CA1322315C - Perfusion of perfluorocarbon compound emulsion during percutaneous transluminal angioplasty - Google Patents

Abstract

PERFUSION OF PERFLUOROCARBON COMPOUND EMULSION
DURING PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY

Abstract of the Disclosure A percutaneous transluminal angioplasty procedure is disclosed which comprises positioning a balloon-tipped catheter within a stenotic region of an artery, inflating the balloon one or more times to enlarge the inner diameter of the artery and passing an oxygenated perfluorocarbon compound emulsion through the lumen of the catheter and into the artery during balloon inflation. The oxygenated perfluorocarbon compound is passed into the artery at a rate of from about 20 cc/min.
to about 150 cc/min. to prevent physiologically damaging ischemia. Balloon inflation times range from 10 seconds to 30 minutes.

Description

~32~31 5 ~0355-54 PERFUSION OF PERFLUOROCARBON COMPOUND EMULSION

This invention relates to percutaneous transluminal angioplasty and more particularly to the perfusion of an oxygenated perfluorocarbon compound emulsion during prolonged angioplasty.

Restricted blood flow to body tissues may be caused by a narrowing of arteries. This narrowing (or stenosis) may be caused by a number of factors, such a athero sclerosis, thrombus formation or trauma. For example, ; atherosclerosis refers to the gradual deposition of fatty material, generally referred as atherosclerotic plaque, on the inside walls of arteries. A build-up of atherosclerotic plaque within an artery restricts the flow of blood through the artery. The body or~an depend-ing on the narrowed ~stenotic) artery eventually reacts to the inadequate blood flow. The types of symptoms that are produced from inadequate blood flow vary, depending on which arteries in the body are narrowed. Percutaneous transluminal angioplasty is a procedure for reopening arteries narrowed by deposits of atherosclerotic plaque~

Angioplasty may be used in numerous sites, such aR
femoral, renal, cerebral and coronary arteries. In the procedure, a small guiding catheter is inserted into a vein and passed to the site of the narrowing or stenosis.
A smaller balloon-tipped catheter is passed through the guiding catheter and positioned so that the balloon is within the stenotic region of the artery.

Once in position, the balloon is inflated to enlarge the inner diameter of the artery. In successful angio-plasty, when the balloon is deflated, the stenosis of the artery is less severe, thus providing a patient artery~
whiah permits more blood to pass through the artery to the organ or tissue which was distal to the stenosis.
$

, . . . ., ,. .: .
" , , ~ , When the balloon is inflated, the blood flow to the tissue supplied by the arte.ry distal to the balloon is cut off. Accordingly, the tima that the balloon can be inflated is limited, particularly when the procedure involves organs, which are extremely sensitive to the lack of oxygen, such as the brain or heart. During a single procedure the balloon may be inflated several times. However, even with multiple inflations, tissue elasticity and stenosis characteristics are such that a significant proportion of the treated patients experience restenosis of the treated artery within a few months.

Prolonged ir.flation of the balloon may result in better resolution of the stenotic region. However~
prolonged balloon inflation results in prolonged periods during which no oxygen is delivered to tissue distal to the balloon. This creates risk to the patient. For example, in percutaneous translum.inal coronary angioplasty, prolonged bal.loon inflation results in myocardial ischemia, arrhythmias and eventually myocardial infarction.

Attempts to oxygenate tissue distal to the balloon to enable a longer period of balloon inflation have included perfusion of blood through the central lumen of the catheter. However, the passage of blood through the small diameter Qf the catheter lumen resulted in severe hemolysis.

It has been found that prolonged balloon inflation during angioplasty can be accomplished by passing an oxygenated perfluorocarbon compound emulsion into the artery through the lumen of the catheter.

Accordingly, the present invention comprises a method for enlarging a stenotic region of an artery by introducing a balloon catheter into the artery so that i ~ , . , , , , ,., ~. , . .
:, ' 'I ,~ . :

` 13~231~

the balloon is positioned in the stenotic region. The balloon is then inflated one or more times to enlarge the inner diameter o~ the artery inflation of the balloon, an oxygenated perfluorocarbon compound emulsion is passed through the lumen of the catheter to supply oxygen to the portion of the artery distal to the inflated balloon.
The flow rate of the perfluorocarbon compound emulsion through the catheter is sufficient to prevent significant ischemia, preferably being maintained within the range of from about 20 cc/min to about 150 cc~minO

The number of balloon inflations at each stenotic site can vary and may range from one up to about ten or more as desired. Likewise, the duration of each inflation may vary, generally being within the range of from about 10 seconds to about 30 minutes.

These and other features and advantages of the present invention will be better understood by reference to the following detailed when considered in conjunction with the accompanying drawings wherein:
FIG. 1 is a schematic view of a patient showing the heart and main arteries involved in a percutaneous transluminal coronary angioplasty;
FIG. 2 is an enlarged schematic view o~ the heart showing the positioning of the guiding and balloon-tipped catheters within a coronary artery; and FIG. 3 is an enlarged fragmentary cutaway view of the coronary artery and the balloon-tipped catheter.

A preferred application of the present invention is in percutaneous transluminal coronary angioplasty. With reference to FIGS. 1 to 3, such a procedure generally consists of introducing an introducer sheath 10 into the femoral artery 11 at the groin. A small guiding catheter 12 is inserted through the introducer sheath 10 and passed through the femoral artery 11 and dorsal aorta 13 . . .

,~
.: . , ~ :
, ~32231~

and in~o the narrowed coronary art~ry 14 of the heart 16.
A smaller balloon-tipped catheter 17 is then passed through the guiding catheter 12 and positioned so that the balloon 18 o~ the balloon tipped catheter lies within the stenotic region of the artery 14.

The balloon-tipped catheter 17 comprises a pair of lumens 19 and 21. The first lumen 19 extends to the balloon 18 and is used for passing a fluid, preferably saline, to the balloon 18 to inflate the balloon, and to pass fluid from the balloon 18 when the balloon is de~lated.

The second lumen 21 extends through the balloon 18 to the distal tip 22 of the catheter 17. The second lumen 21 is open at the distal tip. The second lumen 18 is provided for passing an oxygenated perfluorocarbon emulsion through cathetex 17 into the occluded portion of the artery 14 during balloon inflation.

As used herein, "perfluorocarbon compound emulsion"
refers to an aqueous emulsion of an oxygen-transferable perfluorocarbon compound, preferably having a particle size of less than about 0.3 microns. Suitahle emulsions have good oxygen transferability to ischemic, hypoxic and anoxic tissues, a favorable vapor pressure range to allow reasonahle expiration of the perfluorocarbon compol~nds used in the emulsion and clinically acceptable toxicity, the emulsion may be transparent, translucent or opaque.

The perfluorocarbon compound emulsion comprises at least one perfluorocarbon compound, an emulsifier and physiological salts and monoglycerides thereof~ Such perfluorocarbon compound emulsions are described in U.S.
Patent Nos. 3,911,138 to Clark, Jr., 3,962,439 to Yokoyama et al and 4,252,827 to Yokoyama et al, Yokoyama, K. et al- "A Perfluorochemical Emulsion as an Oxygen ,.~ "

1322~
~ .
Carrier", Artificial Organs 8:34-40, 1984, and Yokoyama, D. et al: "Selection of 53 PFC Substances for Better Stability of Emulsion and Improved Artificial Blood Substances", Advances ln Blood Substitute Research, New York: Liss, Inc., 1983 .

Preferred fluorocarbon compound emulsions comprise at least one perfluorocarbon compound having 9-11 carbon atoms selected from the group consisting of perfluoro-; decalin, perfluoromethyldecalin, perfluoro alkylcyclo-hexanes having 3 to 5 carbon atoms in the alkyl~
perfluoro alkyltetrahydro~urans having 5 to 7 carbon atoms in the alkyl, perfluoro alkyltetrahydropyrans having 4 to 6 carbon atoms in the alkyl, perfluoroalkanes having 9 to 11 carbon atoms, at least one perfluoro tert-amine having 9 to 11 carbon atoms selected from the groupconsisting o~ perfluoro tert-alkylamines having 9 to 11 carbon atoms, perfluoro N-alkylpiperidines having 4 to 6 carbon atoms in the alkyl and perfluoro N-alkylmorpholines having 5 to 7 carbon atoms in the alkyl;
a high-molecularweight nonionic surfactant having a molecular weight of about 2,000 to 20,000; a phospholipid; and at least one fatty acid compound selected from the group consisting of fatty acids having 8 to 22 carbon atoms; and physiologically acceptable salts and monoglycerides thereof. The ratio of the perfluorocarbon compound and the said perfluoro-tert-amine is 95-50 to 5-50 by weight.

The "high-molecular weight nonionic ~urfactant" has a molecular weight of 2,000 to 20,000 and includes poly-oxyethylene-polyoxypropylene copolymers, polyoxyethylene alkyl ethers, and polyoxyethylene alkyl aryl ethers. The concentration of the surfactant in the emulsion i9 about

2.0 to about 5.0%, preferably 3.0 to 3.5% (W/V).

., , .: ~ : : ~

~ 322~1~

The symbol "% (W/V)" means -the amount proportion of a material by weight (gram) based on 100 ml of the resulting emulsion.

Examples of the perfluorocarbons having 9 to 11 carbon atoms are a perfluorocycloalkane or perfluoro alkylcycloalkane which includes, for example/ perEluoro C3s-alkylcyclohexanes such as perfluoromethylpropyl-cyclohaxane, perfluorobutylcyclohexane, perfluorotri-methylcyclohexane, perfluoroethylpropylcyclohexane, perfluorodecalin and perfluoromethyldecalin; a perf:Luoro C4_6-alkyltetrahydropyran such as perfluorohexyltetra-hydropyran; a perfluoro Cs7-alkyltetrahydrofuran such as perfluoro pentyltetrahydrofuran, perfluoro hexyltetra-hydrofuran and perfluoro heptyltetrahydrofuran; and a perfluoroal~ane having 9-11 carbon atoms such as perfluo-rononane and perfluorodecane.

Examples of the perfluoro tert-amine having 9 to 11 carbon atoms are a perfluoro tert-alkylamine having 9 to 11 carbon atoms which includes, for example, perfluoro-trialkylamines such as perfluoro N,N-dibutylmonomethyl-amine, perfluoro N,N-diethylpentylamine, perfluoro N,N-diethylhexylamine, perfluoto N,N-dipropylbutylamine and perfluorotripropylamine; a per~luoro N,N-dialkyl-cyclohexylamine having 9-11 carbon atoms such as perfluoro N,N-diethy]cyclohexylamine; a perfluoro N-C4-6-alkylpiper~idine such as perfluoro N-pentylpiperidine, perfluoro N-hexylpiperidine and perfluoro M-butylpiperidine; and a perfluoro N-C5-7-alkylmorpholine such as perfluoro N~pentylmorpholine, perfluoro N-hexylmorpholine and perfluoro N-heptylmorpholine.

The ratio of the perfluorocarbon compound to the perfluoro tert-amine to be used is 50-95 to 50-5 by weight and the total amount of perfluorocarbon compound

3 ~ ~

and perfluoro tert-amine contained in the emulsion is about 10 to about 50~ (W/V).

~ he phospholipids used as emulsifier adjuvant in the invention are ones commonly used in the art, and those comprising yolk phospholipid or soybean phospholipid are preferable. The amount present in the emulsion ranges from about 0.1 to about 1~0~ (W/V), and preferably about 0.4 to about 0.6% (W/V).

The fatty acid compound used as ernulsifying ad~uvant is a fatty acid having 8 to 22 carbon atoms, a physiologically acceptable salt such as sodium or potassium salt or a monoglyceride thereof, which includes, for example, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, palmitoleic acid, oleic acid, linoleic acid, arachidonic acid and sodium or potassium salt and monoglyceride thereof. These fatty acid compounds may be used alone or as a mixture of two or more kinds thereof in such a minor amount of 0.004 to 0.1% (W/V), and preferably about 0.02 to 0.04% (WIV). Among these fatty acid compounds, the preferable ones are those having 14 to 20 carbon atoms and their physiologically acceptable salts, and the most pre~era~le are potassium palmitate and potassium oleate, taking into consideration of their good solubility and ease of the preparation of the emulsion.

The balloon-tipped catheter can be of any design which comprises an inflatable balloon at its distal end and a lumen which extends through the balloon and is open at the distal tip of the catheter. Such catheters are commercially available. Presently preferred catheters include the Gruntzig Catheter manufactured by United States Catheter, Inc. and the Simpson-Robert Coronary . ' ~: , ' ~

.

:L32231~

Balloon Dilation Catheter manufactured by Advanced Cardiovascular Systems.

Once the balloon is positioned within the stenotic region of the artery, the balloon is i:nflated for a 5 select length of time, preferably from about 10 seconds to about 30 minutes for procedures involving percutaneous : transluminal coronary angioplasty.

During inflation of the balloon 18, an oxygenated fluorocarbon compound emulsion is passed through the ; 10 second lumen 21 of the catheter 17 and into the arte~y 14 distal to the occlusion. The introduction of the fluoxo-carbon compound emulsion into the artery may be commenced before, simultaneously with or after the inflation of the balloon. The fluorocarbon compound emulsion may be administered at temperatures, between ambient (25C~ or body temperature, (37C). The partial pressure of oxygen (P02) in the emulsion is typically maintained in the range of from about 300 mm~g to about 650 mmHg with p02's in the upper portion of the range being preferred.

The rate at which the fluorocarbon compound emulsion is introduced into the artery will depend on the size of the artery which is being treated. The flow rate should be sufficient to prevent physiologically dama~ing ischemia. It is preferred that the flow rates be at least about 20 cc per minute. Lower flow rates are not preferred as they supply an insufficient amount of oxygen to the occluded tissue. It is also preferred that the flow rate does not exceed about 150 cc per minuts.
Greater flows are not preferred because they tend to generate high pressures within the artery which may cause rupture.

In order to minimize flow interruption during the procedure, it is preferred that the fluorochemical com-, , ~ ; , .~; :

.,.. . . -~ .: .

1 ~223~
g pound emulsion be injected into the catheter from a large sterile reservoir, e~g., up to 1000 ml volume, which can be refilled during the procedure.

The present invention is particularly suited to percutaneous transluminal coronary angioplasty procedures during coronary operations, e.g., to inflate a collapsed artery while supplying oxygen to the t:issue cut off by the collapse. It is also applicable to open blockecl coronary arteries and supply oxygen to ischemic tissue during or following myocardial infarction.

A similar, and equally applicable application of the present invention is in retroperfusing oxygenated perfluorocarbon compound emulsion irto coronary veins cut off from oxygen by occlusions in a coronary artery. In such an application, the balloon catheter is introduced into the coronar~ sinus. During diastole, the balloon is inflated and the oxygenated perfluorocarbon emulsion is retroperfused into the coronary veins. Inflation times are generally less than a second.

The preceding de~cription has been presented with reference to a presently preferred application of the invention, i.e., percutaneous transluminal coronary angioplasty. It is apparent that the invention is equally applicable to other percutaneous transluminal angioplasty procedures, e.g., renal, femoral or carotid including inter-operative procedures involving such arteries. It is also apparent that, depending on the specific procedure, the parameters of the procedure may vary. For example, for percutaneous transluminal angioplasty of arteries other than those serving the heart and brain, the preferred duration of each balloon inflation is at least about two minutes. For the carotid artery and other vessels serving the brain, it is . ... . . .

, ~3223~5 believed that durations of from about ten seconds to about fifteen minutes can be used.

It is also apparent that, if desired, oxygenated perfluorocarbon compound emulsion can be administered through the guiding catheter or other catheters to supply oxygen to the tissue proximal to the inflated balloon.
Additional perfluorocarbon compound emulsions may be admini~tered through perepherial I.V. lines, if desired.
The present invention offers the advantages that prolonged balloon inflation times can now be practised without resultant physiologically damaging ischemia~
Moreover, the present invention enables the angioplasty procedure to he per~ormed on multiple sites within a single vessel or in multiple vessels, again without ~ 15 resultant ischemia.

i EXAMPLE I
Twelve adult mongrel dogs, weighing 20 to 30 kg, were anesthetized with pentobarbital, 25 mg/kg I.V., and, after intubation, were placed on a Harvard volume respirator. An electrocardiogram was monitored and recorded continuously throughout the study. Bilaterial carotid artery cutdowns were performed, and a #8 French Millar end-tip manometer catheter was advanced to the left ventricle under fluoroscopic control for continuous monitoring of pressure and dp/dt. A #10 French guiding catheter was advanced to the osti~m of the left coronary artery under fluoroscopy; and a 3.0 mm balloon catheter (either the USCI Gruntzig catheter or the ACS Simpson-Robert catheter) was passed, coaxially through the guiding catheter, into the circumflex branch. In one dog, the balloon catheter was placed in the left anterior descending branch (dog #7)~ Heparin, 5000 units, was given i.v. in each dog. No anti-arrhythmic drugs were given to any dog at any time.

,.. .

- . :: : :.: ~:, ~ . . . .. .

. . . ,. : , . .:
... .. . ...

~322315 Fluosol-DA1 20% was oxygenated ~y bubbling oxygen through a tube into the solution for 30 minutes~ In this manner, a P02 Of 600 mmHg was achieved. When 100% oxygen was passed over Fluosol-DA 20%, in a vlented bottle while the solution was slowly swirling, similar oxygenation (600 mmHg) was obtainable.

The infusion of Fluosol-DA 20% -through the central lumen of the balloon catheter was initiated be~ore balloon inflation and after recording the baseline ECG, ~V pressure; and dp/dt at 50 mm/sec paper speed. A low flow roller pump was used to deliver the Fluosol-DA 20%.
The flow rate, which had been already measured before insertion of the balloon catheter, was again determined.
If the flow rate was satisfactory, the balloon was then inflated; if not, the flow was adjusted to the desired level before balloon inflation. Inflation of the balloon was performed with contrast medium, so that the inflation could be followed fluoroscopically. Contrast medium was injected into a proximal portion of the left main coronary artery through the guiding catheter, after balloon inflation, in order to confirm that the inflation resulted in complete occlusion of the branch to the antegrade flow of blood.

The ECG, LV pressure, and dp/dt were recorded periodically at 50 mm/sec paper speed during the infusion and, in the majority of the dogs, during the 15 to 30 minute period following the completion of the Fluosol-DA
20% perfusion. A postmortem examination of the heart was performed at the end of each study by sectioning the myocardium at 1 cm intervals and by making a longitudinal 1 Fluosol-DA 20% is a trade mark for a perfluorocarbon compound emulsion manufactured by the Green Cro5s Corporation of Osaka, Japan .
, ~
. : :

, : . . .:
.
: ..

1 3223~

incision along the length of all major branches of the coronary arteries.

Dogs were perfused with Fluosol-DA 20% at flow rates ranging from 5 to 30 ml/min while balloon inflation times ranged from 8 to 53 minutes. No dog in the Fluosol-DA
20% group died prematurely, i.e., before comple~ion of the Fluosol-DA 20% perfusion and post-perfusion periods of observation had ended. The baseline data was obtained after approximately 15 to 45 seconds of balloon occlusion with no infusion of any oxygenated material through the distal port of the catheter.

Perfusion with Fluosol-DA 20% was inadequate in Dog #3 (only 5 cc/min), since Silastic tubing was used in the roller pump. This tubing collapses excessively with movement of the roller pump head, so that a higher flow rate could not be achieved in this dog. ST segment depres~ion on the ECG occurred, while no hemodynamic or post-mortem changes were noted. With the use of tygon tubing in the other 11 dogs any desired flow rate was easily achieved.
;

In Dog ~7, the balloon catheter could not be placed in the circumflex branch and was therefore placed in the left anterior descending branch. The latter had numerous large side branches (diagonal and septal perforators), four or five of which were obstructed by the inflated ~alloon. These branches, which were proximal to the tip of the balloon catheter, could not receive Fluosol-DA
20%, and it was not surprising, therefore, that hemorrhage in the distribution of these branches (the septum) was found. Marked ST-T wave changes on the ~CG
occurred wi-thin seconds of balloon inflation, while systemic pressure fell to 75 mmHg. Of interest in this study was the observation that the fre~uency of baseline PVC's, 6.8% of the normal beats, decreased to 4.3% during . .

~,, ~.., . ~ ., .

:: ''' . '. ' .' '. , '' ..

1 3223~5 Fluosol infusion, and increased markedly in the post-infusion period to 19.8%~

In Dog #12, the balloon catheter was advanced quite far distally, due to the large size of the circumflex artery in the dog, and balloon inflation resulted in obstruction of a moderate sized branch. Elevation of the ST segment on the ECG occurred within several minutes and, on postmortem examination~ a smal:L area of hemorrhage over the epicardium only (no intramural changes were seen) was noted in the region corresponding to the obstructed branch. There were no hemodynamic effects of this occlusion, and no arrhythmias occurred.

In the remaining nine dogs, there were no EKG
changes, no arrhythmias, no adverse hemodynamic ~effects, and no abnormal postmortem pathology demonstrable either during or after myocardial perfusion with Fluosol-DA 20%.

EXAMPLE II
An additional control animal was investigated in which oxygenated saline (P02 greater than 600 mmHg) was passed through the distal paxt of the catheter. In this animal the procedure was carried out exactly as in dogs 8 through 12 of Example I, but oxygenated saline was infused at 60 ml/min into the coronary artery. This dog developed ventricular fibrillation and died within two minutes.

EXAMPLE III
A second animal wa~ also prepared similar to dogs 8 though 12 of Example I. This animal received a pre-dose of methylprednisolone (10 mg/kg) at 24 hours and 10 minutes pre-infusion~ This animal received (30 ml/min) Fluosol-DA 20% for eight minutes. No abnormalities were observed, but after a 15 minute recovery period the procedure was aborted.

. , ,: ,, ,, . :

~,, , . . , , ,:
,~ , ~322315 ~ 14 -EXAMPLE IV
Thirty-one human patients were randomized into Fluosol-DA 20% (F-DA) treated (n=14) and control ln=17) groups prior to elective percutaneous transluminal coronary angioplasty (PTCA), which was initially performed in all patients in a routine manner. In the F-DA group, following steroid premedication and a 3.5~c i.v. test dose, i.c. F DA was infused at 0.5cc/sec x 1 min. before and during balloon inflation if routine PTCA
had been performed without difficulty (n=lO). In response to PTCA, the two groups did not differ clinically, angio-graphically, hemodyn~mically, or by serial ECG's. RA, PA, and PA wedge pressures each increased slightly in both groups immediately following PTCA (P .05), but these changes were not different between groups. Coagulation profiles, blood chemistries, and CBC's before and one day after PTCA did not differ between groups, except for a greater W~C rise in the F-DA
group (P .01~, which very likely resulted from the steroid medication.

EXAMPLE V
In a cross-over study involving twenty-five human patients, each patient was treated with a routine (single inflation) PTCA procedure and then randomized to receive additional PTCA procedures using perfusion with oxygenated Fluosol-DA 20% ~F-DA) and then oxygenated lactated Ringer's solution or the reverse.
Electrocardiograms (EKG) (abnormalities in EKG vallles are indicators of physiological ischemia) were obtained for each patient during each procedure and the duration of any EKG abnormalities were assessed for each portion of the study. In 18 of the 25 patients the duration of EKG
abnormalities was significantly longer (P 0.05) during lactated Ringer's PTCA than during F-DA PTCA as shown in Graph I below.

~ .

. ', ,' " ~

223~5 Vl ~ C ~o ` o ,_ C~J

O ~ _ C

O ~ " ~ ~o E E IJ
Ol~ ~ r~ O

O ~ _ C ~ Q~
~ r ~7 -, . I . ~ 61. ~ _ o _ L
O~,_, .n O ~ '-- ~ ~
S p U O ~ ~ S . . -- -- _ ~U
cJ ~ ~

o ~ c: --_ ~ o ~
Ylld-s,~a6Ul~ pa~el~el - . . .

~322315 These EKG abnormalities lasted 15.5 ~ 9.7 seconds longer during lactated Ringer's-PTCA than durin~ F DA
PTCA. This difference is suppressed due to early termination of lactated Ringer's-PTCA procedure in 8 patients after marked EKG changes and/or anginal pain wa~
experienced by the patient.

EXAMPLE VI
The severity of anginal pain (a measure of physio logical ischemia) experienced during each phase of the PTCA procedure described above in Example V was also assessed. The results are shown in Graph II below.

The severity of anginal pain was scored on a ten point scale with zero equal to no pain and nine representing unbearable pain. Of the 25 patients, 11 patients had pain of the same score with either prolonged dilatation procedure. Twelve patients had less severe pain with F-DA-PTCA than with lactated Ringer's-PTCA.
The mean difference in severity pain scores was 1.7.
Pain experienced during F-DA-PTCA was significantly (p=0.002) less than during lactated Ringer's-PTCA.

Although the duration of the pain was similar, the time to onset and the severity of pain were signiicantly improved with F-DA-PTCA as a prolonged dilatation procedure compared to lactated Ringer's-PTCA.

EXAMPLE VII
The stenotic gradients of the treated vessels were also assessedO The results are shown in Graph III below.
The stenotic gradient is the pressure on the proximal side of the stenotic lesion subtracted from the pressure on the distal side of the lesion. A reduction in the stenotic gradient after PTCA is a measure of the improve-ment of vessel architecture afected by the procedure.

. . .: , ~ : , ., . ~ . .

: I
~32~31~

.

.~
:

"
, \

Q~
~s~ . C
\
~ \ i C \ :
C \ ' C
o ~ i ~1 ~, ~ ~ ~ ~ ~ ~ o '~ ~ C C
~ 'i > V~ ': E
., ~ t~ CL \ i Q' ~, , U ~ ,_, _ o C \ . ~ C L- o o ~ ~, C ~
Ct \ ~ ~ ~ ^ CJ
4_ o ~ ~ ta ~ ~ C
L L 0-~--~J `' \ ~ O O i:J
L
\ ' i C C U- ~
_ \ O O U U
_ _ _ ~
~-- 4_ -- L
L ~ ~ 1~) . _ O X _ ____.____._________._ _ _.____.____. _ _.____.___~ .
~ C

a~o~S ~ aAas Uled ~ld--S,Ja6UI`d pa~e~e )~ , ,, :', :"' ~ ' .':, ' . .

1~2231~

A stenotic gradient of less than 20 mm Hg after PTCA
indicated a successful procedure while a procedure giving a gradient of less than 16 mm Hg is considered to give results equivalent to a coronary artery bypass graft procedure (CABG).

In 8 of 25 patients, the trans-stenotic gradient was further reduced as a result of prolonged dilatation of the diseased vessel~ Improved vessels included six L~, one RCA and one CIRC. In 7 of these 8 patients, the gradient was reduced to 20 mm Hg or less with the prolonged dilatation--an indication of successful PTCA
results.

To achieve coronary flow reserve post-PTCA, which would be equivalent to CABG, the achieved gradient should be 16 mmHg. Following Routine-PTCA the success of achieving a trans-stenotic gradient 16 mm Hg was only 60%; the success rate was increased to 76~ with the prolonged dilatation procedures. The prolonged dilatation also improved the gradient in three patient~
to 17, 19 and 20 mm Hg from post Routine-PTCA levels of 35, 28, and 43 mm Hg, respectively.

Following Routine-PTCA, 76% of the patients had reduced gradients lower than the critical gradient associated wikh a loss of hyperemic reserve (32 mmHg).
After prolonged dilatation, the success rate was increased to 96% of the patients.

Overall, prolonged dilatation improved the trans-stenotic gradient in 32% of the patients (mean improvement of 18.6 mmHg) compared to results following routine-PTCA suggesting that the artery lumen contour was improved in those patients.

~( .

,. ,. :: , 23~

_ C

H ¦ V~ C C ~A _ .
~~ nn~
~ V`
-~ 1l n ~ ~ n n _ ~

O CO O O O O O OO
6 ~

`

. ; .

, ,~ , .

Claims (8)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. Use of an oxygenated perfluorocarbon compound emulsion for providing oxygen to a location distal to an inflated balloon of a balloon tipped catheter, the balloon being located in a stenotic region of an artery during angioplasty.

2. Use as claimed in claim 1 in which the perfluorocarbon compound emulsion has an oxygen partial pressure of at least about 300 mm of mercury.

3. Use as claimed in claim 1 in which the oxygenated perfluorocarbon compound emulsion is passed into the artery at a rate sufficient to prevent physiologically damaging ischemia.

4. Use as claimed in claim 3 in which the oxygenated perfluorocarbon compound emulsion is passed into the artery at a rate of from about 20 cc/min. to about 150 cc/min.

5. Use as claimed in claim 1 in which the balloon is inflated during the angioplasty for about 10 seconds to about 30 minutes.

6. Use as claimed in claim 5 in which the artery is a coronary artery and wherein the balloon is inflated for about 30 seconds to about 15 minutes.

7. Use as claimed in claim 5 in which the artery is the carotid artery and wherein the balloon is inflated for about 10 seconds to about 15 minutes.

8. Use as claimed in claim 5 in which the artery is a renal or femoral artery and wherein the balloon is inflated for at least about 2 minutes.