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Structural-Mechanical Changes in the Pericardium During Pregnancy

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Abstract

The pericardium’s collagenous structure limits over-expansion of the heart, couples the left and right ventricles, and keeps the heart in place in the chest cavity. Experimental volume overload studies in dogs have demonstrated consequent pericardial remodeling. By comparison, the maternal heart is subjected to large, natural volume overload but with altered hormonal levels. No current literature exists on the resulting pericardial changes. This study investigates those effects in a bovine model that mimics human pregnancy. Pericardial samples were collected from 10 never-pregnant and 17 pregnant cattle from 13 weeks gestation or later. Biaxial mechanics, hydrothermal isometric tension (HIT) testing, crosslink analysis, histology and biochemical tests for water and collagen contents were conducted. There were no changes in the collagen and water contents, or in the crimp length between pericardia of pregnant and non-pregnant animals. In late pregnancy, pericardial thickness increased with only slight decreases in biomechanical stretch ratios, mainly in the base-to-apex direction. Pericardium from pregnant cattle had a 14.8% decrease in cell density, 1.3° lower collagen denaturation temperature, and a surprising 32.0% lower index of immature crosslinking. Indeed, hydrothermal studies of collagen from the pregnant animals’ pericardia showed greater mature and total crosslinking (40.9 and 22.4% increases in isothermal load decay half-times) respectively. Overall, then, there was evidence on the molecular level of remodeling and growth in the pericardium in early pregnancy (<13 weeks gestation). This is the first study to demonstrate that pericardium remodels and grows to adapt to changes in pregnancy, perhaps as a means to maintaining its functional properties.

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References

  1. Aldous, I. G., J. M. Lee, and S. M. Wells. Differential changes in the molecular stability of collagen from the pulmonary and aortic valves during the fetal-to-neonatal transition. Ann. Biomed. Eng. 38:3000–3009, 2010.

    Article  Google Scholar 

  2. Aldous, I. G., S. P. Veres, A. Jahangir, and J. M. Lee. Differences in collagen cross-linking between the four valves of the bovine heart: a possible role in adaptation to mechanical fatigue. Am. J. Physiol. Heart Circ. Physiol. 296:H1898–H1906, 2009.

    Article  Google Scholar 

  3. Avery, N. C., and A. J. Bailey. Enzymic and non-enzymic cross-linking mechanisms in relation to turnover of collagen: relevance to aging and exercise. Scand. J. Med. Sci. Sports 15:231–240, 2005.

    Article  Google Scholar 

  4. Avery, N., and A. Bailey. Restraining cross-links responsible for the mechanical properties of collagen fibers: Natural and artificial. Collagen: Structure and Mechanics, pp. 1–30, 2008.

  5. Bailey, S. Age related changes in the reducible cross-links of collagen. FEBS Lett. 16:86–88, 1971.

    Article  Google Scholar 

  6. Bailey, A. J., C. M. Peach, and L. J. Fowler. Chemistry of the collagen cross-links. Isolation and characterization of two intermediate intermolecular cross-links in collagen. Biochem. J. 117:819–831, 1970.

    Google Scholar 

  7. Bailey, A. J., S. P. Robins, and G. Balian. Biological significance of the intermolecular crosslinks of collagen. Nature 251:105–109, 1974.

    Article  Google Scholar 

  8. Bartle, S. H., and H. J. Herman. Acute mitral regurgitation in man: hemodynamic evidence and observations indicating an early role for the pericardium. Circulation 36:839–851, 1967.

    Article  Google Scholar 

  9. Blanchard, D. G., and H. C. Dittrich. Pericardial adaptation in severe chronic pulmonary hypertension. An intraoperative transesophageal echocardiographic study. Circulation 85:1414–1422, 1992.

    Article  Google Scholar 

  10. Cannon, D. J., and P. F. Davison. Aging, and crosslinking in mammlian collagen. Exp. Aging Res. 3:87–105, 1977.

    Article  Google Scholar 

  11. Clapp, J. F., and E. Capeless. Cardiovascular function before, during, and after the first and subsequent pregnancies. Am. J. Cardiol. 80:1469–1473, 1997.

    Article  Google Scholar 

  12. Davison, P. F. The contribution of labile crosslinks to the tensile behavior of tendons. Connect. Tissue Res. 18:293–305, 1989.

    Article  Google Scholar 

  13. Davison, P. F. The organization of collagen in growing tensile tissues. Connect. Tissue Res. 28:171–179, 1992.

    Article  MathSciNet  Google Scholar 

  14. Du, X.-J., R. A. D. Bathgate, C. S. Samuel, A. M. Dart, and R. J. Summers. Cardiovascular effects of relaxin: from basic science to clinical therapy. Nat. Rev. Cardiol. 7:48–58, 2010.

    Article  Google Scholar 

  15. Eghbali, M., Y. Wang, L. Toro, and E. Stefani. Heart hypertrophy during pregnancy: a better functioning heart? Trends Cardiovasc. Med. 16:285–291, 2006.

    Article  Google Scholar 

  16. Enein, M., A. A. Zina, and M. Kassem. el-Tabbakh G: echocardiography of the pericardium in pregnancy. Obstet. Gynecol. 69:851–853, 1987.

    Google Scholar 

  17. Esch, B. T. A., S. S. D. Bredin, M. J. Haykowsky, J. M. Scott, and D. E. R. Warburton. The potential role of the pericardium on diastolic filling in endurance-trained athletes under conditions of physiological stress. Appl. Physiol. Nutr. Metab. 32:311–317, 2007.

    Article  Google Scholar 

  18. Evans, H. E., and W. O. Sack. Prenatal development of domestic and laboratory mammals: growth curves, external features and selected references. Zentralbl Veterinarmed C 2:11–45, 1973.

    Google Scholar 

  19. Freeman, G. L., and M. M. LeWinter. Pericardial adaptations during chronic cardiac dilation in dogs. Circ. Res. 54:294–300, 1984.

    Article  Google Scholar 

  20. Freeman, G. L., and M. M. LeWinter. Determinants of intrapericardial pressure in dogs. J. Appl. Physiol. 60:758–764, 1986.

    Google Scholar 

  21. Gathercole, L. J., and A. Keller. Early development of crimping in rat tail tendon collagen: a polarizing optical and SEM study. Micron 1978(9):83–89, 1969.

    Google Scholar 

  22. Gathercole, L. J., and A. Keller. Crimp morphology in the fibre-forming collagens. Matrix 11:214–234, 1991.

    Article  Google Scholar 

  23. Hilbert, S. L., M. K. Barrick, and V. J. Ferrans. Porcine aortic valve bioprostheses: a morphologic comparison of the effects of fixation pressure. J. Biomed. Mater. Res. 24:773–787, 1990.

    Article  Google Scholar 

  24. Hilbert, S. L., L. C. Sword, K. F. Batchelder, M. K. Barrick, and V. J. Ferrans. Simultaneous assessment of bioprosthetic heart valve biomechanical properties and collagen crimp length. J. Biomed. Mater. Res. 31:503–509, 1996.

    Article  Google Scholar 

  25. Hoit, B. D., N. Dalton, V. Bhargava, and R. Shabetai. Pericardial influences on right and left ventricular filling dynamics. Circ. Res. 68:197–208, 1991.

    Article  Google Scholar 

  26. Hunter, S., and S. C. Robson. Adaptation of the maternal heart in pregnancy. Brit. Heart J. 68:540–543, 1992.

    Article  Google Scholar 

  27. Imazio, M., A. Brucato, S. Rampello, F. Armellino, R. Trinchero, D. H. Spodick, and Y. Adler. Management of pericardial diseases during pregnancy. J. Cardiovasc. Med. 11:557–562, 2010.

    Article  Google Scholar 

  28. Kametas, N. A., F. McAuliffe, J. Hancock, J. Chambers, and K. H. Nicolaides. Maternal left ventricular mass and diastolic function during pregnancy. Ultrasound Obstet. Gynecol. Off. J. Int. Soc. Ultrasound Obstet. Gynecol. 18:460–466, 2001.

    Article  Google Scholar 

  29. Kardon, D. E., A. C. Borczuk, and S. M. Factor. Mechanism of pericardial expansion with cardiac enlargement. Cardiovasc. Pathol. 9:9–15, 2000.

    Article  Google Scholar 

  30. Katz, R., J. S. Karliner, and R. Resnik. Effects of a natural volume overload state (pregnancy) on left ventricular performance in normal human subjects. Circulation 58:434–441, 1978.

    Article  Google Scholar 

  31. Keeley, F. W., J. D. Morin, and S. Vesely. Characterization of collagen from normal human sclera. Exp. Eye Res. 39:533–542, 1984.

    Article  Google Scholar 

  32. Kingma, I., G. H. Groves, E. R. Smith, and J. V. Tyberg. Creep of the canine pericardium in vivo. Can. J. Physiol. Pharmacol. 64:892–896, 1986.

    Article  Google Scholar 

  33. Langdon, S. E., R. Chernecky, C. A. Pereira, D. Abdulla, and J. M. Lee. Biaxial mechanical/structural effects of equibiaxial strain during crosslinking of bovine pericardial xenograft materials. Biomaterials 20:137–153, 1999.

    Article  Google Scholar 

  34. Le Lous, M., J. C. Allain, L. Cohen-Solal, and P. Maroteaux. The rate of collagen maturation in rat and human skin. Connect. Tissue Res. 9:253–262, 1982.

    Article  Google Scholar 

  35. Le Lous, M., L. Cohen-Solal, J. C. Allain, J. Bonaventure, and P. Maroteaux. Age related evolution of stable collagen reticulation in human skin. Connect. Tissue Res. 13:145–155, 1985.

    Article  Google Scholar 

  36. Lee, J. M., and D. R. Boughner. Tissue mechanics of canine pericardium in different test environments. Evidence for time-dependent accommodation, absence of plasticity, and new roles for collagen and elastin. Circ. Res. 49:533–544, 1981.

    Article  Google Scholar 

  37. Lee, J. M., and D. R. Boughner. Mechanical properties of human pericardium. Differences in viscoelastic response when compared with canine pericardium. Circ. Res. 57:475–481, 1985.

    Article  Google Scholar 

  38. Lee, J. M., and S. E. Langdon. Thickness measurement of soft tissue biomaterials: a comparison of five methods. J. Biomech. 29:829–832, 1996.

    Article  Google Scholar 

  39. Lee, M. C., M. M. LeWinter, G. Freeman, R. Shabetai, and Y. C. Fung. Biaxial mechanical properties of the pericardium in normal and volume overload dogs. Am. J. Physiol. 249:H222–H230, 1985.

    Google Scholar 

  40. Lee, J. M., C. A. Pereira, D. Abdulla, W. A. Naimark, and I. Crawford. A multi-sample denaturation temperature tester for collagenous biomaterials. Med. Eng. Phys. 17:115–121, 1995.

    Article  Google Scholar 

  41. LeWinter, M. M., and R. Pavelec. Influence of the pericardium on left ventricular end-diastolic pressure-segment relations during early and later stages of experimental chronic volume overload in dogs. Circ. Res. 50:501–509, 1982.

    Article  Google Scholar 

  42. Miles, C. A., N. C. Avery, V. V. Rodin, and A. J. Bailey. The increase in denaturation temperature following cross-linking of collagen is caused by dehydration of the fibres. J. Mol. Biol. 346:551–556, 2005.

    Article  Google Scholar 

  43. Miles, C. A., and M. Ghelashvili. Polymer-in-a-box mechanism for the thermal stabilization of collagen molecules in fibers. Biophys. J . 76:3243–3252, 1999.

    Article  Google Scholar 

  44. Naimark, W. A., J. M. Lee, H. Limeback, and D. T. Cheung. Correlation of structure and viscoelastic properties in the pericardia of four mammalian species. Am. J. Physiol. 263:H1095–H1106, 1992.

    Google Scholar 

  45. Naimark, W. A., S. D. Waldman, R. J. Anderson, B. Suzuki, C. A. Pereira, and J. M. Lee. Thermomechanical analysis of collagen crosslinking in the developing lamb pericardium. Biorheology 35:1–16, 1998.

    Article  Google Scholar 

  46. Persikov, A. V., and B. Brodsky. Unstable molecules form stable tissues. Proc. Natl. Acad. Sci. U.S.A. 99:1101–1103, 2002.

    Article  Google Scholar 

  47. Pratt, D. A., Y. Daniloff, A. Duncan, and S. P. Robins. Automated analysis of the pyridinium crosslinks of collagen in tissue and urine using solid-phase extraction and reversed-phase high-performance liquid chromatography. Anal. Biochem. 207:168–175, 1992.

    Article  Google Scholar 

  48. Robins, S. P. Biochemistry and functional significance of collagen cross-linking. Biochem. Soc. Trans. 35:849–852, 2007.

    Article  Google Scholar 

  49. Robins, S. P., M. Shimokomaki, and A. J. Bailey. Chemistry of collagen crosslinks—age related changes in reducible components of intact bovine collagen fibers. Biochem J 131:771–780, 1973.

    Google Scholar 

  50. Robson, S. C., S. Hunter, R. J. Boys, and W. Dunlop. Serial study of factors influencing changes in cardiac output during human pregnancy. Am. J. Physiol. Heart Circ. Physiol. 256:H1060–H1065, 1989.

    Google Scholar 

  51. Savu, O., R. Jurcut, S. Giusca, T. van Mieghem, I. Gussi, B. A. Popescu, C. Ginghina, F. Rademakers, J. Deprest, and J.-U. Voigt. Morphological and functional adaptation of the maternal heart during pregnancy. Circ Cardiovasc Imaging 5:289–297, 2012.

    Article  Google Scholar 

  52. Schannwell, C. M., T. Zimmermann, M. Schneppenheim, G. Plehn, R. Marx, and B. E. Strauer. Left ventricular hypertrophy and diastolic dysfunction in healthy pregnant women. Cardiology 97:73–78, 2002.

    Article  Google Scholar 

  53. Seneviratne, A., E. Attia, R. J. Williams, S. A. Rodeo, and J. A. Hannafin. The effect of estrogen on ovine anterior cruciate ligament fibroblasts: cell proliferation and collagen synthesis. Am. J. Sports Med. 32:1613–1618, 2004.

    Article  Google Scholar 

  54. Sherwood, O. D. Relaxin’s physiological roles and other diverse actions. Endocr. Rev. 25:205–234, 2004.

    Article  Google Scholar 

  55. Spodick, D. H. The Pericardium: A Comprehensive Textbook. New York: Marcel Dekker, 1997.

  56. Thornburg, K. L., S. L. Jacobson, G. D. Giraud, and M. J. Morton. Hemodynamic changes in pregnancy. Semin. Perinatol. 24:11–14, 2000.

    Article  Google Scholar 

  57. Waldman, S. D., and J. M. Lee. Boundary conditions during biaxial testing of planar connective tissues. Part 1: dynamic behaviour. J. Mater. Sci. Mater. Med. 13:933–938, 2002.

    Google Scholar 

  58. Watkins, M. W., and M. M. LeWinter. Physiologic role of the normal pericardium. Annu. Rev. Med. 44:171–180, 1993.

    Article  Google Scholar 

  59. Wells, S. M., S. L. Adamson, B. L. Langille, and J. M. Lee. Thermomechanical analysis of collagen crosslinking in the developing ovine thoracic aorta. Biorheology 35:399–414, 1998.

    Article  Google Scholar 

  60. Wells, S. M., C. M. Pierlot, and A. D. Moeller. Physiological remodeling of the mitral valve during pregnancy. AJP: Heart Circ. Physiol. 2012, 303:H878–H892.

  61. Woessner, J. F., Jr. Determination of hydroxyproline in connective tissues. In: The Methodology of Connective Tissue Research, edited by D. A. Hall. Oxford: Johnson-Bruvvers Ltd, 1976, pp. 235–245.

  62. Yu, W. D., S. H. Liu, J. D. Hatch, V. Panossian, and G. A. Finerman. Effect of estrogen on cellular metabolism of the human anterior cruciate ligament. Clin. Orthop. Relat. Res. 366:229–238, 1999.

    Google Scholar 

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Acknowledgments

The authors would like to acknowledge the University Health Network Research, Toronto, for providing the “Local Thresholding” ImageJ plugin used in this study’s cell counting protocol. As well, thanks are extended to Dr. Michael Sacks (University of Pittsburgh) and Andrew Moeller (Dalhousie University) for providing their custom-written MathCAD and Labview programs, and to OH Armstrong Foods for their cooperation during sample collection. JAED was supported by a graduate scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC). That agency also provided research grants to JML and SMW in support of this work.

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Correspondence to Sarah M. Wells.

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Associate Editor Jane Grande-Allen oversaw the review of this article.

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Doane, J.A.E., Lee, J.M. & Wells, S.M. Structural-Mechanical Changes in the Pericardium During Pregnancy. Cardiovasc Eng Tech 4, 39–52 (2013). https://doi.org/10.1007/s13239-012-0116-4

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