Nutritive blood flow affects microdialysis O/I ratio for [14C]ethanol and3H2O in perfused rat hindlimb

2001 ◽  
Vol 281 (6) ◽  
pp. H2731-H2737 ◽  
Author(s):  
John M. B. Newman ◽  
Carla A. Di Maria ◽  
Stephen Rattigan ◽  
Michael G. Clark

Changes in the microdialysis outflow-to-inflow (O/I) ratio for [14C]ethanol and3H2O were determined in the perfused rat hindlimb after increases and decreases in nutritive flow mediated by the vasoconstrictors norepinephrine (NE) and serotonin (5-HT), respectively. Microdialysis probes (containing 10 mM [14C]ethanol and 3H2O pumped at 1 or 2 μl/min) were inserted through the calf of the rat. Hindlimb perfusion flow rate was varied from 6 to 56 ml · min−1 · 100 g−1 in the presence of NE, 5-HT, or saline vehicle. The O/I ratios for both tracers were determined at each perfusion flow rate, as was perfusion pressure, oxygen uptake (a surrogate indicator of nutritive flow), and lactate release. Both tracers showed a decreased O/I ratio as hindlimb perfusion flow was increased, with [14C]ethanol being higher than 3H2O. NE decreased the O/I ratio compared with vehicle, and 5-HT increased it for both tracers and both microdialysis flow rates. We conclude that the microdialysis O/I ratio, while able to detect changes in total flow, is also sensitive to changes in nutritive and nonnutritive flow, where the latter still extracts tracer, but less than the former.

1982 ◽  
Vol 242 (3) ◽  
pp. G202-G208 ◽  
Author(s):  
P. R. Kvietys ◽  
D. N. Granger

In autoperfused and pump-perfused preparations of canine ileum, arterial pressure, venous outflow pressure, blood flow, and arteriovenous oxygen difference were measured while blood flow was altered either mechanically or by graded intra-arterial infusions of isoproterenol, adenosine, or 2,4-dinitrophenol. In pump-perfused preparations, mechanical alterations in blood flow resulted in opposite changes in arteriovenous oxygen difference, so that ileal oxygen uptake was independent of blood flow over the range of 30-140 ml.min-1.100 g-1. Only at flow rates below 30 ml.min-1.100 g-1 was oxygen uptake dependent on blood flow. Isoproterenol, adenosine, and dinitrophenol produced dose-dependent increases in blood flow under free-flow conditions and decreases in perfusion pressure under constant-flow conditions. Ileal oxygen uptake was not affected by isoproterenol, decreased by adenosine, and increased by dinitrophenol. The effects of these drugs on intestinal oxygen uptake are in accord with their effects on oxygen consumption in vitro. These results suggest that vasodilators will not alter intestinal oxygen uptake in autoperfused preparations in which oxygen uptake is independent of blood flow, unless they exert an effect on oxidative metabolism.


1985 ◽  
Vol 116 (1) ◽  
pp. 251-269 ◽  
Author(s):  
S. F. PERRY ◽  
C. DAXBOECK ◽  
G. P. DOBSON

An isolated, saline-perfused trout head preparation, irrigated with hyperoxic water (PWoλ = 250 Torr), was used to assess diffusion/perfusion limitations to gill oxygen transfer. In the absence of catecholamines, increasing the perfusion flow rate caused a reduction of the partial pressure of oxygen in the dorsal aortic perfusate, indicating diffusion limitations to oxygen uptake. Physiological concentrations of epinephrine stimulated oxygen uptake in a dose-dependent fashion. Moreover, epinephrine elicited a greater effect during increased perfusion flow rate as a result of larger initial diffusion limitations, caused by the increased flow. By using a variety of adrenergic agonists and antagonists, it was demonstrated that beta-receptor stimulation enhanced oxygen uptake whereas alpha-receptor stimulation had no effect. These results are discussed with reference to changes in gill epithelial permeability to oxygen and/or surface area changes.


1988 ◽  
Vol 255 (5) ◽  
pp. H1114-H1129 ◽  
Author(s):  
M. J. Davis

Regulation of blood flow depends on changes in the sum of arterial (Ra) and venous (Rv) resistances, whereas regulation of capillary pressure (Pc) depends on the ratio of Rv to Ra. If the myogenic response of the arterial system (i.e., delta Ra) is the primary mechanism for controlling pressure and flow when perfusion pressure is lowered, then Pc and total flow should be regulated to the same degree under these conditions. This hypothesis was tested by making direct measurements of Pc and flow in skin and skeletal muscle in the wings of unanesthetized bats. The box method was used to reduce perfusion pressure to the wing. Pressures were measured with a servo-null system; flows were computed from measurements of vascular diameters and red cell velocities using intravital microscopy. All branching orders of arterioles dilated significantly during decreases in box pressure (Pb). For 0 less than Pb less than or equal to -30 mmHg, total flow (1st-order arteriolar flow) remained nearly constant, whereas Pc was "regulated" only approximately 60%. These results cannot be explained by changes in arteriolar resistance alone and suggest that changes in Rv may be important. The possible consequences of flow redistribution, capillary recruitment, and micropressure sampling procedures are discussed in relationship to local regulation of capillary pressure and flow.


1983 ◽  
Vol 6 (3) ◽  
pp. 127-130 ◽  
Author(s):  
C. Woffindin ◽  
N.A. Hoenich ◽  
D.N.S. Kerr

Data collected during the evaluation of a series of hemodialysers were analysed to see the effect of hematocrit on the clearance of urea and creatinine. All evaluations were performed on patients with a range of hematocrits with a mean close to 20%. The urea clearance of those in the upper half of the distribution curve (mean hematocrit 29.4%) was not significantly different from that of patients in the lower half of the distribution curve (mean hematocrit 16.9%) whether the clearance was studied at high or low blood flow rates and with hollow fibre or flat plate disposable hemodialysers. Likewise, there was no correlation between hematocrit and urea clearance by regression analysis. In contrast, the clearance of creatinine was affected by hematocrit being greater at lower hematocrit values. This difference was independent of blood flow rate and dialyser type and was confirmed by regression analysis.


2021 ◽  
Vol 12 ◽  
Author(s):  
M G Vossen ◽  
S Pferschy ◽  
C Milacek ◽  
M Haidinger ◽  
Mario Karolyi ◽  
...  

Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based in vitro pharmacokinetic model for intermittent renal replacement therapy.Methods: Four different drugs were analyzed: gentamicin, doripenem, vancomicin and teicoplanin. The investigated drug was added to a bovine blood reservoir connected to a hemodialysis circuit. In total seven hemofilter models were analyzed using commonly employed flow rates. Pre-filter, post-filter and dialysate samples were drawn, plasmaseparated and analyzed using turbidimetric assays or HPLC. Protein binding of doripenem and vancomycin was measured in bovine plasma and compared to previously published values for human plasma.Results: Clearance values were heavily impacted by choice of membrane material and surface as well as by dialysis parameters such as blood flow rate. Gentamicin clearance ranged from a minimum of 90.12 ml/min in a Baxter CAHP-170 diacetate hemofilter up to a maximum of 187.90 ml/min in a Fresenius medical company Fx80 polysulfone model (blood flow rate 400 ml/min, dialysate flow rate 800 ml/min). Clearance of Gentamicin vs Vancomicin over the F80s hemofilter model using the same flow rates was 137.62 mL vs 103.25 ml/min. Doripenem clearance with the Fx80 was 141.25 ml/min.Conclusion: Clearance values corresponded very well to previously published data from clinical pharmacokinetic trials. In conjunction with in silico pharmacometric models. This model will allow precise dosing recommendations without the need of large scale clinical trials.


1991 ◽  
Vol 261 (5) ◽  
pp. F779-F786 ◽  
Author(s):  
J. Radermacher ◽  
B. Klanke ◽  
S. Kastner ◽  
G. Haake ◽  
H. J. Schurek ◽  
...  

The effect of L-Arg depletion on glomerular hemodynamics and tubular function of isolated rat kidneys perfused with a medium containing 21 amino acids has been studied. A cyclooxygenase inhibitor was added throughout for blockade of prostaglandin synthesis. Arg depletion caused significant (approximately 30%) reductions in renal perfusion flow rate (PFR, 13.9 +/- 1.2 vs. 19.8 +/- 0.6 ml.min-1.g (kidney wt-1), glomerular filtration rate (GFR, 598 +/- 79 vs. 924 +/- 42 microliters.min-1.g kidney wt-1), and urine flow rate (139 +/- 38 vs. 192 +/- 13 microliters.min-1.g kidney wt-1) compared with control kidneys, which were perfused with a physiological concentration of Arg (200 microM). Filtration fraction (FF) increased with Arg depletion (5.1 +/- 0.4 vs. 4.4 +/- 0.4%). Arg-depleted kidneys had a lower absolute sodium (TNa, 75.7 +/- 8.8 vs. 107.9 +/- 6.0 mumol.min-1.g kidney wt-1) and glucose reabsorption (T glucose, 3.7 +/- 0.6 vs. 5.6 +/- 0.5 mumol.min-1.g kidney wt-1), corresponding to a lower sodium and glucose filtration. Potassium handling and reabsorption of free water were not changed. Oxygen consumption (QO2) was lower in Arg-depleted kidneys (4.6 +/- 0.3 vs. 5.5 +/- 0.5 mumol.min-1.g kidney wt-1). The effects of Arg depletion were completely reversed by the addition of Arg (1 mM) at 120 min and partly reversed by the addition of citrulline (1 mM). Ornithine depletion or addition had no effect on PFR, GFR, FF, TNa, T glucose, and QO2. N omega-methyl-L-arginine, a specific inhibitor of nitric oxide endothelium-derived relaxing factor, produced the same effect as Arg depletion.(ABSTRACT TRUNCATED AT 250 WORDS)


2009 ◽  
Vol 17 (2) ◽  
pp. 180-185 ◽  
Author(s):  
Martin W. W. Janssen ◽  
Karl T. Druckrey-Fiskaaen ◽  
Leyla Omidi ◽  
Grzegorz Sliwinski ◽  
Christine Thiele ◽  
...  

1964 ◽  
Vol 207 (3) ◽  
pp. 647-649 ◽  
Author(s):  
Elvin E. Smith ◽  
Jack W. Crowell

The effects of hematocrit, Dibenzyline, and epinephrine on oxygen consumption were studied in 220 dogs whose arterial pressure was lowered to and maintained at 30 mm Hg. Oxygen consumption was recorded previous to and during the period of hypotension. The average oxygen consumption was 7.20 ml/kg min prior to hemorrhage. Ten minutes after hemorrhage the oxygen consumption was 3.58 ml/kg min (50% of control). After 30 min of hypotension the oxygen consumption was 4.70 ml/kg min (65% of control), and the oxygen consumption increased to 5.33 ml/kg min (74% of control) after 1 hr. Pretreatment with Dibenzyline increased the oxygen consumption during the early stages of hypotension but had little effect in the latter stages. Epinephrine administration decreased the oxygen consumption during the entire hypotensive period. Previous studies have shown that the oxygen utilization coefficient approaches its maximal value during the hypotensive period; therefore, oxygen uptake becomes limited by the blood flow and the changes in oxygen consumption indicate changes in flow rate to active tissue. Simultaneous studies showed that the hematocrit influenced oxygen transport by effects on both the blood oxygen content and the blood flow. The results illustrate that animals with hematocrits of 35–39 are able to transport more oxygen than animals with other hematocrits. Evidence is presented to show that the initial fall and the subsequent rise in oxygen consumption during hypotension may be a local autoregulation of blood flow.


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