Increase In Mean Blood Pressure Research Articles

ATTENUATION OF THE PRESSOR RESPONSE TO TRACHEAL INTUBATION IN PREGNANT PATIENTS BY KETOROLAC DURING CAESAREAN SECTION

Objectives: ketorolac may attenuate maternal stress response to tracheal intubation, without subsequent dangers of opioid-induced neonatal depression. The objective of this study is to evaluate the haemodynamic and hormonal effects of pre-emptive ketorolac on surgical stress and the postoperative analgesic consumption, after Cacsarean delivery. Study Design: A prospective randomized double-blinded placebo-controlled study.Methods: After ethical approval, 90 patients scheduled for elective Cacsarean deliveries were randomly allocated U) the ketorolac group (/*=45); received IV ketorolac 15 mg bolus, followed by an infusion of 7.5 mg.lr'.and the saline for placebo group (/;=45). Anaesthesia was maintained with 50% nitrous oxide, 0.5% isoflurane, and vecuronium. The haemodynamic variables and the levels of plasma corlisol were recorded before and after induction, and after delivery, The graded uterine relaxation, the need for supplementary doses of oxylocin, the peri-operative blood loss, bleeding lime, and Apgar scores at 1 and 5 minutes, postoperative pain scores at rest and with movement, and namadol consumptions were assessed.Results: After intubation, parturients receiving ketorolac had a smaller increase in heart rale, systolic and mean arterial blood pressure (P< 0.001) and lower plasma corlisol concentrations, (45± 15.1 vs. 32.2 ± 7.61 Ug. dl', P<0.05). Therefore, they had lower VAS pain scores al rest and on movement, for the first 2 postoperative hours (P<0.001), later lime to first request for analgesia and less iramadol consumption for the first 4 post-operative hours [0 (0-100) mg vs. 100 (0-100) mg, P = 0.004]. There were no differences between groups with regard to peri-operative blood loss, bleeding lime, transfusion requirements, nausea, vomiting or Apgar scores, with no evidence of premature closure of the ductus arteriosus of the newborns.Conclusion: Pre-emptive ketorolac is safe and effective in attenuating the maternal stress response with improved quality of post-operative analgesia in Caesarean delivery patients.

A retrospective pooled analysis of duloxetine safety in 23 983 subjects

ABSTRACTObjective: The safety and tolerability of duloxetine for major depressive disorder (MDD), generalized anxiety disorder (GAD), diabetic peripheral neuropathic pain (DPNP), fibromyalgia, and lower urinary tract disorders (LUTD) (including female stress urinary incontinence [SUI] and other LUTDs) has been established in individual clinical studies. The objective of this manuscript is to characterize the overall safety profile of duloxetine, regardless of indication, based on data from the duloxetine exposures integrated safety database.Research design and methods: The duloxetine exposures integrated safety database was examined using pooled data from 23 983 patients randomized to receive duloxetine in 64 studies for MDD, GAD, DPNP, fibromyalgia, or LUTDs. Evaluated aspects of drug safety included treatment-emergent adverse events (TEAEs), adverse events leading to discontinuation, serious adverse events (SAEs), clinical laboratory tests, vital signs, and electrocardiograms.Results: Common TEAEs included nausea, headache, dry mouth, insomnia, constipation, dizziness, fatigue, somnolence, diarrhea, and hyperhidrosis. Most TEAEs emerged early; the majority were mild to moderate in severity, and did not worsen. Overall, discontinuation rates due to AEs were 20.0%. SAEs occurred at a rate of 3.5% and no single event was predominant. Mean pulse increased by < 2 beats per minute. Mean increases in systolic and diastolic blood pressure were < 1 mmHg. Mean alanine transaminase and aspartate transaminase values increased by < 2 U/L.Conclusions: The safety profile for the molecule from the overall duloxetine exposures integrated safety database suggests that benign and common pharmacologic side effects occur with duloxetine treatment. Because these pooled analyses do not allow for statistical comparison to placebo or active comparator, and include data from five different studied indications, these data do not suggest causality for AEs, nor are they necessarily generalizable to each disease stated studied.

Early Neonatal Hydrocortisone: Study Rather Than Treat

Hydrocortisone at doses corresponding or exceeding the endogenous corticosteroid secretion during stress has been studied in randomized trials since the early 1970s.1 Lately, the aim has been to stabilize very low blood pressure or decrease the risk of bronchopulmonary dysplasia (BPD).2,3 According to experimental studies, the beneficial hemodynamic effects are largely a result of an increase in myocardial smooth muscle contractility.4 Corticosteroids increase cardiovascular adrenergic receptors and enhance the microvascular endothelial barrier function, and hydrocortisone has a mineralocorticoid-mediated effect on cardiac muscle. Closure of patent ductus arteriosus (PDA) is promoted by corticosteroid, which also decreases the synthesis of prostaglandins and endothelial nitric-oxide synthetase.5 The blood pressure is just one function that, together with perfusion resistance and oxygen carrying capacity of the blood, determine the oxygen delivery to the tissue. The pressure-passive cerebral perfusion evident in some very preterm infants argues for interventions that increase and stabilize the perfusion pressures. Beneficial hemodynamic effects of hydrocortisone have been observed in randomized, placebo-controlled trials. In a single-center randomized trial of 48 preterm infants (mean gestational age: 26.6 weeks; birth weight [BW]: <1500 g [mean: 920 g]), hydrocortisone was given at 3 mg/kg per day, divided into 3 intravenous injections for 4 days, starting during the first week (a mean of 11 hours after birth) for treatment of refractory hypotension.3 Despite an increase in mean blood pressure, there was a decrease in the requirement for dopamine, dobutamine, and saline infusions and no detectable effects on PDA or other outcomes. In 3 randomized trials in which the influence of early neonatal hydrocortisone on survival without BPD was studied, the acute hemodynamic changes … Address correspondence to Mikko Hallman, MD, PhD, Department of Pediatrics, University of Oulu, PO Box 5000, University of Oulu, FIN-90014 Oulu, Finland. E-mail: mikko.hallman{at}oulu.fi

Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans

Impaired endothelial-derived NO (eNO) is invoked in the development of many pathological conditions. Systemic inhibition of NO synthesis, used to assess the importance of NO to blood pressure (BP) regulation, increases BP by approximately 15 mm Hg. This approach underestimates the importance of eNO, because BP is restrained by baroreflex mechanisms and does not account for a role of neurally derived NO. To overcome these limitations, we induced complete autonomic blockade with trimethaphan in 17 normotensive healthy control subjects to eliminate baroreflex mechanisms and contribution of neurally derived NO. Under these conditions, the increase in BP reflects mostly blockade of tonic eNO. N(G)-Monomethyl-l-arginine (250 microg/kg per minute IV) increased mean BP by 6+/-3.7 mm Hg (from 77 to 82 mm Hg) in intact subjects and by 21+/-8.4 mm Hg (from 75 to 96 mm Hg) during autonomic blockade. We did not find a significant contribution of neurally derived NO to BP regulation after accounting for baroreflex buffering. To further validate this approach, we compared the effect of NOS inhibition during autonomic blockade in 10 normotensive individuals with that of 6 normotensive smokers known to have endothelial dysfunction but who were otherwise normal. As expected, normotensive smokers showed a significantly lower increase in systolic BP during selective eNO blockade (11+/-4.5 versus 30+/-2.3 mm Hg in normotensive individuals; P<0.005). Thus, we report a novel approach to preferentially evaluate the role of eNO on BP control in normal and disease states. Our results suggest that eNO is one of the most potent metabolic determinants of BP in humans, tonically restraining it by approximately 30 mm Hg.

Stressassoziierte Hypertonie am Arbeitsplatz - Ergebnisse des STARLET-Projekts

To assess the influence of work stress and initial blood pressure on the prognosis of hypertension. In a prospective, controlled, multicentre, observational study, ambulatory 24-hour blood pressure measurements (ABPM) of employees from different work places were recorded at the work place on working days. Recurrent ABPM were performed for up to 5 years on 3448 subjects (mean age 44.6 years) who gave consent for follow-up. Subjects with hypertension were told to consult their family doctor so that they could receive antihypertensive treatment (the angiotensin receptor blocker eprosartan, an ACE-inhibitor or a beta-blocker were recommended for initial treatment). Subjects were classified as being in mental strain (stress-positive [stress+]/ stress-negative [stress-]), using standardized questionnaires. Only 1242 (36.0%) of the 3448 employees (69.% males) were normotensives. Only 166 (7.5%) of the 2206 hypertensives had normal ABPMs (<135/85 mmHg) and received antihypertensive treatment at the time of inclusion into the trial. During follow-up 57.8% of patients were treated with eprosartan or ACE-inhibitors, 34.6% with beta-blockers. By the time of the final visit 80.5% of hypertensives had achieved improvement of systolic and/or diastolic blood pressures (29.1% normotensive). Patients with hypertensive ABPM at baseline had more cardiovascular events than normotensives (normotensives 3.0%; grade 1 7.8%, grade 2-3 9.8%). Hypertensive ABPMs at the last follow up or an increase in blood pressure grade were associated with higher event rates than normotensives (stable normotensives 1.8% events vs. stable hypertensives 7.9%, vs. worsening or grade 2-3: 9.1%) More hypertensives were classified as stress+ than normotensives. Persons classified as stress- (or changing to stress-) had fewer events (6.2%) than those regarded as stress+ or changing to stress+ (7.1%). Persons regarded as stable stress- had lower mean blood pressures than those who were stable stress+. Change to another stress group was associated with an increase or decrease of mean blood pressure. Many employed people are hypertensive at work and are not treated adequately. ABPM control and antihypertensive treatment based on eprosartan, ACE-inhibitors or beta-blockers resulted in a significant increase in the number of patients with lower blood-pressure levels and a reduction in cardiovascular events. Patients under mental strain were more likely to be hypertensive. Mental strain was associated with changes in blood pressure.

Alterations in cerebral dynamics at high altitude following partial acclimatization in humans: wakefulness and sleep

We tested the hypothesis that, following exposure to high altitude, cerebrovascular reactivity to CO2 and cerebral autoregulation would be attenuated. Such alterations may predispose to central sleep apnea at high altitude by promoting changes in brain PCO2 and thus breathing stability. We measured middle cerebral artery blood flow velocity (MCAv; transcranial Doppler ultrasound) and arterial blood pressure during wakefulness in conditions of eucapnia (room air), hypocapnia (voluntary hyperventilation), and hypercapnia (isooxic rebeathing), and also during non-rapid eye movement (stage 2) sleep at low altitude (1,400 m) and at high altitude (3,840 m) in five individuals. At each altitude, sleep was studied using full polysomnography, and resting arterial blood gases were obtained. During wakefulness and polysomnographic-monitored sleep, dynamic cerebral autoregulation and steady-state changes in MCAv in relation to changes in blood pressure were evaluated using transfer function analysis. High altitude was associated with an increase in central sleep apnea index (0.2 +/- 0.4 to 20.7 +/- 23.2 per hour) and an increase in mean blood pressure and cerebrovascular resistance during wakefulness and sleep. MCAv was unchanged during wakefulness, whereas there was a greater decrease during sleep at high altitude compared with low altitude (-9.1 +/- 1.7 vs. -4.8 +/- 0.7 cm/s; P < 0.05). At high altitude, compared with low altitude, the cerebrovascular reactivity to CO2 in the hypercapnic range was unchanged (5.5 +/- 0.7 vs. 5.3 +/- 0.7%/mmHg; P = 0.06), while it was lowered in the hypocapnic range (3.1 +/- 0.7 vs. 1.9 +/- 0.6%/mmHg; P < 0.05). Dynamic cerebral autoregulation was further reduced during sleep (P < 0.05 vs. low altitude). Lowered cerebrovascular reactivity to CO2 and reduction in both dynamic cerebral autoregulation and MCAv during sleep at high altitude may be factors in the pathogenesis of breathing instability.

Effects of Hemopure™ on Maximal Oxygen Uptake and Endurance Performance in Healthy Humans

Haemoglobin-based oxygen carriers (HBOCs) such as Hemopure are touted as a tenable substitute for red blood cells and therefore potential doping agents, although the mechanisms of oxygen transport of HBOCs are incompletely understood. We investigated whether infusion of Hemopure increased maximal oxygen uptake (V.O 2max) and endurance performance in healthy subjects. Twelve male subjects performed two 4-minute submaximal exercise bouts equivalent to 60 % and 75 % of V.O (2max) on a cycle ergometer, followed by a ramped incremental protocol to elicit V.O (2max). A crossover design tested the effect of infusing either 30 g (6 subjects) or 45 g (6 subjects) of Hemopure versus a placebo. Under our study conditions, Hemopure did not increase V.O (2max) nor endurance performance. However, the infusion of Hemopure caused a decrease in heart rate of approximately 10 bpm (p=0.009) and an average increase in mean ( approximately 7 mmHg) and diastolic blood pressure ( approximately 8 mmHg) (p=0.046) at submaximal and maximal exercise intensities. Infusion of Hemopure did not bestow the same physiological advantages generally associated with infusion of red blood cells. It is conceivable that under exercise conditions, the hypertensive effects of Hemopure counter the performance-enhancing effect of improved blood oxygen carrying capacity.

Muscle sympathetic nerve activity responses to dynamic passive muscle stretch in humans

It is suggested that mechanoreceptors in muscle play an important role in the exercise pressor reflex. However, it has not been verified whether isolated stimulation of the mechanoreceptors can induce responses in muscle sympathetic nerve activity (MSNA) in young healthy individuals. We tested the hypothesis that passive stretch of muscle can evoke an increase in MSNA in healthy individuals. In 12 young subjects, leg calf muscles were passively stretched, or actively contracted for 5 s followed by a 15-25 s (random length) relaxation period. Stretch and contraction were each repeated 25 times. MSNA, heart rate and blood pressure were analysed, and averaged according to the onset of the force on a beat-by-beat basis. At the 1st to the 3rd heart beat from the onset of stretch, MSNA (199 +/- 30%, P < 0.05) as well as heart rate (102.5 +/- 0.7%, P < 0.05) increased transiently but significantly from the prior stretch baseline (100%), followed (from 3rd to 7th beat from the onset of stretch) by a transient increase in mean blood pressure (101.9 +/- 0.3%, P < 0.05) from the baseline. Similar response patterns were observed during active muscle contractions. The present data show that MSNA responses to isolated stimulation of mechanoreceptors are measurable. Because of baroreflex engagement, the magnitude of the response is small and transient, and the haemodynamic consequences using this protocol may be limited.

Rate of Morning Increase in Blood Pressure Is Elevated in Hypertensives

We applied a new logistic curve fitting procedure to ambulatory blood pressure (ABP) recordings to determine whether the rate of increase in systolic (SBP), mean (MBP) and diastolic blood pressure (DBP) and heart rate (HR) in the morning is related to the level of BP in subjects. The rate of transition in the morning and evening period was determined using a six-parameter double-logistic equation applied to 528 ABP recordings from a cardiovascular risk assessment clinic. Based on daytime BP (MBP, SBP, or DBP), the upper quartile (UQ, n = 132) and lower quartile (LQ) were compared. Subjects in the UQ of daytime MBP were hypertensive and showed greater day-night differences compared to normotensive subjects in the LQ (29 +/- 1 mm Hg for MBP compared to 20 +/- 1 mm Hg). The rate of morning increase in SBP and DBP was 42% and 30% greater in UQ subjects compared to the LQ subjects (P < .05). The rates of evening decrease in all BPs were 69% to 84% greater in the subjects in the UQ. Similar results were obtained if subjects were divided according to daytime SBP or DBP. The rate of morning increase in MBP was correlated with daytime BP, but not night-time or 24 h MBP. The rate of morning increase in BP is greater in those subjects with the highest daytime BP. The exaggerated rate of morning increase in BP in this group, which were all hypertensive, may also be important for greater cardiovascular risk.

An Open-Label Study of the Tolerability of Mixed Amphetamine Salts in Adults With Attention-Deficit/Hyperactivity Disorder and Treated Primary Essential Hypertension

To evaluate the short-term tolerability of an extended-release preparation of the stimulant medication mixed amphetamine salts (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) whose hypertension has been successfully treated with antihypertensive medications. An 8-week, 2-phase, open-label study design was implemented. All adults had ADHD (DSM-IV diagnosis) and essential hypertension and were required to be normotensive (blood pressure < 135/85 mm Hg, treated) for at least 4 weeks at entry into the study. MAS XR was given for a 6-week period, titrated once each week to a target maximum dose of 60 mg/day given once daily in the morning (phase 1), and then discontinued for 2 weeks at the end of the study (phase 2). At baseline, subjects underwent a comprehensive clinical assessment, medical history, vital signs assessment, and electrocardiogram (ECG). Rating scales were used throughout the study to assess response to treatment, and blood pressure was measured manually at each study visit. The primary outcome was the effect of MAS XR on blood pressure and the development of hypertension. Thirteen subjects receiving antihypertensive therapy were entered and placed on MAS XR treatment and completed the trial. There were no serious adverse events. No sustained elevated blood pressure (> 140/90 mm Hg at 2 consecutive visits) was observed in the subjects treated with MAS XR. Similar rates of single episodes of hypertension were observed in phases 1 and 2. Similarly, there was no group mean increase in systolic or diastolic blood pressure or pulse during treatment with MAS XR. No clinically significant changes in the ECG were observed. During the 6-week medication phase, significant improvement was found on rating scales assessing ADHD symptoms and severity that reversed with discontinuation of MAS XR. The results of this open study suggest that adults with ADHD and controlled hypertension can be safely treated with MAS XR.

Levosimendan for Low Cardiac Output: A Pediatric Experience

This was a retrospective observational study in a pediatric intensive care unit, in which 19 patients received levosimendan. There were no adverse events attributable to levosimendan and no instances where the clinical condition worsened after administration. Arterial lactate levels decreased significantly following levosimendan administration during cardiopulmonary bypass for anticipated low cardiac output. In those with established low cardiac output, trends toward improved hemodynamics were seen, with heart rate reduction, an increase in mean blood pressure, a reduction in arterial lactate, and reduced conventional inotrope use. Levosimendan was safely used in a small number of pediatric patients with established low cardiac output state who demonstrated improved hemodynamics and tissue perfusion, with a tendency to reduced conventional inotrope usage, and this warrants its evaluation as an inotrope in the pediatric population.

Central hemodynamic responses to an acute sodium load in black and white subjects.

Chronically high dietary sodium intake has been associated with elevated blood pressure (BP). Studies have shown that black adults demonstrate a higher degree of sodium sensitivity than white adults. PURPOSE To examine the acute effects of sodium on BP, cardiac output (Qc), and peripheral vascular resistance (PVR) in black and white subjects. We hypothesized that a hypertonic saline infusion (3% NaCl; HSI) would increase BP more in black subjects. METHODS 19 black (age: 22.9 ± 1.4 yrs) and 16 white (age: 25.9 ± 1.5 yrs) healthy subjects underwent a 60-minute HSI. BP (Finometer), Qc (CO2 rebreathing), serum sodium, and osmolality were assessed throughout the HSI. PVR was calculated. Results are reported as mean ± standard error and a two way repeated measures ANOVA was used to compare the effects of time and race. RESULTS During the HSI there was an increase in serum sodium (135.3 ± 0.4 to 141.1 ± 0.4 mmol/L) and osmolality (287.4 ± 0.7 to 296.6 ± 0.7) that was not different between the races. While the increase in mean BP was not different between the races (black: 10.1 mmHg vs. white: 9.5 mmHg, p = 0.795), the time course for the change in Qc (and hence, PVR) was different (ANOVA race, p < 0.05). CONCLUSION Preliminary analysis suggests that the HSI increased BP in all subjects, but the mechanisms underlying the change in BP were different black and white subjects. Supported by NIH grant RI5 HL074851-01.

Muscle sympathetic nerve activity responses to dynamic passive muscle stretch.

It is suggested that mechanoreceptors in muscle play an important role in the exercise pressor reflex, however, it has not been verified whether isolated stimulation of the mechanoreceptors can induce responses in muscle sympathetic nerve activity (MSNA) in young healthy individuals. The purpose of present study was to test the hypothesis that passive stretch of muscle can evoke an increase in MSNA in healthy individuals. In 7 young subjects, calf muscles in a leg were passively stretched, or actively contracted for 5 sec followed by a 15–25 sec (random) relaxation period. Stretch and contraction were each repeated 25 times. MSNA, ECG, heart rate, and blood pressure were recorded, analyzed, and averaged according to the onset of the force on a beat-by-beat basis. At the 1st and/or the 2nd heart beat from the onset of stretch, MSNA increased transiently but significantly (7.27±1.87 units/beat) from the prior stretching baseline (4.80±1.43 units/beat, P<0.01), followed (at 3rd to 5th beat from the onset of stretching) by a transient increase in mean blood pressure from the baseline (change 2.48±0.68 mmHg, P<0.05). After end of stretch, another MSNA increase was observed when blood pressure fell. Similar responses were observed during active muscle contractions. The present data can be considered as evidence to support the concept that isolated stimulation of mechanoreceptors can evoke MSNA responses in young healthy humans. Supported by P01 HL077670 and M01 RR010732.

Secular stroke trends: early life factors and future prospects

Stroke mortality rates have declined during the second half of the 20th century in developed countries. Possible reasons for this include preventive measures, recent environmental changes impacting on adult health risks, and more distant environmental influences on childhood health. Data from a number of populations in Europe and the USA suggest that a decrease in early life blood pressure, occurring since the beginning of the 20th century, may have been an important determinant of declining stroke incidence rates and cardiovascular disease mortality in general. Advances in stroke epidemiology are increasing the accuracy of case ascertainment, and neuroimaging refinements (particularly MRI) are improving the accuracy of stroke type and subtype diagnoses. Although some risk factors are common to ischaemic and haemorrhagic stroke, there is accumulating evidence of differing aetiology. There is also an increasing recognition that early life factors may influence stroke risk. Despite the encouraging decline in stroke incidence, there is evidence of a recent increase in mean blood pressure in young people observed in the USA and UK, prompting concern that favourable trends in stroke risk may not be maintained. Reducing early life blood pressure in a population and delaying the onset of hypertension, along with effective measures to combat obesity, are required to avoid a reversal in stroke incidence trends in developed countries, and to prevent the anticipated increase in the burden of stroke in developing countries.

Landiolol and esmolol prevent tachycardia without altering cerebral blood flow

Several ss-adrenergic-blocking drugs have been used during electroconvulsive therapy (ECT) to stabilize the hemodynamic alterations following electrical stimulation. The effects of two ultra-short acting ss-adrenergic-blocking drugs, esmolol and landiolol, on systemic and cerebral circulation were studied during ECT. In the first study (n = 15), dose-dependent hemodynamic changes were studied when landiolol was administered immediately after induction of anesthesia. In the second study (n = 12), effects of esmolol and landiolol on systemic and cerebral circulation were compared. Patients in Study 1 received three doses of landiolol, and patients in Study 2 received two types of ss-adrenergic-blocking drugs, in a randomized cross-over design in a series of ECT trials. In the first study, 0.25 to 0.5 mg.kg(-1) landiolol induced a lower heart rate after the electrical stimulation compared to vehicle (P < 0.01). Landiolol did not have significant effects on blood pressure. In the second study, heart rate was stabilized by 1.0 mg.kg(-1) esmolol iv or 0.5 mg.kg(-1) landiolol iv. Increase in mean blood pressure was ameliorated by esmolol (P < 0.01), but not by landiolol. Mean cerebral blood flow velocity in the middle cerebral artery increased at one to two minutes after the electrical stimulation regardless of the use of ss-adrenergic-blocking drugs (P < 0.01). Muscular and electroencephalographic seizure durations were not significantly altered by the ss-adrenergic-blocking drugs. Landiolol suppresses heart rate elevation during ECT without affecting blood pressure. Cerebral blood flow velocity in the middle cerebral artery is not affected by the use of either esmolol or landiolol.

Ambulatory Blood Pressure Monitoring in Multiple Myeloma Patients Treated with VAD Protocol.

BACKGROUND: Corticosteroids are still a cornerstone in multiple myeloma (MM) therapy, both as a single agent and as a part of many protocols, including VAD regimen (vincristine, adriblastine, dexamethasone). Corticosteroids are known to be involved in blood pressure (BP) regulation and to affect this parameter. The impact of dexamethasone (Dex) administration on BP in MM patients during VAD protocol treatment is poorly documented.AIM: The purpose of the study was to evaluate the blood pressure changes during Dex administration in patients treated with VAD protocol due to MM.METHODS: Thirteen patients with MM (7 men and 6 women; mean age 62,45 ± 8,14) were assessed. Primary hypertensive patients (7 persons) were not excluded. They were administered Dex in standard dose of 40 mg (day 1–4, 9–12, 17–21) according to VAD protocol. Blood pressure was assessed by the use of commercially available instruments of Ambulatory Blood Pressure Monitoring (ABPM). The BP recordings lasted 48 hours, were started on the day before the first day of VAD and were obtained every 10 minutes during mornings, every 15 minutes during the rest of days and every 20 minutes during nights. Average of systolic and diastolic blood pressure (SBP/DBP) were estimated for the 2-hour time before Dex and for the 14-hour time in the 2-hour periods after Dex. Minimal and maximal range of SBP/DBP increase and the mean amount of SBP/DBP increase were also determined.RESULTS: 48-hour BP recordings revealed a significant increase in systolic and diastolic blood pressure after Dex administration in all patients. SBP and DBP began to increase after 3 hours after Dex, then rose continually and reached the peak in the period from 6 to 10 hour after Dex. In comparison to 2-hour period before Dex, in which SBP/DBP amounted 139,63/82,92 ± 23,47/9,38 mmHg, the mean SBP/DBP increase rate was: in the 2–4 hour period after Dex - 146,68/88,15 ± 24,38/10,51 mmHg (p<0,05), in the 6–8 – 148,07/92,66 ± 14,07/9,04 mmHg (ns), in the 8–10 – 147,8/87,99 ± 14,07/9,04 mmHg (p<0,01), in the 10–12 – 143,44/86,12 ± 17,22/9,77 mmHg (p<0,05) and in the 12–14 – 144,47/88,59 ± 17,04/12,54 mmHg (p<0,01). The minimal range of SBP/DBP increase was 10,50/−2,00 mmHg, maximal range of SBP/DBP increase was 35,43/40,00 mmHg and the mean amount of SBP/DBP increase was 20,06/11,6 ± 8,36/14,23 mmHg.CONCLUSION: Our preliminary study revealed that Dex administration causes an increase in BP in all patients. The mean increase in BP amounted 20,06/11,6 ± 8,36/14,23 mmHg and was similar in all patients, regardless their initial value of BP. So our study demonstrates the need of individualized hypertension treatment with strict control of BP in hypertensive patients when corticosteroid therapy is indicated.

Randomized Trial of Sertraline Versus Venlafaxine XR in Major Depression

The comparative efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) was recently debated. Meta-analyses, based mainly on fluoxetine comparator data, suggest that the SNRI venlafaxine has superior efficacy to SSRIs in treatment of major depression. To compare quality of life (QOL), efficacy, safety, and tolerability associated with sertraline and venlafaxine extended release (XR) for treatment of DSM-IV major depression. This was an 8-week, double-blind, randomized study of sertraline (50-150 mg/day) versus venlafaxine XR (75-225 mg/day), followed by a 2-week taper period. Subjects were recruited from 7 sites in Turkey and 6 sites in Australia between October 2002 and July 2003. The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Questionnaire. Secondary outcome measures included measures of depression (including response and remission), anxiety, pain, safety (e.g., blood pressure), and tolerability (e.g., discontinuation symptoms). A total of 163 subjects received study treatment (women, 69%; mean age, 37.0 [SD = 12.9] years). No significant differences in QOL or efficacy were noted between treatments on the primary or secondary endpoints for the total study population or the anxious depression and severe depression subgroups. A priori analyses of symptoms associated with treatment discontinuation demonstrated no difference between treatment groups. However, in post hoc analyses, sertraline was associated with less burden of moderate to severe discontinuation symptoms. Venlafaxine XR was associated with a relative increase in mean blood pressure (supine diastolic blood pressure, -4.4 mm Hg difference at week 8/last observation carried forward). Sertraline and venlafaxine XR demonstrated comparable effects on QOL and efficacy in treatment of major depression, although sertraline may be associated with a lower symptom burden during treatment discontinuation and a reduced risk of blood pressure increase.

Short- and Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended Release in Children

To assess the short- and long-term cardiovascular effects of once-daily treatment with a mixed amphetamine salts extended-release formulation (MAS XR; Adderall XR(R)) in children age 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD). Short-term cardiovascular effects were assessed during a 4-week, double-blind, randomized, placebo-controlled, forced-dose-titration study of once-daily 10, 20, and 30 mg MAS XR (n = 580). Long-term cardiovascular effects were assessed in 568 subjects during a 2-year, open-label extension study of MAS XR (10 to 30 mg/day). Resting sitting blood pressure and pulse were measured at baseline and weekly during the short-term study, then monthly during long-term treatment. Changes in blood pressure, pulse, and QT interval corrected by Bazett's formula (QTcB) in children receiving MAS XR were not statistically significantly different than those changes seen in children receiving placebo during short-term treatment. Mean increases in blood pressure after 2 years of MAS XR treatment (systolic, 3.5 mm Hg; diastolic, 2.6 mm Hg) and pulse (3.4 bpm) were clinically insignificant, and there was no apparent dose-response relationship. Cardiovascular effects of short- and long-term MAS XR were minimal during short- and long-term MAS XR treatment at doses of </= 30 mg/day in otherwise healthy children.

Effect of nitric oxide synthase modulation on resuscitation success in a swine ventricular fibrillation cardiac arrest model

Background: We have demonstrated previously that the nitric oxide synthase (NOS) inhibitor N G-nitro- l-arginine ( l-NNA) decreases free radical generation and nitrosative injury via peroxynitrite formation after epicardial dc shocks. Objective: Our purpose was to explore the effects of NOS inhibition and NOS donation on cardiopulmonary resuscitation (CPR) success after cardiac arrest of variable duration. We used the non-selective NOS inhibitor l-NNA and the selective neuronal NOS inhibitor ARR-17477, the NOS donor S-nitroso- N-acetylpenicillamine (SNAP) and the vasodilator Enalaprilat, which lowers arterial pressure via a non-NO mechanism. Methods: Part I: 17 pigs undergoing 4 min supported (i.e. with closed-chest compression and ventilation) ventricular fibrillation (VF) were divided into two groups: a no- l-NNA group ( n = 8) receiving IV saline and an l-NNA group ( n = 9) receiving IV l-NNA (5 mg/kg) for 8 min before VF was induced. Part II: 35 pigs undergoing 6–8 min VF were randomized to three groups: a no- l-NNA group ( n = 13) receiving IV saline, an l-NNA group ( n = 11) receiving IV l-NNA (5 mg/kg) and an ARR17477 group ( n = 11) receiving IV ARR17477 (5 mg/kg) before VF. All animals in Part II underwent unsupported VF (no chest compression or ventilation) for 6 min ( n = 13) or 8 min ( n = 22); closed-chest compression, ventilation and epinephrine (adrenaline) were employed after defibrillation. Part III: 12 swine were divided into two groups: control ( n = 6) receiving saline and an LNNA group ( n = 6) receiving IV LNNA (5 mg/kg). Swine underwent 6 min unsupported VF and 2 min supported VF before defibrillation. Part IV: 25 animals were studied to determine the effect of the NO donor SNAP and the angiotensin-converting enzyme inhibitor Enalaprilat on coronary perfusion pressure (CPP). Results: In Part I, after defibrillation, with continued ventilation, chest compression and epinephrine, 8/9 l-NNA pigs achieved ROSC versus 4/8 control pigs ( p = 0.11). After 60 s of CPR, 7/9 pigs in the l-NNA group achieved ROSC versus 2/8 pigs in the no- l-NNA group ( p < 0.05). Only 2/9 pigs receiving l-NNA required epinephrine (1 mg) after defibrillation, compared to 6/8 pigs requiring at least one dose of epinephrine in the no- l-NNA group ( p < 0.05). In Part II, there was no significant difference between l-NNA, ARR17477 and control pigs in ROSC. However, control pigs required 6.8 ± 1.4S.E. mg epinephrine; l-NNA pigs and ARR17477 pigs required less epinephrine (3.7 ± 0.7 and 3.0 ± 0.3 mg, both p = 0.01). Shorter chest compression was required in the l-NNA group (252 ± 38 s, p < 0.05) and in ARR17477 group (222 ± 15 s, p < 0.05) compared to the control group (405 ± 77 s). In Part III, l-NNA infusion caused a significant increase in mean blood pressure at baseline, but did not change CPP throughout the experiment. In Part IV, there were no significant differences in the changes of mean blood pressure and CPP between SNAP and Enalaprilat group in all animals throughout the experiment. Conclusion: NOS inhibition pre-arrest did not improve survival, but did reduce requirements for epinephrine and closed-chest compression in a swine resuscitation model.

Lipoatrophic men 44 months after the diagnosis of lipoatrophy are less lipoatrophic but more hypertensive

To identify clinical factors associated with HIV-associated lipoatrophy and to evaluate body composition changes, blood pressure and lipid levels in lipoatrophic subjects 3-4 years after the atrophy diagnosis. Clinical signs of lipoatrophy were assessed in 308 ambulant HIV-positive patients in 2000-2001. Possible clinical risk factors, such as age, gender, race, wasting, duration of HIV infection, presence or absence of AIDS diagnosis, viral load and CD4 count, and detailed information about drug treatment were analysed and explored in a multivariate model. Lipoatrophic white males with triceps skin fold <10 mm were re-examined after 44 months. Signs of lipoatrophy and associated factors, blood pressure, lipid levels, diet and level of exercise at first and second visits were compared. In the multivariate analysis, significant clinical risk factors for lipoatrophy were weight loss >7 kg compared to normal weight [odds ratio (OR) 3.76; 95% confidence interval (CI) 1.80-7.82; P<0.001], current and/or previous use of stavudine (OR 3.72; 95% CI 1.57-8.83; P=0.003) and duration of HIV infection >80 months (OR 2.28; 95% CI 1.13-4.59; P=0.021). Forty of 47 lipoatrophic white males with skin fold < 10 mm were available for re-examination. Of these, 15 (38%) no longer fulfilled the atrophy diagnosis (P<0.001). The prevalence of arm atrophy fell from 63 to 28% (P=0.001) and facial atrophy from 55 to 43% (P=0.23). Use of stavudine for < 36 months was significantly associated with lipoatrophy reversal (OR 5.00; 95% CI 1.15-21.80; P=0.032), but weight gain and increased CD4 count were not. Prevalence of hypertension increased from 28 to 50% (P=0.035), mean systolic blood pressure from 130+/-14 to 136+/-19 mmHg (P=0.021) and diastolic blood pressure from 82+/-10 to 87+/-12 mmHg (P<0.001). In spite of increased use of lipid-lowering drugs (from two to nine patients), levels of total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were unchanged. In this study, we found that weight loss >7 kg, use of stavudine and long duration of HIV infection were significant risk factors for clinical lipoatrophy. Clinical lipoatrophy was partly reversible, and <36 months on stavudine was significantly associated with atrophy reversal. The prevalence of hypertension and the yearly increase of mean blood pressure were disturbingly high in these patients. However, the number of patients in this study was limited, and prospective studies in larger cohorts are required to confirm these findings.