Multispectral optoacoustic tomography of muscle perfusion and oxygenation under arterial and venous occlusion: A human pilot study

Perfusion and oxygenation are critical parameters of muscle metabolism in health and disease. They have been both the target of many studies, in particular using near‐infrared spectroscopy (NIRS). However, difficulties with quantifying NIRS signals have limited a wide dissemination of the method to the clinics. Our aim was to investigate whether clinical multispectral optoacoustic tomography (MSOT) could enable the label‐free imaging of muscle perfusion and oxygenation under clinically relevant challenges: the arterial and venous occlusion. We employed a hybrid clinical MSOT/ultrasound system equipped with a hand‐held scanning probe to visualize hemodynamic and oxygenation changes in skeletal muscle under arterial and venous occlusions. Four (N = 4) healthy volunteers were scanned over the forearm for both 3‐minute occlusion challenges. MSOT‐recorded pathophysiologically expected results during tests of disturbed blood flow with high resolution and without the need for contrast agents. During arterial occlusion, MSOT‐extracted Hb‐values showed an increase, while HbO₂‐ and total blood volume (TBV)‐values remained roughly steady, followed by a discrete increase during the hyperemic period after cuff deflation. During venous occlusion, results showed a clear increase in intramuscular HbO₂, Hb and TBV within the segmented muscle area. MSOT was found to be capable of label‐free non‐invasive imaging of muscle hemodynamics and oxygenation under arterial and venous occlusion. We introduce herein MSOT as a novel modality for the assessment of vascular disorders characterized by disturbed blood flow, such as acute limb ischemia and venous thrombosis.     

Effects of anesthetics on systemic hemodynamics in mice

The aim of this study was to compare the systemic hemodynamic effects of four commonly used anesthetic regimens in mice that were chronically instrumented for direct and continuous measurements of cardiac output (CO). Mice (CD-1, Swiss, and C57BL6 strains) were instrumented with a transit-time flow probe placed around the ascending aorta for CO measurement. An arterial catheter was inserted into the aorta 4 or 5 days later for blood pressure measurements. After full recovery, hemodynamic parameters including stroke volume, heart rate, CO, mean arterial pressure (MAP), and total peripheral resistance were measured with animals in the conscious state. General anesthesia was then induced in these mice using isoflurane (Iso), urethane, pentobarbital sodium, or ketamine-xylazine (K-X). The doses and routes of administration of these agents were given as required for general surgical procedures in these animals. Compared with the values obtained for animals in the conscious resting state, MAP and CO decreased during all anesthetic interventions, and hemodynamic effects were smallest for Iso (MAP, -24 +/- 3%; CO, -5 +/- 7%; n = 15 mice) and greatest for K-X (MAP, -51 +/- 6%; CO, -37 +/- 9%; n = 8 mice), respectively. The hemodynamic effects of K-X were fully antagonized by administration of the alpha(2)-receptor antagonist atipamezole (n = 8 mice). These results indicate that the anesthetic Iso has fewer systemic hemodynamic effects in mice than the nonvolatile anesthetics.     

Role of endothelium-derived relaxing factor in active hyperemia of the canine diaphragm.

To assess the effect of endothelium-derived relaxing factor (EDRF) on diaphragmatic vascular resistance at rest and during contractions, we studied an in situ isolated diaphragm preparation in anesthetized and mechanically ventilated dogs. The arterial supply of the left diaphragm (phrenic artery) was catheterized and perfused with arterial blood at a fixed flow rate. Drugs were infused through a side port of the arterial catheter at 1/100th of the phrenic arterial flow. The inferior phrenic vein was catheterized to complete the isolation from the systemic circulation. Three sets of experiments were performed. In set 1 (n = 3), we infused endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) dilators at increasing concentrations. ACh and SNP infusion elicited a dose-dependent decline in phrenic vascular resistance (Rphr) at concentrations greater than 10(-8) M and 0.50 micrograms/ml, respectively. In set 2 (n = 15), we infused an inhibitor of EDRF synthesis and release, L-argininosuccinic acid (ArgSA), at increasing concentrations (10(-4), 3 x 10(-4), and 6 x 10(-4) M). ArgSA produced a dose-dependent increase in Rphr. Infusion of another EDRF inhibitor (NG-nitro-L-arginine, LNA, 6 x 10(-4) M) elicited increase in Rphr similar to that induced by ArgSA. In set 3 (n = 25), we infused ArgSA or LNA (6 x 10(-4) M) simultaneously with ACh and SNP and during sustained (2-Hz) contractions of the diaphragm. Both ArgSA and LNA completely reversed ACh vasodilation, whereas SNP vasodilation was reversed by 26 and 11%, respectively. ArgSA or LNA infusion during contractions reversed vasodilation by 48 and 52%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

EDRF inhibition attenuates the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs.

At birth, pulmonary vasodilation occurs during rhythmic distension of the lungs and oxygenation. Inhibition of prostaglandin synthesis prevents pulmonary vasodilation during rhythmic distension of the lungs but not during oxygenation. Because endothelium-derived relaxing factor (EDRF) modulates pulmonary vascular tone at birth, at rest, and during hypoxia in older animals, we hypothesized that EDRF may modulate pulmonary vascular tone during oxygenation in fetal lambs. We studied the responses to N omega-nitro-L-arginine, a competitive inhibitor of EDRF synthesis, in nine near-term fetal lambs and to drug vehicle in six of these lambs and the subsequent responses to in utero ventilation with 95% O2 in these fetal lambs. In all fetal lambs, prostaglandin synthesis was prevented by meclofenamate. N omega-nitro-L-arginine increased pulmonary and systemic arterial pressures by 28% (P < 0.05) and 31% (P < 0.05), respectively, and decreased pulmonary blood flow by 83% (P < 0.05). In the controls, ventilation with 95% O2 increased pulmonary blood flow by 1,050% (P = 0.05) without changing pressures, thereby decreasing pulmonary vascular resistance by 88% (P = 0.05). During N omega-nitro-L-arginine infusion, ventilation with 95% O2 increased pulmonary blood flow by 162% (P = 0.05) and decreased pulmonary vascular resistance by 74% (P = 0.05). This suggests that EDRF may play an important role in modulating resting pulmonary vascular tone in fetal lambs and in the vasodilatory response to ventilation with O2 in utero.     

Pulmonary and systemic vascular effects of ATP in man

ATP induced-vasodilation was studied using Striadyne, on pulmonary and systemic arterial bed on 10 patients with stable chronic obstructive pulmonary disease. Such significant effects varied according to the dose: pulmonary vasodilation reached maximal level during low rate infusion (2 mumoles/kg/20 min) and systemic vasodilation was related to the dose. The latter became dominant at maximal dose (5 mumoles/kg/20 min). Simultaneously, on four patients, circulating blood level of ATP was assessed. It increased in proportion with the infusion rate and reached respectively 167% and 149 of baseline level on arterial and mixed venous blood.     

Systemic hemodynamics affecting cardiac output during hypocapnic and hypercapnic hypoxia

Systemic hemodynamic adjustments involved in the control of cardiac output (CO) were examined in chronically instrumented unanesthetized sheep inhaling gas mixtures resulting in hypocapnic hypoxia (H) [arterial pH (pHa) = 7.53, arterial partial pressure of O2 (Pao2) = 30 Torr, arterial partial pressure of CO2 (Paco2) = 29 Torr] or hypercapnic hypoxia (HCH) (pHa = 7.14, Pao2 = 34 Torr, Paco2 = 72 Torr) for 1 h. H (n = 7) and HCH (n = 6) resulted in 26% and 61% increases in CO, respectively, and mean systemic arterial pressure rose to a greater extent during HCH. Both H and HCH resulted in increased blood flow (microsphere method) to the peripheral systemic circulation including the brain, heart, diaphragm, and nonrespiratory skeletal muscle (the latter blood flow increased 120% during H and 380% during HCH). Gastrointestinal and renal blood flow remained unchanged during H and HCH. Transit time of green dye from the pulmonary artery to regional veins in the hindlimb and intestine was 5.0 and 8.2 s, respectively, during base-line conditions and remained unchanged with HCH. During HCH, regional O2 consumption increased 274% for the hindlimb and decreased 39% for the intestine. Total catecholamines rose 250% during H and 3,700% during HCH. During hypocapnic and hypercapnic hypoxia, CO is augmented in part by systemic hemodynamic adjustments that include a redistribution of blood flow and a translocation of blood volume to the fast transit time peripheral systemic circuit. The sympathetic nervous system may play an important role in mediating these systemic hemodynamic adjustments.     

Acetylcholine-induced vasodilation is mediated by nitric oxide and prostaglandins in human skin.

Acetylcholine (ACh) can effect vasodilation by several mechanisms, including activation of endothelial nitric oxide (NO) synthase and prostaglandin (PG) production. In human skin, exogenous ACh increases both skin blood flow (SkBF) and bioavailable NO levels, but the relative increase is much greater in SkBF than NO. This led us to speculate ACh may dilate cutaneous blood vessels through PGs, as well as NO. To test this hypothesis, we performed a study in 11 healthy people. We measured SkBF by laser-Doppler flowmetry (LDF) at four skin sites instrumented for intradermal microdialysis. One site was treated with ketorolac (Keto), a nonselective cyclooxygenase antagonist. A second site was treated with NG-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase. A third site was treated with a combination of Keto and L-NAME. The fourth site was an untreated control site. After the three treated sites received the different inhibiting agents, ACh was administered to all four sites by intradermal microdialysis. Finally, sodium nitroprusside (SNP) was administered to all four sites. Mean arterial pressure (MAP) was monitored by Finapres, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). For data analysis, CVC values for each site were normalized to their respective maxima as effected by SNP. The results showed that both Keto and L-NAME each attenuated the vasodilation induced by exogenous ACh (ACh control = 79 +/- 4% maximal CVC, Keto = 55 +/- 7% maximal CVC, L-NAME = 46 +/- 6% maximal CVC; P < 0.05, ACh vs. Keto or L-NAME). The combination of the two agents produced an even greater attenuation of ACh-induced vasodilation (31 +/- 5% maximal CVC; P < 0.05 vs. all other sites). We conclude that a portion of the vasodilation effected by exogenous ACh in skin is due to NO; however, a significant portion is also mediated by PGs.     

Hemodynamic responses to heat stress in the resting and exercising human leg: insight into the effect of temperature on skeletal muscle blood flow

Heat stress increases limb blood flow and cardiac output (Q) in humans, presumably in sole response to an augmented thermoregulatory demand of the skin circulation. Here we tested the hypothesis that local hyperthermia also increases skeletal muscle blood flow at rest and during exercise. Hemodynamics, blood and tissue oxygenation, and muscle, skin, and core temperatures were measured at rest and during exercise in 11 males across four conditions of progressive whole body heat stress and at rest during isolated leg heat stress. During whole body heat stress, leg blood flow (LBF), Q, and leg (LVC) and systemic vascular conductance increased gradually with elevations in muscle temperature both at rest and during exercise (r(2) = 0.86-0.99; P < 0.05). Enhanced LBF and LVC were accompanied by reductions in leg arteriovenous oxygen (a-vO(2)) difference and increases in deep femoral venous O(2) content and quadriceps tissue oxygenation, reflecting elevations in muscle and skin perfusion. The increase in LVC occurred despite an augmented plasma norepinephrine (P < 0.05) and was associated with elevations in muscle temperature (r(2) = 0.85; P = 0.001) and arterial plasma ATP (r(2) = 0.87; P < 0.001). Isolated leg heat stress accounted for one-half of the increase in LBF with severe whole body heat stress. Our findings suggest that local hyperthermia also induces vasodilatation of the skeletal muscle microvasculature, thereby contributing to heat stress and exercise hyperemia. The increased limb muscle vasodilatation in these conditions of elevated muscle sympathetic vasoconstrictor activity is closely related to the rise in arterial plasma ATP and local tissue temperature.     

Endothelin induces an initial increase in cardiac output associated with selective vasodilation in rats

The systemic and regional hemodynamic effects of endothelin (ET), a novel endothelial derived vasoconstrictor peptide were studied in Wistar Kyoto rats. A bolus of 1 nmol/Kg ET intravenously induced a transient 43% decrease in blood pressure associated with a 57% decrease in systemic resistance and a 30% increase in cardiac output (p less than 0.01 for all parameters). This was followed by an increase of 20% in arterial pressure and of 71% in systemic resistance and a decrease of 30% in cardiac output at 10 minutes. The initial fall in blood pressure was not abolished by pretreatment with verapamil, captopril, indomethacin, ketanserin, atropine, methylene blue or ethanol. Verapamil abolished the hypertensive phase by markedly decreasing cardiac output. ET had selective effects on the arterial tree; during the hypotensive phase it caused a transient increase in blood flow in the carotid and femoral arteries (+41% and +83% respectively, p less than 0.01) but a decrease in flow in the renal and mesenteric arteries (-53% and -44% respectively, p less than 0.05). Accordingly, there was a decrease in resistance in the carotid and femoral beds (-55% and -67% respectively, p less than 0.01) and an increase in resistance in the renal and mesenteric beds (+102%; p less than 0.01 and +23%; p = N.S. respectively). Subsequently there was an increase in resistance in all vascular beds to variable degrees. The maximal increase in resistance was in the renal bed (+156%). Thus, ET causes initially a potent systemic vasorelaxation and an increase in cardiac output later progressing to systemic vasoconstriction and a decrease in cardiac output. The initial vasodilation is selective, appearing in musculocutaneous beds but not in visceral beds.     

Influence of erythrocyte oxygenation and intravascular ATP on resting and exercising skeletal muscle blood flow in humans with mitochondrial myopathy

Oxygen (O₂) extraction is impaired in exercising skeletal muscle of humans with mutations of mitochondrial DNA (mtDNA), but the muscle hemodynamic response to exercise has never been directly investigated. This study sought to examine the extent to which human skeletal muscle perfusion can increase without reductions in blood oxygenation and to determine whether erythrocyte O₂ off-loading and related ATP vascular mechanisms are impaired in humans with mutations of mtDNA. Leg vascular hemodynamic, oxygenation and ATP were investigated in ten patients with mtDNA mutations and ten matched healthy control subjects: 1) at rest during normoxia, hypoxia, hyperoxia and intra-femoral artery ATP infusion, and 2) during passive and dynamic one-legged knee-extensor exercises. At rest, blood flow (LBF), femoral arterial and venous blood oxygenation and plasma ATP were similar in the two groups. During dynamic exercise, LBF and vascular conductance increased 9–10 fold in the patients despite erythrocyte oxygenation and leg O₂ extraction remained unchanged (p < 0.01). In the patients, workload-adjusted LBF was 28% to 62% higher during submaximal- and maximal exercises and was associated with augmented plasma ATP. The appropriate hemodynamic adjustments during severe hypoxia and ATP infusion suggest that erythrocyte O₂ off-loading and related ATP vascular mechanisms are intact in patients with mtDNA mutations. Furthermore, greater increase in plasma ATP and LBF at a given metabolic demand in the patients, in concert with unchanged oxyhemoglobin, suggest that erythrocyte O₂ off-loading is not obligatory for the exercise-induced increase in blood flow and intravascular ATP concentration.     

Cerebral Hemodynamic Changes of Mild Traumatic Brain Injury at the Acute Stage

Mild traumatic brain injury (mTBI) is a significant public health care burden in the United States. However, we lack a detailed understanding of the pathophysiology following mTBI and its relation to symptoms and recovery. With advanced magnetic resonance imaging (MRI), we can investigate brain perfusion and oxygenation in regions known to be implicated in symptoms, including cortical gray matter and subcortical structures. In this study, we assessed 14 mTBI patients and 18 controls with susceptibility weighted imaging and mapping (SWIM) for blood oxygenation quantification. In addition to SWIM, 7 patients and 12 controls had cerebral perfusion measured with arterial spin labeling (ASL). We found increases in regional cerebral blood flow (CBF) in the left striatum, and in frontal and occipital lobes in patients as compared to controls (p = 0.01, 0.03, 0.03 respectively). We also found decreases in venous susceptibility, indicating increases in venous oxygenation, in the left thalamostriate vein and right basal vein of Rosenthal (p = 0.04 in both). mTBI patients had significantly lower delayed recall scores on the standardized assessment of concussion, but neither susceptibility nor CBF measures were found to correlate with symptoms as assessed by neuropsychological testing. The increased CBF combined with increased venous oxygenation suggests an increase in cerebral blood flow that exceeds the oxygen demand of the tissue, in contrast to the regional hypoxia seen in more severe TBI. This may represent a neuroprotective response following mTBI, which warrants further investigation.     

Remote photonic sensing of cerebral hemodynamic changes via temporal spatial analysis of acoustic vibrations

A novel photonic method for remote monitoring of task‐related hemodynamic changes in human brain activation is presented. Physiological processes associated with neural activity, such as nano‐vibrations due to blood flow and tissue oxygenation in the brain, are detected by remote sensing of nano‐acoustic vibrations using temporal spatial analysis of defocused self‐interference random patterns. Temporal nanometric changes of the speckle pattern due to visual task‐induced hemodynamic responses were tracked by this method. Reversing visual checkerboard stimulation alternated with rest epochs, and responsive signals were identified in occipital lobe using near‐infrared spectroscopy. Temporal vibrations associated with these hemodynamic response functions were observed using three different approaches: (a) single spot illumination at active and control areas simultaneously, (b) subspots cross‐correlation‐based analysis, and (c) multiwavelength measurement using a magnitude‐squared wavelet coherence function. Findings show remote sensing of task‐specific neural activity in the human brain.     

Relationship between muscle sympathetic nerve activity and systemic hemodynamics during nitric oxide synthase inhibition in humans

Large interindividual differences exist in resting sympathetic nerve activity (SNA) among normotensive humans with similar arterial pressure (AP). We recently showed inverse relationships of resting SNA with cardiac output (CO) and vascular adrenergic responsiveness that appear to balance the influence of differences in SNA on blood pressure. In the present study, we tested whether nitric oxide (NO)-mediated vasodilation has a role in this balance by evaluating hemodynamic responses to systemic NO synthase (NOS) inhibition in individuals with low and high resting muscle SNA (MSNA). We measured MSNA via peroneal microneurography, CO via acetylene uptake and AP directly, at baseline and during increasing systemic doses of the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). Baseline MSNA ranged from 9 to 38 bursts/min (13 to 68 bursts/100 heartbeats). L-NMMA caused dose-dependent increases in AP and total peripheral resistance and reflex decreases in CO and MSNA. Increases in AP with L-NMMA were greater in individuals with high baseline MSNA (PANOVA<0.05). For example, after 8.5 mg/kg of L-NMMA, in the low MSNA subgroup (n=6, 28+/-4 bursts/100 heartbeats), AP increased 9+/-1 mmHg, whereas in the high-MSNA subgroup (n=6, 58+/-3 bursts/100 heartbeats), AP increased 15+/-2 mmHg (P<0.01). The high-MSNA subgroup had lower baseline CO and smaller decreases in CO with L-NMMA, but changes in total peripheral resistance were not different between groups. We conclude that differences in CO among individuals with varying sympathetic traffic have important hemodynamic implications during disruption of NO-mediated vasodilation.     

Upright LBPP application attenuates elevated postexercise resting thresholds for cutaneous vasodilation and sweating.

We evaluated postexercise venous pooling as a factor leading to previously reported increases in the postexercise esophageal temperature threshold for cutaneous vasodilation (ThVD) and sweating (ThSW). Six subjects were randomly exposed to lower body positive pressure (LBPP) and to no LBPP after an exercise and no-exercise treatment protocol. The exercise treatment consisted of 15 min of upright cycling at 65% of peak oxygen consumption, and the no-exercise treatment consisted of 15 min upright seated rest. Immediately after either treatment, subjects donned a liquid-conditioned suit used to regulate mean skin temperature and then were positioned within an upright LBPP chamber. The suit was first perfused with 20 degrees C water to control and stabilize skin and core temperature before whole body heating. Subsequently the skin was heated ( approximately 4.0 degrees C/h) until cutaneous vasodilation and sweating occurred. Forearm skin blood flow and arterial blood pressure were measured noninvasively and were used to calculate cutaneous vascular conductance during whole body heating. Sweat rate response was estimated from a 5.0-cm2 ventilated capsule placed on the upper back. Postexercise ThVD and ThSW were both significantly elevated (0.27 +/- 0.04 degrees C and 0.25 +/- 0.04 degrees C, respectively) compared with the no-exercise trial without LBPP (P < 0.05). However, the postexercise increases in both ThVD and ThSW were reversed with the application of LBPP. Our results support the hypothesis that the postexercise warm thermal responses of cutaneous vasodilation and sweating are attenuated by baroreceptor modulation via lower body venous pooling.     

Effects of short-term isocapnic hyperoxia and hypoxia on cardiovascular function.

Both hypoxia and hyperoxia have major effects on cardiovascular function. However, both states affect ventilation and many previous studies have not controlled CO(2) tension. We investigated whether hemodynamic effects previously attributed to modified O(2) tension were still apparent under isocapnic conditions. In eight healthy men, we studied blood pressure (BP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI) and arterial stiffness (augmentation index, AI) during 1 h of hyperoxia (mean end-tidal O(2) 79.6 +/- 2.0%) or hypoxia (pulse oximeter oxygen saturation 82.6 +/- 0.3%). Hyperoxia increased SVRI (18.9 +/- 1.9%; P < 0.001) and reduced HR (-10.3 +/- 1.0%; P < 0.001), CI (-10.3 +/- 1.7%; P < 0.001), and stroke index (SI) (-7.3 +/- 1.3%; P < 0.001) but had no effect on AI, whereas hypoxia reduced SVRI (-15.2 +/- 1.2%; P < 0.001) and AI (-10.7 +/- 1.1%; P < 0.001) and increased HR (18.2 +/- 1.2%; P < 0.001), CI (20.2 +/- 1.8%; P < 0.001), and pulse pressure (13.2 +/- 2.3%; P = 0.02). The effects of hyperoxia on CI and SVRI, but not the other hemodynamic effects, persisted for up to 1 h after restoration of air breathing. Although increased oxidative stress has been proposed as a cause of the cardiovascular response to altered oxygenation, we found no significant changes in venous antioxidant or 8-iso-prostaglandin F(2alpha) levels. We conclude that both hyperoxia and hypoxia, when present during isocapnia, cause similar changes in cardiovascular function to those described with poikilocapnic conditions.     

Diminished baroreflex control of heart rate responses in otoconia-deficient C57BL/6JEi head tilt mice

The maintenance of stable blood pressure during postural changes is known to involve integration of vestibular and cardiovascular central regulatory mechanisms. Sensory activity in the vestibular system plays an important role in cardiovascular regulation. The purpose of this study was to determine the role of vestibular gravity receptors in normal baroreflex function. Baroreflex heart rate (HR) responses to changes in blood pressure (BP) in otoconia-deficient head tilt (het) mice (n = 8) were compared with their wild-type littermates (n = 12). The study was carried out in conscious male mice chronically implanted with arterial and venous catheters for recording BP and HR and for the infusion of vasoactive drugs. Resting HR was higher in the het mice (661 +/- 13 beats/min) than in the wild-type mice (579 +/- 20 beats/min). BP was comparable in the het (113 +/- 4 mmHg) and wild-type mice (104 +/- 4 mmHg). The slopes of reflex decreases in HR in response to phenylephrine (PE) were blunted in the het mice (-5.5 +/- 1.5 beats x min(-1) x mmHg(-1)) compared with the wild-type mice (-8.5 +/- 0.9 beats x min(-1) x mmHg(-1)). Likewise, reflex tachycardic responses to decreases in BP with sodium nitroprusside (SNP) were significantly blunted in the het mice (-0.8 +/- 0.3 beats x min(-1) x mmHg(-1)) versus the wild-type mice (-2.2 +/- 0.6 beats x min(-1) x mmHg(-1)). Frequency-domain analysis of the HR variability suggests that under resting conditions, parasympathetic contribution was lower in the het versus wild-type mice. Mapping of the expression of immediate-early gene product, c-Fos, in forebrain and brain stem nuclei in response to a BP challenge showed no differences between the wild-type and het mice. These results suggest that tonic activity of gravity receptors modulates and is required for normal function of the cardiac baroreflexes.     

Skin blood flow influences near-infrared spectroscopy-derived measurements of tissue oxygenation during heat stress.

Near-infrared (NIR) spectroscopy is a noninvasive optical technique that is increasingly used to assess muscle oxygenation during exercise with the assumption that the contribution of skin blood flow to the NIR signal is minor or nonexistent. We tested this assumption in humans by monitoring forearm tissue oxygenation during selective cutaneous vasodilation induced by locally applied heat (n = 6) or indirect whole body heating (i.e., heating subject but not area surrounding NIR probes; n = 8). Neither perturbation has been shown to cause a measurable change in muscle blood flow or metabolism. Local heating (approximately 41 degrees C) caused large increases in the NIR-derived tissue oxygenation signal [before heating = 0.82 +/- 0.89 optical density (OD), after heating = 18.21 +/- 2.44 OD; P < 0.001]. Similarly, whole body heating (increase internal temperature 0.9 degrees C) also caused large increases in the tissue oxygenation signal (before heating = -0.31 +/- 1.47 OD, after heating = 12.48 +/- 1.82 OD; P < 0.001). These increases in the tissue oxygenation signal were closely correlated with increases in skin blood flow during both local heating (mean r = 0.95 +/- 0.02) and whole body heating (mean r = 0.89 +/- 0.04). These data suggest that the contribution of skin blood flow to NIR measurements of tissue oxygenation can be significant, potentially confounding interpretation of the NIR-derived signal during conditions where both skin and muscle blood flows are elevated concomitantly (e.g., high-intensity and/or prolonged exercise).     

Regional transcranial oximetry with near infrared spectroscopy (NIRS) in comparison with measuring oxygen saturation in the jugular bulb in infants and children for monitoring cerebral oxygenation]

Using a dual channel near infrared (NIR) in vivo optical spectroscopy (INVOS) system (INVOS 3100A, Somanetics Corp. Troy, MI, USA) we investigated the relationship between jugular venous oxygen saturation (SjvO2) and regional cerebral oxygen saturation (rSO2) in 30 infants and children (mean age 4.5 years) with congenital heart disease undergoing cardiac catheterisation. The NIRS-SomaSensor (emitter and dual receiver probe) was applied at a standardised right fronto-temporal location (over the right frontal cortex) on the infant's head and covered with an adhesive flexible bandage. Using NIR light (730 and 810 nm) and two source-detector spacings (3 and 4 cm from the transmitter), percentage values of rSO2 were calculated from detected haemoglobin saturations. Simultaneously, jugular venous oxygen saturation (SjvO2) monitoring was performed via a catheter placed in the right internal jugular vein with its tip positioned in the jugular bulb, as verified by fluoroscopy. To compare the reliability of NIRS measurement characteristics, jugular venous blood was analysed for SjvO2 as a reference measure of global cerebral oxygenation, by co-oximetry (OSM3-Hemoximeter, Radiometer Copenhagen, Denmark). Other measured variables included pulse oximetry, arterial blood pressure, and venous and arterial oxygen saturations. Over a jugular venous oxygen saturation range of 31-83%, a significant positive linear correlation was found between rSO2 (NIRS measurement) and SjvO2 (jugular bulb oximetry) (r = 0.93, p < 0.001). No significant correlation was observed between rSO2 values and arterial blood saturation or pulse oximetry. The quantitative correlation between rSO2 (haemoglobin oxygenation in a small hemi-elliptical area of the brain) and reference SjvO2 measurement (method for monitoring global cerebral oxygenation) suggests that NIRS measurement with subtraction algorithm should identify predominantly intracranial saturation in the pediatric age group, and will tend to reflect global oxygenation under physiological conditions. Transcranial oximetry using dual receiving channel NIRS offers a noninvasive, real-time, reliable and practicable means of monitoring cerebral haemoglobin oxygenation changes infants and children with cyanotic and noncyanotic congenital heart disease.     

Effect of raised portal venous pressure and postocclusive hyperemia on superior mesenteric arterial resistance in control and adenosine receptor blocked state in cats

Superior mesenteric arterial (SMA) blood flow was measured in pentobarbital-anesthetized cats using a noncannulating electromagnetic flowprobe. The selective adenosine antagonist 8-phenyltheophylline (8-PT) antagonized the dilator effect of infused adenosine but not isoproterenol. The vasodilation in response to reduced arterial perfusion pressure (autoregulation) was blocked by the adenosine receptor blockade, which also reduced the degree of postocclusive (1 min) hyperemia by one-half to two-thirds. The remainder of the hyperemia may have been due partially to adenosine, since exogenous adenosine still produced a small vasodilation (26%), so effects of endogenous adenosine could also still be expected to exert a small effect. Myogenic effects appear unlikely to be the mechanism of the small remaining hyperemia, since venous pressure increments within physiologically relevant ranges did not cause altered SMA conductance, and arterial dilation in response to large decreases in arterial pressure could be blocked by adenosine antagonism. Portal pressure was increased using hepatic nerve stimulation (8 Hz) to raise pressure from 7.0 to 12.4 mmHg (1 mmHg = 133.3 Pa). The small vasoconstriction seen in the SMA was due to the rise in systemic blood pressure, since prevention of a rise in SMA pressure prevented the response and 8-PT blocked the response (previously shown to block arterial pressure-flow autoregulation). An equal rise in PVP imposed by partial occlusion of the portal vein did not lead to changes in SMA vascular conductance. Thus, we conclude that within physiologically relevant ranges of arterial and portal venous pressure, the SMA does not show myogenic responses of the resistance vessels.     

Dilazep-induced vasodilation is mediated through adenosine receptors

Administration of dilazep, an inhibitor of adenosine uptake, significantly reduced systemic arterial blood pressure and increased superior mesenteric arterial conductance without affecting the plasma adenosine levels of femoral arterial or portal venous blood. Administration of a bolus dose of 8-phenyltheophylline (8-PT), an antagonist of adenosine receptors, blocked adenosine-mediated autoregulation of the superior mesenteric artery. After the blockade of adenosine receptors by 8-PT, dilazep did not produce vasodilation. These data suggest that dilazep has a vasodilating effect in vivo that is mediated by adenosine.