- Email: [email protected]
Fiberoptic study on the effects of transluminal angioplasty in experimental occlusive arterial thrombosis
Ferreira
et al.
American
31. Llesuy SF, Milei J, Molina H: Boveris A, Milei S. Comparison of lipid peroxidation and myocardial damage induced by adriamycin and 4’-epiadriamycin in mice. Tumori 1985; 71:241. 32. Bernier M, Hearse DJ, Manning AS. Reperfusion-induced
February 1988 Heart Journal
arrhythmias and oxygen derived free radicals. Studies with “anti-free radical” interventions and a free radical-generating system in the isolated perfused rat heart. Circ Res 19%; 58:331.
Fiberoptic study on the effects of transluminal angioplasty in experimental occlusive arterial thrombosis Percutaneous transluminal coronary angioplasty has been proposed as definitive therapy for coronary recanalization of occluded coronary arteries in patients with acute myocardial infarction (AMI). The effects of transluminal angioplasty (TA) on experimental occlusive canine arterial thrombi that closely simulated the clinical condition was examined by a fiberoptic method. Experimental arterial thrombosis was produced by endothelial denudation and induction of iuminal stenosis. Eighteen dogs that showed total occlusion of the iliac artery with thrombi were evaluated. Seven dogs (group A) with 6hour-old thrombi received 20,000 IU/kg intravenous urokinase (UK) but did not show recanalization. TA was performed with a Gruentzig or Simpson-Robert balloon catheter and its effect was evaluated by a vascular fibroscope. Eight dogs (group B) with 6-hour-old thrombi underwent primary TA. After TA, less than 50% luminal obstruction with residual thrombi was visualized in five dogs (71%) of group A and four dogs (50%) of group B. Residual thrombi showed a doughnut-like or globular type shape and consisted of dense fibrin networks and compact platelet aggregates. All dogs in group B received 20,000 IU/kg intravenous UK after TA, but most of them showed progression of thrombus size despite UK infusion. In conclusion, the results suggest (1) that TA is effective in recanalization of an occluded artery with aged thrombus that is resistant to thrombolytic therapy and (2) that vascular fiberscope is a useful method for evaluation of the effects of TA on occlusive arterial thrombus. (AM HEART J 1988;115:312.)
Takanobu Tomaru, Yasumi Uchida, and Tsuneaki Sugimoto. Tokyo, Japan
Percutaneous transluminal coronary recanalization (PTCR) has been widely used to dissolve the coronary thrombi and restore coronary flow in patients with acute myocardial infarction (AMI).1-8 However, in most cases, significant coronary stenosis remains after the treatment. To open persisting high-grade atherosclerotic stenosis in AM1 patients, percutaneous transluminal coronary angioplasty (PTCA) has been used after thrombolytic therapy.vp10 PTCA has also been recommended as initial therapy for coronary recanalization of coronary arteries occluded From Tokyo. Received Reprint Medicine,
312
the
Second for publication
Department May
of 26, 1987;
requests: Takanobu Tomaru, University of Tokyo, 7-3-l
Internal
Medicine,
accepted M.D., Hongo,
Aug.
University 21, 1987.
2nd Department of Internal Bunkyo-ku, Tokyo, Japan.
of
with atherosclerosis and thrombi.g-‘l Compared with PTCR with urokinase (UK) or streptokinase (SK), which often results in a tendency to bleeding, primary PTCA is often beneficial because it can restore coronary flow without the use of thromboiytic agents. Recently, the vascular fiberscope (angioscope) has been used for direct visualization of the coronary or peripheral arteries in clinical or experimental conditions,12-l5and it is considered a useful method for direct visualization of arterial recanalization. In this study, we report an initial experience with direct fiberoptic visualization of transluminal angioplasty (TA) of experimental occlusive canine arterial thrombi that closely simulated the clinical condition.
Volume Number
115 2
Angioscopy
of PTCA
in arterial
thrombosis
313
reservoir
Fig.
1. Schematic representation of the instruments in this study. S = Sigma motor pump.
METHODS
Twenty-one mongrel dogs of either sex, each weighing from 7.5 to 14 kg, were anesthetized with sodium pentobarbital (35 to 40 mg/kg). After medial incision of the abdomen, the abdominal and common iliac arteries on both sides were dissected from surrounding tissue. The abdominal aorta was clamped distal to the renal arteries and both femoral arteries were ligated. After all peripheral branchesbetweeniliac arteries and aorta were ligated, No. 9 French catheter sheaths were inserted in a retrograde fashion into both external iliac arteries. Both catheter sheaths were connected to a perfusion system and were perfused at a constant flow rate (25 ml/min) by a Sigma motor pump (Sigma, Inc., Medina, N.U.). A thin vascular fiberscope (outer diameter 1.8 mm, Olympus Co. Ltd, Hamburg, W. Germany) wasinserted from the left sheath, and the lumen of the left common iliac artery was photographed on color film or 16 mm tine film (25 frames/set). Formation of arterial thrombosis. After photography of the internal surface of the artery, a balloon-tipped pulmonary artery catheter (No. 7 French) was inserted into the proximal portion of the left common iliac artery, the balloon of the catheter was inflated with air, and it was pulled back for about 1 cm. The endothelium of the artery was denudated by this procedure and luminal stenosisup to about 50% of the initial luminal area in percent cross-sectionalarea was induced with thread. An electromagnetic flowmeter was placed more proximally to the narrowed segment to monitor iliac arterial flow. Then blood was perfused into the common iliac arteries. The
arterial lumen was visualized 30 minutes after induction of luminal stenosis.During the fiberoptic visualization, the blood was replaced with 37” C oxygenated KrebsHenseleit solution. Photos thus obtained were used for calculation of the percent luminal obstruction with thrombi asfollows. The stenotic segmentbefore blood perfusion (A) was calculated, and after thrombus was formed, the area not occupied by the thrombi (B) wasalso calculated. A-B/A x 100 was called the percent luminal obstruction. Marked decrease of iliac flow was regarded as total obstruction (lessthan 10% of the initial flow). When the arterial lumen was totally obstructed, the thrombus was visualized by the vascular fiberscope during infusion of oxygenated Krebs-Henseleit solution from the left sheath. Thrombolysis and transluminal angioplasty. Three dogsdid not show total occlusion of the iliac artery with thrombi. The remaining 18 dogsshowedtotal occlusionof the iliac artery with thrombi within 5 hours after induction of stenosis,and three dogsdied within 6 hours after total occlusion of the iliac artery. Therefore, 15 dogswith total occlusionof the iliac artery with 6-hour-old thrombi were evaluated. In these 15 dogs, total occlusion of the iliac artery with thrombi remained for 6 hours after formation of total occlusion. These dogs were separated into two groups. In group A, seven dogs with 6-hour-old thrombus received an intravenous infusion of 20,000 IU/kg UK for 30 minutes following a bolus infusion of 100 U/kg of heparin. If recanalization was not obtained within 30 minutes after initiation of UK infusion, TA, with the use of a 3 mm diameter Simpson-Robert or Gruentzig
February
314
Tomaru,
Plchida, and Sugimoto
American
Heart
1988 Journal
Table I. Luminal changesafter transluminal angioplasty (number of preparations) Percent luminal obstruction with thrombi
Group
A (n = 7)
o-25 25-50 50-75 75-99
Group
B (n = 7)
5 1
4 3
1
100 n = number
Table
of examined
preparations.
II. Luminal changesafter transluminal Time
Percent luminal obstruction with thrombi
0 (control) (n = 7)
O-25 25-50 50-75 75-99 100 2. Fiberoptic observation of effects of TA on occlusive arterial thrombus. Left upper half, After endothelial Fig.
denudation and induction of luminal stenosis,white bellow-like appearance of endothelial lumen is visualized. Right upper half, Six hours after formation of occlusive thrombus, total occlusion of the stenosedsegment with reddish thrombus is visualized from its tail. Left lower half, Tip of Gruentzig balloon catheter is penetrating the thrombus. Right lower half, After TA, artery is recanalized and doughnut-like shaped residual thrombus remains.
balloon catheter for PTCA, was performed. As shown in Fig. 1, a guidewire waspushedinto the occlusivethrombus through a guiding catheter from the right sheath. The balloon catheter wasthen advancedto the occlusiveregion and the balloon was inflated three to four times with 6 atmospheresof pressure to compressthe thrombus and open the obstructed lesion. After the final inflation, the vascular lumen was visualized and photographed. Then the artery wasreperfused with blood. The vascular lumen was visualized 30 minutes, 1 hour, and 3 hours after the reperfusion. In another group of eight dogs (group B), primary TA was performed following a bolus intravenous infusion of 100 U/kg of heparin. Then the luminal changes of the occlusive lesion were visualized and photographed. Then 20,000 IV/kg of UK were infused intravenously for 30 minutes. The vascular lumen wasvisualized 30 minutes, 1 hour, and 3 hours after the blood reperfusion. After the final observation, the left common iliac artery was removed, immediately fixed with 10% formalin, and
UK = urokinase;
after
initiation
of UK infusion
30 min (n = 7)
1 hr (n = 7)
3 hrs (n = 5)
1 3 3
2 3
4 3
n = number
angiopiasty
of examined
2 4 1 preparations.
stained with hematoxylin and eosin,Azan, or PTAH stain. The fibrin network was assessed with PTAII stain. RESULTS
Fifteen dogs were evaluated TA study.
for thrombolysis
and
Thrombus formation and effects of UK. Recanalization was not observed in the totally occluded iliac artery in any of the seven dogs of group A, which received 20,000 IUkg of intravenous UK infusion. Thus none of the 6-hour-old thrombi responded to thrombolytic therapy. Transluminal angiopiasty. TA was performed in all seven dogs of group A and in all eight dogs of group B. Figs. 2 and 3 show the fiberoptic observation of TA of occlusive thrombi. During balloon inflation, the stenosed lesion was completely occupied by the balloon and the thrombi were cornpressed to the vessel wall. As Table I shows, less than 50% luminal obstruction with thrombi were observed in five (71%) of the seven dogs in group A and in four (50%) of the eight dogs in group B after TA. More than 75% luminal obstruction with thrombi remained in one dog in group A. Residual thrombi showed doughnut or eccentric globular type shapes (Figs. 2 and 3). Thrombi were reddish and were
often mixed with a white fibrin network.
Volume
115
Number
2
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of PTCA
in arterial
thrombosis
315
Fig. 3. Fiberoptic observation of TA. Left, Tip of Gruentzig balloon catheter is penetrating the thrombus along the vesselwall. Right, After angioplasty, eccentric globular residual thrombus remains. Fig. 4. Effects of UK on the residual thrombus. Left, After transluminal angioplasty, residual reddish thrombus is visualized. Right, Thirty minutes after UK infusion, the residual thrombus is not reduced in size.
Thrombolytic effects of UK on the residual thrombi after TA. In eight dogs of group B, 20,000 IU/kg of
decrease in residual luminal bus after UK infusion.
UK were administered intravenously after visualization of the residual thrombi after TA. One dog died within 1 hour after recanalization and those data were excluded from the study. As Table II shows, four dogs showed 50% to 75% luminal obstruction, two dogs showed 25% to 50% obstruction, and one dog showed 75% to 99% luminal obstruction 30 minutes after UK infusion (Fig. 4). One hour after UK infusion, six dogs showed more than 75% luminal obstruction and three dogs showed total occlusion. Three hours after UK infusion, three dogs showed total occlusion. There was only one dog that showed transient
Histopathology of vessel and thrombi after TA. The residual thrombi consisted of dense fibrin networks and abundant platelet aggregates incorporating few blood cells (Fig. 5). Disruption of elastic fibers was observed in the vessel wall. However, complete rupture of the media or dissecting aneurysm did not occur.
obstruction
with throm-
DISCUSSION
Thrombolytic therapy is used as a means of achieving early coronary reperfusion in AM1 patients,l-@ but it has been reported to be ineffective in a majority of patients with AM1 more than 6
316
Tomaru,
”
“,.. ‘. ;‘ .i
,, :,
Uchida,
and Sugimoto
.,
“.:.,
5. Photomicrograph of residual thrombus consists of compact amorphousmaterial (aggregatedplatelets) and densefibrin networks incorporating few blood cells. (Azan stain; original magnification X20.) Fig.
hours after the onset of symptoms, suggesting
that the aged thrombi may be resistant to thrombolytic therapy. On the other hand, residual high-grade stenosis, which is often observed after PTCR, was considered a major cause of coronary reocc1usion.4-7 PTCA has been used to open the residual stenosis or to recanalize a coronary artery occluded with thrombi as the initial therapy of AMI.‘-I1 Pepine et al.l” reported that the material comprising the occlusion seemed to be soft and was easily dilated. Coronary thrombosis occurs frequently superimposing on the atheromatous stenotic coronary regions.16 PTCA can theoretically recanalize the occluded coronary artery by penetration of the guidewire, followed by luminal dilatation with inflation of the balloon catheter in those patients in whom PTCR has failed. Thus PTCA is effective, not only in reducing the size of the occlusive thrombi,
Amaricsn
February ?988 Heart .tournsi
but also in dilatation of the residual coronary lumen. Angiographic techniques have been used to evaluate the effects of PTCA, but they could not differentiate between thrombus and atheromatous plaques. The vascular fiberscope (angioscope) can theoretically provide visualization of the vascular lumen12-15 and it can also differentiate occlusion with thrombi from occlusion from other causes, i.e., spasm or atherosclerotic plaques. There have been no reports on fiberoptic observations of the effects of TA upon occlusive arterial thrombi. To evaluate these effects, it is necessary to produce experimental occlusive arterial thrombus that simulates a clinical condition and is different from artificial thrombi produced by a copper coiP7 or by other techniques.18-21 In this study, we produced experimental arterial thrombi by endothelial denudation and induction of luminal stenosis, which closely simulates the clinical condition, and evaluated the effects of TA on the experimental aged thrombi with a vascular fiberscope. Fiberoptic examination revealed that none of the totally occluded vessels with 6-hour-old thrombi responded to thrombolytic therapy with UK, but were recanalized by TA. Percent Iuminal obstruction with residual thrombi at the site of the occlusion ranged from 25 % to $0 % in cross-sectional area of the control sample. Thus, recanalization was successful in all preparations, but doughnut-like or eccentric globular-shaped residual thrombi remained after angioplasty. Thrombolytic therapy following angioplasty was performed in eight dogs that underwent primary TA of the artery occluded with thrombi. However, intravenous infusion of 20,000 IV/kg of UK failed to reduce the thrombus size in the majority of preparations. Residual thrombi consisted of dense fibrin networks and compact platelet aggregates with relatively few blood cells, and they seemed to be resistant to thrombolytic therapy, In clinical cases, residual stenosis is reported to range from 0% to 50% after PTCA of coronary thrombosis.g-l* Although there is a difference in the evaluation of luminal stenosis between angiographic (dimension of luminal diameter) and fiberoptic (dimension of cross-sectional area) methods, the degree of residual stenosis was higher in our study. In clinical cases of AMI, coronary thrombi are formed on the segment stenosed with atherosclerosis and occlusive lesions consist of both atheroma and coronary recanalization is thrombi. Therefore, obtained by penetration and dilatation of the occlusive thrombi followed by dilatation of the atheromatous stenotic lesion. Thus, dilatation of the coronary
Volume
115
Number
2
Angioscopy
arterial lumen is mainly attributable to compression of the atheromatous lesion. This may explain the difference in the degree of residual luminal obstruction between our study and clinical reports. The following conclusions seem warranted. (1) Transluminal angioplasty was effective in recanalization of the artery occluded with aged thrombi that were resistant to thrombolytic therapy. (2) The vascular fiberscope is a useful method for evaluation of TA of the occlusive thrombi. (3) Aged thrombi that were resistant to thrombolytic therapy consisted mainly of dense fibrin networks and compact platelet aggregates. (4) Residual thrombi usually remained after TA, causing residual luminal obstruction. REFERENCES
1. Rentrop P, Blanke H, Kaiser H, Leitz K. Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris. Circulation 1981;63:307. 2. Mathey DG, Kuck KH, Tilsner V, Krebber HJ, Bleifeld W. Nonsurgical coronary artery recanalization in acute transmuml myocardial infarction. Circulation 1981;63:489. 3. Ganz W. Geft I. Maddahi J. Bermann D. Charuzi Y. Shah PK, Swan HJC. ‘Nonsurgical reperfusion in evolving myocardial infarction. J Am Co11 Cardiol 1983;1:1247. 4. Harrison DG, Ferguson DW, Collins SM, Skorton DJ, Ericksen EE, Kiocchos JM, Marcus ML, White CW. Rethrombosis after reperfusion with streptokinase: importance of geometry of residual lesions. Circulation 1984;69:991. 5. Schrijder R. Vohrineer H. Linderer T. Biamino G. Brueeeman T, Leitner ERV. Follow-up after coronary artery reperfusion with intravenous streptokinase in relation to residual myocardial infarct artery narrowings. Am J Cardiol 1985;53:313. 6. Gash AK, Spann JF, Sherry S, Belber AD, Carabello BA, McDonough MT, Mann RH, McCann WD, Gault JH, Gentzler RD, Kent RL. Factors influencing reocclusion after coronary thrombolysis for acute myocardial infarction. Am J Cardiol 1986;57:175. 7. Kaplan K, Darison R, Parker M, Mayberg B, Feiereisel P, Salinger M. Role of heparin after intravenous thrombolysis therapy for acute myocardial infarction. Am J Cardiol 1987;59:241. 8. Murakami T, Kanbara H, Kadota K, Tamaki S, Nakamura Y, Koshimoto C, Nohara R, Hattori R, Takatsu Y, Kawai C. -
,
,
“V
of PTCA in arterial thrombosis
3 17
Effects of intracoronary thrombolysis on infarct size and left ventricular function in patients with anterior myocardial infarction: enzymic, electrocardiographic, radionuclide and hemodynamic evaluations. Jpn Circ J 1985;49:605. 9. Hertzler GO, Rutherfold BD, McConabay DR, Johnson W. Percutaneous transluminal coronary angioplasty with and without thrombolytic therapy for treatment of acute myocardial infarction. AM HEARTJ 1983;106:965. 10. Pepine CJ, Prida X, Hill JA, Feldman RL, Conti CR. Percutaneous transluminal coronary angioplasty in acute myocardial infarction. AM HEART J 1984;107:820. 11. O’Neill WW, Timmis GC, Bourdillon PD, Lai P, Ganghadarhan V, Walton JA Jr, Ramos RG, Laufer N, Gordon S, Schork MA, Pitt B. A prospective randomized clinical trial of intracoronary streptokinase versus coronary angioplasty therapy of acute mvocardial infarction. N Enel J Med 1986;3i4:812. 12. Lee G, Ikeda RM, Stobbe D, Ogata C, Thers J, Hussein H, Mason DT. Laser irradiation of human atherosclerotic obstructive disease: simultaneous visualization and vaporization achieved by a dual fiberoptic catheter. AM HEARTJ 1983;105:167. 13. Spears JR, Spokojuny AM, Marais J. Coronary angioscopy during cardiac catheterization. J Am Co11 Cardiol 1985;6:93. 14. Uchida Y, Masuo M, Tomaru T, Kato A. Fiberoptic observation of coronary luminal changes caused by transluminal coronary angioplasty. Circulation 1985;72(Suppl):III-218. 15. Sherman CT, Litvack F, Grundfest W, Lee MR, Hickey A, Chaux A, Kass R, Blanche C, Matloff J, Morgenstern L, Ganz W, Swan HJC, Forrester J. Coronary angioscopy in patients with unstable angina pectoris. N Engl J Med 1986;315:913. 16. Horie T, Sekiguchi M, Hirosawa K. Coronary thrombosis in pathogenesis of acute myocardial infarction: histopathological study of coronary arteries in 108 necropsied cases using serial sections. Br Heart J 1978;40:153. 17. Kordenat RK, Kezdi P, Stanley EL. A new catheter technique for producing experimental coronary thrombosis and selective coronary visualization. AM HEART J 1972;83:360. 18. Lough J, Moore S. Endothelial injury induced by thrombin or thrombi. Lab Invest 1975;33:130. 19. Shishido M, Katori M. A quantative method using continuous recording of platelet thrombus size in hamster cheek pouch. Microvasc Res 1981;22:179. 20. Ashida S, Ishihara M, Ogata H, Abiko Y. Protective effect of ticlopidine on experimentally induced peripheral arterial occlusive disease in rats. Thromb Res 1980;18:35. 21. Gertz SD, Uretsky G, Worjinberg RS, Navat N, Gotsman MS. Endothelial cell damage and thrombus formation after partial arterial constriction: relevant to the role of coronary artery spasm in the pathogenesis of myocardial infarction. Circulation 1981;63:476.
et al.
American
31. Llesuy SF, Milei J, Molina H: Boveris A, Milei S. Comparison of lipid peroxidation and myocardial damage induced by adriamycin and 4’-epiadriamycin in mice. Tumori 1985; 71:241. 32. Bernier M, Hearse DJ, Manning AS. Reperfusion-induced
February 1988 Heart Journal
arrhythmias and oxygen derived free radicals. Studies with “anti-free radical” interventions and a free radical-generating system in the isolated perfused rat heart. Circ Res 19%; 58:331.
Fiberoptic study on the effects of transluminal angioplasty in experimental occlusive arterial thrombosis Percutaneous transluminal coronary angioplasty has been proposed as definitive therapy for coronary recanalization of occluded coronary arteries in patients with acute myocardial infarction (AMI). The effects of transluminal angioplasty (TA) on experimental occlusive canine arterial thrombi that closely simulated the clinical condition was examined by a fiberoptic method. Experimental arterial thrombosis was produced by endothelial denudation and induction of iuminal stenosis. Eighteen dogs that showed total occlusion of the iliac artery with thrombi were evaluated. Seven dogs (group A) with 6hour-old thrombi received 20,000 IU/kg intravenous urokinase (UK) but did not show recanalization. TA was performed with a Gruentzig or Simpson-Robert balloon catheter and its effect was evaluated by a vascular fibroscope. Eight dogs (group B) with 6-hour-old thrombi underwent primary TA. After TA, less than 50% luminal obstruction with residual thrombi was visualized in five dogs (71%) of group A and four dogs (50%) of group B. Residual thrombi showed a doughnut-like or globular type shape and consisted of dense fibrin networks and compact platelet aggregates. All dogs in group B received 20,000 IU/kg intravenous UK after TA, but most of them showed progression of thrombus size despite UK infusion. In conclusion, the results suggest (1) that TA is effective in recanalization of an occluded artery with aged thrombus that is resistant to thrombolytic therapy and (2) that vascular fiberscope is a useful method for evaluation of the effects of TA on occlusive arterial thrombus. (AM HEART J 1988;115:312.)
Takanobu Tomaru, Yasumi Uchida, and Tsuneaki Sugimoto. Tokyo, Japan
Percutaneous transluminal coronary recanalization (PTCR) has been widely used to dissolve the coronary thrombi and restore coronary flow in patients with acute myocardial infarction (AMI).1-8 However, in most cases, significant coronary stenosis remains after the treatment. To open persisting high-grade atherosclerotic stenosis in AM1 patients, percutaneous transluminal coronary angioplasty (PTCA) has been used after thrombolytic therapy.vp10 PTCA has also been recommended as initial therapy for coronary recanalization of coronary arteries occluded From Tokyo. Received Reprint Medicine,
312
the
Second for publication
Department May
of 26, 1987;
requests: Takanobu Tomaru, University of Tokyo, 7-3-l
Internal
Medicine,
accepted M.D., Hongo,
Aug.
University 21, 1987.
2nd Department of Internal Bunkyo-ku, Tokyo, Japan.
of
with atherosclerosis and thrombi.g-‘l Compared with PTCR with urokinase (UK) or streptokinase (SK), which often results in a tendency to bleeding, primary PTCA is often beneficial because it can restore coronary flow without the use of thromboiytic agents. Recently, the vascular fiberscope (angioscope) has been used for direct visualization of the coronary or peripheral arteries in clinical or experimental conditions,12-l5and it is considered a useful method for direct visualization of arterial recanalization. In this study, we report an initial experience with direct fiberoptic visualization of transluminal angioplasty (TA) of experimental occlusive canine arterial thrombi that closely simulated the clinical condition.
Volume Number
115 2
Angioscopy
of PTCA
in arterial
thrombosis
313
reservoir
Fig.
1. Schematic representation of the instruments in this study. S = Sigma motor pump.
METHODS
Twenty-one mongrel dogs of either sex, each weighing from 7.5 to 14 kg, were anesthetized with sodium pentobarbital (35 to 40 mg/kg). After medial incision of the abdomen, the abdominal and common iliac arteries on both sides were dissected from surrounding tissue. The abdominal aorta was clamped distal to the renal arteries and both femoral arteries were ligated. After all peripheral branchesbetweeniliac arteries and aorta were ligated, No. 9 French catheter sheaths were inserted in a retrograde fashion into both external iliac arteries. Both catheter sheaths were connected to a perfusion system and were perfused at a constant flow rate (25 ml/min) by a Sigma motor pump (Sigma, Inc., Medina, N.U.). A thin vascular fiberscope (outer diameter 1.8 mm, Olympus Co. Ltd, Hamburg, W. Germany) wasinserted from the left sheath, and the lumen of the left common iliac artery was photographed on color film or 16 mm tine film (25 frames/set). Formation of arterial thrombosis. After photography of the internal surface of the artery, a balloon-tipped pulmonary artery catheter (No. 7 French) was inserted into the proximal portion of the left common iliac artery, the balloon of the catheter was inflated with air, and it was pulled back for about 1 cm. The endothelium of the artery was denudated by this procedure and luminal stenosisup to about 50% of the initial luminal area in percent cross-sectionalarea was induced with thread. An electromagnetic flowmeter was placed more proximally to the narrowed segment to monitor iliac arterial flow. Then blood was perfused into the common iliac arteries. The
arterial lumen was visualized 30 minutes after induction of luminal stenosis.During the fiberoptic visualization, the blood was replaced with 37” C oxygenated KrebsHenseleit solution. Photos thus obtained were used for calculation of the percent luminal obstruction with thrombi asfollows. The stenotic segmentbefore blood perfusion (A) was calculated, and after thrombus was formed, the area not occupied by the thrombi (B) wasalso calculated. A-B/A x 100 was called the percent luminal obstruction. Marked decrease of iliac flow was regarded as total obstruction (lessthan 10% of the initial flow). When the arterial lumen was totally obstructed, the thrombus was visualized by the vascular fiberscope during infusion of oxygenated Krebs-Henseleit solution from the left sheath. Thrombolysis and transluminal angioplasty. Three dogsdid not show total occlusion of the iliac artery with thrombi. The remaining 18 dogsshowedtotal occlusionof the iliac artery with thrombi within 5 hours after induction of stenosis,and three dogsdied within 6 hours after total occlusion of the iliac artery. Therefore, 15 dogswith total occlusionof the iliac artery with 6-hour-old thrombi were evaluated. In these 15 dogs, total occlusion of the iliac artery with thrombi remained for 6 hours after formation of total occlusion. These dogs were separated into two groups. In group A, seven dogs with 6-hour-old thrombus received an intravenous infusion of 20,000 IU/kg UK for 30 minutes following a bolus infusion of 100 U/kg of heparin. If recanalization was not obtained within 30 minutes after initiation of UK infusion, TA, with the use of a 3 mm diameter Simpson-Robert or Gruentzig
February
314
Tomaru,
Plchida, and Sugimoto
American
Heart
1988 Journal
Table I. Luminal changesafter transluminal angioplasty (number of preparations) Percent luminal obstruction with thrombi
Group
A (n = 7)
o-25 25-50 50-75 75-99
Group
B (n = 7)
5 1
4 3
1
100 n = number
Table
of examined
preparations.
II. Luminal changesafter transluminal Time
Percent luminal obstruction with thrombi
0 (control) (n = 7)
O-25 25-50 50-75 75-99 100 2. Fiberoptic observation of effects of TA on occlusive arterial thrombus. Left upper half, After endothelial Fig.
denudation and induction of luminal stenosis,white bellow-like appearance of endothelial lumen is visualized. Right upper half, Six hours after formation of occlusive thrombus, total occlusion of the stenosedsegment with reddish thrombus is visualized from its tail. Left lower half, Tip of Gruentzig balloon catheter is penetrating the thrombus. Right lower half, After TA, artery is recanalized and doughnut-like shaped residual thrombus remains.
balloon catheter for PTCA, was performed. As shown in Fig. 1, a guidewire waspushedinto the occlusivethrombus through a guiding catheter from the right sheath. The balloon catheter wasthen advancedto the occlusiveregion and the balloon was inflated three to four times with 6 atmospheresof pressure to compressthe thrombus and open the obstructed lesion. After the final inflation, the vascular lumen was visualized and photographed. Then the artery wasreperfused with blood. The vascular lumen was visualized 30 minutes, 1 hour, and 3 hours after the reperfusion. In another group of eight dogs (group B), primary TA was performed following a bolus intravenous infusion of 100 U/kg of heparin. Then the luminal changes of the occlusive lesion were visualized and photographed. Then 20,000 IV/kg of UK were infused intravenously for 30 minutes. The vascular lumen wasvisualized 30 minutes, 1 hour, and 3 hours after the blood reperfusion. After the final observation, the left common iliac artery was removed, immediately fixed with 10% formalin, and
UK = urokinase;
after
initiation
of UK infusion
30 min (n = 7)
1 hr (n = 7)
3 hrs (n = 5)
1 3 3
2 3
4 3
n = number
angiopiasty
of examined
2 4 1 preparations.
stained with hematoxylin and eosin,Azan, or PTAH stain. The fibrin network was assessed with PTAII stain. RESULTS
Fifteen dogs were evaluated TA study.
for thrombolysis
and
Thrombus formation and effects of UK. Recanalization was not observed in the totally occluded iliac artery in any of the seven dogs of group A, which received 20,000 IUkg of intravenous UK infusion. Thus none of the 6-hour-old thrombi responded to thrombolytic therapy. Transluminal angiopiasty. TA was performed in all seven dogs of group A and in all eight dogs of group B. Figs. 2 and 3 show the fiberoptic observation of TA of occlusive thrombi. During balloon inflation, the stenosed lesion was completely occupied by the balloon and the thrombi were cornpressed to the vessel wall. As Table I shows, less than 50% luminal obstruction with thrombi were observed in five (71%) of the seven dogs in group A and in four (50%) of the eight dogs in group B after TA. More than 75% luminal obstruction with thrombi remained in one dog in group A. Residual thrombi showed doughnut or eccentric globular type shapes (Figs. 2 and 3). Thrombi were reddish and were
often mixed with a white fibrin network.
Volume
115
Number
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Angioscopy
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in arterial
thrombosis
315
Fig. 3. Fiberoptic observation of TA. Left, Tip of Gruentzig balloon catheter is penetrating the thrombus along the vesselwall. Right, After angioplasty, eccentric globular residual thrombus remains. Fig. 4. Effects of UK on the residual thrombus. Left, After transluminal angioplasty, residual reddish thrombus is visualized. Right, Thirty minutes after UK infusion, the residual thrombus is not reduced in size.
Thrombolytic effects of UK on the residual thrombi after TA. In eight dogs of group B, 20,000 IU/kg of
decrease in residual luminal bus after UK infusion.
UK were administered intravenously after visualization of the residual thrombi after TA. One dog died within 1 hour after recanalization and those data were excluded from the study. As Table II shows, four dogs showed 50% to 75% luminal obstruction, two dogs showed 25% to 50% obstruction, and one dog showed 75% to 99% luminal obstruction 30 minutes after UK infusion (Fig. 4). One hour after UK infusion, six dogs showed more than 75% luminal obstruction and three dogs showed total occlusion. Three hours after UK infusion, three dogs showed total occlusion. There was only one dog that showed transient
Histopathology of vessel and thrombi after TA. The residual thrombi consisted of dense fibrin networks and abundant platelet aggregates incorporating few blood cells (Fig. 5). Disruption of elastic fibers was observed in the vessel wall. However, complete rupture of the media or dissecting aneurysm did not occur.
obstruction
with throm-
DISCUSSION
Thrombolytic therapy is used as a means of achieving early coronary reperfusion in AM1 patients,l-@ but it has been reported to be ineffective in a majority of patients with AM1 more than 6
316
Tomaru,
”
“,.. ‘. ;‘ .i
,, :,
Uchida,
and Sugimoto
.,
“.:.,
5. Photomicrograph of residual thrombus consists of compact amorphousmaterial (aggregatedplatelets) and densefibrin networks incorporating few blood cells. (Azan stain; original magnification X20.) Fig.
hours after the onset of symptoms, suggesting
that the aged thrombi may be resistant to thrombolytic therapy. On the other hand, residual high-grade stenosis, which is often observed after PTCR, was considered a major cause of coronary reocc1usion.4-7 PTCA has been used to open the residual stenosis or to recanalize a coronary artery occluded with thrombi as the initial therapy of AMI.‘-I1 Pepine et al.l” reported that the material comprising the occlusion seemed to be soft and was easily dilated. Coronary thrombosis occurs frequently superimposing on the atheromatous stenotic coronary regions.16 PTCA can theoretically recanalize the occluded coronary artery by penetration of the guidewire, followed by luminal dilatation with inflation of the balloon catheter in those patients in whom PTCR has failed. Thus PTCA is effective, not only in reducing the size of the occlusive thrombi,
Amaricsn
February ?988 Heart .tournsi
but also in dilatation of the residual coronary lumen. Angiographic techniques have been used to evaluate the effects of PTCA, but they could not differentiate between thrombus and atheromatous plaques. The vascular fiberscope (angioscope) can theoretically provide visualization of the vascular lumen12-15 and it can also differentiate occlusion with thrombi from occlusion from other causes, i.e., spasm or atherosclerotic plaques. There have been no reports on fiberoptic observations of the effects of TA upon occlusive arterial thrombi. To evaluate these effects, it is necessary to produce experimental occlusive arterial thrombus that simulates a clinical condition and is different from artificial thrombi produced by a copper coiP7 or by other techniques.18-21 In this study, we produced experimental arterial thrombi by endothelial denudation and induction of luminal stenosis, which closely simulates the clinical condition, and evaluated the effects of TA on the experimental aged thrombi with a vascular fiberscope. Fiberoptic examination revealed that none of the totally occluded vessels with 6-hour-old thrombi responded to thrombolytic therapy with UK, but were recanalized by TA. Percent Iuminal obstruction with residual thrombi at the site of the occlusion ranged from 25 % to $0 % in cross-sectional area of the control sample. Thus, recanalization was successful in all preparations, but doughnut-like or eccentric globular-shaped residual thrombi remained after angioplasty. Thrombolytic therapy following angioplasty was performed in eight dogs that underwent primary TA of the artery occluded with thrombi. However, intravenous infusion of 20,000 IV/kg of UK failed to reduce the thrombus size in the majority of preparations. Residual thrombi consisted of dense fibrin networks and compact platelet aggregates with relatively few blood cells, and they seemed to be resistant to thrombolytic therapy, In clinical cases, residual stenosis is reported to range from 0% to 50% after PTCA of coronary thrombosis.g-l* Although there is a difference in the evaluation of luminal stenosis between angiographic (dimension of luminal diameter) and fiberoptic (dimension of cross-sectional area) methods, the degree of residual stenosis was higher in our study. In clinical cases of AMI, coronary thrombi are formed on the segment stenosed with atherosclerosis and occlusive lesions consist of both atheroma and coronary recanalization is thrombi. Therefore, obtained by penetration and dilatation of the occlusive thrombi followed by dilatation of the atheromatous stenotic lesion. Thus, dilatation of the coronary
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Angioscopy
arterial lumen is mainly attributable to compression of the atheromatous lesion. This may explain the difference in the degree of residual luminal obstruction between our study and clinical reports. The following conclusions seem warranted. (1) Transluminal angioplasty was effective in recanalization of the artery occluded with aged thrombi that were resistant to thrombolytic therapy. (2) The vascular fiberscope is a useful method for evaluation of TA of the occlusive thrombi. (3) Aged thrombi that were resistant to thrombolytic therapy consisted mainly of dense fibrin networks and compact platelet aggregates. (4) Residual thrombi usually remained after TA, causing residual luminal obstruction. REFERENCES
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