Altered Physiology of the Pulmonary Vascular Bed

Altered Physiology of the Pulmonary Vascular Bed

Altered Physiology of the Pulmonary Vascular Bed A Factor in Decreased Function of the Reimplanted Lung* SALVATORE O'ITo O L. NIGRO, M.D., RICHARD...

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Altered Physiology of the Pulmonary Vascular Bed A Factor in Decreased Function of the Reimplanted Lung* SALVATORE

O'ITo

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L.

NIGRO, M.D., RICHARD

UT OF THE SEVERAL REPORTED EX-

periments of lung reimplantation, a few basic concepts have been derived. A number of dogs have survived for long periods of time after reimplantation of one lung; however, the animals do not live for more than a few weeks after complete one stage removal of the contralateral normal lung. t - I O The ventilatory function and oxygen consumption value of the transplanted lung is diminished to an average of 35 per cent of normal.Y":" In those animals that have survived reimplantation of one lung, the pulmonary artery pressures are elevated.':" This elevation in pressure becomes higher when the animal is forced to live on the reimplanted lung alone after complete ablation by staged resection and bronchial stenosis of the contralateral normal lung. The exact changes in the vascular bed of the reimplanted lung leading to this elevation in pulmonary artery pressure have not been adequately defined. All data derived from the physiologic studies performed on 23 dogs that have undergone right lung reimplantation in our laboratory were re-evaluated (Table 1). TABLE l-REIMPLANTATION OF THE LUNG IMMEDIATE RESULTS IN 23 DOGS

Pulmonary Compliance Decreased

EVANS, M.D.,

E. ADAMS, Chicago, Illinois

GAGO, M.D. AND WILLIAM

Bronchospirometry Ven tila tion Decreased Oxygen Consumption Decreased Right Cardiac Catheterization Pulmonary Artery Pressure Increased Selective Angiography

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*From the Department of Surgery, University of Chicago. This work was supported in part by the John A. Hartford Foundation, Inc., New York, New York, and United States Public Health Service Heart Research Grant H -1894 (C 13) . Presented at the 29th Annual Meeting, American College of Chest Physicians, Atlantic City, June 13-17, 1963.

M.D., F.C.C.P.

Subsequently, a procedure was devised for studies of the effects of drugs on the pulmonary artery pressures and ventilatory functions in five of these animals. These five had undergone reimplantation of the right lung from three to 24 months prior to this study (the surgical procedure for lung reimplantation was the same as that described in previous communications) .5,10 METHOD

The five animals were anesthetized with pentobarbital sodium solution (Nembutal), given intravenously. A double lumen cardiac catheter, size 5 French, was inserted into the right external jugular vein and the tip of the catheter was advanced through the right heart to a position in the main pulmonary artery. From the distal lumen of the catheter, pulmonary artery pressures were recorded on a Grass multichannel recorder, while 15 ml. of a 0.1 mg. per ml. solution of acetylcholine and 2 ml. of a 25 mg. per ml. solution of tolazoline (Priscoline) were instilled into the proximal lumen to study their effects on pulmonary artery pressure. A bronchospirometric tube was inserted into each dog and six minute samples of expired air were collected in Douglas bags from each lung during each test period. Blood samples for oxygen saturation were collected from the pulmonary artery and femoral artery simultaneously during the three stages of each experiment. In the three stages comprising these experiments, pulmonary artery pressures were studied and concurrent values of ventilation, oxygen consumption, and carbon dioxide production of each lung were determined during six minute periods. In the first stage of the experiments, normal baseline functions were determined for the reimplanted lung versus the contralateral nor-

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TABLE 2-PHYSIOLOGIC STUDIES AND ANALYSIS OF EXPIRED AIR IN DOG 18 AFTER REIMPLANTATION OF RIGHT LUNG

Control Ventilation L./min.

02 Consumption ml./min. CO2 Production ml./min. Respiratory Quotient Ventilation Equivalent Pulmonary Artery Pressure mm.Hg (mean, mm.Hg) 02 Saturation

Rt. Lung Left Lung Rt. Lung Left Lung Rt. Lung Left Lung Rt. Lung Left Lung Rt. Lung Left Lung

Femoral Artery Pulmonary Artery

mal lung. During the second stage, these functions were determined when acetylcholine was instilled into the pulmonary artery, and in the third stage the values of these functions were determined while tolazoline was instilled into the pulmonary artery. RESULTS

In this study it was found that the pulmonary artery pressure was consistently elevated in each of the five animals prior to introduction of drugs into the pulmonary artery (Table 2). The pressures immediately became higher when acetylcholine was instilled directly into the pulmonary artery; after a few seconds, the pressure dropped to a level lower than the resting baseline pressure; and it remained at this level during the test period. As soon as the drug was stopped, the pressure returned to its baseline level. In each of the five animals, tolazoline injected into the pulmonary artery produced an immediate drop in pressure that was maintained at a consistent level during the instillation of the drug. When the tolazoline injection was stopped, the pulmonary artery pressure returned to the resting levels. Concurrently with the pulmonary artery pressure studies, six minute samples of expired air were collected from each lung. During the first stage of the experiments, as was found in our previous studies, ventilation of the reimplanted lung was consist-

0.9 1.04 25 28 20 22 0.80 0.79 3.7 3.7 30/10 (16) 97% 78%

Acetylcholine

1.2 1.6 38 45 30 40 0.79 0.89 3.1 3.6 18/10 (12) 96% 77%

Tolazoline

1.0 1.0 35 59 24 47 0.69 0.80 2.9 3.2 18/8 (12) 98% 76%

ently diminished. However, oxygen uptake was diminished to a greater degree. The depression in carbon dioxide production was equal to the depression in oxygen consumption. The ventilation equivalent was slightly higher for the reimplanted lung; this indicated that oxygen consumption was more depressed than ventilation in the reimplanted lung. When acetylcholine or tolazoline was instilled directly into the pulmonary artery, the volume of expired air collected during the six minute periods increased. The values for oxygen consumption and carbon dioxide production increased in both the reimplanted right lung and the normal left lung to a greater degree than the increase in the value for ventilation. However, the values for the reimplanted lung were consistently lower than those for the contralateral normal lung. These values show that an increased amount of cardiac output went through the right lung although the pulmonary artery pressure was lower during instillation of acetylcholine or tolazo line into the pulmonary artery. These findings demonstrate that the pulmonary vessels in both the normal lungs and the reimplanted lungs dilate and increase the pulmonary vascular bed. Therefore, part of the elevation in pulmonary artery pressure after right lung reimplantation is due to vascular spasm and a decrease in the . pulmonary vascular bed (Fig. 1).

Volume 46, No. 3 September 1964

ALTERED PHYSIOLOGY OF PULMONARY VASCULAR BED

RIGHT LUNG REIMPLANTATION OXYGEN UPTAKE AND CARBON DIOXI DE PRODUCTION

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1: This illustrates average values for oxygen consumption and COl production in the reimplanted right lungs of the five animals that comprise this study. When acetylcholine or tolazoline solution was instilled directly into the main pulmonary artery, the pulmonary artery pressure dropped. However oxygen consumption and C02 production of the reimplanted lungs increased. When the drugs wer~ stopped, all values returned to control levels immediately. FIGURE

DISCUSSION

Several reports have shown that dogs can survive reirnplantation of one lung. However, they seldom survive for more than a few days when the contralateral normal lung is removed. In evaluations of functions of the reimplanted lungs, it has been shown that the pulmonary artery pressure is elevated after lung reimplantation and it is higher whenever the pulmonary artery of the contralateral normal lung is occluded or the normal lung is removed. Consistently, the average values of ventilation, oxygen consumption, and carbon dioxide production of the reimplanted lungs are approximately 35 per cent of normal. In this present study, conducted in three stages for evaluation of the pulmonary vascular bed, a baseline study of the. pulmonary functions of reimplanted lungs versus the contralateral normal lungs co-ordinated with concomitant pulmonary artery pressure studies were determined. At rest after reimplantation of the right lung, it

was found that pulmonary artery pressures of the animals were slightly elevated and ventilatory functions and the oxygen consumption and carbon dioxide production were diminished in the reimplanted, right lungs. However, during the second stage of the experiments when acetylcholine was instilled directly into the pulmonary artery, the pulmonary artery pressure made an initial rise and then dropped to a level which was lower than the level in the control studies. When tolazoline was instilled directly into the pulmonary artery, the pulmonary artery pressure immediately dropped and remained at a constant level. During instillation of acetylcholine and tolazoline, ventilation, oxygen consumption, and carbon dioxide production of the reimplanted lungs were increased. This showed that as the drug was instilled into the pulmonary artery, the pulmonary vessels of the reimplanted lung dilated, the pulmonary vascular bed expanded, and an increased amount of cardiac output went

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through this lung for oxygenation and carbon dioxide production. The increase in oxygen consumption through the reimplanted lung and contralateral normal lung demonstrate that there was an increase in cardiac output through the lungs. Therefore, the drop in pulmonary artery pressure was not due to systemic effects of the drugs. We concluded that part of the diminished pulmonary function found after reimplantation of the lung may be due to complete interruption of innervation with resultant spasm of the vessels and a decreased vascular bed of the lung. However, this study did not completely elucidate the effects of acetylcholine and tolazoline directly on the terminal respiratory units and bronchial tissues that may have altered function due to transplantation procedure. What the bronchial glands and their secretions do in the increased function of the reimplanted lung when acetylcholine was given were not evaluated in this study. SUMMARY

1. The pulmonary vascular bed of the reimplanted lung is diminished. Part of this decrease is secondary to spasm of the pulmonary vessels probably due to complete interruption of innervation during the transplantation procedure. 2. The pulmonary vascular bed can be expanded by injection of acetylcholine or tolazoline. However, the reimplanted lung does not regain function to 100 per cent normal during the injection of these drugs. 3. The elevated pulmonary artery pressures which are found in animals after lung reimplantation can be brought down to more normal levels during drug injections. However, when the drug is stopped, the pressures immediately return to the elevated state. RESUMEN

1. EI lecho vascular pulmonar en el pulm6n reimplantado esta disminuido. Parte de esta disminuci6n resulta de espasmo de los vasos pulmonares probablemente debido a la completa interrupci6n de la inervaci6n durante el reimplante. 2. EI lecho vascular puede expanderse por la inyecci6n de acetilcolina 0 la tolazolina. Sin embargo, el pulm6n reimplantado no recupera la

funci6n normal al 100 por ciento durante la inyecci6n de estas drogas. 3. Las presiones pulmonares elevadas que se encuentran en animales despues de la reimplantaci6n del pulm6n puede traerse a niveles mas normales durante la inyecci6n de las drogas. Sin embargo, cuando estas dejan de administrarse las presiones retornan inmediatamente a su elevaci6n. RESUME

1. Le lit vasculaire pulmonaire d'un poumon reimplante est reduit. Une partie de cette diminution est secondaire au spasme des vaisseaux pulmonaires, probablement en rapport avec l'interruption de l'innervation pendant la realisation de la transplantation. 2. Le lit vasculaire pulmonaire peut subir une extension par l'injection d'acetylcholine ou de tolazoline. Cependant, Ie poumon reimplante ne recupere pas une fonction a 100 pour cent de la normale pendant l'injection de ces medicaments. 3. Les pressions arterielles pulmonaires qui sont trouvees chez les animaux apres la reimplantation d'un poumon peuvent etre rabaissees vers des niveaux plus normaux par l'injection de medicaments. Cependant, quand Ie medicament est arrete, les pressions retombent immediatement aux chiffres eleves. REFERENCES JUVENILLE, A. A., CITRET, C., WILES, C. E. AND STEWART, J. D.: "Pneumonectomy with Reimplantation of Lung in Dog for Physiologic Study," ]. Thor. Surg., 21: 111, 1951. 2 FABER, L. P. AND BEATTIE, E. J., JR.: "Respiration Following Lung Denervation," Surge Forum, 9: 383, 1959. 3 PORTIN, B. A., RASMUSSEN, G. L., STEWART, J. D. AND ANDERSON, M. N.: "Physiologic and Anatomic Studies Thirty-five Months After Successful Replantation of Lung," ]. Thor. Surg., 39: 380, 1960. 4 BLUMENSTOCK, D. A. AND KAHN, D. R.: "Replantation and Transplantation of Canine Lung," I. Surge Res., 1: 40, 1961. 5 NIGRO, S. L., REIMANN, A. F., FRY, W. A., MOCK, L. F. AND ADAMS, W. E.: "Alterations in Cardiovascular Physiology Following Autologous Lung Transplantation," Surge Forum, 12 : 56, 1961. 6 LINBERG, E. J., DEMETRIADES, A., ARMSTRONG, B. W. AND KONSWAN, N.: "Lung Reimplantation in the Dog," I.A.M.A., 178: 146, 1961. 7 BLUMENSTOCK, D. A., COLLINS, J. A., THOMAS, E. D. AND FEREBEE, J. W.: "Homotransplants of the Lung in Dogs, Recent Advances," Surg., 51:541,1962. 8 YEH, T. J., ELLISON, L. T. AND ELLISON, R. G.: "Functional Evaluation of the Autotransplanted Lung in the Dog," Am. Rev. Resp. Dis., 86: 791, 1962. 9 ALICAN, F. AND HARDY, J. D.: "Lung Reimplantation," ].A.M.A., 183:849, 1963. 10 NIGRO, S. L., EVANS, R. H., BENFIELD, J. R., GAGO, 0., FRY, W. A. AND ADAMS, W. E.: "Physiologic Alterations of Cardiopulmonary Function in Dogs Living One and One-half Years on Only a Reimplanted Right Lung," /. Thor. Surg., 46: 598, 1963. For reprints, please write Dr. Adams, 950 East 59th Street, Chicago.