Biomedical subjects

R W Thompson

Publications and source records attributed to R W Thompson.

At least 73 records · Page 4Linked to original sources

PubMed1996

Development and comparison of transperitoneal and retroperitoneal approaches to laparoscopic-assisted aortofemoral bypass in a porcine model.

PURPOSE: Transperitoneal and retroperitoneal approaches to video-assisted aortofemoral bypass were developed and compared using gasless laparoscopic techniques in a porcine model. METHODS: Ten pigs were randomized to either a transperitoneal or retroperitoneal approach. Aortic clamp time, total operative time, and complications were recorded. Both operations used an external lift device to maintain the working space. Retroperitoneal operations first used serial balloon inflation to dissect the retroperitoneum. After exposure of the infrarenal aorta, a graft was tunneled under endoscopic visualization. End-to-side aortic and femoral anastomoses were created with conventional instruments through 4 cm incisions. RESULTS: Mean +/- SEM aortic clamp time, operative duration, and graft patency rates were similar for both approaches (difference not significant by unpaired t test). Intraoperative complications related to the use of the laparoscopic technique included injury to the bladder and small bowel (n=2) and occurred only in the transperitoneal group. CONCLUSIONS: The use of a gasless technique allowed direct visualization, standard instrumentation, and conventional anastomotic techniques. The retroperitoneal approach used the peritoneal sac to exclude the bowel, simplifying the aortic dissection. Gasless laparoscopic-assisted aortofemoral bypass can be performed by both transperitoneal and retroperitoneal approaches and holds promise as a minimally invasive treatment for aortoiliac occlusive disease.

Anastomosis, Surgical↗

PubMed1996

Basic science of abdominal aortic aneurysms: emerging therapeutic strategies for an unresolved clinical problem.

Abdominal aortic aneurysms (AAAs) are an increasingly common and potentially lethal condition. Surgical repair of AAA is now yet performed quite safely, yet ruptured AAAs still carry mortality rates of 50% to 70%. Ultrasound screening may help identify unsuspected AAA, thereby allowing elective repair. Because AAAs too small to warrant operation still expand progressively, therapeutic approaches to suppress AAA growth would be welcome. Current concepts indicate that AAAs arise through pathophysiologic process distinct from occlusive atherosclerosis and dominated by degenerative changes in the elastic media. These include marked alterations in elastin and collagen, chronic inflammation, and features of autoimmunity, medial neovascularization, and a decrease in vascular smooth muscle cells. Proteinases associated with mononuclear inflammatory cells, particularly matrix metalloproteinases, likely mediate the degradation of structural proteins in the aortic wall. Experimental studies demonstrate that similar processes occur in an elastase-induced rodent model of AAA, providing a means by which to develop novel therapeutic strategies for this disease. Pharmacologic inhibitors of matrix metalloproteinases act to suppress aortic elastin degradation and limit the growth of experimental AAA in vivo, suggesting at least one approach that may be useful in clinical application. Further developments can be expected to increase knowledge of the pathophysiology underlying aortic aneurysm disease, ultimately providing new therapies for small AAAs based on sound understanding of disease mechanisms.

Animals↗

PubMed1996

Effect of the slow-component rise in oxygen uptake on VO2max.

During constant-rate high-intensity (CRHI) exercise lasting longer than 3 min, VO2 has been reported to exceed VO2max measured with a traditional graded exercise test (GXT). This could be because VO2max was not achieved on the GXT or because the factors responsible for the slow-component rise in VO2 alter VO2max. The objective of this study was to test the hypothesis that the slow-component rise in VO2 measured during CRHI running leads to a total VO2 that exceeds VO2max measured during a running GXT. VO2max was determined in eight highly trained individuals using data collected from five grade-incremented, treadmill-running GXT. Each subject demonstrated a definitive plateau of VO2 as a function of exercise intensity. Three VO2max values based on different approaches for representing the VO2max plateau were obtained. Subjects also completed two exhaustive CRHI bouts of treadmill running lasting 7-13 min at speeds estimated from the ACSM equation to elicit an average of 99 +/- 5% VO2max. The mean (+/- SD) VO2peak determined during the CRHI runs (4.17 +/- 0.9 l.min-1) was not different form or less than the three VO2max values (4.19-4.32 +/- 0.09 l.min-1). We conclude that in highly trained individuals, the slow-component rise in VO2 during CRHI treadmill running does not lead to a total VO2 that exceeds the VO2max measured during a running graded exercise test.

Adult↗

PubMed1996

Effects of ultraviolet light in vascular cells in vitro and in intact atherosclerotic explants: potential role of apoptosis in vascular biology.

Complex cell-to-cell interactions are known to participate during vascular injury and remodeling, resulting in smooth muscle cell proliferation. Mechanical interventions have yielded little benefit in limiting this process and several site-specific genetic therapies are not yet clinically available. The aim of this study was to delineate the effect of very short wavelength ultraviolet (UVC) light therapy on the viability of macrophage and smooth muscle cells. Vascular cells were both treated in vitro and in intact explanted atherosclerotic aortic segments ex vivo with UVC light. Brief exposure to short wavelength UVC light in the absence of photosensitizers elicited a differential temporal and functional response among treated cells. However, dramatic reduction in both cellular viability and proliferative capacity with eventual cell demise was observed in all UVC-treated cells. Flow cytometry and immunohistochemical analyses revealed the presence of extensive DNA fragmentation, suggestive of apoptosis as a predominant pathway of cell death in these cells exposed to UVC light. We hypothesize that selective induction of apoptosis, in contrast to necrosis, with UVC light may represent a beneficial approach to interdict the complex biologic cascade of messengers that participate in the restenotic response to vascular injury.

Animals↗

PubMed1995

Limb salvage and patency after aortic reconstruction in younger patients.

PURPOSE: The purpose of this report was to compare patient characteristics, treatment, and outcome in younger and older patients with aortoiliac occlusive disease. METHODS: The medical records of 56 patients < or = 50 years of age (Group < or = 50) were retrospectively reviewed and compared to the records of 128 patients > or = 60 years of age (Group > or = 60). All patients were examined and treated between April 1987 and April 1994. Postoperatively, they were enrolled in a vascular laboratory surveillance program to serially monitor the status of the vascular reconstruction. Follow-up averaged more than 3 years in both groups and was available on greater than 90% of patients. RESULTS: Patients in Group < or = 50 had a higher incidence of smoking (68% versus 51%) and a lower incidence of hypertension (29% versus 50%) than patients in group > or = 60 (smoking P = 0.03, hypertension P = 0.007). No other significant differences were noted among cardiovascular risk factors. Preoperative indications for surgery were similar among patients in both groups. An aortoiliac endarterectomy was more commonly used to revascularize the lower extremities in younger patients than in their older counterparts (23% versus 7%, P = 0.002). Graft revisions were more frequently necessary after aortic reconstruction in Group < or = 50 than in Group > or = 60 (29% versus 8%, P = 0.0003); however patency rates computed by life table analysis were not significantly different. The primary patencies for Group < or = 50 and Group > or = 60 at 5 years were 64% and 67%, respectively; their secondary patency rates at 5 years were 84% and 89%, respectively. No significant difference was found in major limb amputation (8% in Group < or = 50 versus 5% in Group > or = 60, P = 0.46). We conclude that aortoiliac reconstruction for occlusive disease can be performed with similar secondary patency and amputation rates in young and old patients. However, close postoperative surveillance and frequent surgical revision are necessary to maintain patency and minimize amputation.

Adult↗

PubMed1995

Medial neovascularization in abdominal aortic aneurysms: a histopathologic marker of aneurysmal degeneration with pathophysiologic implications.

PURPOSE: The purpose of this study was to characterize the distribution of aortic wall microvessels in normal aorta, atheroocclusive disease (AOD), and abdominal aortic aneurysms (AAA) and to evaluate whether medial neovascularization (MNV) is a reliable histopathologic marker of aneurysmal degeneration. METHODS: Aortic tissue specimens (9 normal, 10 AOD, and 10 AAA) were examined for elastin with Verhoeff-van Gieson stain and for Ulex europaeus type I lectin, an endothelial-specific antigen, and laminin, a marker of basement membranes, by immunohistochemistry. The density of MNV was determined by morphometry of aortic sections stained for endothelium. The spatial distribution of aortic microvessels was compared with that of elastin destruction and chronic inflammation. RESULTS: Evidence of medial neovascularization was generally not observed in normal aorta or AOD, whereas AAAs showed strong spatial correlations between MNV, disruption and degradation of elastin, and chronic inflammation in the outer aortic wall. Several specimens of AOD had focal areas of MNV associated with localized elastin fragmentation and monocytic infiltration located at the interface between the atherosclerotic plaque and the inner media. The density of MNV was about fifteenfold higher in AAA compared with normal aorta and about threefold higher compared with AOD (microvessels per high-power field): normal aorta, 0.77 +/- 0.28; AOD, 3.40 +/- 0.51; AAA, 11.32 +/- 1.58 (ANOVA, p < 0.001). CONCLUSIONS: The presence and density of MNV in the abdominal aorta is a consistent histopathologic marker of aneurysmal degeneration that is spatially correlated with the destruction of elastin and chronic inflammation. The observation of focal MNV in some specimens of AOD, associated with partial elastin disruption, raises the possibility that early changes of aneurysm disease might develop by an extension of angiogenic/inflammatory processes from the atherosclerotic plaque into the aortic media.

Adult↗

PubMed1995

Transabdominal versus retroperitoneal incision for abdominal aortic surgery: report of a prospective randomized trial.

PURPOSE: The purpose of this study was to perform a randomized, prospective trial that compares the transabdominal with the retroperitoneal approach to the aorta for routine infrarenal aortic reconstruction. METHODS: From August 1990 through November 1993, patients undergoing surgery for abdominal aortic aneurysm (AAA) disease or aortoiliac occlusive disease (AIOD) were asked to participate in a randomized trial comparing the transabdominal incision (TAI) to the retroperitoneal incision (RPI) for aortic surgery. One hundred forty-five patients were randomized, with 75 (41 with AAA and 34 with AIOD) in the TAI group and 70 (40 with AAA and 30 with AIOD) in the RPI group. There were no significant differences between the groups in terms of age, sex, postoperative pain control (epidural vs patient-controlled analgesia), or comorbid conditions, except for a higher incidence of chronic obstructive pulmonary disease in the TAI group (21 vs 8 patients). RESULTS: The incidence of intraoperative complications was similar for both groups. After surgery, the incidence of prolonged ileus (p = 0.013) and small bowel obstruction (p = 0.05) was higher in the TAI group. Overall, the RPI group had significantly fewer complications (p < 0.0001). The overall postoperative mortality rate (two deaths) was 1.4%, with both occurring in the TAI group (p = 0.507). The RPI group also had significantly shorter stays in the intensive care unit (p = 0.006), a trend toward shorter hospitalization (p = 0.10), lower total hospital charges (p = 0.019), and lower total hospital costs (p = 0.017). There was no difference in pulmonary complications (p = 0.71). In long-term follow-up (mean 23 months), the RPI group reported more incisional pain (p = 0.056), but no difference was found in incisional hernias or bulges (p = 0.297). CONCLUSIONS: We conclude that the RPI approach for abdominal aortic surgery is associated with fewer postoperative complications, shorter stays in the hospital and intensive care unit, and lower cost. There is, however, an increase in long-term incisional pain. Current methods of postoperative pain control seem to decrease the incidence of pulmonary complications.

Abdomen↗

PubMed1995

Production and localization of 92-kilodalton gelatinase in abdominal aortic aneurysms. An elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages.

Abdominal aortic aneurysms (AAA) are characterized by disruption and degradation of the elastic media, yet the elastolytic proteinases involved and their cellular sources are undefined. We examined if 92-kD gelatinase, an elastolytic matrix metalloproteinase, participates in the pathobiology of AAA. Gelatin zymography of conditioned medium from normal, atheroocclusive disease (AOD), or AAA tissues in organ culture showed that all tissues produced 72-kD gelatinase. AOD and AAA cultures also secreted 92-kD gelatinase, but significantly more enzyme was released from AAA tissues. ELISA confirmed that AAA tissues released approximately 2-fold more 92-kD gelatinase than AOD tissue and approximately 10-fold more than normal aorta. Phorbol ester induced a 5.3-fold increase in 92-kD gelatinase secretion by normal aorta and AOD and an 11.5-fold increase by AAA. By immunohistochemistry, 92-kD gelatinase was not detected in normal aorta and was only occasionally seen within the neointimal lesions of AOD tissue. In all AAA specimens, however, 92-kD gelatinase was readily localized to numerous macrophages in the media and at the adventitial-medial junction. The expression of 92-kD gelatinase mRNA by aneurysm-infiltrating macrophages was confirmed by in situ hybridization. These results demonstrate that diseased aortic tissues secrete greater amounts of gelatinolytic activity than normal aorta primarily due to increased production of 92-kD gelatinase. In addition, the localization of 92-kD gelatinase to macrophages in the damaged wall of aneurysmal aortas suggests that chronic release of this elastolytic metalloproteinase contributes to extracellular matrix degradation in AAA.

Aorta↗

PubMed1994

The influence of anesthetic technique on perioperative complications after carotid endarterectomy.

PURPOSE: This study evaluated the influence of anesthetic techniques on perioperative complications after carotid endarterectomy. METHODS: Perioperative complications, the use of a carotid artery shunt, the duration of the operative procedure and postoperative hospital course were retrospectively compared in 584 consecutive patients undergoing 679 carotid endarterectomies with use of either general anesthesia (n = 361) or cervical block regional anesthesia (n = 318). There was no significant difference in the preoperative medical characteristics between the two anesthetic groups. Symptomatic carotid artery disease was the indication for surgery in 247 (68.4%) patients receiving general anesthetics, whereas 180 (56.6%) patients treated with a cervical block anesthetic had a symptomatic carotid artery stenosis (p = 0.02). RESULTS: The perioperative stroke rate and stroke-death rate for the entire series was 2.4% and 3.2%, respectively, and was not significantly different between the anesthetic groups or between patients with symptomatic or asymptomatic disease. A carotid artery shunt was used in 61 (19.2%) patients receiving a cervical block anesthetic and 152 (42.1%) patients treated with a general anesthetic (p < 0.0001). Use of cervical block anesthesia was associated with a significantly shorter operative time, fewer perioperative cardiopulmonary complications, and a shorter postoperative hospitalization when compared with general anesthesia. Multivariate risk factor analysis indicated that age greater than 75 years, operative time greater than 3 hours, and the use of a carotid artery shunt were all independent risk factors for perioperative cardiopulmonary complications. When a carotid artery shunt was not analyzed as a multivariate risk factor, then general anesthesia became a significant risk factor for perioperative cardiopulmonary complications (risk ratio 2.08; p = 0.04). CONCLUSIONS: We conclude that cervical block anesthesia is safer and results in a more efficient use of hospital resources than general anesthesia in the treatment of patients undergoing carotid endarterectomy.

Aged↗

PubMed1994

Long-term effectiveness of extraanatomic renal artery revascularization.

BACKGROUND: The efficacy of direct aortorenal bypass and renal artery endarterectomy are well established. The purpose of this study is to define better the results of extraanatomic renal revascularization procedures. METHODS: From April 1987 to March 1993, 124 patients underwent renal artery revascularization. Forty-eight (39%) of them (33 women, 15 men; average age, 65.9 years) underwent 49 extraanatomic renal artery bypasses. Preoperative risk factors included smoking in 30 patients (61%), history of myocardial infarction in 14 (29%), diabetes mellitus in 11 (22%), congestive heart failure in nine (18%), chronic obstructive pulmonary disease in 11 (22%), and stroke in six (12%). The average creatinine level was 2.3 mg/dl. The average number of antihypertensive medications was 2.4. Thirty iliorenal, 10 gastroduodenal-renal, seven hepatorenal, and two splenorenal bypasses were performed together with 10 contralateral nephrectomies. RESULTS: Six major postoperative complications occurred. There were no deaths. Forty-one (85%) of patients had improvement or cure of their hypertension. Seven (15%) of patients failed to respond to treatment, and three required subsequent nephrectomy. After operation the average creatinine level was 1.7 mg/dl and the average number of medications was 1.7. Mean follow-up period has been 23.2 months (range, 1 to 79 months). CONCLUSIONS: Extraanatomic bypass proved to be efficacious in treating hypertension and preserving renal function and has an acceptable rate of morbidity and mortality. We conclude that these procedures are an acceptable alternative to direct aortorenal artery revascularization.

Aged↗

PubMed1993

Simultaneous surgical management of aortic and renovascular disease.

The results of simultaneous elective infrarenal aortic reconstruction and renovascular surgery were retrospectively reviewed in 102 patients who consecutively underwent operation. The perioperative mortality rate (0 to 54 days) was 5% (5 of 102). Renal function had returned to baseline or was improved at discharge in 89 of 97 (92%) surviving patients. The intraoperative use of renal hypothermia was an independent predictor of improved postoperative renal function, by multivariate analysis. Twenty-five of 29 (86%) patients with severe hypertension had improvement in their blood pressure on the same or fewer medications postoperatively (p = 0.0005). A retroperitoneal incision was associated with less intraoperative crystalloid fluid administration (p = 0.03), more rapid postoperative resumption of an oral diet (p = 0.04), and better long-term survival (p = 0.02) when compared with a transperitoneal incision. We conclude that the simultaneous repair of infrarenal aortic pathology and renovascular lesions is associated with an acceptable perioperative morbidity and preserves or improves renal function in the majority of patients. The frequent use of renal hypothermia and careful consideration of the route of operative exposure will lead to optimal results.

Aged↗

PubMed1993

Combined analysis of tall fescue steer grazing studies in the Eastern United States.

The mixed-models procedure (MMP) was used to analyze pooled data sets from 12 independent studies conducted during the last 13 yr at nine locations in seven states to provide combined estimates of daily gains by beef steers (Bos taurus) grazing tall fescue (Festuca arundinacea Schreb.) pastures free of (E-) or infested (E+) at different levels with the endophytic fungus Acremonium coenophialum. Treatments included low-infestation (< or = 5% E+), moderate-infestation (> or = 20 to < or = 35% E+), and high-infestation (> or = 50 to < or = 97% E+) tall fescue pastures, and, in tall fescue-clover (Trifolium spp.) mixtures, pastures at the same E+ levels with approximately 25 and 10% clover in spring and summer stands, respectively. Spring, summer, and combined spring+summer data were analyzed separately. The MMP permitted estimation of the fixed effects of treatments over a broad inference space of future years and different tall fescue pastures over a wide geographic range; detected relationships that had not been apparent in the individual studies, such as the interactions between clover presence and E+ infestation levels; and provided a more coherent body of information than did the results obtained from each discrete study. Logistical and financial constraints that force undesirable compromises in the conduct of future grazing and other expensive or time-consuming research may be avoided by using MMP within the context of cooperative projects.

Acremonium↗

PubMed1993

Aorta-left renal vein fistula syndrome caused by rupture of a juxtarenal abdominal aortic aneurysm: novel pathologic mechanism for a unique clinical entity.

Spontaneous aorta-left renal vein fistula (ALRVF) caused by abdominal aortic aneurysm (AAA) is a rare form of intravascular aneurysm rupture. The literature series of ALRVF, updated here to 19 reported cases, demonstrates that patients with ALRVF present with a unique clinical syndrome characterized by abdominal or left flank pain (84%), a pulsatile abdominal mass (63%), abdominal bruit or murmur (63%), hematuria (100%), and nonfunction of the left kidney on functional imaging studies (100% of patients studied). Operative findings in ALRVF syndrome have included a large AAA (mean diameter 9.2 cm), with frank rupture in only three; in 17 of 19 patients (89%) the ALRVF was associated with a retroaortic left renal vein anomaly. The patient presented here had a large juxtarenal AAA with rupture into the left retroperitoneal space. The wide aneurysm neck and expanding hematoma created an avulsion of the second left lumbar vein from its junction with an anatomically normal (preaortic) left renal vein; the resulting renal vein tear allowed development of an arteriovenous communication that was responsible for the clinical presentation of ALRVF syndrome. The disease found here demonstrates a novel mechanism for the production of ALRVF syndrome in patients with juxtarenal AAA and otherwise normal pararenal venous anatomy.

Aged↗

PubMed1993

Dextrocholedocholithiasis: calculous obstruction complicating double ductus choledochus in an adult.

Double ductus choledochus is a rare anomaly of the extrahepatic biliary tree in which the common bile duct is represented by two independent hepatic ducts. Patients with this abnormality may have unimpeded biliary drainage and remain symptom free, yet various forms of double ductus choledochus are occasionally encountered in patients undergoing operation for symptomatic cholelithiasis. We describe a patient in whom doubled biliary ducts were identified on exploration for cholecystectomy along with calculous obstruction of the right-sided duct (ductus choledochus dextri). This case illustrates the potential for significant injury to the biliary tree when double ductus choledochus is present. In addition to a means by which to manage this problem at the time of operation, a review of the literature, as well as a description of this rare embryologic abnormality, is presented.

Adult↗

PubMed1992

Surgical recanalization of occluded peripheral arteries.

This article, reflecting on the surgical recanalization of occluded peripheral arteries, has exposed the very essence of vascular surgery. Only the pioneering cardiac anomalies repaired by Gross (patent duct arteriosus, 1938), Blalock and Taussig (tetralogy of Fallot, 1944), and Crafoord and Nylin (coarctation, 1945) and the legendary aortic grafting operations of Oudot (occlusion, 1950) and Dubost and coworkers (aneurysm, 1951) are not a part of this article. The contributions to surgical recanalization of the occluded peripheral arteries are numerous. Some are well conceived, and others are innovative. Perhaps the most significant technique of all, endarterectomy itself, began purely as a serendipitous event. The startling impact of dos Santos' revolutionaly "disobliteration" was realized at once. Intimal injury during the operation did not cause inevitable thrombosis, as historically taught. Thus, all vascular interventions, either endarterectomy, graft repair, or the newer endovascular techniques discussed in this issue, would not have been developed without the understanding of the tolerance of the human intima to injury. Thromboendarterectomy, the basis of surgical recanalization of occluded arteries, unlocked the mystery of arterial rethrombosis after intervention. Recognizing these crucial facts, it will have a lasting place in the expanded discipline of vascular disease and its treatment. Dos Santos, the European founder of endarterectomy, and Wylie, the American pioneer and proponent of endarterectomy, were great friends in life (Fig. 4) and would certainly be pleased to see the further development of technology aimed at the treatment of atherosclerotic obstruction of the peripheral arteries.

Arterial Occlusive Diseases↗

PubMed1992

Circumferential venolysis and paraclavicular thoracic outlet decompression for "effort thrombosis" of the subclavian vein.

Effort thrombosis of the subclavian vein (Paget-Schroetter syndrome) has long been considered a primary thrombotic process, but recent experience suggests that it may commonly result from repeated mechanical compression. Increased awareness of the pathophysiology of this syndrome can allow timely, improved diagnostic screening and the use of specific surgical intervention to relieve the venous consequences. During the past 15 years we have treated six patients with mechanical compression in the thoracic outlet causing surgically correctable venous occlusive problems. There were four men and two women with an average age of 38 years (range 26 to 53 years). All patients exhibited pain, swelling, and cyanosis of the upper extremity, with worsening venous congestion on abduction of the arm. Five of six patients were originally treated for effort thrombosis of the subclavian vein with arm elevation and anticoagulation; two also underwent immediate thrombolytic therapy with urokinase. Venography was prompted in each case by positional symptoms during follow-up and showed irregular stenosis of the subclavian vein adjacent to the first rib. All patients underwent extended first rib resection and circumferential venolysis (one patient underwent bilateral procedures); one was performed through a transaxillary approach, two through a supraclavicular approach, and four through a new, "paraclavicular" approach. All subclavian veins appeared normal after venolysis. Five of six patients also underwent complete scalenectomy and brachial plexus neurolysis. In each patient, venous and neurogenic symptoms resolved and venography confirmed a patent subclavian vein, with follow-up ranging from 11 months to 13 years (mean 3.8 years).

Adult↗

PubMed1992

Correlations between scores on a continuous performance test and parents' ratings of attention problems and impulsivity in children.

This is a study of the relationship between a continuous performance test and parents' behavioral ratings of attention problems and impulsivity in 45 boys who had been referred to a clinic for learning and behavioral problems. No significant correlations obtained between these two methods of assessment. Perhaps the lack of congruence is due to the multidimensional nature of both attention problems and impulsivity. Suggestions for clinical practice and further research are discussed.

Attention↗

PubMed1990

Heparin-mediated release of fibroblast growth factor-like activity into the circulation of rabbits.

Fibroblast growth factors (FGFs) are a family of structurally related proteins that influence the growth and differentiation of a variety of cell types, including the cells of the vascular system. Due to the lack of signal sequence, basic FGF is not actively secreted. However, it has been detected in the extracellular matrix bound, at least in some cases, via heparin-like molecules. Heparin has been shown to displace FGF from cells and matrices in vitro, and we have investigated the possibility that a similar phenomenon might occur in vivo. Heparin was infused intravenously into anesthesized rabbits; plasma samples taken 30 min later and monitored using [3H]thymidine incorporation into BALB/c 3T3 cells were found to contain 3-fold more stimulatory activity than control plasma samples. Addition of heparin directly to the 3T3 cells or to the plasma samples following their collection did not affect the level of stimulatory activity. A time course of stimulatory activity in rabbit plasma following heparin administration revealed that 3T3 cell stimulatory activity rapidly increased following heparin infusion, peaked at 30 min, and declined to control levels by 90-120 min. The anticoagulant action of heparin followed a different time course, providing evidence that these two effects of heparin are functionally distinct. The binding affinity of the plasma-derived stimulatory activity for heparin was used to demonstrate that the activity is FGF-like in nature. Additionally, administration of [125I]bFGF to rabbits that had been "precleared" by heparin infusion resulted in an immediate peak of circulating labeled bFGF that decreased to plateau level by 20-45 min following injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗