Carotid Denervation Research Articles

Hypoxia-induced hypotension elicits adenosine-dependent phrenic long-term facilitation after carotid denervation

Moderate acute intermittent hypoxia (AIH) elicits a persistent, serotonin-dependent increase in phrenic amplitude, known as phrenic long-term facilitation (pLTF). Although pLTF was originally demonstrated by carotid sinus nerve stimulation, AIH still elicits residual pLTF in carotid denervated (CBX) rats via a distinct, but unknown mechanism. We hypothesized that exaggerated hypoxia-induced hypotension after carotid denervation leads to greater spinal tissue hypoxia and extracellular adenosine accumulation, thereby triggering adenosine 2A receptor (A2A)-dependent pLTF. Phrenic activity, arterial pressure and spinal tissue oxygen pressure were measured in anesthetized CBX rats. Exaggerated hypoxia-induced hypotension after CBX was prevented via intravenous phenylephrine; without the hypotension, spinal tissue hypoxia during AIH was normalized, and residual pLTF was no longer observed. Spinal A2A (MSX-3), but not serotonin 2 receptor (5-HT2) inhibition (ketanserin), abolished residual pLTF in CBX rats. Thus, pLTF regulation may be altered in conditions impairing sympathetic activity and arterial pressure regulation, such as spinal cord injury.

Circulatory control of phrenic motor plasticity

Acute intermittent hypoxia (AIH) elicits distinct mechanisms of phrenic motor plasticity initiated by brainstem neural network activation versus local (spinal) tissue hypoxia. With moderate AIH (mAIH), hypoxemia activates the carotid body chemoreceptors and (subsequently) brainstem neural networks associated with the peripheral chemoreflex, including medullary raphe serotonergic neurons. Serotonin release and receptor activation in the phrenic motor nucleus then elicits phrenic long-term facilitation (pLTF). This mechanism is independent of tissue hypoxia, since electrical carotid sinus nerve stimulation elicits similar serotonin-dependent pLTF. In striking contrast, severe AIH (sAIH) evokes a spinal adenosine-dependent, serotonin-independent mechanism of pLTF. Spinal tissue hypoxia per se is the likely cause of sAIH-induced pLTF, since local tissue hypoxia elicits extracellular adenosine accumulation. Thus, any physiological condition exacerbating spinal tissue hypoxia is expected to shift the balance towards adenosinergic pLTF. However, since these mechanisms compete for dominance due to mutual cross-talk inhibition, the transition from serotonin to adenosine dominant pLTF is rather abrupt. Any factor that compromises spinal cord circulation will limit oxygen availability in spinal cord tissue, favoring a shift in the balance towards adenosinergic mechanisms. Such shifts may arise experimentally from treatments such as carotid denervation, or spontaneous hypotension or anemia. Many neurological disorders, such as spinal cord injury or stroke compromise local circulatory control, potentially modulating tissue oxygen, adenosine levels and, thus, phrenic motor plasticity. In this brief review, we discuss the concept that local (spinal) circulatory control and/or oxygen delivery regulates the relative contributions of distinct pathways to phrenic motor plasticity.

Abstract P395: A New Technique for Selective Denervation of the Aortic and Carotid Baroreceptors

The traditional sinoaortic denervation (SAD) technique in rats includes aortic and carotid baroreceptors denervation, but also leads to concomitant denervation of the carotid chemoreceptors. Here we report a new technique to denervate the carotid and aortic baroreceptors, selectively, preserving the carotid chemoreceptors intact. Wistar rats were subjected to selective aortic and carotid baroreceptor denervation sparing the carotid chemoreceptors intact (BAROS-X), or sham surgery (SHAM). The animals were also implanted with femoral arterial and venous catheter for arterial pressure recording and drug administration. In unanesthetized, freely moving rats, baroreflex or peripheral chemoreflex activation was elicited by intravenous injection of phenylephrine or potassium cyanide (KCN), respectively. Phenylephrine caused a significant hypertensive response in SHAM (Δ = 46 ± 3 mmHg, P<0.001) and BAROS-X (Δ = 38 ± 3 mmHg, P<0.001) combined with a reflex bradycardia in SHAM (Δ = -54 ± 11 bpm, P<0.001) but no change in heart rate in BAROS-X subjects (Δ = -5 ± 2 bpm, ns); confirming the absence of aortic and carotid baroreceptors in BAROS-X rats. KCN elicited significant hypertensive response in SHAM (44 ± 6 mmHg, P<0.001) and BAROS-X (39 ± 5 mmHg, P<0.001) subjects followed by bradycardic response in SHAM (-88 ± 17 bpm, P<0.001) and BAROX-S (-103 ± 23 bpm, P<0.01) rats; confirming that the carotid chemoreceptors were intact in both groups. These data provide support to a new surgical technique that allows working with conscious rats exhibiting selective inactivation of the aortic and carotid baroreceptors, combined with intact carotid chemoreceptors.

Carotid chemoreceptors do not mediate hypoxic-induced gasping and autoresuscitation in newborn rats

Experiments were carried out on 48, 5–6-day-old rat pups to investigate the influence of carotid denervation on their time to last gasp during a single period of hypoxia, and on their ability to autoresuscitate from primary apnea during repeated hypoxic challenge. One group of pups was studied with intact carotid chemoreceptors and one group was studied following surgical denervation of the carotid chemoreceptors. Carotid denervation eliminated the early tachypneic phase during exposure to hypoxia and delayed the time to arousal/excitement but did not alter the time to primary apnea, the time to last gasp or the total number of gasps during exposure to a single period of unrelenting hypoxia. Furthermore, carotid denervation did not alter the number of successful autoresuscitations from primary apnea during repeated hypoxic exposure. Thus, the carotid chemoreceptors are not essential for the initiation or maintenance of gasping nor are they are integral to gasping effecting successful autoresuscitation from hypoxic-induced apnea in newborn rats.

Long term safety and efficacy of internal carotid artery adventitial stripping in carotid sinus syndrome.

To investigate the long term efficacy of carotid denervation by adventitial stripping of the internal carotid artery (ICA) for carotid sinus syndrome (CSS). Secondly, the long term safety of this technique is investigated with emphasis on the effects on blood pressure (BP), heart rate (HR) and carotid artery diameter. Characteristics of patients that were operated for CSS in a single institute between 1980-2007 were studied by a retrospective chart review. Alive and fit patients additionally received a standardized interview investigating symptoms of residual CSS or baroreflex failure. They underwent a test panel consisting of office BP measurement, carotid sinus massage (CSM), table tilt testing, 24-hour ECG and ambulatory BP measurement (ABPM) and carotid duplex. Unoperated, age- and sex- matched individuals without CSS served as controls. After a total follow up of 91±34 months, 22 of 26 patients (85%) were asymptomatic and 20 of them (77%) without a pacemaker. Of the 7 surviving and fit patients, six were free of CSS symptoms (follow up 114 ± 81 months). Recurrence of CSS after an initial successful carotid denervation was not observed. BP level, BP variability and carotid diameters were not different compared to controls. Carotid denervation by adventitial stripping of the ICA for CSS seems effective and safe on the long term. A randomized controlled trial comparing the efficacy and safety of carotid denervation, pacing and medical treatment is needed for optimal future treatment of patients suffering from CSS.

Abstract 032: Carotid Chemoreceptor Activation Blunts The Hypotensive Response Caused By The Electrical Stimulation Of The Carotid Sinus In Conscious Rats

The mechanisms involved in Baroreflex Activation Therapy (BAT) in patients with resistant hypertension require better understanding. It was shown that electrical stimulation of the carotid sinus (ESCS), in conscious carotid body-denervated rats, caused bradycardia and greater hypotensive response when compared with intact control rats. In the current study the activation of the chemoreceptors due to ESCS, in conscious rats, was examined in the absence of the carotid baroreceptors. Wistar rats with unilateral denervation of the right carotid chemoreceptors were divided into three groups: 1) control (CONT, n=7); 2) bilateral carotid chemoreceptor denervation (CD, n=7); 3) unilateral denervation of the left carotid baroreceptors (BD, n=4). Under ketamine/xylazine anesthesia bipolar electrodes were implanted around the left carotid sinus combined with arterial and venous catheters into the femoral vessels. On the next day, after basal hemodynamic recordings, the animals received three ESCS (5V, 1 ms) with 15 Hz, 30 Hz and 60 Hz, applied randomly for 20s. Carotid chemoreceptors denervation was confirmed by the lack of hemodynamic responses after the administration of KCN (40 μg iv). The efficacy of left carotid baroreceptor denervation was confirmed by the absence of hemodynamic responses to changes in the left carotid sinus pressure ranging from 60 mmHg to 180 mmHg. The results showed that ESCS was efficient to cause greater hypotensive responses in the CD as compared with the CONT group at 60 Hz (-37 ± 6 vs -19 ± 3 mmHg) and to cause hypertensive responses in the BD group at 30 Hz and 60 Hz (15 ± 2 and 19 ± 2 mmHg). ESCS caused no alteration of the heart rate in the CONT but caused significant bradycardia in the CD group at 30 Hz and 60 Hz (-31 ± 11 and -35 ± 12 bpm) and in the BD group at 15 Hz, 30 Hz and 60 Hz (-38 ± 6, -37 ± 6 and -34 ± 4 bpm). These data demonstrated that carotid chemoreceptor activation in the absence of the carotid baroreceptors caused hypertension and bradycardia, indicating that when the baroreceptors are intact, the chemoreceptors blunt the hypotensive response caused by ESCS. These findings provide important information for the clinical studies using BAT in patients with resistant hypertension and/or heart failure.

Carotid denervation does not influence autoresuscitation from hypoxic‐induced apnea in newborn rat pups (LB782)

Autoresuscitation (AR) failure from hypoxic‐induced apnea by gasping has been suggested to play a role in sudden infant death. Little is known, however, about the factors that influence gasping and its ability to effect AR in the newborn. The present experiments were carried out on 5 to 6 day‐old rat pups to investigate the influence of carotid denervation (CD) on gasping during a single hypoxic exposure, and on AR during repeated hypoxic exposures. CD decreased basal respiratory frequency but not heart rate as compared to sham‐operated pups and eliminated the respiratory frequency response to alveolar hypoxia. CD decreased the time to hypoxic arousal/excitement but did not significantly influence the time to primary apnea, the time to last gasp or the total number of gasps during a single unrelenting hypoxic exposure. Furthermore, CD did not alter the number of hypoxic exposures tolerated before AR failure (Sham 15±2 – CD 15±3) Our data provide evidence that although the carotid chemoreceptors mediate the respiratory and arousal/excitement responses during exposure to hypoxia they do not modulate gasping or influence the ability of gasping to effect successful AR during repeated exposure to hypoxia.Grant Funding Source: CIHR

The Role of Nonpharmacologic Device Interventions in the Management of Drug-Resistant Hypertension

Resistant systemic hypertension in patients is defined as the inability to control blood pressure despite taking at least three antihypertensive drugs, one of which is a diuretic. Two nonpharmacologic approaches are being evaluated in resistant hypertensive patients. First, the Rheos® Baroreflex Hypertension Therapy system is an implantable device that activates the carotid baroreflex through electrical stimulation of the carotid sinus wall. Sustained and clinically lower blood pressure has been observed in patient clinical trials. The second approach is a catheter-based strategy which denervates the renal afferent and efferent autonomic nervous system. This strategy has also been shown to be effective in drug-resistant patients, and has also been shown to decrease renin production, preserve renal function, improve glucose tolerance, and reduce left ventricular hypertrophy. Both carotid sinus stimulation and renal denervation are now being evaluated in clinical trials for the long-term control of hypertension.

Carotid baroreceptors are mainly localized in the medial portions of the proximal internal carotid artery

To visualize baroreceptors in the human carotid bifurcation by light microscopy. Baroreceptor location is investigated in order to provide recommendations for the extent of adventitial stripping in the treatment for carotid sinus syndrome (CSS). Human carotid specimens were transversely cut in 20 μm sections. After immunohistochemical staining using antibodies to vesicular glutamate transporter 2 (VGLUT2) and protein gene product 9.5 (PGP 9.5), the presence of baroreceptor tissue was studied using light microscopic techniques. Visual assessment indicated that VGLUT2 and PGP 9.5 immunoreactivity was present in the adventitia of the carotid arteries and that nerve density was highest in the medial wall of the proximal first cm of the internal carotid artery (ICA). Human carotid baroreceptors, as reflected in immunoreactivity for VGLUT2 and PGP 9.5, are mainly localized in the medial portions of the proximal ICA. If surgical carotid denervation is indicated in patients suffering from carotid sinus syndrome, adventitial stripping of the proximal portion of the ICA should be sufficient.

Carotid chemoafferent activity is not necessary for all phrenic long-term facilitation following acute intermittent hypoxia

Phrenic long-term facilitation (pLTF) is a form of respiratory plasticity induced by acute intermittent hypoxia (AIH) or episodic carotid chemoafferent neuron activation. Surprisingly, residual pLTF is expressed in carotid denervated rats. However, since carotid denervation eliminates baroreceptor feedback and causes profound hypotension during hypoxia in anesthetized rats, potential contributions of these uncontrolled factors or residual chemoafferent neuron activity to residual pLTF cannot be ruled out. Since ATP is necessary for hypoxic carotid chemotransduction, we tested the hypothesis that functional peripheral chemoreceptor denervation (with intact baroreceptors) via systemic P2X receptor antagonism blocks hypoxic phrenic responses and AIH-induced pLTF in anesthetized rats. Pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 100 mg/kg i.v.), a non-selective P2X receptor antagonist, was administered to anesthetized, vagotomized, paralyzed and ventilated male Sprague-Dawley rats prior to AIH (3, 5 min episodes of 10% O(2); 5 min intervals). Although PPADS strongly attenuated the short-term hypoxic phrenic response (20 ± 4% vs. 113 ± 15% baseline; P < 0.001), pLTF was reduced but not eliminated 60 min post-AIH (25 ± 4% vs. 51 ± 11% baseline; n = 8 and 7, respectively; P < 0.002). Thus, AIH initiates residual pLTF out of proportion to the diminished hypoxic phrenic response and chemoafferent neuron activation. Although the mechanism of residual pLTF following functional chemo-denervation remains unclear, possible mechanisms involving direct effects of hypoxia on the CNS are discussed.

Effect of carotid and aortic baroreceptors on cardiopulmonary reflex: the role of autonomic function

We determined the sympathetic and parasympathetic control of heart rate (HR) and the sensitivity of the cardiopulmonary receptors after selective carotid and aortic denervation. We also investigated the participation of the autonomic nervous system in the Bezold-Jarish reflex after selective removal of aortic and carotid baroreceptors. Male Wistar rats (220-270 g) were divided into three groups: control (CG, N = 8), aortic denervation (AG, N = 5) and carotid denervation (CAG, N = 9). AG animals presented increased arterial pressure (12%) and HR (11%) compared with CG, while CAG animals presented a reduction in arterial pressure (16%) and unchanged HR compared with CG. The sequential blockade of autonomic effects by atropine and propranolol indicated a reduction in vagal function in CAG (a 50 and 62% reduction in vagal effect and tonus, respectively) while AG showed an increase of more than 100% in sympathetic control of HR. The Bezold-Jarish reflex was evaluated using serotonin, which induced increased bradycardia and hypotension in AG and CAG, suggesting that the sensitivity of the cardiopulmonary reflex is augmented after selective denervation. Atropine administration abolished the bradycardic responses induced by serotonin in all groups; however, the hypotensive response was still increased in AG. Although the responses after atropine were lower than the responses before the drug, indicating a reduction in vagal outflow after selective denervation, our data suggest that both denervation procedures are associated with an increase in sympathetic modulation of the vessels, indicating that the sensitivity of the cardiopulmonary receptors was modulated by baroreceptor fibers.

The aortic and carotid sinus baroreflexes contribute equally to control blood pressure and heart rate variabilities

Baroreflexes are important in stabilizing blood pressure (BP). Disrupting the reflexes, e.g., via sinoaortic denervation (SAD), largely increases BP variability (BPV), which contributes to end‐organ damage. Because baroreflexes are often destructed separately in clinic, this study examines the individual role of aortic and carotid baroreflexes in BPV.Seven neuromuscular blocked (NMB), Sprague‐Dawley, female (225–275 g) rats were studied. Aortic denervation (AD, 4 rats) and carotid denervation (CD, 3 rats) were made sequentially, with initial denervation chosen in random order. BP and heart rate (HR) were recorded continuously for 10 hrs during baseline and denervation stages. BPV was defined by standard deviation (SD), and very low frequency (0.01–0.2 Hz) power of the BPV spectrum. Results: 1) Independent of denervation order, complete SAD greatly increased BPV: Compared to the baseline, SDs and VLF powers increased ~250% (AD→SAD: t=7.15, p&lt;.01; CD→SAD: t=12.75, p&lt;.01) and 130% (AD→SAD: t=10.59, p&lt;.01; CD→SAD: t=9.78, p=.01), respectively; 2) AD and CD each increased BPV: SDs increased ~100% and VLF powers ~80%; the increase was significant for AD (SD: t=8.88, p&lt;.0; and VLF: t=4.16, p&lt;.05), but not for CD. There was no difference between post‐ AD and CD BPV; and 3) Denervations had no effect on HR variability. Conclusion: Aortic and carotid baroreflexes contribute equally to BP and HR variabilities.

Clinical Results of Carotid Denervation by Adventitial Stripping in Carotid Sinus Syndrome

Aims: Older patients with spells of syncope may suffer from a carotid sinus syndrome (CSS). Patients with invalidating CSS routinely receive pacemaker treatment. This study evaluated the safety and early outcome of a surgical technique termed carotid denervation by adventitial stripping for CSS treatment. Methods: Carotid sinus massage (CSM) during cardiovascular monitoring confirmed CSS in patients with a history of repeated syncope and dizziness. The internal carotid artery was surgically denervated by adventitial stripping over a minimum distance of 3 cm via a standard open approach. Patient characteristics, perioperative complications and 30-day success rate were analyzed. Results: A total of 39 carotid denervation procedures was performed in 27 individuals (23 males, mean age 70 ± 3 years) between 1980 and 2007 in a single institution. Eleven patients had a bilateral hypersensitive carotid sinus. Procedure related complications included wound hematoma (n = 4), neuropraxia of the marginal mandibular branch of the facial nerve (n = 2) and dysrhythmia responding to conservative treatment (n = 3). Significant alterations in systolic and diastolic blood pressure and heart rate were not observed. One patient developed a cerebral ischaemic vascular accident on the 24th postoperative day. One patient with residual disease had a successful redenervation within 1 month after the initial operation. Two patients with persistent symptoms received a pacemaker but also to no avail. At 30-day follow up 25 of 27 patients (93%) were free of syncope, and 24 free of a pacemaker (89%). Conclusion: Carotid denervation by adventitial stripping of the proximal carotid internal artery is effective and safe and may offer a valid alternative for pacemaker treatment in patients with carotid sinus syndrome.

Carotid Denervation by Adventitial Stripping: A Promising Treatment of Carotid Sinus Syndrome?

The baroreflex is an important component of the physiological short-term control of the blood pressure. Baroreceptors are mainly located in the wall of the aortic arch and of the internal carotid artery (ICA). The carotid sinus nerve (CSN) contains afferent fibres travelling from the carotid sinus’ baroreceptors located in the adventitia of the ICA. It joins the glossopharyngeal (IX) nerve and ends in the nucleus tractus solitarius in the brain stem. The efferent loop is conducted by the vagus (X) nerve to the heart leading to a physiologic bradycardia and inhibited atrioventricular conduction, in response to systemic hypertension. Also, a blocked sympathetic nerve system causes venodilatation, decreasing ventricular preload, and vasodilatation, both leading to decreased blood pressure. Carotid sinus syndrome (CSS) is caused by a pathologic overshoot of this baroreflex and is characterised by exaggerated bradycardia and hypotension in response to carotid sinus stimulation, in situations such as shaving, wearing tight collar or head turning. The triggering events might vary considerably overtime in any individual patient, but the syndrome can be reproduced by carotid sinus massage. CSS prevalence could be as high as 45% in elderly patients. If left untreated, CSS mortality rates could exceed 25% within 5 years.

Clinical Results of Carotid Denervation by Adventitial Stripping in Carotid Sinus Syndrome

Older patients with spells of syncope may suffer from a carotid sinus syndrome (CSS). Patients with invalidating CSS routinely receive pacemaker treatment. This study evaluated the safety and early outcome of a surgical technique termed carotid denervation by adventitial stripping for CSS treatment. Carotid sinus massage (CSM) during cardiovascular monitoring confirmed CSS in patients with a history of repeated syncope and dizziness. The internal carotid artery was surgically denervated by adventitial stripping over a minimum distance of 3 cm via a standard open approach. Patient characteristics, perioperative complications and 30-day success rate were analyzed. A total of 39 carotid denervation procedures was performed in 27 individuals (23 males, mean age 70+/-3 years) between 1980 and 2007 in a single institution. Eleven patients had a bilateral hypersensitive carotid sinus. Procedure related complications included wound hematoma (n=4), neuropraxia of the marginal mandibular branch of the facial nerve (n=2) and dysrhythmia responding to conservative treatment (n=3). Significant alterations in systolic and diastolic blood pressure and heart rate were not observed. One patient developed a cerebral ischaemic vascular accident on the 24th postoperative day. One patient with residual disease had a successful redenervation within 1 month after the initial operation. Two patients with persistent symptoms received a pacemaker but also to no avail. At 30-day follow up 25 of 27 patients (93%) were free of syncope, and 24 free of a pacemaker (89%). Carotid denervation by adventitial stripping of the proximal carotid internal artery is effective and safe and may offer a valid alternative for pacemaker treatment in patients with carotid sinus syndrome.

AFFERENT PATHWAYS INVOLVED IN CARDIOVASCULAR ADJUSTMENTS INDUCED BY HYPERTONIC SALINE RESUSCITATION IN RATS SUBMITTED TO HEMORRHAGIC SHOCK

The peripheral hyperosmolarity elicited by intravenous infusion of hypertonic saline (HS) can be beneficial in treating hemorrhagic shock. However, the neural mechanisms involved in this resuscitation remain unknown. The present study sought to determine the effects of selective baroreceptor denervation on arterial blood pressure response during HS resuscitation in rats submitted to hemorrhagic shock. Male Wistar rats (280-320 g) were anesthetized with thiopental sodium (40 mg/kg, i.v.), and the femoral artery and jugular vein were cannulated for MAP and heart rate recording and HS infusion (3 mol/L NaCl; 0.18 mL/100 g body weight, >2 min). Hemorrhagic shock was obtained by withdrawing blood over 30 min until a MAP of 60 mmHg was obtained. This level of MAP was maintained for a further 30 min through subsequent blood withdrawal or reinfusion. Next, animals were divided into selective aortic and/or carotid denervation or sham groups before infusing HS. Results showed that in the sham group (n = 12), HS infusion increased MAP to levels close to baseline (from 65 +/- 3 to 112 +/- 5 mmHg, 10 min after HS). In the aortic denervated group (n = 10), HS infusion also increased MAP (from 54 +/- 3 to 112 +/- 5 mmHg, 10 min after HS). In contrast, in the carotid denervation group (n = 8), the increase in MAP induced by HS infusion was abolished (from 53 +/- 3 to 73 +/- 12 mmHg, 10 min after HS). These results indicate that in hemorrhaged rats, HS infusion produces a pressor effect that is likely to be mediated through carotid rather than aortic baroreceptors.

Adventitial Stripping for Carotid Sinus Syndrome

Patients with a carotid sinus syndrome (CSS) suffer from spells of dizziness and loss of conscience due to an exaggerated carotid baroreflex response. Three types of the syndrome are described: cardioinhibitory, vasodepressor and a mixed form. The gold standard for treatment is insertion of a pacemaker, but this therapy may be effective only in a pure cardioinhibitory type. In contrast, surgically interrupting afferent nerves at the origin may offer relief of symptoms in all three types. The present review analyzes the results of a surgical technique termed "adventitial stripping" of the carotid sinus. Data from 130 procedures demonstrate that carotid denervation is effective in 85% of CSS cases with low complication rates. Postoperative monitoring is mandatory as transient alterations in blood pressure and heart rate may occur.

Excessive vomiting abolished by carotid denervation

The carotid sinus syndrome (CSS) is characterized by repetitive syncope due to prolonged heart rate slowing or a profound drop in systolic blood pressure. CSS is due to an inappropriate response of a hypersensitive carotid sinus following pressure on or stretching of the neck. We report on a patient with excessive gagging and vomiting elicited by pressure on the right side of the neck as an aberrant presentation of the carotid sinus syndrome. Her incapacitating symptoms were abolished by a surgical carotid denervation.

Ambulatory arterial stiffness index (AASI) does not predict baroreflex sensitivity or the pressor response to mental stress in normotensive humans

Ambulatory arterial stiffness index (AASI) is a novel measure of arterial stiffness, which independently predicts cardiovascular mortality, even in nomortensive subjects. Baroreflex sensitivity (BRS) is integral to BP regulation, and varies among healthy persons. Baroreceptors sense arterial pressure indirectly from the degree of stretch of the elastic arterial walls. A reduced ability of baroreflex buffering in elderly, hypertensives, and patients with carotid denervation results in an elevated pressor response to mental stress (MS). We hypothesized that there might be a correlation between BRS and AASI in healthy subjects, and individuals with higher BRS would have a lower pressor response to MS. We measured 24-hour ambulatory BP, BRS (modified Oxford), HR, and intra-arterial pressure (AP) during MS in 53 healthy, normotensive, non-obese individuals (32 women, 21 men, mean age ± SE: 28 ± 1). AASI was defined as 1 minus the regression slope plotted from diastolic over systolic BP using all of the ambulatory BP readings. Although all measures were widely variable among subjects, there was no relationship between AASI, BRS, or pressor response to MS. We conclude that in the absence of aging, cardiovascular, or autonomic disease, the novel stiffness index (AASI) and baroreflex control of heart rate are unable to account for the complex pressor response to MS. Support: K23 RR17520, HL 46493, DFG grant He 4605/1-1.

Hyperglycemic response to hemorrhage is modulated by baroreceptors unloading but not by peripheral chemoreceptors activation

The aim of this study was to assess the relative participation of carotid baro- and chemoreceptors on plasma glucose and lactate level in response to hemorrhagic hypotension. We also evaluated the effects of selective activation of carotid chemoreceptors. One week before the experiments, male Wistar rats (250–300 g) were submitted to bilateral total carotid denervation (BCD-group), or to bilateral ligature of the carotid body artery (ChD-group). During the same surgical procedure, a chronic jugular catheter for blood sampling and hemorrhage (1.2 mL/100 g/2 min) and polyethylene cannula was inserted into the left femoral artery for cardiovascular monitoring. One group submitted to fictitious surgery was used as a surgical control (Sham-group). Carotid chemoreceptors were selectively activated by sodium cyanide (NaCN, 40 μg/0.1 mL i.v.) in the Sham and ChD group. The results showed that hyperglycemic response to hemorrhage in the BCD-group was reduced whereas in the ChD-group there was no significant change in this parameter compared to the Sham group (8.6 ± 0.5 mM, Sham-hemorrhaged, n = 8; 7.2 ± 0.3 mM, BCD-hemorrhaged, n = 8 and 9.4 ± 0.6 mM, ChD, n = 8, p < 0.05). Increased plasma lactate levels following hemorrhage were observed in all the three experimental groups throughout the experimental period and there were no differences between the groups. Chemoreceptor stimulation by NaCN also produced hyperglycemia, as well as an increase in blood pressure and bradycardia but did not affect plasma lactate concentration. Ligature of the carotid body artery annulled the cardiovascular responses induced by NaCN, but did not change the hyperglycemic response to hypoxia. In conclusion, our data indicate that carotid chemoreceptors do not play any major role in overall metabolic response to hypoxia or hemorrhagic hypotension. Furthermore, the results suggest that carotid baroreceptors unloading play a predominant role as main source of afferent impulses leading to the hyperglycemic response to hemorrhage. In addition our data shows that the metabolic response and cardiovascular adjustment to hypoxia can be dissociated by ligature of the carotid body artery.