Blood-tissue transport of substrates in the heart: studies by single circulation tracer dilution.
Passive capillary permeability is usually not the rate limiting step to movement of small lipid-insoluble molecules from plasma into the heart. At physiological concentrations the rate of carrier-mediated transport and or receptor binding of blood-borne substrates is often measurable in a single circulation through the coronary bed. Here I review some studies on uptake measured by the single-circulation multiple tracer dilution technique. The method consists of a sudden intra-arterial injection of a mixture of tracers followed by sequential rapid sampling of the venous outflow. Generally the tracers include a molecule confined to the intravascular space (e.g. albumin), another confined to the extracellular space and a third test tracer. The data analysis can give information about: a) capillary permeability-surface product (PS), b) endothelial cell membrane transport, c) the size of the interstitial space, d) transport across the sarcolemma, e) uptake by nerve endings, f) binding to receptors, g) rapid metabolic transformations. Studies were performed in the isolated perfused heart (dog and rabbit). Early observations on rapid tissue uptake of potassium and ouabain have recently been extended. Kinetics of unidirectional trans-sarcolemmal influx of lactate, a metabolic substrate for the myocardium and the neuronal uptake of amines, were investigated as well as the myocardium and the neuronal uptake of amines, were investigated as well as the effects of specific inhibitors for these transport mechanisms. Uptake was also measured for glucose, the amino acids L-phenylalanine, L-alanine and taurine; and for acetate and palmitate. Recent literature which proposes an important role for uptake and metabolism of adenosine by the endothelium is discussed. These studies are of interest for clinical applications such as positron emission tomography (PET) which makes use of short-life isotopes.
Yudilevich
D L
DL
Department of Physiology, King's College, University of London, United Kingdom.
D000588:Amines / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D002199:Capillary Permeability / Q000502:physiology; D003326:Coronary Circulation; D004285:Dogs; D006168:Guinea Pigs; D008833:Microcirculation; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D011865:Radioisotope Dilution Technique
D000588:Amines; D000596:Amino Acids