title: Local fluid transfer regulation in heart extracellular matrix.
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.
authors.affiliation: Plastic and Reconstructive Surgery, Wake Forest University Medical School, Winston-Salem, NC, USA. mmcgee@wakehealth.edu.
authors.forename: Maria P
authors.initials: MP
authors.lastname: McGee
authors.affiliation: Plastic and Reconstructive Surgery, Wake Forest University Medical School, Winston-Salem, NC, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morykwas
authors.affiliation: Cardiothoracic Surgery, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC, 27157, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Jordan
authors.affiliation: Plastic and Reconstructive Surgery, Wake Forest University Medical School, Winston-Salem, NC, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Plastic and Reconstructive Surgery, Wake Forest University Medical School, Winston-Salem, NC, USA.
authors.forename: Louis C
authors.initials: LC
authors.lastname: Argenta
mesh_terms: D000818:Animals; D048430:Cell Shape; D058948:Cell Tracking; D002478:Cells, Cultured; D004058:Diffusion; D004195:Disease Models, Animal; D004489:Edema, Cardiac / Q000209:etiology*; D045604:Extracellular Fluid / Q000000981:diagnostic imaging; D005109:Extracellular Matrix; D005260:Female; D018495:Fluid Shifts; D006321:Heart / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D058628:Myofibroblasts / Q000473:pathology; D009997:Osmotic Pressure; D034421:Sus scrofa; D046509:Tissue Culture Techniques; D014882:Water-Electrolyte Balance
keywords: Colloid osmotic pressure; Edema; Ischemia-reperfusion injury