A method for quantifying lipoprotein flux rates between plasma and arterial intima in vivo

Abstract

A new method is proposed for measuring in vivo the rates of transfer of plasma lipoprotein into and out of arterial intima in man. The technique requires the injection of a lipoprotein which can be labelled with two different tracers, followed by a single arterial sample during elective surgery. The feasibility of the method was tested by computer simulation and it was found that measurement uncertainties of the order of those likely in practice produced uncertainties of 7% SD in the calculated influx and 16% SD in the calculated efflux rates. The principal assumption, that lipoprotein in arterial intima can be modelled as a single compartment system, was tested in a preliminary study in an anaesthetised dog: reasonable evidence of monocompartmental behaviour was obtained. The new method was used in a preliminary study of three patients undergoing elective arterial surgery. Low density lipoprotein (LDL) labelled with 125I was injected about 24 h before surgery, followed by 131I-labelled LDL 4 to 6 h before surgery. The radioactivities of washed extracts of arterial intima were then measured in a gamma counter. LDL flux rates were higher in atherosclerotic specimens than in less seriously diseased or normal tissue, and were highest in the most hyperlipidaemic patient.

Preferential influx and decreased fractional loss of lipoprotein(a) in atherosclerotic compared with nonlesioned rabbit aorta.

“…Two previous studies have estimated uncertainties in calculated values of intimal clearance and fractional loss that are induced by measurement uncertainties of the order likely in practice (24,26), using experimental conditions quite similar to the present study. Wootton et al (24) appplied random noise with zero mean and 1.5% SD to plasma radioacitvity data and random noise of zero mean and 5% SD to arterial wall radioactivity data, which produced uncertainties of 7% SD in calculated intimal clearance and 16% SD in cal-…”

“…This assumption has previously been tested and was found to be plausible for iodine labeled LDL in nonlesioned and atherosclerotic aortas of rabbits (22) and monkeys (23). In the one-pool compartment model, the kinetics of labeled lipoproteins can be described by the equation (23)(24)(25):…”

Quantitative studies of transfer in vivo of low density, Sf 12-60, and Sf 60-400 lipoproteins between plasma and arterial intima in humans.

“…Using a recently developed procedure, the validity of which has been tested previously, 10 we have compared the influx into and fractional loss from human atherosclerotic intima of LDL, Sf 12-60, and Sf 60-400 lipoproteins. To date, few quantitative studies of lipoprotein transfer have been made in humans; such studies have involved the measurement of influx by the integral or sink method.…”

“…The fractional uptake, kj (hour" 1 x centimeter 2 ), of plasma lipoproteins into the carotid intima and the fractional loss, k,. (hour' 1 ), of newly entered lipoproteins from the same intimal sample were calculated as described by Wootton et al 10 On the principle of conservation of matter, the rate at which the intimal content of labeled lipoproteins changes, dqjd u is the difference between the influx, R, (counts per minutexhour~'xcentimeter~2), and efflux, R e (counts per minutexhour"'xcentimeter"…”

“…We have used a newly described procedure 10 to address these issues by measuring influx in vivo of LDL, Sf 12-60 lipoprotein particles, and Sf 60-400 lipoprotein particles from plasma into the human atherosclerotic intima and the fractional loss in vivo from the arterial intima of newly entered lipoproteins belonging to these lipoprotein classes.…”