Hiroyuki Sonoki

Enhancement of arterial thrombolysis with native tissue type plasminogen activator by pretreatment with heparin or batroxobin: An angioscopic study

The enhancement of canine arterial thrombolysis with native tissue type plasminogen activator (nt-PA) obtained from human-derived normal cells by pretreatment with heparin or the defibrinogenating agent, batroxobin, was evaluated with angioscopy. The nt-PA, 0.25 mg/kg, was infused intravenously to lyse 1-hour-old thrombus (eight thrombosed arteries without medication, seven with nt-PA alone, seven with nt-PA and heparin, and seven with nt-PA plus batroxobin). Angioscopy provided a cross-sectional view of the vessel lumen with clear visualization of the thrombus. Thirty minutes after nt-PA infusion, the percent luminal obstruction decreased from 74 to 61 in nt-PA alone (p less than .025), from 77 to 37 in nt-PA plus heparin (p less than .005), and from 79 to 25 in nt-PA plus batroxobin (p less than .005). Fifteen minutes after drug infusion, plasma fibrinogen levels decreased to 89% of preinfusion value in nt-PA alone, to 84% in nt-PA plus heparin, and to less than 5% in nt-PA plus batroxobin. Thus rapid infusion of nt-PA alone provided slight thrombolytic effects. However, heparin and batroxobin showed marked enhancement of thrombolytic effects of nt-PA.

Fiberoptic angioscopy of cardiac chambers, valves, and great vessels using a guiding balloon catheter in dogs

The applicability of fiberoptic angioscopy with a guiding balloon catheter to observe the cardiac chambers, valves and the great vessels was examined in anesthetized dogs. A No. 11 French guiding balloon catheter (balloon diameter 50 French) was introduced through either the right jugular vein or the right femoral vein into the right heart, and then a fiberscope (4.3 French in diameter) was introduced through the catheter into the right heart in 10 dogs. The balloon was inflated with air and gently pushed against the luminal surface, warm saline was infused through the catheter to displace the blood, and the luminal surfaces were photographed on 16 mm color cinefilms. Pulmonary angioscopy was also performed in these dogs. Similarly, the guiding catheter and fiberscope were introduced through the right common carotid artery into the left ventricle for observation of the luminal changes in the other 10 dogs. The luminal surfaces of the superior vena cava, right atrium, right ventricle, and pulmonary artery could be observed in all dogs. The trabeculae of the left ventricle, contracting and relaxing synchronously with the cardiac beat, could also be observed in all dogs. However, observations of the tricuspid valve, aortic valve, papillary muscle, and chordae were successful in only some dogs. Postmortem examinations revealed no obvious endocardial or intimal damage. The results indicate the applicability and safety of angioscopy guided by a balloon catheter for observations of the luminal changes in the cardiac chambers and great vessels.

Angiographic and angioscopic observations of the arterial luminal changes induced by vasospasm

Angiography and angioscopy were used to examine arterial luminal changes induced by experimental vasospasm. The right common carotid artery of the dog was perfused with Krebs-Henseleit solution at a constant pressure, 3,4-diaminopyridine (DAP), a selective potassium channel blocker was applied on the adventitia, and the luminal changes were observed with angiography and angioscopy. Angiographically vasospasm (defined as a reduction in the internal diameter to less than 50% of the control value) was always induced by the topical application of 5 X 10(-1) mol/L DAP. The internal diameter decreased to 25% +/- 7% (mean +/- standard error, n = 6) 15 minutes after the application. The vasospasms propagated 2.7 +/- 0.6 and 1.1 +/- 0.3 cm downstream and upstream, respectively. Angioscopy showed that the lumen narrowed gradually and concentrically. Perfusion of the artery during vasospasm for 15 minutes with a backflow of blood from the contralateral artery resulted in thrombosis at the spastic segment. The results indicate that carotid vasospasm can be constantly induced by DAP, thrombosis occurs in the spastic artery, and angioscopy is useful for serial observation of the luminal changes induced by vasospasm.

The thrombolytic effects of native tissue-type plasminogen activator (AK-124) on experimental canine coronary thrombosis

To evaluate the thrombolytic effects of the native tissue-type plasminogen activator (t-PA), the authors used a thrombus model simulating clinical situa tions. The native t-PA (AK-124) was obtained from human-derived normal cells. Experimental canine coronary thrombosis was produced by partial con striction and endothelial denudation of the vessel. In 19 dogs, coronary occlu sive thrombus was produced. Three hours after total occlusion of the coronary artery with thrombus, the authors attempted the thrombolytic therapy in 16 dogs. Histologically, three-hour thrombus was composed of a mixture of platelet aggregates, fibrin, and blood cells. They infused 0.375 mg/kg t-PA intraven ously in 7 dogs and 20,000 IU/kg urokinase (UK) in 9. Coronary recanalization was achieved in 5 (71%) with t-PA infusion and 6 (67%) with UK infusion. Plasma fibrinogen levels decreased to 76% of preinfusion value in the dogs with t-PA infusion and to 34% in those with UK infusion. Coronary reocclusion oc curred in 2 dogs with t-PA and 3 with UK. Thus, the native t-PA (AK-124) can provide coronary thrombolysis without severe depletion of plasma fibrinogen levels.