Moxonidine normalizes sympathetic hyperactivity in patients with eprosartan-treated chronic renal failure

Enalapril and losartan reduce but not normalize sympathetic hyperactivity in patients with hypertensive chronic renal failure (CRF). This study assessed the effect of chronic eprosartan on BP and sympathetic activity, and assessed the effect of moxonidine during chronic eprosartan treatment. In 11 stable patients with CRF (creatinine clearance 47 +/- 10 ml/min), muscle sympathetic nerve activity (MSNA; peroneal nerve), BP, and baroreceptor sensitivity were measured in the absence of antihypertensive drugs (except diuretics) during chronic eprosartan therapy (600 mg for 6 wk) and in 9 patients after moxonidine (0.2 mg for 6 wk) was added. Normovolemia was controlled by diuretics and confirmed by extracellular fluid volume measurements. BP, heart rate, and MSNA were higher in patients than in 22 controls. During eprosartan therapy, mean arterial pressure (111 +/- 9 to 98 +/- 7 mmHg, P < 0.001), heart rate (71 +/- 10 to 65 +/- 8 bpm, P < 0.001), and MSNA (35 +/- 10 to 27 +/- 8 bursts/min, P < 0.001) decreased. After the addition of moxonidine (n = 9), a further reduction of mean arterial pressure to 89 +/- 7 mmHg (P < 0.05) and of MSNA to 20 +/- 10 bursts/min (P < 0.05) occurred. Sympathetic activity in patients with CRF can be normalized, and angiotensin II-independent sympathetic hyperactivity contributes to the pathogenesis of renal hypertension. Sympathetic hyperactivity is associated with poor cardiovascular outcomes, implying that reduction might be beneficial to the patients. The addition of moxonidine to angiotensin II antagonist treatment might be appropriate.     

Suppressive effects of remifentanil on hemodynamics in baro-denervated rabbits

PURPOSE: To elucidate mechanisms by which remifentanil, an ultra-short-acting mu-opioid receptor agonist, causes hypotension and bradycardia. METHODS: Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were measured and recorded after bolus injections of 1, 2 or 5 microg x kg(-1) of remifentanil in neuraxis intact (n=6 for each dose) and baro-denervated rabbits (n=6 for each dose). Arterial baroreflex sensitivity was assessed by depressor tests. An additional six baro-denervated animals received remifentanil, 5 microg x kg(-1) after pretreatment with naloxone, 40 microg x kg(-1). RESULTS: All values were expressed in % change from baseline. In the neuraxis intact animals, MAP and HR were decreased briefly immediately after remifentanil injection. RSNA was increased dose-dependently: 137 +/- 8% (mean +/- SE), 170 +/- 14% (P < 0.05) and 225 +/- 29% (P < 0.05) after 1, 2 and 5 microg x kg(-1) remifentanil, respectively. RSNA was increased even after MAP and HR had returned to baseline values. The depressor tests revealed that remifentanil did not attenuate arterial baroreflex sensitivity. In the baro-denervated animals, MAP and HR decreased gradually to 77 +/- 3% (P < 0.05) and 94 +/- 1% (P < 0.05), respectively 300 sec after 5 microg x kg(-1) remifentanil. At that time, increased RSNA (159 +/- 9%, P < 0.05) had returned to baseline. Pretreatment with naloxone in the baro-denervated animals abolished these changes. CONCLUSION: Remifentanil decreases HR and MAP by its central vagotonic effect and by stimulating peripheral mu-opioid receptors. These effects appear to be counteracted and masked by its central sympathotonic effect and by maintaining arterial baroreflex integrity.     

Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure

The aim of this study was to compare the effects on BP and sympathetic activity of chronic treatment with an angiotensin (Ang)-converting enzyme (ACE) inhibitor and an AngII receptor blocker in hypertensive patients with chronic renal failure (CRF). In ten stable hypertensive CRF patients (creatinine clearance, 46 +/- 17 ml/min per 1.73 m(2)), muscle sympathetic nerve activity (MSNA), plasma renin activity (PRA), baroreceptor sensitivity, and 24-h ambulatory BP were measured in the absence of antihypertensive drugs (except diuretics) after 6 wk of enalapril (10 mg orally) and after 6 wk of losartan (100 mg orally). The order of the three phases was randomized. Normovolemia was controlled with diuretics and confirmed with extracellular fluid volume measurements throughout the study. Both enalapril and losartan reduced MSNA (from 33 +/- 10 to 27 +/- 13 and 27 +/- 13 bursts/min, respectively; P < 0.05) and average 24-h BP (from 141 +/- 8/93 +/- 8 to 124 +/- 9/79 +/- 8 and 127 +/- 8/81 +/- 9 mmHg; P < 0.01). PRA was not different during the treatments. The change in BP and the change in MSNA during the treatments were correlated (r = 0.70 and r = 0.63, respectively; both P < 0.05). Baroreceptor sensitivity was not affected by the treatments. This is the first study to compare the effects of ACE inhibition and AngII blockade on MSNA. In hypertensive CRF patients, enalapril and losartan equally reduced BP and MSNA. Differences in modes of action of the two drugs did not result in differences in effects on MSNA, supporting the view that AngII-mediated mechanisms contribute importantly in the pathogenesis of sympathetic hyperactivity in these patients.     

Desflurane-mediated Sympathetic Activation Occurs in Humans Despite Preventing Hypotension and Baroreceptor Unloading

Background: Increasing concentrations of desflurane result in progressive decreases in blood pressure (BP) and, unlike other currently marketed, potent volatile anesthetics, heightened sympathetic nervous system activity. This study aimed to determine whether baroreflex mechanisms are involved in desflurane-mediated sympathetic excitation.

Methods: Healthy volunteers were anesthetized with desflurane (n = 8) or isoflurane (n = 9). Heart rate (HR; measured by electrocardiograph), blood pressure (BP; measured by arterial catheter), and efferent sympathetic nerve activity (SNA; obtained from percutaneous recordings from the peroneal nerve) were monitored. Baroreflex sensitivity was evaluated at baseline while volunteers were conscious and during 0.5, 1, and 1.5 minimum alveolar concentration (MAC) anesthesia via bolus injections of nitroprusside (100 micro gram) and phenylephrine (150 micro gram) to decrease and increase BP. To prevent the BP decline with increasing depths of anesthesia, phenylephrine was infused to maintain mean BP at the 0.5 MAC level.

Results: The HR, BP, and SNA were similar between the groups at the conscious baseline measurement. Efferent SNA did not change during higher MAC of isoflurane, but it increased progressively as desflurane concentrations were increased beyond 0.5 MAC, despite maintaining BP at the 0.5 MAC value with phenylephrine infusions (P < 0.05). Cardiac baroslopes (based on changes in HR) were progressively and similarly decreased with increasing concentrations of isoflurane and desflurane (P < 0.05). Sympathetic baroslopes (based on SNA) decreased with increasing isoflurane concentrations but were maintained with increasing concentrations of desflurane; the response was significantly different between groups.     

Acute device-based blood pressure reduction: electrical activation of the carotid baroreflex in patients undergoing elective carotid surgery

Carotid sinus baroreceptors are involved in controlling blood pressure (BP) by providing input to the cardiovascular regulatory centers of the medulla. The acute effect of temporarily placing an electrode on the carotid sinus wall to electrically activate the baroreflex was investigated. We studied 11 patients undergoing elective carotid surgery. Baseline BP was 146+30/66+/-17 mm Hg and heart rate (HR) 72+/-7 bpm (mean +/- standard deviation). An electrode was placed upon the carotid sinus and after obtaining a steady state baseline of BP and HR, an electric current was applied and increased in 1-volt increments. A voltage dependent and highly significant reduction in BP was observed which averaged 18+/-26* and 8.0+/-12 mm Hg for systolic BP and diastolic BP, respectively. Maximal reductions occurred at 4.4+/-1.2 V: 23+/-24 mm Hg*, 16+/-10 mm Hg* and 7+/-12 bpm* for systolic BP, diastolic BP and HR, respectively ( = p <.05). Thus, electrical stimulation of the carotid sinus activates the carotid baroreflex resulting in a reduction in BP and HR. This presents a proof of concept for device based baroreflex modulation in acute BP regulation and adds to the available data which provide a rationale for evaluating this system in the context of chronic BP reduction in hypertensive patients.     

Arterial pulse pressure and its association with reduced stroke volume during progressive central hypovolemia

BACKGROUND: The reduction of stroke volume (SV) during hemorrhage reflects the degree of blood loss, but accurate assessment of SV in bleeding patients in the field currently is not possible. In a previous pilot study, we reported that arterial pulse pressure and estimated sympathetic nerve activity (SNA) in trauma patients who died of hemorrhagic injuries was significantly lower than that observed in patients who did not die. For the current study, we measured mean arterial blood pressure (MAP), pulse pressure (PP), SV, and muscle sympathetic nerve activity (MSNA) in human subjects during progressive lower body negative pressure (LBNP) to test the hypothesis that a reduction in PP tracks the reduction of SV and change in MSNA during graded central hypovolemia in humans. METHODS: After a 12-minute baseline data collection period, 13 men were exposed to LBNP at -15 mm Hg for 12 minutes followed by continuous stepwise increments to -30, -45, and -60 mm Hg for 12 minutes each. RESULTS: Comparing baseline to -60 mm Hg chamber decompression, systolic blood pressure (SBP) decreased (from 129 +/- 3.0 to 111 +/- 6.1 mm Hg; p = 0.005) and diastolic pressure was unchanged (78 +/- 3.0 versus 81 +/- 4.0 mm Hg; p = 0.55). Pulse pressure decreased (from 50 +/- 2.5 to 29 +/- 4.0 mm Hg; p = 0.0001). LBNP caused linear reductions in PP and SV (from 125 +/- 9.2 to 47 +/- 6.4; r2 = 0.99), and increases in MSNA (from 14 +/- 3.5 to 36 +/- 4.6 bursts/min; r2 = 0.96) without a significant change in MAP (r2 = 0.28). PP was inversely correlated with MSNA (r2 = 0.88) and positively correlated with SV (r2 = 0.91). CONCLUSIONS: Reduced PP resulting from progressive central hypovolemia is a marker of reductions in SV and elevations in SNA. Therefore, when SBP is >90 mm Hg, PP may allow for early, noninvasive identification of volume loss because of hemorrhage and more accurate and timely triage.     

Epidural clonidine suppresses the baroreceptor-sympathetic response depending on isoflurane concentrations in cats

Epidural administration of clonidine induces hypotension and bradycardia secondary to decreased sympathetic nerve activity. In this study, we sought to elucidate the change in baroreflex response caused by epidural clonidine. Thirty-six cats were allocated to six groups (n = 6 each) and were given either thoracic epidural clonidine 4 micro g/kg or lidocaine 2 mg/kg during 0.5, 1.0, or 1.5 minimum alveolar anesthetic concentration (MAC) isoflurane anesthesia. Heart rate (HR), mean arterial blood pressure (MAP), and cardiac sympathetic nerve activity (CSNA) were measured. Depressor and pressor responses were induced by IV nitroprusside 10 micro g/kg and phenylephrine 10 micro g/kg, respectively. Baroreflex was evaluated by the change in both CSNA and HR relative to the peak change in MAP (deltaCSNA/deltaMAP and deltaHR/deltaMAP, respectively). These measurements were performed before and 30 min after epidural drug administration. Epidural clonidine and lidocaine decreased HR, MAP, and CSNA by similar extents. deltaCSNA/deltaMAP and deltaHR/deltaMAP for depressor response were suppressed with epidural lidocaine and clonidine in all groups but the clonidine 0.5 MAC isoflurane group (0.197 +/- 0.053 to 0.063 +/- 0.014 and 0.717 +/- 0.156 to 0.177 +/- 0.038, respectively, by epidural lidocaine [P < 0.05] but 0.221 +/- 0.028 to 0.164 +/- 0.041 and 0.721 +/- 0.177 to 0.945 +/- 0.239, respectively, by epidural clonidine during 0.5 MAC isoflurane). Those for pressor response were suppressed in all groups. We conclude that thoracic epidural clonidine suppresses baroreflex gain during isoflurane anesthesia >1.0 MAC but may offer certain advantages compared with epidural lidocaine during 0.5 MAC isoflurane by virtue of preserving baroreflex sensitivity when inadvertent hypotension occurs.     

Isoflurane depresses baroreflex control of heart rate in decerebrate rats

BACKGROUND: Isoflurane inhibits baroreflex control of heart rate (HR) by poorly understood mechanisms. The authors examined whether suprapontine central nervous system cardiovascular regulatory sites are required for anesthetic depression. METHODS: The effects of isoflurane (1 and 2 rat minimum alveolar concentration [MAC]) on the baroreflex control of HR were determined in sham intact and midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12 microg/kg) and nitroprusside (1-60 microg/kg) were used to measure HR responses to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact and two decerebrate) were studied before, during, and after isoflurane. To assess sympathetic and vagal contributions to HR baroreflex, beta-adrenoceptor (1 mg/kg atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered systemically. RESULTS: Decerebration did not alter resting MAP and HR or baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by depressing peak reflex tachycardia. Maximal reflex bradycardia during increases in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and decreased BP50 in both groups. CONCLUSIONS: Isoflurane depresses HR baroreflex control by actions that do not require suprapontine central nervous system sites. Isoflurane actions seem to inhibit HR baroreflex primarily by the sympathetic nervous system.     

Anesthesiologists and acute perioperative stress: a cohort study

Previous studies have indicated that many anesthesiologists exhibit symptoms of chronic stress. There is a paucity of data, however, regarding the existence of acute stress signs among anesthesiologists. Anesthesiologists from three practice settings (n = 38) were studied while they were anesthetizing 203 patients. Heart rate (HR) was recorded continuously and arterial blood pressure (BP) was measured hourly and immediately after each induction. Anxiety levels and salivary cortisol levels were also assessed after each induction. Comparison BP and HR data were obtained from the anesthesiologists during a nonclinical day. We found that anesthesiologists' HR increased during the anesthetic process compared with morning baseline HR (P = 0.008). This HR increase, however, was not clinically significant; the average HR during the anesthetic pro- cess ranged from 80 +/- 12 to 84 +/- 11 bpm. Similarly, although both systolic and diastolic BP after inductions were increased compared with baseline BP (P = 0.001), this increase was not clinically significant. In 9% of the inductions, however, systolic BP exceeded 140 mm Hg, and in 17% of all inductions, diastolic BP exceeded 90 mm Hg. Finally, the average BP of anesthesiologists during a clinical day was not different from the average BP during a nonclinical day (P = 0.9). Self-reported anxiety did not increase significantly after inductions (P = 0.15). An analysis of Holter tapes revealed no rhythm abnormalities and no signs of myocardial ischemia. We conclude that the practice of anesthesiology is associated with minor manifestations of acute physiologic stress during the perioperative process. IMPLICATIONS: Anesthesiologists experience minor psychologic stress while involved in the anesthetic process.     

Sympathetic activity is increased in polycystic kidney disease and is associated with hypertension.

Hypertension is common in patients with polycystic kidney disease (PKD). This study addresses the hypothesis that sympathetic activity is enhanced in hypertensive PKD patients, not only when renal function is impaired but also when renal function is still normal. Muscle sympathetic nerve activity (MSNA, peroneal nerve), plasma renin activity (PRA), heart rate, and BP were studied in PKD patients with normal and with impaired renal function and in matched controls. In hypertensive patients with normal renal function, MSNA and mean arterial pressure (MAP) were higher than in normotensive patients (23 +/- 5 versus 15 +/- 7 bursts/min; 110 +/- 10 versus 90 +/- 3 mmHg; P < 0.05), whereas PRA and heart rate did not differ. In PKD with chronic renal failure (CRF) (creatinine clearance rate, 39 +/- 19 ml/min), MAP, MSNA and PRA were higher than in controls (resp, 116 +/- 7 versus 89 +/- 9 mmHg; 34 +/- 14 versus 19 +/- 9 bursts/min; 405 [20 to 1640] versus 120 [40 to 730] fmol/L per sec; all P < 0.05). Heart rate in PKD CRF did not differ from controls. MSNA correlated with MAP (r = 0.42; P = 0.01) and age with MSNA (r = 0.45; P < 0.01). Regression line of age and MSNA in patients was steeper than that in controls. This study indicates that MSNA is increased in hypertensive PKD patients regardless of renal function. The data support the idea that sympathetic hyperactivity contributes to the pathogenesis of hypertension in PKD.     

The different effects of intravenous propofol and midazolam sedation on hemodynamic and heart rate variability

Heart rate (HR) and arterial blood pressure (BP) changes have been reported during conscious sedation with propofol and midazolam. One potential mechanism to explain these changes is that propofol and midazolam affect HR and BP via changes in the cardiac autonomic nervous system. Two specific hypotheses were tested by HR variability analysis: 1) propofol induces predominance of parasympathetic activity, leading to decreased HR and BP, and 2) midazolam induces predominance of sympathetic activity, leading to increased HR and decreased BP. Thirty dental patients were included in a prospective, randomized study. HR, BP, low frequency (LF), high frequency (HF), and entropy were monitored during the awake, sedation, and recovery periods and depth of sedation was assessed using the Observer's Assessment of Alertness/Sedation score. Propofol induced a significant decrease in total power (503 +/- 209 ms(2)/Hz versus 162 +/- 92 ms(2)/Hz) and LF/HF ratio (2.5 +/- 1.2 versus 1.0 +/- 0.4), despite the absence of any change in HR during the sedation period compared with baseline. Midazolam decreased normalized HF (34 +/- 10% versus 10 +/- 4%) but did not significantly change LF/HF ratio (2.3 +/- 1.1 versus 2.2 +/- 1.4) and increased HR in the sedation period. Compared with baseline, propofol was associated with a significant increase in normalized HF in the recovery period (34 +/- 11% versus 44 +/- 12%) and a significant decrease in HR, whereas midazolam was associated with an increase in LF/HF ratio (2.3 +/- 1.1 versus 3.7 +/- 1.8) with no change in HR. These results indicated a dominant parasympathetic effect of propofol and a dominant sympathetic effect of midazolam in both periods. These results should be considered during conscious sedation, especially in patients at risk of cardiovascular complications.     

Isoflurane Depresses Baroreflex Control of Heart Rate in Decerebrate Rats

Background: Isoflurane inhibits baroreflex control of heart rate (HR) by poorly understood mechanisms. The authors examined whether suprapontine central nervous system cardiovascular regulatory sites are required for anesthetic depression.

Methods: The effects of isoflurane (1 and 2 rat minimum alveolar concentration [MAC]) on the baroreflex control of HR were determined in sham intact and midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12 [mu]g/kg) and nitroprusside (1-60 [mu]g/kg) were used to measure HR responses to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact and two decerebrate) were studied before, during, and after isoflurane. To assess sympathetic and vagal contributions to HR baroreflex, [beta]-adrenoceptor (1 mg/kg atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered systemically.

Results: Decerebration did not alter resting MAP and HR or baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by depressing peak reflex tachycardia. Maximal reflex bradycardia during increases in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and decreased BP50 in both groups.     

A Comparison of Baroreflex Sensitivity during Isoflurane and Desflurane Anesthesia in Humans

Background: Desflurane anesthesia has been associated with heart rate (HR) and sympathetic nerve activity (SNA) responses that differ from those during isoflurane anesthesia. Whether these differences might be due to better preservation by desflurane of the baroreceptor reflex control of HR or SNA in humans was examined.

Methods: Baroreflex sensitivity was assessed in 18 volunteers anesthetized with either desflurane or isoflurane. Measurements of HR, blood pressure (BP), and efferent SNA (percutaneous recordings from the peroneal nerve) were made, and baroreflex sensitivity was evaluated at conscious baseline and during 0.5, 1.0, and 1.5 MAC anesthesia. Baroreflex responses were triggered by bolus intravenous injections of nitroprusside (100 micro gram) and phenylephrine (150 micro gram). The linear portions of the baroreflex curves relating HR to mean arterial pressure and relating SNA to diastolic pressure were determined to obtain cardiac and sympathetic baroslopes, respectively.

Results: Cardiac (HR) baroslopes were equally diminished at increasing MAC of both anesthetics. Sympathetic baroslopes were preserved at 0.5 MAC isoflurane but diminished at 0.5 MAC desflurane. Higher MAC produced equal depression of sympathetic baroslopes with both anesthetics.     

Ephedrine, dopamine, or doubtamine to treat hypotension with propofol during epidural anesthesia

PURPOSE: To compare the efficacy of ephedrine, dopamine and dobutamine for circulatory support during thoracic epidural anesthesia after anesthetic induction with propofol. METHODS: Forty patients undergoing lobectomy or mastectomy were divided into four groups of 10: a control group received no vasopressor; an ephedrine group received 5 mg ephedrine when the mean arterial pressure (MAP), measured every 2.5 min, decreased by 10% from baseline; dopamine and dobutamine groups received 5 microg x kg(-1) x min(-1) dopamine or 3 microg x kg(-1) x min(-1) dobutamine from five minutes after epidural injection of local anesthetic to the end of tracheal intubation. Anesthesia was induced with 2 mg x kg(-1) propofol. The MAP and heart rate (HR) were measured at baseline, 20 min after epidural injection, three minutes after propofol, and one minute after tracheal intubation. RESULTS: In the control group, MAP and HR decreased from 86+/-9 mmHg, 74+/-8 bpm to 62+/-9 mm Hg; P<0.0001, 60+/-8 bpm; P = 0.0003 after propofol. After tracheal intubation, MAP was restored to (81+/-13 mmHg, 70+/-13 bpm). In the ephedrine, dopamine, and dobutamine groups, MAP and HR remained unchanged during epidural anesthesia and propofol induction. However, after tracheal intubation, MAP and HR increased in the ephedrine (104+/-11 mm Hg; P = 0.004, 87+/-11 bpm; P<0.0001) and dobutamine (117+/-13 mm Hg; P = 0.0005, 100+/-11 bpm; P<0.0001) groups, but not in the dopamine group compared with baseline. CONCLUSION: Dopamine is preferable to ephedrine and dobutamine in providing hemodynamic stability during propofol induction and tracheal intubation following epidural anesthesia.     

Attenuation of arterial baroreceptor reflex response to acute hypovolemia during induced hypotension

Preservation of the arterial baroreflex response is important to restore cardiac output and blood pressure by reflex sympathetic nerve activation in the event of sudden hypotension caused by acute blood loss during surgery. However, the arterial baroreflex may be significantly attenuated by both anesthetics and hypotensive agents. In isoflurane-anesthetized dogs, the authors investigated the arterial baroreflex response 1) to bolus injections of sodium nitroprusside (SNP), prostaglandin E1 (PGE1) and trimethaphan (TM); and 2) to rapid blood loss (5 ml/kg) before and during induced hypotension with SNP, PGE1, and TM by measuring mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). Hypotension produced by both SNP and PGE1 was accompanied by an increase in RSNA and HR. The increase in RSNA and HR following the SNP bolus injection was significantly greater than that following injection of PGE1 (P less than 0.05). Trimethaphan was associated with a decrease in RSNA and HR. Rapid blood loss resulted in the same degree of MAP reduction (20 +/- 2 mmHg) before and during induced hypotension. Sensitivities of baroreflex, as evaluated by ratios of maximum changes in RSNA or HR to MAP (delta RSNA/delta MAP, delta HR/delta MAP), in response to rapid blood loss, were significantly suppressed during continuously induced hypotension, as compared with responses before induced hypotension. Despite the same degree of induced hypotension (70 +/- 5 mmHg of MAP), delta RSNA/delta MAP and delta HR/delta MAP in response to rapid blood loss were significantly greater with PGE1 than those with SNP (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of nitrous oxide on baroreflex control of heart rate and peripheral sympathetic nerve activity in humans

Acute regulation of blood pressure in humans is mediated by arterial baroreflex regulation of heart rate, cardiac contractility, and peripheral sympathetic outflow. Brief pharmacologic reductions of blood pressure were employed in 11 healthy volunteers to determine the effects of N2O on baroreflex-mediated increases in heart rate and efferent muscle sympathetic nerve activity. R-R intervals (ECG), blood pressure (radial artery), central venous pressure, respiratory rate (abdominal bellows), and end-tidal gas concentrations (mass spectrometer) were monitored. Efferent sympathetic nerve activity directed to skeletal muscle blood vessels (MSNA) was recorded from an epoxy-coated tungsten needle placed into the peroneal nerve. Data were obtained from six subjects before and during iv bolus administration of sodium nitroprusside (100 micrograms), during control while breathing 40% N2/60% O2, during administration of N2O (40% N2O/60% O2), and during recovery (40% N2/60% O2). Five subjects served as time controls and breathed 40% N2 in O2 throughout the protocol. Nitrous oxide produced a 59 +/- 18% (P less than 0.05) increase in baseline MSNA but did not alter the reflex augmentations in MSNA produced by nitroprusside. In contrast, there was a 39 +/- 14% decrease in the slope of the relationship between systolic pressure and R-R interval (P less than 0.05) in subjects breathing N2O. N2O thus produces activation of the sympathetic nerves directed to skeletal muscle blood vessels, and it decreases baroreflex-mediated tachycardia without diminishing baroreflex-mediated augmentations in sympathetic outflow.     

Modifications of the hemodynamic consequences of theophylline intoxication with landiolol in halothane-anesthetized dogs

PURPOSE: To examine the effect of landiolol (ONO-1101), a new ultra-short acting, highly selective beta1 blocker, on hemodynamic response to acute theophylline intoxication in anesthetized dogs. METHODS: Thirty-four dogs were studied during halothane anesthesia. Aminophylline (50 mg x kg(-1) over 20 min followed by infusion at 1.75 mg x kg(-1) x hr(-1)) was administered as a model of acute theophylline intoxication. Dogs were randomly enrolled into four landiolol groups (0, 1, 10, 100 microg x kg(-1) x min(-1)) to treat tachyarrhythmias. Hemodynamic variables, heart rate (HR), systemic blood pressure (SBP), pulmonary artery pressure, pulmonary artery occlusion pressure, and cardiac output (CO) were measured along with plasma concentrations of theophylline, epinephrine, and norepinephrine. RESULTS: After 60 min, plasma concentration of theophylline reached 46.6+/-4.0 (mean +/- SD) microg x ml(-1), HR increased from 129+/-21 to 193+/-27 bpm (P<0.0001) and CO increased from 1.6+/-0.5 l x min(-1) to 2.1+/-0.4 l x min(-1) (P<0.0001), whereas SBP decreased from 139+/-25 to 121+/-25 mm Hg (P<0.0001), with decreasing systemic vascular resistance. After intoxication, plasma epinephrine concentration increased from 125 +/-112 to 325+/-239 pg x ml(-1) (P<0.0001), and norepinephrine concentration from 103+/-61 to 133+/-61 pg x ml(-1) (P<0.0011). Landiolol 10 microg x kg(-1) x min(-1) decreased HR to pre-intoxication level, whereas HR returned to the intoxication baseline by 30 min after cessation of landiolol infusion. CONCLUSIONS: Landiolol controlled tachyarrhythmias associated with theophylline toxicity. The optimal effective dose of landiolol was 10 microg x kg(-1) x min(-1).     

Effect of xenon on autonomic cardiovascular control--comparison with isoflurane and nitrous oxide

STUDY OBJECTIVES: To clarify the effect of xenon on the autonomic nervous system by comparing similar effects of isoflurane and nitrous oxide.DESIGN: Prospective, randomized study.Setting: Operating room at a university hospital.PATIENTS: 39 ASA physical status I and II patients scheduled for general anesthesia. INTERVENTIONS: Patients were randomly allocated into one of three groups and received one of the following inhalational anesthetics: 56% of xenon (Group X), 0.94% of isoflurane (Group I), or 70% of nitrous oxide and 0.15% of isoflurane (Group N). Phenylephrine (pressor test) and nicardipine (depressor test) were given to assess baroreflex sensitivity.MEASUREMENTS AND MAIN RESULTS: Continuous blood pressure (BP) and electrocardiogram (ECG) were recorded before and during anesthesia to analyze heart rate (HR) variability and baroreflex sensitivity. Power spectrum of HR variability was calculated by fast Fourier transformation and power spectrum densities at low frequency (LF: 0.04-0.15Hz) and high frequency (HF: 0.15-0.40 Hz) were compared. Baroreflex sensitivity was calculated from the slope of regression for BP changes versus associated changes in R-R intervals. For HR variability, Group X showed lower power spectrum densities (ms(2).Hz(-1)) in LF and HF than did Group I (LF: 0.09 +/- 0.06 vs. 0.35 +/- 0.53; p < 0.05; HF: 0.40 +/- 0.34 vs. 0.98 +/- 0.68, p < 0.01). Group X had the lowest baroreflex sensitivity (ms.mmHg(-1)) via pressor test of the three study groups (Group X: 2.00 +/- 0.87, Group I: 3.53 +/- 2.14, Group N: 3.78 +/- 2. 17, p < 0.05).CONCLUSIONS: Xenon depressed both sympathetic and parasympathetic transmission more than isoflurane at 0.8 MAC. Xenon was also suggested to be relatively vagotonic.     

Intracranial venous hypertension and the effects of venous outflow obstruction in a rat model of arteriovenous fistula

A model of rat arteriovenous fistula (AVF) was created using a proximal common carotid artery to distal external jugular vein anastomosis. Anatomical dissections revealed that the external jugular vein is the primary vessel draining intracranial venous blood. Physiological measurements were made with the AVF open and closed, and during venous outflow occlusion of the contralateral external jugular vein. Opening the AVF increased torcular pressure from 6.5 +/- 0.6 to 13.5 +/- 1.1 mm Hg and decreased mean arterial pressure from 82.7 +/- 1.8 to 62.8 +/- 1.8 mm Hg (both P less than .05), decreasing cerebral perfusion pressure from 76.2 +/- 1.7 to 49.3 +/- 2.2 mm Hg (P less than .05). Middle cerebral artery blood flow velocity (MCA BFV) decreased from 6.8 +/- 1.1 to 4.2 +/- 0.7 cm/s (P less than 0.05). In rats with an AVF, occlusion of venous outflow increased torcular pressure to 34.8 +/- 3.1 mm Hg (P less than 0.05), MCA BFV decreased to 1.8 +/- 0.5 cm/s (P less than 0.05), and severe ischemic changes were seen on the electroencephalogram. Under this condition, torcular pressure and systemic arterial pressure had a positive linear relationship (P less than 0.05), whereas in control rats torcular pressure and arterial pressure had no relationship. Restoration of cerebral perfusion pressure by release of venous outflow occlusion and AVF closure transiently increased MCA BFV to 69% above baseline (P less than 0.05). Histological examination 1 week after permanent venous outflow occlusion revealed venous infarction, subarachnoid hemorrhage, and severe brain edema in rats with an AVF but not in control rats without an AVF. This model of cerebrovascular steal with venous hypertension reproduces both hemodynamic and hemorrhagic complications of human AVF and emphasizes the importance of venous outflow obstruction and venous hypertension in the pathophysiology of these lesions.     

Clonidine premedication modifies responses to adrenoceptor agonists and baroreflex sensitivity

PURPOSE: To evaluate the effects of clonidine on responses to adrenoceptor agonists and baroreflex sensitivity, we examined arterial blood pressure (AP) responses to phenylephrine and heart rate (HR) responses to isoproterenol and baroreflex sensitivity (HR response to AP changes due to phenylephrine or nitroglycerin). METHODS: We studied 60 anaesthetized patients who either did or did not receive 5 micrograms.kg-1 clonidine po before they were anaesthetized. After induction of general anaesthesia, the patients received 3 micrograms.kg-1 phenylephrine, 0.02 microgram.kg-1 isoproterenol, or 2-3 micrograms.kg-1 nitroglycerin, and haemodynamic measurements were taken. Baroreflex sensitivity was expressed as the slope of the linear regression line (msec.mmHg-1; in msec of R-R interval change vs mmHg change in systolic arterial pressure) following the administration of phenylephrine and nitroglycerin. RESULTS: Patients who received clonidine had greater augmented responses in AP to phenylephrine and in HR to isoproterenol (47.2 +/- 15.6% vs 23.7 +/- 11.9% for increase in systolic AP and 59.8 +/- 22.6% vs 26.2 +/- 11.0% for increase in HR, P < 0.05 respectively). There were no differences between the baroreflex sensitivities in the pressor (phenylephrine) test groups (3.77 +/- 1.08 vs 4.41 +/- 1.66 msec.mmHg-1). In contrast, the slopes of depressor (nitroglycerin) test groups were decreased in patients receiving clonidine (1.98 +/- 0.73 vs 3.68 +/- 1.72 msec.mmHg-1, P < 0.05). CONCLUSION: The results suggest that premedication with clonidine might enhance critical hypotension during anaesthesia and surgery, but restoration both of AP and HR decrease can be achieved effectively by phenylephrine and isoproterenol i.v., respectively.