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AN EXPERIMENTAL CYANOTIC CARDIOVASCULAR DISEASE MODEL
A N EXPERIMENTAL C Y A N O T I C CARDIOVASCULAR DISEASE MODEL Lawrence I. Zaroff, Captain, MC, USA, and Edward Captain, MC, USA, Fort Sam Houston,
Lowenstein,
Texas
T
HE recent surge of interest in the clinical use of hyperbaric oxygenation has stimulated the development of experimental models and techniques for laboratory studies. This paper presents a simple and rapid technique for the production of a cyanotic cardiovascular disease model in the dog, by complete diversion of the inferior vena cava into the left atrium without extracorporeal circulation and without removal of lung tissue. TECHNIQUE
Mongrel dogs, 18 kilograms and above, of either sex were utilized, since smaller animals have vessels of a size which makes the operation more difficult. Through a standard right thoracotomy, in the sixth intercostal space, a partial occluding clamp is applied to the inferior vena cava just before it enters the right atrium, and a short, half-inch diameter, woven Teflon or Daeron graft is sutured end-to-side to the inferior vena cava with a continuous 4-0 silk suture. A small bulldog elamp is applied to the pulmonary artery supplying the right lower lobes, and the pericardium is then opened at the point where the right inferior pulmonary vein enters the left atrium. With the inferior pulmonary vein used to elevate the left atrium, a small portion of the left atrium is isolated between clamps. The left atrium is opened and the graft sutured in place (Fig. 1). The operation is completed by tying off the inferior vena cava with an umbilical tape at the point of entrance into the right atrium, thus completely diverting inferior vena cava flow into the left side of the heart (Fig. 2). The procedure takes approximately 1 hour. RESULTS
Of the first 12 animals operated upon with this technique, 7 died immedi ately after operation or within 24 hours (Table I ) . These deaths were asso ciated with a marked fall in pH, which occurred upon sudden shunting of Prom the U.S. Army Surgical Research Unit, Brooke Army Medical Center, Fort Sam Houston, Texas. The principles of laboratory animal care as promulgated by the National Society for Medical Research were observed, AR 70-18, dated 29 March 1963. Received for publication Dec. 14, 1964.
897
898
ZAROFF AND LOWENSTEIN
J. Thoracic and Cardiovas. Surg.
Fig. 1.—Inferior vena cava—left atrium shunt hy means of a half-inch diameter graft.
Fig. 2.—Angiocardiogram shows complete diversion of inferior vena cava flow into left atrium through a Dacron graft.
CARDIOVASCULAR D I S E A S E MODEL
Vol. 49, N o . 5 May, 1965
TABLE I. GROUP I :
No
TREATMENT
OP INITIAL
899
ACIDOSIS
DOG
T I M E OF DEATH POSTOP.
POSTMORTEM F I N D I N G S
1 o 3 4 5 6 7 8 9 10 11 12
Immediate Immediate Immediate Immediate Immediate Immediate 24 hours 7 days 12 days 14 days 56 days Alive (1 yr.)
Pulmonary edema Pulmonary edema Graft angulated and clotted Negative Negative Negative Negative Empyema Pulmonary edema Congestive heart failure Congestive heart failure
TABLE I I .
GROUP I I :
TREATMENT OF INITIAL
T I M E OF DEATH POSTOP.
DOG
4 5 7 12 19 23
POSTMORTEM F I N D I N G S
Atelectasis, left lung Congestive heart failure Pulmonary edema Pulmonary edema Congestive heart failure Sacrificed; massive ascites: graft occluded Congestive heart failure Has ascites with partial graft occlusion
days days days days days days
28 days Alive (4 mo •) 9 10 11 12
Alive Alive Alive Alive
TABLE I I I .
mo ) mo •) mo ) mo )
(4 (4 (6 (9
MEAN pH,
ACIDOSIS
pC0 2 , AND p0 2
IN DOGS BREATHING
AIR
PERIOD POSTOP.
NO. OF DOGS
pH
pC02
po2
Normal Awake Pentobarbital
— —
11 24
7.42 7.42
34.2 34.4
87 84
Cyanotic Awake Awake Pentobarbital
2-4 days 3-10 mo. 2-26 days
9 5 10
7.50 7.51 7.49
24.6 23.7 25.9
39 43 40
unoxygenated blood into the left heart. The mean pH in these first 12 animals decreased from 7.39 to 7.19 within 30 minutes after opening the shunt. In a second group of 12 animals, the inferior vena cava was gradually occluded while titrating the acidosis to normal levels with sodium bicarbonate. There were no immediate deaths in this group. Table I I summarizes the re sults in the second group. Within 2 days, the shunted animals developed a persistent respiratory alkalosis associated with their low p 0 2 (Table I I I ) . Although only a few long-
900
ZAROFF AND LOWENSTEIN
J. Thoracic and Cardiovas. Surg.
term cyanotic dogs have been studied, the hematocrit data suggest the develop ment of polycythemia. DISCUSSION
Experimental cyanosis has been produced by pulmonary A-V fistulas, but these techniques have involved removal of significant amounts of lung tissue.1"3 Inferior vena cava left atrial shunting has been carried out for hyperbaric studies by others,4"6 without any description of the techniques involved. Eiseman and Spencer 7 were able to divert two thirds of the inferior vena cava blood into the left atrium in calves. However, this procedure required extracorporeal cir culation and the creation of an atrial septal defect. Although the usual fate of prosthetic grafts in the venous system has been rapid closure, Baffes8 has had excellent results with short, large diameter, woven Teflon grafts to the inferior vena cava in infants with transposition of the great vessels. We similarly attribute the patency of these grafts to their relatively wide diameter of one-half inch and to their short length of one half to three quarters of an inch. These animals have proved useful in a variety of acute and chronic ex periments.9"11 SUMMARY
A simple, rapid technique for complete diversion of the inferior vena cava into the left atrium, without cardiopulmonary bypass, has been described. This preparation has proved useful as a cyanotic cardiovascular disease model for hyperbaric oxygenation and other studies. REFERENCES
1. Blalock, A.: Effects of an Artificial Duetus Arteriosus on Experimental Cyanosis and Anoxemia, Arch. Surg. 52: 247-252, 1946. 2. Takaro, T., Essex, H. E., and Burchell, H. B . : Experimental Pulmonary Arteriovenous Fistula, Am. J . Physiol. 165: 513-519, 1951. 3. Dalton, M. L., Jr., and Hardy, J. D.: Experimental Pulmonary Arteriovenous Fistulas, Arch. Surg. 86: 455-459, 1963. 4. Fuson, R. L., Boineau, J . P., Smith, W., Saltzman, H. A., Spach, M., and Brown, I. W., J r . : Oxygen Transport and Acid-base Eesponses of Cyanotic Dogs to Hyperbaric Oxygenation, Clin. Res. 12: 182, 1964. (Abst.) 5. Agustsson, M. H., Baffes, T. G., Ketola, F . H., and Baffes, C. 6 . : Effect of Hyperbaric Oxygenation on Shunts, Hypoxia, and Cyanosis, Circulation 30: 39, 1964. (Suppl. No. 3, Abst.) 6. Pinto, D . : Personal communication, November, 1963. 7. Eiseman, B., and Spencer, F . C.: Surgical Technique to Produce Chronic Cyanosis in the Newborn Calf, Med. Thorae. 19: 573-575, 1962. 8. Baffes, T. G.: I n a discussion of "Importance of Porosity in Arterial Prosthesis," by W. J . F r y et al., Arch. Surg. 88: 836-842, 1964. 9. Zaroff, L. I., Lowenstein, E., Walker, H. L., and Villarreal, Y.: Excess Lactate in Cy anotic Dogs During Hyperbaric Oxygenation, S. Forum 15: 202-203, 1964. 10. Lowenstein, E., Walker, H. L., and Zaroff, L. I . : The Effect of a Standard Cyanotic Circulatory Lesion on the Induction Dose of Methohexital in the Dog, Anesthesiology ( I n press). 11. Zaroff, L. I., Lowenstein, E., Walker, H. L., Villarreal, Y., and Walters, R. W.: Hyper baric Versus Atmospheric Oxygen: Metabolic Effects in a Cyanotic Cardiovascular Disease Model. (To be published).
Lowenstein,
Texas
T
HE recent surge of interest in the clinical use of hyperbaric oxygenation has stimulated the development of experimental models and techniques for laboratory studies. This paper presents a simple and rapid technique for the production of a cyanotic cardiovascular disease model in the dog, by complete diversion of the inferior vena cava into the left atrium without extracorporeal circulation and without removal of lung tissue. TECHNIQUE
Mongrel dogs, 18 kilograms and above, of either sex were utilized, since smaller animals have vessels of a size which makes the operation more difficult. Through a standard right thoracotomy, in the sixth intercostal space, a partial occluding clamp is applied to the inferior vena cava just before it enters the right atrium, and a short, half-inch diameter, woven Teflon or Daeron graft is sutured end-to-side to the inferior vena cava with a continuous 4-0 silk suture. A small bulldog elamp is applied to the pulmonary artery supplying the right lower lobes, and the pericardium is then opened at the point where the right inferior pulmonary vein enters the left atrium. With the inferior pulmonary vein used to elevate the left atrium, a small portion of the left atrium is isolated between clamps. The left atrium is opened and the graft sutured in place (Fig. 1). The operation is completed by tying off the inferior vena cava with an umbilical tape at the point of entrance into the right atrium, thus completely diverting inferior vena cava flow into the left side of the heart (Fig. 2). The procedure takes approximately 1 hour. RESULTS
Of the first 12 animals operated upon with this technique, 7 died immedi ately after operation or within 24 hours (Table I ) . These deaths were asso ciated with a marked fall in pH, which occurred upon sudden shunting of Prom the U.S. Army Surgical Research Unit, Brooke Army Medical Center, Fort Sam Houston, Texas. The principles of laboratory animal care as promulgated by the National Society for Medical Research were observed, AR 70-18, dated 29 March 1963. Received for publication Dec. 14, 1964.
897
898
ZAROFF AND LOWENSTEIN
J. Thoracic and Cardiovas. Surg.
Fig. 1.—Inferior vena cava—left atrium shunt hy means of a half-inch diameter graft.
Fig. 2.—Angiocardiogram shows complete diversion of inferior vena cava flow into left atrium through a Dacron graft.
CARDIOVASCULAR D I S E A S E MODEL
Vol. 49, N o . 5 May, 1965
TABLE I. GROUP I :
No
TREATMENT
OP INITIAL
899
ACIDOSIS
DOG
T I M E OF DEATH POSTOP.
POSTMORTEM F I N D I N G S
1 o 3 4 5 6 7 8 9 10 11 12
Immediate Immediate Immediate Immediate Immediate Immediate 24 hours 7 days 12 days 14 days 56 days Alive (1 yr.)
Pulmonary edema Pulmonary edema Graft angulated and clotted Negative Negative Negative Negative Empyema Pulmonary edema Congestive heart failure Congestive heart failure
TABLE I I .
GROUP I I :
TREATMENT OF INITIAL
T I M E OF DEATH POSTOP.
DOG
4 5 7 12 19 23
POSTMORTEM F I N D I N G S
Atelectasis, left lung Congestive heart failure Pulmonary edema Pulmonary edema Congestive heart failure Sacrificed; massive ascites: graft occluded Congestive heart failure Has ascites with partial graft occlusion
days days days days days days
28 days Alive (4 mo •) 9 10 11 12
Alive Alive Alive Alive
TABLE I I I .
mo ) mo •) mo ) mo )
(4 (4 (6 (9
MEAN pH,
ACIDOSIS
pC0 2 , AND p0 2
IN DOGS BREATHING
AIR
PERIOD POSTOP.
NO. OF DOGS
pH
pC02
po2
Normal Awake Pentobarbital
— —
11 24
7.42 7.42
34.2 34.4
87 84
Cyanotic Awake Awake Pentobarbital
2-4 days 3-10 mo. 2-26 days
9 5 10
7.50 7.51 7.49
24.6 23.7 25.9
39 43 40
unoxygenated blood into the left heart. The mean pH in these first 12 animals decreased from 7.39 to 7.19 within 30 minutes after opening the shunt. In a second group of 12 animals, the inferior vena cava was gradually occluded while titrating the acidosis to normal levels with sodium bicarbonate. There were no immediate deaths in this group. Table I I summarizes the re sults in the second group. Within 2 days, the shunted animals developed a persistent respiratory alkalosis associated with their low p 0 2 (Table I I I ) . Although only a few long-
900
ZAROFF AND LOWENSTEIN
J. Thoracic and Cardiovas. Surg.
term cyanotic dogs have been studied, the hematocrit data suggest the develop ment of polycythemia. DISCUSSION
Experimental cyanosis has been produced by pulmonary A-V fistulas, but these techniques have involved removal of significant amounts of lung tissue.1"3 Inferior vena cava left atrial shunting has been carried out for hyperbaric studies by others,4"6 without any description of the techniques involved. Eiseman and Spencer 7 were able to divert two thirds of the inferior vena cava blood into the left atrium in calves. However, this procedure required extracorporeal cir culation and the creation of an atrial septal defect. Although the usual fate of prosthetic grafts in the venous system has been rapid closure, Baffes8 has had excellent results with short, large diameter, woven Teflon grafts to the inferior vena cava in infants with transposition of the great vessels. We similarly attribute the patency of these grafts to their relatively wide diameter of one-half inch and to their short length of one half to three quarters of an inch. These animals have proved useful in a variety of acute and chronic ex periments.9"11 SUMMARY
A simple, rapid technique for complete diversion of the inferior vena cava into the left atrium, without cardiopulmonary bypass, has been described. This preparation has proved useful as a cyanotic cardiovascular disease model for hyperbaric oxygenation and other studies. REFERENCES
1. Blalock, A.: Effects of an Artificial Duetus Arteriosus on Experimental Cyanosis and Anoxemia, Arch. Surg. 52: 247-252, 1946. 2. Takaro, T., Essex, H. E., and Burchell, H. B . : Experimental Pulmonary Arteriovenous Fistula, Am. J . Physiol. 165: 513-519, 1951. 3. Dalton, M. L., Jr., and Hardy, J. D.: Experimental Pulmonary Arteriovenous Fistulas, Arch. Surg. 86: 455-459, 1963. 4. Fuson, R. L., Boineau, J . P., Smith, W., Saltzman, H. A., Spach, M., and Brown, I. W., J r . : Oxygen Transport and Acid-base Eesponses of Cyanotic Dogs to Hyperbaric Oxygenation, Clin. Res. 12: 182, 1964. (Abst.) 5. Agustsson, M. H., Baffes, T. G., Ketola, F . H., and Baffes, C. 6 . : Effect of Hyperbaric Oxygenation on Shunts, Hypoxia, and Cyanosis, Circulation 30: 39, 1964. (Suppl. No. 3, Abst.) 6. Pinto, D . : Personal communication, November, 1963. 7. Eiseman, B., and Spencer, F . C.: Surgical Technique to Produce Chronic Cyanosis in the Newborn Calf, Med. Thorae. 19: 573-575, 1962. 8. Baffes, T. G.: I n a discussion of "Importance of Porosity in Arterial Prosthesis," by W. J . F r y et al., Arch. Surg. 88: 836-842, 1964. 9. Zaroff, L. I., Lowenstein, E., Walker, H. L., and Villarreal, Y.: Excess Lactate in Cy anotic Dogs During Hyperbaric Oxygenation, S. Forum 15: 202-203, 1964. 10. Lowenstein, E., Walker, H. L., and Zaroff, L. I . : The Effect of a Standard Cyanotic Circulatory Lesion on the Induction Dose of Methohexital in the Dog, Anesthesiology ( I n press). 11. Zaroff, L. I., Lowenstein, E., Walker, H. L., Villarreal, Y., and Walters, R. W.: Hyper baric Versus Atmospheric Oxygen: Metabolic Effects in a Cyanotic Cardiovascular Disease Model. (To be published).