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Biomedical subjects

M Ghignone

Publications and source records attributed to M Ghignone.

At least 19 recordsLinked to original sources
PubMed1991

Effect of clonidine on the circulation and vasoactive hormones after aortic surgery.

After completion of abdominal aortic graft, 29 patients received an i.v. infusion of placebo (n = 16) or clonidine 7 micrograms kg-1 (n = 13) over 120 min in a double-blind study. Cardiovascular variables were measured and plasma samples obtained up to 5 h after arrival in the recovery room, for assay of noradrenaline, adrenaline, vasopressin and renin concentrations. Noradrenaline, adrenaline and vasopressin concentrations decreased in the clonidine group throughout recovery (P less than 0.001, 0.05 and 0.05, respectively, vs placebo). Heart rate was less in the clonidine group (P less than 0.01). There was no significant difference in mean arterial pressure between groups. Stroke volume was larger (P less than 0.01) and there were fewer episodes of hypertension (P less than 0.05) and tachycardia in the clonidine group. In addition, a reduction in the number of circulatory interventions (P less than 0.05) and episodes of shivering was noted in the clonidine group. Mean (SD) postoperative volume requirements were larger in the clonidine group (total postoperative input: clonidine 1462 (604) ml; placebo 1064 (348) ml (P less than 0.05]. These data are consistent with the observation that clonidine modifies endocrine and circulatory status after major surgery.

Aorta, Abdominal↗
PubMed1990

Aortic surgery: effect of clonidine on intraoperative catecholaminergic and circulatory stability.

Twenty-eight patients presenting for aortic surgery were randomly assigned in a double-blind, placebo-controlled protocol to receive placebo (n = 14) or clonidine (4.7 +/- 1.2 micrograms.kg-1 po; n = 14), in addition to flunitrazepam 120 min before induction of anesthesia. Plasma catecholamines (CA) and hemodynamic variables were determined at 7 stages during surgery. In the placebo group, plasma epinephrine (E) and norepinephrine (NE) had risen twofold at skin closure compared to baseline (E: from 109 +/- 51 pg.ml-1 to 294 +/- 161 pg.ml-1; NE: from 658 +/- 226 to 1150 +/- 494 pg.ml-1). Plasma CA were significantly lower in the clonidine group (P less than 0.001 and 0.01 vs placebo for NE and E respectively). In both groups, similar directional changes were observed for the circulatory variables, upon aortic clamping and declamping. In the clonidine group, however, mean arterial pressure was lower at most stages (P less than 0.05 vs placebo); moreover, stroke volume index was greater in the clonidine group (P less than 0.05) upon declamping. This improved stability in the clonidine group was achieved with a halving in the number of anesthetic/circulatory interventions (P less than 0.05 vs placebo). Provided intravascular volume is adequate, clonidine suppresses the increase in plasma catecholamines induced by aortic surgery and improves circulatory stability, with a reduced number of anesthetic, circulatory adjustments.

Adult↗
PubMed1989

Continuous volume infusion improves circulatory stability in anesthesized rats.

'Optimized' management (OM) was provided to chloralose-anesthetized rats for 12 h by combining continuous infusion (7 ml.kg-1). mechanical ventilation and strict control of acid-base equilibrium (n = 7). The chloralose-anesthetized rats managed conventionally (conventional management: CM, n = 9) received neither volume infusion, nor mechanical ventilation, nor correction of acid-base disturbances. All the OM rats completed the study while 6 out of 9 CM rats died before the end of the study period. Mean arterial pressure (MAP) remained at 100 mmHg for 12 h in the OM group. MAP stayed close to 70 mmHg in the CM group for 6 h and declined to very low levels thereafter (mean +/- S.E.M.: 46.0 +/- 3.9 mmHg at 12 h, P less than 10(-4) when compared to the other group). Central venous pressure and cardiac output remained close to baseline values for 12 h in the OM group. Acid-base equilibrium was preserved in the OM group in contrast to a severe metabolic acidosis in the CM group (pH = 7.14 +/- 0.03 at 12 h; P less than 10(-4). Such as 'optimized' management involving mechanical ventilation with oxygen, continuous infusion and acid-base monitoring may be of value to maintain circulatory stability in anesthetized rodent preparations during long periods of time, as in neurophysiological experiments.

Anesthesia↗
PubMed1989

Postoperative analgesia with extradural clonidine.

The analgesic effect of extradural clonidine was evaluated in a double-blind study. In the recovery room, following orthopaedic or perineal surgery 20 ASA I and II patients were allocated randomly to two groups. The extradural clonidine (EC) group received clonidine 2 micrograms kg-1 in isotonic saline solution 15 micrograms ml-1. The extradural saline (ES) group received the equivalent volume of plain isotonic saline solution. Pain was evaluated by a visual analogue scale (VAS) at 15-min intervals for the first 2 h and subsequently at 30-min intervals for the following 4 h. Morphine 5 mg was given s.c. when patients complained of pain after extradural saline or clonidine. In the EC group, the mean (SD) maximum pain relief was 68.2 (24.1)% of the initial VAS score, but it was only 14.7 (25.2)% in the ES group. The mean duration of analgesia, before injection of morphine, was significantly longer in the EC group (210 (87) min) compared with the ES group (45 (27) min) (P less than 0.001). Drowsiness and moderate hypotension were observed in the EC group.

Adult↗
PubMed1988

Anesthesia for ophthalmic surgery in the elderly: the effects of clonidine on intraocular pressure, perioperative hemodynamics, and anesthetic requirement.

The effects of clonidine on intraocular pressure and perioperative cardiovascular variables were studied by a randomized double blind design in 80 elderly patients (ASA physical status I-III) scheduled for elective ophthalmic surgery under general anesthesia (GA) and local anesthesia (LA). Group 1 (n = 40), the control group, received diazepam po (0.1 mg.kg-1) 90-120 min prior to arrival to the operating room. Group 2 (n = 40) received clonidine po approximately 5 micrograms.kg-1 po at the same time. Each group was divided into subgroups of 20 patients each to be managed with GA (GA subset) or LA (LA subset). Ninety to 120 minutes after the premedication, a large decrease in IOP from 20 +/- 3 to 12 +/- 3 mmHg (P less than 0.01) and a small but significant reduction of both systolic and diastolic BP and HR were observed in patients receiving clonidine, while no changes occurred in controls. In the patients managed with GA, clonidine effectively prevented IOP rise and attenuated the associated cardiovascular response (P less than 0.01) following laryngoscopy and tracheal intubation, and significantly reduced intraoperative cardiovascular lability and anesthetic requirement for isoflurane (P less than 0.05) and for fentanyl (P less than .001). In patients managed with LA, intraoperative systolic (P less than 0.01) and diastolic BP and HR variability (P less than 0.05) were significantly lower in patients receiving clonidine as compared to controls. Intraoperatively, a significantly higher incidence of hypertension (P less than 0.01) and tachycardia (P less than 0.05) were respectively observed in the LA subset and GA subset of the controls when contrasted with the corresponding subset of those receiving clonidine. Moreover, clonidine was more effective than diazepam as a premedication; in fact, satisfactory intraoperative sedation and cardiovascular stability were observed in 85% of the patients who received clonidine, and in 50% of those patients who did not receive clonidine (P less than 0.01). Thus, clonidine may represent a useful adjunct in the management of the aged patient in the setting of ophthalmic surgery.

Anesthesia↗
PubMed1987

Baroreflex-linked variations of catecholamine metabolism in the caudal ventrolateral medulla: an in vivo electrochemical study.

In vivo electrochemical recordings of the metabolism of catecholamines were obtained in the caudal ventrolateral medulla in anesthetized rats submitted to various experimental changes in systemic arterial pressure. Hypertension induced with phenylephrine and reversal of hypovolemia decreased the catechol metabolic activity. In contrast, controlled or hypovolemic hypotension, induced respectively with sodium nitroprusside or blood withdrawal (30% of blood volume), reversibly elicited the opposite pattern. This was suppressed by deafferentation. The changes in catechol metabolic activity in response to hypovolemia were accompanied by similar trends of variations of plasma vasopressin levels. By contrast with the increased catechol metabolic activity secondary to hypotension induced by either prazosin, sodium nitroprusside or hypovolemia, clonidine elicited a decrease in catechol metabolic activity. These data show a dynamic and specific involvement of the metabolism of catecholamines themselves promoted by changes in systemic arterial pressure. This pattern of functioning of catechol metabolism in the caudal ventrolateral medulla appears to be negatively related to systemic arterial pressure changes, a finding which does not fit with the proposed vasodepressor role of the A1-group.

Animals↗
PubMed1987

Clonidine modulates the ventrolateral medullary catechol metabolic hyperactivity induced by hypotension.

In vivo electrochemistry allowed recording of a catechol oxidation current in the ventrolateral medulla, caudal to the obex, in anesthetized rats whose ventilatory, metabolic and hemodynamic parameters were rigorously controlled. Hemorrhage or controlled hypotension induced an increase in the metabolism of catecholamines in the A1 noradrenergic group, which remained activated after full hemodynamic recovery. Clonidine (200 micrograms.kg-1 i.p.) given 30 min prior to hemorrhage or immediately before controlled hypotension suppressed partially the increased metabolism of catecholamines especially during the recovery period. This suggests that clonidine preserved phasic reactivity upon circulatory disturbances and decreased tonic hyperactivity following circulatory recovery.

Animals↗
PubMed1987

Haemodynamic effects of clonidine injected epidurally in halothane-anaesthetized dogs.

The haemodynamic effects of clonidine administered in the epidural space were studied in 16 halothane-anaesthetized dogs. The animals were randomly assigned to two groups: Group I received three doses of 3 ml of normal saline, Group II received three doses of 3 micrograms X kg-1 of clonidine, through an epidural catheter, whose tip was located between L2-T11. Control haemodynamic measurements were taken one hour after completion of the surgical preparation (period P1); they were repeated every 45 minutes after each incremental dose (periods P2, P3, P4) and 105 minutes after a total cumulative dose of 9 micrograms X kg-1 of clonidine or 9 ml of saline were given (period P5). No significant changes over time were observed in Group I. In Group II clonidine produced statistically significant reductions of systemic blood pressure (BP), mean left ventricular pressure (LV), heart rate (HR), cardiac output (CO) and peak LV dP/dt only after a total clonidine dose of 9 micrograms X kg-1 and these changes were sustained. BP fell 15 per cent, CO 21 per cent, HR 25 per cent, LV 20 per cent and peak LV dP/dt 30 per cent when P5 measurements were compared to control values within Group II (p less than 0.05). These haemodynamic effects of clonidine are likely due to minimal systemic absorption and/or cephalad spread of the drug towards its site of action in the brain stem. The reductions of HR, CO, BP, and isovolemic indices of contractility are likely explained by a reduction of sympathetic outflow at the spinal cord and medulla oblongata levels as well as increased parasympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1987

Effect of clonidine on haemodynamic responses to endotracheal intubation and on gastric acidity.

Sixty-three patients (ASA 1-2), scheduled for elective surgery under general anaesthesia, were randomly given either oral clonidine (225-375 micrograms) + diazepam (5 15 mg), cimetidine (300 mg the night before and 300 mg in the morning) + diazepam or only diazepam for premedication. Anaesthesia was induced with thiopentone and maintained with N2O + O2 (70:30), enflurane and fentanyl. Vecuronium bromide was used as a muscle relaxant. The sleep dose of thiopentone was significantly smaller in the patients pretreated with clonidine than in the other groups. The mean maximal increase in heart rate was lowest in the clonidine-pretreated patients, but there were no significant differences in the mean arterial pressure changes associated with intubation. Before and just after intubation and in the recovery room, the arterial pressures were lowest in the patients pretreated with clonidine. During anaesthesia, marked bradycardia (less than or equal to 45 beats min-1) did not occur more often when clonidine was used, but in the recovery room there were statistically significantly more patients with bradycardia in the clonidine group than in the other groups. On the electrocardiogram (ECG) during the endotracheal intubation, the incidence of bigeminy was higher in the diazepam patients (5/20) than in the cimetidine patients (2/20) and the clonidine patients (0/23). There were significantly more gastric content samples with a pH above 2.5 in the cimetidine group than in the other groups, and clonidine patients did not differ from diazepam patients in this respect. The high incidence of bradycardia with the concomitant hypotension may limit use of this drug to highly selected patients.

Administration, Oral↗
PubMed1987

The ability of the alpha 2-adrenergic agonist clonidine to suppress central noradrenergic hyperactivity secondary to hemodynamic or environmental stimuli.

Metabolism of catecholamines was monitored by in vivo voltammetry in the ventrolateral medulla (encompassing the A1 group of noradrenergic cell bodies) of anesthetized rats and in the locus coeruleus of behaving rats. Activation of metabolism of catecholamines was produced by using: (1) controlled hypotension (sodium nitroprusside, mean arterial pressure reduced to approximately 60 mm Hg for 60 min, n = 5) in anesthetized animals; and (2) immobilization (10 min) of conscious rats (n = 5). Clonidine, 200 micrograms/kg (i.p., n = 3), suppressed almost entirely the activation of the metabolism of catecholamines secondary to controlled hypotension in the ventrolateral medulla. Clonidine, 50 (n = 3) to 200 (n = 5) micrograms/kg (i.p.), produced a dose-dependent suppression of the activation of the metabolism of catecholamines induced by immobilization in the locus coeruleus of conscious rats. The results obtained from this study provide a biochemical rationale for the use of alpha 2-agonists in conditions where central or peripheral noradrenergic activity is heightened.

Animals↗
PubMed1987

Anesthesia and hypertension: the effect of clonidine on perioperative hemodynamics and isoflurane requirements.

Thirty patients (ASA physical status II-III) with a history of arterial hypertension, whose blood pressure (BP) control varied from normotension to moderate hypertension (diastolic BP less than 110 mmHg), scheduled for elective surgery under general anesthesia, were randomly assigned to two groups. Group 1 was premedicated 90-120 min prior to induction with diazepam 0.15 mg X kg-1 po; group 2, in addition, received clonidine 5 micrograms X kg-1 po. Anesthetic depth was assessed by on-line aperiodic analysis of the electroencephalogram. Following lidocaine 1 mg X kg-1 and fentanyl 2 micrograms X kg-1 (group 1 only), anesthesia was induced with thiopental 3-4 mg X kg-1 and vecuronium 0.1 mg X kg-1 was used to facilitate endotracheal intubation. Anesthesia was maintained with isoflurane in N2O/O2 and supplemented by fentanyl. In group 2, clonidine produced a rapid preoperative control of systolic and diastolic BP from 166 +/- 32/95 +/- 14 to 136 +/- 80 +/- 11 (P less than 0.01), was more effective in blunting the reflex tachycardia associated with laryngoscopy and endotracheal intubation than lidocaine-fentanyl pretreatment. It significantly reduced the intraoperative lability (coefficient of variation) of systolic (P less than 0.01) and diastolic BP and heart rate (HR) (P less than 0.05), and resulted in significantly slower HR during recovery (P less than 0.01). Anesthetic requirements for isoflurane were reduced 40% (P less than 0.01) in group 2; narcotic supplementation was also significantly reduced (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1986

Catecholamine metabolism in the rat locus coeruleus as studied by in vivo differential pulse voltammetry. III. Evidence for the existence of an alpha 2-adrenergic tonic inhibition in behaving rats.

One of the various regulations controlling the noradrenergic (NA) locus coeruleus (LC) activity has been proved to be alpha 2 adrenergic specific, on the basis of electrophysiological data obtained in anesthetized preparations. To assess, under rigorously chronic conditions, the existence of such an inhibition, recordings of LC catechol metabolic activity were performed with in vivo differential pulse voltammetry. A guiding cannula and appropriate wires were implanted under anesthesia. After 48 h of recovery a carbon fiber electrode was threaded to the LC through this cannula to monitor the LC catechol oxidation current. Piperoxane 60 mg/kg i.p. and yohimbine 10 mg/kg i.p. induced an increase in catechol oxidation current to approximately 300% of baseline (100%) values. Graded doses of piperoxane (1-100 mg/kg i.p.) induced a dose dependent increase in LC catechol metabolic activity (ED50 = 29.7 mg/kg). These changes in catechol oxidation current were confirmed either by combined electrophysiological and electrochemical recordings in the LC of an anesthetized preparation, or by postmortem HPLC catechol determinations on LC microdissections. By contrast, guanfacine 1 mg/kg and clonidine (10-200 micrograms/kg i.p.) induced a dose dependent decrease in catechol peak height. Clonidine 50 micrograms/kg reversed the effect of piperoxane 30 mg/kg i.p. On the other hand, a highly selective alpha 1 antagonist, such as prazosin (1 mg/kg i.p.), evoked only a small increase in catechol peak (11% above saline effect). This data is consistent with previously reported electrophysiological, biochemical and autoradiographic data. They confirm the presence of a tonic alpha 2 adrenergic inhibition on NA-LC cell activity, in behaving rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Presynaptic effect of clonidine on unmyelinated afferent fibers in the spinal cord of the cat.

The effects of clonidine (Clo) were investigated on the excitability of intraspinal primary afferent terminals of both A- and C-fibers of cutaneous origin. Primary afferent terminal excitability was tested by delivering constant current pulses to the dorsal horn of acutely spinalized cats anesthetized with pentobarbital. Clo given i.v. selectively increased the excitability of the C-fiber primary afferent terminals (mean 85%). Primary afferent terminal excitability of A-fibers was not affected. This effect of Clo was reversed by yohimbine or phentolamine, thus suggesting mediation by alpha2-adrenoceptors. These findings suggest a presynaptic inhibitory effect of Clo in spinal nociceptive pathways that might explain the mechanism of action of this drug.

Action Potentials↗
PubMed1986

Clonidine modulates locus coeruleus metabolic hyperactivity induced by stress in behaving rats.

To assess, under rigorously chronic conditions, whether clonidine would modulate the increased activity engendered by stress in the locus coeruleus (LC), rats implanted for recordings by in vivo voltammetry, were subjected to immobilization (10 min). When injected 30-60 min before stress, clonidine 50-200 micrograms/kg i.p. modulated the increased catechol metabolic activity in a dose-dependent manner. This provides a biochemical basis, obtained in behaving rats, for using clonidine as a stabilizer in syndromes where central noradrenergic or peripheral sympathetic activities are heightened.

3,4-Dihydroxyphenylacetic Acid↗