Jul 18, 1975 - At the end of this time, his minute ventilation was at least 30 liters per minute. Simultaneously respi- ratory response curves were plotted ...
CASE REPORTS
myxoma. The abnormal echoes diminished dramatically during antibiotic therapy over the ensuing six weeks and probably represented a vegetation prolapsing through the mitral orifice. Echographic features considered pathognomonic for left atrial tumor may be shared by mitral valve vegetations. REFERENCES 1. Dillon JC, Feigenbaum H, Konecke LL, et al: Echocardiographic manifestations of valvular vegetations. Am Heart 3 86: 698-704, 1973 2. Hirschfeld D, Schiller NB: Echocardiographic localization of aortic valve vegetations. Circulation 50 (Suppl III) :IlI-143, 1974 3. Gottlieb S, Khuddus SA, Balooki H, et al: Echocardiographic diagnosis of aortic valve vegetations in Candida endocarditis. Circulation 50:826-830, 1974 4. Martinez EC, Burch GE, Giles TD: Echocardiographic diagnosis of vegetative aortic bacterial endocarditis. Am J Cardiol 34: 845-849, 1974 5. Dick HJ, Mullin EW: Myxoma of the heart complicated by bloodstream infection by Staphylococcus aureus and Candida parapsilosis. NY State J Med 56:856-859, 1956 6. Rae A: Two patients with cardiac myxoma-One presenting as bacterial endocarditis, and one as congestive cardiac failure. Postgrad Med J 41:644 648, 1965
Refer to: Bellville JW, Swanson GD, Miyake T, et al: Respiratory stimulation observed following ethanol ingestion. West J Med 124:423425, May 1976
Respiratory Stimulation Observed Following Ethanol Ingestion J. WELDON BELLVILLE, MD GEORGE D. SWANSON, PhD TOSHIYUKI MIYAKE, MD KAMEL A. AQLEH, BS Los Angeles ETHANOL IS REGARDED as a central nervous system depressant. Its sedative effect and its effects on psychomotor performance have been studied in detail. Recently its respiratory depressant effects have been shown to be dose related, that is, as the dose of ethanol is increased its respiratory depressant properties are enhanced.",2 This report summarizes our findings in a young man who has an unusual response to ethanol in that it produces respiratory stimulation and the degree of respiratory stimulation appears to be poorly related to the dose of ethanol ingested. From the Department of Anesthesiology, University of California, Los Angeles, School of Medicine. This study was supported in part by Grant No. DA00138, National Institutes of Health. Submitted July 18, 1975. Reprint requests to: J. Weldon Bellville, MD, Department of Anesthesiology, UCLA School of Medicine, Los Angeles, CA 90024.
7. Malloch CI, Abbott JA, Rapaport E: Left atrial myxoma with bacteremia-Report of a case with a bifid systolic apical impulse. Am J Cardiol 25:353-358, 1970 8. Popp RL, Harrison DC: Ultrasound for the diagnosis of atrial tumor. Ann Intern Med 71:785-787, 1969 9. Wolfe SB, Popp RL, Feigenbaum H: Diagnosis of atrial tumors by ultrasound. Circulation 39:615-622, 1969 10. Nasser WK, Davis RH, Dillon JC, et al: Atrial myxomaII. Phonocardiographic, echocardiographic, hemodynamic, and angiographic features in nine cases. Am Heart J 83:810-824, 1972 11. Spencer WH III, Peter RH, Orgain ES: Detection of a left atrial myxoma by echocardiography. Arch Intern Med 128:787-789, 1971 12. Schattenberg TT: Echocardiographic diagnosis of left atrial myxoma. Mayo Clin Proc 43:620-627, 1968 13. Martinez EC, Giles TD, Burch GE: Echocardiographic diagnosis of left atrial myxoma. Am J Cardiol 33:281-285, 1974 14. Kostis JB, Moghadam AN: Echocardiographic diagnosis of left atrial myxoma. Chest 58:550-552, 1970 15. Johnson ML, Sieker HO, Behar VS, et al: Echocardiographic diagnosis of a left atrial myxoma found attached to the free left atrial wall. J Clin Ultrasound 1:75-81, 1973 16. Srivastava TN, Fletcher E: The echocardiogram in left atrial myxoma. Am J Med 54:136-139, 1973 17. Finegan RE, Harrison DC: Diagnosis of left atrial myxoma by echocardiography. N Engl J Med 282:1022-1023, 1970 18. Spangler RD, Johnson ML, Holmes JH, et al: Echocardiographic demonstration of bacterigl vegetations in active infective endocarditis. J Clin Ultrasound 1:126-128, 1973
Methods These studies were done in a 25-year-old healthy man during the course of an investigation of the respiratory effects of pentobarbital, A9-tetrahydrocannabinol and ethanol. The basic method for measuring respiratory depression or stimulation has already been described by us previously3 and represents a modification of the rebreathing technique of Eckenhoff and co-workers4 except that the rebreathing reservoir is charged with 5 percent carbon dioxide in oxygen as suggested by Read.5 The volunteer subject was allowed his usual meals, but it was requested that coffee and tea as well as alcoholic beverages be omitted for the preceding 12 hours. The subject was fitted with a rubber metabolic mouthpiece and nose clip. While in a semireclining position, he breathed through the apparatus for from three to five minutes to become accustomed to it. Then the system was closed and rebreathing begun, continuing for 10 to 12 minutes. At the end of this time, his minute ventilation was at least 30 liters per minute. Simultaneously respiratory response curves were plotted automatically by an analog computer, and a point was plotted for each breath representing the end-expiratory carbon dioxide rate and the ventilation for that breath (Figure 1). This value was also stored in a PDP/8 computer (Digital Equipment Corporation) for analysis. Following the completion of the response curve determination, a least mean square line was fit and the intercept at 20 liters per minute and slope were printed out as well as THE WESTERN JOURNAL OF MEDICINE
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61 50 55 40 45 35 END EXPIRATORY CO2 (TORR) Figure 1.-End-expiratory carbon dioxide is plotted versus minute ventilation. The open circles represent a control determination while the solid circles show the results 1/2 hour following administration of 120 ml of 80 proof vodka. A least mean square line was fit to the rebreathing data. The control slope was 1.84 liters per minute per torr of carbon dioxide pressure while the 1/2 hour slope was 3.20. The correlation coefficients were 0.98 and 0.97 respectively. The off transient is also plotted.
30
the correlation coefficient and the number of breaths analyzed. After two control runs had agreed within 0.5 torr* of carbon dioxide pressure (Pco2), the test medication in the form of 80 proof vodka in fruit juice was administered. Displacement was determined as the change from the average of all the control curves in the intercept at a ventilation of 20 liters per minute of the best fitting least mean square line through the response curve. Negative values indicate a shift to the left (respiratory stimulation) of the control curve.
Results Typical respiratory response curves are shown in Figure 1 for a control and after administration of ethanol determination. The carbon dioxide response curve displacement results are summarized in Figure 2 in which is plotted the response curve displacement versus time at various doses of 80 proof vodka ranging from 30 to 180 ml given in *One torr is equal to 1 mmn of mercury.
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fruit juice. It is apparent that as the dose is increased, the respiratory stimulation is not notably increased. Also shown is the response after a drug that is a known respiratory stimulant, aspirin (990 mg given orally). We did not plot a dose-effect curve for ethanol since it is apparent that at the higher doses of vodka the subject was not observed for a long enough period of time to define a complete time effect curve. In Table 1 are the data for the respiratory response curve slopes corresponding to the displacement data shown in Figure 2. With displacement of the response curve to the left there was an increase in slope.
124 * 5
Although ethanol has been shown to be a respiratory depressant we have observed in several persons that it may have respiratory stimulant properties. One of these persons was Jewish while the one in whom the most pronounced reaction was seen and who is reported here was of Japanese descent.t Recently attention has been called to the unusual responses seen in Oriental adults who drink ethanol and in whom a characteristic flushing of the face is seen. This was recently discussed by Wolff6 and studied in more detail by Ewing and associates.' Ewing and co-workers showed that the production of acetylaldehyde is higher in these Orientals than in Caucasians who do not have this flushing response. The subject who participated in this study had the characteristic flushing of the face and reported a tightness in his chest following the ingestion of ethanol. Furthermore, neither he nor his father was accustomed to ingesting ethanol and reported they did not enjoy alcoholic beverages. The subjective responses reported by this volunteer are similar to those reported by Ewing. These data suggest that some persons have an tRecently we studied this man's cousin in whom pronounced respiratory stimulation and flushing also was seen following ingestion of 30 ml of vodka.
TABLE 1.-Slope of Respiratory Response Curve in Liters per Minute per Torr of Carbon Dioxide Pressure Ethanol Dose (ml) 80
Prooy
Average
Control
.1.33 2.16 .............. 1.83 .............. 1.72 .............. 2.26 .............. 1.68 ............. 1.96 Aspirin 990 mg ... 1.85 30 60 60 60 90 120 180
..............
1/2
1
2
1.40 2.35 2.62 2.43 3.04 3.20 2.45 1.95
2.14
2.14 2.56 2.30 2.32 2.48 3.11 2.16
0.68 2.32 2.01 2.76 2.18 2.59 2.35 1.97
3
1.30
2.01
1.67 2.31
2.12 2.22 2.46 2.10
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Figure 2.-Time-effect curves following various doses of 80 proof vodka as well as aspirin (990 mg) given orally are shown.
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unusual response to ethanol and that it not only the previously reported flushing of the face but acts as a notable respiratory stimulant. The pharmacologic basis of these effects has not been defined and although acetylaldehyde production has been shown to be higher among these people, we do not know if the respiratory stimulation is due to acetylaldehyde or some other metabolite or hormone. Certainly the degree of respiratory stimulation is dramatic when compared to other mild respiratory stimulants such as aspirin (Figure 2) or caffeine.8 Clearly pharmacologic factors produce this pronounced effect. The large change in respiratory response cannot be explained by physiologic factors such as change in ventilatory mechanics. We believe that an understanding of this phenomenon might aid in explaining why some people do not tolerate alcoholic beverages. We agree with Ewing and co-workers that "cultural explanations will not suffice to explain the phenomena we have observed. Indeed, it is possible that drinking patterns in a culture are built upon a physiologic foundation." causes
Summary Some ethnic groups notably do not abuse ethanol. We have observed in a volunteer who is of Japanese descent, in addition to a previously described flushing of the face seen in some Orientals, a pronounced respiratory stimulation following ingestion of alcohol. This gives strong support to the hypothesis that pharmacologic factors are important in lack of ethanol abuse seen
in these
persons.
REFERENCES 1. Johnston R, Reier C: Acute respiratory effects of ethanol in man. Clin Pharmacol Ther 14:501-508, 1973 2. Sahn S, Lakshminarayan S, Pierson D, et al: Effect of ethanol on the ventilatory responses to oxygen and carbon dioxide in man. Clin Sci Mol Med 49:33-38, 1975 3. Bellville J. Cohen E, Hamilton J: Interaction of morphine and d-Tubocurarine on respiration and grip strength in man. Clin Pharmacol Ther 5:35-43, 1964 4. Eckenhoff J, Helrich M, Hege M: A method for studying respiratory functions in awake or anesthetized patients. Anesthesiology 17:66, 1956 5. Read D: A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med 16:20-32, 1967 6. Wolff P: Ethnic differences in alcohol sensitivity. Science 175:449-450, 1972 7. Ewing J, Rouse B, Pellizzari E: Alcohol sensitivity and ethnic background. Am J Psychiatry 131:206-210, 1974 8. Bellville J, Escarraga L, Wallenstein S, et al: Antagonism by caffeine of the respiratory effects of codeine and morphine. J Pharm Exper Ther 136:3842, 1962
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