Biomedical subjects

A Sassine

Publications and source records attributed to A Sassine.

At least 19 recordsLinked to original sources

PubMed2001

The comparative electrophysiologic and hemodynamic effects of a large dose of ropivacaine and bupivacaine in anesthetized and ventilated piglets.

UNLABELLED: Ropivacaine is less potent and less toxic than bupivacaine. We administered these two local anesthetics in a cardiac electrophysiologic model of sodium thiopental-anesthetized and ventilated piglets. After assessing the stability of the model, bupivacaine (4 mg/kg) and ropivacaine (6 mg/kg) were given IV in two groups (n = 7) of piglets. No alteration in biological variables was reported throughout the study. Bupivacaine and ropivacaine similarly decreased mean aortic pressure from 99 +/- 22 to 49 +/- 31 mm Hg and from 87 +/- 17 to 58 +/- 28 mm Hg, respectively, and decreased the peak of the first derivative of left ventricular pressure from 1979 +/- 95 to 689 +/- 482 mm Hg/s and from 1963 +/- 92 to 744 +/- 403 mm Hg/s, respectively. Left ventricular end-diastolic pressure was similarly increased from 6 +/- 5 to 9 +/- 5 mm Hg and from 6 +/- 4 to 12 +/- 4 mm Hg, respectively. Bupivacaine and ropivacaine similarly lengthened the cardiac cycle length (R-R; from 479 +/- 139 to 706 +/- 228 ms and from 451 +/- 87 to 666 +/- 194 ms, respectively), atria His (from 71 +/- 15 to 113 +/- 53 ms and from 64 +/- 6 to 86 +/- 10 ms, respectively), and QTc (QTc = QT x R-R(-0.5), Bazett formula; from 380 +/- 71 to 502 +/- 86 ms and from 361 +/- 33 to 440 +/- 56 ms, respectively) intervals. Bupivacaine altered to a greater extent the PQ (the onset of the P wave to the Q wave of the QRS complex) (from 97 +/- 20 to 211 +/- 60 ms versus from 91 +/- 8 to 145 +/- 38 ms, P < 0.05), QRS (from 58 +/- 3 to 149 +/- 34 ms versus from 60 +/- 5 to 101 +/- 17 ms, P < 0.05), and His ventricle interval (from 25 +/- 4 to 105 +/- 30 ms vs from 25 +/- 4 to 60 +/- 30 ms, P < 0.05) than ropivacaine. A 6 mg/kg ropivacaine dose induced similar hemodynamic alterations as 4 mg/kg bupivacaine. However, bupivacaine altered the variables of ventricular conduction (QRS and His ventricle) to a greater extent. IMPLICATIONS: A 6 mg/kg ropivacaine dose induced similar hemodynamic alterations as 4 mg/kg bupivacaine. However, bupivacaine altered the variables of ventricular conduction (QRS and His ventricle) to a greater extent.

Amides↗

PubMed1997

Comparison of proarrhythmogenic effects of two potassium channel openers, levcromakalim (BRL 38227) and nicorandil (RP 46417): a high-resolution mapping study on rabbit heart.

This study was designed (a) to test and (b) to compare proarrhythmic effects of levcromakalim and nicorandil; and (c) determine the mechanism of arrhythmia initiation by using high-resolution ventricular epicardial mapping on 44 Langendorff-perfused rabbit hearts. Eighteen hearts were kept intact and received incremental doses (1-500 microM) of levcromakalim, nicorandil, and isosorbide dinitrate. In 26 hearts, a thin layer of epicardium was obtained after endocardial cryotechnique (frozen hearts). In intact hearts, isosorbide dinitrate did not produce any arrhythmia. In contrast, levcromakalim induced spontaneous ventricular fibrillation (VF) in all hearts at 50 microM, whereas only one VF occurred at 500 microM nicorandil. These three drugs produced a dose-dependent bradycardia in intact hearts. In frozen hearts, arrhythmias were induced by 5 microM levcromakalim and 50 microM nicorandil. Isosorbide dinitrate had no proarrhythmogenic effect. Epicardial mapping showed that most of induced ventricular tachycardias were based on reentry around an arc of functional conduction block. Ventricular conduction velocities did not change, but levcromakalim and nicorandil shortened ventricular effective refractory period. We conclude that (a) levcromakalim and nicorandil, used in toxic concentrations, have direct proarrhythmic effects; (b) nicorandil proarrhythmogenic effects are 10 times less marked than those of levcromakalim (arrhythmia is solely the result of the potassium channel opener property of nicorandil); and (c) most of ventricular tachycardias induced are based on reentry.

Animals↗

PubMed1996

Comparative electrophysiologic and hemodynamic effects of several amide local anesthetic drugs in anesthetized dogs.

Large and equipotent doses of several local anesthetics were administered in a cardiac electrophysiologic model on closed-chest dogs. Five groups of pentobarbital-anesthetized dogs were each given intravenously 16 mg/kg lidocaine, 12 mg/kg mepivacaine, 4 mg/kg or 8 mg/kg etidocaine, and 4 mg/kg bupivacaine. Lidocaine induced bradycardia, slowing of atrioventricular node conduction (AH), and marked hemodynamic depression, represented by a decrease in mean aortic pressure (MAoP), in the peak of first derivative of left ventricular pressure (LVdP/dt(max)) and by an increase in left ventricular end-diastolic pressure (LVEDP). Atrial pacing at pacing cycle length (PCL) of 298 ms did not enhance the alteration of variables of ventricular conduction (His ventricle [HV] interval and QRS duration). Mepivacaine induced slight alteration of electrophysiologic variables. Atrial pacing at PCL of 312 ms did not enhance the alteration of HV and QRS duration. Mepivacaine induced transient hemodynamic depression. Etidocaine (4 mg/kg) induced electrophysiologic and hemodynamic alterations similar to mepivacaine but artrial pacing at PCL of 330 ms enhanced HV lengthening and QRS widening (P < 0.05). Etidocaine (8 mg/kg) induced marked impairment of PR, HV, QRS, and QT, and dramatic hemodynamic depression represented by a decrease in MAoP from 123.5 +/- 16.2 at baseline to 36.5 +/- 8.3 mm Hg at 1 min (P < 0.001) and of LVdP/dtmax) from 1446 +/- 379 to 333 +/- 93 mm Hg/s (P < 0.001). Bupivacaine induced dramatic impairment of electrophysiologic variables. Bupivacaine also decreased LVDP/dtmax (from 1333 +/- 347 to 617 +/- 299,P < 0.001) and increased LVEDP. We conclude that mepivacaine induced moderate cardiotoxicity. In contrast, lidocaine induced dramatic hemodynamic depression while etidocaine and bupivacaine markedly impaired both electrophysiologic and hemodynamic variables. This double impairment could explain the great difficulty in resuscitating patients who have had cardiotoxic accidents induced by etidocaine or bupivacaine.

Amides↗

PubMed1994

Ventilatory effects of active compression-decompression in dogs.

STUDY OBJECTIVE: To determine the ventilatory effect of active compression-decompression CPR and to compare it with two other techniques, standard manual cardiac massage and mechanical cardiac massage. DESIGN: Prospective, randomized laboratory investigation. PARTICIPANTS: Mongrel dogs. INTERVENTIONS: Nine adult mongrel dogs were anesthetized, intubated, and mechanically ventilated. They were instrumented to measure arterial pressure, esophageal pressure, airway pressure, end-tidal carbon dioxide concentration, and minute ventilation. RESULTS: After induction of ventricular fibrillation, three sequences of cardiac massage were performed randomly during mechanical ventilation, standard cardiac massage, mechanical cardiac massage, and active compression-decompression technique. The animals then were disconnected from the ventilator, and the three sequences were performed again. Active compression-decompression created negative minimum esophageal pressures and significantly decreased the minimum airway pressure as compared with the other techniques. Whatever the ventilatory condition, minute ventilation was increased dramatically during active compression-decompression. CONCLUSION: In this model of cardiac arrest, an important increase in minute ventilation was observed during active compression-decompression. This effect was significantly greater than the increases observed with other techniques of cardiac massage and was related to the negative pressure generated by active decompression.

Airway Resistance↗

PubMed1994

Mechanisms of the putative cardioprotective effect of hexamethonium in anesthetized dogs given a large dose of bupivacaine.

BACKGROUND: Some reports suggest that activation of the autonomic nervous system by bupivacaine could participate in its cardiotoxicity. This is based in part on the fact that hexamethonium suppresses cardiac disturbances in anesthetized rabbits given small intracerebroventricular doses of bupivacaine. The aims of the current study were to determine, in anesthetized dogs, (1) whether the activation of the autonomic nervous system is deleterious after a large intravenous dose of bupivacaine and (2) whether the parasympathetic or sympathetic system is implicated in the bupivacaine-induced deleterious activation of the autonomic nervous system. METHODS: We used an electrophysiologic model in closed-chest dogs anesthetized with sodium pentobarbital. In group 1 (n = 6), dogs were given 4 mg/kg intravenous bupivacaine over 10 s. In group 2 (n = 6), dogs were given the same dose of bupivacaine 5 min after having received 0.2 mg/kg intravenous atropine sulfate. In group 3 (n = 9), dogs were pretreated with 10 mg/kg intravenous hexamethonium and then given bupivacaine 4 mg/kg. In addition, in group 3, the right atrium was paced at a basic cycle length of 400 ms to obtain a heart rate similar to that of group 1. RESULTS: Bupivacaine in group 1 induced significant bradycardia; lengthening of PR, atria-His, His-ventricle, and QTc intervals; and QRS widening. The first derivative of left ventricular pressure was significantly decreased, whereas left ventricular end-diastolic pressure was increased. Atropine pretreatment did not modify cardiac disturbances induced by bupivacaine. Hexamethonium pretreatment induced significantly less QRS widening and QTc lengthening than was seen in group 1 but worsened the bupivacaine effects on bradycardia, atria-His and PR intervals, mean aortic pressure, and first derivative of left ventricular pressure. Moreover, atrial pacing in group 3 induced alterations of QRS similar to those in group 1. CONCLUSIONS: Considering that marked slowing of ventricular conduction velocity (i.e., QRS widening) is known to facilitate reentrant ventricular arrhythmias, we conclude that (1) the activation of the autonomic nervous system by bupivacaine is not as deleterious as previously suggested; (2) the parasympathetic system is not markedly implicated in the worsening of direct bupivacaine cardiotoxicity; and (3) the sympathetic nervous system acts only by inducing a less marked bradycardia, which slows ventricular conduction velocity in a use-dependent manner, facilitating reentrant arrhythmias.

Anesthesia↗

PubMed1994

Pharmacokinetics of hydroxocobalamin in dogs.

Hydroxocobalamin is a powerful cyanide antidote that prevents sodium nitroprusside-induced cyanide toxicity. The pharmacokinetics of an i.v. bolus of hydroxocobalamin (70 and 140 mg/kg) were studied in conscious dogs (n = 6). Plasma hydroxocobalamin concentrations were measured using derivative spectrophotometry. The pharmacokinetics were compatible with a two-compartment model with a first-order distribution and elimination rate, and pharmacokinetic parameters were not different between the two doses, except for the elimination half-life. At 70 mg/kg, which is the recommended dose in acute cyanide poisoning, the elimination half-life was 7.36 +/- 0.79 h, the volume of distribution was 0.49 +/- 0.10 L/kg, and the total clearance 0.58 +/- 0.11 L/h. At high doses, hydroxocobalamin has a short elimination half-life and a limited volume of distribution that exceeds blood volume. These results could be useful in elaborating guidelines for the administration of hydroxocobalamin, when repetitive bolus and/or continuous infusion is required.

Animals↗

PubMed1994

Receptor mechanisms for clonidine reversal of bupivacaine-induced impairment of ventricular conduction in pentobarbital-anesthetized dogs.

Possible mechanisms of the ability of clonidine to correct bupivacaine-induced ventricular electrophysiologic impairment were evaluated in an electrophysiologic model on closed-chest dogs. Nine groups (n = 6) of pentobarbital-anesthetized dogs were given atropine, 0.2 mg/kg intravenously (i.v.), and bupivacaine, 4 mg/kg i.v., over a 10-s period. Group 1 was then given only saline solution. Group 2 was given clonidine, 0.01 mg/kg i.v., over a 1-min period. Group 3 was given clonidine followed by i.v. administration of yohimbine, 1 mg/kg, an alpha 2-antagonist. Group 4 was given carbachol, 1 mg/kg i.v., a long-lasting cholinergic agonist, over a 1-min period. Group 5 was given electrical stimulation of the left vagus nerve. Group 6 was given physostigmine, 0.1 mg/kg i.v., known to inhibit cholinesterase degradation, 5 min before bupivacaine administration, and Group 7 received a combination of physostigmine pretreatment and electrical vagal stimulation. Group 8 was given physostigmine, 0.1 mg/kg i.v., and pancuronium bromide, 1 mg/kg i.v., known to inhibit nicotinic receptors, 5 min before bupivacaine administration. Then electrical stimulation of the left vagus nerve was performed. Group 9 was given nicotine, 0.1 mg/kg i.v., 1 min after bupivacaine injection over 1 min. Bupivacaine induced bradycardia, markedly increased the His-Purkinje conduction time (HV interval) and QRS duration. Bupivacaine decreased the peak of first derivative of left ventricle pressure (LVdP/dtmax) and increased left ventricular end-diastolic pressure (LVEDP). Clonidine improved QRS duration and HV interval. Yohimbine did not modify the effects of clonidine. QRS duration and HV interval were significantly improved in Groups 4-7. In Group 8, pancuronium pretreatment inhibited the beneficial effects of the combination of physostigmine pretreatment and electrical vagal stimulation. In contrast, in Group 9, like clonidine, nicotine improved QRS duration and HV interval. Three other groups of anesthetized dogs (n = 6) were then studied. All dogs were given hexamethonium, 10 mg/kg i.v. Then, Group 10 was given only saline solution; Group 11 was given bupivacaine, 4 mg/kg, and Group 12 was given bupivacaine and nicotine as in Group 9. In Group 11, bupivacaine induced its usual alterations. In contrast, nicotine did not modify the cardiotoxic profile of bupivacaine after hexamethonium pretreatment. We conclude that the beneficial effect of clonidine on the variables of ventricular conduction altered by bupivacaine 1) is not mediated by central alpha 2-activation, 2) is mediated by the activation of parasympathetic pathways, and 3) is indirect and not mediated by acetylcholine release but is mediated by the activation of parasympathetic ganglionic nicotinic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Lemakalim, a potassium channel agonist, reverses electrophysiological impairments induced by a large dose of bupivacaine in anaesthetized dogs.

We have examined the ability of lemakalim to correct bupivacaine-induced cardiac electrophysiological impairment in an experimental electrophysiological model in closed-chest dogs. Two groups (n = 6) of pentobarbitone-anaesthetized dogs were given atropine 0.2 mg kg-1 i.v., and bupivacine 4 mg kg-1 i.v. over 10 s. Group 2 received also lemakalim 0.03 mg kg-1 i.v. Bupivacaine induced bradycardia, prolonged PR and His-ventricle (HV) intervals, QRS duration, QTc and JTc intervals, decreased left ventricular (LV) dP/dt max and increased LV end-diastolic pressure. Lemakalim reversed bupivacaine-induced PR, HV, QRS, QTc and JTc prolongation, and did not worsen bupivacaine-induced bradycardia and haemodynamic depression. We conclude that lemakalim can antagonize the main deleterious electrophysiological effects induced by a large dose of bupivacaine in anaesthetized dogs.

Anesthesia, General↗

PubMed1993

Electrophysiologic and arrhythmogenic effects of the potassium channel agonist BRL 38227 in anesthetized dogs.

Although potassium channel openers have been demonstrated to induce arterial vasodilation and shortening of the QT interval, the complete in vivo hemodynamic and electrophysiologic profile of these drugs has not been fully established. We evaluated the effects of BRL 38227, the active enantiomer of cromakalim, on the electrophysiologic and hemodynamic parameters in anesthetized dogs. Four intravenous (i.v.) doses (0.01, 0.03, 0.1, and 0.3 mg/kg) of BRL 38227 (lemakalim) were given to four different groups of 6 anesthetized and mechanically ventilated dogs. Electrophysiologic and hemodynamic parameters were measured with bipolar catheters positioned in the right atria and the right ventricle and double micromanometers placed in the left ventricle and the aorta. Nine dogs died of ventricular fibrillation (VF; 6 of 6 after 0.3 mg/kg, 2 of 8 dogs after 0.1 mg/kg, and 1 of 7 dogs after 0.03 mg/kg BRL 38227). Three dogs had atrial tachycardia (1 had atrial flutter and 1 had atrial fibrillation after 0.03 mg/kg, and 1 had atrial fibrillation after 0.01 mg/kg BRL 38227). BRL 38227 did not modify heart rate (HR), corrected sinus recovery time (CSRT), and atrial or atrio-ventricular (A-V) conduction times. In contrast, PR interval, Luciani-Wenckebach cycle length (LW), HV interval, QRS duration, ventricular effective refractory period (VERP), QT interval, and monophasic action potential (AP) were significantly shortened in a dose-dependent manner. Left ventricular end-diastolic pressure (LVEDP) was not modified, whereas LVdP/dtmax decreased significantly at 0.1 mg/kg BRL 38227. Finally, there was a significant dose-dependent decrease in systolic, diastolic, and mean aortic blood pressure (SBP, DBP, MAP). We conclude that BRL 38227 shortens the ventricular parameters of conduction velocity and of repolarization and decreases BP, both in a dose-dependent manner. All doses were arrhythmogenic, suggesting that BRL 38227 has a low safety margin.

Anesthesia↗

PubMed1993

[Cardiotoxicity of local anesthetics].

The intravascular administration and the high blood resorption of local anesthetic agents are known to induce neurotoxic accidents. However, the use of potent local anesthetic drugs such as bupivacaine is responsible for serious cardiotoxic accidents with a mortality of about 50%. Indeed, bupivacaine induces both electrophysiologic and haemodynamic disturbances with the occurrence of conduction blocks, arrhythmias and cardiovascular collapse. Moreover, cardiotoxicity is worsened by: bupivacaine-induced sympathetic activation which facilitates tachycardia and arrhythmias, metabolic abnormalities such as hypoxia, acidosis, hyperkaliemia and hypothermia, pregnancy, diazepam pretreatment, and the antiarrhythmic drugs. In case of cardiac arrest, CPR must be made. In the other cases, the first treatment is to oxygenate, to intubate the trachea and to ventilate the lungs, and then to stop convulsions. Specific cardiac resuscitation remains controversial because it is based principally on experimental results. We demonstrated that the combination of clonidine and dobutamine is efficient to reverse both haemodynamic and electrophysiologic impairments induced by a large dose of bupivacaine in anesthetized dogs. Whatever the efficiency of specific resuscitation, it must be emphasized that prevention of toxic accident must always include: the best choice of local anesthetic drug (e.g.: lidocaine+alpha-2 agonist vs bupivacaine), test dose, aspiration and slow administration. Finally, the monitoring of regional anaesthesia must be similar to that in use for general anaesthesia and drugs and devices for resuscitation must be ready.

Anesthetics, Local↗

PubMed1992

Succinylcholine does not worsen bupivacaine-induced cardiotoxicity in pentobarbital-anaesthetized dogs.

The intravascular injection of a large dose of bupivacaine induces electrophysiological cardiac impairment, mainly by slowing ventricular conduction velocity, and haemodynamic depression, by a decrease in myocardial contractility. When cardiotoxicity occurs, succinylcholine rapidly stops convulsions. However, the possible interactions between bupivacaine and succinylcholine on cardiac electrophysiology and haemodynamic status have never been investigated. Thus, we used an experimental electrophysiological model involving closed-chest dogs. Three groups (n = 6) of pentobarbital-anaesthetized dogs were given 0.2 mg.kg-1 atropine iv. Dogs in Group 1 were given saline. The others received 4 mg.kg-1 bupivacaine iv over ten seconds. Dogs in Group 2 were then given saline and those in Group 3 were then given 2 mg.kg-1 succinylcholine iv from one to two minutes after the administration of bupivacaine. The following electrophysiological variables were measured: heart rate represented by RR interval (RR), PR, atria-His (AH), and His-ventricle (HV) intervals, QRS duration, and QT interval corrected for heart rate (QTc). The following haemodynamic variables were measured: mean aortic pressure (MAoP), the peak of the first derivative of left ventricular pressure (LV dP/dt max), and LV end diastolic pressure (LVEDP). Comparison between Groups 1 and 2 showed that bupivacaine induced more than 100% HV interval lengthening and QRS widening (P less than 0.01), prolonged QTc interval by more than 25% (P less than 0.01), and decreased LV dP/dt max by more than 50% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

PubMed1992

Verrucous carcinoma of the penis: importance of human papillomavirus typing for diagnosis and therapeutic decision.

One case of penile verrucous carcinoma (Buschke-Löwenstein tumor) undergoing anaplastic transformation and containing human papillomavirus type 6 is presented. The viral genome is detected by in situ hybridization using biotin-labeled cDNA probes. The clinical, histological and virologic criteria of verrucous carcinoma are discussed in comparison to giant condyloma and highly differentiated squamous cell carcinoma. The importance of viral typing determination for further diagnostic and therapeutic procedures is emphasized.

Aged↗

PubMed1992

Experimental evidence in favor of role of intracellular actions of bupivacaine in myocardial depression.

Bupivacaine is more cardiodepressant than lidocaine. Nevertheless, the marked depression of contractility induced by bupivacaine cannot be completely explained by its electrophysiologic properties alone. Biophysical differences such as the greater lipid solubility of bupivacaine versus lidocaine must be taken into consideration. Perhaps more bupivacaine enters the cardiac cells and interacts with contractile processes. To test this hypothesis, the entry of lidocaine into the cells was facilitated by a membrane-permeant lipophilic anion, tetraphenylboron. We compared the spontaneous atrial rate and the contractile force of rabbit right atria bathing in solutions containing either 0.5 microgram/mL lidocaine or bupivacaine. Group 1 (n = 8) served to test the stability of the preparation. In group 2 (n = 6), tetraphenylboron (17 micrograms/mL) was added to Tyrode's solution; atrial rate was decreased by 8% and contractile force by 1.7%. In group 3 (n = 6), bupivacaine (0.5 microgram/mL) was added; bupivacaine decreased atrial rate by 11.3% and markedly depressed contractile force by 68.3%. In group 4 (n = 6), lidocaine (0.5 microgram/mL) was added; lidocaine did not change atrial rate but decreased contractile force by 6.0%. In group 5 (n = 6), both lidocaine and tetraphenylboron were added; atrial rate was decreased by 15.5% and contractile force was markedly depressed by 81.1%. In group 6 (n = 6), 0.2 mM adenosine triphosphate, tetraphenylboron, and then lidocaine were added; the addition of adenosine triphosphate partially counteracted the cardiodepressant effects of the combination of lidocaine and tetraphenylboron. Atrial rate was decreased by 10.4% and contractile force was depressed by 13.6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Reversal of electrophysiologic and hemodynamic effects induced by high dose of bupivacaine by the combination of clonidine and dobutamine in anesthetized dogs.

The ability of clonidine and dobutamine to correct bupivacaine-induced cardiac electrophysiologic and hemodynamic impairment was evaluated in an experimental electrophysiologic model on closed-chest dogs. Five groups (n = 6) of pentobarbital-anesthetized dogs were given atropine (0.2 mg/kg IV). Group 1 was given a saline solution; all other dogs were given bupivacaine (4 mg/kg IV) over a 10-s period. Group 2 was given only bupivacaine. Group 3 was given clonidine (0.01 mg/kg IV) over a 1-min period. Group 4 was given a dobutamine infusion at 5 micrograms.kg-1.min-1. Group 5 was given the combination of clonidine and dobutamine. Bupivacaine induced bradycardia, prolonged atrioventricular conduction time (PR interval), atrioventricular node conduction time (AH interval), His-Purkinje conduction time (HV interval), and QRS duration. Bupivacaine decreased left ventricular (LV) dP/dt max and increased LV end-diastolic pressure (LVEDP). Clonidine improved QRS duration and HV interval but enhanced AH interval, bradycardia, and hemodynamic depression induced by bupivacaine. Dobutamine infusion improved LV dP/dt max but did not modify bupivacaine-induced ventricular electrophysiologic impairment. The combination of clonidine and dobutamine corrected not only the electrophysiologic impairment induced by bupivacaine but also the hemodynamic depression. As the HV interval and the QRS duration could be correlated with ventricular conduction velocities, we conclude that (a) clonidine reversed the slowing of ventricular conduction velocities induced by bupivacaine, and (b) the combination of clonidine and dobutamine was able to correct the cardiac disturbances induced by bupivacaine in anesthetized dogs.

Animals↗

PubMed1990

Bupivacaine-induced slow-inward current inhibition: a voltage clamp study on frog atrial fibres.

The effects of various concentrations of bupivacaine on the characteristics of the slow-inward current (isi) were studied over a ten-minute period on isolated frog atria. At a concentration of 10(-7) M, bupivacaine did not modify isi. At 10(-6) M, the maximal amplitude of the slow-inward current (i max) was depressed by 11 per cent. At 10(-5) M, i max was depressed by 24.5 per cent, the time-to-peak current value (tpeak) was increased by 13.4 per cent and the inactivation time constant (tau in) by 29.8 per cent. At 10(-4) M, i max was depressed by 32.9 per cent, tpeak increased by 30.4 per cent and tau in by 58.7 per cent. In conclusion, bupivacaine produced only moderate inhibition of the slow-inward current. The findings might explain the decline in sinus impulse formation with sinus bradycardia, and the slowing of atrio-ventricular node conduction produced by bupivacaine. However, the decrease in contractility previously reported does not seem to be due only to inhibition of the slow-inward current.

Action Potentials↗

PubMed1990

[Do beta adrenergic receptor blockaders increase bupivacaine cardiotoxicity?].

Bupivacaine is known to impair the electrophysiology of the heart as well as haemodynamic parameters. Administration of calcium channel blockers prior to bupivacaine enhances its cardiotoxicity. This study assessed the effects of bupivacaine at toxic dose in dogs with previous beta-adrenergic receptor blockade. It included 12 dogs anaesthetized with thiopentone, allocated in a control group (n = 6) receiving a bolus of bupivacaine (4 mg.kg-1) and a study group (n = 6) treated with the sequence propranolol (0.2 mg.kg-1) and bupivacaine (4 mg.kg-1), 15 min later. Infranodal conduction (HV conduction times and QRS durations) was worsened in both groups. Previous propranolol administration had no potentiating effects on these parameters. Conversely the latter was responsible of a greater decrease in heart rate, and increase in atrio-ventricular conduction time (77.9% vs 18.7%, p less than 0.05), as well as a more severe hypotension. Moreover, 3 out of the 6 animals in the study group suffered a cardiac arrest between the 5th and the 10th min. It is concluded that in anaesthetized dogs the cardiac and circulatory effects of a toxic dose of bupivacaine are increased in case of preexisting blockade of beta adrenergic receptors.

Adrenergic beta-Antagonists↗

PubMed1990

Characterization of gentamicin-resistant respiratory-deficient (res-) variant strains of Staphylococcus aureus.

Exposure of sensitive cells of Staphylococcus aureus to concentrations of gentamicin higher than the minimal inhibitory concentration, results in the recovery of low level resistant strains with a greatly altered phenotype (variants). Because the phenotypic alteration in these strains is so great the expected diagnostic characterization of these variants as S. aureus is obscured. Starting with a genetically-marked parent strain, a comprehensive cytological, physiological, morphological, genetic and biochemical analysis of the variants isolated from it was carried out. The genetic lineage of the variants to the parent was also established by DNA/DNA hybridization. Variants result from mutations in the hemin biosynthesis locus, the effect of which is to disrupt the synthesis of components of the electron transport system, lipid synthesis and selected nucleotide synthesis. Thus the strains are defective in aerobic and anaerobic respiration, (res-), in active transport of aminoglycosides (which confers low level resistance), export of characteristic exo-enzymes, and in cell wall composition and structure.

Bacteriophages↗

PubMed1989

In vitro study on mechanisms of bupivacaine-induced depression of myocardial contractility.

Although several mechanisms have been proposed to explain bupivacaine cardiotoxicity, the predominant effect remains to be determined. In this study, we used an isolated rabbit right atrial model that reproduces the effects on inotropic and chronotropic functions induced by 0.5 micrograms/mL bupivacaine; then we tried to counteract these events by electrical stimulation or by addition of CaCl2 or adenosine triphosphate (ATP) to the bathing solution. Contractile force was dramatically depressed by bupivacaine alone (-68%), even when the preparation was paced (-59%). CaCl2 partially counteracted this decrease (-37%). Inotropic function was almost completely restored (-9%) when ATP was added before administration of bupivacaine. Inhibition of energy metabolism seems to be a major explanation for bupivacaine cardiotoxicity.

Adenosine Triphosphate↗