Baseline Blood Flow Research Articles

Aging Effect on Post-recovery Hypofusion and Mortality Following Cardiac Arrest and Resuscitation in Rats.

In this study we investigated the effect of aging on brain blood flow following transient global ischemia. Male Fisher rats (6 and 24 months old) underwent cardiac arrest (15 min) and resuscitation. Regional brain (cortex, hippocampus, brainstem and cerebellum) blood flow was measured in non-arrested rats and 1-h recovery rats using [14C] iodoantipyrene (IAP) autoradiography; the 4-day survival rate was determined in the two age groups. The pre-arrest baseline blood flows were similar in cortex, brainstem and cerebellum between the 6-month and the 24-month old rats; however, the baseline blood flow in hippocampus was significantly lower in the 24-month old group. At 1 h following cardiac arrest and resuscitation, both 6-month and 24-month groups had significantly lower blood flows in all regions than the pre-arrest baseline values; compared to the 6-month old group, the blood flow was significantly lower (about 40% lower) in all regions in the 24-month old group. The 4-day survival rate for the 6-month old rats was 50% (3/6) whereas none of the 24-month old rats (0/10) survived for 4 days. The data suggest that there is an increased vulnerability to brain ischemic-reperfusion injury in the aged rats; the degree of post-recovery hypoperfusion may contribute to the high mortality in the aged rats following cardiac arrest and resuscitation.

The waveform index of the ophthalmic artery predicts impaired coronary flow reserve

BackgroundCoronary flow reserve (CFR) can decrease with impairment in coronary microcirculation, even in the absence of epicardial conduit obstruction. Recently, the ophthalmic artery (OA), which is the first major branch of the internal carotid artery and is representative of microarterioles, has been identified using color Doppler sonography. However, the features of ultrasound waveform indices suggestive of impaired OA microcirculation and the relationships between these indices and CFR have not been elucidated. The present study aimed to assess the features of ultrasound waveform indices suggestive of impaired OA microcirculation and the relationships between these indices and CFR. Methods and resultsA total of 30 consecutive patients with a normal coronary angiogram and normal left ventricular function were studied. Patients with ≥25% stenosis of the right common or internal carotid artery were excluded. The CFR was defined as the ratio of adenosine-induced hyperemic to baseline blood flow velocity with an intracoronary Doppler guidewire. Color Doppler imaging was used to determine the blood flow velocity of the right OA, and the indices of peripheral resistance (resistance index [RI], pulsatility index [PI], and systolic mean velocity to diastolic mean velocity [Sm/Dm] ratio) were calculated. The ultrasound form showed a distinctive biphasic wave during systole followed by a monophasic wave during diastole. The velocity component in the early-systolic wave was higher than that in the mid-systolic wave or the diastolic wave (31.4±5.1 vs. 26.1±5.4 vs. 15.9±4.0cm/s, P<0.0001). The RI and PI were not related to the CFR, and the Sm/Dm ratio was negatively correlated with the CFR (β=−0.415, P=0.022). However, the relationship was attenuated by clinical variables closely associated with the Sm/Dm ratio or CFR, and hemoglobin A1c was a common mediator. The best Sm/Dm ratio cutoff for predicting an impaired CFR was 2.5 based on a receiver operating characteristic curve analysis. ConclusionsAn increase in the Sm/Dm ratio, which reflects a characteristic waveform, indicates impaired OA microcirculation. The ratio is negatively correlated with CFR, and therefore, it may be applied for the noninvasive evaluation of coronary physiology. Furthermore, hemoglobin A1c may be a common mediator for the OA and coronary microcirculation.

Associations between vasodilatory capacity, physical activity and sleep among younger and older adults.

Exercise promotes cardiovascular health through its direct impact on the vascular endothelium. Conversely, poor sleep quality is associated with endothelial dysfunction, which may explain the increased cardiovascular disease amongst poor sleepers. Yet, the influence of physical activity and poor sleep quality on vascular health is not clear. This study examined the relationships between forearm vasodilatory capacity, self-reported sleep quality and free-living, actigraphy-derived energy expenditure in a group of young and older community dwelling adults. Venous occlusion plethysmography determined baseline and peak forearm blood flow following reactive hyperemia. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Measures of body composition were assessed using dual energy X-ray absorptiometry. A total of 104 (61 young; 43 old) participants completed the study. In general, younger participants were more active, as determined by steps per day and average daily energy expenditure, but reported poorer sleep quality. In the combined sample, those who reported moderate sleep disturbances (PSQI total score; 11-15) had significantly lower vasodilatory capacity (16.8 ± 7.6 ml/100 ml/min) compared to those who reported no sleep disturbance (PSQI total score; 0-5) (22.3 ± 7.2 ml/100 ml/min) or mild sleep disturbance (PSQI total score; 6-10) (22.3 ± 8.1 ml/100 ml/min) (p < 0.01). After adjustment for physical activity, total body fat and age, moderately poor sleep remained an independent predictor of forearm vasodilatory capacity. These findings suggest that any positive vascular benefits accrued through increased physical activity might be offset by the negative consequences of chronically disturbed sleep.

Cerebral blood flow and oximetry response to blood transfusion in relation to chronological age in preterm infants

ObjectivePreterm infants frequently receive blood transfusion (BT) and the aim of this study was to measure the effect of BT on cerebral blood flow and oxygenation in preterm infants in relation to chronological age. PatientsPreterm infants undergoing intensive care recruited to three chronological age groups: 1 to 7 (Group 1; n=20), 8 to 28 (Group 2; n=21) & ≥29days of life (Group 3; n=18). MethodsPre and post-BT anterior cerebral artery (ACA) time averaged mean velocity (TAMV) and superior vena cava (SVC) flow were measured. Cerebral Tissue Haemoglobin Index (cTHI) and Oxygenation Index (cTOI) were measured from 15–20min before to 15–20min post-BT using NIRS. Vital parameters and blood pressure were measured continuously. ResultsMean BP increased significantly, and there was no significant change in vital parameters following BT. Pre-BT ACA TAMV was higher in Group 2 and 3 compared to Group 1 (p<0.001). Pre-BT ACA TAMV decreased significantly (p≤0.04) in all 3 groups; pre-BT SVC flow decreased significantly in Group 1 (p=0.03) and Group 3 (p<0.001) following BT. Pre-BT cTOI was significantly lower in Group 3 compared to Group 1 (p=0.02). cTHI (p<0.001) and cTOI (p<0.05) increased significantly post-BT in all three groups. PDA had no effect on these measurements. ConclusionBaseline cTOI decreases and ACA TAMV increases with increasing chronological age. Blood transfusion increased cTOI and cTHI and decreased ACA TAMV in all groups. PDA had no impact on the baseline cerebral oximetry and blood flow as well as changes following blood transfusion.

Association of the polymorphism in the androgen receptor gene and endothelial function in men with type 2 diabetes

In recent years, actively studied the effect of androgen deficiency on the cardiovascular system, including endothelial function. Genomic effects of testosterone caused by the length of CAG repeats polymorphism in the androgen receptor (AR) gene.Aim. To examine the association of the polymorphism in the AR gene and carbohydrate, lipid metabolism, endothelial function in men with type 2 diabetes.Materials and methods. We examined 88 men, aged 40-65 years (mean age 53±6,4years) with type 2 diabetes. All patients underwent the study of carbohydrate and lipid metabolism, the assessment of vasomotor endothelial function of the brachial artery by ultrasound sonography, were studied biochemical markers of endothelial dysfunction – ICAM-1, VCAM-1, p-selectin, e-selectin, resistin and number of CAG-repeats in the AR gene. Statistical analysis was performed using the application package SPSS 21,0 using regression analysis.Results. The number of CAG repeats had a significant positive regression to the level of total testosterone, a weak negative regression of the number of CAG repeats in the AR gene and lipid metabolism: triglycerides, LDL, atherogenic index. The assessment of the brachial artery ultrasonography revealed negative regression of the baseline brachial artery diameter and blood flow velocity in the endothelium-dependent vasodilation. The number of CAG repeats was significantly correlated with the levels of p-selectin and resistin. Thus, increasing the number of CAG repeats in the AR gene via a weakening of sensitivity to androgens leads to disruption of endothelial function in men with type 2 diabetes. Increasing the number of CAG repeats in the AR gene leads to deterioration of linear flow velocity during the test with reactive hyperemia with increasing production of p-selectin and resistin.Conclusions. The number of CAG repeats in the AR gene can be regarded as a predictor of the development and progression of cardiovascular lesions in men with type 2 diabetes.

Metronomic vinorelbine (oral) in combination with sorafenib in advanced non-small cell lung cancer.

To date, biomarkers to predict benefit from anti-angiogenic therapy are still lacking. Sorafenib and metronomic oral vinorelbine combination was studied and changes in blood and DCE-MRI parameters were investigated as biomarkers for benefit. Patients with advanced NSCLC were recruited to 3 successive cohorts. Each cohort was given a fixed metronomic (3 times a week) dose of oral vinorelbine at 60 mg/week, 90 mg/week, or 120 mg/week respectively. Within each cohort, patients received a starting dose of sorafenib at 200mg bid for 4 weeks. In the absence of dose-limiting toxicities, each patient's dose of sorafenib was escalated to 400mg bid for 4 weeks, 600 mg bid for 4 weeks and finally 800 mg bid. Biomarkers measured include DCE-MRI parameters, circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPs), and plasma thrombospondin (TSP-1). 48 evaluable patients were analyzed. There were 4 (8.9%) patients with partial response (PR) and 7 (15.2%) with cavitary response (CaR). Two subpopulations of CECs (CEC(hi), CEC(lo)) were identified that trended in opposite directions during treatment, with CEC(hi) demonstrating an upward trend in contrast to CEC(lo). Higher baseline CEC(hi) and lower baseline blood flow (F) and fractional intravascular blood volume (V1) predicted for response. Multivariate analysis revealed a lower baseline V1, and dynamic changes of CEC during treatment (CEC increase, sum of CEC(hi) and CEC(lo)) predicted for improved survival. Sorafenib and metronomic oral vinorelbine is active in advanced NSCLC. Baseline levels and changes in DCE parameters and CEC may be useful predictive biomarkers.

Temporal assessment of pancreatic blood flow and perfusion following secretin stimulation using noninvasive MRI.

To dynamically quantify pancreatic perfusion and flow within the arteries supplying the pancreas in response to secretin stimulation. Twelve healthy male subjects were scanned at 1.5T with arterial spin labeling to measure tissue perfusion and phase contrast magnetic resonance imaging (MRI) to measure vessel flow. Superior mesenteric (SMA), gastroduodenal (GDA), common hepatic (HA), and splenic (SA) arterial flow and pancreatic perfusion were serially measured for 50 minutes following 1 IU/kg intravenous secretin. The significance of differences between timepoints was tested using a repeated measures one-way analysis of variance (ANOVA). Baseline blood flow (mean ± SEM or median [IQR]) for SMA, HA, SA, and GDA was 7.6 ± 1.3, 4.0 ± 0.5, 8.2 ± 0.8, and 0.9 (0.8-1.4) ml/s, respectively. Baseline pancreatic perfusion was 200 ± 25 ml/100g/min. Blood flow increased in the SMA (234%, P < 0.0001) and GDA (155%, P = 0.015) immediately after secretin injection. Reduced HA blood flow was observed after 10 minutes (P = 0.066) with no change in SA flow (P = 0.533). Increased pancreatic perfusion was maintained for 40 minutes after injection with a maximal increase at 5 minutes (16.8%, P = 0.025). Intravenous secretin resulted in significant temporal changes in pancreatic perfusion and arterial blood flow.

Surgical treatment for optic neuropathy in high myopia

To improve the effectiveness of surgical treatment for optic neuropathy in high-degree myopia. A total of 54 patients (96 eyes) aged 18-30 with high myopia and signs of optic neuropathy were observed. The main group consisted of 20 patients (28 eyes) who underwent meridional scleral reinforcement with type I collagen-based implant placed over the posterior segment. The control group included 34 patients (68 eyes) who were given a 10-day vitamin and vascular therapy course. In most of the controls (21 patient, 21 eyes) indirect revascularization with ligation of the superficial temporal artery was performed. Ophthalmological examination was done before the beginning of the treatment and then at 1, 6, and 12 months. Results. At the end of the follow-up period best corrected visual acuity in the main group was 19.2% higher, on average, than baseline values, but remained unchanged in the controls. Light sensitivity of the retina in both group increased by 7% and 2% respectively. Electrically evoked phosphene thresholds decreased by 22.5% and 10.4% respectively. The main group also demonstrated a near-constant mean peripapillary nerve fiber layer (RNFL) thickness and a 16.4% higher than baseline blood flow velocity in the ophthalmic artery. In the control group the latter parameter showed no change. Scleral reinforcement surgery in patients with high myopia complicated by optic neuropathy enables improvement of visual functions and regional blood flow as well as stabilization of RNFL thickness and volume, thus, preventing subsequent development of optic nerve atrophy.

Laser-Doppler microvascular measurements in the peri-implant areas of different osseointegrated bone conductor implant systems.

The objective of this study was to evaluate the impact of hydroxyapatite coating of newly designed osseointegrated fixtures' abutments on the postoperative complication rates. The integrity of peri-implant microcirculation was used as a marker to compare tissue viability after different surgical techniques. Laser-Doppler Flowmetry (LDF) measures alone, and coupled with heat provocation tests were applied to test the different microcircular patterns. Measures for 17 consecutively implanted patients (8 women, 9 men, ages ranged from 18 to 77 years) were recruited; seven with soft tissue reduction (STR); and 10 with soft tissue preservation (STP).Thirteen non-operated retro-auricular areas were examined as naive controls. In isotherm conditions the baseline blood flow remained stable in all groups. The naive control patients demonstrated significant changes of blood flux in the intact skin. The non-implanted yet previously operated contralateral sides of the patients demonstrated marginally lower (p = 0.09) blood flux index. The STR sides however, showed significantly lower (average 217 %) provoked blood flux compared to controls (p < 0.001). At the STP sides a maladaptation could be observed (average 316 %) compared to the contralateral sides (p = 0.53). STP sides demonstrated a significantly better blood flow improvement compared to the STR sides (p = 0.02). These results suggest a favorable postoperative condition of vascular microcirculation after STP, than after STR surgery. The possibly faster wound healing and lower potential complication rate may widen the inclusion criteria and maybe beneficial for the patient compliance with a better quality-of-life.

High levels of pigment epithelium-derived factor in diabetes impair wound healing through suppression of Wnt signaling.

Diabetic foot ulcer (DFU) caused by impaired wound healing is a common vascular complication of diabetes. The current study revealed that plasma levels of pigment epithelium-derived factor (PEDF) were elevated in type 2 diabetic patients with DFU and in db/db mice. To test whether elevated PEDF levels contribute to skin wound-healing delay in diabetes, endogenous PEDF was neutralized with an anti-PEDF antibody in db/db mice. Our results showed that neutralization of PEDF accelerated wound healing, increased angiogenesis in the wound skin, and improved the functions and numbers of endothelial progenitor cells (EPCs) in the diabetic mice. Further, PEDF-deficient mice showed higher baseline blood flow in the skin, higher density of cutaneous microvessels, increased skin thickness, improved numbers and functions of circulating EPCs, and accelerated wound healing compared with wild-type mice. Overexpression of PEDF suppressed the Wnt signaling pathway in the wound skin. Lithium chloride-induced Wnt signaling activation downstream of the PEDF interaction site attenuated the inhibitory effect of PEDF on EPCs and rescued the wound-healing deficiency in diabetic mice. Taken together, these results suggest that elevated circulating PEDF levels contribute to impaired wound healing in the process of angiogenesis and vasculogenesis through the inhibition of Wnt/β-catenin signaling.

TCT-335 Validation of pressure-derived coronary flow reserve as an estimate of Doppler flow velocity and thermodilution derived coronary flow reserve

Coronary flow reserve is defined as the ratio of hyperaemic to baseline blood flow and is concomitantly affected by both epicardial patency and microvascular function. Recent insights in the prognostic value of the coronary microcirculation in ischemic heart disease revived the interest of

HABENULA RESPONSES DURING APPETITIVE AND AVERSIVE CONDITIONING IN MAJOR DEPRESSIVE DISORDER

ObjectiveThe lateral habenula (LHb) has been shown to respond to cues that predict aversive stimuli in non-human primates (Matsumoto & Hikosaka, 2009, Nat Neurosci, 12 (1), 77–84) and has been...

Contraction‐evoked vasodilation and functional hyperaemia are compromised in branching skeletal muscle arterioles of young pre‐diabetic mice

To investigate the effects of pre-diabetes on microvascular network function in contracting skeletal muscle. We hypothesized that pre-diabetes compromises contraction-evoked vasodilation of branching second-order (2A), third-order (3A) and fourth-order (4A) arterioles, where distal arterioles would be affected the greatest. Intravital video microscopy was used to measure arteriolar diameter (in 2A, 3A and 4A) and blood flow (in 2A and 3A) changes to electrical field stimulation of the gluteus maximus muscle in pre-diabetic (The Pound Mouse, PD) and control (c57bl6, CTRL) mice. Baseline diameter and blood flow were similar between groups (2A: ~20 μm, 3A: ~14 μm and 4A: ~8 μm; 2A: ~1 nL s(-1) and 3A: ~0.5 nL s(-1) ). Single tetanic contraction (100 Hz; 200, 400, 800 ms duration) evoked rapid-onset vasodilation (ROV) and blood flow responses that were blunted by ~50% and up to 81%, respectively, in PD vs. CTRL (P < 0.05). The magnitude of ROV was up to 2-fold greater at distal arterioles (3A and 4A) vs. proximal arterioles (2A) in CTRL; however, in PD, ROV of only 4A was greater than 2A (P < 0.05). Rhythmic contraction (2 and 8 Hz, 30 s) evoked vasodilatory and blood flow responses that were also attenuated by ~50% and up to 71%, respectively, in PD vs. CTRL (P < 0.05). The magnitude of vasodilatory responses to rhythmic contraction was also up to 2.5-fold greater at 4A vs. 2A in CTRL; however spatial differences in vasodilation across arteriolar branch orders was disrupted in PD. Arteriolar dysregulation in pre-diabetes causes deficits in contraction-evoked dilation and blood flow, where greatest deficits occur at distal arterioles.

Longitudinal alterations in the dynamic autoregulation of optic nerve head blood flow revealed in experimental glaucoma.

To use a novel dynamic autoregulation analysis (dAR) to test the hypothesis that the optic nerve head (ONH) blood flow (BF) autoregulation is disrupted during early stages of experimental glaucoma (EG) in nonhuman primates. Retinal nerve fiber layer thickness (RNFLT, assessed by optical coherence tomography) and ONH BF (assessed by laser speckle imaging technique) were measured biweekly before and after unilateral laser treatment to the trabecular meshwork. Each nonhuman primate was followed until reaching either an early stage of damage (RNFLT loss < 20%, n = 6) or moderate to advanced stages of damage (RNFLT loss > 20%, n = 9). At each test, dAR was assessed by characterizing ONH BF changes during the first minute of rapid manometrical intraocular pressure (IOP) elevation from 10 to 40 mm Hg. The dAR analysis extracted the following parameters: baseline BF, average BF 10 seconds before IOP elevation; BFΔmax, maximum BF change from baseline BF; Tr, time from baseline BF to the BFΔmax; Kr, average descending BF rate. Mean postlaser IOP was 20.2 ± 5.9 and 12.3 ± 2.6 mm Hg in EG and control eyes, respectively (P < 0.0001). Compared with prelaser values, baseline BF was higher in early EG, but lower in moderate to advanced EG (P = 0.01). Tr was increased and Kr was reduced in both stages (P < 0.01). BFΔmax was smaller in the early EG (P = 0.05) and remained low in the moderate to advanced EG (P = 0.15). No changes in the parameters were observed in control eyes. Chronic IOP elevation causes ONH autoregulation dysfunction in the early stage of EG, characterized by a disrupted BF response and delayed Tr, revealed by dAR analysis.

Metabolic syndrome and endothelin-1 mediated vasoconstrictor tone in overweight/obese adults

ObjectiveTo determine whether endothelin (ET)-1 vasoconstrictor tone is greater in overweight and obese adults with the metabolic syndrome (MetS). Materials/MethodsForty overweight/obese middle-aged and older adults (age: 43–71 years; BMI: 25.1–36.9 kg/m2) were studied: 20 without MetS (13 M/7 F) and 20 with MetS (13 M/7 F). MetS was established according to NCEP ATP III guidelines. Forearm blood flow (FBF; plethysmography) responses to intra-arterial infusion of selective ETA receptor blockade (BQ-123; 100 nmol/min; for 60 min) and non-selective ETA/B receptor blockade (BQ-123+BQ-788 [50 nmol/min for 60 min]) were determined. ResultsIn response to the selective ETA antagonism, there was a significant increase in forearm blood flow from baseline in both groups. However, the increase in forearm blood flow was significantly higher (P=0.03; ~45%) in the overweight/obese group with MetS than the group without MetS. In contrast, there were no significant group differences in FBF responses to non-selective ETA/B receptor blockade. Peak vasodilator responses to nonselective ETA/B blockade were ~50% higher than baseline blood flow in the overweight/obese groups without and with MetS. ConclusionMetS is associated with higher ET-1 vasoconstrictor tone in overweight/obese adults. The enhanced ET-1 vasoconstrictor activity with MetS is mediated by the ETA receptor subtype.

Abstract 9959: Chronic Administration of Pioglitazone and Pro-Oxidant Effects Within Chronic Hibernating Pig Hearts

Background: Glitazones have pleomorphic effects on myocardial metabolism. We hypothesized that the PPAR-gamma agent pioglitazone (PIO) would alter mitochondrial function and induce a pro-oxidant effect on chronically ischemic heart tissue. Methods: Eighteen pigs underwent a thoracotomy with placement of a fixed constrictor around the LAD artery. At 8-weeks post-instrumentation, they were given daily PIO (3 mg/kg) or placebo (P) in the chow for 4 weeks. Regional function by ECHO was measured at baseline and regional blood flows by μspheres were determined at baseline and during high-dose dobutamine (40 μg/kg/min). Using a high-speed drill, tissue was harvested and frozen for enzymatic analysis of high-energy nucleotides. Post-sacrifice, state 3 respiration was measured from isolated mitochondria and tissue levels of glutathionyl 4-oxo-2-nonenal (GS-ONE) were determined by liquid chromatography-tendem mass spectrometry measurement. Results: In all pigs, baseline regional wall thickening (%) was lower in the LAD versus Remote region (42±5% vs 58±5%; P&lt;0.05). LAD blood flow when normalized to the remote region was 83±5% at baseline and 64±7% during dobutamine, demonstrating the presence of chronic ischemic myocardium. The energetic state in the PIO group was more unfavorable than the placebo group, as manifested by lower transmural ATP levels (1.61±0.22 vs 2.35±0.25 μmol/g; P&lt;0.05) and depressed Phosphocreatine to ATP ratios (1.59±0.11 vs 2.11±0.16; P&lt;0.05). As shown by the figure, animals that received chronic PIO had higher levels of oxidant stress, as measured by GS-ONE levels and depressed rates of mitochondrial state 3 respiration. In summary, chronic administration of pioglitazone has a pro-oxidant effect on chronically ischemic hearts and an unfavorable effect on myocardial energetics, potentially by altering activity within the mitochondrial electron transport chain.

Isoflurane suppresses cortical spreading depolarizations compared to propofol — Implications for sedation of neurocritical care patients

Sedatives in the neurointensive care unit can strongly influence patients' risks of developing secondary brain damage. In particular, isoflurane, a volatile anesthetic, has been recently re-introduced to the neurointensive care unit, and first clinical studies suggest beneficial effects due to elevation of cerebral blood flow and reduction of metabolism. In contrast, propofol is a commonly used intravenous sedative that reduces cerebral blood flow and intra-cranial pressure. We have here studied the influence of these two sedatives on the occurrence of cortical spreading depolarizations (CSDs), which have emerged over the last decade as a major mechanism of delayed brain injury in stroke and brain trauma, constituting a substantial vascular and metabolic threat to peri-infarct tissue and being associated with poor patient outcome. Two experimental models were tested in Wistar rats anesthetized either with isoflurane or with propofol: KCl-evoked CSDs (n=10) and spontaneous CSDs after occlusion of the middle cerebral artery (n=14). Spatiotemporal patterns of CSD waves were observed by real-time laser speckle imaging of regional cerebral blood flow changes associated with the CSDs. During 30min of cortical KCl application, 5.2±0.7 CSDs were induced under isoflurane compared to 10.2±1.8 CSDs under propofol (p<0.001). After focal ischemia, 2.43±1.0 CSDs/h emerged spontaneously under isoflurane versus 6.83±2.5 CSDs/h under propofol (p<0.001). Furthermore, baseline blood flow and glycemia were much higher under isoflurane compared to propofol, which may set the tissue in better metabolic conditions to recover from the occurrence of CSD waves. We conclude that isoflurane, in comparison to propofol, decreases the occurrence of CSDs and may improve recovery from these metabolically demanding waves. To reduce CSD induced secondary tissue damage, we suggest isoflurane to be favored over propofol to sedate acute stroke and trauma patients in the neurointensive care unit.

Nitric oxide-releasing poly(vinyl alcohol) film for increasing dermal vasodilation

Pathological conditions associated with the impairment of nitric oxide (NO) production in the vasculature, such as Raynaud's syndrome and diabetic angiopathy, have stimulated the development of new biomaterials capable of delivering NO topically. With this purpose, we modified poly(vinyl-alcohol) (PVA) by chemically crosslinking it via esterification with mercaptosuccinic acid. This reaction allowed the casting of sulfhydrylated PVA (PVA-SH) films. Differential scanning calorimetry and X-ray diffractometry showed that the crosslinking reaction completely suppressed the crystallization of PVA, leading to a non-porous film with a homogeneous distribution of -SH groups. The remaining free hydroxyl groups in the PVA-SH network conferred partial hydrophylicity to the material, which was responsible for a swelling degree of ca. 110%. The PVA-SH films were subjected to an S-nitrosation reaction of the –SH groups, yielding a PVA containing S-nitrosothiol groups (PVA-SNO). Amperometric and chemiluminescence measurements showed that the PVA-SNO films were capable of releasing NO spontaneously after immersion in physiological medium. Laser Doppler-flowmetry, used to assess the blood flow in the dermal microcirculation, showed that the topical application of hydrated PVA-SNO films on the health skin led to a dose- and time-dependent increase of more than 5-fold in the dermal baseline blood flow in less than 10min, with a prolonged action of more than 4h during continuous application. These results show that PVA-SNO films might emerge as a new material with potential for the topical treatment of microvascular skin disorders.

Role of nitric oxide in optic nerve head blood flow regulation during an experimental increase in intraocular pressure in healthy humans

The present study set out to investigate whether nitric oxide, a potent vasodilator, is involved in the regulatory processes in optic nerve head blood flow during an experimental increase in intraocular pressure (IOP). The study was conducted in a randomized, double-masked, placebo-controlled, three way cross-over design. 12 healthy subjects were scheduled to receive either L-NMMA (an unspecific nitric oxide synthase inhibitor), phenylephrine (an α-adrenoceptor agonist) or placebo on three different study days. Optic nerve head blood flow was measured using laser Doppler flowmetry and IOP was increased stepwise with a suction cup. Mean arterial pressure (MAP) and IOP were measured non-invasively and ocular perfusion pressure (OPP) was calculated as OPP = 2/3 MAP-IOP. Administration of L-NMMA and phenylephrine significantly increased MAP and therefore OPP at rest (p < 0.01). L-NMMA significantly reduced baseline blood flow in the optic nerve head (p < 0.01). Application of the suction cup induced a significant increase in IOP and a decrease in OPP (p < 0.01). During the stepwise increase in IOP, some autoregulatory potential was observed until OPP decreased approximately −30% below baseline. None of the administered substances had an effect on this autoregulatory behavior (p = 0.49). The results of the present study confirm that the human optic nerve head shows some regulatory capacity during a decrease in OPP. Nitric oxide is involved in the regulation of basal vascular tone in the optic nerve head but does not seem to be involved in the regulatory mechanisms during an acute increase in IOP in young healthy subjects.

Intraperitoneal 1.5% Delflex improves intestinal blood flow in necrotizing enterocolitis

BackgroundNecrotizing enterocolitis (NEC) alters intestinal microvascular control mechanisms causing significant vasoconstriction. Our prior work with intraperitoneal 2.5% dextrose solution demonstrated increased intestinal perfusion in experimentally induced NEC. In the current study, we examine whether a buffered solution with lower glucose and osmolar loads similarly increases intestinal blood flow. We hypothesized that buffered 1.5% dextrose solution would increase ileal blood flow compared with baseline in NEC. MethodsWe randomly assigned pregnant Sprague-Dawley rats to control (n = 103) or NEC (n = 123) groups, by litter. We induced NEC by previously published methods. Control pups were vaginally delivered and dam-fed. We used laser Doppler flowmetry to evaluate perfusion in the terminal ileum at 12, 24, 48, 72, or 96 h after delivery at baseline and after application of topical 1.5% dextrose solution. We evaluated differences between groups and time points by analysis of variance and Tukey post hoc test. ResultsBaseline blood flow in the terminal ileum increased with gestational age in both groups (P < 0.05). Control groups had significantly greater baseline blood flow than NEC groups (P < 0.05), and topical application of buffered 1.5% dextrose solution increased blood flow compared with baseline in both groups at all time points (P < 0.05). ConclusionsTopical 1.5% dextrose solution significantly enhanced blood flow in the terminal ileum to the same degree as 2.5% dextrose solution. Thus, the use of buffered 1.5% dextrose solution might be more beneficial in treating clinical NEC, because it places a lower glucose and osmotic load on NEC-injured intestine.