Abstract
The interstitial myocardial matrix is a complex and dynamic structure that adapts to local fluctuations in pressure and actively contributes to the heart’s fluid exchange and hydration. However, classical physiologic models tend to treat it as a passive conduit for water and solute, perhaps because local interstitial regulatory mechanisms are not easily accessible to experiment in vivo. Here, we examined the interstitial contribution to the fluid-driving pressure ex vivo. Interstitial hydration potentials were determined from influx/efflux rates measured in explants from healthy and ischemia-reperfusion-injured pigs during colloid osmotic pressure titrations. Adaptive responses were further explored by isolating myocardial fibroblasts and measuring their contractile responses to water activity changes in vitro. Results show hydration potentials between 5 and 60 mmHg in healthy myocardia and shifts in excess of 200 mmHg in edematous myocardia after ischemia-reperfusion injury. Further, rates of fluid transfer were temperature-dependent, and in collagen gel contraction assays, myocardial fibroblasts tended to preserve the micro-environment’s hydration volume by slowing fluid efflux rates at pressures above 40 mmHg. Our studies quantify components of the fluid-driving forces in the heart interstitium that the classical Starling’s equation does not explicitly consider. Measured hydration potentials in healthy myocardia and shifts with edema are larger than predicted from the known values of hydrostatic and colloid osmotic interstitial fluid pressures. Together with fibroblast responses in vitro, they are consistent with regulatory mechanisms that add local biological controls to classic fluid-balance models.
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Acknowledgments
Lynne Li, Dana Jasso, and Mary Kearns provided technical skills and assistance with data reduction; Megan Lane provided assistance with animal surgeries; and John Olson provided expert technical assistance with the imaging in the Small Animal MRI facilities of Wake Forest University. IPAM (Institute of Pure and Applied Mathematics) at UCLA contributed to this work by providing a friendly forum for the exchange of perspectives among mathematicians, physicists, and biologists. The research was supported in part by a Cheek Foundation Grant to the Department of Plastic and Reconstructive Surgery, Wake Forest University.
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These animal studies comply with the National Institutes of Health Guide for the Care and Use of Laboratory Animals in protocols approved by the Institutional Animal Care and Use Committee.
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McGee, M.P., Morykwas, M.J., Jordan, J.E. et al. Local fluid transfer regulation in heart extracellular matrix. J Physiol Biochem 72, 255–268 (2016). https://doi.org/10.1007/s13105-016-0473-9
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DOI: https://doi.org/10.1007/s13105-016-0473-9