Skip to main content
SpringerLink
Log in

Impaired left ventricular function in the presence of preserved ejection in chronic hypertensive conscious pigs

  • Original Contribution
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Systolic function is often evaluated by measuring ejection fraction and its preservation is often assimilated with the lack of impairment of systolic left ventricular (LV) function. Considering the left ventricle as a muscular pump, we explored LV function during chronic hypertension independently of increased afterload conditions. Fourteen conscious and chronically instrumented pigs received continuous infusion of either angiotensin II (n = 8) or saline (n = 6) during 28 days. Hemodynamic recordings were regularly performed in the presence and 1 h after stopping angiotensin II infusion to evaluate intrinsic LV function. Throughout the protocol, the mean arterial pressure steadily increased by 55 ± 4 mmHg in angiotensin II-treated animals. There were no significant changes in stroke volume, LV fractional shortening or LV wall thickening, indicating the lack of alterations in LV ejection. In contrast, we observed maladaptive changes with (1) the lack of reduction in isovolumic contraction and relaxation durations with heart rate increases, (2) abnormally blunted isovolumic contraction and relaxation responses to dobutamine and (3) a linear correlation between isovolumic contraction and relaxation durations. None of these changes were observed in saline-infused animals. In conclusion, we provide evidence of impaired LV function with concomitant isovolumic contraction and relaxation abnormalities during chronic hypertension while ejection remains preserved and no sign of heart failure is present. The evaluation under unloaded conditions shows intrinsic LV abnormalities.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Booysen HL, Norton GR, Opie LH, Woodiwiss AJ (2012) Reverse chamber remodelling following adrenergic-induced advanced cardiac dilatation and pump dysfunction. Basic Res Cardiol 107:238. doi:10.1007/s00395-011-0238-0

    Article  PubMed  Google Scholar 

  2. Bruch C, Schmermund A, Marin D, Katz M, Bartel T, Schaar J, Erbel R (2000) Tei-index in patients with mild-to-moderate congestive heart failure. Eur Heart J 21:1888–1895. doi:10.1053/euhj.2000.2246

    Article  PubMed  CAS  Google Scholar 

  3. Brutsaert DL (2006) Cardiac dysfunction in heart failure: the cardiologist’s love affair with time. Prog Cardiovasc Dis 49:157–181. doi:10.1016/j.pcad.2006.08.010

    Article  PubMed  Google Scholar 

  4. Colin P, Ghaleh B, Hittinger L, Monnet X, Slama M, Giudicelli JF, Berdeaux A (2002) Differential effects of heart rate reduction and β-blockade on left ventricular relaxation during exercise. Am J Physiol 282:H672–H679. doi:10.1152/ajpheart.00547.2001

    CAS  Google Scholar 

  5. Correia-Pinto J, Henriques-Coelho T, Roncon-Albuquerque R, Lourenço AP, Melo-Rocha G, Vasques-Nóvoa F, Gillebert TC, Leite-Moreira AF (2009) Time course and mechanisms of left ventricular systolic and diastolic dysfunction in monocrotaline-induced pulmonary hypertension. Basic Res Cardiol 104:535–546. doi:10.1007/s00395-009-0017-3

    Article  PubMed  Google Scholar 

  6. D’Angelo R, Shah N, Rubler S (1975) Diastolic time intervals in ischemic and hypertensive heart disease: a comparison of isovolumic relaxation time and rapid filling time with systolic time intervals. Chest 68:56–61

    Article  PubMed  Google Scholar 

  7. De Keulenaer GW, Brutsaert DL (2007) Diastolic heart failure: a separate disease or selection bias? Prog Cardiovasc Dis 49:275–283. doi:10.1016/j.pcad.2006.08.002

    Article  PubMed  Google Scholar 

  8. Dodek A, Burg JR, Kloster FE (1975) Systolic time intervals in chronic hypertension: alterations and response to treatment. Chest 68:51–55. doi:10.1378/chest.68.1.51

    Article  PubMed  CAS  Google Scholar 

  9. Douglas PS, Berko B, Lesh M, Reichek N (1989) Alterations in diastolic function in response to progressive left ventricular hypertrophy. J Am Coll Cardiol 13:461–467. doi:10.1016/0735-1097(89)90527-5

    Article  PubMed  CAS  Google Scholar 

  10. Elliott EB, Hasumi H, Otani N, Matsuda T, Matsuda R, Kaneko N, Smith GL, Loughrey CM (2011) K201 (JTV-519) alters the spatiotemporal properties of diastolic Ca2+ release and the associated diastolic contraction during β-adrenergic stimulation in rat ventricular cardiomyocytes. Basic Res Cardiol 106:1009–1022. doi:10.1007/s00395-011-0218-4

    Article  PubMed  CAS  Google Scholar 

  11. Falcão-Pires I, Palladini G, Gonçalves N, van der Velden J, Moreira-Gonçalves D, Miranda-Silva D, Salinaro F, Paulus WJ, Niessen HW, Perlini S, Leite-Moreira AF (2011) Distinct mechanisms for diastolic dysfunction in diabetes mellitus and chronic pressure-overload. Basic Res Cardiol 106:801–814. doi:10.1007/s00395-011-0184-x

    Article  PubMed  Google Scholar 

  12. Florea S, Anjak A, Cai WF, Qian J, Vafiadaki E, Figueria S, Haghighi K, Rubinstein J, Lorenz J, Kranias EG (2012) Constitutive phosphorylation of inhibitor-1 at Ser67 and Thr75 depresses calcium cycling in cardiomyocytes and leads to remodeling upon aging. Basic Res Cardiol 107:279. doi:10.1007/s00395-012-0279-z

    Article  PubMed  Google Scholar 

  13. Gelpi RJ, Pasipoularides A, Lader AS, Patrick TA, Chase N, Hittinger L, Shannon RP, Bishop SP, Vatner SF (1991) Changes in diastolic cardiac function in developing and stable perinephritic hypertension in conscious dogs. Circ Res 68:555–567. doi:10.1161/01.RES.68.2.555

    Article  PubMed  CAS  Google Scholar 

  14. Gillebert TC, Leite-Moreira AF, De Hert SG (1997) Relaxation–systolic pressure relation: a load-independent assessment of left ventricular contractility. Circulation 95:745–752. doi:10.1161/01.CIR.95.3.745

    Article  PubMed  CAS  Google Scholar 

  15. Heusch G (2009) Diastolic heart failure: a misNOmer. Basic Res Cardiol 104:465–467. doi:10.1007/s00395-009-0025-3

    Article  PubMed  Google Scholar 

  16. Heusch G (2011) Heart rate and heart failure—not a simple relationship. Circ J 75:229–236. doi:10.1253/circj.CJ-10-0925

    Article  PubMed  Google Scholar 

  17. Inouye I, Massie B, Loge D, Topic N, Silverstein D, Simpson P, Tubau J (1984) Abnormal left ventricular filling: an early finding in mild to moderate systemic hypertension. Am J Cardiol 53:120–126. doi:10.106/0002-9149(84)90695-7

    Article  PubMed  CAS  Google Scholar 

  18. Ito T, Hamada M, Shigematsu Y, Kazatani Y, Nishitani K, Matsuzaki K, Daimon F, Ochi T, Kokubu T (1985) The analysis of systolic and diastolic time intervals: a more sensitive non-invasive method in the assessment of left ventricular dysfunction in the patients with essential hypertension. Clin Exp Hypertens A 7:951–963

    Article  PubMed  CAS  Google Scholar 

  19. Lavine SJ, Lavine JA (2006) The effect of acute hypertension on left ventricular diastolic pressures in a canine model of left ventricular dysfunction with a preserved ejection fraction and elevated left ventricular filling pressures. J Am Soc Echocardiogr 19:1350–1358. doi:10.1016/j.echo.2006.05.008

    Article  PubMed  Google Scholar 

  20. Leite-Moreira AF, Correia-Pinto J, Gillebert TC (1999) Afterload induced changes in myocardial relaxation: a mechanism for diastolic dysfunction. Cardiovasc Res 43:344–353. doi:10.1016/S0008-6363(99)00099-1

    Article  PubMed  CAS  Google Scholar 

  21. Leite-Moreira AF, Gillebert TC (1994) Nonuniform course of left ventricular pressure fall and its regulation by load and contractile state. Circulation 90:2481–2491. doi:10.1161/01.CIR.90.5.2481

    Article  PubMed  CAS  Google Scholar 

  22. Leite-Moreira AF, Lourenço AP, Roncon-Albuquerque R, Henriques-Coelho T, Amorim MJ, Almeida J, Pinho P, Gillebert TC (2012) Diastolic tolerance to systolic pressures closely reflects systolic performance in patients with coronary heart disease. Basic Res Cardiol 107:251. doi:10.1007/s00395-012-0251-y

    Article  PubMed  Google Scholar 

  23. Little WC (2005) Diastolic dysfunction beyond distensibility: adverse effects of ventricular dilatation. Circulation 112:2888–2890. doi:10.1161/CIRCULATIONAHA.105.578161

    PubMed  Google Scholar 

  24. MacIver DH (2010) Is remodeling the dominant compensatory mechanism in both chronic heart failure with preserved and reduced left ventricular ejection fraction? Basic Res Cardiol 105:227–234. doi:10.1007/s00395-009-0063-x

    Article  PubMed  Google Scholar 

  25. Matsubara H, Araki J, Takaki M, Nakagawa ST, Suga H (1995) Logistic characterization of left ventricular isovolumic pressure–time curve. Jpn J Physiol 45:535–552. doi:10.2170/jjphysiol.45.535

    Article  PubMed  CAS  Google Scholar 

  26. Mogelvang R, Goetze JP, Pedersen SA, Olsen NT, Marott JL, Schnohr P, Sogaard P, Jensen JS (2009) Preclinical systolic and diastolic dysfunction assessed by tissue Doppler imaging is associated with elevated plasma pro-B-type natriuretic peptide concentrations. J Card Fail 15:489–495. doi:10.1016/j.cardfail.2009.09.005

    Article  PubMed  CAS  Google Scholar 

  27. Munagala VK, Hart CY, Burnett JC Jr, Meyer DM, Redfield MM (2005) Ventricular structure and function in aged dogs with renal hypertension: a model of experimental diastolic heart failure. Circulation 111:1128–1135. doi:10.1161/01.CIR.0000157183.21404.63

    Article  PubMed  Google Scholar 

  28. Neumann T, Ravens U, Heusch G (1998) Characterization of excitation–contraction coupling in conscious dogs with pacing-induced heart failure. Cardiovasc Res 37:456–466. doi:10.1016/S0008-6363(97)00246-0

    Article  PubMed  CAS  Google Scholar 

  29. Paolocci N, Tavazzi B, Biondi R, Gluzband YA, Amorini AM, Tocchetti CG, Hejazi M, Caturegli PM, Kajstura J, Lazzarino G, Kass DA (2006) Metalloproteinase inhibitor counters high-energy phosphate depletion and AMP deaminase activity enhancing ventricular diastolic compliance in subacute heart failure. J Pharmacol Exp Ther 317:506–513. doi:10.1124/jpet.105.099168

    Article  PubMed  CAS  Google Scholar 

  30. Senzaki H, Gluzban YA, Pak PH, Crow MT, Janicki JS, Kass DA (1998) Synergistic exacerbation of diastolic stiffness from short-term tachycardia-induced cardiodepression and angiotensin II. Circ Res 82:503–512. doi:10.1161/01.RES.82.4.503

    Article  PubMed  CAS  Google Scholar 

  31. Senzaki H, Kass DA (2010) Analysis of isovolumic relaxation in failing hearts by monoexponential time constants overestimates lusitropic change and load dependence: mechanisms and advantages of alternative logistic fit. Circ Heart Fail 3:268–276. doi:10.1161/CIRCHEARTFAILURE.109.865592

    Article  PubMed  Google Scholar 

  32. Song LS, Pi YQ, Kim SJ, Yatani A, Guatimosim S, Kudej RK, Zhang Q, Cheng H, Hittinger L, Ghaleh B, Vatner DE, Lederer WJ, Vatner SF (2005) Paradoxical cellular Ca2+ signaling in severe but compensated canine left ventricular hypertrophy. Circ Res 97:457–464. doi:10.1161/01.RES.0000179722.79295.d4

    Article  PubMed  CAS  Google Scholar 

  33. Tan YT, Wenzelburger F, Lee E, Heatlie G, Leyva F, Patel K, Frenneaux M, Sanderson JE (2009) The pathophysiology of heart failure with normal ejection fraction: exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion, untwist, and longitudinal motion. J Am Coll Cardiol 54:36–46. doi:10.1016/j.jacc.2009.03.037

    Article  PubMed  Google Scholar 

  34. Van Der Hoeven GM, Clerens PJ, Donders JJ, Beneken JE, Vonk JT (1977) A study of systolic time intervals during uninterrupted exercise. Br Heart J 39:242–254. doi:10.1136/hrt.39.3.242

    Article  Google Scholar 

  35. Westermann D, Kasner M, Steendijk P, Spillmann F, Riad A, Weitmann K, Hoffmann W, Poller W, Pauschinger M, Schultheiss HP, Tschöpe C (2008) Role of left ventricular stiffness in heart failure with normal ejection fraction. Circulation 117:2051–2060. doi:10.1161/CIRCULATIONAHA.107.716886

    Article  PubMed  Google Scholar 

  36. Wiggers CJ (1942) Basic hemodynamic principles essential to interpretation of cardiovascular disorders. Bull N Y Acad Med 18:3–17

    PubMed  CAS  Google Scholar 

  37. Yip GW, Zhang Y, Tan PY, Wang M, Ho PY, Brodin LA, Sanderson JE (2002) Left ventricular long-axis changes in early diastole and systole: impact of systolic function on diastole. Clin Sci (Lond) 102:515–522. doi:10.1042/CS20010196

    Article  Google Scholar 

  38. Zile MR, Brutsaert DL (2002) New concepts in diastolic dysfunction and diastolic heart failure: Part I: diagnosis, prognosis, and measurements of diastolic function. Circulation 105:1387–1393. doi:10.1161/hc1102.105289

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from INSERM (Mario Rienzo, poste d’accueil 2008), the Société Française d’Hypertension Artérielle (2010), the Fondation de l’Avenir (ET9-529) and the Région Ile de France (CODDIM). We thank the Laboratoire Roche for providing diazepam (Valium®) and Sanofi-Aventis for providing heparin.

Author information

Authors and Affiliations

  1. Faculté de Médecine, INSERM Unité U955 Equipe 03, 8 rue du Général Sarrail, 94000, Créteil, France

    Mario Rienzo, Alain Bizé, Dionyssis Pongas, Stéphanie Michineau, Jonathan Melka, Hon Lai Chan, Lucien Sambin, Jin Bo Su, Jean-Luc Dubois-Randé, Luc Hittinger, Alain Berdeaux & Bijan Ghaleh

  2. Faculté de Médecine, Université Paris-Est, UMR-S U955, 94000, Créteil, France

    Mario Rienzo, Alain Bizé, Dionyssis Pongas, Stéphanie Michineau, Jonathan Melka, Hon Lai Chan, Lucien Sambin, Jin Bo Su, Jean-Luc Dubois-Randé, Luc Hittinger, Alain Berdeaux & Bijan Ghaleh

  3. Ecole Nationale Vétérinaire d’Alfort, Université Paris-Est, 94000, Maisons-Alfort, France

    Mario Rienzo, Alain Bizé, Dionyssis Pongas, Stéphanie Michineau, Jonathan Melka, Hon Lai Chan, Lucien Sambin, Jin Bo Su, Jean-Luc Dubois-Randé, Luc Hittinger, Alain Berdeaux & Bijan Ghaleh

  4. AP-HP, Groupe Hospitalier Henri Mondor, Fédération de Cardiologie, 94000, Créteil, France

    Dionyssis Pongas, Jean-Luc Dubois-Randé, Luc Hittinger & Alain Berdeaux

Authors
  1. Mario Rienzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alain Bizé
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dionyssis Pongas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stéphanie Michineau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jonathan Melka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hon Lai Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lucien Sambin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jin Bo Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jean-Luc Dubois-Randé
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luc Hittinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Alain Berdeaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Bijan Ghaleh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bijan Ghaleh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rienzo, M., Bizé, A., Pongas, D. et al. Impaired left ventricular function in the presence of preserved ejection in chronic hypertensive conscious pigs. Basic Res Cardiol 107, 298 (2012). https://doi.org/10.1007/s00395-012-0298-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00395-012-0298-9

Keywords

Search

Navigation