Skip to main content

Advertisement

SpringerLink
Log in

Venous Congestion and Endothelial Cell Activation in Acute Decompensated Heart Failure

  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

Despite accumulating clinical evidence supporting a key role for venous congestion in the development of acute decompensated heart failure (ADHF), there remain several gaps in our knowledge of the pathophysiology of ADHF. Specifically, the biomechanically driven effects of venous congestion on the vascular endothelium (the largest endocrine/paracrine organ of the body), on neurohormonal activation, and on renal and cardiac dysfunction remain largely unexplored. We propose that venous congestion is a fundamental, hemodynamic stimulus for vascular inflammation, which plays a key role in the development and possibly the resolution of ADHF through vascular, humoral, renal, and cardiac mechanisms. A better understanding of the role of venous congestion and endothelial activation in the pathophysiology of ADHF may provide a strong rationale for near-future testing of treatment strategies that target biomechanically driven inflammation. Targeting vascular and systemic inflammation before symptoms arise may prevent progression to overt clinical decompensation in the ADHF syndrome.

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

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Lloyd-Jones D, Adams R, Carnethon M, et al.: Heart disease and stroke statistics–2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009, 119:480–486.

    Article  PubMed  Google Scholar 

  2. Gheorghiade M, Zannad F, Sopko G, et al.: Acute heart failure syndromes: current state and framework for future research. Circulation 2005, 112:3958–3968.

    Article  PubMed  Google Scholar 

  3. Fonarow GC, Heywood JT, Heidenreich PA, et al.: Temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, 2002 to 2004: findings from Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 2007, 153:1021–1028.

    Article  PubMed  Google Scholar 

  4. Yu CM, Wang L, Chau E, et al.: Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalization. Circulation 2005, 112:841–848.

    Article  PubMed  Google Scholar 

  5. • Chaudhry SI, Wang Y, Concato J, et al.: Patterns of weight change preceding hospitalization for heart failure. Circulation 2007, 116:1549–1554. This case-control study links increases in body weight, which occur weeks before admission, to hospitalization for heart failure. Close monitoring of body weight identifies a high-risk preadmission period during which new interventions to avert decompensated heart failure are needed.

    Article  PubMed  Google Scholar 

  6. Lucas C, Johnson W, Hamilton MA, et al.: Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure. Am Heart J 2000, 140:840–847.

    Article  CAS  PubMed  Google Scholar 

  7. Gheorghiade M, Gattis WA, O’Connor CM, et al.: Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 2004, 291:1963–1971.

    Article  CAS  PubMed  Google Scholar 

  8. Adamson PB, Magalski A, Braunschweig F, et al.: Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system. J Am Coll Cardiol 2003, 41:565–571.

    Article  PubMed  Google Scholar 

  9. Fonarow GC, Abraham WT, Albert NM, et al.: Factors identified as precipitating hospital admissions for heart failure and clinical outcomes: findings from OPTIMIZE-HF. Arch Intern Med 2008, 168:847–854.

    Article  PubMed  Google Scholar 

  10. Tsuyuki RT, McKelvie RS, Arnold JM, et al.: Acute precipitants of congestive heart failure exacerbations. Arch Intern Med 2001, 161:2337–2342.

    Article  CAS  PubMed  Google Scholar 

  11. Firth JD, Raine AE, Ledingham JG: Raised venous pressure: a direct cause of renal sodium retention in oedema? Lancet 1988, 1:1033–1035.

    Article  CAS  PubMed  Google Scholar 

  12. Blake WD, Wegria R, Keating RP, Ward HP: Effect of increased renal venous pressure on renal function. Am J Physiol 1949, 157:1–13.

    CAS  PubMed  Google Scholar 

  13. Gheorghiade M, De Luca L, Fonarow GC, et al.: Pathophysiologic targets in the early phase of acute heart failure syndromes. Am J Cardiol 2005, 96:11G–17G.

    Article  PubMed  Google Scholar 

  14. Colombo PC, Onat D, Sabbah HN: Acute heart failure as “acute endothelitis”–interaction of fluid overload and endothelial dysfunction. Eur J Heart Fail 2008, 10:170–175.

    Article  PubMed  Google Scholar 

  15. •• Colombo PC, Rastogi S, Onat D, et al.: Activation of endothelial cells in conduit veins of dogs with heart failure and veins of normal dogs after vascular stretch by acute volume loading. J Card Fail 2009, 15:457–463. This recent article provides mechanistic in vivo evidence for the link between systemic venous congestion and activation of the inflammatory/oxidative program in ECs. It shows that systemic fluid loading in normal dogs is sufficient to cause endothelial and neurohormonal activation to levels that approach those in dogs with heart failure.

    Article  CAS  PubMed  Google Scholar 

  16. Gimbrone MA Jr, Nagel T, Topper JN: Biomechanical activation: an emerging paradigm in endothelial adhesion biology. J Clin Invest 1997, 100:S61–S65.

    PubMed  Google Scholar 

  17. Pang CC: Measurement of body venous tone. J Pharmacol Toxicol Methods 2000, 44:341–360.

    Article  CAS  PubMed  Google Scholar 

  18. Vane JR, Anggard EE, Botting RM: Regulatory functions of the vascular endothelium. N Engl J Med 1990, 323:27–36.

    CAS  PubMed  Google Scholar 

  19. Aird WC: Mechanisms of endothelial cell heterogeneity in health and disease. Circ Res 2006, 98:159–162.

    Article  CAS  PubMed  Google Scholar 

  20. Gimbrone MA Jr, Topper JN, Nagel T, et al.: Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci 2000, 902:230–239.

    Article  CAS  PubMed  Google Scholar 

  21. Sumpio BE, Riley JT, Dardik A: Cells in focus: endothelial cell. Int J Biochem Cell Biol 2002, 34:1508–1512.

    Article  CAS  PubMed  Google Scholar 

  22. Sorescu GP, Song H, Tressel SL, et al.: Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a nox1-based NADPH oxidase. Circ Res 2004, 95:773–779.

    Article  CAS  PubMed  Google Scholar 

  23. Harrison DG, Widder J, Grumbach I, et al.: Endothelial mechanotransduction, nitric oxide and vascular inflammation. J Intern Med 2006, 259:351–363.

    Article  CAS  PubMed  Google Scholar 

  24. Hasdai D, Holmes DR Jr, Garratt KN, et al.: Mechanical pressure and stretch release endothelin-1 from human atherosclerotic coronary arteries in vivo. Circulation 1997, 95:357–362.

    CAS  PubMed  Google Scholar 

  25. Kawai M, Naruse K, Komatsu S, et al.: Mechanical stress-dependent secretion of interleukin 6 by endothelial cells after portal vein embolization: clinical and experimental studies. J Hepatol 2002, 37:240–246.

    Article  CAS  PubMed  Google Scholar 

  26. Wang BW, Chang H, Lin S, et al.: Induction of matrix metalloproteinases-14 and -2 by cyclical mechanical stretch is mediated by tumor necrosis factor-alpha in cultured human umbilical vein endothelial cells. Cardiovasc Res 2003, 59:460–469.

    Article  CAS  PubMed  Google Scholar 

  27. Mitchell JA, Ali F, Bailey L, et al.: Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium. Exp Physiol 2008, 93:141–147.

    Article  CAS  PubMed  Google Scholar 

  28. Andrew PJ, Mayer B: Enzymatic function of nitric oxide synthases. Cardiovasc Res 1999, 43:521–531.

    Article  CAS  PubMed  Google Scholar 

  29. Drexler H: Nitric oxide synthases in the failing human heart: a doubled-edged sword? Circulation 1999, 99:2972–2975.

    CAS  PubMed  Google Scholar 

  30. Bauersachs J, Bouloumie A, Fraccarollo D, et al.: Endothelial dysfunction in chronic myocardial infarction despite increased vascular endothelial nitric oxide synthase and soluble guanylate cyclase expression: role of enhanced vascular superoxide production. Circulation 1999, 100:292–298.

    CAS  PubMed  Google Scholar 

  31. Canty TG Jr, Boyle EM Jr, Farr A, et al.: Oxidative stress induces NF-kappaB nuclear translocation without degradation of IkappaBalpha. Circulation 1999, 100:II361–II364.

    PubMed  Google Scholar 

  32. Boyle EM Jr, Canty TG Jr, Morgan EN, et al.: Treating myocardial ischemia-reperfusion injury by targeting endothelial cell transcription. Ann Thorac Surg 1999, 68:1949–1953.

    Article  PubMed  Google Scholar 

  33. Hung TH, Charnock-Jones DS, Skepper JN, Burton GJ: Secretion of tumor necrosis factor-alpha from human placental tissues induced by hypoxia-reoxygenation causes endothelial cell activation in vitro: a potential mediator of the inflammatory response in preeclampsia. Am J Pathol 2004, 164:1049–1061.

    CAS  PubMed  Google Scholar 

  34. Kim SF, Huri DA, Snyder SH: Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2. Science 2005, 310:1966–1970.

    Article  CAS  PubMed  Google Scholar 

  35. Ennezat PV, Malendowicz SL, Testa M, et al.: Physical training in patients with chronic heart failure enhances the expression of genes encoding antioxidative enzymes. J Am Coll Cardiol 2001, 38:194–198.

    Article  CAS  PubMed  Google Scholar 

  36. •• Campese VM, Sindhu RK, Ye S, et al.: Regional expression of NO synthase, NAD(P)H oxidase and superoxide dismutase in the rat brain. Brain Res 2007, 1134:27–32. This study provides evidence for the protective effects of SOD against the pleiotropic damaging effects of reactive oxygen species. The study documents regional distributions of NO, NAD(P)H, and antioxidant enzymes such as SOD throughout the rat brain.

    Article  CAS  PubMed  Google Scholar 

  37. Feng NH, Chu SJ, Wang D, et al.: Effects of various antioxidants on endotoxin-induced lung injury and gene expression: mRNA expressions of MnSOD, interleukin-1beta and iNOS. Chin J Physiol 2004, 47:111–120.

    CAS  PubMed  Google Scholar 

  38. Sies H, Sharov VS, Klotz LO, Briviba K: Glutathione peroxidase protects against peroxynitrite-mediated oxidations. A new function for selenoproteins as peroxynitrite reductase. J Biol Chem 1997, 272:27812–27817.

    Article  CAS  PubMed  Google Scholar 

  39. Colombo PC, Ashton AW, Celaj S, et al.: Biopsy coupled to quantitative immunofluorescence: a new method to study the human vascular endothelium. J Appl Physiol 2002, 92:1331–1338.

    PubMed  Google Scholar 

  40. Feng L, Stern DM, Pile-Spellman J: Human endothelium: endovascular biopsy and molecular analysis. Radiology 1999, 212:655–664.

    CAS  PubMed  Google Scholar 

  41. Onat D, Jelic S, Schmidt AM, et al.: Vascular endothelial sampling and analysis of gene transcripts: a new quantitative approach to monitor vascular inflammation. J Appl Physiol 2007, 103:1873–1878.

    Article  CAS  PubMed  Google Scholar 

  42. Colombo PC, Banchs JE, Celaj S, et al.: Endothelial cell activation in patients with decompensated heart failure. Circulation 2005, 111:58–62.

    Article  CAS  PubMed  Google Scholar 

  43. Wan E, Mecklai A, Klapholz M, et al.: Increased nitric oxide degradation by oxidative stress and decreased nitric oxide production by endothelial nitric oxide synthase cause severe derangement of venous nitric oxide balance in decompensated heart failure. J Am Coll Cardiol 2009 (abstract).

  44. Colombo PC, Kebschull M, Xiang JZ, et al.: Acute venous hypertension and congestion coupled with analysis of endothelial gene expression profiling and circulating neurohormones: a new model to characterize the endothelial and inflammatory response to acute mechanical stress in humans. J Am Coll Cardiol 2009 (abstract).

  45. Testa M, Yeh M, Lee P, et al.: Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol 1996, 28:964–971.

    Article  CAS  PubMed  Google Scholar 

  46. Cernacek P, Stewart DJ: Immunoreactive endothelin in human plasma: marked elevations in patients in cardiogenic shock. Biochem Biophys Res Commun 1989, 161:562–567.

    Article  CAS  PubMed  Google Scholar 

  47. White M, Ducharme A, Ibrahim R, et al.: Increased systemic inflammation and oxidative stress in patients with worsening congestive heart failure: improvement after short-term inotropic support. Clin Sci (Lond) 2006, 110:483–489.

    Article  CAS  Google Scholar 

  48. Yndestad A, Holm AM, Muller F, et al.: Enhanced expression of inflammatory cytokines and activation markers in T-cells from patients with chronic heart failure. Cardiovasc Res 2003, 60:141–146.

    Article  CAS  PubMed  Google Scholar 

  49. Kapadia S, Lee J, Torre-Amione G, et al.: Tumor necrosis factor-alpha gene and protein expression in adult feline myocardium after endotoxin administration. J Clin Invest 1995, 96:1042–1052.

    Article  CAS  PubMed  Google Scholar 

  50. Li X, Moody MR, Engel D, et al.: Cardiac-specific overexpression of tumor necrosis factor-alpha causes oxidative stress and contractile dysfunction in mouse diaphragm. Circulation 2000, 102:1690–1696.

    CAS  PubMed  Google Scholar 

  51. Merrill AJ: Edema and decreased renal blood flow in patients with chronic congestive heart failure: evidence of “forward failure” as the primary cause of edema. J Clin Invest 1946, 25:389–400.

    Article  CAS  PubMed  Google Scholar 

  52. Mokotoff R, Ross G, Leiter L: Renal plasma flow and sodium reabsorption and excretion in congestive heart failure. J Clin Invest 1948, 27:1–9.

    Article  CAS  Google Scholar 

  53. • Tang WH, Mullens W: Cardio-renal syndrome in decompensated heart failure. Heart 2009 Apr 27 (Epub ahead of print). This review highlights changing views of the cardiorenal syndrome by revisiting older literature that emphasizes the important role of elevated renal venous pressure, rather than impaired cardiac output, in the worsening renal function associated with CHF.

  54. Friedman B, Clark G, Resnik H, Harrison TR: Effect of digitalis on the cardiac output of persons with congestive heart failure. Arch Intern Med 1935, 56:710–723.

    Google Scholar 

  55. Katz SD: Blood volume assessment in the diagnosis and treatment of chronic heart failure. Am J Med Sci 2007, 334:47–52.

    Article  PubMed  Google Scholar 

  56. Gibson JG, Evans WA: Clinical studies of the blood volume. III. Changes in blood volume, venous pressure and blood velocity rate in chronic congestive heart failure. J Clin Invest 1937, 16:851–858.

    Article  CAS  PubMed  Google Scholar 

  57. Seymour WB, Pritchard WH, Longley LP, Hayman JM: Cardiac output, blood and interstitial fluid volumes, total circulating serum protein, and kidney function during cardiac failure and after improvement. J Clin Invest 1942, 21:229–240.

    Article  CAS  PubMed  Google Scholar 

  58. Prentice TC, Berlin NI, Hyde GM, et al.: Total red cell volume, plasma volume, and sodium space in congestive heart failure. J Clin Invest 1951, 30:1471–1482.

    Article  CAS  PubMed  Google Scholar 

  59. Feldschuh J, Enson Y: Prediction of the normal blood volume: relation of blood volume to body habitus. Circulation 1977, 56:605–612.

    CAS  PubMed  Google Scholar 

  60. Recommended methods for measurement of red-cell and plasma volume: International Committee for Standardization in Haematology [no authors listed]. J Nucl Med 1980, 21:793–800.

  61. Androne AS, Hryniewicz K, Hudaihed A, et al.: Relation of unrecognized hypervolemia in chronic heart failure to clinical status, hemodynamics, and patient outcomes. Am J Cardiol 2004, 93:1254–1259.

    Article  PubMed  Google Scholar 

  62. Winton FR: The influence of venous pressure on the isolated mammalian kidney. J Physiol 1931, 72:49–61.

    CAS  PubMed  Google Scholar 

  63. Kostreva DR, Seagard JL, Castaner A, Kampine JP: Reflex effects of renal afferents on the heart and kidney. Am J Physiol 1981, 241:R286–R292.

    CAS  PubMed  Google Scholar 

  64. Haddy FJ: Effect of elevation of intraluminal pressure on renal vascular resistance. Circ Res 1956, 4:659–663.

    CAS  PubMed  Google Scholar 

  65. Dilley JR, Corradi A, Arendshorst WJ: Glomerular ultrafiltration dynamics during increased renal venous pressure. Am J Physiol 1983, 244:F650–F658.

    CAS  PubMed  Google Scholar 

  66. Abildgaard U, Henriksen O, Amtorp O: Sympathetic reflex-induced vasoconstriction during renal venous stasis elicited from the capsule in the dog kidney. Acta Physiol Scand 1985, 123:1–8.

    Article  CAS  PubMed  Google Scholar 

  67. Aiken JW, Vane JR: Intrarenal prostaglandin release attenuates the renal vasoconstrictor activity of angiotensin. J Pharmacol Exp Ther 1973, 184:678–687.

    CAS  PubMed  Google Scholar 

  68. Yanagisawa M, Kurihara H, Kimura S, et al.: A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988, 332:411–415.

    Article  CAS  PubMed  Google Scholar 

  69. Sakurai T, Yanagisawa M, Masaki T: Molecular characterization of endothelin receptors. Trends Pharmacol Sci 1992, 13:103–108.

    Article  CAS  PubMed  Google Scholar 

  70. Corradi A, Arendshorst WJ: Rat renal hemodynamics during venous compression: roles of nerves and prostaglandins. Am J Physiol 1985, 248:F810–F820.

    CAS  PubMed  Google Scholar 

  71. Myers SI, Zipser R, Needleman P: Peptide-induced prostaglandin biosynthesis in the renal-vein-constricted kidney. Biochem J 1981, 198:357–363.

    CAS  PubMed  Google Scholar 

  72. Ahlborg G, Lundberg JM: Cyclooxygenase inhibition potentiates the renal vascular response to endothelin-1 in humans. J Appl Physiol 1998, 85:1661–1666.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Dr. Paolo C. Colombo's work is supported by an NIH R01 HL-3001996. Dr. Ryan T. Demmer's work is supported by an NIH K99 DE-018739.

Disclosure

Dr. Paolo C. Colombo has received an investigator-initiated research grant (NCT000698139) from Medtronic, Inc. No other potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Division of Nephrology, College of Physicians and Surgeons, Columbia University, 622 West 168th Street, PH4-124, New York, NY, 10032, USA

    Anjali Ganda

  2. Division of Cardiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, P&S 17-401, New York, NY, 10032, USA

    Duygu Onat

  3. Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, 7th Floor, New York, NY, 10032, USA

    Ryan T. Demmer

  4. Division of Cardiology, College of Physicians and Surgeons, Columbia University, 622 West 168th Street, PH3-342, New York, NY, 10032, USA

    Elaine Wan

  5. Division of Cardiology, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1030, New York, NY, 10029, USA

    Timothy J. Vittorio

  6. Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, 2799 West Grand Boulevard, Detroit, MI, 48202, USA

    Hani N. Sabbah

  7. Division of Cardiology, College of Physicans and Surgeons, Columbia University, 622 West 168th Street, PH12-134, New York, NY, 10032, USA

    Paolo C. Colombo

Authors
  1. Anjali Ganda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Duygu Onat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryan T. Demmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elaine Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Timothy J. Vittorio
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hani N. Sabbah
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paolo C. Colombo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paolo C. Colombo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ganda, A., Onat, D., Demmer, R.T. et al. Venous Congestion and Endothelial Cell Activation in Acute Decompensated Heart Failure. Curr Heart Fail Rep 7, 66–74 (2010). https://doi.org/10.1007/s11897-010-0009-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11897-010-0009-5

Keywords

Search

Navigation