Protein washdown as a defense mechanism against myocardial edema

Abstract

Myocardial edema occurs in many pathological conditions. We hypothesized that protein washdown at the myocardial microvascular exchange barrier would change the distribution of interstitial proteins from large to small molecules and diminish the effect of washdown on the colloid osmotic pressure (COP) of interstitial fluid and lymph. Dogs were instrumented with coronary sinus balloon-tipped catheters and myocardial lymphatic cannulas to manipulate myocardial lymph flow and to collect lymph. Myocardial venous pressure was elevated by balloon inflation to increase transmicrovascular fluid flux and myocardial lymph flow. COP of lymph was measured directly and was also calculated from protein concentration. Decreases occurred in both protein concentration and COP of lymph. The proportion of lymph protein accounted for by albumin increased significantly, whereas that accounted for by beta-lipoprotein decreased significantly. The change in the calculated plasma-to-lymph COP gradient was significantly greater than the change in the measured COP gradient. We conclude that the change in the distribution of interstitial fluid protein species decreases the effect of protein washdown on interstitial fluid COP and limits its effectiveness as a defense mechanism against myocardial edema formation.

Evaluation of gravimetric techniques to estimate the microvascular filtration coefficient

“…Fourth, it was assumed that ⌸ c , ⌸ i , and P out do not change with increasing microvascular pressure. Although ⌸ c would not change with elevated P c , ⌸ i decreases as a result of interstitial protein washdown (40), leading to overestimation of K f . However, recent studies reported that the decrease in ⌸ i with washdown is lower than previously assumed (40).…”

“…Although ⌸ c would not change with elevated P c , ⌸ i decreases as a result of interstitial protein washdown (40), leading to overestimation of K f . However, recent studies reported that the decrease in ⌸ i with washdown is lower than previously assumed (40). Thus, when the increase in P c is small (ϳ15 cmH 2 O), the change in ⌸ i may not be significant.…”

“…Furthermore, this model included variable microvascular fluid filtration and protein extravasation, storage of interstitial fluid and proteins, and lymphatic return of fluid and proteins. The assumption of a variable interstitial protein allows the model to capture the effect of protein washdown, a decrease in the interstitial protein concentration with increased microvascular fluid filtration (40,42). This complexity in particular allowed us to quantify the error in K f estimates arising from the common assumption of constant interstitial protein concentration.…”

The role of the lymphatic circulation in the natural history and expression of cardiovascular disease

“…Such augmentation is driven by increased flow of interstitial fluid into the lymphatic vessel as a consequence of increased interstitial pressure and an inverse decrease in lymphatic resistance [4,8]. To promote lymph flow, interstitial protein concentration is also diluted in "protein washout" during higher rates of filtration [9], thereby reducing oncotic sequestration of interstitial fluid. Influences such as the phasic contraction of the myocardium and extracardiac thoracic movements further contribute to the dynamic regulation of fluid movement.…”

Hepatic transudation barrier properties

“…Hepatic sinusoids, characterized by a fenestrated endothelial lining without a basement membrane, are highly permeable . Because the hepatic interstitial protein concentration is as high as the plasma protein concentration and is unaffected by increases in trans‐sinusoidal fluid flux, “protein washdown” is a relatively unimportant phenomenon in the liver . Therefore, without an appreciable oncotic pressure gradient, increases in sinusoidal hydrostatic pressure lead to a significant increase in the trans‐sinusoidal fluid filtration rate .…”