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B-type natriuretic peptide and wall stress in dilated human heart

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Abstract

Background Although B-type natriuretic peptide (BNP) is used as complimentary diagnostic tool in patients with unknown thoracic disorders, many other factors appear to trigger its release. In particular, it remains unresolved to what extent cellular stretch or wall stress of the whole heart contributes to enhanced serum BNP concentration. Wall stress cannot be determined directly, but has to be calculated from wall volume, cavity volume and intraventricular pressure of the heart. The hypothesis was, therefore, addressed that wall stress as determined by cardiac magnetic resonance imaging (CMR) is the major determinant of serum BNP in patients with a varying degree of left ventricular dilatation or dysfunction (LVD). Methods A thick-walled sphere model based on volumetric analysis of the LV using CMR was compared with an echocardiography-based approach to calculate LV wall stress in 39 patients with LVD and 21 controls. Serum BNP was used as in vivo marker of a putatively raised wall stress. Nomograms of isostress lines were established to assess the extent of load reduction that is necessary to restore normal wall stress and related biochemical events. Results Both enddiastolic and endsystolic LV wall stress were correlated with the enddiastolic LV volume (r = 0.54, P < 0.001; r = 0.81, P < 0.001). LV enddiastolic wall stress was related to pulmonary pressure (capillary: r = 0.69, P < 0.001; artery: r = 0.67, P < 0.001). Although LV growth was correlated with the enddiastolic and endsystolic volume (r = 0.73, P < 0.001; r = 0.70, P < 0.001), patients with LVD exhibited increased LV wall stress indicating an inadequately enhanced LV growth. Both enddiastolic (P < 0.05) and endsystolic (P < 0.01) wall stress were increased in patients with increased BNP. In turn, BNP concentration was elevated in individuals with increased enddiastolic wall stress (>8 kPa: 587 ± 648 pg/ml, P < 0.05; >12 kPa: 715 ± 661 pg/ml, P < 0.001; normal ≤4 kPa: 124 ± 203 pg/ml). Analysis of variance revealed LV enddiastolic wall stress as the only independent hemodynamic parameter influencing BNP (P < 0.01). Using nomograms with “isostress” curves, the extent of load reduction required for restoring normal LV wall stress was assessed. Compared with the CMR-based volumetric analysis for wall stress calculation, the echocardiography based approach underestimated LV wall stress particularly of dilated hearts. Conclusions In patients with LVD, serum BNP was increased over the whole range of stress values which were the only hemodynamic predictors. Cellular stretch appears to be a major trigger for BNP release. Biochemical mechanisms need to be explored which appear to operate over this wide range of wall stress values. It is concluded that the diagnostic use of BNP should primarily be directed to assess ventricular wall stress rather than the extent of functional ventricular impairment in LVD.

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References

  1. Balion CM, Santaguida P, McKelvie R, Hill SA, McQueen MJ, Worster A, Raina PS (2008) Physiological, pathological, pharmacological, biochemical and hematological factors affecting BNP and NT-proBNP. Clin Biochem 41(4–5):231–239

    Article  PubMed  CAS  Google Scholar 

  2. Yasue H, Yoshimura M, Sumida H, Kikuta K, Kugiyama K, Jougasaki M, Ogawa H, Okumura K, Mukoyama M, Nakao K (1994) Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 90(1):195–203

    PubMed  CAS  Google Scholar 

  3. Liang F, Gardner DG (1999) Mechanical strain activates BNP gene transcription through a p38/NF-kappaB-dependent mechanism. J Clin Invest 104(11):1603–1612

    Article  PubMed  CAS  Google Scholar 

  4. Wiese S, Breyer T, Dragu A, Wakili R, Burkard T, Schmidt-Schweda S, Fuchtbauer EM, Dohrmann U, Beyersdorf F, Radicke D, Holubarsch CJ (2000) Gene expression of brain natriuretic peptide in isolated atrial and ventricular human myocardium: influence of angiotensin II and diastolic fiber length. Circulation 102(25):3074–3079

    PubMed  CAS  Google Scholar 

  5. Alter P, Rupp H, Rominger MB, Vollrath A, Czerny F, Klose KJ, Maisch B (2007) Relation of B-type natriuretic peptide to left ventricular wall stress as assessed by cardiac magnetic resonance imaging in patients with dilated cardiomyopathy. Can J Physiol Pharmacol 85(8):790–799

    Article  PubMed  CAS  Google Scholar 

  6. Rupp H (1989) Differential effect of physical exercise routines on ventricular myosin and peripheral catecholamine stores in normotensive and spontaneously hypertensive rats. Circ Res 65(2):370–377

    PubMed  CAS  Google Scholar 

  7. Rupp H, Berger HJ, Pfeifer A, Werdan K (1991) Effect of positive inotropic agents on myosin isozyme population and mechanical activity of cultured rat heart myocytes. Circ Res 68(4):1164–1173

    PubMed  CAS  Google Scholar 

  8. Dell’Italia LJ, Evanochko WT, Blackwell GG, Pearce DJ, Pohost GM (1993) Relationship between shortening load, contractility, and myocardial energetics in intact dog. Am J Physiol 264(6 Pt 2):H2180–H2187

    PubMed  CAS  Google Scholar 

  9. Hikoso S, Yamaguchi O, Higuchi Y, Hirotani S, Takeda T, Kashiwase K, Watanabe T, Taniike M, Tsujimoto I, Asahi M, Matsumura Y, Nishida K, Nakajima H, Akira S, Hori M, Otsu K (2004) Pressure overload induces cardiac dysfunction and dilation in signal transducer and activator of transcription 6-deficient mice. Circulation 110(17):2631–2637

    Article  PubMed  Google Scholar 

  10. Rupp H, Maisch B (2007) Separation of large mammalian ventricular myosin differing in ATPase activity. Can J Physiol Pharmacol 85(3–4):326–331

    Article  PubMed  CAS  Google Scholar 

  11. Turcani M, Rupp H (1997) Etomoxir improves left ventricular performance of pressure-overloaded rat heart. Circulation 96(10):3681–3686

    PubMed  CAS  Google Scholar 

  12. Alter P, Rupp H, Rominger MB, Klose KJ, Maisch B (2008) A new methodological approach to assess cardiac work by pressure–volume and stress-length relations in patients with aortic valve stenosis and dilated cardiomyopathy. Pflugers Arch 455(4):627–636

    Article  PubMed  CAS  Google Scholar 

  13. Vanderheyden M, Goethals M, Verstreken S, De Bruyne B, Muller K, Van Schuerbeeck E, Bartunek J (2004) Wall stress modulates brain natriuretic peptide production in pressure overload cardiomyopathy. J Am Coll Cardiol 44(12):2349–2354

    Article  PubMed  CAS  Google Scholar 

  14. Vickery S, Price CP, John RI, Abbas NA, Webb MC, Kempson ME, Lamb EJ (2005) B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy. Am J Kidney Dis 46(4):610–620

    Article  PubMed  CAS  Google Scholar 

  15. McLean AS, Huang SJ, Nalos M, Tang B, Stewart DE (2003) The confounding effects of age, gender, serum creatinine, and electrolyte concentrations on plasma B-type natriuretic peptide concentrations in critically ill patients. Crit Care Med 31(11):2611–2618

    Article  PubMed  CAS  Google Scholar 

  16. Mussalo H, Vanninen E, Ikaheimo R, Hartikainen J (2003) NT-proANP and BNP in renovascular and in severe and mild essential hypertension. Kidney Blood Press Res 26(1):34–41

    Article  PubMed  CAS  Google Scholar 

  17. Alter P, Rupp H, Czerny F, Vollrath A, Rominger MB, Maisch B (2006) Relation of ventricular wall stress and autonomic tone in patients with dilated cardiomyopathy assessed by cardiac magnetic resonance imaging. Eur Heart J 27(Supp):P4039

    Google Scholar 

  18. Alter P, Rupp H, Maisch B (2006) Activated nuclear transcription factor kappaB in patients with myocarditis and dilated cardiomyopathy-relation to inflammation and cardiac function. Biochem Biophys Res Commun 339(1):180–187

    Article  PubMed  CAS  Google Scholar 

  19. Sandler H, Dodge HT (1963) Left ventricular tension and stress in man. Circ Res 13:91–104

    PubMed  CAS  Google Scholar 

  20. Mirsky I (1969) Left ventricular stresses in the intact human heart. Biophys J 9(2):189–208

    Article  PubMed  CAS  Google Scholar 

  21. Alter P, Rupp H, Rominger MB, Klose KJ, Maisch B (2006) Relation of B-type natriuretic peptide to left ventricular wall stress in patients with dilated cardiomyopathy assessed by cardiac magnetic resonance imaging. Eur J Heart Fail 5(Supp 1):106

    Google Scholar 

  22. Grebe O, Kestler HA, Merkle N, Wohrle J, Kochs M, Hoher M, Hombach V (2004) Assessment of left ventricular function with steady-state-free-precession magnetic resonance imaging. Reference values and a comparison to left ventriculography. Z Kardiol 93(9):686–695

    Article  PubMed  CAS  Google Scholar 

  23. 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(5):845–852

    PubMed  CAS  Google Scholar 

  24. Douglas PS, Reichek N, Plappert T, Muhammad A, John Sutton MG (1987) Comparison of echocardiographic methods for assessment of left ventricular shortening and wall stress. J Am Coll Cardiol 9(4):945–951

    PubMed  CAS  Google Scholar 

  25. Iwanaga Y, Nishi I, Furuichi S, Noguchi T, Sase K, Kihara Y, Goto Y, Nonogi H (2006) B-type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure: comparison between systolic and diastolic heart failure. J Am Coll Cardiol 47(4):742–748

    Article  PubMed  CAS  Google Scholar 

  26. Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA (2002) Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 347(3):161–167

    Article  PubMed  CAS  Google Scholar 

  27. Maisel AS, McCord J, Nowak RM, Hollander JE, Wu AH, Duc P, Omland T, Storrow AB, Krishnaswamy P, Abraham WT, Clopton P, Steg G, Aumont MC, Westheim A, Knudsen CW, Perez A, Kamin R, Kazanegra R, Herrmann HC, McCullough PA (2003) Bedside B-Type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction. Results from the Breathing Not Properly Multinational Study. J Am Coll Cardiol 41(11):2010–2017

    Article  PubMed  Google Scholar 

  28. Alfakih K, Plein S, Thiele H, Jones T, Ridgway JP, Sivananthan MU (2003) Normal human left and right ventricular dimensions for MRI as assessed by turbo gradient echo and steady-state free precession imaging sequences. J Magn Reson Imaging 17(3):323–329

    Article  PubMed  Google Scholar 

  29. Pattynama PM, de Roos A, van der Wall EE, van Voorthuisen AE (1994) Evaluation of cardiac function with magnetic resonance imaging. Am Heart J 128(3):595–607

    Article  PubMed  CAS  Google Scholar 

  30. Semelka RC, Tomei E, Wagner S, Mayo J, Kondo C, Suzuki J, Caputo GR, Higgins CB (1990) Normal left ventricular dimensions and function: interstudy reproducibility of measurements with cine MR imaging. Radiology 174(3 Pt 1):763–768

    PubMed  CAS  Google Scholar 

  31. Nohria A, Givertz MM (2006) B-type natriuretic peptide and the stressed heart. J Am Coll Cardiol 47(4):749–751

    Article  PubMed  CAS  Google Scholar 

  32. de Simone G, Devereux RB, Ganau A, Hahn RT, Saba PS, Mureddu GF, Roman MJ, Howard BV (1996) Estimation of left ventricular chamber and stroke volume by limited M-mode echocardiography and validation by two-dimensional and Doppler echocardiography. Am J Cardiol 78(7):801–807

    Article  PubMed  Google Scholar 

  33. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N (1986) Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 57(6):450–458

    Article  PubMed  CAS  Google Scholar 

  34. Fischer SE, McKinnon GC, Maier SE, Boesiger P (1993) Improved myocardial agging contrast. Magn Reson Med 30(2):191–200

    Article  PubMed  CAS  Google Scholar 

  35. Huisman RM, Sipkema P, Westerhof N, Elzinga G (1980) Comparison of models used to calculate left ventricular wall force. Med Biol Eng Comput 18(2):133–144

    Article  PubMed  CAS  Google Scholar 

  36. Yin FC (1981) Ventricular wall stress. Circ Res 49(4):829–842

    PubMed  CAS  Google Scholar 

  37. Janz RF, Kubert BR, Pate EF, Moriarty TF (1980) Effect of shape on pressure-volume relationships of ellipsoidal shells. Am J Physiol 238(6):H917–H926

    PubMed  CAS  Google Scholar 

  38. Burkhoff D, Mirsky I, Suga H (2005) Assessment of systolic and diastolic ventricular properties via pressure–volume analysis: a guide for clinical, translational, and basic researchers. Am J Physiol Heart Circ Physiol 289(2):H501–H512

    Article  PubMed  CAS  Google Scholar 

  39. Mirsky I (1984) Assessment of diastolic function: suggested methods and future considerations. Circulation 69(4):836–841

    PubMed  CAS  Google Scholar 

  40. Tokola H, Hautala N, Marttila M, Magga J, Pikkarainen S, Kerkela R, Vuolteenaho O, Ruskoaho H (2001) Mechanical load-induced alterations in B-type natriuretic peptide gene expression. Can J Physiol Pharmacol 79(8):646–653

    Article  PubMed  CAS  Google Scholar 

  41. Liang YJ, Lai LP, Wang BW, Juang SJ, Chang CM, Leu JG, Shyu KG (2006) Mechanical stress enhances serotonin 2B receptor modulating brain natriuretic peptide through nuclear factor-kappaB in cardiomyocytes. Cardiovasc Res 72(2):303–312

    Article  PubMed  CAS  Google Scholar 

  42. Silver MA, Maisel A, Yancy CW, McCullough PA, Burnett JC Jr., Francis GS, Mehra MR, Peacock WF, Fonarow G, Gibler WB, Morrow DA, Hollander J (2004) BNP Consensus Panel 2004: A clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases. Congest Heart Fail 10(5 Suppl 3):1–30

    Article  CAS  Google Scholar 

  43. Ware LB, Matthay MA (2005) Clinical practice. Acute pulmonary edema. N Engl J Med 353(26):2788–2796

    Article  PubMed  CAS  Google Scholar 

  44. Saavedra WF, Tunin RS, Paolocci N, Mishima T, Suzuki G, Emala CW, Chaudhry PA, Anagnostopoulos P, Gupta RC, Sabbah HN, Kass DA (2002) Reverse remodeling and enhanced adrenergic reserve from passive external support in experimental dilated heart failure. J Am Coll Cardiol 39(12):2069–2076

    Article  PubMed  CAS  Google Scholar 

  45. Levin HR, Oz MC, Chen JM, Packer M, Rose EA, Burkhoff D (1995) Reversal of chronic ventricular dilation in patients with end-stage cardiomyopathy by prolonged mechanical unloading. Circulation 91(11):2717–2720

    PubMed  CAS  Google Scholar 

  46. Randhawa AK, Singal PK (1992) Pressure overload-induced cardiac hypertrophy with and without dilation. J Am Coll Cardiol 20(7):1569–1575

    Article  PubMed  CAS  Google Scholar 

  47. Pfeffer JM, Pfeffer MA, Braunwald E (1985) Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res 57(1):84–95

    PubMed  CAS  Google Scholar 

  48. Blaufarb IS, Sonnenblick EH (1996) The renin-angiotensin system in left ventricular remodeling. Am J Cardiol 77(13):8C–16C

    Article  PubMed  CAS  Google Scholar 

  49. Strauer BE, Beer K, Heitlinger K, Hofling B (1977) Left ventricular systolic wall stress as a primary determinant of myocardial oxygen consumption: comparative studies in patients with normal left ventricular function, with pressure and volume overload and with coronary heart disease. Basic Res Cardiol 72(2–3):306–313

    Article  PubMed  CAS  Google Scholar 

  50. Schipke JD, Burkhoff D, Kass DA, Alexander J Jr., Schaefer J, Sagawa K (1990) Hemodynamic dependence of myocardial oxygen consumption indexes. Am J Physiol 258(5 Pt 2):H1281–H1291

    PubMed  CAS  Google Scholar 

  51. Clement DL, De Buyzere M, Duprez D (1993) Left ventricular function and regression of left ventricular hypertrophy in essential hypertension. Am J Hypertens 6(3 Pt 2):14S–19S

    PubMed  CAS  Google Scholar 

  52. Rupp H, Benkel M, Maisch B (2000) Control of cardiomyocyte gene expression as drug target. Mol Cell Biochem 212(1–2):135–142

    Article  PubMed  CAS  Google Scholar 

  53. Ruskoaho H, Leskinen H, Magga J, Taskinen P, Mantymaa P, Vuolteenaho O, Leppaluoto J (1997) Mechanisms of mechanical load-induced atrial natriuretic peptide secretion: role of endothelin, nitric oxide, and angiotensin II. J Mol Med 75(11–12):876–885

    Article  PubMed  CAS  Google Scholar 

  54. Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA (2005) A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437(7057):426–431

    Article  PubMed  CAS  Google Scholar 

  55. von Offenberg SN, Cummins PM, Birney YA, Cullen JP, Redmond EM, Cahill PA (2004) Cyclic strain-mediated regulation of endothelial matrix metalloproteinase-2 expression and activity. Cardiovasc Res 63(4):625–634

    Article  CAS  Google Scholar 

  56. Ingber DE (2002) Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. Circ Res 91(10):877–887

    Article  PubMed  CAS  Google Scholar 

  57. Ladilov Y, Schafer C, Held A, Schafer M, Noll T, Piper HM (2000) Mechanism of Ca(2+) overload in endothelial cells exposed to simulated ischemia. Cardiovasc Res 47(2):394–403

    Article  PubMed  CAS  Google Scholar 

  58. Peters SC, Piper HM (2007) Reoxygenation-induced Ca2+ rise is mediated via Ca2+ influx and Ca2+ release from the endoplasmic reticulum in cardiac endothelial cells. Cardiovasc Res 73(1):164–171

    Article  PubMed  CAS  Google Scholar 

  59. Alter P, Grimm W, Vollrath A, Czerny F, Maisch B (2006) Heart rate variability in patients with cardiac hypertrophy–relation to left ventricular mass and etiology. Am Heart J 151(4):829–836

    Article  PubMed  Google Scholar 

  60. Garan AR, Maron BJ, Wang PJ, Estes NA III, Link MS (2005) Role of streptomycin-sensitive stretch-activated channel in chest wall impact induced sudden death (commotio cordis). J Cardiovasc Electrophysiol 16(4):433–438

    PubMed  Google Scholar 

  61. Kelly D, Mackenzie L, Hunter P, Smaill B, Saint DA (2006) Gene expression of stretch-activated channels and mechanoelectric feedback in the heart. Clin Exp Pharmacol Physiol 33(7):642–648

    Article  PubMed  CAS  Google Scholar 

  62. Itabashi Y, Miyoshi S, Yuasa S, Fujita J, Shimizu T, Okano T, Fukuda K, Ogawa S (2005) Analysis of the electrophysiological properties and arrhythmias in directly contacted skeletal and cardiac muscle cell sheets. Cardiovasc Res 67(3):561–570

    Article  PubMed  CAS  Google Scholar 

  63. Garny A, Kohl P (2004) Mechanical induction of arrhythmias during ventricular repolarization: modeling cellular mechanisms and their interaction in two dimensions. Ann N Y Acad Sci 1015:133–143

    Article  PubMed  Google Scholar 

  64. Kamkin A, Kiseleva I, Isenberg G (2003) Activation and inactivation of a non-selective cation conductance by local mechanical deformation of acutely isolated cardiac fibroblasts. Cardiovasc Res 57(3):793–803

    Article  PubMed  CAS  Google Scholar 

  65. de la Sierra A, Munoz A, Arcos E, Lopez JS, Relats J (2004) The effect of treatment with eprosartan on pulse pressure: factors predicting response. Can J Cardiol 20(Suppl C):17C–22C

    Google Scholar 

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The study was supported by a Research Grant of the University Medical Center Giessen and Marburg.

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Alter, P., Rupp, H., Rominger, M.B. et al. B-type natriuretic peptide and wall stress in dilated human heart. Mol Cell Biochem 314, 179–191 (2008). https://doi.org/10.1007/s11010-008-9779-4

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