Baroreflex Function In Patients Research Articles

Arterial Baroreflex Function in Patients with Parkinson’s Disease: a Pharmacological Approach

Parkinson’s disease (PD) is a neurodegenerative disorder that is known for its motor dysfunction. Moreover, PD also causes non‐motor impairments, and approximately 40% of the patients experience coexistent abnormalities, like orthostatic hypotension (OH). The OH induces incapacitating symptoms that can contribute to an increased risk of falls, which have a great impact on patients’ quality of life. The arterial baroreflex system plays a pivotal role in counteracting transient falls in blood pressure during the execution of activities of daily living. Although a plethora of studies have indicated that an impaired baroreflex function is a clinical feature in patients with PD, none of the human studies have used the modified oxford method, which is considered the gold standard approach for assessing arterial baroreflex sensitivity (BRS). Additionally, since the OH and arterial BRS have an age‐dependent effect, studies with younger patients with PD is lacking. In this sense, the aim of the present study was to test the arterial baroreflex function in patients with PD with and without OH and aged‐matched control during rapid changes in blood pressure induced by sequential boluses of vasoactive drugs (Modified‐Oxford Technique). Beat‐to‐beat HR (electrocardiography) and BP (finger photoplethysmography) were obtained during 10‐min of supine rest preceding a modified‐Oxford [bolus injection of 65–100μg sodium nitroprusside (NTP) followed by 65–100μg phenylephrine hydrochloride (PHE) 1 min afterwards] in five patients with PD (50±6yr; Hohen and Yhar: <3a.u.; diagnose time: 8.8±3.7yr) and seven age‐matched controls (48±7yr). Arterial BRS was analyzed using the slopes of the linear portions of the R‐R interval‐systolic BP relationship. Patients with PD had lower BP at rest compared to controls (82±7 vs. 94±5mmHg, P=0.01) and a trend for higher HR (72±13 vs. 59±8bpm, P=0.06). The average of falling (ΔSBP: −37±0.65 vs. −31±0.43, P=0.26) and rising systolic BP (ΔSBP: −27±0.76 vs. −20±0.58, P=0.38) was similar between patients with PD and controls. Our preliminary results showed that arterial BRS was lower in patients with PD compared to controls for falling pressure (NTP trial: 4.52±0.34 vs. 9.81±0.23ms/mmHg, P=0.01) and for rising pressure (PHE trial: 5.08±0.27 vs. 13.60±0.55ms/mmHg, P=0.03). Of note, only one of the patients presented OH, and the baroreflex function was characterized by a marked blunted arterial BRS for failing pressure (NTP trial: 1.83ms/mmHg) and an averaged BRS for rising in pressure. Our preliminary results indicated that the ups and downs of baroreflex function are impaired in patients with PD, and the downs appear to be further impaired in patients with OH. These findings provide a better understanding of the neural control of blood pressure in patients with PD, and future studies should focus on OH.Support or Funding InformationCNPq, FAPDF and CAPES.

Long-term effects of surgical treatment on baroreflex function in patients with obstructive sleep apnea: an 18-month follow-up

ObjectiveDepressed baroreflex sensitivity (BRS) is reported in obstructive sleep apnea (OSA). Improvement of BRS short-term after surgical treatment is also reported. We tested the hypothesis that surgical treatment not only improves clinical outcomes, but also improves BRS after 18 months. MethodsCardiovascular autonomic tests, polysomnography (PSG), and biochemical testing were prospectively evaluated in 54 OSA patients at three time points (preoperatively, 6 months and 18 months postoperatively) and compared with 20, age- and body mass index (BMI)-matched, healthy controls. ResultsThe BRS increased after surgical treatment at 18-month follow-up, with results similar to the healthy control. Additionally, average O2, mO2 <90% (% per night), and lowest O2 showed an increase after surgical treatment at the 18-month follow-up. ConclusionsBesides improvement in clinical outcomes, depressed BRS in OSA patients is reversible and these patients have the potential for total recovery of baroreflex function after 18 months of treatment.

Restoring Sinus Rhythm Improves Baroreflex Function in Patients With Persistent Atrial Fibrillation.

BackgroundStudies have suggested that patients with atrial fibrillation (AF) have impairment in the baroreflex. It is not clear whether these findings are the result of the associated comorbid conditions or the arrhythmia itself. We hypothesized that AF is associated with impairment in baroreflex function and that the arrhythmia itself is a contributing factor.Methods and ResultsTwenty‐four patients with persistent AF referred for cardioversion were enrolled. A second group of patients with no history of AF matched for age and left ventricular ejection fraction was identified and served as the control group. In the AF group, baroreflex gain (BRG) was measured on the day of cardioversion (Day 1) and again at 30 days post‐cardioversion (Day 30) in patients who remained in sinus rhythm (SR). The clinical characteristics of patients with AF were not different than those of the control group. The mean BRG in the AF group on Day 1 was significantly lower than the mean BRG of the control group (5.2±3.6 versus 10.8±5.5 ms/mm Hg, P<0.05). Ten patients experienced AF recurrence before the 30‐day follow‐up and 14 patients remained in SR. In the group that remained in SR, BRG increased from 4.1±3.7 ms/mm Hg on Day 1 to 7.0±6.0 ms/mm Hg on Day 30 (P<0.01).ConclusionWe have shown that AF is associated with impairment of the baroreflex and that restoration of SR improves BRG. Our data suggest that AF might be a contributing factor to the observed impairment in BRG and that restoring SR might help improve baroreflex function.

144 Does Home-Based, Slow Deep Breathing Training Reduce Central Sympathetic Outflow and Enhance Baroreflex Sensivitiy in Primary Hypertension?

Device-guided, home-based slow deep breathing (SDB) training has been shown to lower blood pressure (BP) in some patients with primary hypertension, however, the underlying mechanisms remain obscure. We sought to determine the influence of SDB training on BP, central sympathetic outflow and arterial baroreflex function in patients with primary hypertension. In addition, the effect of SDB training on arterial stiffness, cardiac structure and function were assessed also. Nineteen patients with essential hypertension (mean±SD: age 55 ± 12 years, 11 males, body mass index 28 ± 2.8 kg/m 2 ; median [interquartile range]: duration of hypertension 48 [12–169] month) were recruited. Medication use (58% calcium channel blockers, 42% angiotensin-converting-enzyme inhibitor or angiotensin receptor blockers, 37% thiazide diuretics, 21% beta-blockers and 26% statins) was stable before (3 months) and during the study. Patients were studied before and after 8-weeks of home-based SDB training (10 min/day, 4 times/week) with a RESPERATE O device. On study days, BP (automated sphygmomanometry), respiration (oronasal mask, heated pneumotach), heart rate (HR; electrocardiogram) and muscle sympathetic nerve activity (SNA; microneurography) were measured for 10 min while patients rested in a supine position. Indices of spontaneous cardiac baroreflex sensitivity (sequence technique) and arterial baroreflex control of the muscle SNA were calculated. A measure of central arterial stiffness (aortic augmentation index; AI) was determined using a Sphygmocor device. Cardiac structure and function were assessed by echocardiography. The SDB training decreased office systolic BP from 147 ± 18 to 133 ± 17 mmHg (mean±SD; P = 0.001), diastolic BP from 84 ± 10 to 79 ± 12 mmHg (P = 0.008) and pulse pressure from 63 ± 15 to 55 ± 13 mmHg (P = 0.003). In addition, SDB training significantly reduced muscle SNA burst frequency from 33.8 ± 8.2 to 28.3 ± 7.1 bursts/min (P = 0.03) and burst incidence (i.e., percentage of cardiac cycles associated with a sympathetic burst) from 59.0 ± 19.5 to 48.6 ± 14.4 bursts/100 heartbeats (P = 0.05). Respiratory frequency, tidal volume, and HR were unchanged (61 ± 9 vs. 61 ± 7 beats/min, P = 0.83). Neither spontaneous cardiac baroreflex sensitivity (systolic BP–RR interval index, 9.4 [6.93–14.83] to 9.5 [5.8–14.2] ms/mmHg, P = 0.71) nor arterial baroreflex control of muscle SNA (-2.9 [-5.1 – -1.3] to -2.4 [-7.0 – -1.1] bursts/100 heartbeats/mmHg, P = 0.58) were changed following SDB training. No significant changes in AI, cardiac structure and function were detected following SDB training. Our findings indicate for the first time that reductions in BP following 8-weeks of device-guided, home-based SDB training are accompanied by reductions in central sympathetic outflow in patients with primary hypertension, while arterial baroreflex sensitivity, central arterial stiffness, cardiac structure and function remain unchanged. This work is funded by British Heart Foundation (PG/11/41/28893).

The role of carotid plaque echogenicity in baroreflex sensitivity

The baroreflex sensitivity is impaired in patients with carotid atherosclerosis. The purpose of our study was to assess the impact of carotid plaque echogenicity on the baroreflex function in patients with significant carotid atherosclerosis, who have not undergone carotid surgery. Spontaneous baroreflex sensitivity (sBRS) was estimated in 45 patients with at least a severe carotid stenosis (70%-99%). sBRS calculation was performed noninvasively, with the spontaneous sequence method, based on indirectly estimated central blood pressures from radial recordings. This method failed in three patients due to poor-quality recordings, and eventually 42 patients were evaluated. After carotid duplex examination, carotid plaque echogenicity was graded from 1 to 4 according to Gray-Weale classification and the patients were divided into two groups: the echolucent group (grades 1 and 2) and the echogenic group (grades 3 and 4). Sixteen patients (38%) and 26 patients (62%) were included in the echolucent and echogenic group, respectively. Diabetes mellitus was observed more frequently among echolucent plaques (χ(2) = 8.0; P < .004), while those plaques were also more commonly symptomatic compared with echogenic atheromas (χ(2) = 8.5; P < .003). Systolic arterial pressure, diastolic arterial pressure, and heart rate were similar in the two groups. Nevertheless, the mean value of baroreflex sensitivity was found to be significantly lower in the echogenic group (2.96 ms/mm Hg) compared with the echolucent one (5.0 ms/mm Hg), (F [1, 42] = 10.1; P < .003). These findings suggest that echogenic plaques are associated with reduced baroreflex function compared with echolucent ones. Further investigation is warranted to define whether such an sBRS impairment could be responsible for cardiovascular morbidity associated with echogenic plaques.

P2-25 Long-term effects of baroreflex function in patients who had carotid stenosis underwent carotid stenting

P2-25 Long-term effects of baroreflex function in patients who had carotid stenosis underwent carotid stenting

Long-term effects of baroreflex function after stenting in patients with carotid artery stenosis

Baroreflex sensitivity is recognized for its prognostic relevance to cardio-vascular and cerebro-vascular risks. However, little is known about the long-term outcome of baroreflex function in patients with carotid stenosis undergoing carotid stenting. Heart rate variability and cardio-vascular autonomic function, including baroreflex sensitivity, were examined using non-invasive methods in 22 adult patients who underwent carotid stenting. They were compared with the normal control group with 22 sex- and age-matched normal volunteers and the risk control group with 10 adult patients with severe stenosis or even total occlusion of the carotid artery without stenting. The groups of patients with stenting and risk controls had significantly reduced valsalva ratio and baroreflex sensitivity measured by the valsalva method compared to normal controls. However, there was no significant difference between patients with stenting and risk controls. There was significant decrease in heart rate response to deep breathing and to head-up tilt in patients with carotid stenting compared to normal controls. Other parameters of cardio-vascular autonomic function showed no difference among the three groups. Reduced baroreceptor function in patients with carotid stenting may be due to underlying diseases rather than the stenting itself. There was no short-term parasympathetic hyperactivity after the stenting, suggesting that the effect is transient rather than permanent.

Restoration of baroreflex function in patients with end-stage renal disease after renal transplantation

Renal transplantation improves the uraemic autonomic dysfunction and heart rate variability (HRV). The effects of successful transplantation on blood pressure variability (BPV) and baroreflex function are not well defined. BPV, HRV and baroreceptor indices were determined in (1) 52 non-diabetic chronic haemodialysis patients, (2) 44 transplanted patients, 24 in the first year after renal transplantation (< or =1 year) and 20 at least 1 year (>1 year) after renal transplantation, and (3) 41 control individuals with normal renal function, age-matched to (1) and (2). Power spectrum analysis of interbeat intervals (IBI) and systolic blood pressure (SBP) was performed in the low-frequency (LF 0.04-0.15 Hz) and the high-frequency (HF 0.15-0.40 Hz) bands. Spontaneous baroreceptor sensitivity (BRS) was determined by the sequence (slope) and spectral (alpha coefficient) techniques. In haemodialysis patients, BPV was increased, while HRV, BRS slope and LF alpha and HF alpha coefficients were markedly decreased as compared to control individuals. Renal transplantation was associated with normalization of BPV at short term (< or =1 year) and long term and with improvement of HRV at a long-term (>1 year) follow-up. In patients with long-standing functioning grafts (>1 year), baroreceptor indices were significantly increased and returned to values similar to those of the control subjects. Our data show that renal transplantation improves blood pressure and HRV and restores baroreflex function to near normal range on the long-term follow-up. These effects may contribute to the improvement of blood pressure control and survival after successful transplantation.

Augmented sympathoinhibitory effect of valsartan when added to angiotensin-converting enzyme inhibitor in patients with left ventricular dysfunction

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) effectively interfere with the sympathetic nerve activity in patients with left ventricular (LV) dysfunction. The aim of this study was to examine the effect of ARBs on sympathetic nerve activity and baroreflex function in patients with LV dysfunction already receiving ACE inhibitors. Twenty patients with LV dysfunction already treated with ACE inhibitor (enalapril 5 mg/day) were randomly divided into two groups: treatment with 10 mg/day enalapril (control group) or 5 mg/day enalapril plus 80 mg/day valsartan (combination group). In both groups, resting muscle sympathetic nerve activity (MSNA; microneurography), arterial baroreflex sensitivity, and cardiopulmonary baroreflex sensitivity were measured at baseline and 4 weeks after the treatment. Arterial baroreflexes were perturbed by phenylephrine method, and cardiopulmonary baroreflexes were perturbed by lower body negative pressure (-10 mmHg). Baseline characteristics in both groups were similar. Resting MSNA decreased significantly from 35.4+/-10.8 to 26.4+/-5.1 burst/min (p<0.05), while arterial baroreflex sensitivity improved significantly from 6.0+/-2.0 to 10.1+/-2.6 ms/mmHg in the combination group. Moreover, cardiopulmonary baroreflex control of MSNA improved significantly from 15.8+/-12.2 to 42.0+/-26.7% (p<0.05) in the combination group. However, there were no significant changes in arterial baroreflex sensitivity and cardiopulmonary baroreflex of MSNA in the control group. Addition of ARB to ACE inhibitor treatment reduced sympathetic nerve activity and augmented arterial and cardiopulmonary baroreflex sensitivity in patients with LV dysfunction.

Lack of recovery of baroreflex function in patients after heart surgery

Baroreflex sensitivity (BRS) and heart rate variability (HRV) have significant influence on the patients' prognosis after cardiovascular events. These parameters are supposed to be impaired in patients with essential hypertension. Heart surgery leads to a temporary reduction of BRS and HRV. The following study was performed to assess differences in the response of the autonomic regulation in hypertensive and normotensive patients undergoing cardiac surgery with heart-lung machine.

Daytime variability of baroreflex function in patients with obstructive sleep apnoea: implications for hypertension

Obstructive events during sleep in patients with obstructive sleep apnoea (OSA) cause large alterations in blood pressure, and this may lead to changes in baroreflex function with implications for long-term blood pressure control. This study examined the daytime variations in the responses to carotid baroreceptor stimulation in OSA patients. We determined the cardiac and vascular responses every 3 h between 09.00 and 21.00 h in 20 patients with OSA, using graded suctions and pressures applied to a neck collar. These responses were plotted against estimated carotid sinus pressures and, from these plots, baroreflex sensitivities and operating points were taken as the maximal slopes and the corresponding carotid sinus pressures, respectively. We found that at 09.00 h, sensitivity for the control of vascular resistance was at its lowest (--1.2 +/- 0.2% mmHg(-1), compared with --1.9 +/- 0.3% mmHg(-1) at 12.00 h, P < 0.02) and operating point for control of mean arterial pressure was at its highest (101.1 +/- 5.8 mmHg, compared with 94.1 +/- 5.8 mmHg at 12.00 h, P < 0.05). This is in contrast to previous data from normal subjects, in whom sensitivity was highest and operating point lowest at 09.00 h. We suggest that the higher baroreflex sensitivity and lower operating point seen in the mornings in normal subjects may provide a protective mechanism against hypertension and that this protection is absent in patients with OSA. It is possible that the reduced reflex sensitivity and increased operating point in the mornings may actually promote hypertension.

Effects of spironolactone on sympathetic nerve activity and baroreflex function in patients with early hypertensive heart disease

Activation of the renin-angiotensin-aldosterone system (RAAS) could induce sympathoexcitation mediated by aldosterone in patients with primary hypertension and left ventricular hypertrophy. We hypothesised that aldosterone antagonism may suppress muscle sympathetic nerve activity (MSNA) and improve baroreflex function in subjects with beginning hypertensive heart disease. Eleven patients with mild to moderate primary hypertension and echocardiographic signs of early hypertensive heart disease received either oral spironolactone 25mg/day or placebo for four weeks in a double-blind, cross-over design. On the experimental day, resting biochemical parameters were determined, and MSNA was recorded by microneurography of the peroneal nerve at rest and during intravenous infusion of phenylephrine and nitroprusside. Furthermore, blood pressure (BP) and heart rate were measured non-invasively. Spironolactone increased basal levels of vasopressin, aldosterone and renin. Resting MSNA was higher during treatment with spironolactone compared with placebo (37.0±4.3 vs. 32.4±4.3 bursts/min, p=0.01), while BP and heart rate were not affected. Furthermore, spironolactone altered baroreflex control of MSNA (ΔMSNA / Δdiastolic BP) resulting in higher MSNA levels during nitroprusside infusion (b=-0.57 vs. b=0.05, t-value=2.80, 56 degrees of freedom, p<0.05). However, spironolactone did not affect baroreflex control of MSNA during phenylephrine infusion. Contrary to expectations, spironolactone activates MSNA at rest and during baroreceptor deactivation in patients with early hypertensive heart disease. This sympathoexcitatory effect may be mediated by central mineralocorticoid receptor blockade itself or alternatively, via the RAAS or the vasopressinergic system, which both seem activated during isolated aldosterone antagonism.

Carotid Artery Elasticity and Baroreflex Sensitivity in Patients With Glaucoma

To investigate non-invasively the elasticity of common carotid artery and the arterial baroreflex function in patients with chronic open-angle glaucoma. Data were obtained from patients with chronic open-angle glaucoma (n = 16) [primary open angle- and juvenile open-angle glaucoma] and from age- and sex-matched healthy control subjects (n = 18). End diastolic diameter and pulsatile distension of the common carotid artery were measured with a high-precision, automated ultrasound wall-tracking system (WTS). Spontaneous fluctuation in cardiac interval and systolic pressure were used to determine baroreflex sensitivity. There was no difference in heart rate and pulse pressure between patients with glaucoma and the control subjects. In the glaucoma patients both distensibility coefficient of common carotid artery and baroreflex sensitivity were reduced (two-way factorial ANOVA; P < 0.002). Stiffness (characterizing the rigidity of vessel wall) was higher in the glaucoma patients than in the controls (P = 0.002). Our results suggest that in patients with chronic open-angle glaucoma the arterial rigidity is significantly increased and therefore the baroreflex function is significantly decreased. These findings may have relevance in the understanding of the autonomic dysfunction and vascular dysregulation in glaucoma.

Complex Abnormalities in Baroreflex Function in Patients with Monogenic Hypertension and Neurovascular Contact

P53 We have shown that autosomal-dominant hypertension with brachydactyly regularly features brainstem neurovascular compression (NVC). To seek mechanisms by which NVC could influence blood pressure, we conducted extensive autonomic tests in 5 affected persons (18-34 yrs.). Cold pressor testing, hand-grip testing, and upright posture all increased BP excessively. Baseline muscle sympathetic nerve activity was 15±4.6 bursts/min in patients, 12±6 bursts/min in normotensive controls, and 14±9 bursts/min in borderline hypertensive controls (ns). The increase in nerve traffic during cold pressor testing was not excessive. Urinary norepinephrine excretion was 19±4.0 μg/24 hours (normal range 23-105 μg/ 24 hours). Blood pressure during ganglionic blockade was134±4.9/ 82±4.1 mmHg in patients and 90±6/49±2.4 mmHg in controls (p&lt;0.05). In patients, plasma vasopressin concentration changed from 0.47±0.03 pg/ml at baseline to 0.84±0.23 pg/ml during ganglionic blockade. In contrast, in control subjects, plasma vasopressin concentration increased profoundly from 1.6±0.17 pg/ml at baseline to 39±13 pg/ml during ganglionic blockade. The phenylephrine dose that increased SBP 12.5 mmHg was 8.0±2.0 μg in patients and 135±35 μg in control subjects before ganglionic blockade (p&lt;0.01). During ganglionic blockade, the dose of phenylephrine that increased SBP 12.5 mmHg was 5.4±0.4 μg in patients and 13±4.8 μg in control subjects. The baroreflex slope was 9.4±1.6 msec/mmHg. We conclude that in these patients, basal BP was increased even during interruption of sympathetic and parasympathetic nerve traffic. However, sympathetic stimuli caused an excessive increase in BP. This excessive response cannot be explained by increased sympathetic nerve traffic or increased vascular sensitivity. Instead, we suggest that the ability of the baroreflex to buffer changes in blood pressure is severely impaired despite retained heart rate control.

Impaired baroreflex function and arterial compliance in primary aldosteronism.

The purpose of this study was to evaluate if changes in vascular properties were related to baroreflex function in patients with primary aldosteronism. Twenty-three patients with primary aldosteronism, 22 essential hypertensive patients and 16 normal controls were studied. Continuous finger blood pressure (BP) was recorded by Portapres device during supine rest and active stand up. Compliance was estimated from the time constant of pressure decay during diastole. Baroreflex sensitivity was calculated by autoregressive cross-spectral analysis of systolic BP and interbeat interval. The result was that baroreflex gain and compliance were lower in primary aldosteronism patients in the supine position (P = 0.002 and P < 0.05 respectively). Aldosterone plasma levels (R2 = 0.31, P = 0.01), age, systolic and diastolic BP, high and low frequency components of diastolic BP variability were independently related to compliance in primary aldosteronism. In conclusion primary aldosteronism is associated with an impaired baroreflex function related in part to a reduced arterial compliance. Despite a reduction of BP values and aldosterone levels, surgical or pharmacological treatment did not significantly change compliance values.

Reduced cardiopulmonary baroreflex sensitivity in patients with hypertrophic cardiomyopathy.

We sought to assess baroreflex function in patients with hypertrophic cardiomyopathy (HCM). We have previously demonstrated a specific abnormality in the afferent limb of the cardiopulmonary baroreflex in patients with vasovagal syncope. Patients with HCM exhibit abnormal control of their vasculature during exercise and upright tilt; we therefore hypothesize a similar abnormality in the afferent limb of the cardiopulmonary baroreflex arc. We investigated 29 patients with HCM and 32 control subjects. Integrated baroreceptor sensitivity was assessed after administration of phenylephrine. Cardiopulmonary baroreceptor sensitivity was assessed by measuring forearm vascular resistance (FVR) during lower body negative pressure (LBNP). Carotid artery baroreflex sensitivity was assessed by measuring the in RR interval during manipulation of carotid artery transmural pressure. The integrity of the efferent limb of the reflex arc was determined by studying responses to both handgrip and peripheral alpha-receptor sensitivity. During LBNP, FVR increased by only 2.36+/-9 U in patients, compared with an increase of 123+/-8.76 U in control subjects (p=0.001). FVR paradoxically fell in eight patients, but in none of the control subjects. Furthermore, FVR fell by 4.9+/-5.6 U in patients with a history of syncope, compared with an increase of 4.7+/-7.2 U in those without syncope (p=0.014). Integrated and carotid artery baroreflex sensitivities were similar in patients and control subjects (14+/-7 vs. 14+/-6 ms/mm Hg, p=NS and -3+/-2 vs. -4+/-2 ms/mm Hg, p=NS, respectively). Similarly, handgrip responses and the dose/response ratio to phenylephrine were not significantly different. This study suggests that patients with HCM have a defect in the afferent limb of the cardiopulmonary reflex arc.

Effect of amlodipine on norepinephrine kinetics and baroreflex function in patients with congestive heart failure

Background: The use of calcium channel blocking drugs is controversial in heart failure, partly because of concerns about neurohormonal stimulation. Preliminary data suggest that the newer agent amlodipine may be useful in this syndrome. Suppression of sympathetic activity either directly or by sensitized baroreflex function could be contributing factors to the clinical use of this drug. Objective: To assess the effect of short-term amlodipine therapy on baseline measures of sympathetic activity and baroreflex function in patients with chronic stable congestive heart failure (CHF). Methods: Seven patients with chronic CHF (New York Heart Association functional class II or III, moderate to severe reduction in left ventricular systolic function) were studied. All patients underwent baroreflex testing with head-up tilt, head-down tilt, and head-down tilt with phenylephrine infusion. Heart rate, mean arterial pressure, forearm blood flow and resistance, and plasma norepinephrine (NE) kinetics were assessed at baseline and after each baroreflex perturbation on three occasions: a control test and after 10 days each of placebo and amlodipine therapy. Results: Plasma NE and NE spillover did not significantly increase after amlodipine administration compared with control and placebo tests (488 ± 119 pg/ml vs 350 ± 85 and 325 ± 87 pg/ml). In three subjects, plasma NE levels were essentially unchanged, whereas in four they rose markedly (289 ± 87 pg/ml at control vs 551 ± 158 pg/ml). There was no difference in the response of any variable during baroreflex perturbations after amlodipine administration compared with control and placebo tests. One subject who tolerated head-down tilt coupled with phenylephrine administration during the control and placebo tests became markedly short of breath during the same intervention after amlodipine administration. Plasma NE levels in this patient had risen markedly while receiving amlodipine and were not appropriately suppressed during the baroreflex loading maneuver. Conclusions: Short-term therapy with amlodipine does not suppress sympathetic activity or alter efferent responses to baroreflex perturbation in patients with stable chronic CHF. Significant increases in plasma NE and NE spillover and abnormal responses to baroreflex stimulation are possible after administration of this drug. The relevance of these findings to studies in larger number of patients requires further study. (Am Heart J 1997;134:13-9.)

Limited Utility of the Phenylephrine-Nitroprusside Sigmoid Curve Method of Measuring Baroreflex Function after Myocardial Infarction

Conventional testing of baroreflex function with phenylephrine bolus injection measures reflex vagal tone. To evaluate an alternative pharmacological method of baroreflex testing, which might provide more comprehensive evaluation of the baroreflex function in patients with uncomplicated myocardial infarction. Forty-eight patients, aged 59 +/- 7 years, were evaluated 5-7 days after myocardial infarction and after 6 weeks of rehabilitation. Baroreflex testing was performed with 10-14 incremental injections of nitroprusside and phenylephrine. The peak heart rate and blood pressure point from each injection were fitted to a four parameter (upper plateau, lower plateau, gain and median blood pressure) sigmoid logistic function. The baroreflex sensitivity (BRS) was also measured by conventional linear analysis of the response of the R-R interval to the initial rise in systolic blood pressure induced by phenylephrine bolus injection. Non-linear curve fitting of four logistic curve parameters was possible for results from 91% of tests; in the remaining tests the upper plateau was held constant at the maximum heart-rate response to allow estimation of the other three parameters. When all four parameters had been estimated, the gain parameter could not be precisely determined (the coefficient of variation of the gain parameter was 85 +/- 10%). The upper (R = 0.72, P < 0.001) and lower plateaux (R = 0.76, P < 0.001) were strongly related to the resting heart rate and weakly related to measures of heart-rate variability. There was also a significant inverse correlation between the lower plateau and the BRS (R = -0.57, P < 0.001). The gain parameter was not related to the BRS or any measure of the heart-rate variability. After 6 weeks' rehabilitation there was a significant decrease in the lower plateau (from 54 +/- 2 to 48 +/- 1 beats/min, P < 0.001), an increase in BRS (from 9.4 +/- 0.8 to 12.1 +/- 0.8 ms/mmHg, P < 0.001) and no change in the other three sigmoid curve parameters. Non-linear curve fitting of the heart-rate-blood-pressure relationship for patients after myocardial infarction is feasible but technical limitations and the lack of correlation between the gain parameter and other measures of autonomic function suggest that this method has limited usefulness. The lower plateau is related strongly to the BRS; both are vagal measures of cardiac autonomic function.

Comparison of Arterial Baroreflex Function in Humans Anesthetized with Enflurane or Isoflurane

To compare the depressive effects of isoflurane and enflurane on the arterial baroreflex function, we examined baroreflex control of heart rate during the entire course of clinical anesthesia. Isoflurane and enflurane were found to have similar depressive effects on the baroreflex control of heart rate when used in combination with N2O and O2. Suppression in the baroreflex sensitivity, defined by the slopes of regression line (change in msec of RR interval per mm Hg increase or decrease in systolic blood pressure) was from 7.1 +/- 3.9 to 1.8 +/- 0.7 msec/mm Hg in patients given isoflurane and from 7.8 +/- 4.3 to 3.0 +/- 1.9 msec/mm Hg in those given enflurane when evaluated by a pressor test (bolus IV phenylephrine). The slope of the depressor test (bolus IV nitroglycerin) also decreased from 4.7 +/- 2.8 to 1.9 +/- 1.5 msec/mm Hg with isoflurane and from 5.6 +/- 3.2 to 2.3 +/- 1.2 msec/mm Hg with enflurane. During surgery in which anesthetic concentration invariably needed to be increased, the suppression of the baroreflex sensitivity remained unchanged in both groups of patients. During recovery, the arterial baroreflex function in patients given isoflurane recovered more rapidly than that in patients given enflurane. This difference may be related to a more minor degree of suppression of isoflurane on the autonomic nervous system compared to enflurane.

Comparison of Arterial Baroreflex Function in Humans Anesthetized with Enflurane or Isoflurane

To compare the depressive effects of isoflurane and enflurane on the arterial baroreflex function, we examined baroreflex control of heart rate during the entire course of clinical anesthesia. Isoflurane and enflurane were found to have similar depressive effects on the baroreflex control of heart rate when used in combination with N2O and O2. Suppression in the baroreflex sensitivity, defined by the slopes of regression line (change in msec of RR interval per mm Hg increase or decrease in systolic blood pressure) was from 7.1 ± 3.9 to 1.8 ± 0.7 msec/mm Hg in patients given isoflurane and from 7.8 ± 4.3 to 3.0 ± 1.9 msec/mm Hg in those given enflurane when evaluated by a pressor test (bolus IV phenylephrine), The slope of the depressor test (bolus IV nitroglycerin) also decreased from 4.7 ± 2.8 to 1.9 ± 1.5 msec/mm Hg with isoflurane and from 5.6 ± 3.2 to 2.3 ± 1.2 msec/mm Hg with enflurane. During surgery in which anesthetic concentration invariably needed to be increased, the suppression of the baroreflex sensitivity remained unchanged in both groups of patients. During recovery, the arterial baroreflex function in patients given isoflurane recovered more rapidly than that in patients given enflurane. This difference may be related to a more minor degree of suppression of isoflurane on the autonomic nervous system compared to enflurane.