Abstract 607: Combined Intracerebroventricular Angiotensin-(1-7) and Candesartan Normalizes Blood Pressure and Improves Baroreflex Function in Transgenic (mRen2)27 Hypertensive Rats

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Manisha Nautiyal ◽  
Hossam A Shaltout ◽  
Mark C Chappell ◽  
Debra I Diz
Keyword(s):  
Blood Pressure ◽  
Arterial Pressure ◽  
Baroreflex Sensitivity ◽  
Low Frequency ◽  
Systolic Arterial Pressure ◽  
Therapeutic Benefit ◽  
Receptor Blockade ◽  
Artificial Cerebrospinal Fluid ◽  
Cardiovascular Pathologies ◽  
Sympathovagal Imbalance

Transgenic (mRen2)27 rats that over express the murine Ren2 gene are hypertensive and have impaired baroreflex sensitivity (BRS) for control of heart rate (HR). We previously showed that infusion of central angiotensin-(1-7) [Ang-(1-7)] improved the vagal components of the BRS independent of altering mean arterial pressure (MAP) but that, AT 1 receptor blockade normalized MAP and blood pressure variability (BPV) without correcting the BRS. To determine if the overall sympathovagal imbalance and the BRS function can be corrected by supplementing Ang-(1-7) in combination with AT 1 receptor blockade, we compared intracerebroventricular (ICV) infusions of the AT 1 receptor antagonist candesartan (CV: 4 ug/5uL/hr) and Ang-(1-7) [0.1 ug/5uL/hr; n = 4] or artificial cerebrospinal fluid (aCSF; 5 uL/hr; n = 8) for 4 weeks in 18 week old male (mRen2)27 rats. MAP was significantly reduced in CV/ Ang-(1-7) treated rats [71 ± 13 vs. aCSF: 132 ± 12 mm Hg; p = 0.01] with no changes in HR. Lowering of MAP was associated with a reduction in low frequency systolic arterial pressure, an index of BPV, [LF-SAP%: 32 ± 8 vs. aCSF: 73 ± 10, p = 0.02] in these animals. Both vagal [high frequency alpha: 1.1 ± 0.3 vs. aCSF: 0.6 ± 0.1, p= 0.05 and Sequence UP: 1.7 ± 0.4 vs. aCSF: 0.7 ± 0.1, p= 0.03] and sympathetic [low frequency alpha: 0.65 ± 0.14 vs. aCSF: 0.34 ± 0.03, p= 0.02 and Sequence DOWN: 1.4 ± 0.3 vs. aCSF: 0.76 ± 0.1, p= 0.01] components of the BRS were significantly increased resulting in improvements in the overall BRS [Sequence ALL: 1.6 ± 0.3 vs. aCSF: 0.75 ± 0.1, p= 0.01] as well as the sympathovagal imbalance [LF RRI /HF RRI : 0.2 ± 0.1 vs. aCSF: 2.3 ± 0.6, p= 0.004] in treated animals. Thus, combination ICV therapy normalized MAP and corrected the sympathovagal imbalance leading to improved BRS function. Since impaired BRS significantly associates with cardiovascular pathologies independently from hypertension, specifically targeting an increase in central Ang-(1-7) with reduced Ang II actions to provide improved BRS and lower MAP may achieve a more optimal therapeutic benefit.

Measuring baroreflex sensitivity from the gain function between arterial pressure and heart period

2002 ◽  
Vol 103 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Gian Domenico PINNA ◽  
Roberto MAESTRI ◽  
Grzegorz RACZAK ◽  
Maria Teresa LA ROVERE
Keyword(s):  
Arterial Pressure ◽  
Frequency Band ◽  
Baroreflex Sensitivity ◽  
Low Frequency ◽  
Systolic Arterial Pressure ◽  
Normal Subjects ◽  
Heart Period ◽  
Gain Function ◽  
Limits Of Agreement ◽  
Spectral Technique

We tested an innovative approach for estimating baroreflex sensitivity (BRS) from the gain function between spontaneous oscillations of systolic arterial pressure (SAP) and heart period (HP). The major goal was to assess the practical implications of abandoning the classical coherence criterion (⩾0.5) as regards measurability of BRS, and agreement with values of BRS obtained using the phenylephrine test (Phe-BRS). We studied 19 normal subjects, 44 patients with a history of previous myocardial infarction (MI) and 45 patients with chronic heart failure (CHF). The experimental protocol included recording of SAP and HP for 10min of supine rest, and evaluation of Phe-BRS. From resting SAP and HP, the gain and coherence functions were computed. The new BRS index was obtained in all subjects by averaging the gain function over the whole low-frequency band (0.04-0.15Hz) (whole-band average BRS, WBA-BRS). WBA-BRS was 7.4 (5.8-10.8)ms/mmHg [median (25th-75th percentile)] in normal controls, 3.1 (1.4-5.4)ms/mmHg in MI patients (P<0.001 compared with normals) and 5.0 (3.2-6.9)ms/mmHg in CHF patients (P<0.01 compared with normals). Using the coherence criterion, BRS could be measured in only 43% and 49% of MI and CHF patients respectively, and the proportion of the low-frequency band contributing to the measurement was 21% (14-47%) and 29% (16-35%) respectively. The correlation between WBA-BRS and Phe-BRS was 0.47, 0.63 and 0.36 in the normal, MI and CHF groups respectively (all P<0.001). The relative bias of WBA-BRS was -5.2ms/mmHg (P<0.001) in normals, -1.4ms/mmHg (P = 0.004) in MI patients and -1.0ms/mmHg (P = 0.11) in CHF patients. The limits of agreement were -13 to 2.6, -7.4 to 4.6 and -9.3 to 7.3ms/mmHg in the normal, MI and CHF groups respectively. Thus the WBA-BRS method standardizes the computation of BRS among subjects, and dramatically increases its measurability in subjects with pathology compared with the classical spectral technique based on the coherence criterion. Compared with Phe-BRS, WBA-BRS tends to give negatively biased results. The correlation and the magnitude of the limits of agreement between the two methods are similar to those observed previously using coherence-based spectral methods.

Effect of heavy exercise on spectral baroreflex sensitivity, heart rate, and blood pressure variability in well-trained humans

2008 ◽  
Vol 295 (3) ◽  
pp. H1150-H1155 ◽  
Author(s):  
François Cottin ◽  
Claire Médigue ◽  
Yves Papelier
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Systolic Blood Pressure ◽  
Exercise Test ◽  
Blood Pressure Variability ◽  
Baroreflex Sensitivity ◽  
Low Frequency ◽  
Mechanical Effect ◽  
Heavy Exercise ◽  
Gas Exchange Parameters

The aim of the study was to assess the instantaneous spectral components of heart rate variability (HRV) and systolic blood pressure variability (SBPV) and determine the low-frequency (LF) and high-frequency baroreflex sensitivity (HF-BRS) during a graded maximal exercise test. The first hypothesis was that the hyperpnea elicited by heavy exercise could entail a significant increase in HF-SBPV by mechanical effect once the first and second ventilatory thresholds (VTs) were exceeded. It was secondly hypothesized that vagal tone progressively withdrawing with increasing load, HF-BRS could decrease during the exercise test. Fifteen well-trained subjects participated in this study. Electrocardiogram (ECG), blood pressure, and gas exchanges were recorded during a cycloergometer test. Ventilatory equivalents were computed from gas exchange parameters to assess VTs. Spectral analysis was applied on cardiovascular series to compute RR and systolic blood pressure power spectral densities, cross-spectral coherence, gain, and α index of BRS. Three exercise intensity stages were compared: below (A1), between (A2), and above (A3) VTs. From A1 to A3, both HF-SBPV (A1: 45 ± 6, A2: 65 ± 10, and A3: 120 ± 23 mm2Hg, P < 0.001) and HF-HRV increased (A1: 20 ± 5, A2: 23 ± 8, and A3:40 ± 11 ms2, P < 0.02), maintaining HF-BRS (gain, A1: 0.68 ± 0.12, A2: 0.63 ± 0.08, and A3: 0.57 ± 0.09; α index, A1: 0.58 ± 0.08, A2: 0.48 ± 0.06, and A3: 0.50 ± 0.09 ms/mmHg, not significant). However, LF-BRS decreased (gain, A1: 0.39 ± 0.06, A2: 0.17 ± 0.02, and A3: 0.11 ± 0.01, P < 0.001; α index, A1: 0.46 ± 0.07, A2: 0.20 ± 0.02, and A3: 0.14 ± 0.01 ms/mmHg, P < 0.001). As expected, once VTs were exceeded, hyperpnea induced a marked increase in both HF-HRV and HF-SBPV. However, this concomitant increase allowed the maintenance of HF-BRS, presumably by a mechanoelectric feedback mechanism.

scholarly journals Physiological Sympathetic Activation Reduces Systemic Inflammation: Role of Baroreflex and Chemoreflex

2021 ◽  
Vol 12 ◽  
Author(s):  
Fernanda Brognara ◽  
Jaci Airton Castania ◽  
Alexandre Kanashiro ◽  
Daniel Penteado Martins Dias ◽  
Helio Cesar Salgado
Keyword(s):  
Nervous System ◽  
Arterial Pressure ◽  
Systemic Inflammation ◽  
Inflammatory Responses ◽  
Low Frequency ◽  
Systolic Arterial Pressure ◽  
Sympathetic Activation ◽  
Bilateral Carotid Occlusion ◽  
Bilateral Carotid ◽  
Reflex Activation

Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects of reflex physiological sympathetic activation in endotoxemic rats using bilateral carotid occlusion (BCO), a physiological approach involving the baroreflex and chemoreflex mechanisms and the influence of the baroreceptors and peripheral chemoreceptors in the cardiovascular and systemic inflammatory responses. After lipopolysaccharide (LPS) administration, the arterial pressure was recorded during 360 min in unanesthetized rats, and serial blood samples were collected to analyze the plasma cytokine levels. BCO elicited the reflex activation of the sympathetic nervous system, providing the following outcomes: (I) increased the power of the low-frequency band in the spectrum of the systolic arterial pressure during the BCO period; (II) reduced the levels of pro-inflammatory cytokines in plasma, including the tumor necrosis factor (TNF) and the interleukin (IL)-1β; (III) increased the plasma levels of anti-inflammatory cytokine IL-10, 90 min after LPS administration. Moreover, selective baroreceptor or chemoreceptor denervation deactivated mechanosensitive and chemical sensors, respectively, and decreased the release of the LPS-induced cytokine but did not alter the BCO modulatory effects. These results show, for the first time, that physiological reflex activation of the sympathetic circuit decreases the inflammatory response in endotoxemic rats and suggest a novel function for the baroreceptors as immunosensors during the systemic inflammation.

Age dependency of cardiovascular autonomic responses to head-up tilt in healthy subjects

2004 ◽  
Vol 96 (6) ◽  
pp. 2333-2340 ◽  
Author(s):  
Tomi Laitinen ◽  
Leo Niskanen ◽  
Ghislaine Geelen ◽  
Esko Länsimies ◽  
Juha Hartikainen
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
High Frequency ◽  
Healthy Subjects ◽  
Baroreflex Sensitivity ◽  
Low Frequency ◽  
Upright Position ◽  
Vascular Responses ◽  
Autonomic Responses ◽  
Head Up Tilt

In elderly subjects, heart rate responses to postural change are attenuated, whereas their vascular responses are augmented. Altered strategy in maintaining blood pressure homeostasis during upright position may result from various cardiovascular changes, including age-related cardiovascular autonomic dysfunction. This exploratory study was conducted to evaluate impact of age on cardiovascular autonomic responses to head-up tilt (HUT) in healthy subjects covering a wide age range. The study population consisted of 63 healthy, normal-weight, nonsmoking subjects aged 23–77 yr. Five-minute electrocardiogram and finger blood pressure recordings were performed in the supine position and in the upright position 5 min after 70° HUT. Stroke volume was assessed from noninvasive blood pressure signals by the arterial pulse contour method. Heart rate variability (HRV) and systolic blood pressure variability (SBPV) were analyzed by using spectral analysis, and baroreflex sensitivity (BRS) was assessed by using sequence and cross-spectral methods. Cardiovascular autonomic activation during HUT consisted of decreases in HRV and BRS and an increase in SBPV. These changes became attenuated with aging. Age correlated significantly with amplitude of HUT-stimulated response of the high-frequency component ( r = -0.61, P < 0.001) and the ratio of low-frequency to high-frequency power of HRV ( r = -0.31, P < 0.05) and indexes of BRS (local BRS: r = -0.62, P < 0.001; cross-spectral baroreflex sensitivity in the low-frequency range: r = -0.38, P < 0.01). Blood pressure in the upright position was maintained well irrespective of age. However, the HUT-induced increase in heart rate was more pronounced in the younger subjects, whereas the increase in peripheral resistance was predominantly observed in the older subjects. Thus it is likely that whereas the dynamic capacity of cardiac autonomic regulation decreases, vascular responses related to vasoactive mechanisms and vascular sympathetic regulation become augmented with increasing age.

Abstract 498: Increased Blood Pressure Variability and Baroreflex Impairment in Patients With End-stage Renal Disease Undergoing Hemodialysis

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Kátia B Scapini ◽  
Valéria C Hong ◽  
Janaína B Ferreira ◽  
Sílvia B Souza ◽  
Naomi V Ferreira ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Blood Pressure Variability ◽  
Baroreflex Sensitivity ◽  
Low Frequency ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients ◽  
Alpha Index

Background: Patients with end-stage renal disease (ESRD) undergoing hemodialysis are susceptible to the development of autonomic dysfunction, which is associated with an increased risk of sudden death. Experimental and clinical evidence suggest a crucial role of autonomic dysfunction for both, the progression of renal disease and for the high rate of cardiovascular events in these patients. In the present study, we evaluated the heart rate variability (HRV), the blood pressure variability (BPV) and the baroreflex sensitivity (BRS) in ESRD patients undergoing hemodialysis and normal controls. Methods: Nine ESRD patients undergoing hemodialysis (mean age 53.4±10.2 years, 4 male) and nine age-matched healthy controls (mean age 52.8±10.2 years, 4 male) were assessed. Non−invasive curves of blood pressure (BP) were recorded continuously (Finometer ®) for 10 minutes, at rest, in the supine position. The heart rate variability (HRV) and systolic blood pressure variability (BPV) were estimated in the time and frequency domain (spectral analysis). The BRS was quantified by alpha index. Statistical analyzes were performed by Student's t test and the results were expressed as mean ± standard deviation. Results: ESRD patients presented lower HRV in time domain than healthy controls (SDNN: 25.8±10.7 vs. 44.6±11.7 ms, p<0.01; VAR NN: 768.3±607.4 vs. 2113.9±1261.6 ms 2 , p=0.01). All frequency domain analyzed indexes, i.e., total power (361.9±297.0 vs. 1227.2±696.3 ms 2 , p<0.01), high-frequency (181.8±128.7 vs. 358.7±179.8 ms 2 , p=0.047), low-frequency (55.1±44.2 vs. 444.6±389.9 ms 2 , p=0.02) and very-low-frequency (72.5±75.1 vs. 279.2±119.5 ms 2 , p<0.01) of HRV were lower in ESRD patients. The BPV was higher in ESRD patients when compared to controls (VAR PAS: 98.4±72.0 vs. 35.4±21.4 ms 2 , p=0.03) and BRS was lower in ESRD patients (alpha index: 4.34±3.05 vs. 7.56±2.50 ms/mmHg, p<0.02). Conclusion: ESRD patients undergoing hemodialysis presents reduced HRV, increase in BPV and reduced baroreflex sensitivity. These impairments may be associated with mortality in ESRD.

Comparison of phenylephrine bolus and infusion methods in baroreflex measurements

1990 ◽  
Vol 69 (3) ◽  
pp. 962-967 ◽  
Author(s):  
J. T. Sullebarger ◽  
C. S. Liang ◽  
P. D. Woolf ◽  
A. E. Willick ◽  
J. F. Richeson
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Baroreflex Sensitivity ◽  
Heart Rate Response ◽  
Pressor Response ◽  
Plasma Catecholamines ◽  
Systolic Arterial Pressure ◽  
Normal Subjects ◽  
Vagus Nerves ◽  
Baroreflex Control

Phenylephrine (PE) bolus and infusion methods have both been used to measure baroreflex sensitivity in humans. To determine whether the two methods produce the same values of baroreceptor sensitivity, we administered intravenous PE by both bolus injection and graded infusion methods to 17 normal subjects. Baroreflex sensitivity was determined from the slope of the linear relationship between the cardiac cycle length (R-R interval) and systolic arterial pressure. Both methods produced similar peak increases in arterial pressure and reproducible results of baroreflex sensitivity in the same subjects, but baroreflex slopes measured by the infusion method (9.9 +/- 0.7 ms/mmHg) were significantly lower than those measured by the bolus method (22.5 +/- 1.8 ms/mmHg, P less than 0.0001). Pretreatment with atropine abolished the heart rate response to PE given by both methods, whereas plasma catecholamines were affected by neither method of PE administration. Naloxone pretreatment exaggerated the pressor response to PE and increased plasma beta-endorphin response to PE infusion but had no effect on baroreflex sensitivity. Thus our results indicate that 1) activation of the baroreflex by the PE bolus and infusion methods, although reproducible, is not equivalent, 2) baroreflex-induced heart rate response to a gradual increase in pressure is less than that seen with a rapid rise, 3) in both methods, heart rate response is mediated by the vagus nerves, and 4) neither the sympathetic nervous system nor the endogenous opiate system has a significant role in mediating the baroreflex control of heart rate to a hypertensive stimulus in normal subjects.

scholarly journals Sex differences in blood pressure responsiveness to spontaneous K-complexes during stage II sleep

2020 ◽  
Author(s):  
Ian Mark Greenlund ◽  
Carl A. Smoot ◽  
Jason R. Carter
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arterial Pressure ◽  
Cardiac Cycle ◽  
Pressor Response ◽  
Systolic Arterial Pressure ◽  
Stage Ii ◽  
Men And Women ◽  
Blood Pressures ◽  
Blood Pressure Responses

K-complexes are a key marker of non-rapid eye movement sleep (NREM), specifically during stages II sleep. Recent evidence suggests the heart rate responses to a K-complexes may differ between men and women. The purpose of this study was to compare beat-to-beat blood pressure responses to K-complexes in men and women. We hypothesized that the pressor response following a spontaneous K-complex would be augmented in men compared to women. Ten men (Age: 23 ± 2 years, BMI: 28 ± 4 kg/m2) and ten women (Age: 23 ± 5 years, BMI: 25 ± 4 kg/m2) were equipped with overnight finger plethysmography and standard 10-lead polysomnography. Hemodynamic responses to a spontaneous K-complex during stable stage II sleep were quantified for 10 consecutive cardiac cycles, and measurements included systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and heart rate. K-complex elicited greater pressor responses in men when blood pressures were expressed as SAP (cardiac cycle × sex: p = 0.007) and DAP (cardiac cycle × sex: p = 0.004). Heart rate trended to be different between men and women (cardiac cycle × sex: p = 0.078). These findings suggest a divergent pressor response between men and women following a spontaneous K-complex during normal stage II sleep. These findings could contribute to sex-specific differences in cardiovascular risk that exist between men and women.

scholarly journals A Comparison of Three Fluid-Vasopressor Regimens Used to Prevent Hypotension during Subarachnoid Anaesthesia in the Elderly

1998 ◽  
Vol 26 (5) ◽  
pp. 497-502 ◽  
Author(s):  
J. C. M. Yap ◽  
L. A. H. Critchley ◽  
S. C. Yu ◽  
R. M. Calcroft ◽  
J. L. Derrick
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arterial Pressure ◽  
Elderly Patients ◽  
Hip Fractures ◽  
Normal Saline ◽  
Computer Software ◽  
Systolic Arterial Pressure ◽  
The Elderly ◽  
Group A

We aimed to compare the efficacy of fluid preloading with two recently recommended fluid-vasopressor regimens for maintaining blood pressure during subarachnoid anaesthesia in the elderly. Sixty elderly patients requiring surgery for traumatic hip fractures received subarachnoid anaesthesia using 0.05 ml/kg of 0.5% heavy bupivacaine. Hypotension, i.e. systolic arterial pressure <75% of baseline, was prevented or treated by: A—normal saline 16 ml/kg plus intravenous ephedrine boluses (0.1 mg/kg); B—normal saline 8 ml/kg plus intramuscular depot ephedrine (0.5 mg/kg); or C—Haemaccel 8 ml/kg plus metaraminol infusion. Systolic arterial pressure and heart rate were recorded using custom-written computer software (Monitor, version 1.0). Systolic arterial pressure decreased in all groups after five minutes (P<0.001). Decreases were greatest in group A (P<0.05). Heart rate increased by 7% group A and decreased by 9% in group C (P<0.05). During the first hour, hypotension was present for 47%, 25% and 20% of the time in groups A, B and C respectively and overcorrection of systolic arterial pressure occurred in 19% of the time in group C. We conclude that treatment A was inadequate in preventing hypotension. Treatments B and C were more effective but were associated with an increased heart rate and overcorrection of systolic arterial pressure respectively.

Association between decreased blood pressure and azotaemia in canine babesiosis

2014 ◽  
Vol 17 (1) ◽  
pp. 173-175 ◽  
Author(s):  
W. Zygner ◽  
O. Gójska-Zygner
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Serum Creatinine ◽  
Renal Damage ◽  
Systolic Arterial Pressure ◽  
Babesia Canis ◽  
Canine Babesiosis ◽  
Tubular Necrosis ◽  
Blood Pressures

Abstract Acute tubular necrosis (ATN) was described in canine babesiosis. Hypotension is considered as one of the factors which influence the development of hypoxic renal damage. In this study hypotension defined as mean arterial pressure (MAP) < 80 mmHg was detected in 7 out of 48 dogs (14.6%) infected with Babesia canis. Lower systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and MAP were detected in azotaemic dogs infected with B. canis. Statistically significant negative correlations between blood pressures (SAP, DAP and MAP) and serum creatinine and urea concentrations showed the influence of decreased blood pressure on the development of azotaemia and is probably also associated with ATN in canine babesiosis.

Profound Increase in Epinephrine Concentration in Plasma and Cardiovascular Stimulation after [micro sign]-Opioid Receptor Blockade in Opioid-addicted Patients during Barbiturate-induced Anesthesia for Acute Detoxification 

1998 ◽  
Vol 88 (5) ◽  
pp. 1154-1161 ◽  
Author(s):  
Peter Kienbaum ◽  
Norbert Thurauf ◽  
Martin C. Michel ◽  
Norbert Scherbaum ◽  
Markus Gastpar ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Index ◽  
Arterial Pressure ◽  
Opioid Receptor ◽  
Resistance Index ◽  
Systolic Arterial Pressure ◽  
Mu Opioid Receptor ◽  
Receptor Blockade ◽  
Mu Opioid ◽  
A Minor

Background Acute displacement of opioids from their receptors by administration of large doses of opioid antagonists during general anesthesia is a new approach for detoxification of patients addicted to opioids. The authors tested the hypothesis that mu-opioid receptor blockade by naloxone induces cardiovascular stimulation mediated by the sympathoadrenal system. Methods Heart rate, cardiac index, and intravascular pressures were measured in 10 patients addicted to opioids (drug history; mean +/- SD, 71 +/- 51 months) during a program of methadone substitution (96 +/- 57 mg/day). Cardiovascular variables and concentrations of catecholamine in plasma were measured in the awake state, during methohexital-induced anesthesia (dose, 74 +/- 44 microg x kg(-1) x min(-1)) before administration of naloxone, and repeatedly during the first 3 h of mu-opioid receptor blockade. Naloxone was administered initially in an intravenous dose of 0.4 mg, followed by incremental bolus doses (0.8, 1.6, 3.2, and 6.4 mg) at 15-min intervals until a total dose of 12.4 mg had been administered within 60 min; administration was then continued by infusion (0.8 mg/h). Results Concentration of epinephrine in plasma increased 30-fold (15 +/- 9 to 458 +/- 304 pg/ml), whereas concentration of norepinephrine in plasma only increased to a minor extent (76 +/- 44 to 226 +/- 58 pg/ml, P &lt; 0.05). Cardiac index increased by 74% (2.7 +/- 0.41 to 4.7 +/- 1.7 min(-1) x m(-2)), because of increases in heart rate (89 +/- 16 to 108 +/- 17 beats/min) and stroke volume (+44%), reaching maximum 45 min after the initial injection of naloxone. In parallel, systemic vascular resistance index decreased (-40%). Systolic arterial pressure significantly increased (113 +/- 16 to 138 +/- 16 mmHg), whereas diastolic arterial pressure did not change. Conclusions Despite barbiturate-induced anesthesia, acute mu-opioid receptor blockade in patients addicted to opioids induces profound epinephrine release and cardiovascular stimulation. These data suggest that long-term opioid receptor stimulation changes sympathoadrenal and cardiovascular function, which is acutely unmasked by mu-opioid receptor blockade. Because of the attendant cardiovascular stimulation, acute detoxification using naloxone should be performed by trained anesthesiologists or intensivists.

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