, produced quite variable attachments (range 3.4 to 59.7%, mean 23.4%). In the present investigation the best seeding technique was method II, the two-step incubation procedure. Consistent differences were not noted with various ePTFE graft configurations or surfaces.

Animals↗
PubMed1986

Nuclide imaging of vascular graft-platelet interactions: comparison of indium excess and technetium subtraction techniques.

Indium-111-labeled platelet adherence to ePTFE thoracoabdominal vascular prostheses in a canine model (n = 10) was quantitated by (1) an indium-111 excess technique, contrasting graft radioactivity to that in a reference region, and (2) a technetium-99m subtraction technique, with radioactivity of circulating platelets eliminated by discounting background blood activity. Variation in graft thrombogenicity was provided by seeding six prostheses with enzymatically derived autologous endothelial cells, and implanting four prostheses without seeding. Grafts were imaged at 1, 4, and 6 weeks postimplantation, with platelet labeling using indium-111-oxine and red blood cell labeling using technetium-99m. At 7 weeks grafts were excised and gamma activity was measured in proximal, middle, and distal segments. Luminal generation of TxB2 and 6-keto-PGF1 alpha from midportions of grafts was assayed. Indium-111 excess ratios at 6 weeks correlated with actual gamma activity of excised grafts (proximal r = 0.80, P less than 0.01; middle r = 0.73, P less than 0.05; distal r = 0.48, ns) but such a correlation did not exist for the technetium-99m subtraction technique (r = -0.05, -0.25, and 0.16, in the three segments, respectively, all ns). The ratio of graft to aortic TxB2 production revealed a positive correlation with graft gamma activity (r = 0.87, P less than 0.01), and the ratio of graft 6-keto-PGF1 alpha to TxB2 production also correlated with gamma counts (r = -0.64, P = 0.05). In this experimental setting technetium-99m subtraction analysis was an imprecise method of detecting graft platelet accumulation, whereas indium-111 excess ratios proved to be a more accurate method of quantitating vascular prosthetic thrombogenicity.

Animals↗
PubMed1986

Prostacyclin treatment of ischemic ulcers and rest pain in unreconstructible peripheral arterial occlusive disease.

The efficacy of prostacyclin (PGI2) treatment was assessed in 26 patients with surgically unreconstructible atherosclerotic arterial occlusive disease of the lower extremity manifested by nonhealing ulcers and rest pain. Patients were randomized to receive a 72-hour intravenous infusion of PGI2 (6 ng/kg/min, n = 13) or placebo (n = 13). Ulcer size was measured by photographic planimetry, and rest pain was graded by blinded objective scoring at monthly intervals for 6 months. Ulcer size increased 64% in PGI2-treated patients and 22% in placebo-treated patients by 1 month after infusion. Rest pain decreased slightly in both PGI2 and placebo groups. At the conclusion of the study, 54% of placebo-treated patients and 31% of PGI2-treated patients had a positive treatment response, indicated by at least a 20% decrease in ulcer size and a 33% decrease in rest pain. PGI2 infusion did not improve the high-placebo response rate seen in these patients with severely ischemic extremities. These results emphasize the importance of placebo-controlled studies, even in patients with unreconstructible arterial disease.

Aged↗
PubMed1986

Endothelial cell seeding efficiency onto expanded polytetrafluorethylene grafts with different coatings.

Initial adherence of 111Indium-oxine labeled, cultured canine venous endothelial cells to expanded polytetrafluorethylene (ePTFE) grafts was evaluated using different precoatings of the surface or different pretreated cells. The precoatings evaluated consisted of blood for 5 (Group I) or 15 min (Group II), fibronectin (Group IV), and cryoprecipitate (Group VI). In addition to endothelial cells subcultured immediately before labeling, cells subcultured 48 hours prior to labeling and kept in suspension were studied. Such cells were evaluated on grafts precoated with blood for 5 min (Group III) and fibronectin precoated surfaces (Group V). The amount of fibronectin that adhered to the graft surface with our technique was less den 1%. Seeding efficiency was higher with the blood precoated surfaces (5.3, 3.0, 2.2% in Groups I, II and III respectively) than fibronectin (1.7%, 1.7% in Groups IV, V respectively) or cryoprecipitate (1.9%, Group VI) precoated surfaces. No significant difference between cells immediately subcultured and these kept in suspension for 48 hours regarding adherence to blood (5.3 vs. 2.2%) or fibronectin precoated (1.7 vs. 1.7%) grafts was documented. The seeding efficiency of ePTFE grafts is low and further efforts to improve adherence must be made. From the present studies we recommend the use of blood precoating for about 5 min followed by cell incubation for approximately 10 min in order to achieve optimal seeding efficiency.

Animals↗
PubMed1985

Brachiocephalic arterial occlusions and stenoses. Manifestations and management of complex lesions.

Complex stenotic and occlusive lesions involving multiple brachiocephalic arteries were encountered in 17 symptomatic patients, 25 to 76 years of age. Symptoms included hemispheric transient ischemic attacks (16), visual symptoms (ten), global cerebral ischemia (11), true syncope (six), upper extremity ischemic symptoms (eight), and frank tissue loss (one). Of 68 brachiocephalic arteries, 53 exhibited hemodynamically significant stenoses, including 21 that were totally occluded. Transthoracic surgical reconstruction consisted of bypass grafting (11), innominate artery endarterectomy (five), or proximal left common carotid endarterectomy with reimplantation into the contralateral carotid artery (one). There were no operative deaths and only one transient perioperative neurologic deficit. All patients had relief of symptoms. When multiple brachiocephalic arterial occlusions and stenoses preclude standard cervical reconstructive procedures, direct transthoracic reconstruction is appropriate and may be undertaken with acceptable risk in properly selected patients.

Adult↗
PubMed1985

Nonpenetrating subclavian artery injuries.

Nonpenetrating subclavian artery trauma, a potentially catastrophic injury, has been recognized more frequently with the liberal use of angiography in evaluating blunt cervicothoracic trauma. Six patients, five men and one woman, recently underwent surgical treatment at the University of Michigan Hospital for blunt injury of the subclavian artery. The diagnoses were established by arteriography. Physical findings, chest roentgenograms, and results of noninvasive vascular evaluation were found to be nonspecific or unreliable. Operative treatment with resection of the injured arterial segments and either primary anastomosis or bypass grafting resulted in restoration of distal, upper extremity blood flow in all of the cases. One patient died 20 days after trauma from a severe associated cerebral injury. Among the five survivors, residual soft tissue and neurologic injury compromised full recovery in three. Thus, only two of the six patients survived without sequelae, a fact that underscores the seriousness of this type of subclavian artery injury.

Accidents, Traffic↗
PubMed1985

Enhanced endothelialization of Dacron grafts by external vein wrapping.

The efficacy of external vein wrapping of vascular grafts in promoting the development of a luminal endothelial surface was assessed in 12 dogs who underwent thoracoabdominal bypasses with 26-29 cm X 6-mm i.d. double-velour knitted Dacron grafts. In group I (n = 6) 6-cm segments of the grafts were wrapped with autologous jugular vein with its endothelial surface applied against the outside of the graft. In group II (n = 6) the wrap procedure was performed using abdominal wall fascia. The degree and character of graft incorporation was quantitated in all prostheses at 28 days postimplantation. Group I vein wrap prostheses demonstrated uniform endothelial surface coverage in the vein wrap area (means = 88%) that was significantly greater (P less than 0.04) than coverage in adjacent unwrapped segments (means = 48%). Group II fascial wrap grafts demonstrated variable endothelial coverage in the wrapped area (means = 48%) that was consistently less than in adjacent unwrapped portions (means = 62%), and significantly less than vein wrap sections of group I animals (P less than 0.04). No significant differences existed in endothelial coverage of unwrapped regions of group I and II grafts. This investigation documented that wrapping knitted Dacron grafts with vein enhanced endothelialization of their luminal surface.

Animals↗
PubMed1985

Celiac artery aneurysms: historic (1745-1949) versus contemporary (1950-1984) differences in etiology and clinical importance.

Celiac artery aneurysms were encountered in nine patients, ranging in age from 39 to 76 years, at the University of Michigan Medical Center between 1961 and 1983. Developmental defects and atherosclerosis were etiologic factors in six cases. Four patients were without symptoms, whereas five experienced abdominal pain, including one with a ruptured aneurysm. Eight patients were subjected to surgical treatment; no deaths occurred and symptoms were resolved in all patients. A literature review of 108 celiac artery aneurysms revealed two distinct subgroups. Among 60 celiac artery aneurysms encountered before 1950, representing the historic era, 40% were infectious (usually luetic), 7% were traumatic, and 52% were of undetermined cause. Most were symptomatic, 87% ruptured, and 95% were diagnosed at postmortem examination. The contemporary era since 1950 consisted of 48 cases, including nine in the Michigan experience. Congenital or developmental medial defects of the arterial wall and atherosclerosis were the most common causes of aneurysms. Most aneurysms in the contemporary period were either asymptomatic or accompanied by vague abdominal discomfort. Rupture affected 13% of those aneurysms. Operative therapy was successfully undertaken in 91% of 43 patients during the contemporary era, including eight in the present series.

Adult↗
PubMed1985

Actuarial analysis of variables associated with rupture of small abdominal aortic aneurysms.

This study identified risk factors associated with rupture of small abdominal aortic aneurysms in patients initially selected for nonoperative management. Sixty-seven patients, 53 men and 14 women, 50 to 91 years of age (mean 72 years) were followed 3 to 99 months (mean 36 months). All patients underwent serial aortic ultrasonography. The annual rate of aneurysm rupture was 6%, with an annual mortality rate caused by rupture of 5% and an annual mortality rate caused by coexistent disease of 6%. Thirty potential risk factors, including blood pressure, aneurysm size measured by ultrasonography, rate of aneurysm expansion, smoking, serum cholesterol levels, and cardiac, pulmonary, and renal risks, were analyzed by Cox proportional hazards regression to identify variables related to rupture. Aneurysm anteroposterior expansion rates varied from 0 to 1.5 cm/year but were not different in aneurysms that ruptured. Only diastolic blood pressure, initial aneurysm anteroposterior diameter, and degree of obstructive pulmonary disease were independently predictive of rupture (p less than 0.05, Wald test). With these data, actuarial rupture rates were predicted for patients with selected values of these three covariates. Predicted 5-year rupture rates varied from 2% when these risk factors were absent to 100% when all three risk factors were significant. Obstructive pulmonary disease, initial aneurysm size, and diastolic hypertension must be evaluated prospectively to assess their accuracy in predicting small aneurysm rupture.

Actuarial Analysis↗