Reduction In Arterial Blood Pressure Research Articles

The autonomic control of upright posture tachycardia in the arboreal lizard Iguana iguana.

In terrestrial environments, upright spatial orientation can dramatically influence animals' hemodynamics. Generally, large and elongated species are particularly sensitive to such influence due to the greater extent of their vascular beds being verticalized, favoring the establishment of blood columns in their bodies along with caudal blood pooling, and thus jeopardizing blood circulation through a cascade effect of reductions in venous return, cardiac filling, stroke volume, cardiac output, and arterial blood pressure. This hypotension triggers an orthostatic-(baroreflex)-tachycardia to normalize arterial pressure, and despite the extensive observation of this heart rate (fH ) adjustment in experiments on orthostasis, little is known about its mediation and importance in ectothermic vertebrates. In addition, most of the knowledge on this subject comes from studies on snakes. Thus, our objective was to expand the knowledge on this issue by investigating it in an arboreal lizard (Iguana iguana). To do so, we analyzed fH , cardiac autonomic tones, and fH variability in horizontalized and tilted iguanas (0°, 30°. and 60°) before and after muscarinic blockade with atropine and double autonomic blockade with atropine and propranolol. The results revealed that I. Iguana exhibits significant orthostatic-tachycardia only at 60o inclinations-a condition that is primarily elicited by a withdrawal of vagal drive. Also, as in humans, increases in low-frequency fH oscillations and decreases in high-frequency fH oscillations were observed along with orthostatic-tachycardia, suggesting that the mediation of this fH adjustment may be evolutionarily conserved in vertebrates.

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.

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.

Antihypertensive responses of vasoactive androgens in an in vivo experimental model of preeclampsia

Dehydroepiandrosterone (DHEA), testosterone (TES) and its 5-reduced metabolites induce a nongenomic vasorelaxation in several vascular beds of mammals; similarly these hormones produce systemic hypotensive and antihypertensive responses in normotensive and hypertensive male rats. Thus, it was hypothesized that the antihypertensive response of androgens, whose levels are elevated during gestation, protect against gestational hypertension. An animal model of preeclampsia was induced in female Wistar rats using DOCA-salt-treated pregnant (PT) and normal pregnant (NP) rats. In vivo experiments in conscious rats revealed that bolus intravenous injections of DHEA, TES, 5α- or 5β-dihydrotestosterone (-DHT) log −1.0 to 2.0μmolk−1min−1, produced substantial transient reductions in arterial blood pressure (BP), without significant changes in heart rate (HR). Mean arterial blood pressure (MAP) was reduced significantly in both groups. PT rats were more sensitive to the antihypertensive responses of androgens than NP. DHEA and 5β-DHT were the most potent to reduce MAP: 66±07 and 69±2.0mmHg in PT but only 33±0.5 and 35±1.2mmHg in NP rats, respectively. In isolated aortas of PT and NP, the concentration-response curves to each androgen (0.1–100μM) indicated that KCl-induced pre-contraction is more sensitive to all androgens than phenylephrine (Phe) pre-contractions. Notably, 5β-DHT is the greatest vasorelaxant with KCl-induced contraction than with Phe contraction of both groups, suggesting a preferential blockade on L-VOCCs. TES exhibited minor vasorelaxing effect of aortas pre-contracted with KCl, compared to its precursor DHEA and its 5-reduced metabolites. These data show that these androgens exert acute vasorelaxing effects in vitro and remarkably, reduce the BP in vivo in PT and NP at term pregnancy. Moreover, a deficit in feto-placental androgen production during pregnancy may trigger the development of preeclampsia or gestational hypertension.

Evaluation of the reduction in central and peripheral arterial blood pressure following an oral glucose load.

The clinical significance of measuring central arterial blood pressure has been recently discussed. Although the postprandial reduction in blood pressure is well known, postprandial changes in central blood pressure have not been intensively studied. The present study investigated differences in the reduction of central and peripheral arterial blood pressure after administration of an oral glucose load.An oral glucose tolerance test (75 g) was performed in 360 participants in our physical checkup program. Brachial and central systolic blood pressures were assessed before and after the glucose load. Central arterial blood pressure was measured noninvasively using an automated device.The mean age was 53.6 ± 8.2 years. Both brachial (127.9 ± 17.7 to 125.0 ± 16.3 mm Hg) and central arterial blood pressures were significantly decreased after an oral glucose load (118.9 ± 17.9 to 112.8 ± 16.8 mm Hg). The reduction in blood pressure was greater in central (7.3 ± 11.5 mm Hg) than in brachial blood pressure measurements (3.4 ± 11.3 mm Hg, P < .001). Extreme blood pressure reduction (>20 mm Hg) was recorded more frequently in central (n = 43, 12.3%) than brachial blood pressure measurements (n = 20, 5.6%).An oral glucose load decreases both central and brachial systolic blood pressure, with more pronounced effects on central blood pressure. Postprandial reductions in blood perfusion of the important organs such as the brain may be underestimated when postprandial BP reduction is assessed using brachial BP measurements.

Abstract P394: Reduced Serum Butyrate Is Associated With Dampened Central Effects Of Butyrate On Blood Pressure In The Shr

Introduction: The link between gut dysbiosis and hypertension is characterized by a significant reduction in butyrate-producing bacteria in the spontaneously hypertensive rat (SHR) compared with its Wistar Kyoto (WKY) control. Butyrate, a major end-product of gut microbiota fermentation, has beneficial effects in multiple dysbiosis-related diseases. Here, we investigated the link between serum butyrate levels and central effects of butyrate in regulation of blood pressure (BP) in WKY and SHR. Methods: Serum samples were collected from 12 weeks old male WKY and SHR, and butyrate quantification was performed using LC-MS. Quantitative real time PCR was employed to measure relative expression levels of butyrate sensing receptors (Gpr41, Gpr43) in the hypothalamus of SHR and WKY. Central effects of butyrate on BP were evaluated by acute ICV injection in anaesthetized WKY and SHR. Results: Significantly lower levels of serum butyrate were observed in the SHR (WKY 1.23±0.14μmol/L vs SHR 0.23±0.033μmol/L, N=4, P=0.0005). Moreover, lower expression of Gpr43 were observed in the hypothalamus of SHR (WKY 0.0002 ± 2.7e-005 vs SHR 6.9e-005 ± 1.9e-005, N=4/3, P=0.0152). ICV administration of butyrate reduced BP in both strains; however, the reduction in arterial BP was greater in the WKY at two time points (400s post-injection: WKY -5.83±0.49mmHg vs SHR -2.62±0.63mmHg, N=4, P=0.0235; 1000s post-injection: WKY -19.7±1.85mmHg vs SHR -13.26±1.1mmHg, N=3, P=0.05). Conclusion: Reduced serum butyrate is associated with reduced sensitivity to central butyrate. This may contribute to elevation in BP in the SHR.

Blood pressure reduction in patients with irreversible pulpitis teeth treated by non-surgical root canal treatment

Background/purposeThe hypotension in patients during non-surgical root canal treatment (NSRCT) has not yet investigated. This study aimed to assess the mean systolic blood pressure (MSBP), mean diastolic blood pressure (MDBP), and mean arterial blood pressure (MABP) reduction percentages in patients with irreversible pulpitis teeth treated by NSRCT. Materials and methodsWe prospectively recruited 111 patients with a total of 138 irreversible pulpitis teeth. All patients underwent two NSRCT sessions. The first NSRCT session involved mainly the removal of vital pulp tissue with the direct stimulation of the dental branches of the trigeminal nerve, and the second NSRCT session included the root canal debridement and enlargement with minimal disturbance to the dental nerves. The blood pressure of each patient was recorded before and during both NSRCT sessions. ResultsThere were significantly higher reduction percentages of MSBP, MDBP, and MABP in the first NSRCT session than in the second NSRCT session for all treated patients (all the P-values < 0.001). If the patients were divided into 2 or more groups according to the clinical variables including the patients' gender, age, tooth type, and anesthesia type, we also found significantly higher reduction percentages of MSBP, MDBP, and MABP in the first NSRCT session than in the second NSRCT session for all treated patients except for patients below 40 years of age and for patients with lower anterior teeth treated (all the P-values < 0.05). ConclusionThe decrease in blood pressure in patients receiving vital pulpal extirpation is a relatively common phenomenon.

Pulmonary vein isolation with concomitant renal artery denervation is associated with reduction in both arterial blood pressure and atrial fibrillation burden: Data from implantable cardiac monitor.

Renal artery denervation (RDN) has provided incremental atrial fibrillation (AF) suppression after pulmonary vein isolation (PVI) in patients with AF in the setting of drug-resistant hypertension. To assess the relationship between changes of mean blood pressure (BP) and AF recurrences/AF burden after PVI combined with RDN. All patients from two randomized studies with symptomatic paroxysmal AF and/or persistent AF and resistant hypertension who underwent PVI-only (n=37) or PVI with RDN (n=39), and implantable cardiac monitor (ICM) implantation were eligible for this study. Mixed-effects linear models were used to investigate the effect of RDN on mean BP and mean AF burden and associations between the two during the 12-month follow-up. Concomitant RDN was associated with a significant reduction in both mean AF burden (2.43 [95% CI: 1.76-3.09] % vs 6.95 [95% CI: 5.44-8.45] %) and mean BP (104 [95% CI: 103-106] mmHg vs 112 [95% CI: 110-113] mmHg). Decrease in mean BP was positively correlated with decline in mean AF burden: reduction of 5-10mmHg was accompanied by a 7.0% decreased mean AF burden, with greater reduction (up to 20mmHg) associated with on average 17.7% lower mean AF burden. Renal artery denervation when added to PVI decreases AF recurrences, AF burden, and mean BP. Reduction in mean BP is associated with both AF burden and recurrences. Further large-scale studies are needed to define the mechanistic pathway(s) of the antiarrhythmic effects of RDN.

Acute cardiac functional and mechanical responses to isometric exercise in prehypertensive males.

Isometric exercise (IE) training has been shown to reduce resting arterial blood pressure (ABP) in hypertensive, prehypertensive, and normotensive populations. However, the acute hemodynamic response of the heart to such exercise remains unclear. We therefore performed a comprehensive assessment of cardiac structure, function, and mechanics at rest and immediately post a single IE session in 26 male (age 44.8 ± 8.4 years) prehypertensive participants. Conventional echocardiography recorded standard and tissue Doppler measures of left ventricular (LV) structure and function. Speckle tracking echocardiography was used to measure LV global longitudinal, circumferential, and radial strain and strain rate. From this data, apical and basal rotation and rotational velocities, LV twist, systolic twist velocity, untwist velocity, and torsion were determined. IE led to a significant post exercise reduction in systolic (132.6 ± 5.6 vs. 109.4 ± 19.6 mmHg, P < 0.001) and diastolic (77.6 ± 9.4 vs. 58.8 ± 17.2 mmHg, P < 0.001) blood pressure, with no significant change in heart rate (62 ± 9.4 vs. 63 ± 7.5b·min−1, P = 0.63). There were significant reductions in LV end systolic diameter (3.4 ± 0.2 vs. 3.09 ± 0.3 cm, P = 0.002), LV posterior wall thickness (0.99 ± 0.1 vs. 0.9 ± 0.1 cm, P = 0.013), relative wall thickness (0.4 ± 0.06 vs. 0.36 ± 0.05, P = 0.027) estimated filling pressure (E/E' ratio 6.08 ± 1.87 vs. 5.01 ± 0.82, P = 0.006) and proportion of participants with LV concentric remodeling (30.8% vs. 7.8%, P = 0.035), and significant increases in LV ejection fraction (60.8 ± 3 vs. 68.3 ± 4%, P < 0.001), fractional shortening (31.6 ± 4.5 vs. 39.9 ± 5%, P < 0.001), cardiac output (4.3 ± 0.7 vs. 6.1 ± 1L·min−1, P < 0.001), and stroke volume (74.6 ± 11 vs. 96.3 ± 13.5 ml, P < 0.001). In this setting, there were significant increases in global longitudinal strain (−17.8 ± 2.4 vs. −20 ± 1.8%, P = 0.002) and strain rate (−0.88 ± 0.1 vs. −1.03 ± 0.1%, P < 0.001), basal rotation (−5 ± 3.5 vs. −7.22 ± 3.3°, P = 0.047), basal systolic rotational velocity (−51 ± 21.9 vs. −79.3 ± 41.3°·s−1, P = 0.01), basal diastolic rotational velocity (48.7 ± 18.9 vs. 62.3 ± 21.4°·s−1, P = 0.042), LV twist (10.4 ± 5.8 vs. 13.8 ± 5°, P = 0.049), systolic twist velocity (69.6 ± 27.5 vs. 98.8 ± 35.8°·s−1, P = 0.006), and untwist velocity (−64.2 ± 23 vs. −92.8 ± 38°·s−1, P = 0.007). These results suggest that IE improves LV function and mechanics acutely. This may in turn be partly responsible for the observed reductions in ABP following IE training programs and may have important implications for clinical populations.

Abnormal oxygen homeostasis in the nucleus tractus solitarii of the spontaneously hypertensive rat

New Findings What is the central question of this study? Arterial hypertension is associated with impaired neurovascular coupling in the somatosensory cortex. Abnormalities in activity‐dependent oxygen consumption in brainstem regions involved in the control of cardiovascular reflexes have not been explored previously. What is the main finding and its importance? Using fast‐cyclic voltammetry, we found that changes in local tissue PO2 in the nucleus tractus solitarii induced by electrical stimulation of the vagus nerve are significantly impaired in spontaneously hypertensive rats. This is consistent with previous observations showing that brainstem hypoxia plays an important role in the pathogenesis of arterial hypertension. The effects of arterial hypertension on cerebral blood flow remain poorly understood. Haemodynamic responses within the somatosensory cortex have been shown to be impaired in the spontaneously hypertensive rat (SHR) model. However, it is unknown whether arterial hypertension affects oxygen homeostasis in vital brainstem areas that control cardiovascular reflexes. In this study, we assessed vagus nerve stimulation‐induced changes in local tissue PO2 (PtO2) in the caudal nucleus tractus solitarii (cNTS) of SHRs and normotensive Wistar rats. Measurements of PtO2 were performed using a novel application of fast‐cyclic voltammetry, which allows higher temporal resolution of O2 changes than traditional optical fluorescence techniques. Electrical stimulation of the central cut end of the vagus nerve (ESVN) caused profound reductions in arterial blood pressure along with biphasic changes in PtO2 in the cNTS, characterized by a rapid decrease in PtO2 (‘initial dip’) followed by a post‐stimulus overshoot above baseline. The initial dip was found to be significantly smaller in SHRs compared with normotensive Wistar rats even after ganglionic blockade. The post‐ESVN overshoot was similar in both groups but was reduced in Wistar rats after ganglionic blockade. In conclusion, neural activity‐dependent changes in tissue oxygen in brainstem cardiovascular autonomic centres are significantly impaired in animals with arterial hypertension.

Promise of SGLT2 Inhibitors in Heart Failure: Diabetes and Beyond.

This review provides mechanistic insight in the pleiotropic effects of sodium-glucose transporter-2 (SGLT-2) inhibitors with particular interest to the pathophysiology of heart failure. The SGLT-2 inhibitor empagliflozin has recently demonstrated an unprecedented 38% reduction in cardiovascular mortality in patients with diabetes. Despite modest effects on long-term glycemic control, highly significant reductions in heart failure admissions and end-stage kidney disease were observed. SGLT-2 inhibitors are the latest approved class of glucose-lowering agents. By blocking sodium/glucose uptake in the proximal tubules of the nephron, they induce glycosuria. Treatment with SGLT-2 inhibitors in diabetes leads to a sustained ∼1% reduction in glycated hemoglobin levels, with favorable reductions in both arterial blood pressure (∼3-6mmHg) and body weight (∼2-4kg/m2). However, those effects fail to explain fully the dramatic reduction in cardiovascular mortality, heart failure readmissions, and end-stage kidney disease. The unique pharmacological profile of SGLT-2 inhibitors puts them at the crossroads of important hemodynamic, neurohumoral, metabolic, and vascular endothelial pathways influencing cardiac and renal disease. SGLT-2 inhibitors decrease proximal tubular sodium and chloride reabsorption, leading to a reset of the tubuloglomerular feedback. This induces plasma volume contraction without activation of the sympathetic nerve system, decreases harmful glomerular hyper-filtration leading to better long-term renal preservation, and improves diuretic and natriuretic responses to other diuretic agents. Moreover, SGLT-2 inhibitors might improve the efficiency of myocardial energetics by offering β-hydroxybutyrate as an attractive fuel for oxidation and increase hematocrit improving oxygen transport. Finally, decreased vascular stiffness and improved endothelial function are observed with the use of SGLT-2 inhibitors in diabetes. Those multiple nonglycemic effects reinforce SGLT-2 inhibitors as the preferred glucose-lowering drug to treat diabetic patients with heart failure. In the future, they might even be considered in heart failure or chronic kidney disease patients without diabetes.

Cardiovascular effects of dexmedetomidine, with or without MK-467, following intravenous administration in cats

ObjectiveTo characterize the cardiovascular effects of dexmedetomidine, with or without MK-467, following intravenous (IV) administration in cats. Study designProspective Latin square experimental study. AnimalsSix healthy adult purpose-bred cats. MethodsCats were anesthetized with desflurane in oxygen for instrumentation with a carotid artery catheter and a thermodilution catheter in the pulmonary artery. One hour after discontinuation of desflurane, cats were administered dexmedetomidine (25 μg kg–1), MK-467 (600 μg kg–1), or dexmedetomidine (25 μg kg–1) and MK-467 (600 μg kg–1). All treatments were administered IV as a bolus. Cardiovascular variables were measured prior to drug administration and for 8 hours thereafter. Only data from the dexmedetomidine and dexmedetomidine–MK-467 treatments were analyzed. ResultsDexmedetomidine produced significant decreases in heart rate, cardiac index and right ventricular stroke work index, and significant increases in arterial blood pressure, central venous pressure, pulmonary artery pressure and systemic vascular resistance index. Dexmedetomidine combined with MK-467 resulted in significant but transient decrease in blood pressure and right ventricular stroke work index. Conclusion and clinical relevanceFollowing IV co-administration, MK-467 effectively attenuated dexmedetomidine-induced cardiovascular effects in cats. The drug combination resulted in transient reduction in arterial blood pressure, without causing hypotension.

Comparison between dexmedetomidine versus morphine added to bupivacaine in paravertebral block in patients scheduled for modified radical mastectomy

Purpose The aim of the paper was to compare between dexmedetomidine (DM) versus morphine added to bupivacaine in paravertebral block (PVB) for perioperative analgesia in modified radical mastectomy in relation to hemodynamic stability, efficacy of pain relief, and possible complications. Patients and methods A randomized, double-blind, controlled trial was conducted on 45 American Society of Anesthesiologists I–II patients undergoing elective unilateral modified radical mastectomy. Patients were randomly allocated into three groups: group B (n=15) received 20 ml of 0.25% bupivacaine (as control group), group D (n=15) received 20 ml of 0.25% bupivacaine+100 μg DM, and group M (n=15) received 20 ml of 0.25% bupivacaine+2 mg morphine. Hemodynamic parameters, area of local anesthesia, postoperative oxygen saturation and respiratory rate, visual analog scale (VAS) score, shoulder restriction score, time to first dose, and total amounts of supplementary analgesia (meperidine hydrochloride) were recorded. Postoperative sedation was evaluated using Ramsay sedation scale, and postoperative nausea and vomiting were evaluated using postoperative nausea and vomiting impact scale score. Other side effects were also recorded. Results There were no significant differences between the three studied groups at baseline regarding heart rate, mean arterial blood pressure, arterial oxygen saturation (SpO2), and respiratory rate. There was a significant reduction in heart rate in group D since the initiation of skin incision till the end of operation. There was a significant reduction in mean arterial blood pressure in the three groups from the starting of skin incision till the end of operation, but it was more evidenced in group D. Arterial oxygen saturation (SpO2) and respiratory rate were comparable between the three groups at all measuring times. There was significantly lower postoperative VAS score, longer time to first dose, and lower consumption of meperidine hydrochloride in group D than group B and group M. The present study did not show any serious intraoperative or postoperative complications in the three studied groups. Conclusion The addition of DM to bupivacaine in PVB provides a significant clinical benefit by decreasing VAS score, decreasing postoperative use of analgesics, and prolonging the onset of postoperative analgesic requirement without serious adverse effects and is superior to morphine as an adjuvant in PVB.

Functional pharmacological characterization of SER100 in cardiovascular health and disease.

SER100 is a selective nociceptin (NOP) receptor agonist with sodium-potassium-sparing aquaretic and anti-natriuretic activity. This study was designed to characterize the functional cardiovascular pharmacology of SER100 in vitro and in vivo, including experimental models of cardiovascular disease. Haemodynamic, ECG parameters and heart rate variability (HRV) were determined using radiotelemetry in healthy, conscious mice. The haemodynamic and vascular effects of SER100 were also evaluated in two models of cardiovascular disease, spontaneously hypertensive rats (SHR) and murine hypoxia-induced pulmonary hypertension (PH). To elucidate mechanisms underlying the pharmacology of SER100, acute blood pressure recordings were performed in anaesthetized mice, and the reactivity of rodent aorta and mesenteric arteries in response to electrical- and agonist-stimulation assessed. SER100 caused NOP receptor-dependent reductions in mean arterial blood pressure and heart rate that were independent of NO. The hypotensive and vasorelaxant actions of SER100 were potentiated in SHR compared with Wistar Kyoto. Moreover, SER100 reduced several indices of disease severity in experimental PH. Analysis of HRV indicated that SER100 decreased the low/high frequency ratio, an indicator of sympatho-vagal balance, and in electrically stimulated mouse mesenteric arteries SER100 inhibited sympathetic-induced contractions. SER100 exerts a chronic hypotensive and bradycardic effects in rodents, including models of systemic and pulmonary hypertension. SER100 produces its cardiovascular effects, at least in part, by inhibition of cardiac and vascular sympathetic activity. SER100 may represent a novel therapeutic candidate in systemic and pulmonary hypertension.

Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial

BackgroundGeneralized Anxiety Disorder (GAD) is one of the most common anxiety disorders treated in primary care, yet current therapies have limited efficacy and substantial side effects. PurposeTo evaluate long-term chamomile (Matricaria chamomilla L.) use for prevention of GAD symptom relapse. MethodsOutpatients from primary care practices and local communities with a primary diagnosis of moderate-to-severe GAD were enrolled for this two-phase study at a large US academic medical center. During Phase 1, eligible participants received 12 weeks of open-label therapy with chamomile pharmaceutical grade extract 1500mg (500mg capsule 3 times daily). During Phase 2, treatment responders were randomized to either 26 weeks of continuation chamomile therapy or placebo in a double-blinded, placebo-substitution design. The primary outcome was time to relapse during continuation therapy, analyzed using Cox proportional hazards. Secondary outcomes included the proportion who relapsed, treatment-emergent adverse events, and vital sign changes. This study is registered at ClinicalTrials.gov, identifier NCT01072344. ResultsBetween March 1, 2010, and June 30, 2015, we enrolled 179 participants. Of those, 93 (51.9%) were responders and agreed to continue in the double-blind randomized controlled trial. A numerically greater number of placebo-switched (n=12/47; 25.5%) versus chamomile-continuation (n = 7/46; 15.2%) participants relapsed during follow-up. Mean time to relapse was 11.4 ± 8.4 weeks for chamomile and 6.3 ± 3.9 weeks for placebo. Hazard of relapse was non-significantly lower for chamomile (hazard ratio, 0.52; 95% CI, 0.20–1.33; P = 0.16). During follow-up, chamomile participants maintained significantly lower GAD symptoms than placebo (P = 0.0032), with significant reductions in body weight (P = 0.046) and mean arterial blood pressure (P = 0.0063). Both treatments had similar low adverse event rates. ConclusionsLong-term chamomile was safe and significantly reduced moderate-to-severe GAD symptoms, but did not significantly reduce rate of relapse. Our limited sample size and lower than expected rate of placebo group relapse likely contributed to the non-significant primary outcome finding. Possible chamomile superiority over placebo requires further examination in large-scale studies.

Cardiovascular effect of Nigella sativa L. Aqueous Extract in Normal Rats.

This study aims to evaluate the cardiovascular effect of Nigella sativa L. aqueous extract (NSAE) in normal rats. The in vivo experiment showed that the intravenous injection of NSAE at the doses of 50, 100 and 200 mg/kg of body weight produced a dose dependent reduction in the mean arterial blood pressure (MABP) (p<0.001) accompanied by a significant fall in heart rate (p<0.01). In the in vitro experiment, incubation of NSAE during 30 min caused a right shift of the contraction response curve of aortic ring to Norepinephrine (NE) with a reduction of the maximal contraction response (p<0.01). Endothelium destruction significantly reduced the vasorelaxant effect of NSAE at a dose of 30 mg/ml (p<0.01). Furthermore, Nitric oxide synthase inhibitor: Nω-Nitro-L-Arginine Methyl Ester (L-NAME) produced a significant reduction (p<0.01) of the in vitro vasorelaxant effect of NSAE at a dose of 30 mg/ml. We conclude that NSAE possess a rapid and dose dependent in vivo hypotensive effect in normal rats which may be probably due to the inhibition of parasympathetic tone. In isolated aortic ring, NSAE possess a potent inhibitor of contractile response to NE which may be probably due to an increase in the endothelial nitric oxide synthesis.

216-07: Pulmonary vein isolation with concomitant renal artery denervation is associated with reduction of both arterial blood pressure and atrial fibrillation burden: data from implantable cardiac monitor

216-07: Pulmonary vein isolation with concomitant renal artery denervation is associated with reduction of both arterial blood pressure and atrial fibrillation burden: data from implantable cardiac monitor

Pharmacological evidence of α-adrenergic receptors in the hypotensive effect of Chamaemulum nobile L.

This study aims to evaluate the underlying mechanism of action involved in the hypotensive effect of Chamaemulum nobile L. (Cn) aqueous extract and in anesthetized Wistar rats. Lyophilized aqueous extract was administered in the jugular vein, arterial blood pressure and heart rate were measured in the carotide artery over 120 min of injection throughout an invasive direct blood pressure measuring procedure. Intravenous bolus injection of aqueous Cn extract at the doses of 50, 100 and 200 mg/kg produced a dose dependent reduction in arterial blood pressure and heart rate (p<0.001). Specific receptor antagonists (Phentolamine, Terazosin and Atropine) and pharmacological agents (N(omega)-Nitro-L-Arginine Methyl Ester and Captopril) were used for determining the underlying mechanism involved in the hypotensive effect of Cn. Only Phentolamine treatment (2 mg/kg) reduced significantly the hypotensive effect of aqueous Cn extract at a dose of 200 mg/kg. Intravenous perfusion of aqueous Cn extract caused a significant reduction of arterial blood pressure (p<0.01) and reduced the hypertensive effect of intravenous injection of norepinephrine at a dose of 1 &#181;g/kg. We conclude that aqueous Cn extract exhibits a hypotensive effect which may be probably due to an alpha adrenergic receptor blockade mechanism.

Upregulation of Orexin in the Paraventricular Nucleus Contributes to Salt Sensitive Hypertension

Orexin and orexin receptors are extensively expressed in the hypothalamic paraventricular nucleus (PVN) and the hyperactivity of PVN orexin contributes to increased sympathetic nerve activity (SNA) and elevated blood pressure in several animal models. However, the role of PVN orexin in the development of salt sensitive hypertension (SSHTN) is unknown. In this study, we tested the hypothesis that PVN orexin expression is increased in SSHTN and contributes to the development of SSHTN via regulating vasopressin secretion. Eight‐week‐old Dahl salt sensitive (DS) rats were divided into two groups and were fed either a high salt (HS, 8% NaCl) or normal salt (NS, 0.4% NaCl) diet. Six weeks following diet treatment, rats were anesthetized and their mean arterial pressure (MAP) and sympathetic nerve activity (SNA) response to orexin receptor blockade were recorded. In a separate group of rats PVN orexin mRNA levels were measured. The results showed that HS intake induced significant increases in MAP (HS: 146±2 vs. NS: 112±5; n=5; P&lt;0.05) and PVN orexin mRNA levels (HS: 3.8±0.37 vs. NS: 1.0±0.68; n=3; P&lt;0.05). Bilateral PVN microinjection of orexin receptor 1 (OX1R) antagonist SB408124 (30 pmol/50nl) resulted in a greater reduction in arterial blood pressure in DS rats with a HS intake compared to their cohorts with a NS diet (HS: −16±5 vs. NS: −4±4 mmHg; n=5–6; P&lt;0.05). OX1R blockade also increased splanchnic SNA (HS: 48.2±12.6%) vs. NS: 35.82±9%; P=0.2) and renal SNA (HS: 26.7±7.5% vs. NS: 17.4±9.5%; P=0.2) in DS rats with either HS or NS diet. Incubation of orexin A resulted in a dose‐dependent increase in vasopressin mRNA levels (100nM: 2.9‐fold; 1μM; 5.6 fold; 10μM: 18‐fold) in primary cultured neurons from the hypothalamus containing the PVN of neonatal Sprague Dawley rats. These orexin A‐induced increases of vasopressin mRNA were abolished by OX1R blockade. These results coupled with the evidence that plasma vasopressin is upregulated in DS rats under the condition of HS‐induced hypertension suggest that increased PVN orexin expression may be involved in the development of SSHTN through regulating vasopressin secretion.Support or Funding InformationThis study is supported by AHA 11SDG7420029 and NIH R15‐HL122952.