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Mechanical Disruption of Pulmonary Emboli in Dogs with a Flexible Rotating-tip Catheter (Kensey Catheter)
laboratory and animal investigations Mechanical Disruption of Pulmonary Emboli in Dogs with a Flexible Rotating-tip Catheter (Kensey Catheter)* Paul D. Stein, M.D. , F.G.G .P.; Hani N. Sabbah , Ph.D. ; Michael A. Basha , D .Q ; John Popovich, [r. , M.D., F.G.C.P.; Kenneth R. Kensey, M.D. ; and John E. Nash , P.E.
Pulmonary embolism was induced in 11 dogs by the injection of three- to four-day-old allogeneic blood clots. The clots were made radiopaque by soaking them in contrast material. The resulting clots were firm, 3 to 4 cm long, and 1 cm in diameter. Injection of the clots into the external jugular vein consistently produced occlusion of at least one of the lobar pulmonary arteries. In every instance in which the tip of the catheter could be positioned at the
clot embolus (six dogs), the clots were readily fragmented with a number 8 French (2.67 mm OD) flexible rotating tip catheter (Kenseycatheter) activated at 80,000 rpm. Overall perfusion was shown by posttreatment angiograms to be markedly improved. These studies show that catheter-tip fragmentation of pulmonary emboli with a Kensey catheter has excellent potential for therapeutic application in patients with pulmonary embolism. (Chest 1990; 98:994-98)
Thromholytic agents are often of great benefit in patients with acute pulmonary embolism, but they have two important drawbacks: thrombolytic agents require seve ral hours to be effective, and all cause sigmficant bleeding.!" Low doses of intrapulmonary arterial streptokinase failed to eliminate the bleeding complications." The benefits of thrombolysis, therefore, are incomplete, and the risks are prominent in acute pulmonary embolism. Another extremely important problem with the application of thrombolytic agents to the treatment of pulmonary thromboembolism is that the very group of patients prone to suffer pulmonary embolism is the group in whom the risks of bleeding from thrombolytic agents is greatest. In the majority of patients with acute pulmonary embolism who could potentially benefit from thrombolytic therapy, the drug is contraindicated, because of recent surgery, fracture , trauma, or diseases that are associated with a bleeding diathesis." Clearly, therefore , there is a need for therapy that is both effective, immediate, and safe . The purpose of the present investigation was to explore the potential value of catheter-tip fragmentation of expe rime ntally induced clot emboli in dogs. This technique offers an entirely new potential approach to the treatment of patients whose condition is unstable because of massive acute pulmonary thromboembolism . The technique has two important poten-
tial advantages: (1) relief from the deleterious effects of pulmonary embolism are immediate; (2) the technique is potentially applicahle to a large number of patients in whom thrombolytic therapy is contraindicated .
*From the Henr y Ford Hosp ital. Detroit. /U'print requests: D r. Stein . Hl,"'11 Ford Hospital. 2699 West Grand. De/mit 48202
994
METHODS
Studies were performed in 11 anesthetized healthy mongrel dogs weighing between 20 and 30 kg. All studies were performed with
_.
1 2 mm
.
.
'~·~I
•
I
"
of
• .,-.
.... ~
.
<
FIGUllt: 1. Photographs of tip of the Kensey Aexihle rotat ing lip catheter. Mechanical Disruption of Pulmonary Emboli in Dogs (Stein
at a/)
FllalilE 2A. (Dog I). Plain films slwwinf.( radiopaque blood dot in left lower lohe (caudal lobe} pulmonary artery: T..Jt. hefon' fraf.(lllenlalion with Kensey catheter. Ri/!,ht .aft"r fraf.(mentation with Kensey catheter, the chest closed . Followinf.( anesthesia. dof.(s were intubated and respired with nMUII air usinf.( a Harvard respirator. A femoral vein was used to introduce an 1'\111 sid" hole cutheter in to the pulmonary artery for pulmonary arteriof.(raphy. The jugular vein Wits cannu lated with a 7 111m internal diameter bypass type cannula which was advanced to till' superior vena cava . Clots were introduced through this cannula. Selective right aud left pulmonary arteriograms were oht ained prior to embolization ;,nd were repeated 10 to 30 minutes afh'r embolization. Catheter-tip fraf.(mentatiou of till' embolus was then attempted . The pulmonary arteriograms were then repeated . Followinj; this . the dogs were killed and an autopsy of the lungs was performed .
Preparation of Clots Studk-s were performed with allof.(,-n ..ic blood dots prepared as follows: three days prior to tilt, study. 20 011 of venous hlcM>
each offour 7 011 vacutainers (10 nun internal diameter) ami allowed to dot. Ou tilt' St't'lIld or third day. tlu- dots were n-moved Irom the containers and wert' immersed in radiopnque contrast mall' rial (meglumim- and sodium diatrizoates, "YI>
Se-lective I"ft and right pulmonary arteriograms were p..rlorn ...d usinf.( a 1'\0. 7 Fr..nch NIH anf.(iof.(raphic catheter, Followinf.( a power injection of 30 ml of meghunine and sodium diutrizoate-s (Hypaque 76) at a rate of 20 mils. arteriograms were re-cord.. d on 3.'5 111m cim at 30 frames/so Cineanf.(iof.(raphy has been shown to ht' a useful
FI<:lIIlE 28. (Dog I). T..Jt. control pulmonary arterlogram showinf.( I,'ft lower lohe (left caudal lohe) pulmonary artery. Center, same vessel li,lIowinf.( dot embolus. A fillinf.( d"fed is not visihl» because till' dol was radiopaque . Rij!,ht . same vessel following fraf.(lIlt'ntation with K,'nSt'y catheter, CHEST I 98 I 4 I OCTOBER, 1990
995
FII;I'11E 3A. (Dog 2). Plain films showing radiopaqm- hl.HI
diagnostlc techniqm- in patients with pulmonary embolism." Plain cines of the radiopaque dot embolus 1lt'Ii,re and after catheter-tip fragnwntation were also obtained .
Mrchunica! Disruption IIf 1',,/1110111/11/ Emboli MedJanieal disruption of tilt' pulmonary emboli was attempted in all II dogs with a No. Ii French (2.67 mm diameter) Hexihle rotating tip catheter, Kensey catheters contain a torsional drive wire that revolves a distal instrumentation tip at speeds up to lOO.IlOO rpm . A continuous chaune is provided through till' catheter shaft lilr the supply of irrigation Auid thai exits adjacent 10 the revolving lu-ad . Wlu-n in operation. the irrigation fluid is directed laterally 10 the are-a of instrumentntion for cCl<,ling purposes. A DC electric motor and speed-up transmission assemhly are driven from a power
supply located in a console. The motor assembly includes a eouphng device for mating to the catheter. The console is powered from a remote medical grade isolation transformer. The console controls the speed of catheter-tip rotation and the flow rate of the irrigation Auid. The Kensey catheter is particularly advantageous for fragmentation of pulmonary emboli because of two characteristics. When operational. irrigation Auid exiting near the instrumentation tip forms a vortex which is effective in stopping large particles from passuu; downstream , Fragments of thrombi tend to he pulled into the vortex , Photographs of the tip of the catheter are shown in Figure 1. In the present study. once in contact with the embolus, the rotaling tip catheter was activated at 110,000 rpm and moved genlly hack and forth through the clot embolus under fluoroscopy The duration of activation of the catheter was 5 to 10 seconds.
Fl l a Jll E 3 1\. (Dog 2). I_ft . co ntro l pulmonar y ar t..riogram showing Ic·ft lowe r lobe (It·n caudal )olll') pulmonary artery. (;1'1111'1'. same ve-ssel li,lIowing clot embolus. A filling defect is not visihle because the clot was radiopaque . Ril{hl. same vessel following fragmentation with Kensey catheter.
996
Mechanical Disruption of Pulmonary Emboliin Dogs (Stein al al)
FIGURE 4A, (Dog 3). Plain films showinj; radiopaque hlood clot in left lower lobe (caudal lobe) pulmonary artery. l..eft, before Iragmentatton with Kensey catheter. Right. after Iragmentatton with Kensey catheter.
Autopsy of l.A"l/.(.~
At the conclusion of the study, the pulmonary arteries were carefully dissected and examined for damage that may have resulted from clot fra~mentation with the Kensey catheter, Residual clot embol i were recovered and measured . R":SULTS
Pulmonary clot emholi were readily delivered to the left and right pulmonary arteries. The clot emboli lodged in the left lower lobe (caudal lobe) arteries in several dogs. Because the catheter was most readily directed to the left lower lobe artery, and because this was a feasihility study, we assessed the capability of fragmentation of clot emboli only at that site . In six of 11 dogs, we were ahle to manipulate the
catheter to the site of the clot embolus, In these six dogs, the clots were readily fragmented. Perfusion at the site was improved following fragmentation (Fig 2 to 4). Clot fragments typically were 2 to 3 mm in diameter and 4 to 7 mm in length. Although these fragments occluded suhsegmental or smaller hranches, fragmentation of the clots relieved the proximal occlusion and permitted improved perfusion to the region . The catheter caused a tear in a pulmonary arterial branch in one dog when it was activated in an attempt to assist in manipulating it to an occluded branch . The clot had not been reached , and this was probably an improper use of the catheter. The angiograms showed
FIl :!JIIE 4B. (Dog 3). lejt, control pulmonary arteriogram showim; left lower lobe (left caudal lollt') pulmonary artery. Center, sam e vessel following clot e mbolus, A filling defect is not visibl« because the clot was rad iopaque . Right. same vessel following fragmentation with Kensey catheter.
CHEST I 98 I 4 I OCTOBER. 1990
997
no extravasation of contrast material at that site, although autopsy showed bleeding around the artery. In these preliminary studies, we employed No. 8 French transseptal catheter introducers as substitutes for guiding catheters (which were not available in the proper size). These sheaths have thin walls, and therefore, sharp edges at the tip. On two occasions, they produced nonpenetrating intimal tears. These sheaths will not be employed with future use of the Kensey catheter for catheter-tip fragmentation of thromboemboli. We observed no other complications. However, a slight extravasation of bloody fluid into the periarterial region typically occurs with the Kensey catheter as a result of the lateral jets of cooling fluid produced at the tip during activation. In the coronary arteries of dogs, when contrast material is used as the cooling fluid, the extravasation is visible for about three to ten minutes. In these unpublished chronic studies of the coronary arteries of dogs, this extravasation was no longer apparent after two weeks, and it produced no damaging effects. DISCUSSION
These preliminary studies indicate that mechanical fragmentation of pulmonary emboli is possible with a rotary tip catheter such as the Kensey catheter and that such treatment is associated with immediate improvement of the pulmonary arteriogram. Others, using a similar device, have shown that clot dissolution can be produced in vitro following 10 seconds of activation of the catheter at BO,OOO rpm. The largest residual clots shown in vitro were 208 ~.9 Larger clot fragments, however, occurred in our study in dogs. The fragments typically were 2 to 3 mm in diameter and 4 to 7 mm in length. A problem in our preliminary study was the inability to guide the rotating-tip catheter to the site of the embolus. We believe that this problem can be solved with the addition of wire mesh in the wall of the catheter, which will improve torque, and therefore,
998
ability to manipulate the tip. A curved tip will also be useful for manipulation to the appropriate site. The possibility of tears of the intima of vessels presumably will be eliminated by fabrication of a shield over the rotating tip. In conclusion, a method for catheter-tip fragmentation of massive acute pulmonary embolism which is potentially applicable to patients was described. The potential advantages are immediate beneficial effects and applicability for treatment of large numbers of patients in whom thrombolytic therapy is contraindicated. REFERENCES
1 A National cooperative Study. Tbe urokinase pulmonary embolism trial. Circulation 1973; 47(suppI2):38-49, 66-72 2 A Cooperative Study Urokinase-streptokinase embolism trial, phase 2, results. JAMA 1974; 229:1606-13 3 Goldbaber SZ, Kessler CM, Heit J, Markis J, Sharma GVRK, Dowley D. Randomized controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. Lancet 1988; 2:293-98 4 Goldhaber SZ, Meyerovitz MF, Markis JE, Kim D, Kessler CM, Sbarma GVRK. Tbrombolytic therapy of acute pulmonary embolism: current status and future potential. J Am Coil Cardiol 1987; 10:96-104 5 Verstraete M, Miller GAB, Bounameaux H, Cbarbonnier B, Colle J~ LecorfG. Intravenous and intrapulmonary recombinant tissue-type plasminogen activator in the treatment of acute massive pulmonary embolism. Circulation 1988; 77:353-60 6 Leeper ~ Popovicb Jr J, Lesser BA, Adams D, Froelich J~ Burke MW: Treatment of massive acute pulmonary embolism: the use of low doses of intrapulmonary arterial streptokinase combined with full doses of systemic heparin. Chest 1988; 93:23440 7 A Collaborative Study by the PIOPED Investigators. Tissue plasminogen activator for the treatment of acute pulmonary embolism. Cbest 1990; 97:528-53 8 MeisterSG, Brooks HL, Szucs MM, BanasJS Jr, etal. Pulmonary cineangiograpby in acute pulmonary embolism. Am Heart J 1972; 84:33-37 9 Bildsoe MC, Moradian G~ Hunter D~ Castaneda-Zuniga, et ale Mechanical clot dissolution: new concept. Radiology 1989; 17:231-33
Mechanical Disruption of Pulmonary Emboliin Dogs (Stein et al)
Pulmonary embolism was induced in 11 dogs by the injection of three- to four-day-old allogeneic blood clots. The clots were made radiopaque by soaking them in contrast material. The resulting clots were firm, 3 to 4 cm long, and 1 cm in diameter. Injection of the clots into the external jugular vein consistently produced occlusion of at least one of the lobar pulmonary arteries. In every instance in which the tip of the catheter could be positioned at the
clot embolus (six dogs), the clots were readily fragmented with a number 8 French (2.67 mm OD) flexible rotating tip catheter (Kenseycatheter) activated at 80,000 rpm. Overall perfusion was shown by posttreatment angiograms to be markedly improved. These studies show that catheter-tip fragmentation of pulmonary emboli with a Kensey catheter has excellent potential for therapeutic application in patients with pulmonary embolism. (Chest 1990; 98:994-98)
Thromholytic agents are often of great benefit in patients with acute pulmonary embolism, but they have two important drawbacks: thrombolytic agents require seve ral hours to be effective, and all cause sigmficant bleeding.!" Low doses of intrapulmonary arterial streptokinase failed to eliminate the bleeding complications." The benefits of thrombolysis, therefore, are incomplete, and the risks are prominent in acute pulmonary embolism. Another extremely important problem with the application of thrombolytic agents to the treatment of pulmonary thromboembolism is that the very group of patients prone to suffer pulmonary embolism is the group in whom the risks of bleeding from thrombolytic agents is greatest. In the majority of patients with acute pulmonary embolism who could potentially benefit from thrombolytic therapy, the drug is contraindicated, because of recent surgery, fracture , trauma, or diseases that are associated with a bleeding diathesis." Clearly, therefore , there is a need for therapy that is both effective, immediate, and safe . The purpose of the present investigation was to explore the potential value of catheter-tip fragmentation of expe rime ntally induced clot emboli in dogs. This technique offers an entirely new potential approach to the treatment of patients whose condition is unstable because of massive acute pulmonary thromboembolism . The technique has two important poten-
tial advantages: (1) relief from the deleterious effects of pulmonary embolism are immediate; (2) the technique is potentially applicahle to a large number of patients in whom thrombolytic therapy is contraindicated .
*From the Henr y Ford Hosp ital. Detroit. /U'print requests: D r. Stein . Hl,"'11 Ford Hospital. 2699 West Grand. De/mit 48202
994
METHODS
Studies were performed in 11 anesthetized healthy mongrel dogs weighing between 20 and 30 kg. All studies were performed with
_.
1 2 mm
.
.
'~·~I
•
I
"
of
• .,-.
.... ~
.
<
FIGUllt: 1. Photographs of tip of the Kensey Aexihle rotat ing lip catheter. Mechanical Disruption of Pulmonary Emboli in Dogs (Stein
at a/)
FllalilE 2A. (Dog I). Plain films slwwinf.( radiopaque blood dot in left lower lohe (caudal lobe} pulmonary artery: T..Jt. hefon' fraf.(lllenlalion with Kensey catheter. Ri/!,ht .aft"r fraf.(mentation with Kensey catheter, the chest closed . Followinf.( anesthesia. dof.(s were intubated and respired with nMUII air usinf.( a Harvard respirator. A femoral vein was used to introduce an 1'\111 sid" hole cutheter in to the pulmonary artery for pulmonary arteriof.(raphy. The jugular vein Wits cannu lated with a 7 111m internal diameter bypass type cannula which was advanced to till' superior vena cava . Clots were introduced through this cannula. Selective right aud left pulmonary arteriograms were oht ained prior to embolization ;,nd were repeated 10 to 30 minutes afh'r embolization. Catheter-tip fraf.(mentatiou of till' embolus was then attempted . The pulmonary arteriograms were then repeated . Followinj; this . the dogs were killed and an autopsy of the lungs was performed .
Preparation of Clots Studk-s were performed with allof.(,-n ..ic blood dots prepared as follows: three days prior to tilt, study. 20 011 of venous hlcM>
each offour 7 011 vacutainers (10 nun internal diameter) ami allowed to dot. Ou tilt' St't'lIld or third day. tlu- dots were n-moved Irom the containers and wert' immersed in radiopnque contrast mall' rial (meglumim- and sodium diatrizoates, "YI>
Se-lective I"ft and right pulmonary arteriograms were p..rlorn ...d usinf.( a 1'\0. 7 Fr..nch NIH anf.(iof.(raphic catheter, Followinf.( a power injection of 30 ml of meghunine and sodium diutrizoate-s (Hypaque 76) at a rate of 20 mils. arteriograms were re-cord.. d on 3.'5 111m cim at 30 frames/so Cineanf.(iof.(raphy has been shown to ht' a useful
FI<:lIIlE 28. (Dog I). T..Jt. control pulmonary arterlogram showinf.( I,'ft lower lohe (left caudal lohe) pulmonary artery. Center, same vessel li,lIowinf.( dot embolus. A fillinf.( d"fed is not visihl» because till' dol was radiopaque . Rij!,ht . same vessel following fraf.(lIlt'ntation with K,'nSt'y catheter, CHEST I 98 I 4 I OCTOBER, 1990
995
FII;I'11E 3A. (Dog 2). Plain films showing radiopaqm- hl.HI
diagnostlc techniqm- in patients with pulmonary embolism." Plain cines of the radiopaque dot embolus 1lt'Ii,re and after catheter-tip fragnwntation were also obtained .
Mrchunica! Disruption IIf 1',,/1110111/11/ Emboli MedJanieal disruption of tilt' pulmonary emboli was attempted in all II dogs with a No. Ii French (2.67 mm diameter) Hexihle rotating tip catheter, Kensey catheters contain a torsional drive wire that revolves a distal instrumentation tip at speeds up to lOO.IlOO rpm . A continuous chaune is provided through till' catheter shaft lilr the supply of irrigation Auid thai exits adjacent 10 the revolving lu-ad . Wlu-n in operation. the irrigation fluid is directed laterally 10 the are-a of instrumentntion for cCl<,ling purposes. A DC electric motor and speed-up transmission assemhly are driven from a power
supply located in a console. The motor assembly includes a eouphng device for mating to the catheter. The console is powered from a remote medical grade isolation transformer. The console controls the speed of catheter-tip rotation and the flow rate of the irrigation Auid. The Kensey catheter is particularly advantageous for fragmentation of pulmonary emboli because of two characteristics. When operational. irrigation Auid exiting near the instrumentation tip forms a vortex which is effective in stopping large particles from passuu; downstream , Fragments of thrombi tend to he pulled into the vortex , Photographs of the tip of the catheter are shown in Figure 1. In the present study. once in contact with the embolus, the rotaling tip catheter was activated at 110,000 rpm and moved genlly hack and forth through the clot embolus under fluoroscopy The duration of activation of the catheter was 5 to 10 seconds.
Fl l a Jll E 3 1\. (Dog 2). I_ft . co ntro l pulmonar y ar t..riogram showing Ic·ft lowe r lobe (It·n caudal )olll') pulmonary artery. (;1'1111'1'. same ve-ssel li,lIowing clot embolus. A filling defect is not visihle because the clot was radiopaque . Ril{hl. same vessel following fragmentation with Kensey catheter.
996
Mechanical Disruption of Pulmonary Emboliin Dogs (Stein al al)
FIGURE 4A, (Dog 3). Plain films showinj; radiopaque hlood clot in left lower lobe (caudal lobe) pulmonary artery. l..eft, before Iragmentatton with Kensey catheter. Right. after Iragmentatton with Kensey catheter.
Autopsy of l.A"l/.(.~
At the conclusion of the study, the pulmonary arteries were carefully dissected and examined for damage that may have resulted from clot fra~mentation with the Kensey catheter, Residual clot embol i were recovered and measured . R":SULTS
Pulmonary clot emholi were readily delivered to the left and right pulmonary arteries. The clot emboli lodged in the left lower lobe (caudal lobe) arteries in several dogs. Because the catheter was most readily directed to the left lower lobe artery, and because this was a feasihility study, we assessed the capability of fragmentation of clot emboli only at that site . In six of 11 dogs, we were ahle to manipulate the
catheter to the site of the clot embolus, In these six dogs, the clots were readily fragmented. Perfusion at the site was improved following fragmentation (Fig 2 to 4). Clot fragments typically were 2 to 3 mm in diameter and 4 to 7 mm in length. Although these fragments occluded suhsegmental or smaller hranches, fragmentation of the clots relieved the proximal occlusion and permitted improved perfusion to the region . The catheter caused a tear in a pulmonary arterial branch in one dog when it was activated in an attempt to assist in manipulating it to an occluded branch . The clot had not been reached , and this was probably an improper use of the catheter. The angiograms showed
FIl :!JIIE 4B. (Dog 3). lejt, control pulmonary arteriogram showim; left lower lobe (left caudal lollt') pulmonary artery. Center, sam e vessel following clot e mbolus, A filling defect is not visibl« because the clot was rad iopaque . Right. same vessel following fragmentation with Kensey catheter.
CHEST I 98 I 4 I OCTOBER. 1990
997
no extravasation of contrast material at that site, although autopsy showed bleeding around the artery. In these preliminary studies, we employed No. 8 French transseptal catheter introducers as substitutes for guiding catheters (which were not available in the proper size). These sheaths have thin walls, and therefore, sharp edges at the tip. On two occasions, they produced nonpenetrating intimal tears. These sheaths will not be employed with future use of the Kensey catheter for catheter-tip fragmentation of thromboemboli. We observed no other complications. However, a slight extravasation of bloody fluid into the periarterial region typically occurs with the Kensey catheter as a result of the lateral jets of cooling fluid produced at the tip during activation. In the coronary arteries of dogs, when contrast material is used as the cooling fluid, the extravasation is visible for about three to ten minutes. In these unpublished chronic studies of the coronary arteries of dogs, this extravasation was no longer apparent after two weeks, and it produced no damaging effects. DISCUSSION
These preliminary studies indicate that mechanical fragmentation of pulmonary emboli is possible with a rotary tip catheter such as the Kensey catheter and that such treatment is associated with immediate improvement of the pulmonary arteriogram. Others, using a similar device, have shown that clot dissolution can be produced in vitro following 10 seconds of activation of the catheter at BO,OOO rpm. The largest residual clots shown in vitro were 208 ~.9 Larger clot fragments, however, occurred in our study in dogs. The fragments typically were 2 to 3 mm in diameter and 4 to 7 mm in length. A problem in our preliminary study was the inability to guide the rotating-tip catheter to the site of the embolus. We believe that this problem can be solved with the addition of wire mesh in the wall of the catheter, which will improve torque, and therefore,
998
ability to manipulate the tip. A curved tip will also be useful for manipulation to the appropriate site. The possibility of tears of the intima of vessels presumably will be eliminated by fabrication of a shield over the rotating tip. In conclusion, a method for catheter-tip fragmentation of massive acute pulmonary embolism which is potentially applicable to patients was described. The potential advantages are immediate beneficial effects and applicability for treatment of large numbers of patients in whom thrombolytic therapy is contraindicated. REFERENCES
1 A National cooperative Study. Tbe urokinase pulmonary embolism trial. Circulation 1973; 47(suppI2):38-49, 66-72 2 A Cooperative Study Urokinase-streptokinase embolism trial, phase 2, results. JAMA 1974; 229:1606-13 3 Goldbaber SZ, Kessler CM, Heit J, Markis J, Sharma GVRK, Dowley D. Randomized controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. Lancet 1988; 2:293-98 4 Goldhaber SZ, Meyerovitz MF, Markis JE, Kim D, Kessler CM, Sbarma GVRK. Tbrombolytic therapy of acute pulmonary embolism: current status and future potential. J Am Coil Cardiol 1987; 10:96-104 5 Verstraete M, Miller GAB, Bounameaux H, Cbarbonnier B, Colle J~ LecorfG. Intravenous and intrapulmonary recombinant tissue-type plasminogen activator in the treatment of acute massive pulmonary embolism. Circulation 1988; 77:353-60 6 Leeper ~ Popovicb Jr J, Lesser BA, Adams D, Froelich J~ Burke MW: Treatment of massive acute pulmonary embolism: the use of low doses of intrapulmonary arterial streptokinase combined with full doses of systemic heparin. Chest 1988; 93:23440 7 A Collaborative Study by the PIOPED Investigators. Tissue plasminogen activator for the treatment of acute pulmonary embolism. Cbest 1990; 97:528-53 8 MeisterSG, Brooks HL, Szucs MM, BanasJS Jr, etal. Pulmonary cineangiograpby in acute pulmonary embolism. Am Heart J 1972; 84:33-37 9 Bildsoe MC, Moradian G~ Hunter D~ Castaneda-Zuniga, et ale Mechanical clot dissolution: new concept. Radiology 1989; 17:231-33
Mechanical Disruption of Pulmonary Emboliin Dogs (Stein et al)