Vasopressin in vasodilatory shock: ensure organ blood flow, but take care of the heart!

Supplementary arginine vasopressin infusion in advanced vasodilatory shock may be accompanied by a decrease in cardiac index and systemic oxygen transport capacity in approximately 40% of patients. While a reduction of cardiac output most frequently occurs in patients with hyperdynamic circulation, it is less often observed in patients with low cardiac index. Infusion of inotropes, such as dobutamine, may be an effective strategy to restore systemic blood flow. However, when administering inotropic drugs, systemic blood flow should be increased to adequately meet systemic demands (assessed by central or mixed venous oxygen saturation) without putting an excessive beta-adrenergic stress on the heart. Overcorrection of cardiac index to hyperdynamic values with inotropes places myocardial oxygen supply at significant risk.

Initiation of high-frequency oscillatory ventilation and its effects upon cerebral circulation in pigs: an experimental study

BACKGROUND: Current practice at high-frequency oscillatory ventilation (HFOV) initiation is a stepwise increase of the constant applied airway pressure to achieve lung recruitment. We hypothesized that HFOV would lead to more adverse cerebral haemodynamics than does pressure controlled ventilation (PCV) in the presence of experimental intracranial hypertension (IH) and acute lung injury (ALI) in pigs with similar mean airway pressure settings. METHODS: In 12 anesthetized pigs (24-27 kg) with IH and ALI, mean airway pressure (P(mean)) was increased (to 20, 25, 30 cm H(2)O every 30 min), either with HFOV or with PCV. The order of the two ventilatory modes (cross-over) was randomized. Mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral blood flow (CBF) (fluorescent microspheres), cerebral metabolism, transpulmonary pressures (P(T)), and blood gases were determined at each P(mean) setting. Our end-points of interest related to the cerebral circulation were ICP, CPP and CBF. RESULTS: CBF and cerebral metabolism were unaffected but there were no differences between the values for HFOV and PCV. ICP increased slightly (HFOV median +1 mm Hg, P<0.05; PCV median +2 mm Hg, P<0.05). At P(mean) setting of 30 cm H(2)O, CPP decreased during HFOV (median -13 mm Hg, P<0.05) and PCV (median -17 mm Hg, P<0.05) paralleled by a decrease of MAP (HFOV median -11 mm Hg, P<0.05; PCV median -13 mm Hg, P<0.05). P(T) increased (HFOV median +8 cm H(2)O, P<0.05; PCV median +8 cm H(2)O, P<0.05). Oxygenation improved and normocapnia maintained by HFOV and PCV. There were no differences between both ventilatory modes. CONCLUSIONS: In animals with elevated ICP and ALI, both ventilatory modes had effects upon cerebral haemodynamics. The effects upon cerebral haemodynamics were dependent of the P(T) level without differences between both ventilatory modes at similar P(mean) settings. HFOV seems to be a possible alternative ventilatory strategy when MAP deterioration can be avoided.

Rapid restoration of microcirculatory blood flow with hyperviscous and hyperoncotic solutions lowers the transfusion trigger in resuscitation from hemorrhagic shock

Resuscitation from hemorrhagic shock relies on fluid retransfusion. However, the optimal properties of the fluid have not been established. The aim of the present study was to test the influence of the concentration of hydroxyethyl starch (HES) solution on plasma viscosity and colloid osmotic pressure (COP), systemic and microcirculatory recovery, and oxygen delivery and consumption after resuscitation, which were assessed in the hamster chamber window preparation by intravital microscopy. Awake hamsters were subjected to 50% hemorrhage and were resuscitated with 25% of the estimated blood volume with 5%, 10%, or 20% HES solution. The increase in concentration led to an increase in COP (from 20 to 70 and 194 mmHg) and viscosity (from 1.7 to 3.8 and 14.4 cP). Cardiac index and microcirculatory and metabolic recovery were improved with HES 10% and 20% when compared with 5% HES. Oxygen delivery and consumption in the dorsal skinfold chamber was more than doubled with HES 10% and 20% when compared with HES 5%. This was attributed to the beneficial effect of restored or increased plasma COP and plasma viscosity as obtained with HES 10% and 20%, leading to improved microcirculatory blood flow values early in the resuscitation period. The increase in COP led to an increase in blood volume as shown by a reduction in hematocrit. Mean arterial pressure was significantly improved in animals receiving 10% and 20% solutions. In conclusion, the present results show that the increase in the concentration of HES, leading to hyperoncotic and hyperviscous solutions, is beneficial for resuscitation from hemorrhagic shock because normalization of COP and viscosity led to a rapid recovery of microcirculatory parameters.

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.

Effects of vasopressin on microcirculatory blood flow in the gastrointestinal tract in anesthetized pigs in septic shock

BACKGROUND: Vasopressin increases arterial pressure in septic shock even when alpha-adrenergic agonists fail. The authors studied the effects of vasopressin on microcirculatory blood flow in the entire gastrointestinal tract in anesthetized pigs during early septic shock. METHODS: Thirty-two pigs were intravenously anesthetized, mechanically ventilated, and randomly assigned to one of four groups (n=8 in each; full factorial design). Group S (sepsis) and group SV (sepsis-vasopressin) were made septic by fecal peritonitis. Group C and group V were nonseptic control groups. After 300 min, group V and group SV received intravenous infusion of 0.06 U.kg.h vasopressin. In all groups, cardiac index and superior mesenteric artery flow were measured. Microcirculatory blood flow was recorded with laser Doppler flowmetry in both mucosa and muscularis of the stomach, jejunum, and colon. RESULTS: While vasopressin significantly increased arterial pressure in group SV (P<0.05), superior mesenteric artery flow decreased by 51+/-16% (P<0.05). Systemic and mesenteric oxygen delivery and consumption decreased and oxygen extraction increased in the SV group. Effects on the microcirculation were very heterogeneous; flow decreased in the stomach mucosa (by 23+/-10%; P<0.05), in the stomach muscularis (by 48+/-16%; P<0.05), and in the jejunal mucosa (by 27+/-9%; P<0.05), whereas no significant changes were seen in the colon. CONCLUSION: Vasopressin decreased regional flow in the superior mesenteric artery and microcirculatory blood flow in the upper gastrointestinal tract. This reduction in flow and a concomitant increase in the jejunal mucosa-to-arterial carbon dioxide gap suggest compromised mucosal blood flow in the upper gastrointestinal tract in septic pigs receiving low-dose vasopressin.

Spectral waveform analysis of intranodal arterial blood flow in abnormally large superficial lymph nodes in dogs

Objective-To evaluate pulsed-wave Doppler spectral parameters as a method for distinguishing between neoplastic and inflammatory peripheral lymphadenopathy in dogs. Sample Population-40 superficial lymph nodes from 33 dogs with peripheral lymphadenopathy. Procedures-3 Doppler spectral tracings were recorded from each node. Spectral Doppler analysis including assessment of the resistive index, peak systolic velocity-to-end diastolic velocity (S:D) ratio, diastolic notch velocity-to-peak systolic velocity (N:S) ratio, and end diastolic velocity-to-diastolic notch velocity ratio was performed for each tracing. Several calculation methods were used to determine the Doppler indices for each lymph node. After the ultrasonographic examination, fine needle aspirates or excisional biopsy specimens of the examined lymph nodes were obtained, and lymphadenopathy was classified as either inflammatory or neoplastic (lymphomatous or metastatic) via cytologic or histologic examination. Results of Doppler analysis were compared with cytologic or histopathologic findings. Results-The Doppler index with the highest diagnostic accuracy was the S:D ratio calculated from the first recorded tracing; a cutoff value of 3.22 yielded sensitivity of 91%, specificity of 100%, and negative predictive value of 89% for detection of neoplasia. Overall diagnostic accuracy was 95%. At a sensitivity of 100%, the most accurate index was the N:S ratio calculated from the first recorded tracing; a cutoff value of 0.45 yielded specificity of 67%, positive predictive value of 81%, and overall diagnostic accuracy of 86.5%. Conclusions and Clinical Relevance-Results suggested that noninvasive Doppler spectral analysis may be useful in the diagnosis of neoplastic versus inflammatory peripheral lymphadenopathy in dogs.

Transient raise of endothelin-1 plasma level and reduction of ocular blood flow in a patient with optic neuritis

PURPOSE: To analyze how far an ischemic component might have been involved in optic neuritis. METHODS: Case report: a 32-year-old man with symptoms characteristic for optic neuritis underwent extensive clinical, laboratory/serological and vascular examination for systemic associations and vascular involvement. RESULTS: The patient was found to have a temporary ocular blood flow dysregulation and increased plasma endothelin-1 levels which decreased after the acute phase of the optic nerve. CONCLUSIONS: We conclude that there might be an ischemic component in this patient with optic neuritis and hypothesize that this ischemic component is at least in part due to a temporarily increased endothelin-1 level.

Thermodilution and esophageal Doppler ultrasound in the assessment of blood flow changes induced by endotoxin and dobutamine

BACKGROUND: Intermittent (IT) and continuous (CT) thermodilution and esophageal Doppler (ED), are all used for hemodynamic monitoring. The aim of this study was to test the agreement between these methods during endotoxin (ET) and dobutamine infusion. METHODS: Twenty-two pigs (39 +/- 1.8 kg body weight) were randomized to general anesthesia and either continuous ET (n = 9) or placebo (PL, n = 13) infusion. After 18 hours of ET or PL infusion, the animals were further randomized to receive dobutamine (n = 3 in ET, n = 5 in PL) or PL. A set of measurements using the three methods were obtained every hour, and the relative blood flow changes between two subsequent measurements were calculated. RESULTS: Bias or limits of agreement for flows were 0.73 L/min or 1.80 L/min for IT and CT, -0.33 L/min or 4.29 L/min for IT and ED, and -1.06 or 3.94 for CT and ED (n = 515, each). For flow changes they were 1% or 44%, 2% or 59%, and 3% or 45%, respectively. Bias and limits of agreement did not differ in ET- and PL-treated animals or in animals with or without dobutamine. Despite significant correlation between any two methods, the respective correlation coefficients (r) were small (IT vs. CT: 0.452; IT vs. ED: 0.042; CT vs. ED: 0.069; all p < 0.001). The same directional changes were measured by any two methods in 49%, 40%, and 50%. When IT flows >5 L/min were compared with IT flows 5 L/min.

Quantitative stress echocardiography in coronary artery disease using contrast-based myocardial blood flow measurements: prospective comparison with coronary angiography

AIM: To test whether quantitative stress echocardiography using contrast-based myocardial blood flow (MBF, ml x min(-1) x g(-1)) measurements can detect coronary artery disease in humans. METHODS: 48 patients eligible for pharmacological stress testing by myocardial contrast echocardiography (MCE) and willing to undergo subsequent coronary angiography were prospectively enrolled in the study. Baseline and adenosine-induced (140 microg x kg(-1) x min(-1)) hyperaemic MBF was analysed according to a three-coronary-artery-territory model. Vascular territories were categorised into three groups with increasing stenosis severity defined as percentage diameter reduction by quantitative coronary angiography. RESULTS: Myocardial blood flow reserve (MBFR)-that is, the ratio of hyperaemic to baseline MBF, was obtained in 128 (89%) territories. Mean (SD) baseline MBF was 1.073 (0.395) ml x min(-1) x g(-1) and did not differ between territories supplied by coronary arteries with mild (<50% stenosis), moderate (50%-74% stenosis) or severe (>or=75% stenosis) disease. Mean (SD) hyperaemic MBF and MBFR were 2.509 (1.078) ml x min(-1) x g(-1) and 2.54 (1.03), respectively, and decreased linearly (r2 = 0.21 and r2 = 0.39) with stenosis severity. ROC analysis revealed that a territorial MBFR <1.94 detected >or=50% stenosis with 89% sensitivity and 92% specificity. CONCLUSION: Quantitative stress testing based on MBF measurements derived from contrast echocardiography is a new method for the non-invasive and reliable assessment of coronary artery disease in humans.

Determinants of cerebral extracellular potassium after severe human head injury

The key role players of brain swelling seen after severe human head injury have only been partly determined. We used our human head injury data base to determine relationships between potassium, glutamate, lactate and cerebral blood flow (CBF). A total of 70 severely head injured patients (GCS < or = 8) were studied using intracerebral microdialysis to measure extracellular glutamate, potassium and lactate. Xenon CT was used to determine regional cerebral blood flow (rCBF). The mean +/- SEM of the r value of all patients, between potassium and glutamate, and potassium and lactate was 0.25 +/- 0.04 (p < 0.0001) and 0.17 +/- 0.06 (p = 0.006), respectively, demonstrating in both cases a positive relationship. rCBF was negatively correlated with potassium with marginal significance (r = -0.35, p = 0.08). When separated into two groups, patients with contusion had higher potassium levels than patients without contusion (1.55 +/- 0.03 mmol/l versus 1.26 +/- 0.02 mmol/l, respectively). These results in severely head injured patients confirm previous in vitro and animal studies in which relationships between potassium, glutamate, lactate and CBF were found. Potassium efflux is a major determinant of cell swelling leading to clinically significant cytotoxic edema due to increased glutamate release during reduced cerebral blood flow.

Whole-body vibration dosage alters leg blood flow

The effect of whole-body vibration dosage on leg blood flow was investigated. Nine healthy young adult males completed a set of 14 random vibration and non-vibration exercise bouts whilst squatting on a Galileo 900 plate. Six vibration frequencies ranging from 5 to 30 Hz (5 Hz increments) were used in combination with a 2.5 mm and 4.5 mm amplitude to produce twelve 1-min vibration bouts. Subjects also completed two 1-min bouts where no vibration was applied. Systolic and diastolic diameters of the common femoral artery and blood cell velocity were measured by an echo Doppler ultrasound in a standing or rest condition prior to the bouts and during and after each bout. Repeated measures MANOVAs were used in the statistical analysis. Compared with the standing condition, the exercise bouts produced a four-fold increase in mean blood cell velocity (P<0.001) and a two-fold increase in peak blood cell velocity (P<0.001). Compared to the non-vibration bouts, frequencies of 10-30 Hz increased mean blood cell velocity by approximately 33% (P<0.01) whereas 20-30 Hz increased peak blood cell velocity by approximately 27% (P<0.01). Amplitude was additive to frequency but only achieved significance at 30 Hz (P<0.05). Compared with the standing condition, squatting alone produced significant increases in mean and peak blood cell velocity (P<0.001). The results show leg blood flow increased during the squat or non-vibration bouts and systematically increased with frequency in the vibration bouts.

Culture-induced changes in blood-brain barrier transcriptome: implications for amino-acid transporters in vivo

Tight homeostatic control of brain amino acids (AA) depends on transport by solute carrier family proteins expressed by the blood-brain barrier (BBB) microvascular endothelial cells (BMEC). To characterize the mouse BMEC transcriptome and probe culture-induced changes, microarray analyses of platelet endothelial cell adhesion molecule-1-positive (PECAM1(+)) endothelial cells (ppMBMECs) were compared with primary MBMECs (pMBMEC) cultured in the presence or absence of glial cells and with b.End5 endothelioma cell line. Selected cell marker and AA transporter mRNA levels were further verified by reverse transcription real-time PCR. Regardless of glial coculture, expression of a large subset of genes was strongly altered by a brief culture step. This is consistent with the known dependence of BMECs on in vivo interactions to maintain physiologic functions, for example, tight barrier formation, and their consequent dedifferentiation in culture. Seven (4F2hc, Lat1, Taut, Snat3, Snat5, Xpct, and Cat1) of nine AA transporter mRNAs highly expressed in freshly isolated ppMBMECs were strongly downregulated for all cultures and two (Snat2 and Eaat3) were variably regulated. In contrast, five AA transporter mRNAs with low expression in ppMBMECs, including y(+)Lat2, xCT, and Snat1, were upregulated by culture. We hypothesized that the AA transporters highly expressed in ppMBMECs and downregulated in culture have a major in vivo function for BBB transendothelial transport.

Assessment of splanchnic blood flow using magnetic resonance imaging

BACKGROUND AND AIMS: The splanchnic circulation has an important function in the body under both physiological and pathophysiological conditions. Despite its importance, no reliable noninvasive procedures for estimating splanchnic circulation have been established. The aim of this study was to evaluate MRI as a tool for assessing intra-abdominal blood flows of the aorta, portal vein (VPO) and the major intestinal and hepatic vessels. METHODS: In nine healthy volunteers, the proximal aorta (AOP) and distal abdominal aorta (AOD), superior mesenteric artery (SAM), celiac trunk (CTR), hepatic arteries (common and proper hepatic arteries, AHC and AHP, respectively), and VPO were localized on contrast-enhanced magnetic resonance angiography images. Volumetric flow was measured using a two-dimensional cine echocardiogram-gated phase contrast technique. Measurements were taken before and 30 min after continuous intravenous infusion of somatostatin (250 microg/h) and were independently evaluated by two investigators. RESULTS: Blood flow measured by MRI in the VPO, SAM, AOP, AHP, and CTR significantly decreased after drug infusion. Flows in the AOD and AHC showed a tendency to decrease (P>0.05). Interrater agreement on flows in MRI was very good for large vessels (VPO, AOP, and AOD), with a concordance correlation coefficient of 0.94, as well as for smaller vessels such as the CTR, AHC, AHP, and SAM (concordance correlation coefficient =0.78). CONCLUSION: Somatostatin-induced blood flow changes in the splanchnic region were reliably detected by MRI. MRI may be useful for the noninvasive assessment of blood flow changes in the splanchnic region.