Changes In Microcirculatory Flow Research Articles

Blood-brain Barrier Permeability May Influence Vasopressor Effects in Anesthetized Patients With Brain Tumor: An Analysis of Magnetic Resonance Imaging Data

Objective: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. We hypothesized that vasopressors induce microcirculatory flow changes, characterized by increased capillary transit time heterogeneity (CTH) and decreased mean transit time (MTT), in brain regions exhibiting BBB leakage. Methods: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. Postvasopressor to prevasopressor ratios of CTH, MTT, relative transit time heterogeneity (RTH), cerebral blood flow (CBF), cerebral blood volume, and oxygen extraction fraction (OEF) were calculated in tumor, peritumoral, hippocampal, and contralateral grey matter regions. Comparisons were made between brain regions and vasopressors. Results: During phenylephrine infusion, ratios of CTH, RTH, and CBF were greater, and ratios of MTT and OEF were lower, in the tumor region with contrast leakage compared with corresponding contralateral grey matter ratios. During ephedrine infusion, ratios of CTH, MTT, RTH, CBF, and cerebral blood volume were higher in the tumor region with leakage compared with contralateral grey matter ratios. In addition, the ratio of CBF was higher in all regions, the ratio of RTH was lower in the leaking tumor region, and the ratio of OEF was lower in peritumoral, hippocampal, and grey matter regions with ephedrine compared with phenylephrine. Conclusions: Vasopressors can induce distinct microcirculatory flow alterations in regions with compromised brain tumor barrier or BBB. Ephedrine, a combined α and β-adrenergic agonist, appears to result in fewer flow alterations and less impact on tissue oxygenation compared with phenylephrine, a pure α-adrenergic agonist.

Analysis of Microcirculatory Flow Changes After Hemodialysis

Analysis of Microcirculatory Flow Changes After Hemodialysis

Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery.

IntroductionMicrocirculatory dysfunction after cardiovascular surgery is associated with significant morbidity and worse clinical outcomes. Abnormal capillary blood flow can occur from multiple causes, including cytokine-mediated vascular endothelial injury, microthrombosis, and an inadequate balance between vasoconstriction and vasodilation. In response to proinflammatory cytokines, endothelial cells produce cellular adhesion molecules (CAMs) which regulate leukocyte adhesion, vascular permeability, and thus can mediate tissue injury. The relationship between changes in microcirculatory flow during circulatory shock and circulating adhesion molecules is unclear. The objective of this study was to compare changes in plasma soluble endothelial cell adhesion molecules (VCAM-1, ICAM-1, and E-Selectin) in patients with functional derangements in microcirculatory blood flow after cardiovascular surgery. MethodsAdult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass who exhibited postoperative shock were enrolled in the study. Sublingual microcirculation imaging was performed prior to surgery and within 2 h of ICU admission. Blood samples were taken at the time of microcirculation imaging for biomarker analysis. Plasma soluble VCAM-1, ICAM-1, and E-selectin in addition to plasma cytokines (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunoassay. ResultsOf 83 patients with postoperative shock who were evaluated, 40 patients with clinical shock had a postoperative perfused vessel density (PVD) >1 SD above (High PVD group = 28.5 ± 2.3 mm/mm2, n = 20) or below (Low PVD = 15.5 ± 2.0 mm/mm2, n = 20) the mean postoperative PVD and were included in the final analysis. Patient groups were well matched for comorbidities, surgical, and postoperative details. Overall, there was an increase in postoperative plasma VCAM-1 and E-Selectin compared to preoperative levels, but there was no difference between circulating ICAM-1. When grouped by postoperative microcirculation, patients with poor microcirculation were found to have increased circulating VCAM-1 (2413 ± 1144 vs. 844 ± 786 ng/mL; p < 0.0001) and E-Selectin (242 ± 119 vs. 87 ± 86 ng/mL; p < 0.0001) compared to patients with increased microcirculatory blood flow. Microcirculatory flow was not associated with a difference in plasma soluble ICAM-1 (394 ± 190 vs. 441 ± 256; p = 0.52). ConclusionsPoor postoperative microcirculatory blood flow in patients with circulatory shock after cardiac surgery is associated with increased plasma soluble VCAM-1 and E-Selectin, indicating increased endothelial injury and activation compared to patients with a high postoperative microcirculatory blood flow. Circulating endothelial cell adhesion molecules may be a useful plasma biomarker to identify abnormal microcirculatory blood flow in patients with shock.

Association between mean arterial pressure and sublingual microcirculation during major non-cardiac surgery: Post hoc analysis of a prospective cohort.

To test the hypothesis that there is an association between mean arterial pressure (MAP) and sublingual perfusion during major surgery, and perhaps an identifiable harm threshold. This post hoc analysis of a prospective cohort included patients who had elective major non-cardiac surgery with a duration of ≥2 h under general anesthesia. We assessed sublingual microcirculation every 30min using SDF+ imaging and determined the De Backer score, Consensus Proportion of Perfused Vessels (Consensus PPV), and the Consensus PPV (small). Our primary outcome was the relationship between MAP and sublingual perfusion which was evaluated with linear mixed effects modeling. A total of 100 patients were included, with MAP ranging between 65 mmHg and 120 mmHg during anesthesia and surgery. Over a range of intraoperative MAPs between 65 and 120 mmHg, there were no meaningful associations between blood pressure and various measures of sublingual perfusion. There were also no meaningful changes in microcirculatory flow over 4.5 h of surgery. In patients having elective major non-cardiac surgery with general anesthesia, sublingual microcirculation is well maintained when MAP ranges between 65 and 120 mmHg. It remains possible that sublingual perfusion will be a useful marker of tissue perfusion when MAP is lower than 65 mmHg.

Abstract WP326: Cortical Border Zones Are More Vulnerable to Spreading Depression-Induced Capillary Flow Disturbances

Cortical spreading depression (SD) is a major metabolic challenge to the brain and is followed by a unique hemodynamic response. It has been suggested that the oligemic phase of this response is accompanied by a mild to moderate capillary dysfunction. To test this hypothesis, we directly investigated microcirculatory flow changes during and after SD at the territory of major arteries as well as their hemodynamically vulnerable watershed zones. Swiss mice (n=6) under isoflurane anesthesia were tracheotomized, mechanically ventilated, and imaged under two-photon microscopy through a closed cranial window. Mean transit time (MTT), capillary transit time heterogeneity (CTH) and relative transit time heterogeneity (RTH) were calculated based on an indicator-dilution method using intravenous boluses of Texas-red dextran fluorescent dye (70,000 MW; 0.5%). Boluses were performed at the steady-state and 1 min, 5 min and 30 minutes after potassium chloride-induced SD. MTT, CTH, and RTH were estimated within the territory and border zone of major arteries to reveal any regional differences. Physiological parameters were monitored and kept within normal limits throughout the experiments. Both MTT and CTH increased following SD in the territorial zone from 1.07±0.03 to 1.67±0.15 s (mean±SEM;p&lt;0.01) and from 0.51±0.03 to 0.94±0.07 s (mean±SEM;p&lt;0.01), respectively. However, RTH was only mildly increased in this region from 0.49±0.04 to 0.59±0.06 (p=0.03). In the watershed area, all three parameters showed a more prominent increase following SD and RTH rose from 0.64±0.06 to 1.25±0.22 at 30 minutes (p=0.04). These findings provide direct experimental evidence for prolonged capillary flow disturbances induced by cortical SD, which may account for some lasting neurological symptoms after aura. The particular vulnerability of border zones to SD-induced flow disturbances may be involved in the pathogenesis of some of the white matter MRI lesions observed in migraineurs.

Ageing is a process where the growth effect of neuronal noradrenaline changes progressively in favour of the flow mediated, neurodegenerative and inflammatory effect of plasma noradrenaline

The noradrenaline stimulus has two components, one excitor, the other inhibitory. Neuronal noradrenaline is the excitor component and plasma noradrenaline is the inhibitory. The balance of effect between the two, the noradrenergic balance, is the controlled variable of the sympathetic system and determines the effect of noradrenaline. Neuronal noradrenaline stimulates tissues by diffusion from their sympathetic nerve endings, plasma noradrenaline does so by diffusion from their microcirculations. Changes in microcirculatory flow, by altering the flow mediated effect of plasma noradrenaline, are mainly responsible for altering the noradrenergic balance in the peripheral tissues; changes in CSF flow are speculated to be mainly responsible for doing the same in the brain, by altering the balance between synaptic noradrenaline in the brain and nonsynaptic noradrenaline in the subarachnoid CSF. When plasma noradrenaline alters the noradrenergic balance it triggers afferent sympathetic activity that alerts hypothalamic neurons to the event and they restore the balance and tissue homeostasis, within milliseconds, by adjusting the level of efferent sympathetic activity they project back to the affected tissue. Because the restoration is so rapid the effect of plasma noradrenaline is normally unobservable and dismissed as not having occurred. Because the hypothalamus is not involved with the responses of isolated canine lateral saphenous vein segments to noradrenaline, the effects of plasma noradrenaline in that preparation are not countered by reactive efferent activity and, consequently, are readily apparent in it. Quantitatively, they have been found to be a function of microcirculatory flow and noradrenaline concentration and, qualitatively, to be inhibitory, dilator, pro inflammatory and neurodegenerative. In life, due to a progressive increase in plasma noradrenaline concentration and, more so, in microcirculatory flow, the noradrenergic balance moves progressively in favour of the neurodegenerative and inflammatory effects of plasma noradrenaline. These observations are the basis of an hypothesis that ageing is caused by a genetically programmed shift in balance away from the growth and anti-inflammatory effects of neuronal noradrenaline, early in life, towards the neurodegenerative and pro-inflammatory effects of plasma noradrenalin, later in life. Death is believed to occur when plasma noradrenaline has damaged the structure of the sympathetic system so much that it can no longer create the minimum quantity of neurotransmitter needed to maintain the level of noradrenergic balance and homeostasis necessary for life.

Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis*.

Sepsis treatment guidelines recommend macrocirculatory hemodynamic optimization; however, microcirculatory dysfunction is integral to sepsis pathogenesis. We aimed to test the hypothesis that following macrocirculatory optimization, inhaled nitric oxide would improve microcirculation in patients with sepsis and that improved microcirculation would improve lactate clearance and multiple organ dysfunction. Randomized, sham-controlled clinical trial. Single urban academic medical center. Adult patients with severe sepsis and systolic blood pressure less than 90 mm Hg despite intravascular volume expansion and/or serum lactate greater than or equal to 4.0 mmol/L. After achievement of macrocirculatory resuscitation goals, we randomized patients to 6 hours of inhaled nitric oxide (40 ppm) or sham inhaled nitric oxide administration. We administered study drug via a specialized delivery device that concealed treatment allocation so that investigators and clinical staff remained blinded. We performed sidestream dark-field videomicroscopy of the sublingual microcirculation prior to and 2 hours after study drug initiation. The primary outcome measure was the change in microcirculatory flow index. Secondary outcomes were lactate clearance and change in Sequential Organ Failure Assessment score. We enrolled 50 patients (28 of 50 [56%] requiring vasopressor agents; 15 of 50 [30%] died). Although inhaled nitric oxide significantly raised plasma nitrite levels, it did not improve microcirculatory flow, lactate clearance, or organ dysfunction. In contrast to previous studies conducted during the earliest phase of resuscitation, we found no association between changes in microcirculatory flow and lactate clearance or organ dysfunction. Following macrocirculatory optimization, inhaled nitric oxide at 40 ppm did not augment microcirculatory perfusion in patients with sepsis. Further, we found no association between microcirculatory perfusion and multiple organ dysfunction after initial resuscitation.

Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis

Sepsis mortality is closely linked to multi-organ failure, and impaired microcirculatory blood flow is thought to be pivotal in the pathogenesis of sepsis-induced organ failure. We hypothesized that changes in microcirculatory flow during resuscitation are associated with changes in organ failure over the first 24 h of sepsis therapy. Prospective observational study. Emergency Department and Intensive Care Unit. Septic patients with systolic blood pressure <90 mmHg despite intravenous fluids or lactate >or=4.0 mM/L treated with early goal-directed therapy (EGDT). We performed Sidestream Dark Field (SDF) videomicroscopy of the sublingual microcirculation <3 h from EGDT initiation and again within a 3-6 h time window after initial. We imaged five sites and determined the mean microcirculatory flow index (MFI) (0 no flow to 3 normal) blinded to all clinical data. We calculated the Sequential Organ Failure Assessment (SOFA) score at 0 and 24 h, and defined improved SOFA a priori as a decrease >or=2 points. Of 33 subjects; 48% improved SOFA over 0-24 h. Age, APACHE II, and global hemodynamics did not differ significantly between organ failure groups. Among SOFA improvers, 88% increased MFI during EGDT, compared to 47% for non-improvers (P = 0.03). Median change in MFI was 0.23 for SOFA improvers versus -0.05 for non-improvers (P = 0.04). Increased microcirculatory flow during resuscitation was associated with reduced organ failure at 24 h without substantial differences in global hemodynamics. These data support the hypothesis that targeting the microcirculation distinct from the macrocirculation could potentially improve organ failure in sepsis.

Commentary on Viewpoint: The human cutaneous circulation as a model of generalized microvascular function

VIEWPOINTCommentary on Viewpoint: The human cutaneous circulation as a model of generalized microvascular functionMustafa YildizMustafa YildizPublished Online:01 Jul 2008https://doi.org/10.1152/japplphysiol.90316.2006MoreSectionsPDF (28 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat to the editor: Atherosclerosis begins at an early age, probably initially with a defect or injury of the arterial endothelial protective function and progresses with structural remodeling in the microcirculation. There are several noninvasive measurement techniques to assess vascular function that are associated with cardiovascular outcomes, including arterial pulse wave velocity, applanation tonometry, and carotid intima media thickness (1). These noninvasive techniques provide information about the functional and structural vascular changes at the level of aorta, muscular conduit arteries, the peripheral branches, and a little about microvascular components (3, 5). In recent years, several techniques (i.e., transcutaneous oxygen tension, photo-plethysmography, vital capillaroscopy, orthogonal polarization spectral imaging, iontophoresis, intradermal microdialysis, laser-Doppler flowmetry) have been developed to study the function of the microcirculation (1, 4). The microcirculatory flow changes on variations in concentrations of hormones, blood gases, physical factors like temperature and pressure, and it is controlled by autonomous nervous system as well. These stimuli increase or decrease the microvascular perfusion by regulating vasoconstriction or vasodilatation of the arterioles. Dysfunction of the microcirculation occurs in multiple tissue beds long before the onset of atherosclerotic symptoms. Impaired microcirculatory vasodilatation has been shown to occur in chronic inflammatory disease including peripheral vascular disease, hypertension, chronic renal failure, diabetes mellitus, hypercholesterolemia and obesity (1, 2, 4). In conclusion, although there are some limitations (i.e., minimally invasive, the control mechanisms of cutaneous vascular responses are complex), the cutaneous circulation is an important method for assessing the mechanisms of microcirculatory function and dysfunction.REFERENCES1 Abularrage CJ, Sidawy AN, Aidinian G, Singh N, Weiswasser JM, Arora S. Evaluation of the microcirculation in vascular disease. J Vasc Sur 42: 574–581, 2005.Crossref | PubMed | ISI | Google Scholar2 Holowatz LA, Thompson-Torgerson CS, Kenney WL. Viewpoint: The human cutaneous circulation as a model of generalized microvascular function. J Appl Physiol; doi:10.1152/japplphysiol.00858.2007.Link | ISI | Google Scholar3 Imura R, Yamamoto K, Kanamori K, Mikami T, Yasuda H. Noninvasive ultrasonic measurement of the elastic properties of the human abdominal aorta. Cardiovasc Res 20: 208–214, 1986.Crossref | ISI | Google Scholar4 Stewart J, Kohen A, Brouder D, Rahim F, Adler S, Garrick R, Goligorsky MS. Noninvasive interrogation of microvasculature for signs of endothelial dysfunction in patients with chronic renal failure. Am J Physiol Heart Circ Physiol 287: H2687–H2696, 2004.Link | ISI | Google Scholar5 Yildiz M, Altun A, Ozbay G. Assessment of arterial distensibility in patients with cardiac syndrome X. Angiology 58: 458–462, 2007.Crossref | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: M. Yildiz, Cardiology, Internal Medicine and Physiology, Dept. of Cardiology, Kartal Koşuyolu Yüksek Ihtisas Educational and Research Hospital, Istanbul, Turkey (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByArterial Distensibility in Chronic Inflammatory Rheumatic DisordersThe Open Cardiovascular Medicine Journal, Vol. 4, No. 1 More from this issue > Volume 105Issue 1July 2008Pages 382-382 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.90316.2006PubMed18641224History Published online 1 July 2008 Published in print 1 July 2008 Metrics

Regularities of changes in microcirculatory flow through different parts of the heart in patients with acquired valvular disease before and after surgery

Microcirculation in the subepicardium was studied in 30 patients with aortic acquired valvular disease (AVD) and 20 with mitral AVD with the use of an ALF-21 laser Doppler blood flowmeter (Transonic Systems). In total, 845 measurements were made. Subepimyocardial flow (EMF) was measured on the anterior surface of the right and left atria and on the anterior, posterior, and diaphragmatic surfaces of the left and right ventricles of the heart before and after surgery. A decrease in the hyperfunctioning of the chambers of the heart led to a redistribution of myocardial flow. Differences (ΔEMF) between EMF values observed before and after treatment were analyzed, and the coefficients for the linear equation ΔEMF = a + kEMFbs were computed by the least-squares method. It was found that blood flow decreased when it was enhanced before treatment and increased when it was weak initially. Thus, blood flow was balanced, approaching a value that did not change after treatment, and heterogeneity of coronary flow in the microcirculatory link decreased. Control mechanisms were assumed to change blood flow so that it acquires stability, which is needed to preserve and maintain normal energy parameters of the functioning myocardium.

Microcirculatory flow in the pancreas is markedly decreased in septic shock

O-8 Introduction: The hypothesis tested was that during septic shock changes in organ microcirculation correlate with changes in regional and systemic blood flow. Objective: To study changes in microcirculatory flow (MBF) in different organs in relation to changes in systemic (CI) and regional (superior mesenteric artery flow [SMA flow]) flow during septic shock in a clinically relevant pig model. Methods: During septic shock (induced by faecal peritonitis) CI was measured with thermodilution and SMA flow with ultrasound Doppler in nine anaesthetized pigs. MBF was continuously measured in the pancreas, liver, kidney and skeletal muscle by multi-channel laser Doppler flowmetry. 240 min after induction of shock, colloids (20 mL kg−1) were administered i.v. altering hypodynamic shock to hyperdynamic septic shock. Results: 240 min after induction of shock, CI, SMA flow and MBF in the kidney, liver and skeletal muscle had decreased by ≈ 50%. However, MBF in the pancreas decreased significantly more (66%, P<0.05). After 60 min of hyperdynamic shock (t=300 min) CI and SMA flow had increased to 70% above baseline. In contrast, MBF in liver and pancreas remained significantly below baseline and in kidney and muscle it barely returned to baseline. (Table)TableConclusion: During hyperdynamic septic shock microcirculatory flow in the pancreas was more severely affected than in other organs studied and compared to regional and systemic flow. During hyperdynamic septic shock microcirculatory flow remained low and the distribution of flow was heterogeneous and appeared to bear little relation to changes in systemic and regional flow.

Microcirculatory Flow Changes After Initial Resuscitation of Hemorrhagic Shock with 7.5% Hypertonic Saline/6% Dextran 70

In rabbits, laser Doppler flow probes were placed in the jejunum and on the renal cortex. Pulsed Doppler probes were implanted on the abdominal aorta and superior mesenteric and femoral arteries for measuring blood flow velocity. Cardiac output was measured by thermal dilution. Either 30% or 40% of the calculated blood volume was withdrawn through a carotid catheter. After 30 or 60 minutes, an initial bolus of either lactated Ringer's (LR, 16 ml/kg) or 7.5% hypertonic saline/6% dextran 70 (HSD; 4 ml/kg) IV was followed by unlimited IV LR (administered as rapidly as possible) to restore systemic arterial blood pressure to the prehemorrhage levels. With HSD, arterial pressure corrected more rapidly (p less than 0.05), and the initial hemodilution was greater (p less than 0.05), but there were no differences by two hours. With HSD, cardiac output (90%-100% vs. 130%-160% of control; p less than 0.05), plasma Na+ (139-140 mM vs. 146-148 mM; p less than 0.05) and plasma osmolarity (292-295 mOsm vs. 308-310 mOsm; p less than 0.05) were all significantly higher than the values with LR, but there was no effect on blood flow velocities through the infrarenal aorta, femoral artery, or superior mesenteric artery. Renal cortical perfusion (56% vs. 97% of control; p less than 0.05) and jejunal mucosal perfusion (83% vs. 162% of control; p less than 0.05) were significantly higher with HSD. HSD had no detectable effect on bacterial translocation at 24 hours. Thus: 1) HSD restores blood flow more rapidly to the gut mucosal and kidney microcirculations than initial resuscitation with LR; 2) the mechanism could be associated with a transient hemodilution and persistent increases in plasma Na and osmolarity, which reduce hemorrhage-induced cell swelling and blood viscosity changes; and 3) laser Doppler analysis could aid in the diagnosis of reperfusion injury after shock.

Quantitative Assessment of UV-Induced Changes in Microcirculatory Flow by Laser Doppler Velocimetry

Objective measurements of blood flow changes following UV irradiation in the skin of human volunteers have been made with the noninvasive technique of laser Doppler velocimetry (LDV). This optical procedure allowed perfusion (number of red cells X velocity) alterations in the cutaneous microcirculation to be monitored after exposure of the skin to UVA and UVB + UVC radiation. Response curves were obtained in 6 subjects following irradiation at 4 times the minimal UVB + UVC erythema dose (MED). Measurements were made on control (untreated) skin and on skin pretreated with a sunscreen lotion. It was found that: (1) the lotion vehicle had no protective effect, (2) the active sunscreen constituent (2-ethylhexylcinnamate, 5%) was significantly protective, and (3) the presence of bergapten (5-methoxypsoralen, 30 ppm) did not enhance or diminish the cinnamate protective effect. LDV measurements in 5 subjects were also taken during and subsequent to 5 daily exposures to 1 MED of UVB + UVC radiation. Control and pretreated skin sites were again studied and similar protective effects were observed. However, on subsequent reexposure of these sites to 4 MED of UVB + UVC, 14 days after the first of the 5 single MED doses, no significant change in skin blood perfusion was detected at either control or pretreated sites. In a separate series of experiments, LDV data were collected after UVA radiation exposures up to 15 J/cm2. No changes in microcirculation perfusion were detected in any of the situations considered. All LDV measurements were made with 2 instruments of slightly different design and were compared to subjective assessments of erythema performed by a single observer. The results suggest that LDV has significant potential as a means to quantify (1) UV exposures in excess of the MED and (2) the inhibition of UV-induced changes in microcirculatory flow by chemical protectants.

Microcirculatory flow changes during tissue growth

Red blood cell (RBC) velocities, lumen diameters, and volumetric flow rates were determined as functions of position and time in the microvessels of repairing tissue grown in a transparent rabbit ear chamber. By making repeated measurements in the same region, and in many instances, in exactly the same vessel over the entire growth period, we have discerned a distinct microcirculatory flow trend. The flow to a particular region (vessel) increases rapidly after an initial lag time, peaks out, and eventually decays to a steady-state level. This behavior is analogous to the vessel density pattern previously observed in this laboratory, but is delayed in time 1 to 2 weeks. These observations are consistent with mechanical, biochemical, and physiological mechanisms underlying neovascularization, tissue growth, and blood flow regulation, and provide a quantitative understanding of these processes.

Capillary flow in hemorrhagic shock. I. Hemorrhage in the nonanesthetized pig.

A deficiency in nutritive capillary blood flow is accepted as the basic pathophysiologic defect in hemorrhagic shock.1-4Therefore, we must understand the microcirculatory flow changes produced by hemorrhage, and the ability of therapeutic modalities to correct flow deficits, if we are to adequately evaluate methods of treatment of hemorrhagic shock. Attempts to study the flow changes in shock have been hindered by the lack of a method of measuring capillary flow. Many investigators have attempted to estimate capillary flow by measuring large vessel flow, usually by operative methods in anesthetized animals. These methods fail to differentiate nutritive flow from flow through arteriovenous pathways. Furthermore, enough sufficient hemodynamic variables are introduced by anesthesia,5-10operative manipulation,8-11and the frequently resultant mild hypothermia5,12and hypovolemia to cast doubt upon the validity of these methods. A new method, the tissue-blood radioactive potassium (42K) uptake ratio comparison technique, determines nutritive