Skip to main content
SpringerLink
Log in

The Isolated Work-Performing and Ejecting Mouse Heart Preparation Comparison and Quantification of Cardiac Performance in Transgenic and Wild-Type Mice

  • Chapter
  • First Online:
Book cover Cardiovascular Physiology in the Genetically Engineered Mouse

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 238))

Abstract

Over the past ten years an abundance of transgenic mouse models (gene ablations, overexpressions, or mutations) with variable consequences on heart function have become available. Consequently, quantitative methods had to be developed to analyze cardiac function in the mouse heart. Since the mouse heart is so small (heart weight approximately 125-180 mg) new types of instrumentation for the heart produce new challenges for the cardiovascular and cardiac physiologist. We developed the buffer perfused work-performing mouse heart preparation to analyze myocardial function independent from autonomic or hemodynamic feedback or other compensation. The resultant preparation permits exact control of preload and afterload of the heart. The ejecting heart allows the evaluation of all phases of the intraventricular pressure curve, (systolic, diastolic, and end-diastolic pressure). Furthermore, in order to cover the widest possible range of contractile parameters, ±dP/dt, time to peak pressure (TPP), and 1/2 time to relaxation (RT 1/2) must be recorded. In order to indeed provide reliable quantitative myocardial contractile comparison non-transgenic (NTG) and transgenically (TG) altered littermates have to be directly compared in every case under exactly identical loading conditions. The ideal comparison should be made by the construction of cardiac function curves based upon this pressure and volume loading.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Neely JR, Liebermeister H, Batterby H, Morgan H. Effect of pressure development on 02 consumption by isolated rat hearts. Am J Phys 1967; 212: 804–814.

    CAS  Google Scholar 

  2. Grupp IL, Grupp G. “Isolated heart preparation perfused or superfused with balanced salt solutions.” In Methods in Pharmacology. New York: Plenum Publishing, 5: 111–128, 1984.

    CAS  Google Scholar 

  3. Grupp G. “Derived Indices of Myocardial Function in Isolated Work-Performing Hearts.” In Methods in Pharmacology, New York: Plenum Publishing, 5: 129–139, 1984.

    Google Scholar 

  4. Szymanska G, Grupp IL, Slack JP, Harrer JM, Kranias EG. Alterations in sarcoplasmic reticulum calcium uptake, relaxation parameters and their responses to ß-adrenergic agonists in the developing rabbit heart. J Mol Cell Cardiol 1995; 27: 1819–1829.

    Article  PubMed  CAS  Google Scholar 

  5. Grupp G, Grupp IL, Kojima M, Sperelakis N, Tsuchiya Y, Hosokawa T, Schwartz A. Hemodynamic and electrophysiological effects of a novel positive inotropic drug, OPC-8212, in normal and “failing” guinea pig heart preparations. J Cardiovasc Pharm 1986; 8:428–440.

    Article  CAS  Google Scholar 

  6. Ng WA, Grupp IL, Subramaniam A, and Robbins J. Cardiac myosin heavy chain mRNA expression and myocardial function in the mouse heart. Circ Res 1991; 69:1742–1750.

    Article  Google Scholar 

  7. Grupp IL, Subramaniarn A, Hewett T, Robbins J, Grupp G. Comparison of normal, hypo, and hyperdynamic mouse hearts using isolated work performing heart preparations. Am J Phys 1993; 265 (Heart Circ Phys 34): H1401–1410.

    CAS  Google Scholar 

  8. Hewett TE, Grupp IL, Grupp G, Robbins J. a-Skeletal actin is associated with increased contractility in the mouse heart. Circ Res 1994; 74:740–746.

    Article  PubMed  CAS  Google Scholar 

  9. Grupp IL, Kranias EG, Kiss E, Koss K, Harrer JM, Slack J, Edes I, Low W, Grupp G. The contribution of phospholamban to myocardial contractility. Heart Fail 1995; 11:48–61.

    Google Scholar 

  10. Chen EP, Bittner HB, Petersen DS, Van Trigt P. A Work-performing heart preparation for myocardial performance. J Surg Res 1996; 64: 57–62.

    Article  PubMed  Google Scholar 

  11. Gauthier NS, Matheme GP, Morrison RR, Headrick, JP. Assessment of contractile function in working mouse hearts. FASEB J 1997; 11: A67.

    Google Scholar 

  12. Desai KH, Sato R, Schauble E, Baosli GS, Kobilka BK, Bernstein D. Cardiovascular indexes in the mouse at rest and with exercise: new tools to study models of cardiac disease. Am J Phys 1997; 272: H1053–1061.

    CAS  Google Scholar 

  13. Zack, Radovan. Basic Facts for Basic Science. New York: Raven Press; 235–236, 1990.

    Google Scholar 

  14. Chu G, Luo W, Slack JP, Kranias EG, Grupp IL, et. al. Compensatory mechanisms associated with the hyperdynamic function of phopholamban deficient mouse hearts. Circ Res 1996; 79: 1064–1076.

    Article  PubMed  CAS  Google Scholar 

  15. Luo W, Grupp IL, Harrer J, Ponniah S, Grupp G, Duffy JJ, Doetschmann T, Kranias, E. Targeted ablation of the mouse phospholamban gene results in altered myocardial contractility. Circ Res 1994; 75: 401–409.

    Article  PubMed  CAS  Google Scholar 

  16. Michael LH, Entman ML, Hartley CJ, Youker KA, Zhu J, Hall SR, Hawkins HK, Berens K, Ballantyne CM. Myocardial ischemia and reperfusion: a murine model. Am J Physiol 1995;269:H2147- H2154.

    PubMed  CAS  Google Scholar 

  17. Brooks WW, Garibaldi BA, Conrad CH. Myocardial injury in the mouse induced by transthoracic cauterization. Lab Animal Science 1998;48:374–378.

    CAS  Google Scholar 

  18. Sumeray MS, Yellon DM. Characterisation and validation of a murine model of global ischaemiareperfusion injury. Mol Cell Biochem 1998;186:61–68.

    Article  PubMed  CAS  Google Scholar 

  19. Opie LH. The heart: physiology, from cell to circulation, 3rd ed. Philadelphia:Lippincott-Raven Publishers, 1998.

    Google Scholar 

  20. Hearse DJ, Sutherland FJ. Experimental models for the study of cardiovascular function and disease. Pharmacol Res 2000;41:597–603.

    Article  PubMed  CAS  Google Scholar 

  21. Ytrehus K. The ischemic heart-experimental models. Pharmacol Res 2000;42:193–203.

    Article  PubMed  CAS  Google Scholar 

  22. Tveita T, Mortensen E, Hevroy O, Refsum H, Ytrehus K. Experimental hypothermia: effects of core cooling and rewamting on hemodynamics, coronary blood flow, and myocardial metabolism in dogs. Anesth Analg 1994;79:212–218.

    Article  PubMed  CAS  Google Scholar 

  23. Broderick TL, Currie RW, Paulson DJ. Heat stress induces rapid recovery of mechanical function of ischemic fatty acid perfused hearts by stimulating glucose oxidation during reperfusion. Can J Physiol Pharmacol 1997;75:1273–1279.

    Article  PubMed  CAS  Google Scholar 

  24. Padua RR, Sethi R, Dhalla NS, Kardami E. Basic fibroblast growth factor is cardioprotective in ischemiareperfusion injury. Mol Cell Biochem 1995;143:129–135.

    Article  PubMed  CAS  Google Scholar 

  25. Dhar P, Grupp IL, Schwartz A, Grupp G, Matlib MA; Reduction of Camitine Content by Inhibition of Its Biosynthesis Results in Protection of Isolated Guinea Pig Hearts Against Hypoxia Damage. JCardiovasc Pharmacol Therapeut 1996; I(3):235–242

    Google Scholar 

  26. Grupp IL, Jackson TM, Hake P, Grupp G, Szabo C; Protction against Hypoxia-reoxygenation in the Absence of Poly (ADP-ribose) Synthetase in Isolated Working Hearts. JMol Cell Cardiol 1999; 31:297303

    Google Scholar 

  27. Shamraj OI, Grupp IL, Grupp G, Melvin D, Gradoux N, Kremers W, Lingrel JB, De Pover A. Characterisation of Na/K-ATPase, its isoforms, and the inotropic response to ouabain in isolated failing human hearts. Cardiovasc Res 1993; 27: 2229–2237.

    Article  PubMed  CAS  Google Scholar 

  28. Grupp I, Im WB, Lee CO, Lee SW. Relation of sodium pump inhibition to positive inotropy at low concentrations of ouabain in rat heart muscle. J Physiol 1985; 360: 149–160.

    PubMed  CAS  Google Scholar 

  29. Grupp IL, Grupp G, Schwartz A. Digitalis receptor desensitization in rat ventricle: ouabain produces two inotropic effects. Life Sci 1981; 29:2789–2794.

    Article  PubMed  CAS  Google Scholar 

  30. Shull MM, Diebold RJ, Eis M, Boivin G, Grupp IL, Doetschman T. Homologous recombination and growth factors in molecular genetics and gene therapy of cardiovascular diseases, Stephen C. Mockrin, ed. 26: 14, 371–403, 1996, Marcel Dekker, New York.

    Google Scholar 

  31. Koss KL, Ponniah S, Jones WK, Grupp IL, Kranias EG. Differential phospholamban gene expression in murine cardiac compartments. Circ Res 1995; 77: 342–353.

    Article  PubMed  CAS  Google Scholar 

  32. Koss KL, Grupp IL, Kranias EG. The relative phospholamban and SERCA2 ratio: a critical determinant of myocardial contractility. Basic Res Cardiol 1997; 92 suppl. 1: 17–24.

    Article  PubMed  CAS  Google Scholar 

  33. Askew GR, Lingrel JB, Grupp IL, Grupp G. Direct correlation of Na+/K+-ATPase isoform abundance and myocardial contractility in mouse heart. Biol Chem 1993; 374: 545–624.

    Google Scholar 

  34. Slack JP, Grupp, IL, Luo W, Kranias EG. Phospholabman ablation enhances relaxation in the murine soleus. Am J Phys 1997; 273: C1–C6.

    CAS  Google Scholar 

  35. Slack JP, Grupp IL, Ferguson DG, Rosenthal N, Kranias EG. Ectopic expression of phospholamban in fast-twitch skeletal muscle alters sarcoplasmic reticulum Ca2+ Transport and muscle relaxation. J Biol Chem 1997; 272: 18862–18868.

    Article  PubMed  CAS  Google Scholar 

  36. Grupp IL, Slack JP, Tilgmann C, Luo W, Tamura T, Gerdes AM, Kranias EG. Effects of Age on the Hyperdynamic Cardiac Function of Phospholamban Knockout Mice. AHA 70th Scientific Sessions 1997; 249.

    Google Scholar 

  37. Slack JP, Grupp IL, Holder D, Schmidt A, Gerst MJ, Tamura T, Tilgmann C, James PF, Johnson R, Gerdes AM, Kranias EG. The enhanced contractility of the phospholamban-deficient mouse heart persists with aging. J Biol Chem. Accepted 2001.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pharmacology and Cell Biophysics and Molecular and Cellular Physiology, College of Medicine University of Cincinnati, USA

    Ingrid L. Grupp M.D., Jo El Schultz Ph.D., George Sfyris & Gunter Grupp M.D. Ph.D

Authors
  1. Ingrid L. Grupp M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jo El Schultz Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George Sfyris
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gunter Grupp M.D. Ph.D
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Case Western Reserve University and University Hospitals of Cleveland, USA

    Brian D. Hoit  & Richard A. Walsh  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media New York

About this chapter

Cite this chapter

Grupp, I.L., El Schultz, J., Sfyris, G., Grupp, G. (2001). The Isolated Work-Performing and Ejecting Mouse Heart Preparation Comparison and Quantification of Cardiac Performance in Transgenic and Wild-Type Mice. In: Hoit, B.D., Walsh, R.A. (eds) Cardiovascular Physiology in the Genetically Engineered Mouse. Developments in Cardiovascular Medicine, vol 238. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1653-8_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1653-8_9

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5661-5

  • Online ISBN: 978-1-4615-1653-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation