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Br Heart J 1988;59:429-37 Perforation thresholds and safety factors in in vivo coronary laser angioplasty TIMOTHY J BOWKER,* KIM M FOX,* FRANK W CROSS,t PHILIP A POOLE-WILSON,* STEPHEN G BOWN,t ANTHONY F RICKARDS* From *the National Heart Hospital, and tUniversity Colkge Hospital, London SUMMARY Laser angioplasty can cause early (acute perforation) or late (stenosis or aneurysm) complications. To find how much intravascular laser energy can be delivered via a 100 pm core optical fibre passed down a balloon angioplasty catheter without causing angiographic abnor- malities up to 10 days later, argon laser energy was delivered percutaneously under radiographic screening to the coronary circulation of 12 normal closed chest dogs. With the balloon inflated, sequential laser pulses were delivered to the same site. Angiograms were recorded before, immediately, and again at one week, after laser delivery. There were two laser-induced perforations (both fatal). Mechanical perforation with the 100 pm fibre occurred four times, but there were no haemodynamic sequelae. To find the acute perforation threshold of similar sized arteries to energy delivered via the bare 100 pm core fibre, the tip of which was held in contact with the luminal surface, 32 argon laser pulses were delivered transluminally in vivo to separate sites in normal rabbit iliac and canine coronary arteries. The acute perforation threshold with energy delivered via the angioplasty catheter lay between 6 and 10 J and that without the balloon angioplasty catheter lay between 3 and 4 J. After delivery of up to 6 J via a balloon angioplasty catheter, there were no angiographic abnormalities at one week. Fibre optic transluminal delivery of laser energy may improve the primary success rate of, and perhaps widen the indications for, coronary angioplasty. Since 1977 it has been possible to revascularise human myocardium percutaneously by balloon angioplasty.' Originally application of this technique was thought to be limited, but the indications for percutaneous transluminal coronary balloon angio- plasty have widened. There are now only two main limitations to the technique. These are the ability of the operator to cross the anteromatous lesion with the guide wire and balloon, and restenosis, which occurs in about 30% of patients, usually within 3-6 months of the procedure.23 Laser energy can be delivered transluminally via an optical fibre introduced percutaneously to vapor- ise intraluminally some of the occluding atheroma. This should enhance the operator's ability to cross the lesion. Use of a laser in conjunction with balloon angioplasty ("laser-assisted balloon angioplasty") may extend the technique to those lesions which are Requests for reprints to Dr Timothy J Bowker, The National Heart Hospital, Westmoreland Street, London W1M 8BA. Accepted for publication 8 October 1987 not attempted because current angiographic preselection indicates that they are "uncrossable". Whether laser energy could reduce the limitation of restenosis is uncertain, but this possibility can be evaluated only if the laser technique becomes clin- ically applicable. The safety of the technique depends on the ability to vaporise luminal atheroma without causing undue damage to the subjacent normal arterial wall. This requires a reliable intracoronary delivery system and the definition of the characteristics that will not cause either immediate vessel perforation or longer term thermal damage. There are reports of relatively high in vitro4 and in vivo' vessel perforation rates in various normal and atheromatous models and the late appearance of aneurysms in arteries treated by laser.6 The present study had three aims. The first was to test in vivo a prototype system for the percutaneous transluminal delivery of laser energy to the coronary circulation. The second was to find the acute in vivo perforation threshold of arteries that were the same size as those of the human epicardial coronary circulation. Intravascular argon laser energy was 429 on July 4, 2020 by guest. Protected by copyright. http://heart.bmj.com/ Br Heart J: first published as 10.1136/hrt.59.4.429 on 1 April 1988. Downloaded from

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Page 1: Perforation thresholds andsafetyfactors ininvivo coronary ... · coronarylaserangioplasty TIMOTHYJ BOWKER,*KIMMFOX,*FRANKWCROSS,t PHILIPAPOOLE-WILSON,*STEPHENGBOWN,tANTHONYFRICKARDS*

Br Heart J 1988;59:429-37

Perforation thresholds and safety factors in in vivocoronary laser angioplastyTIMOTHY J BOWKER,* KIM M FOX,* FRANK W CROSS,tPHILIP A POOLE-WILSON,* STEPHEN G BOWN,t ANTHONY F RICKARDS*

From *the National Heart Hospital, and tUniversity Colkge Hospital, London

SUMMARY Laser angioplasty can cause early (acute perforation) or late (stenosis or aneurysm)complications. To find how much intravascular laser energy can be delivered via a 100 pm core

optical fibre passed down a balloon angioplasty catheter without causing angiographic abnor-malities up to 10 days later, argon laser energy was delivered percutaneously under radiographicscreening to the coronary circulation of 12 normal closed chest dogs. With the balloon inflated,sequential laser pulses were delivered to the same site. Angiograms were recorded before,immediately, and again at one week, after laser delivery. There were two laser-induced perforations(both fatal). Mechanical perforation with the 100 pm fibre occurred four times, but there were nohaemodynamic sequelae. To find the acute perforation threshold ofsimilar sized arteries to energy

delivered via the bare 100 pm core fibre, the tip of which was held in contact with the luminalsurface, 32 argon laser pulses were delivered transluminally in vivo to separate sites in normalrabbit iliac and canine coronary arteries. The acute perforation threshold with energy delivered viathe angioplasty catheter lay between 6 and 10 J and that without the balloon angioplasty catheter laybetween 3 and 4 J. After delivery of up to 6 J via a balloon angioplasty catheter, there were no

angiographic abnormalities at one week. Fibre optic transluminal delivery of laser energy may

improve the primary success rate of, and perhaps widen the indications for, coronary angioplasty.

Since 1977 it has been possible to revascularisehuman myocardium percutaneously by balloonangioplasty.' Originally application of this techniquewas thought to be limited, but the indications forpercutaneous transluminal coronary balloon angio-plasty have widened. There are now only two mainlimitations to the technique. These are the ability ofthe operator to cross the anteromatous lesion with theguide wire and balloon, and restenosis, which occursin about 30% of patients, usually within 3-6 monthsof the procedure.23

Laser energy can be delivered transluminally viaan optical fibre introduced percutaneously to vapor-ise intraluminally some of the occluding atheroma.This should enhance the operator's ability to crossthe lesion. Use of a laser in conjunction with balloonangioplasty ("laser-assisted balloon angioplasty")may extend the technique to those lesions which are

Requests for reprints to Dr Timothy J Bowker, The National HeartHospital, Westmoreland Street, London W1M 8BA.

Accepted for publication 8 October 1987

not attempted because current angiographicpreselection indicates that they are "uncrossable".Whether laser energy could reduce the limitation ofrestenosis is uncertain, but this possibility can beevaluated only if the laser technique becomes clin-ically applicable.The safety of the technique depends on the ability

to vaporise luminal atheroma without causing unduedamage to the subjacent normal arterial wall. Thisrequires a reliable intracoronary delivery system andthe definition of the characteristics that will not causeeither immediate vessel perforation or longer termthermal damage. There are reports of relatively highin vitro4 and in vivo' vessel perforation rates invarious normal and atheromatous models and the lateappearance ofaneurysms in arteries treated by laser.6The present study had three aims. The first was to

test in vivo a prototype system for the percutaneoustransluminal delivery of laser energy to the coronarycirculation. The second was to find the acute in vivoperforation threshold of arteries that were the samesize as those of the human epicardial coronarycirculation. Intravascular argon laser energy was

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delivered with the tip of a bare laser fibre deliberatelypositioned tangentially in contact with the luminalsurface of the artery and then with the laser fibre tipprotruding from within an inflated balloon angio-plasty catheter, so as to minimise direct contactbetween the fibre tip and arterial wall. The third aimwas to study the immediate and longer term radiogra-phic effects of different argon laser pulses (identifiedin a previous in vitro study7 as being appropriate forvaporisation of atheroma) delivered via the angio-plasty catheter to the normal canine coronary circula-tion that might have a bearing on the late appearanceof perforations, stenoses, or aneurysms. Thus wehoped to find conditions for the safe delivery of laserenergy to the normal coronary circulation.

Methods

A Cooper Medical Aurora laser, capable of deliveringup to 7W of argon laser power, was coupled to a 100,um core diameter optical fibre via an electronicshutter. The power output from the distal end of thefibre (1 0-30 W) was measured with a calorimeterand power meter, before and after each series ofenergy deliveries to each animal.

ENERGY DELIVERY BY BARE FIBREA left lateral thoracotomy was performed undergeneral anaesthesia on two normal greyhounds. Theleft coronary artery was cannulated directly with thebare optical fibre and the tip was passed distally todifferent sites within its branches. The position ofthefibre tip was checked by direct inspection of thelaser's aiming beam (low power < 1 mW) at the site atwhich it was transilluminating the arterial wall (fig 1).At each arterial site, the fibre tip was deliberately

Fig 1 Dog I at thoracotomy, with heart brought up on

pericardial cradle. An opticalfibre was inserted via an

arteriotomy into left anterior descending coronary artery.There is laser transillumination from the fibre tip seen justbelow the tip of the central pair offorceps.

Bowker, Fox, Cross, Poole- Wilson, Bown, Rickards

positioned up against the luminal surface of thevessel, and a single laser pulse (the energy of whichwas varied from site to site) was delivered. Thepresence or absence of acute vessel perforation wasthen immediately assessed, by the presence orabsence ofblood leaking from the vessel. The animalswere then killed and their hearts excised.The abdominal aorta and iliofemoral arteries were

exposed by laparotomy in five anaesthetised rabbits.A carotid cut down was performed and the artery wascannulated with the bare optical fibre, which waspassed via the descending aorta to the abdominalaorta, the wall of which could be transilluminatedwith the laser's aiming beam. The fibre tip wasadvanced to various different sites in both iliofemoralarteries (its exact position being ascertained from theaiming beam). At each arterial site the fibre tip waspositioned in direct contact with the luminal surfaceof the vessel, and a single laser pulse (the energy ofwhich was varied from site to site) was delivered. Thepresence or absence of acute vessel perforation wasthen assessed. The animals were then killed and thelasered vessels were excised.

Overall in both the rabbit and dog experiments, 32separate laser pulses were delivered to 32 separatearterial sites. The range of pulse energies deliveredwas 0 2-7-0 J.

BALLOON ANGIOPLASTY CATHETER ENERGYDELIVERYFor the experiments with balloon angioplasty cath-eter energy delivery, twelve greyhounds were used.Each dog was anaesthetised and a cut down wasperformed to the left carotid artery, through which a8-3F guide catheter was introduced under radiogra-phic screening and advanced to whichever coronaryostium was most easily cannulated (the left in all butone). A pre-laser coronary angiogram was recorded.The optical fibre was preloaded down the

"through" lumen of a standard 4-3F 3 0 mm balloonangioplasty catheter and adjusted so that the fibre tipprotruded from the catheter tip by 2-3 mmn, and thedevice was inserted into the guide catheter. Thesidearm of a Y connector previously attached to theproximal end of the balloon catheter was used for theinfusion ofHartmann's solution down the "through"lumen alongside the optical fibre, at a pressure of 300mm Hg and at a rate of 1-5 ml/min.

For the first three dogs we used balloon angio-plasty catheters in which the "through" and ballooninflation lumen lay side by side. Thereafter, we usedballoon angioplasty catheters with a "through"lumen that was central to and coaxial with the ballooninflation lumen.

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Perforation thresholds and safety factors in in vivo coronary laser angioplasty

Initial laser delivery and angiographyThe fibre/catheter device was passed via the guidecatheter under radiographic screening several cen-timetres into a major branch of a coronary artery.Energy was delivered according to the followingprotocol. A sequence of three separate laser pulseswas delivered to the same site within the cannulatedartery, in the following order: a 1 J pulse, a 2 J pulse,and then a 3 J pulse. For delivery of each individuallaser pulse we used a set protocol.(a) Radiographic contrast medium was injected to

check vessel patency and integrity.(b) The angioplasty balloon was inflated to occlude

downstream blood flow.(c) The Hartmann's perfusion was then turned on.(d) The measured amount of laser energy was then

delivered via the optical fibre during perfusionwith Hartmann's solution.

(e) The angioplasty balloon was then deflated.(f) The Hartmann's perfusion was then turned off.(g) Radiographic contrast medium was injected to

check vessel patency and integrity.In this way, the laser energy was delivered under

standardised conditions-the optical fibre being per-fused locally with Hartmann's solution, and beingheld as centrally as possible within the vessel lumenso that contact time during the cardiac cycle betweenfibre tip and arterial wall would be minimised. Thefibre/catheter device was then removed from theguide catheter, inspected for damage, and a post-laser coronary angiogram was recorded. The guidecatheter was removed, the carotid artery was

repaired, and the skin was sutured. The dogs were

then allowed to recover from the anaesthetic.

Repeat angiography at 7-10 daysThe dogs were re-anaesthetised 7-10 days later.After a repeat carotid cut down a 8-3F guide catheterwas introduced under radiographic screening to theostium of the coronary artery to which laser energyhad previously been delivered, and a 7-10 day post-laser coronary angiogram was recorded. Whenever itwas possible either the contralateral or the othermajor branch of the left coronary artery was thencannulated and a pre-laser angiogram was recorded.The fibre/catheter device was then passed into thenewly cannulated (and previously "un-lasered")coronary artery branch. A single 5 J laser pulse wasdelivered to this arterial branch, by the same deliverysequence as described above. On one occasion twosequential 5 J laser pulses were delivered to the samesite.The fibre/catheter device was then withdrawn

from the guide catheter and a post-laser coronaryarteriogram was recorded. If the dog survived,ventricular fibrillation was induced with intracoron-

ary potassium chloride. The animal's chest was thenopened and the pericardium was incised. A carefulinspection was made for any free blood, fluid,thrombus, or any epicardial or pericardial damage oradhesions, particularly in the region of the vesselstreated by laser. The animals' hearts were thenexcised.

In all the canine experiments, both initially and atrepeat angiography, the dogs' electrocardiogramswere continually monitored, and recordings weretaken before and after laser treatment.

Results

DELIVERY OF ENERGY BY BARE FIBRETable 1 shows the results ofthe rabbit and open chestdog experiments in which the bare optical fibre wasused. Vessel wall perforation never occurred with the22 laser pulses whose energies were 3 J or less. Threeout of five 4 J laser pulses caused acute vessel wallperforation, and all five of the laser pulses of 5 J ormore caused acute vessel wall perforation.

DELIVERY OF ENERGY BY BALLOONANGIOPLASTY CATHETERTable 2 shows the overall results of the closed chestdog experiments in which the optical fibre was passedwithin the inflated balloon angioplasty catheter.

Short term and long term effects ofcumulative 1, 2, and3 J pulsesOf the ten dogs that received sequential delivery ofthree laser pulses (1 J, 2 J, then 3 J) to the same site intheir coronary circulation, nine had normalimmediate post-laser coronary angiograms andunchanged electrocardiograms. Although the car-diovascular state of the first and third of these ninewas satisfactory and stable for several hours after theprocedure, their ventilation was not (it took over anhour to wean both of them off the ventilator), andboth were found dead the following morning. Post-

Table 1 Energy delivery by bare fibres

Number ofperforations/pulses delivered

Pulse Dogs Rabbitsenergy (J) (2 W) (I W 1 5 W 2 W 3 W) Total

0-2 0/1 .. .. 0/10-5 0/2 0/21 0 0/2 0/2 0/1 0/1 0/2 0/82-0 0/1 0/1 0/1 0/2 0/53-0 0/1 0/1 0/1 0/3 0/64-0 1/1 .. 0/1 2/3 3/55-0 1/1 1/1 .. 2/260 2/2 .. 2/27 0 1/1 1/1

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Table 2 Energy delivery by balloon angioplasty catheter

Angiography Laserpower

Dog Immediate Repeat Perforation Mode of death (W)

3 N - Nil <12h 2anaesthetic

4 Perf 3 J - Laser Immediate 1-5laser

5 N (MP) - Mechanical < 12 h 1-5anaesthetic

6 N N Nil 7 days, killed 37 N (MP) N Mechanical 7 days, killed 18 N (MP) N Mechanical 7 days, killed 2-59 N (5 J) - Nil Immediate, 1-5

killed10 N N Nil 1

Perf 5 + 5 J Laser 10 days, laser 2-511 N (5 J) - Nil Immediate, 1-5

killed12 N (MP) N Mechanical 10 days, killed 213 N N Nil 7 days, killed 214 N N Nil 9 days, killed 2

MP, angiographic evidence of mechanical perforation; Perf,perforated; N, normal; (5 J), single 5 J pulse delivered at initialangiography.

mortem examination did not find any blood in thepericardial space or any other evidence of laserperforation or myocardial damage. Postmortemangiograms of the lasered vessel were normal.

Thereafter the anaesthetic technique was altered.The other seven dogs recovered and survived with-out any complications. Repeat angiography at 7-10days ofthe previously lasered vessels were all normal,and there was no change in the dogs' electrocar-diograms. Postmortem examination of these sevendogs did not show any macroscopic evidence of laserperforation.

In the second of the ten dogs that received thesequential laser pulses (1 J, 2 J, then 3 J) to the sameintracoronary site, laser perforation occurred afterthe 3 J pulse. During the post-laser angiogram thedog went into ventricular fibrillation and died. Post-mortem macroscopic inspection of the laser perfora-tion site (fig 2) showed a discrete hole with littlesurrounding damage. After withdrawal of the fibre/catheter device it was apparent that the tip of theoptical fibre had been pushed back (by about 1-5 mm)relative to the catheter tip, and that the balloon hadbecome deformed into a banana shape such that thefibre tip was protruding obliquely from the cathetertip. In this balloon angioplasty catheter the throughand balloon inflation lumens lay side by side. Suchballoon deformation with oblique displacement ofthe fibre tip did not occur with balloon angioplastycatheters with a central through lumen that rancoaxially within the balloon inflation lumen.

Short term effects of 5 J pulsesIn two dogs (9 and 11), because of radiographic

Bowker, Fox, Cross, Poole- Wilson, Bown, Rickardscontrast induced electrocardiographic instability, asingle 5 J pulse was delivered at the initial generalanaesthetic, and the dogs were killed immediately. Ina third dog (10) it was possible to intubate the othermain left coronary artery branch at repeat angiogra-phy ten days later. In this third dog two separate 5 Jlaser pulses were delivered to the same site.

In all three, there was no difference between thepre- and post-laser angiograms or electrocar-diograms after the single 5 J pulse. In dog 10,however, perforation occurred after delivery of thesecond 5 J laser pulse to the same site (cumulativeenergy dose of 10 J) (fig 3). A haemopericardiumformed, but the heart continued to beat. After about30 minutes (during which there were no arrhyth-mias), the animal was killed by infusion ofintracoronary potassium chloride. Postmortemmacroscopic inspection of the laser perforation site(fig 4) showed a larger hole with more widespread

Fig 2 Pathological specimenfrom dog 4 showing leftanterior descending coronary artery after a 3 J laser pulse(cumulative dose of 6 J) delivered when the laserfibre hadbeen inadvertently positioned obliquely within the vessellumen. Compare with fig 4.

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Perforation thresholds and safety factors in in vivo coronary laser angioplasty

Fig 3 Post-laser left anterior descending coronaryangiogram in dog 10 after delivery via an angioplastycatheter of two S J pulses to the same site. Contrast mediumcan be seen spurtingfrom underside of artery, and beginningto collect in the pericardial space.

surrounding damage than was seen after the laserperforation with the inadvertently obliquelypositioned fibre tip. Postmortem examination of theother two vessels (which had each received only one 5J pulse) did not show macroscopic evidence of laserperforation.

PERF-ORATIONSThroughout the delivery of the 34 different laserpulses, laser perforation only occurred on twooccasions (both described above). On four otheroccasions there was radiographic evidence ofmechanical perforation of the vessel wall by theprotruding optical fibre tip during manipulation ofthe fibre/catheter device within the coronary circula-tion before any laser energy was delivered. This wasshown by the appearance of a small blush ofextravasated contrast medium to one side of thevessel when contrast was injected immediately beforedelivery of the first laser pulse (figs 5a-d).On all four occasions there were no haemodynamic

consequences, the fibre/catheter device was man-ipulated a centimetre or so past the point ofmechan-ical perforation, and the sequence of laser pulses wasdelivered to this more distal site as described above.In all four cases the immediate post-laser angiogramswere normal. Three of the four animals survived to7-10 days, and at this time repeat angiograms of thepreviously lasered vessels were normal, with noevidence of the previous mechanical perforation. Inone of these three dogs, postmortem examination

showed a small subepicardial haematoma (fig 6). Inthe other two there was no postmortem evidence ofvessel perforation.One of the four instances of mechanical perfora-

tion occurred in a dog in which death was attributedto anaesthesia. Postmortem examination showed asmall subepicardial haematoma at the site ofmechan-ical perforation, but no macroscopic evidence oflaserdamage, nor any blood, clot or adhesions within thepericardium. A postmortem angiogram of thislasered vessel was normal.

CATHETER DAMAGEOn three occasions the fibre/catheter device wasdamaged during the procedure. The first occasion(already described) was when the optical fibre tipbecame pushed back relative to the catheter tip, suchthat the fibre protruded obliquely causing laserperforation.On the other two occasions, during delivery of the

first laser pulse the balloon suddenly deflated andcould not be reinflated. An internal perforationbetween the balloon and the through lumen hadoccurred and contrast medium had passed via theballoon into the through lumen and out into thelumen of the coronary artery. There were nohaemodynamic or electrocardiographic consequen-ces. On one occasion the fibre had retracted relativeto the catheter (while it was being manipulated to thecoronary circulation) such that its tip was entirelywithin the tip of the catheter and on the otheroccasion the fibre fractured within that part of thethrough lumen that traverses the balloon.

All three cases of catheter/fibre damage occurredwith balloon angioplasty catheters in which thethrough and balloon inflation lumens ran side byside. Thereafter we used only balloon angioplasty

Fig 4 Pathological specimen of the perforated left anteriordescending coronary artery in dog 10. Perforation occurredafter delivery, via an angioplasty catheter of two 5 J laserpulses. Compare with fig 2.

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Bowker, Fox, Cross, Poole-Wilson, Bown, Rickardsnow,

Fig 5 Mechanical perforation in dog 12. (a) Showing blush of extravascular contrast medium to right of left anteriordescending artery,just downstreamfrom distal radiographic marker (arrowed) of balloon angioplasty catheter. (b) Fibrelcatheter device manipulated distal to site of mechanical perforation (distal radiographic marker arrowed). (c) Immediatepost-laser angiogram with no evidence of laser perforation orfurther extravasation from the mechanical perforation site.(d) Angiogram obtained 10 days after angioplasty showing no evidence of mechanical or laser damage.

catheters with through lumens that were central andcoaxial within the balloon inflation lumens, and nofurther catheter/fibre damage occurred.

Discussion

From a superficial examination of these data it mightappear that the laser perforation threshold washigher when laser delivery was via an angioplastycatheter than when it was not. No definite con-clusions can be drawn about this, however, as thepresence or absence of a balloon angioplasty catheter

was not the only factor that varied between deliveryof energy by bare fibres and by balloon angioplastycatheters.We used bare fibres to deliver 32 laser pulses to 32

separate sites on the luminal surface of 12 arteriesduring blood perfusion in open chest dogs or exposedrabbit iliac vessels. The acute in vivo argon laserperforation threshold lay between 3 and 4 J; energydensity with this fibre is about 50 kJ/cm'.We used a balloon angioplasty catheter to deliver

34 laser pulses to 13 separate sites in 13 differentcoronary arteries: at two sites a single (5 J) pulse was

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Perforation thresholds and safety factors in in vivo coront

Fig 6 Pathological specimen showing subepicardialhaemotoma in dog 7. This was an incidentalfinding when thedog was killed one week after mechanical perforation thathad no sequelae. (A myocardial block was excisedfrom theapical region post mortem.)

given, at one site two sequential pulses (2 x 5 J)were given, and at ten sites three sequential pulses (1J, 2 J, and 3 J) were given. The laser pulses were givenduring Hartmann's perfusion in closed chest dogs.With one exception, laser energy of up to 5 J (singlepulse) or 6 J (cumulative dose) at one site producedno immediate angiographic or electrocardiographicabnormalities; however, a cumulative dose of 10 J atone site produced immediate vessel perforation.The exception was dog 4, in which laser perfora-

tion occurred after a 3 J pulse (6 J cumulative dose),and this was the only case in which deformation oftheballoon had caused the fibre tip to protrude obliquelyfrom the catheter tip. In all subsequent cases we usedangioplasty catheters with a through lumen that wascentral and coaxial within the balloon inflationlumen, and inspection of the fibre/catheter systemafter laser delivery did not show any deformity or

oblique protrusion of the fibre tip. In all we found a

straight balloon with the fibre tip positioned centrally

ary laser angioplasty 435

as it emerged from the catheter tip. Macroscopically,the perforation site in dog 4 (fig 2) was smaller andwith less surrounding damage than that produced by10 J in dog 10 (fig 4) when the fibre had remainedcentral within the catheter tip.

Non-perforating laser pulses (of up to 3 J (singlepulse) or 6 J (cumulative dose)), delivered via balloonangioplasty catheter resulted in no angiographic orelectrocardiographic abnormalities at 7-10 days. Thehigher perforation threshold with the balloon angio-plasty catheter must be the result of several factors,only one of which is the positioning of the fibre tipwithin the vessel lumen to reduce direct contact withthe arterial wall during the cardiac cycle. Otherfactors are the use of closed chest dogs, sequentiallaser pulses, and Hartmann's perfusion with theballoon angioplasty catheter, as opposed to the use ofopen chest dogs, rabbit iliac vessels, single laserpulses, and blood perfusion with the bare fibre.

Initially open chest dogs were chosen so that directintraluminal contact could be ensured and immediatevessel perforation recognised by direct visualexamination. A range of pulse energies was used tofind an approximate perforation threshold. There-after, for the sake of economy we used rabbit iliacarteries of similar size. Results were similar in bothrabbits and dogs. Differences between the thermaldamping of the open preparations (used with barefibres) and that of the closed preparations (used withballoon angioplasty catheters) will influence theperforation threshold. The laser perforation in dog 4at an energy level equivalent to the bare fibreperforation threshold, however, suggests that thethermal damping effect is not large.To imitate clinical practice, we used closed chest

dogs with balloon angioplasty catheters, and in allbut two, sequential pulses were delivered to one site.In the two in which a single 5 J pulse (which exceedsthe bare fibre perforation threshold) was delivered toa single site, perforation did not occur. This suggeststhat the higher perforation threshold with an angio-plasty catheter may not wholly be the result ofsequential pulses.The presence ofblood enhances argon laser vapor-

isation, including that caused radially from thecentral axis of the fibre tip.8 This will have been a(perhaps major) contributory factor in the lowerperforation threshold with the bare fibre. Because inclinical practice we would aim to minimise the lateralspread ofthermal effect by delivering the laser energyin clear fluid we used perfusion with Hartmann's (tomaintain intracoronary normokalaemia in the closedchest dogs). Dangerous localised intracoronaryhyperkalaemia caused by argon laser inducedhaemolysis is unlikely.9

Although with our fibre/catheter device, mechan-

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436 Bowker, Fox, Cross, Poole-Wilson, Bown, Rickards

ical perforation did not cause haemodynamicsequelae, it is none the less undesirable. This riskcould be minimised by modifying our delivery sys-tem such that the fibre/catheter device is advancedinto the coronary circulation without the fibreprotruding from the catheter tip. The fibre tip couldthen be pushed out of the catheter tip once thecatheter has been manipulated to the target lesion.

Fibre fracture and catheter damage occurred onlyin the region of the balloon, and only in thosecatheters in which the "through" and inflationlumens lay side by side, and were immediatelyrecognisable by the failure of the balloon to inflate.But-under these circumstances the catheter could bewithdrawn without complication.

Percutaneous transluminal delivery of argon laserenergy to the canine coronary circulation has beenstudied by others when a bare 200 gm core diameterfibre was used to deliver single 1 J or 2 J laser pulsesto different coronary arterial sites; in nine arteries infive dogs laser perforation occurred in five andmechanical perforation in one.1° In a similar studywith a bare 400 gm core fibre and single laser pulsesof28 to 80 J at coronary sites in four dogs, immediatelaser perforation occurred in all four." In similarwork on canine intracoronary thrombus, single pul-ses of3 to 30 J caused laser perforation in seven out ofnine dogs and recanalisation in one.'2 In these studiesnot only were the fibres of larger diameter than thoseused in our study (making t-hem less flexible), but thefibres-were not within a-balloon angioplasty catheter.These factors, together with the higher deliveredenergies, would explain the high perforation rates atenergies that were consistent with the perforationthresholds that we found. Also in the previousstudies none of the dogs were recovered, so latefollow up repeat angiography of previously laseredcanine coronary arteries was impossible.The delivery of laser energy has been studied in

human peripheral"'5 and coronary'6 17 circulations. Abare fibre with an olive-shaped metal tip was used forpercutaneous intracoronary delivery'>'0 and in 14cases there was one laser perforation and threemyocardial infarctions. There are several potentialdangers of laser angioplasty-acute vessel perfora-tion, toxic byproducts of photovaporisation," distalembolisation,22 23 and delayed effects such as sub-sequent stenosis or aneurysm formation24 but acutevessel perforation is the most important.The risk of vessel perforation can be reduced by

(a) selective enhancement of laser light absorptionby atheroma (as opposed to that ofthe normal arterialwall) by using differential optical absorption peaksthat are either naturally25 or induced by photosensit-isers, (b) keeping the fibre central within thevessel lumen in order to reduce contact between fibre

tip and arterial wall,' (c) modifying the fibre tip,2 29and delivering laser pulses of short duration thatpenetrate only a fraction of a millimetre into thetarget tissue. This may enable the operator to "nib-ble" away the atheroma gradually, while checkingprogress angiographically between laser pulses. Veryshort laser pulses (of nanosecond duration) limit thesubjacent thermal damage, particularly if they are atthe high peak powers obtainable from pulsedultraviolet excimer lasers.'0 31 We have previouslyreported an in vitro dose-response relation betweenlaser energy input and tissue penetration in normaland atheromatous human postmortem arterial wall.7This described a range of energy characteristicswhich, if applied to delivery of laser energy from thefibre tip in contact with and at right angles to thetissue, would not produce penetration further than0 2-1 0 mm. The design ofthe present study is basedon the energy characteristics of the argon laserestablished by that study. In the present study weused pulse energies which in vitro did not penetratefurther than 1 mm into the target tissue, per J ofargon energy delivered, and which were thought tobe appropriate for "nibbling" away of atheroma.We have now established in vivo the short term

and long term angiographic effects of such amountsof argon laser energy and we know the amount thatcan safely be delivered to one site in the normalcanine coronary circulation. If this cautiousapproach (that of "nibbling" away a millimetre ofatheroma at a time without exceeding the maximumsafe dose for normal arterial wall) is used clinically itmay reduce the risk of acute laser perforation. Thelimitation of the system we have described is that therecanalised lumen that it creates is liable to be toosmall for physiological blood flow. But creation ofeven a tiny lumen may enable operators subsequentlyto cross those lesions which hitherto they had beenunable to cross with the guide wire and balloon alone.Modified fibre tips make this appear feasible in theperipheral circulation'5 32; however, further develop-ment is necessary before it can safely be applied to thecoronary circulation.

This work was supported by the British HeartFoundation, and the Stanley Thomas Johnson Foun-dation.

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