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Platelet aggregation stimulates endothelial regeneration
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Platelet aggregation stimulates endothelial regeneration K. Craig Kent, MD, Lynette Wroblewski, Lisa Picard, Robert W. Jackman, and John J. Skillman, Beth Israel Hospital, Boston, Mass. Endothelial cell regeneration (ER) is an important component of the healing process after arterial injury. We wished to study whether platelet aggregation in response to arterial injury influences the rate of ER. Models of ER classically use monolayers of harvested cells grown in tissue culture. Unfortunately, endothelial cells are phenotypically altered and the injury does not expose native basement membrane. To avoid these problems, we have developed a new model of endothelial injury by use of explants of whole vessel wall to study the effect of platelet aggregation on ER. Rabbit thoracic aortas were removed, opened longitudinally, segmented, and placed in tissue culture. After 4 days a defined superkial endothelial injury was made on each explant and either nonaggregated fresh whole platelets (3 x 108/cc), or the supernatant of platelets aggregated by collagen, were added to the culture media. Four days after injury, the endothelial layer was stained, photographed, and the distance that the cells regenerated was calculated. We found an increase in the rate of ER when injured vessels were exposed to fresh whole platelets (p < 0.05 t test each animal, p < 0.0001 ANOVA all animals). There was no increase in regeneration if the supernatant of platelets aggregated with collagen was added to the explants (p > 0.375 each animal, all animals). Platelets increase the rate of ER. Because this effect was not demonstrated with supernatant, it is possible that attachment of the platelets to the area of injury may be necessary for regeneration to occur. Precoating ePTFE grafts alters production of endothelial cell-derived thrombomodulators Jian-ming Li, MD, Michael J. Menconi, PhD, H. Brownell Wheeler, MD, Michael J. Rohrer, MD, and Valerie A. Klassen, MA, University of Massachusetts Medical School, Worcester, Mass. The use of extracellular matrix proteins to precoat small diameter ePTFE grafts before endothelial cell (EC) seeding has been shown to improve cell attachment, proliferation, and adherence. The effect of this precoating on the production of anticoagulant and procoagulant properties by seeded ECs is unknown. Human saphenous vein (HSV) ECs were cultured for 3 days on ePTFE that had been either noncoated or precoated with fibronectin (FN) , type I collagen (COL), or FN and COL (FN/COL). Prostacyclin (PC), thromboxane (TX), and tissue plasminogen activator (tl?A) were measured under basal conditions and in response to stimulation by arachidonate and thrombin. Significantly more PC was synthesized by ECs grown on FN-ePTFE than on COL-ePTFE or FN/COL-ePTFE (1.2 to 1.8 times more), both under basal and stimulatory
Journal of VASCULAR SURGERY
conditions. No statistically significant differences were found between PC production by ECs grown on FNePTFE and noncoated ePTFE. Under stimulatory conditions, ECs grown on FN-ePTFE and FN/COL-ePTFE produced significantly less thromboxane compared to ECs grown on noncoated ePTFE. TPA production by thrombin-stimulated ECs grown on FN-ePTFE was 1.9 and 1.6 times greater than ECs grown on noncoated or FN/COL-ePTFE, respectively. Differences in the production of thrombomodulatory substances was not related simply to the degree of cell coverage. ECs grown on FN-ePTFE show excellent graft coverage and better antithrombotic properties than ECs grown on COL- or FN/COL-ePTFE. Changing patterns in surgery for chronic renal artery occlusive diseases Carl E. Bredenberg, MD, Lawrence Sampson, MD, Ferris S. Ray, MD, Robert Cormier, RN, Sharon Heintz, PA, and Jens Eldrup-Jorgensen, MD, Maine Medical Center, Portland, Me. In the past, renal artery reconstruction was used primarily to treat renovascular hypertension. Fibromuscular disease (FMD) and atherosclerosis localized to the renal artery were the most frequent etiologies, and aortorenal bypass became the most common operation performed. We reviewed 67 patients undergoing 69 operations for chronic renal artery occlusive diseases operated on between January 1985 and June 1990 looking for changes in patient population and surgical approach. Etiology was atherosclerosis in 60 patients (90%); FMD in four (6%), and three children had nonFMD stenosis. Atherosclerosis was diffuse in 50 patients (75%). Salvage of renal function was the indication for operation in 48 (70%) based on > 75% stenosis to a single functioning kidney in 23; bilateral >75% stenosis in 10; or unilateral >75% stenosis with elevated creatinine in the remaining 15. Average serum creatinine was 2.3 mg/dl and was elevated in 37 patients (54%). Donor arteries for reconstruction were aorta 20 (29%), aortic graft 19 (28%), other abdominal arteries 30 (43%). Concomitant vascular procedures were performed in 25 patients including 19 aortic replacements. The two operattve (30-day) deaths (3%) followed aortic replacements (one elective, one ruptured AAA). Follow-up averaged 2 years (range, 1 month to 5 years). Eleven patients (all AS) died during follow-up (one CA, three MI, seven renal failure). Nine patients required chronic dialysis in follow-up including two preoperative dialysis patients. Seven had confirmed patent grafts, one occluded and one is unknown. Seven of the nine died while on chronic dialysis. Five nonatherosclerosis patients are normotensive without medication, and two are improved. All atherosclerosis patients required some antihypertensive medication after operation. Compared with previous experience, currently: the preponderance of surgical patients have far advanced diffuse atherosclerosis; salvage of renal function
Platelet aggregation stimulates endothelial regeneration K. Craig Kent, MD, Lynette Wroblewski, Lisa Picard, Robert W. Jackman, and John J. Skillman, Beth Israel Hospital, Boston, Mass. Endothelial cell regeneration (ER) is an important component of the healing process after arterial injury. We wished to study whether platelet aggregation in response to arterial injury influences the rate of ER. Models of ER classically use monolayers of harvested cells grown in tissue culture. Unfortunately, endothelial cells are phenotypically altered and the injury does not expose native basement membrane. To avoid these problems, we have developed a new model of endothelial injury by use of explants of whole vessel wall to study the effect of platelet aggregation on ER. Rabbit thoracic aortas were removed, opened longitudinally, segmented, and placed in tissue culture. After 4 days a defined superkial endothelial injury was made on each explant and either nonaggregated fresh whole platelets (3 x 108/cc), or the supernatant of platelets aggregated by collagen, were added to the culture media. Four days after injury, the endothelial layer was stained, photographed, and the distance that the cells regenerated was calculated. We found an increase in the rate of ER when injured vessels were exposed to fresh whole platelets (p < 0.05 t test each animal, p < 0.0001 ANOVA all animals). There was no increase in regeneration if the supernatant of platelets aggregated with collagen was added to the explants (p > 0.375 each animal, all animals). Platelets increase the rate of ER. Because this effect was not demonstrated with supernatant, it is possible that attachment of the platelets to the area of injury may be necessary for regeneration to occur. Precoating ePTFE grafts alters production of endothelial cell-derived thrombomodulators Jian-ming Li, MD, Michael J. Menconi, PhD, H. Brownell Wheeler, MD, Michael J. Rohrer, MD, and Valerie A. Klassen, MA, University of Massachusetts Medical School, Worcester, Mass. The use of extracellular matrix proteins to precoat small diameter ePTFE grafts before endothelial cell (EC) seeding has been shown to improve cell attachment, proliferation, and adherence. The effect of this precoating on the production of anticoagulant and procoagulant properties by seeded ECs is unknown. Human saphenous vein (HSV) ECs were cultured for 3 days on ePTFE that had been either noncoated or precoated with fibronectin (FN) , type I collagen (COL), or FN and COL (FN/COL). Prostacyclin (PC), thromboxane (TX), and tissue plasminogen activator (tl?A) were measured under basal conditions and in response to stimulation by arachidonate and thrombin. Significantly more PC was synthesized by ECs grown on FN-ePTFE than on COL-ePTFE or FN/COL-ePTFE (1.2 to 1.8 times more), both under basal and stimulatory
Journal of VASCULAR SURGERY
conditions. No statistically significant differences were found between PC production by ECs grown on FNePTFE and noncoated ePTFE. Under stimulatory conditions, ECs grown on FN-ePTFE and FN/COL-ePTFE produced significantly less thromboxane compared to ECs grown on noncoated ePTFE. TPA production by thrombin-stimulated ECs grown on FN-ePTFE was 1.9 and 1.6 times greater than ECs grown on noncoated or FN/COL-ePTFE, respectively. Differences in the production of thrombomodulatory substances was not related simply to the degree of cell coverage. ECs grown on FN-ePTFE show excellent graft coverage and better antithrombotic properties than ECs grown on COL- or FN/COL-ePTFE. Changing patterns in surgery for chronic renal artery occlusive diseases Carl E. Bredenberg, MD, Lawrence Sampson, MD, Ferris S. Ray, MD, Robert Cormier, RN, Sharon Heintz, PA, and Jens Eldrup-Jorgensen, MD, Maine Medical Center, Portland, Me. In the past, renal artery reconstruction was used primarily to treat renovascular hypertension. Fibromuscular disease (FMD) and atherosclerosis localized to the renal artery were the most frequent etiologies, and aortorenal bypass became the most common operation performed. We reviewed 67 patients undergoing 69 operations for chronic renal artery occlusive diseases operated on between January 1985 and June 1990 looking for changes in patient population and surgical approach. Etiology was atherosclerosis in 60 patients (90%); FMD in four (6%), and three children had nonFMD stenosis. Atherosclerosis was diffuse in 50 patients (75%). Salvage of renal function was the indication for operation in 48 (70%) based on > 75% stenosis to a single functioning kidney in 23; bilateral >75% stenosis in 10; or unilateral >75% stenosis with elevated creatinine in the remaining 15. Average serum creatinine was 2.3 mg/dl and was elevated in 37 patients (54%). Donor arteries for reconstruction were aorta 20 (29%), aortic graft 19 (28%), other abdominal arteries 30 (43%). Concomitant vascular procedures were performed in 25 patients including 19 aortic replacements. The two operattve (30-day) deaths (3%) followed aortic replacements (one elective, one ruptured AAA). Follow-up averaged 2 years (range, 1 month to 5 years). Eleven patients (all AS) died during follow-up (one CA, three MI, seven renal failure). Nine patients required chronic dialysis in follow-up including two preoperative dialysis patients. Seven had confirmed patent grafts, one occluded and one is unknown. Seven of the nine died while on chronic dialysis. Five nonatherosclerosis patients are normotensive without medication, and two are improved. All atherosclerosis patients required some antihypertensive medication after operation. Compared with previous experience, currently: the preponderance of surgical patients have far advanced diffuse atherosclerosis; salvage of renal function