Abstract
1. Isovolumic left ventricular pressure was measured at various coronary arterial pressures in Langendorff-perfused ferret hearts. The concentrations of phosphorus-containing metabolites were measured using 31P nuclear magnetic resonance (NMR). Intracellular free calcium concentration ([Ca2+]i), was measured with 19F NMR in a group of hearts that were loaded with the calcium indicator 5F-BAPTA. 2. Developed pressure increased when coronary arterial pressure was raised from the control value of 80 to 100-160 mmHg and decreased when coronary pressure was lowered to 40-70 mmHg. The changes were reversible. 3. Coronary flow varied directly with coronary pressure over the entire range from 40 to 160 mmHg. 4. The concentrations of phosphorus-containing metabolites and the efflux of lactate from the heart remained unchanged at coronary pressures of 60 mmHg or higher. Below 60 mmHg, intracellular pH decreased, while inorganic phosphate concentration and lactate efflux increased. 5. In contrast to the developed pressure during twitch contractions, maximal Ca2+-activated pressure remained constant at coronary pressures of 60-160 mmHg. Only below a coronary pressure of 60 mmHg did maximal Ca2+-activated pressure decline. 6. An increase in coronary pressure produced an increase in developed pressure even in hearts stretched to the peak of the Frank-Starling relation. 7. When coronary pressure was lowered from 80 to 60 mmHg, [Ca2+]i decreased during systole; the opposite effect was apparent when coronary pressure was raised from 80 to 120 mmHg. 8. We conclude that coronary perfusion (pressure or flow) modulates intracellular calcium and, consequently, contractile force. Ischaemia cannot fully explain this phenomenon, nor can changes in sarcomere length.
Full text
PDF

















Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abel R. M., Reis R. L. Effects of coronary blood flow and perfusion pressure on left ventricular contractility in dogs. Circ Res. 1970 Dec;27(6):961–971. doi: 10.1161/01.res.27.6.961. [DOI] [PubMed] [Google Scholar]
- Allen D. G., Eisner D. A., Morris P. G., Pirolo J. S., Smith G. L. Metabolic consequences of increasing intracellular calcium and force production in perfused ferret hearts. J Physiol. 1986 Jul;376:121–141. doi: 10.1113/jphysiol.1986.sp016145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Allen D. G., Kentish J. C. The cellular basis of the length-tension relation in cardiac muscle. J Mol Cell Cardiol. 1985 Sep;17(9):821–840. doi: 10.1016/s0022-2828(85)80097-3. [DOI] [PubMed] [Google Scholar]
- Allen D. G., Morris P. G., Orchard C. H., Pirolo J. S. A nuclear magnetic resonance study of metabolism in the ferret heart during hypoxia and inhibition of glycolysis. J Physiol. 1985 Apr;361:185–204. doi: 10.1113/jphysiol.1985.sp015640. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Allen D. G., Orchard C. H. Myocardial contractile function during ischemia and hypoxia. Circ Res. 1987 Feb;60(2):153–168. doi: 10.1161/01.res.60.2.153. [DOI] [PubMed] [Google Scholar]
- Arnold G., Kosche F., Miessner E., Neitzert A., Lochner W. The importance of the perfusion pressure in the coronary arteries for the contractility and the oxygen consumption of the heart. Pflugers Arch Gesamte Physiol Menschen Tiere. 1968;299(4):339–356. doi: 10.1007/BF00602910. [DOI] [PubMed] [Google Scholar]
- Bacaner M. B., Lioy F., Visscher M. B. Coronary blood flow, oxygen delivery rate and cardiac performance. J Physiol. 1971 Jul;216(1):111–127. doi: 10.1113/jphysiol.1971.sp009512. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DAY S. B., JOHNSON J. A. Pressure-flow relationships in the isolated perfused rabbit heart. Am J Physiol. 1959 Jun;196(6):1289–1291. doi: 10.1152/ajplegacy.1959.196.6.1289. [DOI] [PubMed] [Google Scholar]
- Daniell H. B. Coronary flow alterations on myocardial contractility, oxygen extraction, and oxygen consumption. Am J Physiol. 1973 Nov;225(5):1020–1025. doi: 10.1152/ajplegacy.1973.225.5.1020. [DOI] [PubMed] [Google Scholar]
- Deussen A., Borst M., Kroll K., Schrader J. Formation of S-adenosylhomocysteine in the heart. II: A sensitive index for regional myocardial underperfusion. Circ Res. 1988 Jul;63(1):250–261. doi: 10.1161/01.res.63.1.250. [DOI] [PubMed] [Google Scholar]
- Downey J. M. Myocardial contractile force as a function of coronary blood flow. Am J Physiol. 1976 Jan;230(1):1–6. doi: 10.1152/ajplegacy.1976.230.1.1. [DOI] [PubMed] [Google Scholar]
- Fabiato A., Fabiato F. Dependence of the contractile activation of skinned cardiac cells on the sarcomere length. Nature. 1975 Jul 3;256(5512):54–56. doi: 10.1038/256054a0. [DOI] [PubMed] [Google Scholar]
- Fedele F. A., Gewirtz H., Capone R. J., Sharaf B., Most A. S. Metabolic response to prolonged reduction of myocardial blood flow distal to a severe coronary artery stenosis. Circulation. 1988 Sep;78(3):729–735. doi: 10.1161/01.cir.78.3.729. [DOI] [PubMed] [Google Scholar]
- Feigl E. O. Coronary physiology. Physiol Rev. 1983 Jan;63(1):1–205. doi: 10.1152/physrev.1983.63.1.1. [DOI] [PubMed] [Google Scholar]
- Hibberd M. G., Jewell B. R. Calcium- and length-dependent force production in rat ventricular muscle. J Physiol. 1982 Aug;329:527–540. doi: 10.1113/jphysiol.1982.sp014317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hori M., Inoue M., Kitakaze M., Koretsune Y., Iwai K., Tamai J., Ito H., Kitabatake A., Sato T., Kamada T. Role of adenosine in hyperemic response of coronary blood flow in microembolization. Am J Physiol. 1986 Mar;250(3 Pt 2):H509–H518. doi: 10.1152/ajpheart.1986.250.3.H509. [DOI] [PubMed] [Google Scholar]
- Isenberg G., Belardinelli L. Ionic basis for the antagonism between adenosine and isoproterenol on isolated mammalian ventricular myocytes. Circ Res. 1984 Sep;55(3):309–325. doi: 10.1161/01.res.55.3.309. [DOI] [PubMed] [Google Scholar]
- Kentish J. C. The effects of inorganic phosphate and creatine phosphate on force production in skinned muscles from rat ventricle. J Physiol. 1986 Jan;370:585–604. doi: 10.1113/jphysiol.1986.sp015952. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kusuoka H., Weisfeldt M. L., Zweier J. L., Jacobus W. E., Marban E. Mechanism of early contractile failure during hypoxia in intact ferret heart: evidence for modulation of maximal Ca2+-activated force by inorganic phosphate. Circ Res. 1986 Sep;59(3):270–282. doi: 10.1161/01.res.59.3.270. [DOI] [PubMed] [Google Scholar]
- Legssyer A., Poggioli J., Renard D., Vassort G. ATP and other adenine compounds increase mechanical activity and inositol trisphosphate production in rat heart. J Physiol. 1988 Jul;401:185–199. doi: 10.1113/jphysiol.1988.sp017157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marban E., Kitakaze M., Chacko V. P., Pike M. M. Ca2+ transients in perfused hearts revealed by gated 19F NMR spectroscopy. Circ Res. 1988 Sep;63(3):673–678. doi: 10.1161/01.res.63.3.673. [DOI] [PubMed] [Google Scholar]
- Marban E., Kitakaze M., Kusuoka H., Porterfield J. K., Yue D. T., Chacko V. P. Intracellular free calcium concentration measured with 19F NMR spectroscopy in intact ferret hearts. Proc Natl Acad Sci U S A. 1987 Aug;84(16):6005–6009. doi: 10.1073/pnas.84.16.6005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marban E., Kusuoka H. Maximal Ca2+-activated force and myofilament Ca2+ sensitivity in intact mammalian hearts. Differential effects of inorganic phosphate and hydrogen ions. J Gen Physiol. 1987 Nov;90(5):609–623. doi: 10.1085/jgp.90.5.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marban E., Kusuoka H., Yue D. T., Weisfeldt M. L., Wier W. G. Maximal Ca2+-activated force elicited by tetanization of ferret papillary muscle and whole heart: mechanism and characteristics of steady contractile activation in intact myocardium. Circ Res. 1986 Sep;59(3):262–269. doi: 10.1161/01.res.59.3.262. [DOI] [PubMed] [Google Scholar]
- Marshall R. C. Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart. J Clin Invest. 1988 Jul;82(1):86–95. doi: 10.1172/JCI113606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Metcalfe J. C., Hesketh T. R., Smith G. A. Free cytosolic Ca2+ measurements with fluorine labelled indicators using 19FNMR. Cell Calcium. 1985 Apr;6(1-2):183–195. doi: 10.1016/0143-4160(85)90043-0. [DOI] [PubMed] [Google Scholar]
- Miller W. P., Shimamoto N., Nellis S. H., Liedtke A. J. Coronary hyperperfusion and myocardial metabolism in isolated and intact hearts. Am J Physiol. 1987 Nov;253(5 Pt 2):H1271–H1278. doi: 10.1152/ajpheart.1987.253.5.H1271. [DOI] [PubMed] [Google Scholar]
- Opie L. H. Coronary flow rate and perfusion pressure as determinants of mechanical function and oxidative metabolism of isolated perfused rat heart. J Physiol. 1965 Oct;180(3):529–541. doi: 10.1113/jphysiol.1965.sp007715. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patterson S. W., Piper H., Starling E. H. The regulation of the heart beat. J Physiol. 1914 Oct 23;48(6):465–513. doi: 10.1113/jphysiol.1914.sp001676. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Poche R., Arnold G., Gahlen D. Uber den Einfluss des Perfusionsdruckes im Coronarsystem des stillgestellten, aerob perfundierten isolierten Meerschweinchenherzens auf Stoffwechsel und Feinstruktur des Herzmuskels. Virchows Arch B Cell Pathol. 1971;8(3):252–266. [PubMed] [Google Scholar]
- Scharf S. M., Bromberger-Barnea B. Influence of coronary flow and pressure on cardiac function and coronary vascular volume. Am J Physiol. 1973 Apr;224(4):918–925. doi: 10.1152/ajplegacy.1973.224.4.918. [DOI] [PubMed] [Google Scholar]
- Schreiber S. S., Klein I. L., Oratz M., Rothschild M. A. Adenyl cyclase activity and cyclic AMP in acute cardiac overload: a method for measuring cyclic AMP production based on ATP specific activity. J Mol Cell Cardiol. 1971 Mar;2(1):55–65. doi: 10.1016/0022-2828(71)90079-4. [DOI] [PubMed] [Google Scholar]
- Smith G. A., Hesketh R. T., Metcalfe J. C., Feeney J., Morris P. G. Intracellular calcium measurements by 19F NMR of fluorine-labeled chelators. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7178–7182. doi: 10.1073/pnas.80.23.7178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steenbergen C., Murphy E., Levy L., London R. E. Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart. Circ Res. 1987 May;60(5):700–707. doi: 10.1161/01.res.60.5.700. [DOI] [PubMed] [Google Scholar]
- Tsien R. W. Cyclic AMP and contractile activity in heart. Adv Cyclic Nucleotide Res. 1977;8:363–420. [PubMed] [Google Scholar]
- Weisfeldt M. L., Shock N. W. Effect of perfusion pressure on coronary flow and oxygen usage of nonworking heart. Am J Physiol. 1970 Jan;218(1):95–101. doi: 10.1152/ajplegacy.1970.218.1.95. [DOI] [PubMed] [Google Scholar]
