Organ Blood Flow Research Articles

A physiologically based pharmacokinetic drug-disease model to predict carvedilol exposure in adult and paediatric heart failure patients by incorporating pathophysiological changes in hepatic and renal blood flows.

Background and ObjectiveChronic diseases are associated with pathophysiological changes that could have profound impacts on drug pharmacokinetic behaviour, with a potential need to modify the administered drug therapy. It is important to acknowledge that most patients with chronic illnesses do not have a single, predominant condition but suffer from multiple comorbidities. The rapid advancement in physiologically based pharmacokinetic (PBPK) modelling, as well as the increasing quantitative knowledge of disease-related pathophysiological changes, facilitate building of drug–disease models. However, there are only a few published examples of PBPK models incorporating the pathophysiological changes that occur with chronic diseases. The objective of this study was to develop PBPK models that incorporate the haemodynamic changes in hepatic and renal blood flows occurring in chronic heart failure (CHF) and to evaluate these changes in adults and children, using carvedilol as a model drug.MethodsAfter a comprehensive literature search to select the model input parameters, two PBPK models were developed. Model 1 was based on human liver and intestinal microsome clearances, and model 2 was based on clearance by specific cytochrome P450 enzymes. After evaluation of both models in healthy adults, the reduced hepatic and renal blood flows were incorporated into the developed models to predict carvedilol exposure in the adult CHF population. The adult carvedilol models were scaled down to children by using Simcyp® (Simcyp Ltd, Sheffield, UK). In order to show the impact of reduced organ blood flows on carvedilol disposition, the predictions in the CHF population were made with and without reductions in organ blood flows.ResultsThe predictions made by both models in healthy adults were comparable and within the 2-fold error range. In adults with CHF, the mean observed/predicted ratio [ratio(Obs/Pred)] for oral clearance (CL/F) without reductions in organ blood flows was outside the 2-fold error range, i.e. 0.34 (95 % confidence interval [CI] 0.31–0.37), with use of both models. The mean CL/F ratio(Obs/Pred) values after incorporation of reduced organ blood flows were 1.0 (95 % CI 0.92–1.08) and 0.95 (95 % CI 0.88–1.03) with use of models 1 and 2, respectively. The mean ratio(Obs/Pred) values for the pharmacokinetic parameters were not improved after incorporation of reduced blood flows in paediatric patients, except in those above 17 years of age, who were categorized according to the New York Heart Association classification of CHF, where the CL/F ratio(Obs/Pred) values in two patients were closer to unity.ConclusionThere was a strong connection between a decrease in hepatic clearance of carvedilol and an increase in the severity of CHF, especially in adults and in paediatric patients above 17 years of age. The incorporated reductions in hepatic and renal blood flows occurring in moderate and severe CHF patients resulted in improved predictions of carvedilol exposure. The developed models can be extended to predict exposures of drugs with high hepatic extraction in the CHF population.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-015-0253-7) contains supplementary material, which is available to authorized users.

TRPV4 Channel Cooperativity in the Resistance Vasculature

TRPV4 Channel Cooperativity in the Resistance Vasculature

Addition of Direct Peritoneal Lavage to Human Cadaver Organ Donor Resuscitation Improves Organ Procurement

Brain dead organ donors have altered central hemodynamic performance, impaired hormone physiology, exaggerated systemic inflammatory response, end-organ microcirculatory dysfunction, and tissue hypoxia. A new treatment, direct peritoneal resuscitation (DPR), stabilizes vital organ blood flow after conventionally resuscitated shock to improve these derangements. A prospective case-control study of adjunctive DPR compared 26 experimental patients (brain dead organ donors) to 52 controls (protocolized conventionally resuscitated donors). Actual organ procurement rates were compared with the Scientific Registry of Transplant Recipient predicted organ yield per patient. Achievement of donor management goals and effective hepatic blood flow were recorded. Fourteen of 26 (53.8%) patients treated with DPR achieved all donor management goals compared with 17 of 52 (32.7%) patients treated with conventionally resuscitated (odds ratio = 2.4; 95% CI, 0.92-6.3; p = 0.06). Patients treated with DPR were more than 2 times as likely to achieve final pO2 >100 on 40% FiO2 compared with controls (odds ratio = 2.8; 95% CI, 1-7.69; p = 0.03). Also, DPR-treated patients required less IV crystalloid during the first 12 hours of management (DPR: 3,167 ± 1,893 mL vs 4,154 ± 2,100 mL; p = 0.046) and required less vasopressor agents at 12 hours post resuscitation (odds ratio = 7.7; 95% CI, 0.82-42; p = 0.02). Direct peritoneal resuscitation patients had enhanced effective hepatic blood flow and significantly higher organs transplanted per donor rates compared with controls (3.7 ± 1.7 vs 3.1 ± 1.3; p = 0.024). Direct peritoneal resuscitation reduced IV fluid requirement and IV pressor use as well as increased hepatic blood flow and organs transplanted per donor. Direct peritoneal resuscitation studies show it to be a safe, effective method to augment organ donor resuscitation and additional large-scale trials should be conducted to validate these findings.

The impact of public investment in medical imaging technology: an interagency collaboration in evaluation

The Canada Foundation for Innovation (CFI) and the Canadian Institutes of Health Research (CIHR) allied to analyze the impact of their investments in medical imaging research. The CFI funds capital and operating programs for research infrastructure, and CIHR's mandate concentrates its funding on research activity. It happens that CIHR-funded research consumes CFI-funded infrastructure as an input in the innovation process. Apart from a few partnered programs, by design there is no coordination between CFI and CIHR funding decisions. Together, these agencies invested $916 million over a 14-year-period. In this paper, we evaluate the economic and health benefits from advancements in one funded area, namely computed tomography perfusion (CTP). CTP is an imaging technique that uses computed tomography to measure blood flow in organs and tissues. It is mostly used to assess acute ischemic stroke. The net social benefits attributable to these investments are substantially positive: the benefit-to-cost ratio is estimated to be between 6.66-to-1 and 9.99-to-1. We review how public investments from multiple funders comingle in the innovation process to deliver social value and improved health outcomes.

Effects of Sevoflurane and Propofol on Organ Blood Flow in Left Ventricular Assist Devices in Pigs.

The aim of this study was to assess the effect of sevoflurane and propofol on organ blood flow in a porcine model with a left ventricular assist device (LVAD). Ten healthy minipigs were divided into 2 groups (5 per group) according to the anesthetic received (sevoflurane or propofol). A Biomedicus centrifugal pump was implanted. Organ blood flow (measured using colored microspheres), markers of tissue injury, and hemodynamic parameters were assessed at baseline (pump off) and after 30 minutes of partial support. Blood flow was significantly higher in the brain (both frontal lobes), heart (both ventricles), and liver after 30 minutes in the sevoflurane group, although no significant differences were recorded for the lung, kidney, or ileum. Serum levels of alanine aminotransferase and total bilirubin were significantly higher after 30 minutes in the propofol group, although no significant differences were detected between the groups for other parameters of liver function, kidney function, or lactic acid levels. The hemodynamic parameters were similar in both groups. We demonstrated that, compared with propofol, sevoflurane increases blood flow in the brain, liver, and heart after implantation of an LVAD under conditions of partial support.

Bone and Calcium Research Update 2015. Role of calcium in the regulation of smooth muscle function

The vascular smooth muscle plays a physiological role in the regulation of the organ blood flow and blood pressure by modulating vascular resistance. The contraction of vascular smooth muscle is regulated by both Ca2+ signal and changes in the sensitivity of the contractile apparatus to Ca2+. The influx of the extracellular Ca2+ and the release of Ca2+ from the intracellular store sites play an important role in generating Ca2+ signal. The regulation of activity of myosin light chain phosphatase plays a critical role in regulating the myofilament Ca2+ sensitivity. It is conceivable that any contractile stimulants or vasorelaxant agents exert their vascular effects by affecting either Ca2+ signal or myofilament Ca2+ sensitivity.

Non-uniformity of Clinical Head, Head and Neck, and Body Coils in Magnetic Resonance Imaging (MRI)

Introduction Signal intensity uniformity in a magnetic resonance (MR) image indicates how well the MR imaging (MRI) system represents an object. One of the major sources of image non-uniformity in high-field MRI scanners is inhomogeneity of radio-frequency coil. The aim of this study was to investigate non-uniformity in head, head and neck, and body coils and compare the obtained results to determine the best clinical coil for future clinical application. Materials and Methods A phantom was designed to investigate the non-uniformity of coils. All evaluations were carried out using a 1.5 T clinical MRI scanner. T1-weighted inversion recovery sequence (linear phase encoding) and turbo fast low angle shot (TurboFLASH) images were used to find non-uniformity in the clinical coils. For testing the uniformity of coils, signal intensity profiles in parts of the coronal image of phantom were measured over X and Y axes. Results The results showed that body coil was the most uniform coil of all; in addition, the head and neck coil was more uniform than the head coil. The results also indicated that signal-to-noise ratio (SNR) of the head and neck coil was higher than the head and body coils. Moreover, SNR of the head coil was higher than that of the body coil. Conclusion In order to accurately find or apply an image signal intensity for measuring organ blood flow or perfusion, coil non-uniformity corrections are required.

Stratum Corneum Hydration and Skin Surface pH Variation Indicate that Organ Blood Flow Is Regulated by Meridian Activity at Certain Hours

Day and night are regular occurrences in nature, and the organs and tissues in living bodies follow this cycle. The sympathetic nervous system (SNS) at various time points regulates organ excitation to maintain healthy functions in the living body. The energy required from basal metabolism can be used to explain living organisms according to the traditional Chinese medicine (TCM) concept of relationships between meridian directions and organs at various times (organs “at rest” and organs “in operation”). By monitoring skin reactions after applying a cream, we speculated regular blood flow changes, and established an animated hourglass-shaped trajectory diagram to visualize these changes. A combination of TCM and physiological perspectives were considered to explain how the cardiovascular system produces energy. These two perspectives were applied to interpret the correlation between the SNS and organ metabolism.

Tilting for perfusion: Head-up position during cardiopulmonary resuscitation improves brain flow in a porcine model of cardiac arrest

IntroductionCerebral perfusion is compromised during cardiopulmonary resuscitation (CPR). We hypothesized that beneficial effects of gravity on the venous circulation during CPR performed in the head-up tilt (HUT) position would improve cerebral perfusion compared with supine or head-down tilt (HDT). MethodsTwenty-two pigs were sedated, intubated, anesthetized, paralyzed and placed on a tilt table. After 6min of untreated ventricular fibrillation (VF) CPR was performed on 14 pigs for 3min with an automated CPR device called LUCAS (L) plus an impedance threshold device (ITD), followed by 5min of L-CPR+ITD at 0° supine, 5min at 30° HUT, and then 5min at 30° HDT. Microspheres were used to measure organ blood flow in 8 pigs. L-CPR+ITD was performed on 8 additional pigs at 0°, 20°, 30°, 40°, and 50° HUT. ResultsCoronary perfusion pressure was 19±2mmHg at 0° vs. 30±3 at 30° HUT (p<0.001) and 10±3 at 30° HDT (p<0.001). Cerebral perfusion pressure was 19±3 at 0° vs. 35±3 at 30° HUT (p<0.001) and 4±4 at 30° HDT (p<0.001). Brain–blood flow was 0.19±0.04mlmin−1g−1 at 0° vs. 0.27±0.04 at 30° HUT (p=0.01) and 0.14±0.06 at 30° HDT (p=0.16). Heart blood flow was not significantly different between interventions. With 0, 10, 20, 30, 40 and 50° HUT, ICP values were 21±2, 16±2, 10±2, 5±2, 0±2, −5±2 respectively, (p<0.001), CerPP increased linearly (p=0.001), and CPP remained constant. ConclusionDuring CPR, HDT decreased brain flow whereas HUT significantly lowered ICP and improved cerebral perfusion. Further studies are warranted to explore this new resuscitation concept.

Abstract 175: Vasopressin Maintains Robust Organ Blood Flow During Resuscitation from Hemorrhagic Shock

Background: We have reported beneficial hemodynamic and survival effects of vasopressin (VP) infusion in swine models of hemorrhagic shock (HS), and attributed the effects to increases in peripheral vascular resistance. However, VP may also exert a minor effect on venous return. In the present study we used fluorescent microspheres to measure the effects of VP on blood flow to organs of interest during HS produced by liver laceration (LL). Methods: Forty male domestic pigs (32.3 to 40.3 kg) had their left lateral liver lobe lacerated with a sharpened steel, X-shaped 5 cm blade clamp. Thirty-two pigs received a second LL in the same lobe 7.5 minutes later and 24 pigs received a third LL in the left medial lobe at 15 minutes from the first LL. Pigs were randomized 1:1 to receive an infusion of VP (0.04 U/kg•min-1) or vehicle intraosseously starting 7 minutes after the first LL until the end of the experiment (240 min). Microspheres were injected into the left ventricle at baseline (BL) and during HS at times shown in the Table. Results: At 60 minutes of HS, VP infusion was associated with higher aortic blood pressure and lower cardiac index (both NS) along with overall reductions in blood flow to various organs (Table) coincident with a statistically significant reduction in heart rate (157±43 vs 184±29 min-1; p≤0.05). At 120 and 180 minutes of HS, the heart rate was only mildly reduced (NS). The aortic pressures remained high but without a reduction in cardiac index. Organ blood flows were all comparable or higher with VP than in control pigs attaining statistical significance for renal cortical blood flow. Conclusion: Contrary to the expected hemodynamic effects of VP redistributing blood flow away from “non-vital organs,” we observed a robust hemodynamic effect that adequately perfused vital and “non-vital” organs during HS without deterioration over time. Early and sustained VP infusion could represent a highly effective intervention for hemodynamic stabilization during severe HS.

Monitoring CO2 in shock states.

The primary end point when treating acute shock is to restore blood circulation, mainly by reaching macrocirculatory parameters. However, even if global haemodynamic goals can be achieved, microcirculatory perfusion may remain impaired, leading to cellular hypoxia and organ damage. Interestingly, few methods are currently available to measure the adequacy of organ blood flow and tissue oxygenation. The rise in tissue partial pressure of carbon dioxide (CO2) has been observed when tissue perfusion is decreased. In this regard, tissue partial pressure of CO2 has been proposed as an early and reliable marker of tissue hypoxia even if the mechanisms of tissue partial pressure in CO2 rise during hypoperfusion remain unclear. Several technologies allow the estimation of CO2 content from different body sites: vascular, tissular (in hollow organs, mucosal or cutaneous), and airway. These tools remain poorly evaluated, and some are used but are not widely used in clinical practice. The present review clarifies the physiology of increasing tissue CO2 during hypoperfusion and underlines the specificities of the different technologies that allow bedside estimation of tissue CO2 content.

Effects of cyclooxygenase inhibition on insulin release and pancreatic islet blood flow in rats

Objectives. To examine the effects of inhibition of cyclooxygenase (COX) on islet hormone secretion in vitro and on pancreatic islet blood flow in vivo.Methods. Insulin release was measured in a static incubation system of islets isolated from Wistar-F rats after inhibition of COX-1 and COX-2 with SC 560 (COX-1), FR 122047 (COX-1), rofecoxib (COX-2), or indomethacin (both COX-1 and COX-2). In other rats organ blood flow values were measured with a microsphere technique during both normo- and hyperglycemia after administration of these enzyme inhibitors.Results. Serum insulin values were lower after pretreatment with a COX-1 inhibitor or a non-selective COX inhibitor in both control and glucose-injected rats in vivo, whereas COX-2 inhibition had no such effects. However, inhibition of COX had only minor effects on insulin release in vitro. Inhibition of COX affected neither total pancreatic nor islet blood flow in normoglycemic rats. Hyperglycemia caused an increase in both these flow values and in the duodenum. The increase in total pancreatic and duodenal blood flow was prevented by inhibition of COX-2 or non-selective COX inhibition. However, no effects on islet blood flow were seen after COX inhibition.Conclusion. Inhibition of COX affects insulin release and blood glucose concentrations in vivo. However, COX inhibition has only minor effects on pancreatic islet blood flow, but prevents the glucose-induced increase in total pancreatic blood flow.

Transcutaneous electrical nerve stimulation regulates organ blood flow and apoptosis during controlled hypotension in dogs.

Transcutaneous electrical nerve stimulation (TENS) is commonly used in clinical practice for alleviating pains and physiological disorders. It has been reported that TENS could counteract the ischemic injury happened in some vital organs. To determine the protective effect of TENS on internal organs during CH in dogs, target hypotension was maintained for 60 min at 50% of the baseline mean arterial pressure (MAP). The perfusion to the brain, liver, stomach, and kidney was recorded and apoptosis within these organs was observed. Results showed that when arriving at the target MAP, and during the maintaining stage for 10 min, perfusion to the stomach and liver in the CH+TENS group was much higher than in the CH group (P<0.05). Perfusion to the cerebral cortex greatly declined in both the controlled pressure groups when compared with the general anesthesia (GA) group (P<0.05). After withdrawing CH, the hepatic blood flow in both the CH and CH+TENS groups, and the gastric and cerebral cortical blood flow in the CH+TENS group, were rapidly increased. By the end of MAP restoration, gastric blood flow in the CH group was still low. At 72 h after applying CH, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in stomach and kidney tissue from the CH group were significantly increased compared with those in the GA group (P<0.05). There was no significant difference in TUNEL-positive cells in the liver and hippocampus among the three groups. Our results demonstrated that CH with a 50% MAP level could cause lower perfusion to the liver, stomach, cerebral cortex, and kidney, with apoptosis subsequently occurring in the stomach and kidney. TENS combined GA is able to improve the blood flow to the liver, stomach, and reduce the apoptosis in the stomach and kidney.

1 Microcirculatory Blood Flow in Hindlimbs During Remote Ischaemic Preconditioning

<h3>Background</h3> Brief ischaemia of one organ protects the heart against a sustained ischaemia-reperfusion insult (Remote ischaemic preconditioning, RIPC). The nature of the signal released from the remote organ and the timing of the triggered changes in the target organs remain controversial. It is not known whether RIPC also alters blood flow in other organs. In this study we investigated the changes in microcirculatory blood flow (MBF) in both hind limbs during RIPC and measured myocardial metabolites (e.g. ATP, AMP and adenosine) after induction of RIPC. <h3>Methods</h3> RIPC was induced in C57/Bl6 mice using four cycles of 5 min ischaemia and 5 min reperfusion of the hind limb (experimental limb) using blood pressure cuff. MBF in both RIPC mouse and in control mouse was measured using Laser Doppler Flowmetry throughout the procedure of 50 min. In separate experiment, hearts were excised from RIPC and control mice and extracted for measuring metabolites using HPLC. <h3>Results</h3> In control mice (no RIPC application) there was no significant change in MBF in both hind limbs. Inflating blood pressure cuff for 5 min resulted in complete occlusion of MBF in the experimental hind limb. Reperfusion in each cycle of RIPC was associated with a hyperaemic response. In contrast, MBF in the un-cuffed hind limb was reduced during the RIPC cycles. Interestingly, HPLC analysis showed that RIPC causes ischaemic stress (increase AMP/ATP). <h3>Conclusion</h3> Our mouse model of RIPC is associated with reduced MBF in the non-conditioned hind limb and metabolic stress in the myocardium. Supported by NIHR BRISTOL BIOMEDICAL RESEARCH UNIT IN CARDIOVASCULAR MEDICINE.

Optimal Blood Pressure in Preterm Infants

Many neonatologists routinely treat infants whose mean arterial blood pressure in mm Hg is less than their gestational age in weeks (GA) but there is uncertainty regarding diagnosis and treatment of hypotension. This addresses the definition of permissive hypotension based on the principles of cardiovascular physiology, and reviews the tools available at the bedside to examine the complex relationship among blood pressure, systemic organ blood flow, and tissue oxygen delivery and oxygen demand in preterm infants (skin color, capillary refill time, urine output, serum lactate level, and acidosis). Importantly, absolute blood pressure values are only one indicator of circulatory status and this review confirms that a mean blood pressure less than gestational age in weeks alone is not a predictor of poor outcome. Global assessment of cardiovascular status and intervention for hypotension restricted to infants with poor perfusion may be associated with good clinical outcomes and should be further evaluated.

Investigating autonomic control of the cardiovascular system: a battery of simple tests

Sympathetic and parasympathetic divisions of the autonomic nervous system constantly control the heart (sympathetic and parasympathetic divisions) and blood vessels (predominantly the sympathetic division) to maintain appropriate blood pressure and organ blood flow over sometimes widely varying conditions. This can be adversely affected by pathological conditions that can damage one or both branches of autonomic control. The set of teaching laboratory activities outlined here uses various interventions, namely, 1) the heart rate response to deep breathing, 2) the heart rate response to a Valsalva maneuver, 3) the heart rate response to standing, and 4) the blood pressure response to standing, that cause fairly predictable disturbances in cardiovascular parameters in normal circumstances, which serve to demonstrate the dynamic control of the cardiovascular system by autonomic nerves. These tests are also used clinically to help investigate potential damage to this control.

Arterial ammonia levels in cirrhosis are determined by systemic and hepatic hemodynamics, and by organ function: a quantitative modelling study

Hyperammonaemia is a common complication of chronic liver failure. Two main factors are thought to underlie this complication: a loss of hepatic detoxification function and the development of portosystemic shunting. However, few studies have tried to quantify the importance of portosystemic shunting. Here, we used a theoretical approach to test the hypothesis that the development of portosystemic shunting is sufficient to cause hyperammonaemia in cirrhosis. Two mathematical models are developed. The first one describes the main vascular resistances of the circulation and is used to provide scenarios for the distributions of organ blood flow in cirrhosis, which are necessary to run the second model. The second model predicts arterial ammonia levels resulting from ammonia metabolism in gut, liver, kidney, muscle and brain, and the distribution of organ blood flow. The fraction of gastrointestinal blood flow shunted through collaterals was estimated to be 41% in mild cirrhosis, 69% in moderate and 85% in severe cases. In the second model, the redistribution of organ blood flow associated with severe cirrhosis was sufficient to cause hyperammonaemia, even when the hepatic detoxification function and the ammonia production were set to normal. The model indicates that the development of portosystemic shunting in cirrhosis is sufficient to cause hyperammonaemia. Interventions that reduce the fraction of shunting may be future targets of therapy to control severity of hyperammonaemia.

Skin blood flow as a predictor of intraventricular hemorrhage in very-low-birth-weight infants

Cardiovascular instability immediately after birth is associated with intraventricular hemorrhage (IVH) in very-low-birth-weight (VLBW) infants. For circulatory management, evaluation of organ blood flow is important. In this study, the relationship between peripheral perfusion within 48 h after birth and IVH was evaluated in VLBW infants. In this prospective observational study involving 83 VLBW infants, forehead blood flow (FBF) and lower-limb blood flow (LBF) were measured for 48 h after birth using a laser Doppler flowmeter. Blood flow was compared between infants with and without IVH. Multivariate logistic regression analysis was performed to identify the risk factors for IVH. IVH developed in nine infants. In eight of these patients, IVH occurred after 24 h. LBF was lower in infants with IVH at 18 and 24 h and increased to the same level as that of infants without IVH at 48 h. Multivariate logistic regression analysis identified a correlation only between LBF and IVH at 18 h. These findings were consistent with the hypoperfusion-reperfusion theory, which states that IVH develops after reperfusion subsequent to hypoperfusion. We speculate that measurement of skin blood flow in addition to systemic and cerebral circulation may be helpful in predicting IVH.

Non-invasive mapping of organ perfusion and blood flow by CT and MRI highlighted by a case of pulmonary artery stenosis

A 65-year-old man with bilateral pulmonary artery stenosis was treated with percutaneous transluminal angioplasty (PTA) and stent implantation in 2002. After being symptom free for 10 years, the patient presented with worsening episodes of acute right ventricular failure and severe dyspnoea. Echocardiography demonstrated a high-grade stenosis of the pulmonary arteries with accelerated flow velocities up to 4.5 m/s. …

Pumpless extracorporeal CO2removal restores normocapnia and is associated with less regional perfusion in experimental acute lung injury

Lung protective ventilation may lead to hypoventilation with subsequent hypercapnic acidosis (HA). If HA cannot be tolerated or occurs despite increasing respiratory rate or buffering, extracorporeal CO2-removal using a percutaneous extracorporeal lung assist (pECLA) is an option. We hypothesised that compensation of HA using pECLA impairs regional perfusion. To test this hypothesis we determined organ blood flows in a lung-injury model with combined hypercapnic and metabolic acidosis. After induction of lung injury using hydrochloric acid (HCl) aspiration and metabolic acidosis by intravenous HCl infusion in nine pigs, an arterial-venous pECLA device was inserted. In randomised order, four treatments were tested: pECLA shunt (1) with and (2) without HA, and clamped pECLA shunt (3) with and (4) without HA. Regional blood flows were measured with the coloured microsphere technique. HA resulted in higher perfusion in adrenal glands, spleen and parts of splanchnic area (P < 0.05) compared with normocapnia. During CO2-removal with pECLA, regional perfusion decreased to levels comparable with those without pECLA and normocapnia. Cardiac output (CO) increased during HA without a pECLA shunt and was highest during HA with a pECLA shunt compared with normocapnia. During CO2-removal with pECLA, this variable decreased but stayed higher than during normocapnia with clamped pECLA shunt (P < 0.05). In our lung-injury model, HA was associated with increased systemic and regional blood flow in several organs. pECLA provides effective CO2 removal, requiring a higher CO for perfusion of the pECLA device without improvement of regional organ perfusion.