Noninvasive functional liver blood flow measurement: comparison between bolus dose and steady-state clearance of sorbitol in a small-rodent model

2010 ◽  
Vol 298 (2) ◽  
pp. G177-G181 ◽  
Author(s):  
Ben van der Hoven ◽  
Hans van Pelt ◽  
Eleonore L. Swart ◽  
Fred Bonthuis ◽  
Huug W. Tilanus ◽  
...  

Plasma clearance of d-sorbitol, a nontoxic polyol, occurs predominantly in the liver and has been used to measure functional liver blood flow after bolus and steady- state intravenous administration. However, it is not known which of these two administration methods is superior. Therefore, plasma d-sorbitol clearance was studied in an animal model both after a bolus dose and under steady-state (SS) conditions and compared directly with liver blood flow, under normal conditions, and after the induction of endotoxin (LPS) sepsis. Adult male Wistar rats (526 ± 38 g body wt; n = 27) were anesthetized and mechanically ventilated. Hemodynamics, hepatic arterial flow, and portal venous flow were measured. Two groups were studied, namely healthy animals that served as controls and a sepsis group that received 5 mg/kg LPS intravenously ( Escherichia coli O127:B8). Each animal received either a SS infusion (0.1 mg/100 g body wt per min) or a bolus (3 mg/100 g body wt) of a 5% d-sorbitol solution intravenously in a randomized order. After the initial measurements and a 60-min pause time in between ( T1/2,sorbitol = 9 min), a crossover was done. The hepatic clearance of d-sorbitol in the control group showed a good correlation between bolus and SS (Spearman's r = 0.7681, P = 0.0004), and both techniques correlated well with total liver blood flow (TLBF) ( r = 0.7239, P = 0.0023 and r = 0.7226, P = 0.0023, respectively). Also in the sepsis group there was a good correlation between bolus and SS sorbitol clearance ( r = 0.6655, P = 0.0182). In the sepsis group, only the SS clearance correlated with TLBF ( r = 0.6434, P = 0.024). In conclusion, in normal and under septic conditions, hepatic clearance of d-sorbitol either by bolus or a SS infusion is comparable. In healthy animals, this also correlated well with TLBF but not in septic conditions. However, this is expected because of the changes in the liver microcirculation, shunting, and decreased hepatocyte function in sepsis.

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 597-602 ◽  
Author(s):  
GP Rodgers ◽  
MS Roy ◽  
CT Noguchi ◽  
AN Schechter

Abstract To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.


1994 ◽  
Vol 266 (2) ◽  
pp. H503-H510
Author(s):  
K. Kroll ◽  
G. V. Martin

Myocardial adenosine production increases transiently during the onset of catecholamine stimulation; however, there is conflicting evidence regarding whether cytosolic adenosine concentrations are increased during sustained steady-state stimulation. If cytosolic adenosine is not elevated during steady-state stimulation, then adenosine produced in the cytosol does not play a role in mediating the sustained increase in myocardial blood flow. The purpose of the present study was to determine whether cytosolic adenosine concentrations in the anesthetized dog heart are increased during steady-state stimulation with norepinephrine, epinephrine, and atrial pacing. Regional cytosolic adenosine concentrations were assessed by measuring myocardial content of S-adenosyl-L-homocysteine (SAH) after 20 min of intravenous administration of L-homocysteine thiolactone. Excess homocysteine causes myocardial accumulation of SAH at a rate dependent on the cytosolic concentration of adenosine. Steady-state metabolic stimulation caused more than twofold increases in myocardial blood flow and oxygen consumption, but there was no increase in left ventricular content of SAH in the stimulation group [6.3 +/- 0.9 nmol/g (SE); n = 6] relative to a parallel unstimulated control group (6.4 +/- 0.9 nmol/g; n = 6). The transmural distribution of SAH was nearly uniform, and there was no correlation between regional measurements of blood flow and myocardial content of SAH or ATP either during metabolic stimulation or under control conditions. In separate experiments, myocardial ischemia caused fivefold increases in SAH content, confirming the sensitivity of the SAH method for increased cytosolic adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)


2014 ◽  
Vol 42 (05) ◽  
pp. 1215-1227 ◽  
Author(s):  
Yun-Liang Cui ◽  
Lv Wang ◽  
Zhao-Tao Tian ◽  
Zhao-Fen Lin ◽  
De-Chang Chen

The intestine plays a vital role in the pathophysiology of sepsis development. The objective of the present study was to explore the effects of rhubarb on intestinal microcirculation in septic rats. We used moorFLPI laser speckle imaging to detect the blood flow of the intestinal mucosa and wall. Using an ELISA, we assayed the concentration of lactate (L) and pyruvic acid (P) in the intestinal tissue to calculate the ratio of lactate to pyruvic acid (L/P ratio). To observe the intestinal mucosal capillaries, gelatin and ink were perfused into the intestine and subsequently stained with hematoxylin and eosin (HE) to measure the ratio of the vessel area. We then used immunohistochemistry to measure CD31 expression. Using an MTT assay, the effect of the rhubarb extract on the proliferation of human umbilical vein endothelial cells (HUVECs) was analyzed. The blood flow in the intestinal wall and mucosa of the control, sham and rhubarb-treated groups was significantly higher, while the sepsis group had relatively low blood flow. The L/P ratio in the intestinal tissue was larger in the sepsis group than in the other three groups. The microvascular area (MVA) in the sepsis group was smaller than in the control group, sham group or rhubarb group. Positive expression for CD31 was observed in the cytoplasm of vascular endothelial cells. The intestinal mucosal capillaries were reduced in septic rats as compared to the other three groups. HUVEC proliferation was enhanced by the rhubarb extract monomers at 1 μmol/L, but suppressed at higher concentrations of 10 to 100 μmol/L. These results suggest that pre-treatment with rhubarb prior to sepsis induction promotes the expansion of the intestinal mucosal capillaries, protects intestinal mucosal capillary endothelial cells and increases the number of functional intestinal capillaries.


Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 597-602
Author(s):  
GP Rodgers ◽  
MS Roy ◽  
CT Noguchi ◽  
AN Schechter

To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.


1987 ◽  
Vol 65 (6) ◽  
pp. 1193-1199 ◽  
Author(s):  
C. V. Greenway ◽  
F. J. Burczynski

Hepatic galactose uptake in cats anesthetized with pentobarbital was determined during (i) steady-state infusions at several doses, (ii) rapidly increasing infusion rates at different blood flows, and (iii) prolonged infusion of a single dose at different blood flows. The hepatic venous long-circuit technique was used to allow frequent sampling of arterial, portal, and hepatic venous blood without depletion of the animal's blood volume and to allow measurement and alteration of total hepatic blood flow. Uptake was shown to follow Michaelis–Menten kinetics and was consistent with the "parallel tube model." The kinetic parameters Vmax and Kmax could be determined under steady-state and nonsteady-state conditions and were independent of hepatic blood flow over the range 60–150% of control flow. Mean Vmax was 80 μmol/(min∙100 g liver) and mean Km was 215 μM. Vmax declined by 50% when flow was reduced to half normal. It is concluded that the parallel tube model can be used to describe and predict hepatic galactose kinetics in anesthetized cats, although other models may fit the data equally well.


1987 ◽  
Vol 4 (3) ◽  
pp. 393-398 ◽  
Author(s):  
Susanne Keiding

1992 ◽  
Vol 67 (01) ◽  
pp. 083-087 ◽  
Author(s):  
A de Boer ◽  
C Kluft ◽  
J M Kroon ◽  
F J Kasper ◽  
H C Schoemaker ◽  
...  

SummaryThe influence of changes in liver blood flow on the clearance of rt-PA was studied both in healthy subjects and in a perfused rat liver model. Liver blood flow in healthy subjects was documented indirectly by the clearance of indocyanine green (ICG). Exercise reduced liver blood flow on average by 57% with a 95% confidence interval (95% Cl) ranging from 51% to 62% (n = 5) and increased plasma levels of rt-PA activity (after an i. v. infusion of 18 mg of rt-PA over 120 min) by 119% (95% Cl, 58% - 203%) and rt-PA antigen by 91% (95% Cl, 30% - 140%). In the perfused rat liver model it was shown that halving or doubling of the physiological flow rate of a perfusate, containing rt-PA caused a proportional change in the clearance of rt-PA, while the extraction of rt-PA by the liver remained similar. In conclusion, liver blood flow is a major determinant of the clearance of rt-PA. This may have important implications for dosage of rt-PA in patients with myocardial infarction.


2014 ◽  
Vol 17 (3) ◽  
pp. 154 ◽  
Author(s):  
Arıtürk Cem ◽  
Ustalar Serpil ◽  
Toraman Fevzi ◽  
Ökten Murat ◽  
Güllü Ümit ◽  
...  

<p><strong>Introduction:</strong> Clear guidelines for red cell transfusion during cardiac surgery have not yet been established. The current focus on blood conservation during cardiac surgery has increased the urgency to determine the minimum safe hematocrit for these patients. The aim of this study was to determine whether monitoring of cerebral regional oxygen saturation (rSO<sub>2</sub>) via near-infrared spectrometry (NIRS) is effective for assessing the cerebral effects of severe dilutional anemia during elective coronary arterial bypass graft surgery (CABG).</p><p><strong>Methods:</strong> The prospective observational study involved patients who underwent cerebral rSO<sub>2</sub> monitoring by NIRS during elective isolated first-time CABG: an anemic group (<em>N</em>=15) (minimum Hemoglobin (Hb) N=15) (Hb &gt;8 g/dL during CPB). Mean arterial pressure (MAP), pump blood flow, blood lactate level, pCO<sub>2</sub>, pO<sub>2</sub> at five time points and cross-clamp time, extracorporeal circulation time were recorded for each patient. Group results statistically were compared.</p><p><strong>Results:</strong> The anemic group had significantly lower mean preoperative Hb than the control group (10.3 mg/dL versus 14.2 mg/dL; <em>P</em> = .001). The lowest Hb levels were observed in the hypothermic period of CPB in the anemic group. None of the controls exhibited a &gt;20% decrease in cerebral rSO<sub>2</sub>. Eleven (73.3%) of the anemic patients required an increase in pump blood flow to raise their cerebral rSO<sub>2</sub>.</p><p><strong>Conclusions:</strong> In this study, the changes in cerebral rSO<sub>2</sub> in the patients with low Hb were within acceptable limits, and this was in concordance with the blood lactate levels and blood-gas analysis. It can be suggested that NIRS monitoring of cerebral rSO<sub>2</sub> can assist in decision making related to blood transfusion and dilutional anemia during CPB.</p>


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