Interaction between areas of the central nervous system in the control of water intake and arterial pressure in rats

1. Water intake induced by injection of 0.2 M-NaCl into the lateral preoptic area was increased by the injection of angiotensin II into the subfornical organ of rats. The injection of hypertonic saline solution into the subfornical organ increased water intake. However, the increase was lower than when the solution was injected into the lateral preoptic area. The injection of 4 μg angiotensin II into the lateral preoptic area further augmented this effect. 2. Injection of angiotensin II into the subfornical organ caused a rise in blood pressure which preceded the thirst-inducing effect. The injection of 0.2 M NaCl into the subfornical organ caused no changes in blood pressure, whereas the injection of angiotensin II into the lateral preoptic area caused some increase. 3. Dehydration of the lateral preoptic area by means of 0.2 M NaCl in combination with intravenous infusion of angiotensin II caused a summation of effects in terms of the water intake, without changing cardiovascular alterations induced by the infusion of angiotensin II. A summation of effects in the water intake, but not in blood pressure, was also observed when 0.5 M NaCl was infused intravenously in combination with the injection of angiotensin II into the subfornical organ and into the lateral preoptic area. 4. The results indicate that there are interactions between the subfornical organ and lateral preoptic area in the regulation of cardiovascular and thirst mechanisms.

Different effects on rat arterial pressure and heart rate when losartan is injected into the third or fourth ventricle

Cardiovascular responses to central losartan (LOS), a non-peptide angiotensin II (ANG II) receptor antagonist, were investigated by comparing the effects of LOS injection into the 3rd and 4th cerebral ventricles (3rdV, 4thV) on mean arterial pressure (MAP) and heart rate (HR). Adult male Holtzman rats were used (N=6 animals per group). Average basal MAP and HR were 114±3 mmHg and 343±9 bpm (N=23), respectively. LOS (50, 100 or 200 nmol/2 μl) injected into the 3rdV induced pressor (peak of 25±3 mmHg) and tachycardic (peak of 60±25 bpm) responses. LOS injected into the 4thV had no effect on MAP, but it induced bradycardia (peak of -35±15 bpm). KCl (200 nmol/2 μl) injected into the 3rdV or into the 4thV had no effect on either MAP or HR compared to 0.9% saline injection. The results indicate that LOS injected into the third ventricle acts on forebrain structures to induce its pressor and tachycardic effects and that bradycardia, likely dependent on hindbrain structures, is obtained when LOS is injected into the fourth ventricle.

Effects of intracerebroventricular injections of losartan or PD123319 on arterial pressure and heart rate of sodium replete and sodium deplete rats

Angiotensin II (Ang II) non-peptide antagonists were injected i.c.v. (6.25-200 nmol, n = 5-8 rats/group): In sodium replete rats, losartan (AT1 receptor antagonist) induced an increase in mean arterial pressure (MAP) and in heart rate (HR) by 3rd ventricular (3rdV) injection, and a weaker pressor response and bradycardia by 4th ventricular (4thV) injection. PD123319 (AT2 receptor antagonist) induced an increase in MAP and in HR by 3rdV injection, and an increase in MAP and no alteration in HR by 4thV injection. In sodium deplete (furosemide plus removal of ambient sodium for 24 h) rats, losartan induced an increase in MAP and no alteration in HR by 3rdV injection, and no alteration in MAP and bradycardia by 4thV injection. PD123319 induced an increase in MAP and in HR by 3rdV injection, and an increase in MAP and bradycardia by 4thV injection. Thus, there was no fall in MAP by central injections of Ang II antagonists. Intravenous injection of losartan, but not of PD123319, induced a fall in MAP in both sodium replete and sodium deplete animals. Therefore, losartan and PD123319 can have similar effects on MAP and HR when injected intracerebroventricularly, although some differences are also present. The bradycardia is consistent with an withdrawal of Ang II inhibitory action on baroreflex.

Echocardiographic Doppler estimation of pulmonary artery pressure in critically ill patients with severe hypoxemia

BACKGROUND: In spontaneously breathing cardiac patients, pulmonary artery pressure (PAP) can be accurately estimated from the transthoracic Doppler study of pulmonary artery and tricuspid regurgitation blood flows. In critically ill patients on mechanical ventilation for acute lung injury, the interposition of gas between the probe and the heart renders the transthoracic approach problematic. This study was aimed at determining whether the transesophageal approach could offer an alternative. METHODS: Fifty-one consecutive sedated and ventilated patients with severe hypoxemia (arterial oxygen tension/fraction of inspired oxygen < 300) were prospectively studied. Mean PAP measured from the pulmonary artery catheter was compared with several indices characterizing pulmonary artery blood flow assessed using transesophageal echocardiography: preejection time, acceleration time, ejection duration, preejection time on ejection duration ratio, and acceleration time on ejection duration ratio. In a subgroup of 20 patients, systolic PAP measured from the pulmonary artery catheter immediately before withdrawal was compared with Doppler study of regurgitation tricuspid flow performed immediately after pulmonary artery catheter withdrawal using either the transthoracic or the transesophageal approach. RESULTS: Weak and clinically irrelevant correlations were found between mean PAP and indices of pulmonary artery flow. A statistically significant and clinically relevant correlation was found between systolic PAP and regurgitation tricuspid flow. In 3 patients (14%), pulmonary artery pressure could not be assessed echocardiographically. CONCLUSIONS: In hypoxemic patients on mechanical ventilation, mean PAP cannot be reliably estimated from indices characterizing pulmonary artery blood flow. Systolic PAP can be estimated from regurgitation tricuspid flow using either transthoracic or transesophageal approach. © 2008 American Society of Anesthesiologists, Inc.

Comparison of epinephrine and felypressin pressure effects in 1K1C hypertensive rats treated or not with atenolol

Epinephrine is considered the gold standard vasoconstrictor for hypertensive patients, but few studies report felypressin’s effects. The present study aimed to analyze and compare the effects of these two vasoconstrictors, injected by the intravenous route, on the arterial pressure of normotensive, hypertensive and atenolol-treated hypertensive rats. Method The hypertension model was one-kidney-one-clip (1K1C): the main left renal artery was partially constricted and the right kidney was surgically removed in 45-day-old male Wistar rats. 1K1C hypertensive rats received atenolol (90 mg/kg/day) by gavage for 2 weeks. 28–35 days after hypertension induction, a catheter was inserted into the left carotid artery to record direct blood pressure values. The following parameters were recorded: minimal hypotensive response, maximal hypertensive response, response duration and heart rate. Results Epinephrine, but not felypressin, exerted an important hypotensive action; non-treated hypertensive rats showed more pronounced vasodilation. Treated and non-treated rats showed hypertensive responses of the same magnitudes in all groups; 1K1C atenolol rats showed reduced hypertensive responses to both vasoconstrictors. Felypressin’s response duration was longer than that of epinephrine in all groups. Epinephrine increased heart rate while felypressin reduced this parameter only in the normotensive group. Conclusions Our results suggest that felypressin has equipotent pressure responses when compared with epinephrine, showing a greater extent of action. Atenolol’s reduction of hypertensive effects surprisingly suggests that atenolol β-blockade may also be important for felypressin’s cardiovascular effect, as is widely known for epinephrine. Our data suggest that felypressin is safe for hypertensive subjects, in particular those receiving atenolol.

Decompressive craniectomy and cerebral blood flow regulation in head injured patients: A case studied by perfusion CT

Previous studies have reported increased cerebral blood flow (CBF) velocity after decompressive craniectomy in traumatic brain injury (TBI) patients. A 27-year-old man presented with clinical and tomographic signs of cerebral herniation secondary to TBI. Prior to decompressive craniectomy, hemodynamic study by perfusion computed tomography (CT) indicated diffuse cerebral hyperperfusion. Following surgical decompression, the patient recovered neurologically and perfusion CT disclosed a decrease in the intensity of cerebral perfusion. The patient's blood pressure levels were similar at both pre- and postoperative perfusion CT examinations. This finding provides indirect evidence that decompressive craniectomy may improve mechanisms of CBF regulation in TBI, providing pathophysiological insights in the cerebral hemodynamics of TBI patients. This is the first report analyzing the hemodynamic changes through perfusion CT (PCT) in a patient with decompressive craniotomy due to TBI. (C) 2012 Elsevier Masson SAS. All rights reserved.

Effect of a single session of aerobic walking exercise on arterial pressure in community-living elderly individuals

Several studies have demonstrated that one exercise session (ES) on a cycloergometer or ergometric treadmill causes a reduction in blood pressure (BP). However, there are few similar studies on walking, which is the exercise modality most available to the elderly. We investigated the immediate and 24-h effects of walking on BP in independent, community-living elderly individuals. Volunteers participated in a single ES and resting control session (CS). Before and after each session, BP was measured by auscultatory and oscillometric methods. After each session, 24-h ambulatory blood pressure monitoring was conducted. An accelerometer was installed 48 h before the sessions and left in place for 5 days. The mean volunteer age was 67.7 +/- 3.5 years; 11 were hypertensive patients under treatment, and 12 were normotensive. In the total sample, there were immediate 14mm Hg and 12 mm Hg reductions in systolic BP (SBP) after the ES according to the auscultatory and oscillometric methods, respectively. Diastolic BP (DBP) was reduced by 4 mm Hg after the ES according to both methods. SBP during wakefulness and sleep and DBP during wakefulness were lower after the ES than after the CS (P<0.01), when wakefulness and sleep were determined individually (variable-time pattern) using data from the activity monitors and provided by the volunteers. The variable-time pattern was more effective in detecting reductions in BP than the fixed-time pattern. Hypertension Research (2012) 35, 457-462; doi: 10.1038/hr.2011.227; published online 9 February 2012

Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload

Objectives: Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. Methods: Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB+AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. Results: Contractile performance was significantly improved in the PAB+AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB+AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor beta genes. Conclusions: Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV. (J Thorac Cardiovasc Surg 2012;144:1494-501)

Observational study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers - protocol study

Abstract Background Obstructive sleep apnea (OSA) is a respiratory disease characterized by the collapse of the extrathoracic airway and has important social implications related to accidents and cardiovascular risk. The main objective of the present study was to investigate whether the drop in expiratory flow and the volume expired in 0.2 s during the application of negative expiratory pressure (NEP) are associated with the presence and severity of OSA in a population of professional interstate bus drivers who travel medium and long distances. Methods/Design An observational, analytic study will be carried out involving adult male subjects of an interstate bus company. Those who agree to participate will undergo a detailed patient history, physical examination involving determination of blood pressure, anthropometric data, circumference measurements (hips, waist and neck), tonsils and Mallampati index. Moreover, specific questionnaires addressing sleep apnea and excessive daytime sleepiness will be administered. Data acquisition will be completely anonymous. Following the medical examination, the participants will perform a spirometry, NEP test and standard overnight polysomnography. The NEP test is performed through the administration of negative pressure at the mouth during expiration. This is a practical test performed while awake and requires little cooperation from the subject. In the absence of expiratory flow limitation, the increase in the pressure gradient between the alveoli and open upper airway caused by NEP results in an increase in expiratory flow. Discussion Despite the abundance of scientific evidence, OSA is still underdiagnosed in the general population. In addition, diagnostic procedures are expensive, and predictive criteria are still unsatisfactory. Because increased upper airway collapsibility is one of the main determinants of OSA, the response to the application of NEP could be a predictor of this disorder. With the enrollment of this study protocol, the expectation is to encounter predictive NEP values for different degrees of OSA in order to contribute toward an early diagnosis of this condition and reduce its impact and complications among commercial interstate bus drivers.

Cardiac output and leg and arm blood flow during incremental exercise to exhaustion on the cycle ergometer

[EN] To determine central and peripheral hemodynamic responses to upright leg cycling exercise, nine physically active men underwent measurements of arterial blood pressure and gases, as well as femoral and subclavian vein blood flows and gases during incremental exercise to exhaustion (Wmax). Cardiac output (CO) and leg blood flow (BF) increased in parallel with exercise intensity. In contrast, arm BF remained at 0.8 l/min during submaximal exercise, increasing to 1.2 +/- 0.2 l/min at maximal exercise (P < 0.05) when arm O(2) extraction reached 73 +/- 3%. The leg received a greater percentage of the CO with exercise intensity, reaching a value close to 70% at 64% of Wmax, which was maintained until exhaustion. The percentage of CO perfusing the trunk decreased with exercise intensity to 21% at Wmax, i.e., to approximately 5.5 l/min. For a given local Vo(2), leg vascular conductance (VC) was five- to sixfold higher than arm VC, despite marked hemoglobin deoxygenation in the subclavian vein. At peak exercise, arm VC was not significantly different than at rest. Leg Vo(2) represented approximately 84% of the whole body Vo(2) at intensities ranging from 38 to 100% of Wmax. Arm Vo(2) contributed between 7 and 10% to the whole body Vo(2). From 20 to 100% of Wmax, the trunk Vo(2) (including the gluteus muscles) represented between 14 and 15% of the whole body Vo(2). In summary, vasoconstrictor signals efficiently oppose the vasodilatory metabolites in the arms, suggesting that during whole body exercise in the upright position blood flow is differentially regulated in the upper and lower extremities.

Effect of blood haemoglobin concentration on V(O2,max) and cardiovascular function in lowlanders acclimatised to 5260 m

[EN] The principal aim of this investigation was to determine the influence of blood haemoglobin concentration ([Hb]) on maximal exercise capacity and maximal O(2) consumption (V(O(2),max)) in healthy subjects acclimatised to high altitude. Secondarily, we examined the effects of [Hb] on the regulation of cardiac output (CO), blood pressure and muscular blood flow (LBF) during exercise. Eight Danish lowlanders (three females and five males; 24 +/- 0.6 years, mean +/- S.E.M.) performed submaximal and maximal exercise on a cycle ergometer after 9 weeks at an altitude of 5260 m (Mt Chacaltaya, Bolivia). This was done first with the high [Hb] resulting from acclimatisation and again 2-4 days later, 1 h after isovolaemic haemodilution with Dextran 70 to near sea level [Hb]. After measurements at maximal exercise while breathing air at each [Hb], subjects were switched to hyperoxia (55 % O(2) in N(2)) and the measurements were repeated, increasing the work rate as tolerated. Hyperoxia increased maximal power output and leg V(O(2),max), showing that breathing ambient air at 5260 m, V(O(2),max) is limited by the availability of O(2) rather than by muscular oxidative capacity. Altitude increased [Hb] by 36 % from 136 +/- 5 to 185 +/- 5 g l(-1) (P < 0.001), while haemodilution (replacing 1 l of blood with 1 l of 6 % Dextran) lowered [Hb] by 24 % to 142 +/- 6 g l(-1) (P < 0.001). Haemodilution had no effect on maximal pulmonary or leg V(O(2),max), or power output. Despite higher LBF, leg O(2) delivery was reduced and maximal V(O(2)) was thus maintained by higher O(2) extraction. While CO increased linearly with work rate irrespective of [Hb] or inspired oxygen fraction (F(I,O(2))), both LBF and leg vascular conductance were systematically higher when [Hb] was low. Close and significant relationships were seen between LBF (and CO) and both plasma noradrenaline and K(+) concentrations, independently of [Hb] and F(I,O(2)). In summary, under conditions where O(2) supply limits maximal exercise, the increase in [Hb] with altitude acclimatisation does not improve maximal exercise capacity or V(O(2),max), and does not alter peak CO. However, LBF and vascular conductance are higher at altitude when [Hb] is lowered to sea level values, with both relating closely to catecholamine and potassium concentrations. This suggests that the lack of effect of [Hb] on V(O(2),max) may involve reciprocal changes in LBF via local metabolic control of the muscle vasculature.

500 ml of blood loss does not decrease non-invasive tissue oxygen saturation (StO2) as measured by near infrared spectroscopy - A hypothesis generating pilot study in healthy adult women

Background The goal when resuscitating trauma patients is to achieve adequate tissue perfusion. One parameter of tissue perfusion is tissue oxygen saturation (StO2), as measured by near infrared spectroscopy. Using a commercially available device, we investigated whether clinically relevant blood loss of 500 ml in healthy volunteers can be detected by changes in StO2 after a standardized ischemic event. Methods We performed occlusion of the brachial artery for 3 minutes in 20 healthy female blood donors before and after blood donation. StO2 and total oxygenated tissue hemoglobin (O2Hb) were measured continuously at the thenar eminence. 10 healthy volunteers were assessed in the same way, to examine whether repeated vascular occlusion without blood donation exhibits time dependent effects. Results Blood donation caused a substantial decrease in systolic blood pressure, but did not affect resting StO2 and O2Hb values. No changes were measured in the blood donor group in the reaction to the vascular occlusion test, but in the control group there was an increase in the O2Hb rate of recovery during the reperfusion phase. Conclusion StO2 measured at the thenar eminence seems to be insensitive to blood loss of 500 ml in this setting. Probably blood loss greater than this might lead to detectable changes guiding the treating physician. The exact cut off for detectable changes and the time effect on repeated vascular occlusion tests should be explored further. Until now no such data exist.

Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia

Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle (n = 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 μg/kg per minute or another vehicle (n = 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 ± 11 mmHg vs. 58 ± 8 mmHg (mean ± SD); P = 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18-1.32) mmHg/ml vs. 0.22 (0.08-0.60) mmHg/ml; P = 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia (P = 0.031; constriction-time-group interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22-134%) in controls vs. 53% (37-85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12-47%) of baseline (P = 0.043) vs. 17% (-7-32%) in endotoxemia (P = 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR.

Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis

OBJECTIVE: The use of vasopressors for treatment of hypotension in sepsis may have adverse effects on microcirculatory blood flow in the gastrointestinal tract. The aim of this study was to measure the effects of three vasopressors, commonly used in clinical practice, on microcirculatory blood flow in multiple abdominal organs in sepsis. DESIGN: Random order, cross-over design. SETTING: University laboratory. SUBJECTS: Eight sedated and mechanically ventilated pigs. INTERVENTIONS: Pigs were exposed to fecal peritonitis-induced septic shock. Mesenteric artery flow was measured using ultrasound transit time flowmetry. Microcirculatory flow was measured in gastric, jejunal, and colon mucosa; jejunal muscularis; and pancreas, liver, and kidney using multiple-channel laser Doppler flowmetry. Each animal received a continuous intravenous infusion of epinephrine, norepinephrine, and phenylephrine in a dose increasing mean arterial pressure by 20%. The animals were allowed to recover for 60 mins after each drug before the next was started. MEASUREMENTS AND MAIN RESULTS: During infusion of epinephrine (0.8 +/- 0.2 mug/kg/hr), mean arterial pressure increased from 66 +/- 5 to 83 +/- 5 mm Hg and cardiac index increased by 43 +/- 9%. Norepinephrine (0.7 +/- 0.3 mug/kg/hr) increased mean arterial pressure from 70 +/- 4 to 87 +/- 5 mm Hg and cardiac index by 41 +/- 8%. Both agents caused a significant reduction in superior mesenteric artery flow (11 +/- 4%, p < .05, and 26 +/- 6%, p < .01, respectively) and in microcirculatory blood flow in the jejunal mucosa (21 +/- 5%, p < .01, and 23 +/- 3%, p < .01, respectively) and in the pancreas (16 +/- 3%, p < .05, and 8 +/- 3%, not significant, respectively). Infusion of phenylephrine (3.1 +/- 1.0 mug/kg/min) increased mean arterial pressure from 69 +/- 5 to 85 +/- 6 mm Hg but had no effects on systemic, regional, or microcirculatory flow except for a 30% increase in jejunal muscularis flow (p < .01). CONCLUSIONS: Administration of the vasopressors phenylephrine, epinephrine, and norepinephrine failed to increase microcirculatory blood flow in most abdominal organs despite increased perfusion pressure and-in the case of epinephrine and norepinephrine-increased systemic blood flow. In fact, norepinephrine and epinephrine appeared to divert blood flow away from the mesenteric circulation and decrease microcirculatory blood flow in the jejunal mucosa and pancreas. Phenylephrine, on the other hand, appeared to increase blood pressure without affecting quantitative blood flow or distribution of blood flow.

Vasopressin in septic shock: effects on pancreatic, renal, and hepatic blood flow

INTRODUCTION: Vasopressin has been shown to increase blood pressure in catecholamine-resistant septic shock. The aim of this study was to measure the effects of low-dose vasopressin on regional (hepato-splanchnic and renal) and microcirculatory (liver, pancreas, and kidney) blood flow in septic shock. METHODS: Thirty-two pigs were anesthetized, mechanically ventilated, and randomly assigned to one of four groups (n = 8 in each). Group S (sepsis) and group SV (sepsis/vasopressin) were exposed to fecal peritonitis. Group C and group V were non-septic controls. After 240 minutes, both septic groups were resuscitated with intravenous fluids. After 300 minutes, groups V and SV received intravenous vasopressin 0.06 IU/kg per hour. Regional blood flow was measured in the hepatic and renal arteries, the portal vein, and the celiac trunk by means of ultrasonic transit time flowmetry. Microcirculatory blood flow was measured in the liver, kidney, and pancreas by means of laser Doppler flowmetry. RESULTS: In septic shock, vasopressin markedly decreased blood flow in the portal vein, by 58% after 1 hour and by 45% after 3 hours (p < 0.01), whereas flow remained virtually unchanged in the hepatic artery and increased in the celiac trunk. Microcirculatory blood flow decreased in the pancreas by 45% (p < 0.01) and in the kidney by 16% (p < 0.01) but remained unchanged in the liver. CONCLUSION: Vasopressin caused marked redistribution of splanchnic regional and microcirculatory blood flow, including a significant decrease in portal, pancreatic, and renal blood flows, whereas hepatic artery flow remained virtually unchanged. This study also showed that increased urine output does not necessarily reflect increased renal blood flow.