Total Splanchnic Blood Flow Research Articles

Chronic intestinal ischemia and splanchnic blood-flow: Reference values and correlation with body-composition

To determine the splanchnic blood flow and oxygen uptake in healthy-subjects and patients and to relate the findings to body-composition. The total splanchnic blood flow (SBF) and oxygen uptake (SO₂U) were measured in 20 healthy volunteers (10 women) and 29 patients with suspected chronic intestinal ischemia (15 women), age 40-85 years, prior to and after a standard meal. The method is based on the Fick principle using the continuous infusion of an indicator (99mTechnetium-labelled mebrofenin) and catheterization of an artery and the hepatic vein. An angiography of the intestinal arteries was performed during the same investigation. A whole-body dual-energy x-ray absorptiometry scan was performed in healthy volunteers to determine body composition. Angiography revealed no atherosclerotic lesions in the intestinal arteries. The mean baseline SBF was 1087 mL/min (731-1390), and this value increased significantly to 1787 mL/min after the meal in healthy volunteers (P < 0.001). The baseline SBF in patients was 1080 mL/min, which increased to 1718 mL/min postprandially (P < 0.001). The baseline SBF was independent of age, sex, lean body mass and percentage of body fat. The mean meal-induced increase in SBF was equal to 282 mL/min + 5.4 mL/min × bodyweight, (P = 0.025). The SO₂U in healthy volunteers and patients was 50.7 mL/min and 48.0 mL/min, respectively, and these values increased to 77.5 mL/min and 75 mL/min postprandially, respectively. Both baseline and postprandial SO₂U were directly related to lean body mass. Age and sex exerted no impact on SO₂U. A direct correlation between body weight and the postprandial increase in SBF was observed. The effect of body weight should be considered in the diagnosis of chronic intestinal ischemia.

Validation of 99mTechnetium-labeled mebrofenin hepatic extraction method to quantify meal-induced splanchnic blood flow responses using a porcine model

The aim of this study was to evaluate the measurement of the total splanchnic blood flow (SBF) using a clinical diagnostic method based on Fick's principle and hepatic extraction of 99mTc-mebrofenin (99mTc-MBF) compared with a paraaminohippuric acid (pAH) dilution method in a porcine model. Another aim was to investigate whether enterohepatic cycling of 99mTc-MBF affected the SBF measurement. Five indwelling catheters were placed in each pig (n = 15) in the portal, mesenteric, and hepatic veins, as well as in the aorta and the vena cava. The SBF was measured using both methods. The portal blood flow; the intestinal and hepatic oxygen uptake; the net fluxes of oxygen, lactate, and glucose; and the extraction fraction (EF) of 99mTc-MBF were measured before and for 70 min after feeding. The mean baseline SBF was 2,961 ml/min vs. 2,762 ml/min measured by pAH and 99mTc-MBF, respectively, and increased significantly to 3,977 ml/min and 3,981 ml/min postprandially. The hepatic EF of 99mTc-MBF decreased from 40% at the start of the investigation to 16% 70 min after feeding. The arterial-portal difference in 99mTc-MBF concentration was 0.21% (P = 0.48), indicating no intestinal extraction or metabolism. The clinical method for measuring the SBF based on hepatic 99mTc-MBF extraction is robust compared with the indicator dilution method, despite the decrease seen in hepatic extraction of 99mTc-MBF. Because there was no difference in the content of 99mTc-MBF between the arterial and portal vein plasma, the SBF can be calculated from an arterial and a hepatic vein sample.

Validation of 99m-Technetium Labelled Mebrofenin Hepatic Extraction Method to Quantify Meal Induced Splanchnic Blood Flow Responses Using a Porcine Model

Purpose: The objective of this study was to evaluate a clinical diagnostic method to measure the total splanchnic blood flow (SBF) using the Fick principle and a tracer (99m-Technetium labelled mebrofenin) (Tc99-M) extracted by the liver(1; 2). The method was tested against an indicator dilution method independent of liver extraction using paraaminohippuric acid (PAH) as the indicator in a multi-catheterized porcine model. We also wanted to investigate whether Tc99-M was metabolized in any way in the intestines. Methods: Five permanent indwelling catheters were placed in the abdominal aorta, the inferior vena cava, the portal vein, the hepatic vein, and the superior mesenteric vein in 15 pigs (average weight 60 kg). Two weeks after surgery the SBF was measured by both methods and the portal blood flow, intestinal, and hepatic oxygen uptake, and net intestinal and hepatic fluxes of lactate, and glucose, were measured before and for 70 minutes after ingestion of a standard meal. The concentration of Tc99-M was measured in plasma from the hepatic vein, the portal vein, and the abdominal aorta for each sampling time. The placement of catheters was confirmed at autopsy. Results: The mean baseline SBF was 2961 and 2762 mL/min measured by PAH and Tc99-M, respectively, with a non-significant difference (p = 0.12) between the two methods. The SBF increased significantly after the meal to 3977 measured by Tc99-M and 3981 mL/min measured by PAH, respectively, with no significant difference (p = 0.98) between the two methods. Total splanchnic O2-flux was at baseline 7.19 ± 0.20 mmol/min and 9.81 ± 0.30 after feeding (p < 0.001), the intestinal O2-flux 3.75 ± 0.16mmol/min vs. 4.92 ± 0.13 mmol/min postprandial (p < 0.001). The arterial-portal difference in Tc99-M concentration was 0.21% of the arterial concentration (p = 0.48), indicating no net intestinal extraction or metabolism. Conclusion: The Fick principle is a robust technique for measuring the total SBF when compared to the indicator dilution method. Because there was no difference in the content of Tc99-M between the arterial and portal vein plasma, the SBF can be determined from an arterial and a hepatic vein sample. Tc99-M may potentially detect splanchnic ischemia and other perfusion disturbances in man.

Functional versus radiological assessment of chronic intestinal ischaemia

The diagnosis chronic intestinal ischaemia (CII) is based on the clinical symptoms postprandial pain and weight loss combined with abnormal findings during angiography. Despite the well-known poor correlation between symptoms and morphology, physiological tests are rarely performed. It is possible to measure the total splanchnic blood flow (SBF) before and after a test meal, and the results supply additional information to the morphologic investigations. To date, no papers have addressed the impact of morphologic changes of the mesenteric arteries on the SBF. Forty-six consecutive patients suspected of CII were investigated. The routine investigation included angiography and measurements of the SBF before and after a test meal. Measurements of the total SBF were performed using the 'Fick principle'. (99m)Technetium-labelled Mebrofenin was used as a tracer. Digital subtraction angiography was performed. Agreement between SBF and angiography was found in 44 of 46 patients. Mean baseline SBF for all patients was 985 ml/min, total range (525-1932) and within the reported normal range. The mean postprandial increase in SBF was 480 mL min(-1) (-130 to 1353), thus 36 patients were categorized as normal by both angiography and SBF, eight patients were abnormal by both methods and two patients had abnormal SBF but normal angiography. In this cohort, SBF detects CII with sensitivity of 1.0, and specificity of 0.95. SBF supplies additional information in patients with convincing symptoms and normal angiography. In these patients, the affection of the intestinal arteries may be too distant or too subtle to be visualized on angiography.

Effects of levosimendan on indocyanine green plasma disappearance rate and the gastric mucosal–arterial pCO2 gradient in abdominal aortic aneurysm surgery

Levosimendan has a dual mechanism of action: it improves myocardial contractility and causes vasodilatation without increasing myocardial oxygen demand. In a laboratory setting, it selectively increases gastric mucosal oxygenation in particular and splanchnic perfusion in general. The aim of our study was to describe the effects of levosimendan on systemic and splanchnic circulation during and after abdominal aortic surgery. Twenty abdominal aortic aneurysm surgery patients were randomized to receive either levosimendan (n=10) or placebo (n=10) in a double-blinded manner. Both the mode of anaesthesia and the surgical procedures were performed according to the local guidelines. Automatic gas tonometry was used to measure the gastric mucosal partial pressure of carbon dioxide. Systemic indocyanine green clearance plasma disappearance rate (ICG-PDR) was used to estimate the total splanchnic blood flow. The immediate post-operative recovery was uneventful in the two groups with a comparable, overnight length of stay in the intensive care unit. Cumulative doses of additional vasoactive drugs were comparable between the groups, with a tendency towards a higher cumulative dose of noradrenaline in the levosimendan group. After aortic clamping, the cardiac index was higher [4(3.8-4.7) l/min/m(2) vs. 2.6(2.3-3.6) l/min/m(2); P<0.05] and the gastric mucosal-arterial pCO(2) gradient was lower in levosimendan-treated patients [0.9(0.6-1.2) kPa vs. 1.7(1.2-2.1) kPa; (P<0.05)]. However, the total splanchnic blood flow, estimated by ICG-PDR, was comparable [29(21-29)% vs. 20(19-25)%; NS]. Organ dysfunction scores (sequential organ dysfunction assessment) were similar between the groups on the fifth post-operative day. Levosimendan favours gastric perfusion but appears not to have a major effect on total splanchnic perfusion in patients undergoing an elective aortic aneurysm operation.

Membrane microdialysis: Evaluation of a new method to assess splanchnic tissue metabolism*

Measuring peritoneal lactate concentrations could be useful for detecting splanchnic hypoperfusion. The aims of this study were to evaluate the properties of a new membrane-based microdialyzer in vitro and to assess the ability of the dialyzer to detect a clinically relevant decrease in splanchnic blood flow in vivo. A membrane-based microdialyzer was first validated in vitro. The same device was tested afterward in a randomized, controlled animal experiment. University experimental research laboratory. Twenty-four Landrace pigs of both genders. In vitro: Membrane microdialyzers were kept in warmed sodium lactate baths with lactate concentrations between 2 and 8 mmol/L for 10-120 mins, and microdialysis lactate concentrations were measured repeatedly (210 measurements). In vivo: An extracorporeal shunt with blood reservoir and roller pump was inserted between the proximal and distal abdominal aorta, and a microdialyzer was inserted intraperitoneally. In 12 animals, total splanchnic blood flow (measured by transit time ultrasound) was reduced by a median 43% (range, 13% to 72%) by activating the shunt; 12 animals served as controls. In vitro: The fractional lactate recovery was 0.59 (0.32-0.83) after 60 mins and 0.82 (0.71-0.87) after 90 mins, with no further increase thereafter. At 60 and 90 mins, the fractional recovery was independent of the lactate concentration. In vivo: Abdominal blood flow reduction resulted in an increase in peritoneal microdialysis lactate concentration from 1.7 (0.3-3.8) mmol/L to 2.8 (1.3-6.2) mmol/L (p = .006). At the same time, mesenteric venous-arterial lactate gradient increased from 0.1 (-0.2-0.8) mmol/L to 0.3 (-0.3 -1.8) mmol/L (p = .032), and mesenteric venous-arterial Pco2 gradients increased from 12 (8-19) torr to 21 (11-54) torr (p = .005). Peritoneal membrane microdialysis provides a method for the assessment of splanchnic ischemia, with potential for clinical application.

Epinephrine induces tissue perfusion deficit in porcine endotoxin shock: evaluation by regional CO2 content gradients and lactate-to-pyruvate ratios

Epinephrine is widely used as a vasoconstrictor or inotrope in shock, although it may typically induce or augment lactic acidosis. Ongoing debate addresses the question of whether hyperlactatemia per se is a sign of tissue perfusion deficit or aerobic glycolysis. We wanted to test the hypothesis that epinephrine has selective detrimental effects on visceral perfusion and metabolism. We performed rigorous regional venous blood gas analyses as well as intraperitoneal microdialysis. We used a mathematical model to calculate regional arteriovenous CO(2) content gradients and estimated the magnitude of the Haldane effect in a porcine model of prolonged hypotensive shock induced by endotoxin infusion (mean arterial blood pressure < 60 mmHg). Subsequently, vasopressors (epinephrine or norepinephrine) were administered and adjusted to maintain systemic mean arterial pressure > 70 mmHg for 4 h. Epinephrine caused systemic hyperlactatemia and acidosis. Importantly, both systemic and regional venous lactate-to-pyruvate ratios increased. Epinephrine was associated with decreasing portal blood flow despite apparently maintained total splanchnic blood flow. Epinephrine increased gastric venous-to-arterial Pco(2) gradients and CO(2) content gradients with decreasing magnitude of the Haldane effect, and the regional gastric respiratory quotient remained higher after epinephrine as opposed to norepinephrine infusion. In addition, epinephrine induced intraperitoneal lactate and glycerol release. We did not observe these adverse hemodynamic or metabolic changes related to norepinephrine with the same arterial pressure goal. We conclude that high CO(2) content gradients with decreasing magnitude of the Haldane effect pinpoint the most pronounced perfusion deficiency to the gastric wall when epinephrine, as opposed to norepinephrine, is used in experimental endotoxin shock.

Jejunal and gastric mucosal perfusion versus splanchnic blood flow and metabolism: an observational study on postcardiac surgical patients.

To evaluate the association between changes in total splanchnic and mucosal perfusion, assessed either by gastric tonometry or jejunal laser Doppler flowmetry in postcardiac surgical patients. A prospective, observational study. A general intensive care unit in a tertiary care center. Twelve, postoperative cardiac surgery patients were studied. Patients were treated according to clinical routine. Total splanchnic blood flow (indocyanine green extraction), jejunal mucosal perfusion (laser Doppler flowmetry), gastric mucosal-arterial PCO2 gradients, and splanchnic lactate uptake were studied during four 30-min measurements periods, each separated by a period of 1 hr. There was no consistent association between either total splanchnic and local mucosal perfusion or between gastric and jejunal perfusion as assessed by two different techniques. The PCO2 gradient increased from 0.73+/-0.21 kPa to 1.15+/-0.30 kPa (p < .05), and splanchnic oxygen extraction increased from 40%+/-9% to 49%+/-14% (p < .01). In this observational study on postcardiac surgical patients, local mucosal perfusion did not reflect total splanchnic blood flow and vice versa. Either changes in gastric and jejunal mucosal perfusion were different or increasing tissue metabolism was responsible for the observed lack of association between tonometry, laser Doppler flowmetry, and total splanchnic blood flow. Increasing mucosal arterial PCO2 gradient and splanchnic oxygen extraction may reflect a mismatch between splanchnic perfusion and metabolic demands.

The Haldane effect—an alternative explanation for increasing gastric mucosal PCO2 gradients?

When venous oxygen saturation increases as a result of increased blood flow, changes in venous blood PCO2 and carbon dioxide content may differ because of the Haldane effect. The Haldane effect may also explain increases in gastric mucosal-arterial PCO2 gradient despite major increases in splanchnic blood flow. We re-analysed data from 22 patients after cardiac surgery who were randomized to receive either dobutamine or placebo, and a separate group of patients who received dobutamine for low cardiac output (n = 6). Three different values of gastric mucosal oxygen extraction at baseline were assumed (0.3, 0.5 and 0.7). In nine of 14 patients with both increasing splanchnic blood flow and mucosal-arterial PCO2 gradient, an equal increase in mucosal and total splanchnic blood flow, oxygen consumption and carbon dioxide production together with the Haldane effect would have caused an increase in mucosal-arterial PCO2 gradients from a mean value of 0.53 (SD 0.88) kPa at baseline to 0.68-0.82 (0.89-0.90) kPa (P < 0.01). In the remaining patients, disproportionate changes in flow and metabolism must have been involved in addition to the Haldane effect. We conclude that whenever major changes in mucosal tissue oxygen extraction are likely to occur, an increase in the mucosal-arterial PCO2 gradient may be explained in part or completely by the Haldane effect, and may therefore not reflect worsening perfusion.

Splanchnic circulatory changes during development of renal hypertension.

Total and regional splanchnic blood flows were measured with radiolabeled microspheres (15 micron) in one-kidney, one-clip renal hypertensive rats at 2, 4, and 6 wk after induction of hypertension. Arterial pressures (mean +/- SE, mmHg) for the normotensive rats (N) and age-matched hypertensive rats (H) were 110 +/- 5 and 114 +/- 6 at 2 wk, 104 +/- 4 and 148 +/- 13 at 4 wk, and 117 +/- 6 and 164 +/- 11 at 6 wk, respectively. Total splanchnic blood flow was increased in H compared with N at 4 wk but not at 2 or 6 wk. The blood flow changes among individual splanchnic organs varied in N and H. For example, at 2 and 4 wk, stomach, small intestine, large intestine, pancreas, hepatic artery, and portal venous blood flows in H were unchanged compared with N. At 6 wk, small intestinal and hepatic arterial blood flows were increased in H compared with N, and pancreatic blood flow was decreased. Vascular resistance was not different for any splanchnic organs between N and H at 2 wk, but it was elevated in H for all organs at 4 and 6 wk except for the hepatic artery. In another group of rats, the renal and superior mesenteric arteries (SMA) were instrumented with ultrasonic Doppler flow probes. Acute one-kidney, one-clip hypertension was produced by removing one kidney and mechanically reducing flow to the remaining kidney with a pneumatic occluder. After 2 h of stenosis, mean arterial pressure and SMA flow velocity was decreased by 6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes of regional blood flow induced by atrial natriuretic factor (ANF) in conscious rats

The effect of synthetic atrial natriuretic factor (ANF 101-126) has been studied on regional blood flow distribution. Microspheres (15 ± 3 μm), labelled with either 113Sn or 57Co, were injected through an intraventicular cannula into conscious rats while a reference blood sample was withdrawn. Two minutes after the first microspheres injection either ANF or NaCl were injected. Five minutes later, the second microspheres injection was administered, and after two minutes the animals were sacrificed, and several tissues removed and counted. Percent of flow distribution, cardiac output and tissue blood flow were calculated by standard formulas. ANF produced a significant increase in absolute blood flow in lungs, heart, spleen, kidneys and testes. Total renal blood flow and total splanchnic blood flow were also increased in ANF-injected animals. No significant changes were observed in cardiac output. It is suggested that the natriuretic and hypotensive responses to ANF in vivo may be, at least partially, explained by its hemodynamic effects.

Regional distribution of blood flow during mild dynamic leg exercise in the baboon.

Five chair-restrained baboons were trained with operant techniques and a food reward to perform dynamic leg exercise. Cardiac output and blood flows to most tissues were determined by radioactive microsphere distribution. After 2 min of exercise mean arterial blood pressure had increased by 11 +/- 3% (SE), heart rate by 34 +/- 7%, cardiac output by 50 +/- 12%, and O2 consumption by 157 +/- 17%. The blood flow to exercising leg muscle increased by 585 +/- 338% and to the myocardium by 35 +/- 19%. Blood flow to torso and limb skin fell by 38 +/- 4 and 38 +/- 6%, respectively, and similar reductions occurred in adipose tissue blood flow. Nonworking skeletal muscle blood flow decreased by 30 +/- 10%. Renal blood flow was lowered by 16 +/-2%. The lower visceral organs had more variable responses, but when grouped together total splanchnic blood flow fell by 21 +/- 9%. Blood flow to the brain was unchanged with exercise, whereas spinal cord perfusion increased 23 +/- 3%. Thus during short dynamic exercise baboons redistributed blood flow away from skin, fat, nonworking muscles, and visceral organs to supply the needs of exercising muscles. Our data suggest the baboon is a useful animal model for investigating vascular responses of tissues, such as torso skin, adipose, individual visceral organs, and the spinal cord, that cannot be examined in humans.

Effects of acute, passive hepatic congestion on blood flow and oxygen uptake in the intact liver of the cat.

Raising the hepatic venous pressure experimentally duplicates the type of hepatic congestion seen in many clinical situations including congestive heart failure. Venous pressure was controlled using a hepatic venous long circuit preparation and was raised by 6 cm blood (4.7 mm Hg) or 10 cm (7.8 mm Hg). Total splanchnic blood flow and oxygen uptake were reduced by these maneuvers but hepatic arterial flow was not altered nor was hepatic oxygen uptake. Blood flow in the portal vein decreased to 65 +/- 12% of control and gut oxygen uptake decreased to 60 +/- 14% of control. The data confirm that raised hepatic venous pressure does not produce hepatic edema in spite of massive prolonged fluid filtration across the liver into the peritoneum. In spite of a reduced (to 84 +/- 3% of control) hepatic oxygen delivery, the liver can maintain oxygen uptake (99 +/- 7% of control) by increasing oxygen extraction to appropriate levels. The hepatic artery in these cats were capable of myogenic vasoconstriction in response to altered arterial pressure, but in response to raised venous pressure no tendency for constriction was seen. This is in marked contrast to the vasoconstriction seen in isolated perfused livers where portal blood flow is held constant during the raised venous pressure.

Gastric secretory and splanchnic blood flow studies in man after severe trauma and hemorrhagic shock

A group of thirty-three patients with severe multiple trauma and hemorrhagic shock and a group of nineteen normal control subjects were studied in a special trauma research unit to determine the effect of severe acute stress on multiple aspects of human gastric secretion and splanchnic blood flow in relation to stress ulceration. Simultaneous studies of gastric acid, pepsin, nondialyzable solids, fucose, sialic acid, and total splanchnic blood flow were carried out on both patients and control subjects. These studies were performed during basal conditions over a period of two hours and also for two hours after subcutaneous injection of Histalog. On the basis of these studies, it was concluded that excessive acid or pepsin secretion or deficient quantitative or qualitative gastric mucus production was probably not a significant etiologic factor in the production of gastroduodenal stress ulceration. The splanchnic blood flow studies and the presence of blood in gastric juice samples after Histalog injection in approximately 35 per cent of the severely injured patients supported previous opinions that ischemic damage to the superficial gastric mucosa may induce stress ulceration.