Methods for the simultaneous measurement of pressure differentials and flow in single unbranched vessels of the microcirculation for rheological studies

Methods and illustrative applications for in vivo study of the rheological behavior of blood in the microcirculation are presented. Techniques were developed for the simultaneous measurement of pressure differential (drop) and red blood cell velocity in single unbranched microvessels ranging in luminal diameter from 7 to 54 μm. The servo-null micropressure technique was modified by hydraulically coupling two separate systems to a high-resolution differential pressure transducer to facilitate measurement of pressure drops to within ±0.02 cm H₂O. Simultaneous flow measurements of red cells plus plasma were made by a variation of the “two-slit” photometric technique. Measurements of these parameters and vessel geometry (length and diameter) in the mesentery of the cat permitted computation of rheological parameters such as resistance, resistivity, “apparent viscosity,” and intravascular wall shear stress. The results indicate the persistence of a pulsatile component in pressure drop throughout all levels of the microvasculature. Apparent viscosity was found to increase dramatically in the “true capillaries,” from 1.0 to 5.6 cP, as luminal diameter decreased from 9 μm to the size of a red blood cell, nominally 7 μm. The concomitant rise in capillary wall shear stress was from 18 to 40 dynes/cm². In larger microvessels, flow vs ΔP curves were established and found to be reasonably well represented by a Casson rheological model. Asymptotic apparent viscosities decreased from approximately 3.3 cP in arterioles and venules 45 to 54 μm in diameter to on the order of 2 cP in microvessels from 17 to 23 μm in diameter. For this illustrative sampling of data, wall shear stresses as great as 88 dynes/cm² were found in the immediate precapillary vessels, 23 μm in diameter.     

Mechanism of the age-related decline in lymphocyte proliferation: Role of IL-2 production and protein synthesis

Although an age-related decline in mitogen-induced proliferation in spleen lymphocytes has been reported by numerous investigators, the molecular mechanism responsible is unknown. In this study, we compared the mitogen-induced proliferation, IL-2 production, and protein synthesis in spleen lymphocytes isolated from 4, 12, 20 and 30 month-old male Fischer F344 rats. IL-2 production by Con A-stimulated lymphocytes, as determined by the ability of the culture supernatants to support the growth of cultured T cells, declined over 72% between 4 and 30 months of age. This decline in IL-2 production paralleled a similar decrease in proliferation. Early protein synthesis by Con A-stimulated spleen lymphocytes was determined by measuring the incorporation of [³H]-valine into acid insoluble material, and this dropped 74% between 4 and 30 months of age. There was a strong correlation between the age-related decline in the three parameters tested. Based on these results, we propose that the age-related decline in protein synthesis may be the molecular basis for the similar decrease in IL-2 production and mitogenesis.     

Effects of dietary substitution of mixed amino acids for glucose on the splanchnic metabolism of plasma triglycerides, cholesterol, carbohydrates, and amino acids in conscious fed baboons

Splanchnic metabolism was studied in the fed state during prolonged constant intravenous administration of tracer amounts of [9,10]-3H palmitic acid and the calculated isocaloric intraduodenal administration (13 mg/min X kg body wt0.75) of either (1) glucose, (2) 15% mixed amino acids and 85% glucose or (3) 45% mixed amino acids and 55% glucose to conscious, restrained female baboons that had been maintained on a similar diet (supplemented in essential nutrients) for the previous 9 days. Secretion of plasma triglycerides from the splanchnic region was quantified from splanchnic flow and radiochemical measurements of transsplanchnic gradients of 3H-labeled free fatty acids and triglycerides. Mean splanchnic secretion of plasma triglycerides increased significantly as the proportion of dietary calories derived from amino acids was varied from 0 to 15 to 45% (mean values 1.1 +/- 0.1, 2.6 +/- 0.2 and 4.2 +/- 0.3 mumol/min kg body wt0.75, respectively, p less than 0.05). Increased triglyceride secretion was attributable to both significantly higher rates of esterification of free fatty acids taken up in the splanchnic region to triglycerides released into hepatic venous blood plasma (mean values 10 +/- 1, 16 +/- 2 and 34 +/- 5%, respectively) and to significantly higher rates of secretion of triglycerides derived from precursors other than free fatty acids. Higher intake of amino acids was also associated with both higher plasma concentrations of cholesterol and higher values for hepatic oxidation of cholesterol to bile acids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased dietary calcium lowers blood pressure in the spontaneously hypertensive rat

The effect of increased dietary calcium on the development of hypertension in spontaneously hypertensive (SH) rats was investigated by feeding lab chow fortified with calcium carbonate (2.5% calcium, hCa) beginning at 4 wk of age. A control SH group was fed regular lab chow (1.2% calcium, rCa). Two groups of age-matched Wistar-Kyoto (WKY) rats were treated in parallel. Systolic blood pressure (BP) was measured weekly until the age of 18 wk using a tail cuff method. The hCa diet significantly attenuated the time course of hypertension in SH rats even though both SH groups eventually developed hypertension. The hCa also lowered BP in WKYs, but to a lesser extent. Urine output (24-hr volumes) was not affected by hCa, but in both SH and WKY groups fed the hCa diet, the excretion of Na+, K+ and Ca++ was markedly elevated at 11, 15, and 19 wk of age. Urine osmolality was also elevated. Plasma Na+, Ca++ and osmolality were not significantly altered by the diet in either SH or WKY rats; plasma potassium was significantly lower in the SH group fed the hCa diet than in the group given rCa. The hCa diet did not significantly affect the body or heart, kidney, adrenal, or thymus weights. The results suggest that hCa diet may attenuate genetic hypertension by inducing an osmotic diuresis.     

Sterol balance in abetalipoproteinemia: studies in a patient with homozygous familial hypobetalipoproteinemia.

A new case of homozygous familial hypobetalipoproteinemia is reported in a 16-yr-old girl. Apoprotein B was absent from plasma and the patient had acanthocytes and steatorrhea, but minimal neurologic dysfunction. Total body cholesterol synthesis was assessed intermittently over a 30-mo period by sterol balance techniques. The rate of synthesis of cholesterol was higher (15.0 +/- 2.9 mg/kg/day) in the patient (8.3 +/- 0.4 mg/kg/day than in 3 control children, p less than 0.005). Bile acid synthesis was similar (4.6 +/- 1.8 versus 4.0 +/- 1.7 mg/kg/day) in the patient and controls, but total body sterol synthesis was significantly higher (19.6 +/- 3.0 versus 12.2 +/- 2.0, p less than 0.005). The absorption of orally administered [1,2,(3)H] cholesterol in the patient was low and less than 0.5% of the label appeared in the total plasma volume at all times up to 48 hr. Estimates of the extent that malabsorption of biliary cholesterol contributes to the enhanced excretion of neutral sterols in this case indicate that all of the increase can be explained on this basis. Thus, although the mechanisms for the increased sterol synthesis in this case may relate to the absence of chylomicrons and low density lipoproteins in plasma, the magnitude of the increase can be fully explained on the basis of a compensatory mechanism to maintain cholesterol homeostasis in the face of enhanced fecal losses.     

Magnesium balance and distribution during total parenteral nutrition: effect of calcium additives

Homeostatic alterations and derangements in magnesium (and phosphate) metabolism may occur during total parenteral nutrition (TPN) and may be influenced by the amounts of calcium supplied daily. We tested these possibilities in previously fasted or nonfasted animals receiving TPN with variable amounts of calcium. Large calcium additives (90 mg/d) produced hypomagnesemia in nonfasted animals and increased the degree of hypomagnesemia observed in some of the fasted groups. Bone and muscle magnesium were occasionally altered, by high-calcium additives. Urine magnesium was increased, metabolism may have been dependent upon the amount of calcium added and magnesium supplied in TPN. Some of the derangements may have been dependent upon the state of fasting (and resultant phosphate-depletion syndrome).     

Steroidogenic cellular sites in the cat ovary: a histochemical study.

The distribution of lipids, NADH, NADPH diaphorase, glucose 6-phospate, the isocitrate dehydrogenases, Δ⁵-3β- and 17β-hydroxysteroid dehydrogenases, and acid phosphatase in immature, cycling, and pregnant cat ovaries has been histochemically studied. Corpora lutea were found only in pregnant cats. Acid phosphatase was present in the degenerating follicles and only in trace amounts in the corpora lutea and was absent in the interstitial gland cells, germinal epithelium, and the normal developing follicles. Lipids and the various enzymes studied were localized in the theca interna of preantral and antral follicles, interstitial gland cells, and in the corpora lutea. Germinal epithelium lacked lipids, diaphorases, and all the enzymes investigated. It is suggested that theca interna and the interstitial gland cells form principal sites of steroid synthesis in the ovaries of immature as well as cycling cats while corpora lutea form additional sites of steroidogenesis during pregnancy.     

Ethanol-insulin interrelationships in the rat studied in vitro and in vivo: Evidence for direct ethanol inhibition of biphasic glucose-induced insulin secretion

The effect of ethanol (ETOH) on glucose-stimulated insulin secretion was studied using: (1) an in vitro isolated pancreas perfusion system, and (2) an in vivo preparation utilizing unrestrained, unanesthetized rats with indwelling jugular and aortic catheters. ETOH exposure in vitro resulted in a decrease in glucose-stimulated insulin secretion from the perfused rat pancreas. Second phase secretion (min 30–60) was inhibited at low ETOH exposure (100 mg/dl) and both first (min 2–8) and second phase secretion were inhibited at higher ETOH levels (1000 mg/dl). This indicates that second phase secretion of insulin from the pancreas is more sensitive to the acute effects of ETOH than is first phase secretion. ETOH preinfusion of 4 hr in vivo resulted in an approximate 20 mg/dl decrease in plasma glucose concentrations with little or no alteration in plasma insulin levels. One hour ETOH preinfusion produced a modest 8 mg/dl fall in plasma glucose. Intravenous glucose tolerance tests following low level ETOH infusion of 4 hr resulted in an enhancement in the insulin response with no change in glucose removal. This enhancement was not observed at higher ETOH levels or after high-level, short (1 hr) ETOH preinfusion. The data suggest that stimulus-induced insulin secretion may be enhanced by an ETOH metabolite if the ETOH exposure is prolonged and at a low level. Higher ETOH concentration appears to directly block this enhancement. Due to response similarities the rat model may be of considerable value to study the effects of ETOH on stimulus-induced insulin secretion in human subjects.     

Alterations in liver nucleic acids and nucleotides in arginine deficient rats

Dietary arginine deficiency is associated with retarded growth and depressed feed intake. Nucleic acid biosynthesis as indicated by the incorporation of [6-¹⁴C]-orotic acid and [³²p]-orthophosphate was significantly depressed in rats fed an arginine deficient diet. The activities of the pyrimidine enzymes, aspartate transcarbamylase (ATC) and dihydroorotate dehydrogenase (DHODH) were significantly increased in rats fed an arginine deficient diet. ATC and DHODH activities in rats fed the arginine deficient diet returned to control activities after 3 wk of feeding. Orotidine 5′ phosphate decarboxylase and orotate phosphoribosyl transferase activities were not affected by dietary arginine availability. In the rat fed an arginine deficient diet there was an increase in total liver pyrimidine nucleotides and a decrease in the total purine nucleotides. Significant alterations in the individual liver nucleotides were also observed. Incubation of various tissues obtained from rats fed an arginine deficient diet or a complete diet with glutamine (5mM) revealed that the liver is the major site of orotic acid synthesis. Orotic acid production in liver slices using glutamine as the nitrogen source was significantly greater in rats fed an arginine deficient diet compared to controls. The orotic aciduria occurring in rats fed an arginine deficient diet is associated with increased synthesis and decreased utilization of pyrimidines.     

Hepatic and extrahepatic splanchnic glucose metabolism in the postabsorptive and glucose fed dog

In awake dogs we measured the glucose balance across the liver and extrahepatic splanchnic tissues in the postabsorptive state and during two hours of IV infusion of glucose or for three hours following ingestion of oral glucose and during four hours of sequential intraportal followed by oral glucose. The IV glucose infusion rate was adjusted to maintain a steady state glucose concentration of either euglycemic levels (insulin clamp, group 1, N = 4), 125 mg/100 mL above the postabsorptive glucose concentration (+125 mg glucose clamp, group 2, N = 3) or 200 mg/100 mL above basal glucose levels (+200 mg glucose clamp, group 3, N = 7). Oral glucose was given at a dose of either 1.5 g/kg (group 4, N = 7) or 2.5 g/kg (group 5, N = 12). In dogs that received IV glucose, basal gut glucose uptake (0.5 +/- 0.1 mg/min X kg) was stimulated by hyperglycemia (1.5 +/- 0.5 and 1.4 +/- 0.1 mg/min X kg for group 2 and 3, respectively, P less than 0.05). In these same animals basal hepatic glucose output (-2.7 +/- 0.3 mg/min X kg) was promptly suppressed and net hepatic glucose uptake occurred (2.8 +/- 0.2 and 2.4 +/- 0.5 mg/min X kg in group 2 and 3 respectively). Euglycemic hyperinsulinemia (group 1) suppressed postabsorptive hepatic glucose release but did not enhance glucose removal by either the liver or gut tissues. After oral glucose gut tissues released absorbed glucose into portal blood. Over three hours following the glucose meal 74% and 59% of the ingested glucose was absorbed in group 4 and 5, respectively. As with IV glucose, postabsorptive hepatic glucose production was suppressed and over the first two hours after feeding the liver took up glucose (3.4 +/- 1.0 and 3.1 +/- 0.7 mg/min X kg groups 4 and 5, respectively) at a rate similar to that seen with IV glucose. To further examine the effect of the route of glucose administration on liver glucose handling, hepatic glucose balance was measured serially over four hours in three dogs that received IV glucose into a mesenteric vein to produce portal hyperglycemia (+125 mg/dL portal glucose clamp N = 3). Oral glucose (2.5 mg/kg) was given at two hours, and the rate of the mesenteric glucose infusion adjusted to maintain portal glycemia constant. The hepatic glucose balance averaged 5.5 mg/min X kg over the 0 to 2 hour period and 4.2 +/- 1.0 mg/min X kg over the 2 to 4 hour time.(ABSTRACT TRUNCATED AT 400 WORDS)     

The peritoneal absorption of insulin in diabetic man: A potential site for a mechanical insulin delivery system

The potential of the peritoneum as a site for an “artificial beta cell” was studied. Three 14-hr studies were performed in an insulin-dependent diabetic male maintained on chronic peritoneal dialysis. All studies were performed between dialyses and throughout three standard American Diabetes Association (ADA) 600 calorie meals. The degree of insulin absorption from the peritoneal space was assessed by measuring the changes in plasma-free insulin concentration during these studies. The results of this study demonstrate that normalization of plasma insulin profiles may be observed with the administration of insulin into the peritoneal space. This absorbed insulin exerts hypoglycemic activity that suppresses the meal-induced rise in plasma glucose concentration. Thus, the peritoneal space may be a feasible route into which insulin may be delivered by an artificial beta cell.     

A selective decline of postheparin plasma hepatic triglyceride lipase in hypothyroid rats

The present study aimed to define the effect of thyroid status on two postheparin plasma lipases, i.e., lipoprotein lipase and hepatic triglyceride lipase. Rats with hypo- and hyperthyroidism were used for this purpose. Separate measurement of these two lipases was done by an immunochemical method utilizing antiserum specific to hepatic triglyceride lipase. The 5-wk thyroidectomized, hypothyroid rats had normal plasma concentrations of both triglyceride and cholesterol. These rats showed a selective decline in the activity of postheparin plasma hepatic triglyceride lipase with normal lipoprotein lipase activity. The rats made thyrotoxic by thyroxine treatment had normal plasma levels of both triglyceride and cholesterol. These rats showed normal activities of both hepatic triglyceride lipase and lipoprotein lipase. The observed finding of a selective decline of hepatic triglyceride lipase in hypothyroid rats is discussed in connection with the possible function of this enzyme in lipoprotein metabolism.     

The relation between urinary 5-hydroxyindoleacetic acid levels and the ratio of tryptophan to other large neutral amino acids placed in the stomach.

We assayed 5-hydroxyindoleacetic acid (5-HIAA) in urine samples (3- or 6 1/2-hr collection) after individual rats received 6-8 ml of water, of amino acids in solution, or of glucose by stomach tube. Tryptophan (Trp) solutions caused dose-related increases in urinary 5-HIAA; these were blocked when animals received carbidopa, an inhibitor of peripheral aromatic amino acid decarboxylase. The concurrent administration of a large neutral amino acid (LNAA; valine or isoleucine) with oral Trp, in high doses probably sufficient to compete with Trp for transport into gut cells, blocked the Trp-induced rise in urinary 5-HIAA. Concurrent administration of glycine (not a LNAA) in equivalent doses did not. Pretreatment with pyridoxine blocked the Trp-induced rise in urinary 5-HIAA but not that in brain serotonin (5-hydroxytryptamine, 5HT). These observations confirm the previous suggestion that while brain serotonin synthesis depends on the plasma Trp/LNAA ratio (which varies inversely with the proportion of protein to total calories in the diet), gut serotonin synthesis depends largely on the Trp/LNAA ratio in the dietary protein itself (and, probably, within the gut lumen postprandially). The range of molar Trp/LNAA ratios at which free LNAAs significantly diminish the effects of ingested Trp on gut serotonin synthesis (as reflected by urinary 5-HIAA) is similar to the range found in dietary proteins.     

Selective total removal of a growth-hormone-secreting adenoma: evidence that acromegaly is a primary pituitary disease.

Acromegaly is caused by hypersecretion of growth hormone by the pituitary. There is some debate as to whether the primary etiology of the disease is abnormal hypothalamic stimulation of the pituitary or a primary pituitary tumor. This paper presents a case of acromegaly in which growth hormone dynamics in response to stimulation and suppression tests were abnormal. After transsphenoidal adenomectomy of a small tumor, growth hormone levels returned to normal and suppression and stimulation test results reverted to normal within 1 wk postoperatively and remained normal for 2 yr. The findings suggest that the acromegaly in this case was due to a primary pituitary dysfunction. Microsurgical removal of growth-hormone-secreting tumors provides a unique opportunity to study the etiology of acromegaly.     

The effects of prednisone therapy on plasma lipoproteins and apolipoproteins: a prospective study

The effect of prednisone therapy on plasma lipoproteins and apolipoproteins A-I, A-II, and E levels was studied prospectively in a heterogeneous group of six male and six female subjects. All patients were in a good general condition. The patients had normal hepatocellular, renal, and thyroid functions. During the first month of therapy, the following changes were noted: Plasma triglyceride (TG) levels increased slightly in female patients only. In the entire group, plasma cholesterol level increased (17.3% of initial value, P less than 0.01). Plasma high-density lipoprotein cholesterol (HDL-C) level increased by 68% (P less than 0.001), while plasma low-density lipoprotein cholesterol (LDL-C) level increased by only 10.9% (not significant), resulting in an increased ratio of cholesterol in the two (P less than 0.01). No change in levels of plasma apolipoproteins A-I, A-II, and E was evident. The ratio of HDL-C to plasma apolipoprotein A-I increased (P less than 0.01), indicating an increased lipid to protein ratio for this lipoprotein. Most of these changes were already apparent and significant 48 hours after initiation of treatment and persisted throughout the follow-up period (up to 18 months in some patients). Our results show that in patients with no major metabolic abnormality, prednisone induces significant changes of the lipoprotein system, especially in HDL.     

Neurohypophyseal peptides in hypothyroid rats: plasma levels and kidney response.

A degree of impairment of water excretion may be associated with hypothyroidism. The involvement of vasopressin has been suggested, but its role continues to be debated because of lack of studies where vasopressin was directly assayed. In this study, water excretion was assessed and arginine vasopressin was directly measured in unanesthetized and nonstressed normal and thyroidectomized rats at a basal state and after water loading. Following water load, both groups decreased their plasma osmolality. Plasma vasopressin demonstrated an elevated level in hypothyroid rats compared to control (2.04 and 1.04 μU/ml), respectively, at baseline and (1.32 and 0.68 μU/ml), respectively, after water loading. There was a significant and similar correlation between plasma vasopressin and plasma osmolality in both groups. The regression lines for urine osmolality and plasma vasopressin of the two groups were parallel but with a significantly greater vasopressin level for the hypothyroid rats at any given urine osmolality. This suggested that circulating plasma vasopressin was less active in hypothyroid than control rats; a hypothesis that was tested by measuring the responsiveness of renal medullary adenylate cyclase to vasopressin. Both basal and vasopressin stimulated cyclic AMP levels were less in hypothyroid than control rats. Thus, these studies demonstrate that hypothyroidism in the rat was associated with an elevated plasma vasopressin that did not appear to be fully effective in inducing an antidiuresis. Factors other than vasopressin may be more important in the water imbalance of hypothyroidism.     

The role of fractional glucose extraction in the regulation of splanchnic glucose metabolism in normal and diabetic man

In order to express in equivalent terms seemingly divergent results obtained with isotopic tracer studies as compared to hepatic venous catheter studies on the role of the liver in the metabolism of oral glucose, our previously published studies using the hepatic venous catheter technique in normals and diabetics given intravenous and/or oral glucose were analyzed with respect to the splanchnic fractional extraction of glucose, total splanchnic glucose influx, and the proportion of total glucose metabolism accounted for by net splanchnic glucose uptake. In normal subjects during extreme hyperinsulinemia (plasma insulin, 500–1,200 μU/ml) induced by i.v. insulin while maintaining the blood glucose concentration at basal levels (insulin clamp), total glucose metabolism rose to 10.5 ± 0.9 mg/min · kg, while splanchnic fractional extraction of glucose was 4.2 ± 1.1%, and net splanchnic glucose uptake accounted for only 5 ± 2% of total glucose turnover. During hyperglycemic (blood glucose, 200 mg/dl) hyperinsulinemia induced by i.v. glucose, net splanchnic glucose uptake was twice that observed with euglycemic hyperinsulinemia, and the proportion of total glucose metabolism occurring in the splanchnic bed rose to 14 ± 4%. These increments were due entirely to a rise in splanchnic glucose influx since the fractional extraction (3.4 ± 0.5%) remained unchanged from that observed with euglycemic hyperinsulinemia. After oral glucose (100 g), splanchnic glucose influx was comparable to hyperglycemic hyperinsulinemia induced with i.v. glucose, but splanchnic fractional extraction rose to 13.1 ± 1.9% (p < 0.001 versus i.v. glucose), a value comparable to that observed with isotopic studies of oral glucose metabolism. Total glucose turnover was, however, 30% lower than after i.v. insulin (p < 0.01), so that net splanchnic glucose uptake accounted for 54 ± 5% of total glucose metabolism. In maturity-onset diabetics, after 100 g oral glucose splanchnic glucose influx was 69% greater than in controls (p < 0.001), but net splanchnic glucose uptake was 44% below controls (2.3 ± 0.5 versus 4.1 ± 0.5 mg/min · kg, p < 0.02). This reduction in glucose uptake could be accounted for by a splanchnic fractional extraction ratio (4.7 ± 1.4%) that was 64% lower than in controls given oral glucose (p < 0.001). It is concluded that: (1) in normal subjects, the ability of the splanchnic area to extract circulating glucose (as reflected by the splanchnic fractional extraction) is 2–3-fold greater after oral glucose than after intravenous glucose; (2) the rise in splanchnic fractional extraction to levels of 13% in association with only moderate increases in total glucose turnover fully accounts for the predominance of the splanchnic area in the metabolism of oral as compared to intravenous glucose; and (3) in maturity-onset diabetics, oral glucose fails to induce a rise in splanchnic fractional extraction of glucose comparable to that observed in normal subjects.     

The relative contribution of the nervous system, hormones, and metabolites to the total insulin response during a meal in the rat

An attempt was made to quantitatively determine the relative contribution of the nervous system, hormonal factors, and metabolites to the total peripheral plasma insulin response (integrated incremental area) during a ten-minute liquid meal in conscious freely moving rats. The neurally mediated insulin response, as measured in the gastric-fistula bearing sham-feeding rat, amounted to at least 26%. The possible contribution of neural mechanisms triggered by the gastric, intestinal, and postabsorptive phases of the meal were, however, not determined. Hormonal factors were found to contribute at least 30% to the total insulin response on the basis of the insulin response to real feeding in atropinized rats, in the absence of any increases of plasma glucose and with only small elevations of plasma alpha-amino nitrogen. A possible atropine-suppressible hormonal factor was not isolated in the present study. Finally, the relative contribution of rising plasma glucose as determined by intravenous glucose infusions was found to amount to no more than 20%; however, the contribution of rising plasma amino acids was not determined. Thus, 23% of the total insulin response could not be segregated, but it is thought that a good part of it can be attributed to synergistic mechanisms. Because of such interactions, the sum of the effects of the isolated factors is less than the effect of the combined factors.     

Sampling of arterialized heated-hand venous blood as a noninvasive technique for the study of ketone body kinetics in man

To determine if sampling of arterialized-hand venous (HV) blood is a suitable alternative for arterial (A) blood to study ketone body metabolism, concentrations of unlabeled and labeled ketone bodies were measured during continuous infusion of 3-¹⁴C-acetoacetate in simultaneously drawn samples from A and HV blood in normal subjects. The mean difference of acetoacetate between A and HV blood was in the basal state 1.5%, and that of β-hydroxybutyrate 6% (n.s.). Similarly, the ¹⁴C-content of ketone bodies and their calculated rates of production and metabolic clearance were not significantly different between A and HV blood. Following induction of ketosis by acetoacetate loading infusions, the difference of concentrations and ¹⁴C-content of total ketone bodies between HV and A blood remained insignificant (average 3%), and ketone body kinetics calculated from A and HV blood were similar. Furthermore, concentrations of glucose, lactate and PCO₂ did not differ significantly between the two sampling sites. In contrast, concentrations of ketone bodies, glucose and pO2₂ were significantly lower, and the metabolic clearance rate of ketone bodies and PCO₂ higher in antecubital venous blood compared to heated-hand venous blood. Thus, the similarity of heated-hand venous and arterial blood suggests that the noninvasive technique is suited for kinetic analyses using tracer methods and for arteriovenous balance studies of ketone bodies.