Stephen R. Hanson

Healing of polytetrafluoroethylene arterial grafts is influenced by graft porosity

The importance of porosity in synthetic arterial graft healing has not been adequately defined. To determine the effect of porosity on graft healing, we measured the extent of cellular response at late times in 4 mm internal diameter polytetrafluoroethylene grafts of varying porosity (between 10 and 90 microns internodal distance) inserted into the arterial system of baboons. After 1 and 3 months the grafts were retrieved and examined for endothelial coverage, intimal thickening, and endothelial cell and smooth muscle cell proliferation. The pattern of intimal healing with endothelial cells and smooth muscle cells was only related to porosity in the sense that there was an abrupt switch in the pattern of healing as porosity was increased from 30 to 60 microns. In low porosity grafts (10 and 30 microns internodal distances) endothelial coverage of the luminal surface was incomplete and, along with intimal thickening, was limited to graft near the anastomosis. In high porosity grafts (60 and 90 microns internodal distances) luminal endothelial coverage was complete, and intimal thickening was uniformly distributed throughout the graft. The highest porosity graft studied (90 microns) developed areas of focal loss of endothelial cells at late time periods. In this limited series there does appear to be an optimal porosity for polytetrafluoroethylene grafts near 60 microns, since 10 and 30 micron grafts fail to achieve luminal endothelial cell coverage, and 90 micron grafts exhibit instability of the intima with focal endothelial cell loss.

Application of radiation-grafted hydrogels as blood-contacting biomaterials

Abstract This article reviews the interactions of radiation-grafted hydrogels with blood and its components, both in vitro and in vivo . It has been found that as the hydrogel water content increases for radiation-grafted hydrogels of moderate to high water contents (15–85%) they tend a) to adsorb fewer protein molecules, and to desorb them more readily in vitro , b) to form thrombus but to adhere the thrombi less readily in the in vivo canine ring tests, and c) to cause more rapid formation and greater volumes of platelet microemboli in the ex vivo A-V femoral baboon shunt. At low water contents (below 10%) the grafted HEMA/EMA copolymer “hydrogels” exhibit an unexpected minimum in platelet consumption, which may be related less to the absorbed water in the graft copolymer than to the polymer composition at the surface. These results suggest that special radiation graft copolymer compositions may be selected to fit specific biological needs.

On the multiplicity of platelet prostaglandin receptors. II: The use of N-0164 for distinguishing the Loci of action for PGI2, PGD2, PGE2 and hydantoin analogs

The omega-chain variant analogs of prostacyclin (PGI2) and PGD2 in which n-amyl side-chain has been replaced by a cyclohexyl group have been prepared and their cardiovascular activities have been compared to those of BW-245C(Fig. 1) a potent anti-aggregatory vasodilator bearing a cyclohexyl-terminated side-chain on a hydantoin skeleton. The cyclohexyl group has little effect on PGI2, but converts PGD2 to a long lasting hypotensive agent and increases the platelet anti-aggregatory potency of PGD2 by a factor of 8. The prostaglandin antagonist N-0164 selectively blocks the anti-aggregatory actions of PGD2, cyclohexyl-PGD2, and BW-245C; with essentially no effect on PGI2, cyclohexyl-PGI2 and PGE2 at comparably effective doses. The latter observation is contrary to an earlier report by MacIntyre, but supports the view that the anti-aggregatory effect of high doses of PGE2 (EC50=50 microM) is mediated by the PGI2 receptor. The hydantoin acts at the platelet PGD2 receptor.

Factors influencing platelet consumption by polyacrylamide hydrogels

Using a baboon arteriovenous shunt model platelet consumption by poly (acrylamide) grafted substrates (Silastic and Pellethane) has been found to depend strongly on the water content of the grafted layer but was independent of graft level (1.13–5.72 mg/cm2), substrate type, or method of initiating polymerization (60Co radiation or Ce4+ions). Poly (acrylamide) grafted materials were typically ten times as consumptive towards platelets than the untreated substrates.

PLATELET KINETIC EVALUATION OF PROSTHETIC MATERIAL IN VIVO

Thrombosis and thromboembolism constitute the major deterrent to the use of cardiovascular The process of platelet thrombogenesis predominates in the development of thrombotic complications when grafts are positioned in the arterial system as shown by: 1) direct visualization of prosthetic luminal surfaces after exposure to circulating blood; 6-10 2) renal microinfarction produced by platelet microemboli following prosthetic aortic grafts; llr 3) selective platelet consumption regularly observed in patients with cardiovascular devices; 13-15 and 4) interruption of platelet consumption and thromboembolism by antiplatelet drugs.13-19 Traditionally the thrombogenicity of vascular grafts in vivo has been assessed by measuring the amount of thrombus present at some point in time after surgical placement. The uncontrolled variables that seriously compromise the quantitative usefulness of this measurement include: 1) loss of thrombus by embolization; 2) loss of thrombus by fibrinolysis; 3) differences in effects of surgery; 4) timing of observations; and 5 ) hemodynamic characteristics of the test In order to quantify the overall rate of graftinduced thrombus formation in vivo in a manner that includes thromboembolization and thromboiysis and that is free of surgical and nonsteady state effects, the rate of platelet consumption by prosthetic material is being measured. In this paper we discuss the development of the platelet kinetic approach in baboons to the in vivo evaluation of prosthetic materials, antiplatelet drugs, and graft endothelialization. 12, 13, 23,

Survival of baboon platelets labeled with diazotized (125-1)-iodosulfanilic acid: No effect of drugs that modify platelet behavior

A baboon animal model has been developed to study the kinetics of platelets doubly labeled with 51-Cr, a cytoplasmic label, and diazotized 125-I-iodosulfanilic acid (D 125-ISA), which binds to glycoprotein components of the platelet membrane. This study was undertaken to evaluate the possible usefulness of this platelet label, and to extend to primates previous observations of D 125-ISA-labeled platelets in rabbits. D 125-ISA-platelet activity disappeared exponentially with a mean t12 of 0.90 days ± 0.11. Labeling 51-Cr-platelets with D 125-ISA resulted in a modest but significant reduction in the baseline 51-Cr-platelet survival time (from 5.5 ± 0.2 days to 4.7 ± 0.4; p < 0.02). 51-Cr and D 125-ISA kinetics were not changed by the administration of aspirin-dipyridamole, sudoxicam, or high molecular weight dextran. These studies suggest that platelet membrane components are continually lost during circulation in vivo, but that this process is unaffected by pharmacologic inhibition of platelet function.