Decrease In Mean Arterial Blood Pressure Research Articles

8-Aminoguanine and its actions in the metabolic syndrome.

The metabolic syndrome is characterized by obesity, insulin resistance, dyslipidemia and hypertension and predisposes to cardiorenal injury. Here, we tested our hypothesis that 8-aminoguanine, an endogenous purine, exerts beneficial effects in Zucker Diabetic-Sprague Dawley (ZDSD) rats, a preclinical model of the metabolic syndrome. ZDSD rats were instrumented for blood pressure radiotelemetry and randomized to vehicle or 8-aminoguanine (10mg/kg/day, po). The protocol was divided into four phases: Phase 1: 17days of tap water/normal diet; Phase 2: 30days of 1% saline/normal diet; Phase 3: 28days of 1% saline/diabetogenic diet; Phase 4: acute/terminal measurements. 8-Aminoguanine: (1) decreased mean arterial blood pressure (P = 0.0004; 119.5 ± 1.0 (vehicle) versus 116.3 ± 1.0 (treated) mmHg) throughout all three phases of the radiotelemetry study; (2) rebalanced the purine metabolome away from hypoxanthine (pro-inflammatory) and towards inosine (anti-inflammatory); (3) reduced by 71% circulating IL-1β, a cytokine that contributes to hypertension-induced adverse cardiovascular events and type 2 diabetes; (4) attenuated renovascular responses to angiotensin II; (5) improved cardiac and renal histopathology; (6) attenuated diet-induced polydipsia/polyuria; and (7) reduced HbA1c. In the metabolic syndrome, 8-aminoguanine lowers blood pressure, improves diabetes and reduces organ damage, likely by rebalancing the purine metabolome leading to reductions in injurious cytokines such as IL-1β.

Early Prediction of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants using Non-invasive Electrical Cardiometry

Abstract Background Prematurity is a term for the broad category of neonates born at less than 37 weeks' gestation following onset of the last menstrual period. Different degrees of prematurity are defined by gestational age (GA) or birth weight (BW). Prematurity is associated with approximately one- third of all infant deaths. Complications of prematurity are the underlying cause of the higher rate of infant mortality and morbidity in preterm infants compared to full term infants. Objective To identify hemodynamic changes during the first 48hrs in life using non-invasive cardiometry and how these changes can predict which infants would develop clinical and echocardiographic criteria for PDA treatment. Patients and Methods This Prospective cohort study was conducted at tertiary care hospital at the neonatal intensive care units of Ain Shams University, Children’s Hospital from October 2021 till April 2022 and performed on preterm neonates who are less than 35 weeks gestational age and admitted to the NICU of pediatric hospital. Results Hemodynamically-significant PDA group had significantly lower systolic, diastolic blood pressure and mean arterial blood pressure than hemodynamically not significant PDA group at each time of follow up and significantly higher heart rate at (12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 45, 48) hours in patients with hemodynamically-significant PDA. There was statistically significant difference between the two studied groups as regards vital data of Oxygen saturation (SpO2) and UOP which were significantly lower in hemodynamically-significant PDA. Conclusion in our prospective cohort study increased heart rate, decreased mean arterial blood pressure predict a clinically significant PDA requiring treatment. Furthermore, vital data seem to be a good non invasive tools to monitor hemodynamic changes in preterms with hemodynamically significant PDA. However, further studies with a higher number of patients are necessary to ground the outcomes of these preliminary considerations.

Targeting mevalonate pathway by zoledronate ameliorated pulmonary fibrosis in a rat model: Promising therapy against post-COVID-19 pulmonary fibrosis.

Rho kinase (ROCK) pathway plays a critical role in post-COVID-19 pulmonary fibrosis (PCPF) and its intervention with angiotensin-converting enzyme 2 (ACE2) and vascular endothelial growth factor (VEGF) will be a potential therapeutic target. The present study was conducted to investigate the efficacy of zoledronate (ZA) on carbon tetrachloride (CCl4) induced pulmonary fibrosis (PF) in rats through targeting ACE2, ROCK, and VEGF signaling pathways. Fifty male Wistar rats were divided into five groups: control, vehicle-treated, PF, PF-ZA 50, and PF-ZA 100 groups. ZA was given in two different doses 100 and 50 μg/kg/week intraperitoneally. After anesthesia, mean arterial blood pressure (MBP) was measured. After scarification, lung coefficient was calculated. Lung levels of ACE 2, interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), VEGF, glutathione (GSH), and superoxide dismutase (SOD) were measured. Expression of ROCK, phosphorylated myosin phosphatase target subunit 1 (P-MYPT1), and matrix metalloproteinase (MMP-1), along with histopathological changes and immune-histochemical staining for lung α-smooth muscle actin (α-SMA), tumor necrosis factor-alpha (TNFα), and caspase-3, were evaluated. ZA significantly prevented the decrease in MBP. ZA significantly increased ACE2, GSH, and SOD and significantly decreased IL-1β, TGF-β, and VEGF in lung in comparison to PF group. ZA prevented the histopathological changes induced by CCl4. ZA inhibited lung expression of ROCK, P-MYPT1, MMP-1, α-SMA, TNFα, and caspase-3 with significant differences favoring the high dose intervention. ZA in a dose-dependent manner prevented the pathological effect of CCl4 in the lung by targeting mevalonate pathway. It could be promising therapy against PCPF.

Evaluation of Caralluma edulis for its Potential Against Obesity, Atherosclerosis and Hypertension.

Obesity, a chronic metabolic condition, is an increase in fat mass and blood lipid levels mainly causing atherosclerosis and hypertension, which further lead to cardiovascular complications. The objective of the study was to investigate the crude extract of Caralluma edulis (CE.Cr) for its potential against high-fat diet (HFD)-induced obesity and its related complications. Hyperlipidemia was induced in Wistar albino rats with HFD (1% cholesterol + 0.5% cholic acid) for 28days. Treatment groups were administered with different doses of CE.Cr (100, 300 and 500mg/Kg, p.o.) and the standard group received atorvastatin. At the end of study, sera were analyzed for biochemical markers and the aorta was dissected for microscopic examination. Antioxidant potential was evaluated and high-performance liquid chromatography (HPLC) analysis was performed. The hypotensive potential of CE.Cr was evaluated through an invasive technique. HPLC analysis of CE.Cr showed the presence of chlorogenic acid, caffeic acid, apigenin and naringenin. Histological examination of the aorta section showed anti-atherosclerotic effects which were also evident from decrease in serum total cholesterol, triglycerides and low-density lipoproteins levels. CE.Cr decreased mean arterial blood pressure and evoked significant hypotensive effects. The crude extract of C. edulis showed anti-obesity, antihypertensive, anti-atherosclerotic and antioxidant potential.

The effect of continuous intravenous norepinephrine infusion on systemic hemodynamics in a telemetrically-monitored mouse model of sepsis.

Sepsis, a life-threatening organ dysfunction, results from dysregulated host responses to infection and still has a high incidence and mortality. Although administration of vasopressors to treat septic shock is standard of care, the benefits are not well established. We evaluated the effect of continuous intravenous norepinephrine infusion in a septic cecal ligation and puncture (CLP) mouse model, evaluating systemic hemodynamics and body temperature post-hoc. CLP surgery significantly decreased mean arterial blood pressure (MAP), heart rate, and body temperature within six hours. Continuous norepinephrine infusion (NE+, n = 12) started at the time of CLP surgery significantly increased MAP at 24 and 30 hours and heart rate at 6, 18, 24, and 30 hours after CLP vs CLP alone (NE-, n = 12). However, addition of norepinephrine did not improve survival rate (NE+ n = 34, NE- n = 31). Early (6 hours or earlier, when the animal became visibly sick) MAP did not predict 7-day mortality. However, heart rates at 3 and at 6 hours after CLP/norepinephrine (NE+) were highly predictive of mortality, as also been found in one clinical study. We conclude that limited hemodynamic support can be provided in a mouse sepsis model. We propose that heart rate can be used to stratify severity of illness in rodent preclinical studies of sepsis therapeutics.

Pharmacological evaluation of Typha domingensis for its potentials against diet-induced hyperlipidemia and associated complications

Purpose: To evaluate the hyperlipidemic potential of the methanolic-aqueous extract of Typha domingensis Pers.Method: Hyperlipidemia was induced in Wistar rats with high fat diet (HFD). The animals were divided into five groups; normal control group was administered normal diet and water ad libitum; whereas, all other groups were given HFD along with respective treatment; i.e., positive control group (normal saline, 1 ml/kg; p.o.), standard control group (atrovastatin 5 mg/kg; p.o.) and treatment groups received 70 % methanolic-aqueous extract of Typha domingensis (TD.Cr) at the 100 and 300 mg/kg p.o. After 28 days, the animals were weighed, blood was collected and sera separated. Aortas were dissected out for histological studies. Sera were analyzed for total cholesterol, triglycerides, HDL and LDL. Hypotensive effects were evaluated through invasive technique followed by diuretic activity.Results: Typha domingensis extract significantly lowered the levels of total cholesterol, triglycerides, and LDL to 132.30 ± 1.145, 161.50 ± 1.33 and 41.67 ± 1.28 mg/dL, respectively, at 100 mg/kg (p < 0.001) and 111.50 ± 1.05, 157.70 ± 1.74 and 29.17 ± 0.98 mg/dL, at 300 mg/kg, respectively (p < 0.001). It produced anti-obesity effects represented as reduction in body weight by 17.00 ± 1.29 to 1.5 ± 7.63 g (p < 0.001) from 100 to 300 mg/kg, respectively, compared to control. Histological studies revealed the anti-atherosclerotic effect of the plant extract. A decreasing mean arterial blood pressure revealed hypotensive effects.Conclusion: Typha domingensis has a potential for the treatment of diet-induced hyperlipidemia and associated complications. However, clinical investigations are required to buttress these assertions.

Effects of Fumarate on Blood Pressure and Renal Hemodynamics in Normotensive Rats: Possible Contribution of Sodium Potassium Co‐transporter (NKCC)

The tricarboxylic acid cycle product, fumarate, and its related products, have been implicated in the etiology of genetic and non‐genetic models of hypertension. Fumarate showed a mechanistic link to nitric oxide (NO) production and thus impacted blood pressure and renal hemodynamics in both models. This study evaluated the possibility of a role of fumarate in regulation of blood pressure and renal hemodynamics in normotensive rats and elucidate possible mechanisms involved. Animals were anaesthetized with Thiobutabarbital (100 mg/kg, ip). The carotid artery was cannulated for mean arterial blood pressure (MABP) measurement and the left kidney was exposed to measure cortical blood flow (CBF) and medullary blood flow (MBF). Blood and urine were collected to determine glomerular filtration rate (GFR), urine volume (Uv) and sodium excretion (UNaV). The fumarase inhibitor, pyromellitic acid (PMA) (0.1 mg/kg/h), or fumarate (0.1 mg/kg/h) were infused in these animals. To determine renal sodium excretory mechanisms involved with fumarate, fumarate (1 mg/kg, po) was administered to normotensive rats treated with hydrochlorothiazide (HCTZ) (10 mg/kg, po) or furosemide (10 mg/kg, po), urine was collected hourly for five (5) hours and assayed for sodium. Fumarate elicited a hypotensive effect, with peak effect at the 45th minute (126 ± 6.2 vs 93 ±2.6 mmHg, p<0.05). Similarly, inhibition of fumarase caused a time‐dependent decrease in MABP (p<0.05). There was a consistent drop in CBF in fumarate‐infused rats and although PMA caused an initial rise in CBF at 15 mins, there was a 10‐fold increase in CBF at 60 min when compared to fumarate‐infused rats (p<0.05). MBF also decreased in a time‐dependent fashion in rats infused with fumarate. Consistent with the drop in MABP and CBF, GFR reduced (0.89 ± 0.26 vs 0.39 ± 0.11 mL/min, p<0.05) at 30 mins before to returning to baseline levels at 60 mins in fumarate‐infused rats. Uv was unchanged in rats infused with fumarate but there was a 1‐fold reduction in UNaV at 30 mins (p<0.05). Also, PMA, tended to increase UNaV at 30 mins, compared to baseline. However, there was an exacerbation in UNaV in PMA‐infused rats (24.2 ± 3.8 µmol/L) compared to fumarate‐infused rats at 30 mins (4.56 ±1.4 µmol/L, p<0.05). Fumarate increased UNaV compared to control (p<0.05), however, there was no significant difference in UNaV between furosemide‐treated and furosemide‐treated fumarate rats. These data indicate that fumarate and its products elicited vasodilatory effects that reduced blood pressure and exerted vascular and tubular effects on renal hemodynamics. Also, the tubular effects, possibly involves inhibition of sodium potassium co‐transporter (NKCC).

Cardiovascular and hemodynamic consequences of recombinant placental growth factor administration in Guinea pigs

ABSTRACT Placental growth factor (PlGF), a member of the vascular endothelial growth factor family of proteins regulating angiogenesis, has been shown to have acute vasodilatory effects on human resistance arteries. However, the acute hemodynamic effects of PlGF in vivo are not known. The aim of this study was to report acute cardiovascular changes induced by recombinant human PlGF administered intravenously in male Guinea Pigs with implanted telemeters. PlGF decreased mean arterial blood pressure by 10–20% within minutes. The magnitude of reduction was similar at three dose levels; however, the duration of relative hypotension was dose-dependent. Blood pressure reduction resulted in a compensatory increase in heart rate, or reflex tachycardia. To rule out any direct effect on the heart, PlGF was tested in the ex vivo Langendorff heart preparation, and no cardiac changes were found. Together these results suggest that the PlGF-related changes in blood pressure are largely mediated by its actions in the vasculature.

Transient Hypoperfusion to Ischemic/Anoxic Spreading Depolarization is Related to Autoregulatory Failure in the Rat Cerebral Cortex

BackgroundIn ischemic stroke, cerebral autoregulation and neurovascular coupling may become impaired. The cerebral blood flow (CBF) response to spreading depolarization (SD) is governed by neurovascular coupling. SDs recur in the ischemic penumbra and reduce neuronal viability by the insufficiency of the CBF response. Autoregulatory failure and SD may coexist in acute brain injury. Here, we set out to explore the interplay between the impairment of cerebrovascular autoregulation, SD occurrence, and the evolution of the SD-coupled CBF response.MethodsIncomplete global forebrain ischemia was created by bilateral common carotid artery occlusion in isoflurane-anesthetized rats, which induced ischemic SD (iSD). A subsequent SD was initiated 20–40 min later by transient anoxia SD (aSD), achieved by the withdrawal of oxygen from the anesthetic gas mixture for 4–5 min. SD occurrence was confirmed by the recording of direct current potential together with extracellular K+ concentration by intracortical microelectrodes. Changes in local CBF were acquired with laser Doppler flowmetry. Mean arterial blood pressure (MABP) was continuously measured via a catheter inserted into the left femoral artery. CBF and MABP were used to calculate an index of cerebrovascular autoregulation (rCBFx). In a representative imaging experiment, variation in transmembrane potential was visualized with a voltage-sensitive dye in the exposed parietal cortex, and CBF maps were generated with laser speckle contrast analysis.ResultsIschemia induction and anoxia onset gave rise to iSD and aSD, respectively, albeit aSD occurred at a longer latency, and was superimposed on a gradual elevation of K+ concentration. iSD and aSD were accompanied by a transient drop of CBF (down to 11.9 ± 2.9 and 7.4 ± 3.6%, iSD and aSD), but distinctive features set the hypoperfusion transients apart. During iSD, rCBFx indicated intact autoregulation (rCBFx < 0.3). In contrast, aSD was superimposed on autoregulatory failure (rCBFx > 0.3) because CBF followed the decreasing MABP. CBF dropped 15–20 s after iSD, but the onset of hypoperfusion preceded aSD by almost 3 min. Taken together, the CBF response to iSD displayed typical features of spreading ischemia, whereas the transient CBF reduction with aSD appeared to be a passive decrease of CBF following the anoxia-related hypotension, leading to aSD.ConclusionsWe propose that the dysfunction of cerebrovascular autoregulation that occurs simultaneously with hypotension transients poses a substantial risk of SD occurrence and is not a consequence of SD. Under such circumstances, the evolving SD is not accompanied by any recognizable CBF response, which indicates a severely damaged neurovascular coupling.

Effect of anesthesia induction on cerebral tissue oxygen saturation in hypertensive patients: an observational study

ObjectiveIn hypertensive patients, the autoregulation curve shifts rightward, making these patients more sensitive than normotensive individuals to hypotension. Hypotension following the induction of anesthesia has been studied in normotensive patients to determine its effects on brain tissue oxygenation, but not enough studies have examined the effect of hypotension on brain oxygenation in hypertensive patients. The current study aimed to use near-infrared spectroscopy to evaluate brain tissue oxygen saturation after the induction of anesthesia in hypertensive patients, who may have impaired brain tissue oxygen saturation. MethodsThe study included a total of 200 patients aged > 18 years old with ASA I–III. Measurements were taken while the patient was breathing room air, after the induction of anesthesia, when the lash reflex had disappeared following the induction of anesthesia, after intubation, and in the 5th, 10th, and 15th minutes of surgery. The patients were divided into nonhypertensive and hypertensive groups. ResultsThere was a significant difference in age between the groups (p = 0.000). No correlation was found between cerebral tissue oxygen saturation and age (r = 0.015, p = 0.596). Anesthesia induction was observed to decrease mean arterial blood pressure in both groups (p = 0.000). Given these changes, there was no significant difference in brain tissue oxygen saturation between the nonhypertensive and hypertensive groups (p > 0.05). ConclusionThere was no difference between hypertensive and normotensive groups in terms of the change rates in cSO2 values. However, there was a difference between the groups in terms of cSO2 values.

Early Renal Vasodilator and Hypotensive Action of Epoxyeicosatrienoic Acid Analog (EET-A) and 20-HETE Receptor Blocker (AAA) in Spontaneously Hypertensive Rats.

Cytochrome P450 (CYP-450) metabolites of arachidonic acid: epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) have established role in regulation of blood pressure (BP) and kidney function. EETs deficiency and increased renal formation of 20-HETE contribute to hypertension in spontaneously hypertensive rats (SHR). We explored the effects of 14,15-EET analog (EET-A) and of 20-HETE receptor blocker (AAA) on BP and kidney function in this model. In anesthetized SHR the responses were determined of mean arterial blood pressure (MABP), total renal (RBF), and cortical (CBF) and inner-medullary blood flows, glomerular filtration rate and renal excretion, to EET-A, 5 mg/kg, infused i.v. for 1 h to rats untreated or after blockade of endogenous EETs degradation with an inhibitor (c-AUCB) of soluble epoxide hydrolase. Also examined were the responses to AAA (10 mg/kg/h), given alone or together with EET-A. EET-A significantly increased RBF and CBF (+30% and 26%, respectively), seen already within first 30 min of infusion. The greatest increases in RBF and CBF (by about 40%) were seen after AAA, similar when given alone or combined with EET-A. MABP decreased after EET-A or AAA but not significantly after the combination thereof. In all groups, RBF, and CBF increases preceded the decrease in MABP. We found that in SHR both EET-A and AAA induced renal vasodilation but, unexpectedly, no additive effect was seen. We suggest that both agents have a definite therapeutic potential and deserve further experimental and clinical testing aimed at introduction of novel antihypertensive therapy.

Animal models for analysis of hypersensitivity reactions to Shuanghuanglian injection

Among a variety of traditional Chinese medicines, Shuanghuanglian injection (SHLI), has the highest incidence of injection-induced immediate hypersensitivity reactions (IHRs). However, the precise mechanisms of SHLI-induced IHRs remain to be understood. In the present study, we characteriszed IHRs as induced by SHLI by recording changes in physiological and hemodynamic indicators following intravenous injections of SHLI in rats and dogs. The results indicate that SHLI induced the release of histamine, decreased mean arterial blood pressure (MAP), increased SC5b-9 in rats and dogs, increased C4d and Bb in dogs without any changes in IgE. n vitro incubation of SHLI with serum from dogs in the presence of an inhibitor of complement activation (EGTA/Mg2+) resulted in an increase in C4d. These results suggest that SHLI induces anaphylactoid reactions in rats and dogs. Furthermore, SHLI appears to activate the complement system through classical and alternative pathways in dogs in vivo. Additional experiments in mice demonstrated that SHLI induces locus coeruleus infiltration and results in significant increase in vascular permeability within the skin of mice. We established a reliable method for the evaluation of anaphylactoid reactions induced by complex compounds, using multiple physiological indicators, different experimental models in vivo and in vitro.

Acute hypotensive effect of EET‐A, a stable analog of epoxyeicosatrienic acid (EET), in spontaneously hypertensive rats: dependence on endogenous EETs activity

IntroductionArterial hypertension and related disorders are one of the main mortality causes world‐wide. Recent evidence points to epoxyeicosatrienoic acids (EETs) as significant factors in blood pressure regulation. These cytochrome P‐450 dependent metabolites of arachidonic acid, exhibit vasodilator and natriuretic activity. Therefore EETs might contribute to reduction of elevated blood pressure and have therapeutic potential. In our spontaneously hypertensive rats (SHR), potential hypotensive efficiency was examined of EET‐A (disodium (S)‐2‐(13‐(3‐entyl)ureido)‐tridec‐8(Z)‐enamido) succinate), a stable 14,15‐EET analog. EET‐A effects were studied in animals that were or were not pretreated with c‐AUCB (cis‐4‐[4‐(3‐adamantan‐1‐yl‐ureido)‐ cyclohexyloxy]‐benzoic acid), an inhibitor of soluble epoxide hydrolase (sEH) which prevents degradation of EETs. Inhibition of sEH increases endogenous EETs levels.MethodsAnesthetized SHR aged 16 weeks (established hypertension) received 1‐hour infusion of EET‐A (5 mg/kg BW iv) or its solvent. These acute experiments were performed in rats pretreated for 14 days with oral c‐AUCB (8.5 mg/kg/24 h, in drinking water) or in untreated rats receiving c‐AUCB solvent. Throughout experiments mean arterial blood pressure (MABP) and left kidney total blood flow (RBF, renal artery probe) and perfusion of the cortex, outer‐ and inner medulla (CBF, OMBF, IMBF; laser‐Doppler fluxes) were measured, along with renal excretion of water (V), total solute (UosmV), and sodium (UNaV).ResultsBasal MABP measured after chronic treatments tended to be lower after c‐AUCB compared to solvent‐treated group; otherwise no meaningful between‐group differences in renal hemodynamics and excretion parameters were seen. In control group pretreated with c‐AUCB‐solvent, EET‐A administration was followed by a delayed significant progressive decrease in MABP, down to a value 6% below control (p=0.01). In AUCB‐pretreated group no significant post‐EET‐A change in MABP was seen. During EET‐A infusion RBF and CBF significantly and fairly rapidly increased, to 130% and 124% of the control levels, respectively, comparably in untreated and c‐AUCB pretreated group and became almost always significant within the first 30 minutes of EET‐A infusion.SummaryIn acute experiments with anesthetized SHR, administration of EET analog (EET‐A) caused a significant delayed reduction of MABP. Not unexpectedly, previous enhancement of endogenous EETs activity after sEH blockade tended to reduce baseline MABP and virtually abolished the pressure reduction in response to exogenous EET analog. Irrespective of the baseline endogenous EET activity, EET‐A invariably induced renal vasodilation. The data indicate that in adult SHR a hypotensive effect can be obtained both by administration of EET analog and by enhancing endogenous EETs activity. On the other hand, only EET‐A treatment was found to improve renal hemodynamics.Support or Funding InformationNational Science Centre 2017/26/M/NZ5/00367

Prognostic Value of Serum Lactate Levels in Critically Ill Patients in an Intensive Care Unit.

IntroductionThe patient in critical condition, regardless of the cause of admission, continues to be a challenge for health systems due to the high mortality that it reports. There is a need to identify some marker of early obtaining, easy to interpret and with high relevance in the prognosis of these patients.ObjectiveTo determine the prognostic value of serum lactate in an Intensive Care Unit (ICU).MethodOne hundred and forty-five patients admitted to an ICU were enrolled in the study. The Acute Physiology and Chronic Health Evaluation II (APACHE) prognosis score, Sequential Organ Failure Assessment, hemodynamic support need, mechanical ventilation, cause of admission, stay in ICU, analytical and physiological variables were determined. The probability of survival of patients who had elevated and normal serum lactate levels was calculated. The risk of dying was determined using the Cox regression model.ResultsTwenty-eight patients died (19%) in the ICU. The serum lactate value was higher in the group of patients with trauma, infections, APACHE II and high creatinine levels; as well as with decreased mean arterial blood pressure, need for hemodynamic support and mechanical ventilation. The survival capacity was higher in patients who had normal serum lactate. Serum lactate was the sole independent predictor of mortality (AHR 1.28 [1.07-1.53], p = 0.008).ConclusionsPatient assessment through the determination of serum lactate levels provides useful information in the initial evaluation of the critical patient.

Potential Protective Role of Vitamin E in Lung of Adult Male Albino Rat Exposed to Bisphenol A

Abstract Background: Bisphenol A (BPA) is a worldwide manu-factured chemical in plastic industry. Exposure to BPA through food and drinking water in plastic containers leads to human health problems. Aim of Study: This study intends to explore the possible protective role of vitamin E against BPA induced functional and structural changes in the lungs of adult male albino rats. Material and Method: Twenty four adult male albino rats were divided randomly into 4 equal groups of 6 rats each; Group I (controls) divided into 2 subgroups: Subgroup (A) (negative control group): Fed on regular diet and water for 8 weeks. Subgroup (B) (vehicle control group): Received (1ml of corn oil) by oral gavage/day for 8 weeks. Group II (vitamin E alone) received 200mg Vitamin E/kg/day; Group III (BPA alone) received 500mg BPA/kg/day; Group IV (BPA and vitamin E co-administered) as in groups II and III. The drugs were administered through oral gavage for 8 weeks, at the end of the experiment, heart rate (HR) and mean arterial blood pressure (MABP) were estimated for all the animals. Blood samples were withdrawn for chemical examinations, and after sacrifice fresh lung specimens were collected for histological examination. Results: Administration of Vitamin E in cooperation with BPA significantly decreased MDA levels, MPO and Caspase-3 activities. In addition, it increased GSH, CAT and SOD activities significantly in rat lung tissues. Also, plasma levels of TNF-a, IL-1b, IL-6 and LDH were significantly decreased. Blood gases analysis showed no significant difference in pH, but showed increase in PaO2 decrease in PaCO2 significantly. Moreover hemodynamics changes in the form of significant decrease in MABP and HR. Vitamin E protected lungs against BPA induced histopathological changes like inflammation, congestion, inter alveolar septum thickening, alveolar damage, collagen fibers percent area and fatty infiltration, also the immunohistochemical changes were altered as depicted by significant decrease in the cluster of differentiation 68 (CD68) +ve cell count and decreased expression of nuclear factor kappa B (NF-kB) in immunestained cells of the lung tissue.Conclusion: BPA exposure induced oxidative stress, inflammation and structural lung injury which were signifi-cantly less by coadminstration of vitamin E supplementation.

Effect of TRPA1 activator allyl isothiocyanate (AITC) on rat dural and pial arteries.

Transient receptor potential ankyrin 1 (TRPA1) channels may have a role in migraine as some substances known to cause headache activate the channel. In the craniovascular system such activation causes a calcitonin gene-related peptide (CGRP)-dependent increase in meningeal blood flow. TRPA1 channels in the endothelium of cerebral arteries cause vasodilation when activated. The headache preventive substance feverfew inhibits activation of TRPA1 channels. In this study we aim to compare and characterize the effect of the TRPA1 agonist allyl isothiocyanate (AITC) on the diameter of rat dural and pial arteries in vivo. The genuine closed-cranial window technique in rats was used to examine changes in dural and pial artery diameter and mean arterial blood pressure (MABP) after intracarotid infusion of AITC. Blockade experiments were performed by intravenous infusion of olcegepant, HC-030031, sumatriptan or capsazepine immediately after infusion of AITC, in four different groups of rats. AITC caused a significant dilation of dural arteries, which was inhibited by HC-030031, olcegepant and sumatriptan, but not by capsazepine. In pial arteries AITC caused a significant dilation, which was not inhibited by any of the pre-treatments, suggesting a poor penetration of the blood-brain barrier or autoregulation due to dimethyl sulfoxide (DMSO) mediated decrease in MABP during HC-030031 infusion. AITC did not cause a significant change in MABP. AITC causes dilation of dural arteries via a mechanism dependent on CGRP and TRPA1 that is sensitive to sumatriptan. AITC causes a small but significant dilation of pial arteries.

The role of small and intermediate conductance calcium-activated potassium channels in endothelial-dependent hyperpolarization in physiology and arterial hypertension

The endothelium plays a crucial role in modulating vascular tone by synthesizing and releasing endothelium-derived relaxing factors, including nitric oxide (NO) and prostacyclin I2 (PGI2). Additionally, endothelium-dependent hyperpolarization (EDH) that is NO – and PGI2–independent participates in the relaxation of small-diameter blood vessels (&lt;300 μm). EDH response is initiated by agonists (e.g. acetylcholine, bradykinin) – or shear stress – induced increase of calcium ions level in the endothelium and involves opening of the endothelial small (KCa2.3) and intermediate conductance (KCa3.1) calcium-activated potassium channels. The efflux of potassium ions could elicit the hyperpolarization of the surrounding myocytes by the activation of the inward-rectifier potassium ion channel (KIR) and/or Na+/K+-ATPase. The reduced release and/or bioavailability of NO, which is characteristic for endothelial dysfunction and may result in arterial hypertension, stimulate the generation of EDH signals, as a compensatory mechanism to maintain the endothelial control of vasodilator tone. The contribution of EDH in endothelium-dependent relaxation varies between vascular beds, animal and experimental model. In arterial hypertension the reduced expression/activity of KCa3.1 and KCa2.3 results in impaired vasorelaxation. Currently, the use of modulatory compounds (activators and inhibitors) of KCa3.1 and KCa2.3 as the potential therapeutic targets in cardiovascular diseases is under intensive investigation. It has already been known that application of activators of KCa3.1 and KCa2.3 potassium channels such (as SKA-31) can improve the EDH-type responses, the endothelial function and decrease mean arterial blood pressure. This may suggest the usefulness of these compounds in the treatment of arterial hypertension.

Intra-Articular Morphine versus Dexmedetomedine for Knee Arthroscopy under Local Anesthesia.

Background:Knee arthroscopy has both diagnostic and therapeutic applications which can be performed under general, regional, or local anesthesia. Morphine is used as an additive to local anesthetics. Dexmedetomedine, the highly selective alpha-2 (α2)-adrenoceptor agonist with the sedative and analgesic effect can be used also to augment local anesthetic effect.Patients and Methods:Sixty patients submitted for elective knee arthroscopy whose age between 25 and 45 years, of either sex, the American society of anethesiologists physical status Classes I and II at a university hospital were enrolled in this study. Patients were classified into two groups. Morphine Group (M) (n = 30): Patients received 20 ml of 0.5% bupivacaine plus 5 ml of 0.2% lidocaine with epinephrine 1:200,000 plus 1 mg morphine. Dexmedetomedine Group (D) (n = 30): Patients received 20 ml of 0.5% bupivacaine plus 5 ml of 0.2% lidocaine with epinephrine 1:200,000 plus 1 μg/kg dexmedetomedine.Results:Demographic data of patients showed no significant difference among the studied groups. Heart rate (HR) was significantly lower in (D) Group compared to that of (M) Group 5 min from the start of procedure to immediately postoperatively. Moreover, (D) Group showed a significant decrease in HR 10 min up to 35 min intraoperatively compared to the basal value. Furthermore, mean arterial blood pressure (MBP) was significantly lower in (D) Group compared to that of (M) Group 15 min from the start of surgery up to 1 h postoperatively. Furthermore, (D) Group showed a significant decrease in MBP 15 min intraoperative up to 2 h postoperatively compared to the basal value. While there was no significant difference in (visual analogue score [VAS], onset and total consumption of ketorolac, surgeon and patients’ satisfaction, side effects in (D) Group compared to (M) Group, respectively.Conclusion:Addition of either morphine or dexmedetomidine to bupivacaine intraarticularly improved both intraoperative anesthesia and postoperative analgesia with minimal side effects or complications in knee arthroscopy, with superiority of dexmedetomidine compared to morphine on hemodynamic stability.

Dietary Anthocyanins: A Review of the Exercise Performance Effects and Related Physiological Responses.

Foods and supplements high in anthocyanins are gaining popularity within sports nutrition. Anthocyanins are pigments within berries and other colorful fruits and vegetables. They have antioxidative and anti-inflammatory actions that improve recovery from exercise. Furthermore, anthocyanins can also affect vasoactive properties, including decreasing mean arterial blood pressure and increasing vasodilation during exercise. In vitro observations have shown anthocyanin- and metabolite-induced activation of endothelial nitric oxide synthase and human vascular cell migration. However, effects of anthocyanins on exercise performance without a prior muscle-damaging or metabolically demanding bout of exercise are less clear. For example, exercise performance effects have been observed for blackcurrant but are less apparent for cherry, therefore indicating that the benefits could be due to the specific source-dependent anthocyanins. The mechanisms by which anthocyanin intake can enhance exercise performance may include effects on blood flow, metabolic pathways, and peripheral muscle fatigue, or a combination of all three. This narrative review focuses on the experimental evidence for anthocyanins to improve exercise performance in humans.

Dynamic TSPO-PET for assessing early effects of cerebral hypoxia and resuscitation in new born pigs

IntroductionInflammation associated with microglial activation may be an early prognostic indicator of perinatal hypoxic ischemic injury, where translocator protein (TSPO) is a known inflammatory biomarker. This piglet study used dynamic TSPO-PET with [18F]GE180 to evaluate if microglial activation after global perinatal hypoxic injury could be detected. MethodsNew born anesthetized pigs (n = 14) underwent hypoxia with fraction of inspired oxygen (FiO2)0.08 until base excess −20 mmol/L and/or a mean arterial blood pressure decrease to 20 mm Hg, followed by resuscitation with FiO2 0.21 or 1.0. Three piglets served as controls and one had intracranial injection of lipopolysaccharide (LPS). Whole body [18F]GE180 Positron emission tomography-computed tomography (PET-CT) was performed repeatedly up to 32 h after hypoxia and resuscitation. Volumes of interest were traced in the basal ganglia, cerebellum and liver using MRI as anatomic correlation. Standardized uptake values (SUVs) were measured at baseline and four time-points, quantifying microglial activity over time. Statistical analysis used Mann Whitney- and Wilcoxon rank test with significance value set to p < 0.05. ResultsAt baseline (n = 5), mean SUVs ±1 standard deviation were 0.43 ± 0.10 and 1.71 ± 0.62 in brain and liver respectively without significant increase after hypoxia at the four time-points (n = 5–13/time point). Succeeding LPS injection, SUV increased 80% from baseline values. ConclusionsCerebral inflammatory response caused by severe asphyxia was not possible to detect with [18F]GE180 PET CT the first 32 h after hypoxia and only sparse hepatic uptake was revealed. Advances in knowledgeEarly microglial activation as indicator of perinatal hypoxic ischemic injury was not detectable by TSPO-PET with [18F]GE180. Implications for patient careTSPO-PET with [18F]GE180 might not be suitable for early detection of perinatal hypoxic ischemic brain injury.