[Intra-anesthetic arterial hypotension in elderly patients during emergency surgery: what are the risk factors?

PubMed

Boubacar Ba, El Hadji; Leye, Papa Alassane; Traoré, Mamadou Mour; Ndiaye, Pape Ibrahima; Gaye, Ibrahima; Bah, Mamadou Diawo; Fall, Mamadou Lamine; Diouf, Elisabeth

2017-01-01

Emergency anesthesia in elderly patients aged 65 years and older is complex. The occurrence of intraoperative incidents and arterial hypotension is conditioned by patients' initial health status and by the quality of intraoperative management. This study aimed to determine the incidence of intra-anesthetic arterial hypotension in elderly patients during emergency surgery and to assess the involvement of certain factors in its occurrence: age, sex, patient's history, ASA class, anesthetic technique. We conducted a retrospective descriptive and analytical study in the Emergency Surgery Department at the Aristide Le Dantec University Hospital from 1 March 2014 to 28 February 2015. We collected data from 210 patients out of 224 elderly patients aged 65 years and older undergoing emergency anesthesias (10.93%). Data of 101 men and 109 women were included in the analysis, of whom 64.3% had at least one defect. Patients' preoperative status was assessed using American Society of Anesthesiology (ASA) classification: 71% of patients were ASA class 1 and 2 and 29% were ASA class 3 and 4. Locoregional anesthesia was the most practiced anesthetic technique (56.7%). 28 patients (13.33%) had intra-anesthetic arterial hypotension, of whom 16 under general anesthesia and 12 under locoregional anesthesia. It was more frequent in patients with high ASA class and a little less frequent in patients with PAH and underlying heart disease. Arterial hypotension in elderly patients during emergency surgery exposes the subject to the risk of not negligible intraoperative hypotension, especially in patients with high ASA class. Prevention is based on adequate preoperative assessment and anesthetic management.

Glyburide, a K(+)(ATP)channel blocker, improves hypotension and survival in anaphylactic shock induced in Wistar rats sensitized to ovalbumin.

PubMed

Dhanasekaran, Subramanian; Nemmar, Abderrahim; Aburawi, Elhadi H; Kazzam, Elsadig E; Abdulle, Abdishakur; Bellou, Moufida; Bellou, Abdelouahab

2013-11-15

Allergens can induce anaphylactic shock and death due to serve hypotension. Potassium channel blockers (K(+)(ATP)) such as glyburide (GLY) induce vasoconstriction. The effect of (K(+)(ATP)) channel blockers on anaphylactic shock is poorly understood. Objective of the study was to test the hypothesis that GLY reduces hypotension induced in anaphylactic shock and increases survival. Rats were grouped into: G1-N=Naïve; G2-SC=Sensitized-Control; G3-SG=Sensitized-GLY (glyburide 40 mg/kg); G4-SE=Sensitized-EPI (epinephrine 10 mg/kg). G2 to G4 groups were sensitized with ovalbumin (OVA) and shock was induced by i.v. injection of OVA. Treatments were administered intravenously 5 min later. Mean arterial pressure (MAP), heart rate (HR), and mean survival time (MST) were measured for 60 min following OVA injection and treatments administration. At the end of the experiment, blood withdrawal was performed to measure plasma levels of histamine, leukotriene B(4) (LTB(4)), prostaglandin E(2) (PGE(2)) and prostaglandin F(2) (PGF(2)). Additionally blood gas (paO2, paCO2, SaO2) and electrolytes (Na(+), K(+) and Ca (++)) were measured. MAP was normal in G1-N; severe hypotension, negative inotropic and short MST were observed in G2-SC; normalization of MAP, with lesser negative inotropism and increased MST were observed in G3-SG; full recovery was observed in G4-SE. Histamine level was significantly higher in G2-SC; reduced in G3-SG and G4-SE. PGE(2) increased in G3-SG; PGF(2) increased in G2-SC and G3-SG. Na(+) and Ca (++) concentration decreased in sensitized rats but reversed in treated groups, without change in K(+) concentration. In conclusion, our data suggest that administration of GLY reduced hypotension and increases survival time in rat anaphylactic shock.

Orthostatic hypotension predicts motor decline in early Parkinson disease.

PubMed

Kotagal, Vikas; Lineback, Christina; Bohnen, Nicolaas I; Albin, Roger L

2016-11-01

Orthostatic hypotension is increasingly reported as a risk factor for development of late-stage disease features in Parkinson disease (PD). Less is known about its significance in individuals with early PD who are often targeted for neuroprotective trials. Using data from the CALM-PD trial (n = 275), we explored whether early orthostatic hypotension predicts a decline in the Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living) or UDPRS III (motor) score after 102 weeks. We also explored risk factors for worsening orthostatic hypotension over a nearly 2-year period. After controlling for age, disease duration, gender, study drug, change in mini-mental status exam score, levodopa equivalent dose, and baseline UPDRS II or III score respectively, the degree of orthostatic hypotension at enrollment associated with a worsening in UPDRS motor score (t = 2.40, p = 0.017) at week 102 but not with UPDRS ADL score (t = 0.83, p = 0.409). Worsening in orthostatic hypotension during the study associated with longer disease duration (t = 2.37, p = 0.019) and lower body mass index (BMI) (t = -2.96, p = 0.003). Baseline orthostatic hypotension is a predictor of UPDRS motor decline in individuals with early PD and should be accounted for in clinical trial design. Low BMI may predict orthostatic hypotension in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Postprandial hypotension in older survivors of critical illness.

PubMed

Nguyen, Thu Anh Ngoc; Ali Abdelhamid, Yasmine; Weinel, Luke M; Hatzinikolas, Seva; Kar, Palash; Summers, Matthew J; Phillips, Liza K; Horowitz, Michael; Jones, Karen L; Deane, Adam M

2018-06-01

In older people postprandial hypotension occurs frequently; and is an independent risk factor for falls, cardiovascular events, stroke and death. The primary aim of this pilot study was to estimate the frequency of postprandial hypotension and evaluate the mechanisms underlying this condition in older survivors of an Intensive Care Unit (ICU). Thirty-five older (>65 years) survivors were studied 3 months after discharge. After an overnight fast, participants consumed a 300 mL drink containing 75 g glucose, labelled with 20 MBq 99m Tc-calcium phytate. Patients had concurrent measurements of blood pressure, heart rate, blood glucose and gastric emptying following drink ingestion. Proportion of participants is presented as percent (95% CI) and continuous variables as mean (SD). Postprandial hypotension was evident in 10 (29%; 95% CI 14-44), orthostatic hypotension in 2 (6%; 95% CI 0-13) and cardiovascular autonomic dysfunction in 2 (6%; 95% CI 0-13) participants. The maximal postprandial nadir for systolic blood pressure and diastolic blood pressures were -29 (14) mmHg and -18 (7) mmHg. In this cohort of older survivors of ICU postprandial hypotension occurred frequently . This suggests that postprandial hypotension is an unrecognised issue in older ICU survivors. Copyright © 2018. Published by Elsevier Inc.

Clinical application of diadenosine tetraphosphate (Ap4A:F-1500) for controlled hypotension.

PubMed

Kikuta, Y; Ohiwa, E; Okada, K; Watanabe, A; Haruki, S

1999-01-01

In our animal study, it was revealed that diadenosine tetraphosphate (Ap4A:F-1500) has a dose-dependent hypotension effect of up to 60% decrease in mean arterial pressure compared to control value. Furthermore, in healthy male volunteers, the safety of Ap4A up to 4 mg.min-1 was confirmed. In patients who require surgical procedures under general anesthesia together with controlled hypotension, hypotension was induced by Ap4A in order to examine its hypotensive effect and modulating action on the blood pressure. Ten patients who required controlled hypotension and who were scheduled for elective surgery under general anesthesia were studied. Anesthesia was maintained with isoflurane (n = 7) or sevoflurane (n = 3) in oxygen-nitrous oxide. Controlled hypotension was induced by Ap4A administered at a rate of 10-20 micrograms.kg-1.min-1. The dose was adjusted at a maximum rate of 80 micrograms.kg-1.min-1 until the target blood pressure was achieved. Arterial blood pressure and heart rate were monitored. Arterial samples were drawn at 4 separate time points to measure the concentration of Ap4A in the plasma. The time required for attaining the target blood pressure after initiation of Ap4A infusion was about 16 min, and the time lapse between withdrawal of infusion to recovery of blood pressure was about 18 min. No reflex tachycardia was observed during infusion of Ap4A and no rebound hypertension was evident after withdrawal. The plasma Ap4A concentration increased in response to the acceleration rate of Ap4A administration with a tendency of augmented hypotensive effect. As it produces an excellent hypotensive effect together with a modulating action on blood pressure, Ap4A was assessed as useful in producing controlled hypotension.

A centrally mediated prolonged hypotension produced by oxotremorine or pilocarpine

PubMed Central

Dage, R.C.

1979-01-01

1 Oxotremorine, methyloxotremorine, pilocarpine or arecoline were given intravenously to anaesthetized cats, dogs or rats, and intraperitoneally to conscious normotensive and spontaneously hypertensive rats, pretreated with doses of methylatropine that completely blocked peripheral muscarinic receptors, to ascertain their effects on blood pressure and heart rate. 2 Oxotremorine but not methyloxotremorine produced a prolonged hypotension in cats and dogs but not in rats. Heart rate was not changed. Pilocarpine, although less potent, produced an identical effect, whereas the effect of arecoline was short by comparison. The hypotensive effect of these drugs was reversed by atropine. 3 In dogs, oxotremorine produced a prolonged hypotension with no change in heart rate or cardiac output. 4 A decrease in spontaneous sympathetic nerve activity accompanied the hypotension in cats. Both effects were reversed by atropine but could be reinvoked by large doses of oxotremorine. 5 The oxotremorine-induced hypotension in cats was not altered by decerebration but was abolished by high cervical spinal section. 6 The results indicate that the prolonged hypotension elicited by oxotremorine is mediated by an action at muscarinic receptors in the brain stem resulting in a decrease in sympathetic nerve activity and peripheral resistance but not heart rate or cardiac output. PMID:760887

Orthostatic hypotension as an unusual clinical manifestation of pheochromocytoma: a case report.

PubMed

Bortnik, Miriam; Occhetta, Eraldo; Marino, Paolo

2008-08-01

Pheochromocytoma is a rare endocrine tumor which can have a highly variable presentation related to increased catecholamine secretion. We report the case of a 74-year-old man in whom recurrent episodes of syncope due to orthostatic hypotension were the only clinical manifestations of this challenging entity. Diagnosis of pheochromocytoma was achieved by biochemical test samples and computed tomography scans. Surgical excision of the tumor resulted in clinical improvement with normalization of catecholamine concentrations and no more episodes of orthostatic hypotension during a follow-up of 24 months. Although rare, pheochromocytoma may frequently cause disorders of orthostatic tolerance; because of its meaningful implications, screening for this entity should be considered in case of recurrent syncopal episodes due to new-onset orthostatic hypotension.

Comparison of surgical conditions in 2 different anesthesia techniques of esmolol-induced controlled hypotension in breast reduction surgery

PubMed Central

Besir, Ahmet; Cekic, Bahanur; Kutanis, Dilek; Akdogan, Ali; Livaoglu, Murat

2017-01-01

Abstract Background: Breast reduction surgery is a common cosmetic surgery with a high incidence of blood loss and transfusion. In this surgery, the reduction of blood loss related to surgical manipulation and the volume of resected tissue is a target. In the present study, we compared the effects of esmolol-induced controlled hypotension on surgical visibility, surgical bleeding, and the duration of surgery in patients anesthetized with propofol/remifentanil (PR) or sevoflurane/remifentanil (SR). Methods: Patients in the American Society of Anesthesiologists I/II risk group undergoing breast reduction surgery were prospectively randomized into PR (n = 25) and SR (n = 25) groups. Controlled hypotension was induced with esmolol in both groups. During the intraoperative period, the heart rate (HR), mean arterial pressure (MAP), operation duration, volume of intraoperative blood loss, volume of blood received through postoperative drains, volume of resected tissues, and surgical area bleeding score were recorded. Results: The duration of operation in the incisional period was shorter in group PR compared to group SR (P = 0.04). The change in HR was lower in incision and hemostasis periods in the group PR compared to the group SR (P < 0.001). Total intraoperative intraoperative bleeding volume and volume of blood received through drains on postoperative postoperative day 1, day 2, and in total were found to be significantly lower in group PR compared to group SR. Surgical visibility scoring was more effective in group PR compared to SR. Conclusion: In the breast reduction surgery performed under esmolol-induced controlled hypotension, the effect of propofol + remifentanil anesthesia on the duration of incisional surgery, surgical visibility, and volume of surgical blood loss was more reliable and effective compared to that of sevoflurane + remifentanil, which seems to be an advantage. PMID:28272228

Audiovestibular impairments associated with intracranial hypotension.

PubMed

Choi, Jae-Hwan; Cho, Kee-Yong; Cha, Seung-Yi; Seo, Jae-Deuk; Kim, Min-Ji; Choi, Yu Ri; Kim, Sung-Hee; Kim, Ji-Soo; Choi, Kwang-Dong

2015-10-15

To investigate the patterns and mechanisms of audiovestibular impairments associated with intracranial hypotension. We had consecutively recruited 16 patients with intracranial hypotension at the Neurology Center of Pusan National University Hospital for two years. Spontaneous, gaze-evoked, and positional nystagmus were recorded using 3D video-oculography in all patients, and the majority of them also had pure tone audiometry and bithermal caloric tests. Of the 16 patients, five (31.3%) reported neuro-otological symptoms along with the orthostatic headache while laboratory evaluation demonstrated audiovestibular impairments in ten (62.5%). Oculographic analyses documented spontaneous and/or positional nystagmus in six patients (37.5%) including weak spontaneous vertical nystagmus with positional modulation (n=4) and pure positional nystagmus (n=2). One patient presented with recurrent spontaneous vertigo and tinnitus mimicking Meniere's disease, and showed unidirectional horizontal and torsional nystagmus with normal head impulse tests during the attacks. Bithermal caloric tests were normal in all nine patients tested. Audiometry showed unilateral (n=6) or bilateral (n=1) sensorineural hearing loss in seven (53.8%) of the 13 patients tested. Intracranial hypotension frequently induces audiovestibular impairments. In addition to endolymphatic hydrops and irritation of the vestibulocochlear nerve, compression or traction of the brainstem or cerebellum due to loss of CSF buoyancy may be considered as a mechanism of frequent spontaneous or positional vertical nystagmus in patients with intracranial hypotension. Copyright © 2015 Elsevier B.V. All rights reserved.

Causes of chronic orthostatic hypotension

NASA Technical Reports Server (NTRS)

Robertson, D.; Robertson, R. M.

1994-01-01

OBJECTIVE: To determine the frequency of various causes of orthostatic hypotension. DESIGN: Survey. SETTING: Tertiary referral center. PATIENTS: One hundred patients with moderate to severe orthostatic hypotension. RESULTS: Twenty-seven percent of the patients had primary autonomic failure, 35% had secondary autonomic failure, and 38% had hypotension without evidence of generalized autonomic degeneration. CONCLUSIONS: In a tertiary referral center, only a minority of patients with severe orthostatic hypotension will have Shy-Drager syndrome or Bradbury-Eggleston syndrome as their primary disease. Occasional patients who initially appear to have Bradbury-Eggleston syndrome ultimately prove to have Shy-Drager syndrome or paraneoplastic autonomic failure. Antidepressant drugs, even in low doses, remain a major overlooked cause of orthostatic hypotension.

Hypovolemia-induced Orthostatic Hypotension Relates To Hypo-sympathetic Responsiveness

NASA Technical Reports Server (NTRS)

Meck, Janice V.

2007-01-01

We report a new model which uses hypovolemia to force humans into a hemodynamic state that is similar to that after spaceflight. This model can be used to test candidate countermeasures for postflight orthostatic hypotension and to identify crewmembers who will be most susceptible to that symptom on landing day.

Crisis management during anaesthesia: hypotension.

PubMed

Morris, R W; Watterson, L M; Westhorpe, R N; Webb, R K

2005-06-01

Hypotension is commonly encountered in association with anaesthesia and surgery. Uncorrected and sustained it puts the brain, heart, kidneys, and the fetus in pregnancy at risk of permanent or even fatal damage. Its recognition and correction is time critical, especially in patients with pre-existing disease that compromises organ perfusion. To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK", supplemented by a specific sub-algorithm for hypotension, in the management of hypotension when it occurs in association with anaesthesia. Reports of hypotension during anaesthesia were extracted and studied from the first 4000 incidents reported to the Australian Incident Monitoring Study (AIMS). The potential performance of the COVER ABCD algorithm and the sub-algorithm for hypotension was compared with the actual management as reported by the anaesthetist involved. There were 438 reports that mentioned hypotension, cardiovascular collapse, or cardiac arrest. In 17% of reports more than one cause was attributed and 550 causative events were identified overall. The most common causes identified were drugs (26%), regional anaesthesia (14%), and hypovolaemia (9%). Concomitant changes were reported in heart rate or rhythm in 39% and oxygen saturation or ventilation in 21% of reports. Cardiac arrest was documented in 25% of reports. As hypotension was frequently associated with abnormalities of other vital signs, it could not always be adequately addressed by a single algorithm. The sub-algorithm for hypotension is adequate when hypotension occurs in association with sinus tachycardia. However, when it occurs in association with bradycardia, non-sinus tachycardia, desaturation or signs of anaphylaxis or other problems, the sub-algorithm for hypotension recommends cross referencing to other relevant sub-algorithms. It was considered that, correctly applied, the core algorithm COVER ABCD would have diagnosed 18% of cases and led to resolution in

Perfusion index derived from a pulse oximeter can predict the incidence of hypotension during spinal anaesthesia for Caesarean delivery.

PubMed

Toyama, S; Kakumoto, M; Morioka, M; Matsuoka, K; Omatsu, H; Tagaito, Y; Numai, T; Shimoyama, M

2013-08-01

Hypotension during spinal anaesthesia for Caesarean delivery is a result of decreased vascular resistance due to sympathetic blockade and decreased cardiac output due to blood pooling in blocked areas of the body. Change in baseline peripheral vascular tone due to pregnancy may affect the degree of such hypotension. The perfusion index (PI) derived from a pulse oximeter has been used for assessing peripheral perfusion dynamics due to changes in peripheral vascular tone. The aim of this study was to examine whether baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery. Parturients undergoing elective Caesarean delivery under spinal anaesthesia with hyperbaric bupivacaine 10 mg and fentanyl 20 μg were enrolled in this prospective study. The correlation between baseline PI and the degree of hypotension during spinal anaesthesia and also the predictability of spinal anaesthesia-induced hypotension during Caesarean delivery by PI were investigated. Baseline PI correlated with the degree of decreases in systolic and mean arterial pressure (r=0.664, P<0.0001 and r=0.491, P=0.0029, respectively). The cut-off PI value of 3.5 identified parturients at risk for spinal anaesthesia-induced hypotension with a sensitivity of 81% and a specificity of 86% (P<0.001). The change of PI in parturients with baseline PI ≤ 3.5 was not significant during the observational period, while PI in parturients with baseline PI>3.5 demonstrated marked decreases after spinal injection. We demonstrated that higher baseline PI was associated with profound hypotension and that baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery.

Chronic Renin-Angiotensin System (RAS) Blockade May Not Induce Hypotension During Anaesthesia for Bariatric Surgery.

PubMed

Salvetti, Guido; Di Salvo, Claudio; Ceccarini, Giovanni; Abramo, Antonio; Fierabracci, Paola; Magno, Silvia; Piaggi, Paolo; Vitti, Paolo; Santini, Ferruccio

2016-06-01

The use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) for the treatment of hypertensive obese patients is steadily increasing. Some studies have reported that the use of these drugs was associated with an increased risk of hypotensive episodes, during general anaesthesia. The number of bariatric procedures is also increasing worldwide, but there is a lack of studies investigating the hypotensive effect of renin-angiotensin system (RAS) blockers in severely obese patients during general anaesthesia for bariatric surgery. The aim of this pilot study was to evaluate hemodynamic changes induced by general anaesthesia in obese patients chronically treated with ACE-I or ARB compared to a control group not treated with antihypertensive therapy. Fourteen obese subjects (mean body mass index (BMI) 47.5 kg/m(2)) treated with ACE-I or ARB and twelve obese (mean BMI 45.7 kg/m2) controls not treated with antihypertensive therapy underwent general anaesthesia to perform laparoscopic bariatric surgery. Systolic blood pressure, diastolic blood pressure, and heart rate were monitored continuously and registered at different time points: T0 before induction, then at 2, 5, 7, 10, 15, 20, 30, 60, 90, 120, and 150 min after induction, and the last time point taken following recovery from anaesthesia. A progressive reduction of both systolic and diastolic blood pressure values was observed without significant differences between the two groups. A similar trend of heart rate values was observed. In conclusion, our pilot study suggests that RAS blockers may be continued during the perioperative period in patients undergoing bariatric surgery, without increasing the risk of hypotensive episodes.

Treatment of Post-SCI Hypotension

ClinicalTrials.gov

2018-02-15

Spinal Cord Injury; Autonomic Dysreflexia; Orthostatic Hypotension; Baroreceptor Integrity; Sympathetic Integrity; Vagal Integrity; Hypotension; Cerebral Blood Flow; Blood Pressure; Venous Occlusion Plethysmography

Prevalence of hypotension and its association with cognitive function among older adults.

PubMed

Momtaz, Yadollah Abolfathi; Hamid, Tengku Aizan; Haron, Sharifah Azizah; Bagat, Mohamad Fazdillah; Mohammadi, Fatemeh

2018-04-01

The negative effect of hypertension has overshadowed possible health problems associated with hypotension. The purposes of this study were to describe the prevalence of hypotension in older adults and to determine the association between hypotension and cognitive function, after adjusting for possible covariates. The data for the study consisting of 1067 community-dwelling older adults were obtained from a national survey entitled "Identifying Psychosocial and Identifying Economic Risk Factor of Cognitive Impairment among Elderly", conducted in Malaysia. The hypotension was considered as blood pressure <120/75 mm Hg, measuring by standard mercury manometer. Data analysis was performed using the SPSS Version 22.0. The mean age of the respondents was 68.27 (SD = 5.93). Mean score of cognitive function as measured by MMSE was 22.70 (SD = 4.95). The prevalence of hypotension was 29.3%. The prevalence of cognitive impairment for hypotension group was 25.6%. Results of multiple linear regression analysis revealed that hypotension is negatively associated with cognitive function (Beta = -0.11, p<.01), after adjusting for age, gender, education, marital status, employment status, diabetes, heart disease, stroke and gastritis. The study showing hypotension is significantly associated with decreased cognitive function in later life, implies more attention to low blood pressure in old age.

Orthostatic hypotension in patients, bed rest subjects, and astronauts

NASA Technical Reports Server (NTRS)

Lathers, C. M.; Charles, J. B.

1994-01-01

Orthostatic hypotension after even short space flights has affected a significant number of astronauts. Given the need for astronauts to function at a high level of efficiency during and after their return from space, the application of pharmacologic and other treatments is strongly indicated. This report addresses the clinical problem of orthostatic hypotension and its treatments to ascertain whether pharmacologic or physiologic treatment may be useful in the prevention of orthostatic hypotension associated with space flight. Treatment of orthostatic hypotension in patients now includes increasing intravascular volume with high sodium intake and mineralocorticoids, or increasing vascular resistance through the use of drugs to stimulate alpha or block beta vascular receptors. Earlier treatment used oral sympathomimetic ephedrine hydrochloride alone or with "head-up" bed rest. Then long-acting adrenocortical steroid desoxycorticosterone preparations with high-salt diets were used to expand volume. Fludrocortisone was shown to prevent the orthostatic drop in blood pressure. The combination of the sympathomimetic amine hydroxyamphetamine and a monoamine oxidase inhibitor tranylcypromine has been used, as has indomethacin alone. Davies et al. used mineralocorticoids at low doses concomitantly with alpha-agonists to increase vasoconstrictor action. Schirger et al used tranylcypromine and methylphenidate with or without a Jobst elastic leotard garment or the alpha-adrenergic agonist midodrine (which stimulates both arterial and venous systems without direct central nervous system or cardiac effects). Vernikos et al established that the combination of fludrocortisone, dextroamphetamine, and atropine exhibited a beneficial effect on orthostatic hypotension induced by 7-day 6 degrees head-down bed rest (a model used to simulate the weightlessness of space flight). Thus, there are numerous drugs that, in combination with mechanical techniques, including lower body negative

Hypotensive and vasorelaxant effects induced by the ethanolic extract of the Mimosa caesalpiniifolia Benth. (Mimosaceae) inflorescences in normotensive rats.

PubMed

Santos, M E P; Moura, L H P; Mendes, M B; Arcanjo, D D R; Monção, N B N; Araújo, B Q; Lopes, J A D; Silva-Filho, J C; Fernandes, R M; Oliveira, R C M; Citó, A M G L; Oliveira, A P

2015-04-22

slight increase in heart rate was observed. When administered orally, MC-EtOH/flowers (100mg/kg, v.o.) promoted a decrease in the arterial pressure from 90 min on, without a significant alteration in the heart rate in relation to the control. In the in vitro study, a pharmacological trial was performed with the extracts obtained from parts of the species M. caesalpiifolia (leaves, bark, fruit and inflorescences). Among all extracts tested, the ethanolic extract from the inflorescences (MC-EtOH/flowers) presented higher vasorelaxant potency in relation to the other parts of the plant. Henceforth, MC-EtOH/flowers was used in the sequence. In mesenteric preparations pre-contracted with phenylephrine (10(-5)M), the MC-EtOH/flowers (0.1-750 µg/ml) promoted vasorelaxant effect regardless of the vascular endothelium. MC-EtOH/flowers inhibited the contractions induced by the cumulative addition of phenylephrine (10(-9)-10(-5)mol/l) or CaCl2 (10(-6)-3 × 10(-2)M), in a concentration-dependent way. In contractions induced by S(-)Bay K 8644, a Cav-L activator, the MC-EtOH/flowers promoted concentration-dependent relaxation, corroborating previous results. The tea of flowers of M. caesalpiniifolia promotes hypotension and tachycardia, whereas ethanolic extract (MC-EtOH) promotes hypotension and bradycardia involving the participation of the muscarinic and ganglionic pathways, as well as vasorelaxant action involving the Ca(2+) influx inhibition blockade. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prophylaxis against the systemic hypotension induced by propofol during rapid-sequence intubation.

PubMed

el-Beheiry, H; Kim, J; Milne, B; Seegobin, R

1995-10-01

The objective of this study was to determine the effectiveness of two prophylactic approaches against the anticipated hypotension induced by propofol during rapid-sequence intubation. Thirty-six male or female nonpremedicated ASA class I-II patients aged 21-60 yr undergoing elective outpatient surgery were included in the study. Patients were randomly allocated to receive pre-induction ephedrine sulphate (70 micrograms x kg(-1)iv), pre-induction volume loading (12 ml x kg(-1) Ringer's lactate) or no treatment. Rapid-sequence intubation with cricoid pressure was then performed with propofol (2.5 mg. x kg(-1)) and succinylcholine (1.5 mg x kg(-1). The lungs were subsequently ventilated with 0.25-0.5% isoflurane in a 2:1 N2O/O2 mixture. Vecuronium was given once neuromuscular function had recovered from the succinylcholine. Heart rate and systemic arterial blood pressure were measured non-invasively before induction, after propofol administration and every minute for ten minutes after intubation. Pre-induction volume loading prevented the hypotension observed before surgical stimulation in control and ephedrine groups. Moreover, pre-induction volume loading was not associated with increases in heart rate after intubation as was ephedrine administration. The intubating conditions were excellent to satisfactory in most patients and the overall incidence of adverse events during intubation was mainly due to pain during injection of propofol. The present study showed that preoperative volume loading is more efficacious than pre-induction administration of ephedrine sulphate in maintaining haemodynamic stability during rapid-sequence induction with propofol and succinylcholine. In addition, propofol in combination with succinylcholine provides excellent conditions for rapid-sequence intubation.

Dynamic regulation of heart rate during acute hypotension: new insight into baroreflex function

NASA Technical Reports Server (NTRS)

Zhang, R.; Behbehani, K.; Crandall, C. G.; Zuckerman, J. H.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

2001-01-01

To examine the dynamic properties of baroreflex function, we measured beat-to-beat changes in arterial blood pressure (ABP) and heart rate (HR) during acute hypotension induced by thigh cuff deflation in 10 healthy subjects under supine resting conditions and during progressive lower body negative pressure (LBNP). The quantitative, temporal relationship between ABP and HR was fitted by a second-order autoregressive (AR) model. The frequency response was evaluated by transfer function analysis. Results: HR changes during acute hypotension appear to be controlled by an ABP error signal between baseline and induced hypotension. The quantitative relationship between changes in ABP and HR is characterized by a second-order AR model with a pure time delay of 0.75 s containing low-pass filter properties. During LBNP, the change in HR/change in ABP during induced hypotension significantly decreased, as did the numerator coefficients of the AR model and transfer function gain. Conclusions: 1) Beat-to-beat HR responses to dynamic changes in ABP may be controlled by an error signal rather than directional changes in pressure, suggesting a "set point" mechanism in short-term ABP control. 2) The quantitative relationship between dynamic changes in ABP and HR can be described by a second-order AR model with a pure time delay. 3) The ability of the baroreflex to evoke a HR response to transient changes in pressure was reduced during LBNP, which was due primarily to a reduction of the static gain of the baroreflex.

Predictors of intraoperative hypotension and bradycardia.

PubMed

Cheung, Christopher C; Martyn, Alan; Campbell, Norman; Frost, Shaun; Gilbert, Kenneth; Michota, Franklin; Seal, Douglas; Ghali, William; Khan, Nadia A

2015-05-01

Perioperative hypotension and bradycardia in the surgical patient are associated with adverse outcomes, including stroke. We developed and evaluated a new preoperative risk model in predicting intraoperative hypotension or bradycardia in patients undergoing elective noncardiac surgery. Prospective data were collected in 193 patients undergoing elective, noncardiac surgery. Intraoperative hypotension was defined as systolic blood pressure <90 mm Hg for >5 minutes or a 35% decrease in the mean arterial blood pressure. Intraoperative bradycardia was defined as a heart rate of <60 beats/min for >5 minutes. A logistic regression model was developed for predicting intraoperative hypotension or bradycardia with bootstrap validation. Model performance was assessed using area under the receiver operating curves and Hosmer-Lemeshow tests. A total of 127 patients developed hypotension or bradycardia. The average age of participants was 67.6 ± 11.3 years, and 59.1% underwent major surgery. A final 5-item score was developed, including preoperative Heart rate (<60 beats/min), preoperative hypotension (<110/60 mm Hg), Elderly age (>65 years), preoperative renin-Angiotensin blockade (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers), Revised cardiac risk index (≥3 points), and Type of surgery (major surgery), entitled the "HEART" score. The HEART score was moderately predictive of intraoperative bradycardia or hypotension (odds ratio, 2.51; 95% confidence interval, 1.79-3.53; C-statistic, 0.75). Maximum points on the HEART score were associated with an increased likelihood ratio for intraoperative bradycardia or hypotension (likelihood ratio, +3.64). The 5-point HEART score was predictive of intraoperative hypotension or bradycardia. These findings suggest a role for using the HEART score to better risk-stratify patients preoperatively and may help guide decisions on perioperative management of blood pressure and heart rate

Level of adherence to ocular hypotensive agents and its determinant factors among glaucoma patients in Menelik II Referral Hospital, Ethiopia.

PubMed

Mehari, Tesfay; Giorgis, Abeba T; Shibeshi, Workineh

2016-08-02

Good adherence to ocular hypotensive agents is important to control intraocular pressure and hence to prevent progressive glaucomatous optic nerve head damage. Periodic investigation of adherence is crucial in glaucoma treatment. The purpose of this study was to assess level of adherence to ocular hypotensive agents and to identify factors affecting adherence among glaucoma patients at a tertiary public eye care center. The study was a hospital-based cross-sectional study that was conducted in Menelik II Referral Hospital from June 1, 2015 to July 31, 2015. A systematic random sampling technique was used to select 359 study participants from the source population. The study patients were interviewed and their medical charts were reviewed using a pretested structured questionnaire. Adherence was assessed using Morisky Medication Adherence Scale - 8 and adherence determinant factors were identified using multivariate binary logistic regression analysis. The association was declared statistically significant at p < 0.05. Among the 359 study glaucoma patients, 42.6 % were adherent to their prescribed hypotensive agents. Higher educational level (AOR = 4.60, 95 % CI: 1.01-21.03, p < 0.049), being self - employed (AOR = 6.14, 95 % CI: 1.37-27.50, p < 0.018) and taking lesser frequency of drops (AOR = 2.89, 95 % CI: 1.25-6.66, p < 0.013) were significantly associated with adherence, whereas being a farmer (AOR = 0.07, 95 % CI: 0.01-0.75, p < 0.028), having very low monthly family income (AOR = 0.22, 95 % CI: 0.06-0.77, p < 0.019) and self - purchasing of medications (AOR = 0.30, 95 % CI: 0.10-0.93, p < 0.036) were significantly associated with non-adherence. The study has identified the adherence level to the prescribed ocular hypotensive agents to be sub-optimal and is influenced by different factors among glaucoma patients of the public tertiary center. We recommend glaucoma care providers to pay due attention

Vertigo and nystagmus in orthostatic hypotension.

PubMed

Choi, J-H; Seo, J-D; Kim, M-J; Choi, B-Y; Choi, Y R; Cho, B M; Kim, J S; Choi, K-D

2015-04-01

Generalized cerebral ischaemia from cardiovascular dysfunction usually leads to presyncopal dizziness, but several studies reported a higher frequency of rotatory vertigo in cardiovascular patients. Whether generalized cerebral ischaemia due to cardiovascular disorders may produce objective vestibular dysfunction was investigated. Thirty-three patients with orthostatic dizziness/vertigo due to profound orthostatic hypotension and 30 controls were recruited. All participants underwent recording of eye movements during two orthostatic challenging tests: the Schellong and the squatting-standing tests. Most patients had neuroimaging, and patients with abnormal eye movements were subjected to follow-up evaluations. Symptoms associated with orthostatic dizziness/vertigo included blurred vision, fainting and tinnitus. Ten (30%) of 33 patients developed rotatory vertigo and nystagmus during the Schellong (n = 5) or squatting-standing test (n = 5). Four of them showed pure downbeat nystagmus whilst five had downbeat and horizontal nystagmus with or without torsional component. Patients with orthostatic nystagmus had shorter duration of orthostatic intolerance than those without nystagmus (1.0 ± 1.6 vs. 11.0 ± 9.7 months, P < 0.001). In two patients, orthostatic nystagmus disappeared during follow-up despite the persistence of profound orthostatic hypotension. Generalized cerebral ischaemia caused by orthostatic hypotension induces rotatory vertigo due to objective vestibular dysfunction. The presence of orthostatic vertigo and nystagmus has an association with the duration of orthostatic intolerance. © 2014 EAN.

Orthostatic hypotension-related hospitalizations in the United States.

PubMed

Shibao, Cyndya; Grijalva, Carlos G; Raj, Satish R; Biaggioni, Italo; Griffin, Marie R

2007-11-01

Orthostatic hypotension has been commonly described in elderly persons and is associated with an increased risk of falls, syncope, and cerebrovascular events. Nevertheless, the precise burden of this condition in the US is currently unknown. We analyzed discharge data from the Nationwide Inpatient Sample to identify orthostatic hypotension-related hospitalizations and associated comorbidities after excluding acute causes of this condition. National hospitalization rates were estimated using US census population estimates, and the medical conditions most frequently associated with orthostatic hypotension were assessed. In 2004, there were an estimated 80,095 orthostatic hypotension-related hospitalizations, yielding an overall rate of 36 (95% confidence interval, 34 to 38) hospitalizations per 100,000 US adults. Orthostatic hypotension was the primary diagnosis in 35% of these hospitalizations. The number of orthostatic hypotension-related hospitalizations increased steadily with age, and patients aged 75 years or older had the highest annual hospitalization rate, 233 per 100,000 (95% confidence interval, 217 to 249). The median length of hospital stay was 3 days (IQR 2-6) and the overall in-hospital mortality was 0.9%. Caucasian males were most likely to be hospitalized with orthostatic hypotension. Syncope was the most common comorbid condition reported among orthostatic hypotension patients. Orthostatic hypotension is a relatively common condition among hospitalized US elderly patients. In light of the progressive aging of the US population, the contribution of orthostatic hypotension to morbidity and mortality is likely to increase, and deserves further scrutiny.

Fludrocortisone does not prevent orthostatic hypotension in astronauts after spaceflight.

PubMed

Shi, Shang-Jin; South, Donna A; Meck, Janice V

2004-03-01

During stand/tilt tests after spaceflight, 20% of astronauts experience orthostatic hypotension and presyncope. Spaceflight-induced hypovolemia is a contributing factor. Fludrocortisone, a synthetic mineralocorticoid, has been shown to increase plasma volume and orthostatic tolerance in Earth-bound patients. The efficacy of fludrocortisone as a treatment for postflight hypovolemia and orthostatic hypotension in astronauts has not been studied. Our purpose was to test the hypothesis that astronauts who ingest fludrocortisone prior to landing would have less loss of plasma volume and greater orthostatic tolerance than astronauts who do not ingest fludrocortisone. There were 25 male astronauts who were randomized into 2 groups: placebo (n = 18) and fludrocortisone (n = 7), and participated in stand tests 10 d before launch and 2-4 h after landing. Subjects took either 0.3 mg fludrocortisone or placebo orally 7 h prior to landing. Supine plasma and red cell volumes, supine and standing HR, arterial pressure, aortic outflow, and plasma norepinephrine and epinephrine were measured. On landing day, 2 of 18 in the placebo group and 1 of 7 in the fludrocortisone group became presyncopal (chi2 = 0.015, p = 0.90). Plasma volumes were significantly decreased after flight in the placebo group, but not in the fludrocortisone group. During postflight stand tests, standing plasma norepinephrine was significantly less in the fludrocortisone group compared with the placebo group. Treatment with a single dose of fludrocortisone results in protection of plasma volume but no protection of orthostatic tolerance. Fludrocortisone is not recommended as a countermeasure for spaceflight-induced orthostatic intolerance.

A sequential compression mechanical pump to prevent hypotension during elective cesarean section under spinal anesthesia.

PubMed

Sujata, N; Arora, D; Panigrahi, B P; Hanjoora, V M

2012-04-01

Spinal anesthesia is a standard technique for cesarean section but can cause hypotension which may be related to venous pooling secondary to progesterone-induced decreases in vascular tone. This study investigated the use of a sequential compression mechanical pump with thigh-high sleeves with compression cycles timed to venous refilling. We hypothesized that this would recruit pooled venous blood from the lower limbs, maintain the central blood volume and thus decrease the incidence of hypotension. One hundred parturients scheduled for elective cesarean section under spinal anesthesia were recruited and randomly assigned to use of either a mechanical pump (Group M) or control (Group C). A standardized protocol for co-hydration and anesthesia was followed. Hypotension, defined as a decrease in systolic blood pressure by >20% from baseline, was treated with 6-mg boluses of intravenous ephedrine. The incidence of hypotension was defined as the primary outcome. Median ephedrine requirement was taken as a measure of the severity of hypotension. Hypotension occurred in 12 of 47 (25.5%) patients in Group M compared to 27 of 45 (60%) in Group C (P=0.001). The median [range] ephedrine dose was greater in Group C (12 [0-24]mg) compared to Group M (0 [0-12]mg) (P<0.001). There was no difference between groups in the time to onset of hypotension. The use of a sequential compression mechanical pump that detects venous refilling and cycles accordingly, reduced the incidence and severity of hypotension after spinal anesthesia for cesarean section. Copyright © 2012 Elsevier Ltd. All rights reserved.

Orthostatic hypotension

NASA Technical Reports Server (NTRS)

Grimm, J. J.

1980-01-01

Following a brief physiopathological review, orthostatic hypotension is classified into three groups: organic, functional and medication-dependent. The importance of etiological diagnosis, the use of objective tests and appropriate therapy, especially concerning the organic forms, is stressed.

Recurrence of non-cardiogenic pulmonary edema and sustained hypotension shock in cystic pheochromocytoma.

PubMed

Dai, Jin; Chen, Shen-Jie; Yang, Bing-Sheng; Lü, Shu-Min; Zhu, Min; Xu, Yi-Fei; Chen, Jie; Cai, Hong-Wen; Mao, Wei

2017-05-01

Pheochromocytoma is a rare neuroendocrine tumor which derives from chromaffin cells of the adrenal gland or relevant to sympathetic nerves and ganglia. The clinical features of pheochromocytoma are various. Paroxysmal episodes of serious hypertension, headache, palpitation, and diaphoresis are the typical manifestations (Bravo, 2004). Hypotension shock, pulmonary edema, and acute coronary syndrome induced by pheochromocytoma are uncommon (Malindretos et al., 2008; Batisse-Lignier et al., 2015). In this study, we present a rare case of cystic pheochromocytoma causing recurrent hypotension shock, non-cardiogenic pulmonary edema, and acute coronary syndrome, and the possible mechanisms are discussed.

The contributions of adrenal hormones, hemodynamic factors, and the endotoxin-related stress reaction to stable prostaglandin analog-induced peripheral lymphopenia and neutrophilia.

PubMed

Ulich, T R; Keys, M; Ni, R X; del Castillo, J; Dakay, E B

1988-01-01

Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal

Prediction of hypotension during spinal anesthesia for elective cesarean section by altered heart rate variability induced by postural change.

PubMed

Sakata, K; Yoshimura, N; Tanabe, K; Kito, K; Nagase, K; Iida, H

2017-02-01

Maternal hypotension is a common complication during cesarean section performed under spinal anesthesia. Changes in maternal heart rate with postural changes or values of heart rate variability have been reported to predict hypotension. Therefore, we hypothesized that changes in heart rate variability due to postural changes can predict hypotension. A total of 45 women scheduled to undergo cesarean section under spinal anesthesia were enrolled. A postural change test was performed the day before cesarean section. The ratio of the power of low and high frequency components contributing to heart rate variability was assessed in the order of supine, left lateral, and supine. Patients who exhibited a ⩾two-fold increase in the low-to-high frequency ratio when moving to supine from the lateral position were assigned to the postural change test-positive group. According to the findings of the postural change test, patients were assigned to the positive (n=22) and negative (n=23) groups, respectively. Hypotension occurred in 35/45 patients, of whom 21 (60%) were in the positive group and 14 (40%) were in the negative group. The incidence of hypotension was greater in the positive group (P<0.01). The total dose of ephedrine was greater in the positive group (15±11 vs. 7±7mg, P=0.005). The area under the receiver operating characteristic curve was 0.76 for the postural change test as a predictor of hypotension. The postural change test with heart rate variability analysis may be used to predict the risk of hypotension during spinal anesthesia for cesarean section. Copyright © 2016 Elsevier Ltd. All rights reserved.

Permissive hypotension in extremely low birth weight infants (≤1000 gm).

PubMed

Ahn, So Yoon; Kim, Eun Sun; Kim, Jin Kyu; Shin, Jeong Hee; Sung, Se In; Jung, Ji Mi; Chang, Yun Sil; Park, Won Soon

2012-07-01

We performed this study to evaluate the safety of permissive hypotension management in extremely low birth weight infants (ELBWIs). Medical records of all inborn ELBWIs admitted to Samsung Medical Center from January 2004 to December 2008 were reviewed retrospectively. Of a total of 261 ELBWIs, 47 (18%) required treatment for hypotension (group T), 110 (42%) remained normotensive (group N), and 104 (40%) experienced more than one episode of hypotension without treatment (group P) during the first 72 hours of life. Treatment of hypotension included inotropic support and/or fluid loading. Birth weight and Apgar scores were significantly lower in the T group than the other two groups. In the N group, the rate of pathologically confirmed maternal chorioamnionitis was significantly higher than other two groups, and the rate was higher in the P group than the T group. After adjusting for covariate factors, no significant differences in mortality and major morbidities were found between the N and P groups. However, the mortality rate and the incidence of intraventricular hemorrhage (≥stage 3) and bronchopulmonary dysplasia (≥moderate) were significantly higher in the T group than the other two groups. Long term neurodevelopmental outcomes were not significantly different between the N and P groups. Close observation of hypotensive ELBWIs who showed good clinical perfusion signs without intervention allowed to avoid unnecessary medications and resulted in good neurological outcomes.

Droxidopa for Symptomatic Neurogenic Hypotension.

PubMed

Ferguson-Myrthil, Nadia

Droxidopa is a first-in-class, orally available, synthetic amino acid precursor of norepinephrine that received accelerated Food and Drug Administration approval in February 2014 after Orphan Drug status for a debilitating condition known as symptomatic neurogenic orthostatic hypotension. Neurogenic disorders often lead to postural hypotension as a result of poor norepinephrine release from its storage sites. Clinical data suggest increases in standing systolic blood pressure and improvements in many other markers for subjective relief in patients with symptomatic neurogenic hypotension who received droxidopa therapy over 1-2 weeks. Studies evaluating the sustained effects of droxidopa are ongoing. With minimal drug interactions (even with carbidopa use) or adverse effects, droxidopa therapy can be used safely in patients with a variety of neurologic conditions; however, more data are needed to determine its appropriate pharmacotherapeutic role. In all, droxidopa is a safe and effective medication for the treatment of orthostatic dizziness/lightheadedness, or the "feeling that you are about to black out" in adult patients with symptomatic neurogenic orthostatic hypotension secondary to primary autonomic failure (Parkinson's disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.

Permissive hypotension in bleeding trauma patients: helpful or not and when?

PubMed

Gourgiotis, Stavros; Gemenetzis, George; Kocher, Hemant M; Aloizos, Stavros; Salemis, Nikolaos S; Grammenos, Stylianos

2013-12-01

Severity of hemorrhage and rate of bleeding are fundamental factors in the outcomes of trauma. Intravenous administration of fluid is the basic treatment to maintain blood pressure until bleeding is controlled. The main guideline, used almost worldwide, Advanced Trauma Life Support, established by the American College of Surgeons in 1976, calls for aggressive administration of intravenous fluids, primarily crystalloid solutions. Several other guidelines, such as Prehospital Trauma Life Support, Trauma Evaluation and Management, and Advanced Trauma Operative Management, are applied according to a patient's current condition. However, the ideal strategy remains unclear. With permissive hypotension, also known as hypotensive resuscitation, fluid administration is less aggressive. The available models of permissive hypotension are based on hypotheses in hypovolemic physiology and restricted clinical trials in animals. Before these models can be used in patients, randomized, controlled clinical trials are necessary.

[Prophylaxis and treatment of arterial hypotension during caesarean with spinal anaesthesia].

PubMed

Arias, J; Lacassie, H J

2013-11-01

Caesarean section is one of the most common surgical procedures worldwide. Arterial hypotension is the most prevalent adverse effect after spinal anaesthesia. Various methods have been used to prevent or treat hypotension. Since there is no treatment 100% effective by itself, a multimodal management is required to achieve an optimum balance and avoidance of hemodynamic imbalance. Strategies to avoid this side effect are analyzed on the basis of the best evidence available so far, summarized as mechanical factors, anesthetics, fluids and vasopressors. After spinal anaesthesia for caesarean section, the best strategy available for prevention of hypotension appears to be the combination of crystalloids along with an alpha 1 agonist vasopressor. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Prehospital Nitroglycerin in Tachycardic Chest Pain Patients: A Risk for Hypotension or Not?

PubMed

Proulx, Marie-Hélène; de Montigny, Luc; Ross, Dave; Vacon, Charlene; Juste, Louis Enock; Segal, Eli

2017-01-01

The American Heart Association guidelines (AHA) guidelines list tachycardia as a contraindication for the administration of nitroglycerin (NTG), despite limited evidence of adverse events. We sought to determine whether NTG administered for chest pain was a predictor of hypotension (systolic blood pressure <90 mmHg) in patients with tachycardia, compared to patients without tachycardia (50≥ heart rate ≤100). We performed a retrospective cohort study using patient care reports completed by basic life support (BLS) providers in a large urban Canadian EMS system for the period 2010-2012. We used logistic regression to test the association between post-NTG hypotension and tachycardia, independent of pre-NTG blood pressure, age, sex, and comorbidities. Using identical models, we tested four secondary outcomes (drop in blood pressure, reduced consciousness, bradycardia, and cardiac arrest). The cohort included 10,308 patients who were administered NTG by BLS in the prehospital setting; 2,057 (20%) of patients were tachycardic before NTG administration. Hypotension occurred in 320 of all patients (3.1%): 239 without tachycardia (2.9%) and 81 with tachycardia (3.9%). Compared to non-tachycardic patients, tachycardic patients showed increased adjusted odds of hypotension (AOR: 1.60; 95% CI: 1.23-2.08) or of a drop in blood pressure of 30mm Hg or greater (AOR: 1.11; CI: 1.00-1.24). Tachycardia was associated with decreased odds of bradycardia (OR: 0.33; CI: 0.17-0.64). We did not find a significant association between tachycardia and either post-NTG reduced level of consciousness or cardiac arrest. We did find a strong, significant association between pre-NTG blood pressure and post-NTG hypotension (AOR for units of 10mmHg: 0.64; CI: 0.61-0.69). Hypotension following prehospital administration of NTG was infrequent in patients with chest pain. However, while the absolute risk of NTG-induced hypotension was low, patients with pre-NTG tachycardia had a significant increase

Increase in gastric pH reduces hypotensive effect of oral sodium nitrite in rats.

PubMed

Pinheiro, Lucas C; Montenegro, Marcelo F; Amaral, Jefferson H; Ferreira, Graziele C; Oliveira, Alisson M; Tanus-Santos, Jose E

2012-08-15

The new pathway nitrate-nitrite-nitric oxide (NO) has emerged as a physiological alternative to the classical enzymatic pathway for NO formation from l-arginine. Nitrate is converted to nitrite by commensal bacteria in the oral cavity and the nitrite formed is then swallowed and reduced to NO under the acidic conditions of the stomach. In this study, we tested the hypothesis that increases in gastric pH caused by omeprazole could decrease the hypotensive effect of oral sodium nitrite. We assessed the effects of omeprazole treatment on the acute hypotensive effects produced by sodium nitrite in normotensive and L-NAME-hypertensive free-moving rats. In addition, we assessed the changes in gastric pH and plasma levels of nitrite, NO(x) (nitrate+nitrite), and S-nitrosothiols caused by treatments. We found that the increases in gastric pH induced by omeprazole significantly reduced the hypotensive effects of sodium nitrite in both normotensive and L-NAME-hypertensive rats. This effect of omeprazole was associated with no significant differences in plasma nitrite, NO(x), or S-nitrosothiol levels. Our results suggest that part of the hypotensive effects of oral sodium nitrite may be due to its conversion to NO in the acidified environment of the stomach. The increase in gastric pH induced by treatment with omeprazole blunts part of the beneficial cardiovascular effects of dietary nitrate and nitrite. Copyright © 2012 Elsevier Inc. All rights reserved.

Risk of intraoperative hypotension with loop diuretics: a randomized controlled trial.

PubMed

Khan, Nadia A; Campbell, Norman R; Frost, Shaun D; Gilbert, Ken; Michota, Frank A; Usmani, Ali; Seal, Doug; Ghali, William A

2010-11-01

There is growing concern regarding the safety of blood pressure-lowering medications administered during the perioperative period. Whether loop diuretics also induce intraoperative hypotension is uncertain. Our objective was to compare the effects of continuing or withholding furosemide on the day of noncardiac elective surgery on intraoperative hypotension among chronic users of furosemide. A double blind, randomized, placebo controlled trial was conducted at 3 North American university centers between September 2000 and December 2006. Participants were randomly assigned in a 1:1 ratio to receive either furosemide or placebo on the day of surgery. The primary outcome was risk of developing intraoperative hypotension. A priori secondary outcomes included risk of heart failure; composite cardiovascular event (myocardial infarction, arrhythmia, stroke or transient ischemic attack, or death); and change in renal function and electrolytes. Of the 212 patients enrolled, 193 patients underwent surgery. There was no significant difference in risk of developing intraoperative hypotension between the furosemide (49%) and placebo (51.9%) groups (relative risk [RR], 0.95; 95% confidence interval [CI], 0.72-1.24; P = .78). The intraoperative administration of vasopressors and fluids were similar between both groups. The risk of developing postoperative cardiovascular events was not significantly different between those randomized to furosemide (4.8%) or placebo (2.8%) (RR, 1.73; 95% CI, 0.42-7.06; P = .49). There was no significant difference in renal function or electrolytes between the 2 groups. Among elective, noncardiac surgeries in patients chronically treated with furosemide, the administration of furosemide on the day of surgery did not significantly increase the risk for intraoperative hypotension. Copyright © 2010 Elsevier Inc. All rights reserved.

Recurrence of non-cardiogenic pulmonary edema and sustained hypotension shock in cystic pheochromocytoma*#

PubMed Central

Dai, Jin; Chen, Shen-jie; Yang, Bing-sheng; Lü, Shu-min; Zhu, Min; Xu, Yi-fei; Chen, Jie; Cai, Hong-wen; Mao, Wei

2017-01-01

Pheochromocytoma is a rare neuroendocrine tumor which derives from chromaffin cells of the adrenal gland or relevant to sympathetic nerves and ganglia. The clinical features of pheochromocytoma are various. Paroxysmal episodes of serious hypertension, headache, palpitation, and diaphoresis are the typical manifestations (Bravo, 2004). Hypotension shock, pulmonary edema, and acute coronary syndrome induced by pheochromocytoma are uncommon (Malindretos et al., 2008; Batisse-Lignier et al., 2015). In this study, we present a rare case of cystic pheochromocytoma causing recurrent hypotension shock, non-cardiogenic pulmonary edema, and acute coronary syndrome, and the possible mechanisms are discussed. PMID:28471119

Risk Factors for Orthostatic Hypotension: Differences Between Elderly Men and Women.

PubMed

Méndez, Andrea S; Melgarejo, Jesús D; Mena, Luis J; Chávez, Carlos A; González, Alicex C; Boggia, José; Terwilliger, Joseph D; Lee, Joseph H; Maestre, Gladys E

2018-06-11

Orthostatic hypotension (OH) occurs when mechanisms regulating blood pressure (BP) levels after standing-up are altered. It is unclear how prevalence and risk factors for OH are different between sexes. We aimed to investigate sex differences in prevalence and risk factors for OH elderly individuals. We included 882 participants from Maracaibo Aging Study. OH was a sustained reduction of ≥20 mm Hg in systolic BP, ≥10 mm Hg in diastolic BP, or both, after 3 minutes of changing positions from supine to standing. Multivariable logistic regression models were used to examine the relationships among risk factors for OH in men and women considering interaction sex-term and stratified by sex. The mean age was 66.7 ± 8.5 years, being similar by sex. Women and men 55-74 years had similar prevalence of OH+ (18.5% vs. 20.9%, respectively). After 75 years, the proportion of women with OH+ was lower than men (11% vs. 30%, respectively). Hypertension, specifically systolic BP ≥140 mm Hg, and high pulse pressure (PP) were related with OH+ accounted by interaction sex-term, while diastolic BP ≥90 mm Hg, antihypertensive treatment, body mass index (BMI), diabetes mellitus and age were not. Systolic BP ≥140 mm Hg increases the risk of OH only among women, while BMI showed an inverse association in both sexes. Although the prevalence of OH is similar in both sexes, there are different risk factors associated by sex. Systolic BP ≥140 mm Hg was associated with increased risk of OH only with women while BMI was a protective factor for OH in men and women.

Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor

PubMed Central

Callaghan, Brid; Kosari, Samin; Pustovit, Ruslan V; Sartor, Daniela M; Ferens, Dorota; Ban, Kung; Baell, Jonathan; Nguyen, Trung V; Rivera, Leni R; Brock, James A; Furness, John B

2014-01-01

BACKGROUND AND PURPOSE Some agonists of ghrelin receptors cause rapid decreases in BP. The mechanisms by which they cause hypotension and the pharmacology of the receptors are unknown. EXPERIMENTAL APPROACH The effects of ligands of ghrelin receptors were investigated in rats in vivo, on isolated blood vessels and on cells transfected with the only molecularly defined ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR1a). KEY RESULTS Three agonists of GHSR1a receptors, ulimorelin, capromorelin and CP464709, caused a rapid decrease in BP in the anaesthetized rat. The effect was not reduced by either of two GHSR1a antagonists, JMV2959 or YIL781, at doses that blocked effects on colorectal motility, in vivo. The rapid hypotension was not mimicked by ghrelin, unacylated ghrelin or the unacylated ghrelin receptor agonist, AZP531. The early hypotension preceded a decrease in sympathetic nerve activity. Early hypotension was not reduced by hexamethonium or by baroreceptor (sino-aortic) denervation. Ulimorelin also relaxed isolated segments of rat mesenteric artery, and, less potently, relaxed aorta segments. The vascular relaxation was not reduced by JMV2959 or YIL781. Ulimorelin, capromorelin and CP464709 activated GHSR1a in transfected HEK293 cells at nanomolar concentrations. JMV2959 and YIL781 both antagonized effects in these cells, with their pA2 values at the GHSR1a receptor being 6.55 and 7.84. CONCLUSIONS AND IMPLICATIONS Our results indicate a novel vascular receptor or receptors whose activation by ulimorelin, capromorelin and CP464709 lowered BP. This receptor is activated by low MW GHSR1a agonists, but is not activated by ghrelin. PMID:24670149

Sympathoinhibition and hypotension in carotid sinus hypersensitivity

NASA Technical Reports Server (NTRS)

Smith, M. L.; Ellenbogen, K. A.; Eckberg, D. L.

1992-01-01

Carotid sinus reflex hypersensitivity is a known cause of syncope in humans. The condition is characterized by cardioinhibition and vasodepression, each to varying degrees. The extent and importance of sympathoinhibition has not been determined in patients with carotid sinus hypersensitivity. This study reports on the extent of sympathoinhibition measured directly directly during carotid massage with and without atrioventricular sequential pacing, in a patient with symptomatic carotid sinus reflex hypersensitivity. Carotid massage elicited asystole, hypotension and complete inhibition of muscle sympathetic nerve activity. Carotid massage during atrioventricular pacing produced similar sympathoinhibition, but with minimal hypotension. Therefore, sympathoinhibition did not contribute importantly to the hypotension during carotid massage in the supine position in this patient. Further investigations are required to elucidate the relation of sympathoinhibition to hypotension in patients with carotid sinus hypersensitivity in the upright position.

Respective contributions of α-adrenergic and non-adrenergic mechanisms in the hypotensive effect of imidazoline-like drugs

PubMed Central

Bruban, Véronique; Feldman, Josiane; Greney, Hugues; Dontenwill, Monique; Schann, Stephan; Jarry, Christian; Payard, Marc; Boutin, Jean; Scalbert, Elizabeth; Pfeiffer, Bruno; Renard, Pierre; Vanhoutte, Paul; Bousquet, Pascal

2001-01-01

The hypotensive effect of imidazoline-like drugs, such as clonidine, was first attributed to the exclusive stimulation of central α2-adrenoceptors (α2ARs). However, a body of evidence suggests that non-adrenergic mechanisms may also account for this hypotension. This work aims (i) to check whether imidazoline-like drugs with no α2-adrenergic agonist activity may alter blood pressure (BP) and (ii) to seek a possible interaction between such a drug and an α2ARs agonist α-methylnoradrenaline (α-MNA). We selected S23515 and S23757, two imidazoline-like drugs with negligible affinities and activities at α2ARs but with high affinities for non-adrenergic imidazoline binding sites (IBS). S23515 decreased BP dose-dependently (−27±5% maximal effect) when administered intracisternally (i.c.) to anaesthetized rabbits. The hypotension induced by S23515 (100 μg kg−1 i.c.) was prevented by S23757 (1 mg kg−1 i.c.) and efaroxan (10 μg kg−1 i.c.), while these compounds, devoid of haemodynamic action by themselves, did not alter the hypotensive effect of α-MNA (3 and 30 μg kg−1 i.c.). Moreover, the α2ARs antagonist rauwolscine (3 μg kg−1 i.c.) did not prevent the effect of S23515. Finally, whilst 3 μg kg−1 of S23515 or 0.5 μg kg−1 of α-MNA had weak hypotensive effects, the sequential i.c. administration of these two drugs induced a marked hypotension (−23±2%). These results indicate that an imidazoline-like drug with no α2-adrenergic properties lowers BP and interacts synergistically with an α2ARs agonist. PMID:11350862

MRI Reveals Edema in Larynx (But Not in Brain) During Anaphylactic Hypotension in Anesthetized Rats

PubMed Central

Toyota, Ichiro; Tanida, Mamoru; Wang, Mofei; Kurata, Yasutaka; Tonami, Hisao

2013-01-01

Purpose Anaphylactic shock is sometimes accompanied by local interstitial edema due to increased vascular permeability. We performed magnetic resonance imaging (MRI) to compare edema in the larynx and brain of anesthetized rats during anaphylactic hypotension versus vasodilator-induced hypotension. Methods Male Sprague Dawley rats were subjected to hypotension induced by the ovalbumin antigen (n=7) or a vasodilator sodium nitroprusside (SNP; n=7). Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on MRI performed repeatedly for up to 68 min after the injection of either agent. The presence of laryngeal edema was also examined by histological examination. Separately, the occurrence of brain edema was assessed by measuring brain water content using the wet/dry method in rats with anaphylaxis (n=5) or SNP (n=5) and the non-hypotensive control rats (n=5). Mast cells in hypothalamus were morphologically examined. Results Mean arterial blood pressure similarly decreased to 35 mmHg after an injection of the antigen or SNP. Hyperintensity on T2-weighted images (as reflected by elevated T2RT) was found in the larynx as early as 13 min after an injection of the antigen, but not SNP. A postmortem histological examination revealed epiglottic edema in the rats with anaphylaxis, but not SNP. In contrast, no significant changes in T2RT or ADC were detectable in the brains of any rats studied. In separate experiments, the quantified brain water content did not increase in either anaphylaxis or SNP rats, as compared with the non-hypotensive control rats. The numbers of mast cells with metachromatic granules in the hypothalamus were not different between rats with anaphylaxis and SNP, suggesting the absence of anaphylactic reaction in hypothalamus. Conclusion Edema was detected using the MRI technique in the larynx during rat anaphylaxis, but not in the brain. PMID:24179686

MRI reveals edema in larynx (but not in brain) during anaphylactic hypotension in anesthetized rats.

PubMed

Toyota, Ichiro; Tanida, Mamoru; Shibamoto, Toshishige; Wang, Mofei; Kurata, Yasutaka; Tonami, Hisao

2013-11-01

Anaphylactic shock is sometimes accompanied by local interstitial edema due to increased vascular permeability. We performed magnetic resonance imaging (MRI) to compare edema in the larynx and brain of anesthetized rats during anaphylactic hypotension versus vasodilator-induced hypotension. Male Sprague Dawley rats were subjected to hypotension induced by the ovalbumin antigen (n=7) or a vasodilator sodium nitroprusside (SNP; n=7). Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on MRI performed repeatedly for up to 68 min after the injection of either agent. The presence of laryngeal edema was also examined by histological examination. Separately, the occurrence of brain edema was assessed by measuring brain water content using the wet/dry method in rats with anaphylaxis (n=5) or SNP (n=5) and the non-hypotensive control rats (n=5). Mast cells in hypothalamus were morphologically examined. Mean arterial blood pressure similarly decreased to 35 mmHg after an injection of the antigen or SNP. Hyperintensity on T2-weighted images (as reflected by elevated T2RT) was found in the larynx as early as 13 min after an injection of the antigen, but not SNP. A postmortem histological examination revealed epiglottic edema in the rats with anaphylaxis, but not SNP. In contrast, no significant changes in T2RT or ADC were detectable in the brains of any rats studied. In separate experiments, the quantified brain water content did not increase in either anaphylaxis or SNP rats, as compared with the non-hypotensive control rats. The numbers of mast cells with metachromatic granules in the hypothalamus were not different between rats with anaphylaxis and SNP, suggesting the absence of anaphylactic reaction in hypothalamus. Edema was detected using the MRI technique in the larynx during rat anaphylaxis, but not in the brain.

Orthostatic hypotension: epidemiology, pathophysiology and management

NASA Technical Reports Server (NTRS)

Jacob, G.; Robertson, D.

1995-01-01

Orthostatic hypotension is characterized by low upright blood pressure levels and symptoms of cerebral hypoperfusion. Whereas orthostatic hypotension is heterogeneous, correct pathophysiologic diagnosis is important because of therapeutic and prognostic considerations. Although therapy is not usually curative, it can be extraordinarily beneficial if it is individually tailored. Management of the Shy-Drager syndrome (multiple-system atrophy) remains a formidable challenge.

Cognitive performance in hypotensive persons with spinal cord injury.

PubMed

Jegede, Adejoke B; Rosado-Rivera, Dwindally; Bauman, William A; Cardozo, Christopher P; Sano, Mary; Moyer, Jeremy M; Brooks, Monifa; Wecht, Jill Maria

2010-02-01

Due to sympathetic de-centralization, individuals with spinal cord injury (SCI), especially those with tetraplegia, often present with hypotension, worsened with upright posture. Several investigations in the non-SCI population have noted a relationship between chronic hypotension and deficits in memory, attention and processing speed and delayed reaction times. To determine cognitive function in persons with SCI who were normotensive or hypotensive over a 24-h observation period while maintaining their routine activities. Subjects included 20 individuals with chronic SCI (2-39 years), 13 with tetraplegia (C4-8) and 7 with paraplegia (T2-11). Individuals with hypotension were defined as having a mean 24-h systolic blood pressure (SBP) below 110 mmHg for males and 100 mmHg for females, and having spent >or=50% of the total time below these gender-specific thresholds. The cognitive battery used included assessment of memory (CVLT), attention and processing speed (Digit Span, Stroop word and color and Oral Trails A), language (COWAT) and executive function (Oral Trails B and Stroop color-word). Demographic parameters did not differ among the hypotensive and normotensive groups; the proportion of individuals with tetraplegia (82%) was higher in the hypotensive group. Memory was significantly impaired (P < 0.05) and there was a trend toward slowed attention and processing speed (P < 0.06) in the hypotensive compared to the normotensive group. These preliminary data suggest that chronic hypotension in persons with SCI is associated with deficits in memory and possibly attention and processing speed, as previously reported in the non-SCI population.

Bed Rest and Orthostatic-Hypotensive Intolerance

NASA Technical Reports Server (NTRS)

Schneider, Suzanne M.

2000-01-01

Orthostatic tolerance may be defined as the ability of humans to maintain cerebral perfusion and consciousness upon movement from a supine or sitting position to the upright posture; for example, subjects can stand suddenly or be tilted to the head-up body position. Similar but not identical physiological responses can be induced by positive G(sub Z) (head to foot) acceleration or exposure to lower body negative pressure (LBNP). The objective is to suddenly shift blood to the lower body to determine how effectively cardiovascular and neural-hormonal compensatory responses react to maintain blood pressure. In the most precise method for measuring tolerance, individuals would be stressed until they faint (syncope). However, the potential consequences and discomforts of such a test usually prohibit such a procedure so that few investigators actually induce syncope. In a more common approach, subjects are exposed to a given level of stress, for example, head-up tilt for 15 min, and any increases in heart rate or decreases in blood pressure are interpreted as indicators of progress toward syncope. Presumably, the greater the perturbation of heart rate and blood pressure, the closer to "tolerance," i.e., point of unconsciousness. Another more appropriate approach is to induce a progressively increasing hypotensive stress until pre-determined physiological responses or pre-syncopal symptoms appear. The physiological criteria may include a sudden drop in systolic blood pressure (greater than 25 mm/min), a sudden drop in heart rate (greater than 15 beats/min), or a systolic blood pressure less than 70 mmHg. The most common pre-syncopal symptoms include lightheadedness, stomach awareness or distress, feelings of warmth, tingly skin, and light to profuse sweating. Usually a combination of physiological responses and symptoms occurs such that, on different days, the tolerance time to the same orthostatic protocol is reproducible for a given individual. The assumption is that

Induction of rat hepatic aryl sulfotransferase (SULT1A1) gene expression by triamcinolone acetonide: impact on minoxidil-mediated hypotension.

PubMed

Duanmu, Z; Dunbar, J; Falany, C N; Runge-Morris, M

2000-05-01

The hypotensive agent minoxidil (6-imino-1, 2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine) depends upon aryl sulfotransferase (SULT1)-catalyzed sulfation for its bioactivation. Previous reports suggest that glucocorticoids induce class-specific SULT1 and isoform-specific SULT1A1 gene expression in rat liver. In the present study, rats were treated with the glucocorticoid triamcinolone acetonide (TA, 5 mg/kg/day i.p. x 3 days) or its vehicle, 2% Tween-20, prior to minoxidil, and subsequent effects on mean arterial pressure (MAP), heart rate (HR), and hepatic SULT1 gene expression were characterized. Minoxidil treatment (1.5 mg/kg) resulted in a steady decline in MAP values of 16.3 to 18.6% relative to basal control levels at 35 to 60 min following minoxidil injection. Pentachlorophenol (PCP, 40 micromol/kg i.p.), an inhibitor of SULT1 enzyme activity, effectively ablated the hypotensive effects of minoxidil. By contrast, pretreatment with TA significantly enhanced minoxidil-induced hypotension. Relative to vehicle-treated controls, TA-treated rats displayed a steeper rate of decline in MAP and more profound levels of hypotension with decreases in MAP following minoxidil administration of 27.8%. TA also produced significant increases in hepatic SULT1 mRNA expression (of 271%) and SULT1A1 immunoreactive protein levels (of 273%), relative to vehicle-treated controls. These results provide physiological evidence to support the biological relevance of SULT1A1 induction by glucocorticoids. The data indicate that steroid treatment induces SULT1A1 gene expression and, as a consequence, accentuates the hypotensive effects of minoxidil. Copyright 2000 Academic Press.

Aortic stiffness and hypotension episodes are associated with impaired cognitive function in older subjects with subjective complaints of memory loss.

PubMed

Scuteri, Angelo; Tesauro, Manfredi; Guglini, Letizia; Lauro, Davide; Fini, Massimo; Di Daniele, Nicola

2013-11-20

Though CV risk factors and markers of arterial aging are recognized risky for cognition, no study has simultaneously investigated the impact of multiple cardiac, arterial (large and small vessels), and hemodynamic parameters on cognitive function in older subjects. Two hundred eighty older subjects with subjective complaints of memory loss and no previous stroke (mean age 78.3 ± 6.3 years) were studied. Global cognitive function was evaluated with the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as a MMSE < 21. We measured: traditional CV risk factors; aorta stiffness (Pulse Wave Velocity, PWV); LV mass; presence of WML at neuroimaging; episodes of hypotension (SBP <100 mmHg during 24 h Ambulatory Blood Pressure Monitoring). In both cross-sectional and longitudinal analyses PWV, WML, and episodes of hypotension were significantly associated with poorer cognitive function-controlling for age, sex, education, depression, traditional CV risk factors, and medications. LV mass was no longer associated with cognition in multiple regression. Older subjects with stiffer arteries or episodes of hypotension presented a 4-fold and an 11-fold, respectively, greater odds for progression from normal cognitive function to cognitive impairment. A synergistic effect between PWV, WML, and hypotension was observed: the occurrence of any two of PWV, WML, or hypotension was accompanied by lower MMSE; in the presence of all three factors, a further significant decline in cognitive function was observed. Systemic hemodynamic parameters (higher PWV and hypotension) together with cerebral microvascular damage (WML) are significantly associated with poorer cognitive function and may identify older subjects with subjective complaints of memory loss at higher risk of cognitive decline. © 2013.

Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones.

PubMed

Clyman, Ronald I; Wickremasinghe, Andrea; Merritt, T Allen; Solomon, Tabitha; McNamara, Patrick; Jain, Amish; Singh, Jaideep; Chu, Alison; Noori, Shahab; Sekar, Krishnamurthy; Lavoie, Pascal M; Attridge, Joshua T; Swanson, Jonathan R; Gillam-Krakauer, Maria; Reese, Jeff; DeMauro, Sara; Poindexter, Brenda; Aucott, Sue; Satpute, Monique; Fernandez, Erika; Auchus, Richard J

2014-06-01

To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. We performed a multicenter study of infants born at <32 weeks' gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured 3 times: before and after a cosyntropin (1.0 μg/kg) stimulation test (performed before the ligation), and at 10-12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified inotrope score (1 × dopamine [μg/kg/min] + 1 × dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their greatest inotrope score was >15. Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low postoperative cortisol levels were not associated with the overall incidence of hypotension after ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the OR for developing catecholamine-resistant hypotension was OR 36.6, 95% CI 2.8-476, P = .006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not attributable to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged, and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Infants with low cortisol concentrations after PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones

PubMed Central

Clyman, Ronald I.; Wickremasinghe, Andrea; Merritt, T. Allen; Solomon, Tabitha; McNamara, Patrick; Jain, Amish; Singh, Jaideep; Chu, Alison; Noori, Shahab; Sekar, Krishnamurthy; Lavoie, Pascal M.; Attridge, Joshua T.; Swanson, Jonathan R.; Gillam-Krakauer, Maria; Reese, Jeff; DeMauro, Sara; Poindexter, Brenda; Aucott, Sue; Satpute, Monique; Fernandez, Erika; Auchus, Richard J.

2014-01-01

Objective To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. Study design We performed a multicenter study of infants born at <32 weeks gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured three times: before and after a cosyntropin (1.0 microgram/kg) stimulation test (performed prior to the ligation), and at 10–12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified Inotrope Score (1 x dopamine (μg/kg/min) + 1 x dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their highest Inotrope Score was >15. Results Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low post-operative cortisol levels were not associated with the overall incidence of hypotension following ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the odds ratio for developing catecholamine-resistant hypotension was OR=36.6, CI=2.8–476, p=0.006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not due to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. Conclusion Infants with low cortisol concentrations following PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production. PMID:24636853

Postural hypotension and the anti-gravity suit.

PubMed

Brook, W H

1994-10-01

An air force anti-gravity suit, as used by fighter pilots to prevent loss of consciousness, has been successfully employed to treat severe postural hypotension in a patient with Shy-Drager syndrome. The definition of postural hypotension is reviewed, and reference is made to the previous use of the anti-gravity suit in the treatment of this condition.

Involvement of nitric oxide in the mediation of the hypotensive action of the essential oil of Mentha x villosa in normotensive conscious rats.

PubMed

Lahlou, Saad; Magalhães, Pedro Jorge Caldas; Carneiro-Leão, Ricardo Ferreira Lima; Leal-Cardoso, José Henrique

2002-08-01

Recently, we showed that intravenous (i.v.) treatment with the essential oil of Mentha x villosa (EOMV) in pentobarbitone-anaesthetised rats decreased blood pressure; the effect occurred independently of the presence of an operational central autonomic drive to the cardiovascular system. This finding suggested that the hypotensive activity of EOMV may result from its vasodilatory effects directly upon vascular smooth muscle. The present study examines this possibility and whether EOMV-induced hypotension is mediated, at least in part, by an endothelial L-arginine/nitric oxide pathway. In conscious rats, i.v. injections of bolus doses (1 to 20 mg/kg) of EOMV elicited immediate and dose-dependent decreases in mean aortic pressure (MAP) and heart rate (HR). Pretreatment with i.v. hexamethonium (30 mg/kg) reduced the EOMV-induced bradycardia without affecting the hypotension. However, i.v. pretreatment with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl (L-NAME, 20 mg/kg), reduced partially, but significantly, the maximal percent decreases in MAP elicited by EOMV without affecting the bradycardia. In rat isolated thoracic aorta preparations, EOMV (1 - 130 microg/ml) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction. This smooth muscle-relaxant activity of EOMV was significantly reduced by the incubation of endothelium-intact rings with L-NAME (20 microM), as evidenced by the significant enhancement in the IC50 for EOMV-induced reduction of potassium-induced contraction (133.8 +/- 26.5 vs. 65.2 +/- 8.2 microg/ml in the absence of L-NAME). Furthermore, the vasorelaxant effects of EOMV in endothelium-denuded aortic rings were also significantly reduced (IC50 = 109 +/- 10 microg/ml), compared to those observed in segments with intact endothelium (IC50 = 61 +/- 13 microg/ml). These results show that i.v. treatment with EOMV dose-dependently decreases blood pressure in conscious rats, and that this action is due to an

Autonomic Cardiovascular Control and Executive Function in Chronic Hypotension.

PubMed

Duschek, Stefan; Hoffmann, Alexandra; Reyes Del Paso, Gustavo A; Ettinger, Ulrich

2017-06-01

Chronic low blood pressure (hypotension) is characterized by complaints such as fatigue, reduced drive, dizziness, and cold limbs. Additionally, deficits in attention and memory have been observed. Autonomic dysregulation is considered to be involved in the origin of this condition. The study explored autonomic cardiovascular control in the context of higher cognitive processing (executive function) in hypotension. Hemodynamic recordings were performed in 40 hypotensive and 40 normotensive participants during execution of four classical executive function tasks (number-letter task, n-back task, continuous performance test, and flanker task). Parameters of cardiac sympathetic control, i.e., stroke volume, cardiac output, pre-ejection period, total peripheral resistance, and parasympathetic control, i.e., respiratory sinus arrhythmia and baroreflex sensitivity, were obtained. The hypotensive group exhibited lower stroke volume and cardiac output, as well as higher pre-ejection period and baroreflex sensitivity during task execution. Increased error rates in hypotensive individuals were observed in the n-back and flanker tasks. In the total sample, there were positive correlations of error rates with pre-ejection period, baroreflex sensitivity and respiratory sinus arrhythmia, and negative correlations with cardiac output. Group differences in stroke volume, cardiac output, and pre-ejection period suggest diminished beta-adrenergic myocardial drive during executive function processing in hypotension, in addition to increased baroreflex function. Although further research is warranted to quantify the extent of executive function impairment in hypotension, the results from correlation analysis add evidence to the notion that higher sympathetic inotropic influences and reduced parasympathetic cardiac influences are accompanied by better cognitive performance.

Low Blood Pressure (Hypotension)

MedlinePlus

... Low blood pressure on standing up (orthostatic, or postural, hypotension). This is a sudden drop in blood ... progressive damage to the autonomic nervous system, which controls involuntary functions such as blood pressure, heart rate, ...

Orthostatic hypotension and overall mortality in 1050 older patients of the outpatient comprehensive geriatric assessment unit.

PubMed

Freud, Tamar; Punchik, Boris; Kagan, Ella; Barzak, Alex; Press, Yan

2018-03-02

Orthostatic hypotension is a common problem in individuals aged ≥65 years. Its association with mortality is not clear. The aim of the present study was to evaluate associations between orthostatic hypotension and overall mortality in a sample of individuals aged ≥65 years who were seen at the Outpatient Comprehensive Geriatric Assessment Unit, Clalit Health Services, Beer-Sheva, Israel. Individuals who were evaluated in the Outpatient Comprehensive Geriatric Assessment Unit between January 2005 and December 2015, and who had data on orthostatic hypotension were included in the study. The database included sociodemographic characteristics, body mass index, functional and cognitive state, geriatric syndromes reached over the course of the assessment, and comorbidity. Data on mortality were also collected. The study sample included 1050 people, of whom 626 underwent comprehensive geriatric assessment and 424 underwent geriatric consultation. The mean age was 77.3 ± 5.4 years and 35.7% were men. Orthostatic hypotension was diagnosed in 294 patients (28.0%). In univariate analysis, orthostatic hypotension was associated with overall mortality only in patients aged 65-75 years (HR 1.5, 95% CI 1.07-2.2), but in the multivariate model this association disappeared. In older frail patients, orthostatic hypotension was not an independent risk factor for overall mortality. Geriatr Gerontol Int 2018; ••: ••-••. © 2018 Japan Geriatrics Society.

Orthostatic hypotension acutely impairs executive functions in Parkinson's disease.

PubMed

Sforza, Michela; Assogna, Francesca; Rinaldi, Domiziana; Sette, Giuliano; Tagliente, Stefania; Pontieri, Francesco E

2018-04-07

Orthostatic hypotension is a frequent non-motor symptom of Parkinson's disease, with negative prognostic role on cognitive functions. Here we measured the acute effects of orthostatic hypotension on executive functions in Parkinson's disease patients devoid of hypertension, carotid artery stenosis, and significant chronic cerebrovascular pathology. Measurements were carried out during regular visits in outpatient setting. Twenty-eight Parkinson's disease patients were recruited and studied along scheduled outpatient visits. They were divided into two groups (n = 14 each) based on the presence or lack of orthostatic hypotension. This was diagnosed according to international guidelines. All patients were submitted to the Stroop's test and to the phonological and semantic verbal fluency test after 10-min resting in supine position and immediately upon standing in upright position. Testing lasted less than 5 min in either position. In upright position, subjects with orthostatic hypotension displayed significantly worse performances at the Stroop's test word reading time (22.1 ± 4.1 vs. 14.9 ± 4.0 s), interference time (56.1 ± 12.3 vs. 41.4 ± 11.8 s), and number of errors at the interference section (5.8 ± 3.2 vs. 1.3 ± 2.1) as compared to those without orthostatic hypotension. These results demonstrate that worsening of attentive function upon standing can be measured in Parkinson's disease patients with orthostatic hypotension during routine outpatient visits. These findings suggest that clinically asymptomatic orthostatic hypotension in Parkinson's disease patients may acutely worsen neuropsychological performances with possible negative impact on daily functioning.

Histopathological analysis of spontaneous large necrosis of adrenal pheochromocytoma manifested as acute attacks of alternating hypertension and hypotension: a case report.

PubMed

Ohara, Nobumasa; Uemura, Yasuyuki; Mezaki, Naomi; Kimura, Keita; Kaneko, Masanori; Kuwano, Hirohiko; Ebe, Katsuya; Fujita, Toshio; Komeyama, Takeshi; Usuda, Hiroyuki; Yamazaki, Yuto; Maekawa, Takashi; Sasano, Hironobu; Kaneko, Kenzo; Kamoi, Kyuzi

2016-10-12

Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Hypertension secondary to pheochromocytoma is often paroxysmal, and patients occasionally present with sudden attacks of alternating hypertension and hypotension. Spontaneous, extensive necrosis within the tumor that is associated with catecholamine crisis is an infrequent complication of adrenal pheochromocytoma, but its pathogenesis remains unclear. A 69-year-old Japanese man developed acute-onset episodic headaches, palpitations, and chest pains. During the episodes, both marked fluctuations in blood pressure (ranging from 40/25 to 300/160 mmHg) and high plasma levels of catecholamines were found simultaneously. Radiological findings indicated a 4-cm left adrenal pheochromocytoma. These episodic symptoms disappeared within 2 weeks with normalization of plasma catecholamine levels. Two months later, the patient underwent adrenalectomy. Microscopic examinations revealed pheocromocytoma with a large central area of coagulative necrosis. The necrotic material was immunohistochemically positive for chromogranin A. Granulation tissue was adjacent to the necrotic area, accompanied by numerous hemosiderin-laden macrophages and histiocytes with vascular proliferation. Viable tumor cells, detected along the periphery of the tumor, demonstrated pyknosis, and the Ki-67 labeling index was 2 % in the hot spot. No embolus or thrombus formation was found in the resected specimen harboring the whole tumor. The Pheochromocytoma of the Adrenal gland Scaled Score was 2 out of 20. The patient's postoperative course was unremarkable for > 7 years. Presumed causal factors for the extensive necrosis of adrenal pheochromocytoma in previously reported cases include hemorrhage into the tumor, hypotension induced by a phentolamine administration, embolic infarction, high intracapsular pressure due to malignant growth of the tumor, and catecholamine-induced vasoconstriction. In the present case, histopathological

Identification of Hypotensive Emergency Department Patients with Cardiogenic Etiologies.

PubMed

Henning, Daniel J; Kearney, Kathleen E; Hall, Michael Kennedy; Mahr, Claudius; Shapiro, Nathan I; Nichol, Graham

2018-02-01

Identify predictors of cardiogenic etiology among emergency department (ED) patients with hypotension, and use these predictors to create a clinical tool to discern cardiogenic etiology of hypotension. This secondary analysis evaluated a prospective cohort of consecutive patients with hypotension in an urban, academic, tertiary care ED from November 2012 to September 2013. We included adults with hypotension, defined as a new vasopressor requirement, systolic blood pressure (SBP) < 90 mm Hg after at least 1 L of crystalloid or 2 units packed red blood cells, or SBP < 90 mm Hg and fluids withheld due to concern for fluid overload. The primary outcome was cardiogenic etiology, adjudicated by two physician chart review, with 25% paired chart review (kappa = 0.92). We used multivariable logistic regression to predict cardiogenic etiology, utilizing clinical data abstracted from the electronic medical record. We created a prediction score from significant covariates and calculated its test characteristics for cardiogenic hypotension. Of 700 patients with hypotension, 107 (15.3%, 95% CI: 12.6%-18.0%) had cardiogenic etiology. Independent predictors of cardiogenic etiology were shortness of breath (OR 4.1, 95% CI: 2.5-6.7), troponin > 0.1 ng/mL (37.5, 7.1-198.2), electrocardiographic ischemia (8.9, 4.0-19.8), history of heart failure (2.0, 1.1-3.3), and absence of fever (4.5, 2.3-8.7) (area under the curve [AUC] = 0.83). The prediction score created from these predictors yielded 78% sensitivity and 77% specificity for cardiogenic etiology (AUC = 0.827). Clinical predictors offer reasonable ED screening sensitivity for cardiogenic hypotension, while demonstrating sufficient specificity to facilitate early cardiac interventions.

Refractory hypotension due to Rogaine® (minoxidil) ingestion managed with midodrine.

PubMed

Garrard, Alexander; Wood, Adam; Sollee, Dawn; Aaronson, Patrick

2011-12-01

Minoxidil (Rogaine®) is a direct vasodilator that can cause significant toxicity when ingested. We report a case of ingestion of topical minoxidil [Rogaine® (Johnson & Johnson Healthcare Products, Division of McNeil-PPC, Inc)] resulting in refractory hypotension that was successfully managed with the oral α (1) agonist midodrine. A 48-year-old male who ingested an eight ounce bottle of Rogaine® presented to the emergency department. The patient presented with a blood pressure of 57/45 mmHg and a pulse of 84 beats per minute. The patient received IV fluids and multiple vasopressors to maintain an adequate mean arterial pressure. Midodrine, an oral α (1) vasopressor, was added 10 hours post ingestion and was able to maintain an adequate mean arterial pressure. Over the next two days, midodrine was titrated down as his blood pressure returned to baseline. Midodrine may serve as an additional option to treat toxicant induced hypotension.

Low-Volume Intense Exercise Elicits Post-exercise Hypotension and Subsequent Hypervolemia, Irrespective of Which Limbs Are Exercised.

PubMed

Graham, Matthew J; Lucas, Samuel J E; Francois, Monique E; Stavrianeas, Stasinos; Parr, Evelyn B; Thomas, Kate N; Cotter, James D

2016-01-01

Exercise reduces arterial and central venous blood pressures during recovery, which contributes to its valuable anti-hypertensive effects and to facilitating hypervolemia. Repeated sprint exercise potently improves metabolic function, but its cardiovascular effects (esp. hematological) are less well-characterized, as are effects of exercising upper versus lower limbs. The purposes of this study were to identify the acute (<24 h) profiles of arterial blood pressure and blood volume for (i) sprint intervals versus endurance exercise, and (ii) sprint intervals using arms versus legs. Twelve untrained males completed three cycling exercise trials; 50-min endurance (legs), and 5(*)30-s intervals using legs or arms, in randomized and counterbalanced sequence, at a standardized time of day with at least 8 days between trials. Arterial pressure, hemoglobin concentration and hematocrit were measured before, during and across 22 h after exercise, the first 3 h of which were seated rest. The post-exercise hypotensive response was larger after leg intervals than endurance (AUC: 7540 ± 3853 vs. 3897 ± 2757 mm Hg·min, p = 0.049, 95% CI: 20 to 6764), whereas exercising different limbs elicited similar hypotension (arms: 6420 ± 3947 mm Hg·min, p = 0.48, CI: -1261 to 3896). In contrast, arterial pressure at 22 h was reduced after endurance but not after leg intervals (-8 ± 8 vs. 0 ± 7 mm Hg, p = 0.04, CI: 7 ± 7) or reliably after arm intervals (-4 ± 8 mm Hg, p = 0.18 vs. leg intervals). Regardless, plasma volume expansion at 22 h was similar between leg intervals and endurance (both +5 ± 5%; CI: -5 to 5%) and between leg and arm intervals (arms: +5 ± 7%, CI: -8 to 5%). These results emphasize the relative importance of central and/or systemic factors in post-exercise hypotension, and indicate that markedly diverse exercise profiles can induce substantive hypotension and subsequent hypervolemia. At least for endurance exercise, this hypervolemia may not depend on the

Adverse Drug Reactions for Medicines Newly Approved in Japan from 1999 to 2013: Hypertension and Hypotension.

PubMed

Nagayama, Takashi; Nishida, Minoru; Hizue, Masanori; Ogino, Yamato; Fujiyoshi, Masato

2016-04-01

In this survey, the correlation between adverse drug reactions (ADRs) in human and animal toxicities was investigated for 393 medicines which were approved in Japan from September 1999 to March 2013. ADRs were collected from each Japanese package insert. Comparable animal toxicities with ADRs were collected by thorough investigation of common technical documents. The results of this survey show that hypertension and/or hypotension were mainly observed in medicines affecting the central nervous system. Hypertension was also observed in antipyretics, analgesics, anti-inflammatory agents, vasoconstrictors and agents using antibody. Concordance between human ADRs and animal toxicities was analysed. True-positive rate for hypertension and hypotension is 0.29 and 0.52, respectively. Positive likelihood ratio and inverse negative likelihood ratio are 1.98 and 1.21, respectively, in hypertension and 1.67 and 1.44, respectively, in hypotension. Concordance between human ADRs and animal toxicities is not so high in hypertension and hypotension. Identified mechanisms as on-target for hypertension and hypotension are 29.8% and 30.5%, respectively. More than half of the causative factors of hypertension and hypotension were unable to be elucidated. Our results show that the intake of medicines is often linked to blood pressure variations that are not predicted in animal toxicity studies. Improvement of drug development processes may be necessary to provide safer medicines because current animal toxicity studies are insufficient to predict all ADRs in human beings. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Dilator and constrictor response of renal vasculature during acute renal hypotension in anesthetized goats. Role of nitric oxide.

PubMed

Diéguez, Godofredo; García-Villalón, Angel Luis

2011-01-01

The relative role of NO derived from endothelium NO synthase (eNOS) and neuronal NO synthase (nNOS) in renovascular reactivity during renal hypotension is unknown. To examine this issue, we recorded the effects of unspecific inhibitor of NO synthase N(w)-nitro-L-arginine methyl esther (L-NAME) and inhibitor of nNOS 7-nitroindazole monosodium salt (7-NINA) on renal vasodilator and vasoconstrictor responses in anesthetized goats during renal hypotension by constricting the abdominal aorta. Intrarenal administration of L-NAME and hypotension, either untreated or treated with L-NAME, decreased resting renal blood flow, and the increases in renal blood flow by acetylcholine but not those by sodium nitroprusside were tempered, and the decreases by norepinephrine and angiotensin II were augmented. Intraperitoneal administration of 7-NINA did not affect, and 7-NINA+hypotension decreased renal blood flow, and under these conditions the increases in renal blood flow by acetylcholine and sodium nitroprusside were not modified, and the decreases by norepinephrine and angiotensin II were slightly (during 7-NINA) or consistently augmented (7-NINA+hypotension). Therefore, NO derived from eNOS plays a significant role, while that derived from nNOS plays a little role, if any, to regulate renal blood flow and to mediate acetylcholine-induced vasodilation, as well to modulate renal vasoconstriction by norepinephrine and angiotensin II. Copyright © 2011 Elsevier Inc. All rights reserved.

Neurocirculatory abnormalities in Parkinson disease with orthostatic hypotension: independence from levodopa treatment.

PubMed

Goldstein, David S; Eldadah, Basil A; Holmes, Courtney; Pechnik, Sandra; Moak, Jeffrey; Saleem, Ahmed; Sharabi, Yehonatan

2005-12-01

Patients with Parkinson disease often have orthostatic hypotension. Neurocirculatory abnormalities underlying orthostatic hypotension might reflect levodopa treatment. Sixty-six Parkinson disease patients (36 with orthostatic hypotension, 15 off and 21 on levodopa; 30 without orthostatic hypotension) had tests of reflexive cardiovagal gain (decrease in interbeat interval per unit decrease in systolic pressure during the Valsalva maneuver; orthostatic increase in heart rate per unit decrease in pressure); reflexive sympathoneural function (decrease in pressure during the Valsalva maneuver; orthostatic increment in plasma norepinephrine); and cardiac and extracardiac noradrenergic innervation (septal myocardial 6-[18F]fluorodopamine-derived radioactivity; supine plasma norepinephrine). Severity of orthostatic hypotension did not differ between the levodopa-untreated and levodopa-treated groups with Parkinson disease and orthostatic hypotension (-52+/-6 [SEM] versus -49+/-5 mm Hg systolic). The 2 groups had similarly low reflexive cardiovagal gain (0.84+/-0.23 versus 1.33+/-0.35 ms/mm Hg during Valsalva; 0.43+/-0.09 versus 0.27+/-0.06 bpm/mm Hg during orthostasis); and had similarly attenuated reflexive sympathoneural responses (97+/-29 versus 71+/-23 pg/mL during orthostasis; -82+/-10 versus -73+/-8 mm Hg during Valsalva). In patients off levodopa, plasma norepinephrine was lower in those with (193+/-19 pg/mL) than without (348+/-46 pg/mL) orthostatic hypotension. Low values for reflexive cardiovagal gain, sympathoneural responses, and noradrenergic innervation were strongly related to orthostatic hypotension. Parkinson disease with orthostatic hypotension features reflexive cardiovagal and sympathoneural failure and cardiac and partial extracardiac sympathetic denervation, independent of levodopa treatment.

Hypotensive Activity of Ethanolic Extracts of Morinda citrifolia L. Leaves and Fruit in Dexamethasone-Induced Hypertensive Rat

PubMed Central

Wigati, Dyan; Anwar, Khoerul; Sudarsono; Nugroho, Agung Endro

2016-01-01

The effect of ethanolic extract of Morinda citrifolia leaves and fruit on blood pressure in dexamethasone-induced hypertension rat was evaluated. Total phenolic content of Morinda citrifolia leaves ethanolic extract (MCLEE) and Morinda citrifolia leaves ethanolic extract (MCFEE) was 1.789 ± 0.116 and 1.677 ± 0.051 mg of gallic acid equivalents per gram sample, respectively. Rutin level in MCLEE was 0.92 ± 0.19%, and scopoletin level in MCFEE was 0.46 ± 0.05%. MCLEE, MCFEE, and its extract combination significantly decreased the blood pressure of hypertensive rats. The combination group showed highest hypotensive activity by lowering systolic blood pressure by 16.71 ± 3.95%, diastolic blood pressure by 21.49 ± 7.90%, and mean arterial blood pressure by 19.58% ± 6.35. All extract treatments have not been able to repair or inhibit renal damage caused by dexamethasone induction. PMID:27313228

The effect of naloxone and cyproheptadine on pulmonary platelet trapping, hypotension, and platelet aggregability in traumatized dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Almqvist, P.; Kuenzig, M.; Schwartz, S.I.

1983-05-01

Adult respiratory distress syndrome (ARDS) is a serious complication of trauma and sepsis. We have earlier shown naloxone, an opiate antagonist, and cyproheptadine, an antiserotonin drug, to be effective in reducing pulmonary platelet trapping (PPT), which is thought to play an important role in the evolution of ARDS in endotoxin-shocked dogs. Endorphins are implicated as pathophysiologic factors in shock, and serotonin is a possible mediator of their action. The present study shows naloxone and cyproheptadine to be equally effective in protecting against PPT in dogs subjected to trauma, and when naloxone is given before the trauma it also obviates themore » hypotension associated with trauma. In addition, the naloxone- and cyproheptadine-treated animals did not show the increased platelet aggregability usually seen in traumatized dogs.« less

Midodrine as a Countermeasure for Post-Spaceflight Orthostatic Hypotension

NASA Technical Reports Server (NTRS)

Stenger, Michael B.; Stein, Sydney P.; Meck, Janice V.; Platts, Steven H.

2008-01-01

One possible mechanism for post-spaceflight orthostatic hypotension, which affects approximately 30% of astronauts after short duration shuttle missions, is inadequate norepinephrine release during upright posture. We performed a two phased study to determine the effectiveness of an alpha1-adrenergic agonist, midodrine, as a countermeasure to post-spaceflight orthostatic hypotension. The first phase of the study examined the landing day orthostatic responses of six veteran astronauts after oral midodrine (10 mg) administered on the ground within approximately two hours of wheel stop. One female crewmember exhibited orthostatic hypotension in a previous flight but not after midodrine. Five male crewmembers, who did not exhibit orthostatic hypotension during previous flights, also did not show signs of orthostatic hypotension after midodrine. Additionally, phase one showed that midodrine did not cause hypertension in these crewmembers. In the second phase of this study, midodrine is ingested inflight (near time of ignition, TIG) and orthostatic responses are determined immediately upon landing via an 80 degree head-up tilt test performed on the crew transport vehicle (CTV). Four of ten crewmembers have completed phase two of this study. Two crewmembers completed the landing day tilt tests, while two tests were ended early due to presyncopal symptoms. All subjects had decreased landing day stroke volumes and increased heart rates compared to preflight. Midodrine appears to have increased total peripheral resistance in one crewmember who was able to complete the landing day tilt test. The effectiveness of midodrine as a countermeasure to immediate post-spaceflight orthostatic hypotension has yet to be determined; interpretation is made more difficult due to low subject number and the lack of control subjects on the CTV.

Genetics and molecular biology of hypotension

NASA Technical Reports Server (NTRS)

Robertson, D.

1994-01-01

Major strides in the molecular biology of essential hypertension are currently underway. This has tended to obscure the fact that a number of inherited disorders associated with low blood pressure exist and that these diseases may have milder and underrecognized phenotypes that contribute importantly to blood pressure variation in the general population. This review highlights some of the gene products that, if abnormal, could cause hypotension in some individuals. Diseases due to abnormalities in the catecholamine enzymes are discussed in detail. It is likely that genetic abnormalities with hypotensive phenotypes will be as interesting and diverse as those that give rise to hypertensive disorders.

The Association Between Mild Intraoperative Hypotension and Stroke in General Surgery Patients.

PubMed

Hsieh, Jason K; Dalton, Jarrod E; Yang, Dongsheng; Farag, Ehab S; Sessler, Daniel I; Kurz, Andrea M

2016-10-01

Intraoperative hypotension may contribute to perioperative strokes. We therefore tested the hypothesis that intraoperative hypotension is associated with perioperative stroke. After institutional review board approval for this case-control study, we identified patients who had nonneurological, noncardiac, and noncarotid surgery under general anesthesia at the Cleveland Clinic between 2005 and 2011 and experienced a postoperative stroke. Control patients not experiencing postoperative stroke were matched in a 4-to-1 ratio using propensity scores and restriction to the same procedure type as stroke patients. The association between intraoperative hypotension, measured as time-integrated area under a mean arterial pressure (MAP) of 70 mm Hg, and postoperative stroke was assessed using zero-inflated negative binomial regression. Among 106 337 patients meeting inclusion criteria, we identified 120 who had confirmed postoperative stroke events based on manual chart review. Four-to-one propensity matching yielded a final matched sample of 104 stroke cases and 398 controls. There was no association between stroke and intraoperative hypotension. Stroke patients were not more likely than controls to have been hypotensive (odds ratio, 0.49 [0.18-1.38]), and among patients with intraoperative hypotension, stroke patients did not experience a greater degree of hypotension than controls (ratio of geometric means, 1.07 [0.76-1.53]). In our propensity score-matched case-control study, we did not find an association between intraoperative hypotension, defined as MAP < 70 mm Hg, and postoperative stroke.

The organizational structure of an intensive care unit influences treatment of hypotension among critically ill patients: A retrospective cohort study

PubMed Central

Boone, M. Dustin; Massa, Jennifer; Mueller, Ariel; Jinadasa, Sayuri P; Lee, Joon; Kothari, Rishi; Scott, Daniel J.; Callahan, Julie; Celi, Leo Anthony; Hacker, Michele R.

2016-01-01

Purpose Prior studies report that weekend admission to an intensive care unit is associated with increased mortality, potentially attributed to the organizational structure of the unit. This study aims to determine whether treatment of hypotension, a risk factor for mortality, differs according to level of staffing. Methods Using the Multiparameter Intelligent Monitoring in Intensive Care database, we conducted a retrospective study of patients admitted to an intensive care unit at Beth Israel Deaconess Medical Center who experienced one or more episodes of hypotension. Episode(s) were categorized according to the staffing level, defined as high during weekday daytime (7am–7pm) and low during weekends or nighttime (7pm–7am). Results Patients with a hypotensive event on a weekend were less likely to be treated compared to those that occurred during the weekday daytime (p=0.02). No association between weekday daytime versus weekday nighttime staffing levels and treatment of hypotension was found (RR 1.02; 95% CI 0.98–1.07). Conclusion Patients with a hypotensive event on a weekend were less likely to be treated than patients with an event during high-staffing periods. No association between weekday nighttime staffing and hypotension treatment was observed. We conclude that treatment of a hypotensive episode relies on more than solely staffing levels. PMID:26975737

Orthostatic hypotension

NASA Technical Reports Server (NTRS)

Ninet, J.

1981-01-01

Basic orientation of the article, by the leader of a group of medical researchers associated with hospitals in Lyon, France, is toward definition and classification. A table divides OH (orthostatic hypotension) according to physiopathological classification into sympathicotonic and asympathicotonic types and then each of these into primary and secondary with subdivisions. The figure sketches organization and functioning of the baroreflex arc. Applications to clinical study of circulatory reflexes, listing measurement tests and the biological study of hormonal regulation listing the appropriate kinds of studies. Data are not given.

[The role of hypotension as a factor of unfavorable prognosis in patients with chronic heart failure].

PubMed

Kapanadze, L G; Petrukhina, A A; Nasonova, S N; Skvortsov, A A; Mareev, V Iu

2011-01-01

Despite obvious achievements during last decades in studies of pathogenesis and search for effective ways of treatment of chronic heart failure (CHF) it remains one of most severe and prognostically unfavorable diseases of the cardiovascular system. Thereby determination of predictors of death and detection of high risk patients for more active drug interventions on CHF progression appears to be actual. It has been shown in a number of epidemiological and cohort studies that low arterial pressure (AP) serves as an independent risk factor of prognosis in patients with CHF. In this paper we present short literature review on this theme, consideration of possible mechanisms of negative effect of arterial hypotension on function of vitally important organs in patients with CHF, and summation of data of studies which have demonstrated relationship between low level of AP and worsening of prognosis.

Mitochondrial N-formyl peptides induce cardiovascular collapse and sepsis-like syndrome

PubMed Central

McCarthy, Cameron G.; Szasz, Theodora; Goulopoulou, Styliani; Webb, R. Clinton

2015-01-01

Fifty percent of trauma patients who present sepsis-like syndrome do not have bacterial infections. This condition is known as systemic inflammatory response syndrome (SIRS). A unifying factor of SIRS and sepsis is cardiovascular collapse. Trauma and severe blood loss cause the release of endogenous molecules known as damage-associated molecular patterns. Mitochondrial N-formyl peptides (F-MIT) are damage-associated molecular patterns that share similarities with bacterial N-formylated peptides and are potent immune system activators. The goal of this study was to investigate whether F-MIT trigger SIRS, including hypotension and vascular collapse via formyl peptide receptor (FPR) activation. We evaluated cardiovascular parameters in Wistar rats treated with FPR or histamine receptor antagonists and inhibitors of the nitric oxide pathway before and after F-MIT infusion. F-MIT, but not nonformylated peptides or mitochondrial DNA, induced severe hypotension via FPR activation and nitric oxide and histamine release. Moreover, F-MIT infusion induced hyperthermia, blood clotting, and increased vascular permeability. To evaluate the role of leukocytes in F-MIT-induced hypotension, neutrophil, basophil, or mast cells were depleted. Depletion of basophils, but not neutrophils or mast cells, abolished F-MIT-induced hypotension. Rats that underwent hemorrhagic shock increased plasma levels of mitochondrial formylated proteins associated with lung damage and antagonism of FPR ameliorated hemorrhagic shock-induced lung injury. Finally, F-MIT induced vasodilatation in isolated resistance arteries via FPR activation; however, F-MIT impaired endothelium-dependent relaxation in the presence of blood. These data suggest that F-MIT may be the link among trauma, SIRS, and cardiovascular collapse. PMID:25637548

The Treatment of Primary Orthostatic Hypotension.

PubMed

Hale, Genevieve M; Valdes, Jose; Brenner, Michael

2017-05-01

To review the efficacy and safety of pharmacological and nonpharmacological strategies used to treat primary orthostatic hypotension (OH). A literature review using PubMed and MEDLINE databases searching hypotension, non-pharmacological therapy, midodrine, droxidopa, pyridostigmine, fludrocortisone, atomoxetine, pseudoephedrine, and octreotide was performed. Randomized or observational studies, cohorts, case series, or case reports written in English between January 1970 and November 2016 that assessed primary OH treatment in adult patients were evaluated. Based on the chosen criteria, it was found that OH patients make up approximately 15% of all syncope patients, predominantly as a result of cardiovascular or neurological insults, or offending medication. Nonpharmacological strategies are the primary treatment, such as discontinuing offending medications, switching medication administration to bedtime, avoiding large carbohydrate-rich meals, limiting alcohol, maintaining adequate hydration, adding salt to diet, and so on. If these fail, pharmacotherapy can help ameliorate symptoms, including midodrine, droxidopa, fludrocortisone, pyridostigmine, atomoxetine, sympathomimetic agents, and octreotide. Midodrine and droxidopa possess the most evidence with respect to increasing blood pressure and alleviating symptoms. Pyridostigmine and fludrocortisone can be used in patients who fail to respond to these agents. Emerging evidence with low-dose atomoxetine is promising, especially in those with central autonomic failure, and may prove to be a viable alternative treatment option. Data surrounding other therapies such as sympathomimetic agents or octreotide are minimal. Medication management of primary OH should be guided by patient-specific factors, such as tolerability, adverse effects, and drug-drug and drug-disease interactions.

Exercise training hypotension - Implications for plasma volume, renin, and vasopressin

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Sciaraffa, D.; Shvartz, E.; Keil, L. C.; Brock, P. J.

1981-01-01

The relation of changes in plasma volume, plasma renin activity and arginine vasopressin to changes in resting blood pressure during exercise training is investigated. Resting supine, sitting, and standing systolic and fifth-phase diastolic blood pressures were measured in ten men before and after an eight-day training period on a cycle ergometer in either a hot (39.8 C) or cool (23.8 C) environment, and compared with plasma volume, renin and vasopressin levels, heart rates, maximal oxygen uptakes, rectal temperatures and sweat rates. Following acclimatization, resting supine and sitting diastolic pressures are observed to decrease by 6 and 9 mm Hg, respectively, while no significant changes are found in the diastolic pressures of the control group or the systolic pressures of either group. Resting plasma volume is found to increase by 12.2% in the controls and by 17.6% after acclimatization following the exercise training. Results suggest that the resting hypotension produced is not attributable to changes in resting plasma volume, renin or vasopressin, although heat acclimatization, which leads to large decreases in plasma volume and increases in vasopressin and renin activity, may be useful in the treatment of hypertension.

Hypotensive Activity of Ethanolic Extracts of Morinda citrifolia L. Leaves and Fruit in Dexamethasone-Induced Hypertensive Rat.

PubMed

Wigati, Dyan; Anwar, Khoerul; Sudarsono; Nugroho, Agung Endro

2017-01-01

The effect of ethanolic extract of Morinda citrifolia leaves and fruit on blood pressure in dexamethasone-induced hypertension rat was evaluated. Total phenolic content of Morinda citrifolia leaves ethanolic extract (MCLEE) and Morinda citrifolia leaves ethanolic extract (MCFEE) was 1.789 ± 0.116 and 1.677 ± 0.051 mg of gallic acid equivalents per gram sample, respectively. Rutin level in MCLEE was 0.92 ± 0.19%, and scopoletin level in MCFEE was 0.46 ± 0.05%. MCLEE, MCFEE, and its extract combination significantly decreased the blood pressure of hypertensive rats. The combination group showed highest hypotensive activity by lowering systolic blood pressure by 16.71 ± 3.95%, diastolic blood pressure by 21.49 ± 7.90%, and mean arterial blood pressure by 19.58% ± 6.35. All extract treatments have not been able to repair or inhibit renal damage caused by dexamethasone induction. © The Author(s) 2016.

Orthostatic hypotension: prevalence and associated risk factors among the ambulatory elderly in an Asian population

PubMed Central

Zhu, Qing Olivia; Tan, Choon Seng Gilbert; Tan, Hwee Leong; Wong, Ruining Geraldine; Joshi, Chinmaya Shrikant; Cuttilan, Ravi Amran; Sng, Gek Khim Judy; Tan, Ngiap Chuan

2016-01-01

INTRODUCTION The prevalence of orthostatic hypotension (OH) among the elderly population in Singapore, as defined by a decline in blood pressure upon a change in position, is not well-established. Studies associate OH with clinically significant outcomes such as falls. This study aims to determine the prevalence of OH among elderly patients attending a public primary care clinic (polyclinic) for chronic disease management, and examine the relationships between postulated risk factors and OH. METHODS Patients aged ≥ 65 years attending a typical polyclinic in Geylang were identified and targeted for recruitment at the study site. A questionnaire on symptoms and postulated risk factors was administered, followed by supine and standing blood pressure measurements. Cross-sectional analysis was performed with independent sample t-test for continuous data and chi-square test for categorical data. Prevalence rate ratios with 95% confidence interval were calculated for the latter. RESULTS A total of 364 multiethnic patients participated in the study. The prevalence of OH was 11.0%. Older age, comorbidities such as cardiac failure and kidney disease, being physically inactive at work, fatigue, self-reported dizziness in the past year, and the use of loop diuretics were found to be significantly associated with OH. CONCLUSION About one in ten elderly patients at a local polyclinic was affected by OH, which was associated with multiple factors. Some of these factors are modifiable and can be addressed to reduce the incidence of OH. PMID:27549316

Controlled hypotension versus normotensive resuscitation strategy for people with ruptured abdominal aortic aneurysm.

PubMed

Moreno, Daniel H; Cacione, Daniel G; Baptista-Silva, Jose C C

2016-05-13

An abdominal aortic aneurysm (AAA) is the pathological enlargement of the aorta and can develop in both men and women. Progressive aneurysm enlargement can lead to rupture. The rupture of an AAA is frequently fatal and accounts for the death from haemorrhagic shock of at least 45 people per 100,000 population. The outcome of people with ruptured AAA varies among countries and healthcare systems, with mortality ranging from 53% to 90%. Definitive treatment for ruptured AAA includes open surgery or endovascular repair. The management of haemorrhagic shock is crucial for the person's outcome and aims to restore organ perfusion and systolic blood pressure above 100 mm Hg through immediate and aggressive fluid replacement. This rapid fluid replacement is known as the normotensive resuscitation strategy. However, evidence suggests that infusing large volumes of cold fluid causes dilutional and hypothermic coagulopathy. The association of these factors may exacerbate bleeding, resulting in a 'lethal triad' of hypothermia, acidaemia, and coagulopathy. An alternative to the normotensive resuscitation strategy is the controlled (permissive) hypotension resuscitation strategy, with a target systolic blood pressure of 50 to 100 mm Hg. The principle of controlled or hypotensive resuscitation has been used in some management protocols for endovascular repair of ruptured AAA. It may be beneficial in preventing blood loss by avoiding the clot disruption caused by the rapid increase in systolic blood pressure; avoiding dilution of clotting factors, platelets and fibrinogen; and by avoiding the temperature decrease that inhibits enzyme activity involved in platelet and clotting factor function. To compare the effects of controlled (permissive) hypotension resuscitation and normotensive resuscitation strategies for people with ruptured AAA. The Cochrane Vascular Information Specialist searched the Specialised Register (April 2016) and the Cochrane Register of Studies (CENTRAL (2016

Effects of hypotensive anesthesia on blood transfusion rates in craniosynostosis corrections.

PubMed

Fearon, Jeffrey A; Cook, T Kevin; Herbert, Morley

2014-05-01

Hypotensive anesthesia is routinely used during craniosynostosis corrections to reduce blood loss. Noting that cerebral oxygenation levels often fell below recommended levels, the authors sought to measure the effects of hypotensive versus standard anesthesia on blood transfusion rates. One hundred children undergoing craniosynostosis corrections were randomized prospectively into two groups: a target mean arterial pressure of either 50 mm Hg or 60 mm Hg. Aside from anesthesiologists, caregivers were blinded and strict transfusion criteria were followed. Multiple variables were analyzed, and appropriate statistical testing was performed. The hypotensive and standard groups appeared similar, with no statistically significant differences in mean age (46.5 months versus 46.5 months), weight (19.25 kg versus 19.49 kg), procedure [anterior remodeling (34 versus 31) versus posterior (19 versus 16)], or preoperative hemoglobin level (13 g/dl versus 12.9 g/dl). Intraoperative mean arterial pressures differed significantly (56 mm Hg versus 66 mm Hg; p < 0.001). The captured cell saver amount was lower in the hypotensive group (163 cc versus 204 cc; p = 0.02), yet no significant differences were noted in postoperative hemoglobin levels (8.8 g/dl versus 9.3 g/dl). Fifteen of 100 patients (15 percent) received allogenic transfusions, but no statistically significant differences were noted in transfusion rates between the hypotensive [nine of 53 (17.0 percent)] and standard anesthesia [six of 47 (13 percent)] group (p = 0.056). No significant difference in transfusion requirements was found between hypotensive and standard anesthesia during craniosynostosis corrections. Considering potential benefits of improved cerebral blood flow and total body perfusion, surgeons might consider performing craniosynostosis corrections without hypotension. Therapeutic, II.

Interaction of mianserin and some hypotensive drugs in Wistar rats.

PubMed

Górska, Dorota; Andrzejczak, Dariusz

2004-01-01

Mianserin is thought to exert little effect on the cardiovascular system. In fact its safety in comparison with tricyclic drugs is high. Various experiments gave varying results as for the influence of the drug on arterial blood pressure in people and animals. Therefore, a study was undertaken in Wistar rats to evaluate interactions of mianserin administered intraperitoneally as a single dose, and for 21 days with 3 hypotensive drugs showing different mechanism of action (propranolol, enalapril, prazosine). The systolic, diastolic and mean blood pressure was measured with a LETICA apparatus. The results of the study revealed that administration of mianserin in normotensive rats leads to a short-term decrease in blood pressure and significantly enhanced the hypotensive effect of prazosine. Repeated doses of mianserin lead to a temporary increase in blood pressure after 2 weeks of administration. Single and repeated administration of mianserin did not change the hypotensive effect of propranolol and enalapril. Three-week therapy with mianserin significantly enhanced the hypotensive effect of prazosine.

Influence of intraoperative hypotension on leaks after sleeve gastrectomy.

PubMed

Nienhuijs, Simon W; Kaymak, Uzay; Korsten, Erik; Buise, Marc P

2016-01-01

Leak after a sleeve gastrectomy (SG) is a severe complication. Risk factors, such as regional ischemia, increased intraluminal pressure, technical failure of the stapling device, and surgeon error, have been reported. It was hypothesized that intraoperative hypotension is another risk factor for leak, similar to that reported for colorectal surgery. Tertiary teaching hospital in The Netherlands. Results of a 7-year cohort of primary SGs were reviewed in relation to multiple intraoperative blood pressure measurements. The thresholds for the mean pressure were 40 to 70 mm Hg and for the systolic pressure 70 to 100 mm Hg. Only continuous episodes of 15 and 20 minutes were included. Twenty-four leaks were identified in a cohort of 1041 primary SGs. Episodes of systolic blood pressure<100 mm Hg for 15 min (P = .027) and 20 minutes (P = .008) were significantly related to a staple line leak. An episode of mean blood pressure<70 mm Hg for 20 min was significantly related to leak (P = .014). Episodes with lower thresholds of pressure occurred less frequently and revealed no significant differences. Other identified risk factors were smoking (P = .019), fast-track recovery program (P = .006), use of a tri-stapler (P = .004), and duration of surgery (P = .000). In a multivariate analysis, only intraoperative systolic pressure<100 mm Hg for 20 minutes remained significant (odds ratio, 2.45; P = .012). Intraoperative hypotension may contribute independently to a leak after SG. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Hypotensive effect of aqueous extract of Averrhoa carambola L. (Oxalidaceae) in rats: an in vivo and in vitro approach.

PubMed

Soncini, Roseli; Santiago, Michael B; Orlandi, Lidiane; Moraes, Gabriel O I; Peloso, André Luiz M; dos Santos, Marcelo H; Alves-da-Silva, Geraldo; Paffaro, Valdemar A; Bento, Antonio C; Giusti-Paiva, Alexandre

2011-01-27

Averrhoa carambola L. (Oxalidaceae) leaves are used in Brazilian traditional medicine to treat hypertension. This study was conducted to evaluate the hypotensive effect of the aqueous extract of Averrhoa carambola (AEAc) and its underlying mechanisms in the isolated rat aorta. The effect of AEAc on the mean arterial pressure (MAP) was determined in vivo in anesthetized rats. In vitro, thoracic aortic rings were isolated and suspended in organ baths, and the effects of AEAc were studied by means of isometric tension recording experiments. In HPLC analysis, the fingerprint chromatogram of AEAc was established. In normotensive rats, AEAc (12.5-50.0 mg/kg, i.v.) induced dose-dependent hypotension. In vitro, AEAc caused a depression in the E(max) response to phenylephrine without a change in sensibility. Also, in a depolarized Ca(2+)-free medium, AEAc inhibited CaCl(2)-induced contractions and caused a concentration-dependent rightward shift of the response curves, indicating that AEAc inhibited the contractile mechanisms involving extracellular Ca(2+) influx. These results demonstrate the hypotensive effects of AEAc, and these effects may, in part, be due to the inhibition of Ca(2+), which supports previous claims of its traditional use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Point-of-care ultrasound leads to diagnostic shifts in patients with undifferentiated hypotension.

PubMed

Shokoohi, Hamid; Boniface, Keith S; Zaragoza, Michelle; Pourmand, Ali; Earls, James P

2017-12-01

To assess the impact of an ultrasound hypotension protocol in identifying life-threatening diagnoses that were missed in the initial evaluation of patients with hypotension and shock. A subset of cases from a previously published prospective study of hypotensive patients who presented at the Emergency Department in a single, academic tertiary care hospital is described. An ultrasound-trained emergency physician performed an ultrasound on each patient using a standardized hypotension protocol. In each case, the differential diagnosis and management plan was solicited from the treating physician immediately before and after the ultrasound. This is a case series of patients with missed diagnoses in whom ultrasound led to a dramatic shift in diagnosis and management by detecting life threatening pathologies. Following a published prospective study of the effect on an ultrasound protocol in 118 hypotensive patients, we identified a series of cases that ultrasound protocol unexpectedly determined serious life threatening diagnoses such as Takotsubo cardiomyopathy, pulmonary embolism, pericardial effusion with tamponade physiology, abdominal aortic aneurysm and perforated viscus resulting in proper diagnoses and management. These hypotensive patients had completely unsuspected but critical diagnoses explaining their hypotension, who in every case had their management altered to target the newly identified life-threatening condition. A hypotension protocol is an optimal use of ultrasound that exemplifies "right time, right place", and impacts decision-making at the bedside. In cases with undifferentiated hypotension, ultrasound is often the most readily available option to ensure that the most immediate life-threatening conditions are quickly identified and addressed in the order of their risk potential. Copyright © 2017 Elsevier Inc. All rights reserved.

Midodrine as a Countermeasure for Post-spaceflight Orthostatic Hypotension

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Ziegler, Michael G.; Waters, Wendy W.; Meck, Janice V.

2007-01-01

Up to 30 % of astronauts exhibit post-spaceflight orthostatic hypotension due to inadequate norepinephrine release during upright posture following short duration spaceflight. We hypothesize that the (alpha)1-adrenergic agonist midodrine will be an effective countermeasure. This study is being conducted in 2 phases. The first phase is complete and consisted testing six short duration crew members. All of these subjects participated in preflight and postflight tilt testing on a control flight as well as on the test flights, where midodrine was administered after landing, 1 hour before testing. Hemodynamic variables were compared between the 2 flights. Midodrine improved stroke volume, cardiac output, systolic pressure and heart rate, without increasing vascular resistance. None of these subjects experienced orthostatic hypotension on landing day. Phase II is similar to phase I, except that midodrine is ingested in flight (near TIG) and the tilt test is performed immediately after landing on the CTV. One crewmember has completed phase II testing. This crewmember had no evidence of orthostatic hypotension or presyncope, four additional crewmembers have volunteered for this study. To date, midodrine has been shown to be a safe and effective countermeasure to post-spaceflight orthostatic hypotension.

Suppression of Peripheral Sympathetic Activity Underlies Protease-Activated Receptor 2-Mediated Hypotension

PubMed Central

Kim, Young-Hwan; Ahn, Duck-Sun; Joeng, Ji-Hyun

2014-01-01

Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ω-conotoxin GVIA (CgTx), a selective N-type Ca2+ channel (ICa-N) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension. PMID:25598663

The association between orthostatic hypotension, falling and successful rehabilitation in a nursing home population.

PubMed

Hartog, L C; Cizmar-Sweelssen, M; Knipscheer, A; Groenier, K H; Kleefstra, N; Bilo, H J G; van Hateren, K J J

2015-01-01

Our objectives were to identify the prevalence of orthostatic hypotension (OH) in frail, elderly nursing home residents, and assess its possible association with falling and chances of successful rehabilitation. A prospective observational cohort study. A total of 290 patients participated in this study, of which 128 were admitted to the rehabilitation department. OH was defined as a drop in systolic blood pressure of >20mmHg and diastolic blood pressure of >10mmHg after postural change within 3min. The analyses regarding falling and successful rehabilitation were only performed in the rehabilitation group. Multivariate binary logistic regression analyses were used to describe risk factors related with falling. Cox proportional hazard modeling was used to investigate the relation between OH and the time to successful rehabilitation. The prevalence of OH in the studied nursing home population was 36.6% (95% CI (confidence interval): 31.1-42.1%). The prevalence varied from 28.6% (95% CI: 16.8-40.4%) in somatic patients, 36.7% (95% CI: 28.4-45.1%) in rehabilitation patients, to 40.6% (95% CI: 31.3-50.0%) in psychogeriatric patients. The association between orthostatic hypotension and previous falling was not significant; Odds ratio 0.66 (95% CI: 0.30-1.48). The Hazard ratio of the relationship between OH and successful rehabilitation was 2.88 (95% CI:1.77-4.69). OH is highly prevalent in nursing home residents. Surprisingly, patients with OH were found to have a higher chance of successful rehabilitation compared to patients without OH. If confirmed in other studies, these results may change our view of the implications of OH. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Early blood pressure, anti-hypotensive therapy and outcomes at 18 to 22 month corrected age in extremely preterm infants

PubMed Central

Batton, Beau; Li, Lei; Newman, Nancy S.; Das, Abhik; Watterberg, Kristi L.; Yoder, Bradley A.; Faix, Roger G.; Laughon, Matthew M.; Stoll, Barbara J.; Higgins, Rosemary D.; Walsh, Michele C.

2016-01-01

Objective Investigate relationships between early blood pressure (BP) changes, receipt of anti-hypotensive therapy, and 18 – 22 month corrected age (CA) outcomes for extremely preterm infants. Design Prospective observational study of infants 230/7 – 266/7 weeks gestational age (GA). Hourly BP values and anti-hypotensive therapy exposure in the first 24 hours were recorded. Four groups were defined: infants who did or did not receive anti-hypotensive therapy in whom BP did or did not rise at the expected rate (defined as an increase in the mean arterial BP of ≥5 mmHg/day). Random-intercept logistic modeling controlling for center clustering, GA, and illness severity was used to investigate the relationship between BP, anti-hypotensive therapies, and infant outcomes. Setting Sixteen academic centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Main Outcome Measures Death or neurodevelopmental impairment / developmental delay (NIDD) at 18 – 22 months CA. Results Of 367 infants, 203 (55%) received an anti-hypotensive therapy, 272 (74%) survived to discharge, and 331 (90%) had a known outcome at 18 – 22 months CA. With logistic regression, there was an increased risk of death/NIDD with anti-hypotensive therapy versus no treatment (odds ratio: 1.836, 95% confidence interval: 1.092 – 3.086), but not NIDD alone (odds ratio: 1.53, 95% confidence interval: 0.708 – 3.307). Conclusion Independent of early BP changes, anti-hypotensive therapy exposure was associated with an increased risk of death/NIDD at 18 to 22 months CA when controlling for risk factors known to affect survival and neurodevelopment. PMID:26567120

Camphor-Crataegus berry extract combination dose-dependently reduces tilt induced fall in blood pressure in orthostatic hypotension.

PubMed

Belz, G G; Butzer, R; Gaus, W; Loew, D

2002-10-01

In order to test the efficacy of a combination of natural D-camphor and an extract of fresh crataegus berries (Korodin Herz-Kreislauf-Tropfen) on orthostatic hypotension, two similar, controlled, randomized studies were carried out in a balanced crossover design in 24 patients each with orthostatic dysregulation. The camphor-crataegus berry combination (CCC) was orally administered as a single regimen in 3 different dosages of 5 drops, 20 drops and 80 drops; a placebo with 20 drops of a 60% alcoholic solution served as control. Orthostatic hypotension was assessed with the tilt table test before and after medication. Source data of both studies were pooled and meta-analytically evaluated for all 48 patients. CCC drops decreased the orthostatic fall in blood pressure versus placebo, as almost uniformly established at all times by mean arterial pressure and diastolic blood pressure. Mean arterial pressure demonstrated the very fast onset of action by a clearly dose-dependent statistically significant effect even after 1-minute orthostasis. Increase of mean arterial pressure as compared to the orthostasis test before medication was on average 4.5 mmHg. CCC affected diastolic blood pressure after 1 minute of orthostasis in all dosages as compared to placebo. A statistically significant effect of the highest dose of 80 drops on diastolic blood pressure could be demonstrated after 1-, 3-, and 5-minute orthostasis. The hemodynamic findings of a stabilizing effect on arterial pressure in orthostasis corroborate the long-term medical experience with CCC and justify the indication orthostatic hypotension.

Controlled hypotension versus normotensive resuscitation strategy for people with ruptured abdominal aortic aneurysm.

PubMed

Moreno, Daniel H; Cacione, Daniel G; Baptista-Silva, Jose Cc

2018-06-13

An abdominal aortic aneurysm (AAA) is the pathological enlargement of the aorta and can develop in both men and women. Progressive aneurysm enlargement can lead to rupture. The rupture of an AAA is frequently fatal and accounts for the death from haemorrhagic shock of at least 45 people per 100,000 population. The outcome of people with ruptured AAA varies among countries and healthcare systems, with mortality ranging from 53% to 90%. Definitive treatment for ruptured AAA includes open surgery or endovascular repair. The management of haemorrhagic shock is crucial for the person's outcome and aims to restore organ perfusion and systolic blood pressure above 100 mmHg through immediate and aggressive fluid replacement. This rapid fluid replacement is known as the normotensive resuscitation strategy. However, evidence suggests that infusing large volumes of cold fluid causes dilutional and hypothermic coagulopathy. The association of these factors may exacerbate bleeding, resulting in a 'lethal triad' of hypothermia, acidaemia, and coagulopathy. An alternative to the normotensive resuscitation strategy is the controlled (permissive) hypotension resuscitation strategy, with a target systolic blood pressure of 50 mmHg to 100 mmHg. The principle of controlled or hypotensive resuscitation has been used in some management protocols for endovascular repair of ruptured AAA. It may be beneficial in preventing blood loss by avoiding the clot disruption caused by the rapid increase in systolic blood pressure; avoiding dilution of clotting factors, platelets and fibrinogen; and by avoiding the temperature decrease that inhibits enzyme activity involved in platelet and clotting factor function. This is an update of a review first published in 2016. To compare the effects of controlled (permissive) hypotension resuscitation and normotensive resuscitation strategies for people with ruptured AAA. The Cochrane Vascular Information Specialist searched the Specialised Register (August

A New Orally Active, Aminothiol Radioprotector-Free of Nausea and Hypotension Side Effects at Its Highest Radioprotective Doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soref, Cheryl M.; Hacker, Timothy A.; Fahl, William E., E-mail: fahl@oncology.wisc.edu

Purpose: A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721). Methods and Materials: PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats tomore » score drug-induced hypotension. Results: Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30-90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and rat equivalent doses of the 0.5 maximum tolerated dose (MTD) PrC-210 dose in mice. The human equivalent of this mouse 0.5 MTD PrC-210 dose would likely be the highest PrC-210 dose used in humans. By comparison, the mouse 0.5 MTD amifostine dose, 400 {mu}g/g body weight (equivalent to the human amifostine dose of 910 mg/m{sup 2}), when tested at equivalent ferret and rat doses in the above models produced 100% retching/vomiting in ferrets and 100% incidence of significant, progressive hypotension in rats. Conclusions: The PrC-210 aminothiol, with no detectable nausea/vomiting or hypotension side effects in these preclinical models, is a logical candidate for human drug development to use in

New developments in the management of neurogenic orthostatic hypotension.

PubMed

Biaggioni, Italo

2014-11-01

Orthostatic hypotension (OH) is defined as a sustained reduction of ≥ 20 mmHg systolic blood pressure or ≥ 10 mmHg diastolic blood pressure upon standing for ≤ 3 min. Orthostatic hypotension is commonly associated with hypertension, and its prevalence is highest in those with uncontrolled hypertension compared to those with controlled hypertension or normotensive community elderly subjects. Orthostatic hypotension can cause significant disability, with patients experiencing dizziness, lightheadedness or syncope, and other problems that potentially have a profound negative impact on activities of daily living that require standing or walking. Furthermore, OH increases the risk of falls and, importantly, is an independent risk factor of mortality. Despite its importance, there is a paucity of treatment options for this condition. Most of the advances in treatment options have relied on small studies of repurposed drugs done in patients with severe OH due to rare neurodegenerative conditions. Midodrine, an oral prodrug converted to the selective α1-adrenoceptor agonist desglymidodrine, was approved by the FDA for the treatment of OH in 1996. For almost two decades, no other pharmacotherapy was developed specifically for the treatment of OH until 2014, when droxidopa was approved by the FDA for the treatment of neurogenic OH associated with primary autonomic neuropathies including Parkinson disease, multiple system atrophy, and pure autonomic failure. These are neurodegenerative diseases ultimately characterized by failure of the autonomic nervous system to generate norepinephrine responses appropriate to postural challenge. Droxidopa is a synthetic amino acid that is converted to norepinephrine by dopa-decarboxylase, the same enzyme that converts levodopa into dopamine in the treatment of Parkinson disease. We will review this and other advances in the treatment of OH in an attempt to provide a practical guide to its management.

Imaging Signs in Spontaneous Intracranial Hypotension: Prevalence and Relationship to CSF Pressure.

PubMed

Kranz, P G; Tanpitukpongse, T P; Choudhury, K R; Amrhein, T J; Gray, L

2016-07-01

Patients with spontaneous intracranial hypotension often exhibit low CSF pressure and changes on brain MR imaging and/or evidence of CSF leak on myelography. We investigated whether individual imaging signs of spontaneous intracranial hypotension correlate with measured CSF pressure and how frequently these 2 markers of spontaneous intracranial hypotension were concordant. We performed a retrospective, cross-sectional study of 99 subjects with spontaneous intracranial hypotension. Prevalence of brain and myelographic imaging signs of spontaneous intracranial hypotension was recorded. CSF pressure among subjects with or without individual imaging signs was compared by using a 2-tailed t test and ANOVA. Concordance between low CSF pressure (≤6 cm H2O) and imaging was defined as the presence of the sign in a subject with low CSF pressure or absence of the sign when pressure was not low. Dural enhancement, brain sagging, and venous distension sign were present in 83%, 61%, and 75% of subjects, respectively, and myelographic evidence of CSF leak was seen in 55%. Marginal correlations between CSF pressure and brain sagging (P = .046) and the venous distension sign (P = .047) were found. Dural enhancement and myelographic evidence of leak were not significantly correlated with CSF pressure. Rates of concordance between imaging signs and low CSF pressure were generally low, ranging from 39% to 55%. Brain and myelographic signs of spontaneous intracranial hypotension correlate poorly with CSF pressure. These findings reinforce the need to base the diagnosis of spontaneous intracranial hypotension on multiple diagnostic criteria and suggest the presence of patient-specific variables that influence CSF pressure in these individuals. © 2016 by American Journal of Neuroradiology.

Changes in arterial blood pressure induced by passive leg raising predict hypotension during the induction of sedation in critically ill patients without severe cardiac dysfunction.

PubMed

Yu, Tao; Pan, Chun; Guo, Feng-mei; Yang, Yi; Qiu, Hai-bo

2013-07-01

Hypotension due to the induction of sedation with dexmedetomidine infusion may be harmful in critically ill patients. Changes in pulse pressure induced by the passive leg raising test (PLR-ΔPP) as marker of fluid responsiveness, assessed prior to sedation, may predict hemodynamic changes. The present study was to investigate the power of the PLR test in critically ill patients in predicting hypotension induced by the induction of dexmedetomidine sedation. Fluid responsiveness was estimated by a passive leg raising (PLR) test before dexmedetomidine sedation. Patients were assigned to either the "Nonresponders" or "Responders" group according to their hemodynamic responses to the PLR test ("Nonresponders", PLR-ΔPP < 10.3%; "Responders", PLR-ΔPP ≥ 10.3%). Sedation was performed with a dexmedetomidine infusion (0.5 µg/kg over a 10-minute loading period, then 0.2 - 0.7 µg×kg(-1)×h(-1)) and titrated to maintain the target Richmond agitation sedation scale (RASS) score in the range of -2 to -1 and the bispectral index value in the range of 60 to 75. Radial artery pulse pressure, heart rate (HR), and central venous pressure (CVP) were measured at each phase of the study procedure. Hemodynamic fluctuations during the use of dexmedetomidine sedation were recorded and compared between the two groups. Fifty patients had a median (25% - 75% interquartile range) of 71 (61 - 78) years old were studied. At baseline, 39 of the 50 patients were "Nonresponders" and 11 were "Responders". Following dexmedetomidine sedation, patients classified as "Responders" had a significantly greater systolic blood pressure decrease during the induction of dexmedetomidine sedation than the "Nonresponders" ((-26.3 ± 6.8)% vs. -11.8 ± 8.5)%, P < 0.001). In addition, the "Responders" group required significantly more fluid boluses (8 vs. 3; P < 0.001) and vasopressors (2 vs. 0; P < 0.05) than the "Nonresponders" group to restore blood pressure. Finally, PLR-ΔPP was positively correlated

Magnitude of Hypotension Based on Office and Ambulatory Blood Pressure Monitoring: Results From a Cohort of 5066 Treated Hypertensive Patients Aged 80 Years and Older.

PubMed

Divisón-Garrote, Juan A; Ruilope, Luis M; de la Sierra, Alejandro; de la Cruz, Juan J; Vinyoles, Ernest; Gorostidi, Manuel; Escobar-Cervantes, Carlos; Velilla-Zancada, Sonsoles M; Segura, Julián; Banegas, José R

2017-05-01

Elderly patients can be particularly susceptible to the adverse effects of excessive blood pressure (BP) lowering by antihypertensive treatment. The identification of hypotension is thus especially important. Ambulatory BP monitoring (ABPM) is a more accurate technique than office for classifying BP status. This study examined the prevalence of hypotension and associated demographic and clinical factors among very old treated hypertensive patients undergoing ABPM. Cross-sectional study in which 5066 patients aged 80 years and older with treated hypertension drawn from the Spanish ABPM Registry were included. Office BP and 24-hour ambulatory BP were determined using validated devices under standardized conditions. Based on previous studies, hypotension was defined as systolic/diastolic BP <110 and/or 70 mmHg with office measurement, <105 and/or 65 mmHg with daytime ABPM, <90 and/or 50 mmHg with nighttime ABPM, and <100 and/or 60 mmHg with 24-hour ABPM. Participants' mean age was 83.2 ± 3.1 years (64.4% women). Overall, 22.8% of patients had office hypotension, 33.7% daytime hypotension, 9.2% nighttime hypotension, and 20.5% 24-hour ABPM hypotension. Low diastolic BP values were responsible for 90% of cases of hypotension. In addition, 59.1% of the cases of hypotension detected by daytime ABPM did not correspond to hypotension according to office BP. The variables independently associated with office and ABPM hypotension were diabetes, coronary heart disease, and a higher number of antihypertensive medications. One in 3 very elderly treated hypertensive patients attended in usual clinical practice were potentially at risk of having hypotension according to daytime ABPM. More than half of them had masked hypotension; that is, they were not identified if relying on office BP alone. Thus, ABPM could be especially helpful for identifying ambulatory hypotension and avoiding overtreatment, in particular, in patients with diabetes, heart disease, or on

Orthostatic hypotension, cerebral hypoperfusion, and visuospatial deficits in Lewy body disorders.

PubMed

Robertson, Andrew D; Messner, Michelle A; Shirzadi, Zahra; Kleiner-Fisman, Galit; Lee, Joyce; Hopyan, Julia; Lang, Anthony E; Black, Sandra E; MacIntosh, Bradley J; Masellis, Mario

2016-01-01

Orthostatic hypotension and cognitive impairment are two non-motor attributes of Lewy body spectrum disorders that impact independence. This proof-of-concept study examined cerebral blood flow (perfusion) as a mediator of orthostatic hypotension and cognition. In fifteen patients with Lewy body disorders, we estimated regional perfusion using pseudo-continuous arterial spin labeling MRI, and quantified orthostatic hypotension from the change in systolic blood pressure between supine and standing positions. Executive, visuospatial, attention, memory, and language domains were characterized by neuropsychological tests. A matching sample of non-demented adults with cerebral small vessel disease was obtained to contrast perfusion patterns associated with comorbid vascular pathology. Compared to the vascular group, patients with Lewy body disorders exhibited lower perfusion to temporal and occipital lobes than to frontal and parietal lobes (q < 0.05). A greater orthostatic drop in systolic pressure was associated with lower occipito-parietal perfusion in these patients (uncorrected p < 0.005; cluster size ≥ 20 voxels). Although orthostatic hypotension and supine hypertension were strongly correlated (r = -0.79, p < 0.001), the patterns of association for each with perfusion were distinct. Specifically, supine hypertension was associated with high perfusion to anterior and middle cerebral arterial territories, as well as with low perfusion to posterior regions. Perfusion within orthostatic hypotension-defined regions was directly related to performance on visuospatial and attention tasks, independent of dementia severity (p < 0.05). These findings provide new insight that regional cerebral hypoperfusion is related to orthostatic hypotension, and may be involved in domain-specific cognitive deficits in Lewy body disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vasopressor choice for hypotension in elective Cesarean section: ephedrine or phenylephrine?

PubMed Central

Gunda, Chandrakala P.; Malinowski, Jennifer; Tegginmath, Aruna; Suryanarayana, Venkatesh G.

2010-01-01

Introduction Hypotensive episodes are a common complication of spinal anesthesia during Cesarean section. The purpose of this study was to compare the effectiveness and the side effects of vasopressors, ephedrine and phenylephrine, administered for hypotension during elective Cesarean section under spinal anesthesia. Material and methods The study consisted of 100 selected ASA I/II females scheduled for elective Cesarean section under spinal anesthesia. Each patient was randomly assigned to one of the two double-blind study groups. Group E received 1 ml ephedrine (5 mg/ml) with normal saline if hypotension was present (n=50). Group P received 1 ml phenylephrine (100 µg/ml) with normal saline if hypotension developed (n=50). Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) were compared within and between groups to basal levels at time increments of 0, 2, 4, 6, 8, 10, 15, 20, 25, 30, 45, and 60 min from start of surgery. Incidence of side effects and neonatal outcomes were studied between groups. Results All patients required vasopressor therapy for hypotension. Administration of phenylephrine was associated with significant drop in HR. Changes in SBP, DBP, and MAP were similar in both groups for most observed times. The incidences of nausea/vomiting and tachycardia were significantly higher in the ephedrine group. Conclusions Phenylephrine and ephedrine are acceptable choices to combat maternal hypotension related to spinal anesthesia in elective Cesarean section. Complications of intra-operative nausea and vomiting, tachycardia and bradycardia should be considered when choosing a vasopressor, suggesting phenylephrine may be more appropriate when considering maternal well-being. PMID:22371756

Central Methysergide Prevents Renal Sympathoinhibition and Bradycardia during Hypotensive Hemorrhage

NASA Technical Reports Server (NTRS)

Veelken, Roland; Johnson, Kim; Scrogin, Karie E.

1998-01-01

Central methysergide prevents renal sympathoinhibition and bradycardia during hypotensive hemorrhage. Mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured in conscious rats during either hemorrhage or cardiopulmonary receptor stimulation with phenylbiguanide (PBG) after intracerebroventricular injection of the 5-HT1/5-HT2-receptor antagonist, methysergide (40 microg). Progressive hemorrhage caused an initial rise (109 +/- 33%) followed by a fall in RSNA (-60 +/- 7%) and a fall in HR (-126 +/- 7 beats/min). Methysergide delayed the hypotension and prevented both the sympathoinhibitory and bradycardic responses to hemorrhage. Systemic 5-HT3-receptor blockade did not influence responses to hemorrhage. The PBG infusion caused transient depressor(-25 +/- 6 mmHg), bradycardic (-176 +/- 40 beats/min), and renal sympathostimulatory (182 +/-47% baseline) responses that were not affected by central methysergide (-20 +/- 6 mmHg, -162 +/- 18 beats/min, 227 +/- 46% baseline). These data indicate that a central serotonergic receptor-mediated component contributes to the sympathoinhibitory and bradycardic responses to hypotensive hemorrhage in conscious rats. Furthermore, the same central 5-HT-receptor populations involved in reflex responses to hypotensive hemorrhage probably do not mediate the sympathoinhibitory response to cardiopulmonary chemosensitive 5-HT3 receptors.

Effects of weight-based ultrafiltration rate limits on intradialytic hypotension in hemodialysis.

PubMed

Pirkle, James L; Comeau, Mary E; Langefeld, Carl D; Russell, Gregory B; Balderston, Somer S; Freedman, Barry I; Burkart, John M

2018-04-01

High ultrafiltration (UF) rates can result in intradialytic hypotension and are associated with increased mortality. The effects of a weight-based UF rate limit on intradialytic hypotension and the potential for unwanted fluid weight gain and hospitalizations for volume overload are unknown. This retrospective cohort study examined 123 in-center hemodialysis patients at one facility who transitioned to 13 mL/kg/h maximum UF rates. Patients were studied for an 8 week UF rate limit exposure period and compared to the 8-week period immediately prior, during which the cohort served as its own historical control. The primary outcomes were frequency of intradialytic hypotension events and percentage of treatments with a hypotension event. The delivered UF rate was lower during the exposure compared to the baseline period (mean UF rate 7.90 ± 4.45 mL/kg/h vs. 8.92 ± 5.64 mL/kg/h; P = 0.0005). The risk of intradialytic hypotension was decreased during the exposure compared to baseline period (event rate per treatment 0.0569 vs. 0.0719, OR 0.78 [95% CI 0.62-1.00]; P = 0.0474), as was the risk of having a treatment with a hypotension event (percentage of treatments with event 5.2% vs. 6.8%, OR 0.75 [95% CI 0.58-0.96]; P = 0.0217). Subgroup analyses demonstrated that these findings were attributable to patients with high baseline UF rates. Statistically significant differences in all-cause or volume overload-related hospitalization were not observed during the exposure period. A weight-based UF rate limit of 13 mL/kg/h was associated with a decrease in the rate of intradialytic hypotension events among in-center hemodialysis patients. © 2017 International Society for Hemodialysis.

Recent advances in the treatment of orthostatic hypotension

NASA Technical Reports Server (NTRS)

Robertson, D.; Davis, T. L.

1995-01-01

Orthostatic hypotension is a fall in blood pressure on standing that causes symptoms of dizziness, visual changes, and discomfort in the head and neck. The goal of treatment is the improvement of the patient's functional capacity, rather than a target blood pressure. For treatment to be successful, it must be individualized. Non-pharmalogic interventions include carefully managed exercise, scheduled activities, and monitoring of the environmental temperature. Agents such as fludrocortisone, midodrine, and epoetin alfa offer successful pharmacologic interventions. Although these measures ease the symptoms of orthostatic hypotension, current approaches neither reverse nor stabilize the disease process in autonomic disorders.

The non-diuretic hypotensive effects of thiazides are enhanced during volume depletion states

PubMed Central

Alshahrani, Saeed; Rapoport, Robert M.; Zahedi, Kamyar; Jiang, Min; Nieman, Michelle; Barone, Sharon; Meredith, Andrea L.; Lorenz, John N.; Rubinstein, Jack

2017-01-01

Thiazide derivatives including Hydrochlorothiazide (HCTZ) represent the most common treatment of mild to moderate hypertension. Thiazides initially enhance diuresis via inhibition of the kidney Na+-Cl- Cotransporter (NCC). However, chronic volume depletion and diuresis are minimal while lowered blood pressure (BP) is maintained on thiazides. Thus, a vasodilator action of thiazides is proposed, likely via Ca2+-activated K+ (BK) channels in vascular smooth muscles. This study ascertains the role of volume depletion induced by salt restriction or salt wasting in NCC KO mice on the non-diuretic hypotensive action of HCTZ. HCTZ (20mg/kg s.c.) lowered BP in 1) NCC KO on a salt restricted diet but not with normal diet; 2) in volume depleted but not in volume resuscitated pendrin/NCC dKO mice; the BP reduction occurs without any enhancement in salt excretion or reduction in cardiac output. HCTZ still lowered BP following treatment of NCC KO on salt restricted diet with paxilline (8 mg/kg, i.p.), a BK channel blocker, and in BK KO and BK/NCC dKO mice on salt restricted diet. In aortic rings from NCC KO mice on normal and low salt diet, HCTZ did not alter and minimally decreased maximal phenylephrine contraction, respectively, while contractile sensitivity remained unchanged. These results demonstrate 1) the non-diuretic hypotensive effects of thiazides are augmented with volume depletion and 2) that the BP reduction is likely the result of HCTZ inhibition of vasoconstriction through a pathway dependent on factors present in vivo, is unrelated to BK channel activation, and involves processes associated with intravascular volume depletion. PMID:28719636

Management of Patient Care in Hemodialysis While Focusing on Cardiovascular Disease Events and the Atypical Role of Hyper- and/or Hypotension: A Systematic Review

PubMed Central

Khan, Amer Hayat; Syed Sulaiman, Syed Azhar; Khan, Irfanullah

2016-01-01

Background. Hemodialysis related hemodynamic instability is a major but an underestimated issue. Moreover, cardiovascular events are the leading cause of morbidity and mortality associated with blood pressure in hemodialysis patients. However, there have been many controversies regarding the role and management of hyper- and/or hypotension during hemodialysis that needs to be addressed. Objective. To critically review the available published data on the atypical role of hyper- and/or hypotension in cardiovascular associated morbidity and mortality in patients on hemodialysis and to understand the discrepancies in this context. Methods. A comprehensive search of literature employing electronic as well as manual sources and screening 2783 papers published between Jan 1980 and Oct 2015 was conducted to collect, identify, and analyze relevant information through peer-reviewed research articles, systematic reviews, and other published works. The cardiovascular events, including accelerated atherosclerotic cardiovascular disease (ASCVD), stroke, heart failure, myocardial infarction, myocardial ischemia, and stress induced myocardial dysfunction, leading to death were considered relevant. Results. A total of 23 published articles met the inclusion criteria and were included for in-depth review and analysis to finalize a comprehensive systematic review article. All the studies showed a significant association between the blood pressure and cardiovascular disease events in hemodialysis patients. Conclusions. Both intradialytic hypertension/hypotension episodes are major risk factors for cardiovascular mortality with a high percentage of probable causality; however, clinicians are faced with a dilemma on how to evaluate blood pressure and treat this condition. PMID:27833921

Extreme Conditioning Program Induced Acute Hypotensive Effects are Independent of the Exercise Session Intensity

PubMed Central

TIBANA, RAMIRES ALSAMIR; ALMEIDA, LEONARDO MESQUISTA; DE SOUSA NETO, IVO VIEIRA; DE SOUSA, NUNO MANUEL FRADE; DE ALMEIDA, JEESER ALVES; DE SALLES, BELMIRO FREITAS; BENTES, CLAUDIO MELIBEU; PRESTES, JONATO; COLLIER, SCOTT R.; VOLTARELLI, FABRICIO AZEVEDO

2017-01-01

The aim of the study was to determine the acute systolic (SBP) and diastolic (DBP) blood pressure, rating of perceived exertion (RPE) and heart rate (HR) responses following two intense training sessions (24 hours apart). Nine male extreme conditioning program (ECP) practitioners with more than 6 months of experience (age 26.7 ± 6.6 years; body mass 78.8 ± 13.2 kg; body fat 13.5 ± 6.2 %) completed two experimental ECP sessions. Cardiovascular variables were measured before, immediately after and every 15 min during a 45 min recovery following each experimental session. Compared with pre-exercise data, our results showed a SBP decrease at 30 min post exercise session 1 (P≤0.05) and at 45 min following exercise session 2. DBP decreased (P≤0.05) at 15 min and 30 min following exercise session 1 and at 30 min after the exercise session 2, respectively. HR remained significantly higher (P≤0.05) 45 min following the first and second exercise session compared with pre-exercise values. Exercise session 1 induced a higher increase in HR (86 ± 11% of HRmax versus 82 ± 12% of HRmax, p = 0.01) and RPE (8.8 ± 1.2 versus 8.0 ± 1.2, p = 0.02) when compared to exercise session 2. In conclusion, post-exercise hypotension occurs following strenuous exercise sessions, regardless of the session design, which may have an important role in the prevention of cardiovascular diseases. PMID:29399246

Agonistic autoantibodies as vasodilators in orthostatic hypotension: a new mechanism.

PubMed

Li, Hongliang; Kem, David C; Reim, Sean; Khan, Muneer; Vanderlinde-Wood, Megan; Zillner, Caitlin; Collier, Daniel; Liles, Campbell; Hill, Michael A; Cunningham, Madeleine W; Aston, Christopher E; Yu, Xichun

2012-02-01

Agonistic autoantibodies to the β-adrenergic and muscarinic receptors are a novel investigative and therapeutic target for certain orthostatic disorders. We have identified the presence of autoantibodies to β2-adrenergic and/or M3 muscarinic receptors by ELISA in 75% (15 of 20) of patients with significant orthostatic hypotension. Purified serum IgG from all 20 of the patients and 10 healthy control subjects were examined in a receptor-transfected cell-based cAMP assay for β2 receptor activation and β-arrestin assay for M3 receptor activation. There was a significant increase in IgG-induced activation of β2 and M3 receptors in the patient group compared with controls. A dose response was observed for both IgG activation of β2 and M3 receptors and inhibition of their activation with the nonselective β blocker propranolol and muscarinic blocker atropine. The antibody effects on β2 and/or M3 (via production of NO) receptor-mediated vasodilation were studied in a rat cremaster resistance arteriole assay. Infusion of IgG from patients with documented β2 and/or M3 receptor agonistic activity produced a dose-dependent vasodilation. Sequential addition of the β-blocker propranolol and the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester partially inhibited IgG-induced vasodilation (percentage of maximal dilatory response: from 57.7±10.4 to 35.3±4.6 and 24.3±5.8, respectively; P<0.01; n=3), indicating that antibody activation of vascular β2 and/or M3 receptors may contribute to systemic vasodilation. These data support the concept that circulating agonistic autoantibodies serve as vasodilators and may cause or exacerbate orthostatic hypotension.

Severe bradycardia and prolonged hypotension in ciguatera.

PubMed

Chan, Thomas Yan Keung

2013-06-01

Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

Vitamin D deficiency is associated with orthostatic hypotension in oldest-old women.

PubMed

Annweiler, C; Schott, A-M; Rolland, Y; Beauchet, O

2014-09-01

Orthostatic hypotension, a condition that mostly affects 'oldest-old' (i.e. ≥80 years) adults, is primarily explained by age-related dysfunction of blood pressure control. Vitamin D may contribute to blood pressure control. The aim of this study was to determine whether vitamin D deficiency is associated with orthostatic hypotension in oldest-old adults. Cross-sectional analysis at baseline of the EPIDOS study. Five French areas. A total of 329 community-dwelling oldest-old women (mean age 83.3 ± 0.2 years). Orthostatic hypotension was defined as a systolic blood pressure drop of ≥20 mmHg and/or a diastolic blood pressure drop of ≥10 mmHg within 3 min of standing. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25OHD) concentration ≤10 ng mL(-1) . Covariates included in the models were age, body mass index, diabetes mellitus, supine mean arterial pressure, number of drugs taken per day, use of antihypertensive or psychoactive drugs, cognition, quadriceps strength, current smoking, alcohol consumption, serum concentrations of parathyroid hormone, calcium and creatinine and season of testing. Diastolic orthostatic hypotension was observed more often among women with vitamin D deficiency (19.2%) compared to those without (10.0%; P = 0.03). There was an inverse linear association between 25OHD concentration and change in diastolic blood pressure after 3 min of standing (adjusted β = -0.07, P = 0.046). Similarly, 25OHD deficiency was associated with orthostatic hypotension [adjusted odds ratio (OR) 3.36, P = 0.004], specifically with diastolic orthostatic hypotension (adjusted OR 3.81, P = 0.003). 25OHD deficiency was associated with orthostatic hypotension in oldest-old women, due to a greater drop in diastolic blood pressure on standing. This finding may lead to better understanding of the pathophysiology of falls in oldest-old adults with vitamin D deficiency. © 2014 The Association for the Publication of the Journal of

Investigation of postural hypotension due to static prolonged standing in female workers.

PubMed

Kabe, Isamu; Tsuruoka, Hiroko; Tokujitani, Yoko; Endo, Yuichi; Furusawa, Mami; Takebayashi, Toru

2007-07-01

The "Just-in-Time system" improves productivity and efficiency through cost reduction while it makes workers work in a standing posture. The aim of this study was to investigate the prevalence of postural hypotension in females during prolonged standing work, and to discuss preventive methods. Twelve female static standing workers (mean age+/-standard deviation; 32+/-14 yr old), 6 male static standing workers (30+/-4 yr old), 10 female walking workers (27+/-7 yr old) and 9 female desk workers (31+/-5 yr old) in a certain telecommunications equipment manufacturing factory agreed to participate in this study. All participants received an interview with an occupational physician, and performed the standing up test before working and ambulatory blood pressure monitoring (ABPM) while working. Although the blood pressure of the standing up test did not differ among the groups, mean pulse rates on standing up significantly increased in every group. Hypotension rates in the female standing workers' group by ABPM were 9 persons of 12 participants (75%) for systolic blood pressure (SBP), and were 11 persons of 12 participants (92%) for diastolic blood pressure (DBP). There were significantly higher than those in the female desk workers' group, none of 9 participants (0%) for SBP and 2 of 9 participants (22%) for DBP. The hypotension rates both male standing and female walking worker groups did not differ. Because all 8 workers who were found to have postural hypotension by the standing up test had decreased SBP and/or DBP by ABPM, it is suggested that persons at high risk of postural hypotension during standing work could be screened by the standing up test. The mechanism of postural hypotension may be a decrease of venous return due to leg swelling, and neurocardiogenic or vasovagal response. Preventing the congestion of the lower limbs by walking, managing standing time and wearing elastic hose to keep the amount of the venous return could prevent postural hypotension

Randomized Withdrawal Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension Responsive to Droxidopa

PubMed Central

Freeman, Roy; Mathias, Christopher J.; Low, Phillip; Hewitt, L. Arthur; Kaufmann, Horacio

2015-01-01

Abstract— We evaluated whether droxidopa, a prodrug converted to norepinephrine, is beneficial in the treatment of symptomatic neurogenic orthostatic hypotension, which results from failure to generate an appropriate norepinephrine response to postural challenge. Patients with symptomatic neurogenic orthostatic hypotension and Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa titration (100–600 mg, 3× daily). Responders then received an additional 7-day open-label treatment at their individualized dose. Patients were subsequently randomized to continue with droxidopa or withdraw to placebo for 14 days. We then assessed patient-reported scores on the Orthostatic Hypotension Questionnaire and blood pressure measurements. Mean worsening of Orthostatic Hypotension Questionnaire dizziness/lightheadedness score from randomization to end of study (the primary outcome; N=101) was 1.9±3.2 with placebo and 1.3±2.8 units with droxidopa (P=0.509). Four of the other 5 Orthostatic Hypotension Questionnaire symptom scores and all 4 symptom-impact scores favored droxidopa, with statistical significance for the patient’s self-reported ability to perform activities requiring standing a short time (P=0.033) and standing a long time (P=0.028). Furthermore, a post hoc analysis of a predefined composite score of all symptoms (Orthostatic Hypotension Questionnaire composite) demonstrated a significant benefit for droxidopa (P=0.013). There was no significant difference between groups for standing systolic blood pressure (P=0.680). Droxidopa was well tolerated. In summary, this randomized withdrawal droxidopa study failed to meet its primary efficacy end point. Additional clinical trials are needed to confirm that droxidopa is beneficial in symptomatic neurogenic orthostatic hypotension, as suggested by the positive secondary outcomes of this trial. Clinical Trial Registration— URL: http

Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa.

PubMed

Biaggioni, Italo; Freeman, Roy; Mathias, Christopher J; Low, Phillip; Hewitt, L Arthur; Kaufmann, Horacio

2015-01-01

We evaluated whether droxidopa, a prodrug converted to norepinephrine, is beneficial in the treatment of symptomatic neurogenic orthostatic hypotension, which results from failure to generate an appropriate norepinephrine response to postural challenge. Patients with symptomatic neurogenic orthostatic hypotension and Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa titration (100-600 mg, 3× daily). Responders then received an additional 7-day open-label treatment at their individualized dose. Patients were subsequently randomized to continue with droxidopa or withdraw to placebo for 14 days. We then assessed patient-reported scores on the Orthostatic Hypotension Questionnaire and blood pressure measurements. Mean worsening of Orthostatic Hypotension Questionnaire dizziness/lightheadedness score from randomization to end of study (the primary outcome; N=101) was 1.9±3.2 with placebo and 1.3±2.8 units with droxidopa (P=0.509). Four of the other 5 Orthostatic Hypotension Questionnaire symptom scores and all 4 symptom-impact scores favored droxidopa, with statistical significance for the patient's self-reported ability to perform activities requiring standing a short time (P=0.033) and standing a long time (P=0.028). Furthermore, a post hoc analysis of a predefined composite score of all symptoms (Orthostatic Hypotension Questionnaire composite) demonstrated a significant benefit for droxidopa (P=0.013). There was no significant difference between groups for standing systolic blood pressure (P=0.680). Droxidopa was well tolerated. In summary, this randomized withdrawal droxidopa study failed to meet its primary efficacy end point. Additional clinical trials are needed to confirm that droxidopa is beneficial in symptomatic neurogenic orthostatic hypotension, as suggested by the positive secondary outcomes of this trial. http://www.clinicaltrials.gov. Unique identifier: NCT00633880

Lack of causal association between spontaneous intracranial hypotension and cranial cerebrospinal fluid leaks.

PubMed

Schievink, Wouter I; Schwartz, Marc S; Maya, M Marcel; Moser, Franklin G; Rozen, Todd D

2012-04-01

Spontaneous intracranial hypotension is an important cause of headaches and an underlying spinal CSF leak can be demonstrated in most patients. Whether CSF leaks at the level of the skull base can cause spontaneous intracranial hypotension remains a matter of controversy. The authors' aim was to examine the frequency of skull base CSF leaks as the cause of spontaneous intracranial hypotension. Demographic, clinical, and radiological data were collected from a consecutive group of patients evaluated for spontaneous intracranial hypotension during a 9-year period. Among 273 patients who met the diagnostic criteria for spontaneous intracranial hypotension and 42 who did not, not a single instance of CSF leak at the skull base was encountered. Clear nasal drainage was reported by 41 patients, but a diagnosis of CSF rhinorrhea could not be established. Four patients underwent exploratory surgery for presumed CSF rhinorrhea. In addition, the authors treated 3 patients who had a postoperative CSF leak at the skull base following the resection of a cerebellopontine angle tumor and developed orthostatic headaches; spinal imaging, however, demonstrated the presence of a spinal source of CSF leakage in all 3 patients. There is no evidence for an association between spontaneous intracranial hypotension and CSF leaks at the level of the skull base. Moreover, the authors' study suggests that a spinal source for CSF leakage should even be suspected in patients with orthostatic headaches who have a documented skull base CSF leak.

Hypotensive effects of hemopressin and bradykinin in rabbits, rats and mice. A comparative study.

PubMed

Blais, Paul-André; Côté, Jérôme; Morin, Josée; Larouche, Annie; Gendron, Gabrielle; Fortier, Audrey; Regoli, Domenico; Neugebauer, Witold; Gobeil, Fernand

2005-08-01

Hemopressin is a novel vasoactive nonapeptide derived from hemoglobin's alpha-chain as recently reported by Rioli et al. [Rioli V, Gozzo FC, Heimann AS, Linardi A, Krieger JE, Shida CS, et al. Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme. J Biol Chem 2003;278(10):8547-55]. In anesthetized male Wistar rats, this peptide exhibited hypotensive actions similar to those of bradykinin (BK) when administered intravenously (i.v.), and was found to be metabolized both in vitro and in vivo by several peptidases, including the angiotensin-converting enzyme (ACE). In this study, these findings were expanded upon by examining: (i) the degradation kinetics following incubation with ACE purified from rabbit lung and (ii) the blood pressure lowering effects of HP and BK injected i.v. or intra-arterially (i.a.) in male rabbits, rats, and mice. Our findings demonstrate that, in vitro, HP and BK are both degraded by ACE, but at different velocity rates. Furthermore, both HP and BK induced transient hypotension in all animals tested, although the responses to HP relative to the administration sites were significantly lower (by 10-100-fold) on an equimolar basis compared to those of BK. In rabbits, the decrease of blood pressure induced by HP (10-100 nmol/kg) did not differ whether it was administered i.v. or i.a., suggesting an absence of pulmonary/cardiac inactivation in contrast to BK (0.1-1 nmol/kg). The in vivo effect of HP was significantly potentiated in rabbits immunostimulated with bacterial lipopolysaccharide (LPS), but was unaffected by both the B2 receptor antagonist HOE 140 (0.1 micromol/kg) and captopril (100 microg/kg), contrary to BK. Therefore, HP acts as a weak hypotensive mediator, which does not activate kinin B2 receptors, but uses a functional site and/or signaling paths appearing to be up-regulated by LPS.

A conscious rat model involving bradycardia and hypotension after oral administration: a toxicokinetical study of aconitine.

PubMed

Zhang, Panpan; Kong, Dezhi; Du, Qian; Zhao, Jing; Li, Qing; Zhang, Jianghua; Li, Tonghui; Ren, Leiming

2017-06-01

1. A model of aconitine-induced bradycardia and hypotension, which is similar to aconitine poisoning in humans, was constructed in conscious rats by oral administration. 2. Blood pressure (BP) and heart rate (HR) of Sprague-Dawley rats were measured using a volume pressure recording (VPR) system. The pharmacokinetics of toxic doses of aconitine and its metabolites were analyzed using UPLC-MS/MS. 3. The HR was significantly decreased by 29% at 2 h after oral administration of 200 μg/kg aconitine. When the dose was increased to 400 μg/kg, systolic BP and diastolic BP were significantly decreased by 11% and 12% at 2 h after the administration, except when bradycardia occurred at 2 h and 4 h. The drug concentration-time curve showed a double-peak phenomenon in rats administered a 400 μg/kg dose. The AUC 0-12 h value in the 400 μg/kg group significantly increased 0.8-fold compared to the 200 μg/kg group. Moreover, a high plasma concentration of 16-O-demethyaconitine was found in the rats that received two toxic doses. 4. In conclusion, bradycardia and hypotension are induced in conscious rats by a toxic dose of aconitine (400 μg/kg), and there was no significant difference in dose-normalized AUC 0-12 h values between oral administrations of 200 μg/kg and that of 400 μg/kg. However, the dose-normalized C max and AUC 0-12 h values in 200 μg/kg and 400 μg/kg groups were significantly smaller than those in 100 μg/kg group. The metabolites of aconitine, 16-O-demethyaconitine, and benzoylaconitine may also contribute to the hypotensive response.

Hypotensive effect of agmatine, arginine metabolite, is affected by NO synthase.

PubMed

Gerová, M; Török, J

2004-01-01

The metabolites of arginine were recently shown to be involved in cardiovascular control. The study addresses the general cardiovascular response of anaesthetized rats to agmatine, a decarboxylated arginine. The relation between two arginine metabolic pathways governed by arginine decarboxylase and nitric oxide synthase was investigated. Intravenous administration of agmatine 30 and 60 microM/0.1 ml saline elicited remarkable hypotension of 42.6+/-4.6 and 70.9+/-6.5 mm Hg, respectively. The hypotension was characterized by long duration with half-time of return 171.6+/-2.9 and 229.2+/-3.8 s, respectively. The time of total blood pressure BP recovery was about 10 min. Dose-dependent relaxation to agmatine was also found in aorta rings in vitro. Both doses of agmatine administered 60-180 min after NO synthase inhibition L-NAME 40 mg/kg i.v. caused greater hypotension 59.0+/-7.6 and 95.8 8.8 mm Hg P<0.01 both compared to animals with intact NO synthase, but this was accompanied by a significant shortening of the half-time of BP return. If agmatine was administered to hypertensive NO-deficient rats treated with 40 mg/kg/day L-NAME for 4 weeks, similar significant enhancement of hypotension was observed at both agmatine doses, again with a significant shortening of half-time of BP return. It can be summarized that the long-lasting hypotension elicited by agmatine was amplified after acute or chronic NO synthase inhibition, indicating a feedback relation between the two metabolic pathways of arginine.

Response by the corpuscles of Stannius to hypotensive stimuli in three divergent ray-finned fishes (Amia calva, Anguilla rostrata, and Catastomus commersoni): cardiovascular and morphological changes.

PubMed

Butler, D G; Zhang, D H; Villadiego, R; Oudit, G Y; Youson, J H; Cadinouche, M Z A

2003-06-15

In accordance with their vital role in cardiovascular physiology () corpuscles of Stannius (CS) from two teleosts and an holostean species showed marked and consistent degranulation and exocytotic responses to hypotensive stimuli. In eels (Anguilla rostrata LeSueur) acute blood withdrawal (hypovolemic hypotension) was followed by a prompt decrease in cardiac output (CO) and dorsal aortic pressure (P(DA)), a compensatory tachycardic response and an increase in systemic vascular resistance (R(SYS)). Isovolemic hypotension induced by papaverine i.v., led to a similar, but more prolonged, decrease in P(DA) but the heart rate (HR) continued to accelerate, thereby counterbalancing the severe and persistent decrease in R(SYS). Both hypovolemic and isovolemic hypotension were followed by a significant depletion of cytoplasmic granules from eel CS even though plasma concentrations of Ca, Mg, Na(+), and K(+) were normal. In an ancient holostean fish, the bowfin, Amia calva and a generalized teleost fish, Catastomus commersoni, the number of cytoplasmic granules decreased by 39% and 54%, respectively, 120 min after the acute withdrawal of 8 ml kg bw(-1) of blood. These findings suggest that a primary role of the CS is to release cytoplasmic granules containing renin or isorenin into the blood circulation, in response to hypotension and/or hypovolemia.

Hypotensive Anesthesia versus Normotensive Anesthesia during Major Maxillofacial Surgery: A Review of the Literature

PubMed Central

Yoav, Leiser; Abu el-Naaj, Imad

2015-01-01

Steady blood pressure within normal limits during surgery is one of the markers of the ideal and skillful anesthesia. Yet, reduced blood pressure is advantageous in some settings because it can contribute to a reduction in overall blood loss and improve the surgical field conditions. Controlled hypotension during anesthesia or hypotensive anesthesia is often used in major maxillofacial operations. Since hypotensive anesthesia carries the risk of hypoperfusion to important organs and tissues, mainly the brain, heart, and kidneys, it cannot be applied safely in all patients. In this paper we review the medical literature regarding hypotensive anesthesia during major maxillofacial surgery, the means to achieve it, and the risks and benefits of this technique, in comparison to normotensive anesthesia. PMID:25811042

Histamine-releasing properties of Polysorbate 80 in vitro and in vivo: correlation with its hypotensive action in the dog.

PubMed

Masini, E; Planchenault, J; Pezziardi, F; Gautier, P; Gagnol, J P

1985-09-01

The solvent of commercial amiodarone (Polysorbate 80) has been reported to produce haemodynamic responses in humans and in dogs similar to those produced by histamine infusion. We therefore evaluated the correlation between hypotension induced by the solvent of amiodarone and its histamine-releasing properties in the awake dog. The solvent of amiodarone administered to a dog, over 5 min in a dose of 10 mg/kg of Polysorbate 80, produced severe hypotension after the first administration; the second injection (24 h later) caused fewer hypotensive effects. Histamine release in the peripheral tissues was demonstrated by a marked increase in plasma histamine concentrations, with the maximum value 10 min after the solvent administration. H1- and H2-receptor blockade with mepyramine (5 mg/kg) and cimetidine (10 mg/kg) significantly reduced the cardiovascular effects of the solvent. Isolated peritoneal mast cells from rats also released histamine in response to Polysorbate 80. These studies show that Polysorbate 80 releases histamine both in vitro and in isolated mast cells from rats and in vivo in the dog, and that the plasma concentrations are correlated with the haemodynamic responses.

Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.

PubMed

Clemency, Brian M; Thompson, Jeffrey J; Tundo, Gina N; Lindstrom, Heather A

2013-10-01

High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous (IV) nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional Emergency Medical Services (EMS) protocol was introduced allowing advanced providers to treat CHF with high-dose oral nitroglycerin. The protocol calls for patients to be treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as needed. Hypothesis/Problem To assess the protocol's safety, the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers was studied. This study was a retrospective cohort study of patients from a single commercial EMS agency over a 6-month period. Records from patients with at least one administration of MSN were reviewed. For each administration, the first documented vital signs pre- and post-administration were compared. Administrations were excluded if pre- or post-administration vital signs were missing. One hundred case-patients had at least one MSN administration by an advanced provider during the study period. Twenty-five case-patients were excluded due to incomplete vital signs. Seventy-five case-patients with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50 and 66/47). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100. The incidence of hypotension following MSN

Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness

NASA Technical Reports Server (NTRS)

Fadel, P. J.; Stromstad, M.; Hansen, J.; Sander, M.; Horn, K.; Ogoh, S.; Smith, M. L.; Secher, N. H.; Raven, P. B.

2001-01-01

We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness.

PubMed

Fadel, P J; Stromstad, M; Hansen, J; Sander, M; Horn, K; Ogoh, S; Smith, M L; Secher, N H; Raven, P B

2001-06-01

We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

Hypotensive and vasorelaxant effects of citronellol, a monoterpene alcohol, in rats.

PubMed

Bastos, Joana F A; Moreira, Italo J A; Ribeiro, Thaís P; Medeiros, Isac A; Antoniolli, Angelo R; De Sousa, Damião P; Santos, Márcio R V

2010-04-01

Citronellol is an essential oil constituent from the medicinal plants Cymbopogon citratus, Cymbopogon winterianus and Lippia alba which are thought to possess antihypertensive properties. Citronellol-induced cardiovascular effects were evaluated in this study. In rats, citronellol (1-20 mg/kg, i.v.) induced hypotension, which was not affected by pre-treatment with atropine, hexamethonium, N(omega)-nitro-L-arginine methyl ester hydrochloride or indomethacin, and tachycardia, which was only attenuated by pre-treatment with atropine and hexamethonium. These responses were less than those obtained for nifedipine, a reference drug. In intact rings of rat mesenteric artery pre-contracted with 10 microM phenylephrine, citronellol induced relaxations (pD(2) = 0.71 +/- 0.11; E(max) = 102 +/- 5%; n = 6) that were not affected by endothelium removal, after tetraethylamonium in rings without endothelium pre-contracted with KCl 80 mM. Citronellol strongly antagonized (maximal inhibition = 97 +/- 4%; n = 6) the contractions induced by CaCl(2) (10(-6) to 3 x 10(-3 )M) and did not induce additional effects on the maximal response of nifedipine (10 microM). Finally, citronellol inhibited the contractions induced by 10 microM phenylephrine or 20 mM caffeine. The present results suggest that citronellol lowers blood pressure by a direct effect on the vascular smooth muscle leading to vasodilation.

A polymorphism in the glucocorticoid receptor gene is associated with refractory hypotension in premature infants.

PubMed

Ogasawara, Kei; Sato, Maki; Hashimoto, Koichi; Imamura, Takashi; Go, Hayato; Hosoya, Mitsuaki

2018-06-01

Glucocorticoids play an important role in endocrine control. The association of glucocorticoid receptor (GR) gene polymorphisms with altered sensitivity to glucocorticoid therapy has been reported in adults. However, there are few such reports in infants. The present study analyzed the prevalence of four GR polymorphisms in preterm infants born before 30 weeks of gestation and determined the associations between these polymorphisms and clinical outcomes in the infants. Totally, 41 preterm infants born at two hospitals in Fukushima were retrospectively screened for the presence of four GR gene polymorphisms, using a TaqMan single-nucleotide polymorphism genotyping assay. The effect of GR gene polymorphisms on clinical outcomes during hospitalization was evaluated. The following primary clinical outcomes were assessed: refractory hypotension in the acute phase and/or severe bronchopulmonary dysplasia, maximum dopamine and dobutamine doses administered, and total hydrocortisone dose administered in the first 48 h of life. Multivariate analysis with logistic regression was used to assess the association between clinical factors and refractory hypotension. Of the four GR polymorphisms, only the BclI polymorphism was detected. The genotype distribution was as follows: C/C, 33; C/G, 8; and G/G, 0 infants. Significant differences were observed between the C/C and C/G genotypes with respect to the following variables: refractory hypotension (6% vs. 50%), dopamine dose [3.0 (2.0-4.0) vs. 4.8 (4.0-7.5) μg/kg/min], dobutamine dose [2.4 (0.0-3.6) vs. 4.0 (0-10.0) μg/kg/min], and total hydrocortisone dose administered in the first 48 h of life [2.0 (0-10.0) vs. 6.0 (0-12.0) mg/kg]. Multivariate analysis showed that the BclI genotype (C/C) was significantly less associated with refractory hypotension in the acute phase (odds ratio, 0.008; 95% confidence interval, 0.000-0.371; p = 0.013). The incidence of refractory hypotension in infants with the C/C genotype was initially

Helicobacter pylori induces vascular endothelial growth factor production in gastric epithelial cells through hypoxia-inducible factor-1α-dependent pathway.

PubMed

Kang, Min-Jung; Song, Eun-Jung; Kim, Bo-Yeon; Kim, Dong-Jae; Park, Jong-Hwan

2014-12-01

Although Helicobacter pylori have been known to induce vascular endothelial growth factor (VEGF) production in gastric epithelial cells, the precise mechanism for cellular signaling is incompletely understood. In this study, we investigated the role of bacterial virulence factor and host cellular signaling in VEGF production of H. pylori-infected gastric epithelial cells. We evaluated production of VEGF, activation of nuclear factor nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) and hypoxia-inducible factor-1α (HIF-1α) stabilization in gastric epithelial cells infected with H. pylori WT or isogenic mutants deficient in type IV secretion system (T4SS). H. pylori induced VEGF production in gastric epithelial cells via both T4SS-dependent and T4SS-independent pathways, although T4SS-independent pathway seems to be the dominant signaling. The inhibitor assay implicated that activation of NF-κB and MAPKs is dispensable for H. pylori-induced VEGF production in gastric epithelial cells. H. pylori led to HIF-1α stabilization in gastric epithelial cells independently of T4SS, NF-κB, and MAPKs, which was essential for VEGF production in these cells. N-acetyl-cysteine (NAC), a reactive oxygen species (ROS) inhibitor, treatment impaired H. pylori-induced HIF-1α stabilization and VEGF production in gastric epithelial cells. We defined the important role of ROS-HIF-1α axis in VEGF production of H. pylori-infected gastric epithelial cells, and bacterial T4SS has a minor role in H. pylori-induced VEGF production of gastric epithelial cells. © 2014 John Wiley & Sons Ltd.

Outcomes following trauma laparotomy for hypotensive trauma patients: a UK military and civilian perspective.

PubMed

Marsden, Max; Carden, Rich; Navaratne, Lalin; Smith, Iain M; Penn-Barwell, Jowan G; Kraven, Luke M; Brohi, Karim; Tai, Nigel R M; Bowley, Douglas M

2018-05-25

The management of trauma patients has changed radically in the last decade and studies have shown overall improvements in survival. However, reduction in mortality for the many may obscure a lack of progress in some high-risk patients. We sought to examine the outcomes for hypotensive patients requiring laparotomy in UK military and civilian cohorts. We undertook a review of two prospectively maintained trauma databases; the UK Joint Theatre Trauma Registry (JTTR) for the military cohort (4th February 2003 to 21st September 2014), and the trauma registry of the Royal London Hospital MTC (1st January 2012 to 1st January 2017) for civilian patients. Adults undergoing trauma laparotomy within 90 minutes of arrival at the Emergency Department (ED) were included. Hypotension was present on arrival at the ED in 155/761 (20.4%) military patients. Mortality was higher in hypotensive casualties 25.8% vs 9.7% normotensive casualties (p<0.001). Hypotension was present on arrival at the ED in 63/176 (35.7%) civilian patients. Mortality was higher in hypotensive patients 47.6% vs 12.4% normotensive patients (p<0.001). In both cohorts of hypotensive patients neither the average injury severity, the prehospital time, the ED arrival SBP, nor mortality rate changed significantly during the study period. Despite improvements in survival after trauma for patients overall, the mortality for patients undergoing laparotomy who arrive at the Emergency Department with hypotension has not changed and appears stubbornly resistant to all efforts. Specific enquiry and research should continue to be directed at this high-risk group of patients. IV; Observational Cohort Study.

Droxidopa: a review of its use in symptomatic neurogenic orthostatic hypotension.

PubMed

Keating, Gillian M

2015-02-01

The norepinephrine prodrug droxidopa (NORTHERA™) is approved in the US for the treatment of orthostatic dizziness, lightheadedness, or the 'feeling that you are about to black out' in adults with symptomatic neurogenic orthostatic hypotension associated with primary autonomic failure (e.g. Parkinson's disease, multiple system atrophy or pure autonomic failure), dopamine β-hydroxylase deficiency or nondiabetic autonomic neuropathy. This article reviews the clinical efficacy and tolerability of droxidopa in symptomatic neurogenic orthostatic hypotension, as well as summarizing its pharmacological properties. Oral droxidopa was effective in the shorter-term treatment of patients with symptomatic neurogenic orthostatic hypotension, with improvements seen in symptoms, the impact of symptoms on daily activities and standing systolic blood pressure. More data are needed to confirm the longer-term efficacy of droxidopa. Droxidopa was generally well tolerated, although patients should be monitored for supine hypertension.

Defining hypotension in moderate to severely injured trauma patients: raising the bar for the elderly.

PubMed

Edwards, Meghan; Ley, Eric; Mirocha, James; Hadjibashi, Anoushiravan Amini; Margulies, Daniel R; Salim, Ali

2010-10-01

Hypotension, defined as systolic blood pressure less than 90 mm Hg, is recognized as a sign of hemorrhagic shock and is a validated prognostic indicator. The definition of hypotension, particularly in the elderly population, deserves attention. We hypothesized that the systolic blood pressure associated with increased mortality resulting from hemorrhagic shock increases with increasing age. The Los Angeles County Trauma Database was queried for all moderate to severely injured patients without major head injuries admitted between 1998 and 2005. Several fit statistic analyses were performed for each systolic blood pressure from 50 to 180 mm Hg to identify the model that most accurately defined hypotension for three age groups. The optimal definition of hypotension for each group was determined from the best fit model. A total of 24,438 patients were analyzed. The optimal definition of hypotension was systolic blood pressure of 100 mm Hg for patients 20 to 49 years, 120 mm Hg for patients 50 to 69 years, and 140 mm Hg for patients 70 years and older. The optimal systolic blood pressure for improved mortality in hemorrhagic shock increases significantly with increasing age. Elderly trauma patients without major head injuries should be considered hypotensive for systolic blood pressure less than 140 mm Hg.

Influence of mianserin on the activity of some hypotensive drugs in spontaneously hypertensive rats.

PubMed

Górska, Dorota; Andrzejczak, Dariusz

2003-01-01

Mianserin might be an alternative drug in patients with depression accompanied by hypertension because of its effectiveness and lack of side effects in the circulatory system. However, a few studies reported in literature show influence of the drug on blood pressure. We investigate interactions between mianserin and commonly used hypotensive drugs (propranolol, enalapril and prazosin) in spontaneously hypertensive rats (SHR). The experiments were performed in two experimental designs: a single administration of both mianserin and a hypotensive drug, and repeated administration of mianserin with a single administration of a hypotensive drug. Arterial blood pressure was measured by bloodless method with manometer made by LETICA. A single administration of mianserin caused a statistically significant decrease in systolic, diastolic and mean blood pressure in the 60th minute of observation and intensified hypotensive effect of prazosin. However, long-term administration of mianserin in SHR rats had no significant influence on arterial blood pressure. Chronic and single administration of mianserin with propranolol or enalapril did not influence the circulatory system. A long-term administration of mianserin intensified the hypotensive effect of prazosin. This interaction might suggest possibility of dangerous complications in the treatment of humans with this drug combination.

L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience.

PubMed

Kaufmann, Horacio

2008-03-01

Neurogenic orthostatic hypotension results from failure to release norepinephrine, the neurotransmitter of sympathetic postganglionic neurons, appropriately upon standing. In double blind, cross over, placebo controlled trials, administration of droxidopa, a synthetic amino acid that is decarboxylated to norepinephrine by the enzyme L: -aromatic amino acid decarboxylase increases standing blood pressure, ameliorates symptoms of orthostatic hypotension and improves standing ability in patients with neurogenic orthostatic hypotension due to degenerative autonomic disorders. The pressor effect results from conversion of droxidopa to norepinephrine outside the central nervous system both in neural and non-neural tissue. This mechanism of action makes droxidopa effective in patients with central and peripheral autonomic disorders.

Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine

NASA Technical Reports Server (NTRS)

Jankovic, J.; Gilden, J. L.; Hiner, B. C.; Kaufmann, H.; Brown, D. C.; Coghlan, C. H.; Rubin, M.; Fouad-Tarazi, F. M.

1993-01-01

PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

Pre-existing arterial stiffness can predict hypotension during induction of anaesthesia in the elderly.

PubMed

Alecu, C; Cuignet-Royer, E; Mertes, P M; Salvi, P; Vespignani, H; Lambert, M; Bouaziz, H; Benetos, A

2010-11-01

The aim of the present study was to establish whether elevated carotid-femoral pulse wave velocity (c-fPWV), an indicator of aortic stiffness, assessed before surgery, is correlated with variations in arterial pressure (AP) during induction of anaesthesia in elderly patients undergoing non-cardiovascular surgery. c-fPWV was measured with the PulsePen(®) device during pre-surgical anaesthetic evaluation. Monitoring included electrocardiography, pulse oximetry, non-invasive AP, heart rate, bispectral index (BIS), and oxygen concentration during induction of anaesthesia with propofol and remifentanil. Anaesthesia was induced so as to maintain BIS values between 40 and 50. Forty-five patients, aged [mean (sd)] 71.1 (5.8) yr, were studied. The mean value of c-fPWV was 12.1 (3.9) m s⁻¹. There was no correlation between hypotension during anaesthesia induction and total dosage or rate of administration of propofol or remifentanil. In univariate analysis, only age and PWV significantly correlated with the decreases in AP, and the association between c-fPWV and a decrease in AP was also seen in multivariate analysis (r = 0.36, P< 0.05). Patients classified as having 'high stiffness' (c-fPWV ≥ 12.9 m s⁻¹) had 25% further decrease in systolic AP during anaesthesia induction than those with lower PWV [75.2 (5.7) vs 60.2 (4.2) mm Hg, P < 0.05]. Increased aortic stiffness, as assessed by PWV measured during preoperative anaesthetic evaluation, is associated with more pronounced hypotension during induction of anaesthesia. Measurement of aortic stiffness in the elderly may thus represent a valid indicator of the risk of hypotension during anaesthesia induction.

Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli.

PubMed Central

Wakabayashi, G; Gelfand, J A; Jung, W K; Connolly, R J; Burke, J F; Dinarello, C A

1991-01-01

Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism. Images PMID:2040686

Superoxide and Nitric Oxide Mechanisms in Traumatic Brain Injury and Hemorrhagic Hypotension.

DTIC Science & Technology

1999-12-01

DISTRIBUTION CODE 13. ABSTRACT (Maximum 200 Words) Traumatic brain injury (TBI) renders the brain vulnerable to secondary ischemia and poor outcome...cerebral blood flow (CBF) and renders the brain vulnerable to secondary ischemia. There is clinical evidence that hypotension contributes to poor...without TBI. These data indicate that even moderate TBI renders the brain sensitive to ischemic injury during relative mild levels of hypotension that

Automatic adaptive system dialysis for hemodialysis-associated hypotension and intolerance: a noncontrolled multicenter trial.

PubMed

Colì, Luigi; La Manna, Gaetano; Comai, Giorgia; Ursino, Mauro; Ricci, Davide; Piccari, Matteo; Locatelli, Francesco; Di Filippo, Salvatore; Cristinelli, Luciano; Bacchi, Massimo; Balducci, Alessandro; Aucella, Filippo; Panichi, Vincenzo; Ferrandello, Francesco Paolo; Tarchini, Renzo; Lambertini, Domenica; Mura, Carlo; Marinangeli, Giancarlo; Di Loreto, Ermanno; Quarello, Francesco; Forneris, Giacomo; Tancredi, Maurizio; Morosetti, Massimo; Palombo, Giuditta; Di Luca, Marina; Martello, Mauro; Emiliani, Giuseppe; Bellazzi, Roberto; Stefoni, Sergio

2011-07-01

Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. A noncontrolled (single arm), multicenter, prospective, clinical trial. 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. A noncontrolled (single arm) study, no crossover from AASD to standard treatment. This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma

NASA Technical Reports Server (NTRS)

Conlay, L. A.; Maher, T. J.; Roberts, C. H.; Wurtman, R. J.

1988-01-01

Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord were examined. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial (H-3)tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of (H-3)tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

Association between postexercise hypotension and long-term training-induced blood pressure reduction: a pilot study.

PubMed

Hecksteden, Anne; Grütters, Teresa; Meyer, Tim

2013-01-01

The interindividual variability in the efficacy of regular endurance exercise to lower blood pressure is high. Therefore, to optimize training prescriptions, predictors would be desirable. The main hypothesis of the present study was an association between postexercise hypotension after an exhaustive exercise test and chronic blood pressure reductions in response to an endurance training program. Uncontrolled prospective training study. University department. Healthy untrained subjects were recruited by flyers. Inclusion criteria were age 30 to 60 years, body mass index 25 to 35 kg/m(2), untrained status (<1 hour/week regular activity; V[Combining Dot Above]O(2max) < 45 mL·min(-1)·kg(-1)), blood pressure 150/95 mm Hg, nonsmoker; 14 subjects were included, 12 could be analyzed. Walking/running 4 times per week at 60% heart rate reserve for 4 weeks. Difference in blood pressure from the initial resting value to 1 and 24 hours after the initial test (acute) and the resting value before the final test (chronic), respectively. Initial resting systolic blood pressure was 134 ± 18 mm Hg. Values were significantly reduced at all time points thereafter (1 hour: 125 ± 13 mm Hg; 24 hours: 128 ± 12 mm Hg; final: 125 ± 18 mm Hg). Acute and chronic changes correlated significantly (1 hour: P = 0.003; r = 0.77; 24 hours: P = 0.017; r = 0.67). Results for diastolic blood pressure were comparable yet less pronounced. The magnitude of postexercise hypotension is a promising candidate for the prediction of individual blood pressure-related training efficacy. Easily determined, it might be used to improve training prescriptions. However, further studies are needed to assess predictive accuracy.

More hypotension in patients taking antihypertensives preoperatively during shoulder surgery in the beach chair position.

PubMed

Trentman, Terrence L; Fassett, Sharon L; Thomas, Justin K; Noble, Brie N; Renfree, Kevin J; Hattrup, Steven J

2011-11-01

Hypotension is common in patients undergoing surgery in the sitting position under general anesthesia, and the risk may be exacerbated by the use of antihypertensive drugs taken preoperatively. The purpose of this study was to compare hypotensive episodes in patients taking antihypertensive medications with normotensive patients during shoulder surgery in the beach chair position. Medical records of all patients undergoing shoulder arthroscopy during a 44-month period were reviewed retrospectively. The primary endpoint was the number of moderate hypotensive episodes (systolic blood pressure ≤ 85 mmHg) during the intraoperative period. Secondary endpoints included the frequency of vasopressor administration, total dose of vasopressors, and fluid administered. Values are expressed as mean (standard deviation). Of 384 patients who underwent shoulder surgery, 185 patients were taking no antihypertensive medication, and 199 were on at least one antihypertensive drug. The antihypertensive medication group had more intraoperative hypotensive episodes [1.7 (2.2) vs 1.2 (1.8); P = 0.01] and vasopressor administrations. Total dose of vasopressors and volume of fluids administered were similar between groups. The timing of the administration of angiotensin-converting enzyme inhibitors and of angiotensin receptor antagonists (≤ 10 hr vs > 10 hr before surgery) had no impact on intraoperative hypotension. Preoperative use of antihypertensive medication was associated with an increased incidence of intraoperative hypotension. Compared with normotensive patients, patients taking antihypertensive drugs preoperatively are expected to require vasopressors more often to maintain normal blood pressure.

Role of the median preoptic nucleus in the chronic hypotensive effect of losartan in sodium-replete normal rats.

PubMed

Ployngam, Trasida; Katz, Stephen S; Collister, John P

2010-01-01

1. We have shown previously that the chronic hypotensive effect of the angiotensin II AT1 receptor antagonist losartan is mediated, in part, by the subfornical organ (SFO). However, the neural pathway(s) mediating this central effect of losartan downstream from the SFO has not been completely elucidated. 2. The present study was designed to test the hypothesis that the median preoptic nucleus (MnPO) is a crucial part of the neural pathway necessary for the chronic hypotensive effect of losartan. To test this hypothesis, male Sprague-Dawley rats were subjected to either Sham or electrolytic lesion of the MnPO (MnPOx). Rats were instrumented with radiotelemetric transducers and aortic flow probes for the continuous measurement of mean arterial pressure (MAP) and heart rate and cardiac output (CO), respectively. Total peripheral resistance (TPR) was calculated as MAP/CO. After 3 days of baseline measurements, rats were infused intraperitoneally with losartan (10 mg/kg per day) via an osmotic minipump at a rate of 5 microL/min. 3. The data revealed that, by Day 9 of losartan treatment, MAP had decreased 34 +/- 2 mmHg in MnPOx rats (n = 9), whereas the MAP of Sham-lesioned rats (n = 8) had only decreased 24 +/- 3 mmHg. These findings were accompanied by a greater decrease in TPR in MnPOx compared with Sham rats (-0.464 vs-0.237 mmHg/mL per min, respectively), whereas CO remained unchanged throughout the study protocol. 4. These results do not support the hypothesis that an intact MnPO is necessary to mediate the full chronic hypotensive effect of losartan in normal rats. Instead, they appear to suggest that the MnPO may play an important role in buffering the profound hypotension induced by losartan.

[How can we improve symptomatic hypotension in hemodialysis patients: cold dialysis vs isothermic dialysis].

PubMed

Ramos, R; Soto, C; Mestres, R; Jara, J; Zequera, H; Merello, J I; Moreso, F

2007-01-01

Symptomatic hypotension is the most frequent acute complication affecting patients during chronic hemodialysis treatment sessions. Many reports have demonstrated that the use of cool dialysate has a protective effect on blood pressure during hemodialysis treatments. In the present study, we investigated whether preventing the hyperthermic response had favourable effects on hemodynamic stability during the hemodialysis procedure while affording good tolerance to patients. We investigated the effect of thermal control of dialysate on hemodynamic stability in hypotension-prone patients in our center. Patients were eligible for the study if they had symptomatic hypotensive episodes (> 3/12session/ month) during the screening phase. The study was designed with two phases for the same selected patients and two treatment arms, each phase lasting 4 weeks. In the first phase, we adjusted dialysate temperature on 36 masculineC for 12 sessions (cold dialysis) and in the second phase we used a device allowing the regulation of thermal balance (Blood Temperature Monitor; Fresenius Medical Care, Bad Homberg, Germany), that keep body temperature unchanged (isothermic dialysis). Nine HD patients were enrolled and completed the study. During the screening phase the mean ultrafiltration was 4 1% of dry weight, and blood pressure decreased from 9916 to 8016 mm Hg (p<0.001). In 5.01.7 sessions of 12 treatments were complicated by hypotension. In the first and second phase we observed a decrease of complicated treatments with symptomatic hypotension (5.01.7 versus 2.71.6 y 2.81.7; p<0.01). Both procedures: Cold dialysis and Isothermic dialysis was well tolerated by patients. Results show that active control of body temperature can significantly improve intradialytic tolerance in hypotension-prone patients.

Hypotension and Bradycardia Caused by the Inadvertent Ingestion of Rhododendron japonicum.

PubMed

Koda, Ryo; Honma, Miho; Suzuki, Kazuo; Kasai, Akio; Takeda, Tetsuro; Narita, Ichiei; Yoshida, Kazukiyo

2016-01-01

A 61-year-old man was transferred to our hospital with the complaints of dizziness, severe nausea and abdominal discomfort after consuming approximately 50 g of the flowers of Rhododendron japonicum. On admission, hypotension and sinus bradycardia were evident. Symptoms including hypotension and bradycardia completely recovered within 12 hours following normal saline infusion and intravenous atropine. The ingestion of certain types of Rhododendron species can cause intoxication, referred to as "mad honey poisoning", due to the action of grayanotoxins. This is the first local case of acute intoxication caused by Rhododendron japonicum.

Orthostatic hypotension: pathophysiology, assessment, treatment and the paradox of supine hypertension.

PubMed

Chisholm, Peter; Anpalahan, Mahesan

2017-04-01

Both hypertension and orthostatic hypotension (OH) are strongly age-associated and are common management problems in older people. However, unlike hypertension, management of OH has unique challenges with few well-established treatments. Not infrequently, they both coexist, further compounding the management. This review provides comprehensive information on OH, including pathophysiology, diagnostic workup and treatment, with a view to provide a practical guide to its management. Special references are made to patients with supine hypertension and postprandial hypotension and older hypertensive patients. © 2016 Royal Australasian College of Physicians.

Postural headache in marfan syndrome associated with spinal cysts and liquor hypotension.

PubMed

Voermans, N C; Dijk, K G J van; Bos, M M; Geus-Oei, L-F de; Verrips, A; Lindert, E J van

2009-08-01

We here report a 13-year-old Marfan patient who suffered from severe, medication-resistant, intermittent headache, which was provoked when getting into an upright position and immediately relieved by lying down or after intravenous rehydration. The postural benefit and the sudden relief after intravenous hydration suggested (intermittent) intracranial hypotension, although a normal opening pressure on lumbar punction was observed and no cerebrospinal fluid (CSF) leakage was identified. Imaging studies revealed severe dural ectasia at lumbosacral level, and two intradural cysts and two extradural presacral cysts were detected. Most likely, altered hydrodynamics in intra- and extracranial spinal meningeal cysts caused intermittent CSF hypotension above these cysts, resulting in intermittent intracranial hypotension. Surgical marsupialisation of the intradural cysts proved to be effective. This resulted in a significant reduction of the headache during the clinical follow-up of eight years. Georg Thieme Verlag KG Stuttgart New York.

Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles.

PubMed

Ekdahl, Kristina N; Davoodpour, Padideh; Ekstrand-Hammarström, Barbro; Fromell, Karin; Hamad, Osama A; Hong, Jaan; Bucht, Anders; Mohlin, Camilla; Seisenbaeva, Gulaim A; Kessler, Vadim G; Nilsson, Bo

2018-04-01

Iron-oxide nanoparticles (NPs) generated by environmental events are likely to represent health problems. α-Fe 2 O 3 NPs were synthesized, characterized and tested in a model for toxicity utilizing human whole blood without added anticoagulant. MALDI-TOF of the corona was performed and activation markers for plasma cascade systems (complement, contact and coagulation systems), platelet consumption and release of growth factors, MPO, and chemokine/cytokines from blood cells were analyzed. The coronas formed on the pristine α-Fe 2 O 3 NPs contained contact system proteins and they induced massive activation of the contact (kinin/kallikrein) system, as well as thrombin generation, platelet activation, and release of two pro-angiogeneic growth factors: platelet-derived growth factor and vascular endothelial growth factor, whereas complement activation was unaffected. The α-Fe 2 O 3 NPs exhibited a noticeable toxicity, with kinin/kallikrein activation, which may be associated with hypotension and long-term angiogenesis in vivo, with implications for cancer, arteriosclerosis and pulmonary disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Anesthesia information management system-based near real-time decision support to manage intraoperative hypotension and hypertension.

PubMed

Nair, Bala G; Horibe, Mayumi; Newman, Shu-Fang; Wu, Wei-Ying; Peterson, Gene N; Schwid, Howard A

2014-01-01

Intraoperative hypotension and hypertension are associated with adverse clinical outcomes and morbidity. Clinical decision support mediated through an anesthesia information management system (AIMS) has been shown to improve quality of care. We hypothesized that an AIMS-based clinical decision support system could be used to improve management of intraoperative hypotension and hypertension. A near real-time AIMS-based decision support module, Smart Anesthesia Manager (SAM), was used to detect selected scenarios contributing to hypotension and hypertension. Specifically, hypotension (systolic blood pressure <80 mm Hg) with a concurrent high concentration (>1.25 minimum alveolar concentration [MAC]) of inhaled drug and hypertension (systolic blood pressure >160 mm Hg) with concurrent phenylephrine infusion were detected, and anesthesia providers were notified via "pop-up" computer screen messages. AIMS data were retrospectively analyzed to evaluate the effect of SAM notification messages on hypotensive and hypertensive episodes. For anesthetic cases 12 months before (N = 16913) and after (N = 17132) institution of SAM messages, the median duration of hypotensive episodes with concurrent high MAC decreased with notifications (Mann Whitney rank sum test, P = 0.031). However, the reduction in the median duration of hypertensive episodes with concurrent phenylephrine infusion was not significant (P = 0.47). The frequency of prolonged episodes that lasted >6 minutes (sampling period of SAM), represented in terms of the number of cases with episodes per 100 surgical cases (or percentage occurrence), declined with notifications for both hypotension with >1.25 MAC inhaled drug episodes (δ = -0.26% [confidence interval, -0.38% to -0.11%], P < 0.001) and hypertension with phenylephrine infusion episodes (δ = -0.92% [confidence interval, -1.79% to -0.04%], P = 0.035). For hypotensive events, the anesthesia providers reduced the inhaled drug concentrations to <1.25 MAC 81% of

Deliberate fingolimod overdose presenting with delayed hypotension and bradycardia responsive to atropine.

PubMed

Stephenson, M; Wong, A; Rotella, J A; Crump, N; Kerr, F; Greene, S L

2014-06-01

Fingolimod is an immunomodulating agent used in multiple sclerosis (MS). It is a sphingosine-1-phosphate (S1P) receptor agonist prescribed for relapsing forms of MS to delay onset of physical disability. As fingolimod is known to cause first-dose bradycardia, telemetry is recommended for the first 6 h post-dose. We present the first reported case of deliberate fingolimod overdose requiring atropine administration for bradycardia and hemodynamic instability. A 33-year-old woman ingested 14 mg of fingolimod and 2 g of phenoxymethylpenicillin. After presenting to the emergency department 19 h later, she was initially hemodynamically stable (heart rate (HR) 60, blood pressure (BP) 113/89 mmHg). Two hours later, she then developed bradycardia (HR 48) and hypotension (87/57 mmHg). Despite intravenous fluids, stabilisation was only achieved after administration of atropine (300 μg). She was then admitted to the intensive care unit (ICU) for further monitoring where another episode of bradycardia and hypotension required atropine. She was monitored in the ICU for 48 h and then discharged on day 5 with no further episodes. Fingolimod is known to cause bradycardia in the first 6 h post first therapeutic dose. Following intentional overdose, onset of bradycardia occurred at 21 h post-ingestion and was associated with hypotension. Atropine was successful in treating bradycardia and associated hypotension.

Atomoxetine for Orthostatic Hypotension in an Elderly Patient Over 10 Weeks: A Case Report.

PubMed

Hale, Genevieve M; Brenner, Michael

2015-09-01

Several nonpharmacologic strategies for orthostatic hypotension exist including avoiding large carbohydrate-rich meals; limiting alcohol consumption; maintaining adequate hydration; adding salt to foods; and using compression stockings, tilt-table exercises, or abdominal binders. If these fail, however, only limited evidence-based pharmacologic treatment options are available including the use of fludrocortisone, midodrine, pyridostigmine, and droxidopa as well as pseudoephedrine, ocetreotide, and atomoxetine. This report discusses a case of atomoxetine use for 10 weeks in an elderly patient with primary orthostatic hypotension. An 84-year-old man with long-standing primary orthostatic hypotension presented to our ambulatory cardiology pharmacotherapy clinic after several unsuccessful pharmacologic therapies including fludrocortisone, midodrine, and pyridostigmine. Nonpharmacologic strategies were also implemented. Atomoxetine was initiated, and the patient showed gradual improvements in symptoms and blood pressure control over the course of 10 weeks. Our data suggest that low-dose atomoxetine is an effective and safe agent for symptom improvement and blood pressure control in elderly patients with primary orthostatic hypotension. © 2015 Pharmacotherapy Publications, Inc.

The effect of pre-donation hypotension on whole blood donor adverse reactions: a systematic review.

PubMed

Pauwels, Nele S; Cusack, Leila; De Buck, Emmy; Compernolle, Veerle; Vandekerckhove, Philippe

2014-06-01

Blood services are reliant upon healthy blood donors to provide a safe and adequate supply of blood products. Inappropriate variables contained within blood donor exclusion criteria can defer potentially appropriate donors. The aim of this systematic review was to examine the effect of low pre-donation blood pressure, as compared with normal blood pressure, on adverse events in allogeneic whole blood donors. A systematic review was performed using highly sensitive search strategies within five databases (Cochrane Central Register of Controlled Trials, CINAHL, Embase, MEDLINE, and Web of Science) from inception date until April 12, 2013. Out of 8305 records, 10 observational studies were identified that addressed the question. Five of these studies (with a combined total of 1,482,020 donations and 2903 donors) included either a statistical analysis or an appropriate study design that controlled for possible confounding factors. Based on the currently available evidence, hypotension has not been shown to be an independent predictive factor for donor complications. However, the overall quality of evidence was rather limited and rated 'low,' using the GRADE approach. In conclusion there is currently no evidence that hypotensive blood donors have a greater risk for donor adverse events compared with their normotensive counterparts. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Intraoperative bradycardia and hypotension associated with timolol and pilocarpine eye drops.

PubMed

Mishra, P; Calvey, T N; Williams, N E; Murray, G R

1983-09-01

A 69-yr-old man, who was concurrently being treated with pilocarpine nitrate and timolol maleate eye drops, developed a bradycardia and became hypotensive during halothane anaesthesia. Both timolol and pilocarpine were subsequently identified in a 24-h collection of urine. Timolol (but not pilocarpine) was detected in a sample of plasma removed during surgery; the plasma concentration of timolol (2.6 ng ml-1) was consistent with partial beta-adrenoceptor blockade. It is postulated that this action may have been enhanced during halothane anaesthesia with resultant bradycardia and hypotension. Pilocarpine may have had a contributory effect.

Dosage variability of topical ocular hypotensive products: a densitometric assessment.

PubMed

Gaynes, Bruce I; Singa, Ramesh M; Cao, Ying

2009-02-01

To ascertain consequence of variability in drop volume obtained from multiuse topical ocular hypotensive products in terms of uniformity of product dosage. Densitometric assessment of drop volume dispensed from 2 alternative bottle positions. All except one product demonstrated a statistically significant difference in drop volume when administered at either a 45-degree or 90-degree bottle angle (Student t test, P<0.001). Product-specific drop volume ranged from a nadir of 22.36 microL to a high of 53.54 microL depending on bottle angle of administration. Deviation in drop dose was directly proportional to variability in drop volume. Variability in per drop dosage was conspicuous among products with a coefficient of variation from 1.49% to 15.91%. In accordance with drop volume, all products demonstrated a statistically significant difference in drop dose at 45-degree versus 90-degree administration angles. Drop volume was found unrelated to drop uniformity (Spearman r=0.01987 and P=0.9463). Variability and lack of uniformity in drop dosage is clearly evident among select ocular hypotensive products and is related to angle of drop administration. Erratic dosage of topical ocular hypotensive therapy may contribute in part to therapeutic failure and/or toxicity.

Hydrocortisone administration for the treatment of refractory hypotension in critically ill newborns.

PubMed

Baker, C F W; Barks, J D E; Engmann, C; Vazquez, D M; Neal, C R; Schumacher, R E; Bhatt-Mehta, V

2008-06-01

The purpose of this observation was to evaluate the safety and efficacy of hydrocortisone (HC) for the treatment of refractory hypotension in term and preterm infants. A secondary purpose was to determine the utility of serum cortisol concentrations in predicting the response to treatment. This is a retrospective observational study of 117 infants treated with a standardized HC protocol for refractory hypotension. Refractory hypotension was defined as a mean arterial pressure (MAP) less than the gestational age (GA) despite a total inotrope dose of 20 microg per kg per min. Baseline serum cortisol concentrations were determined prior to treatment with stress dose HC. Treatment with HC increased the MAP at 2, 6, 12 and 24 h after initiation, decreased the total inotrope dose at 6, 12 and 24 h, and was associated with resolution of oliguria. There was no correlation between the pretreatment baseline cortisol concentration and GA, birth weight or the response to treatment. The incidence of grades III to IV intraventricular hemorrhage, periventricular leukomalacia, bacterial or fungal sepsis and spontaneous intestinal perforation (SIP) after HC treatment was similar to institutional historic controls prior to institution of this standardized HC protocol. HC treatment was associated with a rapid resolution of cardiovascular compromise. The incidence of significant side effects was similar to that in previously published reports, including a comparable incidence of SIP. On the basis of our results, measuring baseline serum cortisol concentration to guide the management of refractory hypotension is unwarranted.

Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor.

PubMed

Callaghan, Brid; Kosari, Samin; Pustovit, Ruslan V; Sartor, Daniela M; Ferens, Dorota; Ban, Kung; Baell, Jonathan; Nguyen, Trung V; Rivera, Leni R; Brock, James A; Furness, John B

2014-03-01

Some agonists of ghrelin receptors cause rapid decreases in BP. The mechanisms by which they cause hypotension and the pharmacology of the receptors are unknown. The effects of ligands of ghrelin receptors were investigated in rats in vivo, on isolated blood vessels and on cells transfected with the only molecularly defined ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR1a). Three agonists of GHSR1a receptors, ulimorelin, capromorelin and CP464709, caused a rapid decrease in BP in the anaesthetized rat. The effect was not reduced by either of two GHSR1a antagonists, JMV2959 or YIL781, at doses that blocked effects on colorectal motility, in vivo. The rapid hypotension was not mimicked by ghrelin, unacylated ghrelin or the unacylated ghrelin receptor agonist, AZP531. The early hypotension preceded a decrease in sympathetic nerve activity. Early hypotension was not reduced by hexamethonium or by baroreceptor (sino-aortic) denervation. Ulimorelin also relaxed isolated segments of rat mesenteric artery, and, less potently, relaxed aorta segments. The vascular relaxation was not reduced by JMV2959 or YIL781. Ulimorelin, capromorelin and CP464709 activated GHSR1a in transfected HEK293 cells at nanomolar concentrations. JMV2959 and YIL781 both antagonized effects in these cells, with their pA2 values at the GHSR1a receptor being 6.55 and 7.84. Our results indicate a novel vascular receptor or receptors whose activation by ulimorelin, capromorelin and CP464709 lowered BP. This receptor is activated by low MW GHSR1a agonists, but is not activated by ghrelin. © 2013 The British Pharmacological Society.

Spontaneous intracranial hypotension.

PubMed

Gordon, Neil

2009-12-01

Since the introduction of magnetic resonance imaging (MRI), spontaneous intracranial hypotension has been diagnosed much more frequently. The aim of this review is to discuss the symptoms and signs of the condition, in particular the characteristics of the associated headache, with sudden onset after sitting or standing, so that it can be included under the rubric of 'thunderclap headache'. This type of headache, like post lumbar puncture headaches, may be caused by cerebral vasodilatation and exacerbated by lowered pressure of the cerebrospinal fluid (CSF). Other symptoms include neck stiffness, nausea, vomiting, vertigo, tinnitus, deafness, and cognitive abnormalities. The clinical picture can sometimes mimic frontotemporal dementia, and the behaviour of some patients can sometimes be described as hypoactive-hypoalert, with somnolence, impaired attention, and stereotyped motor activity. Sagging of the brain, caused by leakeage of the CSF, can cause lesions in the brainstem with stupor, gaze palsies, and cranial nerve palsies. The condition can be a risk factor for cerebral venous thrombosis because of slowing of the blood flow and distortion of the blood vessels. The clinical picture may well suggest the diagnosis, but the headache may possibly indicate a subarachnoid haemorrhage. However, MRI will help to confirm the diagnosis and to localize the site of the CSF leak. MRI myelograms are of particular value, but if they are equivocal a computed tomography myelogram should be performed. The leakage of CSF is due to a tear in the dura, most frequently where the spinal roots leave the subarachnoid space. If this does not heal with bedrest, an epidural blood patch or a percutaneous injection of fibrin glue may be needed. More information is required on long-term follow-up.

Idiopathic orthostatic hypotension treated with levodopa and MAO inhibitor: a preliminary report

PubMed Central

Sharpe, J.; Marquez-Julio, A.; Ashby, P.

1972-01-01

The clinical and pathophysiological features of a case of idiopathic orthostatic hypotension (Shy-Drager syndrome) are presented. Recent reports on the pathological findings in this condition indicate that there may be a defect in catecholamine synthesis in the pigmented brain stem nuclei and sympathetic ganglia similar to that in idiopathic parkinsonism. On this basis a new form of therapy using levodopa combined with MAO inhibition is derived. The results of a trial of this therapy, which produced improvements in both the hypotension and in the extrapyramidal features of the disease, are reported. PMID:5056115

Prehospital management and fluid resuscitation in hypotensive trauma patients admitted to Karolinska University Hospital in Stockholm.

PubMed

Talving, Peep; Pålstedt, Joakim; Riddez, Louis

2005-01-01

significant factors affecting outcome in the exact logistic regression analysis. The time interval at the scene of injury exceeded PHTLS guidelines. The vast majority of the hypotensive trauma patients were fluid-resuscitated on-scene regardless of the type, mechanism, or severity of injury. A predefined fluid resuscitation regimen is not employed in hypotensive trauma victims with different types of injuries. The outcome was worsened by male gender, progressive age, and ISS > 20 in the exact multiple regression analysis.

New fluoroprostaglandin F(2alpha) derivatives with prostanoid FP-receptor agonistic activity as potent ocular-hypotensive agents.

PubMed

Nakajima, Tadashi; Matsugi, Takeshi; Goto, Wakana; Kageyama, Masaaki; Mori, Nobuaki; Matsumura, Yasushi; Hara, Hideaki

2003-12-01

To find new prostanoid FP-receptor agonists possessing potent ocular-hypotensive effects with minimal side effects, we evaluated the agonistic activities of newly synthesized prostaglandin F(2alpha) derivatives for the prostanoid FP-receptor both in vitro and in vivo. The iris constrictions induced by the derivatives and their effects on melanin content were examined using cat isolated iris sphincters and cultured B16 melanoma cells, respectively. The effects of derivative ester forms on miosis and intraocular pressure (IOP) were evaluated in cats and cynomolgus monkeys, respectively. Of these derivatives, 6 out of 12 compounds were more potent iris constrictors, with EC(50) values of 0.6 to 9.4 nM, than a carboxylic acid of latanoprost (EC(50)=13.6 nM). A carboxylic acid of latanoprost (100 microM) significantly increased the melanin content of cultured B16 melanoma cells, but some 15,15-difluoro derivatives, such as AFP-157 and AFP-172, did not. Topically applied AFP-168, AFP-169 and AFP-175 (isopropyl ester, methyl ester and ethyl ester forms, respectively, of AFP-172) induced miosis in cats more potently than latanoprost. AFP-168 (0.0005%) reduced IOP to the same extent as 0.005% latanoprost (for at least 8 h). These findings indicate that 15,15-difluoroprostaglandin F(2alpha) derivatives, especially AFP-168, have more potent prostanoid FP-receptor agonistic activities than latanoprost. Hence, AFP-168 may be worthy of further evaluation as an ocular-hypotensive agent.

[Headhache secondary to intracranial hypotension in a Lumbar Spinal Stenosis Surgery].

PubMed

Hidalgo-Mendía, Begoña; Angulo-Tabernero, Marina; Jaroid-Audes, Ricardo; Untoria-Agustín, Carmen; Rivero-Zelada, David

2016-01-01

Intracraneal hypotension headache is a well known syndrome in neurosurgery practice. In most cases cerebrospinal fluid leaks are caused by medical interventions, such as lumbar puncture, peridural anesthesia and surgical interventions on the spine. Clinical symptoms tipically show orthostatic headache that resolves in supine position, and other symptoms like neck tightness, vertigo and diplopia. RMI diagnostic confirms paquimeningeal enhancement and subdural hygromas. Conservative treatment usually includes bed resting, hydratation and administration of caffeine or glucocorticoids, resolving spontaneously in one to four months. The importance of the diagnosis lies in the differential diagnosis with other causes of headache, as symptomatic limiting factor in the rehabilitation of the patient and the same favorable prognosis.

Subclinical decelerations during developing hypotension in preterm fetal sheep after acute on chronic lipopolysaccharide exposure

PubMed Central

Lear, Christopher A.; Davidson, Joanne O.; Galinsky, Robert; Yuill, Caroline A.; Wassink, Guido; Booth, Lindsea C.; Drury, Paul P.; Bennet, Laura; Gunn, Alistair J.

2015-01-01

Subclinical (shallow) heart rate decelerations occur during neonatal sepsis, but there is limited information on their relationship with hypotension or whether they occur before birth. We examined whether subclinical decelerations, a fall in fetal heart rate (FHR) that remained above 100 bpm, were associated with hypotension in preterm fetal sheep exposed to lipopolysaccharide (LPS). Chronically-instrumented fetal sheep at 0.7 gestation received continuous low-dose LPS infusions (n = 15, 100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h) or saline (n = 8). Boluses of 1 μg LPS or saline were given at 48 and 72 h. FHR variability (FHRV) was calculated, and sample asymmetry was used to assess the severity and frequency of decelerations. Low-dose LPS infusion did not affect FHR. After the first LPS bolus, 7 fetuses remained normotensive, while 8 developed hypotension (a fall in mean arterial blood pressure of ≥5 mmHg). Developing hypotension was associated with subclinical decelerations, with a corresponding increase in sample asymmetry and FHRV (p < 0.05). The second LPS bolus was associated with similar but attenuated changes in FHR and blood pressure (p < 0.05). In conclusion, subclinical decelerations are not consistently seen during prenatal exposure to LPS, but may be a useful marker of developing inflammation-related hypotension before birth. PMID:26537688

Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

PubMed

Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

2016-04-01

Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

Effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment: the DANTE Study Leiden.

PubMed

Moonen, Justine E F; Foster-Dingley, Jessica C; de Ruijter, Wouter; van der Grond, Jeroen; de Craen, Anton J M; van der Mast, Roos C

2016-03-01

the relationship between antihypertensive medication and orthostatic hypotension in older persons remains ambiguous, due to conflicting observational evidence and lack of data of clinical trials. to assess the effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment. a total of 162 participants with orthostatic hypotension were selected from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study. This randomised clinical trial included community-dwelling participants aged ≥75 years, with mild cognitive impairment, using antihypertensive medication and without serious cardiovascular disease. Participants were randomised to discontinuation or continuation of antihypertensive treatment (ratio 1:1). Orthostatic hypotension was defined as a drop of at least 20 mmHg in systolic blood pressure and/or 10 mmHg in diastolic blood pressure on standing from a seated position. Outcome was the absence of orthostatic hypotension at 4-month follow-up. Relative risks (RR) were calculated by intention-to-treat and per-protocol analyses. at follow-up, according to intention-to-treat analyses, of the 86 persons assigned to discontinuation of antihypertensive medication, 43 (50%) were free from orthostatic hypotension, compared with 29 (38%) of the 76 persons assigned to continuation of medication [RR 1.31 (95% confidence interval (CI) 0.92-1.87); P = 0.13]. Per-protocol analysis showed that recovery from orthostatic hypotension was significantly higher in persons who completely discontinued all antihypertensive medication (61%) compared with the continuation group (38%) [RR 1.60 (95% CI 1.10-2.31); P = 0.01]. in older persons with mild cognitive impairment and orthostatic hypotension receiving antihypertensive medication, discontinuation of antihypertensive medication may increase the probability of recovery from orthostatic hypotension. © The Author 2016. Published by Oxford

Epidemiology, Diagnosis, and Management of Neurogenic Orthostatic Hypotension

PubMed Central

Palma, Jose-Alberto; Kaufmann, Horacio

2017-01-01

Background Orthostatic hypotension (OH) is a sustained fall in blood pressure on standing which can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity and mortality and leads to a significant number of hospital admissions particularly in the elderly (233 per 100,000 patients over 75 years of age in the US). OH can be due to volume depletion, blood loss, large varicose veins, medications, or due to defective activation of sympathetic nerves and reduced norepinephrine release upon standing (i.e., neurogenic OH). Methods and Findings Literature review. Neurogenic OH is a frequent and disabling problem in patients with synucleinopathies such as Parkinson disease, multiple system atrophy, and pure autonomic failure, and is commonly associated with supine hypertension. Several pharmacological and non-pharmacological therapeutic options are available. Conclusions Here we review the epidemiology, diagnosis, and management of neurogenic OH, and provide an algorithm for its treatment emphasizing the importance of removing aggravating factors, implementing non-pharmacologic measures, and selecting appropriate pharmacological treatments. PMID:28713844

Report on 50 cases of severe acute hypotension at donor plasmaphereses: treatment and course.

PubMed

Evers, Josef; Schreiber, George B; Taborski, Uwe

2017-05-29

This paper reports our experience in 50 cases with severe hypotensive reactions at plasma donations (synonymous with donor plasmaphereses). Plasma donors who developed a severe acute hypotensive reaction at donor plasmapheresis, and were treated by placing the donor in the Trendelenburg position and rapid infusion of 1,000 mL saline were investigated. Plasmaphereses were performed with the Haemonetics® plasma collecting system 2 (PCS2). The results were analyzed using Excel. We observed 50 severe hypotensive reactions in plasma donors. The average systolic and diastolic blood pressures (SBP, DBP) were 128/75 mmHg - and heart rates were 78 beats/min (B/M) before plasmaphereses, 83/56 mmHg - 60 B/M at the event, and after treatment 119/71 mmHg - 69 B/M at the time of discharge. The volume of collected plasma was 602 ± 240 mL including anticoagulant (AC). The time until the event was 45 ± 20 minutes. With treatment 49 ± 18 minutes after the event all plasma donors had normal blood pressures and heart rates and could safely leave the center. Treatment by placing the donor in the Trendelenburg position and rapid infusion of 1,000 mL saline appears to be an effective procedure for resolving severe acute hypotension associated with donor plasmaphereses.

Hypotensive effect of aqueous extract of jamu antiatherosclerosis in male rats

NASA Astrophysics Data System (ADS)

Tristantini, Dewi; Amelinda, Kelly

2018-02-01

For many years, Averrhoa carambola L leaves, Mimusops elengi Linn leaves and Curcuma xanthorrhiza Roxb are used empirically in Indonesian traditional medicine to treat hypertension. This study was conducted to investigate the hypotensive effect of Averrhoa carambola L leaves, Mimusops elengi Linn leaves, and Curcuma xanthorrhiza Roxb extract (Jamu Antiatherosclerosis) in hypertensive induced rats. The effect of aqueous extract of jamu antiatherosclerosis on diastolic and systolic blood pressure was determined in sodium chloride induced rats. Twenty-four male rats weighted 160-200 g were randomly divided into 6 groups of 4 rats. The groups are consisting of normal control (without treatment), positive control (induced and given captopril 1.35 mg / 200 g body weight of rats), negative control (induced and standard feed), dosage controls (induced and given the extract of jamu antiatherosclerosis) each group with 3 different doses. The composition is dose I (13.2 mg / 200 g body weight of rats), dose II (26.4 mg / 200 g body weight of rats ml) and dose III (52.8 mg / 200 g body weight of rats). Blood pressure were measured via non-invasive blood pressure. The blood pressure was decreased in all dose. However, dose III has the highest blood pressure reducing effect that is 29.42 mmHg or 25.14% for diastolic blood pressure and 34.58 mmHg or 22.03% for systolic blood pressure. This performance equals to 91.15% and 93.56% of captopril activity in decreasing diastolic and systolic blood pressure. The aqueous extract has blood pressure lowering property that can be used as antihypertension herbal medicine.

Vasorelaxant and Hypotensive Effects of an Ethanolic Extract of Eulophia macrobulbon and Its Main Compound 1-(4′-Hydroxybenzyl)-4,8-Dimethoxyphenanthrene-2,7-Diol

PubMed Central

Wisutthathum, Sutthinee; Chootip, Krongkarn; Martin, Hélène; Ingkaninan, Kornkanok; Temkitthawon, Prapapan; Totoson, Perle; Demougeot, Céline

2018-01-01

Background: Ethnopharmacological studies demonstrated the potential for Eulophia species to treat inflammation, cancer, and cardio-metabolic diseases. The aim of the study was to investigate the vasorelaxant effect of ethanolic Eulophia macrobulbon (EM) extract and its main phenanthrene on rat isolated mesenteric artery and to investigate the hypotensive effect of EM. Methods: The vasorelaxant effects of EM extract or phenanthrene and the underlying mechanisms were evaluated on second-order mesenteric arteries from Sprague Dawley rats. In addition, the acute hypotensive effect was evaluated in anesthetized rats infused with cumulative concentrations of the EM extract. Results: Both EM extract (10-4–1 mg/ml) and phenanthrene (10-7–10-4 M) relaxed endothelium-intact arteries, an effect that was partly reduced by endothelium removal (p < 0.001). A significant decrease in the relaxant effect of the extract and the phenanthrene was observed with L-NAME and apamin/charybdotoxin in endothelium-intact vessels, and with iberiotoxin in denuded vessels. SNP (sodium nitroprusside)-induced relaxation was significantly enhanced by EM extract and phenanthrene. By contrast, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one), 4-aminopyridine and glibenclamide (endothelium-denuded vessels) and indomethacin (endothelium-intact vessels) had no effect. In calcium-free solution, both the EM extract and phenanthrene inhibited extracellular Ca2+-induced contraction in high KCl and phenylephrine (PE) pre-contracted rings. They also inhibited the intracellular Ca2+ release sensitive to PE. The acute infusion of EM extract (20 and 70 mg/kg) induced an immediate and transient dose-dependent hypotensive effect. Conclusion: The ethanolic extract of EM tubers and its main active compound, 1-(4′-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (phenanthrene) induced vasorelaxant effects on rat resistance vessels, through pleiotropic effects including endothelium-dependent effects (NOS

Stress-induced EGFR trafficking: mechanisms, functions, and therapeutic implications

PubMed Central

Tan, Xiaojun; Lambert, Paul F.; Rapraeger, Alan C.; Anderson, Richard A.

2016-01-01

Epidermal growth factor receptor (EGFR) has fundamental roles in normal physiology and in cancer, making it a rational target for cancer therapy. Surprisingly, however, inhibitors that target canonical, ligand-stimulated EGFR signaling have proven to be largely ineffective in treating many EGFR-dependent cancers. Recent evidence indicates that both intrinsic and therapy-induced cellular stress triggers robust, non-canonical pathways of ligand-independent EGFR trafficking and signaling, which provides cancer cells with a survival advantage and resistance to therapeutics. Here we review the mechanistic regulation of non-canonical EGFR trafficking and signaling, the pathological and therapeutic stresses that activate it, and discuss the implications of this pathway in clinical treatment of EGFR-overexpressing cancers. PMID:26827089

Pulse Rate and Transit Time Analysis to Predict Hypotension Events After Spinal Anesthesia During Programmed Cesarean Labor.

PubMed

Bolea, Juan; Lázaro, Jesús; Gil, Eduardo; Rovira, Eva; Remartínez, José M; Laguna, Pablo; Pueyo, Esther; Navarro, Augusto; Bailón, Raquel

2017-09-01

Prophylactic treatment has been proved to reduce hypotension incidence after spinal anesthesia during cesarean labor. However, the use of pharmacological prophylaxis could carry out undesirable side-effects on mother and fetus. Thus, the prediction of hypotension becomes an important challenge. Hypotension events are hypothesized to be related to a malfunctioning of autonomic nervous system (ANS) regulation of blood pressure. In this work, ANS responses to positional changes of 51 pregnant women programmed for a cesarean labor were explored for hypotension prediction. Lateral and supine decubitus, and sitting position were considered while electrocardiographic and pulse photoplethysmographic signals were recorded. Features based on heart rate variability, pulse rate variability (PRV) and pulse transit time (PTT) analysis were used in a logistic regression classifier. The results showed that PRV irregularity changes, assessed by approximate entropy, from supine to lateral decubitus, and standard deviation of PTT in supine decubitus were found as the combination of features that achieved the best classification results sensitivity of 76%, specificity of 70% and accuracy of 72%, being normotensive the positive class. Peripheral regulation and blood pressure changes, measured by PRV and PTT analysis, could help to predict hypotension events reducing prophylactic side-effects in the low-risk population.

Droxidopa for orthostatic hypotension: a systematic review and meta-analysis.

PubMed

Strassheim, Victoria; Newton, Julia L; Tan, Maw Pin; Frith, James

2016-10-01

The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent approvals in the United States. MEDLINE, EMBASE, PubMed, Cochrane Controlled Trials Register, Web of Science, ProQuest, and the WHO Clinical Trials Registry were searched. Studies were included if they randomized adults with orthostatic hypotension to droxidopa or to control, and outcomes related to symptoms, daily activity, blood pressure, or adverse events. Data were extracted independently by two reviewers. Risk of bias was judged against the Cochrane risk of bias tool and quality of evidence measured using Grading of Recommendations Assessment, Development and Evaluation criteria. A fixed-effects model was used for pooled analysis. Of 224 identified records, four studies met eligibility, with a pooled sample size of 494. Study duration was between 1 and 8 weeks. Droxidopa was effective at reducing dizziness [mean difference -0.97 (95% confidence interval -1.51, -0.42)], overall symptoms [-0.52 (-0.98, -0.06)] and difficulty with activity [-0.86 (-1.34, -0.38)]. Droxidopa was also effective at improving standing SBP [3.9 (0.1, 7.69)]. Rates of adverse events were similar between droxidopa and control groups, including supine hypertension [odds ratio 1.93 (0.87, 4.25)]. Droxidopa is well tolerated and effective at reducing the symptoms associated with neurogenic orthostatic hypotension without increasing the risk of supine hypertension. PROSPERO ID CRD42015024612.

Alanine increases blood pressure during hypotension

NASA Technical Reports Server (NTRS)

Conlay, L. A.; Maher, T. J.; Wurtman, R. J.

1990-01-01

The effect of L-alanine administration on blood pressure (BP) during haemorrhagic shock was investigated using anesthetized rats whose left carotid arteries were cannulated for BP measurement, blood removal, and drug administration. It was found that L-alanine, in doses of 10, 25, 50, 100, and 200 mg/kg, increased the systolic BP of hypotensive rats by 38 to 80 percent (while 100 mg/kg pyruvate increased BP by only 9.4 mmhg, not significantly different from saline). The results suggest that L-alanine might influence cardiovascular function.

Minoxidil for severe hypertension after failure of other hypotensive drugs.

PubMed Central

Devine, B L; Fife, R; Trust, P M

1977-01-01

Forty-four patients with severe hypertension who were resistant to treatment with more conventional hypotensive drugs or could not tolerate the side effects were treated with minoxidil, a potent peripheral vasodilator. A beta-blocking drug and a diuretic were used routinely to control, respectively, the tachycardia and fluid retention caused by minoxidil. During treatment the outpatient supine blood pressure fell from a mean of 221/134 mm Hg to 162/98 mm Hg. Eleven patients required additional or alternative hypotensive agents before blood pressure was adequately controlled. Side effects were minor, although the invariable hirsuties caused by minoxidil was unacceptable to three women. The possibility of cardiotoxic effects, raised by early studies in dogs, has not been excluded, and therefore this drug should be used only in patients with severe hypertension. In such patients minoxidil appears to be most effective. PMID:902045

Predicting the Occurrence of Hypotension in Stable Patients With Nonvariceal Upper Gastrointestinal Bleeding: Point-of-Care Lactate Testing.

PubMed

Ko, Byuk Sung; Kim, Won Young; Ryoo, Seung Mok; Ahn, Shin; Sohn, Chang Hwan; Seo, Dong Woo; Lee, Yoon-Seon; Lim, Kyoung Soo; Jung, Hwoon-Yong

2015-11-01

It is difficult to assess risk in normotensive patients with upper gastrointestinal bleeding. The aim of this study was to evaluate whether the initial lactate value can predict the in-hospital occurrence of hypotension in stable patients with acute nonvariceal upper gastrointestinal bleeding. Retrospective, observational, single-center study. Emergency department of a tertiary-care, university-affiliated hospital during a 5-year period. Medical records of 3,489 patients with acute upper gastrointestinal bleeding who were normotensive at presentation to the emergency department. We analyzed the ability of point-of-care testing of lactate at emergency department admission to predict hypotension development (defined as systolic blood pressure <90 mm Hg) within 24 hours after emergency department admission. None. Of the 1,003 patients with acute nonvariceal upper gastrointestinal bleeding, 157 patients experienced hypotension within 24 hours. Lactate was independently associated with hypotension development (odds ratio, 1.6; 95% CI, 1.4-1.7), and the risk of hypotension significantly increased as the lactate increased from 2.5-4.9 mmol/L (odds ratio, 2.2) to 5.0-7.4 mmol/L (odds ratio, 4.0) and to greater than or equal to 7.5 mmol/L (odds ratio, 39.2) (p<0.001). Lactate elevation (≥2.5 mmol/L) was associated with 90% specificity and an 84% negative predictive value for hypotension development. When the lactate levels were greater than 5.0 mmol/L, the specificity and negative predictive value increased to 98% and 87%, respectively. Point-of-care testing of lactate can predict in-hospital occurrence of hypotension in stable patients with acute nonvariceal upper gastrointestinal bleeding. However, subsequently, prospective validate research will be required to clarify this.

Diagnosing and treating neurogenic orthostatic hypotension in primary care.

PubMed

Kuritzky, Louis; Espay, Alberto J; Gelblum, Jeffrey; Payne, Richard; Dietrich, Eric

2015-01-01

In response to a change in posture from supine or sitting to standing, autonomic reflexes normally maintain blood pressure (BP) by selective increases in arteriovenous resistance and by increased cardiac output, ensuring continued perfusion of the central nervous system. In neurogenic orthostatic hypotension (NOH), inadequate vasoconstriction and cardiac output cause BP to drop excessively, resulting in inadequate perfusion, with predictable symptoms such as dizziness, lightheadedness and falls. The condition may represent a central failure of baroreceptor signals to modulate cardiovascular function, a peripheral failure of norepinephrine release from cardiovascular sympathetic nerve endings, or both. Symptomatic patients may benefit from both non-pharmacologic and pharmacologic interventions. Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the sympathomimetic prodrug midodrine, approved in 1996 for symptomatic orthostatic hypotension, and the norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson's disease, multiple system atrophy and pure autonomic failure). A wide variety of off-label options also have been described (e.g. the synthetic mineralocorticoid fludrocortisone). Because pressor agents may promote supine hypertension, NOH management requires monitoring of supine BP and also lifestyle measures to minimize supine BP increases (e.g. head-of-bed elevation). However, NOH has been associated with cognitive impairment and increases a patient's risk of syncope and falls, with the potential for serious consequences. Hence, concerns about supine hypertension - for which the long-term prognosis in patients with NOH is yet to be established - must sometimes be balanced by the need to address a patient's immediate risks.

Induced seismicity and implications for CO2 storage risk

NASA Astrophysics Data System (ADS)

Gerstenberger, M. C.; Nicol, A.; Bromley, C.; Carne, R.; Chardot, L.; Ellis, S. M.; Jenkins, C.; Siggins, T.; Viskovic, P.

2012-12-01

We provide an overview of a recently completed report for the IEA GHG that represents a comprehensive review of current research and observations in induced seismicity, its risk to successful completion of Carbon Capture and Storage (CCS) projects and potential mitigation measures. We focus on two topics: a meta-analysis of related data from multiple injection projects around the globe and the implications of these data for CCS induced seismicity risk management. Published data have been compiled from injection and extraction projects around the globe to examine statistical relationships between possible controlling factors and induced seismicity. Quality control of such observational earthquake data sets is crucial to ensure robust results and issues with bias and completeness of the data set will be discussed. Analyses of the available data support previous suggestions that the locations, numbers and magnitudes of induced earthquakes are dependent on a range of factors, including the injection rate, total injected fluid volume, the reservoir permeability and the proximity of pre-existing faults. Increases in the injection rates and total volume of fluid injected, for example, typically raise reservoir pressures and increase the likelihood of elevated seismicity rates and maximum magnitudes of induced earthquakes. The risks associated with induced seismicity at CCS sites can be reduced and mitigated using a systematic and structured risk management programme. While precise forecasts of the expected induced seismicity may never be possible, a thorough risk management procedure should include some level of knowledge of the possible behaviour of induced seismicity. Risk management requires estimates of the expected magnitude, number, location and timing of potential induced earthquakes. Such forecasts should utilise site specific observations together with physical and statistical models that are optimised for the site. Statistical models presently show the most

Patients' choice of portable folding chairs to reduce symptoms of orthostatic hypotension

NASA Technical Reports Server (NTRS)

Smit, A. A.; Wieling, W.; Opfer-Gehrking, T. L.; van Emmerik-Levelt, H. M.; Low, P. A.

1999-01-01

Patients with neurogenic orthostatic hypotension may use portable folding chairs to prevent or reduce symptoms of low blood pressure. However, a concomitant movement disorder may limit the use of these chairs in daily living. In this prospective study, 13 patients with orthostatic hypotension, balance disturbance associated with motor disability, or both examined three commercially available portable folding chairs. A questionnaire was used to document the characteristics in chair design that were relevant for satisfactory use to these patients. Armrests, seat width, and an adjustable sitting height were found to be important features of a portable folding chair. One chair was selected by 11 of 13 patients to fit most needs.

Activation of muscarinic receptors by a hydroalcoholic extract of Dicksonia sellowiana Presl. HooK (Dicksoniaceae) induces vascular relaxation and hypotension in rats.

PubMed

Rattmann, Yanna D; Crestani, Sandra; Lapa, Fernanda R; Miguel, Obdúlio G; Marques, Maria C A; da Silva-Santos, J Eduardo; Santos, Adair R S

2009-01-01

Dicksonia sellowiana (Presl.) Hook is a native plant from the Central and South Americas that contain high levels of polyphenols, antioxidant compounds involved in protection against inflammation, cancer and cardiovascular risk. A phytomedicinal preparation obtained from aerial parts of D. sellowiana is currently under clinical evaluation in Brazil against asthma, and has been associated with several other beneficial effects. This study demonstrates that a hydroalcoholic extract obtained from D. sellowiana leaves (HEDS) fully relax, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine. Moreover, administration of HEDS (10, 20 and 40 mg/kg, i.v.) in anaesthetized rats resulted in a strong but reversible hypotension. Aortic relaxation induced by HEDS was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylate cyclase inhibitor ODQ. In addition, this effect was partially inhibited by indomethacin (a cyclooxygenase inhibitor) and KT 5730 (a PKA inhibitor). The potassium channels blockade by either tetraethylammonium or charybdotoxin also resulted in a potent inhibition of HEDS-induced aortic relaxation, whereas apamine only slightly reduced it. In addition HEDS-induced relaxation was unchanged by 4-amynopiridine and glibenclamide. The selective muscarinic receptor antagonist atropine counteracted both aortic relaxation and blood pressure reduction generated by HEDS. Experiments using HPLC revealed the presence of high amounts of phenolic compounds in this extract. Taken together, our results reveal that the D. sellowiana possess substances with both in vivo and in vitro activities and that the vascular effect of HEDS involves activation of muscarinic receptors, stimulation of the nitric oxide pathway and opening of calcium-activated potassium channels.

IRREVERSIBLE HEMORRHAGIC SHOCK IN GERMFREE RATS

PubMed Central

Zweifach, B. W.; Gordon, H. A.; Wagner, M.; Reyniers, J. A.

1958-01-01

Evidence has been provided that a state of irreversible hemorrhagic shock can be induced in a bacteria-free environment in rats reared under germfree conditions. The response to bleeding, the duration of the hypotensive episode and the pathological changes were the same in the germfree and in normal stock rats. The findings are interpreted as evidence opposed to the concept that bacteria or bacterial products are implicated, as primary factors, in the pathogenicity of shock. PMID:13513911

Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants

PubMed Central

Ng, P; Lee, C; Lam, C; Ma, K; Fok, T; Chan, I; Wong, E

2004-01-01

Objectives: A proportion of preterm, very low birthweight (VLBW, < 1500 g) infants may show inadequate adrenal response to stress in the immediate postnatal period. The human corticotrophin releasing hormone (hCRH) stimulation test was used to: (a) determine the relation between pituitary-adrenal response and systemic blood pressure in these infants; (b) characterise the endocrinological features of transient adrenocortical insufficiency of prematurity (TAP). Study design: A total of 226 hCRH tests were performed on 137 VLBW infants on day 7 and 14 of life in a tertiary neonatal centre. Results: Basal, peak, and incremental rise in serum cortisol (ΔCort0–30) on day 7 were associated significantly with the lowest systolic, mean, and diastolic blood pressures recorded during the first two weeks of life (r > 0.25, p < 0.005). These cortisol concentrations also correlated significantly but negatively with the maximum and total cumulative dose of dopamine (r > -0.22, p < 0.02), dobutamine (r > -0.18, p < 0.04), and adrenaline (r > -0.26, p < 0.004), total volume of crystalloid (r > -0.22, p < 0.02), and duration of inotrope treatment (r > -0.25, p < 0.006). Multivariate regression analysis of significant factors showed that the lowest systolic, mean, and diastolic blood pressures remained independently associated with serum cortisol (basal, peak, and ΔCort0–30) on day 7. Hypotensive infants requiring inotropes (group 2) were significantly less mature and more sick than infants with normal blood pressure (group 1). The areas under the ACTH response curves were significantly greater in group 2 than in group 1, on both day 7 (p = 0.004) and day 14 (p = 0.004). In contrast, the area under the cortisol response curve was significantly greater in group 1 than in group 2 on day 7 (p = 0.001), but there was no significant difference between the two groups on day 14. In addition, serum cortisol at the 50th centile in hypotensive infants had high specificity and positive

Predictors of Arterial Blood Pressure Control During Deliberate Hypotension with Sodium Nitroprusside in Children

PubMed Central

Spielberg, David R; Barrett, Jeffrey S; Hammer, Gregory B; Drover, David R; Reece, Tammy; Cohane, Carol A; Schulman, Scott R

2014-01-01

Background Sodium nitroprusside (SNP) is used to decrease arterial blood pressure (BP) during certain surgical procedures. There are limited data regarding efficacy of BP control with SNP. There are no data on patient and clinician factors that affect BP control. We evaluated the dose-response relationship of SNP in infants and children undergoing major surgery and performed a quantitative assessment of BP control. Methods One hundred fifty-three subjects at 7 sites received a blinded infusion followed by open-label SNP during operative procedures requiring controlled hypotension. SNP was administered by continuous infusion and titrated to maintain BP control (mean arterial BP [MAP] within ±10% of clinician-defined target). BP was recorded using an arterial catheter. Statistical Process Control methodology was used to quantify BP control. A multivariable model assessed the effects of patient and procedural factors. Results BP was controlled an average 45.4% (SD 23.9%, 95% CI 41.5%-49.18%) of the time. Larger changes in infusion rate were associated with worse BP control (7.99% less control for 1 mcg•kg−•min− increase in average titration size, p=0.0009). A larger difference between a patient's baseline and target MAP predicted worse BP control (0.93% worse control per 1 mmHg increase in MAP difference, p=0.0013). Both effects persisted in multivariable models. Conclusions : SNP was effective in reducing BP. However, BP was within the target range less than half of the time. No clinician or patient factors were predictive of BP control, although two inverse relationships were identified. These relationships require additional study and may be best coupled with exposure-response modeling to propose improved dosing strategies when using SNP for controlled hypotension in the pediatric population. PMID:25099924

Predictors of arterial blood pressure control during deliberate hypotension with sodium nitroprusside in children.

PubMed

Spielberg, David R; Barrett, Jeffrey S; Hammer, Gregory B; Drover, David R; Reece, Tammy; Cohane, Carol A; Schulman, Scott R

2014-10-01

Sodium nitroprusside (SNP) is used to decrease arterial blood pressure (BP) during certain surgical procedures. There are limited data regarding efficacy of BP control with SNP. There are no data on patient and clinician factors that affect BP control. We evaluated the dose-response relationship of SNP in infants and children undergoing major surgery and performed a quantitative assessment of BP control. One hundred fifty-three subjects at 7 sites received a blinded infusion followed by open-label SNP during operative procedures requiring controlled hypotension. SNP was administered by continuous infusion and titrated to maintain BP control (mean arterial BP [MAP] within ±10% of clinician-defined target). BP was recorded using an arterial catheter. Statistical process control methodology was used to quantify BP control. A multivariable model assessed the effects of patient and procedural factors. BP was controlled an average 45.4% (SD 23.9%; 95% CI, 41.5%-49.18%) of the time. Larger changes in infusion rate were associated with worse BP control (7.99% less control for 1 μg·kg·min increase in average titration size, P = 0.0009). A larger difference between a patient's baseline and target MAP predicted worse BP control (0.93% worse control per 1-mm Hg increase in MAP difference, P = 0.0013). Both effects persisted in multivariable models. SNP was effective in reducing BP. However, BP was within the target range less than half of the time. No clinician or patient factors were predictive of BP control, although 2 inverse relationships were identified. These relationships require additional study and may be best coupled with exposure-response modeling to propose improved dosing strategies when using SNP for controlled hypotension in the pediatric population.

Controlled hypotension for middle ear surgery: a comparison between remifentanil and magnesium sulphate.

PubMed

Ryu, J-H; Sohn, I-S; Do, S-H

2009-10-01

This prospective, randomized study was designed to compare remifentanil and magnesium sulphate during middle ear surgery in terms of postoperative pain and other complications. Eighty patients undergoing middle ear surgery were enrolled in the study. Patients were randomized into two groups of 40 to receive remifentanil (Group R) or magnesium sulphate (Group M) infusion. Propofol 2 mg kg(-1) was administered to induce anaesthesia, which was maintained using sevoflurane. Group R received a continuous infusion of remifentanil titrated between 3 and 4 ng ml(-1) using target-controlled infusion, whereas Group M received an i.v. magnesium sulphate bolus of 50 mg kg(-1) followed by a 15 mg kg(-1) h(-1) continuous infusion to maintain a mean arterial pressure (MAP) between 60 and 70 mm Hg. Haemodynamic variables, surgical conditions, postoperative pain, and adverse effects, such as postoperative nausea and vomiting (PONV) and shivering, were recorded. Controlled hypotension was well maintained in both groups. MAP and heart rate were higher in Group R than in Group M after operation. Surgical conditions were not different between the two groups. Postoperative pain scores were significantly lower in Group M than in Group R (P<0.05). Seventeen patients in Group R (43%) and seven patients in Group M (18%) developed PONV (P=0.01). Both magnesium sulphate and remifentanil when combined with sevoflurane provided adequate controlled hypotension and proper surgical conditions for middle ear surgery. However, patients administered magnesium sulphate had a more favourable postoperative course with better analgesia and less shivering and PONV.

[Effects of the renal blood flow at different levels by transcutaneous electrical acupoint stimulation combined general anesthesia induced controlled hypotension].

PubMed

Fang, Jian-Qiao; Zhang, Le-Le; Shao, Xiao-Mei

2012-11-01

To observe the intervention of transcutaneous electrical acupoint stimulation (TEAS) on the renal blood flow at different levels of mean arterial pressure (MAP) in controlled hypotension. Forty-two male beagle dogs were randomly divided into seven groups, i. e., the general anesthesia group, the 50% controlled group, the 40% controlled group, the 30% controlled group, the 50% experimental group, the 40% experimental group, and the 30% experimental group, 6 in each group. Beagles in the general anesthesia group were not treated with controlled hypotension, and the target MAP was achieved in those of the rest groups and maintained for 60 min. In the experimental groups, TEAS was applied to bilateral Hegu (LI4), Zusanli (ST36), Sanyinjiao (SP6), and Quchi (LI11) at 2/100 Hz with the stimulation strength of (4 +/- 1) mA starting from the stability of their physiological conditions to 60 min of maintaining the target MAP level. The changes of the renal blood flow were monitored at different time points using laser Doppler. From starting pressure control to the target MAP level, the renal blood flow was significantly lower in the 30% controlled group than in the general anesthesia group and the basic level of the same group (P < 0.05), while there was no obvious change in the 30% experimental group. In maintaining the blood pressure, the renal blood flow was significantly lower in the 50% controlled group, the 40% controlled group, the 30% controlled group, and the 30% experimental group than in the general anesthesia group (P < 0.05), while there was no obvious change in the 50% experimental group or the 40% experimental group. By the end of blood pressure recovery, the renal blood flow restored to the basic level in the 50% controlled group, the 50% experimental group, and the 40% experimental group (P > 0.05), while it was not restored to the basic level in the 40% controlled group, the 30% controlled group, and the 30% experimental group (P < 0.05). TEAS combined

Forewarning of hypotensive events using a Bayesian artificial neural network in neurocritical care.

PubMed

Donald, Rob; Howells, Tim; Piper, Ian; Enblad, P; Nilsson, P; Chambers, I; Gregson, B; Citerio, G; Kiening, K; Neumann, J; Ragauskas, A; Sahuquillo, J; Sinnott, R; Stell, A

2018-05-24

Traumatically brain injured (TBI) patients are at risk from secondary insults. Arterial hypotension, critically low blood pressure, is one of the most dangerous secondary insults and is related to poor outcome in patients. The overall aim of this study was to get proof of the concept that advanced statistical techniques (machine learning) are methods that are able to provide early warning of impending hypotensive events before they occur during neuro-critical care. A Bayesian artificial neural network (BANN) model predicting episodes of hypotension was developed using data from 104 patients selected from the BrainIT multi-center database. Arterial hypotension events were recorded and defined using the Edinburgh University Secondary Insult Grades (EUSIG) physiological adverse event scoring system. The BANN was trained on a random selection of 50% of the available patients (n = 52) and validated on the remaining cohort. A multi-center prospective pilot study (Phase 1, n = 30) was then conducted with the system running live in the clinical environment, followed by a second validation pilot study (Phase 2, n = 49). From these prospectively collected data, a final evaluation study was done on 69 of these patients with 10 patients excluded from the Phase 2 study because of insufficient or invalid data. Each data collection phase was a prospective non-interventional observational study conducted in a live clinical setting to test the data collection systems and the model performance. No prediction information was available to the clinical teams during a patient's stay in the ICU. The final cohort (n = 69), using a decision threshold of 0.4, and including false positive checks, gave a sensitivity of 39.3% (95% CI 32.9-46.1) and a specificity of 91.5% (95% CI 89.0-93.7). Using a decision threshold of 0.3, and false positive correction, gave a sensitivity of 46.6% (95% CI 40.1-53.2) and specificity of 85.6% (95% CI 82.3-88.8). With a decision threshold of 0

Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dumortier, Jerome; Streblow, Daniel N.; Moses, Ashlee V.

2008-07-01

Human cytomegalovirus (HCMV) is implicated in the acceleration of a number of vascular diseases including transplant vascular sclerosis (TVS), the lesion associated with chronic rejection (CR) of solid organ transplants. Although the virus persists in the allograft throughout the course of disease, few cells are directly infected by CMV. This observation is in contrast to the global effects that CMV has on the acceleration of TVS/CR, suggesting that CMV infection indirectly promotes the vascular disease process. Recent transcriptome analysis of CMV-infected heart allografts indicates that the virus induces cytokines and growth factors associated with angiogenesis (AG) and wound healing (WH),more » suggesting that CMV may accelerate TVS/CR through the induction and secretion of AG/WH factors from infected cells. We analyzed virus-free supernatants from HCMV-infected cells (HCMV secretomes) for growth factors, by mass spectrometry and immunoassays, and found that the HCMV secretome contains over 1,000 cellular proteins, many of which are involved in AG/WH. Importantly, functional assays demonstrated that CMV but not herpes simplex virus secretomes not only induce AG/WH but also promote neovessel stabilization and endothelial cell survival for 2 weeks. These findings suggest that CMV acceleration of TVS occurs through virus-induced growth factors and cytokines in the CMV secretome.« less

Burr hole drainage for complicated spontaneous intracranial hypotension syndrome.

PubMed

Liu, Yu-Fang; Lin, Hung-Lin; Cho, Der-Yang; Chen, Chun-Chung; Lo, Yu-Chien; Chiou, Shang-Ming

2008-09-01

Spontaneous intracranial hypotension is a potentially severe condition that is caused by continuous cerebrospinal fluid leakage. Clinically, most patients have a benign course and the condition remits after conservative management. We report two consecutive patients who presented with acute expansion of subdural collection and disturbed consciousness. Both patients recovered completely after undergoing burr hole drainage.

[Experimental study on ocular hypotensive efficacy of parenteral metoprolol].

PubMed

Onishchenko, A L; Kolbasko, A V; Safronova, M A; Tarash, O S; Dimaksyan, M V

2015-01-01

to evaluate ocular hypotensive efficacy of parenteral metoprolol in an experiment. A total of 3 series of experiments on 24 rabbits were performed. The first series involved a single subconjunctival injection of 0.3 mg of metoprolol in the right eye, while the left served as a control. During the second series the rabbits received 0.5 mg of metoprolol intramuscularly. The third series also implied a subconjunctival injection of 0.3 mg of metoprolol in the right eye, however, supplemented with timolol 0.5% instilled in the left. In all rabbits tonometry was performed before the injection and then in 30 min, 1, 2, 3, 6, 8, and 24 hours. Biomicroscopy and ophthalmoscopy were also performed before and 1, 3, and 7 days after the injection. The maximum reduction (down to 30% from the baseline) of intraocular pressure (IOP) was registered in intramuscular metoprolol rabbits. Subconjunctival metoprolol was associated with a faster and more pronounced decrease in IOP as compared to timolol instillations. In case of local or systemic parenteral administration the hypotensive effect of metoprolol lasts for more than a day.

The effect of permissive hypotension in combined traumatic brain injury and blunt abdominal trauma: an experimental study in swines.

PubMed

Vrettos, T; Poimenidi, E; Athanasopoulos, P; Balasis, S; Karagiorgos, N; Siklis, T; Gatzounis, G; Fligkou, F

2016-01-01

Optimal hemodynamic resuscitation strategy of the trauma patient with uncontrolled hemorrhage and severe head injury in the pre-hospital setting remains a special challenge. Permissive hypotension prior to definite surgical haemostasis promotes coagulation, decreases blood loss and favors survival. However, hypotension is associated with poor outcome in severe head injury. The purpose of this experimental animal study was to assess the impact of permissive hypotension on survival, hemodynamic profile and brain oxygenation parameters before and/or after definite surgical haemostasis. Six-week-old pigs (n=12) underwent general anesthesia and brain injury was produced by the fluid percussion model. Animals were instrumented to measure hemodynamic parameters and cerebral blood flow. All animals (n=12) were subjected to laparotomy and a surgical knot was placed through the abdominal aorta wall. Uncontrolled hemorrhage was simulated by pulling out the intentionally left protruding free ends of the suture (goal MAP=30 mmHg). Animals were randomly divided into two groups; group A (n=6) was subjected to aggressive fluid resuscitation (goal SAP >80 mmHg) and group B (n=6) was left hypotensive (permissive hypotension). Animals who survived one hour of hypotensive shock underwent definite surgical haemostasis and were resuscitated for one hour. We measured survival, hemodynamic and brain oxygenation parameters at different time points before and after surgical haemostasis. All animals from Group A and 50% from Group B died before surgical haemostasis. In surviving animals (Group B, 50%, p=0.033), MAP, CO, rCBF, SjO2 and AVDO2 were restored to pre-procedural levels. Permissive hypotension by delaying fluid resuscitation up to definite surgical haemostasis improves survival, hemodynamics and allows restoration of cerebral oxygenation in severe head injury.

Effect of physical countermaneuvers on orthostatic hypotension in familial dysautonomia.

PubMed

Tutaj, Marcin; Marthol, Harald; Berlin, Dena; Brown, Clive M; Axelrod, Felicia B; Hilz, Max J

2006-01-01

Familial dysautonomia (FD) patients frequently experience debilitating orthostatic hypotension. Since physical countermaneuvers can increase blood pressure (BP) in other groups of patients with orthostatic hypotension, we evaluated the effectiveness of countermaneuvers in FD patients. In 17 FD patients (26.4 +/- 12.4 years, eight female), we monitored heart rate (HR), blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR) and calf volume while supine, during standing and during application of four countermaneuvers: bending forward, squatting, leg crossing, and abdominal compression using an inflatable belt. Countermaneuvers were initiated after standing up,when systolic BP had fallen by 40mmHg or diastolic BP by 30mmHg or presyncope had occurred. During active standing, blood pressure and TPR decreased, calf volume increased but CO remained stable. Mean BP increased significantly during bending forward (by 20.0 (17 - 28.5) mmHg; P = 0.005) (median (25(th) - 75(th) quartile)), squatting (by 50.8 (33.5 - 56) mmHg; P = 0.002), and abdominal compression (by 5.8 (-1 - 34.7) mmHg; P = 0.04) - but not during leg-crossing. Squatting and abdominal compression also induced a significant increase in CO (by 18.1 (-1.3 - 47.9) % during squatting (P = 0.02) and by 7.6 (0.4 - 19.6) % during abdominal compression (P=0.014)). HR did not change significantly during the countermaneuvers. TPR increased significantly only during squatting (by 37.2 (11.8 - 48.2) %; P = 0.01). However, orthopedic problems or ataxia prevented several patients from performing some of the countermaneuvers. Additionally, many patients required assistance with the maneuvers. Squatting, bending forward and abdominal compression can improve orthostatic BP in FD patients, which is achieved mainly by an increased cardiac output. Squatting has the greatest effect on orthostatic blood pressure in FD patients. Suitability and effectiveness of a specific countermaneuver depends on the orthopedic

Effects of Preoperative Serotonin-Receptor-Antagonist Administration in Spinal Anesthesia-Induced Hypotension: A Randomized, Double-blind Comparison Study of Ramosetron and Ondansetron.

PubMed

Shin, Hyun-Jung; Choi, Eun-Su; Lee, Gwan-Woo; Do, Sang-Hwan

2015-01-01

The adverse effects of spinal anesthesia (SA) include arterial hypotension and bradycardia. The aim of this study was to compare the effects of 2 type 3 serotonin receptor antagonists in SA-induced adverse effects. Specifically, we assessed whether ramosetron was more effective than ondansetron in reducing SA-induced decreases in blood pressure (BP) and heart rate (HR). A total of 117 patients undergoing orthopedic surgery and receiving SA were intravenously administered 0.3 mg of ramosetron (n = 39, group R), 4 mg of ondansetron (n = 39, group O4), or 8 mg of ondansetron (n = 39, group O8). Systolic BP (SBP), diastolic BP (DBP), mean BP (MBP), HR, and the lowest SBP, DBP, MBP, and HR values were measured preoperatively (baseline) and intraoperatively. The incidence of postoperative nausea and vomiting, the need for rescue antiemetics, the amount of patient-controlled analgesia consumption, and pain score in the first 48 hours after surgery were determined. Baseline values did not significantly differ among the 3 groups. After SA, SBP, DBP, MBP, and HR were lower than their baseline values in all 3 groups. The differences between the baseline and the lowest values were significantly less in group R than in groups O4 and O8 with respect to SBP (P < 0.001), DBP (P = 0.001), and MBP (P < 0.001) less in group R than in group O4 with respect to HR (P = 0.032). Intergroup differences were not significant for postoperative nausea and vomiting, the need for rescue antiemetics, patient-controlled analgesia consumption, or pain score. The administration of ramosetron (0.3 mg) significantly attenuated the SA-induced decrease in BP compared with 4 or 8 mg of ondansetron and HR compared with 4 mg of ondansetron.

Pharmacological observations on the hypotensive action of extracts of teleost fish urophyses (urotensin I) in the rat

PubMed Central

Lederis, K.; Medaković, M.

1974-01-01

1 Intravenous injections of urotensin I regularly caused a long-lasting, dose-related, lowering of blood pressure and an increase in heart rate in conscious rats, or a reduction in perfusion pressure in the isolated hind limb of the rat. 2 After subcutaneous administration, the hypotensive effect of urotensin I was greater in extent and in duration (> 24 hours). 3 Anaesthesia with ether, chloralose, pentobarbitone and thiobarbitone caused a decrease in blood pressure and only slightly diminished the hypotensive effect of urotensin. 4 Mecamylamine, hexamethonium, atropine, phenoxybenzamine, propranolol and diphenhydramine did not alter the effect of urotensin in conscious rats or in the isolated hind limb, although the effects of the respective agonists, i.e. nicotine, acetylcholine, noradrenaline, isoprenaline and histamine were inhibited. 5 In conscious rats, pressor effects of adrenaline, noradrenaline, nicotine and angiotensin II, and depressor effects of acetylcholine and bradykinin, were decreased or inhibited, whereas the hypotensive effect of phenoxybenzamine was potentiated by previous administration of urotensin I. Carotid occlusion reflex was partially inhibited by lower doses of urotensin and abolished by higher doses in rats lightly anaesthetized with chloralose. Urotensin elicited postural hypotension in rats anaesthetized with pentobarbitone. 6 The increase in heart rate produced by urotensin was not affected by phenoxybenzamine, but was abolished by propranolol or ganglion blocking agents (mecamylamine or hexamethonium). 7 It is concluded that urotensin elicits hypotension in the rat by a direct dilatory action on the resistance vessels causing a simultaneous reflex tachycardia. PMID:4375526

[Comparison of metaraminol, phenylephrine and ephedrine in prophylaxis and treatment of hypotension in cesarean section under spinal anesthesia].

PubMed

Aragão, Fábio Farias de; Aragão, Pedro Wanderley de; Martins, Carlos Alberto de Souza; Salgado Filho, Natalino; Barroqueiro, Elizabeth de Souza Barcelos

2014-01-01

Maternal hypotension is a common complication after spinal anesthesia for cesarean section, with deleterious effects on the fetus and mother. Among the strategies aimed at minimizing the effects of hypotension, vasopressor administration is the most efficient. The aim of this study was to compare the efficacy of phenylephrine, metaraminol, and ephedrine in the prevention and treatment of hypotension after spinal anesthesia for cesarean section. Ninety pregnant women, not in labor, undergoing cesarean section were randomized into three groups to receive a bolus followed by continuous infusion of vasopressor as follows: phenylephrine group (50μg+50μg/min); metaraminol group (0.25mg+0.25mg/min); ephedrine group (4mg+4mg/min). Infusion dose was doubled when systolic blood pressure decreased to 80% of baseline and a bolus was given when systolic blood pressure decreased below 80%. The infusion dose was divided in half when systolic blood pressure increased to 120% and was stopped when it became higher. The incidence of hypotension, nausea and vomiting, reactive hypertension, bradycardia, tachycardia, Apgar scores, and arterial cord blood gases were assessed at the 1st and 5th minutes. There was no difference in the incidence of hypotension, bradycardia, reactive hypertension, infusion discontinuation, atropine administration or Apgar scores. Rescue boluses were higher only in the ephedrine group compared to metaraminol group. The incidence of nausea and vomiting and fetal acidosis were greater in the ephedrine group. The three drugs were effective in preventing hypotension; however, fetal effects were more frequent in the ephedrine group, although transient. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Circulatory Insufficiency and Hypotension Related to the Ductus Arteriosus in Neonates

PubMed Central

Rios, Danielle R.; Bhattacharya, Soume; Levy, Philip T.; McNamara, Patrick J.

2018-01-01

The biological role of the ductus arteriosus (DA) in neonates varies from an innocent bystander role during normal postnatal transition, to a supportive role when there is compromise to either systemic or pulmonary blood flow, to a pathological state in the presence of hemodynamically significant systemic to pulmonary shunts, as occurs in low birth weight infants. Among a wide array of clinical manifestations arising due to the ductal entity, systemic circulatory insufficiency and hypotension are of significant concern as they are particularly challenging to manage. An understanding of the physiologic interplay between the DA and the circulatory system is the key to developing appropriate targeted therapeutic strategies. In this review, we discuss the relationship of systemic hypotension to the DA, emphasizing the importance of critical thinking and a precise individual approach to intensive care support. We particularly focus on the variable states of hypotension arising directly due to a hemodynamically significant DA or seen in the period following successful surgical ligation. In addition, we explore the mechanistic contributions of the ductus to circulatory insufficiency that may manifest during the transitional period, states of maladapted transition (such as acute pulmonary hypertension of the newborn), and congenital heart disease (both ductal dependent and non-ductal dependent lesions). Understanding the dynamic modulator role of the ductus according to the ambient physiology enables a more precise approach to management. We review the pathophysiology, clinical manifestations, diagnosis, monitoring, and therapeutic intervention for the spectrum of DA-related circulatory compromise. PMID:29600242

CADASIL accelerated by acute hypotension: Arterial and venous contribution to leukoaraiosis.

PubMed

Pettersen, Jacqueline A; Keith, Julia; Gao, Fuqiang; Spence, J David; Black, Sandra E

2017-03-14

To underline the importance of blood pressure regulation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to describe changes that occur in the veins in this condition, specifically venous collagenosis associated with leukoaraiosis. Case report with neuroimaging and pathologic data. A 61-year-old man with genetically confirmed CADASIL was initially lucid following a motor vehicle accident but subsequently became hypotensive (60/40 mm Hg) due to an open femur fracture and required intubation. Multiple new white matter infarcts appeared on brain imaging. A second hypotensive episode days later was associated with new coin-sized infarcts in the bilateral corona radiata and cerebellar peduncles, and resulted in quadriplegia. No embolic source was found on cardiac or vascular imaging. He died 5 weeks post trauma. Autopsy revealed extensive subcortical and periventricular leukoencephalopathy and multiple cavitations involving deep subcortical gray and white matter. Small arteries had thickened walls, disruption of the muscularis, and intimal periodic acid-Schiff (PAS)-positive material. Both larger periventricular and small caliber veins had thickened walls that were PAS-negative and trichrome-positive, consistent with venous collagenosis. There was no pathologic evidence of global hypoxia or diffuse axonal injury. The findings suggest rapid acceleration of CADASIL pathology from acute hypotension in the setting of impaired vasoreactivity. In addition, collagenosis of veins in the affected white matter regions suggests that the veins may play an important, though largely overlooked, role in maintaining white matter integrity. © 2017 American Academy of Neurology.

Sequential compression pump effect on hypotension due to spinal anesthesia for cesarean section: A double blind clinical trial.

PubMed

Zadeh, Fatemeh Javaherforoosh; Alqozat, Mostafa; Zadeh, Reza Akhond

2017-05-01

Spinal anesthesia (SA) is a standard technique for cesarean section. Hypotension presents an incident of 80-85% after SA in pregnant women. To determine the effect of intermittent pneumatic compression of lower limbs on declining spinal anesthesia induced hypotension during cesarean section. This double-blind clinical prospective study was conducted on 76 non-laboring parturient patients, aged 18-45 years, with the American Society of Anesthesiologist physical status I or II who were scheduled for elective cesarean section at Razi Hospital, Ahvaz, Iran from December 21, 2015 to January 20, 2016. Patients were divided into treatment mechanical pump (Group M) or control group (Group C) with simple random sampling. Fetal presentation, birth weight, Apgar at 1 and 5 min, time taken for pre-hydration (min), pre-hydration to the administration of spinal anesthesia (min), initiation of spinal to the delivery (min) and total volume of intravenous fluids, total dose of ephedrine and metoclopramide were recorded. Data were analyzed by SPSS version 19, using repeated measures of ANOVA and Chi square test. Heart rate, MPA, DAP and SAP changes were significantly higher in off-pump group in the baseline and 1st-minute (p<0.05), and in the other times, this change was significantly different with control groups. This research showed the suitability of the use of Sequential Compression Device (SCD) in reducing hypotension after spinal anesthesia for cesarean section, also this method can cause reducing vasopressor dosage for increased blood pressure, but the approval of its effectiveness requires repetition of the study with a larger sample size. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2015011217742N3. The authors received no financial support for the research, authorship, and/or publication of this article.

Sequential compression pump effect on hypotension due to spinal anesthesia for cesarean section: A double blind clinical trial

PubMed Central

Zadeh, Fatemeh Javaherforoosh; Alqozat, Mostafa; Zadeh, Reza Akhond

2017-01-01

Background Spinal anesthesia (SA) is a standard technique for cesarean section. Hypotension presents an incident of 80–85% after SA in pregnant women. Objective To determine the effect of intermittent pneumatic compression of lower limbs on declining spinal anesthesia induced hypotension during cesarean section. Methods This double-blind clinical prospective study was conducted on 76 non-laboring parturient patients, aged 18–45 years, with the American Society of Anesthesiologist physical status I or II who were scheduled for elective cesarean section at Razi Hospital, Ahvaz, Iran from December 21, 2015 to January 20, 2016. Patients were divided into treatment mechanical pump (Group M) or control group (Group C) with simple random sampling. Fetal presentation, birth weight, Apgar at 1 and 5 min, time taken for pre-hydration (min), pre-hydration to the administration of spinal anesthesia (min), initiation of spinal to the delivery (min) and total volume of intravenous fluids, total dose of ephedrine and metoclopramide were recorded. Data were analyzed by SPSS version 19, using repeated measures of ANOVA and Chi square test. Results Heart rate, MPA, DAP and SAP changes were significantly higher in off-pump group in the baseline and 1st-minute (p<0.05), and in the other times, this change was significantly different with control groups. Conclusion This research showed the suitability of the use of Sequential Compression Device (SCD) in reducing hypotension after spinal anesthesia for cesarean section, also this method can cause reducing vasopressor dosage for increased blood pressure, but the approval of its effectiveness requires repetition of the study with a larger sample size. Trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2015011217742N3. Funding The authors received no financial support for the research, authorship, and/or publication of this article. PMID:28713516

Effect of perturbations and a meal on superior mesenteric artery flow in patients with orthostatic hypotension

NASA Technical Reports Server (NTRS)

Fujimura, J.; Camilleri, M.; Low, P. A.; Novak, V.; Novak, P.; Opfer-Gehrking, T. L.

1997-01-01

Our aims were to evaluate to role of superior mesenteric blood flow in the pathophysiology of orthostatic hypotension in patients with generalized autonomic failure. METHODS: Twelve patients with symptomatic neurogenic orthostatic hypotension and 12 healthy controls underwent superior mesenteric artery flow measurements using Doppler ultrasonography during head-up tilt and tilt plus meal ingestion. Autonomic failure was assessed using standard tests of the function of the sympathetic adrenergic, cardiovagal and postganglionic sympathetic sudomotor function. RESULTS: Superior mesenteric flow volume and time-averaged velocity were similar in patients and controls at supine rest; however, responses to cold pressor test and upright tilt were attenuated (p < 0.05) in patients compared to controls. Head-up tilt after the meal evoked a profound fall of blood pressure and mesenteric blood flow in the patients; the reduction of mesenteric blood flow correlated (r = 0.89) with the fall of blood pressure in these patients, providing another manifestation of failed baroreflexes. We make the novel finding that the severity of postprandial orthostatic hypotension regressed negatively with the postprandial increase in mesenteric flow in patients with orthostatic hypotension. CONCLUSION: Mesenteric flow is under baroreflex control, which when defective, results in, or worsens orthostatic hypotension. Its large size and baroreflexivity renders it quantitatively important in the maintenance of postural normotension. The effects of orthostatic stress can be significantly attenuated by reducing the splanchnic-mesenteric volume increase in response to food. Evaluation of mesenteric flow in response to eating and head-up tilt provide important information on intra-abdominal sympathetic adrenergic function, and the ability of the patient to cope with orthostatic stress.

The effect of intraoperative hypotension on the outcomes of initial hybrid palliation for single ventricle congenital heart disease: an historical cohort study.

PubMed

Koziol, James; Gertler, Ralph; Manlhiot, Cedric; McCrindle, Brian; Holtby, Helen; Caldarone, Christopher A; Taylor, Katherine

2013-05-01

The "hybrid procedure" is an alternative surgical palliation strategy for single ventricle congenital heart disease. The purported benefit is improved cognitive ability secondary to avoidance of cardiopulmonary bypass in the neonatal period when neuronal apoptosis is greater. It is unknown whether survival is improved after this procedure. Intraoperative hypotension is common in these patients, and we hypothesized that this hypotension was associated with mortality or morbidity. We reviewed the records of 58/58 patients undergoing a first-stage hybrid procedure from 2004 to 2010 in a tertiary pediatric academic centre. Risk factors for poor outcome and the association between intraoperative hypotension and morbidity or mortality were investigated. Average preoperative arterial blood pressure (ABP) [systolic/diastolic presented as mean (standard deviation)] were 68 (12.7) / 38 (9.4) mmHg. Post-induction ABP was 65 (15.2) / 37 (8.6) mmHg. The average intraoperative nadir of ABP was 45 (7.0) / 26 (4.8) mmHg. On return to the intensive care unit (ICU), the average ABP was 69 (13.7) / 38 (11.6) mmHg. The nadir lasted longer than ten minutes in 32/58 patients. The mortality at 48 hr, 60 days, and 12 months was 3/58 (5%), 10/58 (17%), and 15/58 (26%), respectively. Six patients returned to the ICU on extracorporeal membrane oxygenation (ECMO). There was a weak statistical correlation between the average mean and diastolic BP pre-induction and changes of > 20% in systolic and diastolic BP during the case. In this patient cohort, we can show an association between short periods of intraoperative hypotension and mortality or return to the ICU on ECMO, but the importance of this is not certain.

Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure.

PubMed

Ramirez, Claudia E; Okamoto, Luis E; Arnold, Amy C; Gamboa, Alfredo; Diedrich, André; Choi, Leena; Raj, Satish R; Robertson, David; Biaggioni, Italo; Shibao, Cyndya A

2014-12-01

The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension-related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence [CI], -7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% CI, 0.6 to 15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% CI, 0.1 to 0.8; P=0.02), but not midodrine (means difference=0.5; 95% CI, -0.1 to 1.0; P=0.08), improved orthostatic hypotension-related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure. © 2014 American Heart Association, Inc.

A systematic review of vasopressor blood pressure targets in critically ill adults with hypotension.

PubMed

Hylands, Mathieu; Moller, Morten Hylander; Asfar, Pierre; Toma, Augustin; Frenette, Anne Julie; Beaudoin, Nicolas; Belley-Côté, Émilie; D'Aragon, Frédérick; Laake, Jon Henrik; Siemieniuk, Reed Alexander; Charbonney, Emmanuel; Lauzier, François; Kwong, Joey; Rochwerg, Bram; Vandvik, Per Olav; Guyatt, Gordon; Lamontagne, François

2017-07-01

Clinicians must balance the risks from hypotension with the potential adverse effects of vasopressors. Experts have recommended a mean arterial pressure (MAP) target of at least 65 mmHg, and higher in older patients and in patients with chronic hypertension or atherosclerosis. We conducted a systematic review of randomized-controlled trials comparing higher vs lower blood pressure targets for vasopressor therapy administered to hypotensive critically ill patients. We searched MEDLINE®, EMBASE™, and the Cochrane Central Register of Controlled Trials for studies of higher vs lower blood pressure targets for vasopressor therapy in critically ill hypotensive adult patients. Two reviewers independently assessed trial eligibility based on titles and abstracts, and they then selected full-text reports. Outcomes, subgroups, and analyses were prespecified. We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the overall confidence in the estimates of intervention effects. Of 8001 citations, we retrieved 57 full-text articles and ultimately included two randomized-controlled trials (894 patients). Higher blood pressure targets were not associated with lower mortality (relative risk [RR], 1.05; 95% confidence interval [CI], 0.90 to 1.23; P = 0.54), and neither age (P = 0.17) nor chronic hypertension (P = 0.32) modified the overall effect. Nevertheless, higher blood pressure targets were associated with a greater risk of new-onset supraventricular cardiac arrhythmia (RR, 2.08; 95% CI, 1.28 to 3.38; P < 0.01). Current evidence does not support a MAP target > 70 mmHg in hypotensive critically ill adult patients requiring vasopressor therapy.

Influence of endogenous opiates on the hypotensive action of taurine in DOCA-salt rats.

PubMed

Sato, Y; Fujita, T

1988-12-01

We studied the role of endogenous opiate activation in the hypotensive action of taurine, a sulphur amino acid, in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Previous work had shown that supplementation with 1% taurine reduced blood pressure when given after DOCA-salt hypertension had been established. In the present study, in conscious rats, intraperitoneal injection of naloxone, an opiate antagonist, increased blood pressure in taurine-supplemented DOCA-salt rats, but not in DOCA-salt rats or vehicle-treated control rats. These results suggest that activation of an endogenous opiate might contribute to the hypotensive action of taurine in DOCA-salt hypertensive rats.

Droxidopa for neurogenic orthostatic hypotension

PubMed Central

Freeman, Roy; Biaggioni, Italo; Low, Phillip; Pedder, Simon; Hewitt, L. Arthur; Mauney, Joe; Feirtag, Michael; Mathias, Christopher J.

2014-01-01

Objective: To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH). Methods: Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100–600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities. Results: From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in “dizziness/lightheadedness.” Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for “standing a long time.” Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events. Conclusions: In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated. Classification of evidence: This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days. PMID:24944260

The SLUScore: A Novel Method for Detecting Hazardous Hypotension in Adult Patients Undergoing Noncardiac Surgical Procedures

PubMed Central

Yuan, Hui; Dryden, Jefferson K.; Strehl, Kristen E.; Cywinski, Jacek B.; Ehrenfeld, Jesse M.; Bromley, Pamela

2017-01-01

BACKGROUND: It has been suggested that longer-term postsurgical outcome may be adversely affected by less than severe hypotension under anesthesia. However, evidence-based guidelines are unavailable. The present study was designed to develop a method for identifying patients at increased risk of death within 30 days in association with the severity and duration of intraoperative hypotension. METHODS: Intraoperative mean arterial blood pressure recordings of 152,445 adult patients undergoing noncardiac surgery were analyzed for periods of time accumulated below each one of the 31 thresholds between 75 and 45 mm Hg (hypotensive exposure times). In a development cohort of 35,904 patients, the associations were sought between each of these 31 cumulative hypotensive exposure times and 30-day postsurgical mortality. On the basis of covariable-adjusted percentage increases in the odds of mortality per minute elapsed of hypotensive exposure time, certain sets of exposure time limits were calculated that portended certain percentage increases in the odds of mortality. A novel risk-scoring method was conceived by counting the number of exposure time limits that had been exceeded within each respective set, one of them being called the SLUScore. The validity of this new method in identifying patients at increased risk was tested in a multicenter validation cohort consisting of 116,541 patients from Cleveland Clinic, Vanderbilt and Saint Louis Universities. Data were expressed as 95% confidence interval, P < .05 considered significant. RESULTS: Progressively greater hypotensive exposures were associated with greater 30-day mortality. In the development cohort, covariable-adjusted (age, Charlson score, case duration, history of hypertension) exposure limits were identified for time accumulated below each of the thresholds that portended certain identical (5%–50%) percentage expected increases in the odds of mortality. These exposure time limit sets were shorter in patients

Quercetin Reduces Tumor Necrosis Factor Alpha-Induced Muscle Atrophy by Upregulation of Heme Oxygenase-1.

PubMed

Kim, Yeji; Kim, Chu-Sook; Joe, Yeonsoo; Chung, Hun Taeg; Ha, Tae Youl; Yu, Rina

2018-06-01

The inflammatory cytokine tumor necrosis factor α (TNFα), upregulated in the obese condition, promotes protein degradation and is implicated in obesity-related skeletal muscle atrophy and age-related sarcopenia. Quercetin, a flavonoid, elicits antioxidative and anti-inflammatory activities. In this study, we investigated the effect of quercetin on TNFα-induced skeletal muscle atrophy as well as its potential mechanism of action. In this study, we observed that quercetin suppressed expression of TNFα-induced atrophic factors such as MAFbx/atrogin-1 and MuRF1 in myotubes, and it enhanced heme oxygenase-1 (HO-1) protein level accompanied by increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in myotubes. The HO-1 inhibitor ZnPP suppressed the inhibitory actions of quercetin on TNFα-induced atrophic responses and degradation of IκB-α in myotubes. Moreover, quercetin supplementation to high-fat diet-fed obese mice inhibited obesity-induced atrophic responses in skeletal muscle, accompanied by upregulation of HO-1 and inactivation of nuclear factor-kappa B (NF-κB), and the quercetin actions were attenuated in Nrf2-deficient mice. These findings suggest that quercetin protects against TNFα-induced muscle atrophy under obese conditions through Nrf2-mediated HO-1 induction accompanied by inactivation of NF-κB. Quercetin may be used as a dietary supplement to protect against obesity-induced skeletal muscle atrophy.

Droxidopa in neurogenic orthostatic hypotension

PubMed Central

Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto

2015-01-01

Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy, pure autonomic failure and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise blood pressure by acting at the neurovascular junction to increase vascular tone. This review summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials. PMID:26092297

Droxidopa in neurogenic orthostatic hypotension.

PubMed

Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto

2015-01-01

Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure (BP) on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy (MSA), pure autonomic failure (PAF), and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise BP by acting at the neurovascular junction to increase vascular tone. This article summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials.

Biphasic changes in fetal heart rate variability in preterm fetal sheep developing hypotension after acute on chronic lipopolysaccharide exposure.

PubMed

Lear, Christopher A; Davidson, Joanne O; Booth, Lindsea C; Wassink, Guido; Galinsky, Robert; Drury, Paul P; Fraser, Mhoyra; Bennet, Laura; Gunn, Alistair J

2014-08-15

Perinatal exposure to infection is highly associated with adverse outcomes. Experimentally, acute, severe exposure to gram-negative bacterial lipopolysaccharide (LPS) is associated with increased fetal heart rate variability (FHRV). It is unknown whether FHRV is affected by subclinical infection with or without acute exacerbations. We therefore tested the hypothesis that FHRV would be associated with hypotension after acute on chronic exposure to LPS. Chronically instrumented fetal sheep at 0.7 gestation were exposed to a continuous low-dose LPS infusion (n = 12, 100 ng/kg over 24 h, followed by 250 ng·kg(-1)·24 h(-1) for a further 96 h) or the same volume of saline (n = 10). Boluses of either 1 μg LPS or saline were given at 48, 72, and 96 h. Low-dose infusion was not associated with hemodynamic or FHRV changes. The first LPS bolus was associated with tachycardia and suppression of nuchal electromyographic activity in all fetuses. Seven of twelve fetuses developed hypotension (a fall in mean arterial blood pressure ≥5 mmHg). FHRV was transiently increased only at the onset of hypotension, in association with increased cytokine induction and electroencephalogram suppression. FHRV then fell before the nadir of hypotension, with transient suppression of short-term FHRV. After the second LPS bolus, the hypotension group showed a biphasic pattern of a transient increase in FHRV followed by more prolonged suppression. These findings suggest that infection-related hypotension in the preterm fetus mediates the transient increase in FHRV and that repeated exposure to LPS leads to progressive loss of FHRV. Copyright © 2014 the American Physiological Society.

Hemodynamic response to fluid removal during hemodialysis: categorization of causes of intradialytic hypotension.

PubMed

Levin, Nathan W; de Abreu, Marcia H F G; Borges, Lucas E; Tavares Filho, Helcio A; Sarwar, Rabia; Gupta, Surendra; Hafeez, Tahir; Lev, Shaul; Williams, Caroline

2018-04-14

Intradialytic hypotension is a clinically significant problem, however, the hemodynamics that underlie ultrafiltration and consequent hypotensive episodes has not been studied comprehensively. Intradialytic cardiac output, cardiac power and peripheral resistance changes from pretreatment measurements were evaluated using a novel regional impedance cardiographic device (NICaS, NI Medical, Peta Tikva, Israel) in 263 hemodialysis sessions in 54 patients in dialysis units in the USA and Brazil with the goal of determining the various hemodynamic trends as blood pressure decreases. Hypotensive episodes occurred in 99 (13.5%) of 736 intra- and postdialytic evaluations. The hemodynamic profiles of the episodes were categorized: (i) The cardiac power index significantly decreased in 35% of episodes by 36%, from 0.66 [95% confidence interval (CI) 0.60-0.72] to 0.43 (95% CI 0.37-0.48) [w/m2] with a small reduction in the total peripheral resistance index. (ii) The total peripheral resistance index significantly decreased in 37.4% of episodes by 33%, from 3342 (95% CI 2824-3859) to 2251 (95% CI 1900-2602) [dyn × s/cm5 × m2] with a small reduction in the cardiac power index. (iii) Both the cardiac power index and total peripheral resistance index significantly decreased in 27.3% of episodes, the cardiac power index by 25% from 0.63 (95% CI 0.57-0.70) to 0.48 (95% CI 0.42-0.53) [w/m2] and the total peripheral resistance index by 23% from 2964 (95% CI 2428-3501) to 2266 (95% CI 1891-2642). The hemodynamic profiles clearly define specific hemodynamic mechanisms of cardiac power reduction and/or vasodilatation as underlying intradialytic hypotensive episodes. A reduction in cardiac power (reduction of both blood pressure and cardiac output) could be the result of preload reduction due to a high ultrafiltration rate with not enough refilling or low target weight. A reduction in peripheral resistance (reduction in blood pressure and increase in cardiac output) could be the result

Tumor Environmental Factors Glucose Deprivation and Lactic Acidosis Induce Mitotic Chromosomal Instability – An Implication in Aneuploid Human Tumors

PubMed Central

Zhu, Chunpeng; Hu, Xun

2013-01-01

Mitotic chromosomal instability (CIN) plays important roles in tumor progression, but what causes CIN is incompletely understood. In general, tumor CIN arises from abnormal mitosis, which is caused by either intrinsic or extrinsic factors. While intrinsic factors such as mitotic checkpoint genes have been intensively studied, the impact of tumor microenvironmental factors on tumor CIN is largely unknown. We investigate if glucose deprivation and lactic acidosis – two tumor microenvironmental factors – could induce cancer cell CIN. We show that glucose deprivation with lactic acidosis significantly increases CIN in 4T1, MCF-7 and HCT116 scored by micronuclei, or aneuploidy, or abnormal mitosis, potentially via damaging DNA, up-regulating mitotic checkpoint genes, and/or amplifying centrosome. Of note, the feature of CIN induced by glucose deprivation with lactic acidosis is similar to that of aneuploid human tumors. We conclude that tumor environmental factors glucose deprivation and lactic acidosis can induce tumor CIN and propose that they are potentially responsible for human tumor aneuploidy. PMID:23675453

Hyperthermia combined with ethanol administration induces c-fos expression in the central amygdaloid nucleus of the mouse brain. A possible mechanism of heatstroke under the influence of ethanol intake.

PubMed

Kibayashi, Kazuhiko; Nakao, Ken-ichiro; Shojo, Hideki

2009-09-01

Heatstroke is defined as a core body temperature that rises above 40.6 degrees C and is accompanied by mental status abnormalities such as delirium, convulsions, or coma resulting from exposure to environmental heat. There is fairly wide agreement that ethanol intake is a predisposing factor in heatstroke. This study was performed to identify the brain changes induced by heatstroke, using a mouse hyperthermia model with and without preceding ethanol administration. Exposure to heat of 42 degrees C until the core temperature reached to 43 degrees C followed by exposure to 37 degrees C for 15 min decreased the levels of partial pressures of O(2) in blood. Preceding ethanol administration and heat exposure induced hypotension, severe metabolic acidosis and respiratory failure, and, accordingly, produced heatstroke. Immunohistochemistry of the brains showed that preceding ethanol administration increased the number of c-fos-immunoreactive neurons, as a marker of neuronal activation, in the central amygdaloid nucleus, which is involved in thermoregulation. These results indicate that combined effects of ethanol and heat exposure induce heatstroke that is associated with activation of the central amygdaloid nucleus, implicating the pathophysiology and mechanisms of heatstroke under the influence of ethanol intake.

Accuracy and Precision of Noninvasive Blood Pressure in Normo-, Hyper-, and Hypotensive Standing and Anesthetized Adult Horses.

PubMed

Heliczer, N; Lorello, O; Casoni, D; Navas de Solis, C

2016-05-01

Blood pressure is relevant to the diagnosis and management of many medical, cardiovascular and critical diseases. The accuracy of many commonly used noninvasive blood pressure (NIBP) monitors and the accuracy of NIBP measurements in hypo- and hypertensive standing horses has not been determined. The objective of this study was to investigate the accuracy of an oscillometric BP monitor in standing horses before and during pharmacologically induced hyper- and hypotension and to compare results in standing and anesthetized horses. Eight standing mares from a research herd (SG) and eight anesthetized horses from a hospital population (AG). Prospective experimental and observational studies. Invasive blood pressure (IBP) and NIBP, corrected to heart level, were measured simultaneously. In the SG hyper- and hypotension were induced by administration of phenylephrine (3 μg/kg/min IV for 15 minutes) and acepromazine (0.05 mg/kg IV), respectively. In the AG NIBP and IBP were recorded during regular hospital procedures. There was a significant correlation between mean NIBP and IBP in standing (R = 0.88, P < .001) and anesthetized horses (R = 0.81, P < .001). The mean bias (lower, upper limit of agreement) was 16.4(-16.1, 48.9) mmHg for mean BP in the SG and 0.5(-22.3, 23.2) mmHg in the AG. The NIBP device was capable of identifying the increase and decrease in BP in all horses, but in the SG significant correlation between NIBP and IBP was only detected for the normotensive phase. While the evaluated oscillometric BP device allowed estimation of BP and adequately differentiated marked trends, the accuracy and precision were low in standing horses. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems

PubMed Central

Singh, Shweta; Siddiqi, Nikhat J.

2014-01-01

Several workers have extensively worked out the metal induced toxicity and have reported the toxic and carcinogenic effects of metals in human and animals. It is well known that these metals play a crucial role in facilitating normal biological functions of cells as well. One of the major mechanisms associated with heavy metal toxicity has been attributed to generation of reactive oxygen and nitrogen species, which develops imbalance between the prooxidant elements and the antioxidants (reducing elements) in the body. In this process, a shift to the former is termed as oxidative stress. The oxidative stress mediated toxicity of heavy metals involves damage primarily to liver (hepatotoxicity), central nervous system (neurotoxicity), DNA (genotoxicity), and kidney (nephrotoxicity) in animals and humans. Heavy metals are reported to impact signaling cascade and associated factors leading to apoptosis. The present review illustrates an account of the current knowledge about the effects of heavy metals (mainly arsenic, lead, mercury, and cadmium) induced oxidative stress as well as the possible remedies of metal(s) toxicity through natural/synthetic antioxidants, which may render their effects by reducing the concentration of toxic metal(s). This paper primarily concerns the clinicopathological and biomedical implications of heavy metals induced oxidative stress and their toxicity management in mammals. PMID:25184144

Seminal Plasma Induces Ovulation in Llamas in the Absence of a Copulatory Stimulus: Role of Nerve Growth Factor as an Ovulation-Inducing Factor

PubMed Central

Berland, Marco A.; Ulloa-Leal, Cesar; Barría, Miguel; Wright, Hollis; Dissen, Gregory A.; Silva, Mauricio E.; Ojeda, Sergio R.

2016-01-01

Llamas are considered to be reflex ovulators. However, semen from these animals is reported to be rich in ovulation-inducing factor(s), one of which has been identified as nerve growth factor (NGF). These findings suggest that ovulation in llamas may be elicited by chemical signals contained in semen instead of being mediated by neural signals. The present study examines this notion. Llamas displaying a preovulatory follicle were assigned to four groups: group 1 received an intrauterine infusion (IUI) of PBS; group 2 received an IUI of seminal plasma; group 3 was mated to a male whose urethra had been surgically diverted (urethrostomized male); and group 4 was mated to an intact male. Ovulation (detected by ultrasonography) occurred only in llamas mated to an intact male or given an IUI of seminal plasma and was preceded by a surge in plasma LH levels initiated within an hour after coitus or IUI. In both ovulatory groups, circulating β-NGF levels increased within 15 minutes after treatment, reaching values that were greater and more sustained in llamas mated with an intact male. These results demonstrate that llamas can be induced to ovulate by seminal plasma in the absence of copulation and that copulation alone cannot elicit ovulation in the absence of seminal plasma. In addition, our results implicate β-NGF as an important mediator of seminal plasma-induced ovulation in llamas because ovulation does not occur if β-NGF levels do not increase in the bloodstream, a change that occurs promptly after copulation with an intact male or IUI of seminal plasma. PMID:27355492

Seminal Plasma Induces Ovulation in Llamas in the Absence of a Copulatory Stimulus: Role of Nerve Growth Factor as an Ovulation-Inducing Factor.

PubMed

Berland, Marco A; Ulloa-Leal, Cesar; Barría, Miguel; Wright, Hollis; Dissen, Gregory A; Silva, Mauricio E; Ojeda, Sergio R; Ratto, Marcelo H

2016-08-01

Llamas are considered to be reflex ovulators. However, semen from these animals is reported to be rich in ovulation-inducing factor(s), one of which has been identified as nerve growth factor (NGF). These findings suggest that ovulation in llamas may be elicited by chemical signals contained in semen instead of being mediated by neural signals. The present study examines this notion. Llamas displaying a preovulatory follicle were assigned to four groups: group 1 received an intrauterine infusion (IUI) of PBS; group 2 received an IUI of seminal plasma; group 3 was mated to a male whose urethra had been surgically diverted (urethrostomized male); and group 4 was mated to an intact male. Ovulation (detected by ultrasonography) occurred only in llamas mated to an intact male or given an IUI of seminal plasma and was preceded by a surge in plasma LH levels initiated within an hour after coitus or IUI. In both ovulatory groups, circulating β-NGF levels increased within 15 minutes after treatment, reaching values that were greater and more sustained in llamas mated with an intact male. These results demonstrate that llamas can be induced to ovulate by seminal plasma in the absence of copulation and that copulation alone cannot elicit ovulation in the absence of seminal plasma. In addition, our results implicate β-NGF as an important mediator of seminal plasma-induced ovulation in llamas because ovulation does not occur if β-NGF levels do not increase in the bloodstream, a change that occurs promptly after copulation with an intact male or IUI of seminal plasma.

Autophagy degrades hypoxia inducible factors

PubMed Central

DePavia, Adela; Jonasch, Eric; Liu, Xian-De

2016-01-01

ABSTRACT Hypoxia inducible factors are subjected to degradation by the ubiquitin-proteasome system (UPS), macroautophagy, and chaperone-mediated autophagy. The E3 ligases, ubiquitination, autophagy receptor proteins, and oxygen are determinants that direct hypoxia-inducible factors to different degradation pathways. PMID:27308629

Harmane produces hypotension following microinjection into the RVLM: possible role of I(1)-imidazoline receptors.

PubMed

Musgrave, I F; Badoer, E

2000-03-01

The beta-carboline, harmane (0.1 - 1.0 nmol) produces dose dependent hypotension when microinjected unilaterally into the rostral ventrolateral medulla (RVLM) of the anaesthetized rat. The potency of harmane on blood pressure is similar to that of the imidazoline, clonidine. The hypotensive effects of both clonidine and harmane are reversed by microinjection of the relatively I(1)-receptor selective antagonist efaroxan (20 nmol). These results are consistent with harmane acting at an I(1)-receptor in the RVLM. This is the first report of an endogenous ligand for I(1)-receptors that has central effects on blood pressure.

Vascular endothelial growth factor is upregulated by l-dopa in the parkinsonian brain: implications for the development of dyskinesia

PubMed Central

Francardo, Veronica; Lindgren, Hanna S.; Sillivan, Stephanie E.; O’Sullivan, Sean S.; Luksik, Andrew S.; Vassoler, Fair M.; Lees, Andrew J.; Konradi, Christine

2011-01-01

Angiogenesis and increased permeability of the blood–brain barrier have been reported to occur in animal models of Parkinson’s disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood–brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson’s disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson’s disease. PMID:21771855

Glucocorticoids suppress hypoxia-induced COX-2 and hypoxia inducible factor-1α expression through the induction of glucocorticoidinduced leucine zipper

PubMed Central

Lim, Wonchung; Park, Choa; Shim, Myeong Kuk; Lee, Yong Hee; Lee, You Mie; Lee, YoungJoo

2014-01-01

Background and Purpose The COX-2/PGE2 pathway in hypoxic cancer cells has important implications for stimulation of inflammation and tumourigenesis. However, the mechanism by which glucocorticoid receptors (GRs) inhibit COX-2 during hypoxia has not been elucidated. Hence, we explored the mechanisms underlying glucocorticoid-mediated inhibition of hypoxia-induced COX-2 in human distal lung epithelial A549 cells. Experimental Approach The expressions of COX-2 and glucocorticoid-induced leucine zipper (GILZ) in A549 cells were determined by Western blot and/or quantitative real time-PCR respectively. The anti-invasive effect of GILZ on A549 cells was evaluated using the matrigel invasion assay. Key Results The hypoxia-induced increase in COX-2 protein and mRNA levels and promoter activity were suppressed by dexamethasone, and this effect of dexamethasone was antagonized by the GR antagonist RU486. Overexpression of GILZ in A549 cells also inhibited hypoxia-induced COX-2 expression levels and knockdown of GILZ reduced the glucocorticoid-mediated inhibition of hypoxia-induced COX-2 expression, indicating that the inhibitory effects of dexamethasone on hypoxia-induced COX-2 are mediated by GILZ. GILZ suppressed the expression of hypoxia inducible factor (HIF)-1α at the protein level and affected its signalling pathway. Hypoxia-induced cell invasion was also dramatically reduced by GILZ expression. Conclusion and Implications Dexamethasone-induced upregulation of GILZ not only inhibits the hypoxic-evoked induction of COX-2 expression and cell invasion but further blocks the HIF-1 pathway by destabilizing HIF-1α expression. Taken together, these findings suggest that the suppression of hypoxia-induced COX-2 by glucocorticoids is mediated by GILZ. Hence, GILZ is a potential key therapeutic target for suppression of inflammation under hypoxia. PMID:24172143

Long-Lasting Orthostatic Hypotension and Constipation After Celiac Plexus Block; A Case Report.

PubMed

Yousefshahi, Fardin; Tahmasebi, Mamak

2018-02-01

This case report presents a 55 years old man, presented with abdominal pain and diagnosed with a metastatic pancreatic tumor, who developed long lasting orthostatic hypotension and constipation following a celiac plexus block.

Hypotension, lipodystrophy, and insulin resistance in generalized PPARγ-deficient mice rescued from embryonic lethality

PubMed Central

Duan, Sheng Zhong; Ivashchenko, Christine Y.; Whitesall, Steven E.; D’Alecy, Louis G.; Duquaine, Damon C.; Brosius, Frank C.; Gonzalez, Frank J.; Vinson, Charles; Pierre, Melissa A.; Milstone, David S.; Mortensen, Richard M.

2007-01-01

We rescued the embryonic lethality of global PPARγ knockout by breeding Mox2-Cre (MORE) mice with floxed PPARγ mice to inactivate PPARγ in the embryo but not in trophoblasts and created a generalized PPARγ knockout mouse model, MORE-PPARγ knockout (MORE-PGKO) mice. PPARγ inactivation caused severe lipodystrophy and insulin resistance; surprisingly, it also caused hypotension. Paradoxically, PPARγ agonists had the same effect. We showed that another mouse model of lipodystrophy was hypertensive, ruling out the lipodystrophy as a cause. Further, high salt loading did not correct the hypotension in MORE-PGKO mice. In vitro studies showed that the vasculature from MORE-PGKO mice was more sensitive to endothelial-dependent relaxation caused by muscarinic stimulation, but was not associated with changes in eNOS expression or phosphorylation. In addition, vascular smooth muscle had impaired contraction in response to α-adrenergic agents. The renin-angiotensin-aldosterone system was mildly activated, consistent with increased vascular capacitance or decreased volume. These effects are likely mechanisms contributing to the hypotension. Our results demonstrated that PPARγ is required to maintain normal adiposity and insulin sensitivity in adult mice. Surprisingly, genetic loss of PPARγ function, like activation by agonists, lowered blood pressure, likely through a mechanism involving increased vascular relaxation. PMID:17304352

[Ocular hypotensive effect of alpha-adrenoceptor agonist and antagonist in the conscious pigmented rabbit].

PubMed

Moriwaki, Y; Iizuka, T; Nakamura, A; Nakata, K; Masaoka, Y; Ueda, T; Koide, R; Inatomi, M; Fukado, Y; Uchida, E

1992-02-01

It has been reported that some of the topically-used antiglaucomatics have a central ocular hypotensive effect. In this study, the influence of topical and intracerebroventricular (i.c.v.) administration of phenylephrine, clonidine, guanfacine, prazosin, yohimbine on the intraocular pressure (IOP) was investigated in the rabbit. Male pigmented rabbits were used throughout the experiments. For measurement of IOP, an applanation pneumatonograph was used. By unilateral topical administration of phenylephrine, an increase in IOP in the eye in which instillation was performed was observed. On the other hand, a slight decrease in IOP was observed by similar treatment of prazosin and yohimbine. No significant change of IOP in the contralateral eye was observed with these drugs. On the contrary, unilateral topical administration of clonidine or guanfacine decreased the IOP of both eyes. Furthermore, the decrease of IOP was more remarkable in the contralateral eye compared to the eye which received instillation. The IOP of both eyes was decreased in a dose-related fashion by i.c.v. administration of clonidine or guanfacine. The ocular hypotensive effects of clonidine were diminished by the pretreatment by i.c.v. administration with yohimbine. These results suggest that the ocular hypotensive effect of clonidine and guanfacine is due to their alpha 2-adrenoceptor stimulation in the central nervous system.

Long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

PubMed

Isaacson, Stuart; Vernino, Steven; Ziemann, Adam; Rowse, Gerald J; Kalu, Uwa; White, William B

2016-10-01

The long-term safety of droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension in patients with Parkinson disease, pure autonomic failure, multiple system atrophy, or nondiabetic autonomic neuropathy was evaluated in a phase 3, multinational, open-label study in patients who previously participated in a double-blind, placebo-controlled clinical trial of droxidopa. A total of 350 patients received droxidopa 100 to 600 mg three times daily. Mean duration of droxidopa exposure was 363 days (range, 2-1133 days). Rates of serious adverse events (AEs), cardiac-related AEs, and supine hypertension were 24%, 5%, and 5%, respectively. Most AEs, including those of a cardiovascular nature, were not attributed by investigators to droxidopa. In this large cohort of patients with neurogenic orthostatic hypotension, droxidopa was well tolerated during long-term use. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Alcohol-induced blackouts: A review of recent clinical research with practical implications and recommendations for future studies

PubMed Central

Wetherill, Reagan R.; Fromme, Kim

2016-01-01

Background Alcohol-induced blackouts, or memory loss for all or portions of events that occurred during a drinking episode, are reported by approximately 50% of drinkers and are associated with a wide range of negative consequences, including injury and death. As such, identifying the factors that contribute to and result from alcohol-induced blackouts is critical in developing effective prevention programs. Here, we provide an updated review (2010–2015) of clinical research focused on alcohol-induced blackouts, outline practical and clinical implications, and provide recommendations for future research. Methods A comprehensive, systematic literature review was conducted to examine all articles published between January 2010 through August 2015 that focused on examined vulnerabilities, consequences, and possible mechanisms for alcohol-induced blackouts. Results Twenty-sex studies reported on alcohol-induced blackouts. Fifteen studies examined prevalence and/or predictors of alcohol-induced blackouts. Six publications described consequences of alcohol-induced blackouts, and five studies explored potential cognitive and neurobiological mechanisms underlying alcohol-induced blackouts. Conclusions Recent research on alcohol-induced blackouts suggests that individual differences, not just alcohol consumption, increase the likelihood of experiencing an alcohol-induced blackout, and the consequences of alcohol-induced blackouts extend beyond the consequences related to the drinking episode to include psychiatric symptoms and neurobiological abnormalities. Prospective studies and a standardized assessment of alcohol-induced blackouts are needed to fully characterize factors associated with alcohol-induced blackouts and to improve prevention strategies. PMID:27060868

Alcohol-Induced Blackouts: A Review of Recent Clinical Research with Practical Implications and Recommendations for Future Studies.

PubMed

Wetherill, Reagan R; Fromme, Kim

2016-05-01

Alcohol-induced blackouts, or memory loss for all or portions of events that occurred during a drinking episode, are reported by approximately 50% of drinkers and are associated with a wide range of negative consequences, including injury and death. As such, identifying the factors that contribute to and result from alcohol-induced blackouts is critical in developing effective prevention programs. Here, we provide an updated review (2010 to 2015) of clinical research focused on alcohol-induced blackouts, outline practical and clinical implications, and provide recommendations for future research. A comprehensive, systematic literature review was conducted to examine all articles published between January 2010 through August 2015 that focused on vulnerabilities, consequences, and possible mechanisms for alcohol-induced blackouts. Twenty-six studies reported on alcohol-induced blackouts. Fifteen studies examined prevalence and/or predictors of alcohol-induced blackouts. Six publications described the consequences of alcohol-induced blackouts, and 5 studies explored potential cognitive and neurobiological mechanisms underlying alcohol-induced blackouts. Recent research on alcohol-induced blackouts suggests that individual differences, not just alcohol consumption, increase the likelihood of experiencing an alcohol-induced blackout, and the consequences of alcohol-induced blackouts extend beyond the consequences related to the drinking episode to include psychiatric symptoms and neurobiological abnormalities. Prospective studies and a standardized assessment of alcohol-induced blackouts are needed to fully characterize factors associated with alcohol-induced blackouts and to improve prevention strategies. Copyright © 2016 by the Research Society on Alcoholism.

Long-Lasting Orthostatic Hypotension and Constipation After Celiac Plexus Block; A Case Report

PubMed Central

Yousefshahi, Fardin; Tahmasebi, Mamak

2018-01-01

This case report presents a 55 years old man, presented with abdominal pain and diagnosed with a metastatic pancreatic tumor, who developed long lasting orthostatic hypotension and constipation following a celiac plexus block. PMID:29868459

Inducible nitric oxide synthase evoked nitric oxide counteracts capsaicin-induced airway smooth muscle contraction, but exacerbates plasma extravasation.

PubMed

Li, Ping-Chia; Shaw, Chen-Fu; Kuo, Tin-Fan; Chien, Chiang-Ting

2005-04-18

The contribution of nitric oxide (NO) to capsaicin-evoked airway responses was investigated in rats. The measurement of plasma NO level, airway dynamics, airway smooth muscle electromyogram, and plasma extravasation by India ink and Evans blue leakage technique was adapted. Capsaicin-evoked hypotension, bronchoconstriction, trachea plasma extravasation as well as increases in plasma NO level in a dose-dependent manner. L-732138 (NK1 receptor antagonist) or SR-48968 (NK2 receptor antagonist) pretreatment reduced capsaicin-enhanced hypotension, bronchoconstriction, plasma extravasation, and plasma NO level. N(G)-nitro-L-Arginine methyl ester (L-NAME, 10 mg/kg, i.v.), a non-selective NO synthase (NOS) inhibitor, or aminoguanidine (10 mg/kg, i.v.), a selective inducible NOS (iNOS) inhibitor, reduced capsaicin-induced increases in plasma NO level and protected against capsaicin-induced plasma extravasation, whereas L-arginine (150 mg/kg, i.v.), a NO precursor, enhanced capsaicin-evoked plasma NO level and plasma extravasation. L-Arginine pretreatment ameliorated capsaicin-induced bronchoconstriction, whereas L-NAME and aminoguanidine exaggerated capsaicin-induced bronchoconstriction. In summary, NK1 and NK2 receptors and iNOS play a role in NO formation and on capsaicin-induced bronchoconstriction and plasma extravasation. NO generated by iNOS counteracts tachykinin-mediated bronchoconstriction, but exacerbates tachykinin-mediated plasma extravasation.

Droxidopa and Reduced Falls in a Trial of Parkinson Disease Patients With Neurogenic Orthostatic Hypotension.

PubMed

Hauser, Robert A; Heritier, Stephane; Rowse, Gerald J; Hewitt, L Arthur; Isaacson, Stuart H

2016-01-01

Droxidopa is a prodrug of norepinephrine indicated for the treatment of orthostatic dizziness, lightheadedness, or the "feeling that you are about to black out" in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure including Parkinson disease (PD). The objective of this study was to compare fall rates in PD patients with symptomatic neurogenic orthostatic hypotension randomized to droxidopa or placebo. Study NOH306 was a 10-week, phase 3, randomized, placebo-controlled, double-blind trial of droxidopa in PD patients with symptomatic neurogenic orthostatic hypotension that included assessments of falls as a key secondary end point. In this report, the principal analysis consisted of a comparison of the rate of patient-reported falls from randomization to end of study in droxidopa versus placebo groups. A total of 225 patients were randomized; 222 patients were included in the safety analyses, and 197 patients provided efficacy data and were included in the falls analyses. The 92 droxidopa patients reported 308 falls, and the 105 placebo patients reported 908 falls. In the droxidopa group, the fall rate was 0.4 falls per patient-week; in the placebo group, the rate was 1.05 falls per patient-week (prespecified Wilcoxon rank sum P = 0.704; post hoc Poisson-inverse Gaussian test P = 0.014), yielding a relative risk reduction of 77% using the Poisson-inverse Gaussian model. Fall-related injuries occurred in 16.7% of droxidopa-treated patients and 26.9% of placebo-treated patients. Treatment with droxidopa appears to reduce falls in PD patients with symptomatic neurogenic orthostatic hypotension, but this finding must be confirmed.

Droxidopa and Reduced Falls in a Trial of Parkinson Disease Patients With Neurogenic Orthostatic Hypotension

PubMed Central

Hauser, Robert A.; Heritier, Stephane; Rowse, Gerald J.; Hewitt, L. Arthur; Isaacson, Stuart H.

2016-01-01

Objectives Droxidopa is a prodrug of norepinephrine indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure including Parkinson disease (PD). The objective of this study was to compare fall rates in PD patients with symptomatic neurogenic orthostatic hypotension randomized to droxidopa or placebo. Methods Study NOH306 was a 10-week, phase 3, randomized, placebo-controlled, double-blind trial of droxidopa in PD patients with symptomatic neurogenic orthostatic hypotension that included assessments of falls as a key secondary end point. In this report, the principal analysis consisted of a comparison of the rate of patient-reported falls from randomization to end of study in droxidopa versus placebo groups. Results A total of 225 patients were randomized; 222 patients were included in the safety analyses, and 197 patients provided efficacy data and were included in the falls analyses. The 92 droxidopa patients reported 308 falls, and the 105 placebo patients reported 908 falls. In the droxidopa group, the fall rate was 0.4 falls per patient-week; in the placebo group, the rate was 1.05 falls per patient-week (prespecified Wilcoxon rank sum P = 0.704; post hoc Poisson-inverse Gaussian test P = 0.014), yielding a relative risk reduction of 77% using the Poisson-inverse Gaussian model. Fall-related injuries occurred in 16.7% of droxidopa-treated patients and 26.9% of placebo-treated patients. Conclusions Treatment with droxidopa appears to reduce falls in PD patients with symptomatic neurogenic orthostatic hypotension, but this finding must be confirmed. PMID:27332626

Methylene blue, midodrine, and pseudoephedrine: a review of alternative agents for refractory hypotension in the intensive care unit.

PubMed

Van Berkel, Megan A; Fuller, Laura A; Alexandrov, Anne W; Jones, G Morgan

2015-01-01

Hypotensive episodes are common among patients in the intensive care unit and can lead to multiorgan failure if uncontrolled. Fluid administration and continuous infusion of vasoactive agents are frequently used for management of hypotension; however, both therapies may be associated with adverse effects including pulmonary edema and tissue necrosis. In addition, availability of these first-line agents has been impacted by the increasing occurrence of drug shortages. Methylene blue, pseudoephedrine, and midodrine have been considered potential alternatives to standard therapy. These agents may not only be used when first-line agents are unavailable due to shortages, but they may also aid in reducing the cumulative dose of other vasoactive agents used. The purpose of this review was to discuss strategies for the safe and effective use of methylene blue, pseudoephedrine, and midodrine for the treatment of hypotension in the critically ill.

Fruit-induced FPIES masquerading as hereditary fructose intolerance.

PubMed

Fiocchi, Alessandro; Dionisi-Vici, Carlo; Cotugno, Giovanna; Koch, Pierluigi; Dahdah, Lamia

2014-08-01

Hereditary fructose intolerance (HFI) symptoms develop at first introduction of fruit during weaning. We report on an infant with suspected HFI who presented with repeated episodes of vomiting and hypotension after ingestion of fruit-containing meals. The first episode occurred at age 4 months. Despite negative genetic testing for HFI, strict avoidance of fruit ingestion resulted in lack of recurrence of symptoms. Oral-fructose-tolerance testing conducted with an apple mousse did not determine hypoglycemia or fructosuria but caused severe hypotension. Allergy evaluations were negative, and the history was diagnostic for fruit-induced food protein-induced enterocolitis syndrome. Because this non-immunoglobulin E-mediated gastrointestinal food hypersensitivity manifests as profuse, repetitive vomiting, often with diarrhea, leading to acute dehydration and lethargy, it may be misinterpreted as HFI. We advise pediatricians to consider food protein-induced enterocolitis syndrome in the differential diagnosis when there is a suspicion of HFI. Copyright © 2014 by the American Academy of Pediatrics.

Harmane produces hypotension following microinjection into the RVLM: possible role of I1-imidazoline receptors

PubMed Central

Musgrave, I F; Badoer, E

2000-01-01

The β-carboline, harmane (0.1–1.0 nmol) produces dose dependent hypotension when microinjected unilaterally into the rostral ventrolateral medulla (RVLM) of the anaesthetized rat. The potency of harmane on blood pressure is similar to that of the imidazoline, clonidine. The hypotensive effects of both clonidine and harmane are reversed by microinjection of the relatively I1-receptor selective antagonist efaroxan (20 nmol). These results are consistent with harmane acting at an I1-receptor in the RVLM. This is the first report of an endogenous ligand for I1-receptors that has central effects on blood pressure. PMID:10725251

Prostacyclin-induced hyperthermia - Implication of a protein mediator

NASA Technical Reports Server (NTRS)

Kandasamy, S. B.; Williams, B. A.

1982-01-01

The mechanism of the prostacyclin-linked hyperthermia is studied in rabbits. Results show that intracerebroventricular administration of prostacyclin (PGI2) induces dose-related hyperthermia at room temperature (21 C), as well as at low (4 C) and high (30 C) ambient temperatures. It is found that this PGI2-induced hyperthermia is not mediated by its stable metabolite 6-keto prostaglandin F-1(alpha). Only one of the three anion transport systems, the liver transport system, appears to be important to the central inactivation of pyrogen, prostaglandin E2, and PGI2. Phenoxybenzamine and pimozide have no thermolytic effect on PGI2-induced hyperthermia, while PGI2 still induces hyperthermia after norepinephrine (NE) and dopamine levels are depleted by 6-hydroxydopamine. Indomethacin and SC-19220 (a PG antagonist) do not antagonize PGI2 induced hyperthermia, while theophylline does not accentuate the PGI2-induced hyperthermia. However, the hyperthermic response to PGI2 is attenuated by central administration of the protein synthesis inhibitor, anisomycin. It is concluded that PGI2-induced hyperthermia is not induced by NE, dopamine, or cyclic AMP, but rather that a protein mediator is implicated in the induction of fever by PG12.

[Can Glasgow-Blatchford Score and Pre-endoscopic Rockall Score Predict the Occurrence of Hypotension in Initially Normotensive Patients with Non-variceal Upper Gastrointestinal Bleeding?].

PubMed

Kim, June Sung; Ko, Byuk Sung; Son, Chang Hwan; Ahn, Shin; Seo, Dong Woo; Lee, Yoon Seon; Lee, Jae Ho; Oh, Bum Jin; Lim, Kyoung Soo; Kim, Won Young

2016-01-25

The aim of this study was to identify the ability of Glasgow-Blatchford score (GBS) and pre-endoscopic Rockall score (pre-E RS) to predict the occurrence of hypotension in patients with non-variceal upper gastrointestinal bleeding who are initially normotensive at emergency department. Retrospective observational study was conducted at Asan Medical Center emergency department (ED) in patients who presented with non-variceal upper gastrointestinal bleeding from January 1, 2011 to December 31, 2013. Study population was divided according to the development of hypotension, and demographics, comorbidities, and laboratory findings were compared. GBS and pre-E RS were estimated to predict the occurrence of hypotension. A total of 747 patients with non-variceal upper gastrointestinal bleeding were included during the study period, and 120 (16.1%) patients developed hypotension within 24 hours after ED admission. The median values GBS and pre-E RS were statistically different according to the occurrence of hypotension (8.0 vs. 10.0, 2.0 vs. 3.0, respectively; p<0.001). In the receiver operating characteristic curve analysis of hypotension development, the area under the curve of GBS and pre-E RS were 66% and 64%, respectively. The sensitivity and the specificity of GBS using optimal cut-off value were 81% and 46%, respectively, while those based on the pre-E RS were 74% and 46%, respectively. GBS and pre-E RS were both not sufficient for predicting the occurrence of hypotension in non-variceal upper gastrointestinal bleeding. Development of other scoring systems are needed.

Pediatric Diabetic Ketoacidosis With Hypotensive Shock and Rash-An Unusual Presentation.

PubMed

Pasternak, Yehonatan; Niv, Omer; Waisman, Yehezkel Hezi

2018-05-15

We describe a previously healthy adolescent boy who presented with respiratory distress, hypotensive shock, and a diffuse erythematous rash. The final diagnosis was diabetic ketoacidosis. Caregivers should be alert to this unusual combination of symptoms in the emergency department setting in order to improve the recognition and management of children with new-onset diabetes.

Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF-1-induced macrophage migration.

PubMed

Dwyer, Amy R; Mouchemore, Kellie A; Steer, James H; Sunderland, Andrew J; Sampaio, Natalia G; Greenland, Eloise L; Joyce, David A; Pixley, Fiona J

2016-07-01

A major role of colony-stimulating factor-1 is to stimulate the differentiation of mononuclear phagocytic lineage cells into adherent, motile, mature macrophages. The colony-stimulating factor-1 receptor transduces colony-stimulating factor-1 signaling, and we have shown previously that phosphatidylinositol 3-kinase p110δ is a critical mediator of colony-stimulating factor-1-stimulated motility through the colony-stimulating factor-1 receptor pY721 motif. Src family kinases are also implicated in the regulation of macrophage motility and in colony-stimulating factor-1 receptor signaling, although functional redundancy of the multiple SFKs expressed in macrophages makes it challenging to delineate their specific functions. We report a comprehensive analysis of individual Src family kinase expression in macrophage cell lines and primary macrophages and demonstrate colony-stimulating factor-1-induced changes in Src family kinase subcellular localization, which provides clues to their distinct and redundant functions in macrophages. Moreover, expression of individual Src family kinases is both species specific and dependent on colony-stimulating factor-1-induced macrophage differentiation. Hck associated with the activated colony-stimulating factor-1 receptor, whereas Lyn associated with the receptor in a constitutive manner. Consistent with this, inhibitor studies revealed that Src family kinases were important for both colony-stimulating factor-1 receptor activation and colony-stimulating factor-1-induced macrophage spreading, motility, and invasion. Distinct colony-stimulating factor-1-induced changes in the subcellular localization of individual SFKs suggest specific roles for these Src family kinases in the macrophage response to colony-stimulating factor-1. © Society for Leukocyte Biology.

Recurrent syncope, orthostatic hypotension and volatile hypertension: think outside the box.

PubMed

Aung, Thein; Fan, Wuqiang; Krishnamurthy, Mahesh

2013-01-01

The baroreceptors in the neck and aortic arch are important regulators of sudden blood pressure changes. They are innervated by CN IX and X and synapse in the brainstem. Baroreceptor failure is an under-recognized cause of recurrent syncope, orthostatic hypotension, and volatile hypertension, which is refractory to and may in fact worsen with conventional treatments. Baroreflex failure can be the result of neck and chest radiation, head and neck surgery, and cerebrovascular accidents involving the brainstem nuclei. The management of baroreflex failure is a challenge since patient education, lifestyle changes, and family support are extremely important in managing blood pressure. Leg exercises and Thrombo-Embolic Deterrent Stockings (TED) stockings are important in treating orthostatic hypotension. Clonidine is the antihypertensive of choice for supine hypertension. Low-dose benzodiazepines are helpful in suppressing sympathetic surges. We have encountered two patients with baroreflex failure after chemotherapy and radiation to the neck or upper chest. Temporal relationship between symptoms onset and the history of head, neck, and upper chest radiation or trauma is important in reaching a diagnosis.

Hypoxia and hypotension in patients intubated by physician staffed helicopter emergency medical services - a prospective observational multi-centre study.

PubMed

Sunde, Geir Arne; Sandberg, Mårten; Lyon, Richard; Fredriksen, Knut; Burns, Brian; Hufthammer, Karl Ove; Røislien, Jo; Soti, Akos; Jäntti, Helena; Lockey, David; Heltne, Jon-Kenneth; Sollid, Stephen J M

2017-07-11

The effective treatment of airway compromise in trauma and non-trauma patients is important. Hypoxia and hypotension are predictors of negative patient outcomes and increased mortality, and may be important quality indicators of care provided by emergency medical services. Excluding cardiac arrests, critical trauma and non-trauma patients remain the two major groups to which helicopter emergency medical services (HEMS) are dispatched. Several studies describe the impact of pre-hospital hypoxia or hypotension on trauma patients, but few studies compare this in trauma and non-trauma patients. The primary aim was to describe the incidence of pre-hospital hypoxia and hypotension in the two groups receiving pre-hospital tracheal intubation (TI) by physician-staffed HEMS. Data were collected prospectively over a 12-month period, using a uniform Utstein-style airway template. Twenty-one physician-staffed HEMS in Europe and Australia participated. We compared peripheral oxygen saturation and systolic blood pressure before and after definitive airway management. Data were analysed using Cochran-Mantel-Haenszel methods and mixed-effects models. Eight hundred forty three trauma patients and 422 non-trauma patients receiving pre-hospital TI were included. Non-trauma patients had significantly lower predicted mean pre-intervention SpO 2 compared to trauma patients. Post-intervention and admission SpO 2 for the two groups were comparable. However, 3% in both groups were still hypoxic at admission. For hypotension, the differences between the groups were less prominent. However, 9% of trauma and 10% of non-trauma patients were still hypotensive at admission. There was no difference in short-term survival between trauma (97%) and non-trauma patients (95%). Decreased level of consciousness was the most frequent indication for TI, and was associated with increased survival to hospital (cOR 2.8; 95% CI: 1.4-5.4). Our results showed that non-trauma patients had a higher incidence of

CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot Trial: rationale and design.

PubMed

Potter, J; Robinson, T; Ford, G; James, M; Jenkins, D; Mistri, A; Bulpitt, C; Drummond, A; Jagger, C; Knight, J; Markus, H; Beevers, G; Dewey, M; Lees, K; Moore, A; Paul, S

2005-03-01

High and low blood pressure (BP) levels are common following acute stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly 20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours of ictus, both conditions being associated with an adverse prognosis. At present, the optimum management of blood pressure in the immediate post-stroke period is unclear. The primary aim of the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether hypertension and relative hypotension, manipulated therapeutically in the first 24 h following acute stroke, affects short-term outcome measures. The CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo-controlled, titrated dose trial. Acute stroke and medical units in teaching and district general hospitals, in the UK. The CHHIPS Pilot Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed by brain imaging, who have no compelling indication or contraindication for BP manipulation. The primary outcome measure will be the effects of acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post-stroke. Secondary outcome measures will include the influence of therapy on early neurological deterioration, the effectiveness of treatment in manipulating BP levels, the influence of time to treatment and stroke type on response and a cost-effectiveness analysis.

STATs MEDIATE FIBROBLAST GROWTH FACTOR INDUCED VASCULAR ENDOTHELIAL MORPHOGENESIS

PubMed Central

Yang, Xinhai; Qiao, Dianhua; Meyer, Kristy; Friedl, Andreas

2009-01-01

The fibroblast growth factors (FGFs) play diverse roles in development, wound healing and angiogenesis. The intracellular signal transduction pathways which mediate these pleiotropic activities remain incompletely understood. We show here that the proangiogenic factors FGF2 and FGF8b can activate signal transducers and activators of transcription (STATs) in mouse microvascular endothelial cells. Both FGF2 and FGF8b activate STAT5 and to a lesser extent STAT1, but not STAT3. The FGF2-dependent activation of endothelial STAT5 was confirmed in vivo with the matrigel plug angiogenesis assay. In tissue samples of human gliomas, a tumor type where FGF-induced angiogenesis is important, STAT5 is detected in tumor vessel endothelial cell nuclei, consistent with STAT5 activation. By forced expression of constitutively active or dominant-negative mutant STAT5A in mouse brain endothelial cells, we further show that STAT5 activation is both necessary and sufficient for FGF-induced cell migration, invasion and tube formation, which are key events in vascular endothelial morphogenesis and angiogenesis. In contrast, STAT5 is not required for brain endothelial cell mitogenesis. The cytoplasmic tyrosine kinases Src and Janus kinase 2 (Jak2) both appear to be involved in the activation of STAT5, as their inhibition reduces FGF2 and FGF8b induced STAT5 phosphorylation and endothelial cell tube formation. Constitutively active STAT5A partially restores tube formation in the presence of Src or Jak2 inhibitors. These observations demonstrate that FGFs utilize distinct signaling pathways to induce angiogenic phenotypes. Together, our findings implicate the FGF-Jak2/Src-STAT5 cascade as a critical angiogenic FGF signaling pathway. PMID:19176400

Minnesota logging utilization factors, 1975-1976--development, use, implications.

Treesearch

James E. Blyth; W. Brad Smith

1979-01-01

Discusses Minnesota saw log and pulpwood logging utilization factors developed during 1975-1976 and their implications. Compares factors for several species groups and shows their use in estimating growing stock cut for pulpwood and saw logs.

Hemodynamic Effects of Midodrine After Space Flight in Astronauts Without Orthostatic Hypotension

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Ziegler, Michael G.; Waters, Wendy W.; Meck, Janice V.

2006-01-01

Orthostatic hypotension and presyncope are common and potentially serious risks for astronauts returning from space. Susceptible subjects fail to generate an adequate adrenergic response to upright posture. The -1 adrenergic agonist, midodrine, may be an effective countermeasure. We tested the hypothesis that midodrine would have no negative hemodynamic effect on healthy astronauts returning from space. Five male astronauts participated in preflight and postflight tilt testing on a control flight as well as on the test flights, where midodrine (10 mg, orally) was administered after landing, approximately 1 hour before testing. None of these astronauts exhibited orthostatic hypotension or presyncope before or after either flight. Midodrine did not cause any untoward reactions in these subjects before or after flight, in fact a modest beneficial effect was seen on postflight tachycardia (p=0.036). These data show that midodrine protected against post-spaceflight increases in heart rate, without having any adverse hemodynamic effects on non-presyncopal, male astronauts. Among these subjects, midodrine was a safe cardiovascular countermeasure.

Population pharmacokinetics of unbound hydrocortisone in critically ill neonates and infants with vasopressor-resistant hypotension.

PubMed

Vezina, Heather E; Ng, Chee M; Vazquez, Delia M; Barks, John D; Bhatt-Mehta, Varsha

2014-07-01

To determine the population pharmacokinetics of unbound hydrocortisone in critically ill neonates and infants receiving IV hydrocortisone for treatment of vasopressor-resistant hypotension and to identify patient-specific sources of pharmacokinetic variability. Prospective observational cohort study. Level 3 neonatal ICU. Sixty-two critically ill neonates and infants receiving IV hydrocortisone as part of standard of care for the treatment of vasopressor-resistant hypotension: median gestational age 28 weeks (range, 23-41), median weight 1.2 kg (range, 0.5-4.4), and 29 females. None. Unbound baseline cortisol and postdose hydrocortisone concentrations measured from blood samples being drawn for routine laboratory tests. A one-compartment model best described the data. Allometric weight and postmenstrual age were significant covariates on unbound hydrocortisone clearance and volume of distribution. Final population estimates for clearance, volume of distribution, and baseline cortisol concentration were 20.2 L/hr, 244 L, and 1.37 ng/mL, respectively. Using the median weight and postmenstrual age of our subjects (i.e., 1.2 kg and 28 wk) in the final model, the typical unbound hydrocortisone clearance and volume of distribution were 1.0 L/hr and 4.2 L, respectively. The typical half-life for unbound hydrocortisone was 2.9 hours. A sharp and continuous increase in unbound hydrocortisone clearance was observed at 35 weeks postmenstrual age. We report the first pharmacokinetic data for unbound hydrocortisone, the pharmacologically active moiety, in critically ill neonates and infants with vasopressor-resistant hypotension. Unbound hydrocortisone clearance increased with body weight and was faster in children with an older postmenstrual age. Unbound hydrocortisone clearance increased sharply at 35 weeks postmenstrual age and continued to mature thereafter. This study lays the groundwork for evaluating unbound hydrocortisone exposure-response relationships and drawing

An enantiomerically pure formulation of esmolol attenuates hypotension and preserves heart rate control in dogs.

PubMed

McKee, Jeffrey S; Rabinow, Barrett E; Daller, Justin R; Brooks, Benjamin D; Baumgartner, Bernhard; Rohatgi, Priyanka

2014-12-01

Esmolol is marketed as a racemate (RS-esmolol) with hypotension being the most frequently reported adverse event. Previously, it has been shown that the S-enantiomer (S-esmolol) possesses all of the heart rate (HR) control. The authors studied whether S-esmolol alone mitigates hypotension at similar degrees of HR control compared with RS-esmolol. The effects of RS- and S-esmolol on blood pressure (BP) were compared at multiple infusion rates producing similar HR control in dogs (N=21). Differences in BP were further interrogated by monitoring global cardiovascular function and included the R-enantiomer (R-esmolol) (N=3). S-esmolol at half the rate (μg kg min) of RS-esmolol provided the same degree of HR control over all infusion rates. RS-esmolol lowered BP by 3, 6, 11, 20, and 38 mmHg at 90, 300, 600, 1,000, and 2,000 μg kg min, compared with 2, 4, 5, 10, and 16 mmHg at 45, 150, 300, 500, and 1,000 μg kg min for S-esmolol. Decreased BP with RS-esmolol was attributed to decreases in left ventricular developed pressure (LVDP) (-34 mmHg), LVdP/dt+max (-702 mmHg/s), and cardiac output (-1 l/min). R-esmolol also decreased BP (-10 mmHg), LVDP (-10 mmHg), LVdP/dt+max (-241 mmHg/s), and cardiac output (to -0.2 l/min). S-esmolol reversed these trends toward pre-esmolol values by increasing BP (+13 mmHg), LVDP (+12 mmHg), LVdP/dt+max (+76 mmHg/s), and cardiac output (+0.4 l/min). R-enantiomer provided no HR control, but contributed to the hypotension with RS-esmolol, which appears to be due to negative inotropy. Thus, an S-enantiomer formulation of esmolol may provide similar HR control with less hypotension.

Comparison of hypotensive, diuretic and renal effects between cladodes of Opuntia ficus-indica and furosemide.

PubMed

Bakour, Meryem; Al-Waili, Noori; El-Haskoury, Redouan; El-Menyiy, Nawal; Al-Waili, Thia; Al-Waili, Ali; Lyoussi, Badiaa

2017-09-01

To investigate the diuretic, hypotensive and renal effect of Opuntia ficus-indica in two different species in oral and intravenous administration. Diuretic activity was evaluated in rats with the plant cladode gel and aqueous extract administrated orally, and was evaluated in rabbits with plant extract administered intravenously. Single and repeated doses of cladode gel or aqueous extract of cladode were tested. Urine volume and blood and urine creatinine, sodium and potassium were measured, and creatinine clearance was calculated. The hypotensive effect of lyophilized extract of cladode was evaluated in rabbits. Two polyethylene PE50 catheters were used: one in the jugular vein for the infusion of the plant extract and the other in the carotid for the evaluation of the arterial pressure. The cladode gel or aqueous extract increased urine volume, creatinine clearance and urinary excretion of sodium and potassium without significant effect on serum creatinine or blood urea. Furosemide, gel and aqueous extract of cladode insignificantly lowered plasma potassium in rats. Intravenous administration of the lyophilized extract caused a significant decrease in mean arterial pressure in rabbits with a significant increase in urine volume and urine sodium and potassium; the effect was dose dependent. Intravenous administration of lyophilized extract did not affect plasma sodium or potassium. Gel and aqueous extract of Opuntia ficus-indica cladode have a significant diuretic effect on rats, and the lyophilized extract has a diuretic and hypotensive effect on normotensive rabbits without deterioration in renal function test. Additional studies on active ingredients are essential to pave the way for clinical studies on diuretic and hypotensive effect of the plant. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Characterization of Human Torso Vascular Morphometry in Normotensive and Hypotensive Trauma Patients

DTIC Science & Technology

2015-07-01

Aorta Wall Measures Merged for Analysis Landmarks & User-aided Segmentation 5cm Volume...with Centerline Measures AORTA PROCESSING VENA CAVA PROCESSING Basic Morphomics Scan Identification Aorta Centerline Segmented Aorta and Vena...Analysis 49 Data Presentation Aorta  Radius  Popula/on       Normotensive   Hypotensive  

Sympatho-vagal balance, as quantified by ANSindex, predicts post spinal hypotension and vasopressor requirement in parturients undergoing lower segmental cesarean section: a single blinded prospective observational study.

PubMed

Prashanth, Anitha; Chakravarthy, Murali; George, Antony; Mayur, Rohini; Hosur, Rajathadri; Pargaonkar, Sumant

2017-08-01

Hypotension subsequent to spinal anesthesia occurs in a significant number of parturients undergoing lower segment caesarian section. Currently available methods to predict the incidence of hypotension, its severity and the outcome are sub-optimal. Many workers have used basal heart rate as one of the predictors. But using this method it is not possible to objectively analyze and predict the extent and severity of hypotension. We used an equipment measuring the level of sympatho-vagal balance, ANSiscope™, which derives these values from computed value of RR interval variability. We made a single measure of the value which was blinded to the patient and the anesthesiologist. We studied one hundred eight patients who underwent lower segment caesarian section under spinal anesthesia and found the variability of preoperative ANSindex (% activity displayed by the equipment) from 9 to 65 %. Higher ANSindex value was significantly associated with post spinal hypotension (p 0.017). A value of 24 % indicated the critical level above which hypotension appeared commonly. The ANSindex value might help anesthesiologist to anticipate and prepare for hypotension that is likely to ensue.

Modulation of cardiac autonomic tone in non-hypotensive hypovolemia during blood donation.

PubMed

Yadav, Kavita; Singh, Akanksha; Jaryal, Ashok Kumar; Coshic, Poonam; Chatterjee, Kabita; Deepak, K K

2017-08-01

Non-hypotensive hypovolemia, observed during mild haemorrhage or blood donation leads to reflex readjustment of the cardiac autonomic tone. In the present study, the cardiac autonomic tone was quantified using heart rate and blood pressure variability during and after non-hypotensive hypovolemia of blood donation. 86 voluntary healthy male blood donors were recruited for the study (age 35 ± 9 years; weight 78 ± 12 kg; height 174 ± 6 cms). Continuous lead II ECG and beat-to-beat blood pressure was recorded before, during and after blood donation followed by offline time and frequency domain analysis of HRV and BPV. The overall heart rate variability (SDNN and total power) did not change during or after blood donation. However, there was a decrease in indices that represent the parasympathetic component (pNN50 %, SDSD and HF) while an increase was observed in sympathetic component (LF) along with an increase in sympathovagal balance (LF:HF ratio) during blood donation. These changes were sustained for the period immediately following blood donation. No fall of blood pressure was observed during the period of study. The blood pressure variability showed an increase in the SDNN, CoV and RMSSD time domain measures in the post donation period. These results suggest that mild hypovolemia produced by blood donation is non-hypotensive but is associated with significant changes in the autonomic tone. The increased blood pressure variability and heart rate changes that are seen only in the later part of donation period could be because of the progressive hypovolemia associated parasympathetic withdrawal and sympathetic activation that manifest during the course of blood donation.

Feasibility of intermittent back-filtrate infusion hemodiafiltration to reduce intradialytic hypotension in patients with cardiovascular instability: a pilot study.

PubMed

Koda, Yutaka; Aoike, Ikuo; Hasegawa, Shin; Osawa, Yutaka; Nakagawa, Yoichi; Iwabuchi, Fumio; Iwahashi, Chikara; Sugimoto, Tokuichiro; Kikutani, Toshihiko

2017-04-01

Intradialytic hypotension (IDH) is one of the major problems in performing safe hemodialysis (HD). As blood volume depletion by fluid removal is a major cause of hypotension, careful regulation of blood volume change is fundamental. This study examined the effect of intermittent back-filtrate infusion hemodiafiltration (I-HDF), which modifies infusion and ultrafiltration pattern. Purified on-line quality dialysate was intermittently infused by back filtration through the dialysis membrane with a programmed dialysis machine. A bolus of 200 ml of dialysate was infused at 30 min intervals. The volume infused was offset by increasing the fluid removal over the next 30 min by an equivalent amount. Seventy-seven hypotension-prone patients with over 20-mmHg reduction of systolic blood pressure during dialysis or intervention-requirement of more than once a week were included in the crossover study of 4 weeks duration for each modality. In a total of 1632 sessions, the frequency of interventions, the blood pressure, and the pulse rate were documented. During I-HDF, interventions for symptomatic hypotension were reduced significantly from 4.5 to 3.0 (per person-month, median) and intradialytic systolic blood pressure was 4 mmHg higher on average. The heart rate was lower during I-HDF than HD in the later session. Older patients and those with greater interdialytic weight gain responded to I-HDF. I-HDF could reduce interventions for IDH. It is accompanied with the increased intradialytic blood pressure and the less tachycardia, suggesting less sympathetic stimulation occurs. Thus, I-HDF could be beneficial for some hypotension-prone patients. 000013816.

Hypoxia inducible factors in hepatocellular carcinoma

PubMed Central

Chen, Chu; Lou, Tao

2017-01-01

Hepatocellular carcinoma is one of the most prevalent and lethal cancers with limited therapeutic options. Pathogenesis of this disease involves tumor hypoxia and the activation of hypoxia inducible factors. In this review, we describe the current understanding of hypoxia signaling pathway and summarize the expression, function and target genes of hypoxia inducible factors in hepatocellular carcinoma. We also highlight the recent progress in hypoxia-targeted therapeutic strategies in hepatocellular carcinoma and discuss further the future efforts for the study of hypoxia and/or hypoxia inducible factors in this deadly disease. PMID:28493839

Effect of hypotensive therapy combined with modified diet or zinc supplementation on biochemical parameters and mineral status in hypertensive patients.

PubMed

Suliburska, Joanna; Skrypnik, Katarzyna; Szulińska, Monika; Kupsz, Justyna; Bogdański, Paweł

2018-05-01

Hypotensive therapy leads to a number of trace elements metabolism disturbances. Zinc balance is frequently affected by antihypertensive treatment. To evaluate the effect of a hypotensive treatment, modified diet and zinc supplementation on mineral status and selected biochemical parameters in newly diagnosed hypertensive patients on monotherapy. In the first stage, arterial hypertension in ninety-eight human subjects was diagnosed. In the second stage, antihypertensive monopharmacotherapy was implemented. In the third stage, patients were randomized into three groups and continued antihypertensive monotherapy: group D received an optimal-mineral-content diet, group S received zinc supplementation, and group C had no changes in diet or zinc supplementation. Iron, zinc, and copper concentrations in serum, erythrocytes, urine, and hair were determined. Lipids, glucose, ceruloplasmin, ferritin, albumin, C-reactive protein (CRP), tumor necrosis factor α (TNF-α), nitric oxide (NO), superoxide dismutase (SOD) and catalase (CAT) were assayed in serum. Antihypertensive monotherapy decreased zinc concentration in serum and erythrocytes and increased the level of zinc in urine, decreased CAT and SOD activity, TNF-α concentration in serum, and increased the level of NO in the serum. Zinc supply led to an increase in zinc concentration in serum, erythrocytes, and hair (in group S only). In the groups with higher zinc intake, decreased glucose concentration in the serum was observed. Significant correlation was seen between the zinc and glucose serum concentrations. Hypotensive drugs disturb zinc status in newly diagnosed hypertensive patients. Antihypertensive monotherapy combined with increased zinc supply in the diet or supplementation favorably modify zinc homeostasis and regulate glucose status without blood pressure affecting in patients with hypertension. Copyright © 2018 Elsevier GmbH. All rights reserved.

Recent advances in orthostatic hypotension presenting orthostatic dizziness or vertigo.

PubMed

Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

2015-11-01

Orthostatic hypotension (OH), a proxy for sympathetic adrenergic failure, is the most incapacitating sign of autonomic failure. Orthostatic dizziness (OD) is known to be the most common symptom of OH. However, recent studies have demonstrated that 30-39 % of patients with OH experienced rotatory vertigo during upright posture (i.e., orthostatic vertigo, OV), which challenges the dogma that OH induces dizziness and not vertigo. A recent population-based study on spontaneously occurring OD across a wide age range showed that the one-year and lifetime prevalence of OD was 10.9 and 12.5 %, respectively. Approximately 83 % of patients with OD had at least one abnormal autonomic function test result. So far, 11 subtypes of OD have been proposed according to the pattern of autonomic dysfunction, and generalized autonomic failure of sympathetic adrenergic and parasympathetic cardiovagal functions was the most common type. Four different patterns of OH, such as classic, delayed, early, and transient type have been found in patients with OD. The head-up tilt test and Valsalva maneuver should be performed for a comprehensive evaluation of sympathetic adrenergic failure in patients with OD/OV. This review summarizes current advances in OH presenting OD/OV, with a particular focus on the autonomic dysfunction associated with OD.

Hypotensive anesthesia with esmolol. Assessment of hemodynamics, consumption of anesthetic drugs, and recovery.

PubMed

Gökçe, Biricik M; Karabiyik, Lale; Karadenizli, Yener

2009-06-01

To assess the effect of esmolol added to propofol-remifentanil combination for hypotensive anesthesia on hemodynamic conditions, consumption of anesthetic drugs, and recovery, during elective septorhinoplasty. This prospective, randomized study was carried out at Gazi University, Faculty of Medicine, Ankara, Turkey in 2005. Following Institutional Ethical Committee approval, 40 American Society of Anesthesiologists (ASA) I patients were divided into 2 equal groups group remifentanil infusion RP and group esmolol infusion (RP-E). After anesthesia induction with propofol (2-2.5 mg/kg), the mean arterial pressure was aimed to be between 50 mm Hg and 65 mm Hg for controlled hypotensive anesthesia in both groups. In group RP, a remifentanil infusion of 0.1-0.5 microg/kg/min was titrated, following a bolus of 1 microg/kg; for group RP-E, an esmolol infusion of 100-300 mg/kg/min was titrated, following a bolus of 500 microg/kg; to achieve a target blood pressure. In addition, propofol was infused according to depth of anesthesia to maintain anesthesia in both groups. Electrocardiography, heart rate, blood pressure, cardiac output, and consumption of anesthetic drugs were recorded. Postoperatively, recovery times, visual analog pain scores, and side effects were observed. The decrease in the intraoperative heart rate was more significant in group RP-E than in group RP. The remifentanil consumption was much lower in group RP-E. The recovery times were similar in both groups. Addition of esmolol to propofol-remifentanil combination leads to a decrease in remifentanil consumption, without a decrease in cardiac output during hypotensive anesthesia.

Antibody Immunity Induced by H7N9 Avian Influenza Vaccines: Evaluation Criteria, Affecting Factors, and Implications for Rational Vaccine Design

PubMed Central

Hu, Zenglei; Jiao, Xinan; Liu, Xiufan

2017-01-01

Severe H7N9 avian influenza virus (AIV) infections in humans have public health authorities around the world on high alert for the potential development of a human influenza pandemic. Currently, the newly-emerged highly pathogenic avian influenza A (H7N9) virus poses a dual challenge for public health and poultry industry. Numerous H7N9 vaccine candidates have been generated using various platforms. Immunization trials in animals and humans showed that H7N9 vaccines are apparently poorly immunogenic because they induced low hemagglutination inhibition and virus neutralizing antibody titers. However, H7N9 vaccines elicit comparable levels of total hemagglutinin (HA)-reactive IgG antibody as the seasonal influenza vaccines, suggesting H7N9 vaccines are as immunogenic as their seasonal counterparts. A large fraction of overall IgG antibody is non-neutralizing antibody and they target unrecognized epitopes outside of the traditional antigenic sites in HA. Further, the Treg epitope identified in H7 HA may at least partially contribute to regulation of antibody immunity. Here, we review the latest advances for the development of H7N9 vaccines and discuss the influence of serological criteria on evaluation of immunogenicity of H7N9 vaccines. Next, we discuss factors affecting antibody immunity induced by H7N9 vaccines, including the change in antigenic epitopes in HA and the presence of the Treg epitope. Last, we present our perspectives for the unique features of antibody immunity of H7N9 vaccines and propose some future directions to improve or modify antibody response induced by H7N9 vaccines. This perspective would provide critical implications for rational design of H7N9 vaccines for human and veterinary use. PMID:29018438

Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis.

PubMed

Goodwin, Justin; Choi, Hyunsung; Hsieh, Meng-Hsiung; Neugent, Michael L; Ahn, Jung-Mo; Hayenga, Heather N; Singh, Pankaj K; Shackelford, David B; Lee, In-Kyu; Shulaev, Vladimir; Dhar, Shanta; Takeda, Norihiko; Kim, Jung-Whan

2018-02-01

Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are the primary pathological driver of fibrotic progression, yet how various microenvironmental influences, such as hypoxia, contribute to their sustained activation and differentiation is poorly understood. As a defining feature of hypoxia is its impact on cellular metabolism, we sought to investigate how hypoxia-induced metabolic reprogramming affects myofibroblast differentiation and fibrotic progression, and to test the preclinical efficacy of targeting glycolytic metabolism for the treatment of pulmonary fibrosis. Bleomycin-induced pulmonary fibrotic progression was evaluated in two independent, fibroblast-specific, promoter-driven, hypoxia-inducible factor (Hif) 1A knockout mouse models and in glycolytic inhibitor, dichloroacetate-treated mice. Genetic and pharmacological approaches were used to explicate the role of metabolic reprogramming in myofibroblast differentiation. Hypoxia significantly enhanced transforming growth factor-β-induced myofibroblast differentiation through HIF-1α, whereas overexpression of the critical HIF-1α-mediated glycolytic switch, pyruvate dehydrogenase kinase 1 (PDK1) was sufficient to activate glycolysis and potentiate myofibroblast differentiation, even in the absence of HIF-1α. Inhibition of the HIF-1α/PDK1 axis by genomic deletion of Hif1A or pharmacological inhibition of PDK1 significantly attenuated bleomycin-induced pulmonary fibrosis. Our findings suggest that HIF-1α/PDK1-mediated glycolytic reprogramming is a critical metabolic alteration that acts to promote myofibroblast differentiation and fibrotic progression, and demonstrate that targeting glycolytic metabolism may prove to be a potential therapeutic strategy for the treatment of pulmonary fibrosis.

Post-exercise hypotension and heart rate variability response after water- and land-ergometry exercise in hypertensive patients.

PubMed

Bocalini, Danilo Sales; Bergamin, Marco; Evangelista, Alexandre Lopes; Rica, Roberta Luksevicius; Pontes, Francisco Luciano; Figueira, Aylton; Serra, Andrey Jorge; Rossi, Emilly Martinelli; Tucci, Paulo José Ferreira; Dos Santos, Leonardo

2017-01-01

systemic arterial hypertension is the most prevalent cardiovascular disease; physical activity for hypertensive patients is related to several beneficial cardiovascular adaptations. This paper evaluated the effect of water- and land-ergometry exercise sessions on post-exercise hypotension (PEH) of healthy normotensive subjects versus treated or untreated hypertensive patients. Forty-five older women composed three experimental groups: normotensive (N, n = 10), treated hypertensive (TH, n = 15) and untreated hypertensive (UH, n = 20). The physical exercise acute session protocol was performed at 75% of maximum oxygen consumption (VO2max) for 45 minutes; systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure were evaluated at rest, peak and at 15, 30, 45, 60, 75 and 90 minutes after exercise cessation. Additionally, the heart rate variability (HRV) was analyzed by R-R intervals in the frequency domain for the assessment of cardiac autonomic function. In both exercise modalities, equivalent increases in SBP were observed from rest to peak exercise for all groups, and during recovery, significant PEH was noted. At 90 minutes after the exercise session, the prevalence of hypotension was significantly higher in water- than in the land-based protocol. Moreover, more pronounced reductions in SBP and DBP were observed in the UH patients compared to TH and N subjects. Finally, exercise in the water was more effective in restoring HRV during recovery, with greater effects in the untreated hypertensive group. Our data demonstrated that water-ergometry exercise was able to induce expressive PEH and improve cardiac autonomic modulation in older normotensive, hypertensive treated or hypertensive untreated subjects when compared to conventional land-ergometry.

Effects of two novel tachykinin antagonists, FK224 and FK888, on neurogenic airway plasma exudation, bronchoconstriction and systemic hypotension in guinea-pigs in vivo.

PubMed Central

Hirayama, Y.; Lei, Y. H.; Barnes, P. J.; Rogers, D. F.

1993-01-01

1. We compared the effects of two novel tachykinin receptor antagonists, FK888 (selective at the tachykinin NK1 receptor) and FK224 (dual antagonist at NK1 and NK2 tachykinin receptors) on stimulus-evoked airway plasma exudation, bronchoconstriction and systemic hypotension in guinea-pigs in vivo. Plasma exudation was induced by substance P (SP), synthetic tachykinin receptor agonists, platelet activating factor (PAF), electrical stimulation of the cervical vagus nerves or by inhalation of cigarette smoke. Changes in airway tone and in carotid artery blood pressure (BP) were induced by synthetic tachykinin agonists, PAF and vagal stimulation. 2. Both FK224 and FK888 dose-dependently inhibited SP-induced plasma exudation in the lower trachea and main bronchi (ID50 values respectively of 1.1 and 0.1 mumol kg-1 in lower trachea, and of 0.5 and 0.1 mumol kg-1 in main bronchi) with complete inhibition at both airway levels at 10 mumol kg-1 for FK224 and at 2 mumol kg-1 for FK888. 3. The NK1-selective tachykinin receptor agonist, [Sar9,Met(O2)11]substance P ([Sar]SP), induced plasma exudation, a response which was blocked by both FK888 and FK224. The NK2-selective agonist, [beta-Ala8]neurokinin A-(4-10) ([beta-Ala]NKA), did not induce plasma exudation: neither FK888 nor FK224 affected this lack of response to [beta-Ala]NKA. 4. [beta-Ala]NKA induced bronchoconstriction, a response which was blocked by FK224 but which was completely unaffected by FK888. [Sar]SP induced a small but significant bronchoconstriction which was completely inhibited by both tachykinin antagonists. 5. In animals pretreated with capsaicin to deplete sensory neuropeptides, PAF induced both plasma exudation and bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7682142

Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury.

PubMed

Kan, Wen-Hong; Hsu, Jun-Te; Schwacha, Martin G; Choudhry, Mashkoor A; Raju, Raghavan; Bland, Kirby I; Chaudry, Irshad H

2008-10-01

Although trauma-hemorrhage produces tissue hypoxia, systemic inflammatory response and organ dysfunction, the mechanisms responsible for these alterations are not clear. Using a potent selective inducible nitric oxide (NO) synthase inhibitor, N-[3-(aminomethyl) benzyl]acetamidine (1400W), and a nonselective NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), we investigated whether inducible NO synthase plays any role in producing hepatic injury, inflammation, and changes of protein expression following trauma-hemorrhage. To investigate this, male Sprague-Dawley rats were subjected to midline laparotomy and hemorrhagic shock (mean blood pressure 35-40 mmHg for approximately 90 min) followed by fluid resuscitation. Animals were treated with either vehicle (DMSO) or 1400W (10 mg/kg body wt ip), or L-NAME (30 mg/kg iv), 30 min before resuscitation and killed 2 h after resuscitation. Trauma-hemorrhage/resuscitation induced a marked hypotension and increase in markers of hepatic injury (i.e., plasma alpha-glutathione S-transferase, tissue myeloperoxidase activity, and nitrotyrosine formation). Hepatic expression of iNOS, hypoxia-inducible factor-1alpha, ICAM-1, IL-6, TNF-alpha, and neutrophil chemoattractant (cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2) protein levels were also markedly increased following trauma-hemorrhage/resuscitation. Administration of the iNOS inhibitor 1400W significantly attenuated hypotension and expression of these mediators of hepatic injury induced by trauma-hemorrhage/resuscitation. However, administration of L-NAME could not attenuate hepatic dysfunction and tissue injury mediated by trauma-hemorrhage, although it improved mean blood pressure as did 1400W. These results indicate that increased expression of iNOS following trauma-hemorrhage plays an important role in the induction of hepatic damage under such conditions.

Neonatal capsaicin treatment impairs vasopressin-mediated blood pressure recovery following acute hypotension.

PubMed Central

Bennett, T.; Gardiner, S. M.

1984-01-01

Rats were treated with a single injection of either capsaicin (50 mg kg-1 s.c.) or vehicle on day 2 after birth. When the animals were adult, they were challenged with osmotic (water deprivation) and haemodynamic (acute hypotension) stimuli that normally evoke vasopressin release. Capsaicin-treated and vehicle-injected rats showed similar body weight losses and plasma osmolalities following 48 h of water deprivation. Thus it appears that neonatal treatment with capsaicin does not impair the antidiuretic response to plasma hyperosmolality. Following acute ganglion blockade in the presence of angiotensin converting enzyme inhibition, there was some recovery of blood pressure in the vehicle-injected rats, but recovery was significantly (P less than 0.001) less in the capsaicin-treated animals. The recovery may be attributed to vasopressin since it was abolished by an antagonist selective for the pressor action of the peptide (d(CH2)5DAVP). These results suggest that neonatal treatment with capsaicin impairs vasopressin-mediated recovery of blood pressure following acute hypotension. The possible involvement of baro- or chemoreceptor afferents is discussed. PMID:6704593

Increased incidence of clinical hypotension with etomidate compared to ketamine for intubation in septic patients: A propensity matched analysis.

PubMed

Van Berkel, Megan A; Exline, Matthew C; Cape, Kari M; Ryder, Lindsay P; Phillips, Gary; Ali, Naeem A; Doepker, Bruce A

2017-04-01

This study compared the incidence of clinical hypotension between ketamine and etomidate within a 24 hour period following endotracheal intubation. This single-center, retrospective propensity-matched cohort study included septic patients admitted to our medical intensive care unit who received either etomidate or ketamine for intubation. Clinical hypotension was defined as any one of the following: mean arterial pressure (MAP) decrease >40% compared to baseline and MAP <70 mmHg, MAP <60 mmHg, initiation of a vasopressor, or increase to >30% of the initial vasopressor dose. Patients were matched based on propensity scores determined by demographics and baseline characteristics. A total of 384 (200 etomidate and 184 ketamine) patients were included for analysis with 230 patients (115 in each group) matched. Clinical hypotension was less prevalent in patients who received ketamine as compared to etomidate [51.3% vs. 73% (odds ratio=0.39, 95% confidence interval=0.22-0.67, P=.001]. The etomidate group experienced significantly lower MAPs at time periods 6.1-12 hours (65.1 mmHg vs. 69.3 mmHg, P=.01) and 12.1-24 hours (63.9 mmHg vs. 68.4 mmHg, P=.003). Ketamine was associated with a lower incidence of clinical hypotension within the 24 hour period following endotracheal intubation in septic patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Sleep-inducing factors.

PubMed

García-García, Fabio; Acosta-Peña, Eva; Venebra-Muñoz, Arturo; Murillo-Rodríguez, Eric

2009-08-01

Kuniomi Ishimori and Henri Piéron were the first researchers to introduce the concept and experimental evidence for a chemical factor that would presumably accumulate in the brain during waking and eventually induce sleep. This substance was named hypnotoxin. Currently, the variety of substances which have been shown to alter sleep includes peptides, cytokines, neurotransmitters and some substances of lipidic nature, many of which are well known for their involvement in other biological activities. In this chapter, we describe the sleep-inducing properties of the vasoactive intestinal peptide, prolactin, adenosine and anandamide.

Kefiran suppresses antigen-induced mast cell activation.

PubMed

Furuno, Tadahide; Nakanishi, Mamoru

2012-01-01

Kefir is a traditional fermented milk beverage produced by kefir grains in the Caucasian countries. Kefiran produced by Lactobacillus kefiranofaciens in kefir grains is an exopolysaccharide having a repeating structure with glucose and galactose residues in the chain sequence and has been suggested to exert many health-promoting effects such as immunomodulatory, hypotensive, hypocholesterolemic activities. Here we investigated the effects of kefiran on mast cell activation induced by antigen. Pretreatment with kefiran significantly inhibited antigen-induced Ca(2+) mobilization, degranulation, and tumor necrosis factor-α production in bone marrow-derived mast cells (BMMCs) in a dose-dependent manner. The phosphorylation of Akt, glycogen synthase kinase 3β, and extracellular signal-regulated kinases (ERKs) after antigen stimulation was also suppressed by pretreatment of BMMCs with kefiran. These findings indicate that kefiran suppresses mast cell degranulation and cytokine production by inhibiting the Akt and ERKs pathways, suggesting an anti-inflammatory effect for kefiran.

Effects of orthostatic hypotension on cognition in Parkinson disease

PubMed Central

Centi, Justin; Freeman, Roy; Gibbons, Christopher H.; Neargarder, Sandy; Canova, Alexander O.

2017-01-01

Objective: To investigate the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in Parkinson disease (PD) using a cross-sectional and within-group design. Methods: Individuals without dementia with idiopathic PD included 18 with OH (PDOH) and 19 without OH; 18 control participants were also included. Neuropsychological tests were conducted in supine and upright-tilted positions. Blood pressure was assessed in each posture. Results: The PD groups performed similarly while supine, demonstrating executive dysfunction in sustained attention and response inhibition, and reduced semantic fluency and verbal memory (encoding and retention). Upright posture exacerbated and broadened these deficits in the PDOH group to include phonemic fluency, psychomotor speed, and auditory working memory. When group-specific supine scores were used as baseline anchors, both PD groups showed cognitive changes following tilt, with the PDOH group exhibiting a wider range of deficits in executive function and memory as well as significant changes in visuospatial function. Conclusions: Cognitive deficits in PD have been widely reported with assessments performed in the supine position, as seen in both our PD groups. Here we demonstrated that those with PDOH had transient, posture-mediated changes in excess of those found in PD without OH. These observed changes suggest an acute, reversible effect. Understanding the effects of OH due to autonomic failure on cognition is desirable, particularly as neuroimaging and clinical assessments collect data only in the supine or seated positions. Identification of a distinct neuropsychological profile in PD with OH has quality of life implications, and OH presents itself as a possible target for intervention in cognitive disturbance. PMID:27903817

Two syringe spinal anesthesia technique for cesarean section: A controlled randomized study of a simple way to achieve more satisfactory block and less hypotension.

PubMed

Keera, Amr Aly Ismail; Elnabtity, Ali Mohamed Ali

2016-01-01

Multiple trials have been tried to prevent hypotension during spinal anesthesia. However, the drug choice and mode of administration is still a matter of debate. To compare the outcome of spinal injection of hyperbaric bupivacaine and fentanyl separately to standard injection of mixed fentanyl with hyperbaric bupivacaine. A randomized, controlled clinical trial. One hundred twenty-four parturient scheduled for elective cesarean section were randomly allocated into two groups, each 62 parturient: Group M received spinal anesthesia using 10 mg bupivacaine 0.5% premixed with 25 μg fentanyl in the same syringe and Group S received 25 μg fentanyl in one syringe and 10 mg bupivacaine 0.5% without barbotage in a second syringe. Patients with intraoperative pain that was controllable without the need for a shift to general anesthesia was significantly lower in Group S (3.2%) than in Group M (16.1%). The frequency of hypotension was significantly lower in Group S compared to Group M (P < 0.05). Time till the onset of sensory block was nonsignificantly shorter with nonsignificantly higher mean level of maximal sensory block in Group S compared to Group M (P > 0.05). There was no significant difference in the time till occurrence of hypotension, duration of hypotension, mean dose of ephedrine used for the treatment of hypotension and frequency of patients developed itching between the groups (P > 0.05). Separate intrathecal injection of fentanyl and hyperbaric bupivacaine provided a significant improvement in the quality of sensory block and significant reduction of the frequency of hypotension compared to injection of mixed medications.

Population pharmacokinetics of unbound hydrocortisone in critically ill neonates and infants with vasopressor-resistant hypotension

PubMed Central

Vezina, Heather E.; Ng, Chee M.; Vazquez, Delia M.; Barks, John D.; Bhatt-Mehta, Varsha

2014-01-01

Objective To determine the population pharmacokinetics of unbound hydrocortisone (HC) in critically ill neonates and infants receiving intravenous HC for treatment of vasopressor-resistant hypotension and to identify patient-specific sources of pharmacokinetic variability. Design Prospective observational cohort study. Setting Level 3 neonatal intensive care unit. Patients Sixty-two critically ill neonates and infants receiving intravenous HC as part of standard of care for the treatment of vasopressor-resistant hypotension: median gestational age 28 weeks (range, 23 to 41), median weight 1.2 kg (range, 0.5 to 4.4), 29 females. Interventions None. Measurements Unbound baseline cortisol and post-dose HC concentrations measured from blood samples being drawn for routine laboratory tests. Main Results A one compartment model best described the data. Allometric weight and postmenstrual age (PMA) were significant covariates on unbound HC clearance (CL) and volume of distribution (V). Final population estimates for CL, V, and baseline cortisol concentration were 20.2 L/h, 244 L, and 1.37 ng/mL, respectively. Using the median weight and PMA of our subjects (i.e. 1.2 kg and 28 weeks) in the final model, the typical unbound HC CL and V were 1.0 L/h and 4.2 L, respectively. The typical half-life for unbound HC was 2.9 hours. A sharp and continuous increase in unbound HC CL was observed at 35 weeks PMA. Conclusions We report the first pharmacokinetic data for unbound HC, the pharmacologically active moiety, in critically ill neonates and infants with vasopressor-resistant hypotension. Unbound HC CL increased with body weight and was faster in children with an older PMA. Unbound HC CL increased sharply at 35 weeks PMA and continued to mature thereafter. This study lays the groundwork for evaluating unbound HC exposure-response relationships and drawing definitive conclusions about the dosing of intravenous HC in critically-ill neonates and infants with vasopressor

Orthostatic Hypotension in Middle-Age and Risk of Falls.

PubMed

Juraschek, Stephen P; Daya, Natalie; Appel, Lawrence J; Miller, Edgar R; Windham, Beverly Gwen; Pompeii, Lisa; Griswold, Michael E; Kucharska-Newton, Anna; Selvin, Elizabeth

2017-02-01

One-third of older adults fall each year. Orthostatic hypotension (OH) has been hypothesized as an important risk factor for falls, but findings from prior studies have been inconsistent. We conducted a prospective study of the association between baseline OH (1987-1989) and risk of falls in the Atherosclerosis Risk in Communities (ARIC) Study. Falls were ascertained during follow-up via ICD-9 hospital discharge codes or Centers for Medicare & Medicaid Services claims data. OH was defined as a drop in systolic blood pressure (SBP) ≥20mm Hg or diastolic blood pressure (DBP) ≥10mm Hg within 2 minutes of moving from the supine to standing position. Changes in SBP or DBP during OH assessments were also examined as continuous variables. During a median follow-up of 23 years, there were 2,384 falls among 12,661 participants (mean age 54 years, 55% women, 26% black). OH was associated with risk of falls even after adjustment for demographic characteristics and other risk factors (hazard ratio (HR): 1.30; 95% confidence interval (CI): 1.10, 1.54; P = 0.002). Postural change in DBP was more significantly associated with risk of falls (HR 1.09 per -5mm Hg change in DBP; 95% CI: 1.05, 1.13; P < 0.001) than postural change in SBP (HR 1.03 per -5mm Hg change in SBP; 95% CI: 1.01, 1.05; P = 0.002). In a community-based, middle-aged population, OH, and in particular, postural change in DBP, were independent risk factors for falls over 2 decades of follow-up. Future studies are needed to examine OH thresholds associated with increased risk of falls. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Orthostatic Hypotension in Middle-Age and Risk of Falls

PubMed Central

Juraschek, Stephen P.; Daya, Natalie; Appel, Lawrence J.; Miller, Edgar R.; Windham, Beverly Gwen; Pompeii, Lisa; Griswold, Michael E.; Kucharska-Newton, Anna

2017-01-01

BACKGROUND One-third of older adults fall each year. Orthostatic hypotension (OH) has been hypothesized as an important risk factor for falls, but findings from prior studies have been inconsistent. METHODS We conducted a prospective study of the association between baseline OH (1987–1989) and risk of falls in the Atherosclerosis Risk in Communities (ARIC) Study. Falls were ascertained during follow-up via ICD-9 hospital discharge codes or Centers for Medicare & Medicaid Services claims data. OH was defined as a drop in systolic blood pressure (SBP) ≥20mm Hg or diastolic blood pressure (DBP) ≥10mm Hg within 2 minutes of moving from the supine to standing position. Changes in SBP or DBP during OH assessments were also examined as continuous variables. RESULTS During a median follow-up of 23 years, there were 2,384 falls among 12,661 participants (mean age 54 years, 55% women, 26% black). OH was associated with risk of falls even after adjustment for demographic characteristics and other risk factors (hazard ratio (HR): 1.30; 95% confidence interval (CI): 1.10, 1.54; P = 0.002). Postural change in DBP was more significantly associated with risk of falls (HR 1.09 per −5mm Hg change in DBP; 95% CI: 1.05, 1.13; P < 0.001) than postural change in SBP (HR 1.03 per −5mm Hg change in SBP; 95% CI: 1.01, 1.05; P = 0.002). CONCLUSIONS In a community-based, middle-aged population, OH, and in particular, postural change in DBP, were independent risk factors for falls over 2 decades of follow-up. Future studies are needed to examine OH thresholds associated with increased risk of falls. PMID:27638848

Acute Radiation Hypotension in the Rabbit: a Model for the Human Radiation Shock Syndrome.

NASA Astrophysics Data System (ADS)

Makale, Milan Theodore

This study has shown that total body irradiation (TBI) of immature (40 to 100 day old) rabbits leads to an acute fall in mean arterial pressure (MAP) 30 to 90 minutes after exposure, which takes no more than about three minutes, and often results in pressures which are less than 50% of the lowest pre-exposure MAP. This is termed acute cardiovascular collapse (ACC). ACC is often accompanied by ECG T-wave elevation, a sharp rise in ear temperature, labored breathing, pupillary constriction, bladder emptying, and loss of abdominal muscle tone. About 73% of 40 to 100 day rabbits exhibit ACC; the others and most older rabbits display gradual pressure reductions (deliberate hypotension) which may be profound, and which may be accompanied by the same changes associated with ACC. ACC and deliberate hypotension occurred in rabbits cannulated in the dorsal aorta, and in non-operated animals. The decline in MAP for all 40 to 100 day cannulated rabbits (deliberate and ACC responders) is 55.4%. The experiments described below only involved 40 to 100 day cannulated TBI rabbits. Heart region irradiation resulted in an average MAP decline of 29.1%, with 1/15 rabbits showing ACC. Heart shielding during TBI reduced the decline in MAP to 19%, with 1/10 rabbits experiencing ACC. These results imply that the heart region, which includes the heart, part of the lungs, neural receptors, roots of the systemic vessels, and the blood, is a sensitive target. Bilateral vagotomy reduced the decline in MAP to 24.9%, and abolished ACC. Atropine (6 mg/kg) reduced the frequency of ACC to 26%, and the decline in MAP to 41.4%. In 11/13 rabbits the voltage generated by left vagal transmission rose after TBI. The vagi appear to participate in radiation hypotension. Heart shielding together with bilateral vagotomy reduced the decline in MAP to only 9.9%, with no ACC responders. The mean right ventricular pressure (MRVP) rose after TBI in 8/10 rabbits. In animals which displayed either ACC or steep

Cardiovascular Autonomic Dysfunction in Patients with Drug-Induced Parkinsonism

PubMed Central

Ryu, Dong-Woo; Oh, Ju-Hee; Lee, Yang-Hyun; Park, Sung-Jin; Jeon, Kipyung; Lee, Jong-Yun; Ho, Seong Hee; So, Jungmin; Im, Jin Hee; Lee, Kwang-Soo

2017-01-01

Background and Purpose Recent studies have shown that several nonmotor symptoms differ between Parkinson's disease (PD) and drug-induced parkinsonism (DIP). However, there have been no reports on cardiovascular autonomic function in DIP, and so this study investigated whether cardiovascular autonomic function differs between PD and DIP patients. Methods This study consecutively enrolled 20 DIP patients, 99 drug-naïve PD patients, and 25 age-matched healthy controls who underwent head-up tilt-table testing and 24-h ambulatory blood pressure monitoring. Results Orthostatic hypotension was more frequent in patients with PD or DIP than in healthy controls. In DIP, orthostatic hypotension was associated with the underlying psychiatric diseases and neuroleptics use, whereas prokinetics were not related to orthostatic hypotension. The supine blood pressure, nighttime blood pressure, and nocturnal blood pressure dipping did not differ significantly between the DIP and control groups. Supine hypertension and nocturnal hypertension were more frequent in PD patients than in controls. Conclusions The included DIP patients frequently exhibited orthostatic hypotension that was associated with the underlying diseases as well as the nature of and exposure time to the offending drugs. Clinicians should individualize the manifestations of DIP according to underlying diseases as well as the action mechanism of and exposure time to each offending drug. PMID:27730767

Effect of time to operation on mortality for hypotensive patients with gunshot wounds to the torso: The golden 10 minutes.

PubMed

Meizoso, Jonathan P; Ray, Juliet J; Karcutskie, Charles A; Allen, Casey J; Zakrison, Tanya L; Pust, Gerd D; Koru-Sengul, Tulay; Ginzburg, Enrique; Pizano, Louis R; Schulman, Carl I; Livingstone, Alan S; Proctor, Kenneth G; Namias, Nicholas

2016-10-01

Timely hemorrhage control is paramount in trauma; however, a critical time interval from emergency department arrival to operation for hypotensive gunshot wound (GSW) victims is not established. We hypothesize that delaying surgery for more than 10 minutes from arrival increases all-cause mortality in hypotensive patients with GSW. Data of adults (n = 309) with hypotension and GSW to the torso requiring immediate operation from January 2004 to September 2013 were retrospectively reviewed. Patients with resuscitative thoracotomies, traumatic brain injury, transfer from outside institutions, and operations occurring more than 1 hour after arrival were excluded. Survival analysis using multivariate Cox regression models was used for comparison. Hazard ratios (HRs) and 95% confidence intervals (CIs) are reported. Statistical significance was considered at p ≤ 0.05. The study population was aged 32 ± 12 years, 92% were male, Injury Severity Score was 24 ± 15, systolic blood pressure was 81 ± 29 mm Hg, Glasgow Coma Scale score was 13 ± 4. Overall mortality was 27%. Mean time to operation was 19 ± 13 minutes. After controlling for organ injury, patients who arrived to the operating room after 10 minutes had a higher likelihood of mortality compared with those who arrived in 10 minutes or less (HR, 1.89; 95% CI, 1.10-3.26; p = 0.02); this was also true in the severely hypotensive patients with systolic blood pressure of 70 mm Hg or less (HR, 2.67; 95% CI, 0.97-7.34; p = 0.05). The time associated with a 50% cumulative mortality was 16 minutes. Delay to the operating room of more than 10 minutes increases the risk of mortality by almost threefold in hypotensive patients with GSW. Protocols should be designed to shorten time in the emergency department. Further prospective observational studies are required to validate these findings. Therapeutic study, level IV.

What is the definition of intraoperative hypotension in dogs? Results from a survey of diplomates of the ACVAA and ECVAA.

PubMed

Ruffato, Marco; Novello, Lorenzo; Clark, Louise

2015-01-01

Determine arterial blood pressure range that diplomates of the American College of Veterinary Anesthesia and Analgesia (ACVAA) and European College of Veterinary Anaesthesia and Analgesia (ECVAA) use to define intraoperative hypotension in dogs and identify the threshold values used for intervention. Survey of veterinary anesthesia specialists. Diplomates of the ACVAA and ECVAA. ACVAA and ECVAA diplomates (n = 313) were invited to participate in an Internet-based survey regarding anesthetized healthy dogs undergoing two types of procedures (diagnostic or surgical). There were 151 respondents to the survey; 70.2% were ACVAA diplomates and 29.8% were ECVAA diplomates. The majority of the respondents (70.9%) worked in academia while the others were in private practice (19.2%), or research, diagnostic or pharmaceutical fields (9.9%). Hypotension was defined (mean ± SD) by the respondents as systolic arterial blood pressure (SAP) <87 ± 8 mmHg for surgical cases and <87 ± 6 mmHg for diagnostic cases, or mean arterial pressure (MAP) <62 ± 4 mmHg for both types of cases. Arterial pressures reported to prompt treatment were SAP 85 ± 13 mmHg or MAP 61 ± 4 mmHg in surgical cases, and SAP 84 ± 11 mmHg or MAP 63 ± 8 mmHg in diagnostic cases. There was agreement between ACVAA and ECVAA diplomates on the definition of intraoperative hypotension in dogs during anesthesia. The blood pressures used to define hypotension were similar to the pressures that would prompt diplomates to start treatment. Readers could infer that diplomates define hypotension as a clinical condition that requires treatment at the time of diagnosis. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Tumor necrosis factor alpha induces gamma-glutamyltransferase expression via nuclear factor-kappaB in cooperation with Sp1.

PubMed

Reuter, Simone; Schnekenburger, Michael; Cristofanon, Silvia; Buck, Isabelle; Teiten, Marie-Hélène; Daubeuf, Sandrine; Eifes, Serge; Dicato, Mario; Aggarwal, Bharat B; Visvikis, Athanase; Diederich, Marc

2009-02-01

Gamma-glutamyltransferase (GGT) cleaves the gamma-glutamyl moiety of glutathione (GSH), an endogenous antioxidant, and is involved in mercapturic acid metabolism and in cancer drug resistance when overexpressed. Moreover, GGT converts leukotriene (LT) C4 into LTD4 implicated in various inflammatory pathologies. So far the effect of inflammatory stimuli on regulation of GGT expression and activity remained to be addressed. We found that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) induced GGT promoter transactivation, mRNA and protein synthesis, as well as enzymatic activity. Remicade, a clinically used anti-TNFalpha antibody, small interfering RNA (siRNA) against p50 and p65 nuclear factor-kappaB (NF-kappaB) isoforms, curcumin, a well characterized natural NF-kappaB inhibitor, as well as a dominant negative inhibitor of kappaB alpha (IkappaBalpha), prevented GGT activation at various levels, illustrating the involvement of this signaling pathway in TNFalpha-induced stimulation. Over-expression of receptor of TNFalpha-1 (TNFR1), TNFR-associated factor-2 (TRAF2), TNFR-1 associated death domain (TRADD), dominant negative (DN) IkappaBalpha or NF-kappaB p65 further confirmed GGT promoter activation via NF-kappaB. Linker insertion mutagenesis of 536 bp of the proximal GGT promoter revealed NF-kappaB and Sp1 binding sites at -110 and -78 relative to the transcription start site, responsible for basal GGT transcription. Mutation of the NF-kappaB site located at -110 additionally inhibited TNFalpha-induced promoter induction. Chromatin immunoprecipitation (ChIP) assays confirmed mutagenesis results and further demonstrated that TNFalpha treatment induced in vivo binding of both NF-kappaB and Sp1, explaining increased GGT expression, and led to RNA polymerase II recruitment under inflammatory conditions.

Hypotensive and neurometabolic effects of intragastric Reishi (Ganoderma lucidum) administration in hypertensive ISIAH rat strain.

PubMed

Shevelev, Oleg B; Seryapina, Alisa A; Zavjalov, Evgenii L; Gerlinskaya, Lyudmila A; Goryachkovskaya, Tatiana N; Slynko, Nikolay M; Kuibida, Leonid V; Peltek, Sergey E; Markel, Arcady L; Moshkin, Mikhail P

2018-03-01

As the standard clinically used hypotensive medicines have many undesirable side effects, there is a need for new therapeutic agents, especially ones of a natural origin. One possible candidate is extract from the mushroom Reishi (Ganoderma lucidum), which is used in the treatment and prevention of many chronic diseases. To study the effectiveness of Reishi, which grows in the Altai Mountains, as an antihypertensive agent, we intragastrically administered Reishi water extract to adult male hypertensive ISIAH (inherited stress-induced arterial hypertension) rats. After seven weeks, Reishi therapy reduced blood pressure in experimental animals at a level comparable to that of losartan. Unlike losartan, intragastric Reishi introduction significantly increases cerebral blood flow and affects cerebral cortex metabolic patterns, shifting the balance of inhibitory and excitatory neurotransmitters toward excitation. Changes in cerebral blood flow and ratios of neurometabolites suggests Reishi has a potential nootropic effect. Copyright © 2018 Elsevier GmbH. All rights reserved.

A non-human primate model for investigating drug-induced risk of orthostatic hypotension and sympathetic dysfunction: Preclinical correlate to a clinical test.

PubMed

Bhatt, Siddhartha; Foote, Stephen; Smith, Andrew; Butler, Paul; Steidl-Nichols, Jill

2015-01-01

Drug induced orthostatic hypotension (OH) is an important clinical concern and can be an unexpected hurdle during drug development. OH is defined as an abnormal decrease in blood pressure (BP) triggered by a rapid postural change. The sympathetic nervous system is critical for controlling normal cardiovascular function and compensatory responses to changes in posture. Thus, OH can also serve as a surrogate indicator of sympathetic dysfunction. However, preclinical conscious models for investigating risk of OH and/or sympathetic dysfunction are lacking. Herein, we describe a conscious nonhuman primate (NHP) model which mimics the widely used clinical tilt table test for OH. Male, Cynomolgus NHPs (n = 7-8) implanted with radio-telemetry transmitters were placed in modified tilt chairs in a supine position. Subsequently, a 90° head up tilt was performed for 3 min followed by return to the supine position. BP and heart rate were continuously monitored. Test compounds were administered either intravenously or via oral gavage in a crossover design, with blood samples collected at the end of the each tilt to assess total drug concentrations. Tilt responses were assessed following treatment with positive control compounds that cause sympathetic dysfunction; hexamethonium (ganglionic blocker) and prazosin (alpha-1 adrenergic receptor antagonist). Both compounds induced marked OH as evidenced by robust and sustained BP reduction in response to a head up tilt (decrease of 25-35 mmHg for hexamethonium, decrease of 21-44 mmHg for prazosin). OH incidence rates increased in a dose-dependent manner. OH incidences following treatment with minoxidil (vasodilator) were markedly lower to those observed with hexamethonium and prazosin indicating the role of sympathetic dysfunction in causing OH. These data demonstrate that the NHP tilt test is a valuable model for investigating OH risk. This model fills an important preclinical gap for assessing such a safety concern and can be

Mechanism of action of hypotensive prostaglandins in patients with essential hypertension.

PubMed

Michibayashi, Tsutomu

2002-06-01

Despite extensive investigation, the biological mechanisms causing essential hypertension (EHT) remain unclear. To clarify the means by which hypotensive prostaglandins (Hypo-PGs, mainly PGE1 and PGE2) act in patients with EHT, the interaction between intravenously infused Hypo-PGs and pressor substances such as an adrenergic neurotransmitter, noradrenaline (NA) and angiotensin II (AII) was examined both in patients with EHT and in perfused isolated rabbit ear artery preparations. In patients with EHT, Hypo-PGs were shown to reduce the pressor responses to intravenously infused NA or AII, although no significant difference was found between the pressor responses to NA under basal conditions and the responses during intravenous infusion of Hypo-PGs. Animal studies were undertaken to investigate the inhibitory action of Hypo-PGs on the vasoconstrictive responses to electrical stimulation of the perivascular sympathetic nerves (VSNS) and to exogenous NA at pre- and postjunctional sites in blood vessel walls. The suppressive action of Hypo-PGs on the response to VSNS was shown to be more potent than that to their action on the response to exogenous NA. Thus, it was concluded that the hypotensive action of intravenously infused Hypo-PGs in patients with EHT may be more dependent on prejunctional sites than on the postjunctional sites in the walls of blood vessels.

Hypoxia-inducible factor 1α is a critical downstream mediator for hypoxia-induced mitogenic factor (FIZZ1/RELMα)-induced pulmonary hypertension

PubMed Central

Johns, Roger A.; Takimoto, Eiki; Meuchel, Lucas W.; Elsaigh, Esra; Zhang, Ailan; Heller, Nicola M.; Semenza, Gregg L.; Yamaji-Kegan, Kazuyo

2017-01-01

Objective Pulmonary hypertension (PH) is characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown that in rodents, hypoxia-induced mitogenic factor (HIMF; also known as FIZZ1 or RELMα) causes PH by initiating lung vascular inflammation. We hypothesized that hypoxia-inducible factor-1 (HIF-1) is a critical downstream signal mediator of HIMF during PH development. Approach and Results In this study, we compared the degree of HIMF-induced pulmonary vascular remodeling and PH development in wild-type (HIF-1α+/+) and HIF-1α heterozygous null (HIF-1α+/−) mice. HIMF-induced PH was significantly diminished in HIF-1α+/− mice and was accompanied by a dysregulated VEGF-A–VEGF receptor 2 pathway. HIF-1α was critical for bone marrow-derived cell migration and vascular tube formation in response to HIMF. Furthermore, HIMF and its human homolog, resistin-like molecule-β (RELMβ), significantly increased IL-6 in macrophages and lung resident cells through a mechanism dependent on HIF-1α and, at least to some extent, on nuclear factor κB. Conclusions Our results suggest that HIF-1α is a critical downstream transcription factor for HIMF-induced pulmonary vascular remodeling and PH development. Importantly, both HIMF and human RELMβ significantly increased IL-6 in lung resident cells and increased perivascular accumulation of IL-6–expressing macrophages in the lungs of mice. These data suggest that HIMF can induce HIF-1, VEGF-A, and interleukin-6, which are critical mediators of both hypoxic inflammation and PH pathophysiology. PMID:26586659

Post-suspension hypotension is attenuated in Sprague-Dawley rats by prostacyclin synthase inhibition

NASA Technical Reports Server (NTRS)

Bayorh, M. A.; Eatman, D.; Walton, M.; Socci, R. R.; Emmett, N.

2002-01-01

Cardiovascular deconditioning, sometimes manifested in astronauts during standing postflight, may be related to the impairment of autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, we examined the cardiovascular responses to 7-day 30 degrees tail-suspension and a subsequent 6-h post-suspension period in conscious male Sprague-Dawley rats to determine the role of prostacyclin in the observed post-suspension reduction in mean arterial pressure (MAP). The specific prostacyclin synthase inhibitor U-51605 (0.3 mg/kg), or saline, was administered intravenously prior to release from suspension and at 2 and 4 h post-suspension. During 7 days of suspension, MAP did not change, however, there was a post-suspension reduction in MAP which was associated with significant increases in plasma prostacyclin and nitric oxide. U-51605 attenuated the observed post-suspension hypotension and reduced plasma prostacyclin levels, but not nitric oxide levels. The baroreflex sensitivity for heart rate was modified by U-51605: increased MAP threshold and effective MAP range. Thus, the post-suspension reduction in mean arterial pressure may be due to overproduction of prostacyclin and/or other endothelium-dependent relaxing factors and alteration in baroreflex activity.

FACTORS IMPLICATED IN AMPHIBIAN POPULATION DECLINES IN THE UNITED STATES

EPA Science Inventory

Factors adversely affecting amphibian populations in the US were evaluated using information from species accounts written in a standardized format by multiple authors (Volume 2 of this book). For each species, factors implicated by the authors (i.e., known or suspected) as affec...

Neural mechanism of electroacupuncture's hypotensive effects

PubMed Central

Li, Peng; Longhurst, John C.

2010-01-01

EA at P 5–6 and S 36–37 using low current and low frequency may be able to reduce elevated blood pressure in a subset of patients (~70%) with mild to moderate hypertension. The effect is slow in onset but is long-lasting. Experimental studies have shown that EA inhibition of cardiovascular sympathetic neurons that have been activated through visceral reflex stimulation is through activation of neurons in the arcuate nucleus of the hypothalamus, vlPAG in the midbrain and NRP in the medulla, which, in turn, inhibit the activity of premotor sympathetic neurons in the rVLM. The arcuate also provides direct projections to the rVLM that contain endorphins. Glutamate, acetylcholine, opioids, GABA, nociceptin, serotonin and endocannabinoids all appear to participate in the EA hypotensive response although their importance varies between nuclei. Thus, a number of mechanisms underlying the long-lasting effect of EA on cardiovascular function have been identified but clearly further investigation is warranted. PMID:20444652

Post-exercise hypotension and heart rate variability response after water- and land-ergometry exercise in hypertensive patients

PubMed Central

Bocalini, Danilo Sales; Bergamin, Marco; Evangelista, Alexandre Lopes; Rica, Roberta Luksevicius; Pontes, Francisco Luciano; Figueira, Aylton; Serra, Andrey Jorge; Rossi, Emilly Martinelli; Tucci, Paulo José Ferreira

2017-01-01

Background systemic arterial hypertension is the most prevalent cardiovascular disease; physical activity for hypertensive patients is related to several beneficial cardiovascular adaptations. This paper evaluated the effect of water- and land-ergometry exercise sessions on post-exercise hypotension (PEH) of healthy normotensive subjects versus treated or untreated hypertensive patients. Methods Forty-five older women composed three experimental groups: normotensive (N, n = 10), treated hypertensive (TH, n = 15) and untreated hypertensive (UH, n = 20). The physical exercise acute session protocol was performed at 75% of maximum oxygen consumption (VO2max) for 45 minutes; systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure were evaluated at rest, peak and at 15, 30, 45, 60, 75 and 90 minutes after exercise cessation. Additionally, the heart rate variability (HRV) was analyzed by R-R intervals in the frequency domain for the assessment of cardiac autonomic function. Results In both exercise modalities, equivalent increases in SBP were observed from rest to peak exercise for all groups, and during recovery, significant PEH was noted. At 90 minutes after the exercise session, the prevalence of hypotension was significantly higher in water- than in the land-based protocol. Moreover, more pronounced reductions in SBP and DBP were observed in the UH patients compared to TH and N subjects. Finally, exercise in the water was more effective in restoring HRV during recovery, with greater effects in the untreated hypertensive group. Conclusion Our data demonstrated that water-ergometry exercise was able to induce expressive PEH and improve cardiac autonomic modulation in older normotensive, hypertensive treated or hypertensive untreated subjects when compared to conventional land-ergometry. PMID:28658266

Dialysate bicarbonate variation in maintenance hemodiafiltration patients: Impact on serum bicarbonate, intradialytic hypotension and interdialytic weight gain.

PubMed

Viegas, Márcio; Cândido, Cristina; Felgueiras, Joana; Clemente, José; Barros, Sara; Farbota, Rostislav; Vera, Filipa; Matos, Antero; Sousa, Francisco

2017-07-01

The dialysate bicarbonate (DB) influences the acid-base balance in dialysis patients. Very low and high serum bicarbonate (SB) have been related with a higher mortality. Acid-base balance also has been associated with hemodynamic effects in these patients. The trial aim was to compare the effect of DB concentration variation on SB levels in maintenance hemodiafiltration (HDF) patients and the effect on intradialytic hypotension and interdialytic weight gain. A prospective study, with 9 months of follow-up, involving 93 patients, divided in two groups: group 1 and group 2 with a DB of 34 mmol/L and 30 mmol/L, respectively, with monitoring of pre and post HDF SB, intradialytic hypotension, and interdialytic weight gain. Pre dialysis SB was higher in group 1: median concentration of 22.7 mmol/L vs. 21.1 mmol/L (P < 0.001). Post dialysis SB levels were higher in group 1: median concentration of 28.0 mmol/L vs. 25.3 mmol/L (P < 0.001). Post dialysis SB in alkalotic range was only detected in group 1 (51.2% of the patients). No significant differences were detected in intradialytic hypotension rate [28.0 vs. 27.4 episodes per 1000 sessions in group 1 and 2, respectively, (P = 0.906)] or in average interdialytic weight gain [2.9% vs. 3.0% in group 1 and 2, respectively, (P = 0.710)]. DB of 30 mmol/L appears to be associated with SB levels closer to physiological levels than 34 mmol/L. The bicarbonate dialysate, in the tested concentrations, did not appear to have a significant impact on intradialytic hypotension and interdialytic weight gain in maintenance HDF patients. © 2016 International Society for Hemodialysis.

Meta-analysis of the safety and efficacy of droxidopa for neurogenic orthostatic hypotension.

PubMed

Elgebaly, Ahmed; Abdelazeim, Bassant; Mattar, Omar; Gadelkarim, Mohamed; Salah, Rehab; Negida, Ahmed

2016-06-01

Droxidopa has been approved for the treatment of neurogenic orthostatic hypotension (NOH) under the US Food and Drug Administration accelerated approval program, which warrants confirmatory evidence on long-term efficacy of droxidopa. Hereby, we synthesize evidence from published randomized controlled trials (RCTs) about the safety and efficacy of droxidopa for patients with neurogenic orthostatic hypotension. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager version 5.3 for Windows. Subgroup analysis and sensitivity analysis were conducted to investigate long-term durability of droxidopa against placebo. Four RCTs with a total of 485 patients (droxidopa, n = 246; placebo, n = 239) were eligible for the final analysis. The mean difference (MD) of change in the main outcomes from baseline to endpoint favored droxidopa than placebo [Orthostatic Hypotension Questionnaire (OHQ) MD -0.61, P = 0.004; dizziness/lightheadedness score MD -0.83, P = 0.008; and standing systolic blood pressure (SBP) MD 4.09, P = 0.03]. The efficacy of droxidopa decreased gradually after 2 weeks, and its statistical significance was lost after 8 weeks (OHQ score MD -0.18, P = 0.61; dizziness/lightheadedness score MD -0.71, P = 0.11; and standing SBP MD 2.96, P = 0.29). None of the adverse events were significantly higher in the case of droxidopa compared to placebo. Droxidopa is a safe and effective drug for the short-term management of NOH symptoms. However, current evidence is insufficient to confirm the efficacy of droxidopa for long-term use. Therefore, further studies with increased sample size are needed.

PACAP and VIP regulate hypoxia-inducible factors in neuroblastoma cells exposed to hypoxia.

PubMed

Maugeri, Grazia; D'Amico, Agata Grazia; Rasà, Daniela Maria; Saccone, Salvatore; Federico, Concetta; Cavallaro, Sebastiano; D'Agata, Velia

2018-06-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two related peptides acting as neurotransmitters/neuromodulators in central and peripheral nervous system. They are also involved in cancer showing a controversial role. Particulary, they are implicated in neuroblastoma differentiation (NB). This pediatric tumor can evolve to a malignant metastatic disease or spontaneously regress towards a benign form, known as ganglioneuroblastoma/ganglioneuroma. A negative hallmark of neoplasia progression is represented by hypoxic microenvironment. Low oxygen tension induces activation of hypoxia-inducible factors (HIFs) promoting cells proliferation and metastasis formation. Moreover, HIFs trigger vascular endothelial growth factor (VEGF) release favouring high-risk NB phenotype development. In the present work, we have investigated for the first time, if PACAP and VIP interfere with NB differentiation through modulation of hypoxic/angiogenic process. To this end, we analyzed their effect in malignant undifferentiated and all-trans retinoic acid (RA) differentiated SH-SY5Y cells, representing the benign form of this tumor. Our results have suggested tha both peptides, but predominantly VIP, induce NB differentiation into benign form by regulating HIFs, VEGF and VEGFRs expression and distribution. All these data give new insight regarding PACAP/VIP regulatory role in NB progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Orthostatic Hypotension and Mortality in Elderly Frail Patients

PubMed Central

Freud, Tamar; Punchik, Boris; Yan, Press

2015-01-01

Abstract Orthostatic hypotension (OH) is a common problem in the elderly age group, and some studies have reported an association between OH and increased mortality. We evaluated possible associations between OH and mortality in a retrospective study of frail elderly patients who came for a comprehensive geriatric assessment. The study included all patients ≥65 years who were assessed in the outpatient Comprehensive Geriatric Assessment Unit. Data were collected from the computerized medical record, including blood pressure, sociodemographic data, lifestyle, falls, pulse rate, body mass index, functional and cognitive status, and comorbidity. Data on mortlaity were also collected. The study population consisted of 571 patients who underwent assessment over a 9-year study period. The mean age was 83.7 ± 6.1, 35.9% were males, and 183 (32.1%) were diagnosed with OH. Systolic OH (OHS) was more common than diastolic OH (25.2% vs 15.6%). In univariate analyses, OHS was associated with increased overall mortality. Over the follow-up period, 30.2% of the OHS patients died compared with 22.3% (P = 0.037), but in the Cox models there was no statistically significant associations between OHS and overall mortality. In contrast, age, burden of comorbidity, a low high-density lipoprotein level, and low creatinine clearance were independent predictors of increased overall mortality. In a population of frail elderly patients with a high burden of comorbidity, OH was not an independent risk factor for overall mortality. PMID:26091470

Post-Exercise Hypotension and Its Mechanisms Differ after Morning and Evening Exercise: A Randomized Crossover Study

PubMed Central

da Silva Junior, Natan D.; Tinucci, Tais; Casarini, Dulce E.; Cipolla-Neto, José

2015-01-01

Post-exercise hypotension (PEH), calculated by the difference between post and pre-exercise values, it is greater after exercise performed in the evening than the morning. However, the hypotensive effect of morning exercise may be masked by the morning circadian increase in blood pressure. This study investigated PEH and its hemodynamic and autonomic mechanisms after sessions of aerobic exercise performed in the morning and evening, controlling for responses observed after control sessions performed at the same times of day. Sixteen pre-hypertensive men underwent four sessions (random order): two conducted in the morning (7:30am) and two in the evening (5pm). At each time of day, subjects underwent an exercise (cycling, 45 min, 50%VO2peak) and a control (sitting rest) session. Measurements were taken pre- and post-interventions in all the sessions. The net effects of exercise were calculated for each time of day by [(post-pre exercise)-(post-pre control)] and were compared by paired t-test (P<0.05). Exercise hypotensive net effects (e.g., decreasing systolic, diastolic and mean blood pressure) occurred at both times of day, but systolic blood pressure reductions were greater after morning exercise (-7±3 vs. -3±4 mmHg, P<0.05). Exercise decreased cardiac output only in the morning (-460±771 ml/min, P<0.05), while it decreased stroke volume similarly at both times of day and increased heart rate less in the morning than in the evening (+7±5 vs. +10±5 bpm, P<0.05). Only evening exercise increased sympathovagal balance (+1.5±1.6, P<0.05) and calf blood flow responses to reactive hyperemia (+120±179 vs. -70±188 U, P<0.05). In conclusion, PEH occurs after exercise conducted at both times of day, but the systolic hypotensive effect is greater after morning exercise when circadian variations are considered. This greater effect is accompanied by a reduction of cardiac output due to a smaller increase in heart rate and cardiac sympathovagal balance. PMID:26186444

The efficacy and hemodynamic response to Dexmedetomidine as a hypotensive agent in posterior fixation surgery following traumatic spine injury

PubMed Central

Jamaliya, Ramila H; Chinnachamy, Rajesh; Maliwad, Jyotsna; Deshmukh, Varun P; Shah, Bharat J; Chadha, Indu A

2014-01-01

Aim: This study was designed to evaluate the efficacy of dexmedetomidine (DEX) as a hypotensive agent in comparison to nitroglycerin (NTG) in posterior fixation surgery for traumatic spine injury. Materials and Methods: Forty patients ASA I or II aged 18-65 years scheduled for posterior fixation surgery were randomly assigned to receive either DEX 1 μg/kg over 10 min before induction of anesthesia followed by 0.2-0.7 μg/kg/h infusion during maintenance in DEX group or NTG 3-5 μg/kg/min infusion after induction of anesthesia in NTG group to maintain mean arterial blood pressure (MAP) between 65 and 70 mmHg. The two groups were compared for achievement of target MAP, intraoperative blood loss, and reversibility of hypotensive state. Student's t-test was used for continuous variables and chi-square test for categorical variables. P-value < 0.05 was considered significant. Results: Patients in DEX group achieved the target MAP with better heart rate (HR) control, as compared to NTG group during the period of observation. The blood loss was significantly lesser in the DEX group (422.11 ± 149.34 ml) than the NTG group (564.51 ± 160.88 ml), P = 0.01. The time to hypotension reversal in NTG group (5.63 ± 1.93 min) was lesser compared to DEX group (9.15 ± 2.16 min), P = 0.65. Conclusion: DEX is an effective and safe agent in achieving controlled hypotension in adults undergoing posterior fixation spine surgery. PMID:24803758

Role of prostaglandin/cAMP pathway in the diuretic and hypotensive effects of purified fraction of Maytenus ilicifolia Mart ex Reissek (Celastraceae).

PubMed

Leme, Thiago dos Santos Vilhena; Prando, Thiago Bruno Lima; Gasparotto, Francielly Mourão; de Souza, Priscila; Crestani, Sandra; de Souza, Lauro Mera; Cipriani, Thales Ricardo; Lourenço, Emerson Luiz Botelho; Gasparotto, Arquimedes

2013-10-28

Although Maytenus ilicifolia is used in Brazilian folk medicine as a diuretic drug, no study has been conducted to this date in order to evaluate this ethnopharmacological statement. So, the aim of this study was to evaluate possible mechanisms involved in acute diuretic activity of the ethanolic supernatant of the infusion (SEI) obtained from Maytenus ilicifolia and to assess its relationship with a hypotensive activity by a bioassay-guided fractionation using normotensive Wistar rats. The preparation obtained from the infusion (SEI) and their respective fractions (Fr·H2O and Fr·EtOAc) were orally administered in a single dose to rats. The urine excretion rate, pH, density, conductivity and content of Na(+), K(+), Cl(-) and HCO3(-) were measured in the urine of saline-loaded animals. Samples of the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated in collected serum. The hypotensive activity and the involvement of nitric oxide, bradykinin and prostaglandin/cAMP pathway in the hypotensive and diuretic effects were also determined. Water and Na(+) excretion rate were significantly increased by Fr·EtOAc and the arterial pressure was significantly reduced, while the urinary excretion of potassium and chloride were reduced. Pre-treatment with indomethacin or DDA (2',5'-dideoxyadenosine) significantly reduced the hypotensive and diuretic activity observed. All other parameters evaluated were not affected by any treatment. The present study reveals that Fr·EtOAc obtained from Maytenus ilicifolia may present compounds responsible for diuretic and hypotensive activities, and this effect, could involve the prostaglandin/cAMP pathway. © 2013 Elsevier Ireland Ltd. All rights reserved.

[Studying the association between genetic polymorphism of growth factors and the development of primary open-angle glaucoma].

PubMed

Kirilenko, M Yu; Tikunova, E V; Sirotina, S S; Polonikov, A V; Bushueva, O Yu; Churnosov, M I

Primary open-angle glaucoma (POAG) is a multifactorial disease, etiopathogenesis of which largely depends on growth factors. Possessing a variety of medical and biological effects, these cytokines may influence the development and progression of POAG. to reveal the role of genetic polymorphisms of growth factors in predisposition to developing POAG that is refractory to local hypotensive therapy. The object of the study were 162 patients with stage II-III POAG, in whom local hypotensive therapy was inefficient, 90 patients with stage II-III POAG well controlled on local hypotensive therapy, and 191 controls. The material for the study was venous blood taken from the cubital vein of a proband. Isolation of genomic DNA was performed by phenol-chloroform extraction. Analysis of genetic polymorphisms of growth factors was performed through allelic discrimination. For that, synthesis of DNA was carried out via polymerase chain reaction (PCR). It is found that the T IGFR-1 genetic variant (OR=1.34) and a combination of the C VEGF-A and T IGFR-1 genetic variants (OR=1.90) are risk factors of developing POAG that is refractory to local hypotensive therapy. A statistical model for predicting such a risk has been proposed that includes: VEGF-A с.-958C>T genetic marker (rs 833,061), age, concomitant non-inflammatory ocular diseases, microvascular changes in the conjunctiva, the degree of pigmentation of the angle of the anterior chamber, and pseudoexfoliative syndrome. Recognition accuracy of the model is 90.42%. The T IGFR-1 genetic variant and a combination of the C VEGF-A and T IGFR-1 genetic variants increase the risk of developing POAG that is refractory to local hypotensive therapy.

Angiotensin peptides attenuate platelet-activating factor-induced inflammatory activity in rats.

PubMed

Sato, Akira; Yokoyama, Izumi; Ebina, Keiichi

2015-11-01

Angiotensin (Ang)--a peptide that is part of the renin-angiotensin system-induces vasoconstriction and a subsequent increase in blood pressure; Ang peptides, especially AngII, can also act as potent pro-inflammatory mediators. Platelet-activating factor (PAF) is a potent phospholipid mediator that is implicated in many inflammatory diseases. In this study, we investigated the effects of Ang peptides (AngII, AngIII, and AngIV) on PAF-induced inflammatory activity. In experiments using a rat hind-paw oedema model, AngII markedly and dose-dependently attenuated the paw oedema induced by PAF. The inhibitory effects of AngIII and AngIV on PAF-induced paw oedema were lower than that of AngII. Two Ang receptors, the AT1 and AT2 receptors, did not affect the AngII-mediated attenuation of PAF-induced paw oedema. Moreover, intrinsic tyrosine fluorescence studies demonstrated that AngII, AngIII, and AngIV interact with PAF, and that their affinities were closely correlated with their inhibitory effects on PAF-induced rat paw oedema. Also, AngII interacted with metabolite/precursor of PAF (lyso-PAF), and an oxidized phospholipid, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), which bears a marked structural resemblance to PAF. Furthermore, POVPC dose-dependently inhibited AngII-mediated attenuation of PAF-induced paw oedema. These results suggest that Ang peptides can attenuate PAF-induced inflammatory activity through binding to PAF and lyso-PAF in rats. Therefore, Ang peptides may be closely involved in the regulation of many inflammatory diseases caused by PAF. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure.

PubMed

Shibao, Cyndya; Okamoto, Luis E; Gamboa, Alfredo; Yu, Chang; Diedrich, Andre'; Raj, Satish R; Robertson, David; Biaggioni, Italo

2010-11-01

Orthostatic hypotension affects patients with autonomic failure producing considerable disability because of presyncopal symptoms. Severely affected patients may have residual sympathetic tone that can be engaged to increase blood pressure (BP) with the α-2 adrenergic antagonist yohimbine. This medication activates sympathetic outflow centrally and unrestrains norepinephrine release from noradrenergic neurons. Alternatively, the acetylcholinesterase inhibitor, pyridostigmine, can increase sympathetic tone by improving ganglionic cholinergic neurotransmission. Our purpose was to compare these complementary approaches and to explore whether the combination would lead to synergistic increases in BP. We compared the effects of 60 mg of pyridostigmine and 5.4 mg of yohimbine in a single-blind, randomized, placebo-controlled, crossover fashion. In a subset of patients we tested the combination of pyridostigmine and yohimbine. Our primary outcome was the change in standing diastolic BP 60 minutes after drug administration from baseline. We studied a total of 31 patients with severe autonomic failure. Yohimbine significantly improved standing diastolic BP as compared with placebo (11±3 mm Hg [95% CI: 6 to 16 mm Hg]; P<0.001). On the contrary, pyridostigmine did not increase the standing diastolic BP (0.6±3 mm Hg [95% CI: -5 to 5 mm Hg]; P=0.823). Only yohimbine showed a significant improvement in presyncopal symptoms. Sixteen patients received the combination of pyridostigmine and yohimbine, but no evidence of synergistic pressor effect was found. Engaging residual sympathetic tone with yohimbine is a more effective approach to improve orthostatic hypotension as compared with pyridostigmine in patients with severe orthostatic hypotension.

COMPARATIVE EFFICACY OF YOHIMBINE AGAINST PYRIDOSTIGMINE FOR THE TREATMENT OF ORTHOSTATIC HYPOTENSION IN AUTONOMIC FAILURE

PubMed Central

Shibao, Cyndya; Okamoto, Luis E.; Gamboa, Alfredo; Yu, Chang; Diedrich, Andre'; Raj, Satish R.; Robertson, David; Biaggioni, Italo

2010-01-01

Orthostatic hypotension affects patients with autonomic failure producing considerable disability because of pre-syncopal symptoms. Severely affected patients may have residual sympathetic tone that can be engaged to increase blood pressure with the alpha-2 adrenergic antagonist yohimbine. This medication activates sympathetic outflow centrally and unrestrains norepinephrine release from noradrenergic neurons. Alternatively, the acetylcholinesterase inhibitor, pyridostigmine, can increase sympathetic tone by improving ganglionic cholinergic neurotransmission. Our purpose was to compare these complementary approaches and test the hypothesis that the combination would lead to synergistic increases in blood pressure. We compared the effects of pyridostigmine 60 mg and yohimbine 5.4 mg in a single-blind, randomized, placebo-controlled, crossover fashion. In a subset of patients we tested the combination of pyridostigmine and yohimbine. Our primary outcome was the change in standing diastolic blood pressure 60 minutes after drug administration from baseline. We studied a total of 31 patients with confirmed severe autonomic failure. Yohimbine significantly improved standing diastolic blood pressure as compared to placebo (11±3 mm Hg 95%CI: 6 to 16, P <0.001). On the contrary, Pyridostigmine did not increase the standing diastolic blood pressure (0.6±3 mm Hg 95%CI: −5 to 5, P =0.823). Only yohimbine showed a significant improvement in presyncopal symptoms. Sixteen patients received the combination of pyridostigmine and yohimbine, but no evidence of synergistic pressor effect was found. Engaging residual sympathetic tone with yohimbine is a more effective approach to improve orthostatic hypotension as compared to pyridostigmine in patients with severe orthostatic hypotension. PMID:20837887

Hypovolemia Induced Orthostatic Hypotension in Presyncopal Astronauts and Normal Subjects Related to Hypoadrenergic Responsiveness

NASA Technical Reports Server (NTRS)

Meck, Janice V.; Platts, Steven H.; Waters, Wendy W.; Shi, Shang-Jin; Hayashi, Yuho; Perez, Sondra A.; Ziegler, Michael G.

2006-01-01

Circulating blood volume is reduced during spaceflight, making astronauts hemodynamically compromised. After landing, astronauts separate into two groups. One group compensates for the hypovolemia with a hyper-sympathetic response during upright tilt testing and can complete a tilt test with few symptoms. The other group is unable to mount a hyper-sympathetic response and experiences orthostatic hypotension and presyncope during upright tilt tests. We tested the hypothesis that hypovolemia alone, in the absence of spaceflight, also would cause subjects to separate into presyncopal and non-presyncopal groups according to their sympathetic responses during tilt. We studied 20 subjects, including 10 veteran astronauts, on three occasions. On Days 1 (normovolemia) and 3 (hypovolemia), plasma volume, tilt tolerance and supine and standing plasma norepinephrine levels were measured. Forty hours prior to Day 3, subjects were given intravenous furosemide, followed by 36 hours of a 10MEq Na diet. Statistical comparisons were made between normovolemia and hypovolemia responses. This protocol reproduced landing day tilt test outcomes with 100% fidelity in the astronauts. Similarly to patterns reported after flight, non-presyncopal subjects had greater norepinephrine responses to tilt during hypovolemia compared to normovolemia (580 plus or minus 79 vs. 298 plus or minus 37 pg/ml, P less than 0.05), but presyncopal subjects had no increase (180 plus or minus 44 vs. 145 plus or minus 32 pg/ml, P=NS). This model can be used to predict astronauts who will become presyncopal on landing day, so that prospective, individualized countermeasures can be developed. Within patient populations, it can be used to study the interaction of volemic state and the sympathetic nervous system.

Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial).

PubMed

Anstey, Matthew H; Wibrow, Bradley; Thevathasan, Tharusan; Roberts, Brigit; Chhangani, Khushi; Ng, Pauline Yeung; Levine, Alexander; DiBiasio, Alan; Sarge, Todd; Eikermann, Matthias

2017-03-21

Patients admitted to intensive care units (ICU) are often treated with intravenous (IV) vasopressors. Persistent hypotension and dependence on IV vasopressors in otherwise resuscitated patients lead to delay in discharge from ICU. Midodrine is an oral alpha-1 adrenergic agonist approved for treatment of symptomatic orthostatic hypotension. This trial aims to evaluate whether oral administration of midodrine is an effective adjunct to standard therapy to reduce the duration of IV vasopressor treatment, and allow earlier discharge from ICU and hospital. The MIDAS trial is an international, multicenter, randomized, double-blind, placebo-controlled clinical trial being conducted in the USA and Australia. We are targeting 120 patients. Adult patients admitted to the ICU who are resuscitated and otherwise stable on low dose IV vasopressors for at least 24 h will be considered for recruitment. Participants will be randomized to receive midodrine (20 mg) or placebo three times a day, in addition to standard care. The primary outcome is time (hours) from initiation of midodrine or placebo to discontinuation of IV vasopressors. Secondary outcomes include time (hours) from ICU admission to discharge readiness, ICU length of stay (LOS) (days), hospital LOS (days), rates of ICU readmission, and rates of adverse events related to midodrine administration. Midodrine is approved by the Food and Drug Administration (FDA) for the treatment of symptomatic orthostatic hypotension. In August 2010, FDA proposed to withdraw approval of midodrine because of lack of studies that verify the clinical benefit of the drug. We obtained Investigational New Drug (IND 113,330) approval to study its effects in critically ill patients who require IV vasopressors but are otherwise ready for discharge from the ICU. A pilot observational study in a cohort of surgical ICU patients showed that the rate of decline in vasopressor requirements increased after initiation of midodrine treatment. We

Nitric oxide synthase inhibition depresses the height of the cerebral blood flow-pressure autoregulation curve during moderate hypotension.

PubMed

Jones, Stephen C; Easley, Kirk A; Radinsky, Carol R; Chyatte, Douglas; Furlan, Anthony J; Perez-Trepichio, Alejandro D

2003-09-01

Variations in the height of the CBF response to hypotension have been described recently in normal animals. The authors evaluated the effects of nitric oxide synthase (NOS) inhibition on these variations in height using laser Doppler flowmetry in 42 anesthetized (halothane and N2O) male Sprague-Dawley rats prepared with a superfused closed cranial window. In four groups (time control, enantiomer control, NOS inhibition, and reinfusion control) exsanguination to MABPs from 100 to 40 mm Hg was used to produce autoregulatory curves. For each curve the lower limit of autoregulation (the MABP at the first decrease in CBF) was identified; the pattern of autoregulation was classified as "peak" (15% increase in %CBF), "classic" (plateau with a decrease at the lower limit of autoregulation), or "none" (15% decrease in %CBF); and the autoregulatory height as the %CBF at 70 mm Hg (%CBF(70)) was determined. NOS inhibition decreased %CBF(70) in the NOS inhibition group (P = 0.014), in the control (combined time and enantiomer control) group (P = 0.015), and in the reinfusion control group (P = 0.025). NOS inhibition via superfusion depressed the autoregulatory pattern (P = 0.02, McNemar test on changes in autoregulatory pattern) compared with control (P = 0.375). Analysis of covariance showed that changes induced by NOS inhibition in the parameters of autoregulatory height are not related to changes in the lower limit, but are strongly (P < 0.001) related to each other. NOS inhibition depressed the autoregulatory pattern, decreasing the seemingly paradoxical increase in CBF as blood pressure decreases. These results suggest that nitric oxide increases CBF near the lower limit and augments the hypotensive portion of the autoregulatory curve.

Evaluation of the advantageous anesthetic properties of dexmedetomidine used as hypotensive agent compared with nitroglycerin in orthognathic surgery.

PubMed

Rummasak, Duangdee; Apipan, Benjamas

2014-12-01

To evaluate the advantageous anesthetic properties, such as the decrease of intraoperative analgesic requirement, time to extubation and recovery, and early postoperative pain, of dexmedetomidine used as hypotensive agent compared with nitroglycerin in orthognathic surgery. The authors implemented a prospective, single-blinded, randomized clinical trial. The sample was composed of healthy patients who were admitted for bimaxillary osteotomies and were assigned to 1 of 2 groups by a computer-generated random number and blinded to the group. Dexmedetomidine or nitroglycerin was used as the hypotensive drug for each group. All patients underwent hypotensive anesthesia and surgery according to standard protocol. Intraoperative amount of fentanyl, time to eye opening, time to follow basic verbal commands, time to extubation, early postoperative pain scores, and analgesics were recorded. Compared means were analyzed using the unpaired Student t test. A 2-sided statistical test was used. A P value less than .05 was considered significant. The sample was composed of 40 participants. The intraoperative fentanyl requirement was significantly lower in the dexmedetomidine group than in the nitroglycerin group (168.75±56.29 and 222.50±96.12 μg, respectively; P=.037). Times to eye opening and following commands were considerably longer in the dexmedetomidine group, but the time to extubation showed no meaningful difference. Early postoperative pain after 30 and 60 minutes and the requirement for meperidine were not meaningfully different between the 2 groups. Dexmedetomidine, used as a hypotensive drug, has anesthetic benefits compared with nitroglycerin. Dexmedetomidine decreases the intraoperative fentanyl requirement and does not meaningfully change the time to extubation, early postoperative pain, and analgesic drug requirement. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Impact of hypotension after return of spontaneous circulation on survival in patients of out-of-hospital cardiac arrest.

PubMed

Chiu, Yu Koon; Lui, Chun Tat; Tsui, Kwok Leung

2018-01-01

To investigate the relationship between hypotension in the first 3h after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest. This retrospective cohort study occurred at two regional hospitals and included adult OHCA patients who experienced ROSC from July 1, 2014 to December 31, 2015. Hemodynamic and inotrope administration data were retrieved for 3h after ROSC. We calculated the hypotensive exposure index (HEI) as the surrogate marker of the exposure of hypotension. The area under the ROC curve and multivariate logistic regression models were performed to analyze the effect of HEI on survival. Mean arterial pressure (MAP) was explored in the surviving and non-surviving patient groups using repeated measures MANCOVA, adjusted for the use of inotropes and down time. A total of 289 patients were included in the study, and 29 survived. The median 1-hour HEI and 3-hour HEI were significantly lower in the survival group (p<0.001). The area under the ROC curve for 3-hour HEI was 0.861. The repeated measures MANCOVA indicated that an interaction existed between post-ROSC time and downtime [F(5,197)=2.31, p=0.046]. No significant change in the MAP was observed in the 3h after ROSC, except in the group with a prolonged down time. According to the tests examining the effects of the use of inotropes on the survival outcomes of the different subjects, the MAP was significantly higher in the surviving group [F(1,201)=4.11; p=0.044; ηp2=0.020]. Among the patients who experienced ROSC after OHCA, post-ROSC hypotension was an independent predictor of survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors influencing the thermally-induced strength degradation of B/Al composites

NASA Technical Reports Server (NTRS)

Dicarlo, J. A.

1982-01-01

Literature data related to the thermally-induced strength degradation of B/Al composites were examined in the light of fracture theories based on reaction-controlled fiber weakening. Under the assumption of a parabolic time-dependent growth for the interfacial reaction product, a Griffith-type fracture model was found to yield simple equations whose predictions were in good agreement with data for boron fiber average strength and for B/Al axial fracture strain. The only variables in these equations were the time and temperature of the thermal exposure and an empirical factor related to fiber surface smoothness prior to composite consolidation. Such variables as fiber diameter and aluminum alloy composition were found to have little influence. The basic and practical implications of the fracture model equations are discussed.

Traditional systolic blood pressure targets underestimate hypotension-induced secondary brain injury.

PubMed

Brenner, Megan; Stein, Deborah M; Hu, Peter F; Aarabi, Bizhan; Sheth, Kevin; Scalea, Thomas M

2012-05-01

predictive of 12-month GOSE (p = 0.02). PTD/D SBP <120 mm Hg in the first 24 hours and PTD and PTD/D in the first 48 hours were also predictive of 12-month GOSE (p < 0.05). Within the first 48 hours of intensive care unit admission, hypotension was found to be predictive of mortality and functional outcomes at higher thresholds than traditionally defined. Systemic blood pressure targets closer to 120 mm Hg may be more efficacious in minimizing secondary insults and particularly useful in settings without invasive intracranial monitoring capabilities. III, prognostic study.

Cationic solid lipid nanoparticles enhance ocular hypotensive effect of melatonin in rabbit.

PubMed

Leonardi, Antonio; Bucolo, Claudio; Drago, Filippo; Salomone, Salvatore; Pignatello, Rosario

2015-01-15

The study was aimed at evaluating whether the ocular hypotensive effect of melatonin (MEL) was enhanced by its encapsulation in cationic solid lipid nanoparticles (cSLN), as well as at determining the tolerability of these formulations on the ocular surface. MEL was loaded in cSLN that had already been shown to be suitable for ophthalmic use. The formulations were prepared using Softisan(®) 100 as the main lipid matrix, with the presence of either stearic (SA) or palmitic acid (PA) as lipid modifiers. A fixed positive charge was provided by the addition of a cationic lipid (didecyldimethylammonium bromide). The ocular hypotensive effect was evaluated by measuring the intraocular pressure (IOP) during 24h in albino rabbits. MEL elicited a significant (p<0.01) IOP reduction in rabbit eye. All the formulations tested in vivo demonstrated a good tolerability. The nanocarrier containing SA was the most effective in terms of IOP reduction (maximum IOP reduction: -7 mmHg), and its effect lasted approximately 24h. The experimental data indicate that the new formulations based on cSLN loaded with MEL represent a potent anti-glaucoma treatment with a safe profile, warranting further clinical evaluation of the proposed nanotechnological strategy. Copyright © 2014. Published by Elsevier B.V.

Severe hypotension during the decreasing phase of Gz stress in anesthetized rats wearing an anti-G suit.

PubMed

Maruyama, Satoshi; Kemuriyama, Takehito; Manabe, Tomoko; Takahata, Tomofumi; Shoji, Ichiro; Nishida, Yasuhiro

2011-11-01

Physiological responses to +Gz stress have been reported in several studies. However, no reports exist on differences in arterial pressure responses between increasing and decreasing G phases. We hypothesized that +Gz stress and/or an anti-G support might disturb the circulation system and cause potential brain hypoperfusion, even if the anti-G support protects against G-induced loss of consciousness. Dependency of +Gz magnitude, hemodynamic changes, renal sympathetic nerve activity (RSNA), and aortic blood flow (AoBF) were estimated in anesthetized rats to analyze the effects of +Gz stress and/or an anti-G support on arterial pressure at a level of the brain (APLB). The rats were exposed to +Gz using a centrifuge for small animals while wearing an anti-G suit. APLB remained at the control level while the anti-G suit was inflated. However, a decrease in APLB was observed twice during increasing and decreasing G phases using the anti-G suit. Hypotension in the decreasing C phase at +5 Gz was significantly deeper than that in the increasing G phase (47.5 +/- 7.7 vs. 29.6 +/- 3.0 mmHg). RSNA responses to Gz loads were greater in the decreasing G than in the increasing G phase (129.7 +/- 8.6 vs. 147.3 +/- 10.4%). Both AoBF and calculated vascular resistance were suppressed more significantly in the decreasing G than in the increasing G phase (38.3 +/- 4.4 vs. 34.4 +/- 3.4 ml x min(-1), 1.44 +/- 0.22 vs. 1.09 +/- 0.14 mmHg x min(-1) x ml(-1)). We conclude that transient excessive decreasing G hypotension may occur during the decreasing G phase, which may be due to anti-G suit functioning.

Profound Obstructive Hypotension From Prone Positioning Documented by Transesophageal Echocardiography in a Patient With Scoliosis: A Case Report.

PubMed

Abcejo, Arnoley S; Diaz Soto, Juan; Castoro, Courtney; Armour, Sarah; Long, Timothy R

2017-08-01

In a healthy 12-year-old female with scoliosis, prone positioning resulted in pressor-refractory cardiovascular collapse. Resumption of supine position immediately improved hemodynamics. Intraoperative transesophageal echocardiography (TEE) revealed a collapsed left atrium and biventricular failure. Repeat prone positioning resulted in a recurrence of hypotension. However, hemodynamic stabilization was restored and maintained by repositioning chest pads caudally. The patient successfully underwent a 6-hour scoliosis repair without perioperative morbidity. With this case, we aim to: (1) reintroduce awareness of this mechanical obstructive cause of reversible hypotension; (2) highlight the use of intraoperative TEE during prone hemodynamic collapse; and (3) suggest an alternative prone positioning technique if chest compression results in hemodynamic instability.

Chronic social isolation in the prairie vole induces endothelial dysfunction: implications for depression and cardiovascular disease

PubMed Central

Peuler, Jacob D.; Scotti, Melissa-Ann L.; Phelps, Laura E.; McNeal, Neal; Grippo, Angela J.

2012-01-01

Humans with depression show impaired endothelium-dependent vasodilation, one recent demonstration of which was in the form of a reduced acetylcholine (ACh)-induced relaxation of adrenergically-precontracted small arteries biopsied from older depressed patients. Results from such uses of ACh in general have been validated as the most predictive marker of endothelium-related cardiovascular diseases. Accordingly, we examined vascular reactivity to ACh in the socially isolated prairie vole, a new animal model relevant to human depression and cardiovascular disease. Thoracic aortas were carefully dissected from female prairie voles after one month of social isolation (versus pairing with a sibling). Only aortas that contracted to the adrenergic agent phenylephrine (PE) and then relaxed to ACh were evaluated. Among those, ACh-induced relaxations were significantly reduced by social isolation (p<0.05), with maximum relaxation reaching only 30% (of PE-induced precontraction) compared to 47% in aortas from paired (control) animals. Experimental removal of the endothelium from an additional set of aortic tissues abolished all ACh relaxations including that difference. In these same tissues, maximally-effective concentrations of the nitric oxide-donor nitroprusside still completely relaxed all PE-induced precontraction of the endothelial-free smooth muscle, and to the same degree in tissues from isolated versus paired animals. Finally, in the absence of PE-induced precontraction ACh did not relax but rather contracted aortic tissues, and to a significantly greater extent in tissues from socially isolated animals if the endothelium was intact (p<0.05). Thus, social isolation in the prairie vole may 1) impair normal release of protective anti-atherosclerotic factors like nitric oxide from the vascular endothelium (without altering the inherent responsiveness of the vascular smooth muscle to such factors) and 2) cause the endothelium to release contracting factors. To our

Injection speed of spinal anaesthesia for Caesarean delivery in Asian women and the incidence of hypotension: A randomised controlled trial.

PubMed

Chiang, Chun Fai; Hasan, M Shahnaz; Tham, Sin Wan; Sundaraj, Sebastian; Faris, Ahmad; Ganason, Nagappan

2017-06-01

The purpose of this investigation was to determine if a slower speed of spinal anaesthesia injection would reduce the incidence of hypotension. Randomised controlled trial. Tertiary level hospital in Malaysia. 77 patients undergoing elective Caesarean delivery. Differing speeds of spinal injection. Systolic blood pressure was assessed every minute for the first 10min and incidence of hypotension (reduction in blood pressure of >30% of baseline) was recorded. The use of vasopressor and occurrence of nausea/vomiting were also recorded. 36 patients in SLOW group and 41 patients in FAST group were recruited into the study. There was no significant difference in blood pressure drop of >30% (p=0.497) between the two groups. There was no difference in the amount of vasopressor used and incidence of nausea/vomiting in both groups. In our study population, there was no difference in incidence of hypotension and nausea/vomiting when spinal injection time is prolonged beyond 15s to 60s. ClinicalTrials.govNCT02275897. Registered on 15 October 2014. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors associated with maternal death in an intensive care unit

PubMed Central

Saintrain, Suzanne Vieira; de Oliveira, Juliana Gomes Ramalho; Saintrain, Maria Vieira de Lima; Bruno, Zenilda Vieira; Borges, Juliana Lima Nogueira; Daher, Elizabeth De Francesco; da Silva Jr, Geraldo Bezerra

2016-01-01

Objective To identify factors associated with maternal death in patients admitted to an intensive care unit. Methods A cross-sectional study was conducted in a maternal intensive care unit. All medical records of patients admitted from January 2012 to December 2014 were reviewed. Pregnant and puerperal women were included; those with diagnoses of hydatidiform mole, ectopic pregnancy, or anembryonic pregnancy were excluded, as were patients admitted for non-obstetrical reasons. Death and hospital discharge were the outcomes subjected to comparative analysis. Results A total of 373 patients aged 13 to 45 years were included. The causes for admission to the intensive care unit were hypertensive disorders of pregnancy, followed by heart disease, respiratory failure, and sepsis; complications included acute kidney injury (24.1%), hypotension (15.5%), bleeding (10.2%), and sepsis (6.7%). A total of 28 patients died (7.5%). Causes of death were hemorrhagic shock, multiple organ failure, respiratory failure, and sepsis. The independent risk factors associated with death were acute kidney injury (odds ratio [OR] = 6.77), hypotension (OR = 15.08), and respiratory failure (OR = 3.65). Conclusion The frequency of deaths was low. Acute kidney injury, hypotension, and respiratory insufficiency were independent risk factors for maternal death. PMID:28099637

Comparison of two different approaches to hypotension following spinal anaesthesia for Caesarean delivery: effects on neonatal and maternal wellbeing.

PubMed

Zasa, Michele; Conci, Eleonora; Marchignoli, Alessandro; Pini, Rita; Passeri, Lorenzo; Fanelli, Guido; Cornini, Andrea

2015-04-27

Maternal hypotension during spinal anaesthesia for Caesarean delivery is a common event, with potential detrimental consequences. We led a prospective, randomized study to compare the effects of two strategies on neonatal and maternal wellbeing. Parturients scheduled for elective Caesarean section in spinal anaesthesia were preoperatively studied with a supine stress test. Those with a positive test were enrolled in the study and received a solution of 0.5% hyperbaric bupivacaine 12.5 mg and 0.02% morphine 200 µg intrathecally. Patients received a 37.5 mg/h preventive intravenous (IV) infusion of ephedrine (Pharmacologic Group), or a 15° left lateral tilt (Non-Pharmacologic Group). In Pharmacolgic Group hypotension was treated for 20% drops in systolic blood pressure; in Non-Pharmacolgic Group only severe hypotension - defined as a 40% drop in systolic blood pressure - was treated. Thirty-six patients were studied. Study groups were statistically similar in terms of demographic variables and intraoperative times. No statistical differences were found in terms of umbilical arterial blood base excess [-1.4 (-3.7 to -0.3) mEq/l Pharmacologic Group vs. -1.7 (-2.7 to -1.0) mEq/l Non-Pharmacologic Group; p=0.815] and other umbilical blood gas values. Apgar scores were statistically similar between study groups. Treatment for hypotension was required by 13 (72.2%) patients in Pharmacologic Group and 9 (50%) patients in Non-Pharmacologic Group (p=0.171). No differences were found at the analysis of serial changes in vital signs. Both studied strategies guaranteed a comparable safe outcome in terms of maternal and neonatal wellbeing. (www.actabiomedica.it).

Orthostatic Hypotension: Epidemiology, Prognosis, and Treatment.

PubMed

Ricci, Fabrizio; De Caterina, Raffaele; Fedorowski, Artur

2015-08-18

Orthostatic hypotension (OH) is a common cardiovascular disorder, with or without signs of underlying neurodegenerative disease. OH is diagnosed on the basis of an orthostatic challenge and implies a persistent systolic/diastolic blood pressure decrease of at least 20/10 mm Hg upon standing. Its prevalence is age dependent, ranging from 5% in patients <50 years of age to 30% in those >70 years of age. OH may complicate treatment of hypertension, heart failure, and coronary heart disease; cause disabling symptoms, faints, and traumatic injuries; and substantially reduce quality of life. Despite being largely asymptomatic or with minimal symptoms, the presence of OH independently increases mortality and the incidence of myocardial infarction, stroke, heart failure, and atrial fibrillation. In this review, we outline the etiology and prevalence of OH in the general population, summarize its relationship with morbidity and mortality, propose a diagnostic and therapeutic algorithm, and delineate current challenges and future perspectives. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Risk factors associated with short-term outcome and development of perioperative complications in dogs undergoing surgery because of gastric dilatation-volvulus: 166 cases (1992-2003).

PubMed

Beck, Jennifer J; Staatz, Andrew J; Pelsue, Davyd H; Kudnig, Simon T; MacPhail, Catriona M; Seim, Howard B; Monnet, Eric

2006-12-15

To evaluate risk factors associated with death and development of perioperative complications in dogs undergoing surgery for treatment of gastric dilatation-volvulus (GDV). Retrospective case series. 166 dogs. Records of dogs with confirmed GDV that underwent surgery were reviewed. Logistic regression was performed to identify factors associated with development of complications (ie, hypotension, arrhythmias, gastric necrosis necessitating gastrectomy, disseminated intravascular coagulation, peritonitis, sepsis, postoperative dilatation, postoperative vomiting, and incisional problems) and with short-term outcome (ie, died vs survived to the time of suture removal). Short-term mortality rate was 16.2% (27/166). Risk factors significantly associated with death prior to suture removal were clinical signs for > 6 hours prior to examination, combined splenectomy and partial gastrectomy, hypotension at any time during hospitalization, peritonitis, sepsis, and disseminated intravascular coagulation. Partial gastrectomy was not a significant risk factor for death but was for peritonitis, disseminated intravascular coagulation, sepsis, and arrhythmias. Age, gastrectomy, and disseminated intravascular coagulation were risk factors for development of hypotension. Use of a synthetic colloid or hypertonic saline solution was associated with a significantly decreased risk of hypotension. Results suggest that the prognosis for dogs undergoing surgery because of GDV is good but that certain factors are associated with an increased risk that dogs will develop perioperative complications or die.

[Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

PubMed

Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

2009-08-18

It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a

Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled Pilot Study in a Swine Model

DTIC Science & Technology

2014-11-01

ORIGINAL CONTRIBUTION Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant...and chronic pain. Intravenous lipid emulsion (ILE) is a recent antidote for lipophilic drug overdose with unclear effectiveness. ILE has been studied in...Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled

Improved management of intradialytic hypotension (IDH) using vitamin E-bonded polysulfone membrane dialyzer.

PubMed

Matsumura, Masaki; Sasaki, Hisako; Sekizuka, Kumiko; Sano, Hiroyuki; Ogawa, Kouji; Shimizu, Chihiro; Yoshida, Hiroaki; Kobayashi, Satsuki; Koremoto, Masahide; Aritomi, Masaharu; Ueki, Kazue

2010-03-01

Intradialytic hypotension (IDH) is a common clinical trait in hemodialysis (HD) which is caused by poor biocompatibility of the dialyzer membrane. Aiming to improve IDH, vitamin E-bonded polysulfone dialyzer (VPS-H) was evaluated in a pilot study. Eight IDH patients on standard HD were switched from their conventional high-flux dialyzers to VPS-H, and intradialytic blood pressure (BP) was monitored regularly for 10 months. The results showed that hypotension of systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) during the session were improved after changing the dialyzer. Notably, almost all the values recorded from 120 minutes into the session until the end of the treatment in the period between the second and tenth month after treatment were significantly different from the corresponding baseline values. Moreover, after 8 to 10 months, the SBP prior to a dialysis session was significantly reduced compared with baseline values. On the other hand, the pulse rate showed no difference throughout the study period. This study provides early evidence of the beneficial role that vitamin E-bonded dialyzers may have in preventing IDH. Larger controlled trials are needed to confirm this original finding.

Hypoxia-Induced Mitogenic Factor Promotes Cardiac Hypertrophy via Calcium-Dependent and Hypoxia-Inducible Factor-1α Mechanisms.

PubMed

Kumar, Santosh; Wang, Gang; Liu, Wenjuan; Ding, Wenwen; Dong, Ming; Zheng, Na; Ye, Hongyu; Liu, Jie

2018-06-11

HIMF (hypoxia-induced mitogenic factor/found in inflammatory zone 1/resistin like α) is a secretory and cytokine-like protein and serves as a critical stimulator of hypoxia-induced pulmonary hypertension. With a role for HIMF in heart disease unknown, we explored the possible roles for HIMF in cardiac hypertrophy by overexpressing and knocking down HIMF in cardiomyocytes and characterizing HIMF gene ( himf ) knockout mice. We found that HIMF mRNA and protein levels were upregulated in phenylephrine-stimulated cardiomyocyte hypertrophy and our mouse model of transverse aortic constriction-induced cardiac hypertrophy, as well as in human hearts with dilated cardiomyopathy. Furthermore, HIMF overexpression could induce cardiomyocyte hypertrophy, as characterized by elevated protein expression of hypertrophic biomarkers (ANP [atrial natriuretic peptide] and β-MHC [myosin heavy chain-β]) and increased cell-surface area compared with controls. Conversely, HIMF knockdown prevented phenylephrine-induced cardiomyocyte hypertrophy and himf ablation in knockout mice significantly attenuated transverse aortic constriction-induced hypertrophic remodeling and cardiac dysfunction. HIMF overexpression increased the cytosolic Ca 2+ concentration and activated the CaN-NFAT (calcineurin-nuclear factor of activated T cell) and MAPK (mitogen-activated protein kinase) pathways; this effect could be prevented by reducing cytosolic Ca 2+ concentration with L-type Ca 2+ channel blocker nifedipine or inhibiting the CaSR (Ca 2+ sensing receptor) with Calhex 231. Furthermore, HIMF overexpression increased HIF-1α (hypoxia-inducible factor) expression in neonatal rat ventricular myocytes, and HIMF knockout inhibited HIF-1α upregulation in transverse aortic constriction mice. Knockdown of HIF-1α attenuated HIMF-induced cardiomyocyte hypertrophy. In conclusion, HIMF has a critical role in the development of cardiac hypertrophy, and targeting HIMF may represent a potential therapeutic

Orthostatic Hypotension: Mechanisms, Causes, Management

PubMed Central

Tomalia, Victoria A.

2015-01-01

Orthostatic hypotension (OH) occurs when mechanisms for the regulation of orthostatic BP control fails. Such regulation depends on the baroreflexes, normal blood volume, and defenses against excessive venous pooling. OH is common in the elderly and is associated with an increase in mortality rate. There are many causes of OH. Aging coupled with diseases such as diabetes and Parkinson's disease results in a prevalence of 10-30% in the elderly. These conditions cause baroreflex failure with resulting combination of OH, supine hypertension, and loss of diurnal variation of BP. The treatment of OH is imperfect since it is impossible to normalize standing BP without generating excessive supine hypertension. The practical goal is to improve standing BP so as to minimize symptoms and to improve standing time in order to be able to undertake orthostatic activities of daily living, without excessive supine hypertension. It is possible to achieve these goals with a combination of fludrocortisone, a pressor agent (midodrine or droxidopa), supplemented with procedures to improve orthostatic defenses during periods of increased orthostatic stress. Such procedures include water bolus treatment and physical countermaneuvers. We provide a pragmatic guide on patient education and the patient-orientated approach to the moment to moment management of OH. PMID:26174784

Endotoxin-induced shock in the rat. A role for C5a.

PubMed Central

Smedegård, G.; Cui, L. X.; Hugli, T. E.

1989-01-01

Administration of endotoxin from gram-negative bacteria to rats results in systemic hypotension, an increased hematocrit, and decreased numbers of circulating leukocytes (polymorphonuclear), monocytes, and platelets. These potentially lethal physiologic changes may be partially attributed to complement activation and generation of anaphylatoxins by the endotoxin (LPS). We demonstrated an elevation in the plasma levels of both C3a and C5a in LPS-treated rats. Injection of 5 micrograms C5ades Arg (rat) into rats produced effects similar to those induced by LPS, including decreased mean arterial pressure (systemic hypotension) and decreased numbers of circulating polymorphonuclear leukocytes, monocytes, and platelets. Unlike the response to LPS, C5a did not increase the hematocrit, indicating little effect on vascular permeability at the doses used. When LPS-treated animals were pretreated with F(ab')2 fragments of rabbit anti-rat C5a, no changes were measured in the circulating cell counts compared with LPS alone; however a significant improvement in the mean arterial pressure and a decrease in hematocrit was observed. We conclude that LPS-induced (septic) shock in the rat may result, in part, from the effects of complement activation and particularly from the generation of C5a. The influence of C5a on the LPS effect in the rat appears to enhance both the hypotensive (mean arterial pressure) and vascular permeability (hematocrit) responses. These results appear to support and confirm earlier observations that anti-human C5a increased survival in a septic-shock monkey model by eliminating circulating C5a and presumably thereby reducing the effects of endotoxin on blood pressure. Our results demonstrate that C5a plays a significant role in the hemodynamic changes associated with endotoxin-induced shock. Neutralization of C5a with specific antibodies may reduce the hypotensive response to endotoxin sufficiently to prevent lethal septic shock both in animals and in man

Incidence, Predictors, and Outcomes Associated With Hypotensive Episodes Among Heart Failure Patients Receiving Sacubitril/Valsartan or Enalapril: The PARADIGM-HF Trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure).

PubMed

Vardeny, Orly; Claggett, Brian; Kachadourian, Jessica; Pearson, Scott M; Desai, Akshay S; Packer, Milton; Rouleau, Jean; Zile, Michael R; Swedberg, Karl; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

2018-04-01

In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure), heart failure treatment with sacubitril/valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared with enalapril but resulted in more symptomatic hypotension. Concern on hypotension may be limiting use of sacubitril/valsartan in appropriate patients. We characterized patients in PARADIGM-HF by whether they reported hypotension during study run-in periods (enalapril, followed by sacubitril/valsartan) and after randomization and assessed whether hypotension modified the efficacy of sacubitril/valsartan. Of the 10 513 patients entering the enalapril run-in, 136 (1.3%) experienced hypotension and 93 (68%) were unable to continue to the next phase; of 9419 patients entering the sacubitril/valsartan run-in period, 228 (2.4%) patients experienced hypotension and 51% were unable to successfully complete the run-in. After randomization, 388 (9.2%) participants had 501 hypotensive events with enalapril, and 588 (14.0%) participants had 803 hypotensive events with sacubitril/valsartan ( P <0.001). There was no difference between randomized treatment groups in the number of participants who discontinued therapy because of hypotension. Individuals with a hypotensive event in either group were older, had lower blood pressure at randomization, and were more likely to have an implantable cardioverter defibrillator. Participants with hypotensive events during run-in who were ultimately randomized derived similar efficacy from sacubitril/valsartan compared with enalapril as those without hypotensive events ( P interaction>0.90). Hypotension was more common with sacubitril/valsartan relative to enalapril in PARADIGM-HF but did not differentially affect permanent discontinuations. Patients with hypotension during run-in derived

Cardiovascular Safety of Droxidopa in Patients With Symptomatic Neurogenic Orthostatic Hypotension.

PubMed

White, William B; Hauser, Robert A; Rowse, Gerald J; Ziemann, Adam; Hewitt, L Arthur

2017-04-01

The norepinephrine prodrug droxidopa improves symptoms of neurogenic orthostatic hypotension, a condition that is associated with diseases of neurogenic autonomic failure (e.g., Parkinson disease, multiple system atrophy, pure autonomic failure). These conditions are more prevalent in older patients who also have cardiovascular co-morbidities. Hence, we evaluated the cardiovascular safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension who participated in randomized controlled studies (short-term studies of 1 to 2 weeks and an intermediate 8- to 10-week study) and long-term open-label studies. Rates of cardiovascular adverse events (AEs) for patients treated with droxidopa were 4.4% in the intermediate study and 10.8% in the long-term open-label studies. Adjusting for exposure time, cardiovascular AE rates were 0.30 events/patient-year in the short-term and intermediate studies and 0.15 events/patient-year in the long-term open-label studies. The incidence of treatment discontinuation due to blood pressure-related events was approximately 2.5%. Among patients with a history of cardiac disorders at baseline, the rates of cardiovascular-related and blood pressure-related AEs were nominally higher with droxidopa compared to placebo. Most of these events were minor atrial arrhythmias; none were major adverse cardiovascular events or deaths. In conclusion, small increases in cardiovascular AEs were observed with droxidopa compared to placebo; this was most evident in patients with preexisting cardiac disorders. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Temazepam, but not zolpidem, causes orthostatic hypotension in astronauts after spaceflight

NASA Technical Reports Server (NTRS)

Shi, Shang-Jin; Garcia, Kathleen M.; Meck, Janice V.

2003-01-01

Insomnia is a common symptom, not only in the adult population but also in many astronauts. Hypnotics, such as temazepam (a benzodiazepine) and zolpidem (an imidazopyridine), are often taken to relieve insomnia. Temazepam has been shown clinically to have hemodynamic side effects, particularly in the elderly; however, the mechanism is not clear. Zolpidem does not cause hemodynamic side effects. The purpose of this study was to determine whether the use of different hypnotics during spaceflight might contribute significantly to the high incidence of postflight orthostatic hypotension, and to compare the findings in astronauts with clinical research. Astronauts were separated into three groups: control (n = 40), temazepam (15 or 30 mg; n = 9), and zolpidem (5 or 10 mg; n = 8). In this study, temazepam and zolpidem were only taken the night before landing. The systolic and diastolic blood pressures and heart rates of the astronauts were measured during stand tests before spaceflight and on landing day. On landing day, systolic pressure decreased significantly and heart rate increased significantly in the temazepam group, but not in the control group or in the zolpidem group. Temazepam may aggravate orthostatic hypotension after spaceflight when astronauts are hemodynamically compromised. Temazepam should not be the initial choice as a sleeping aid for astronauts. These results in astronauts may help to explain the hemodynamic side effects in the elderly who are also compromised. Zolpidem may be a better choice as a sleeping aid in these populations.

Contribution of vasoactive eicosanoids and nitric oxide production to the effect of selective cyclooxygenase-2 inhibitor, NS-398, on endotoxin-induced hypotension in rats.

PubMed

Tunctan, Bahar; Korkmaz, Belma; Cuez, Tuba; Kemal Buharalioglu, C; Sahan-Firat, Seyhan; Falck, John; Malik, Kafait U

2010-11-01

Our previous studies with the use of non-selective cyclooxygenase (COX) inhibitor, indomethacin, demonstrated that prostanoids produced during endotoxaemia increase inducible nitric oxide synthase (iNOS) protein expression and nitric oxide synthesis, and decrease cyctochrome P450 (CYP) 4A1 protein expression and CYP 4A activity. The results suggest that dual inhibition of iNOS and COX by indomethacin restores blood pressure presumably due to increased production of 20-hydroxyeicosatetraenoic acid (20-HETE) derived from CYP 4A in endotoxaemic rats. The present study examined whether increased levels of vasoconstrictor eicosanoids, 20-HETE, prostaglandin F(2α) (PGF(2α) )and thromboxane A(2) (TxA(2) ), would contribute to the effect of selective COX-2 inhibition to prevent endotoxin (ET)-induced fall in blood pressure associated with an increase in the production of vasodilator prostanoids, prostaglandin I(2) (PGI(2) ) and prostaglandin E(2) (PGE(2) ) and nitric oxide synthesis. Mean arterial blood pressure fell by 31 mmHg and heart rate (HR) rose by 90 beats/min. in male Wistar rats treated with ET (10 mg/kg, i.p.). The fall in mean arterial pressure and increase in HR were associated with increased levels of 6-keto-prostaglandin F(1α) (6-keto-PGF(1α) ), PGE(2) , TxB(2) , and nitrite in the serum, kidney, heart, thoracic aorta and/or superior mesenteric artery. Systemic and renal 20-HETE and PGF(2α) levels were also decreased in endotoxaemic rats. These effects of ET were prevented by a selective COX-2 inhibitor, N-(2-cyclohexyloxy-4-nitrophenyl)methansulphonamide (10 mg/kg, i.p.), given 1 hr after injection of ET. These data suggest that an increase in 20-HETE and PGF(2α) levels associated with decreased production of PGI(2) , PGE(2) , and TxA(2) , and nitric oxide synthesis contributes to the effect of selective COX-2 inhibitor to prevent the hypotension during rat endotoxaemia. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic

Brain Slump Caused by Jugular Venous Stenoses Treated by Stenting: A Hypothesis to Link Spontaneous Intracranial Hypotension with Idiopathic Intracranial Hypertension

PubMed Central

Higgins, Nicholas; Trivedi, Rikin; Greenwood, Richard; Pickard, John

2015-01-01

Spontaneous intracranial hypotension, of which brain slump is an extreme expression, is caused by a cerebrospinal fluid leak. The reason the leak develops in the first place, however, is unknown, and some cases can be very difficult to manage. We describe a patient with severe symptoms of spontaneous intracranial hypotension and brain slump documented by magnetic resonance imaging whose clinical syndrome and structural brain anomaly resolved completely after treatment directed exclusively at improving cranial venous outflow. Diagnostics included computed tomography (CT) venography, catheter venography, and jugular venoplasty. CT venography showed narrowing of both internal jugular veins below the skull base. Catheter venography confirmed that these were associated with pressure gradients. Jugular venoplasty performed on two separate occasions as a clinical test gave temporary respite. Lasting remission (2 years of follow-up) was achieved by stenting the dominant internal jugular vein. These findings and this outcome suggest a mechanism for the development of spontaneous intracranial hypotension that would link it to idiopathic intracranial hypertension and have cranial venous outflow obstruction as the underlying cause. PMID:26251803

Brain Slump Caused by Jugular Venous Stenoses Treated by Stenting: A Hypothesis to Link Spontaneous Intracranial Hypotension with Idiopathic Intracranial Hypertension.

PubMed

Higgins, Nicholas; Trivedi, Rikin; Greenwood, Richard; Pickard, John

2015-07-01

Spontaneous intracranial hypotension, of which brain slump is an extreme expression, is caused by a cerebrospinal fluid leak. The reason the leak develops in the first place, however, is unknown, and some cases can be very difficult to manage. We describe a patient with severe symptoms of spontaneous intracranial hypotension and brain slump documented by magnetic resonance imaging whose clinical syndrome and structural brain anomaly resolved completely after treatment directed exclusively at improving cranial venous outflow. Diagnostics included computed tomography (CT) venography, catheter venography, and jugular venoplasty. CT venography showed narrowing of both internal jugular veins below the skull base. Catheter venography confirmed that these were associated with pressure gradients. Jugular venoplasty performed on two separate occasions as a clinical test gave temporary respite. Lasting remission (2 years of follow-up) was achieved by stenting the dominant internal jugular vein. These findings and this outcome suggest a mechanism for the development of spontaneous intracranial hypotension that would link it to idiopathic intracranial hypertension and have cranial venous outflow obstruction as the underlying cause.

Factors influencing the thermally-induced strength degradation of B/Al composites

NASA Technical Reports Server (NTRS)

Dicarlo, J. A.

1983-01-01

Literature data related to the thermally-induced strength degradation of B/Al composites were examined in the light of fracture theories based on reaction-controlled fiber weakening. Under the assumption of a parabolic time-dependent growth for the interfacial reaction product, a Griffith-type fracture model was found to yield simple equations whose predictions were in good agreement with data for boron fiber average strength and for B/Al axial fracture strain. The only variables in these equations were the time and temperature of the thermal exposure and an empirical factor related to fiber surface smoothness prior to composite consolidation. Such variables as fiber diameter and aluminum alloy composition were found to have little influence. The basic and practical implications of the fracture model equations are discussed. Previously announced in STAR as N82-24297

Spleen tyrosine kinase mediates high glucose-induced transforming growth factor-{beta}1 up-regulation in proximal tubular epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Won Seok; Chang, Jai Won; Han, Nam Jeong

The role of spleen tyrosine kinase (Syk) in high glucose-induced intracellular signal transduction has yet to be elucidated. We investigated whether Syk is implicated in high glucose-induced transforming growth factor-{beta}1 (TGF-{beta}1) up-regulation in cultured human proximal tubular epithelial cells (HK-2 cell). High glucose increased TGF-{beta}1 gene expression through Syk, extracellular signal-regulated kinase (ERK), AP-1 and NF-{kappa}B. High glucose-induced AP-1 DNA binding activity was decreased by Syk inhibitors and U0126 (an ERK inhibitor). Syk inhibitors suppressed high glucose-induced ERK activation, whereas U0126 had no effect on Syk activation. High glucose-induced NF-{kappa}B DNA binding activity was also decreased by Syk inhibitors. Highmore » glucose increased nuclear translocation of p65 without serine phosphorylation of I{kappa}B{alpha} and without degradation of I{kappa}B{alpha}, but with an increase in tyrosine phosphorylation of I{kappa}B{alpha} that may account for the activation of NF-{kappa}B. Both Syk inhibitors and Syk-siRNA attenuated high glucose-induced I{kappa}B{alpha} tyrosine phosphorylation and p65 nuclear translocation. Depletion of p21-activated kinase 2 (Pak2) by transfection of Pak2-siRNA abolished high glucose-induced Syk activation. In summary, high glucose-induced TGF-{beta}1 gene transcription occurred through Pak2, Syk and subsequent ERK/AP-1 and NF-{kappa}B pathways. This suggests that Syk might be implicated in the diabetic kidney disease.« less

Risk factors for intraoperative bradycardia during ear, nose, throat and maxillofacial surgery.

PubMed

Ivošević, Tjaša; Miličić, Biljana; Dimitrijević, Milovan; Ivanović, Branislava; Pavlović, Aleksandar; Stojanović, Marina; Lakićević, Mirko; Stevanović, Ksenija; Kalezić, Nevena

2018-02-01

Intraoperative bradycardia (IOB) is one of the most common cardiac arrhythmias observed in clinical anaesthetic practice. Controlled hypotension, as a strategy of lowering patient's blood pressure during anesthesia has been practiced for decades in head and neck surgery. The aim of our study was to determine the incidence and the risk factors for intraoperative bradycardia in maxillofacial, ear, nose and throat surgery, as well as to determine whether controlled hypotension affects the occurrence of IOB. The retrospective study included 2304 patients who underwent maxillofacial, ear, nose or throat surgery. We studied the influence of: sex, age, comorbidity, type of surgery, duration of anesthesia and controlled hypotension on the occurrence of IOB. IOB was registered in 473 patients (20.5%). Patients with controlled hypotension had IOB significantly more often than patients without controlled hypotension (33.9 vs 15.1%) (p = 0.000). The significant predictors of IOB were: age (OR = 1.158; 95% CI = 1.068-1.256; p = 0.000), sex (OR = 0.786; 95% CI = 0.623-0.993; p = 0.043), ischemic heart disease (OR = 2.016; 95% CI = 1.182-3.441; p = 0.010); ear surgery (OR = 1.593; 95% CI = 1.232-2.060; p = 0.000), anesthesia duration, (OR = 1.006; 95% CI = 1.004-1.007; p = 0.000) and controlled hypotension (OR = 2.204; 95% CI = 1.761-2.758; p = 0.000). IOB is common in maxillofacial, ear, nose and throat surgery, particularly in male, older age and patients with ishemic heart disease. The ear surgery, longer anesthesia duration and controlled hypotension raise the risk for occurrence of IOB.

Vasopressor Use for Severe Hypotension-A Multicentre Prospective Observational Study.

PubMed

Lamontagne, Francois; Cook, Deborah J; Meade, Maureen O; Seely, Andrew; Day, Andrew G; Charbonney, Emmanuel; Serri, Karim; Skrobik, Yoanna; Hebert, Paul; St-Arnaud, Charles; Quiroz-Martinez, Hector; Mayette, Michaël; Heyland, Daren K

2017-01-01

The optimal approach to titrate vasopressor therapy is unclear. Recent sepsis guidelines recommend a mean arterial pressure (MAP) target of 65 mmHg and higher for chronic hypertensive patients. As data emerge from clinical trials comparing blood pressure targets for vasopressor therapy, an accurate description of usual care is required to interpret study results. Our aim was to measure MAP values during vasopressor therapy in Canadian intensive care units (ICUs) and to compare these with stated practices and guidelines. In a multicenter prospective cohort study of critically ill adults with severe hypotension, we recorded MAP and vasopressor doses hourly. We investigated variability across patients and centres using multivariable regression models and Analysis of variance (ANOVA), respectively. We included data from 56 patients treated in 6 centers. The mean (standard deviation [SD]) age and Acute Physiology and Chronic Health Evaluation (APACHE) II score were 64 (14) and 25 (8). Half (28 of 56) of the patients were at least 65 years old, and half had chronic hypertension. The patient-averaged MAP while receiving vasopressors was 75 mm Hg (6) and the median (1st quartile, 3rd quartile) duration of vasopressor therapy was 43 hours (23, 84). MAP achieved was not associated with history of underlying hypertension (p = 0.46) but did vary by center (p<0.001). In this multicenter, prospective observational study, the patient-level average MAP while receiving vasopressors for severe hypotension was 75 mmHg, approximately 10 mmHg above current recommendations and stated practices. Moreover, our results do not support the notion that clinicians tailor vasopressor therapy to individual patient characteristics such as underlying chronic hypertension but MAP achieved while receiving vasopressors varied by site.

Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment (Final Report)

EPA Science Inventory

EPA announced the release of the final report, Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment . This report provides an overview of the types of mechanisms underlying the lymphohematopoietic cancers induc...

Effects of the amount of rice in meals on postprandial blood pressure in older people with postprandial hypotension: a within-subjects design.

PubMed

Son, Jung Tae; Lee, Eunjoo

2015-08-01

To determine the effect of the amount of rice carbohydrates consumed during mealtime on the extent of decrease in postprandial blood pressure in older people with postprandial hypotension. The incidence of postprandial hypotension is as high as 74% in older people with hypertension. A within-subjects repeated measures design was used. Thirty-nine older people in nursing homes received a full serving and a half-serving of rice on two separate days, in random order blood pressure and heart rate were measured before each meal and every 15 minutes for a total of 120 minutes after each meal. Data were analysed using repeated measures analysis of variance and the paired t-test with a Bonferroni adjustment using IBM spss version 19.0. The control and intervention conditions yielded significantly different patterns in systolic blood pressure and diastolic blood pressure. Postprandial hypotension was less frequent under the intervention condition; however, decrease in rice intake did not significantly affect heart rate. Reducing the amount of rice intake per meal prevents postprandial blood pressure decreases in the older people. Small and frequent meals with decreased carbohydrate content are recommended to prevent postprandial hypotension and its complications in the older people. Patients, dieticians and caregivers of older patients should be aware of the importance of diet, especially of decreasing the amount of carbohydrate in a meal. Smaller and more frequent meals are recommended for older people to slow gastric emptying. © 2015 John Wiley & Sons Ltd.

Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases

PubMed Central

Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

2009-01-01

Background Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Design and Methods Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Results Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-α) and also induced allogeneic naive CD4+ T cells to proliferate and to produce type 1 cytokines such as interferon-γ and tumor necrosis factor-α. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Conclusions Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in

Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases.

PubMed

Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

2009-11-01

Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-alpha) and also induced allogeneic naive CD4(+) T cells to proliferate and to produce type 1 cytokines such as interferon-gamma and tumor necrosis factor-alpha. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and

BMP2-Induced Inflammation Can Be Suppressed by the Osteoinductive Growth Factor NELL-1

PubMed Central

Shen, Jia; James, Aaron W.; Zara, Janette N.; Asatrian, Greg; Khadarian, Kevork; Zhang, James B.; Ho, Stephanie; Kim, Hyun Ju

2013-01-01

Bone-morphogenetic protein 2 (BMP2) is currently the only Food and Drug Administration-approved osteoinductive growth factor used in clinical settings for bone regeneration and repair. However, the use of BMP2 is encumbered by numerous clinical complications, including postoperative inflammation and life-threatening cervical swelling. Thus, methods to prevent BMP2-induced inflammation would have far-reaching clinical implications toward improving current BMP2-based methods for bone regeneration. For the first time, we investigate the potential role of the growth factor Nel-like molecule-1 (NELL-1) in inhibiting BMP2-induced inflammation. Adult rats underwent a femoral bone onlay procedure, treated with either BMP2 protein (4 mg/mL), NELL-1 protein (4 mg/mL), or both proteins combined. Animals were evaluated at 3, 7, and 14 days postoperatively by histology, histomorphometry, immunohistochemistry, and real-time PCR for markers of inflammation (TNFα, IL6). The relative levels of TNFα and IL6 in serum were also detected by ELISA. The mechanism for NELL-1's anti-inflammatory effect was further assessed through examining inflammatory markers and generation of reactive oxygen species (ROS) in the mouse embryonic fibroblast NIH3T3 cells. BMP2 significantly induced local inflammation, including an early and pronounced polymorphonuclear cell infiltration accompanied by increased expression of TNFα and IL6. Treatment with NELL-1 alone elicited no significant inflammatory response. However, NELL-1 significantly attenuated BMP2-induced inflammation by all markers and at all timepoints. These local findings were also confirmed using systemic serum inflammatory biomarkers (TNFα, IL6). In each case, NELL-1 fully reversed BMP2-induced systemic inflammation. Lastly, our findings were recapitulated in vitro, where NELL-1 suppressed BMP2 induced expression of inflammatory markers, as well as NF-κB transcriptional activity and generation of ROS. BMP2-induced inflammation is a

In vivo and in vitro hypotensive effect of aqueous extract of Moringa stenopetala.

PubMed

Mengistu, M; Abebe, Y; Mekonnen, Y; Tolessa, T

2012-12-01

Moringa stenopetala, Baker f. (Moringaceae) is used for food and medicine in Southern Ethiopia. To substantiate the hypotensive effect of M. stenopetala in vivo and in vitro. An in vivo experiment was carried out on male guinea pigs anaesthetized with pentobarbital. The arterial blood pressure was recorded from a carotid artery filled with heparinized saline via an arterial cannula connected to a pressure transducer. For the in vitro experiment the descending thoracic aorta was removed and kept moistened in Krebs-Henseleit solution and then mounted in a 20ml tissue bath maintained at 37°C and bubbled with a mixture of 95% oxygen and 5% carbon dioxide. Crude aqueous leaf extract of M. stenopetala caused significant fall in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MABP) at doses of 10, 20, 30 and 40 mg/kg in normotensive anaesthetized guinea pigs (n = 12). The effect might have been mediated by non-autonomic nervous system as the effect is not altered by atropine and propranolol. The extract also caused significant dose and time dependent inhibition of K(+) induced contraction on guinea pig aorta. M.stenopetala has blood pressure lowering effect substantiating the use of the plant in traditional medicine.

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

NASA Technical Reports Server (NTRS)

Gaffney, F. A.

1987-01-01

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained

Spacelab life sciences flight experiments. An integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

NASA Astrophysics Data System (ADS)

Gaffney, F. Andrew

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO 2 and C 2H 2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be

Pathophysiology and management of spontaneous intracranial hypotension--a review.

PubMed

Syed, Nadir Ali; Mirza, Farhan Arshad; Pabaney, Aqueel Hussain; Rameez-ul-Hassan

2012-01-01

Spontaneous Intracranial Hypotension is a syndrome involving reduced intracranial pressure secondary to a dural tear which occurs mostly due to connective tissue disorders such as Marfans Syndrome, and Ehler Danlos Syndrome. Patients with dural ectasias leading to CSF leakage into the subdural or epidural space classically present with orthostatic headaches and cranial nerve deficits mostly seen in cranial nerves V-VIII. Diagnosis of SIH is confirmed with the aid of neuroimaging modalities of which Cranial MR imaging is most widely used. SIH can be treated conservatively or with epidural blood patches which are now widely being used to repair dural tears, and their effectiveness is being recognized. Recently epidural injection of fibrin glue has also been used which has been found to be effective in certain patients.

Antioxidant and Vasodilator Activity of Ugni molinae Turcz. (Murtilla) and Its Modulatory Mechanism in Hypotensive Response

PubMed Central

Jofré, Ignacio; Pezoa, Cesar; Scheuermann, Erick; Rosalen, Pedro Luiz; Romero, Fernando

2016-01-01

Hypertension is a systemic condition with high morbidity and mortality rates worldwide, which poses an increased risk for cardiovascular diseases. In this study, we demonstrated the antioxidant and vasodilator activity of Ugni molinae Turcz. (Murtilla) fruit, a berry native to Chile and proposed models to explain its modulatory mechanism in hypotensive response. Murtilla fruits were cultivated in a germplasm bank and submitted to chemical and biological analyses. The phenolic compounds gallic acid, Catechin, Quercetin-3-β-D-glucoside, Myricetin, Quercetin, and Kaempferol were identified. Murtilla extract did not generate toxic effects on human endothelial cells and had significant antioxidant activity against ROS production, lipid peroxidation, and superoxide anion production. Furthermore, it showed dose-dependent vasodilator activity in aortic rings in the presence of endothelium, whose hypotensive mechanism is partially mediated by nitric oxide synthase/guanylate cyclase and large-conductance calcium-dependent potassium channels. Murtilla fruits might potentially have beneficial effects on the management of cardiovascular diseases. PMID:27688827

Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial

PubMed Central

Walker, Ann F; Marakis, Georgios; Simpson, Eleanor; Hope, Jessica L; Robinson, Paul A; Hassanein, Mohamed; Simpson, Hugh CR

2006-01-01

Background Hawthorn (Crataegus laevigata) leaves, flowers and berries are used by herbal practitioners in the UK to treat hypertension in conjunction with prescribed drugs. Small-scale human studies support this approach. Aim To investigate the effects of hawthorn for hypertension in patients with type 2 diabetes taking prescribed drugs. Design of study Randomised controlled trial. Setting General practices in Reading, UK. Method Patients with type 2 diabetes (n = 79) were randomised to daily 1200 mg hawthorn extract (n = 39) or placebo (n = 40) for 16 weeks. At baseline and outcome a wellbeing questionnaire was completed and blood pressure and fasting blood samples taken. A food frequency questionnaire estimated nutrient intake. Results Hypotensive drugs were used by 71% of the study population with a mean intake of 4.4 hypoglycaemic and/or hypotensive drugs. Fat intake was lower and sugar intake higher than recommendations, and low micronutrient intake was prevalent. There was a significant group difference in mean diastolic blood pressure reductions (P = 0.035): the hawthorn group showed greater reductions (baseline: 85.6 mmHg, 95% confidence interval [CI] = 83.3 to 87.8; outcome: 83.0 mmHg, 95% CI = 80.5 to 85.7) than the placebo group (baseline: 84.5 mmHg, 95% CI = 82 to 87; outcome: 85.0 mmHg, 95% CI = 82.2 to 87.8). There was no group difference in systolic blood pressure reduction from baseline (3.6 and 0.8 mmHg for hawthorn and placebo groups, respectively; P = 0.329). Although mean fat intake met current recommendations, mean sugar intake was higher and there were indications of potential multiple micronutrient deficiencies. No herb–drug interaction was found and minor health complaints were reduced from baseline in both groups. Conclusions This is the first randomised controlled trial to demonstrate a hypotensive effect of hawthorn in patients with diabetes taking medication. PMID:16762125

Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial.

PubMed

Walker, Ann F; Marakis, Georgios; Simpson, Eleanor; Hope, Jessica L; Robinson, Paul A; Hassanein, Mohamed; Simpson, Hugh C R

2006-06-01

Hawthorn (Crataegus laevigata) leaves, flowers and berries are used by herbal practitioners in the UK to treat hypertension in conjunction with prescribed drugs. Small-scale human studies support this approach. To investigate the effects of hawthorn for hypertension in patients with type 2 diabetes taking prescribed drugs. Randomised controlled trial. General practices in Reading, UK. Patients with type 2 diabetes (n = 79) were randomised to daily 1200 mg hawthorn extract (n = 39) or placebo (n = 40) for 16 weeks. At baseline and outcome a wellbeing questionnaire was completed and blood pressure and fasting blood samples taken. A food frequency questionnaire estimated nutrient intake. Hypotensive drugs were used by 71% of the study population with a mean intake of 4.4 hypoglycaemic and/or hypotensive drugs. Fat intake was lower and sugar intake higher than recommendations, and low micronutrient intake was prevalent. There was a significant group difference in mean diastolic blood pressure reductions (P = 0.035): the hawthorn group showed greater reductions (baseline: 85.6 mmHg, 95% confidence interval [CI] = 83.3 to 87.8; outcome: 83.0 mmHg, 95% CI = 80.5 to 85.7) than the placebo group (baseline: 84.5 mmHg, 95% CI = 82 to 87; outcome: 85.0 mmHg, 95% CI = 82.2 to 87.8). There was no group difference in systolic blood pressure reduction from baseline (3.6 and 0.8 mmHg for hawthorn and placebo groups, respectively; P = 0.329). Although mean fat intake met current recommendations, mean sugar intake was higher and there were indications of potential multiple micronutrient deficiencies. No herb-drug interaction was found and minor health complaints were reduced from baseline in both groups. This is the first randomised controlled trial to demonstrate a hypotensive effect of hawthorn in patients with diabetes taking medication.

Hypotensive effect of Gentiana floribunda is mediated through Ca++ antagonism pathway

PubMed Central

2012-01-01

Background Gentiana floribunda was investigated for the possible hypotensive and vasodilator activities in an attempt to rationalize its traditional use in hypertension. Methods The crude extract of Gentiana floribunda (Gf.Cr) was studied in anaesthetized rats and isolated thoracic aorta tissues. Results Gf.Cr which tested positive for presence of flavonoids, saponins, sterols, tannins and terpenes caused dose-dependent (3.0-100 mg/kg) fall in arterial blood pressure (BP) of rats under anaesthesia. In rat aortic ring preparations denuded of endothelium, Gf.Cr at concentration range of 1.0-10 mg/mL relaxed high K+ (80 mM) and phenylephrine (PE, 1 μM)-induced contractions and shifted Ca++ dose–response curves to right, similar to that caused by verapamil. It also suppressed PE (1 μM) control peak responses at 0.3-1.0 mg/mL, obtained in Ca++-free medium, as exhibited by verapamil. Pre-treatment of tissues with Gf.Cr produced rightward non-parallel shift of PE-curves with decline of maximum contractile response. The vasodilator effect of Gf.Cr was endothelial-independent, as it was not blocked by Nω-nitro-L-arginine methyl ester hydrochloride, atropine and indomethacin in endothelium-intact aortic tissues. Conclusions These data indicate that BP-lowering action of Gentiana floribunda occurred via Ca++ antagonism (inhibition of Ca++ ingress and release from intracellular stores), which provides pharmacological basis to justify its effectiveness in hypertension. PMID:22883710

Effects of dopamine and dobutamine on isoflurane-induced hypotension in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Schnellbacher, Rodney W; da Cunha, Anderson F; Beaufrère, Hugues; Queiroz, Patricia; Nevarez, Javier G; Tully, Thomas N

2012-07-01

To assess the effects of dopamine and dobutamine on the blood pressure of isoflurane-anesthetized Hispaniolan Amazon parrots (Amazona ventralis). 8 Hispaniolan Amazon parrots. A randomized crossover study was conducted. Each bird was anesthetized (anesthesia maintained by administration of 2.5% isoflurane in oxygen) and received 3 doses of each drug during a treatment period of 20 min/dose. Treatments were constant rate infusions (CRIs) of dobutamine (5, 10, and 15 μg/kg/min) and dopamine (5, 7, and 10 μg/kg/min). Direct systolic, diastolic, and mean arterial pressure measurements, heart rate, esophageal temperature, and end-tidal partial pressure of CO(2) were recorded throughout the treatment periods. Mean ± SD of the systolic, mean, and diastolic arterial blood pressures at time 0 (initiation of a CRI) were 132.9 ± 22.1 mm Hg, 116.9 ± 20.5 mm Hg, and 101.9 ± 22.0 mm Hg, respectively. Dopamine resulted in significantly higher values than did dobutamine for the measured variables, except for end-tidal partial pressure of CO(2). Post hoc multiple comparisons revealed that the changes in arterial blood pressure were significantly different 4 to 7 minutes after initiation of a CRI. Overall, dopamine at rates of 7 and 10 μg/kg/min and dobutamine at a rate of 15 μg/kg/min caused the greatest increases in arterial blood pressure. Dobutamine CRI at 5, 10, and 15 μg/kg/min and dopamine CRI at 5, 7, and 10 μg/kg/min may be useful in correcting severe hypotension in Hispaniolan Amazon parrots caused by anesthesia maintained with 2.5% isoflurane.

[Orthostatic hypotension in the elderly].

PubMed

Ferrer-Gila, Teresa; Rízea, Cristian

2013-03-16

Orthostatic hypotension (OH) is defined as a decrease in systolic blood pressure of 20 mmHg, or a decrease in diastolic blood pressure of 10 mmHg within three minutes of standing. It results from an inadequate response to postural changes in blood pressure. Common symptoms include dizziness, light-headedness, blurred vision, weakness, fatigue, nausea, palpitations, sweating, head and neck ache, slow cognitive performance and transient loss of conscientiousness. OH is a common problem among elderly patients and its aetiology is diverse, including autonomic nervous system dysfunction, cardiac problems, medication side effects, ageing changes or transitory deregulation of blood volume. The instrumental diagnosis can be easily accomplished by the tilt-table test, with continuous monitoring of blood pressure and cardiac parameters. It is a non-invasive technique and needs minimal collaboration from the patient. In our experience, when reviewing 327 patients, aged over 40 years and examined because of clinical suspicion of OH, the prevalence thereof was 51% whereas if focused in subjects older than 70, OH was proven in 90% of the cases. The older the patients, the more frequently they presented general deterioration, neurological or cardiac problems as well as pharmacological side effects. Ruling out neurological or cardiac malfunction can drastically improve the prognosis with possible reversibility of symptoms. Some nonpharmacological and pharmacological approaches to improve management of OH and life quality are described for guidance.

Mechanisms of Stress-Induced Visceral Pain: Implications in Irritable Bowel Syndrome.

PubMed

Greenwood-Van Meerveld, B; Moloney, R D; Johnson, A C; Vicario, M

2016-08-01

Visceral pain is a term describing pain originating from the internal organs of the body and is a common feature of many disorders, including irritable bowel syndrome (IBS). Stress is implicated in the development and exacerbation of many visceral pain disorders. Recent evidence suggests that stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviours. The Young Investigator Forum at the International Society of Psychoneuroendocrinology (ISPNE) annual meeting reported experimental evidence suggesting the gut microbiota can affect the stress response to affect visceral pain. Building upon human imaging data showing abnormalities in the central processing of visceral stimuli in patients with IBS and knowledge that the amygdala plays a pivotal role in facilitating the stress axis, the latest experimental evidence supporting amygdala-mediated mechanisms in stress-induced visceral pain was reviewed. The final part of the session at ISPNE reviewed experimental evidence suggesting that visceral pain in IBS may be a result, at least in part, of afferent nerve sensitisation following increases in epithelial permeability and mucosal immune activation. © 2016 British Society for Neuroendocrinology.

Evaluation of cerebral vasomotor reactivity in Parkinson's disease: is there any association with orthostatic hypotension?

PubMed

Zamani, Babak; Mehrabani, Mehrnoush; Fereshtehnejad, Seyed-Mohammad; Rohani, Mohammad

2011-06-01

Our aim was to look for a probable relationship between cerebral vasomotor reactivity (VMR) and orthostatic hypotension (OH) in Parkinson's disease (PD). This study was conducted on 44 patients with PD. Assessment of cerebral VMR was performed by means of transcranial Doppler (TCD) of middle cerebral artery (MCA) before and after a vasodilatory stimulus, carbon dioxide test. Moreover, orthostatic hypotension was evaluated. OH was presented in 12 (27.3%) Parkinson's patients. The average resting blood flow velocity (BFV) in the MCA was 30.20 (SD=9.58)cms(-1) which significantly increased to 46.25 (SD=16.23)cms(-1) after carbon dioxide test (P<0.001). Impaired VMR was observed in 15 (34.1%) of the subjects, while it was not associated with the presence of OH (P=0.770). Evaluation of VMR in patients affected by PD, could assist in early diagnosis of cerebral autonomic dysfunction and prevent its serious consequences prior and more valid to OH. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Leptin induces SIRT1 expression through activation of NF-E2-related factor 2: Implications for obesity-associated colon carcinogenesis.

PubMed

Song, Na-Young; Lee, Yeon-Hwa; Na, Hye-Kyung; Baek, Jeong-Heum; Surh, Young-Joon

2018-07-01

Leptin, a representative adipokine secreted from the white adipose tissue, is considered as a potential linker between obesity and cancer. SIRT1 is an NAD + -dependent histone/protein deacetylase speculated to function as an oncogene. In the present study, we found that leptin signaling-defective ob/ob and db/db mice had lower colonic expression of SIRT1 compared with leptin signaling-intact C57BL/6J mice, implying that leptin signaling is crucial for SIRT1 expression in vivo. Moreover, leptin induced up-regulation of SIRT1 in human colon cancer (HCT-116) cells. Leptin stimulated migration and invasion of cultured HCT-116 cells and tumor growth in the xenograft assay, and these effects were abrogated by a SIRT1 inhibitor sirtinol, suggesting that SIRT1 plays a role in leptin-induced colon carcinogenesis. Leptin-induced SIRT1 expression was regulated by the redox-sensitive transcription factor NF-E2-related factor 2 (Nrf2). Leptin stimulated nuclear accumulation of Nrf2 as well as its binding to the antioxidant response elements located in the SIRT1 promoter. Moreover, siRNA knockdown of Nrf2 abrogated the leptin-induced SIRT1 expression. Notably, SIRT1 was significantly reduced in colon tissues of Nrf2-null mice, lending further support to Nrf2-dependent SIRT1 expression. Expression of leptin, Nrf2 and SIRT1 was coordinately increased in human colon tumor tissues. In conclusion, leptin might play a role in colon carcinogenesis by inducing Nrf2-dependent SIRT1 overexpression. Copyright © 2018 Elsevier Inc. All rights reserved.

Thrombin-induced p38 mitogen-activated protein kinase activation is mediated by epidermal growth factor receptor transactivation pathway

PubMed Central

Kanda, Yasunari; Mizuno, Katsushige; Kuroki, Yasutomi; Watanabe, Yasuhiro

2001-01-01

Thrombin is a potent mitogen for vascular smooth muscle cells (VSMC) and has been implicated its pathogenic role in vascular remodelling. However, the signalling pathways by which thrombin mediates its mitogenic response are not fully understood.We have previously reported that thrombin activates p38 mitogen-activated protein kinase (p38 MAPK) by a tyrosine kinase-dependent mechanism, and that p38 MAPK has a role in thrombin-induced mitogenic response in rat VSMC.In the present study, we examine the involvement of epidermal growth factor (EGF) receptor in thrombin-induced p38 MAPK activation. We found that thrombin induced EGF receptor tyrosine phosphorylation (transactivation) in A10 cells, a clonal VSMC cell line. A selective inhibitor of EGF receptor kinase (AG1478) inhibited the p38 MAPK activation in a dose-dependent manner, whereas it had no effect on the response to platelet-derived growth factor (PDGF). EGF receptor phosphorylation induced by thrombin was inhibited by BAPTA-AM and GF109203X, which suggest a requirement for intracellular Ca2+ increase and protein kinase C.We next examined the effect of AG1478 on thrombin-induced DNA synthesis. AG1478 inhibited thrombin-induced DNA synthesis in a dose-dependent manner. In contrast, PDGF-induced DNA synthesis was not affected by AG1478.In conclusion, these data suggest that the EGF receptor transactivation and subsequent p38 MAPK activation is required for thrombin-induced proliferation of VSMC. PMID:11309236

Fingolimod induces neuroprotective factors in human astrocytes.

PubMed

Hoffmann, Franziska S; Hofereiter, Johann; Rübsamen, Heike; Melms, Johannes; Schwarz, Sigrid; Faber, Hans; Weber, Peter; Pütz, Benno; Loleit, Verena; Weber, Frank; Hohlfeld, Reinhard; Meinl, Edgar; Krumbholz, Markus

2015-09-30

Fingolimod (FTY720) is the first sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of multiple sclerosis. The phosphorylated active metabolite FTY720-phosphate (FTY-P) interferes with lymphocyte trafficking. In addition, it accumulates in the CNS and reduces brain atrophy in multiple sclerosis (MS), and neuroprotective effects are hypothesized. Human primary astrocytes as well as human astrocytoma cells were stimulated with FTY-P or S1P. We analyzed gene expression by a genome-wide microarray and validated induced candidate genes by quantitative PCR (qPCR) and ELISA. To identify the S1P-receptor subtypes involved, we applied a membrane-impermeable S1P analog (dihydro-S1P), receptor subtype specific agonists and antagonists, as well as RNAi silencing. FTY-P induced leukemia inhibitory factor (LIF), interleukin 11 (IL11), and heparin-binding EGF-like growth factor (HBEGF) mRNA, as well as secretion of LIF and IL11 protein. In order to mimic an inflammatory milieu as observed in active MS lesions, we combined FTY-P application with tumor necrosis factor (TNF). In the presence of this key inflammatory cytokine, FTY-P synergistically induced LIF, HBEGF, and IL11 mRNA, as well as secretion of LIF and IL11 protein. TNF itself induced inflammatory, B-cell promoting, and antiviral factors (CXCL10, BAFF, MX1, and OAS2). Their induction was blocked by FTY-P. After continuous exposure of cells to FTY-P or S1P for up to 7 days, the extent of induction of neurotrophic factors and the suppression of TNF-induced inflammatory genes declined but was still detectable. The induction of neurotrophic factors was mediated via surface S1P receptors 1 (S1PR1) and 3 (S1PR3). We identified effects of FTY-P on astrocytes, namely induction of neurotrophic mediators (LIF, HBEGF, and IL11) and inhibition of TNF-induced inflammatory genes (CXCL10, BAFF, MX1, and OAS2). This supports the view that a part of the effects of fingolimod may be mediated via astrocytes.

Neurogenic orthostatic hypotension: roles of norepinephrine deficiency in its causes, its treatment, and future research directions.

PubMed

Loavenbruck, Adam; Sandroni, Paola

2015-11-01

Although a diversity of neurotransmitters and hormones participate in controlling blood pressure, norepinephrine released from postganglionic sympathetic nerve terminals is an important mediator of the rapid regulation of cardiovascular function required for homeostasis of cerebral perfusion. Hence, neurogenic orthostatic hypotension (NOH) often represents a deficiency of noradrenergic responsiveness to postural change. PubMed searches with 'orthostatic hypotension' and 'norepinephrine' as conjoint search terms and no restriction on language or date, so as to survey the pathophysiologic and clinical relevance of norepinephrine deficiency for current NOH interventions and for future directions in treatment and research. Norepinephrine deficiency in NOH can arise peripherally, due to cardiovascular sympathetic denervation (as in pure autonomic failure, Parkinson's disease, and a variety of neuropathies), or centrally, due to a failure of viscerosensory signals to generate adequate sympathetic traffic to intact sympathetic nerve endings (as in multiple system atrophy). Nonpharmacologic countermeasures such as pre-emptive water intake may yield blood-pressure increases exceeding those achieved pharmacologically. For patients with symptomatic NOH unresponsive to such strategies, a variety of pharmacologic interventions have been administered off-label on the basis of drug mechanisms expected to increase blood pressure via blood-volume expansion or vasoconstriction. Two pressor agents have received FDA approval: the sympathomimetic midodrine and more recently the norepinephrine prodrug droxidopa. Pressor agents are important for treating symptomatic NOH in patients unresponsive to lifestyle changes alone. However, the dysautonomia underlying NOH often permits blood-pressure excursions toward both hypotension and hypertension. Future research should aim to shed light on the resulting management issues, and should also explore the possibility of pharmacotherapy selectively

Pentoxifylline inhibits hypoxia-induced upregulation of tumor cell tissue factor and vascular endothelial growth factor.

PubMed

Amirkhosravi, A; Meyer, T; Warnes, G; Amaya, M; Malik, Z; Biggerstaff, J P; Siddiqui, F A; Sherman, P; Francis, J L

1998-10-01

Tissue factor (TF), the membrane glycoprotein that initiates blood coagulation, is constitutively expressed by many tumor cells and is implicated in peri-tumor fibrin deposition and hypercoagulability in cancer. Upregulation of tumor TF correlates with enhanced metastatic potential. Furthermore, TF has been colocalized with VEGF in breast cancer, specially at sites of early angiogenesis. There are no data on the effect of hypoxia on tumor cell TF expression. Since hypoxia is known to stimulate VEGF production, we studied whether this also induces tumor cell TF expression. Confluent monolayers of A375 melanoma, MCF-7 breast carcinoma and A549 lung carcinoma were cultured in either 95% air, 5% CO2 (normoxic) or 95% N2, 5% CO2 (hypoxic; 25-30 mmHg) for 24 h. Procoagulant activity (PCA) was measured by amidolytic and clotting assays, surface TF antigen by flow cytometry, early apoptosis by annexin V binding and VEGF levels in culture supernatants by ELISA. Hypoxia significantly increased tumor cell PCA in all three cell lines tested and TF antigen on A375 cells was increased four-fold (P <0.05). Pentoxifylline (PTX), a methylxanthine derivative, significantly inhibited the hypoxia-induced increase in PCA as well as VEGF release in all three cell lines tested. In A375 cells, PTX significantly inhibited TF antigen expression by both normoxic and hypoxic cells. Hypoxia induced a slight (5%) but not significant, increase in early apoptosis. Intravenous injection of hypoxic A375 cells into nude rats produced more pronounced thrombocytopenia (n = 5, P <0.01) and more lung metastases (n = 3, P <0.05) compared to normoxic cells. We conclude that hypoxia increases TF expression by malignant cells which enhances tumor cell-platelet binding and hematogenous metastasis. Hypoxia-induced upregulation of TF appears to parallel that of VEGF, although the mechanism remains unclear.

Role of physical countermaneuvers in the management of orthostatic hypotension: efficacy and biofeedback augmentation

NASA Technical Reports Server (NTRS)

Bouvette, C. M.; McPhee, B. R.; Opfer-Gehrking, T. L.; Low, P. A.

1996-01-01

OBJECTIVE: To evaluate the efficacy of various physical countermaneuvers in reducing orthostatic hypotension and its associated symptoms and to assess the efficacy of biofeedback training in enhancing the effectiveness of physical countermaneuvers. MATERIAL AND METHODS: In nine study subjects with neurogenic orthostatic hypotension, four training sessions on physical countermaneuvers were performed after tilt-up, three with visual feedback on the effect of physical countermaneuvers on blood pressure and other cardiovascular variables. Blood pressure change and orthostatic symptoms during tilt-up were determined, as were the changes in total peripheral resistance, stroke index, and heart rate. RESULTS: The five female and four male patients had a mean age of 53 years and a mean duration of symptoms of 4.2 years. On an orthostatic symptom scale of 0 to 10, these patients had a mean symptom score of 7.3. The increment in systolic blood pressure was better for some maneuvers (such as leg crossing and a combination) than others (such as neck flexion and abdominal contraction). Three patterns of responses to biofeedback were found. Simple maneuvers such as squatting did not improve with training; visual feedback was needed for maneuvers such as thigh contraction, and performance declined without biofeedback; the third pattern, seen in maneuvers such as leg crossing, showed continued improvement with training, even without biofeedback. A survey at 3 to 4 months after training revealed continued use of physical maneuvers (3.8 +/- 3.1 per day), increased standing time with each episode of presyncopal symptoms (8.3 +/- 5.8 minutes), and continued global symptomatic improvement. Total peripheral resistance, but not heart rate or stroke index, showed significant regression with blood pressure improvement. CONCLUSION: Physical countermaneuvers are efficacious in reducing orthostatic hypotension, can be augmented by use of biofeedback, and may significantly improve the

Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis.

PubMed

Lee, Yee Mei; Lang, Dora; Lockwood, Craig

Increasing numbers of studies identify new prognostic factors for categorising chemotherapy-induced febrile neutropenia adult cancer patients into high- or low-risk groups for adverse outcomes. These groupings are used to tailor therapy according to level of risk. However many emerging factors with prognostic significance remain controversial, being based on single studies only. A systematic review was conducted to determine the strength of association of all identified factors associated with the outcomes of chemotherapy-induced febrile neutropenia patients. The participants included were adults of 15 years old and above, with a cancer diagnosis and who underwent cancer treatment.The review focused on clinical factors and their association with the outcomes of cancer patients with chemotherapy-induced febrile neutropenia at presentation of fever.All quantitative studies published in English which investigated clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia were considered.The primary outcome of interest was to identify the clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia. Electronic databases searched from their respective inception date up to December 2011 include MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Science-Direct, Scopus and Mednar. The quality of the included studies was subjected to assessment by two independent reviewers. The standardised critical appraisal tool from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used to assess the following criteria: representativeness of study population; clearly defined prognostic factors and outcomes; whether potential confounders were addressed and appropriate statistical analysis was undertaken for the study design. Data extraction was performed using a modified version of

Intracranial hypotension and hypertension in children and adolescents.

PubMed

Ozge, Aynur; Bolay, Hayrunnisa

2014-07-01

The specific aim of this review is to report the features of intracranial pressure changes [spontaneous intracranial hypotension (SIH) and idiopathic intracranial hypertension (IIH)] in children and adolescents, with emphasis on the presentation, diagnosis, and treatment modalities. Headache associated with intracranial pressure changes are relatively rare and less known in children and adolescents. SIH is a specific syndrome involving reduced intracranial pressure with orthostatic headache, frequently encountered connective tissue disorders, and a good prognosis with medical management, initial epidural blood patching, and sometimes further interventions may be required. IIH is an uncommon condition in children and different from the disease in adults, not only with respect to clinical features (likely to present with strabismus and stiff neck rather than headache or pulsatile tinnitus) but also different in outcome. Consequently, specific ICP changes of pediatric ages required specific attention both of exact diagnosis and entire management.

Integrated analysis of droxidopa trials for neurogenic orthostatic hypotension.

PubMed

Biaggioni, Italo; Arthur Hewitt, L; Rowse, Gerald J; Kaufmann, Horacio

2017-05-12

Droxidopa, a prodrug of norepinephrine, was approved for treatment of neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based on 3 randomized double-blind studies. We performed safety and efficacy analyses of this pooled dataset (n = 460). Efficacy was assessed using Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual items). Safety and tolerability were also examined. Droxidopa improved virtually all nOH symptom scores compared with placebo, significantly reducing OHQ composite score (-2.68 ± 2.20 vs -1.82 ± 2.34 units; P < 0.001), dizziness/lightheadedness score (-3.0 ± 2.9 vs -1.8 ± 3.1 units; P < 0.001), and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue [P ≤ 0.010]). Droxidopa significantly improved 3 of 4 measures of activities of daily living (standing a long time, walking a short time, and walking a long time [P ≤ 0.003]) and significantly increased upright systolic blood pressure (11.5 ± 20.5 vs 4.8 ± 21.0 mmHg for placebo; P < 0.001). Droxidopa was effective in patients using inhibitors of dopa decarboxylase (DDCI; the enzyme that converts droxidopa to norepinephrine), but its efficacy was numerically greater in non-DDCI users. Droxidopa was well-tolerated. Rates of most adverse events were similar between groups. Supine hypertension rates were low, but slightly higher in patients receiving droxidopa (≤7.9% vs ≤4.6% for placebo); patients with severe hypertension at screening were excluded from these studies. Droxidopa is effective for the treatment of nOH in patients with primary autonomic disorders and is generally well-tolerated. A longer trial is underway to confirm efficacy beyond the ≤2 to 10 - week period assessed in the current trials. ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

A randomized, placebo-controlled, phase 2 study of the efficacy and safety of droxidopa in patients with intradialytic hypotension.

PubMed

Vannorsdall, Mark D; Hariachar, Srinivas; Hewitt, L Arthur

2015-03-01

Intradialytic hypotension (IDH) is the most common complication of hemodialysis (HD), and it plays a significant role in the morbidity and mortality associated with maintenance HD. This was a placebo-controlled, parallel-group study evaluating efficacy and safety of droxidopa in improving intradialytic blood pressure (BP) responses in 85 adults with end-stage renal disease (ESRD) and prone to IDH. Following screening and baseline periods, patients received 400 mg or 600 mg droxidopa, or placebo, orally 1 hour before HD for 4 weeks. Primary outcome endpoint was the change between baseline and last 2 treatment weeks in average mean arterial pressure (MAP) during HD. Also assessed were changes from baseline in systolic BP (SBP) and diastolic BP (DBP) during and after HD; number of hypotension-induced interventions and symptoms; and adverse events. Increase in droxidopa intra-HD MAP were not significantly different from placebo, although droxidopa groups showed significant improvements in mean SBP after HD of +4.8 ± 11.6 mm Hg (600-mg) and +3.4 ± 13.1 (400-mg) compared with -4.4 ± 17.9 mm Hg in placebo, and the drop seen in mean nadir SBP pre- to intra-HD was also reduced. Changes in mean DBP pre- and post-HD, changes in mean nadir SBP post-HD, or intra-HD SBP were not significant over the treatment period. HD terminations decreased 5-fold in the 600-mg group and 2-fold in the 400-mg group, whereas the number of discontinuations stayed unchanged in the placebo group. Overall, treatment with 600-mg or 400-mg droxidopa was well tolerated in this population. These data suggest that droxidopa may have a role in reducing IDH complications in patients with ESRD on chronic HD.

Hypoxia-inducible factors promote alveolar development and regeneration.

PubMed

Vadivel, Arul; Alphonse, Rajesh S; Etches, Nicholas; van Haaften, Timothy; Collins, Jennifer J P; O'Reilly, Megan; Eaton, Farah; Thébaud, Bernard

2014-01-01

Understanding how alveoli and the underlying capillary network develop and how these mechanisms are disrupted in disease states is critical for developing effective therapies for lung regeneration. Recent evidence suggests that lung angiogenesis promotes lung development and repair. Vascular endothelial growth factor (VEGF) preserves lung angiogenesis and alveolarization in experimental O2-induced arrested alveolar growth in newborn rats, but combined VEGF+angiopoietin 1 treatment is necessary to correct VEGF-induced vessel leakiness. Hypoxia-inducible factors (HIFs) are transcription factors that activate multiple O2-sensitive genes, including those encoding for angiogenic growth factors, but their role during postnatal lung growth is incompletely understood. By inducing the expression of a range of angiogenic factors in a coordinated fashion, HIF may orchestrate efficient and safe angiogenesis superior to VEGF. We hypothesized that HIF inhibition impairs alveolarization and that HIF activation regenerates irreversible O2-induced arrested alveolar growth. HIF inhibition by intratracheal dominant-negative adenovirus (dnHIF-1α)-mediated gene transfer or chetomin decreased lung HIF-1α, HIF-2α, and VEGF expression and led to air space enlargement and arrested lung vascular growth. In experimental O2-induced arrested alveolar growth in newborn rats, the characteristic features of air space enlargement and loss of lung capillaries were associated with decreased lung HIF-1α and HIF-2α expression. Intratracheal administration of Ad.HIF-1α restored HIF-1α, endothelial nitric oxide synthase, VEGF, VEGFR2, and Tie2 expression and preserved and rescued alveolar growth and lung capillary formation in this model. HIFs promote normal alveolar development and may be useful targets for alveolar regeneration.

'Non-hypotensive' hypovolaemia reduces ascending aortic dimensions in humans

NASA Technical Reports Server (NTRS)

Taylor, J. A.; Halliwill, J. R.; Brown, T. E.; Hayano, J.; Eckberg, D. L.

1995-01-01

1. The notion that small, 'non-hypotensive' reductions of effective blood volume alter neither arterial pressure nor arterial baroreceptor activity is pervasive in the experimental literature. We tested two hypotheses: (a) that minute arterial pressure and cardiac autonomic outflow changes during hypovolaemia induced by lower body suction in humans are masked by alterations in breathing, and (b) that evidence for arterial baroreflex engagement might be obtained from measurements of thoracic aorta dimensions. 2. In two studies, responses to graded lower body suction at 0 (control), 5, 10, 15, 20 and 40 mmHg were examined in twelve and ten healthy young men, respectively. In the first, arterial pressure (photoplethysmograph), R-R interval, and respiratory sinus arrhythmia amplitude (complex demodulation) were measured during uncontrolled and controlled breathing (constant breathing frequency and tidal volume). In the second, cross-sectional areas of the ascending thoracic aorta were calculated from nuclear magnetic resonance images. 3. Lower body suction with controlled breathing resulted in an increased arterial pulse pressure at mild levels (5-20 mmHg; ANOVA, P < 0.05) and a decreased arterial pulse pressure at moderate levels (40 mmHg; ANOVA, P < 0.05). Both R-R intervals and respiratory sinus arrhythmia were negatively related to lower body suction level, whether group averages (general linear regression, r > 0.92) or individual subjects (orthogonal polynomials, 12 of 12 subjects) were assessed. 4. Aortic pulse area decreased progressively and significantly during mild lower body suction, with 47% of the total decline occurring by 5 mmHg. 5. These results suggest that small reductions of effective blood volume reduce aortic baroreceptive areas and trigger haemodynamic adjustments which are so efficient that alterations in arterial pressure escape detection by conventional means.

Natural products with hypoglycemic, hypotensive, hypocholesterolemic, antiatherosclerotic and antithrombotic activities.

PubMed

Wang, H X; Ng, T B

1999-01-01

This article reviews compounds of botanical origin which are capable of lowering plasma levels of glucose and cholesterol and blood pressure, as well as compounds inhibiting atherosclerosis and thrombosis. Hypoglycemic natural products comprise flavonoids, xanthones, triterpenoids, alkaloids, glycosides, alkyldisulfides, aminobutyric acid derivatives, guanidine, polysaccharides and peptides. Hypotensive compounds include flavonoids, diterpenes, alkaloids, glycosides, polysaccharides and proteins. Among natural products with hypocholesterolemic activity are beta-carotene, lycopene, cycloartenol, beta-sitosterol, sitostanol, saponin, soybean protein, indoles, dietary fiber, propionate, mevinolin (beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor) and polysaccharides. Heparins, flavonoids, tocotrienols, beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors (statins), garlic compounds and fungal proteases exert antithrombotic action. Statins and garlic compounds also possess antiatherosclerotic activity.

The Arabidopsis transcription factor ABIG1 relays ABA signaled growth inhibition and drought induced senescence.

PubMed

Liu, Tie; Longhurst, Adam D; Talavera-Rauh, Franklin; Hokin, Samuel A; Barton, M Kathryn

2016-10-04

Drought inhibits plant growth and can also induce premature senescence. Here we identify a transcription factor, ABA INSENSITIVE GROWTH 1 (ABIG1) required for abscisic acid (ABA) mediated growth inhibition, but not for stomatal closure. ABIG1 mRNA levels are increased both in response to drought and in response to ABA treatment. When treated with ABA, abig1 mutants remain greener and produce more leaves than comparable wild-type plants. When challenged with drought, abig1 mutants have fewer yellow, senesced leaves than wild-type. Induction of ABIG1 transcription mimics ABA treatment and regulates a set of genes implicated in stress responses. We propose a model in which drought acts through ABA to increase ABIG1 transcription which in turn restricts new shoot growth and promotes leaf senescence. The results have implications for plant breeding: the existence of a mutant that is both ABA resistant and drought resistant points to new strategies for isolating drought resistant genetic varieties.

Prevalence of intradialytic hypotension, clinical symptoms and nursing interventions--a three-months, prospective study of 3818 haemodialysis sessions.

PubMed

Kuipers, Johanna; Oosterhuis, Jurjen K; Krijnen, Wim P; Dasselaar, Judith J; Gaillard, Carlo A J M; Westerhuis, Ralf; Franssen, Casper F M

2016-02-27

Intradialytic hypotension (IDH) is considered one of the most frequent complications of haemodialysis with an estimated prevalence of 20-50 %, but studies investigating its exact prevalence are scarce. A complicating factor is that several definitions of IDH are used. The goal of this study was, to assess the prevalence of IDH, primarily in reference to the European Best Practice Guideline (EBPG) on haemodynamic instability: A decrease in systolic blood pressure (SBP) ≥20 mmHg or in mean arterial pressure (MAP) ≥10 mmHg associated with a clinical event and the need for nursing intervention. During 3 months we prospectively collected haemodynamic data, clinical events, and nursing interventions of 3818 haemodialysis sessions from 124 prevalent patients who dialyzed with constant ultrafiltration rate and dialysate conductivity. Patients were considered as having frequent IDH if it occurred in >20 % of dialysis sessions. Decreases in SBP ≥20 mmHg or MAP ≥10 mmHg occurred in 77.7 %, clinical symptoms occurred in 21.4 %, and nursing interventions were performed in 8.5 % of dialysis sessions. Dialysis hypotension according to the full EBPG definition occurred in only 6.7 % of dialysis sessions. Eight percent of patients had frequent IDH. The prevalence of IDH according to the EBPG definition is low. The dominant determinant of the EBPG definition was nursing intervention since this was the component with the lowest prevalence. IDH seems to be less common than indicated in the literature but a proper comparison with previous studies is complicated by the lack of a uniform definition.

The use of antigravity suits in the treatment of idiopathic orthostatic hypotension

NASA Technical Reports Server (NTRS)

Landmark, K.; Kravik, S.

1980-01-01

Idiopathic orthostatic hypotension is an uncommon disease characterized by a drop in blood pressure when going from a recumbent to a standing position. Treatment by medication generally produces poor results. Three patients at the Royal Hospital in Oslo were treated with antigravity suits and all were able to maintain adequate blood pressures in the standing position. One patient improved dramatically and was able to take short walks while wearing the suit. The two other patients, however, felt that wearing the suits eventually became uncomfortable. This treatment represents a useful treatment alternative for intractable cases.

Headaches caused by decreased intracranial pressure: diagnosis and management.

PubMed

Mokri, Bahram

2003-06-01

More patients with spontaneous intracranial hypotension are now being diagnosed, and it is realized that most cases result from spontaneous cerebrospinal fluid leaks. A broader clinical and imaging spectrum of the disorder is recognized. This paper reviews new insights into the variability of clinical manifestations, imaging features, etiological factors, anatomy of leaks, and implications of these in patient management. Spontaneous intracranial hypotension should not be equated with post-lumbar puncture headaches. In a substantial minority of patients, headaches are not orthostatic and may mimic other types of headache. Additional diverse neurological manifestations may dominate the clinical picture and patients may occasionally have no headache at all. Reports on unusual presentations of the disorder continue to appear in the literature. Furthermore, additional imaging features of cerebrospinal fluid leaks are recognized. High-flow and slow-flow leaks may present diagnostic challenges, and require modification of diagnostic studies aimed at locating the site of the leak. Stigmata of connective tissue abnormality, especially abnormalities of fibrillin and elastin, are seen in a notable minority of patients, pointing to weakness of the dural sac as one of the etiological factors. After treatment of spontaneous intracranial hypotension, surgically or by epidural blood patch, a rebound and self-limiting intracranial hypertension may sometimes develop. In the past decade, interest in spontaneous intracranial hypotension has been rekindled, with a substantial growth of knowledge on various aspects of the disorder. We are in the learning phase, and new information will probably appear in the future, with notable diagnostic and therapeutic implications.

Evaluation of Hypotensive and Antihypertensive Effects of Velvet Bean (Mucuna pruriens L.) Hydrolysates.

PubMed

Chel-Guerrero, Luis; Galicia-Martínez, Saulo; Acevedo-Fernández, Juan José; Santaolalla-Tapia, Jesus; Betancur-Ancona, David

2017-01-01

Hypertension could cause significant worldwide health problems that affect 15-20% of all adults; according to National Health and Nutrition Examination Survey, about 29% of the adult population in the United States are hypertensive. Recent research has shown that peptides derived from the hydrolysis of food proteins can decrease blood pressure. This study was carried out to evaluate the hypotensive and antihypertensive potential of Mucuna pruriens protein hydrolysates in in vitro and in vivo models. M. pruriens protein concentrate was prepared by wet fractionation and enzymatically hydrolyzed using Alcalase ® , Flavourzyme ® , and the sequential system Alcalase-Flavourzyme at different times (5-120 min). The biological potential was measured in vitro based on the IC 50 value as well as in vivo effect, measuring the systolic (SBP) and diastolic (DBP) blood pressure in normotensive and antihypertensive Wistar-Kyoto rats by the tail-cuff method. Hydrolysis of M. pruriens protein concentrates with commercial enzymes generated extensive hydrolysates with angiotensin-converting enzyme (ACE-I) inhibitory activity (IC 50 : 0.589-0.993 mg/mL) and hypotensive (SBP: 0.6-47.43%, DBP: 1.94-43.47%) and antihypertensive (SBP: 8.84-27.29% DBP: 16.1-29.37%) effect. These results indicate that Mucuna pruriens protein hydrolysate (MPPH) could be used as a functional ingredient to prevent blood pressure increase.

Adding hydrocortisone as 1st line of inotropic treatment for hypotension in very low birth weight infants.

PubMed

Hochwald, Ori; Palegra, Gustavo; Osiovich, Horacio

2014-08-01

In this pilot study the authors demonstrate the feasibility, effectiveness and safety of the combined early treatment with hydrocortisone and dopamine for refractory hypotension in preterm newborns. Very low birth weight infants born at gestational age < 30 wk or birth weight < 1250 g in the first 48 h of life with hypotension after receiving 10-20 mL/kg bolus of normal saline, were randomized to receive concurrently with the initiation of dopamine, intravenous hydrocortisone (11 infants) or an equivalent volume of placebo (11 infants). Despite no significant clinical difference between the groups including gestational age, birth weight, prevalence of chorioamnionitis, prenatal steroid treatment, cord PH, baseline cortisol level, there was a trend towards lower incidence of bronchopulmonary dysplasia (BPD), and higher survival without BPD rate in the hydrocortisone group. In this very sick small group of infants, hydrocortisone was not associated with more adverse effects, but rather showed a trend toward association with better outcome, including survival without BPD.

The relationship between orthostatic hypotension and falling in older adults.

PubMed

Shaw, Brett H; Claydon, Victoria E

2014-02-01

Falls are devastating events and are the largest contributor towards injury-related hospitalization of older adults. Orthostatic hypotension (OH) represents an intrinsic risk factor for falls in older adults. OH refers to a significant decrease in blood pressure upon assuming an upright posture. Declines in blood pressure can reduce cerebral perfusion; this can impair consciousness, lead to dizziness, and increase the likelihood of a fall. Although theoretical mechanisms linking OH and falls exist, the magnitude of the association remains poorly characterized, possibly because of methodological differences between previous studies. The use of non-invasive beat-to-beat blood pressure monitoring has altered the way in which OH is now defined, and represents a substantial improvement for detecting OH that was previously unavailable in many studies. Additionally, there is a lack of consistency and standardization of orthostatic assessments and analysis techniques for interpreting blood pressure data. This review explores the previous literature examining the relationship between OH and falls. We highlight the impact of broadening the timing, degree, and overall duration of blood pressure measurements on the detection of OH. We discuss the types of orthostatic stress assessments currently used to evaluate OH and the various techniques capable of measuring these often transient blood pressure changes. Overall, we identify future solutions that may better clarify the relationship between OH and falling risk in order to gain a more precise understanding of potential mechanisms for falls in older adults.

PTB-associated splicing factor inhibits IGF-1-induced VEGF upregulation in a mouse model of oxygen-induced retinopathy.

PubMed

Dong, Lijie; Nian, Hong; Shao, Yan; Zhang, Yan; Li, Qiutang; Yi, Yue; Tian, Fang; Li, Wenbo; Zhang, Hong; Zhang, Xiaomin; Wang, Fei; Li, Xiaorong

2015-05-01

Pathological retinal neovascularization, including retinopathy of prematurity and age-related macular degeneration, is the most common cause of blindness worldwide. Insulin-like growth factor-1 (IGF-1) has a direct mitogenic effect on endothelial cells, which is the basis of angiogenesis. Vascular endothelial growth factor (VEGF) activation in response to IGF-1 is well documented; however, the molecular mechanisms responsible for the termination of IGF-1 signaling are still not completely elucidated. Here, we show that the polypyrimidine tract-binding protein-associated splicing factor (PSF) is a potential negative regulator of VEGF expression induced by IGF stimulation. Functional analysis demonstrated that ectopic expression of PSF inhibits IGF-1-stimulated transcriptional activation and mRNA expression of the VEGF gene, whereas knockdown of PSF increased IGF-1-stimulated responses. PSF recruited Hakai to the VEGF transcription complex, resulting in inhibition of IGF-1-mediated transcription. Transfection with Hakai siRNA reversed the PSF-mediated transcriptional repression of VEGF gene transcription. In summary, these results show that PSF can repress the transcriptional activation of VEGF stimulated by IGF-1 via recruitment of the Hakai complex and delineate a novel regulatory mechanism of IGF-1/VEGF signaling that may have implications in the pathogenesis of neovascularization in ocular diseases.

Factors Implicated in Safety-related Firefighter Fatalities.

PubMed

Kahn, Steven A; Palmieri, Tina L; Sen, Soman; Woods, Jason; Gunter, Oliver L

Firefighting is wrought with risk, as 80-100 firefighters (FFs) die on the job each year in the United States. Many of the fatalities have been analyzed by the National Institute for Occupational Safety and Health (NIOSH) to determine contributing factors. The purpose of this study is to determine variables that put FFs at risk for potentially preventable workplace mortality such as use of personal protective equipment (PPE), seat belts, and appropriate training/fitness/clearance for duty. The NIOSH FF Fatality Database reports from 2009 to 2014 were analyzed. Data including age, gender, years on the job, weather, other calls on the same shift, and department type were compared between FFs who employed PPE, seat belts, or wellness/fitness and those who did not. A second group of FFs was determined by NIOSH to have inexperience, lack of training, or inappropriate clearance for duty implicated in their fatalities. Comparisons for the second group were between those whose department used training and safety-related standard operating protocols and those who did not. In 84/176 deaths, PPE/seat belts/fitness was implicated in the fatality. Lack of PPE was more likely on clear days (P = .03) but less likely on cloudy and windy days (P < .001). These FFs dying with lack of PPE had more time on the job in a single department, 18 vs 13 years (P = .03), and more time in a volunteer department, 17 vs 8 years (P < .01). Being deployed on another call during the same shift was associated with lack of PPE-34 vs 16% of those who had not been on another call (P = .005). Lack of training, experience, or medical clearance was implicated in fatalities for 100/176 FFs. FFs who worked in departments that lacked standard operating protocols for respirator fit testing, PPE, fitness testing, rapid intervention, medical clearance, safety/distress alarms, vehicle maintenance, or incident command were statistically more likely to have lack of experience/training/clearance implicated in the

Spinal instrumentation for Duchenne's muscular dystrophy: experience of hypotensive anaesthesia to minimise blood loss.

PubMed

Fox, H J; Thomas, C H; Thompson, A G

1997-01-01

Nineteen patients with Duchenne's muscular dystrophy underwent segmental spinal instrumentation and posterior fusion between 1989 and 1994. The indication for surgery was loss of the ability to walk and development of scoliosis with sitting discomfort. Preoperative assessment included evaluation of pulmonary function. Average age at operation was 12.5 years. Instrumentation and fusion extended from upper thoracic levels to L-5 or the sacrum. A Hartshill rectangle was used in all cases, with banked allograft bone. Severe intraoperative blood loss was avoided by use of hypotensive anaesthesia. Peroperatively, systolic blood pressure was maintained between 75 and 85 mm Hg. Average blood loss was 1,246 ml (range, 400-3,100) or 30% of estimated total blood volume. Average transfusion requirements were 3 units of packed cells. Postoperative analgesia was provided by infusion via an epidural catheter. There were no postoperative wound or chest infections. Three patients required catheterisation for urinary retention. Postoperatively patients were fitted with a Neofract jacket to allow early mobilisation and discharge. Mean postoperative length of stay was 16 days. Posterior spinal fusion by using the Hartshill rectangle provided good correction and fixation. Hypotensive anaesthesia permitted surgery to be performed rapidly in a relatively dry field and avoided the complications of severe intraoperative blood loss and massive transfusion.

Reversible Holmes' tremor due to spontaneous intracranial hypotension.

PubMed

Iyer, Rajesh Shankar; Wattamwar, Pandurang; Thomas, Bejoy

2017-07-27

Holmes' tremor is a low-frequency hand tremor and has varying amplitude at different phases of motion. It is usually unilateral and does not respond satisfactorily to drugs and thus considered irreversible. Structural lesions in the thalamus and brainstem or cerebellum are usually responsible for Holmes' tremor. We present a 23-year-old woman who presented with unilateral Holmes' tremor. She also had hypersomnolence and headache in the sitting posture. Her brain imaging showed brain sagging and deep brain swelling due to spontaneous intracranial hypotension (SIH). She was managed conservatively and had a total clinical and radiological recovery. The brain sagging with the consequent distortion of the midbrain and diencephalon was responsible for this clinical presentation. SIH may be considered as one of the reversible causes of Holmes' tremor. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Hemodynamic and autonomic nervous system responses to mixed meal ingestion in healthy young and old subjects and dysautonomic patients with postprandial hypotension

NASA Technical Reports Server (NTRS)

Lipsitz, L. A.; Ryan, S. M.; Parker, J. A.; Freeman, R.; Wei, J. Y.; Goldberger, A. L.

1993-01-01

BACKGROUND. Although postprandial hypotension is a common cause of falls and syncope in elderly persons and in patients with autonomic insufficiency, the pathophysiology of this disorder remains unknown. METHODS AND RESULTS. We examined the hemodynamic, splanchnic blood pool, plasma norepinephrine (NE), and heart rate (HR) power spectra responses to a standardized 400-kcal mixed meal in 11 healthy young (age, 26 +/- 5 years) and nine healthy elderly (age, 80 +/- 5 years) subjects and 10 dysautonomic patients with symptomatic postprandial hypotension (age, 65 +/- 16 years). Cardiac and splanchnic blood pools were determined noninvasively by radionuclide scans, and forearm vascular resistance was determined using venous occlusion plethysmography. In healthy young and old subjects, splanchnic blood volume increased, but supine blood pressure remained unchanged after the meal. In both groups, HR increased and systemic vascular resistance remained stable. Forearm vascular resistance and cardiac index increased after the meal in elderly subjects, whereas these responses were highly variable and of smaller magnitude in the young. Young subjects demonstrated postprandial increases in low-frequency HR spectral power, representing cardiac sympatho-excitation, but plasma NE remained unchanged. In elderly subjects, plasma NE increased after the meal but without changes in the HR power spectrum. Patients with dysautonomia had a large postprandial decline in blood pressure associated with no change in forearm vascular resistance, a fall in systemic vascular resistance, and reduction in left ventricular end diastolic volume index. HR increased in these patients but without changes in plasma NE or the HR power spectrum. CONCLUSIONS. 1) In healthy elderly subjects, the maintenance of blood pressure homeostasis after food ingestion is associated with an increase in HR, forearm vascular resistance, cardiac index, and plasma NE. In both young and old, systemic vascular resistance is

The efficacy of Labetalol versus Nitroglycerin for induction of controlled hypotension during sinus endoscopic surgery. A prospective, double-blind and randomized study.

PubMed

El-Shmaa, Nagat S; Ezz, Hoda Alsaid Ahmed; Younes, Ahmed

2017-06-01

To assess the efficacy of labetalol versus nitroglycerin for induction of controlled hypotension during sinus endoscopic surgery. A prospective, double-blind and randomized study. Carried out in operating room in university hospital. 60 patients of both sexes, American Society of Anesthesiologists (ASA) physical status I and II, age range from 20 to 60years; scheduled for elective sinus endoscopic surgery under general anesthesia (GA). Patients were divided into two groups (30 each). NTG group received nitroglycerin infusion at a dose of 2-5μg/kg/min, LAB group received labetalol infusion at a dose of 0.5-2mg/min. Surgical condition was assessed by surgeon using average category scale (ACS) of 0-5, a value of 2-3 being ideal. In both groups mean arterial blood pressure (MAP) was gradually reduced till the ideal ACS for assessment of surgical condition, the target of ACS was 2-3 or lower. Both studied drugs achieved desired hypotension and improved visualization of surgical field by decreasing bleeding in the surgical site, but ideal surgical conditions were created at mild hypotension (MAP 70-75) in LAB group while same conditions were created at MAP of 65-69mmHg in NTG group. Mean heart rate (HR) was significantly higher in NTG group as compared to LAB group. Blood loss decreased significantly in LAB group. Both labetalol and NTG are effective and safe drugs for induction of controlled hypotension during sinus endoscopic surgery. While, labetalol was better as it offered optimum operative condition with mild decrease in blood pressure, decreased surgical bleeding and less tachycardia during the surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Hypotensive Anesthesia on Reducing Intraoperative Blood Loss, Duration of Operation, and Quality of Surgical Field During Orthognathic Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Lin, Susie; McKenna, Samuel J; Yao, Chuan-Fong; Chen, Yu-Ray; Chen, Chit

2017-01-01

The objective of this study was to evaluate the efficacy of hypotensive anesthesia in reducing intraoperative blood loss, decreasing operation time, and improving the quality of the surgical field during orthognathic surgery. A systematic review and meta-analysis of randomized controlled trials addressing these issues were carried out. An electronic database search was performed. The risk of bias was evaluated with the Jadad Scale and Delphi List. The inverse variance statistical method and a random-effects model were used. Ten randomized controlled trials were included for analysis. Our meta-analysis indicated that hypotensive anesthesia reduced intraoperative blood loss by a mean of about 169 mL. Hypotensive anesthesia was not shown to reduce the operation time for orthognathic surgery, but it did improve the quality of the surgical field. Subgroup analysis indicated that for blood loss in double-jaw surgery, the weighted mean difference favored the hypotensive group, with a reduction in blood loss of 175 mL, but no statistically significant reduction in blood loss was found for anterior maxillary osteotomy. If local anesthesia with epinephrine was used in conjunction with hypotensive anesthesia, the reduction in intraoperative blood loss was increased to 254.93 mL. Hypotensive anesthesia was effective in reducing blood loss and improving the quality of the surgical field, but it did not reduce the operation time for orthognathic surgery. The use of local anesthesia in conjunction with hypotensive general anesthesia further reduced the amount of intraoperative blood loss for orthognathic surgery. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Involvement of WRKY Transcription Factors in Abscisic-Acid-Induced Cold Tolerance of Banana Fruit.

PubMed

Luo, Dong-Lan; Ba, Liang-Jie; Shan, Wei; Kuang, Jian-Fei; Lu, Wang-Jin; Chen, Jian-Ye

2017-05-10

Phytohormone abscisic acid (ABA) and plant-specific WRKY transcription factors (TFs) have been implicated to play important roles in various stress responses. The involvement of WRKY TFs in ABA-mediated cold tolerance of economical fruits, such as banana fruit, however remains largely unknown. Here, we reported that ABA application could induce expressions of ABA biosynthesis-related genes MaNCED1 and MaNCED2, increase endogenous ABA contents, and thereby enhance cold tolerance in banana fruit. Four banana fruit WRKY TFs, designated as MaWRKY31, MaWRKY33, MaWRKY60, and MaWRKY71, were identified and characterized. All four of these MaWRKYs were nuclear-localized and displayed transactivation activities. Their expressions were induced by ABA treatment during cold storage. More importantly, the gel mobility shift assay and transient expression analysis revealed that MaWRKY31, MaWRKY33, MaWRKY60, and MaWRKY71 directly bound to the W-box elements in MaNCED1 and MaNCED2 promoters and activated their expressions. Taken together, our findings demonstrate that banana fruit WRKY TFs are involved in ABA-induced cold tolerance by, at least in part, increasing ABA levels via directly activating NECD expressions.

[Severe hypotension as a complication of intramyometrial injection of vasopressin: a case report].

PubMed

Kitamura, Takayuki; Saito, Yuichiro; Yamada, Yoshitsugu

2008-12-01

A thirty-year-old woman was scheduled for laparoscopic myomectomy. After insertion of an epidural catheter at the L4-5 interspace, general anesthesia was induced with thiopental 250 mg followed by vecuronium 8mg intravenously to facilitate tracheal intubation. General anesthesia was maintained with sevoflurane and nitrous oxide. Just after intramyometrial injection of vasopressin, blood pressure decreased from 122/66 to 45/25 mmHg, and heart rate decreased from 52 to 45 beats x min(-1). The patient was ventilated with 100% oxygen, and we administered atropine 0.25 mg and ephedrine 16 mg intravenously. Blood pressure increased to 150/100 mmHg and heart rate increased to 135 beats x min(-1). Since electrocardiogram showed ST-segment depression and premature ventricular contraction, we administered nicorandil 3 mg followed by continuous infusion at a rate of 3 mg x hr(-1), and lidocaine 60 mg, intravenously. The ST depression and premature ventricular contraction disappeared immediately. To decrease blood pressure and heart rate, we increased inspiratory concentrations of sevoflurane and nitrous oxide and administered local anesthetics via epidural catheter, and hemodynamic parameters became gradually stable. We estimate that severe hypotension observed in this case is associated with intramyometrial injection of vasopressin. Increased blood concentration of vasopressin might cause vasoconstriction of coronary artery, increases in afterload, and/or direct myocardial depression resulting in decreased cardiac output.

Factors implicated in the initiation of human parturition in term and preterm labor: a review.

PubMed

Ravanos, Konstantinos; Dagklis, Themistoklis; Petousis, Stamatios; Margioula-Siarkou, Chrysoula; Prapas, Yannis; Prapas, Nikolaos

2015-01-01

After accommodating the pregnancy for an average of 40 weeks, the uterus expels the fetus, the placenta and the membranes through the birth canal in a process named parturition. The absolute sequence of events that trigger and sustain human parturition are not yet fully clarified. Evidence suggests that spontaneous preterm and term labor seem to share a common inflammatory pathway. However, there are several other factors being involved in the initiation of human parturition. Placental corticotropin releasing hormone production seems to serve as a placental clock that might be set to ring earlier or later determining the duration of pregnancy and timing of labor. Estrogens do not cause contractions but their properties seem to capacitate uterus to coordinate and enhance contractions. Cytokines, prostaglandins, nitric oxide and steroids seem also to induce ripening by mediating remodeling of the extracellular matrix and collagen. Infection and microbe invasion resulting in chorioamnionitis also represents a common cause of early preterm labour. This review provides an overview of all these factors considered to be implicated in the initiation of human parturition.

A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients

PubMed Central

Zandvliet, Maarten L.; Koolen, Stijn L. W.; Mathijssen, Ron H. J.; van der Rijt, Carin C. D.

2016-01-01

Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer‐related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter‐ and intrapatient variability. This systematic review summarizes multiple studied factors that potentially influence fentanyl pharmacokinetics with a focus on implications for cancer patients. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way. In elderly patients, current data suggest that we should carefully dose fentanyl due to alterations in absorption and metabolism. The influence of BMI and gender on fentanyl pharmacokinetics is questionable, most probably due to a large heterogeneity in the published studies. Pharmacogenetics, e.g. the CYP3A5*3 gene polymorphism, may influence fentanyl pharmacokinetics as well, although further study is warranted. Several other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetics. Unfortunately, most of the published papers that studied factors influencing fentanyl pharmacokinetics describe healthy volunteers instead of cancer patients. Results from the studies in volunteers may not be simply extrapolated to cancer patients because of multiple confounding factors. To handle fentanyl treatment in a population of cancer patients, it is essential that physicians recognize factors that influence fentanyl pharmacokinetics, thereby preventing potential side‐effects and increasing its efficacy. PMID:27619152

Graded Compression Stockings Prevent Post-spaceflight Orthostatic Hypotension

NASA Technical Reports Server (NTRS)

Platts, S. H.; Brown, A. K.; Locke, J.; Stenger, M. B.

2008-01-01

Post-spaceflight orthostatic intolerance is characterized by hypotension and presyncope in 20-30% of returning astronauts. Previous data from our laboratory suggests that this is largely a result of decreased venous return. Currently, NASA astronauts wear an anti-gravity suit (AGS) which consists of inflatable air bladders over the calves, thighs and abdomen, which are typically pressurized from 0.5 to 1.5 PSI (27 to 78 mmHg). ISS crew members sometimes wear Russian Kentavr suits which consist of laced compression shorts and gaiters, providing 30 mmHg nominally. While these garments are effective during reentry, there are a number of drawbacks that make them impractical for postflight use. We studied the ability of commercially available, custom fit, graded compression stockings (Jobst, 55 mmHg at ankle to 6 mmHg at top of thigh, 25 mmHg mean compression) to prevent postflight orthostatic intolerance, hypothesizing that these garments would prevent orthostatic intolerance following short duration space flight. Crew members from a single Space Shuttle flight were tilted to 80 degrees for 10 min while wearing the stockings (n=5 males) upon arrival at the clinic (2 hrs after landing). Hemodynamic data were compared to data from all crewmembers tilted (without countermeasures) since return to flight (n=9). Two-way, repeated measures ANOVA, using the entire tilt time curve (0-10 min) show that systolic blood pressure (SBP, group effect p=0.008), stroke volume (SV, group effect p=0.003), and cardiac output (CO, group effect p=0.004) were higher in crewmembers who wore the Jobst stockings. A one-way ANOVA comparing the last minute standing also showed that SV (p=0.001) and CO (p less than 0.001) were higher and SBP tended to be higher (p=0.06) in Jobst subjects compared to controls. Control subjects had a higher rate of presyncope than Jobst subjects (3/9 vs 0/5) during the tilt on landing day. Orthostatic hypotension continues to present following spaceflight, despite

Transforming Growth Factor-β-Activated Kinase 1 Is Required for Human FcγRIIIb-Induced Neutrophil Extracellular Trap Formation.

PubMed

Alemán, Omar Rafael; Mora, Nancy; Cortes-Vieyra, Ricarda; Uribe-Querol, Eileen; Rosales, Carlos

2016-01-01

Neutrophils (PMNs) are the most abundant leukocytes in the blood. PMN migrates from the circulation to sites of infection where they are responsible for antimicrobial functions. PMN uses phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. Several stimuli, including bacteria, fungi, and parasites, and some pharmacological compounds, such as Phorbol 12-myristate 13-acetate (PMA), are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. Recently, it was reported that FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. Direct cross-linking of FcγRIIA or integrins did not promote NET formation. FcγRIIIb-induced NET formation presented different kinetics from PMA-induced NET formation, suggesting differences in signaling. Because FcγRIIIb also induces a strong activation of extracellular signal-regulated kinase (ERK) and nuclear factor Elk-1, and the transforming growth factor-β-activated kinase 1 (TAK1) has recently been implicated in ERK signaling, in the present report, we explored the role of TAK1 in the signaling pathway activated by FcγRIIIb leading to NET formation. FcγRIIIb was stimulated by specific monoclonal antibodies, and NET formation was evaluated in the presence or absence of pharmacological inhibitors. The antibiotic LL Z1640-2, a selective inhibitor of TAK1 prevented FcγRIIIb-induced, but not PMA-induced NET formation. Both PMA and FcγRIIIb cross-linking induced phosphorylation of ERK. But, LL Z1640-2 only inhibited the FcγRIIIb-mediated activation of ERK. Also, only FcγRIIIb, similarly to transforming growth factor-β-induced TAK1 phosphorylation. A MEK (ERK kinase)-specific inhibitor was able to prevent ERK phosphorylation induced by both PMA and FcγRIIIb. These data show for the first time that FcγRIIIb cross-linking activates TAK1, and that this kinase is required for triggering the MEK/ERK signaling pathway to NETosis.

Oleic acid content is responsible for the reduction in blood pressure induced by olive oil.

PubMed

Terés, S; Barceló-Coblijn, G; Benet, M; Alvarez, R; Bressani, R; Halver, J E; Escribá, P V

2008-09-16

Numerous studies have shown that high olive oil intake reduces blood pressure (BP). These positive effects of olive oil have frequently been ascribed to its minor components, such as alpha-tocopherol, polyphenols, and other phenolic compounds that are not present in other oils. However, in this study we demonstrate that the hypotensive effect of olive oil is caused by its high oleic acid (OA) content (approximately 70-80%). We propose that olive oil intake increases OA levels in membranes, which regulates membrane lipid structure (H(II) phase propensity) in such a way as to control G protein-mediated signaling, causing a reduction in BP. This effect is in part caused by its regulatory action on G protein-associated cascades that regulate adenylyl cyclase and phospholipase C. In turn, the OA analogues, elaidic and stearic acids, had no hypotensive activity, indicating that the molecular mechanisms that link membrane lipid structure and BP regulation are very specific. Similarly, soybean oil (with low OA content) did not reduce BP. This study demonstrates that olive oil induces its hypotensive effects through the action of OA.

Neurogenic orthostatic hypotension in Parkinson's disease: evaluation, management, and emerging role of droxidopa.

PubMed

Isaacson, Stuart H; Skettini, Julia

2014-01-01

Neurogenic orthostatic hypotension (nOH) is due to failure of the autonomic nervous system to regulate blood pressure in response to postural changes due to an inadequate release of norepinephrine, leading to orthostatic hypotension and supine hypertension. nOH is common in Parkinson's disease (PD). Prevalence varies throughout the course of PD, ranging from 40% to 60%, and resulting in symptomatic nOH in approximately half. Symptomatic nOH, including lightheadedness, can limit daily activities and lead to falls. Symptomatic nOH can also limit therapeutic options for treating PD motor symptoms. Clinical evaluation should routinely include symptom assessment and blood pressure measurement of supine, sitting, and 3-minute standing; 24-hour ambulatory blood pressure monitoring can also be helpful. Non-pharmacological management of symptomatic nOH involves education, physical maneuvers, and adequate hydration. Current pharmacological treatment of symptomatic nOH includes salt supplement, fludrocortisone, midodrine, pyridostigmine, and other empiric medications. Despite these options, treatment of symptomatic nOH remains suboptimal, often limited by severe increases in supine blood pressure. Droxidopa, an oral prodrug converted by decarboxylation to norepinephrine, is a promising therapeutic option for symptomatic nOH in PD, improving symptoms of nOH, daily activities, falls, and standing systolic blood pressure in several recent trials. These trials demonstrated short-term efficacy and tolerability, with comparable increases in standing and supine blood pressures. Longer-term studies are ongoing to confirm durability of treatment effect.

Semicarbazide-sensitive amine oxidase substrates potentiate hydralazine hypotension: possible role of hydrogen peroxide.

PubMed

Vidrio, Horacio; Medina, Martha; González-Romo, Pilar; Lorenzana-Jiménez, Marte; Díaz-Arista, Patricia; Baeza, Alejandro

2003-11-01

The relation between inhibition of semicarbazide-sensitive amine oxidase (SSAO) and vasodilation by hydralazine (HYD) was evaluated in chloralose/urethane-anesthetized rats pretreated with various substrates of the enzyme and subsequently administered a threshold hypotensive dose of the vasodilator. The SSAO substrates benzylamine, phenethylamine, and methylamine potentiate the hypotensive response to HYD. Methylamine, which was studied in greater detail because of its status as a possible endogenous SSAO substrate, does not influence the response to the reference vasodilator pinacidil; it does enhance HYD relaxation in aortic rings obtained from pretreated rats. Experiments designed to identify the product of SSAO activity responsible for potentiation by methylamine suggest involvement of hydrogen peroxide (H2O2), as evidenced by the findings that such potentiation is abolished by additional pretreatment with the H2O2-metabolizing enzyme catalase, and that the plasma concentration of H2O2 is increased by methylamine and decreased by HYD. These results are interpreted as a substantiation of the relation between the known SSAO inhibitory effect of HYD and its vasodilator activity. Pretreatment with the SSAO substrates would increase production of H2O2 in vascular smooth muscle and thus magnify the influence of this vasoconstrictor agent on vascular tone. In these conditions, the decrease in H2O2 production and hence in vascular tone caused by SSAO inhibition by HYD would also be magnified. It is speculated that inhibition of vascular SSAO could represent a novel mechanism of vasodilation.

Androgenic-anabolic steroids inhibited post-exercise hypotension: a case control study.

PubMed

Junior, Jefferson F C R; Silva, Alexandre S; Cardoso, Glêbia A; Silvino, Valmir O; Martins, Maria C C; Santos, Marcos A P

There is evidence of hypertensive effects caused by anabolic androgenic steroids (AAS). A single exercise session promotes the acute reduction of blood pressure, but the effects of AAS on this phenomenon are unknown. To investigate the post-exercise blood pressure response in androgenic-anabolic steroid users. Thirteen AAS users (23.9±4.3 years old) and sixteen controls (22.1±4.5 years old) performed a session of aerobic exercise. Heart rate and blood pressure were assessed before exercise and during a 60min post-exercise resting period. Repeated ANOVA measures were used to determine differences between the groups. While the control group had a significant reduction in post-exercise systolic blood pressure of up to 13.9±11.6mmHg at 40min, this phenomenon was limited among AAS users who reached a maximum of 6.2±11.5mmHg at 60min. The between groups comparison revealed significant higher post-exercise hypotension (PEH) for the control group at 30min (-12.9±14.1mmHg versus -2.9±7.6mmHg), 40min (-13.9±11.6mmHg versus -2.5±8.3mmHg), 50min (-13.9±13.9mmHg versus -5.0±7.9mmHg) and 60min (-12.5±12.8mmHg versus -6.2±11.5mmHg). There was no significant diastolic PEH in any of the groups. This study demonstrated impaired systolic post-exercise hypotension as a new adverse effect of AAS usage. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Side effects resulting from the use of growth hormone and insulin-like growth factor-I as combined therapy to frail elderly patients.

PubMed

Sullivan, D H; Carter, W J; Warr, W R; Williams, L H

1998-05-01

The objective of this study was to examine the relationship between serum IGF-I concentration and the incidence of side effects of therapy with recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor-I (rhIGF-I). Thirteen high-risk, undernourished elderly males were started on a 15-day course of rhGH and rhIGF-I by subcutaneous injection. The dose of rhGH was held constant at .0125 mg/kg/day, whereas the dose of rhIGF-I was increased in a stepwise fashion from 10 micrograms/kg to the targeted dose of 40 micrograms/kg twice a day. Nine subjects completed the protocol and reached the full target dose of both hormones. Fluid retention, gynecomastia, and orthostatic hypotension were the most common complications. The hormone injections increased the serum concentration of IGF-I (from 72.7 +/- 40.9 to 483.7 +/- 251.4 eta g/ml, p = .001) and IGFBP-3 (from 1.82 +/- 0.66 to 2.72 +/- 1.18 mg/L, p = .012), and decreased serum albumin (from 34.3 +/- 5.5 to 31.4 +/- 4.6 g/L, p = .009). The magnitude of the initial increase in the serum IGF-I concentration was a powerful risk factor for severe orthostatic hypotension, diffuse myalgias, and drug-induced hepatitis. There was no association between the serum IGF-I concentration and fluid retention or gynecomastia. Treatment of the undernourished frail elderly with the anabolic agents rhGH and rhIGF-I at the specified dosages may produce undesirable side effects including fluid retention, gynecomastia, and orthostatic hypotension. Although these agents hold therapeutic promise, they must be used with caution in this high-risk population.

Pathophysiology and implications of intradialytic hypertension.

PubMed

Van Buren, Peter Noel

2017-07-01

Intradialytic hypertension occurs regularly in 10--15% of hemodialysis patients. A large observational study recently showed that intradialytic hypertension of any magnitude increased mortality risk comparable to the most severe degrees of intradialytic hypotension. The present review review discusses the most recent evidence underlying the pathophysiology of intradialytic hypertension and implications for its management. Patients with intradialytic hypertension typically have small interdialytic weight gains, but bioimpedance spectroscopy shows these patients have significant chronic extracellular volume excess. Intradialytic hypertension patients have lower albumin and predialysis urea nitrogen levels, which may contribute to small reductions in osmolarity that prevents blood pressure decreases. Intradialytic vascular resistance surges remain implicated as the driving force for blood pressure increases, but mediators other than endothelin-1 may be responsible. Beyond dry weight reduction, the only controlled intervention shown to interrupt the blood pressure increase is lowering dialysate sodium. Patients with recurrent intradialytic hypertension should be identified as high-risk patients. Dry weight should be re-evaluated, even if patients do not clinically appear volume overloaded. Antihypertensive drugs should be prescribed because of the persistently elevated ambulatory blood pressure. Dialysate sodium reduction should be considered, although the long term effects of this intervention are uncertain.

Adenosine and Hypoxia-Inducible Factor Signaling in Intestinal Injury and Recovery

PubMed Central

Eltzschig, Holger K.

2013-01-01

The gastrointestinal mucosa has proven to be an interesting tissue in which to investigate disease-related metabolism. In this review, we outline some of the evidence that implicates hypoxia-mediated adenosine signaling as an important signature within both healthy and diseased mucosa. Studies derived from cultured cell systems, animal models, and human patients have revealed that hypoxia is a significant component of the inflammatory microenvironment. These studies have revealed a prominent role for hypoxia-induced factor (HIF) and hypoxia signaling at several steps along the adenine nucleotide metabolism and adenosine receptor signaling pathways. Likewise, studies to date in animal models of intestinal inflammation have demonstrated an almost uniformly beneficial influence of HIF stabilization on disease outcomes. Ongoing studies to define potential similarities with and differences between innate and adaptive immune responses will continue to teach us important lessons about the complexity of the gastrointestinal tract. Such information has provided new insights into disease pathogenesis and, importantly, will provide insights into new therapeutic targets. PMID:21942704

Neurogenic orthostatic hypotension - management update and role of droxidopa.

PubMed

Vijayan, Joy; Sharma, Vijay K

2015-01-01

Orthostatic hypotension (OH) is defined as a significant decrease in blood pressure (BP) during the first 3 minutes of standing or a head up on a tilt table. Symptoms of OH are highly variable, ranging from mild light-headedness to recurrent syncope. OH occurs due to dysfunction of one or more components of various complex mechanisms that interplay closely to maintain BP in a normal range during various physiological and associated disease states. Various biochemical and electrophysiological studies are often undertaken to assess the severity and etiology of OH. In addition to the lifestyle modifications, various medications that stimulate the adrenergic receptors or increase central blood volume are used in patients with OH. Droxidopa is a newer agent that increases the levels of norepinephrine in postganglionic sympathetic neurons. Management strategies for OH are presented, including the mechanism of action of droxidopa and various studies performed to assess its efficacy.

Low hypoxia inducible factor-1α (HIF-1α) expression in testicular germ cell tumors - a major reason for enhanced chemosensitivity?

PubMed

Shenoy, Niraj; Dronca, Roxana; Quevedo, Fernando; Boorjian, Stephen A; Cheville, John; Costello, Brian; Kohli, Manish; Witzig, Thomas; Pagliaro, Lance

2017-08-01

The molecular basis for enhanced chemosensitivity of testicular germ cell tumors (GCT) has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far, however, the increased sensitivity of GCT has been variously attributed to multiple factors - an inability to detoxify cisplatin, a lack of export pumps, an inability to repair the DNA damage, an intact apoptotic cascade and lack of p53 mutation; but a unifying underlying etiology leading to the aforementioned processes and having a translational implication has so far been elusive. Herein, we offer evidence to support a potential significant role for the previously demonstrated low hypoxia inducible factor-1α (HIF-1α) expression in mediating the general exquisite chemosensitivity of testicular GCT, through the aforementioned processes. This molecular mechanism based hypothesis could have a significant translational implication in platinum refractory GCT as well as other platinum resistant malignancies.

Hypotensive effects and angiotensin-converting enzyme inhibitory peptides of reishi (Ganoderma lingzhi) auto-digested extract.

PubMed

Tran, Hai-Bang; Yamamoto, Atsushi; Matsumoto, Sayaka; Ito, Hisatomi; Igami, Kentaro; Miyazaki, Toshitsugu; Kondo, Ryuichiro; Shimizu, Kuniyoshi

2014-08-29

Reishi (Ganoderma lingzhi) has been used as a traditional medicine for millennia. However, relatively little is known about this mushroom's proteins and their bioactivities. In this study, we used reishi's own proteases to hydrolyze its protein and obtained auto-digested reishi (ADR) extract. The extract was subjected to in vitro assays and administered to spontaneous hypertensive rats (SHRs) to determine its potential for use as a hypotensive medication. Bioassay-guided fractionation and de novo sequencing were used for identifying the active compounds. After 4 h administration of ADR, the systolic pressure of SHRs significantly decreased to 34.3 mmHg (19.5% change) and the effect was maintained up to 8 h of administration, with the decrease reaching as low as 26.8 mmHg (15% reduction-compare to base line a decrease of 26.8 mmHg is less than a decrease of 34.3 mmHg so it should give a smaller % reduction). Eleven peptides were identified and four of them showed potent inhibition against ACE with IC50 values ranging from 73.1 μM to 162.7 μM. The results showed that ADR could be a good source of hypotensive peptides that could be used for antihypertensive medication or incorporation into functional foods.

Contribution of the leg vasculature to hypotensive effects of an antiorthostatic posture change in humans

PubMed Central

Pump, Bettina; Schou, Morten; Gabrielsen, Anders; Norsk, Peter

1999-01-01

Previous results from our laboratory have shown that vasodilatation in the legs prevents mean arterial pressure (MAP) from increasing during water immersion. Therefore, we tested the hypothesis that vasodilatation in the legs is necessary for the hypotensive effects to occur during a moderate antiorthostatic posture change. Ten healthy males underwent a 5 min posture change from upright seated to horizontal supine (SUP) and back to seated again with (OCCL-SUP) and without simultaneous total arterial (154 ± 1 mmHg) thigh occlusion, and a control seated period, also with and without arterial occlusion. Cardiac output (CO) was measured by a non-invasive foreign (N2O) gas rebreathing technique. MAP (brachial auscultation) decreased during SUP from 94 ± 3 to 84 ± 2 mmHg (P < 0.0001) and total peripheral vascular resistance (TPR = MAP/CO, n = 8) decreased by 15 ± 4 % (P < 0.001). During OCCL-SUP, MAP decreased from 98 ± 2 to 90 ± 2 mmHg (P < 0.005) and TPR decreased by 14 ± 3 % (P < 0.01). In conclusion, vasodilatation in the legs is not necessary for the decrease in MAP to occur during a moderate antiorthostatic manoeuvre. Therefore, vasodilatation in more central vascular beds (e.g. abdomen) can alone account for the hypotensive effects. PMID:10457077

Granulocyte colony-stimulating factor induces in vitro lymphangiogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Ae Sin; Kim, Dal; Wagle, Susbin Raj

2013-07-12

Highlights: •G-CSF induces tube formation, migration and proliferation of lymphatic cells. •G-CSF increases phosphorylation of MAPK and Akt in lymphatic endothelial cells. •MAPK and Akt pathways are linked to G-CSF-induced in vitro lymphangiogenesis. •G-CSF increases sprouting of a lymphatic ring. •G-CSF produces peritoneal lymphangiogenesis. -- Abstract: Granulocyte-colony stimulating factor (G-CSF) is reported to induce differentiation in cells of the monocyte lineage and angiogenesis in vascular endothelial cells, but its effects on lymphangiogenesis is uncertain. Here we examined the effects and the mechanisms of G-CSF-induced lymphangiogenesis using human lymphatic endothelial cells (hLECs). Our results showed that G-CSF induced capillary-like tube formation,more » migration and proliferation of hLECs in a dose- and time-dependent manner and enhanced sprouting of thoracic duct. G-CSF increased phosphorylation of Akt and ERK1/2 in hLECs. Supporting the observations, specific inhibitors of phosphatidylinositol 3′-kinase and MAPK suppressed the G-CSF-induced in vitro lymphangiogenesis and sprouting. Intraperitoneal administration of G-CSF to mice also stimulated peritoneal lymphangiogenesis. These findings suggest that G-CSF is a lymphangiogenic factor.« less

Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Gang; Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang; Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp

Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation,more » whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.« less

Abacavir-induced fulminant hepatic failure in a HIV/HCV co-infected patient

PubMed Central

Haas, Christopher; Ziccardi, Mary Rodriguez; Borgman, Jody

2015-01-01

Abacavir hypersensitivity is a rare, yet significant adverse reaction that results in a spectrum of physical and laboratory abnormalities, and has been postulated to stem from a variety of aetiological factors. The major histocompatibility complex haplotype human leucocyte antigen (HLA)-B5701 is a significant risk factor in development of hypersensitivity reactions, yet only 55% of HLA-B5701+ individuals develop such reactions, suggesting a multifactorial aetiology. Nevertheless, prospective screening and avoidance of abacavir in these patients has limited adverse events. Within this spectrum of adverse events, abacavir-induced liver toxicity is exceedingly rare and reported events have ranged from mild elevations of aminotransferases to fulminant hepatic failure. We report the case of a 50-year-old Caucasian woman with a history significant for HIV, hepatitis C virus and a HLA-B5701+ status, transferred to our emergency department in a hypotensive state and found to have acute liver failure, acute renal failure and significant rhabdomyolysis following a change of highly active antiretroviral therapy regimen. PMID:26670894

L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience.

PubMed

Mathias, Christopher J

2008-03-01

Neurogenic orthostatic hypotension is a cardinal feature of generalised autonomic failure and commonly is the presenting sign in patients with primary autonomic failure. Orthostatic hypotension can result in considerable morbidity and even mortality and is a major management problem in disorders such as pure autonomic failure, multiple system atrophy and also in Parkinson's disease. Treatment is ideally two pronged, using non-pharmacological and pharmacological measures. Drug treatment ideally is aimed at restoring adequate amounts of the neurotransmitter noradrenaline. This often is not achievable because of damage to sympathetic nerve terminals, to autonomic ganglia or to central autonomic networks. An alternative is the use of sympathomimetics (that mimic the effects of noradrenaline, but are not identical to noradrenaline), in addition to other agents that target physiological mechanisms that contribute to blood pressure control.L-threo-dihydroxyphenyslerine (Droxidopa) is a pro-drug which has a structure similar to noradrenaline, but with a carboxyl group. It has no pressor effects in this form. It can be administered orally, unlike noradrenaline, and after absorption is converted by the enzyme dopa decarboxylase into noradrenaline thus increasing levels of the neurotransmitter which is identical to endogenous noradrenaline. Experience in Caucasians and in Europe is limited mainly to patients with dopamine beta hydroxylase deficiency. This review focuses on two studies performed in Europe, and provides information on its efficacy, tolerability and safety in patients with pure autonomic failure, multiple system atrophy and Parkinson's disease. It also addresses the issue of whether addition of dopa decarboxylase inhibitors, when combined with l-dopa in the treatment of the motor deficit in Parkinson's disease, impairs the pressor efficacy of Droxidopa.

A diminished aortic-cardiac reflex during hypotension in aerobically fit young men

NASA Technical Reports Server (NTRS)

Shi, X.; Crandall, C. G.; Potts, J. T.; Williamson, J. W.; Foresman, B. H.; Raven, P. B.

1993-01-01

We compared the aortic-cardiac baroreflex sensitivity in eight average fit (AF: VO2max = 44.7 +/- 1.3 ml.kg-1 x min-1) and seven high fit (HF: VO2max = 64.1 +/- 1.7 ml.min-1 x kg-1) healthy young men during hypotension elicited by steady state sodium nitroprusside (SN) infusion. During SN mean arterial pressure (MAP) was similarly decreased in AF (-12.6 +/- 1.0 mm Hg) and HF (-12.1 +/- 1.1 mm Hg). However, the increases in heart rate (HR) were less (P < 0.023) in HF (15 +/- 3 bpm) than AF (25 +/- 1 bpm). When sustained neck suction (NS, -22 +/- 1 torr in AF and -20 +/- 1 torr in HF, P > 0.05) was applied to counteract the decreased carotid sinus transmural pressure during SN, thereby isolating the aortic baroreceptors, the increased HR remained less (P < 0.021) in HF (8 +/- 2 bpm) than AF (16 +/- 2 bpm). During both SN infusion and SN+NS, the calculated gains (i.e., delta HR/delta MAP) were significantly greater in AF (2.1 +/- 0.3 and 1.3 +/- 0.2 bpm.mm Hg-1) than HF (1.2 +/- 0.2 and 0.6 +/- 0.2 bpm.mm Hg-1). However, the estimated carotid-cardiac baroreflex sensitivity (i.e., the gain difference between the stage SN and SN + NS) was not different between AF (0.7 +/- 0.2 bpm.mm Hg-1) and HF (0.6 +/- 0.1 bpm.mm Hg-1). These data indicated that the aortic-cardiac baroreflex sensitivity during hypotension was significantly diminished with endurance exercise training.

Hypotensive effect of alpha-lipoic acid after a single administration in rats.

PubMed

Dudek, Magdalena; Razny, Katarzyna; Bilska-Wilkosz, Anna; Iciek, Malgorzata; Sapa, Jacek; Wlodek, Lidia; Filipek, Barbara

2016-05-01

The effect of alpha-lipoic acid on blood pressure was investigated many times in chronic studies, but there are no studies on the effect of this compound after a single administration. Alpha-lipoic acid is a drug used in diabetic neuropathy, often in obese patients, to treat hypertension. Therefore, knowledge of the potential antihypertensive effect of alpha-lipoic acid even after a single dose and possibly too much pressure reduction is interesting and useful. The mechanism of the hypotensive effect of alpha-lipoic acid was examined in normotensive rats in vivo after a single intraperitoneal administration, blood pressure in the left carotid artery of the rats was measured prior to the administration of the compounds (alpha- lipoic acid and/or glibenclamide) and 80 min thereafter. Alpha-lipoic acid at a dosage of 50 mg/kg b.w. i.p. significantly decreased the blood pressure from the 50th min after drug administration. This cardiovascular effect of this compound was reversed by glibenclamide, a selective KATP blocker. Glibenclamide alone at this dose did not significantly affect the blood pressure. Statistical significance was evaluated using two-way ANOVA. This suggests that alpha-lipoic acid affects ATP-dependent potassium channels. It is possible that this is an indirect effect of hydrogen sulfide because alpha-lipoic acid can increase its concentration. The results obtained in this study are very important because the patients taking alpha-lipoic acid may be treated for co-existing hypertension. Therefore, the possibility of blood pressure lowering by alpha-lipoic acid should be taken into account, although it does not lead to excessive orthostatic hypotension.

Midodrine as a Countermeasure to Orthostatic Hypotension Immediately After Space Shuttle Landing

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Stenger, Michael B.; Ribeiro, L. Christine; Lee, Stuart M. C.

2010-01-01

Midodrine prevents post-space flight orthostatic intolerance when testing is conducted in a controlled laboratory setting within 2-4 hours after Space Shuttle landing. It is unknown if midodrine is as effective during re-entry and immediately following landing. METHODS: Cardiovascular responses to 10 minutes of 80 head-up tilt in five male astronauts were compared before and immediately after Space Shuttle missions. Preflight tests were conducted in the Johnson Space Center Cardiovascular Laboratory without midodrine. Post-flight testing was performed in the Crew Transport Vehicle on the Space Shuttle runway within 60 minutes of landing; midodrine was self-administered before re-entry. Survival analysis was performed (Gehan-Breslow test) to compare presyncope rates pre- to post-flight. Cardiovascular responses (last minute standing minus supine) to tilt before and after space flight were compared using paired t-tests. RESULTS: Midodrine did not prevent post-flight orthostatic hypotension in two of the five astronauts, but the rate of presyncope across the group did not increase (p=0.17) from pre- to post-flight. Also, although the change in heart rate from supine to the last minute of standing was not affected by space flight, systolic blood pressure decreased more (p=0.05) and diastolic blood pressure tended to decrease (p=0.08) after space flight. CONCLUSIONS: Accurate interpretation of the current results requires that similar data be collected in control subjects (without midodrine) on the CTV. However, drug interaction concerns with commonly used anti-emetics and potentiation of prolonged QTc intervals observed in long duration astronauts make the routine use of midodrine for immediate post-flight orthostatic hypotension unlikely. 2

Evidence for hysteresis in the cerebral pressure-flow relationship in healthy men.

PubMed

Brassard, Patrice; Ferland-Dutil, Hélène; Smirl, Jonathan D; Paquette, Myriam; Le Blanc, Olivier; Malenfant, Simon; Ainslie, Philip N

2017-04-01

The cerebrovasculature is more efficient at compensating for pharmacologically induced transient hypertension versus transient hypotension. Whether this phenomenon exists during nonpharmacologically induced hypertension and hypotension is currently unknown. We compared the percent change in mean velocity in the middle cerebral artery (MCAvmean) per percent change in mean arterial pressure (MAP) (%ΔMCAVmean/%ΔMAP) during transient hypertension and hypotension induced during squat-stand maneuvers performed at 0.05 Hz (20-s cycles) and 0.10 Hz (10-s cycles) in 58 male volunteers. %ΔMCAvmean/%ΔMAP was attenuated by 25% ( P = 0.03, 0.05 Hz) and 47% ( P < 0.0001, 0.10 Hz) during transient hypertension versus hypotension. Thus, these findings indicate that the brain in healthy men is better adapted to compensate for physiologically relevant transient hypertension than hypotension. NEW & NOTEWORTHY The novel finding of this study is that the change in middle cerebral artery mean flow velocity is attenuated during hypertension compared with hypotension physiologically induced by oscillations in blood pressure in men. These results support that the human brain is more effective at compensating for transient hypertension than hypotension. Copyright © 2017 the American Physiological Society.

Spontaneous Intracranial Hypotension: A Review and Introduction of an Algorithm For Management.

PubMed

Davidson, Benjamin; Nassiri, Farshad; Mansouri, Alireza; Badhiwala, Jetan H; Witiw, Christopher D; Shamji, Mohammed F; Peng, Philip W; Farb, Richard I; Bernstein, Mark

2017-05-01

Spontaneous intracranial hypotension (SIH) is a condition of low cerebrospinal fluid volume and pressure caused by a leak of cerebrospinal fluid through a dural defect. Diagnosis and management can be difficult, often requiring coordination between multiple disciplines for myelography, blood patching, and possible surgical repair. Patients should be monitored closely, because they can deteriorate into a coma or even death. There are no widely accepted guidelines for the management of SIH. We review the existing SIH literature, illustrate management challenges via a case review, and propose an algorithm developed by neurosurgeons, radiologists, and anesthesiologists intended to simplify and streamline the management of SIH. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute effect of oral water intake during exercise on post-exercise hypotension.

PubMed

Endo, M Y; Kajimoto, C; Yamada, M; Miura, A; Hayashi, N; Koga, S; Fukuba, Y

2012-11-01

Post-exercise hypotension (PEH) is a sustained reduction in mean arterial blood pressure (MAP) after prolonged exercise. As water drinking is known to elicit a large acute pressor response, we aimed to explore the effect of drinking water during exercise on PEH. Ten normotensive male volunteers performed the control protocol: 30 min supine rest, 60 min cycling exercise in moderate intensity, and 60 min supine rest recovery. In the water drinking protocol, the same procedure was followed but with water intake during exercise to compensate for exercise-induced body weight lost. Heart rate, MAP, cardiac output and blood flow in the brachial artery were measured pre- and post-exercise. The total vascular conductance (TVC) and the vascular conductance (VC) in the brachial artery were calculated pre- and post-exercise, and the relative change in plasma volume (ΔPV) was also measured. Body weight loss during exercise was 0.65 ± 0.24 kg in the control. ΔPV was not different during recovery in either protocol. MAP in the control was significantly reduced during the latter half of the recovery compared with baseline. In contrast, MAP in the water drinking showed no reduction during recovery, and was significantly higher than in the control. TVC and VC in the brachial artery were lower in the water drinking, in which vasoconstriction was relatively exaggerated. Prevention of dehydration after exercise by oral water intake, or oral water intake per se has a role in maintaining post-exercise MAP and it may be related to reduction in TVC.

Dexamethasone impairs hypoxia-inducible factor-1 function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagner, A.E.; Huck, G.; Stiehl, D.P.

2008-07-25

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription-factor composed of {alpha}- and {beta}-subunits. HIF-1 is not only necessary for the cellular adaptation to hypoxia, but it is also involved in inflammatory processes and wound healing. Glucocorticoids (GC) are therapeutically used to suppress inflammatory responses. Herein, we investigated whether GC modulate HIF-1 function using GC receptor (GR) possessing (HepG2) and GR deficient (Hep3B) human hepatoma cell cultures as model systems. Dexamethasone (DEX) treatment increased HIF-1{alpha} levels in the cytosol of HepG2 cells, while nuclear HIF-1{alpha} levels and HIF-1 DNA-binding was reduced. In addition, DEX dose-dependently lowered the hypoxia-induced luciferase activity in amore » reporter gene system. DEX suppressed the hypoxic stimulation of the expression of the HIF-1 target gene VEGF (vascular endothelial growth factor) in HepG2 cultures. DEX did not reduce hypoxically induced luciferase activity in HRB5 cells, a Hep3B derivative lacking GR. Transient expression of the GR in HRB5 cells restored the susceptibility to DEX. Our study discloses the inhibitory action of GC on HIF-1 dependent gene expression, which may be important with respect to the impaired wound healing in DEX-treated patients.« less

Mutant SOD1-expressing astrocytes release toxic factors that trigger motoneuron death by inducing hyperexcitability

PubMed Central

Fritz, Elsa; Izaurieta, Pamela; Weiss, Alexandra; Mir, Franco R.; Rojas, Patricio; Gonzalez, David; Rojas, Fabiola; Brown, Robert H.; Madrid, Rodolfo

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motoneurons starting in adulthood. Recent studies using cell or animal models document that astrocytes expressing disease-causing mutations of human superoxide dismutase 1 (hSOD1) contribute to the pathogenesis of ALS by releasing a neurotoxic factor(s). Neither the mechanism by which this neurotoxic factor induces motoneuron death nor its cellular site of action has been elucidated. Here we show that acute exposure of primary wild-type spinal cord cultures to conditioned medium derived from astrocytes expressing mutant SOD1 (ACM-hSOD1G93A) increases persistent sodium inward currents (PCNa), repetitive firing, and intracellular calcium transients, leading to specific motoneuron death days later. In contrast to TTX, which paradoxically increased twofold the amplitude of calcium transients and killed motoneurons, reduction of hyperexcitability by other specific (mexiletine) and nonspecific (spermidine and riluzole) blockers of voltage-sensitive sodium (Nav) channels restored basal calcium transients and prevented motoneuron death induced by ACM-hSOD1G93A. These findings suggest that riluzole, the only FDA-approved drug with known benefits for ALS patients, acts by inhibiting hyperexcitability. Together, our data document that a critical element mediating the non-cell-autonomous toxicity of ACM-hSOD1G93A on motoneurons is increased excitability, an observation with direct implications for therapy of ALS. PMID:23486205

Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-alpha.

PubMed

Fernández, Ricardo; González, Sergio; Rey, Sergio; Cortés, Paula P; Maisey, Kevin R; Reyes, Edison-Pablo; Larraín, Carolina; Zapata, Patricio

2008-07-01

In the absence of information on functional manifestations of carotid body (CB) inflammation, we studied an experimental model in which lipopolysaccharide (LPS) administration to pentobarbitone-anaesthetized cats was performed by topical application upon the CB surface or by intravenous infusion (endotoxaemia). The latter caused: (i) disorganization of CB glomoids, increased connective tissue, and rapid recruitment of polymorphonuclear cells into the vascular bed and parenchyma within 4 h; (ii) increased respiratory frequency and diminished ventilatory chemoreflex responses to brief hypoxia (breathing 100% N(2) for 10 s) and diminished ventilatory chemosensory drive (assessed by 100% O(2) tests) during normoxia and hypoxia; (iii) tachycardia, increased haematocrit and systemic hypotension in response to LPS i.v.; and (iv) increased basal frequency of carotid chemosensory discharges during normoxia, but no change in maximal chemoreceptor responses to brief hypoxic exposures. Lipopolysaccharide-induced tachypnoea was prevented by prior bilateral carotid neurotomy. Apoptosis was not observed in CBs from cats subjected to endotoxaemia. Searching for pro-inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha) was localized by immunohistochemistry in glomus and endothelial cells; reverse transcriptase-polymerase chain reaction revealed that the CB expresses the mRNAs for both type-1 (TNF-R1) and type-2 TNF-alpha receptors (TNF-R2); Western blot confirmed a band of the size expected for TNF-R1; and histochemistry showed the presence of TNF-R1 in glomus cells and of TNF-R2 in endothelial cells. Experiments in vitro showed that the frequency of carotid nerve discharges recorded from CBs perfused and superfused under normoxic conditions was not significantly modified by TNF-alpha, but that the enhanced frequency of chemosensory discharges recorded along responses to hypoxic stimulation was transiently diminished in a dose-dependent manner by TNF-alpha injections

Retrospective analysis of risk factors and predictors of intraoperative complications in neuraxial blocks at Faculdade de Medicina de Botucatu-UNESP.

PubMed

Pereira, Ivan Dias Fernandes; Grando, Marcela Miguel; Vianna, Pedro Thadeu Galvão; Braz, José Reinaldo Cerqueira; Castiglia, Yara Marcondes Machado; Vane, Luís Antônio; Módolo, Norma Sueli Pinheiro; do Nascimento, Paulo; Amorim, Rosa Beatriz; Rodrigues, Geraldo Rolim; Braz, Leandro Gobbo; Ganem, Eliana Marisa

2011-01-01

Cardiovascular changes associated with neuraxial blocks are a cause of concern due to their frequency and because some of them can be considered physiological effects triggered by the sympathetic nervous system blockade. The objective of this study was to evaluate intraoperative cardiovascular complications and predictive factors associated with neuraxial blocks in patients ≥ 18 years of age undergoing non-obstetric procedures over an 18-year period in a tertiary university hospital--HCFMB-UNESP. A retrospective analysis of the following complications was undertaken: hypertension, hypotension, sinus bradycardia, and sinus tachycardia. These complications were correlated with anesthetic technique, physical status (ASA), age, gender, and preoperative co-morbidities. The Tukey test for comparisons among proportions and logistic regression was used for statistical analysis. 32,554 patients underwent neuraxial blocks. Intraoperative complications mentioned included hypotension (n=4,109), sinus bradycardia (n=1,107), sinus tachycardia (n=601), and hypertension (n=466). Hypotension was seen more often in patients undergoing continuous subarachnoid anesthesia (29.4%, OR=2.39), ≥ 61 years of age, and female (OR=1.27). Intraoperative hypotension and bradycardia were the complications observed more often. Hypotension was related to anesthetic technique (CSA), increased age, and female. Tachycardia and hypertension may not have been directly related to neuraxial blocks. Copyright © 2011 Elsevier Editora Ltda. All rights reserved.

Nitric oxide production contributes to Bacillus anthracis edema toxin-associated arterial hypotension and lethality: ex vivo and in vivo studies in the rat

PubMed Central

Li, Yan; Cui, Xizhong; Xu, Wanying; Ohanjanian, Lernik; Sampath-Kumar, Hanish; Suffredini, Dante; Moayeri, Mahtab; Leppla, Stephen; Fitz, Yvonne

2016-01-01

We showed previously that Bacillus anthracis edema toxin (ET), comprised of protective antigen (PA) and edema factor (EF), inhibits phenylephrine (PE)-induced contraction in rat aortic rings and these effects are diminished in endothelial-denuded rings. Therefore, employing rat aortic ring and in vivo models, we tested the hypothesis that nitric oxide (NO) contributes to ET's arterial effects. Compared with rings challenged with PA alone, ET (PA + EF) reduced PE-stimulated maximal contractile force (MCF) and increased the PE concentration producing 50% MCF (EC50) (P < 0.0001). Compared with placebo, l-nitro-arginine methyl-ester (l-NAME), an NO synthase (NOS) inhibitor, reduced ET's effects on MCF and EC50 in patterns that approached or were significant (P = 0.06 and 0.03, respectively). In animals challenged with 24-h ET infusions, l-NAME (0.5 or 1.0 mg·kg−1·h−1) coadministration increased survival to 17 of 28 animals (60.7%) compared with 4 of 27 (14.8%) given placebo (P = 0.01). Animals receiving l-NAME but no ET all survived. Compared with PBS challenge, ET increased NO levels at 24 h and l-NAME decreased these increases (P < 0.0001). ET infusion decreased mean arterial blood pressure (MAP) in placebo and l-NAME-treated animals (P < 0.0001) but l-NAME reduced decreases in MAP with ET from 9 to 24 h (P = 0.03 for the time interaction). S-methyl-l-thiocitrulline, a selective neuronal NOS inhibitor, had effects in rings and, at a high dose in vivo models, comparable to l-NAME, whereas N′-[3-(aminomethyl)benzyl]-acetimidamide, a selective inducible NOS inhibitor, did not. NO production contributes to ET's arterial relaxant, hypotensive, and lethal effects in the rat. PMID:27448553

Growth factor involvement in tension-induced skeletal muscle growth

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.

1993-01-01

Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

Impact of Minocycline on Extracellular Matrix Metalloproteinase Inducer, a Factor Implicated in Multiple Sclerosis Immunopathogenesis.

PubMed

Hahn, Jennifer N; Kaushik, Deepak K; Mishra, Manoj K; Wang, Jianxiong; Silva, Claudia; Yong, V Wee

2016-11-15

Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a transmembrane glycoprotein that is upregulated on leukocytes in active lesions in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Administration of anti-EMMPRIN Abs reduces the severity of EAE. Minocycline is a tetracycline antibiotic with immune-modulatory properties that decreases the severity of EAE; it was recently found to attenuate the conversion from a first demyelinating event to clinically definite MS in a phase III trial. We investigated whether and how minocycline affects the expression of EMMPRIN on T cells in culture and in mice afflicted with EAE. EMMPRIN expression in cultures of mouse splenocytes or human PBMCs was elevated upon polyclonal T cell activation, and this was reduced by minocycline correspondent with decreased P-Akt levels. An established MS medication, IFN-β, also diminished EMMPRIN levels on human cells whereas this was not readily observed for fingolimod or monomethylfumarate. In EAE-afflicted mice, minocycline treatment significantly reduced EMMPRIN levels on splenic lymphocytes at the presymptomatic (day 7) phase, and prevented the development of disease. Day 7 spleen transcripts from minocycline-treated EAE mice had a significantly lower MMP-9/TIMP-1 ratio, and significantly lower MCT-1 and CD98 levels, factors associated with EMMPRIN function. Day 16 (peak clinical severity) CNS samples from EAE mice had prominent representation of inflammatory perivascular cuffs, inflammatory molecules and EMMPRIN, and these were abrogated by minocycline. Overall, minocycline attenuated the activation-induced elevation of EMMPRIN on T cells in culture and in EAE mice, correspondent with reduced immune function and EAE CNS pathology. Copyright © 2016 by The American Association of Immunologists, Inc.

Neurogenic orthostatic hypotension in Parkinson’s disease: evaluation, management, and emerging role of droxidopa

PubMed Central

Isaacson, Stuart H; Skettini, Julia

2014-01-01

Neurogenic orthostatic hypotension (nOH) is due to failure of the autonomic nervous system to regulate blood pressure in response to postural changes due to an inadequate release of norepinephrine, leading to orthostatic hypotension and supine hypertension. nOH is common in Parkinson’s disease (PD). Prevalence varies throughout the course of PD, ranging from 40% to 60%, and resulting in symptomatic nOH in approximately half. Symptomatic nOH, including lightheadedness, can limit daily activities and lead to falls. Symptomatic nOH can also limit therapeutic options for treating PD motor symptoms. Clinical evaluation should routinely include symptom assessment and blood pressure measurement of supine, sitting, and 3-minute standing; 24-hour ambulatory blood pressure monitoring can also be helpful. Non-pharmacological management of symptomatic nOH involves education, physical maneuvers, and adequate hydration. Current pharmacological treatment of symptomatic nOH includes salt supplement, fludrocortisone, midodrine, pyridostigmine, and other empiric medications. Despite these options, treatment of symptomatic nOH remains suboptimal, often limited by severe increases in supine blood pressure. Droxidopa, an oral prodrug converted by decarboxylation to norepinephrine, is a promising therapeutic option for symptomatic nOH in PD, improving symptoms of nOH, daily activities, falls, and standing systolic blood pressure in several recent trials. These trials demonstrated short-term efficacy and tolerability, with comparable increases in standing and supine blood pressures. Longer-term studies are ongoing to confirm durability of treatment effect. PMID:24729712

Comparison of clinical efficacy among remifentanil, nicardipine, and remifentanil plus nicardipine continuous infusion for hypotensive anesthesia during arthroscopic shoulder surgery.

PubMed

Kim, Joon Yub; Song, Seong Hun; Cho, Jae Ho; Cho, Hyung Rae

2017-01-01

Hypotensive anesthesia is crucial during arthroscopic shoulder surgery to reduce bleeding and allow for clear visibility. The aim of this study was to compare the clinical efficacy of continuous infusion of remifentanil, nicardipine, and remifentanil plus nicardipine to control hypotensive anesthesia in arthroscopic shoulder surgery. For this study, we enrolled 45 consecutive patients who were scheduled to have arthroscopic rotator cuff repair surgery and randomly allocated them into remifentanil (group R, n = 15), nicardipine (group N, n = 15), and remifentanil plus nicardipine (group RN, n = 15) groups. During the surgeries, these drugs were administered with continuous infusion. We analyzed the mean arterial pressure (MAP) and heart rate during surgery, stay time in the recovery room, visual analogue scale (VAS) scores, use of antiemetics in the recovery room, and postoperative blood urea nitrogen and creatinine changes. The VAS score in the recovery room was higher for group R (mean 5.6, SD 1.4) than for groups N (mean 3.9, SD 0.9) and RN (mean 4.0, SD 1.1; p = 0.000). There were no statistical differences regarding other clinical variables among the three groups (all p > 0.05) except for MAP at 120 min of surgery between groups N and RN (N: 84.67 (SD 10.7) mmHg, RN: 65.4 (SD 9.2) mmHg, p = 0.027). The continuous infusion of remifentanil plus nicardipine appeared to be advantageous for maintaining hypotensive anesthesia until 120 min of arthroscopic shoulder surgery without rebound pain in a postanesthesia care unit.

Transforming growth factor-β1 induces expression of human coagulation factor XII via Smad3 and JNK signaling pathways in human lung fibroblasts.

PubMed

Jablonska, Ewa; Markart, Philipp; Zakrzewicz, Dariusz; Preissner, Klaus T; Wygrecka, Malgorzata

2010-04-09

Coagulation factor XII (FXII) is a liver-derived serine protease involved in fibrinolysis, coagulation, and inflammation. The regulation of FXII expression is largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that has been linked to several pathological processes, including tissue fibrosis by modulating procoagulant and fibrinolytic activities. This study investigated whether TGF-beta1 may regulate FXII expression in human lung fibroblasts. Treatment of human lung fibroblasts with TGF-beta1 resulted in a time-dependent increase in FXII production, activation of p44/42, p38, JNK, and Akt, and phosphorylation and translocation into the nucleus of Smad3. However, TGF-beta1-induced FXII expression was repressed only by the JNK inhibitor and JNK and Smad3 antisense oligonucleotides but not by MEK, p38, or phosphoinositide 3-kinase blockers. JNK inhibition had no effect on TGF-beta1-induced Smad3 phosphorylation, association with Smad4, and its translocation into the nucleus but strongly suppressed Smad3-DNA complex formation. FXII promoter analysis revealed that the -299/+1 region was sufficient for TGF-beta1 to induce FXII expression. Sequence analysis of this region detected a potential Smad-binding element at position -272/-269 (SBE-(-272/-269)). Chromatin immunoprecipitation and streptavidin pulldown assays demonstrated TGF-beta1-dependent Smad3 binding to SBE-(-272/-269). Mutation or deletion of SBE-(-272/-269) substantially reduced TGF-beta1-mediated activation of the FXII promoter. Clinical relevance was demonstrated by elevated FXII levels and its co-localization with fibroblasts in the lungs of patients with acute respiratory distress syndrome. Our results show that JNK/Smad3 pathway plays a critical role in TGF-beta1-induced FXII expression in human lung fibroblasts and implicate its possible involvement in pathological conditions characterized by elevated TGF-beta1 levels.

Effectiveness of droxidopa compared to midodrine in standing blood pressure and orthostatic tolerance in adults with neurogenic orthostatic hypotension: a systematic review protocol.

PubMed

Patrick, Kelli; Martin, Tina

2017-09-01

The question of this review is: what is the effectiveness of droxidopa compared to midodrine on standing blood pressure and orthostatic intolerance symptoms in adults with neurogenic orthostatic hypotension?

[Indices of 24-hour monitoring of arterial blood pressure in patients with neurogenic syncope and patients with chronic constitution- dependent hypotension].

PubMed

Musaeva, Z A; Khapaev, B A; Fedotova, A V; Oknin, V Iu

1999-01-01

Clinical-psychologic study, spectral analysis of heart rate variability, 24-h monitoring of arterial pressure (AP) were performed in 20 patients with chronic constitutional arterial hypotension and in 18 patients with neurogenic syncopal states. Both groups were characterised by considerable manifestations of the syndrome of autonomic dystonia, by emotional-personal disorders that correlated with elevated level of slow-waves of the second order in heart rhythms' spectrum. That testified activation of supersegmental sympathetic-adrenal systems. Disorders in sympathetic-parasympathetic correlations were specific in each group. In patients with arterial hypotension disorder of circadian rhythm was observed in the form of superfluous decrease of diastolic AP during sleep. Circadian rhythms in patients with neurogenic syncopes have parameters characteristic for normals showing a preverved chronobiologic AP regulation. A role of the alterations revealed in pathogenesis of arterial hypotensionis discussed.

Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial.

PubMed

Kaufmann, Horacio; Freeman, Roy; Biaggioni, Italo; Low, Phillip; Pedder, Simon; Hewitt, L Arthur; Mauney, Joe; Feirtag, Michael; Mathias, Christopher J

2014-07-22

To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH). Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100-600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities. From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in "dizziness/lightheadedness." Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for "standing a long time." Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥ 3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events. In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated. This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days. © 2014 American Academy of Neurology.

Modified rice bran hemicellulose inhibits vascular endothelial growth factor-induced angiogenesis in vitro via VEGFR2 and its downstream signaling pathways

PubMed Central

ZHU, Xia; OKUBO, Aya; IGARI, Naoki; NINOMIYA, Kentaro; EGASHIRA, Yukari

2016-01-01

Angiogenesis is implicated in diverse pathological conditions such as cancer, rheumatoid arthritis, psoriasis, atherosclerosis, and retinal neovascularization. In the present study, we investigated the effects of modified rice bran hemicellulose (MRBH), a water-soluble hemicellulose preparation from rice bran treated with shiitake enzymes, on vascular endothelial growth factor (VEGF)-induced angiogenesis in vitro and its mechanism. We found that MRBH significantly inhibited VEGF-induced tube formation in human umbilical vein endothelial cells (HUVECs) co-cultured with human dermal fibroblasts. We also observed that MRBH dose-dependently suppressed the VEGF-induced proliferation and migration of HUVECs. Furthermore, examination of the anti-angiogenic mechanism indicated that MRBH reduced not only VEGF-induced activation of VEGF receptor 2 but also of the downstream signaling proteins Akt, extracellular signal-regulated protein kinase 1/2, and p38 mitogen-activated protein kinase. These findings suggest that MRBH has in vitro anti-angiogenic effects that are partially mediated through the inhibition of VEGF signaling. PMID:28439487

Xenon/remifentanil anesthesia protects against adverse effects of losartan on hemodynamic challenges induced by anesthesia and acute blood loss.

PubMed

Francis, Roland C E; Philippi-Höhne, Claudia; Klein, Adrian; Pickerodt, Philipp A; Reyle-Hahn, Matthias S; Boemke, Willehad

2010-12-01

The authors aimed to test the hypothesis that xenon anesthesia limits adverse hypotensive effects of losartan during acute hemorrhage. In six conscious unsedated Beagle dogs, the systemic and pulmonary circulation were monitored invasively, and two subsequent 60-min hypotensive challenges were performed by (a) induction (propofol) and maintenance of anesthesia with isoflurane/remifentanil or xenon/remifentanil and by (b) subsequent hemorrhage (20 mL kg⁻¹ within 5 min) from a central vein. The same amount of blood was retransfused 1 h after hemorrhage. Experiments were performed with or without acute angiotensin II receptor subtype 1 blockade by i.v. losartan (100 μg·kg⁻¹·min⁻¹) starting 45 min before induction of anesthesia. Four experiments were performed in each individual dog. Xenon/remifentanil anesthesia provided higher baseline mean arterial blood pressure (85 ± 6 mmHg) than isoflurane/remifentanil anesthesia (67 ± 3 mmHg). In losartan-treated animals, isoflurane/remifentanil caused significant hypotension (42 ± 4 mmHg for isoflurane/remifentanil vs. 71 ± 6 mmHg for xenon/remifentanil). Independent of losartan, hemorrhage did not induce any further reduction of mean arterial blood pressure or cardiac output in either group. Spontaneous hemodynamic recovery was observed in all groups before retransfusion was started. Losartan did not alter the adrenaline, noradrenaline, and vasopressin response to acute hemorrhage. Losartan potentiates hypotension induced by isoflurane/remifentanil anesthesia but does not affect the hemodynamic stability during xenon/remifentanil anesthesia. Losartan does not deteriorate the hemodynamic adaptation to hemorrhage of 20 mL kg⁻¹ during xenon/remifentanil and isoflurane/remifentanil anesthesia. Therefore, xenon/remifentanil anesthesia protects against circulatory side effects of losartan pretreatment and thus may afford safer therapeutic use of losartan during acute hemorrhage.

Oxytocin for labour and caesarean delivery: implications for the anaesthesiologist.

PubMed

Dyer, Robert A; Butwick, Alexander J; Carvalho, Brendan

2011-06-01

The implications of the obstetric use of oxytocin for obstetric anaesthesia practice are summarised. The review focuses on recent research on the uterotonic effects of oxytocin for prophylaxis and management of uterine atony during caesarean delivery. Oxytocin remains the first-line agent in the prevention and management of uterine atony. In-vitro and in-vivo studies show that prior exposure to oxytocin induces uterine muscle oxytocin receptor desensitization. This may influence oxytocin dosing for adequate uterine tone following delivery. Oxytocin has important cardiovascular side-effects (hypotension, tachycardia and myocardial ischaemia). Recent studies suggest that the effective dose of oxytocin for prophylaxis against uterine atony during caesarean delivery is significantly lower than the 5-10 IU historically used by anaesthesiologists. Slow administration of small bolus doses of oxytocin minimises maternal haemodynamic disturbance. Continuous oxytocin infusions are recommended for maintaining uterine tone after bolus administration, although ideal infusion rates are still to be established. The efficacy of the long-acting oxytocin analogue carbetocin requires further investigation. Recommendations are presented for oxytocin dosing during caesarean delivery. Oxytocin remains the first-line uterotonic after vaginal and caesarean delivery. Recent research elucidates the therapeutic range of oxytocin during caesarean delivery, as well as receptor desensitization. Evidenced-based protocols for the prevention and treatment of uterine atony during caesarean delivery are recommended.

Heat shock factor 1 suppresses the HIV-induced inflammatory response by inhibiting nuclear factor-κB.

PubMed

Pan, Xiaoyan; Lin, Jian; Zeng, Xiaoyun; Li, Wenjuan; Wu, Wenjiao; Lu, Wan Zhen; Liu, Jing; Liu, Shuwen

2018-05-01

The persistent inflammation aggravated by a disordered immune response is considered to be the major cause of CD4 + T cell depletion in lymphoid tissue, which impels the progression of AIDS. Here, we report that heat shock factor 1 (HSF1) works as an innate repressor of HIV-induced inflammation. The activation of HSF1 was found to accompany inflammation during HIV infection. Further research uncovered that HSF1 activation inhibited HIV-induced inflammation. In addition, HSF1 overexpression suppressed the inflammatory response induced by HIV, while HSF1 deficiency exacerbated that inflammation. Mechanistically, HSF1 was found to compete with nuclear factor-κB (NF-κB) in the nucleus. Generally, our report highlights that HSF1 is an important host factor in regulating HIV-induced inflammation and may work as a potential target for curing AIDS. Copyright © 2018 Elsevier Inc. All rights reserved.

Myeloid hypoxia-inducible factor 1α prevents airway allergy in mice through macrophage-mediated immunoregulation.

PubMed

Toussaint, M; Fievez, L; Drion, P-V; Cataldo, D; Bureau, F; Lekeux, P; Desmet, C J

2013-05-01

Hypoxia-inducible factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1α in the myeloid lineage consequently results in decreased inflammatory responses in classical models of acute inflammation in mice. By contrast, we report here that mice conditionally deficient for Hif1α in myeloid cells display enhanced sensitivity to the development of airway allergy to experimental allergens and house-dust mite antigens. We support that upon allergen exposure, MyD88-dependent upregulation of Hif1α boosts the expression of the immunosuppressive cytokine interleukin (IL)-10 by lung interstitial macrophages (IMs). Hif1α-dependent IL-10 secretion is required for IMs to block allergen-induced dendritic cell activation and consequently for preventing the development of allergen-specific T-helper cell responses upon allergen exposure. Thus, this study supports that, in addition to its known pro-inflammatory activities, myeloid Hif1α possesses immunoregulatory functions implicated in the prevention of airway allergy.

Krüppel-like factor 4 regulates the expression of inducible nitric oxide synthase induced by TNF-α in human fibroblast-like synoviocyte MH7A cells.

PubMed

Mo, Xuanrong; Chen, Jie; Wang, Xinjuan; Pan, Zhenyu; Ke, Yuping; Zhou, Zhidong; Xie, Jiangwen; Lv, Guoju; Luo, Xinjing

2018-01-01

Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, has been implicated in the inflammation mediated by macrophages and endothelial cells by regulating the expression of inflammatory mediators. Here, we investigated whether KLF4 affects the expression of inducible nitric oxide synthase (iNOS), an important inflammatory mediator, in the human RA fibroblast-like synovial cell line MH7A. A pcDNA3.1-KLF4 plasmid or short interfering RNA KLF4 was transfected into MH7A cells, and the iNOS expression and nitric oxide (NO) production were analyzed by quantitative PCR, immunoblotting, and nitrite measurement. The iNOS promoter activity was determined by luciferase assay. The results showed overexpression of KLF4 increased iNOS expression and NO production in the presence or absence of TNF-α. Conversely, KLF4 knockdown markedly reduced iNOS expression and NO production induced by TNF-α. KLF4 activated the transcription activity of iNOS promoter in MH7A cells stimulated by TNF-α. This study indicates that KLF4 is important for regulating the expression of iNOS by TNF-α in human synoviocytes.

Myostatin is a novel tumoral factor that induces cancer cachexia

PubMed Central

Lokireddy, Sudarsanareddy; Wijesoma, Isuru Wijerupage; Bonala, Sabeera; Wei, Meng; Sze, Siu Kwan; McFarlane, Craig; Kambadur, Ravi; Sharma, Mridula

2012-01-01

Humoral and tumoral factors collectively promote cancer-induced skeletal muscle wasting by increasing protein degradation. Although several humoral proteins, namely TNFα (tumour necrosis factor α) and IL (interleukin)-6, have been shown to induce skeletal muscle wasting, there is a lack of information regarding the tumoral factors that contribute to the atrophy of muscle during cancer cachexia. Therefore, in the present study, we have characterized the secretome of C26 colon cancer cells to identify the tumoral factors involved in cancer-induced skeletal muscle wasting. In the present study, we show that myostatin, a procachectic TGFβ (transforming growth factor β) superfamily member, is abundantly secreted by C26 cells. Consistent with myostatin signalling during cachexia, treating differentiated C2C12 myotubes with C26 CM (conditioned medium) resulted in myotubular atrophy due to the up-regulation of muscle-specific E3 ligases, atrogin-1 and MuRF1 (muscle RING-finger protein 1), and enhanced activity of the ubiquitin–proteasome pathway. Furthermore, the C26 CM also activated ActRIIB (activin receptor type II B)/Smad and NF-κB (nuclear factor κB) signalling, and reduced the activity of the IGF-I (insulin-like growth factor 1)/PI3K (phosphoinositide 3-kinase)/Akt pathway, three salient molecular features of myostatin action in skeletal muscles. Antagonists to myostatin prevented C26 CM-induced wasting in muscle cell cultures, further confirming that tumoral myostatin may be a key contributor in the pathogenesis of cancer cachexia. Finally, we show that treatment with C26 CM induced the autophagy–lysosome pathway and reduced the number of mitochondria in myotubes. These two previously unreported observations were recapitulated in skeletal muscles collected from C26 tumour-bearing mice. PMID:22621320

Implication of multiple mechanisms in apoptosis induced by the synthetic retinoid CD437 in human prostate carcinoma cells.

PubMed

Sun, S Y; Yue, P; Lotan, R

2000-09-14

The synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) induces apoptosis in several types of cancer cell. CD437 inhibited the growth of both androgen-dependent and -independent human prostate carcinoma (HPC) cells in a concentration-dependent manner by rapid induction of apoptosis. CD437 was more effective in killing androgen-independent HPC cells such as DU145 and PC-3 than the androgen-dependent LNCaP cells. The caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK blocked apoptosis induced by CD437 in DU145 and LNCaP cells, in which increased caspase-3 activity and PARP cleavage were observed, but not in PC-3 cells, in which CD437 did not induce caspase-3 activation and PARP cleavage. Thus, CD437 can induce either caspase-dependent or caspase-independent apoptosis in HPC cells. CD437 increased the expression of c-Myc, c-Jun, c-Fos, and death receptors DR4, DR5 and Fas. CD437's potency in apoptosis induction in the different cell lines was correlated with its effects on the expression of oncogenes and death receptors, thus implicating these genes in CD437-induced apoptosis in HPC cells. However, the importance and contribution of each of these genes in different HPC cell lines may vary. Because CD437 induced the expression of DR4, DR5 and Fas, we examined the effects of combining CD437 and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand, respectively, in HPC cells. We found synergistic induction of apoptosis, highlighting the importance of the modulation of these death receptors in CD437-induced apoptosis in HPC cells. This result also suggests a potential strategy of using CD437 with TRAIL for treatment of HPC. Oncogene (2000) 19, 4513 - 4522.

Transcranial Doppler monitoring in Parkinson's disease: cerebrovascular compensation of orthostatic hypotension.

PubMed

Haubrich, Christina; Pies, Katrin; Dafotakis, Manuel; Block, Frank; Kloetzsch, Christof; Diehl, Rolf R

2010-10-01

Despite of precipitous blood pressure falls in Parkinson's Disease (PD) patients, they may not experience syncope or postural complaints. Can cerebral blood flow regulation explain why orthostatic hypotension (OH) has often no accompanying symptoms? In patients with PD and OH (18 asymptomatic; 8 symptomatic), arterial blood pressure (ABP) as well as Doppler-detected cerebral blood flow velocity (CBFV) in middle and posterior cerebral arteries (MCA and PCA) were monitored during head-up tilt and compared with 25 controls and eight non-PD-OH patients. Analysis included the transfer function between slow spontaneous pressure and flow-oscillations. ABP and CBFV were maintained at significantly higher levels in asymptomatic than symptomatic PD-OH (ABP: 85.7 ± 10.5 vs. 66.9 ± 12.5%; MCA-FV: 83.3 ± 9.3 vs. 66.1 ± 6.8%; PCA-FV: 84.4 ± 12.2 vs. 65.9 ± 9.3% of supine). When orthostatic complaints occurred, CBFV depended directly on ABP changes (MCA r(2) = 0.64; PCA r(2) = 0.62; both p < 0.05). Despite of a tilt-induced blood pressure instability in PD-OH, the transfer function parameters did not differ from normal [phase: MCA: 46.6 ± 20.5°; PCA 39.2 ± 28.8°, gain: MCA 2.0 ± 0.7; PCA 2.9 ± 1.6)]. Results showed a normal autoregulatory response to downward blood pressure shifts in PD. Moreover, orthostatic blood pressure instability is compensated equally sufficient in anterior and posterior parts of cerebral circulation. Whether in PD patients, OH becomes symptomatic rather seems to depend on blood pressure falling below the autoregulated range. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha.

PubMed Central

Montrucchio, G.; Lupia, E.; de Martino, A.; Battaglia, E.; Arese, M.; Tizzani, A.; Bussolino, F.; Camussi, G.

1997-01-01

We evaluated the role of an endogenous production of nitric oxide (NO) in the in vitro migration of endothelial cells and in the in vivo angiogenic response elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF), and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model, the angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These results suggest that NO mediates the angiogenesis induced by PAF as well as that induced by TNF, which is dependent on the production of PAF. In contrast, the angiogenic effect of bFGF appears to be both PAF and NO independent. Images Figure 3 Figure 4 PMID:9250168

Ketamine induces brain-derived neurotrophic factor expression via phosphorylation of histone deacetylase 5 in rats.

PubMed

Choi, Miyeon; Lee, Seung Hoon; Park, Min Hyeop; Kim, Yong-Seok; Son, Hyeon

2017-08-05

Ketamine shows promise as a therapeutic agent for the treatment of depression. The increased expression of brain-derived neurotrophic factor (BDNF) has been associated with the antidepressant-like effects of ketamine, but the mechanism of BDNF induction is not well understood. In the current study, we demonstrate that the treatment of rats with ketamine results in the dose-dependent rapid upregulation of Bdnf promoter IV activity and expression of Bdnf exon IV mRNAs in rat hippocampal neurons. Transfection of histone deacetylase 5 (HDAC5) into rat hippocampal neurons similarly induces Bdnf mRNA expression in response to ketamine, whereas transfection of a HDAC5 phosphorylation-defective mutant (Ser259 and Ser498 replaced by Ala259 and Ala498), results in the suppression of ketamine-mediated BDNF promoter IV transcriptional activity. Viral-mediated hippocampal knockdown of HDAC5 induces Bdnf mRNA and protein expression, and blocks the enhancing effects of ketamine on BDNF expression in both unstressed and stressed rats, and thereby providing evidence for the role of HDAC5 in the regulation of Bdnf expression. Taken together, our findings implicate HDAC5 in the ketamine-induced transcriptional regulation of Bdnf, and suggest that the phosphorylation of HDAC5 regulates the therapeutic actions of ketamine. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurogenic orthostatic hypotension – management update and role of droxidopa

PubMed Central

Vijayan, Joy; Sharma, Vijay K

2015-01-01

Orthostatic hypotension (OH) is defined as a significant decrease in blood pressure (BP) during the first 3 minutes of standing or a head up on a tilt table. Symptoms of OH are highly variable, ranging from mild light-headedness to recurrent syncope. OH occurs due to dysfunction of one or more components of various complex mechanisms that interplay closely to maintain BP in a normal range during various physiological and associated disease states. Various biochemical and electrophysiological studies are often undertaken to assess the severity and etiology of OH. In addition to the lifestyle modifications, various medications that stimulate the adrenergic receptors or increase central blood volume are used in patients with OH. Droxidopa is a newer agent that increases the levels of norepinephrine in postganglionic sympathetic neurons. Management strategies for OH are presented, including the mechanism of action of droxidopa and various studies performed to assess its efficacy. PMID:26089676

Post-resistance exercise hypotension in spontaneously hypertensive rats is mediated by nitric oxide.

PubMed

Lizardo, J H F; Silveira, E A A; Vassallo, D V; Oliveira, E M

2008-07-01

1. Postexercise hypotension (PEH) plays an important role in the non-pharmacological treatment of hypertension. It is characterized by a decrease in blood pressure (BP) after a single bout of exercise in relation to pre-exercise levels. 2. The present study investigated the effect of a single session of resistance exercise, as well as the effect of nitric oxide (NO) and the autonomic nervous system (ANS), in PEH in spontaneously hypertensive rats (SHR). 3. Catheters were inserted into the left carotid artery and left jugular vein of male SHR (n = 37) for the purpose of measuring BP or heart rate (HR) and drug or vehicle administration, respectively. Haemodynamic measurements were made before and after acute resistance exercise. The roles of NO and the ANS were investigated by using N(G)-nitro-L-arginine methyl ester (L-NAME; 15 mg/kg, i.v.) and hexamethonium (20 mg/kg, i.v.) after a session of acute resistance exercise. 4. Acute resistance exercise promoted a pronounced reduction in systolic and diastolic BP (-37 +/- 1 and -8 +/- 1 mmHg, respectively; P < 0.05), which was suppressed after treatment with L-NAME. The reduction in systolic BP caused by exercise (-37 +/- 1 mmHg) was not altered by the administration of hexamethonium (-38 +/- 2 mmHg; P > 0.05). After exercise, the decrease in diastolic BP was greater with hexamethonium (-26 +/- 1 mmHg; P < 0.05) compared with the decrease caused by exercise alone. 5. The results suggest that acute resistance exercise has an important hypotensive effect on SHR and that NO plays a crucial role in this response.

Features and prognostic factors for elderly with acute poisoning in the emergency department.

PubMed

Hu, Yu-Hui; Chou, Hsiu-Ling; Lu, Wen-Hua; Huang, Hsien-Hao; Yang, Cheng-Chang; Yen, David H T; Kao, Wei-Fong; Deng, Jou-Fan; Huang, Chun-I

2010-02-01

Elderly persons with acute poisoning in the emergency department (ED) and prognostic factors of outcomes have not been well addressed in previous research. This study aimed to investigate the characteristics of elderly patients with acute poisoning visiting the ED, and to identify the possible predictive factors of mortality. Patients aged > or = 65 years with acute poisoning who visited the ED in Taipei Veterans General Hospital from January 1, 2006 through to September 30, 2008 were enrolled in the study. We collected demographic information on underlying diseases, initial presentations, causes and toxic substances, complications, dispositions, and outcomes. Analyses were conducted among different groups categorized according to age, suicide attempt, and outcome. Multiple logistic regression was applied to identify possible predictive clinical factors influencing mortality in the elderly with acute poisoning. A total of 250 patients were enrolled in the study, with a mean age of 77 years and male predominance. The most common cause of intoxication was unintentional poisoning. Medication accounted for 57.6% of poisonous substances, of which benzodiazepine was the most common drug, followed by warfarin. The overall mortality rate was 9.6%. The average length of stay in the ED increased significantly in the old (65-74 years), very old (75-84 years) and extremely old (> or = 85 years) groups. Suicide attempt patients experienced more complications including respiratory failure, aspiration pneumonia, hypotension and mortality. Three clinical predictive factors of mortality were identified: herbicide poisoning, hypotension and respiratory failure upon presentation. Our results demonstrated that elderly patients with acute poisoning had a mortality rate of 9.6%. Suicide attempts resulted in more serious complications. The risk factors for mortality were herbicide intoxication, hypotension and respiratory failure. Copyright 2010 Elsevier. Published by Elsevier B.V. All

CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo

PubMed Central

Passier, Robert; Zeng, Hong; Frey, Norbert; Naya, Francisco J.; Nicol, Rebekka L.; McKinsey, Timothy A.; Overbeek, Paul; Richardson, James A.; Grant, Stephen R.; Olson, Eric N.

2000-01-01

Hypertrophic growth is an adaptive response of the heart to diverse pathological stimuli and is characterized by cardiomyocyte enlargement, sarcomere assembly, and activation of a fetal program of cardiac gene expression. A variety of Ca2+-dependent signal transduction pathways have been implicated in cardiac hypertrophy, but whether these pathways are independent or interdependent and whether there is specificity among them are unclear. Previously, we showed that activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin or its target transcription factor NFAT3 was sufficient to evoke myocardial hypertrophy in vivo. Here, we show that activated Ca2+/calmodulin-dependent protein kinases-I and -IV (CaMKI and CaMKIV) also induce hypertrophic responses in cardiomyocytes in vitro and that CaMKIV overexpressing mice develop cardiac hypertrophy with increased left ventricular end-diastolic diameter and decreased fractional shortening. Crossing this transgenic line with mice expressing a constitutively activated form of NFAT3 revealed synergy between these signaling pathways. We further show that CaMKIV activates the transcription factor MEF2 through a posttranslational mechanism in the hypertrophic heart in vivo. Activated calcineurin is a less efficient activator of MEF2-dependent transcription, suggesting that the calcineurin/NFAT and CaMK/MEF2 pathways act in parallel. These findings identify MEF2 as a downstream target for CaMK signaling in the hypertrophic heart and suggest that the CaMK and calcineurin pathways preferentially target different transcription factors to induce cardiac hypertrophy. PMID:10811847

Enhanced/Synthetic Vision Systems - Human factors research and implications for future systems

NASA Technical Reports Server (NTRS)

Foyle, David C.; Ahumada, Albert J.; Larimer, James; Sweet, Barbara T.

1992-01-01

This paper reviews recent human factors research studies conducted in the Aerospace Human Factors Research Division at NASA Ames Research Center related to the development and usage of Enhanced or Synthetic Vision Systems. Research discussed includes studies of field of view (FOV), representational differences of infrared (IR) imagery, head-up display (HUD) symbology, HUD advanced concept designs, sensor fusion, and sensor/database fusion and evaluation. Implications for the design and usage of Enhanced or Synthetic Vision Systems are discussed.

Interferon response factor 3 is essential for house dust mite-induced airway allergy.

PubMed

Marichal, Thomas; Bedoret, Denis; Mesnil, Claire; Pichavant, Muriel; Goriely, Stanislas; Trottein, François; Cataldo, Didier; Goldman, Michel; Lekeux, Pierre; Bureau, Fabrice; Desmet, Christophe J

2010-10-01

Pattern-recognition receptors (PRRs) are critically involved in the pathophysiology of airway allergy, yet most of the signaling pathways downstream of PRRs implicated in allergic airway sensitization remain unknown. We sought to study the effects of genetic depletion of interferon response factor (IRF) 3 and IRF7, important transcription factors downstream of various PRRs, in a murine model of house dust mite (HDM)-induced allergic asthma. We compared HDM-induced allergic immune responses in IRF3-deficient (IRF3(-/-)), IRF7(-/-), and wild-type mice. Parameters of airway allergy caused by HDM exposure were strongly attenuated in IRF3(-/-), but not IRF7(-/-), mice compared with those in wild-type mice. Indeed, in HDM-exposed IRF3(-/-) mice HDM-specific T(H)2 cell responses did not develop. This correlated with impaired maturation and migration of IRF3(-/-) lung dendritic cells (DCs) on HDM treatment. Furthermore, adoptive transfer of HDM-loaded DCs indicated that IRF3(-/-) DCs had an intrinsic defect rendering them unable to migrate and to prime HDM-specific T(H)2 responses. Intriguingly, we also show that DC function and allergic airway sensitization in response to HDM were independent of signaling by type I interferons, the main target genes of IRF3. Through its role in DC function, IRF3, mainly known as a central activator of antiviral immunity, is essential for the development of T(H)2-type responses to airway allergens. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1.

PubMed

Abán, C; Martinez, N; Carou, C; Albamonte, I; Toro, A; Seyahian, A; Franchi, A; Leguizamón, G; Trigubo, D; Damiano, A; Farina, M

2016-10-01

During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed towards the relevance of endocannabinoids (ECs) and hypoxia as modulators of trophoblast cell death. However, the relation between these factors is still unknown. In this report, we evaluated the participation of ECs in placental apoptosis induced by cobalt chloride (CoCl2), a hypoxia mimicking agent that stabilizes the expression of hypoxia inducible factor-1 alpha (HIF-1α). We found that HIF-1α stabilization decreased FAAH mRNA and protein levels, suggesting an increase in ECs tone. Additionally, CoCl2 incubation and Met-AEA treatment reduced cell viability and increased TUNEL-positive staining in syncytiotrophoblast layer. Immunohistochemical analysis demonstrated Bax and Bcl-2 protein expression in the cytoplasm of syncytiotrophoblast. Finally, HIF-1α stabilization produced an increase in Bax/Bcl-2 ratio, activation of caspase 3 and PARP cleavage. All these changes in apoptotic parameters were reversed with AM251, a CB1 antagonist. These results demonstrate that HIF-1α may induce apoptosis in human placenta via intrinsic pathway by a mechanism that involves activation of CB1 receptor suggesting a role of the ECs in this process.

L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure.

PubMed

Mathias, C J; Senard, J M; Braune, S; Watson, L; Aragishi, A; Keeling, J E; Taylor, M D

2001-08-01

This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (-22+/-28 mm Hg reduction from a baseline decrease of 54.3+/-27.7 mm Hg, p = 0.0001, n = 32; supine systolic BP at final visit was 118.9+/-28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mg L-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p = 0.0125), and blurred vision (p = 0.0290). L-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.

Nuclear factor κB–inducing kinase activation as a mechanism of pancreatic β cell failure in obesity

PubMed Central

Malle, Elisabeth K.; Zammit, Nathan W.; Walters, Stacey N.; Koay, Yen Chin; Wu, Jianmin; Tan, Bernice M.; Villanueva, Jeanette E.; Brink, Robert; Loudovaris, Tom; Cantley, James; McAlpine, Shelli R.; Hesselson, Daniel

2015-01-01

The nuclear factor κB (NF-κB) pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic β cell dysfunction in the metabolic syndrome. Whereas canonical NF-κB signaling is well studied, there is little information on the divergent noncanonical NF-κB pathway in the context of pancreatic islet dysfunction. Here, we demonstrate that pharmacological activation of the noncanonical NF-κB–inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. We identify NIK as a critical negative regulator of β cell function, as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of noncanonical NF-κB components p100 to p52, and accumulation of RelB. TNF and receptor activator of NF-κB ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive β cell–intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the noncanonical NF-κB transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to β cell failure. These studies reveal that NIK contributes a central mechanism for β cell failure in diet-induced obesity. PMID:26122662

Granulocyte-macrophage colony-stimulating factor induces the differentiation of murine erythroleukaemia cells into dendritic cells.

PubMed Central

Cao, X; Zhao, Y; Yu, Y; Wang, Y; Zhang, M; Zhang, W; Wang, J

1998-01-01

Dendritic cells (DC) are professional antigen-presenting cells (APC) within the immune system and antigen-pulsed DC can be used as an effective vaccine for active immunotherapy of cancer. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the generation of DC. We previously showed that GM-CSF can induce murine erythroleukaemia cells (FBL-3) to differentiate into monocyte-like cells. To develop a new vaccinating method to stimulate the host immune response to leukaemia, we further investigate whether FBL-3 cells induced by GM-CSF can differentiate into DC in the present study. After being treated with GM-CSF, FBL-3 cells expressed high levels of 33D1 and NLDC-145, which are the specific markers of DC. The expression of MHC-II, B7-1, B7-2 and vascular cell adhesion molecule-1 (VCAM-1) was up-regulated markedly; the typical morphology of DC were also observed by electron microscopy. Functionally, the GM-CSF-induced FBL-3 cells could apparently stimulate the proliferation of naive allogeneic and autologous T lymphocytes and induce the generation of specific CTL more efficiently than the wild-type FBL-3 cells. Mice immunized with GM-CSF-induced FBL-3 cells could resist the subsequent challenge with the wild-type FBL-3 cells. Collectively, these data indicate that GM-CSF differentiates murine erythroleukaemia cells into DC phenotypically, morphologically and functionally. FBL-3-derived DC can be used as a new type of vaccine. Our results may have important implications for the immunotherapy of leukaemia. Images Figure 3 Figure 4 PMID:9767469

Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

PubMed

Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

2017-05-01

Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

The involvement of brain-derived neurotrophic factor in 3,4-methylenedioxymethamphetamine-induced place preference and behavioral sensitization.

PubMed

Mouri, Akihiro; Noda, Yukihiro; Niwa, Minae; Matsumoto, Yurie; Mamiya, Takayoshi; Nitta, Atsumi; Yamada, Kiyofumi; Furukawa, Shoei; Iwamura, Tatsunori; Nabeshima, Toshitaka

2017-06-30

3,4-Methylenedioxymethamphetamine (MDMA) is known to induce dependence and psychosis in humans. Brain-derived neurotrophic factor (BDNF) is involved in the synaptic plasticity and neurotrophy in midbrain dopaminergic neurons. This study aimed to investigate the role of BDNF in MDMA-induced dependence and psychosis. A single dose of MDMA (10mg/kg) induced BDNF mRNA expression in the prefrontal cortex, nucleus accumbens, and amygdala, but not in the striatum or the hippocampus. However, repeated MDMA administration for 7 days induced BDNF mRNA expression in the striatum and hippocampus. Both precursor and mature BDNF protein expression increased in the nucleus accumbens, mainly in the neurons. Additionally, rapidly increased extracellular serotonin levels and gradually and modestly increased extracellular dopamine levels were noted within the nucleus accumbens of mice after repeated MDMA administration. Dopamine receptor antagonists attenuated the effect of repeated MDMA administration on BDNF mRNA expression in the nucleus accumbens. To examine the role of endogenous BDNF in the behavioral and neurochemical effects of MDMA, we used mice with heterozygous deletions of the BDNF gene. MDMA-induced place preference, behavioral sensitization, and an increase in the levels of extracellular serotonin and dopamine within the nucleus accumbens, were attenuated in BDNF heterozygous knockout mice. These results suggest that BDNF is implicated in MDMA-induced dependence and psychosis by activating the midbrain serotonergic and dopaminergic neurons. Copyright © 2017 Elsevier B.V. All rights reserved.

Roles of tumour necrosis factor-related weak inducer of apoptosis/fibroblast growth factor-inducible 14 pathway in lupus nephritis.

PubMed

Chen, Jingyun; Wei, Linlin; Xia, Yumin

2017-02-01

As one of the manifestations of patients with systemic lupus erythematosus, lupus nephritis (LN) has high morbidity and mortality. Although the explicit mechanism of LN remains to be fully elucidated, there is increasing evidence to support the notion that tumour necrosis factor-related weak inducer of apoptosis (TWEAK), acting via its sole receptor, fibroblast growth factor-inducible 14 (Fn14), plays a pivotal role in such pathologic process. TWEAK/Fn14 interactions occur prominently in kidneys of LN, inducing inflammatory responses, angiogenesis, mesangial proliferation, filtration barrier injuries, renal fibrosis, etc. This review will specify the important roles of TWEAK/Fn14 pathway in the pathogenesis of LN with experimental data from cellular and animal models. Additionally, the raised levels of urinary and serum soluble TWEAK correlate with renal disease activity in patients with LN. The neutralizing antibodies targeting TWEAK or other approaches inhibiting TWEAK/Fn14 signals can attenuate renal damage in the murine lupus models. Therefore, to focus on TWEAK/Fn14 signalling may be promising in both clinical evaluation and the treatment of patients with LN. © 2016 Asian Pacific Society of Nephrology.

Reversible coma and Duret hemorrhage after intracranial hypotension from remote lumbar spine surgery: case report.

PubMed

Bonow, Robert H; Bales, James W; Morton, Ryan P; Levitt, Michael R; Zhang, Fangyi

2016-03-01

Intracranial hypotension is a rare condition caused by spontaneous or iatrogenic CSF leaks that alter normal CSF dynamics. Symptoms range from mild headaches to transtentorial herniation, coma, and death. Duret hemorrhages have been reported to occur in some patients with this condition and are traditionally believed to be associated with a poor neurological outcome. A 73-year-old man with a remote history of spinal fusion presented with syncope and was found to have small subdural hematomas on head CT studies. He was managed nonoperatively and discharged with a Glasgow Coma Scale score of 15, only to return 3 days later with obtundation, fixed downward gaze, anisocoria, and absent cranial nerve reflexes. A CT scan showed Duret hemorrhages and subtle enlargement of the subdural hematomas, though the hematomas remained too small to account for his poor clinical condition. Magnetic resonance imaging of the spine revealed a large lumbar pseudomeningocele in the area of prior fusion. His condition dramatically improved when he was placed in the Trendelenburg position and underwent repair of the pseudomeningocele. He was kept flat for 7 days and was ultimately discharged in good condition. On long-term follow-up, his only identifiable deficit was diplopia due to an internuclear ophthalmoplegia. Intracranial hypotension is a rare condition that can cause profound morbidity, including tonsillar herniation and brainstem hemorrhage. With proper identification and treatment of the CSF leak, patients can make functional recoveries.

Alkaloids in Erythrina by UPLC-ESI-MS and In Vivo Hypotensive Potential of Extractive Preparations

PubMed Central

Merlugo, Liara; Santos, Marí C.; Sant'Anna, Liane S.; Cordeiro, Everson W. F.; Batista, Luiz A. C.; Miotto, Silvia T. S.; Garcia, Cássia V.; Moreira, Cleci M.; Mendez, Andreas S. L.

2015-01-01

Erythrina species are used in popular medicine as sedative, anxiolytic, anti-inflammatory, and antihypertensive. In this work, we investigated the chemical composition of extracts obtained from leaves of E. falcata and E. crista-galli. The hypotensive potential of E. falcata and the mechanism of action were also studied. The extracts were obtained by maceration and infusion. The total content of phenolic compounds and flavonoids was estimated by spectrophotometric methods. The chemical constituents were studied performing a chromatographic analysis by UPLC-ESI-MS. For in vivo protocols, blood pressure and heart rate were measured by the invasive hemodynamic monitoring method. Different concentrations of extracts and drugs such as L-NAME, losartan, hexamethonium, and propranolol were administrated i.v. The results of total phenolic contents for E. falcata and E. crista-galli were 1.3193–1.4989 mgGAE/mL for maceration and 0.8771–0.9506 mgGAE/mL for infusion. In total flavonoids, the content was 7.7829–8.1976 mg RE/g for maceration and 9.3471–10.4765 RE mg/g for infusion. The chemical composition was based on alkaloids, suggesting the presence of erythristemine, 11β-methoxyglucoerysodine, erysothiopine, 11β-hydroxyerysodine-glucose, and 11-hydroxyerysotinone-rhamnoside. A potent dose-dependent hypotensive effect was observed for E. falcata, which may be related to the route of β-adrenergic receptors. PMID:26356581

Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor.

PubMed

Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

2010-07-16

Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1alpha and HIF-2alpha immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1alpha-positive, 15 HIF-2alpha-positive and 10 positive for HIF-1alpha and HIF-2alpha. Expression of HIF-1alpha and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1alpha and HIF-2alpha in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2alpha in Ewing's. Downstream transcription was HIF-1alpha-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by >or= 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1alpha and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

Induction of Shock After Intravenous Injection of Adenovirus Vectors: A Critical Role for Platelet-activating Factor

PubMed Central

Xu, Zhili; Smith, Jeffrey S.; Tian, Jie; Byrnes, Andrew P.

2009-01-01

Innate immune responses are a major barrier to safe systemic gene therapy with adenovirus (Ad) vectors. We show that intravenous (IV) injection of rats with Ad5 vectors causes a novel rapid shock reaction that involves hypotension, hemoconcentration, tissue edema, and vasocongestion, with notable pathology in the pancreas and the gastrointestinal system. We show for the first time that this reaction is dependent on platelet-activating factor (PAF), a lipid signaling molecule that is a known shock inducer. Ad upregulated PAF within 5 minutes in vivo, and antagonists of the PAF receptor were able to prevent Ad-induced shock. Ad upregulated PAF via the reticuloendothelial system (RES), because splenectomy or depletion of phagocytes blocked the ability of Ad to induce both PAF and shock. Rats were considerably more sensitive to Ad-induced shock than were mice, but PAF mediated shock in both species. Other Ad-induced innate immune responses such as cytokine induction and thrombocytopenia were not mediated by PAF. In summary, systemic IV injection of Ad stimulates the RES to upregulate PAF within a matter of minutes, which results in shock. The identification of this novel pathway suggests strategies to improve the safety of systemic gene therapy with Ad vectors. PMID:19953082

Therapeutic Effects of Procainamide on Endotoxin-Induced Rhabdomyolysis in Rats

PubMed Central

Shih, Chih-Chin; Hii, Hiong-Ping; Tsao, Cheng-Ming; Chen, Shiu-Jen; Ka, Shuk-Man; Liao, Mei-Hui; Wu, Chin-Chen

2016-01-01

Overt systemic inflammatory response is a predisposing mechanism for infection-induced skeletal muscle damage and rhabdomyolysis. Aberrant DNA methylation plays a crucial role in the pathophysiology of excessive inflammatory response. The antiarrhythmic drug procainamide is a non-nucleoside inhibitor of DNA methyltransferase 1 (DNMT1) used to alleviate DNA hypermethylation. Therefore, we evaluated the effects of procainamide on the syndromes and complications of rhabdomyolysis rats induced by lipopolysaccharide (LPS). Rhabdomyolysis animal model was established by intravenous infusion of LPS (5 mg/kg) accompanied by procainamide therapy (50 mg/kg). During the experimental period, the changes of hemodynamics, muscle injury index, kidney function, blood gas, blood electrolytes, blood glucose, and plasma interleukin-6 (IL-6) levels were examined. Kidneys and lungs were exercised to analyze superoxide production, neutrophil infiltration, and DNMTs expression. The rats in this model showed similar clinical syndromes and complications of rhabdomyolysis including high levels of plasma creatine kinase, acute kidney injury, hyperkalemia, hypocalcemia, metabolic acidosis, hypotension, tachycardia, and hypoglycemia. The increases of lung DNMT1 expression and plasma IL-6 concentration were also observed in rhabdomyolysis animals induced by LPS. Treatment with procainamide not only inhibited the overexpression of DNMT1 but also diminished the overproduction of IL-6 in rhabdomyolysis rats. In addition, procainamide improved muscle damage, renal dysfunction, electrolytes disturbance, metabolic acidosis, hypotension, and hypoglycemia in the rats with rhabdomyolysis. Moreover, another DNMT inhibitor hydralazine mitigated hypoglycemia, muscle damage, and renal dysfunction in rhabdomyolysis rats. These findings reveal that therapeutic effects of procainamide could be based on the suppression of DNMT1 and pro-inflammatory cytokine in endotoxin-induced rhabdomyolysis. PMID:26918767

Therapeutic Effects of Procainamide on Endotoxin-Induced Rhabdomyolysis in Rats.

PubMed

Shih, Chih-Chin; Hii, Hiong-Ping; Tsao, Cheng-Ming; Chen, Shiu-Jen; Ka, Shuk-Man; Liao, Mei-Hui; Wu, Chin-Chen

2016-01-01

Overt systemic inflammatory response is a predisposing mechanism for infection-induced skeletal muscle damage and rhabdomyolysis. Aberrant DNA methylation plays a crucial role in the pathophysiology of excessive inflammatory response. The antiarrhythmic drug procainamide is a non-nucleoside inhibitor of DNA methyltransferase 1 (DNMT1) used to alleviate DNA hypermethylation. Therefore, we evaluated the effects of procainamide on the syndromes and complications of rhabdomyolysis rats induced by lipopolysaccharide (LPS). Rhabdomyolysis animal model was established by intravenous infusion of LPS (5 mg/kg) accompanied by procainamide therapy (50 mg/kg). During the experimental period, the changes of hemodynamics, muscle injury index, kidney function, blood gas, blood electrolytes, blood glucose, and plasma interleukin-6 (IL-6) levels were examined. Kidneys and lungs were exercised to analyze superoxide production, neutrophil infiltration, and DNMTs expression. The rats in this model showed similar clinical syndromes and complications of rhabdomyolysis including high levels of plasma creatine kinase, acute kidney injury, hyperkalemia, hypocalcemia, metabolic acidosis, hypotension, tachycardia, and hypoglycemia. The increases of lung DNMT1 expression and plasma IL-6 concentration were also observed in rhabdomyolysis animals induced by LPS. Treatment with procainamide not only inhibited the overexpression of DNMT1 but also diminished the overproduction of IL-6 in rhabdomyolysis rats. In addition, procainamide improved muscle damage, renal dysfunction, electrolytes disturbance, metabolic acidosis, hypotension, and hypoglycemia in the rats with rhabdomyolysis. Moreover, another DNMT inhibitor hydralazine mitigated hypoglycemia, muscle damage, and renal dysfunction in rhabdomyolysis rats. These findings reveal that therapeutic effects of procainamide could be based on the suppression of DNMT1 and pro-inflammatory cytokine in endotoxin-induced rhabdomyolysis.

Kruppel-like factor 2 inhibits hypoxia-inducible factor 1alpha expression and function in the endothelium.

PubMed

Kawanami, Daiji; Mahabeleshwar, Ganapati H; Lin, Zhiyong; Atkins, G Brandon; Hamik, Anne; Haldar, Saptarsi M; Maemura, Koji; Lamanna, Joseph C; Jain, Mukesh K

2009-07-31

Hypoxia-inducible factor 1 (HIF-1) is a central regulator of the hypoxic response in many cell types. In endothelial cells, HIF-1 induces the expression of key proangiogenic factors to promote angiogenesis. Recent studies have identified Kruppel-like factor 2 (KLF2) as a potent inhibitor of angiogenesis. However, the role of KLF2 in regulating HIF-1 expression and function has not been evaluated. KLF2 expression was induced acutely by hypoxia in endothelial cells. Adenoviral overexpression of KLF2 inhibited hypoxia-induced expression of HIF-1alpha and its target genes such as interleukin 8, angiopoietin-2, and vascular endothelial growth factor in endothelial cells. Conversely, knockdown of KLF2 increased expression of HIF-1alpha and its targets. Furthermore, KLF2 inhibited hypoxia-induced endothelial tube formation, whereas endothelial cells from mice with haploinsufficiency of KLF2 showed increased tube formation in response to hypoxia. Consistent with this ex vivo observation, KLF2 heterozygous mice showed increased microvessel density in the brain. Mechanistically, KLF2 promoted HIF-1alpha degradation in a von Hippel-Lindau protein-independent but proteasome-dependent manner. Finally, KLF2 disrupted the interaction between HIF-1alpha and its chaperone Hsp90, suggesting that KLF2 promotes degradation of HIF-1alpha by affecting its folding and maturation. These observations identify KLF2 as a novel inhibitor of HIF-1alpha expression and function. Therefore, KLF2 may be a target for modulating the angiogenic response in disease states.

Lactobacillus rhamnosus GG Treatment Potentiates Intestinal Hypoxia-Inducible Factor, Promotes Intestinal Integrity and Ameliorates Alcohol-Induced Liver Injury

PubMed Central

Wang, Yuhua; Kirpich, Irina; Liu, Yanlong; Ma, Zhenhua; Barve, Shirish; McClain, Craig J.; Feng, Wenke

2012-01-01

Gut-derived endotoxin is a critical factor in the development and progression of alcoholic liver disease (ALD). Probiotics can treat alcohol-induced liver injury associated with gut leakiness and endotoxemia in animal models, as well as in human ALD; however, the mechanism or mechanisms of their beneficial action are not well defined. We hypothesized that alcohol impairs the adaptive response-induced hypoxia-inducible factor (HIF) and that probiotic supplementation could attenuate this impairment, restoring barrier function in a mouse model of ALD by increasing HIF-responsive proteins (eg, intestinal trefoil factor) and reversing established ALD. C57BJ/6N mice were fed the Lieber DeCarli diet containing 5% alcohol for 8 weeks. Animals received Lactobacillus rhamnosus GG (LGG) supplementation in the last 2 weeks. LGG supplementation significantly reduced alcohol-induced endotoxemia and hepatic steatosis and improved liver function. LGG restored alcohol-induced reduction of HIF-2α and intestinal trefoil factor levels. In vitro studies using the Caco-2 cell culture model showed that the addition of LGG supernatant prevented alcohol-induced epithelial monolayer barrier dysfunction. Furthermore, gene silencing of HIF-1α/2α abolished the LGG effects, indicating that the protective effect of LGG is HIF-dependent. The present study provides a mechanistic insight for utilization of probiotics for the treatment of ALD, and suggests a critical role for intestinal hypoxia and decreased trefoil factor in the development of ALD. PMID:22093263

L-NAME, a nitric oxide synthase inhibitor, as a potential countermeasure to post-suspension hypotension in rats

NASA Technical Reports Server (NTRS)

Bayorh, M. A.; Socci, R. R.; Watts, S.; Wang, M.; Eatman, D.; Emmett, N.; Thierry-Palmer, M.

2001-01-01

A large number of astronauts returning from spaceflight experience orthostatic hypotension. This hypotension may be due to overproduction of vasodilatory mediators, such as nitric oxide (NO) and prostaglandins. To evaluate the role of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) as a countermeasure against the post-suspension reduction in mean arterial pressure (MAP), we assessed the cardiovascular responses and vascular reactivity to 7-day 30 degrees tail-suspension and a subsequent 6 hr post-suspension period in conscious rats. After a pre-suspension reading, direct MAP and heart rate (HR) were measured daily and every 2 hrs post-suspension. The NO synthase inhibitor L-NAME (20 mg/kg, i.v.), or saline, were administered after the 7th day reading prior to release from suspension and at 2 and 4 hrs post-suspension. At 6 hrs post-suspension, vascular reactivity was assessed. While MAP did not change during the suspension period, it was reduced post-suspension. Heart rate was not significantly altered. L-NAME administration reversed the post-suspension reduction in MAP. In addition, the baroreflex sensitivity for heart rate was modified by L-NAME. Thus, the post-suspension reduction in MAP may be due to overproduction of NO and altered baroreflex activity.

Mesenchymal stem cells derived from human exocrine pancreas express transcription factors implicated in beta-cell development.

PubMed

Baertschiger, Reto M; Bosco, Domenico; Morel, Philippe; Serre-Beinier, Veronique; Berney, Thierry; Buhler, Leo H; Gonelle-Gispert, Carmen

2008-07-01

Transplantation of in vitro generated islets or insulin-producing cells represents an attractive option to overcome organ shortage. The aim of this study was to isolate, expand, and characterize cells from human exocrine pancreas and analyze their potential to differentiate into beta cells. Fibroblast-like cells growing out of human exocrine tissue were characterized by flow cytometry and by their capacity to differentiate into mesenchymal cell lineages. During cell expansion and after differentiation toward beta cells, expression of transcription factors of endocrine pancreatic progenitors was analyzed by reverse transcription polymerase chain reaction. Cells emerged from 14/18 human pancreatic exocrine fractions and were expanded up to 40 population doublings. These cells displayed surface antigens similar to mesenchymal stem cells from bone marrow. A culture of these cells in adipogenic and chondrogenic differentiation media allowed differentiation into adipocyte- and chondrocyte-like cells. During expansion, cells expressed transcription factors implicated in islet development such as Isl1, Nkx2.2, Nkx6.1, nestin, Ngn3, Pdx1, and NeuroD. Activin A and hepatocyte growth factor induced an expression of insulin, glucagon, and glucokinase. Proliferating cells with characteristics of mesenchymal stem cells and endocrine progenitors were isolated from exocrine tissue. Under specific conditions, these cells expressed little insulin. Human pancreatic exocrine tissue might thus be a source of endocrine cell progenitors.

Subdural hematoma caused by intracranial hypotension after syringosubarachnoid shunting--case report.

PubMed

Yamazaki, Tomosato; Yanaka, Kiyoyuki; Uemura, Kazuya; Tsukada, Atsuro

2004-09-01

A 32-year-old man developed an extremely rare subdural hematoma after syringosubarachnoid shunting for syringomyelia. He presented with a 4-year history of neck pain and spastic paraparesis resulting from T-7 and T-8 vertebral body fracture suffered in a traffic accident at age 22 years. Magnetic resonance imaging revealed syringomyelia between the craniocervical junction and the T-10 level. The symptoms were slowly progressive, and a syringosubarachnoid shunting was performed. His spasticity improved after surgery, but he developed orthostatic headache 7 days after surgery. Magnetic resonance imaging of the brain demonstrated a thin subdural hematoma over the right cerebral convexity. The subdural hematoma resolved spontaneously within a week with conservative treatment. Vigorous cerebrospinal fluid outflow observed during surgery presumably lowered the pressure in the syrinx cavity, leading to significant but transient intracranial hypotension and consequently the formation of subdural hematoma.

Contact Karate Promotes Post-Exercise Hypotension in Young Adult Males

PubMed Central

Magalhaes Sales, Marcelo; Victor de Sousa, Caio; Barbosa Sampaio, Wellington; Ernesto, Carlos; Alberto Vieira Browne, Rodrigo; Fernando Vila Nova de Moraes, Jose; Motta-Santos, Daisy; Rocha Moraes, Milton; Eugene Lewis, John; Gustavo Simões, Herbert; Martins da Silva, Francisco

2016-01-01

Background Worldwide, systemic arterial hypertension is a leading cause of death and non-communicable cardiovascular disease. A major factor contributing to this disease is a sedentary lifestyle. However, physical exercise, such as martial arts, may be an option for blood pressure (BP) control. The magnitude of post-exercise hypotension is associated with a prolonged decrease in BP in normotensive and hypertensive individuals. Objectives The present study aimed to verify the effects of a Contact Karate (CK) session on BP responses during a post-exercise recovery period in young adults. Patients and Methods Thirty-two male CK athletes volunteered (28.2 ± 6.7 years; 77.0 ± 5.7 kg; and 176.0 ± 4.7 cm) and underwent one CK session (50 minutes) and a control session in which no exercise was performed and the individuals remain seated during the whole time. BP was measured during rest (before sessions), as well as on the 15th, 30th, 45th, and 60th minutes of the post-exercise recovery. Results The systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP) were significantly lower at the post-exercise period compared to pre-exercise rest (P < 0.05), with the largest reductions being observed at the 60th minutes of recovery [SBP (rest: 125.9 ± 4.7 vs. 60th minutes of recovery: 111.7 ± 5.4 mmHg); DBP (rest: 78.8 ± .7 vs. 60th minutes of recovery: 69.8 ± 2.7 mmHg)] and at the same periods of post-exercise recovery of the control session. Conclusions A single CK session can promote a decrease in BP for at least 60 minutes after performing this type of exercise in young adults. PMID:27826399

Acute respiratory distress syndrome in blunt trauma: identification of independent risk factors.

PubMed

Miller, Preston R; Croce, Martin A; Kilgo, Patrick D; Scott, John; Fabian, Timothy C

2002-10-01

Acute respiratory distress syndrome (ARDS) is a major contributor to morbidity and mortality in trauma patients. Although many injuries and conditions are believed to be associated with ARDS independent risk factors in trauma patients and their relative importance in development of the syndrome are undefined. The aim of this project is to identify independent risk factors for the development of ARDS in blunt trauma patients and to examine the contributions of each factor to ARDS development. Patients with ARDS were identified from the registry of a Level I trauma center over a 4.5-year period. Records were reviewed for demographics, injury characteristics, transfusion requirements, and hospital course. Variables examined included age >65 years, Injury Severity Score (ISS) >25, hypotension on admission (systolic blood pressure <90), significant metabolic acidosis (base deficit <-5.0), severe brain injury as shown by a Glasgow Coma Scale score (GCS) <8 on admission, 24-hour transfusion requirement >10 units packed red blood cells, pulmonary contusion (PC), femur fracture, and major infection (pneumonia, empyema, or intra-abdominal abscess). Both univariate and stepwise logistic regression were used to identify independent risk factors, and receiver operating characteristic curve (ROC) analysis was used to determine the relative contribution of each risk factor. A total of 4397 patients having sustained blunt trauma were admitted to the intensive care unit and survived >24 hours between October 1995 and May 2000. Of these patients 200 (4.5%) developed ARDS. All studied variables were significantly associated with ARDS in univariate analyses. Stepwise logistic regression, however, demonstrated age >65 years, ISS >25, hypotension on admission, 24-hour transfusion requirement >10 units, and pulmonary contusion as independent risk factors, whereas admission metabolic acidosis, femur fracture, infection, and severe brain injury were not. Using a model based on the logistic

Kelch-like ECH-associated Protein 1-dependent Nuclear Factor-E2-related Factor 2 Activation in Relation to Antioxidation Induced by Sevoflurane Preconditioning.

PubMed

Cai, Min; Tong, Li; Dong, Beibei; Hou, Wugang; Shi, Likai; Dong, Hailong

2017-03-01

The authors have reported that antioxidative effects play a crucial role in the volatile anesthetic-induced neuroprotection. Accumulated evidence shows that endogenous antioxidation could be up-regulated by nuclear factor-E2-related factor 2 through multiple pathways. However, whether nuclear factor-E2-related factor 2 activation is modulated by sevoflurane preconditioning and, if so, what is the signaling cascade underlying upstream of this activation are still unknown. Sevoflurane preconditioning in mice was performed with sevoflurane (2.5%) 1 h per day for five consecutive days. Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. Expression of nuclear factor-E2-related factor 2, kelch-like ECH-associated protein 1, manganese superoxide dismutase, thioredoxin-1, and nicotinamide adenine dinucleotide phosphate quinolone oxidoreductase-1 was detected (n = 6). The antioxidant activities and oxidative product expression were also examined. To determine the role of kelch-like ECH-associated protein 1 inhibition-dependent nuclear factor-E2-related factor 2 activation in sevoflurane preconditioning-induced neuroprotection, the kelch-like ECH-associated protein 1-nuclear factor-E2-related factor 2 signal was modulated by nuclear factor-E2-related factor 2 knockout, kelch-like ECH-associated protein 1 overexpression lentivirus, and kelch-like ECH-associated protein 1 deficiency small interfering RNA (n = 8). The infarct volume, neurologic scores, and cellular apoptosis were assessed. Sevoflurane preconditioning elicited neuroprotection and increased nuclear factor-E2-related factor 2 nuclear translocation, which in turn up-regulated endogenous antioxidation and reduced oxidative injury. Sevoflurane preconditioning reduced kelch-like ECH-associated protein 1 expression. Nuclear factor-E2-related factor 2 ablation abolished neuroprotection and reversed sevoflurane preconditioning by mediating the up-regulation of antioxidants. Kelch

Abacavir-induced fulminant hepatic failure in a HIV/HCV co-infected patient.

PubMed

Haas, Christopher; Ziccardi, Mary Rodriguez; Borgman, Jody

2015-12-15

Abacavir hypersensitivity is a rare, yet significant adverse reaction that results in a spectrum of physical and laboratory abnormalities, and has been postulated to stem from a variety of aetiological factors. The major histocompatibility complex haplotype human leucocyte antigen (HLA)-B5701 is a significant risk factor in development of hypersensitivity reactions, yet only 55% of HLA-B5701+ individuals develop such reactions, suggesting a multifactorial aetiology. Nevertheless, prospective screening and avoidance of abacavir in these patients has limited adverse events. Within this spectrum of adverse events, abacavir-induced liver toxicity is exceedingly rare and reported events have ranged from mild elevations of aminotransferases to fulminant hepatic failure. We report the case of a 50-year-old Caucasian woman with a history significant for HIV, hepatitis C virus and a HLA-B5701+ status, transferred to our emergency department in a hypotensive state and found to have acute liver failure, acute renal failure and significant rhabdomyolysis following a change of highly active antiretroviral therapy regimen. 2015 BMJ Publishing Group Ltd.

Droxidopa for the short-term treatment of symptomatic neurogenic orthostatic hypotension in Parkinson's disease (nOH306B).

PubMed

Hauser, Robert A; Isaacson, Stuart; Lisk, Jerome P; Hewitt, L Arthur; Rowse, Gerry

2015-04-15

Neurogenic orthostatic hypotension (nOH) results from failure of norepinephrine responses to postural change to maintain standing systolic blood pressure (s-SBP). Droxidopa is an oral prodrug of norepinephrine. Study nOH306 enrolled patients with Parkinson's disease (PD) and symptomatic nOH. Subjects underwent up to 2 weeks of double-blind titration of droxidopa or placebo, followed by 8 weeks of double-blind maintenance treatment (100-600 mg thrice-daily). For the initial 51 subjects (study nOH306A, previously reported), the primary efficacy measure, Orthostatic Hypotension Questionnaire (OHQ) composite score, did not demonstrate significant change versus placebo at maintenance week 8. For the subsequent 171 subjects (study nOH306B, reported here), the primary efficacy measure was change versus placebo on item 1 ("dizziness, lightheadedness, feeling faint, or feeling like you might black out") of the Orthostatic Hypotension Symptom Assessment (OHSA) subsection of the OHQ at maintenance week 1. At week 1, mean (standard deviation) improvement on OHSA item 1 was 2.3 (2.95) for droxidopa versus 1.3 (3.16) for placebo (P = 0.018). In addition, mean increase in s-SBP at week 1 was 6.4 (18.85) for droxidopa versus 0.7 (20.18) mmHg for placebo (nominal P value: 0.032). Differences in change in OHSA item 1 scores from baseline to maintenance weeks 2, 4, and 8 were not statistically significant. Adverse-event (AE) incidence was similar across groups, but 12.4% of droxidopa and 6.1% of placebo subjects withdrew because of AEs. The most common AEs on droxidopa (vs. placebo) were headache (13.5% vs. 7.3%) and dizziness (10.1% vs. 4.9%). Study nOH306B demonstrated subjective (OHSA item 1) and objective (s-SBP) evidence of short-term droxidopa efficacy (vs. placebo) for symptomatic nOH in PD. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients.

PubMed

Iida, Nobutoshi; Koshikawa, Syozo; Akizawa, Tadao; Tsubakihara, Yoshiharu; Marumo, Fumiaki; Akiba, Takashi; Kawaguchi, Yoshindo; Imada, Akio; Yamazaki, Chikao; Suzuki, Masashi

2002-01-01

Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine (L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase. A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24-52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD. The drug was administered orally 30 min before the start of each HD period in both studies. Doses of 400 mg of L-DOPS or placebo were given to HD patients with OH (45 and 41 patients, respectively) in the double-blind study, and doses of 200 or 400 mg of L-DOPS were given to 74 HD patients in the long-term study. In the double-blind study, L-DOPS significantly ameliorated subjective symptoms related to OH, including dizziness/light-headed feeling, and malaise, throughout the interdialytic period. For 19 patients with delayed-type OH, hypotension with the lowest blood pressure recorded 10 min after standing, the decrease in blood pressure was suppressed significantly after L-DOPS treatment (10 patients) as compared with the placebo-treated group (9 patients). In the long-term study, the efficacy of L-DOPS was not attenuated, and the marked fluctuations in the plasma L-DOPS and norepinephrine levels were not noted after long-term use, without increases in incidence or severity of adverse reactions. These results indicate that L-DOPS is effective for improving OH-related interdialytic subjective symptoms in HD patients after short-term as well as after long-term administration. Copyright 2002 S. Karger AG, Basel