Summary
We developed methods to revive human hearts, obtained at the time of cardiac transplantation, and study them in the physiology laboratory. The hearts were arrested with cardioplegic solution at the time of explantation and transported to the laboratory at 4°C. The hearts were perfused with a human blood based solution whose flow rate, temperature, and ionic concentration were controlled. Six hearts with various endstage cardiomyopathies were revived in this manner. Once perfusion was started, the hearts maintained a steady contractile state for approximately 30 min during which time data could be collected. Within this time period we could measure end-systolic and end-diastolic pressure-volume relations, the time courses of contraction and relaxation, and the influence of heart rate and premature stimulation on contractile state. The results suggest that evidence of specific cellular abnormalities in human heart disease might be obtained from measurements of global ventricular performance. Furthermore, the type of abnormality identified, namely sarcoplasmic reticulum dysfunction, in several forms of cardiomyopathy was in concordance with results obtained in muscle bath studies of similarly diseased human and animal myocardium.
Similar content being viewed by others
References
Swynghedauw B, Schwartz K, Degeorges M (ed) (1984) Symposium on biology of cardiac overload. Eur Heart J 5 (Suppl F): F-1-353
Strobeck JE, Sonnenblick EH (1985) Pathophysiology of heart failure. In: Levine HJ, Gaasch WH (eds) The ventricle. Martinus Nijhoff, Boston, pp 209–224
Sonnenblick EH, Braunwald E, Morrow AG (1965) The contractile properties of human heart muscle: studies on myocardial mechanics of surgically excised papillary muscles. J Clin Invest 44: 966–977
Sonnenblick EH, Morrow AG, Willians JF (1966) Effects of heart rate on the dynamics of force development in the intact human ventricle. Circulation 33: 945–951
Yue DT, Sagawa K (1987) Insight into excitation-contraction coupling of heart derived from studies of the force-interval relationship. In: Sideman S, Beyar R (eds) Activation, metabolism and perfusion of the heart. Martinus Nijhoff, Boston, pp 261–279
Limas CJ, Olivari MT, Goldenberg IF, Levine TB, Benditt DG, Simon A (1987) Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. Cardiovasc Res 21: 601–605
Suga H, Sagawa K. (1974) Instantaneous pressure-volume relationships and their ratio in the excised, supported canine left ventricle. Circ Res 35: 117–126
Suga H, Sagawa K (1977) End-diastolic and end-systolic ventricular volume clamper for isolated canine heart. Am J Physiol 233: H718-H722
Mirsky I (1984) Assessment of diastolic function: suggested methods and future considerations. Circulation 69: 836–841
Draper NR, Smith H (1981) Applied regression analysis, 2nd edn. Wiley-Interscience, New York, pp 462–468
Burkhoff D, Yue DT, Franz MR, Hunter WC, Sagawa K (1984) Mechanical restitution of isolated perfused canine left ventricles. Am J Physiol 246: H8-H16
Anderson PAW, Manring A, Serwer GA, Benson DW, Edwards SB, Armstrong BE, Sterba RJ, Floyd RD (1979) The force-interval relationship of the left ventricle. Circulation 60: 334–348
Keren A, Billingham ME, Weintraub D, Stinson EB, Popp RL (1985) Mildly dilated congestive cardiomyopathy. Circulation 72: 302–309
Siegel JR, Shah PK, Fishbein MC (1984) Idiopathic restrictive cardiomyopathy. Circulation 70: 165–169
Benotti JR, Grossman W, Cohn PF (1980) Clinical profile of restrictive cardiomyopathy. Circulation 61: 1206–1212
Rubin SA, Fishbein MC, Swan HJC (1983) Compensatory hypertrophy in the heart after myocardial infarction in the rat. J Am Coll Cardiol 6: 1435–1441
Badeer HS (1972) Pathogenesis of cardiac hypertrophy in coronary atherosclerosis and myocardial infarction. Am Heart J 84: 256–264
Norman T, Goers CR (1960) Cardiac hypertrophy after coronary artery ligation in rats. Arch Pathol 69: 181–184
Henning H, O'Rourke RA, Crawford MH, Righetti A, Karliner JS (1978) Inferior myocardial infarction as a cause of asymmetric septal hypertrophy. An echocardiographic study. Am J Cardiol 41: 817–822
Burkhoff D, Yue DT, Franz MR, Sunagawa K, Maughan WL, Hunter WC, Sagawa K (1984) Quantitative comparison of the force-interval relationships of the canine right and left ventricles. Circ Res 54: 595–602
Burkhoff D (1985) The myocardial force-interval relationship studied in isolated canine hearts. Doctoral Dissertation, The Johns Hopkins University, Maryland
Grossman W, Braunwald E, Mann T, McLaurin LP, Green LH (1977) Contractile state of the left ventricle in man as evaluated from end-systolic pressure-volume relations. Circulation 56: 845–852
Sagawa K (1981) (editorial) The end-systolic pressure-volume relation of the ventricle: definition, modification and clinical use. Circulation 63: 1223–1227
Suga H, Sagawa K, Shoukas AA (1973) Load independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res 32: 314–322
Kass DA, Maughan WL (1988) From ‘Emax’ to pressure-volume relations: a broader view. Circulation 77: 1203–1212
Burkhoff D, Sugiura S, Yue DT, Sagawa K (1987) Contractility-dependent curvilinearity of end-systolic pressure-volume relations. Am J Physio 252: H1218-H1227
Suga H, Yamada O, Goto Y, Igarashi Y, Yasumura Y, Nozawa T (1986) Reconsideration of normalization of Emax for heart size. Heart Vessels 2: 67–73
van der Velde ET, Baan J (1988) Sensitivity of left ventricular end-systolic pressure-volume relation to the type of loading intervention in dogs. Circ Res 62: 1247–1258
Freeman GL, Little WC, O'Rourke RA (1986) The effect of vasoactive agents on the left ventricular end-systolic pressure-volume relation in closed-chest dogs. Circulation 74: 1107–1113
Khullar S, Lewis RP (1976) Usefulness of systolic time intervals in differential diagnosis of constrictive pericarditis and restrictive cardiomyopathy. Br Heart J 38: 43–46
Hirota Y, Kohriyama T, Hayashi T, Kaku K, Nishimura H, Saito T, Nakayama Y, Suwa M, Kino M, Kawamura K (1983) Idiopathic restrictive cardiomyopathy: differences of left ventricular relaxation and diastolic wave forms from constrictive pericarditis. Am J Cardiol 52: 421–423
Grossman W, McLaurin LP, Rolett EL (1979) Alterations in left ventricular relaxation and diastolic compliance in congestive cardiomyopathy. Cardiovasc Res 13: 514–522
Gwathmey JK, Morgan JP (1985) Altered calcium handling in experimental pressure-overload hypertrophy in the ferret. Circ Res 57: 836–43
Gwathmey JK, Copelas L, MacKinnon R, Schoen FJ, Feldman MD, Grossman W, Morgan JP (1987) Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 61: 70–76
Pidgeon J, Miller GAH, Noble MIM, Papadoyannis D, Seed WA (1982) The relationship between the strength of the human heart beat and the interval between beats. Circulation 65: 1404–1410
Anderson PAW, Manring A, Arentzen CE, Rankin JS, Johnson EA (1977) Pressure-induced hypertrophy of cat right ventricle. An evaluation with the force-interval relationship. Circ Res 41: 582–588
Wier WG, Yue DT (1986) Intracellular calcium transients underlying the short-term force-interval relationship in ferret ventricular myocardium. J Physiol (Lond) 376: 507–530
Wood EH, Heppner RL, Weidmann S (1969) Inotropic effects of electric currents. Circ Res 24: 409–445
Morad M, Goldman Y (1973) Excitation-contraction coupling in heart muscle: membrane control of development of tension. Prog Biophys Mol Bio 27: 257–313
Sutko, JL, Kenyon JL (1983) Ryanodine modification of cardiac muscle responses to potassium-free solutions: evidence for inhibition of sarcoplasmic reticulum calcium release. J Gen Physiol 82: 385–404
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Burkhoff, D., Flaherty, J.T., Yue, D.T. et al. In vitro studies of isolated supported human hearts. Heart Vessels 4, 185–196 (1988). https://doi.org/10.1007/BF02058586
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02058586