Thrombosis In Dogs Research Articles

Six-month follow-up after thermal balloon angioplasty in canine iliac arteries

We performed thermal balloon angioplasty in 10 iliac arteries in 5 mongrel dogs. By perfusing a modified angioplasty balloon with hot (100 degrees C) saline, a mean balloon temperature of 84 degrees C was obtained. Angiographic and histologic follow-up at 6 months revealed no thrombosis or aneurysm formation but it did reveal fibrotic transformation of the media. Initial overdilatation was maintained in 9 of 10 arteries. We conclude that medial sclerosis induced by thermal balloon angioplasty does not result in aneurysm or thrombosis in dogs.

Effect of aspirin on local prostaglandin production and serotonin accumulation in a canine model with coronary cyclic flow variations or thrombosis

We have reported that thromboxane A 2 and serotonin are two important mediators of coronary cyclic flow variations (CFVs) caused by recurrent platelet aggregation and dislodgement on a stenosed coronary arterial wall with endothelial injury. To test the hypothesis that blocking the synthesis of thromboxane A 2 would not prevent serotonin release, 1.1, 4.6, and 9.2 mg/kg of aspirin were administered through the left atrium to 27 dogs with CFVs. The CFV elimination rate was 70% in the aspirin-treated dogs. Thromboxane B 2 and serotonin concentrations were measured in different coronary arterial segments. There were significantly lower thromboxane B 2 and 6-keto-PFG 1a levels in the stenosed left arterior descending (LAD) segments with increasing dosage of aspirin-208 ± 36, 24 ± 31, 50 ± 6 ng/g ( P<0.0001) and 125 ± 27, 58 ± 38, 25 ± 5 ng/g ( P<0.0001), respectively. Serotonin levels were significantly higher in stenosd LAD (265.7 ± 131.2 ng/g) than in LAD segments proximal or distal to the stenosis and in corresponding circumflex coronary artery segments, 17.1 ± 3.7, 18.6 ± 3.7, and 19.2 ± 5.1 ng/g, respectively ( P<0.05) following the highest dose of aspirin. In 41 additional dogs, electrical injury was used to initiate thrombosis in the circumflex artery and in those receiving aspirin (15mg/kg) ( n=5), occlusive thrombus formation was inhibited. However, the local accumulation of serotonin was not significantly different between the control (194 ± 27 ng/g) ( n=36) and the aspirin-treated group (167 ± 19 ng/g) ( n=5). In vitro platelet aggregation induced by arachidonic acid was inhibited by the in vivo adminstration of 1.1 mg/kg of aspirin and abolished by 4.6 + 1.1 and 9.2 + 4.6 + 1.1 mg/kg of aspirin. However, serotonin-induced platelet aggregation was not affected following all doses of aspirin. Thus, aspirin eliminates CFVs in 70% of dogs, and markedly diminishes thromboxane A 2 and prostacyclin concentrations in stenosed canine coronary arteries, but it does not prevent local serotonin accumulation. Similarly, aspirin prevents occlusive coronary thrombosis in dogs with electrically-induced endothelial injury, but it did not prevent local assumulation of serotonin. These experimental findings suggest that cyclo-oxygenese inhibition does not prevent serotonin accumulation at sites of coronary artery endothelial injury, and they thereby help provide a potential explanation of the lack of complete protection provided by aspirin in eliminating CFVs in this experimental model.

Effect of Diltiazem on Experimental Coronary Artery Thrombosis in Dogs

The effect of the calcium channel blocker diltiazem on arterial thrombosis was determined in anesthetized dogs subjected to continuous anodal stimulation of the intimal surface of the left circumflex coronary artery (LCCA). Infusion of saline (n = 6) or diltiazem (80 micrograms/kg plus 20 micrograms/kg/min i.v.; n = 6) was begun 15 min before electrical stimulation. Diltiazem prolonged the P-R interval by 28% and reduced mean arterial blood pressure (ABP) by 9%. All animals developed occlusive thrombosis. Saline- and diltiazem-treated dogs did not differ in the time to occlusion (204 +/- 30 and 153 +/- 27 min, respectively) and LCCA thrombus mass (25 +/- 4 and 24 +/- 3 mg, respectively). LCCA flows measured intermittently during thrombogenesis also did not differ between treatment groups, although the frequency of spontaneous flow increases which interrupted the flow declines was reduced 53% by diltiazem. In separate diltiazem-treated dogs (80 micrograms/kg plus 20 micrograms/kg/min i.v. for 2 h; n = 7) the ex vivo platelet aggregation response to platelet-activating factor (PAF) was inhibited (-45%), but not the response to collagen. When 5 and 25 mumols/l diltiazem was tested in vitro, again the aggregation response to PAF was reduced (-25 and -81%, respectively) while that to collagen was unaffected. These results demonstrate that diltiazem does not impede thrombus formation in vivo when given at a dose that exerts threshold hemodynamic activity and significantly impairs platelet function.

Prevention of the formation of arterial thrombi using different antiplatelet drugs: Experimental study in dogs

We have induced the formation of arterial thrombosis in dogs by means of an intima lesion produced by continuous current. The platelets were labeled with 111-In-oxine. Groups of 7 mongrel dogs received treatment for 7 days prior to the trial: Group I, control; Group II, 5 mg/kg body weight/day acetylsalicylic acid; Group III, 20 mg/kg body wt/day acetylsalicylic acid; Group IV, 15 mg/kg body wt/day triflusal + 5 mg/kg body wt/day dipyridamole; Group V, 15 mg/kg body wt/day triflusal; and Group VI, 5 mg/kg body wt/day acetylsalicylic acid + 5 mg/kg body wt/day dipyridamole. The only effective treatment for arterial thrombosis prevention was that employed in Group II (p < 0.05).

New model of cerebral thrombosis in dogs.

Experimental in situ thrombosis of the middle cerebral artery was produced in dogs by use of intravasally placed copper coils, which subsequently gave rise to an obstructing autologous thromboembolus. The resulting thrombosis was produced in the middle or rostral cerebral artery within 5-15 minutes after delivery of the thrombogenic device. The correlation of location of the coil in the intracranial vasculature of the internal carotid artery with the anatomic distribution of resulting cerebral infarcts suggests that this experimental model can produce a selective acute local occlusion of cerebral vessels in a high proportion of dogs without violating the cranium. The composition of the autologous thromboembolus, the low mortality rate, and the excellent reproducibility will make the correlative study of thrombolytic agents and their therapeutic efficacy possible.

Effect of defibrotide in electrically induced thrombosis in dogs.

Thrombi were electrically induced in dogs. The alterations of the vessel wall were studied in samples obtained on the 8th day from control and treated animals. Changes in coagulation parameters were monitored daily. Animals were treated with 600 mg defibrotide (Crinos) daily for a week, starting 24 h after the induction of thrombi. In the control dogs there was thickening of intima with endothelial hyperplasia and smooth muscle proliferation. The treated animals did not show any morphological or ultrastructural alterations (SEM). This observation encourages us to examine the role of fibrinolytic and endothelial supportive therapy for prevention of development of vascular changes.

Reduction of thrombosis in canine coronary bypass vein grafts with dipyridamole and aspirin

The potential benefit of platelet inhibitor drugs in reducing early thrombosis of coronary arterial vein bypass grafts was assessed in dogs. There were 26 control dogs and 24 dogs treated with dipyridamole, 55 mg/day plus aspirin, 325 mg/day. The dogs in both groups were killed at 2 hours and 1, 2, 3, 7 and 14 days after operation. The grafts were perfused with flxative in vivo, harvested and examined with light microscopy. Severe alterations of the graft wall were observed in the dogs in both groups. The grafts in the control group had a high incidence rate of thrombosis, which occurred early after the operation; those in the treated group had a significantly reduced incidence of thrombosis (p = 0.025). Our study indicates that a combined regimen of dipyridamole and aspirin is effective in reducing early graft thrombosis in dogs.

Correlation of the Serial-dilution Protamine Sulfate Test with Models of “Hypercoagulability” and Thrombosis in Dogs

In a dog model, combinations of venous-injury thrombosis, homologous serum-induced "hypercoagulability," and fibrinolytic blockade were evaluated to determine the factors involved in the generation of a positive serial-dilution protamine sulfate test. Stasis and operative procedures did not produce a positive test. Small local thrombi induced by electrical current produced a positive test that tended to persist only during the initial formation and propagation of the thrombus, and was blocked by pretreatment with epsilon-aminocaproic acid, suggesting in this model that the test was detecting mainly early fibrin degradation products. Homologous serum infusion without venous-injury thrombosis also produced positive serial-dilution protamine sulfate test results that could not be blocked with epsilon-aminocaproic acid suggesting here that the serial-dilution protamine sulfate test was detecting mainly soluble complexes of fibrin monomer rather than early fibrin degradation products. The serial-dilution protamine sulfate test is therefore capable of detecting both small local thrombi and serum-induced "hypercoagulability" without thrombosis in the dog model.

Silicone embolism, fat embolism, and fibrin thrombosis in dogs after extracorporeal circulation using a bubble-oxygenator (author's transl)

Following extracorporeal circulation with a bubble oxygenator (Rygg-Kyvsgaard) silicone emboli were found in the brain-and-kidney-capillaries of all dogs evaluated. There was no obvious correlation between intensity of silicone embolism and pump time. No cellular reaction was seen around the anti-foam agent. Occasionally single small areas of embolic brain damage were found. During extracorporeal circulation and within a recovery period up to one hour no silicone excretion through the kidneys could be demonstrated. Systemic fat embolism occurred less frequent than previously reported. Use of a filter in the cardiotomy suction line reduced its intensity further. In neither of the various organs examined, disseminated intravascular thrombosis could be found.

Effect of aspirin upon experimental coronary and non-coronary thrombosis and arrhythmia

The effect of aspirin upon platelet function led to speculation on the potential effects of salicylates upon arterial thrombogenesis, in which platelets play a primary role. Aspirin was given by mouth or intravenously before attempting induction of coronary or femoral artery thrombosis in dogs by means of a catheter electrode. The incidence of thrombus formation in all animals receiving aspirin was comparable to that of the control groups. Although in several animals of coronary thrombus group receiving aspirin, the thrombus was smaller than in the controls, this was not statistically significant. An unexpected finding was the distinct decrease in incidence of arrhythmias and ventricular fibrillation in the coronary thrombus group treated with aspirin. The reason for the differences is not clear at this time.

Inhibition of experimental arterial thrombosis in dogs with platelet - deaggregating agents

Inhibition of experimental arterial thrombosis in dogs with platelet - deaggregating agents

Protection by Aspirin against Experimentally Induced Arterial Thrombosis in Dogs

SummaryThe possible anti-thrombotic properties of drugs which interfere with platelet aggregation were studied. Segments of the peripheral arteries of dogs were isolated, injured either by endarterectomy or chemically by instillation of 0.1 N H2 S04 (chemical injury). Two days later, the segments were examined for the presence of thrombosis. In animals which received only a placebo, 29% of the chemically-injured segments and 43% of the endarterectomized segments became totally occluded with thrombi. Treatment with aspirin (600 mg per day) reduced this incidence to 2 and 11% respectively (p &lt; .05) while treatment with dipyridamole (DPM) (200 mg per day) had no effect. In a second study, aspirin ingestion reduced the incidence of total occlusion in chemically-injured segments from 38 to 0%. Connective-tissue induced platelet aggregation decreased in aspirin treated animals, while DPM had no effect. The findings support previous suggestions that aspirin, perhaps by inhibiting platelet aggregation, has anti-thrombotic properties.

Streptokinase in myocardial infarction: A co-operative controlled australian trial

Experimental coronary thrombosis in dogs has been treated with thrombolytic therapy with considerable reduction in the extent of myocardial necrosis compared to that in control animals. Such a favourable result has not been demonstrated in human myocardial infarction although there have been many trials of thrombolytic agents in this condition. Most of these trials suffer from defects in methodology. A multicentre trial of Streptokinase in acute myocardial infarction was being conducted in four university teaching hospitals. Patients aged less than 65 yr. and with a diagnosis of myocardial infarction of less than 24 hr. duration were admitted to the trial providing there were no contra-indications to the use of Streptokinase. After admission to the trial they were randomly allocated to the treatment group (Streptokinase) or the control group (Heparin). Both agents were given in standard dosage. Evidence of adequate fibrinolysis in the Streptokinase group was based on thrombin clotting times and fibrin plate assays during the infusion. All patients were treated in coronary care units with continuous monitoring equipment, and following the initial infusion, anticoagulation was continued with Warfarin during hospitalization. Patients were assessed 3 mth. after their admission. The hospital mortality was 11 out of 125 (8.8%) in the Streptokinase and 14 out of 120 (11.7%) in the control group. At 3 mth. the overall mortality was 13 out of 99 (13.1 %) in the Streptokinase group and 19 out of 94 (20.2%) in the control group. These differences were not statistically significant. One hundred and twenty-six electrocardiograms of patients with proven infarction were analysed at 3 mth. Of 61 in the Streptokinase group, 14 had returned to normal, while 6 of 65 in the Heparin had returned to normal. This difference was significant. Although the reduction in mortality in the Streptokinase-treated group was not statistically significant at the time of the report, the results suggested an extension of the trial to be worthwhile.

Magnetically controlled focal intravascular thrombosis in dogs.

HE mortality and morbidity resulting from ruptured intracranial aneurysms serves as an impetus to the surgeon to develop improved methods of therapy. Although it might seem logical to employ early craniotomy in the treatment of the patient with a ruptured aneurysm and thereby remove the risk of recurrent hemorrhage, numerous authors have demonstrated the high operative mortality of such a procedure. 5-11 One cause of this mortality is the vasospasm and subsequent infarction which follows surgical manipulation of the already irritated blood vessels. It is possible, however, that a stereotaxic method of treatment which would produce immediate thrombosis of the aneurysm but not require manipulation and retraction of the traumatized brain might significantly improve the aneurysm patient's

109. Experimental Studies on Electrically Induced Arterial Thrombosis in Dogs, with Special Refence to the Treatment of Intracranial Aneurysms and Angiomas

109. Experimental Studies on Electrically Induced Arterial Thrombosis in Dogs, with Special Refence to the Treatment of Intracranial Aneurysms and Angiomas

The occurrence of arterial thrombosis in dogs fed an “infarct-producing” diet

Four Boxer pups were fed a diet similar to one that has been previously used to induce arterial thromboses with infarcts of hearts and kidneys in rats. Feeding was continued for slightly over one year. One of the dogs developed advanced generalized “cholesterol-type” atherosclerosis and died with mesenteric arterial thrombosis and infarction of the small bowel. The results indicate that dogs could be successfully used in other studies pertaining to dietary-induced arterial thrombosis.

Use of Trypsin in the Treatment of Experimental Coronary Thrombosis

A method for the production of experimental coronary thrombosis in dogs by the injection of thrombin into the anterior descending branch of the left coronary artery is presented. The clot-dissolving properties of trypsin in the form of Tryptar and Enzar were evaluated. The effect of trypsin was also studied in relation to changes in the clotting mechanism of the blood for the purpose of determining tolerated doses. Regardless of amounts of enzyme or time of administration, there was no evidence to indicate prevention of myocardial infarction.

The natural history of changing patterns of angina pectoris.

Excerpt The clinical course of coronary artery disease is punctuated by bouts of coronary insufficiency of variable intensity and duration. Patients who exhibit a distinct alteration in a previousl...

Studies in intravascular coagulation. IV. The effect of heparin and dicumarol on serum-induced venous thrombosis.

A method has been previously described whereby the infusion of canine serun and serum fractions rich in convertin, but essentially devoid of thromboplastin, prothrombin, ac-globulin and thrombin, initiates venous thrombosis in dogs at sites of partial or complete venous stasis far removed from the site of infusion. It has been suggested that the pathogenesis of venous thrombosis in various clinical states may be referable to local stasis combined with a transient increase in circulating convertin activity. The present study demonstrates that heparin is superior to dicumarol in inhibiting the evolution of such serum-induced intravascular thrombi in dogs.

Long term dicumarol therapy.

Case Reports1 April 1950LONG TERM DICUMAROL THERAPYRAYMOND L. RICE, M.D., M. SC. (Med.), F.A.C.P., JACK S. ACKERMAN, M.D., ROBERT SAICHEK, M.D.RAYMOND L. RICE, M.D., M. SC. (Med.), F.A.C.P.Search for more papers by this author, JACK S. ACKERMAN, M.D.Search for more papers by this author, ROBERT SAICHEK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-32-4-735 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptGround work in the use of Dicumarol for preventing the extension of coronary thrombosis and the development of mural thrombi in the presence of myocardial infarction was laid by Solandt, Nassim, and Best1 in 1938. Using the anticoagulant, heparin, they were able to prevent the formation of coronary thrombi and intracardiac mural thrombi when deliberate experiments were performed to produce these lesions in experimental animals.With the advent of Dicumarol numerous workers2, 3, 4 began its use in the treatment of coronary thrombosis with myocardial infarction and its complications.Recently the Committee for the Evaluation of Anticoagulants in the Treatment...Bibliography1. SolandtBest DYDH: Heparin and coronary thrombosis in experimental animals, Lancet 2: 130-152, 1939. Solandt, D. Y., Nassim, R., and Best, C. H.: Production and prevention of cardiac mural thrombosis in dogs, Lancet 2: 592-595, 1939. Google Scholar2. Wright IS: Experiences with Dicumarol in the treatment of coronary thrombosis, Proc. Am. Federation Clin. Research 2: 101-102, 1945. Experiences with myocardial infarction, Am. Heart J. 32: 20-31, 1946. MedlineGoogle Scholar3. NicholPage ESSW: Dicumarol therapy in acute coronary thrombosis: results in 50 attacks, J. Florida M. A. 32: 365-370, 1946. MedlineGoogle Scholar4. PetersGuytherBrambel HRJREC: Dicumarol in acute coronary thrombosis, J. A. M. A. 130: 398-403, 1946. CrossrefMedlineGoogle Scholar5. WrightMarpleBeck ISCDDF: Anticoagulant therapy of coronary thrombosis with myocardial infarction, J. A. M. A. 138: 1074-1079, 1948. CrossrefMedlineGoogle Scholar6. Wright IS: The use of anticoagulants in the treatment of diseases of the heart and blood vessels, Ann. Int. Med. 30: 80-91, 1949. LinkGoogle Scholar7. ZiffrenOwenHoffmanSmith SECAGRHP: A simple bedside test for control of vitamin K therapy, Tech. Bull. Reg. Med. Tech. 1: 13-16, 1940. Google Scholar8. ZiffrenOwenHoffmanSmith SECAGRHP: Control of vitamin K therapy compensatory mechanisms at low prothrombin levels, Proc. Soc. Exper. Biol. and Med. 40: 595-597, 1939. CrossrefGoogle Scholar9. NicholFassett ESDW: An attempt to forestall acute coronary thrombosis: preliminary note on the continuous use of Dicumarol, South M. J. 40: 63l-637, 1947. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Milwaukee, Wisconsin*Received for publication June 11, 1949.From the Department of Medicine, Mount Sinai Hospital, and the Marquette University School of Medicine, Milwaukee, Wisconsin. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAn Evaluation of the Effect of Continuous Long-Term Anticoagulant Therapy on the Prognosis of Myocardial InfarctionLong Term Dicumarol Therapy in Thromboembolic Conditions, Especially Coronary Thrombosis.1 1 April 1950Volume 32, Issue 4Page: 735-745KeywordsAnticoagulantsHeparinHospital medicineLesionsMyocardial infarctionThrombosis ePublished: 1 December 2008 Issue Published: 1 April 1950 PDF downloadLoading ...