Marked Decrease In Blood Pressure Research Articles

Evaluation of the Cardiovascular Effects of Coriandrum sativum and Citrus limon to Treat Arsenic-Induced Endothelial Damage and Hypertension in Rats.

Based on the vernacular reputation of Coriandrum sativum and Citrus limon to treat hypertension, this study was designed to explore the cardiovascular effects of C. sativum (CS) and C. limon (CL) on arsenic-induced hypertension and endothelial damage. Hypertension was induced by arsenic (100 ppm) in drinking water. The crude methanolic extracts of CS and CL were tested for in vivo and in vitro activities using Power Lab. High performance liquid chromatography analysis of CS and CL showed the presence of phenolic compounds. In anesthetized rats, CS (50 mg) and CL (10 mg) showed a marked decrease in blood pressure of 51% and 35%, respectively. Similarly, ascorbic acid (10 mg) also showed a decreased blood pressure (41%). The CS and CL caused complete relaxation (0.003-5 mg/mL) against phenylephrine (1µM) and high K+ (80 mM)-induced contraction. The CS and CL, independently and in combination, exhibited marked (p < 0.001) attenuation in the blood pressure of the arsenic-induced hypertensive rats when compared with the controls. The beneficial effects of the CS and CL were also observed on lipid peroxidation and eNOS. These data suggest that CS and CL possess significant antihypertensive activity, possibly mediated via endothelium protection, and anti-oxidant effects. Thus, this study provides a rationale for the medicinal use of CS and CL in hypertension and also against arsenic-induced cardiovascular complications.

Tracheal Intubation in Emergency Departments in China: A National Cross-Sectional Survey.

BackgroundTracheal intubation is a necessary but risky procedure performed in emergency departments (EDs) around the world. Relatively high morbidity has been encountered in Chinese EDs, which has raised concerns about peri-intubation ED management. This study aimed to investigate intubation procedures and identify any areas for improvement in Chinese EDs.MethodsThis was a questionnaire-based survey lasting 1 month (March 2021) in 41 tertiary-care hospital EDs in mainland China. The primary outcome was complications associated with intubation. Secondary outcomes were the first-pass success rate and blood pressure variations during intubation. Univariate and binary logistic regression analyses were used to find possible risk factors for first-pass intubation failure.ResultsIn total, 1,020 replies were analyzed out of 1,080 surveys submitted (94.4% response rate). Most patients were elderly men with severe medical conditions like cardiac arrest (24.8%). In total, 97.2% of patients were given preoxygenation, and 48.1% received some form of pretreatment. Induction drugs (e.g., etomidate and ketamine) were less often used: 39.9% of intubations used sedatives, 5.5% used analgesics, and only 5.3% used muscle relaxants. The overall first-pass intubation success rate was 85.7% and was accompanied by a 19.8% adverse event rate. A marked decrease in blood pressure after intubation was also identified.ConclusionThis survey found an 85.7% tracheal intubation first-pass success rate (which is relatively high compared to other countries) and a 19.8% adverse event rate (which is also relatively high). Given the very low rate of using induction medications (5.3% used muscle relaxants), future education should focus on induction drugs and traditional intubation techniques.

Regression of left ventricular hypertrophy in primary aldosteronism after adrenalectomy: a meta-analysis of echocardiographic studies.

Available evidence on regression of left ventricular (LV) hypertrophy in patients with primary aldosteronism after unilateral adrenalectomy is scanty. We performed a systematic meta-analysis of echocardiographic studies to provide an updated and comprehensive information on this issue. The PubMed, OVID-MEDLINE and Cochrane library databases were analyzed to search English-language articles published from 1 January 1990 up to 30 June 2020. Studies were identified by using MeSH terms and crossing the following search items: 'primary aldosteronism' 'Conn's syndrome' 'adrenalectomy', with 'cardiac damage', 'hypertensive heart disease' 'left ventricular mass', 'left ventricular hypertrophy', 'left ventricular hypertrophy regression', 'echocardiography'. A total of 629 hypertensive patients with primary aldosteronism (mean age 49 years, 45% men) were included in 14 studies. Baseline and postintervention pooled mean LV mass/BSA values were 134 ± 4 and 108 ± 3 g/m2 [standard means difference (SMD) -0.42 ± 0.05, confidence interval (CI) -0.52/-0.32, P < 0.0001]; corresponding values for LV mass/h2.7 were 56 ± 2 and 49 ± 1 g/h2.7 (SMD -0.45 ± 0.06, CI -0.52/-0.36, P < 0.0001). Adrenalectomy, followed by a marked decrease in blood pressure, was associated with a decrease in relative wall thickness (SMD -0.17 ± 0.06, CI -0.31/-0.03, P < 0.01) as well as in the number of antihypertensive drugs (SMD -0.45 ± 0.04, CI -0.50-0.32, P < 0.0001). The present meta-analysis suggests that adrenalectomy in patients with primary aldosteronism exerts a beneficial effect on LV structure and geometry by reducing the burden of LV hypertrophy and LV concentric geometry.

P4481NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase A inhibitor prodrug for treating hypertension

Abstract Background Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We previously showed that aminopeptidase A (APA) generates in the brain, angiotensin III, which exerts a tonic stimulatory control over blood pressure in hypertensive rats. Thus, the central injection of the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), by blocking the formation of brain angiotensin III, normalizes blood pressure in experimental models of hypertension. Therefore, brain APA appears as a potential new therapeutic target for the treatment of hypertension. We then developed RB150/firibastat, a prodrug of EC33, able of inhibiting brain APA activity and decreasing blood pressure in hypertensive rats after oral administration. Purpose However, considering the high dose of orally active RB150/firibastat required to decrease BP in spontaneously hypertensive rats (SHR) (150 mg/kg) and deoxycorticosterone acetate-salt (DOCA-salt) (50 mg/kg) rats, the aim of our work was to develop new more potent APA inhibitor prodrugs with greater bioavailability for inhibiting brain APA activity. Methods We used a salt- and volume-dependent model of hypertension, the DOCA-salt rat. For in vivo assessments of brain APA activity, brains were collected 4 hours after the oral administration. A catheter was inserted into the right femoral artery to monitor mean arterial blood pressure in alert rats. We evaluated plasma arginine-vasopressin (AVP) levels by radioimmunoassay. Rats were individually housed in metabolic cages for urine and electrolyte output measurements. Results We report here the development of a new APA inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929 ((3S,4S)-3-amino-4-mercapto-6-phenyl-hexane-1-sulfonic acid). NI929 is 10 more efficient than EC33 at inhibiting recombinant mouse APA activity in vitro. Following oral administration at a dose of 4 mg/kg in conscious DOCA-salt rats, NI956/QGC006 normalized brain APA activity and induced a marked decrease in blood pressure of −44±13 mmHg four hours after treatment (p&lt;0.001), sustained over ten hours (−21±12 mmHg, p&lt;0.05). Moreover, NI956/QGC006 decreased plasma AVP levels, and increased diuresis and natriuresis, that may decrease blood pressure by reducing the size of the fluid compartment. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations. Conclusions This study shows that NI956/QGC006 is a “best-in-class” central-acting APA inhibitor prodrug, belonging to the same drug class as RB150/firibastat, supporting the strategy of brain APA inhibition for hypertension treatment. Acknowledgement/Funding ANR (Agence Nationale de la Recherche) grant to Catherine Llorens-Cortes (LabCom CARDIOBAPAI) and Quantum Genomics financial support.

Echocardiographic assessment of left ventricular systolic function in neonatal calves with naturally occurring sepsis or septic shock due to diarrhea

Sepsis is associated with clinically relevant cardiovascular changes. The objectives of this study were to evaluate the clinical value of echocardiography for monitoring left ventricular (LV) systolic function in septic calves. A prospective longitudinal study was performed using a convenience sample. Twenty septic calves and 10 healthy calves were enrolled in the study. Arterial blood pressure (BP) was measured and M-mode echocardiography performed to characterize LV systolic function; the latter included measurement of ejection fraction, EF; stroke volume, SVI and cardiac output indexed to body weight, CI; E-point of septal separation, EPSS; pre-ejection period, PEP; ejection time, LVET; ratio of PEP to LVET; velocity of circumferential shortening, Vcf, LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI) on admission and 6, 24, 48 and 72 h later in septic calves and once in healthy calves. Admission data were compared using the Mann-Whitney U test and P < .05 was considered significant. Decreased preload and afterload were present in septic calves, as indicated by marked decreases in BP, LVEDVI, LVESVI, SVI, CI, EPSS when compared to healthy calves. Systolic function appeared adequate in septic calves, based on EF and FS compared to control calves. There was no difference in heart rate, LVET, PEP:LVET, or Vcf between septic and health calves. We conclude that circulatory dysfunction, rather than systolic dysfunction predominates in septic calves. Positive associations on admission between CI and LVEDVI, LVESVI, and SVI support this conclusion. Echocardiographic determination of LVEDVI and CI appears useful in directing treatment in septic calves.

NI956/QGC006, a Potent Orally Active, Brain-Penetrating Aminopeptidase A Inhibitor for Treating Hypertension.

Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We have shown that aminopeptidase A is involved in the formation of brain angiotensin III, which exerts tonic stimulatory control over blood pressure in hypertensive deoxycorticosterone acetate-salt rats and spontaneously hypertensive rats. We have also shown that injection of the specific and selective aminopeptidase A inhibitor, (3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid (EC33), by central route or its prodrug, RB150/firibastat, by oral route inhibited brain aminopeptidase A activity and blocked the formation of brain angiotensin III, normalizing blood pressure in hypertensive rats. These findings identified brain aminopeptidase A as a potential new therapeutic target for hypertension. We report here the development of a new aminopeptidase A inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929. NI929 is 10× more efficient than EC33 at inhibiting recombinant mouse aminopeptidase A activity in vitro. After oral administration at a dose of 4 mg/kg in conscious deoxycorticosterone acetate-salt rats, NI956/QGC006 normalized brain aminopeptidase A activity and induced a marked decrease in blood pressure of -44±13 mm Hg 4 hours after treatment ( P<0.001), sustained over 10 hours (-21±12 mm Hg; P<0.05). Moreover, NI956/QGC006 decreased plasma arginine-vasopressin levels, and increased diuresis and natriuresis, that may participate to the blood pressure decrease. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations. This study shows that NI956/QGC006 is a best-in-class central-acting aminopeptidase A inhibitor prodrug. Our results support the development of hypertension treatments targeting brain aminopeptidase A.

Anti-hypertensive mechanisms of cyclic depsipeptide inhibitor ligands for Gq/11 class G proteins

Augmented vasoconstriction is a hallmark of hypertension and is mediated partly by hyper-stimulation of G protein couple receptors (GPCRs) and downstream signaling components. Although GPCR blockade is a key component of current anti-hypertensive strategies, whether hypertension is better managed by directly targeting G proteins has not been thoroughly investigated. Here, we tested whether inhibiting Gq/11 proteins in vivo and ex vivo using natural cyclic depsipeptide, FR900359 (FR) from the ornamental plant, Ardisia crenata, and YM-254890 (YM) from Chromobacterium sp. QS3666, or it’s synthetic analog, WU-07047 (WU), was sufficient to reverse hypertension in mice. All three inhibitors blocked G protein-dependent vasoconstriction, but to our surprise YM and WU and not FR inhibited K+-induced Ca2+ transients and vasoconstriction of intact vessels. However, each inhibitor blocked whole-cell L-type Ca2+ channel current in vascular smooth muscle cells. Subcutaneous injection of FR or YM (0.3 mg/kg, s.c.) in normotensive and hypertensive mice elicited bradycardia and marked blood pressure decrease, which was more severe and long lasting after the injection of FR relative to YM (FRt1/2 ≅ 12 h vs. YMt1/2 ≅ 4 h). In deoxycorticosterone acetate (DOCA)-salt hypertension mice, chronic injection of FR (0.3 mg/kg, s.c., daily for seven days) reversed hypertension (vehicle SBP: 149 ± 5 vs. FR SBP: 117 ± 7 mmHg), without any effect on heart rate. Our results together support the hypothesis that increased LTCC and Gq/11 activity is involved in the pathogenesis of hypertension, and that dual targeting of both proteins can reverse hypertension and associated cardiovascular disorders.

Sedation with dexmedetomidine in elderly patients during dental surgery: a retrospective case series

ObjectivesThe number of elderly patients with systemic basal disease requiring invasive dental treatment has increased. Appropriate prediction of surgical invasiveness and combined use of psychosedation are thought to contribute to safe whole-body management. Dexmedetomidine (DEX) exhibits analgesic and anti-anxiolytic properties and causes mild respiratory depression. Studies regarding DEX use in elderly non-intubated patients are scarce. We aimed to use retrospective data to determine an effective dose of DEX to induce adequate sedation in elderly patients undergoing invasive dental surgery under local anesthesia.Materials and MethodsOne hundred two patients aged 70 to 96 years were presumably appropriately controlled with sedation. DEX was administered at an initial loading dose of 2.0 to 3.1 µg/kg/hr for 10 minutes. We divided the patients into five groups by age and compared their blood pressures and heart rates.ResultsIn all five groups, blood pressure decreased suddenly at approximately 15 and 20 minutes after DEX administration. A marked decrease in blood pressure was noted in patients aged 75 to 79 years.ConclusionFor elderly patients aged 75 years and above, the initial loading dose of DEX needs to be reduced to lower than half that required for young and middle-age adults.

Cardiogenic shock: can the well-forgotten old become the new?

Cardiogenic shock (CS) is considered to be the most severe variant of acute heart failure. It occurs against the background of myocardial infarction or non-coronary myocardial disease with the loss of 40-50% contractile ability by the left ventricular mass and acute heart overload of another genesis. The marked decrease of blood pressure is accompanied by generalized impairment of microcirculation in all organs. The acting recommendations for emergency assistance suggest to recover blood perfusion pressure in ischemic tissues by inotropic drugs vasopressors, crystalloids that eliminate hypovolemia. However, the recovery of hemodynamic parameters using these medicines is accompanied by increased load on the myocardium and causes only a slight temporary increase of blood pressure. Death rapidly occurs in almost 100% of cases because offast heart energy depletion There is no doubt that stable recovery of hemodynamic in CS is not possible without sustainable recovery of myocardial contractility. The effective discharge of myocardium by drugs should not be accompanied by deterioration of blood supply to peripheral organs. Taking into account the literature data and pharmacological properties of different groups of drugs, there is every reason to believe that nitroglycerin may be the drug of choice for the treatment of cardiogenic shock. It reduces myocardium preload without impairment of microcirculation in the peripheral organs. This conclusion is preliminary and requires verification in randomized trials.

Anti-hypertensive Effects of Diminazene Aceturate: An Angiotensin- Converting Enzyme 2 Activator in Rats.

Previous studies have shown that activation of endogenous angiotensin-converting enzyme 2 (ACE2) results in various beneficial effects in the cardiovascular system. Recently, a new ACE2 activator, named diminazene aceturate (DIZE), was described. Here, we evaluated the actions of this compound in blood pressure (BP) and heart rate (HR) of conscious normotensive and hypertensive rats, as well as explored its mechanism of actions using isolated vessels. The renovascular model of hypertension was utilized. The participation of the Angiotensin-(1-7) receptor Mas and nitric oxide (NO) in the effects of DIZE was evaluated using A-779 and L-NAME, respectively. It was observed that DIZE caused a marked decrease in BP with a compensatory increase in HR in nornotensive rats. Accordingly, a significant reduction in the blood flow of the mesenteric bed was evidenced using intravital microscopy. Moreover, in rats with renovascular hypertension, DIZE caused a decrease in BP similar to the hypotensive effect induced by captopril. Importantly, this compound also prevented the development of cardiac hypertrophy induced by hypertension. The isolated vessels technique revealed that the vasodilator effects of DIZE were dependent on Mas activation and NO release. Thus, our findings demonstrated that DIZE reduces the BP of normotensinve and hypertensive rats possibly by a mechanism involving Mas and NO.

Melatonin attenuates hypertension-induced renal injury partially through inhibiting oxidative stress in rats.

The aim of the present study was to investigate the protective effects of melatonin (MLT) on hypertension-induced renal injury and identify its mechanism of action. Twenty-four healthy male Wistar rats were divided into a sham control group (n=8), which was subjected to sham operation and received vehicle treatment (physiological saline intraperitoneally at 0.1 ml/100 g), a vehicle group (n=8), which was subjected to occlusion of the left renal artery and vehicle treatment, and the MLT group (n=8), which was subjected to occlusion of the left renal artery and treated with MLT (10 mg/kg/day). Pathological features of the renal tissues were determined using hematoxylin and eosin staining and Masson staining. Urine protein, serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Immunohistochemical analysis was performed to determine the expression of heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, reverse transcription polymerase chain reaction was conducted to determine the mRNA expression of HO-1, ICAM-1, eNOS and iNOS. A marked decrease in blood pressure was noticed in the MLT group at week 4 compared with that of the vehicle group (P<0.01). Furthermore, MLT treatment attenuated the infiltration of inflammatory cells and oedema/atrophy of renal tubules. MLT attenuated hypertension-induced increases in urine protein excretion, serum creatinine and MDA as well as decreases in SOD activity in renal tissues. Furthermore, MLT attenuated hypertension-induced increases in iNOS and ICAM-1 as well as decreases in eNOS and HO-1 expression at the mRNA and protein level. In conclusion, the results of the present study indicated that MLT had protective roles in hypertension-induced renal injury. Its mechanism of action is, at least in part, associated with the inhibition of oxidative stress.

Atracurium-induced anaphylaxis and angioedema: a case report

Drug-induced anaphylaxis has increased in frequency with the more widespread use of pharmaceutical agents. Neuromuscular blocking agents (NMBAs) are one of the most common causes of anaphylaxis during general anesthesia. However, the incidence of anaphylaxis due to atracurium is very rare (<1/10,000) according to UK Summary of Product Characteristics. NMBAs can induce two types of reactions: one is immune mediated - immunoglobulin E dependent and the second one is associated with non-specific stimulation of mast cells. Systemic manifestations of anaphylaxis can be in the form of hypotension, difficulty in breathing. Rarely, it can be associated with cutaneous manifestations such as urticaria, angioedema, and flushing. If it is not promptly diagnosed and treated, it can be fatal. In the present case, the patient was posted for submandibular gland surgery. She was well-stabilized after general anesthesia and within the seconds of giving injection atracurium; she had difficulty in breathing and marked decrease in blood pressure that was soon followed by periorbital swelling and swelling of lips. The patient was diagnosed with anaphylaxis with angioedema due to atracurium and was promptly managed in operation theater. She was kept under observation for 2 days. Anaphylaxis along with angioedema with atracurium is a very rare event, and hence it is being reported here.

Antihypertensive and neuroprotective effects of catestatin in spontaneously hypertensive rats: Interaction with GABAergic transmission in amygdala and brainstem

The chromogranin A-derived peptide catestatin (CST) exerts sympathoexcitatory and hypertensive effects when microinjected into the rostral ventrolateral medulla (RVLM: excitatory output); it exhibits sympathoinhibitory and antihypertensive effects when microinjected into the caudal ventrolateral medulla (CVLM: inhibitory output) of vagotomized normotensive rats. Here, continuous infusion of CST into the central amygdalar nucleus (CeA) of spontaneously hypertensive rats (SHRs) for 15days resulted in a marked decrease of blood pressure (BP) in 6-month- (by 37mmHg) and 9-month- (by 65mmHg)old rats. Whole-cell patch-clamp recordings on pyramidal CeA neurons revealed that CST increased both spontaneous inhibitory postsynaptic current (sIPSC) amplitude plus frequency, along with reductions of sIPSC rise time and decay time. Inhibition of GABAA receptors (GABAARs) by bicuculline completely abolished CST-induced sIPSC, corroborating that CST signals occur through this major neuroreceptor complex. Hypertension is a major risk factor for cerebrovascular diseases, leading to vascular dementia and neurodegeneration. We found a marked neurodegeneration in the amygdala and brainstem of 9-month-old SHRs, while CST and the GABAAR agonist Muscimol provided significant neuroprotection. Enhanced phosphorylation of Akt and ERK accounted for these neuroprotective effects through anti-inflammatory and anti-apoptotic activities. Overall our results point to CST exerting potent antihypertensive and neuroprotective effects plausibly via a GABAergic output, which constitute a novel therapeutic measure to correct defects in blood flow control in disorders such as stroke and Alzheimer’s disease.

Triphasic cardiovascular response to cannabinoids – Focus on underlying mechanisms

The endocannabinoid anandamide exerts complex effects on the cardiovascular system [Malinowska et al., Br J Pharmacol, 2011]. Thus, rapid intravenous injection of anandamide and its stable analogue methanandamide in anaesthetized rats and mice induces typical triphasic changes. Phase I, the so-called BezoldJarisch reflex, is characterized by a rapid bradycardia and hypotension associated with a decrease in cardiac contractility and an increase in total peripheral resistance. Phase II is a brief pressor response associated with an increase in cardiac contractility and blood flow in the mesenteric and renal arteries. Phase III comprises a prolonged (lasting up to 10 min) and marked decrease in blood pressure, mesenteric and renal blood flow, a marked decrease in cardiac contractility and a slight decrease in heart rate and total peripheral resistance. Phase I is mediated via vanilloid TRPV1 receptors since it was induced also by the TRPV1 receptor agonist capsaicin (but not by the CB1 receptor agonist CP55940), blocked by the TRPV1 receptor antagonists capsazepine and ruthenium red (but not by the CB1 receptor antagonist rimonabant) and absent in TRPV1 / mice. Phase II consists of a peripheral component that is most probably located in blood vessels, is sensitive to nifedipine, ruthenium red and pentobarbitone and, hence, probably represents a Ca-dependent mode of action and a central component. The paraventricular nucleus of the hypothalamus (PVN) may contribute to the latter since a pressor effect was obtained after injection of anandamide, methanandamide or CP55940 (intraventricularly or directly into the PVN). This effect only occurred when the peripheral CB1 receptors were blocked by administration of CB1 receptor antagonists, including AM6545 that does not reach the brain. It was sensitive to adrenalectomy and counteracted by antagonists of CB1, NMDA, thromboxane A2 and b2adrenergic receptors [AM251 (directly into the PVN), MK-801, SQ29548 and ICI118551, respectively] suggesting that the latter four receptors are involved in the events ultimately leading to the anandamide-induced adrenal secretion of catecholamines. Importantly, the hypotensive effect of intravenously administered CP55940 was reversed into a hypertensive one in the presence of AM6545 and both responses were abolished by chemical lesion of the PVN by kainic acid. Phase III is mediated mainly by presynaptic inhibitory CB1 receptors located on the postganglionic (although a preganglionic localization cannot be excluded) sympathetic nerve endings innervating resistance vessels and heart. The CB1 receptor antagonist-sensitive inhibitory effect of these receptors was detected after electrical stimulation of the preganglionic sympathetic nerve fibres in pithed rabbits or rats or following injection of nicotine but not phenylephrine/noradrenaline or isoprenaline (increasing blood pressure and heart rate, respectively). The prolonged hypotension might also be related to the activation of CB1 and/or vanilloid TRPV1 receptors in the spinal cord or to a direct vasodilatation via O-1918 sensitive receptors. In conscious rats anandamide and methanandamide induced a brief pressor (phase II) response connected with renal and mesenteric vasoconstriction and hindquarters vasodilatation. In addition, higher doses of anandamide elicited an initial bradycardia, hypotension and hindquarters vasoconstriction (phase I). However, unlike in anaesthetized rats, none of the cannabinoids led to a prolonged hypotension (phase III). Cardiovascular effects of anandamide are changed under pathophysiological conditions. Thus, in anaesthetized rats myocardial ischemia enhanced phase I and reduced phase III whereas hypertension enhanced phase III. Acknowledgement: B.M. and E.S. would like to express their gratitude to Professor Manfred Gothert for his continuous encouragement extending over a time period of decades.

Preoperative Embolization Reduces the Risk of Cathecolamines Release at the Time of Surgical Excision of Large Pelvic Extra-Adrenal Sympathetic Paraganglioma

A 30-year-old woman with severe hypertension was admitted to the hospital with a history of headache, palpitations, and diaphoresis following sexual intercourse. Twenty-four hour urinary excretion of free catecholamines and metabolites was markedly increased as was serum chromogranin A. Computed tomography scan revealed a large mass in the left adnex site and magnetic resonance imaging confirmed the computer tomography finding, suggesting the presence of extra-adrenal sympathetic paraganglioma. I-metaiodobenzyl guanidine scintigram revealed an increased uptake in the same area. Transcatheter arterial embolization of the mass resulted in marked decreases in blood pressure and urinary excretion of free catecholamines and metabolites. Surgical excision of the mass was then accomplished without complication. Preoperative embolization is a useful and safe procedure which may reduce the risk of catecholamines release at the time of surgical excision in large pelvic extra-adrenal sympathetic paraganglioma.

Role of the central autonomic nervous system in the hypotension and bradycardia induced by (-)-delta 9-trans-tetrahydrocannabinol.

Abstract (-)-Δ9-trans-Tetrahydrocannabinol (Δ9-THC), when given intravenously (2 mg kg−1) to cats, produced marked decreases in blood pressure and heart rate which developed gradually and were of prolonged duration. Cervical spinal transection (C1-C2) abolished these effects whereas surgical removal of neurogenic tone to the myocardium selectively eliminated the bradycardia. Bilateral vagotomy alone did not modify the action of Δ9-THC upon heart rate or blood pressure. Recordings of spontaneous sympathetic outflow in the inferior cardiac nerve indicated a rapid reduction in neural discharge rate after Δ9-THC administration. These observations support the hypothesis that Δ9-THC produces a cardiodecellerator and hypotensive effect by acting at some level within the sympathetic nervous system. Experiments conducted to investigate transmission in the superior cervical and stellate ganglia demonstrated that Δ9-THC did not alter ganglionic function. Also, responses to intravenous isoprenaline and noradrenaline were unchanged which suggested that Δ9-THC did not interact with α- or β- adrenoceptors. The possible action of Δ9-THC on central sympathetic structures was investigated by perfusion of Δ9-THC into the lateral cerebral ventricle. Δ9-THC so administered produced a significant reduction in heart rate without a substantial lowering of blood pressure. Tritiated or 14C-Δ9-THC perfused into the lateral ventricle demonstrated that the amount of radioactive compound passing into the peripheral circulation was insignificant and could not account for the decrease in heart rate. The current data are in agreement with the proposal that Δ9-THC produces cardiovascular alterations by an action on the central nervous system which results in a decrease in sympathetic tone.

Postreperfusion syndrome during liver transplantation for cirrhosis: Outcome and predictors

During orthotopic liver transplantation (OLT), a marked decrease in blood pressure following unclamping of the portal vein and liver reperfusion is frequently observed and is termed postreperfusion syndrome (PRS). The predictive factors and clinical consequences of PRS are not fully understood. The goal of this study was to identify predictors of PRS and morbidity/mortality associated with its occurrence during OLT in patients with cirrhosis. During a 3-year period, all consecutive OLT procedures performed in patients with cirrhosis were studied. Exclusion criteria were OLT for acute liver failure, early retransplantation, combined liver/kidney transplantation, and living-donor related transplantation. PRS was defined as a decrease in the mean arterial pressure of more than 30% of the value observed in the anhepatic stage, for more than 1 minute during the first 5 minutes after reperfusion of the graft. Transplantation was performed with preservation of the inferior vena cava with or without temporary portocaval shunt. Associations between PRS and donor and recipient demographic data, recipient operative and postoperative outcomes were tested with bivariate statistics. Independent predictors of PRS were determined in multivariable logistic regression analysis. Of the 75 patients included in the study, 20 patients (25%) developed PRS. In a multivariable analysis, absence of a portocaval shunt [odds ratio (95% confidence interval) = 4.42 (1.18-17.6)] and duration of cold ischemia [odds ratio (95% confidence interval) = 1.34 (1.07-1.72)] were independent predictors of PRS. Patients who experienced PRS displayed more postoperative renal failure and lower early (<15 days after OLT) survival (80% versus 96%; P = 0.04). In conclusion, the absence of portocaval shunt and the duration of cold ischemia were independent predictors of intraoperative PRS. PRS was associated with significant adverse postoperative outcome. These results provide realistic clinical targets to improve patient outcome after OLT for cirrhosis.

Metformin Increases HDL3–Cholesterol and Decreases Subcutaneous Truncal Fat in Nondiabetic Patients with HIV-Associated Lipodystrophy

The purpose of this study was to assess metformin effects on high-density lipoprotein (HDL) composition of patients with HIV-associated lipodystrophy (LDHIV). Twenty-four adult outpatients were enrolled to receive metformin (1700 mg/d) during 6 months, but 2 were lost to follow-up and 6 stopped the drug due to adverse events (gastrointestinal in 5, and excessive weight loss in 1). From the 16 subjects who completed the study, 69% were female. At baseline, 3 and 6 months, we assessed: weight, waist and hip circumferences, blood pressure, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), lipids, and HDL subfractions by microultracentrifugation. At 0 and 6 months, body fat distribution was assessed by computed tomography (CT) scan (L4 and middle femur). Metformin use was associated with reduction of mean weight (-2.4Kg at 6 months; p < 0.001), body mass index, waist, waist-to-hip ratio and a marked decrease in blood pressure (p < 0.001). Subcutaneous (p = 0.01) and total abdominal fat (p = 0.002) were reduced, but no change was found in visceral or thigh fat. No difference was detected on plasma glucose, insulin, HOMA2-IR, cholesterol or triglycerides, except for an increase in HDL3-cholesterol (from 21 mg/dL to 24 mg/dL, p = 0.002) and a reduction of nascent HDL (the fraction of plasma HDL-cholesterol not associated to subfractions HDL2 or HDL3) (p = 0.008). Adverse effects were very common, but most were gastrointestinal and mild. Thus, metformin use in LDHIV increases HDL3-cholesterol (probably due to improved maturation of HDL) and decreases blood pressure, weight, waist, and subcutaneous truncal fat, making this an attractive option for preventing cardiovascular disease in this population.

Blood pressure lowering in acute ischaemic stroke: an update on the role of angiotensin receptor blockers

Blood pressure lowering in acute ischaemic stroke: an update on the role of angiotensin receptor blockers

Low-Dosage Adrenaline Induces Transient Marked Decrease of Blood Pressure during Functional Endoscopic Sinus Surgery

Low-dosage adrenaline contained in local anesthetics is commonly used for hemostasis during functional endoscopic sinus surgery (FESS), but often causes significant hemodynamic side effects that might be neglected. A randomized, controlled, prospective clinical trial was designed to find out these effects after local infiltration of different concentrations and/or different dosages of adrenaline during FESS under general anesthesia. One hundred eight adult patients were randomized into one of four groups to receive 2 mL of 2% lidocaine and adrenaline 1:200,000 (group I), 4 mL of 1% lidocaine and adrenaline 1:400,000 (group II), 4 mL of 1% lidocaine and adrenaline 1:200,000 (group III), or 4 mL of 1% lidocaine (group IV) for local infiltration, respectively. Heart rate, systolic blood pressure (BP), diastolic BP, and mean arterial pressure were monitored continuously in radial artery. Significant hemodynamic changes, particularly decrease of BP (p < 0.001) with slightly increased heart rate (p < 0.001) approximately 1.5 minutes after local infiltration, were observed in group I, group II, and group III compared with the baseline, but not in group IV. However, no significant hemodynamic changes were observed between group I, group II, and group III at the same time points (p > 0.05). Local infiltration of low-dosage adrenaline causes temporary significant hemodynamic changes, particularly marked decrease of BP during FESS, and there were no significant hemodynamic changes between adrenaline 1:200,000 and 1:400,000.