The immediate environment of cardiomyocytes: substantial concentration differences between the interstitial fluid and plasma water for substrates and transmitters.

Substantial transcapillary concentration differences can be inferred from published data on capillary permeability, and from tissue uptake applying Fick's Law for membrane transfer. Concentration differences caused by the diffusive resistance of the capillary wall will be enhanced additionally, if the permeating substrates are metabolized by the endothelial cells. These concentration differences can be verified by sampling and analysing interstitial fluid/transudate from colloid free perfused hearts. With colloid free perfusion, concentration differences can be even underestimated, since the lack of plasma proteins will increase capillary permeability. The observed concentration differences expressed as percentage of interstitial to vascular values amount--for glucose down to 50% for lactate up to 700%, for glutathion, uric acid, adenosine, and catecholamines up to 200-600% when these substances are released from the myocardium, and down to 10-20%, when e.g. adenosine or catecholamines are taken up. The magnitude of these gradients has to be taken into consideration in many respects. In particular, interstitial accumulation of metabolites and mediators (lactate, adenosine, uric acid, catecholamines) are obviously of physiological and pathophysiological importance.