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Effect of oxygen intoxication on pulmonary surfactant in dogs, rabbits and rats
118
A b s t r a c t s - - M i d w e s t Soc. Pediat. Res.
July 1964
medical history and yet the pathogenesis of chorea is still a matter of contention. Studies of the incidence of rheumatic criteria among subjects with chorea vary widely in their percentage results; there was a range of 10 to 72 per cent. T h e purpose of this study was to attempt to discover an area in which more conclusive evidence of the association of chorea and rheumatic fever could be investigated. Various investigators have reported characteristic changes in the electroencephalogram in chorea consisting in the absence of normal alpha rhythm and continuous slow activity of increased amplitude. Electroencephalograms were taken on 49 patients included in this study. Forty of the patients were cases of rheumatic fever without chorea. All cases satisfied the Jones criteria as unquestioned cases of rheumatic fever. The remaining nine cases were cases of clinical chorea. Six of the patients with chorea had elevated sedimentation rates and at least one other major manifestation of rheumatic fever. Electroencephalographie tracings were taken on all patients while the rheumatic fever a n d / o r chorea were active by clinical and laboratory standards. None of the patients was known to have an overt convulsive disorder. Seven of the nine patients with clinical chorea demonstrated electroencephalographic abnormalities consisting in slow wave activity of increased amplitude. T h e patients with active rheumatic fever without chorea failed to show" electroencephalographic evidence of rheumatic brain disease. Nonspecific abnormalities were found in only 5 per cent of the tracings. The findings of this study suggest that individual variations in cortical excitability could not account for the infrequency of chorea as a manifestation of rheumatic fever. I t is more likely that rheumatic encephalopathy of sufficient severity to produce electroencephalographic abnormalities is uncommon and, when present, it is most likely to be accompanied by clinical chorea.
28. The course of artificially produced main pulmonary artery stenosis in
DISCUSSION DR. DAVID GOLDRINO, St. Louis. Did any of the children who had normal electroencephalograms initially demonstrate electroencephalographic abnormality a m o n t h or two after the acute episode ? DR. DIAUONO. In a n u m b e r of patients electroencephalograms were made 60 days after the acute attack and we failed to detect abnormality in any patient whose electroencephalogram had been normal initially. DR. GOLDRINO. I n those patients with an abnormal pattern before onset of chorea, did the pattern change during chorea? DR. DIAMOND. NO. In addition, when an electroencephalogram was abnormal initially, the abnormality persisted even after chorea had subsided.
the dog Arygyrios A. Tsifutis,* Peter Lekkas,* Marvin J. F r i e d e n b e r g , * M. Remsen Behrer, David Goldring, and John Kiss a n i , * St. L o u i s , M o . The genesis of the obstructive infundibular hypertrophy which is seen often in association with pulmonary v a l v a r stenosis, especially beyond infancy, has been explained upon an acquired basis (compensatory),~ but this has not been substantiated. Also, there are conflicting opinions about the necessity for resecting the infundibular muscle when the pulmonary valve is lysed. Experiments were devised using 8 puppies in which the main pulmonary artery was banded with an umbilical tape. T h e animals were studied at periodic intervals by cardiac catheterization, angiocardiography, and cardiac o u t p u t determination. There was progressive increase in the right ventricular pressure, and at the end of 14 to 22 months, this reached 124 ram. Hg (Av. 4 dogs), and marked infundibular hypertrophy was demonstrated by anglocardiography. T h e cardiac output decreased (4.4 ~ 2.6 L. per m i n u t e - - A v . 3 dogs). After 14 to 22 months, the pulmonary stenosis was relieved surgically in 4 dogs and all survived. After 2 to 10 months' follow-up, there was still significant infundihular hypertrophy by angiocardiography. Although there was an immediate drop in the right ventrieular pressure at the time of operation of 40 mm. Hg (Av. 4 dogs), the pressure remained elevated (64 mm. H g - - A v . 3 dogs) 2 to 5 months postoperatively. I n conclusion, in[undibular hypertrophy is an acquired complication of main pulmonary artery stenosis in the dog. In the human, valvotomy in infancy may prevent the development of infundibular hypertrophy. Valvotomy alone may be all that is needed, when there is an immediate drop in the right ventricular pressure at time of operation of 34 per cent or more of the original pressure. DISCUSSION DR. J. C. PETERSON, Milwaukee. W h a t was the duration of observation after surgery? DR. BE~I~ER. Thirteen months.
29. Effect o] oxygen intoxication on pulmonary surfactant in dogs, rabbits and rats Samuel Giammona,* Regina Frayser,* P e t e r R . C a l d w e | l , "x" a n d S t u a r t Bondurant,* I n d i a n a p o l i s , I n d i a n a Introduced by Paul R . L u r i e
Volurne 65 Number 1
A b s t r a c t s - - M i d w e s t Soc. Pedlar. Res.
With increasing use of 100 per Cent oxygen therapy at one or more atmospheres for prolonged periods, the role of pulmonary surfactant in the pathogenesis of oxygen intoxication (O. I.) requires clarification. Conflicting reports of the effect of O.I. on pulmonary surfactant may be related to differences in species studied or techniques of surfactant extraction. Six dogs, 9 rabbits, and 33 rats were placed in sealed chambers and ventilated with 95 to 100 per cent oxygen at one atmosphere until death (3 to 5 days). Control animals remained at one atmosphere and breathed room air. Humidity varied between 40 to 60 ~ and carbon dioxide was kept below 1 per cent. Pulmonary surfactant was obtained by both the methods of Bondurant and of Clements. Surface tensions of the extracts were measured on a modified Wilhelmy balance. Maximal and minimal (80 per cent compression of surface area) surface tensions in dyne per centimeter for the perfusion extracts are shown in Table I. Saline extracts give similar results. Minimal surface tension of the extracts of control and O.I. dogs and rabbits were significantly different (p < 0.001). Surface tensions of extracts from control and O.I. rats were not different. Ten milliliter blood samples from each dog were added to normal dog extract. Blood from 5 of the six O.I. dogs raised minimal surface tension from 2 to 16 dynes per centimeter while control dogs' blood produced no change. The relationship between changes in surfactant and pulmonary pathology of O.I. requires further study in order to evaluate therapeutic manipulations of pulmonary surface forces in the prevention and treatment of O.I.
this did not change the results. We did not measure pCO2 in blood. DR. WEmMAN. In patients who die following operations including extracorporeal circulation, the amount of pulmonary surfactant is found to be diminished in atelectatic areas of lung but to be normal in well-expanded portions. Oxygen may exert its effect by producing atelectasis. Have you considered the possibility that the amount of pulmonary surfactant was diminished because of atelectasis rather than because of the high partial pressure of oxygen? DR. GIAMMONA. We have analyzed sections of atelectatic and nonatelectatic lung and have found no difference in concentration of surfactant.
DISCUSSION DR. WILLIAM H. WEIDMAN, Rochester. Since it is known that increased concentrations of carbon dioxide in inspired air result in decreased concentrations of pulmonary surfactant in the lung, I wonder whether the elevated concentrations of carbon dioxide to which the animals were exposed was of any significance in the results. Did you determine pCO2 in blood of these animals ? DR. GIAMMONA. Concentrations of carbon dioxide in inspired air were in all cases below 1 per cent and in most instances below 0.1 per cent. In a few experiments, the concentrations of carbon dioxide were kept below 0.01 per cent and
Table I Group
t Maximal
I Minimal
Control dogs O.I. dogs
45 + 6 57 4- 2
2 +- 1 22 "2- 3
Control rabbits O.I. rabbits
58 "Z-_5 60 • 6
5 + 3 21 + 5
Control rats O.I. rats
53 + 6 54 + 10
4 -+ 4 4 -+ 4
1 19
30. Surgical closure of ventricular septal defects in infants J. M. Sigmann, A. M. Stern, H. Sloan, Ann Arbor, Mich. Introduced by James L. Wilson Forty-three infants ranging in age from 10 weeks to 24 months and weighing from 6 to 24 pounds had open heart surgery for closure of their interventricular defects during the period from December, 1956, through August, 1963. This direct approach was selected in preference to the banding procedure because it should obviate the necessity of a second operation. Indications for surgery were (1) intractable congestive heart failure, (2) severe pulmonary hypertension, ( 3 ) r e c u r rent pneumonias, and (4) failure to gain weight. All 32 living patients are improved, the defects of 21 having been fully corrected with initial surgery. Three of 5 residual interventricular defects have been corrected subsequently. Four patients who had their interventricular defects successfully closed still have other uncorrected cardiac lesions. One patient has been lost for follow-up after 6 months. To establish criteria upon which to judge the advisability of surgery, the preoperative status was evaluated in all 43 patients. Correlation was made between survival and severity of congestive heart failure, pulmonary hypertension, electrocardiographic findings, age, and weight at the time of surgery. Ten patients failed to survive the immediate postoperative period. Death was attributed in the majority of cases to early technical difficulties in perfusing the very small infants. Other contributing causes included severe pulmonary arterial disease, heart block, and digitoxin intoxication. One infant died of widespread infection 15 days after surgery. The results of surgery in the surviving group were further evaluated in terms of disappearance of symptoms and improved growth. DISCUS'SION DR. PAUL R. LURIE, Indianapolis. The quality of surgical treatment and postoperative manage-
A b s t r a c t s - - M i d w e s t Soc. Pediat. Res.
July 1964
medical history and yet the pathogenesis of chorea is still a matter of contention. Studies of the incidence of rheumatic criteria among subjects with chorea vary widely in their percentage results; there was a range of 10 to 72 per cent. T h e purpose of this study was to attempt to discover an area in which more conclusive evidence of the association of chorea and rheumatic fever could be investigated. Various investigators have reported characteristic changes in the electroencephalogram in chorea consisting in the absence of normal alpha rhythm and continuous slow activity of increased amplitude. Electroencephalograms were taken on 49 patients included in this study. Forty of the patients were cases of rheumatic fever without chorea. All cases satisfied the Jones criteria as unquestioned cases of rheumatic fever. The remaining nine cases were cases of clinical chorea. Six of the patients with chorea had elevated sedimentation rates and at least one other major manifestation of rheumatic fever. Electroencephalographie tracings were taken on all patients while the rheumatic fever a n d / o r chorea were active by clinical and laboratory standards. None of the patients was known to have an overt convulsive disorder. Seven of the nine patients with clinical chorea demonstrated electroencephalographic abnormalities consisting in slow wave activity of increased amplitude. T h e patients with active rheumatic fever without chorea failed to show" electroencephalographic evidence of rheumatic brain disease. Nonspecific abnormalities were found in only 5 per cent of the tracings. The findings of this study suggest that individual variations in cortical excitability could not account for the infrequency of chorea as a manifestation of rheumatic fever. I t is more likely that rheumatic encephalopathy of sufficient severity to produce electroencephalographic abnormalities is uncommon and, when present, it is most likely to be accompanied by clinical chorea.
28. The course of artificially produced main pulmonary artery stenosis in
DISCUSSION DR. DAVID GOLDRINO, St. Louis. Did any of the children who had normal electroencephalograms initially demonstrate electroencephalographic abnormality a m o n t h or two after the acute episode ? DR. DIAUONO. In a n u m b e r of patients electroencephalograms were made 60 days after the acute attack and we failed to detect abnormality in any patient whose electroencephalogram had been normal initially. DR. GOLDRINO. I n those patients with an abnormal pattern before onset of chorea, did the pattern change during chorea? DR. DIAMOND. NO. In addition, when an electroencephalogram was abnormal initially, the abnormality persisted even after chorea had subsided.
the dog Arygyrios A. Tsifutis,* Peter Lekkas,* Marvin J. F r i e d e n b e r g , * M. Remsen Behrer, David Goldring, and John Kiss a n i , * St. L o u i s , M o . The genesis of the obstructive infundibular hypertrophy which is seen often in association with pulmonary v a l v a r stenosis, especially beyond infancy, has been explained upon an acquired basis (compensatory),~ but this has not been substantiated. Also, there are conflicting opinions about the necessity for resecting the infundibular muscle when the pulmonary valve is lysed. Experiments were devised using 8 puppies in which the main pulmonary artery was banded with an umbilical tape. T h e animals were studied at periodic intervals by cardiac catheterization, angiocardiography, and cardiac o u t p u t determination. There was progressive increase in the right ventricular pressure, and at the end of 14 to 22 months, this reached 124 ram. Hg (Av. 4 dogs), and marked infundibular hypertrophy was demonstrated by anglocardiography. T h e cardiac output decreased (4.4 ~ 2.6 L. per m i n u t e - - A v . 3 dogs). After 14 to 22 months, the pulmonary stenosis was relieved surgically in 4 dogs and all survived. After 2 to 10 months' follow-up, there was still significant infundihular hypertrophy by angiocardiography. Although there was an immediate drop in the right ventrieular pressure at the time of operation of 40 mm. Hg (Av. 4 dogs), the pressure remained elevated (64 mm. H g - - A v . 3 dogs) 2 to 5 months postoperatively. I n conclusion, in[undibular hypertrophy is an acquired complication of main pulmonary artery stenosis in the dog. In the human, valvotomy in infancy may prevent the development of infundibular hypertrophy. Valvotomy alone may be all that is needed, when there is an immediate drop in the right ventricular pressure at time of operation of 34 per cent or more of the original pressure. DISCUSSION DR. J. C. PETERSON, Milwaukee. W h a t was the duration of observation after surgery? DR. BE~I~ER. Thirteen months.
29. Effect o] oxygen intoxication on pulmonary surfactant in dogs, rabbits and rats Samuel Giammona,* Regina Frayser,* P e t e r R . C a l d w e | l , "x" a n d S t u a r t Bondurant,* I n d i a n a p o l i s , I n d i a n a Introduced by Paul R . L u r i e
Volurne 65 Number 1
A b s t r a c t s - - M i d w e s t Soc. Pedlar. Res.
With increasing use of 100 per Cent oxygen therapy at one or more atmospheres for prolonged periods, the role of pulmonary surfactant in the pathogenesis of oxygen intoxication (O. I.) requires clarification. Conflicting reports of the effect of O.I. on pulmonary surfactant may be related to differences in species studied or techniques of surfactant extraction. Six dogs, 9 rabbits, and 33 rats were placed in sealed chambers and ventilated with 95 to 100 per cent oxygen at one atmosphere until death (3 to 5 days). Control animals remained at one atmosphere and breathed room air. Humidity varied between 40 to 60 ~ and carbon dioxide was kept below 1 per cent. Pulmonary surfactant was obtained by both the methods of Bondurant and of Clements. Surface tensions of the extracts were measured on a modified Wilhelmy balance. Maximal and minimal (80 per cent compression of surface area) surface tensions in dyne per centimeter for the perfusion extracts are shown in Table I. Saline extracts give similar results. Minimal surface tension of the extracts of control and O.I. dogs and rabbits were significantly different (p < 0.001). Surface tensions of extracts from control and O.I. rats were not different. Ten milliliter blood samples from each dog were added to normal dog extract. Blood from 5 of the six O.I. dogs raised minimal surface tension from 2 to 16 dynes per centimeter while control dogs' blood produced no change. The relationship between changes in surfactant and pulmonary pathology of O.I. requires further study in order to evaluate therapeutic manipulations of pulmonary surface forces in the prevention and treatment of O.I.
this did not change the results. We did not measure pCO2 in blood. DR. WEmMAN. In patients who die following operations including extracorporeal circulation, the amount of pulmonary surfactant is found to be diminished in atelectatic areas of lung but to be normal in well-expanded portions. Oxygen may exert its effect by producing atelectasis. Have you considered the possibility that the amount of pulmonary surfactant was diminished because of atelectasis rather than because of the high partial pressure of oxygen? DR. GIAMMONA. We have analyzed sections of atelectatic and nonatelectatic lung and have found no difference in concentration of surfactant.
DISCUSSION DR. WILLIAM H. WEIDMAN, Rochester. Since it is known that increased concentrations of carbon dioxide in inspired air result in decreased concentrations of pulmonary surfactant in the lung, I wonder whether the elevated concentrations of carbon dioxide to which the animals were exposed was of any significance in the results. Did you determine pCO2 in blood of these animals ? DR. GIAMMONA. Concentrations of carbon dioxide in inspired air were in all cases below 1 per cent and in most instances below 0.1 per cent. In a few experiments, the concentrations of carbon dioxide were kept below 0.01 per cent and
Table I Group
t Maximal
I Minimal
Control dogs O.I. dogs
45 + 6 57 4- 2
2 +- 1 22 "2- 3
Control rabbits O.I. rabbits
58 "Z-_5 60 • 6
5 + 3 21 + 5
Control rats O.I. rats
53 + 6 54 + 10
4 -+ 4 4 -+ 4
1 19
30. Surgical closure of ventricular septal defects in infants J. M. Sigmann, A. M. Stern, H. Sloan, Ann Arbor, Mich. Introduced by James L. Wilson Forty-three infants ranging in age from 10 weeks to 24 months and weighing from 6 to 24 pounds had open heart surgery for closure of their interventricular defects during the period from December, 1956, through August, 1963. This direct approach was selected in preference to the banding procedure because it should obviate the necessity of a second operation. Indications for surgery were (1) intractable congestive heart failure, (2) severe pulmonary hypertension, ( 3 ) r e c u r rent pneumonias, and (4) failure to gain weight. All 32 living patients are improved, the defects of 21 having been fully corrected with initial surgery. Three of 5 residual interventricular defects have been corrected subsequently. Four patients who had their interventricular defects successfully closed still have other uncorrected cardiac lesions. One patient has been lost for follow-up after 6 months. To establish criteria upon which to judge the advisability of surgery, the preoperative status was evaluated in all 43 patients. Correlation was made between survival and severity of congestive heart failure, pulmonary hypertension, electrocardiographic findings, age, and weight at the time of surgery. Ten patients failed to survive the immediate postoperative period. Death was attributed in the majority of cases to early technical difficulties in perfusing the very small infants. Other contributing causes included severe pulmonary arterial disease, heart block, and digitoxin intoxication. One infant died of widespread infection 15 days after surgery. The results of surgery in the surviving group were further evaluated in terms of disappearance of symptoms and improved growth. DISCUS'SION DR. PAUL R. LURIE, Indianapolis. The quality of surgical treatment and postoperative manage-