Measuring Water Distribution in the Heart: Preventing Edema Reduces Ischemia–Reperfusion Injury

Abstract

BackgroundEdema is present in many heart diseases, and differentiation between intracellular (ICW) and extracellular (ECW) myocardial water compartments would be clinically relevant. In this work we developed a magnetic resonance imaging–based method to differentiate ICW and ECW and applied it to analyze ischemia–reperfusion–induced edema.Methods and ResultsIsolated rat hearts were perfused with gadolinium chelates as a marker of extracellular space. Total water content was measured by desiccation. Gadolinium quantification provided ECW, and ICW was calculated by subtraction of ECW from total water content. In separate experiments, T1, T2, diffusion‐weighted imaging and proton‐density parameters were measured in isolated saline‐perfused hearts. In in‐situ rat hearts, ECW and ICW were 79±10 mL and 257±8 mL of water per 100 g of dry tissue, respectively. After perfusion for 40 minutes, ECW increased by 92.4±3% without modifying ICW (−1±3%). Hyposmotic buffer (248 mOsm/L) increased ICW by 16.7±2%, while hyperosmotic perfusion (409 mOsm/L) reduced ICW by 26.5±3%. Preclinical imaging showed good correlation between T2 and diffusion‐weighted imaging with ECW, and proton‐density correlated with total water content. Ischemia–reperfusion resulted in marked myocardial edema at the expense of ECW, because of cellular membrane rupture. When cell death was prevented by blebbistatin, water content and distribution were similar to normoxic perfused hearts. Furthermore, attenuation of intracellular edema with hyperosmotic buffer reduced cell death.ConclusionsWe devised a method to determine edema and tissue water distribution. This method allowed us to demonstrate a role of edema in reperfusion‐induced cell death and could serve as a basis for the study of myocardial water distribution using magnetic resonance imaging.

Cardiac MRI Endpoints in Myocardial Infarction Experimental and Clinical Trials

“…CMR offers the possibility of identifying areas of increased myocardial free water content or edema ( 3 ). The differentiation between intracellular and extracellular edema is technically challenging; however, CMR better reflects an increase in the extracellular compartment ( 33 ). As the extracellular compartment is the one showing the largest change in water content after MI, CMR closely correlates with changes in total myocardial water content ( 34 , 35 ).…”

“…One of the important challenges in the field is the development of methods to differentiate intracellular from extracellular water. The role of edema as potential therapeutic target in I/R could serve as a basis for the study of myocardial water distribution using CMR ( 15 , 33 ).…”

Bipolar ablation with contact force‐sensing of swine ventricles shows improved acute lesion features compared to sequential unipolar ablation

“…Acute thermal lesions were classified as the area inside an observed hemorrhagic ring (see Figure 3A,B). Edema was excluded by the absence of rings, local wall thickening 18 and an increased T2 signal compared to the surrounding myocardium 19 . Lesion areas were obtained for each section and position as the region of interest encircled by the hemorrhagic ring (Figure 3D).…”

Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

“…Plasma osmolality plays a crucial role in the function of cardiac aquaporins. Hyperosmolality increases the mRNA of aquaporin-1, mRNA of upregulated aquaporin-7, protein glycosylation, and intracellular translocation, which may modulate water transport in cardiac myocytes [ 41 , 42 , 43 ]. A rapid increase in plasma osmolality following hypertonic saline administration depresses the sensitivity of the cardiac baroreflex independently of changes in blood pressure, causing an increase in heart rate [ 44 ].…”