Reduction In Mean Arterial Pressure Research Articles

Effect of perioperative dexmedetomidine infusion on blood glucose levels in non-diabetic morbid obese patients undergoing laparoscopic bariatric surgery

BackgroundThis study was designed to assess the clinical efficacy of dexmedetomidine premedication on neuroendocrine stress response by analysis of perioperative fluctuation of blood sugar level during laparoscopic bariatric surgery. Dexmedetomidine when used as an additive to general anesthesia blocks stress response to various noxious stimuli, maintains perioperative hemodynamic stability.Settings and designSixty patients undergoing laparoscopic sleeve gastrectomy were divided randomly into two groups. The dexmedetomidine group (Group D), received dexmedetomidine infusion, while the control group (Group C) received normal saline 0.9% in the same amount and rate as placebo. In group D, dexmedetomidine was given intravenously (IV) as loading dose of 1 μg/kg over 10 min prior to induction. After induction, it was given as infusion at a dose of 0.5 μg/kg/h for maintenance.Perioperative blood sugar levels were analyzed preoperatively, at 30 min after beginning of surgery then hourly till surgery ends, and six h after surgery. Anesthetic and surgical procedures were standardized. All patients were also assessed for intraoperative hemodynamic changes at specific timings, intraoperative narcotic consumption and recovery profile.ResultsPerioperative administration of dexmedetomidine infusion had essentially weakened the stress response. In the C group there was significantly higher blood sugar values compared to group D one hour after start of surgery up to 6 h later. Also, regarding hemodynamics there was significant reduction in heart rate (HR) and mean arterial blood pressure (MAP) in D group.ConclusionsDuring the laparoscopic sleeve gastrectomy, dexmedetomidine premedication has effectively regulated the neuroendocrine stress response of general anesthesia as analyzed by perioperative blood sugar variation. Also, it maintained the hemodynamic stability.

Accelerated conversion of atrial fibrillation to normal sinus rhythm by pulmonary delivery of flecainide acetate in a porcine model

Pulmonary delivery of antiarrhythmic agents has the potential to increase rapidly targeted drug concentrations in pulmonary veins and left atrium to terminate atrial fibrillation (AF). We evaluated the efficacy of flecainide administered via intratracheal instillation in terminating AF in a reliable preclinical model. In 11 closed-chest anesthetized Yorkshire pigs, AF was induced by intrapericardial administration of acetylcholine (1 mL of 102.5 mM solution) followed by burst pacing and allowed to continue for 2 minutes before intratracheal flecainide (0.4 or 0.75 mg/kg) administration. Both the 0.4- and 0.75-mg/kg doses of intratracheal flecainide significantly reduced AF duration by 35% (P = .02) and 54% (P = .001), respectively, compared to no-drug baseline. There was a strong inverse correlation (r2 = 0.87; P = .03) between the duration of AF and the change in atrial depolarization duration in response to intratracheal flecainide. Induction of AF resulted in a marked increase in ventricular rate and corresponding reduction in mean arterial pressure, which returned to baseline levels within 5 minutes after conversion. Intratracheal flecainide instillation is effective in rapidly converting AF to normal sinus rhythm and restoring mean arterial pressure and heart rate to baseline values. The basis for this efficacy is likely rapid absorption of the drug through the lungs and delivery as a first-pass bolus to the left atrial and ventricular chambers and then to the coronary arterial circulation. The anti-AF effect of flecainide is inversely correlated with the drug's prolongation of atrial depolarization, implicating slowing of intra-atrial conduction as an important mechanism underlying conversion of AF to normal sinus rhythm.

Colorectal and cardiovascular effects of [Lys5,MeLeu9,Nle10]-NKA(4-10) in anesthetized macaques.

The effects of the tachykinin NK2 receptor agonist LMN-NKA ([Lys5,MeLeu9,Nle10]-NKA(4-10)) on colorectal and arterial blood pressure were examined in anesthetized macaques. Intravenous (IV) administration of 1-100μg/kg caused dose-related increases in colorectal pressure up to 120mmHg above baseline, and area under the curve (AUC) up to 24,987mmHg*s. This was accompanied at all doses by transient hypotension, with up to 26% reduction in mean arterial pressure (MAP) from baseline. Hypotension, but not the increase in colorectal pressure, was inhibited by a 10-min pretreatment with the NK1 receptor antagonist CP-99,994. In a pilot experiment using subcutaneous (SC) injection, a similar dose range of LMN-NKA (3-100μg/kg) again appeared to increase colorectal pressure with a similar AUC (up to 18,546mmHg*s) to that seen after IV injection, but lower peak amplitude (up to 49mmHg). Unlike the effects of IV injection, hypotension was only present after the highest SC dose (100μg/kg) in one of two animals. Pharmacokinetic analysis revealed markedly lower plasma exposures after SC compared with IV administration. Cmax was 39.6 versus 1070ng/mL, and AUCinf was 627 versus 2090ng/mL*min, respectively. These findings are consistent with previous observations in anesthetized dogs and indicate that the prokinetic effects of LMN-NKA may be achieved without hypotension using a route of administration that avoids unnecessarily high plasma exposures.

Influence of fitness and age on the endothelial response to acute inflammation.

What is the central question of the study? What are the effects of age and fitness on the vascular response to acute inflammation in younger and older adults? What is the main finding and its importance? In older adults, cardiorespiratory fitness level has a differential impact on endothelial function after acute inflammation. Compared with older adults with low fitness, older, moderately fit adults have a greater decrease in endothelial function, similar to that of younger adults. These findings have important implications in support of the beneficial effects of higher cardiorespiratory fitness in maintaining vascular reactivity and the ability to respond to stressors. Inflammation is associated with greater risk of cardiovascular events and reduced vascular function with ageing. Higher cardiorespiratory fitness is associated with lower risk of cardiovascular events and better vascular function. We evaluated the role of fitness in the vascular response to acute inflammation in 26 younger adults (YA) and 62 older adults (OA). We used an influenza vaccine to induce acute inflammation. Blood pressure, flow-mediated dilatation (FMD), augmentation index, carotid elastic modulus and inflammatory markers were measured before and 24h after vaccination. Peak oxygen uptake was measured via a treadmill test. 'Fit' was defined as a peak oxygen uptake greater than the age- and sex-determined 50th percentile according to the American College of Sports Medicine. An interaction effect existed for the FMD response during acute inflammation (P<0.05). The YA (low fit, from 11.5±1.8 to 9.2±1.3%; moderately fit, from 11.9±0.8 to 9.0±0.8%) and moderately fit OA (from 7.5±1.0 to 3.9±0.8%) had similar reductions in FMD at 24h (P<0.05). Low-fit OA did not reduce FMD at 24h (from 5.5±0.4 to 5.2±0.5%, P>0.05). The reduction in FMD in YA was similar between fitness groups (P>0.05). All groups had similar reductions in mean arterial pressure and increases in inflammatory markers. The augmentation index and carotid elastic modulus did not change during acute inflammation. In conclusion, in OA, higher fitness is associated with a greater decrease in endothelial function during acute inflammation, and this response is similar to that of young adults. This suggests that moderately fit OA may maintain vascular reactivity in response to stress, indicating preserved vascular function in moderately fit versus low-fit OA.

Population Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Children Undergoing Ambulatory Surgery.

BACKGROUND:Dexmedetomidine (DEX) is an α-2 adrenergic agonist with sedative and analgesic properties. Although not approved for pediatric use by the Food and Drug Administration, DEX is increasingly used in pediatric anesthesia and critical care. However, very limited information is available regarding the pharmacokinetics of DEX in children. The aim of this study was to investigate DEX pharmacokinetics and pharmacodynamics (PK–PD) in Mexican children 2–18 years of age who were undergoing outpatient surgical procedures.METHODS:Thirty children 2–18 years of age with American Society of Anesthesiologists physical status score of I/II were enrolled in this study. DEX (0.7 μg/kg) was administered as a single-dose intravenous infusion. Venous blood samples were collected, and plasma DEX concentrations were analyzed with a combination of high-performance liquid chromatography and electrospray ionization-tandem mass spectrometry. Population PK–PD models were constructed using the Monolix program.RESULTS:A 2-compartment model adequately described the concentration–time relationship. The parameters were standardized for a body weight of 70 kg by using an allometric model. Population parameters estimates were as follows: mean (between-subject variability): clearance (Cl) (L/h × 70 kg) = 20.8 (27%); central volume of distribution (V1) (L × 70 kg) = 21.9 (20%); peripheral volume of distribution (V2) (L × 70 kg) = 81.2 (21%); and intercompartmental clearance (Q) (L/h × 70 kg) = 75.8 (25%). The PK–PD model predicted a maximum mean arterial blood pressure reduction of 45% with an IC50 of 0.501 ng/ml, and a maximum heart rate reduction of 28.9% with an IC50 of 0.552 ng/ml.CONCLUSIONS:Our results suggest that in Mexican children 2–18 years of age with American Society of Anesthesiologists score of I/II, the DEX dose should be adjusted in accordance with lower DEX clearance.

The Effects Of Ethynylestradiol‐3‐Sulfate (EE‐3‐S) On Blood Volume and Organ Function In Pigs With Severe Traumatic Hemorrhage

IntroductionThe beneficial effects of estrogens to improve survival from hemorrhage have been suggested in experimental studies of rodents and minipigs, as well as some clinical observations. However, the underlying possible protective mechanisms remain unclear. This study investigated the effects of ethynylestradiol‐3‐sulfate (EE‐3‐S) on blood volume and organ functions in pigs following severe traumatic hemorrhage and hypotensive resuscitation.MethodsTwenty anesthetized and instrumented pigs were randomized into saline (n=10) and EE‐3‐S(n=10) groups. Femur fracture was performed in each pig's left leg, followed byhemorrhage of 55% of estimated blood volume and 15 min shock period. Afterwards, pigs were hypotensively resuscitated with a small volume of saline(4 ml/kg) or EE‐3‐S (1 mg/kg at concentration of 1 mg/ml, plus 3 ml saline/kg). Indocyanine green dye (5 ml of 1 mg/ml) was injected before femur fracture and hemorrhage and 15 min after EE‐3‐S administration with serial blood samples taken accordingly to determine changes of blood volume. Pigs remained anesthetized and were monitored for 6 h or until death, and blood samples were taken every 2 h for measurements of blood gases and chemistry.ResultsAll baseline measurements are similar between the two groups. Femur fracture and hemorrhage reduced mean arterial pressure to 54±6% of baseline values and reduced blood volume from 104±4 ml/kg to 67±4 ml/kg (both p&lt;0.05) and reduced Hctfrom 31±1% to 28±1% in the saline resuscitated group. Similar reductions were observed with EE‐3‐S resuscitation in blood volume (from 109±4 ml/kg to 68±3 ml/kg, p&lt;0.05) and Hct (30±1% to 27±1%, p&lt;0.05). Compared to baseline value, creatinine, asparate aminotransferase (AST), and lactate dehydrogenase(LDH) were elevated at 6 h or death from 1.3±0.1 mg/dL to 3.1± 0.2 mg/dL, 33±3 U/L to 98±16 U/L, and 450± 55 U/L to 645±122 U/L, respectively (all p&lt;0.05). Similar increases were observed in creatinine (1.4±0.2 mg/dL to 2.9±0.1 mg/dL), AST (32±3 U/L to 135±46 U/L) and LDH (450±35 U/L to 501±95 U/L) in the EE‐3‐S group (all p&lt;0.05). Survival time was similar between the saline (212±43 min) and EE‐3‐S (212±39 min) groups.ConclusionsFollowing severe traumatic hemorrhage and small volume resuscitation, administration of EE‐3‐S did not affect blood volume, organ function or short term survival in this model.Support or Funding InformationUS Army Medical Research and Materiel CommandThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of Resuscitation Adjuncts on Indices of Inflammation and Oxidant Stress in Tissues from Swine Subjected to Traumatic Hemorrhage

IntroductionIn the absence of blood products, pre‐hospitaluse of small volume adjuncts to enhance crystalloid resuscitation has beenproposed to reduce inflammation and improve outcomes in the bleeding traumapatient. However, the most effective drugs for this purpose remain underintense investigation. The present study investigated the effects of Poloxamer‐188(P‐188), a surfactant with membrane resealing activity andethynylestradiol‐3‐sulfate (EE‐3‐S), an estrogen compound, on indices ofinflammation and oxidant stress in tissues from swine subjected to traumatichemorrhage. Both compounds are suggested to have anti‐inflammatory andpotentially anti‐oxidant activity.MethodsThirty anesthetized and instrumented pigs weresubjected to a left leg femur fracture followed by hemorrhage of 55% of the estimatedblood volume and a 15 min shock period. Pigs were then randomized into 3 groups(n=10/group) and resuscitated with equal small total volumes of normal saline (NS;4ml/kg) alone or NS containing P188 (200 mg/kg) or EE‐3‐S (1 mg/kg). Animalswere continuously monitored under anesthesia for 6h or until death. At death oreuthanasia, samples of liver, kidney, lung, heart and jejunum were flash‐frozenand stored at −80°C until assayed for antioxidant status, antioxidantenzyme activities and select cytokines.ResultsHemorrhage reduced mean arterial pressure to 54±6%of baseline levels (p&lt;0.05). In all tissues, total antioxidant status, reduced glutathione and antioxidant enzyme activities were similar amonggroups. In lung, however, nitric oxidelevels were 28% lower in the P‐188 treated than NS group (p&lt;0.05). In liver, levels of IL‐1β, TNF‐α and IL‐6 were 25–30% lower in the P‐188 and EE3‐S treatedthan NS resuscitated swine (p&lt;0.05), whereas IL‐10 levels were similar amonggroups. No statistically significant differences in cytokine concentrationswere observed in kidney, lung, heart or jejunum among the groups.ConclusionsThese data suggest that in this swine model oftraumatic hemorrhage and small volume resuscitation with crystalloid containingP‐188 or EE3‐S, any anti‐inflammatory activity was only observed in the liver.Support or Funding InformationUS Army Institute of Surgical Research, San Antonio, TX 78234This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Antihypertensive properties of aqueous extracts of vegetable leaf‐fortified bread after oral administration to spontaneously hypertensive rats

SummaryThis study investigated the potential cardiovascular health benefits of leavened bread produced from wheat flour that contained 1%, 2% and 3% additions of leafy vegetable powders obtained from Amaranthus viridis (AO), Solanum macrocarpon (SM) or Telfairia occidentalis (TO). Dried breads were extracted with water at 60 °C followed by analysis for total polyphenolic content (TPC), as well as in vitro inhibitions of angiotensin‐converting enzyme and renin activities. HPLC analysis of the bread extracts indicated the presence of mainly rutin, gallic acid, myricetin and caffeic acid. TPC of the vegetable‐fortified breads was significantly (P &lt; 0.05) higher (5.8–7.6 mg gallic acid equivalent, GAE/g) than that of control bread (5.5 mg GAE/g). Oral administration of 100 mg dried extract/kg body weight to spontaneously hypertensive rats led to reductions (up to 42 mmHg) in systolic, diastolic and mean arterial blood pressure in comparison with 20 mmHg for the control bread.

Acute hypotensive and diuretic activities of Berberis vulgaris root bark aqueous extract in normal rats

The aim of this study is to investigate the effectiveness of intravenous administration of Berberis vulgaris root bark aqueous extract (BRBD) on the cardiovascular and renal functions of healthy normotensive rats. The different doses of BRBD 1, 10 and 20 mg/kg were administered intravenously (i.v) in normal rats. Blood pressure, diuretic activity and serum renal profile were analyzed. Intravenous injection of BRBD at the different doses of 1, 10 and 20 mg/kg showed a dose-dependent reduction in mean arterial blood pressure (P<0.001). At different doses of 1, 10 and 20 mg/kg, the hypotensive effect remained for more than one hour. Single dose administration of BRBD at doses of 10 and 20 mg/kg caused a significant increase in urine output (P<0.001) as compared to the control rats. Serum renal profile test (albumin, Urea, Uric Acid, creatinine and BUN) did not show any significant alteration. The authors conclude that the BRBD is a potent hypotensive and possesses diuretic potential

Effects of dexmedetomidine combined with commonly administered opioids on clinical variables in dogs.

OBJECTIVE To evaluate cardiopulmonary, sedative, and antinociceptive effects of dexmedetomidine combined with commonly administered opioids in dogs. ANIMALS 8 healthy Beagles. PROCEDURES Dogs were sedated by IM administration of each of 7 treatments. Treatments comprised dexmedetomidine (0.01 mg/kg; Dex) and the same dose of dexmedetomidine plus butorphanol (0.15 mg/kg; Dex-But), meperidine (5 mg/kg; Dex-Mep), methadone (0.5 mg/kg; Dex-Meth), morphine (0.5 mg/kg; Dex-Mor), nalbuphine (0.5 mg/kg; Dex-Nal), or tramadol (5 mg/kg; Dex-Tram). Cardiorespiratory and arterial blood gas variables and sedative and antinociceptive scores were measured before drug injection (time 0; baseline) and at 15-minute intervals for 120 minutes. RESULTS Heart rate was reduced at all time points after injection of Dex-But, Dex-Mep, Dex-Meth, and Dex-Mor treatments. There was a significant reduction of mean arterial blood pressure for Dex-But, Dex-Mep, and Dex-Mor treatments at all time points, compared with baseline. There was a significant decrease in respiratory rate, compared with the baseline value, for Dex, Dex-But, Dex-Meth, and Dex-Tram treatments from 15 to 120 minutes. A significant decrease in arterial blood pH was detected from baseline to 120 minutes for all treatments, with differences among Dex, Dex-Mep, and Dex-Mor. Reduction in Pao2 was greater for the Dex-Mep treatment than for the other treatments. The highest sedation scores were detected for Dex-Mep and Dex-Meth treatments. Antinociceptive effects were superior for Dex-But, Dex-Meth, Dex-Mor, and Dex-Nal treatments. CONCLUSIONS AND CLINICAL RELEVANCE Drug combinations caused similar cardiorespiratory changes, with greater sedative effects for Dex-Mep and Dex-Meth and superior antinociceptive effects for Dex-But, Dex-Meth, Dex-Mor, and Dex-Nal.

Penehyclidine hydrochloride inhibits TLR4 signaling and inflammation, and attenuates blunt chest trauma and hemorrhagic shock-induced acute lung injury in rats.

Blunt chest trauma with hemorrhagic shock (THS) frequently induces pulmonary inflammation that leads to acute lung injury (ALI). Penehyclidine hydrochloride (PHC) possesses anti-inflammatory properties that may attenuate the systemic inflammatory response. The present study aimed to evaluate the molecular mechanism of PHC in modifying THS-induced ALI in rats. Rats underwent either THS or a sham procedure. At 6 h subsequent to blunt chest trauma, arterial blood was drawn for blood gas and pro-inflammatory factors analyses, and lung tissue samples were collected to examine pulmonary histopathological alterations, the wet/dry weight ratio, myeloperoxidase activity, and the protein expression levels of Toll-like receptor 4 (TLR4), phosphorylated (p-)p38 mitogen-activated protein kinase (MAPK), nuclear factor (NF)-κB and activator protein-1 (AP-1). THS caused significant reductions in heart rate and mean arterial blood pressure, and was associated with significant increases in tumor necrosis factor-α, interleukin (IL)-6, IL-1β, p-p38MAPK, NF-κB and AP-1 activation, in addition to TLR4 expression, in the lung. PHC effectively attenuated THS-induced ALI, and inhibited TLR4 expression, reduced the activation of p-p38MAPK, NF-κB and AP-1, and downregulated the expression of pro-inflammatory mediators. In conclusion, the results of the present study demonstrated that PHC may exert an anti-inflammatory effect and attenuate THS-induced ALI by inhibiting the TLR4 signaling pathway. These preclinical findings may offer a novel therapeutic strategy to restrict TLR4 overactivation in ALI.

Effect of acute hypoxemia on cerebral blood flow velocity control during lower body negative pressure.

The ability to maintain adequate cerebral blood flow and oxygenation determines tolerance to central hypovolemia. We tested the hypothesis that acute hypoxemia during simulated blood loss in humans would cause impairments in cerebral blood flow control. Ten healthy subjects (32 ± 6 years, BMI 27 ± 2 kg·m−2) were exposed to stepwise lower body negative pressure (LBNP, 5 min at 0, −15, −30, and −45 mmHg) during both normoxia and hypoxia (FiO2 = 0.12–0.15 O2 titrated to an SaO2 of ~85%). Physiological responses during both protocols were expressed as absolute changes from baseline, one subject was excluded from analysis due to presyncope during the first stage of LBNP during hypoxia. LBNP induced greater reductions in mean arterial pressure during hypoxia versus normoxia (MAP, at −45 mmHg: −20 ± 3 vs. −5 ± 3 mmHg, P < 0.01). Despite differences in MAP, middle cerebral artery velocity responses (MCAv) were similar between protocols (P = 0.41) due to increased cerebrovascular conductance index (CVCi) during hypoxia (main effect, P = 0.04). Low frequency MAP (at −45 mmHg: 17 ± 5 vs. 0 ± 5 mmHg2, P = 0.01) and MCAv (at −45 mmHg: 4 ± 2 vs. −1 ± 1 cm·s−2, P = 0.04) spectral power density, as well as low frequency MAP‐mean MCAv transfer function gain (at −30 mmHg: 0.09 ± 0.06 vs. −0.07 ± 0.06 cm·s−1·mmHg−1, P = 0.04) increased more during hypoxia versus normoxia. Contrary to our hypothesis, these findings support the notion that cerebral blood flow control is not impaired during exposure to acute hypoxia and progressive central hypovolemia despite lower MAP as a result of compensated increases in cerebral conductance and flow variability.

Abstract TP211: Gray and White Matter Hemodynamics and Metabolism Measured Using Magnetic Resonance Imaging

Background: Reliable methods used to measure cerebral hemodynamics, metabolism and autoregulation are time-consuming and invasive. Objectives: We sought to measure cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ), in the whole brain, gray and white matter and detect physiological changes in humans under normal and ≈10% reductions in mean arterial pressure (MAP). Methods: CBF was measured using pseudo continuous arterial spin labeling (pCASL). OEF was measured using a MRI asymmetric spin echo-planar imaging (EPI). The arterial content of oxygen (CaO 2 ) was computed. CMRO 2 was calculated using the equation CMRO 2 =CaO 2 xCBFxOEF. Cerebral autoregulation was determined by measuring changes in CBF, OEF and CMRO 2 in response to ≈10% reductions in MAP in stroke-free controls induced by IV Nicardipine infusion. Autoregulation was measured in the whole brain, gray matter and white matter. Autoregulatory Index (AI) was computed using the equation AI = %CBF change/% MAP change supplemented by CBF associated OEF changes. Results: A total of 30 subjects were consented (Mean age 31, 93% male, 40% white, 43% black and 17% others). At baseline, CBF was measured in the whole brain (52.5±9.5 ml/100g/min), gray matter (72.0±13.0 ml/100g/min) and white matter (30.2±8.4 ml/100g/min). OEF was measured in the whole brain (0.32±0.02), gray matter (0.33±0.02) and white matter (0.30±0.01). CMRO 2 was measured in the whole brain (3.2±0.8 ml/100g/min), gray matter (4.6±1.1 ml/100g/min) and white matter (1.8±0.5 ml/100g/min). A target of 10% MAP lowering was successfully achieved in 18 subjects, resulting in a change of mean CBF in the whole brain (52 vs. 50, p=0.1), gray matter (72 vs. 69, p=0.2) and white matter (30 vs. 28, p=0.08). This translated to a AI of 0.3 ± 0.9 in the whole brain, 0.2±1.0 in the gray matter and 0.5±1.7 in the white matter. These CBF changes corroborated with no significant changes in OEF and CMRO 2 . Conclusions: MR measurement of CBF, OEF and CMRO 2 , in the whole brain, gray and white matter was comparable to measures obtained by invasive methods. Differences in these measures, as well as AI in the gray and white matter, may help understand cerebrovascular diseases that affect white matter such as lacunar strokes.

318: Endothelial function is unaltered by prophylactic nitric oxide donor in women at high-risk for preeclampsia

To study the effect of low dose prophylactic isosorbide mononitrate (ISMN) 20mg/d on the endothelial function in high-risk women receiving standard aspirin prophylaxis Design: As part of a randomized double blind placebo-controlled parallel arm superiority trial. Setting: Antenatal clinic of a tertiary teaching hospital, south India Participants and methods: One hundred women fulfilling NICE guideline criteria for aspirin prophylaxis were recruited at 12 - 16 weeks and randomised to receive either 20mg/d of ISMN or placebo, in addition to 75mg/d of oral aspirin from recruitment till delivery. Outcome measure: Changes in indices of endothelial function Sample Size (for the primary outcome): One hundred women (50 in each arm) to detect a decrease of hypertensive disorders from 20% in the placebo group to 5% in the ISMN group with a power of 80% and α at 0.05 The groups were comparable in terms of age, BMI, parity, and risk factor for preeclampsia. The vascular indices of endothelial function were recorded at recruitment and again at 24 weeks. These included flow-mediated vasodilatation index (FMVD-i), brachial-ankle pulse wave velocity, ankle-brachial index, brachial arterial stiffness index, and ankle arterial stiffness index. (Table 1). There was no significant improvement in these indices following ISMN intake. The FMVD-i actually showed a decrease following ISMN treatment. Concomitantly, there was a reduction in mean arterial pressure. The composite rate of hypertensive disorders (gestational hypertension, preeclampsia, or superimposed preeclampsia) was not significantly different between the groups (14/50, 28% in ISMN vs. 12/50, 24% in placebo group; p = 0.7). Addition of nitric oxide donor, ISMN, does not improve the endothelial function in high risk women who are on low-dose aspirin. However, it results in a slight lowering of mean arterial pressure without a concomitant reduction in the clinical event rate of hypertensive disorders.

The Effects of the Quincke Spinal Needle Bevel Insertion on Postdural Puncture Headache and Hemodynamics in Obstetric Patients.

Aim:Spinal anesthesia is a widely used procedure in modern anesthesia. Although it is a reliable and frequently used anesthetic procedure, it involves complications, including postdural puncture headache caused by arachnoid punctured, which significantly affects postoperative well-being. In this study, we aimed to observe headache frequency with 26-G Quincke spinal needle in either transverse or sagittal planes.Materials and Methods:One hundred patients with American Society of Anesthesiologists status classes I and II who were scheduled for elective cesarean delivery with no contraindications for performing spinal anesthesia were randomly divided into two groups: Group I (transverse n = 50) and Group II (sagittal n = 50). Spinal anesthesia was performed with a 26-G Quincke needle, using 1.5–2.0 ml 0.75% hyperbaric bupivacaine. The anesthesiologists' experience, number of attempts for spinal anesthesia, volume of fluid administered preoperatively and intraoperatively, intervertebral space where spinal anesthesia was administered, and patient movements during the attempts were recorded. Mean arterial pressure and peak heart rates were recorded for 60 min intraoperatively and postoperatively. Headache and back pain complications were observed for 1 week postoperatively. Chi-square tests and statistical comparisons of the rates (statistical significance, P < 0.05) were used for assessments.Results and Conclusions:No significant differences were observed with respect to age, height, weight, headache, or incidence of back pain. No significant differences were observed for the number of spinal attempts, intervertebral space where spinal anesthesia was administered, experience of the anesthesiologists, patient movements during the attempts, volumes of fluid administered preoperatively and intraoperatively, or low back pain incidence. Significant reductions in mean arterial pressure were observed between groups after 10, 15, 30, 40, and 50 min. No significant differences were observed in headache or back pain frequency with 26-G Quincke spinal needle in either transverse or sagittal planes. Hypotension was frequently observed in the transverse group.

Hypotensive Response to Continuous Aerobic and High-Intensity Interval Exercise Matched by Volume in Sedentary Subjects

Abstract Background: Systemic arterial hypertension (SAH) is one of the main risk factors for heart disease. Among the benefits linked to different modalities of physical exercise, post-exercise hypotension (PEH) is a key point for exercise prescription in this condition. Objective: To investigate and compare PEH in response to continuous aerobic exercise (CONT) and high-intensity interval exercise (HIIE), matched by volume, in sedentary individuals. Methods: A randomized cross-over study, composed of sedentary, healthy male subjects submitted to two acute physical exercise protocols matched by volume, HIIE and CONT, on a treadmill. Hemodynamic measures for the evaluation of PEH were performed pre, immediately after exercise and every five minutes thereafter, during one hour of recovery. Two-way ANOVA with repeated measurements was used for comparisons between groups and Bonferroni post hoc test as appropriate. P < 0.05 was considered significant. Results: Both exercise protocols promoted significant PEH, with reductions in systolic blood pressure (SBP) and mean arterial pressure (MAP). HIIE promoted a reduction of SBP and MAP at the 15th minute, whereas the same effect was observed at the 30th following CONT. Conclusion: Both HIIE and CONT, matched by volume, promote PEH of similar magnitude. However, PEH occurs earlier following HIIE, suggesting a better time / effectiveness ratio, and an additional beneficial effect of this modality.

Caudal Analgesia for Hypospadias in Pediatrics: Comparative Evaluation of Adjuvants Dexamethasone and Dexmedetomidine Combination versus Dexamethasone or Dexmedetomidine to Bupivacaine: A Prospective, Double-Blinded, Randomized Comparative Study.

Background:Caudal block is the most commonly used regional anesthetic technique in pediatric surgeries; different additives have been used for better and safer outcome.Aim:The aim of this study is to compare the combination of dexamethasone and dexmedetomidine as adjuvants to bupivacaine versus using each agent solely with bupivacaine in pediatric caudal block as regards their efficiency in pain relief (the duration of postoperative analgesia, first time to request analgesia, and modified objective pain score [MOPS]).Study Design:This was a prospective, double-blinded, randomized study.Patients and Methods:Patients and Methods: Sixty-three children scheduled for hypospadias surgery wererandomized into three groupsaccording to the adjuvant drug added to caudal bupivacaine : Group I (n = 21): dexamethasone 0.1 mg/kg + 0.5 mg/kg bupivacaine 0.25%, Group II (n = 21): dexmedetomidine0.01 μg/kg + 0.5 mg/kg bupivacaine 0.25% and Group III (n = 21): dexamethasone 0.1 mg/kg + dexmedetomidine 0.01 μg/kg + 0.5 mg/kgbupivacaine 0.25%. Intraoperative and postoperative hemodynamics were recorded. In postoperative anesthesia care unit and then the ward, MOPS and sedation score were recorded at 30 min and 1, 2, 3, 6 and 12 h. Further, the time of first analgesic request and side effects were recorded.Statistical Analysis:Categorical data were presented as frequencies (%) and analyzed using Chi-square test. Continuous data were presented as mean (standard deviation) and median (quartiles). Continuous data were analyzed using one-way analysis of variance for single measures and two-way mixed model for repeated measures. Kaplan–Meier analysis was performed for the duration of analgesia.Results:In Group III, MOPS was lower than Groups I and II at the study times. Further, Group III had prolonged time for first request of analgesic. Sedation scores were prolonged in Group III and Group II than in Group I. There was a reduction in heart rates in Group III more than Group I and Group II but with no significant difference. However, there was a significant reduction in mean arterial blood pressure 30 min intraoperatively and postoperatively in Group III as compared to Groups I and II.Conclusion:The addition of combined dexmedetomidine at a dose of 1 μg/kg and dexamethasone 0.1 mg/kg to caudal bupivacaine seemed to be an attractive alternative to each drug if used alone with more prolonged analgesia and almost no adverse effects.

Burst patterning of hypothalamic paraventricular nucleus-driven sympathetic nerve activity in ANG II-salt hypertension.

ANG II-salt hypertension selectively increases splanchnic sympathetic nerve activity (sSNA), but the extent to which this reflects increased respiratory versus cardiac rhythmic bursting is unknown. Here, integrated sSNA was elevated in ANG II-infused rats fed a high-salt (2% NaCl) diet (ANG II-HSD) compared with vehicle-infused rats fed a normal-salt (0.4% NaCl) diet (Veh-NSD; P < 0.01). Increased sSNA was not accompanied by increased inspiratory or expiratory bursting, consistent with no group difference in central inspiratory drive. Consistent with preserved inhibitory baroreflex entrainment of elevated sSNA in ANG II-HSD rats, the time integral ( P < 0.05) and amplitude ( P < 0.01) of cardiac rhythmic sSNA were increased. Consistent with activity of hypothalamic paraventricular nucleus (PVN) neurons supporting basal SNA in ANG II-salt hypertension, inhibition of PVN with the GABA-A receptor agonist muscimol reduced mean arterial pressure (MAP) and integrated sSNA only in the ANG II-HSD group ( P < 0.001). PVN inhibition had no effect on respiratory rhythmic sSNA bursting in either group but reduced cardiac rhythmic sSNA in ANG II-HSD rats only ( P < 0.01). The latter likely reflected reduced inhibitory baroreflex entrainment subsequent to the fall of MAP. Of note is that MAP as well as integrated and rhythmic burst patterns of sSNA were similar in vehicle-infused rats whether they were fed a normal or high-salt diet. Findings indicate that PVN neurons support elevated sSNA in ANG II-HSD rats by driving a tonic component of activity without altering respiratory or cardiac rhythmic bursting. Because sSNA was unchanged in Veh-HSD rats, activation of PVN-driven tonic sSNA appears to require central actions of ANG II. NEW & NOTEWORTHY ANG II-salt hypertension is strongly neurogenic and depends on hypothalamic paraventricular nucleus (PVN)-driven splanchnic sympathetic nerve activity (sSNA). Here, respiratory and cardiac bursts of sSNA were preserved in ANG II-salt rats and unaltered by PVN inhibition, suggesting that PVN neurons drive a tonic component of sSNA rather than modulating dominant patterns of burst discharge.

BP Reduction, Kidney Function Decline, and Cardiovascular Events in Patients without CKD.

In the Systolic Blood Pressure Intervention Trial (SPRINT), intensive systolic BP treatment (target <120 mm Hg) was associated with fewer cardiovascular events and higher incidence of kidney function decline compared with standard treatment (target <140 mm Hg). We evaluated the association between mean arterial pressure reduction, kidney function decline, and cardiovascular events in patients without CKD. We categorized patients in the intensive treatment group of the SPRINT according to mean arterial pressure reduction throughout follow-up: <20, 20 to <40, and ≥40 mm Hg. We defined the primary outcome as kidney function decline (≥30% reduction in eGFR to <60 ml/min per 1.73 m2 on two consecutive determinations at 3-month intervals), and we defined the secondary outcome as cardiovascular events. In a propensity score analysis, patients in each mean arterial pressure reduction category from the intensive treatment group were matched with patients from the standard treatment group to calculate the number needed to treat regarding cardiovascular events and the number needed to harm regarding kidney function decline. In the intensive treatment group, 1138 (34%) patients attained mean arterial pressure reduction <20 mm Hg, 1857 (56%) attained 20 to <40 mm Hg, and 309 (9%) attained ≥40 mm Hg. Adjusted hazard ratios for kidney function decline were 2.10 (95% confidence interval, 1.22 to 3.59) for mean arterial pressure reduction between 20 and 40 mm Hg and 6.22 (95% confidence interval, 2.75 to 14.08) for mean arterial pressure reduction ≥40 mm Hg. In propensity score analysis, mean arterial pressure reduction <20 mm Hg presented a number needed to treat of 44 and a number needed to harm of 65, reduction between 20 and <40 mm Hg presented a number needed to treat of 42 and a number needed to harm of 35, and reduction ≥40 mm Hg presented a number needed to treat of 95 and a number needed to harm of 16. In the intensive treatment group of SPRINT, larger declines in mean arterial pressure were associated with higher incidence of kidney function decline. Intensive treatment seemed to be less favorable when a larger reduction in mean arterial pressure was needed to attain the BP target.

Phenotypic Consequences of a Genetic Predisposition to Enhanced Nitric Oxide Signaling.

Nitric oxide signaling plays a key role in the regulation of vascular tone and platelet activation. Here, we seek to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on risk for cardiovascular diseases, thus informing the potential utility of pharmacological stimulation of the nitric oxide pathway as a therapeutic strategy. We analyzed the association of common and rare genetic variants in 2 genes that mediate nitric oxide signaling (Nitric Oxide Synthase 3 [NOS3] and Guanylate Cyclase 1, Soluble, Alpha 3 [GUCY1A3]) with a range of human phenotypes. We selected 2 common variants (rs3918226 in NOS3 and rs7692387 in GUCY1A3) known to associate with increased NOS3 and GUCY1A3 expression and reduced mean arterial pressure, combined them into a genetic score, and standardized this exposure to a 5 mm Hg reduction in mean arterial pressure. Using individual-level data from 335 464 participants in the UK Biobank and summary association results from 7 large-scale genome-wide association studies, we examined the effect of this nitric oxide signaling score on cardiometabolic and other diseases. We also examined whether rare loss-of-function mutations in NOS3 and GUCY1A3 were associated with coronary heart disease using gene sequencing data from the Myocardial Infarction Genetics Consortium (n=27 815). A genetic predisposition to enhanced nitric oxide signaling was associated with reduced risks of coronary heart disease (odds ratio, 0.37; 95% confidence interval [CI], 0.31-0.45; P=5.5*10-26], peripheral arterial disease (odds ratio 0.42; 95% CI, 0.26-0.68; P=0.0005), and stroke (odds ratio, 0.53; 95% CI, 0.37-0.76; P=0.0006). In a mediation analysis, the effect of the genetic score on decreased coronary heart disease risk extended beyond its effect on blood pressure. Conversely, rare variants that inactivate the NOS3 or GUCY1A3 genes were associated with a 23 mm Hg higher systolic blood pressure (95% CI, 12-34; P=5.6*10-5) and a 3-fold higher risk of coronary heart disease (odds ratio, 3.03; 95% CI, 1.29-7.12; P=0.01). A genetic predisposition to enhanced nitric oxide signaling is associated with reduced risks of coronary heart disease, peripheral arterial disease, and stroke. Pharmacological stimulation of nitric oxide signaling may prove useful in the prevention or treatment of cardiovascular disease.