* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Detection of Pulmonic and Tricuspid Valvular
Cardiac contractility modulation wikipedia , lookup
Heart failure wikipedia , lookup
Management of acute coronary syndrome wikipedia , lookup
Coronary artery disease wikipedia , lookup
Myocardial infarction wikipedia , lookup
Rheumatic fever wikipedia , lookup
Artificial heart valve wikipedia , lookup
Aortic stenosis wikipedia , lookup
Hypertrophic cardiomyopathy wikipedia , lookup
Cardiac surgery wikipedia , lookup
Quantium Medical Cardiac Output wikipedia , lookup
Arrhythmogenic right ventricular dysplasia wikipedia , lookup
Lutembacher's syndrome wikipedia , lookup
Atrial septal defect wikipedia , lookup
Mitral insufficiency wikipedia , lookup
Dextro-Transposition of the great arteries wikipedia , lookup
Detection of Pulmonic and Tricuspid Valvular Regurgitation by Means of Indicator Solutions By N. PERRYMAN COLLINS, M.D., EUGENE BRAUNWALD, M.D., AND ANDREW G. MORROW, M.D. The presence of pulmnonic and tricuspid valvular regurgitation may often be suspected from careful clinical examination. However, the validity of the generally accepted clinical criteria remain to be established by technics that permit the direct demonstration of reverse flow across these valves during life. This has been made possible by the detection of cardiogreen and of radioactive krypton (Kr85) in the right atrium or right ventricle after injection of these substances into a distal chamber. Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 heart catheterizatioii, and to present the results obtained ill 29 patients studied at the National Heart Institute. A similar approach to diagnosis has also been described recently by Bajec, Birkhead, Carter, and Wood.10 A LTHOUGH the presence of valvular regurgitation may be suspected from clinical studies, the actual demonstration of blood traversing a valve in reverse direction is necessary for a definitive diagnosis. Indicatordilution curves recorded from a systemic artery following injections into the right side of the heart are often modified by the presence of a regurgitant valve between the sites of injection and of sampling.1-3 Decreased cardiac output or a left-to-right shunt may, however, obscure the changes produced in such curves by valvular regurgitation. Mitral regurgitation has been demonstrated by the prompt appearance in the left atrium of either an indicator dye4' 5or of a radiopaque medium" following injection into the left ventricle. In the presence of aortic regurgitation, indicator dye injected into the descending thoracic aorta regurgitates to the ascending aorta and may be detected in the right ear. This lesion may also be demonstrated by thoracic aortography.8 The reflux of radiopaque dye into the right ventricle following its injection into the pulmonary artery has recently been observed in the presence of pulmonic regurgitation.9 It is the purpose of this report to describe 2 technics for the detection of pulmonic and tricuspid valvular regurgitation that may be applied conveniently at the time of right ,tL METHODS From the Clinic of Surgery, National Heart Institute, Bethesda, Md. *Manufactured by Nuclear Corporation of America, Brooklyn, N. Y. 561 Right heart catheterization was performed with a no.-9 double-lumen Cournand catheter, modified so that the openings of the 2 lumina were 5 cia. apart. When the competency of the pulnmonic valve was studied, the catheter was positioned so that the distal opening was in the pulmonary artery and the proximnal one in the right ventricle. When tricuspid valve function was examined, the distal lumen opened into the right ventricle, while the proximal opened into the right atrium. Simultaneous pressures were recorded from each chamnber immediately prior to and following injection of the indicator in order to confirm the position of the catheter. Cardiogreen (tricarboeyanine) dye" was injected through the distal opening of the catheter as blood was sampled continuously from the proximal opening (fig. 1). The concentration of the indicator was determined by withdrawal through a euvette densitometer12 by means of a constantrate motor-driven syringe. Time-coneentration curves were recorded either with a photographic cathode-ray instrument or a direct-writing recorder. The order of magnitude of the relationship between regurgitant and forward flows was estimated by the "forward triangle" method described by Hetzel and collaborators.13 14 The "regurgitant fraction" was calculated as the ratio of the product of the build-up time and peak-concentration of the "regurgitant curve" to that of the "recirculation curve" (fig. 2). It is realized that this ratio does not provide precise quantification. Circulation, Volume XX, October 1951 , COLLINS, BRAUNWALD, MORROW r.) Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 FIG. 1. Representation of the test for competency of the pulmonic valve with cardiogreen dye. Dye is injected through the distal opening of the catheter, and regurgitates back into the right ventricle. It is detected by sampling right ventricular blood from the proximal opening of the catheter through a cuvette densitometer. In 12 of the 29 patients valvular competency studied in a similar manner with injections of 30 to 50 jac. of radioactive krypton (Kr85) solution into the distal opening of the catheter. Immediately after injection blood was sampled at a constant rate for 10 seconds from the proximal lumen and for 15 seconds from a systemic artery. The radioactivity in these samples was then measured by inserting themn into a continuous gas-flow Geiger-Muller tube. was RESULTS In the presence of a competent valve, either no dye or only a minimal quantity appeared in the proximal chamber immediately after injection; Fifteen to 20 seconds after injection, dye that had recirculated through the systemic circuit appeared (figs. 3 and 4). When valvular regurgitation was present, a substantial amount of dye appeared in the proximal chamber within 2 seconds of the onset of the injection, well before the appearance of the recirculation curve (figs. 2 and 5). In the presence of valvular regurgitation combined with a left-to-right shunt entering upstream to the proximal catheter opening, the curve produced by the regurgitant valvular flow was inscribed significantly earlier than the curve produced by the shunted blood; the latter, while delayed in its path through the. pulmonary circulation and to the right side of the heart, nevertheless appeared earlier than the systemic recirculation curve (fig. 6). The competency of the pulmonic valve was examined in 28 patients, and in 7 of these significant regurgitation was considered to be present with "regurgitant f -actions" ranging from 17 to 72 per cent. Three of these 7 patients (W.J., J.B., J.S.) had previously had portions of their pulmonic valves excised at the time of pulmonary valvulotomy, but only 2 (J.B., J.S.) had murmurs considered typical of pulmonic regurgitation. Another patient (M.B.) had previously undergone pulmonic valvulotomy and closure of a small ventricular septal defect in which no valvular tissue was removed. A murmur typical of pulmonic regurgitation developed. One patient (C.C.) had mitral regurgitation, pulmonary hypertension, and a typical Graham Steell murmur. DYE DETECTION OF REGURGITATION Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 Patient J.K., who had not been operated upon, had the murmurs considered typical of pulmonic stenosis and regurgitation. At right heart catheterization, there was a gradient of 26 mm. Hg across the pulmonary valve, and the diastolic pressures in the pulmona; y artery and right ventricle were identical. The seventh patient (S.C.) had an atrial septal defect, pulmonary hypertension and a typical Graham Steell murmur; the presence of pulmonic regurgitation was confirmed at the time of operative closure of the defect when a distinct jet of blood was felt in the right ventricle during diastole. In only 3 (W.J., J.K., M.B.) of these 7 patients was the enddiastolic pressure in the pulmonary artery identical to that in the right ventricle. Pulmonary regurgitation was not suspected in 5 other patients who had "regurgitant fi actions" ranging from 2 to 6 per cent. It is believed that such minute amounts of reflux do not necessarily indicate organic valvular dysfunction, but are presumably artifacts produced by the presence of the catheter. There was no relation between the presence of this small degree of regurgitation and the pulmonary artery pressure. The competency of the tricuspid valve was tested in 17 patients and in 8 of these significant regurgitant flow was demonstrated. The " regurgitant fractions" ranged from 11 to 65 per cent in 7 of the patients and could not be calculated in the eighth, a patient with a very prolonged circulation time in whom no recirculation curve had appeared after 55 seconds of sampling. In all 8 of these patients there was clinical evidence of tricuspid regurgitation and the right ventricular pressure was elevated (table 1); in 5 of these, the mean right atrial pressure and the right atrial "v" wave pressures were elevated. In 2 of the patients with significant tricuspid regurgitation the diagnosis was confirmed at subsequent postmortem examination. In one of these patients, J.O., the tricuspid ring was widely dilated and the valve leaflets were held in a position of partial inversion into the right ventricle. Ill the other patient, A.R., the tricuspid valve was both stenotic and regurgi- 5 63 1) S E4 Injection R.A.Sampli R.V. T. R. W7 P. A. Injection R.V. Sampling 1M ECIRC, tOQ LLIIi R.V. Injection R.A.Sampling SEC-. _ h h FIG. 2 Top. Indicator-dilution curve obtained after right ventricular injection and right atrial sampling in a patient with rheumatic heart disease, mitral stenosis and regurgitation and tricuspid regurgitation. Verlical arrow, time of injection. The first upward deflection (T.R.) represents the dye that regurgitated across the tricuspid valve. The systemic recirculation curve is seen on the right (RECIRC.). 1-2, build-up timie; 2'-3, peak concentration of the regurgitant curve; 4-5, build-up time; 5-6, the peak concentration of the recirculation curve. Tricuspid regurgitation was also revealed waith the Kr' test performed on this lPatiellt. FIG. 3 Middle. Dye-dilution curve resulting from pulmonary artery injection and right ventricular sampling in patient L.R. with rheumatic heart disease, mitral stenosis, and aortic insufficiency. The absence of dye in right ventricular blood prior to recirculation is thought to exclude pulmonic regurgitation. The Kr' test also showed the absence of pulmnonic regurgitatioln. FIG. 4 Bottom. Dye-dilution curve after right ventricular injection and right atrial sampling in a patient without tricuspid regurgitation. taut, rigid and immobile with a fixed opening 1.5 cm. in diameter. Patient S.C. had an atrial septal defect with pulmonary and right ventricular systolie hypertension. The tricuspid regurgitant fraction was 11 per cent and a small regurgitant jet was palpable at opera- 564 COLLINS, BRAUNWALD, MORROW P.A. Injection R.V. Sampling 'i 110 SEC-j Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 FIG. 5 Top. Dye-dilution curve obtained from the right ventricle following pulmonary artery injection in a patient with pulmonary regurgitation. The dye that appears immediately (P.R.) indicates pulmonic reflux and precedes the recirculation curve (RECIRC.). FIG. 6 Bottom. Dilution curve resulting from pulmonary artery injection and right ventricular sampling in a patient who had a portion of his pulmonic valve excised at the time of pulmonary valvotomy for pulmonic stenosis. A left-to-right shunt due to an atrial septal defect persisted. The first component of the curve (P.R.) is indicative of pulmonic regurgitation, the second (L.R.) is related to blood that has been shunted across the atrial septal defect, and the third component (RECIRC.) is due to systemic recirculation. tion. In only one instance minimal ("catheter induced ") tricuspid regurgitation was encountered with regurgitant fraction of 3 per cent. It has been demonstrated previously that approximately 95 per cent of Kr85 injected into the venous system or right side of the heart is eliminated into the expired air during its passage through the pulmonary cireulation.15-18 The small remaining fraction that reaches the systemic arterial bed does not behave in a fashion similar to a simple intravascular indicator such as cardiogreen. A portion leaves the intravascular compartment and diffuses into the interstitial fluid as well as into the cells,19 further diminishing the quantity of Kr85 in the systemic venous blood immediately after injection into the right side of the heart or pulmonary artery. The presence of Kr85 in the blood sampled from the right atrium or right ventricle immediately after injection into the right ventricle or pulmonary artery could therefore result only from valvular regurgitation. Twelve patients had both Kr85 and cardiogreen dye tests for pulmonic regurgitation while 5 had both tests for tricuspid regurgitation. The results were in general agreement. In 8 tests the cardiogreen "regurgitant fraction" exceeded 15 per cent and the right heart Kr85 count per minute (c.p.m.) exceeded background by more than 100 c.p.m. Similarly, in 7 tests the cardiogreen regurgitant fraction ranged between 0 and 3 per cent while the right heart Kr85 activity ranged between 0 and 54 c.p.m. above background. However, the results in the other 2 patients indicated a discrepancy between the 2 tests. In patient J.B., significant pulmonic regurgitation was revealed only by cardiogreen dye while in patient M.E., it was demonstrated only with Kr85 DISCUSSION The technics for the detection of pulmonic and tricuspid valvular regurgitation described herein have been found simple and convenient to apply at the time of right heart catheterization and should prove of considerable clinical value. The diagnosis of pulmonary regurgitation is usually made when a patient with evidence of pulmonary hypertension presents with a high-pitched, decrescendo, blowing diastolic murmur along the left sternal border, unaccompanied by the peripheral dynamics of aortic regurgitation. Seven such patients wvere studied with an indicator-dilution method for the detection and estimation of aortic regurgitant flow.7 It was with considerable surprise that mild aortic 565 DYE DETECTION OF REGURGITATION TABLE 1.-Results of Dye-Dilution Tests for Valvular Regurgitation Regurgitant fraction Pressure PA S/D Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 J. P. R. J. M. S. A. L. D. D. M. B. P. D. A. R. AI. P. T. L. L. M. R. P. W. J. J. B. C. C. H. E. S. C. J. S. C. M. C. H. J. 0. R. J. IL. R. D. M. M. E. D. W. J. K. B. S. M. B. 27/11 22/7 42/20 29/10 54/12 34/14 47/34 80/40 72/34 25/9 40,20 41/23 20/3 64/30 RV S/D 28/1 22/4 42/8 33/1 54/0 35/4 48/4 80/10 73/7 28/5 43/4 42/0 45/3 66/10 RA Mean V Wave 4 3 7 2 1 5 5 10 8 5 4 5 4 6 2 10 4 1 2 7 7 2 4 3 10 5 4 4 - 6 6 10 3 3 8 7 14 18 6 7 6 6 7 4 16 3 3 3 8 11 3 5 4 15 6 5 4 Tricuspid Pulmonic 0 57 50 65 0 0 0 0 0 0 0 0 0 0 0 0 3 2 53 29 17 2 23 18 Diagnosis ASD ASD MS, MI PDA VSD MS, AI VSD rMS, MI, TS, TI MlS, M I, TI AS MS, MI, TI MS, AI, TS PS, PI, ASD (postop.) PI, Tet. of Fallot (postop.) MI, PI MS, MI, TI ASD, PI, TI PS, PI (postop.) 0 50/3 22 58/5 11 80/4 3 35/0 -MI 0 16/0 2 AI, MS 0 23/6 * MS, MI, AS, AI, TI 0 70/7 ASD 0 6 16/3 MS, AI 0 54/4 MS, AI 0 22/10 22/10 19 MS, MI, TI 0 40/6 40/20 MS, TI 0 59 75/7 73/34 PS, PI 72 48/8 22/8 AI, MI 0 0 43/5 43/22 VSD, PS, PI (postop.) 55 28/2 28/2 All pressures expressed in mm. Hg: S/D, systolic/diastolic pressures; *large regurgitant curve but no recirculation curve recorded; ASD, atrial septal defect; MS, mitral stenosis; MI, mitral insufficiency; PDA, patent ductus arteriosus; AI, aortic insufficiency; VSD, ventricular septal defect; TI, tricuspid insufficiency; TS, tricuspid stenosis; AS, aortic stenosis; PS, pulmonic stenosis; PI, pulmonic insufficiency. 50/20 56/14 78/30 15/5 15/7 23/7 68/38 18/6 50/30 regurgitation was discovered in 6 of these 7 patients believed on clinical grounds to have pulmonary regurgitation. If the indicatordilution methods are applied to the study of both the aortic and pulnionic valves, the origin of any diastolic murmur due to regurgitation may be determined. A patient recently studied illustrates the clinical application of these technics. L.R. (Clinical Center #00-24-61), an 18year-old girl, was admitted for diagnostic study and the treatment of rheumatic heart disease. She had had acute rheumatic fever at 8 years of age and was told shortly thereafter that she had a heart murmur. No symp- toms ensued until 1 year prior to admission when exertional dyspnea, easy fatigability, occasional paroxysmal nocturnal dyspnea, and hemoptysis began. On physical examination the blood pressure was 106/70; the pulse was 94 and regular. The point of maximal impulse was in the left midelavicular line in the fifth left intercostal space and there was only a slight right ventricular lift. At the apex the first heart sound was accentuated. The second heart sound in the pulmonic area was loud and showed normal respiratory splitting. In the pulmonic area and along the left sternal border there was a grade-II high-pitched, decrescendo, blowing diastolic murmur, and CO56CLLINS, BRAUNWALD, MORROW 566 TABLE 2.-Results of Radioactive Krypton Tests for Valvular Regurgitation Right ventricular injection Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 L. R. W. J. H. E. C. H. J. O. L. AI. J. B. J. S. S. C. D.M. M. E. M. B. - 12 5 79 345 230 0 2 * 65 - - 139 59 Pulmonary artery injection 3 301 44 54 0 31 7 199 245 7 1223 0 53 2 2 0 3 29 18 23 0 0 -m30 55 All counts have been corrected for background. RA, right atrium; RV, right ventricle; *, very large regurgitant curve, but no recirculation curve recorded. a grade-TI rumbling diastolie murmur with presystolic accentuation was heard at the apex. The electrocardiogram showed right ventricular hypertrophy and right axis deviation. X-rays revealed the heart to be slightly enlarged in its transverse diameter and there was prominence of the main pulmonary artery segment and enlargement of the left atrium. Right heart catheterization revealed the pulmonary artery pressure to be 50/30, the cardiac index was 1.98 lJ./miln./M.2, and no shunts were preseIit. Transbronchial left heart catheterization revealed a mean left atrial pressure of 22 mm. Hg and the enddiastolic gradient across the mitral valve was 20 mm. Hg. It was considered that this patient had mitral stenosis and that the diastolic murmur along the left sternal border represented pulmonic regurgitation. However, no regurgitation was demonstrated either by the dye-dilution method (table 1, fig. 3) or by the Kr`1S technic (table 2). Retrograde aortic catheterization and quantification of aortic regurgitation was then carried out and revealed regurgitation of dye from the thoracic aorta at the level of the eighth thoracic vertebra to the origin of the innominate artery. The final diagnosis was severe mitral stenosis and moderate aortic regurgitation. In the past, the definitive diagnosis of tricuspid regurgitation has rested primarily on elinieopathologic correlations. It was suggested by the contour of the right atrial pressure pulse in 60 patients studied by Sepulveda and Lucas.20 However, tricuspid regurgitation had been suspected clinically in only 23 per cent of this group. On the other hand, in the present investigation, substantial tricuspid regurgitation was demonstrated in patients L.M., S.C., and D.W. in whom the right atrial pressure pulse was normal. In this connection it is also of interest that the right atrial pressure pulse was not modified in the 4 patients with congenital left ventriculo-right atrial communications whom we have recently studied.2' In this malformation, blood is ejected into the right atrium during ventricular systole in a manner similar to tricuspid regurgitation. It is anticipated that the methods described herein will provide a more precise approach to the diagnosis of tricuspid regurgitation and make clinico-hemodylamici-pathologic correlations more meaningful than heretofore. The recognition of tricuspid regurgitation may be of considerable clinical importance. It has been pointed out by Schilder and Harvey22 that patients with mitral stenosis and tricuspid regurgitation have been denied commissurotomy because the presence of a loud systolic murmur led to the erroneous diagnosis of mitral regurgitation. Such diagnostic errors should be obviated by the recognition of tricuspid regurgitation with the indicator-dilution or radioactive gas technics. SUMMARY Technics for the demonstration of pulmonic and tricuspid regurgitation and the estimation of the magnitude of regurgitant flow are described. The pulnmonic valve was studied by positioning a modified double-lumen catheter so that the distal lumen opened into the pulmonary artery and the proximal lumen opened into the right ventricle. When tricuspid function was examined, the distal lumen Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 DYE DETECTION OF REGURGITATION 567 opened into. the right ventricle and the proximal one into the right atrium. Cardiogreen dye and radioactive krypton (Kr85) were injected through the distal opening of the catheter and sampled from the proximal opening. With a competent valve, either no dye or Kr85 or only a minimal quantity could be detected in the proximal chamber immediately after injection. In the presence of valvular regurgitation, substantial amounts appeared in the proximal chamber immediately after injection. Regurgitation was present in 7 of the 28 patients in whom the pulmoilic valve was examined, with regurgitant fractions ranging from 17 to 72 per cent. Tricuspid regurgitation was proved in 8 of the 17 patients studied; the regurgitant fractions were 11 to 65 per cent. The methods described appear reliable, simple to apply in the course of right heart catheterization, and of clinical value in the study of patients with known or suspected valvular heart disease or with heart murmurs of uncertain etiology. 28 patientes in qui le valvula pulmonic esseva examinate. lie fractiones regurgitante variava inter 17 e 72 pro cento. Regurgitation tricuspide esseva constatate in 8 del 17 patientes studiate. Le fi actiones regurgitante variava inter 11 e 65 pro cento. Le methodos describite es apparenitemenite digne de confidentia, simple a applicar in le curso de catheterismo dextero-cardiac, e de valor clinic in le studio de pacientes con establite o suspicite morbo de valvula cardiac o con murinures cardiac de etiologia inicerte. SUMMARIO IN INTERLINGUA Es describite technicas pro le demonstration de regurgitation pulmonic e tricuspide e pro le estimation del magnitude del fluxo regurgitante. Lie valvula pulmonic esseva studiate per positionar un modificate catheter a lumine duple de inaniera que le lumine distal commnunicava con le arteria pulmonar e le lumime proximal con le ventriculo dextere. In le examinie del function tricuspide, le catheter esseva positionate de maniera que le lumine distal conimunicava con le ventriculo dextere e le lumine proximal con le atrio dextere. Un colorante cardio-verde e krypton radioactive (r1r85) esseva injicite via le lumine distal del catheter e specimens esseva obtenite ab le lumine proximal. Quando le valvula es competente, nulle colorante e nulle Kr85 - o al minus solmente un quantitate minimal de illos - poteva esser detegite in le camera proximal iInmnediatemente post le injection. In le presentia de regurgitation valvular, quantitates substantial del indicatores appareva in le camera proximal inimediatemente post le injection. Regurgitation esseva presente in 7 del REFERENCES 1. KORNER, P. I., AND SHILLINGFORD, J. P.: Further observations on the estimation of valvular incompetence from indicator dilution curves. Clin. Se. 15: 417, 1956. 2. WRIGHT, J. L., AND W.XOOD, E. H.: Localization of valvular regurgitation. Proc. Staff Meet., Mayo Clin. 32: 491, 1957. 3. WOODWARD, F.. J., BURCHELL, H. B., AND /WOOD, E. H.: Dilution curves associated with valvular regurgitation. Proc. Staff Meet., Mayo Clin. 32: 518, 1957. 4. KEYS, J. R., SWAN, H. J. C., AND WOOD, E. H.: Dye dilution curves from systemic arteries and left atrium of patients with valvular heart disease. Proc. Staff Meet., Mayo Clin. 31: 138, 1956. 5. WOODWARD, E., JR., SWAN, H. J. C., AND WOOD, E. H.: Evaluation of a method for detection of mitral regurgitation from indicator dilution curves recorded from the left atrium. Proc. Staff Meet., Mayo Clin. 32: 525, 1957. 6. LEHMAN, J. S., MUSSER, B. G., AND LYKENS, H. D.: Cardiac ventriculography. Direct transtliori cic needle puncture opacification of the left (or right) ventricle. Am. J. Roentgenol. 77: 207, 1957. 7. BRAUNWALD, E., AND MORROW, A. G.: A method for the detection and estimation of aortic regurgitant flow in man. Circulation 17: 505, 1958. 8. GRANT, R. P., SANDERS, R. J., MORROW, A. G., AND BRAUNWALD, E.: Symposium on diagnostic methods in the study of left-to-right shunts. Circulation 16: 791, 1957. 9. COLLINS, N. P., BRAUNWALD, E., AND MORROW, A. G.: Isolated congenital pulmonic valvular regurgitation. Diagnosis by cardiac catheterization and angiocardiography. Am. J. Med. In press. 10. BAJEc, D. F., BIRKHEAD, N. C., CARTER, S. A., COLLINS, BRAUNWALD, MORROW 568 11. 12. Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 13. 14. 15. 16. AND WOOD, E. H.: Localization and estimation of severity of regurgitant flow at the pulmonary and tricuspid valves. Proc. StafY Meet., Mayo Clin. 33: 569, 1958. Fox, I. J., BROOKER, L. G. S., HESELTINE, D. W., ESSEX, H. E., AND WOOD, E. H.: A tricarboeyanine dye for continuous recording of dilution curves in whole blood independent of variations in blood oxygen saturation. Proc. Staff Meet., Mayo Clin. 32: 478, 1957. GILFORD, S. R., GREGG, E. D., SHADLE, 0. W., FERGUSON, T. B., AND MARZETTA, L. A.: An improved cuvette densitometer for cardiac output determined by dye dilution method. Rev. Scient. Inst.unients 2'-: 696, 1953. HETZEEL, P. S., RAMIREZ DE ARELLANO, A. A., AND WOOD, E. H.: Estinmation of cardiac output from initial portion of arterial indicator-dilution curves. Fed. Proc. 14: 72, 1955. -, SWAN, H. J. C., RAMIREZ DE ARELLANO, A. A., AND WOOD, E. H.: Estimation of cardiac output from first part of arterial dyedilution curves. J. Appl. Physiol. 13: 92, 1958. CHIDSEY, C. A., III, FRITTS, H. W., JR., HARDEWIG, A., RICHARDS, D. Wy., AND COURNAND, A.: Fate of radioactive krypton (Kr85) introduced intravenously in man. J. Appl. Physiol. 14: 63, 1959. BRAUNWALD, E., MORROW, A. G., SANDERS, R. J., AND LONG, R. T. L.: The characteri- 17. 18. 19. 20. 21. 22. zation of circulatory shunts by foreign gas technics. Symposium, Am. Assoc. Advan. Science, Dec. 1958. In press. -, LONG, R. T. L., AND MORROW, A. G.: Injections of radioactive krypton (Kr 85) solutions in the detection and localization of cardiac shunts. Abstracted, J. Clin. Invest. 38: 990, 1959. LONG, R. T. I., WVALDHAUSEN, J. A., CORNELL, W. P., AND SANDERS, R. J.: The detection of right-to-left circulatory shunts. A new method utilizing injections of a radioactive gas, Kr85. Proc. Soc. Exper. Biol. & Med. In press. -, LOMBARDO, C. R., AND BRAUNWALD, E.: The use of radioactive krypton and eardiogreen dilution curves in the detection of experimental portal-systemic venous shunts. Ann. Surg. In press. SEPULVEDA, G., AND LUKAS, D. S.: The diagnosis of tricuspid insufficiency. Clinical features in 60 cases with mitral valve disease. Circulation 11: 552, 1955. BRAUNWALD, E., AND MORROW, A. G.: Left ventriculo-right atrial communication: Diagnosis by clinical, hemodynamic and angiographic methods. Am. J. Med. In press. SCHILDER, D. P., AND HARVEY, W. P.: Confusion of tricuspid incompetence with mitral insufficiency. A pitfall in the selection of patients for mitral surgery. Am. Heart J. 54: 359, 1957. e. With the invention of the microscope we can mark the first positive step towards the goal to-day. A Jesuit priest, Kircher, in 1671, was the first to investigate putrefying meat, milk, and cheese with the crude microscope of his day, and left us indefinite remarks concerning 'very minute living worms' found therein. Four years after Kircher a Dutch linen merchant, Antonius von Leeuwenhoek, by improving the lenses of the microscope saw in rain-water, putrefying fluids, intestinal contents, and saliva, minute, moving, living particles, which he called 'animalculae.' In medical circles of his day these observations aroused the keenest interest, and the theory that these 'animalculae' might be the cause of all disease was eagerly discussed. Plenciz, of Vienna, after much observation of various fluids, putrefying and otherwise, wrote, in 1762, that it was his firm belief that the phenomena of diseases and the decomposition of animal fluids were wholly caused by minute living things.-WILLIAM OSLER. Aequanimitas and Other Addresses. Blakiston & Co., Philadelphia, and T. K. Lewis, London, 1904. Detection of Pulmonic and Tricuspid Valvular Regurgitation by Means of Indicator Solutions N. PERRYMAN COLLINS, EUGENE BRAUNWALD and ANDREW G. MORROW Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 Circulation. 1959;20:561-568 doi: 10.1161/01.CIR.20.4.561 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1959 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/20/4/561 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/