Phenylephrine alters phase synchronization between cerebral blood velocity and blood pressure in ME/CFS with orthostatic intolerance.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CBV) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60° head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decreased end-tidal CO2 (ETCO2; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, P < 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CBV compared with control (-22.5% vs. -8.7%, P < 0.005). To mitigate the orthostatic CBV reduction, we administered supplemental CO2, phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct n = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS + PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO2 and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS + PE= 0.69 ± 0.04, P < 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CBV.NEW & NOTEWORTHY We evaluated cognitive function before and after CO2, acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO2 nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO2 significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation.

Assessment of transcranial Doppler indices after MgSO4 administration in severe preeclamptic women with neurologic symptoms.

PURPOSE: To investigate the effect of intravenous MgSO4 on maternal cerebral hemodynamics as well as the association between altered Doppler indices of the ophthalmic arteries and ocular lesions in patients with preeclampsia. METHODS: After each of the 15 included patients was diagnosed with preeclampsia, MgSO4 was infused followed by transcranial Doppler tests of the indices of the ophthalmic, anterior, middle, posterior cerebral, vertebral, and basilar arteries, followed by a second MgSO4 infusion. The peak, mean, diastolic velocity, and pulsatile and resistance indices of each artery were automatically measured during testing. Based on the emergent data, the cerebral perfusion pressure, resistance-area product, and cerebral flow index were calculated. RESULTS: The cerebral perfusion pressure of the posterior cerebral arteries significantly decreased following the infusion of MgSO4 (p < 0.05). Before the infusion of MgSO4, cerebral perfusion pressure and cerebral flow index of the ophthalmic arteries were significantly increased (p < 0.05) in the preeclamptic pregnant patients with ocular lesions compared those without ocular lesions. After the infusion of MgSO4, the cerebral perfusion pressure and cerebral flow index of both ophthalmic arteries were slightly decreased, but the difference was not significant. CONCLUSIONS: Altered Doppler indices following the infusion of MgSO4 suggest significant changes in the hemodynamics of the posterior cerebral and ophthalmic arteries that are particularly related to the neurological signs and symptoms of women with preeclampsia. These findings may improve the understanding of the mechanism of the cerebral complications of preeclampsia. Advancing comprehension of these underlying mechanisms is postulated to play a pivotal role in the mitigation of hypertensive encephalopathy associated with preeclampsia.

Metformin improves skeletal muscle microvascular insulin resistance in metabolic syndrome.

Microvascular insulin resistance is present in metabolic syndrome and may contribute to increased cardiovascular disease risk and the impaired metabolic response to insulin observed. Metformin improves metabolic insulin resistance in humans. Its effects on macro and microvascular insulin resistance have not been defined. Eleven subjects with nondiabetic metabolic syndrome were studied four times (before and after 12 wk of treatment with placebo or metformin) using a crossover design, with an 8-wk washout interval between treatments. On each occasion, we measured three indices of large artery function [pulse wave velocity (PWV), radial pulse wave separation analysis (PWSA), brachial artery endothelial function (flow-mediated dilation-FMD)] as well as muscle microvascular perfusion [contrast-enhanced ultrasound (CEU)] before and at 120 min into a 150 min, 1 mU/min/kg euglycemic insulin clamp. Metformin decreased body mass index (BMI), fat weight, and % body fat (P < 0.05, each), however, placebo had no effect. Metformin (not placebo) improved metabolic insulin sensitivity, (clamp glucose infusion rate, P < 0.01), PWV, and FMD after insulin were unaffected by metformin treatment. PWSA improved with insulin only after metformin P < 0.01). Insulin decreased muscle microvascular blood volume measured by contrast ultrasound both before and after placebo and before metformin (P < 0.02 for each) but not after metformin. Short-term metformin treatment improves both metabolic and muscle microvascular response to insulin. Metformin's effect on microvascular insulin responsiveness may contribute to its beneficial metabolic effects. Metformin did not improve aortic stiffness or brachial artery endothelial function, but enhanced radial pulse wave properties consistent with relaxation of smaller arterioles.NEW & NOTEWORTHY Metformin, a first-line treatment for type 2 diabetes, is often used in patients with insulin resistance and metabolic syndrome. Here, we provide the first evidence for metformin improving muscle microvascular insulin sensitivity in insulin-resistant humans. Simultaneously, metformin improved muscle glucose disposal, supporting a close relationship between insulin's microvascular and its metabolic actions in muscle. Whether enhanced microvascular insulin sensitivity contributes to metformin's ability to decrease microvascular complications in diabetes remains to be resolved.

Dose Escalation and Safety of Capsaicin for Cerebral Perfusion Augmentation: A Pilot Study.

Background and Purpose: Sphenopalatine ganglion (SPG) electrical stimulation has been studied in the setting of acute ischemic stroke to enhance collateral flow. Capsaicin poses an alternative to chemically stimulate the sphenopalatine ganglion. Therefore, the objective of this study was to determine the safety and effect of increasing doses of capsaicin upon serial transcranial Doppler markers of cerebral blood flow. Methods: We performed serial transcranial Doppler testing in 30 healthy volunteers divided into 5 equal groups. Capsaicin doses ranged from 33 to 165 µMol. We recorded peak systolic and end-diastolic velocities in the middle cerebral artery, arterial pressure, and perceived pungency in 5-minute intervals up to 20 minutes. We then calculated the mean velocity, the pulsatility index, and the cerebral blood flow index. Results: The participants' median age was 21 years (range, 5 years); all reported consumption of capsaicin in their diets. After and during the study, none reported side effects. Perceived pungency peaked at 5 minutes, and by the 20-minute mark, none perceived any pungency. All the tested doses produced the same pattern, consisting of augmentation of the middle cerebral artery mean velocity with the pulsatility index's diminution. The effects peaked between the 5- and the 10-minute measurements and then returned to basal levels except for the 66-µMol doses, which produced a sustained effect. We found no correlation between perceived pungency and dose, but the middle cerebral artery mean velocity was strongly correlated with the dose administered. Conclusions: This study provides evidence supporting the safety and tolerability of oral capsaicin in a population of healthy volunteers. Capsaicin appears to produce effects similar to those of sphenopalatine ganglion electrical stimulation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04545892.

What drives transcranial Doppler velocity improvement in paediatric sickle cell anaemia: analysis from the Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study.

Children with sickle cell anaemia (SCA) and conditional transcranial Doppler (TCD) flow velocities (conditional: 170-199 cm/s; normal: <170 cm/s) have an increased risk of stroke. The Sickle Cell Clinical Research and Intervention Program (SCCRIP), a lifetime observational study, assessed the influence of haematological markers on TCD velocities. In children (≤16 years) with SCA (HbSS/HbSß0 -thalassaemia) and conditional TCD velocities (n = 32), increases in haemoglobin and in fetal haemoglobin after hydroxyurea initiation were significantly associated with decreases in TCD velocities. The benefit of pharmacological intervention to increase haemoglobin and fetal haemoglobin and normalise TCD velocities was demonstrated in this real-world dataset.

Pilot assessment of omega-3 fatty acids and potassium thiocyanate in sickle cell anemia patients with conditional peak systolic cerebral artery blood velocity.

OBJECTIVE: The purpose of this pilot study was to explore the effect of omega-3 fatty acids and potassium thiocyanate on conditional peak systolic cerebral artery blood velocity in children with sickle cell anemia (SCA). METHODS: Transcranial doppler ultrasonography (TCD) was done on 232 SCA children, and 21 found with conditional peak systolic blood velocity (PSV) of 200-249 cm/s in internal carotid, middle or anterior cerebral arteries. These were randomized to receive omega-3 fatty acids and potassium thiocyanate with standard treatment of SCA (test group, N = 14), or standard treatment only (control group, N = 7). After 3 months of treatment, PSV was measured again. RESULTS: Right middle cerebral artery PSV was significantly reduced in the test relative to the control groups (p = 0.04). PSV returned to normal in 79% of the test versus 43% of the control group; and increased to abnormal in one member of the control group, but none of the test group. CONCLUSIONS: The pilot data suggest that in SCA, omega-3 fatty acids and potassium thiocyanate might reduce conditional blood velocity to normal, or prevent progression to abnormal values. A larger, randomized, clinical trial is required to further address the current gap in management of conditional TCD blood velocity.

Acute pharmacodynamic effects of pimobendan in client-owned cats with subclinical hypertrophic cardiomyopathy.

BACKGROUND: Prior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability. RESULTS: Heart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations. Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02). No adverse events were observed following pimobendan administration. Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected. CONCLUSIONS: In client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted.

The impact of betamethasone on fetal pulmonary, umbilical and middle cerebral artery Doppler velocimetry and its relationship with neonatal respiratory distress syndrome.

BACKGROUND: Prenatal corticosteroid administration is known to be an effective strategy in improving fetal pulmonary maturity. This study aimed to evaluate the impact of maternal betamethasone administration on fetal pulmonary and other arteries Doppler velocity and the correlation between RDS development and Doppler indices results. METHODS: Fifty one singleton pregnancies between 26 and 34 gestational weeks with a diagnosis of preterm labor were included in the exposed group and received betamethasone. Fifty one uncomplicated pregnancies were included in the non-exposed group. Fetal pulmonary, umbilical and middle cerebral arteries Doppler parameters were evaluated before and 24 to 48 h after steroid administration in the exposed group and two times at same intervals in the non-exposed group. Maternal records were matched to neonatal charts if delivery happened, and demographic and outcome data were abstracted. RESULTS: When compared with the nonexposed group, fetuses treated with corticosteroids demonstrated significantly decreased umbilical artery Pulsatility index (PI) and significantly increased the middle cerebral artery PI, pulmonary artery Acceleration time (AT) and pulmonary artery AT/ET (Ejection time), while all other indices remained similar. We found significantly decreased pulmonary artery AT in the fetuses with respiratory distress syndrome (RDS) compared to those that did not. CONCLUSIONS: The results of our study showed that maternal antenatal betamethasone administration caused significant changes in the fetus blood velocity waveforms and also affected the blood flow in the pulmonary artery which led to an increase in the pulmonary artery AT and AT/ET. Among those fetuses with RDS, we found a significant decrease in the pulmonary artery AT, but we did not observe any pulmonary artery AT/ET differences.

Blood flow changes in the forearm arteries after ultrasound-guided costoclavicular brachial plexus blocks: a prospective observational study.

BACKGROUND: An increase in blood flow in the forearm arteries has been reported after brachial plexus block (BPB). However, few studies have quantitatively analysed the blood flow of the forearm arteries after BPB or have studied only partial haemodynamic parameters. The purpose of the present study was to comprehensively assess blood flow changes in the distal radial artery (RA) and ulnar artery (UA) after BPB performed via a new costoclavicular space (CCS) approach using colour Doppler ultrasound. METHODS: Thirty patients who underwent amputated finger replantation and received ultrasound-guided costoclavicular BPB were included in the study. The haemodynamic parameters of the RA and UA were recorded before the block and 10 min, 20 min, and 30 min after the block using colour Doppler ultrasound to determine the peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (Vmean), pulsatility index (PI), resistance index (RI) and area. The volumetric flow rate (VFR) was calculated using the formula Q = area×Vmean. The aforementioned parameters were compared not only before and after the BPB but also between the RA and UA. RESULTS: Compared with those of the respective baselines, there was a significant increase in the PSV, EDV, Vmean, area, and VFR and a significant decrease in the PI and RI of the RA and UA 10 min, 20 min, and 30 min post-block. The increase 30 min post-block in EDV (258.68 % in the RA, 279.63 % in the UA) was the most notable, followed by that in the Vmean (183.36 % in the RA, 235.24 % in the UA), and the PSV (139.11 % in the RA, 153.15 % in the UA) changed minimally. The Vmean and VFR of the RA were significantly greater than those of the UA before the BPB; however, there was no significant difference in the VFR between the RA and UA after the BPB. CONCLUSIONS: A costoclavicular BPB can increase blood flow in the forearm arteries. The RA had a higher volumetric flow rate than the UA before the BPB; however, the potential blood supply capacity of the UA was similar to that of the RA after a BPB. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/searchproj.aspx, clinical trial number: ChiCTR 1900023796, date of registration: June 12, 2019).

Salmon oil supplementation in dogs affects the blood flow of testicular arteries.

The administration of fish oils is known to cause changes in several reproductive parameters of domestic animals. The ingestion of polyunsaturated fatty acids (PUFAs) of the omega-3 family, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been described and correlated with changes in the semen quality, testosterone levels and male fertility. Nevertheless, few studies monitored and registered effects after ceasing supplementation. In the present study, we monitored the Doppler velocimetric and ultrasonographic parameters of nine dogs' testis for 90 days (D90) checking the effect of salmon oil supplementation, and monitoring continued for 60 days more, after ceasing supplementation (D150). Ultrasonographic evaluations comprised determining the Doppler velocimetric parameters, testicular and epididymal volume, and testicular echotexture. Peak systolic velocity (PSV) as well as final diastolic velocity (EDV) in the supratesticular arteries (STA), and marginal artery (MA) increased during the period of treatment and kept that level up to D150. There was no difference between the fish-oil supplementation period and the unsupplemented one regarding the testicular and epididymal volume and echogenicity and heterogeneity characteristics. A negative correlation was found between heterogeneity of testis and sperm production (r = -.41, p = .008). Doppler velocimetry indices were affected by the supplementation, leading to an increase in testicular blood flow.

Effect of NG -monomethyl l-arginine on microvascular blood flow and glucose metabolism after an oral glucose load.

OBJECTIVE: The aim of this study was to investigate whether the effects on local blood flow and metabolic changes observed in the skin after an endogenous systemic increase in insulin are mediated by the endothelial nitric oxide pathway, by administering the nitric oxide synthase inhibitor NG -monomethyl l-arginine using microdialysis. METHODS: Microdialysis catheters, perfused with NG -monomethyl l-arginine and with a control solution, were inserted intracutaneously in 12 human subjects, who received an oral glucose load to induce a systemic hyperinsulinemia. During microdialysis, the local blood flow was measured by urea clearance and by laser speckle contrast imaging, and glucose metabolites were measured. RESULTS: After oral glucose intake, microvascular blood flow and glucose metabolism were both significantly suppressed in the NG -monomethyl l-arginine catheter compared to the control catheter (urea clearance: P < .006, glucose dialysate concentration: P < .035). No significant effect of NG -monomethyl l-arginine on microvascular blood flow was observed with laser speckle contrast imaging (P = .81). CONCLUSION: Local delivery of NG -monomethyl l-arginine to the skin by microdialysis reduces microvascular blood flow and glucose delivery in the skin after oral glucose intake, presumably by decreasing local insulin-mediated vasodilation.

PACAP27 induces migraine-like attacks in migraine patients.

INTRODUCTION: Pituitary adenylate cyclase-activating polypeptide (PACAP) is found in two functional isoforms, namely PACAP38 and PACAP27. The migraine-inducing properties of PACAP38 are well studied. However, it is not known whether the lesser-known and under-studied protein isoform, PACAP27, can also induce migraine attacks. Here, we studied the effect of human PACAP27 infusion on induction of migraine in a provocation model. METHODS: In a crossover study, 20 migraine without aura patients were randomly assigned to receive human PACAP27 (10 picomol/kg/min) or saline (placebo) infusion over 20 min. We recorded the migraine and associated symptoms. RESULTS: All patients completed the study. PACAP27 provoked migraine-like attacks in 11 patients (55%) and two developed attacks after placebo (10%) (p = 0.022). The headache intensity and duration after PACAP27 was significantly greater compared to placebo (p = 0.003). CONCLUSION: PACAP27 triggers migraine attacks without aura. These novel data strengthen the role of PACAP and its receptors in migraine pathogenesis.

Altered cerebral perfusion in children with Langerhans cell histiocytosis after chemotherapy.

BACKGROUND AND PURPOSE: Children with Langerhans cell histiocytosis (LCH) may develop a wide array of neurological symptoms, but associated cerebral physiologic changes are poorly understood. We examined cerebral hemodynamic properties of pediatric LCH using arterial spin-labeling (ASL) perfusion magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective study was performed in 23 children with biopsy-proven LCH. Analysis was performed on routine brain MRI obtained before or after therapy. Region of interest (ROI) methodology was used to determine ASL cerebral blood flow (CBF) (mL/100 g/min) in the following bilateral regions: angular gyrus, anterior prefrontal cortex, orbitofrontal cortex, dorsal anterior cingulate cortex, and hippocampus. Quantile (median) regression was performed for each ROI location. CBF patterns were compared between pre- and posttreatment LCH patients as well as with age-matched healthy controls. RESULTS: Significantly reduced CBF was seen in posttreatment children with LCH compared to age-matched controls in angular gyrus (P = .046), anterior prefrontal cortex (P = .039), and dorsal anterior cingulate cortex (P = .023). Further analysis revealed dominant perfusion abnormalities in the right hemisphere. No significant perfusion differences were observed in the hippocampus or orbitofrontal cortex. CONCLUSION: Perfusion in specific cerebral regions may be consistently reduced in children with LCH, and may represent effects of underlying disease physiology and/or sequelae of chemotherapy. Studies that combine a formal cognitive assessment and hemodynamic data may further provide insight into perfusion deficits associated with the disease and the potential neurotoxic effects in children treated by chemotherapy.

Cerebral blood flow alterations associated with high volume caudal block in infants.

BACKGROUND: High-volume (1.5 ml kg-1) caudal block in infants results in major reductions of cerebral blood flow velocity (CBFV) and cerebral oxygenation, caused by rostral CSF movement which increases intracranial pressure. The primary aim of this study was to determine the relationship between injected volume and CBFV changes. We hypothesised that this volume-blood flow relationship would have a similar albeit inverted shape to the well-known intracranial pressure volume-pressure curve. METHODS: Fifteen subjects, age 0-6 months, mean (range) weight 4.9 (2.1-6.4) kg, were studied. A 1.5 ml kg-1 caudal injection of 0.2% ropivacaine was administered in three phases separated by two pauses. Subjects were randomised into five groups, in whom the pauses were implemented at different pre-set proportions of the total injected volume. Middle cerebral artery Doppler ultrasonography was used for CBFV measurements (Vmax, peak CBF velocity; Vmin, lowest CBF velocity; velocity time index). Mean flow velocity, pulsatility index, and resistivity index were calculated, and haemodynamic parameters were recorded. RESULTS: CBFV parameters decreased in all patients. The most affected parameter, Vmin, was reduced by ∼50% (range 15-68%) compared with baseline. There was a nonlinear relationship between the volume of the first phase injection and the CBFV measurement during the first pause. Across all time points, there was a linear relationship between volume administered and CBFV. Systemic haemodynamic parameters remained stable throughout the study. CONCLUSIONS: Injection pauses appear to attenuate adverse CBFV increases during administration of a high-volume caudal block.

Argatroban Increased the Basal Vein Drainage and Improved Outcomes in Acute Paraventricular Ischemic Stroke Patients.

BACKGROUND Since venous drainage in acute arterial ischemic stroke has not been thoroughly researched, we evaluate the effect of argatroban, a selective direct thrombin inhibitor, as a therapy to increase the rate of basal vein Rosenthal (BVR) drainage and improve patients' post-stroke outcomes. MATERIAL AND METHODS In this multicenter clinical trial, 60 eligible patients at 4.5 to 48 hours after the stroke onset were recruited. After being randomly allocated into 2 groups, they were treated with standard therapy either alone or with argatroban. RESULTS Compared to the contralateral brain hemisphere, the mean flow velocity (MFV) in BVR drainage was significantly reduced in the stroke-afflicted ipsilateral hemisphere. After treatment with argatroban for 7 days, the MFV from BVR of the ipsilateral hemisphere in the argatroban treated group was significantly increased when compared to the control group. At 90 days after the onset of stroke, the MFV of BVR in the ipsilateral hemisphere was similar in both groups. Compared with controls, the argatroban-treated patients had smaller lesions from baseline to 7 days. Argatroban also improved National Institutes of Health Stroke Scale (NIHSS) scores on day 7 after the onset of stroke. Furthermore, the argatroban group's neurological functions were superior to those of their untreated counterparts after 90 days. No difference was found in the incidence of adverse reactions between the 2 groups. CONCLUSIONS These observations indicate that vein drainage change may contribute to the acute phase of brain edema and the outcomes of ischemic stroke patients.

Carotid Artery Corrected Flow Time and Respiratory Variations of Peak Blood Flow Velocity for Prediction of Hypotension After Induction of General Anesthesia in Adult Patients Undergoing Elective Surgery: A Prospective Observational Study.

OBJECTIVES: Hypotension is common after induction of general anesthesia, and intraoperative hypotension is associated with postoperative end-organ injury such as acute kidney injury and myocardial ischemia. This study was designed to determine the utility of the carotid corrected flow time (cFT) and carotid artery peak blood flow velocity variation (ðVpeak ) for prediction of hypotension after induction of general anesthesia. METHODS: Adult patients (n = 112) undergoing any elective surgery under general anesthesia who fasted for at least 6 to 8 hours were recruited in this prospective observational study. The common carotid artery cFT and ðVpeak were measured with ultrasound 10 minutes before induction of general anesthesia. After that, general anesthesia with propofol was used, and hemodynamic data were collected until 3 minutes after induction of anesthesia. RESULTS: The carotid cFT was significantly correlated with percentages of the fall in the systolic blood pressure at 2 minutes (P < .0001) and 3 minutes (P < .0001) and percentages of the fall in the mean arterial pressure at 1 minute (P = .0006), 2 minutes (P < .0001), and 3 minutes (P < .0001). The cFT was a predictor of hypotension after induction of general anesthesia, with an area under the receiver operating characteristic curve of 0.91. The best cutoff value obtained from this study was 330.2 milliseconds or less, which predicted postinduction hypotension with sensitivity and specificity of 85.7% and 96.8%, respectively. The ðVpeak was an inferior predictor of postinduction hypotension, with an area under the receiver operating characteristic curve of 0.68. The optimum cutoff value was 18.8%, with sensitivity and specificity of 61.9% and 67.4%. CONCLUSIONS: The cFT measured in the common carotid artery is a reasonable predictor of hypotension after induction of general anesthesia in American Society of Anesthesiologists physical status I and II patients. Further studies are required to identify its role in high-risk patients such as older groups and patients with cardiovascular diseases and also to identify interobserver and intraobserver variability of cFT and ðVpeak measurements.

The Effect of Antenatal Vaginal Progesterone Administration on Uterine, Umbilical, and Fetal Middle Cerebral Artery Doppler Flow: A Cohort Study.

OBJECTIVE: This study aimed to evaluate the effect of vaginal progesterone (P) administration during the second and third trimesters of pregnancy on Doppler velocimetry of uterine, umbilical, and middle cerebral vessels. STUDY DESIGN: A prospective cohort study conducted on 80 women at risk for preterm labor. Uterine artery, umbilical artery, and middle cerebral artery (MCA) Doppler indices were measured before and after 1 week of administration of 200 mg twice daily vaginal P. The primary outcome parameter was the change of MCA pulsatility index (PI) after P administration. Secondary outcomes included changes in uterine artery and umbilical artery Doppler measurement. RESULTS: There was no significant changes of umbilical artery resistance index (RI) (0.69 ± 0.049 vs. 0.68 ± 0.041), umbilical artery PI (1.14 ± 0.118 vs. 1.11 ± 0.116), uterine artery RI (0.66 ± 0.12 vs. 0.66 ± 0.107), uterine artery PI (1.00 ± 0.26 vs. 1.016 ± 0.24), and MCA PI (1.27 ± 0.18 vs. 1.26 ± 0.23) measurements before and after 1 week of P administration, respectively. CONCLUSION: Administration of vaginal P has no significant effects on uterine artery, umbilical artery, and MCA Doppler indices.

Higher doses of Melatonin affect ovarian and middle uterine arteries vascular blood flow and induce oestrus earlier in acyclic ewes.

The present study aimed to evaluate the effect of a single intramuscular injection of melatonin on response of oestrus, rate of conception, ovarian and uterine blood supply during the non-breeding season. Melatonin powder was dissolved in dimethyl sulfoxide (DMSO) and olive oil and injected in two dose of 25 mg (MEL-1; n = 10) and 50 mg (MEL-2; n = 10) in May. Ten ewes were served as the control (CON). Results showed that oestrous response was higher in the MEL-2 group than in other groups (p < .01). The time to onset of oestrus in both the MEL-1 and MEL-2 groups was significantly shorter, compared with the CON group (p < .01). Pregnancy rates reached 80% and 90% at 45 days of gestation. Doppler indices of the right and left ovarian artery were lower in the melatonin groups than in normal groups (p < .01). Both Doppler indices in uterine arteries were not different among two treatment groups (p > .05), but there was a significant difference when compared with the CON group (p < .01), no difference found between two treatment group in the Doppler velocities of middle uterine arteries (p > .05). In conclusion, the definite changes in the studied parameters showed two novel findings; (a) the increase in melatonin dose results in increasing the blood flow expressed by increased Doppler velocities in fatty tailed ewes, (b) as well as, melatonin can initiate the breeding season regardless of the season earlier by 1-2 months in ewes.

Ovarian and uterine arteries blood flow waveform response in the first two cycles following superstimulation in cows.

To investigate the ovarian and uterine blood flow responses, hemodynamic, circulating ovarian hormones and nitric oxide (NO) after end of treatment by Folltropin. Holstein Friesian (12) cows previously synchronized with CIDR underwent Doppler ultrasound after administrating of FSH daily for 4 days in eight injections started on day 10 of the second ovulation (day -5). Oestradiol (E2), progesterone (P4) and nitric oxide (NOMs) were measured. During the follicular phase, follicle area and antrum area of the second cycle reached maximum value on the day of ovulation compared with that in the first cycle, while during the luteal phase, both showed a pattern of increase and decrease. The luteal area and total coloured area increased till day 10 in the first and second cycle. The first cycle ipsilateral ovarian artery (Ov.A) had higher pulsatility (PI) (p = .001), resistance (RI) (p = .001), peak velocity (PSV) (p = .009) and lower end-diastolic velocity (EDV) (p = .003) compared with the second cycle. The increased ipsilateral Ov.A PSV (p = .009) was accompanied by lower EDV. The first cycle ipsilateral middle uterine artery (MUA) had higher PI (p = .001) and RI (p = .001), with lower PSV (p = .001) and EDV (p = .001). It was concluded that blood flow of ovarian and middle uterine arteries changed after the end of superstimulation as the increased ipsilateral Ov. A and MUA PSVs accompanied by lower EDV and both Doppler indices that reflect the amount of ovarian and uterine blood flow waveform.

Ginsenoside CK-loaded self-nanomicellizing solid dispersion with enhanced solubility and oral bioavailability.

Ginsenoside compound K (CK) is a major ginsenoside metabolite of protopanaxadiol, which exhibits numerous pharmacological activity such as cardioprotective and antidiabetic. However, the therapeutic application of CK is hampered by its physicochemical characteristics and low oral bioavailability (BA). The present work aims at the preparation of CK to improve its dissolution and enhance the oral BA for the management of arrhythmia by using self-nanomicellizing solid dispersion system (SSD). The formulations were characterized by advanced techniques like DSC, XRD, FTIR, SEM and XRD. In the in vivo pharmacokinetic study, UPLC-MS/MS was used to measure the concentration of CK in plasma. Mapping Lab was applied in the experiment of perfused intact hearts to determine the ventricular rate and ventricular conduction velocity. The solubility of CK-SSD8 was 4658.11 ± 6.66 µg/ml, which is 130-fold than free CK, and the dissolution rate was faster than any other dosage forms. The average diameters of CK-SSD were smaller than 100 nm. The in vivo pharmacokinetic study revealed that the AUC(0-24) of CK-SSD8 formulation was 2.02-fold higher than pure CK. Moreover, the study performed to evaluate the efficiency in arrhythmia treatment showed a reduced ventricular rate and ventricular conduction velocity. Thus, CK-SSD could serve as potential carrier candidate in improving the clinical application of CK.