Red Thrombus Research Articles

The Vicious Cycle of Nonhealing Neointima in Fabric Vascular Prostheses

Delayed neointimal healing of a fabric vascular prosthesis was investigated in an animal study focusing on the relationship between red thrombus, fibrinolysis, and endothelialization on the luminal surface. Fabric vascular prostheses were implanted into the descending aortas of 72 dogs. Fifty-nine grafts were explanted from 1 h to 1,705 days after implantation. One hour after implantation, the graft wall was red in color due to fresh thrombus; however, at 1 day the luminal surface became white. Red thrombus reappeared at 1 week and remained present in the long-term. Microscopically the initial red thrombus contained numerous erythrocytes. The white thrombus at 1 day was composed of a dense fibrin network without erythrocytes. At 2 days numerous lacunae appeared in the fibrin layer, and at 3-5 days cavernae and low density fibrin areas were present secondary to fibrinolysis. These areas allowed the blood components to infiltrate into the fibrin layer, and as a result red thrombus reformed within it. The thrombi on the luminal surface in the long-term was always red in color and composed of complicated, multiple stages of thrombus formation, i.e., fresh thrombus with erythrocytes, dense fibrin without erythrocytes, low fibrin density areas, lacunae and cavernae in the fibrin layer, and blood component infiltration into these spaces. Thrombus was always newly formed and present, and involuted in parallel due to fibrinolysis, suggesting that these phenomena perpetuated in a vicious cycle. However, at the anastomoses fibrinolysis was present, but blood component infiltration was prevented by the endothelial cell lining. These results suggest that endothelialization may arrest the vicious cycle of nonhealing neointima in fabric vascular prostheses.

Ischemia-related lesion characteristics in patients with stable or unstable angina. A study with intracoronary angioscopy and ultrasound.

Postmortem-derived findings support the common beliefs that lipid-rich coronary plaques with a thin, fibrous cap are prone to rupture and that rupture and superimposed thrombosis are the primary mechanisms causing acute coronary syndromes. In vivo imaging with intracoronary techniques may disclose differences in the characterization of atherosclerotic plaques in patients with stable or unstable angina and thus may provide clues to which plaques may rupture and whether rupture and thrombosis are active. We assessed the characteristics of the ischemia-related lesions with coronary angiography and intracoronary angioscopy and determined their compositions with intracoronary ultrasound in 44 patients with unstable and 23 patients with stable angina. The angiographic images were classified as noncomplex (smooth borders) or complex (irregular borders, multiple lesions, thrombus). Angioscopic images were classified as either stable (smooth surface) or thrombotic (red thrombus). The ultrasound characteristics of the lesion were classified as poorly echo-reflective, highly echo-reflective with shadowing, or highly echo-reflective without shadowing. There was a poor correlation between clinical status and angiographic findings. An angiographic complex lesion (n = 33) was concordant with unstable angina in 55% (24 of 44); a noncomplex lesion (n = 34) was concordant with stable angina in 61% (14 of 23). There was a good correlation between clinical status and angioscopic findings. An angioscopic thrombotic lesion (n = 34) was concordant with unstable angina in 68% (30 of 44); a stable lesion (n = 33) was concordant with stable angina in 83% (19 of 23). The ultrasound-obtained composition of the plaque was similar in patients with unstable and stable angina. Angiography discriminates poorly between lesions in stable and unstable angina. Angioscopy demonstrated that plaque rupture and thrombosis were present in 17% of stable angina and 68% of unstable angina patients. Currently available ultrasound technology does not discriminate stable from unstable plaques.

A New Cardiac Wall Substitute Made of Dacron Fabric Prosthesis Sealed with Autologous Tissue Fragments: Comparative Studies of Neointima Formation and Bleeding Resistant Property Against Fibrinolysis Phenomenon with Those of a Preclotted Sealing Graft

A cardiac wall substitute made of a Dacron fabric prosthesis sealed with minced-autologous tissue fragments was developed. An animal study showed rapid neointima formation on the graft luminal surface and no bleeding problem under load test with tissue plasminogen activator (tPA) administration. To evaluate the efficacy of the sealing method, a special substitute that was sealed with tissue fragments in one half and preclotted with fresh blood in the other half was prepared. The grafts were implanted into the right ventricular outflow tract in 14 dogs. During a load test with administration of tPA intravenously, the preclotted area bled quite remarkably; however, the area sealed with tissue fragments did not bleed. Two weeks after implantation, red thrombus adhered on the preclotted area, while a white, glistening surface was noticed on the tissue fragments area. Light microscopical observation showed complete neointima formation in the tissue fragmented area but a thrombus layer in the preclotted area. These results indicated that the tissue fragmentation was a superior method compared with preclotting for creating a cardiac wall substitute.

Transluminal Extraction Coronary Atherectomy

The TEC is a forward-cutting atherectomy catheter that has the unique potential to excise and aspirate atheroma, especially intraluminal thrombus. This device has been under clinical investigation for more than 6 years and received final marketing approval by the FDA for the treatment of lesions in the coronary vasculature in 1993. In the US TEC Multicenter Registry, the overall clinical and lesion successes were favorable. The success rates were similar for both native coronary vessels and saphenous vein bypass grafts. Importantly, the procedural success rates were maintained even in the presence of several unfavorable angiographic features, such as ostial location, intraluminal thrombus, and total occlusion. Further insights into the mechanisms of action of the TEC were made from studies using percutaneous angioscopy and intravascular ultrasound. Angioscopy clearly demonstrated that the TEC was indeed able to remove intraluminal thrombus, especially loosely adherent red thrombus, in a population of patients with unstable coronary syndromes. However, the TEC frequently leaves behind multiple intimal disruptions which not only create a possible nidus for restenosis but also explain the frequent hazy angiographic appearance of the vessel after TEC atherectomy. As is true for all new interventional devices, the specific niche for the TEC in interventional cardiology will best be determined in randomized clinical trials. There are several areas in which the TEC appears promising. First, this device may have a role in the management of patients with diffusely diseased saphenous vein grafts. Second, the TEC may be an effective primary therapy in lesions with intraluminal thrombus. Treatment with the TEC may then be followed by an adjunctive therapy to maximize the final vessel diameters. Finally, the TEC may be valuable in the treatment of lesions in patients with high-risk unstable coronary syndromes.

The 'Ermenonville' classification of observations at coronary angioscopy--evaluation of intra- and inter-observer agreement. European Working Group on Coronary Angioscopy.

A European coronary angioscopy working group has been established to create and evaluate a classification system for angioscopic observation. The 'Ermenonville' classification features items, graded in 3-5 categories, such as lumen diameter, shape of narrowing, colours of surface, atheroma, dissection, thrombus, etc. Inter- and intra-observer agreement on the interpretation of angioscopic images, using this classification system, was studied within the working group. Kappa values for chance-corrected intra-observer agreement of the diagnostic items were 0.51-0.67. The mean kappa values for inter-observer agreement were very low at 0.13-0.29. The important items, such as red thrombus and dissection were studied after recoding as either present or absent. These items proved to have a good intra-observer agreement, and an acceptable inter-observer agreement after recoding. Other angioscopic diagnoses should be made with caution. Multicentre angioscopy studies should make use of an angioscopy core laboratory. A set of definitions for coronary angioscopy is proposed, and this working group will re-evaluate observer agreements using these definitions.

Effects of ultrasound energy on total peripheral artery occlusions: initial angiographic and angioscopic results.

Ultrasonic energy has been shown to ablate atherosclerotic plaques and arterial and venous thrombi. We used an ultrasonic angioplasty device developed by our group in ten patients with totally occluded femoral artery during surgical bypass. Ultrasonic angioplasty was performed with a 130-cm long and 0.8-cm diameter titanium probe with a 2- or 2.5-mm titanium ball-tip. In one patient, angioplasty could not be performed. Angiographic and angioscopic examination were performed before and after angioplasty in nine patients. Before ultrasound recanalization, angioscopic examination showed that the proximal end of the occlusion was formed by atheromatous material in 3 cases, red thrombus in 3 cases, amd white thrombus in 3 cases. After ultrasound recanalization, angioscopy showed residual stenosis at the site of entry in only one case. In three other cases, the artery was free of residual stenosis without persistent clot. In the five other patients, a residual stenosis was present beyond the proximal occlusion point with some fibrin mesh and small clots. At angiography, flow was restored in 4 cases; in 4 patients flow rate of entry was slow in the distal segment; and in 1 patient, the distal arterial bed could not be opacified. Altogether, ultrasonic angioplasty was able to recanalize a complete occlusion in nine out of ten patients, with partial or complete dissolution of clots and with no complication. At its present stage of development, adjunctive balloon angioplasty would be needed in most cases to obtain unrestricted flow and unsignificant residual stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved spontaneous endothelialization by postfixation treatment of bovine pericardium

The longstanding release of locally cytotoxic glutaraldehyde concentrations from fixed biological materials is one reason for the lack of spontaneous endothelialization in vivo and in vitro of biological grafts (and valves). Preliminary studies have shown that bovine pericardium postfixation-treated with aminoacids may be endothelialized in vitro. To test whether such treatment improves spontaneous endothelialization in vivo 8 cm long segments grafts (6 mm I.D.) were interposed into the carotid arteries of 10 sheep. Ten grafts were sewn from postfixation treated pericardium (PTP), 4 from standard glutaraldehyde fixed pericardium (GAP) and 6 polytetrafluoroethylane (PTFE) grafts were implanted to study the degree of spontaneous endothelialization. In two pregnant animals, all grafts occluded (2 PTP, 1 GAP, 1 PTFE). In the remaining animals 1 additional PTFE graft occluded and 2 PTFE and 1 GA grafts showed significant thrombotic obstruction. The patent grafts were harvested at 3 months and the surface covered with red thrombus was determined by planimetry. PTP grafts had significantly less (12.2% +/- 15%) thrombotic appositions than glutaraldehyde treated grafts (49% +/- 20%; P = 0.01) and PTFE grafts (40.5% +/- 13%; P = 0.01). In the central areas of the PTP grafts, endothelial cells spread directly on the collagenous matrix and produced a basal lamina. In GAP, endothelial cells spread on amorphous material or macrophages and in PTFE grafts, only a neointima composed of myofibroblasts was endothelialized. Neutralization of glutaraldehyde concentrations by postfixation with aminoacids improves spontaneous endothelialization in vivo in biological materials.

The Characterisation of Thrombus Development in an Improved Model of Arterio-Venous Shunt Thrombosis in the Rat and the Effects of Recombinant Desulphatohirudin (CGP 39393), Heparin, and lloprost

An existing arterio-venous shunt thrombosis model in the rat has been modified to increase its usefulness for the testing of anti-thrombotic agents and characterised using morphological and radiometric techniques. The thrombus formed on the cotton thread held in the shunt was found to be composed of platelet aggregates surrounded by red thrombus. After 30 min of blood flow there was a 15-fold increase in the platelet content of the thrombus and a 4-fold increase in the fibrin(ogen) content compared with an equivalent weight of whole blood. Use of the anticoagulants recombinant desulphatohirudin (CGP 39393, 4 mg/kg, s.c.) and unfractionated heparin (800 IU/kg, s.c.) showed that approx. 90% inhibition of thrombus weight and approx. 80% inhibition of fibrin(ogen) content could be achieved without significant effect on the platelet content. Conversely, using the platelet inhibitor Iloprost (1 microgram kg-1 min-1), a reduction in thrombus weight of 50% was associated with 75% inhibition of platelet content and only 20% inhibition of fibrin(ogen). These observations suggest that the growth of this type of thrombus is largely the result of continued fibrin formation rather than continued platelet recruitment and activation.

Comparison of Lymphatic and Venous Interpositional Autografts in Experimental Microsurgery of the Canine Lymphatics

In mongrel dogs, 56 autologous lymphatic and vein grafts were interpositioned to bridge a defect in the femoral collecting lymphatics. In one group, 26 lymphatic autografts were interpositioned with good results. No obstruction was observed over 6 months. In another group, 20 venous autografts were interpositioned after irrigation with heparinized saline and another 10 autografts were interpositioned without irrigation. After 1 week, four irrigated grafts were partially occluded with a red thrombus; after 6 months, all grafts were totally occluded. In a third group, 15 lymphaticolymphatic anastomoses were enveloped by a silicone sheet to provoke prolonged devascularization. None of the vessels was patent. Anastomotic patency was inspected in vivo postoperatively. The specimens were studied with light microscopy and scanning and transmission electron microscopy. Prolonged devascularization damaged the endothelial cells. The results show that the lymphatic vessel autograft is the best choice for an interpositional autografting to bridge a defect in lymphatic vessels.

Rapid cellular luminal coverage of Dacron inferior vena cava prostheses in dogs by immediate seeding of autogenous endothelial cells derived from omental tissue: Results of a preliminary trial

Endothelial cell seeding methods might reduce the high failure rates of venous vascular prostheses, but low flow rates in venous vascular prostheses impose a need to protect early patency and to attain early endothelial cell coverage without waiting several weeks for relatively small endothelial cell innocula from autologous veins to form confluent linings. To obtain large number of autologous endothelial cells for high-density seeding, canine omental microvascular endothelial cells were harvested by collagenase digestion and density gradient centrifugation, with yields of 1.34 ± 0.24 (SD) × 106 cells/gm of omentum (N = 8 harvests). Primary culture of a subfraction from each harvest showed the cell population to be dominated by factor VIII—related antigen-positive endothelial cells with only a few nonstaining cells (estimated to be 10% or less of total cell number) visible. Freshly harvested omental cells were seeded onto double velour knitted Dacron prostheses at densities of 5 × 105 cells/cm2 of graft luminal surface in an autologous plasma suspension by use of prior preclotting with cell-free autologous plasma, followed by endothelial cell seeding in autologous plasma, with plasma recalcification during endothelial cell instillation. Six seeded and two control (sham-seeded) vascular prostheses 5 cm long with 10 mm inner diameter were used as inferior vena cava interposition grafts. A distal arteriovenous fistula and aspirin (300 mg) and dipyridamole (50 mg orally every day) starting 3 days before surgery were used to protect early patency of all grafts. Seeded venous vascular prostheses were explanted for study at intervals of 1, 5 and 10 days after surgery (N = 2 prostheses at each time); the two control venous vascular prostheses were explanted at 10 days. All venous vascular prostheses were patent at time of removal. In seeded venous vascular prostheses, light, scanning, and transmission electron microscopy showed emergence of numerous flattened endothelial cell-like cells on the luminal surface 24 hours after surgery, followed by formation of a confluent cellular lining without adherent platelets by 5 to 10 days after surgery. Control venous vascular prostheses, in contrast, remained covered by an irregularly thickened fibrin and red cell thrombus, which sometimes encroached on the lumen. Our results suggest that (1) omental tissue can furnish endothelial cells for high-density immediate seeding of venous vascular prostheses, and (2) that the method we used to combine features of both so-called high density “seeding” and “sodding” techniques offers both more rapid prosthesis coverage than the former and shorter intraoperative times for cell attachment to prostheses than the latter. The relatively rapid coverage by endothelial cell-like cells we observed at 5 to 10 days with this method may be of particular value for low-flow venous vascular prostheses.

Local prevention of trombosis in animal arteries by means of magnetic targeting of aspirin-loaded red cells

Trombosis was induced in I8 dog and I6 rabbit arteries by surgically inverting a vascular wall flap into its lumen. A completely occluding red thrombus was formed inside the vessel 4 to 5 hours later in 80% of cases. SmCo5 magnet was secured externally to one of the arteries. The constant magnetic field produced by the magnet had no influence on the clit formation. Autologous red cells loaded with ferromagnetic colloid compound and aspirin were administered intravenously and completely aborted arteriothrombosis on magnet-suplied side with no deterioratory effect on clot formation in the control artery.

New Directions in the Use of Carbon as Vascular Graft Material

Carbon has been used to improve the thromboresistance of synthetic vascular prostheses, and for this pur pose, dacron grafts have been coated with carbon. Owing to the contradic tory results reported in the literature, a new kind of vascular conduit, ex clusively textured from carbon fi bers, has been developed. The pres ent research study was undertaken to compare carbon and expanded poly tetrafluoroethylene (e-PTFE) grafts when used as vascular substitutes. Fifty-six experimental animals were divided into four equal groups and underwent substitution of segments of infrarenal aorta or inferior vena cava (IVC), through use of either carbon or e-PTFE grafts. Prosthetic segments were removed fifteen sec onds, or sixty minutes, or seven, fif teen, thirty, sixty, or one hundred twenty days after implantation. Spec imens were examined by light and scanning electron microscopy. Cumu lative patency rates, calculated by the life-table method at 120 days after surgery, were 72% for aortic carbon grafts, 41 % for aortic e-PTFE grafts, and 0% for both carbon and e-PTFE grafts implanted on the IVC. Carbon conduits performed significantly bet ter than e-PTFE conduits when used as small-caliber arterial substitutes (p < 0.05). Fifteen seconds after blood contact, the inner surface of carbon prostheses, regardless of the implantation site, was covered with a thin proteinaceous layer, whereas e- PTFE grafts appeared almost com pletely free from hematic deposits. One hour after implantation, a red thrombus was found to overlay the luminal surface of both carbon and e- PTFE prostheses. This layer ap peared to be thicker on the e-PTFE grafts than on the carbon grafts and thicker on the venous grafts than on the arterial. The endothelialization process of the blood-prosthesis inter face seemed to be slightly more rapid on the carbon than on the e-PTFE aortic grafts. In conclusion, this new carbon graft would appear to possess promising specifications, making it suitable for small-caliber arterial (but not venous) replacement.

In vivo evaluations of a new thromboresistant polyurethane for artificial heart blood pumps

To reduce the risk of thromboembolic complications in prosthetic blood pumps, we have developed a new segmented polyurethane elastomer. This material is unique because its mechanical properties for long-term durability and surface properties for biocompatibility have been separated and developed in two distinct materials. Improved thromboresistance is then obtained by a 1% concentration of a new polymeric surface-modifying additive blended with the base polyurethane before fabrication of the blood pump. To evaluate this material in vivo, we performed 10 implants, in calves, of the Pierce-Donachy prosthetic ventricle with blood-pumping sacs and cannulas fabricated from the new surface-modifying additive copolymer blend (Thoratec's BPS-215M). In four control implants the blood sacs and cannulas were fabricated from Ethicon's Biomer segmented polyurethane, which is the present clinical standard for most artificial hearts and circulatory support devices. The blood pumps were connected from the apex of the left ventricle to the descending aorta in male Holstein calves weighing 82 to 108 kg and were driven pneumatically in the full-to-empty mode with flows averaging 5 to 6 L/min. Each calf was medicated with aspirin and dipyridamole throughout the study period and was electively put to death after 4 weeks for evaluation of explanted blood sacs and for examination of the kidneys for infarction. All 10 explanted blood sacs made with the surface-modifying additive copolymer blend were shiny and completely free of thrombus. Three of the four explanted Biomer blood sacs showed visible red thrombus, and all four showed small areas of white thrombus. The average surface area of the Biomer blood sacs covered with thrombus was 45 +/- 32 mm2. Use of a semiquantitative scale to assess renal infarction demonstrated that nine of 10 animals with a surface-modifying additive copolymer blend blood sac had infarction less severe than the mean infarct score of the animals with a Biomer sac. The surface-modifying additive copolymer blend has excellent mechanical and physical properties necessary for use in artificial heart blood pumps. From these experiments, we conclude that the surface-modified polyurethane blend is superior to Biomer polyurethane in blood compatibility and in freedom from thromboembolic risk. This material is now approved by the Food and Drug Administration for investigational device exemption studies in the Pierce-Donachy prosthetic ventricle.

Experimental canine arterial thrombus formation and thrombolysis: A fiberoptic study

We produced arterial thrombi that simulated the clinical condition in canine iliac arteries by endothelial denudation and partial occlusion. The processes of thrombus formation and thrombolysis were examined by vascular fiberscope. Laminar mural thrombi developed in all 21 preparations 10 minutes after blood reperfusion, with stenosis formation. Over 50% luminal obstruction with thrombi occurred in 10 preparations 30 minutes after inducing stenosis. Total occlusion with thrombi occurred in four preparation (31%) at 1 hour, and in all nine at 3 hours after inducing stenosis. Usually, red thrombus at the denudated region grew in size distal to the sited of stenosis. Histologically, thrombi of less than 1 hour duration consisted of a loose fibrin network and those of over 3 hours' duration consisted of a dense fibrin network. Infusion of 144,000 IU of urokinase (UK) reduced the size of thrombi less than 1 hour old during fiberoptic observation. However, UK infusion of similar dose failed to recanalize two of four preparations with 3-hour-old thrombi. In conclusion, arterial thrombi that closely simulate those observed clinically can be made by endothelial denudation and partial occlusion, and the vascular fiberscope provides a useful method for analysis of thrombosis and thrombolysis.

Arteriovenous difference in levels of vascular and platelet factors of hemostasis

The authors study arteriovenous differences that lie at the basis of the mechanism of thrombus formation in arteries and veins. The experiments were carried out on rats. ADP-induced platelet aggregation, the malonic dialdehyde concentration, and the cAMP concentration, the last by radioimmunoassay, were determined in the platelet-enriched plasma. The antiaggregation activity of the aorta and posterior vena cava was estimated by determination of the antiaggregation properties and cAMP level in the vessel walls by radioimmunoassay. It is concluded that great importance in the mechanism of white thrombus formation must be ascribed to disturbance of the vascular-platelet component of the hemostasis system, and in the mechanism of formation of the red thrombus - to disturbance of the coagulation component.

Clinicopathological study of sclerotherapy of esophageal varices. I. A review of 26 autopsy cases.

Twenty six autopsy cases treated by endoscopic injection sclerotherapy (an intravariceal injection method) using ethanolamine oleate were examined for morphological changes in relation to the time intervals following injection. Red thrombi obliterated in the varices were recognized within 20 days of the treatment, and after a month, organization and shrinkage had occurred. Neutrophil infiltration of the esophageal wall was present within four days, and hemorrhage within six days. Edema and necrosis, the degree of which tended to decrease gradually with time, were observed within 20 days. Granulation tissue was first seen 10 days after treatment, followed by increased transformation of fibroblasts into fibrocytes. After two and a half months, an almost cell-free fibrotic-sclerotic stroma was recognized. The results obtained suggest that this treatment creates not only thrombi in vessels which are at risk of bleeding but also fibrosis which prevents rupture of the varices when a sclerosant is leaked or injected into the interstitial tissue. The results might furthermore serve as a basis for a prospective morphological study of patients with varices treated with ethanolamine oleate.

Demonstration of In Situ Fibrin Degradation in Pathologic Thrombi

Fibrin prepared from 15 pathologic thrombi was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine the extent and pattern of fibrinolysis that occurs in vivo. Two groups of patients could be distinguished on the basis of the polypeptide chain composition of fibrin in their thrombi. Those patients who presented with acute vascular obstruction, either arterial or venous, showed a minimal degree of fibrin degradation, with a dominance of intact, undegraded crosslinked gamma-gamma dimers. On the other hand, patients with long-standing symptoms associated with chronic aortic aneurysms had thrombi containing extensively degraded fibrin. Thrombi in large aortic aneurysms were dissected into concentric layers that showed different degrees of fibrinolysis. The luminal surface consisted of fresh, red thrombus and contained undegraded crosslinked fibrin similar to that found in patients with acute occlusive disease. Deeper layers of the thrombus showed gamma-gamma chain degradation throughout, indicating that this portion was undergoing active thrombolysis. The findings demonstrate that the variability in the pathophysiologic balance between coagulation and fibrinolysis is reflected in vivo by the polypeptide chain composition of crosslinked fibrin in thrombi. The results support the hypothesis of a dynamic equilibrium between clotting and lysis, but indicate that the balance between these two processes may be distinctly different in separate areas of a single clot.

Demonstration of in situ fibrin degradation in pathologic thrombi

Fibrin prepared from 15 pathologic thrombi was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine the extent and pattern of fibrinolysis that occurs in vivo. Two groups of patients could be distinguished on the basis of the polypeptide chain composition of fibrin in their thrombi. Those patients who presented with acute vascular obstruction, either arterial or venous, showed a minimal degree of fibrin degradation, with a dominance of intact, undegraded crosslinked gamma-gamma dimers. On the other hand, patients with long-standing symptoms associated with chronic aortic aneurysms had thrombi containing extensively degraded fibrin. Thrombi in large aortic aneurysms were dissected into concentric layers that showed different degrees of fibrinolysis. The luminal surface consisted of fresh, red thrombus and contained undegraded crosslinked fibrin similar to that found in patients with acute occlusive disease. Deeper layers of the thrombus showed gamma-gamma chain degradation throughout, indicating that this portion was undergoing active thrombolysis. The findings demonstrate that the variability in the pathophysiologic balance between coagulation and fibrinolysis is reflected in vivo by the polypeptide chain composition of crosslinked fibrin in thrombi. The results support the hypothesis of a dynamic equilibrium between clotting and lysis, but indicate that the balance between these two processes may be distinctly different in separate areas of a single clot.

Histological change in permanently clipped or ligated cerebral arterial wall. Part II: Autopsy cases of aneurysmal neck clipping.

An investigation was carried out on clinical autopsy cases into histological changes in the vessel wall and into the surrounding tissue reaction after permanent clipping. 1. There were 17 autopsy cases of cerebral aneurysm, which included seven cases treated with the Yaşargil clip, five with the Heifetz clip, and five control cases. 2. Clipping period ranged from 6 days to 11 months. Both the Yaşargil and the Heifetz clips, even with long duration of clipping, caused no changes, and inflammatory reaction was slight. 3. As for the necrosis of the vessel wall beneath the blade, the Yaşargil clip produced marked necrosis at the blade edge in 4 of 7 cases (57%), while the Heifetz clip caused necrosis under the midconvexity of the blades in all 5 cases (100%). 4. The granulation tissue reaction round the clip began to occur after one month, and was enough to embed the blade of the clip after three months. We considered it very unlikely for a slip-out accident to occur after this stage. 5. Formation of mural red thrombus and deposition of fibrin with irregular intimal thickening were noted in the aneurysmal lumen in cases clipped for less than 13 days. After one month the intimal thickening was diffuse, and organized thrombus was noted. After three months or more, the aneurysmal lumen was found to have been filled almost completely by intimal thickening. Based on the above finding, the optimum condition for temporary and permanent clips was also considered.

Vessel healing in dogs after endarterectomy with and without aspirin administration--observations by light and scanning electron microscopy.

Healing of the carotid artery after endarterectomy in adult mongrel dogs was investigated at intervals from 15 minutes to two weeks after surgery by light and scanning electron microscopy. In the control group, a fibrin-platelet carpet was found on the surface of the endarterectomized wall of the vessel soon after surgery. A large, typical, red thrombus was noted on the endarterectomized surface in three of six control animals 15 minutes after the operation, and in another one hour after the operation. On Day 1 after surgery, no new thrombus formation was detectable. On Day 3, most of the mural thrombi had disappeared, and formation of new-endothelium had started and was completed about one week after the operation. In the group treated with aspirin, thrombus formation in the wall was much less just after operation, and no large thrombi were seen in any animals. Almost no newly formed endothelium was detectable on Day 3. After one week, new endothelium covered only about 60% of the inner surface of the artery, but after two weeks the formation of new-endothelium was almost complete in all dogs. Thus, with aspirin treatment, formation of new endothelium seemed to be delayed and the new endothelial cells seemed to grow somewhat differently from those in the control group.