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SINGLE AND DOUBLE CONTRAST CORONARY ARTERIOGRAPHY
SINGLE A N D DOUBLE CONTRAST CORONARY ARTERIOGRAPHY Utilizing Acetylcholine Asystole With Controlled Return of Heart Rate Using a Cardiac Pacemaker Aydin M. Bilgutay,
M.D.
(by invitation),
C. Walton
M.D.,
Minneapolis,
Lillehei,
and Minn.
T
o achieve well-opacified filling of diseased and narrowed coronary arteries has been a challenging problem to overcome in angiography. The coronary arteries receive their major share of blood supply during diastole when the myocardium relaxes and the direction of blood flow in the aorta reverses. Anatomically the oblique exit of coronary arteries from the root of the aorta in the direction opposite that of the blood stream also favors diastolic filling. To direct more blood flow to coronaries during angiography, Dotter 5 described balloon-aortic occlusion during injection for coronary arteriography. Arnulf 1 had achieved this simply by arresting the heart in diastole with acetylcholine. This latter method permitted favorable conditions, both for injection of contrast media for better coronary filling when the coronaries were more receptive and also for better filming when the heart was motionless. Wider clinical application of this procedure, however, was delayed because of the obvious dangers of stopping a heart, especially a diseased one, without a more positive method of restarting than that offered by an injection of atropine which under these circumstances of arrested circulation may not reach the myocardium in sufficient time and concentration. The methods herein described utilize acetylcholine arrest and a means for positive and controlled return of the heart rate using an internal pacemaker electrode placed in the right ventricle, for both single and double contrast coronary arteriography. EXPERIMENTAL DEVELOPMENT
In the experimental animal, acetylcholine, when given in sufficient doses, induces asystole. When the same amount of acetylcholine is injected in the From The Department of Surgery, University of Minnesota Medical School, and Variety Club Heart Hospital, Minneapolis, Minn. Supported by research grants from (1) Graduate School, University of Minnesota; (2) Life Insurance Medical Research F u n d ; (3) Minnesota Heart Association; (4) U. S. Public Health Service, Grant No. H-830; and (5) Benefactors of Cardiovascular Surgical Research Fund. Read at the Forty-second Annual Meeting of The American Association for Thoracic Surgery a t St. Louis, Mo., April 16-18, 1962. 617
BILGUTAY AND LILLEHEI
618
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same or different animals under the same conditions, the duration of asystole is variable and often unpredictable. The mode of recovery after induced asystole is also of unpredictable type and duration. I t may be followed by unconducted P waves, slow nodal beats, irregular ventricular escapes, complete and changing atrioventricular block, atrial fibrillation, atrial flutter, or ventricular tachycardia before sinus tachycardia and pre-asystole rates return (Fig. 1). Aeetylcholine has a more pronounced effect upon the atrial wall and the atrioventricular node
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Fig. 1.—Effect of 100 mg. of aeetylcholine on canine heart following intra-aortic administration. Continuous electrocardiogram (Dog No. 2649, 12.1 Kg.). A, Note prolonged asystole upon injection of aeetylcholine. Many unconducted P waves and an idioventricular rate are seen. B, Development of atrioventricular block, atrial nutter, and ventricular tachycardia following arrest. C, Ventricular tachycardia and atrial nutter. D, Atrial fibrillation. E, Thirty seconds later, prearrest rhythm has returned.
synapse. 2 ' *•7 Its initial effect appears to block any pacemaker activity at the supraventricular level, thus dissociating the ventricles from any atrial pacemaker control. The ventricles are the last to be suppressed by aeetylcholine. Therefore, they may still preserve their irritability and contractility, and, indeed, given time, they may start their own idioventricular rate after a brief period of asystole. Such ventricles are also able to respond to any direct stimulation, either mechanical or electrical, 2 ' 9 for reasons mentioned above, and can, therefore, be paced at a desired rate artificially. Thus, induced controlled heartbeat, following asystole, can be maintained at a regular rate until the heart recovers completely from the effect of aeetylcholine without going through the dangerous arrhythmias that occur during the recovery phase (Fig. 2).
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CORONARY ARTERIOGRAPHY
Vol. 44, No. 5 November, 1962
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Fig. 2.—Effect of 100 mg. acetylcholine after intra-aortic administration. Continuous electrocardiogram (Dog No. 2880, 12 Kg.). A, Note prolonged asystole following injection of acetylcholine. Undulations are due to respiratory efforts. B, Slow idioventricular beats, merging into ventricular fibrillation in C. Myocardial anoxia incident to a more prolonged asystole was probably also instrumental in development of ventricular tachycardia and fibrillation in this case.
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Fig. 3.—Continuous electrocardiogram showing controlled maintenance of heart rate by pacemaker stimulation after asystole induced by 200 mg. acetylcholine (Dog No. 329, 12.5 Kg.). Heretofore this dose has been uniformly fatal in dogs even with immediate atropine treatment. Note the initiation and maintenance of a regular rate without arrythmias with the use of the pacemaker during the phase of recovery (A and B). O, The return of the heart's own beat was checked by turning off the pacemaker temporarily with immediate arrest. D, The heart is still maintained on the pacemaker. E, The heart's own beats begin to appear independently from those of the pacemaker. F, The pacemaker is discontinued, pre-injection rate has returned, and the animal survived.
620
BILGUTAY AND LILLEHEI
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We have tested this response in eighty attempts in 20 dogs with varying doses of acetylcholine up to 10 mg. per kilogram. "With the cardiac rate maintained by the pacemaker after acetylcholine induced asystole, the blood pressure is immediately restored and the dangers of serious or fatal arrhythmias due to myocardial anoxia are obviated. The phase of recovery with its associated arrhythmias, when acetylcholine arrest alone is utilized, is replaced by a regular beat of the pacemaker and the time for return of the previously present heart rhythm is greatly shortened 2 (Fig. 3).
INJECTOR
Fig. 4.—Technique for coronary arteriography with acetylcholine arrest and pacemaker restoration of heartbeat. The pacemaker electrode is placed in the right ventricle. The polyethylene catheter is positioned Just above the aortic valve. Acetylcholine is injected through the arterial catheter. Arrest is observed on the visoscope. The arterial catheter is then switched to the injector, the contrast medium is injected, and biplane angiography films are exposed; The heartbeat is started immediately at the desired time by turning on the pacemaker. SINGLE CONTRAST CORONARY ARTERIOGRAPHY
The method for clinical coronary arteriography developed is as follows: Through a saphenous vein cutdown, a long intracardiac pacemaker electrode is introduced and advanced to make contact with the right ventricular wall. Through the same cutdown, the common femoral artery is also exposed and a multiple side-holed, closed-end, inverted J-shaped, No. 320 polyethylene catheter is introduced into the aorta and positioned just above the aortic valve. Both procedures are done under fluoroscopy with the use of an image intensifier. The elec-
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November, 1962
CORONARY ARTERIOGRAPHY
621 V£,L
trode is then connected to the negative pole of a transistorized pacemaker and the positive pole is grounded to the edge of the wound (Pig. 4). The pacemaker is turned on for an initial test prior to injection to check its position, and the response of the heart is recorded on the electrocardiogram (Fig. 5, A ) . The aortic catheter is connected to an automatic pressure injector by means of a three-way stopcock. The injector is timed with the Elema-Schonander apparatus to take biplane roentgenograms simultaneously. Acetylcholine is then injected, the stopcock is switched to the injector, and, with the onset of asystole followed on the electrocardiogram or visoscope, the injector and the Schonander apparatus are triggered. Thirty-five cubic centimeters of 75 per cent Hypaque under a pressure of 5 kilograms per square centimeter is used for injection. After allowing 3 to 5 seconds for asystole and exposure of the films, the pacemaker is turned on
Pig. 5.—Electrocardiogram of patient (Mrs. A. P.) during coronary arteriography with acetylcholine asystole and pacemaker restoration. (July 21, 1962.) A, Response of the heartbeat to electrical stimulation as checked before the arrest was induced. B, Forty-five milligrams of acetylcholine was delivered into the root of the aorta. Arrest was immediate and the injection of the contrast medium and simultaneous x-ray filming were started with the onset of the arrest. After allowing 3% seconds of arrest, during which time the filming was completed, the pacemaker was turned on. C, The heart's response to the pacemaker. Atropine was given during this time while the heartbeat was maintained by the pacemaker. D, The patient's own beats begin to appear independently from those of the pacemaker. E, The pacemaker is turned off after 3 minutes. There are still S-T elevations and positive T waves a t this time. F, Fifteen minutes later. The electrocardiogram reading has now returned to the prearrest tracing.
622
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and is kept on until the patient's own heartbeat has returned without arrhythmias (Fig. 5, B-F). This fact is easily cheeked by turning off the pacemaker temporarily. In the meantime, an equivalent dose of atropine can be given to counteract the effect of the remaining acetylcholine but is not necessary and may even be better omitted so as not to trigger a tachycardia.
Fig:. 6.—Coronary arteriography of a normal and surgically infarcted canine heart performed under acetylcholine asystole aid with pacemaker restoration of the heart rate. The cardiac electrode for pacemaker stimulation is in contact with the right ventricular endocardium. A, Normal canine heart. B, Infarcted canine heart. Note the occlusion site (arrow) and retrograde Ailing of the left circumflex artery via the well-developed collaterals.
Thus, in summary, after the desired time of asystole the heartbeat is positively induced and controlled by the pacemaker for a period (1 to 3 minutes) until the patient's own heartbeat is well established again. The various arrhythmias and their side effects are eliminated. Most important is that the return of the heartbeat is assured by the electrical stimulation. This method has been tested extensively in animals (Fig. 6, A and B) prior to its acceptance
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for clinical application. Currently it is being used clinically as the method of choice at the University of Minnesota Hospitals as it provides significantly superior visualization of the coronary arteries with safety insured by the ability to restore immediate cardiac function by electrical stimulation. The first clinical application of this method15 was in a patient who had had a preoperative coronary
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angiogram without arrest (Pig. 7, A) and then a myocardial revascularization procedure. 13 Nine months after operation a postoperative coronary arteriography was carried out utilizing acetylcholine arrest with pacemaker control as shown in Fig. 7, B. So far the coronary arteriograms obtained in 4 patients with this new technique have confirmed the fact that visualization is significantly superior (Pig. 8). DOUBLE CONTRAST CORONARY
ARTERIOGRAPHY
To facilitate further improvements for demonstrating detailed coronary arterial anatomy from their origins to their distal ramifications, we have combined this method with a technique for double contrast angiography utilizing a spe-
624
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cially designed unit for controlled injection of carbon dioxide 3 (Fig. 9). In this latter technique, the preliminary steps are similar to the method described above. After positioning of the cardiac electrode and injection catheter in place, the catheter is filled with 75 per'cent Hypaque (5 c.c.) and then it is connected to the C0 2 injection control unit. The injector is set to deliver 25 c.c. of carbon dioxide under pressure of 75 to 100 pounds per square inch and asystole is in-
,., T F ' S ; s 8 - — 9 ? r o n a r y arteriogram with acetylcholine arrest and pacemaker control (Patient Mr. R. D.). (A, Anteroposterior view. B, Lateral view.) Pacemaker electrode is seen in the right ventricle. Note diffuse, pathologic narrowing and beading of left circumflex and complete obstruction of anterior descending and right coronary arteries. " "s"<.
Fig. 9.—Gas control injection unit for double contrast cardioangiography utilizing carbon dioxide.
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duced by intravenous injection of acetylcholine. Controlled restoration of the heartbeat upon completion of the injection and the exposure of the films is achieved by turning on the pacemaker as described above. "With this method, the ostia and lumina of the coronary arteries and narrowings or occlusions and, even, the arteriosclerotic plaques may be clearly outlined in double contrast (Fig. 10).
Fig-. 10.—Double contrast coronary arteriography utilizing acetylcholine for asystole and pacemaker stimulation for controlled restoration of the heart rate (Dog No. 182, 15 Kg.). Injection of 4 c.c. of 75 per cent Hypaque and 25 c.c. of carbon dioxide was made by the gas injection control unit. The pacemaker electrode is seen in the right ventricle. Note the details visible in the great vessels and coronary arteries as well as the anatomy of the individual aortic valve cusps. The arrow points to the left circumflex coronary artery which has been surgically occluded near its origin. DISCUSSION
As is well known, diseased coronary arteries fill poorly and thus contrast is more difficult to achieve as the severity of the obstruction increases. To obtain better coronary filling for radiographie demonstration, Dotter 5 has used
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balloon aortic occlusion during injection. Thai 12 developed phasic injection triggered by the E wave of the patient. Sones11 utilized cine-coronary arteriography with selective catheterization of the individual ostia. The injection of contrast medium during asystole is an excellent means for outlining narrowed and poorly perfused vessels and may offer the best means of obtaining coronary opacification, but wider application of this procedure has awaited further improvements to make it safer and more reliable. The analysis of the response of hearts to acetylcholine in electrocardiograms of 70 dogs and our experimental and clinical work with development of pacemaking equipment for control of complete heart block 10 ' 14 suggested the combination of acetylcholine for asystole and pacemaker restoration of the heartbeat for obtaining coronary arteriograms more safely. Extensive experiments and initial clinical application have proved this procedure to be simple, feasible, and to have a wider margin of safety. "With the development of a technique for double contrast angiography accomplished by the design and construction of a new unit for controlled injection of carbon dioxide3, we have combined the method of inducing asystole and controlling restoration of the heart rate with double contrast angiography for more direct visualization of detailed changes within the coronary arteries. The C0 2 injection control unit permits use of minimal amounts of contrast medium (5 c.c.) with 25 c.c. of carbon dioxide with maximum effect. Carbon dioxide is readily diffusible in blood, especially on the arterial side (C0 2 is twenty times more soluble in serum than a i r 3 ' 6 ) . Upon injection of double contrast for coronary arteriography, carbon dioxide may be seen in the coronary arteries to dissolve more readily and to disappear in a few cardiac cycles without interrupting the coronary circulation or interfering with the pacemaker restoration of the heartbeat. Electrocardiographic changes upon injection of double contrast without arrest may show slight diastolic prolongation for one beat with no other changes. No neurologic changes have been observed, either clinically or by blood brain barrier tests 8 with dosages in dogs of carbon dioxide up to 50 c.c. repeated three times at 2 minute intervals. The fact that this sensitive test remained negative further attests to the safety of the procedure. Moreover, the doses injected exceeded significantly those needed for good double contrast visualization. SUMMARY
Two new methods for coronary arteriography have been described. For single contrast coronary arteriography, asystole is induced by acetylcholine. Contrast medium is then injected while biplane films are exposed. The heartbeat is then started immediately upon completion of injection and controlled at the desired rate with pacemaker stimulation via an electrode previously introduced into the right ventricle through the saphenous vein. For double contrast coronary arteriography, a specially designed C0 2 injection control unit is utilized. For dogs only, 5 c.c. of 75 per cent Hypaque and 25 c.c. carbon dioxide under a pressure of 100 pounds per square inch need be delivered during induced asystole to obtain double contrast coronary arterio-
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grams. The restoration of heartbeat is again achieved by pacemaker stimulation. There are no sequelae from several times this amount of carbon dioxide. ADDENDUM
Sixteen patients have now had single or double contrast coronary arteriography by these methods without undesirable sequelae. REFERENCES
1. Arnulf, G.: De l'arteriographie methodique des coronaires grace a l'acetylcholine, Arch. mal coeur 52: 1121, 1959. 2. Bilgutay, A. M., Tuna, N., and Lillehei, C. W.: Mechanism of Conduction Disturbances in Hearts Arrested by Acetylcholme and Its Correction by Use of an Electronic Pacemaker. (To be published.) 3. Bilgutay, A. M., Wingrove, R. C , and Lillehei, C. W.: Double Contrast Left Cardioangiography Utilizing Carbon Dioxide. A Safe Method for Direct Vision of Luminal and Valvular Lesions Employing a New Device for Gas Injection, Surgery: 52: 77, 1962. 4. Cohn, A. E., and Macleod, A. G.: The Effect of Acetylcholine on the Mammalian Heart, Am. Heart J . 2 1 : 356, 1941. 5. Dotter, C. T., and Frische, L. H . : Visualization of Coronary Circulation by Occlusion Aortography: A Practical Method, Radiology 7 1 : 502, 1958. 6. Durant, M. T., Stauffer, H. M., Oppenheimer, M. J., and Paul, R. E . : The Safety of Intravascular C0 2 and Its Use for Roentgenologic Visualization of Intracardiac Structures, Ann. I n t . Med. 47: 191, 1957. 7. Goodman, L. S., and Gilman, A.: The Pharmacological Basis of Therapeutics, New York, 1956, The Macmillan Company, p. 426. 8. Hodges, P . C , Sellers, R. D., Story, J . L., Stanley, H., Torres, F., and Lillehei, C. W.: The Effects of Total Cardiopulmonary Bypass Procedures Upon Cerebral Function Evaluated by the Electroencephalogram and a Blood Brain Barrier Test in Extracorporeal Circulation, Springfield, 111., 1958, Charles C Thomas, Publisher, p. 279. 9. Lam, C. R., Gahagant, S. C , and Green, E : Acetylcholine Induced Asystole in Extracorporeal Circulation, Springfield, 111., 1958, Charles C Thomas, Publisher, p. 451. 10. Lillehei, C. W., Gott, V. L., Hodges, P . C , Long, D. M., and Bakken ; E. E . : Transistor Pacemaker for Treatment of Complete Atrioventricular Dissociation, J . A. M. A. 172: 2006, 1960. 11. Sones, F . M., J r . , Shirley, E. K., Proudfit, W. L., and Westcott, R. N . : Cine-Coronary Arteriography. Proceedings of the 32nd Annual Scientific Sessions, American Heart Association, 773, 1959. 12. Thai, A. P . : The Clinical Usage of Coronary Arteriography, Angiology 2: 238, 1960. 13. Vineberg, A., Deliyannis, T., and Pablo, G.: The Ivalon Sponge Procedure for Myocardial Revascularization, Surgery 47: 268 1960. 14. Weirich, W. L., Gott, V. L., Paneth, M., and Lilleliei, C. W.: The Control of Complete Heart Block by Use of an Artificial Pacemaker and a Myocardial Electrode, Circulation Res. 6: 410, 1958. 15. Bilgutay, A. M., and Lillehei, C. W : . New Method for Coronary Arteriography. Acetylcholine Asystole With Controlled Return of H e a r t Rate Using a Pacemaker, J.A.M.A. 180: 69, 1962. (For Discussion,
see page
633)
M.D.
(by invitation),
C. Walton
M.D.,
Minneapolis,
Lillehei,
and Minn.
T
o achieve well-opacified filling of diseased and narrowed coronary arteries has been a challenging problem to overcome in angiography. The coronary arteries receive their major share of blood supply during diastole when the myocardium relaxes and the direction of blood flow in the aorta reverses. Anatomically the oblique exit of coronary arteries from the root of the aorta in the direction opposite that of the blood stream also favors diastolic filling. To direct more blood flow to coronaries during angiography, Dotter 5 described balloon-aortic occlusion during injection for coronary arteriography. Arnulf 1 had achieved this simply by arresting the heart in diastole with acetylcholine. This latter method permitted favorable conditions, both for injection of contrast media for better coronary filling when the coronaries were more receptive and also for better filming when the heart was motionless. Wider clinical application of this procedure, however, was delayed because of the obvious dangers of stopping a heart, especially a diseased one, without a more positive method of restarting than that offered by an injection of atropine which under these circumstances of arrested circulation may not reach the myocardium in sufficient time and concentration. The methods herein described utilize acetylcholine arrest and a means for positive and controlled return of the heart rate using an internal pacemaker electrode placed in the right ventricle, for both single and double contrast coronary arteriography. EXPERIMENTAL DEVELOPMENT
In the experimental animal, acetylcholine, when given in sufficient doses, induces asystole. When the same amount of acetylcholine is injected in the From The Department of Surgery, University of Minnesota Medical School, and Variety Club Heart Hospital, Minneapolis, Minn. Supported by research grants from (1) Graduate School, University of Minnesota; (2) Life Insurance Medical Research F u n d ; (3) Minnesota Heart Association; (4) U. S. Public Health Service, Grant No. H-830; and (5) Benefactors of Cardiovascular Surgical Research Fund. Read at the Forty-second Annual Meeting of The American Association for Thoracic Surgery a t St. Louis, Mo., April 16-18, 1962. 617
BILGUTAY AND LILLEHEI
618
J. Thoracic and Cardiovas. Surg.
same or different animals under the same conditions, the duration of asystole is variable and often unpredictable. The mode of recovery after induced asystole is also of unpredictable type and duration. I t may be followed by unconducted P waves, slow nodal beats, irregular ventricular escapes, complete and changing atrioventricular block, atrial fibrillation, atrial flutter, or ventricular tachycardia before sinus tachycardia and pre-asystole rates return (Fig. 1). Aeetylcholine has a more pronounced effect upon the atrial wall and the atrioventricular node
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Fig. 1.—Effect of 100 mg. of aeetylcholine on canine heart following intra-aortic administration. Continuous electrocardiogram (Dog No. 2649, 12.1 Kg.). A, Note prolonged asystole upon injection of aeetylcholine. Many unconducted P waves and an idioventricular rate are seen. B, Development of atrioventricular block, atrial nutter, and ventricular tachycardia following arrest. C, Ventricular tachycardia and atrial nutter. D, Atrial fibrillation. E, Thirty seconds later, prearrest rhythm has returned.
synapse. 2 ' *•7 Its initial effect appears to block any pacemaker activity at the supraventricular level, thus dissociating the ventricles from any atrial pacemaker control. The ventricles are the last to be suppressed by aeetylcholine. Therefore, they may still preserve their irritability and contractility, and, indeed, given time, they may start their own idioventricular rate after a brief period of asystole. Such ventricles are also able to respond to any direct stimulation, either mechanical or electrical, 2 ' 9 for reasons mentioned above, and can, therefore, be paced at a desired rate artificially. Thus, induced controlled heartbeat, following asystole, can be maintained at a regular rate until the heart recovers completely from the effect of aeetylcholine without going through the dangerous arrhythmias that occur during the recovery phase (Fig. 2).
619
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Vol. 44, No. 5 November, 1962
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Fig. 2.—Effect of 100 mg. acetylcholine after intra-aortic administration. Continuous electrocardiogram (Dog No. 2880, 12 Kg.). A, Note prolonged asystole following injection of acetylcholine. Undulations are due to respiratory efforts. B, Slow idioventricular beats, merging into ventricular fibrillation in C. Myocardial anoxia incident to a more prolonged asystole was probably also instrumental in development of ventricular tachycardia and fibrillation in this case.
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Fig. 3.—Continuous electrocardiogram showing controlled maintenance of heart rate by pacemaker stimulation after asystole induced by 200 mg. acetylcholine (Dog No. 329, 12.5 Kg.). Heretofore this dose has been uniformly fatal in dogs even with immediate atropine treatment. Note the initiation and maintenance of a regular rate without arrythmias with the use of the pacemaker during the phase of recovery (A and B). O, The return of the heart's own beat was checked by turning off the pacemaker temporarily with immediate arrest. D, The heart is still maintained on the pacemaker. E, The heart's own beats begin to appear independently from those of the pacemaker. F, The pacemaker is discontinued, pre-injection rate has returned, and the animal survived.
620
BILGUTAY AND LILLEHEI
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We have tested this response in eighty attempts in 20 dogs with varying doses of acetylcholine up to 10 mg. per kilogram. "With the cardiac rate maintained by the pacemaker after acetylcholine induced asystole, the blood pressure is immediately restored and the dangers of serious or fatal arrhythmias due to myocardial anoxia are obviated. The phase of recovery with its associated arrhythmias, when acetylcholine arrest alone is utilized, is replaced by a regular beat of the pacemaker and the time for return of the previously present heart rhythm is greatly shortened 2 (Fig. 3).
INJECTOR
Fig. 4.—Technique for coronary arteriography with acetylcholine arrest and pacemaker restoration of heartbeat. The pacemaker electrode is placed in the right ventricle. The polyethylene catheter is positioned Just above the aortic valve. Acetylcholine is injected through the arterial catheter. Arrest is observed on the visoscope. The arterial catheter is then switched to the injector, the contrast medium is injected, and biplane angiography films are exposed; The heartbeat is started immediately at the desired time by turning on the pacemaker. SINGLE CONTRAST CORONARY ARTERIOGRAPHY
The method for clinical coronary arteriography developed is as follows: Through a saphenous vein cutdown, a long intracardiac pacemaker electrode is introduced and advanced to make contact with the right ventricular wall. Through the same cutdown, the common femoral artery is also exposed and a multiple side-holed, closed-end, inverted J-shaped, No. 320 polyethylene catheter is introduced into the aorta and positioned just above the aortic valve. Both procedures are done under fluoroscopy with the use of an image intensifier. The elec-
Vol. 44No. 5
November, 1962
CORONARY ARTERIOGRAPHY
621 V£,L
trode is then connected to the negative pole of a transistorized pacemaker and the positive pole is grounded to the edge of the wound (Pig. 4). The pacemaker is turned on for an initial test prior to injection to check its position, and the response of the heart is recorded on the electrocardiogram (Fig. 5, A ) . The aortic catheter is connected to an automatic pressure injector by means of a three-way stopcock. The injector is timed with the Elema-Schonander apparatus to take biplane roentgenograms simultaneously. Acetylcholine is then injected, the stopcock is switched to the injector, and, with the onset of asystole followed on the electrocardiogram or visoscope, the injector and the Schonander apparatus are triggered. Thirty-five cubic centimeters of 75 per cent Hypaque under a pressure of 5 kilograms per square centimeter is used for injection. After allowing 3 to 5 seconds for asystole and exposure of the films, the pacemaker is turned on
Pig. 5.—Electrocardiogram of patient (Mrs. A. P.) during coronary arteriography with acetylcholine asystole and pacemaker restoration. (July 21, 1962.) A, Response of the heartbeat to electrical stimulation as checked before the arrest was induced. B, Forty-five milligrams of acetylcholine was delivered into the root of the aorta. Arrest was immediate and the injection of the contrast medium and simultaneous x-ray filming were started with the onset of the arrest. After allowing 3% seconds of arrest, during which time the filming was completed, the pacemaker was turned on. C, The heart's response to the pacemaker. Atropine was given during this time while the heartbeat was maintained by the pacemaker. D, The patient's own beats begin to appear independently from those of the pacemaker. E, The pacemaker is turned off after 3 minutes. There are still S-T elevations and positive T waves a t this time. F, Fifteen minutes later. The electrocardiogram reading has now returned to the prearrest tracing.
622
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and is kept on until the patient's own heartbeat has returned without arrhythmias (Fig. 5, B-F). This fact is easily cheeked by turning off the pacemaker temporarily. In the meantime, an equivalent dose of atropine can be given to counteract the effect of the remaining acetylcholine but is not necessary and may even be better omitted so as not to trigger a tachycardia.
Fig:. 6.—Coronary arteriography of a normal and surgically infarcted canine heart performed under acetylcholine asystole aid with pacemaker restoration of the heart rate. The cardiac electrode for pacemaker stimulation is in contact with the right ventricular endocardium. A, Normal canine heart. B, Infarcted canine heart. Note the occlusion site (arrow) and retrograde Ailing of the left circumflex artery via the well-developed collaterals.
Thus, in summary, after the desired time of asystole the heartbeat is positively induced and controlled by the pacemaker for a period (1 to 3 minutes) until the patient's own heartbeat is well established again. The various arrhythmias and their side effects are eliminated. Most important is that the return of the heartbeat is assured by the electrical stimulation. This method has been tested extensively in animals (Fig. 6, A and B) prior to its acceptance
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for clinical application. Currently it is being used clinically as the method of choice at the University of Minnesota Hospitals as it provides significantly superior visualization of the coronary arteries with safety insured by the ability to restore immediate cardiac function by electrical stimulation. The first clinical application of this method15 was in a patient who had had a preoperative coronary
Fig. 7. -JL, l"i'j,ji.».ii.iU\'. L'jiuiiui} jri'irioi-i..mi (>_-•(?i>
angiogram without arrest (Pig. 7, A) and then a myocardial revascularization procedure. 13 Nine months after operation a postoperative coronary arteriography was carried out utilizing acetylcholine arrest with pacemaker control as shown in Fig. 7, B. So far the coronary arteriograms obtained in 4 patients with this new technique have confirmed the fact that visualization is significantly superior (Pig. 8). DOUBLE CONTRAST CORONARY
ARTERIOGRAPHY
To facilitate further improvements for demonstrating detailed coronary arterial anatomy from their origins to their distal ramifications, we have combined this method with a technique for double contrast angiography utilizing a spe-
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cially designed unit for controlled injection of carbon dioxide 3 (Fig. 9). In this latter technique, the preliminary steps are similar to the method described above. After positioning of the cardiac electrode and injection catheter in place, the catheter is filled with 75 per'cent Hypaque (5 c.c.) and then it is connected to the C0 2 injection control unit. The injector is set to deliver 25 c.c. of carbon dioxide under pressure of 75 to 100 pounds per square inch and asystole is in-
,., T F ' S ; s 8 - — 9 ? r o n a r y arteriogram with acetylcholine arrest and pacemaker control (Patient Mr. R. D.). (A, Anteroposterior view. B, Lateral view.) Pacemaker electrode is seen in the right ventricle. Note diffuse, pathologic narrowing and beading of left circumflex and complete obstruction of anterior descending and right coronary arteries. " "s"<.
Fig. 9.—Gas control injection unit for double contrast cardioangiography utilizing carbon dioxide.
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v*-**
duced by intravenous injection of acetylcholine. Controlled restoration of the heartbeat upon completion of the injection and the exposure of the films is achieved by turning on the pacemaker as described above. "With this method, the ostia and lumina of the coronary arteries and narrowings or occlusions and, even, the arteriosclerotic plaques may be clearly outlined in double contrast (Fig. 10).
Fig-. 10.—Double contrast coronary arteriography utilizing acetylcholine for asystole and pacemaker stimulation for controlled restoration of the heart rate (Dog No. 182, 15 Kg.). Injection of 4 c.c. of 75 per cent Hypaque and 25 c.c. of carbon dioxide was made by the gas injection control unit. The pacemaker electrode is seen in the right ventricle. Note the details visible in the great vessels and coronary arteries as well as the anatomy of the individual aortic valve cusps. The arrow points to the left circumflex coronary artery which has been surgically occluded near its origin. DISCUSSION
As is well known, diseased coronary arteries fill poorly and thus contrast is more difficult to achieve as the severity of the obstruction increases. To obtain better coronary filling for radiographie demonstration, Dotter 5 has used
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balloon aortic occlusion during injection. Thai 12 developed phasic injection triggered by the E wave of the patient. Sones11 utilized cine-coronary arteriography with selective catheterization of the individual ostia. The injection of contrast medium during asystole is an excellent means for outlining narrowed and poorly perfused vessels and may offer the best means of obtaining coronary opacification, but wider application of this procedure has awaited further improvements to make it safer and more reliable. The analysis of the response of hearts to acetylcholine in electrocardiograms of 70 dogs and our experimental and clinical work with development of pacemaking equipment for control of complete heart block 10 ' 14 suggested the combination of acetylcholine for asystole and pacemaker restoration of the heartbeat for obtaining coronary arteriograms more safely. Extensive experiments and initial clinical application have proved this procedure to be simple, feasible, and to have a wider margin of safety. "With the development of a technique for double contrast angiography accomplished by the design and construction of a new unit for controlled injection of carbon dioxide3, we have combined the method of inducing asystole and controlling restoration of the heart rate with double contrast angiography for more direct visualization of detailed changes within the coronary arteries. The C0 2 injection control unit permits use of minimal amounts of contrast medium (5 c.c.) with 25 c.c. of carbon dioxide with maximum effect. Carbon dioxide is readily diffusible in blood, especially on the arterial side (C0 2 is twenty times more soluble in serum than a i r 3 ' 6 ) . Upon injection of double contrast for coronary arteriography, carbon dioxide may be seen in the coronary arteries to dissolve more readily and to disappear in a few cardiac cycles without interrupting the coronary circulation or interfering with the pacemaker restoration of the heartbeat. Electrocardiographic changes upon injection of double contrast without arrest may show slight diastolic prolongation for one beat with no other changes. No neurologic changes have been observed, either clinically or by blood brain barrier tests 8 with dosages in dogs of carbon dioxide up to 50 c.c. repeated three times at 2 minute intervals. The fact that this sensitive test remained negative further attests to the safety of the procedure. Moreover, the doses injected exceeded significantly those needed for good double contrast visualization. SUMMARY
Two new methods for coronary arteriography have been described. For single contrast coronary arteriography, asystole is induced by acetylcholine. Contrast medium is then injected while biplane films are exposed. The heartbeat is then started immediately upon completion of injection and controlled at the desired rate with pacemaker stimulation via an electrode previously introduced into the right ventricle through the saphenous vein. For double contrast coronary arteriography, a specially designed C0 2 injection control unit is utilized. For dogs only, 5 c.c. of 75 per cent Hypaque and 25 c.c. carbon dioxide under a pressure of 100 pounds per square inch need be delivered during induced asystole to obtain double contrast coronary arterio-
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grams. The restoration of heartbeat is again achieved by pacemaker stimulation. There are no sequelae from several times this amount of carbon dioxide. ADDENDUM
Sixteen patients have now had single or double contrast coronary arteriography by these methods without undesirable sequelae. REFERENCES
1. Arnulf, G.: De l'arteriographie methodique des coronaires grace a l'acetylcholine, Arch. mal coeur 52: 1121, 1959. 2. Bilgutay, A. M., Tuna, N., and Lillehei, C. W.: Mechanism of Conduction Disturbances in Hearts Arrested by Acetylcholme and Its Correction by Use of an Electronic Pacemaker. (To be published.) 3. Bilgutay, A. M., Wingrove, R. C , and Lillehei, C. W.: Double Contrast Left Cardioangiography Utilizing Carbon Dioxide. A Safe Method for Direct Vision of Luminal and Valvular Lesions Employing a New Device for Gas Injection, Surgery: 52: 77, 1962. 4. Cohn, A. E., and Macleod, A. G.: The Effect of Acetylcholine on the Mammalian Heart, Am. Heart J . 2 1 : 356, 1941. 5. Dotter, C. T., and Frische, L. H . : Visualization of Coronary Circulation by Occlusion Aortography: A Practical Method, Radiology 7 1 : 502, 1958. 6. Durant, M. T., Stauffer, H. M., Oppenheimer, M. J., and Paul, R. E . : The Safety of Intravascular C0 2 and Its Use for Roentgenologic Visualization of Intracardiac Structures, Ann. I n t . Med. 47: 191, 1957. 7. Goodman, L. S., and Gilman, A.: The Pharmacological Basis of Therapeutics, New York, 1956, The Macmillan Company, p. 426. 8. Hodges, P . C , Sellers, R. D., Story, J . L., Stanley, H., Torres, F., and Lillehei, C. W.: The Effects of Total Cardiopulmonary Bypass Procedures Upon Cerebral Function Evaluated by the Electroencephalogram and a Blood Brain Barrier Test in Extracorporeal Circulation, Springfield, 111., 1958, Charles C Thomas, Publisher, p. 279. 9. Lam, C. R., Gahagant, S. C , and Green, E : Acetylcholine Induced Asystole in Extracorporeal Circulation, Springfield, 111., 1958, Charles C Thomas, Publisher, p. 451. 10. Lillehei, C. W., Gott, V. L., Hodges, P . C , Long, D. M., and Bakken ; E. E . : Transistor Pacemaker for Treatment of Complete Atrioventricular Dissociation, J . A. M. A. 172: 2006, 1960. 11. Sones, F . M., J r . , Shirley, E. K., Proudfit, W. L., and Westcott, R. N . : Cine-Coronary Arteriography. Proceedings of the 32nd Annual Scientific Sessions, American Heart Association, 773, 1959. 12. Thai, A. P . : The Clinical Usage of Coronary Arteriography, Angiology 2: 238, 1960. 13. Vineberg, A., Deliyannis, T., and Pablo, G.: The Ivalon Sponge Procedure for Myocardial Revascularization, Surgery 47: 268 1960. 14. Weirich, W. L., Gott, V. L., Paneth, M., and Lilleliei, C. W.: The Control of Complete Heart Block by Use of an Artificial Pacemaker and a Myocardial Electrode, Circulation Res. 6: 410, 1958. 15. Bilgutay, A. M., and Lillehei, C. W : . New Method for Coronary Arteriography. Acetylcholine Asystole With Controlled Return of H e a r t Rate Using a Pacemaker, J.A.M.A. 180: 69, 1962. (For Discussion,
see page
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