L. Quintin

Spontaneous Cardiac Baroreflex in Humans Comparison With Drug-Induced Responses

We compared two methods of assessment of baroreflex sensitivity in eight supine healthy volunteers during repeated baseline measurements and various conditions of cardiac autonomic blockade. The spontaneous baroreflex method involved computer scanning of recordings of continuous finger arterial pressure and electrocardiogram to locate sequences of three or more beats in which pressure spontaneously increased or decreased, with parallel changes in pulse intervals. The mean regression slope of all these sequences during each study condition was considered to represent the mean spontaneous baroreflex slope. In the drug-induced method, sigmoidal curves were constructed from data obtained by bolus injections of phenylephrine and nitroprusside; the tangents taken at the resting pressure of each of these curves were compared with the mean spontaneous baroreflex slopes. The two methods yielded slopes that were highly correlated (r = .96, P < .001), with significant but similar intraindividual baseline variability. Atropine virtually eliminated the baroreflex slope; subsequent addition of propranolol did not alter it further. Propranolol or clonidine alone increased average baroreflex slope to the extent that they increased resting pulse interval (r = .69 to .83). The spontaneous baroreflex method provides a reliable, noninvasive assessment of human vagal cardiac baroreflex sensitivity within its physiological operating range.

Local Scale Exponents of Blood Pressure and Heart Rate Variability by Detrended Fluctuation Analysis: Effects of Posture, Exercise, and Aging

Heart rate self-affinity is often assessed by detrended fluctuations analysis, obtaining two coefficients only: a short-term (alpha1) exponent and a long-term (alpha2) exponent. Our aim is to show the limits of this approach and alternatively propose the estimation of the whole spectrum of local exponents alpha(n) for heart rate and blood pressure. To illustrate the advantages of this approach, we assess the effects of autonomic activations and age on alpha(n). We measured ECG and arterial pressure in 60 volunteers for 10 min, considering three conditions at increasing sympathetic activation: supine rest, sitting, and sitting during exercise. We computed alpha(n) of R-R intervals and systolic, mean, and diastolic blood pressures, as the slope of the detrended fluctuations function in a log-log plot. Volunteers were divided into age groups and compared. Results indicate that: 1) alpha1 cannot be defined because short-term coefficients decrease with n, while alpha2 cannot be defined only for blood pressure during supine rest; 2) heart rate and blood pressure scaling structures differ during supine rest but not during exercise; and 3) age effects appear mainly in supine rest, explaining discrepant results in literature. In conclusion, we recommend estimating the whole alpha(n) spectrum before possibly providing the two-exponent description only.

Long-Term Effects of RU24722 on Tyrosine Hydroxylase of the Rat Brain

Abstract: The effects of RU24722 (14,15‐dihydro‐20,21‐di‐noreburnamine‐14‐ol) on tyrosine hydroxylase in central catecholaminergic neurons were studied in rats treated with different quantities of the molecule, and a time course was done for the minimal dose that gave the maximal effect. RU24722 induced increases in tyrosine hydroxylase activities and specific protein content in noradrenergic cells of the locus ceruleus and decreased all these parameters in dopaminergic neurons of the substantia nigra and ventral tegmental area. The results pointed out that the specific activity of newly synthesized tyrosine hydroxylase in the loci cerulei was potentially greater but was not expressed “in vivo” except 7 days after injection. The phenotypic specificity and the time course pattern of the action could be considered as a consequence of an induction mechanism. The comparison of long‐term change in tyrosine hydroxylase values after pipe‐roxane, RU24722, clonidine, and combined RU24722‐clon‐idine treatment demonstrated that an activation during a few hours did not induce tyrosine hydroxylase in central noradrenergic neurons. Clonidine antagonized the activating effect of RU24722 following its injection but did not affect its long‐term induction properties.

Effect of clonidine on catechol metabolism in the rostral ventrolateral medulla: an in vivo electrochemical study

The dose-dependent reduction in catechol metabolism induced by an imidazoline with alpha 2-adrenoceptor agonist specificity, clonidine, was assessed (ED50 = 7 micrograms.kg-1 i.v.) with in vivo voltammetry in the rostral ventrolateral medulla of rats kept under halothane anesthesia and strictly controlled circulatory and ventilatory conditions. This reduction in catechol metabolism was observed in intact as well as in barodeafferented rats.

Sympathovagal effects of spinal anesthesia assessed by the spontaneous cardiac baroreflex

Background: The changes in sympathovagal balance induced by spinal anesthesia remain controversial. The spontaneous baroreflex method allows the continuous assessment of the spontaneous engagement of the cardiac baroreflex, giving an index of sympathovagal balance. The purpose of this study was to follow the effects of spinal anesthesia on spontaneous baroreflex sensitivity. Methods: Continuous electrocardiogram and noninvasive blood pressure were recorded in 24 patients scheduled for elective inguinal hernia repair and randomly assigned to three groups: (1) no volume loading, (2) volume loading of 15 ml/kg lactated Ringers solution, and (3) continuous infusion of etilefrine (an ephedrine‐like drug). Each patient was studied before, during, and after bupivacaine‐induced spinal anesthesia (mean sensory block: T4). Spontaneous baroreflex sensitivity and parameters of time‐domain analysis of heart rate variability were calculated from 30 min of recording of each period. Results: No significant change in spontaneous baroreflex slope or parameters of time‐domain analysis were observed after regional anesthesia in any group. However, three patients experienced episodes of bradycardia and hypotension in the absence of a high block; these three patients showed an increase in spontaneous baroreflex sensitivity and time‐domain parameters. Conclusions: Using a noninvasive, continuous technique to estimate cardiac sympathovagal balance, no significant variation in autonomic balance induced by spinal anesthesia was observed. However, untoward episodes of bradycardia and hypotension occurred in three patients, who could not be prospectively identified by the parameters studied.

Pharmacological and functional evidence for extracellular 3,4-dihydroxyphenylacetic acid as an index of metabolic activity of the adrenergic neurons: An in vivo voltammetry study in the rat rostral ventrolateral medulla

Catecholamine metabolism was studied in vivo in the C1 adrenergic area of the rostral ventrolateral medulla oblongata in rats, using differential normal pulse voltammetry coupled with an activated carbon fiber microelectrode. Pharmacological evidence indicates that 3,4-dihydroxyphenylacetic acid, the major dopamine metabolite, is responsible for the electrochemical signal appearance in the C1 group, and that it reflects the catecholamine synthesis rate, as previously reported in the locus coeruleus. Indeed, 3,4-dihydroxyphenylacetic acid was estimated to be formed from 77% of the intracellular dopamine, since its synthesis was increased by only 23%, after blockade of the dopamine-beta-hydroxylase activity. Neuronal activation by retrograde electrical stimulation increased the electrochemical signal, as well as hemorrhage and hypotension, suggesting that the level of extracellular 3,4-dihydroxyphenylacetic acid is a good biochemical index of the C1 adrenergic cellular activity in baseline conditions and during cellular activation.

Local-Scale Analysis of Cardiovascular Signals by Detrended Fluctuations Analysis: Effects of Posture and Exercise

The fractal structure of heart rate is usually quantified by estimating a short-term (alpha1) and a long-term (alpha2) scaling exponent by detrended fluctuations analysis (DFA). Evidence, however, has been provided that heart rate is a multifractal signal, better characterized by a large number of scaling exponents. Aim of this study is to verify whether two scaling exponents only from DFA provide a sufficiently accurate description of the possibly multifractal nature of cardiovascular signals. We measured ECG and finger arterial pressure in 33 volunteers for 10 minutes during each of 3 conditions: supine rest (SUP); sitting at rest (SIT); light physical exercise (EXE). DFA was applied on the beat-by-beat series of R-R interval (RRI) and mean arterial pressure (MAP). We then computed the local scaling exponent alpha(n), defined as the slope of the detrended fluctuation function F(n) around the beat scale n, in a log-log plot. If alpha1 and alpha2 correctly model the multiscale structure of blood pressure and heart rate, we should find that alpha(n) is constant over a short-term and a long-term range of beat scales. Results show that only the long-term alpha2 exponent provides a relatively good approximation of the multiscale structure of RRI and MAP. Moreover, posture and physical activity have important effects on local scaling exponents, and on the range of beat scales n where alpha(n) can be approximated by a constant alpha2 coefficient.

Catechol activation in the vasomotor center upon emergence from anesthesia: specificity.

The rostral ventrolateral medulla (RVLM) controls the vascular system. It may contribute to postoperative hypertension observed upon emergence from anesthesia. This structure contains adrenergic cardiovascular neurons. Therefore, one question was addressed: does a change in RVLM catechol activity occur upon emergence from anesthesia? Halothane‐anesthetized, paralyzed rats had their ventilatory, circulatory, and acid‐base stability controlled. All pressure points and incisions were infiltrated with local anesthetic. With in vivo electrochemistry, a catechol signal was recorded in the RVLM in the following circumstances: (1) under stable halothane anesthesia for 120 minutes (halothane group), (2) during 120 minutes after halothane discontinuation (saline‐emergence group), (3) during 60 minutes after halothane discontinuation followed by 60 minutes after halothane readministration (readministration group), (4) emergence in rats treated with atenolol and nitroprusside to hold blood pressure as close as possible to baseline, (5) emergence after morphine 1 mg.kg−1 i.v., (6) emergence after decerebration, and (7) emergence upon recording in the mid‐brain dopaminergic A10 area. Stable halothane anesthesia (n = 6) led to no change in mean arterial pressure (MAP), heart rate (HR), and catechol signal (CAOC). During emergence from anesthesia (n = 6), MAP, HR, and catechol signal increased and did not return to baseline. By contrast, a return of MAP, HR, and catechol signal to baseline was observed upon readministration of halothane (n = 6). Whereas blood pressure and heart rate were maintained as closely as possible to baseline, a large catechol activation (n = 5) was observed upon emergence from anesthesia. A catechol activation from a lowered baseline was observed upon emergence following morphine administration (n = 5). A minor circulatory activation without RVLM catechol activation was observed upon emergence following decerebration (n = 5). Recordings in the A10 area revealed no increase in the catechol signal following emergence (n = 5). Adrenergic RVLM neurons appear to be responsive upon emergence from anesthesia, possibly being activated by suprapontine afferents impinging on the RVLM. Synapse 30:130–139, 1998.

Post-operative pressure lability and cardiac baroreflex in normotensive patients as a function of age

Background: Pressure lability may be linked to the loss of the cardiac baroreflex. The reduction of the sensitivity of the cardiac baroreflex has not been delineated in the post‐operative period according to age in normotensive patients. This study addresses pressure lability and slope of the cardiac baroreflex as a function of age.