A technique was developed for measurement of blood flow in the coronary sinus in man by continuous thermodilution. For single determinations, 5% dextrose at room temperature is injected at a constant rate of 35 ml/min for a period of about 20 sec. In 14 subjects with normal coronary arteries the mean coronary sinus blood flow was 122 ± 25 ml/min (range, 83 to 159 ml/min). The blood flow computed per 100 g of left ventricle was 82 ± 16 ml/min, which is in the range of values obtained by nitrous oxide and coincidence counting methods. In 35 patients with arteriographically confirmed coronary artery disease the mean flow was similar (128 ± 20 ml/min; range, 92 to 167 ml/min). A special catheter was used for simultaneous measurement of blood flow in the coronary sinus and great cardiac vein. In eight normal subjects the mean great cardiac vein flow was 68 ± 11 ml/min (range, 51 to 78 ml/min) or 65 ± 10% of the coronary sinus blood flow. The method allowed continuous measurement of flow over a period of severa...

Measurement of Coronary Sinus Blood Flow by Continuous Thermodilution in Man

A compartmental model is presented to account for transient and steady-state changes in blood glucose concentration which result from transit through the forearm and hand in man. This model permits...

Effects of arterial versus venous sampling on analysis of glucose kinetics in man

Of 20 amino acids measured, alanine is the principal amino acid released by forearm muscle of man, in accord with its being the principal amino acid extracted by liver for gluconeogenesis. This occurs in both the postabsorptive state and after 4 to 6 weeks of starvation, when total amino acid release is markedly diminished.

https://science.sciencemag.org/content/sci/167/3920/1003.full.pdf

Alanine: Key Role in Gluconeogenesis

Although insulin stimulates protein synthesis and inhibits protein breakdown in skeletal muscle in vitro, the actual contribution of these actions to its anabolic effects in man remains unknown. Using the forearm perfusion method together with systemic infusion of L-[ring-2,6-3H]phenylalanine and L-[1-14C]leucine, we measured steady state amino acid exchange kinetics across muscle in seven normal males before and in response to a 2-h intraarterial infusion of insulin. Postabsorptively, the muscle disposal (Rd) of phenylalanine (43 +/- 5 nmol/min per 100 ml forearm) and leucine (113 +/- 13) was exceeded by the concomitant muscle production (Ra) of these amino acids (57 +/- 5 and 126 +/- 9 nmol/min per dl, respectively), resulting in their net release from the forearm (-14 +/- 4 and -13 +/- 5 nmol/min per dl, respectively). In response to forearm hyperinsulinemia (124 +/- 11 microU/ml), the net balance of phenylalanine and leucine became positive (9 +/- 3 and 61 +/- 8 nmol/min per dl, respectively (P less than 0.005 vs. basal). Despite the marked increase in net balance, the tissue Rd for both phenylalanine (42 +/- 2) and leucine (124 +/- 9) was unchanged from baseline, while Ra was markedly suppressed (to 33 +/- 5 and 63 +/- 9 nmol/min per dl, respectively, P less than 0.01). Since phenylalanine is not metabolized in muscle (i.e., its only fates are incorporation into or release from protein) these results strongly suggest that in normal man, physiologic elevations in insulin promote net muscle protein anabolism primarily by inhibiting protein breakdown, rather than by stimulating protein synthesis.

/pdf/effect-of-physiologic-hyperinsulinemia-on-skeletal-muscle-54u7e14n20.pdf

Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man.

Amino acid balance across skeletal muscle and across subcutaneous adipose tissue plus skin of the forearm has been quantified in postabsorptive man before and after insulin infusion into the brachial artery.

Skeletal muscle released significant amounts of alpha amino nitrogen after an overnight fast. Most individual amino acids were released. Alanine output was by far the greatest. The pattern of release probably reflects both the composition of muscle protein undergoing degradation and de novo synthesis of alanine by transamination. A significant correlation was observed between the extent of release of each amino acid and its ambient arterial concentration.

Elevation of forearm insulin in eight subjects from postabsorptive (12 μU/ml) to high physiologic levels (157 μU/ml) in addition to stimulating muscle glucose uptake blocked muscle alpha amino nitrogen release by 74%. Consistent declines in output were seen for leucine, isoleucine, tyrosine, phenylalanine, threonine, glycine, and α-aminobutyric acid. Alanine output was insignificantly affected. Doubling forearm insulin levels (from 10 to 20 μU/ml) in eight subjects increased muscle glucose uptake in three and blocked alpha amino nitrogen output in two although both effects were seen concurrently in only one subject. Changes in net amino acid balance after insulin could be accounted for by increased transport of amino acids into muscle cells or retardation of their exit.

It is likely that ambient arterial amino acid concentrations are established and maintained primarily by the extent of muscle amino acid release. The individual amino acids whose outputs from forearm muscle decline after forearm insulinization correspond well with those whose levels fall systematically after systemic insulinization. This suggests that declines in amino acid levels after systemic insulinization are due to inhibition of muscle release. Doubling basal insulin approaches the threshold both for blockade of muscle amino acid output and stimulation of glucose uptake, effects which appear to occur independently.

/pdf/amino-acid-balance-across-tissues-of-the-forearm-in-45wykn7juc.pdf

Amino acid balance across tissues of the forearm in postabsorptive man. Effects of insulin at two dose levels

/pdf/measurement-of-blood-flow-and-volume-in-the-forearm-of-man-1zcb8hbth7.pdf

Measurement of blood flow and volume in the forearm of man; with notes on the theory of indicator-dilution and on production of turbulence, hemolysis, and vasodilatation by intra-vascular injection.

On the mechanism of action of alpha-tocopheryl phosphate, with special reference to carbohydrate metabolism of striated muscle. III. Inhibition of insulin-induced glycogenesis in isolated rat diaphragm.

On the mechanism of action of alpha-tocopheryl phosphate, with special reference to carbohydrate metabolism of striated muscle. II. Effect on the capacity of rat diaphragm to dissimilate hexose phosphates.

Lilienthal Jl

Papers

Measurement of blood flow and volume in the forearm of man; with notes on the theory of indicator-dilution and on production of turbulence, hemolysis, and vasodilatation by intra-vascular injection.

On the mechanism of action of alpha-tocopheryl phosphate, with special reference to carbohydrate metabolism of striated muscle. III. Inhibition of insulin-induced glycogenesis in isolated rat diaphragm.

On the mechanism of action of alpha-tocopheryl phosphate, with special reference to carbohydrate metabolism of striated muscle. II. Effect on the capacity of rat diaphragm to dissimilate hexose phosphates.