Pressor Research Articles

Early studies with the novel 5-HT 1-like agonist GR43175 in healthy volunteers.

A series of single dose studies has been undertaken after intravenous, subcutaneous and oral administration to healthy volunteers to determine safety, tolerability and pharmacokinetics of GR43175, a novel 5-HT 1-like receptor agonist. GR43175 proved to be well tolerated using all routes of administration. Minor side effects were reported including scalp tingling, sensations of bodily warmth, lightheadedness and heavyheadedness. In addition, short-lasting vasopressor effects were encountered, although no drug-related changes were seen in heart rate and ECG or in laboratory safety screens. The drug was rapidly absorbed after oral dosing and had a mean absolute bioavailability of 14% due at least in part to first-pass metabolism. Plasma concentrations in healthy volunteers fell within the range for producing relief of headaches in migraine patients. GR43175 had a high mean plasma clearance (1313 ml/min), the majority of which was due to non-renal clearance and a large volume of distribution (2351). The mean half-lives were 1.7 h and 2.3 h after intravenous and oral doses, respectively.

Effects of beta-antagonists and beta 1-partial agonists on the pulmonary pressor response to 5-HT

The effects of beta-antagonists (propranolol, pindolol, atenolol) and beta 1-partial agonists (xamoterol, denopamine) on the pulmonary circulation, and on the pressor response to 5-HT were investigated and compared with those of a beta-agonist, isoproterenol. These agents (at doses of 0.002-20 mg) were administrated into the isolated lung lobe perfusion system excised from mongrel dogs (7-12 kg in weight). Under standard conditions (mean pulmonary inflow pressure, 15 mmHg; mean outflow pressure, 5 mmHg), propranolol and atenolol had no effect on pulmonary vascular resistance (PVR) at the tested doses, but pindolol which has intrinsic sympathomimetic activity (ISA) and two beta 1-partial agonists significantly decreased PVR in a dose-dependent manner (each n = 7). Isoproterenol, up to a dose of 0.2 mg, markedly decreased PVR, but induced vasoconstriction in larger doses (n = 7). Propranolol and xamoterol similarly reduced the pressor response to 30 micrograms of 5-HT from a dose of 2 mg, and these inhibitory actions were greater than those of the other drugs. Pindolol and denopamine inhibited the 5-HT response in a dose of 20 mg, whereas atenolol only augmented the response in a dose-dependent manner. In conclusion, beta-antagonists with ISA (including beta 1-partial agonist activity) can dilate the pulmonary vessels in a dose-dependent manner, but not beta-antagonists without ISA. Furthermore, the 5-HT inhibitory effects caused by relatively large doses of beta-antagonists, except for atenolol, may be related to the 5-HT receptor blockade or other unknown mechanisms, including calcium influx or prostaglandin synthesis, but not to the beta-receptor blockade.

Isometric Handgrip Reduces Symptoms of Initial Orthostatic Hypotension

Initial orthostatic hypotension (IOH) is a large transient (<1 minute) abrupt drop in blood pressure (BP) and cardiac output that occurs within 15 seconds of standing and is associated with postural symptoms in otherwise healthy people. Isometric handgrip evokes an exercise pressor reflex that increases BP by increasing cardiac output. Investigators examined the …

Analysis of factors influenceing patients' family to make decision to reject resuscitation to the patients

Objective To study the factors influenceing patients' family members to make own relative fac-tors patients' families making decision on refusal of cardiopulmonary resuscitation (CPR) to the critical patients. Method Data were registered based on Utstein Style of 522 patients aged over 15 years, who subjected to in-hos-pital cardiac arrest(CA) in Department of Emergency of The First Affiliated Hospital of Wenzhou Medical College from January 2005 to December 2008. A total of 157 patients' family made refusal decision among the 522 pa-tients, who belonged to the refusal group, and others belonged to the attempt resuscitation group. The associated factors included age, sex, marriage, household register, cause of CA, underlying diseases, capability of activity before CA, life supported with mechanical ventilation, and administration of pressor agents. The refusal decisions were evaluated by using univariate Logistical regression analysis, and then the statistical significant variables were analyzed by using muhivanate Logistical regression analysis. Results Age, household register, cause of CA(car-diac or traumatic),stroke, sudden death, cancer, capability of activity before CA, life supported with mechanical ventilation,and administration of pressor agents were the important factors of making refusal decision (P 0. O5). The independent risk factors re-lated to refusal decision were age (P = 0.034),cancer (P = 0.006),stroke (P = 0.003), and life supported with mechanical ventilation (P = 0.000) in multivariate Logistical regression analysis, but the protective factors were sudden death (P =0.000),cardiac CA (P =0.020) and traumatic CA(P =0.000). Conclusions Age over 60 years, cancer, stroke, and life suppoted with assisted ventilation before CA were factors associated with re-fusal decision making, yet sudden death, cardiac CA and traumatic CA were factors of accepting CPR. Key words: Cardiac arrest (CA) ; Cardioplmonary resuscitation (CPR) ; Utstein Style; Logistical regression analysis

Successful treatment of a patient with severe H1N1 Flu anti multiple organ dysfunction syndrome

Objective To investigate the causes of severe H1N1 Flu with multiple organ dysfunction, and measures to reduce mortality. Method The data of the patient, who was diagnosed as severe H1N1 Flu and mul-tiple organ dysfunction syndrome in First People's Hospital Affiliated to Shanghai Jiaotong University in September 2009, were retrospectively analyzed. The patient was male, 35 year-old, obese, high fever, sore throat, cough, progressive dyspnea, severe hypoxemia and hypotension. Effective measures were carried out, including protective lung ventilation, recruitment maneuver, vasopressor support, limited fluid resuscitation, appropriate corticosteroid, anfiviral plasma, anticoagulafion and antiviral medicine (Oseltamivir)in early stage and full dose. Results After one-month intensive care, clinical symptoms was improved obviously, oxygen pressure reached 74 mmHg without oxygen supply, CT scan showed diffused interstitial ehange. Neuromyopathy developed at approximately 3 weeks after the onset of H1N1. Conclusions H1N1 Flu can develop in healthy adults, and obesity is one of the inde-pendent risk factors. Effective measures should be taken as soon as possible to reduce the mortality. Key words: Influenza A(H1N1) virus infection; Multiple organ dysfunction syndrome(MODS) ; Mortality

Pharmacological options in the management of orthostatic hypotension in older adults

Orthostatic hypotension (OH) is a common disorder in older adults with potentially serious clinical consequences. Understanding the key underlying pathophysiological processes that predispose individuals to OH is essential when making treatment decisions for this group of patients. In this article, we discuss the key antihypotensive agents used in the management of OH in older adults. Commonly, midodrine is used as a first-line agent, given its supportive data in randomized, controlled trials. Fludrocortisone has been evaluated in open-label trials and has long-established usage in clinical practice. Other agents are available and in clinical use, either alone or in combination, but larger randomized trial evaluations are yet to be published. It is important to bear in mind that a patient may be taking medications that predispose to or exacerbate the symptoms of OH. Withdrawal of such medications, where possible, should be considered before commencing other pharmacological agents that attenuate the symptoms of OH.

Significance of new parameters in evaluation the function of carotid artery

Objective To evaluate the parameters of inner diameter different rate (D%), mean wave intensity(MWl) and diameter-adjusted mean wave intension(DAMWI) in assessing the function of common carotid artery(CCA) by quality intima-media thickness(QIMT) technique. Methods Twenty-four healthy subjects were performed 2D and CDFI examination under the normal quiescent and cold pressor test(CPT) condition respectively. The diastolic and systolic diameters of left-CCA were measured by QIMT respectively. Corresponding the inner diameter different range,rate,MWI and DAMWI were calculated respectively. The curves of their ROC were drawn. Results The different range and rate of diameters were decreased when subjects suffered CPT (P 0. 05). Conclusions Conclusions The changed rate of diameter can be measured exactly by QIMT. The function of CCA can Be evaluated by MW1 and DAMWI which were calculated by conventional parameters. Key words: Ultrasonography; Carotid arteries ; Cold pressor test

Study on the effects of blood pressure and vasoreactivity on the parameters of arterial elasticity via cold pressor test

Objective To investigate the interferences of the variations in the blood pressure and vasoreactivity to the parameters of arterial elasticity via cold pressor test(CPT) in healthy young men. Methods The wave intensities(WI) of the right common carotid artery(RCCA) in twenty-two healthy young men during CPT were measured by echo-tracking technique. The parameters of arterial elasticity, including stiffness parameter (β),pressure-strain etastic modulus(Ep), arlerial compliance(AC),augument index(AI) , pulse wave veloctiy-β (PWVβ),and pulse wave velocity_WI(PWV_WI) from WI analysis during CPT were recorded and statistically compared with the baseline data. Results During CPT, the heart rates increased slightly ( P <0. 05) and the mean arterial pressures increased obviously ( P <0. 05); As to the parameters of arterial elasticity, the Ep,AI, PWVβ,and PWV_WI increased obviously ( P <0. 05), AC decreased ( P <0. 05), while the (3 didn't change. Conclusions The β is affected little by the blood pressure and vasoreactivity, and can reflect the actual arterial elasticity; while the Ep, AC, AI, PWVβ, and PWV_WI are affected much by blood pressure and vasoreactivity. When the latter parameters are used to evaluate the arterial elasticity, the interferences of variations in blood pressure and vasoreactivity must be excluded. Key words: Ultrasonography; Carotid artery,common; Blood pressure; Elasticity; Echo-tracking technique

Evaluation of compliance with bundle treatment in the management of severe infection

To evaluate compliance with bundle treatment in the management of severe infection in a tertiary hospital, aiming at analyzing clinical data in order to popularize guidelines for management of severe sepsis and septic shock. A 14-month (from November 1, 2006 to December 31, 2007) prospective observational study of a group of 43 patients admitted to the respiratory intensive care unit in First Affiliated Hospital (tertiary hospital) of Guangzhou Medical College meeting the criteria for severe pneumonia and septic shock was carried out. Implementation of 6-hour and 24-hour bundle treatment for severe infection was divided into three phases consisting of education, trial, and application. A cohort of 43 patients with matched disease history admitted during January 1, 2004 to October 31, 2006 were enrolled as control group. (1) In 6-hour bundle treatment for severe infection, 20.9% (9/43) had serum lactate measured, blood culture was obtained prior to antibiotic administration in 7.0% (3/43) of patients, 100% (43/43) had empirical antibiotics administration within 1 hour, an infusion of an initial minimum of 20 ml/kg of crystalloid or colloid equivalent (1.1 ml/kg of 20% albumin or 4.8 ml/kg of 6% hydroxyethyl starch) was given in 44.2% (19/43), with infused fluid (converted into 6% hydroxyethyl starch) reaching (503.95+/-176.19) ml within 6 hours, in 94.7% (18/19) of patients had received vasopressors , and inotropic dobutamine and/or transfusion of packed red blood cells were administered in 7.0% (3/43). (2) In 24-hour bundle treatment for severe infection group, 31.6% (6/19) had received low-dose steroids, 34.9% (15/43) had their blood glucose controlled<8.3 mmol/L, mechanical ventilation with inspiratory plateau pressures maintained<30 cm H(2)O (1 cm H(2)O=0.098 kPa, 6 ml/kg tidal volume) was instituted in 97.6% (40/41) of patients. (3) The percentage of compliance with 6-hour and 24-hour bundle treatment for severe infection were 0 and 21.4% respectively, total compliance was also 0. (4) As compared with control group, a 23.30% absolute mortality reduction was found in bundle group (18.6% vs. 41.9%, P=0.019). Bundle treatment for severe infection is complied with partially in our hospital, suggesting that it is still quite arduous to popularize guidelines for management of severe sepsis and septic shock in our country.

Application of low-dose vasopressin in the management of septic shock

A number of recent reports suggest that vasopressin may improve organ perfusion and contribute usefully to the cardiovascular management of septic shock. The rationale for the use of vasopressin is its relative deficiency of plasma levels and hypersensitivity to its vasopressor effects during septic shock. Although it is being used more frequently, there are no randomized clinical trials comparing vasopressin as a first-line vasopressor. Key words: septic shock ; vasopressin; vasoconstrictor agents

Vasopressin Not Helpful for Out-of-Hospital Cardiac Arrest

The ideal drug regimen for use in CPR is a subject of controversy. Epinephrine is the recommended vasopressor agent, but results of some studies

Review and Update on Inotropes and Vasopressors

Review and Update on Inotropes and Vasopressors

Review and Update on Inotropes and Vasopressors

Review and Update on Inotropes and Vasopressors

Vasopressin in Septic Shock

Previous studies have identified a relative deficiency of endogenous vasopressin in patients with septic shock, suggesting that vasopressin use might reduce the need for vasopressor support in these patients. To determine whether vasopressin has a norepinephrine-sparing effect, researchers conducted a multicenter, double-blind, randomized trial of 778 patients with septic shock who did not respond to fluids and low-dose norepinephrine. Patients were randomized to receive either low-dose vasopressin (0.01–0.03 U per minute) …

Review and Update on Inotropes and Vasopressors

Review and Update on Inotropes and Vasopressors

Review and Update on Inotropes and Vasopressors

Review and Update on Inotropes and Vasopressors

Description, mechanisms and control of reactions to treatment in the human filariases.

Since diethylcarbamazine at the dosages used to treat filarial infections has little direct toxicity, most of the post-treatment reactions (termed Mazzotti reactions in onchocerciasis) result from the immunological inflammatory mechanisms activated in the process of clearing and killing the skin-swelling or blood-borne microfilariae. These reactions may be either localized to the skin, eyes or lymphatics or generalized systemically (e.g. headache, fever, adenopathy, arthralgia, tachypnoea, tachycardia, hypotension and even death). The occurrence and intensity of such reactions can be shown to be related to the intensity of infection. It had previously been speculated that the best candidates for triggering these post-treatment reactions were activation of complement, immediate hypersensitivity responses mediated by immunoglobulin E, and degranulation of eosinophils with resultant inflammatory reactivity. Recent detailed studies have given little support to the primacy of either complement or immediate hypersensitivity responses in triggering such reactions, but eosinophil degranulation with the release of inflammatory mediators into the tissues and peripheral blood is extremely prominent in all patients undergoing post-treatment reactions and develops with a time course generally consistent with what would be required of an initiator of such reactions. Other inflammatory mediators and pathways may be involved (e.g. kinins, prostaglandins, immune complexes, leukotrienes, platelets and parasite-derived inflammatory molecules), but there is currently no evidence to implicate any of these mechanisms as initiators of the response. Symptomatic treatment of these post-treatment reactions with analgesics, antipyretics, antihypotensive agents etc. has been successful, but their prevention has been achieved only with the broadly anti-inflammatory corticosteroids.

Vasopressors in Obstetrics

Vasopressors in Obstetrics

What Vasopressors Should Be Used to Treat Shock?

What Vasopressors Should Be Used to Treat Shock?

Midodrine Hydrochloride and l‐threo‐3,4‐dihydroxy‐Phenylserine Preserve Cerebral Blood Flow in Hemodialysis Patients With Orthostatic Hypotension

Orthostatic hypotension (OH) after hemodialysis (HD) is a serious complication, as it causes various neurological symptoms and even ischemic brain damage. The aim of the present study was to evaluate the effects of antihypotensive agents, midodrine hydrochloride (MID) and L-threo-3,4-dihydroxyphenylserine (L-DOPS), on OH after HD. We measured systolic blood pressure (SBP) and cerebral blood flow velocity in the middle cerebral artery (MCVm, by transcranial Doppler sonography), in patients with OH during a 5-min 60-degree head-up tilt test at both before and after 4-week treatment with MID at 4 mg/day (N = 6) or L-DOPS at 400 mg/day (N = 7). Both MID and L-DOPS did not significantly protect against falls in systolic BP (SBP) after passive head-up tilt. However, a significant improvement was achieved in MCVm-decrement in the MID group at 3 min and the L-DOPS group at 0, 1 and 3 min during head-up tilt. Although MID and L-DOPS did not prevent OH after HD in HD patients, both agents preserved cerebral blood flow during orthostasis in HD patients with OH.