Correlating Heart Interstitium Structure and Function using Hydration and Magnetic Resonance Image (MRI) Analyses

Abstract

Interstitial edema forms during myocardial infarction and is associated with poor clinical outcomes. To clarify tissue responses to excess fluid, we studied structure and function in ischemic (at-risk, AR) and nonischemic (not-at-risk, NAR) myocardial regions of injured pig hearts. Myocardial ischemia-reperfusion injury was induced as described (Argenta et al. 2010) using protocols approved by the institutional animal use committee. Colloidosmotic stress, MRI including diffusion tensor analyses and histology were used to determine the extent of edema from changes in (a) hydration parameters, (b) water molecules’ freedom of motion (T2), and (c) tissue structure. Comparing AR to NAR, T2 values were 44±5 and 35±2 ms (n = 16, 1mm-thick slices from 4 animals ); the apparent diffusion coefficients were 1.20±0.07 and 1.01±0.04 mm2/s, respectively. Fractional anisotropy was 0.292±0.046 vs 0.425±0.053. Diffusion-tensor eigenvalues representing flux in directions normal to myocardial fibers increased in AR. All differences were significant (p-values < 0.0001 in ANOVA and Fisher's post-hoc least significant difference tests). Qualitative histological examination of tissue sectioned perpendicular to the fibers showed markedly enlarged interlaminar spaces in AR regions. Equilibrium and dynamic hydration parameters measured by colloidosmotic titrations (McGee et al., 2012) also differed between regions; fluid efflux was faster, and hydration potential lower in AR than NAR regions, while hydraulic conductance was similar. These findings suggest that flow-resistance scales with interstitial fluid-transfer surface, together with diffusion-tensor results presented here, are consistent with increased local pressure gradients driving fluid in the edematous myocardial interstitial matrix. Functionally, these changes suggest that in vivo interstitial water transfers from flooded, nonbeating myocardia toward healthier, better drained regions, limiting local edema and improving transcapillary exchange.