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Biomedical subjects

L M Graham

Publications and source records attributed to L M Graham.

At least 37 records · Page 2Linked to original sources
PubMed1992

Elevated platelet-derived growth factor production by aortic grafts implanted on a long-term basis in a canine model.

An endothelial cell lining in a prosthetic vascular graft has been shown to decrease graft thrombogenicity. However, previous studies in our laboratory demonstrated that grafts seeded with endothelial cells produced platelet-derived growth factor, a potent smooth muscle cell mitogen that may promote intimal hyperplasia. This study was undertaken to assess temporal changes in platelet-derived growth factor production by grafts seeded with endothelial cells and unseeded grafts and adjacent arteries. Adult beagles underwent placement of 20 to 22 cm long, 8 mm inner diameter, expanded polytetrafluoroethylene thoracoabdominal aortic grafts that were either seeded with autologous jugular vein endothelial cells or were unseeded controls. Grafts and adjacent arteries were removed at times up to 2 years after implantation. The tissue was studied in organ culture and platelet-derived growth factor production was measured after 72 hours with use of a radioreceptor assay. Platelet-derived growth factor production by endothelialized grafts increased significantly over the period studied, especially at the anastomoses, whereas that by arterial segments did not change significantly. The increase in platelet-derived growth factor production was greater in the distal than the proximal anastomotic segment suggesting a possible explanation for the clinical finding of more severe intimal hyperplasia at the distal anastomosis.

Animals↗
PubMed1991

The role of an endothelial cell lining in limiting distal anastomotic intimal hyperplasia of 4-mm-I.D. Dacron grafts in a canine model.

The effect of an endothelial cell (EC) lining on intimal hyperplasia at the distal anastomosis of Dacron grafts was assessed in a canine model. Enzymatically derived autologous EC were used to seed 14 to 17 cm long, 4 mm I.D., knitted Dacron aortoiliac grafts implanted in an end-to-side manner in six dogs (Group I). Unseeded grafts were similarly implanted in six control dogs (Group II). All animals received acetylsalicylic acid (325 mg po qd) 24 h prior to graft placement and for 2 weeks postoperatively. Distal anastomotic intimal hyperplasia (AIH) and luminal surface EC coverage were quantitated at the conclusion of a 16-week study period. Patency for Group I and Group II grafts were 90% and 55%, respectively (p = 0.07). Maximum AIH, defined as the maximum reduction of luminal cross-sectional area at the distal anastomosis, was not significantly different between Group I (13.1 +/- 8.0%) and Group II (15.1 +/- 7.3%) conduits. However, AIH was inversely related to the extent of luminal EC coverage (r = -0.6, p less than 0.05), thus greater endothelialization was associated with decreased AIH. These data support the idea that EC coverage of the luminal surface of prosthetic vascular grafts may limit the development of AIH.

Animals↗
PubMed1991

Effect of controlled hemorrhage on tissue and serum cefazolin clearance.

Effects of blood loss on tissue and serum antibiotic levels were investigated in 30 New Zealand white rabbits. Studies were conducted over a 3.5-hr period after intravenous administration of cefazolin, 30 mg/kg, in control animals (Groups I and IV, n = 5 each) and animals having 50% (Groups II and V, n = 5 each) or 100% (Groups III and VI, n = 5 each) of their blood volume removed and replaced with either Ringer's solution (Groups I, II, and III) or rabbit whole blood (Groups IV, V, and VI) sufficient to maintain central venous pressures at baseline levels. Periodic samples of retroperitoneal fat, iliac artery, and serum were assayed for cefazolin concentration by disc diffusion. Decreased tissue antibiotic levels were observed in animals undergoing 100% blood replacement (Groups III and VI) compared to controls (Groups I and IV) in both fat (P less than or equal to 0.01) and artery (P less than or equal to 0.01) at 90 min. Decreased antibiotic serum half-life accompanying hemorrhage existed when comparing Group II to I (P less than or equal to 0.05), Group III to I (P less than or equal to 0.01), and Group IV to V (P less than or equal to 0.01). The increased antibiotic clearance related to blood loss in this study justifies reassessment of intraoperative dosing intervals. More frequent dosing may be required to maintain stable tissue and serum antibiotic levels during substantial operative hemorrhage.

Animals↗
PubMed1991

Extracellular matrix preparation of expanded polytetrafluoroethylene grafts seeded with endothelial cells: influence on early platelet deposition, cellular growth, and luminal prostacyclin release.

The importance of blood and extracellular matrix precoating of expanded polytetrafluoroethylene (ePTFE) grafts on the effectiveness of endothelial cell (EC) seeding was assessed in a canine experimental model. Part I of the study documented ex vivo platelet deposition in 256 ePTFE grafts, 6 cm x 4 mm internal diameter, after implantation as femoral artery-femoral vein or carotid artery-jugular vein arteriovenous shunts. These conduits were precoated with blood, fibronectin, laminin, or collagen type IV with laminin, after which they were seeded with enzymatically derived and cultivated venous canine endothelium at a density of 30,000 to 40,000 EC/cm2 of graft surface. Luminal deposition of Indium 111-labeled platelets, expressed as 10(8) platelets/cm2, at 30 minutes (n = 176) and 24 hours (n = 80), respectively, was 2.29 and 0.30 for blood, 2.83 and 0.37 for fibronectin, 0.99 and 0.08 for laminin, and 0.98 and 0.11 for collagen type IV with laminin. Part II of the study documented in vivo luminal EC coverage at 14 days of 6 cm x 4 mm internal diameter ePTFE femoral or carotid arterial grafts (n = 8) prepared in the same manner as part I ex vivo shunt grafts. EC coverage with blood, fibronectin, laminin, and collagen type IV with laminin preparation was 42%, 49%, 44%, and 52%, respectively. The graft:carotid artery ratio of luminal 6-keto-PGF1 alpha release at 14 days with these same four preparations was 0.38, 0.31, 0.35, and 0.32, respectively. Precoatings of ePTFE prostheses with fibronectin, laminin, and collagen type IV are known to enhance the initial attachment of seeded EC. Fibronectin caused an insignificant increase in early platelet accumulation; laminin or laminin with collagen type IV preparations were associated with significantly less (p less than 0.005) deposition of platelets when compared to whole blood preparations. Most importantly, none of the four preparation techniques resulted in different in vivo rates of EC growth or luminal release of prostacyclin from conduits studied 14 days after implantation.

Animals↗
PubMed1990

Effects of plasma on PGI2 release from prolonged perfused canine veins.

Prostacyclin release from endothelial cells in culture appears increased by the presence of plasma, but occurrence of a similar phenomenon in intact vessels has not been established. In the present investigation release of 6-keto-PGF1 alpha, the stable breakdown product of prostacyclin, was quantitated from canine veins perfused ex vivo for 15 minute periods, using three different perfusates: 1) Hank's balanced salt solution (HBSS), 2) 20% platelet poor plasma (PPP) derived from heparinized blood, in HBSS, and 3) 20% PPP in HBSS with added arachidonic acid (AA). No differences in initial 6-keto-PGF1 alpha release existed among the three perfusates. However, PPP and PPP + AA solutions were associated with lesser declines in release, than occurred with HBSS alone, these differences being statistically significant after 60 min of perfusion (p less than 0.05). When PPP derived from heparinized and citrated blood rather than from only heparinized blood was used, there was a significantly lower release of prostacyclin (p less than 0.05). The latter may be due to citrate binding of calcium. These data indicate that autologous plasma does not alter initial prostacyclin release from freshly harvested canine veins, but that it weakens the decline in release usually following prolonged periods of perfusion.

Animals↗
PubMed1990

Small-caliber polyurethane and polytetrafluoroethylene grafts: a comparative study in a canine aortoiliac model.

In vivo stability of a new small-caliber polyurethane graft (n8) was assessed in a canine aortoiliac model and compared to that of a conventional expanded polytetrafluoroethylene (ePTFE) graft (n8). Six months following implantation, marked aneurysmal dilatation to 230 +/- 80% (mean +/- SD) of the original diameter occurred in polyurethane grafts, while dilatation to 110 +/- 8% of the original diameter occurred in ePTFE grafts (p less than 0.005). Interval patency was 75% for each graft type. Luminal thrombus affected 59% of polyurethane graft surfaces compared to 22% of ePTFE graft surfaces (p less than 0.01). Qualitative examination of representative sections of polyurethane conduits demonstrated thick inner capsules with numerous small islands of graft material surrounded by macrophages and bands of mature fibrous tissue, in contrast to the thinner neointima and limited anastomotic pannus ingrowth observed in ePTFE grafts.

Animals↗
PubMed1990

Decreased pulmonary vasoreactivity in an animal model of chronic Pseudomonas pneumonia.

Chronic pulmonary infection/colonization caused by Pseudomonas aeruginosa accounts for much of the morbidity and mortality in cystic fibrosis (CF). The effect of chronic pulmonary P. aeruginosa infection on the pulmonary circulation has not been studied. Therefore, we investigated the effect of chronic P. aeruginosa infection on pulmonary hemodynamics in a rat model. Two groups of rats were inoculated with either agar beads containing 1.0 x 10(4) colony-forming units of P. aeruginosa (infected) or an equal volume of sterile beads alone (control). In vivo, pulmonary vasoreactivity measured as the percent change in total pulmonary resistance during hypoxia was decreased at 1 wk (22 +/- 7% versus 57 +/- 3%), 2 wk (29 +/- 5% versus 73 +/- 17%), 3 wk (41 +/- 8% versus 77 +/- 14%), and 6 to 9 wk (23 +/- 10 versus 53 +/- 7; p less than 0.05 all time points; mean +/- SEM) postinoculation in infected animals when compared with that in time-matched control animals. At 6 to 9 wk postinoculation, pulmonary artery pressure was significantly elevated in infected rats (25.8 +/- 1.6 versus 21.0 +/- 1.0 mm Hg; p less than 0.05) when compared with that in control animals. Histopathologic findings were characterized by bronchiectasis as well as by chronic bronchial, parenchymal, and perivascular inflammation at all time points in infected animals.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Diagnosis of tracheal injury in mechanically ventilated premature infants by flexible bronchoscopy. A pilot study.

Flexible bronchoscopy (FB) is uniquely suited for the study of large airway lesions in the ventilated premature infant. However, no standardized clinical scoring system of distal tracheal injury exists and the adverse consequences of FB in ventilated premature infants are not well described. Using a prototype Olympus fiberoptic ultrathin bronchoscope with a directable tip and an outer diameter of 2.2 mm, we serially scored distal tracheal injury in conventionally ventilated premature infants on the basis of mucosal and obstructive changes observed at bronchoscopy. In addition, we prospectively evaluated the incidence of adverse cardiovascular and pulmonary effects during, immediately after, and within 1 h of FB. We performed 21 FBs in eight conventionally ventilated premature infants with birth weight of 1,239 +/- 438 g and gestational age of 30 +/- 3 weeks. The carina and mainstem bronchi were easily visualized in all infants using the prototype bronchoscope. During the first several days of life, moderate-to-severe distal tracheal mucosal injury occurred frequently, while moderate-to-severe obstructive injury occurred infrequently. Distal mucosal injury appeared to improve during the fourth week of life. Mild distal obstructive injury began to appear during the second week of life. Adverse consequences of FB observed in our patient population included transient hypoxemia and bradycardia during FB, changes in systolic blood pressure immediately and within 1 h after FB, and emesis immediately after FB. Serious adverse cardiovascular or pulmonary effects were not observed. We conclude that FB can be performed safely with appropriate monitoring and is a useful tool in the clinical assessment and serial evaluation of distal tracheal injury in ventilated premature infants. We speculate that moderate-to-severe distal tracheal mucosal injury may be associated with the development of later obstructive injury. On the basis of this preliminary study, further prospective investigations of tracheal injury in ventilated premature infants appear to be warranted.

Blood Pressure↗
PubMed1989

Prostanoid release from ex vivo perfused canine arteries and veins: effects of prolonged perfusion, intermittent perfusion, as well as exposure to exogenous arachidonic acid, thrombin and bradykinin.

Regulation of prostanoid release from ex vivo perfused vessel segments is not fully understood. A series of perfusion experiments were performed with canine arteries and veins to define certain regulatory phenomena. Arteries were perfused with pulsatile flow of 90 ml/min at a pressure of 100 mmHg, and veins with nonpulsatile flow of 90 ml/min at a pressure of 7 mmHg. Segments were perfused with Hanks' balanced salt solution for five 15-min periods with the perfusate exchanged after each study period. With onset of perfusion, there was an initial burst of prostacyclin release to 127 +/- 40 pg/mm2, declining to 32 +/- 10 pg/mm2 after 60 minutes (p less than 0.005). If perfusion continued for 5.5 hours, there was a stable release period between 1 and 3 hours, followed by a very slow decline. At that time addition of arachidonic acid (AA) increased prostacyclin release six-fold (p less than 0.01). Vessels perfused for 1 hour and then rested for another hour, responded to reperfusion at the second onset of flow with a two-fold increase in prostacyclin release (p less than 0.01). Vessels perfused with thrombin, bradykinin or AA (either added to each perfusate or only to the last perfusate) exhibited greater prostacyclin release than did control segments. Release of thromboxane steadily declined with time in all parts of the study, and only increased with the addition of AA to the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Femoral-tibial bypass for calcific arterial disease.

Overt calcification of the recipient artery and outflow bed has been regarded as a poor prognostic factor for femoral-distal arterial bypass patency and subsequent wound healing. In order to determine the short- and long-term limb salvage and graft patency rates achieved in these patients, the records of 35 patients undergoing 38 attempted femoral-tibial bypasses to a calcified recipient artery were reviewed. Two patients were unreconstructable at the time of surgery. Thirty-one of the 36 operations (86 percent) were performed using in situ saphenous vein bypass techniques, 3 were performed with polytetrafluoroethylene (PTFE), 1 with a composite sequential, and 1 with a composite vein graft. Immediate limb salvage was achieved in 31 of 36 limbs (86 percent). Five early below-knee amputations (14 percent) were required, two due to graft thromboses and three due to progressive foot necrosis despite patent grafts. One patient (3 percent) died secondary to sepsis. Three-year primary graft patency and limb salvage rates did not differ significantly from bypasses to noncalcified vessels. Femoral-distal bypass in the presence of overt calcific arterial disease may be successfully accomplished and offers an excellent prognosis for long-term graft patency and limb salvage.

Adult↗
PubMed1989

Effects of thromboxane synthetase inhibition on patency and anastomotic hyperplasia of vascular grafts.

The efficacy of a thromboxane synthetase inhibitor (U-63,557A, Upjohn) in promoting early patency and inhibiting anastomotic intimal hyperplasia in ePTFE grafts was compared to that of acetylsalicylic acid (ASA) in a canine model. Animals were started on ASA 5 gr po qd (Group I, n = 12) or U-63,557A 10 mg/kg po bid (Group II, n = 12) 1 day before placement of bilateral 5-mm-i.d., 13- to 16.5-cm-long ePTFE aortoiliac grafts and continued on the medication for the 16-week study. Six dogs in each group received autologous endothelial cell-seeded grafts, while the other six received unseeded grafts. Patency was determined weekly by assessment of femoral pulses. At the conclusion of the study anastomotic intimal hyperplasia was measured on serial sections through the distal anastomosis using a computer-linked digitizer. In Group I the patencies of seeded and unseeded grafts were not significantly different, being 100 and 83%, respectively. Furthermore, luminal narrowing due to intimal hyperplasia was not significantly different being 9.1 +/- 7.6% (chi +/- SD) in seeded grafts and 8.8 +/- 8.1% in unseeded grafts. On the other hand, in Group II the seeded grafts had significantly improved patency when compared to the unseeded grafts (83% vs 33%, P less than 0.05) and less luminal narrowing (11.4 +/- 11.1% vs 21.9 +/- 19.5%, P less than 0.01). Although U-63,557A administration promoted patency of unseeded grafts compared to no antiplatelet medication (0% patency), it was significantly less effective than ASA in improving patency (P less than 0.05) and inhibiting luminal narrowing (P less than 0.01).

Anastomosis, Surgical↗
PubMed1989

Arterial 6-keto-PGF1 alpha and TxB2 release in ex vivo perfused canine vessels: effects of pulserate, pulsatility, altered pressure and flow rate.

Certain experimental conditions are known to influence the release of prostacyclin and thromboxane from the vessel wall. The specific effects of altered pulsatility, pressure, and flow rate on intraluminal release of 6-keto-PGF1 alpha and thromboxane B2 were assessed in canine arteries perfused ex vivo for five 15 min periods with arachidonic acid (AA) added during the last period. Control arteries were perfused at 100 mmHg with pulsatile flow of 90 ml/min. Experimental arteries were perfused at 7, 50 and 200 mmHg with pulsatile flow of 90 ml/min, and at 100 mmHg pressure with pulsatile flow of 20, 60, 130 and 180 ml/min, as well as at 100 mmHg with 90 ml/min nonpulsatile flow. Perfusion pump rates of 44 and 96 beats/min were also assessed. The lowest perfusion pressure, 7 mmHg, resulted in a lesser initial release of prostacyclin compared to higher pressures, and there was a tendency to a higher release of prostacyclin with increasing pressures. There was also a tendency for a lesser response to AA in arteries perfused at 200 mmHg, perhaps due to endothelial cell damage. Nonpulsatile flow was associated with a decreased initial release of prostacyclin, and diminished release following addition of AA when compared to pulsatile flow. Altered flow rate elicited no difference in prostacyclin release, although there was a tendency towards a lesser release when perfused at 20 ml/min compared to 130 ml/min or 180 ml/min. Thromboxane release was decreased by nonpulsatile flow but was otherwise unaffected by the experimental conditions tested. It is concluded that pulsatility enhances release of prostacyclin from arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Lack of effect of dihydroergotamine on endothelial and smooth muscle cell proliferation and endothelial cell prostanoid production.

The most important effect of dihydroergotamine is venoconstriction, but certain metabolic effects and changes in vessel prostanoid activity have also been suggested. In this study endothelial cell production of 6-keto PGF1 alpha and TxB2 was quantitated in vitro. No evidence of altered prostanoid production was noted after incubation with dihydroergotamine (exposure ranging from 5 x 10(-3) to 5 x 10(-7) g/l). Similarly, no effect of dihydroergotamine on the growth rates of endothelial cells or smooth muscle cells in vitro was documented.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Comparison of static incubation versus physiologic perfusion techniques for quantitation of luminal release of prostacyclin and thromboxane in canine arteries and veins.

Intraluminal release of 6-keto-PGF1 alpha and TxB2 in ex vivo canine arteries and veins was assessed during five consecutive 15-min periods using static incubation and physiologic perfusion techniques. Arterial segments were perfused with 90 ml/min pulsatile flow at 100 mm Hg and vein segments with 90 ml/min nonpulsatile flow at 7 mm Hg. During the final 15-min period vessels were stimulated with arachidonic acid (AAS). Perfusion of vein segments caused a higher release of 6-keto-PGF1 alpha during the first 30 min (P less than 0.05) and following AAS (P less than 0.05) than did static incubation. Perfused arterial segments exhibited a higher release than did incubated segments of 6-keto-PGF1 alpha for 45 min (P less than 0.01) as well as following AAS (P less than 0.01). TxB2 release was higher during the entire observation period in perfused arteries and veins compared to incubated vessels (P less than 0.01 and less than 0.05, respectively). There was no correlation between the amounts of 6-keto-PGF1 alpha or TxB2 released when comparing values obtained by one technique to values obtained by the other (P greater than 0.1). These data suggest that flow related shear stress alters vascular prostanoid production, and that such should be accounted for when interpreting results of studies on prostacyclin and thromboxane release from intact vessels.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Do operative results justify tibial artery reconstruction in the presence of pedal sepsis?

An aggressive surgical approach is warranted in all patients with a salvageable weight-bearing pedal surface. Although patients with pedal sepsis (69 limbs) had a lower 30 day limb salvage rate and higher morbidity and mortality rates than those without sepsis (34 limbs), the long-term salvage rates of both groups by life table analysis were not statistically different and remained at the 70 percent level 3 years postoperatively. Peribypass amputation, debridement of the septic foot, or both should be carried out when deemed necessary to decrease the risk of septic complications after revascularization. Other risk factors such as diabetes or heart disease had no bearing on the short-term results of bypass in either the septic or nonseptic group. Autogenous saphenous vein is preferable to synthetic bypass material, especially in patients with ongoing infection. Lastly, even though the medical climate in 1988 must reflect the stark reality of economic restrictions imposed by third-party payors, optimal patient care remains our primary responsibility. We believe that long-term pedal salvage, as achieved by arterial reconstruction, aggressive wound management, and rehabilitation, attains this goal.

Amputation, Surgical↗
PubMed1988

Influence of pressure, flow rate, and pulsatility on release of 6-keto-PGF1 alpha and thromboxane B2 in ex vivo-perfused canine veins.

The influence of pressure, flow, and pulsatility on the release of prostacyclin (measured as 6-keto-PGF1 alpha) and thromboxane (measured as TxB2) was assessed in canine jugular veins perfused ex vivo with Hanks' balanced salt solution for five consecutive 15-minute periods. Control segments were perfused at 7 mm Hg with nonpulsatile flow at a rate of 90 ml/min, whereas experimental segments were perfused with pulsatile flow as well as nonpulsatile flow at pressures of 50 or 100 mm Hg and flow rates of 60 or 130 ml/min. Prostacyclin release from control segments during the first 15-minute period was 49.5 +/- 7.4 pg/mm2/15 min, which declined to 13.9 +/- 2.5 pg/mm2/15 min after 60 minutes (p less than 0.002). Arachidonic acid stimulation during the last 15-minute perfusion period increased the release to 56.1 +/- 9.4 pg/mm2/15 min (p less than 0.002). Thromboxane release from control segments was initially 4.4 +/- 1.2 pg/mm2/15 min, which declined to 0.8 +/- 0.2 pg/mm2/15 min after 60 minutes (p less than 0.002), and subsequently increased with arachidonic acid stimulation to 1.3 +/- 0.1 pg/mm2/15 min (p less than 0.01). In contrast to control perfusion conditions, changes in nonpulsatile flow rates did not affect prostacyclin release, whereas thromboxane release was lower when perfused at 60 ml/min. Pressures of 50 and 100 mm Hg increased the initial release of prostacyclin. Similarly, pulsatile flow enhanced prostacyclin release at both low and high pressures, being more pronounced with the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗