Electrophysiologic effects of bepridil in the anesthetized dog studied by endocardiac electrodes.

The electrophysiologic effects of bepridil in the anesthetized closed-chest dog were studied with intracardiac electrodes using the extrastimulus technique to measure the refractory periods of atria, atrioventricular (AV) junction and ventricles. Intravenous administration of 5 mg/kg of bepridil caused a reduction in sinus node rate and prolonged the sinus node recovery time. Refractory periods in the atrium, especially the effective refractory period, increased. Anterograde AV nodal conduction was slowed and refractoriness increased, often resulting in AV nodal Wenckebach periods, during atrial pacing, and retrograde conduction was always completely abolished. Refractory periods of the AV junction were altered in a comparable fashion to conduction through the AV node. No significant actions on conduction or the refractory period were noticed in the His-Purkinje system or the ventricle. The mechanism of action of bepridil seems to be correlated to its membrane effects, namely, inhibition of pathways responsible for the slow inward current, which explains its selective action on myocardial sites where this current is particularly involved.

Modified corporoplasty for penile curvature: 10 years' experience.

OBJECTIVES: To treat penile curvature, a modification of corporoplasty consisting of horizontal closing of a longitudinal incision of the corpora cavernosa was performed during the last 10 years in 55 patients. METHODS: The technique was used in congenital (32 patients) as well as acquired penile curvature patients (23 with Peyronie's disease). RESULTS: Successful results, up to 10-year follow-up, were achieved in 95% of the patients without any injury to the neurovascular bundle. CONCLUSIONS: The simplicity of this technique and its minimal aggressivity have the advantage of not removing corporeal tissue and being very flexible and adaptable to individual situations.

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.

Electrophysiological effects of penticainide in the anaesthetized dog.

The cardiac electrophysiological effects of Penticainide, a new antiarrhythmic agent, were studied by means of intracardiac electrodes in the anaesthetized dog. Intravenous administration of 5 mg/kg of Penticainide reduced the sinus rate and prolonged the sinus node recovery time. Atrial refractory periods increased. Anterograde intranodal conduction slowed and nodal refractoriness increased. Conduction time in the His-Purkinje tissue and ventricle increased, as did the ventricular refractory periods. Monophasic action potential duration was not altered by the drug in the atrium or the ventricle. The mechanism of action of Penticainide as an antiarrhythmic drug seems to be correlated to its membrane effects: inhibition of the fast-inward current, responsible for the marked effects on His-Purkinje and ventricular tissues; and inhibition of the slow-inward current, suggested by its effects on sinus node and atrio-ventricular node.

Electrophysiological effects of the new cardioactive drug CERM 4205: a comparative study in an animal model and in man.

The cardiac electrophysiological effects of CERM 4205, a new cardioactive agent, were studied by means of intracardiac electrodes in man and in anaesthetized dogs. The results show that CERM 4205 is a cardioactive drug with a main inhibitory effect on slow-response structures (sinus and atrioventricular node) with an associated effect on fast-response structures (atrial, His-Purkinje and ventricular tissues). No qualitative differences were observed between the effects observed in man and dogs. In conclusion, the present study confirms that CERM 4205 is a compound with combined class IV and class I electrophysiological effects in dogs and man. The anaesthetized dog appears to be a satisfactory model for the evaluation of the electrophysiological effects of cardioactive drugs.

Endoscopic treatment of vesicoureteral reflux.

Since 1985 we treated 180 cases of vesicoureteral reflux with endoscopic injection of polytetrafluoroethylene (Teflon). Follow-up, from 1985 to 1990, was available for 256 refluxing ureters (93% primary reflux, 7% secondary after reimplantation or neurogenic bladder). The distribution according to the grade was the following: Grade I: 26 cases (always associated with higher grade contralateral reflux), Grade II: 94 cases, Grade III: 97 cases, Grade IV: 28 cases and Grade V: 11 cases. For primary reflux, correction was observed after a single injection in 87% of the cases and 93% after a second injection. So far no long-term morbidity and complications have been observed. The procedure is simple, reliable and successful. We are aware of the ongoing discussion about the safety of the polytetrafluoroethylene paste, particularly in children, and are waiting for the ideal substance preferably prepared from the patient's own tissue.

[Mode of action of purinergic derivatives of adenine on auriculo-ventricular conduction. Experimental study in dogs]. / Mode d'action des substances purinergiques dérivées de l'adénine sur la conduction auriculo-ventriculaire. Etude expérimentale chez le chien.

The effects of three purine derivatives of adenine, adenosine triphosphate (Striadyne), purified adenosine triphosphate and adenosine, on conduction tissue, were studied in closed chest dogs with endocavitary recording catheters. The dogs were anaesthetised with pentobarbital and ventilated, then three bipolar catheters were positioned to allow atrial pacing and recordings of atrial and His bundle potentials. The purines studied were administered by rapid bolus intravenous injection. The dosage was identical based on a predetermined dose-response curve (dose of 2 mg/kg). The study of the effects on atrioventricular conduction was carried out before and after administration of antagonists: atropine, 0.08 mg/kg and aminophylline, 10 mg/kg. Twelve dogs were studied for each purine: 6 with initial premedication with atropine and then aminophylline, and 6 with the inverse sequence. Lengthening of AV conduction was due exclusively to nodal depression. No variation in the HV interval was observed (HV = 35 +/- 4 ms). Lengthening of AH interval was observed very soon after injection of the drugs (5 to 10 seconds) with a peak effect between 20 and 40 seconds. Reversion to the initial value always occurred in under 2 minutes. In the model studied, Striadyne and purified adenosine triphosphate were much more powerful than adenosine, both in intensity and duration; high degree AV block was obtained in 10 out of 12 cases with Striadyne and in 8 out of 12 cases with purified adenosine triphosphate, but in only 2 out of 12 cases with adenosine. The use of specific antagonists demonstrated the different modes of action of the three purines.(ABSTRACT TRUNCATED AT 250 WORDS)

[Analysis of the electrophysiological effects of amiodarone using simultaneous recordings of monophasic and bundle-of-his action potentials]. / Analyse des effets électrophysiologiques de l'amiodarone par l'enregistrement simultané des potentiels d'action monophasiques et du faisceau de His

The effects of amiodarone given by rapid intravenous injection at a dosage of 10 mg/kg have been studied in the dog. The peak activity is found between the fifth and the tenth minute. The rate of discharge of the sinus is lowered by 36%. At the atrial level, the duration of the monophasic action potential (MAP) is increased by 9% and its dv/dt is lowered slightly, the total refractory period is increased by 22%, the effective refractory period is increased by 27%, the functional refractory period is increased by 19%, the ratio of the length of the effective period/duration of the MAP becomes slightly greater than unity, conduction facilitation disappears, and the period of slow conduction increases. In the A/V node the AH interval increases by 44% under normal rhythm, while atrial stimulation at 200/min. results in conversion to total AV block in more than half of the cases. The potential of the bundle of His and the HV interval are not altered. At ventricular level the duration of the monophasic action potential increases by 25%, its dv/dt decreases slightly, the total refractory period is increased by 8%, and the effective refractory period is increased by 14%.

[The supernormal phase of cardiac conduction. An experimental study in the dog]. / La phase supernormale de conduction cardiaque. Etude expérimentale chez le chien.

The existence of a cardiac phase of supernormal excitability is not fully proved at the cellular level. As far as the whole heart is concerned, the phenomenon of supernormal conduction is still under discussion. Intracardiac conduction has been studied both in the right atrium (13 dogs) and in the right ventricle (14 dogs) by programmed stimulation (extrastimulus technique), while monophasic action potential (MAP) was recorded. The phenomenon of supernormal conduction was noted in 67.7% of cases, starting at 59.0% and ending at 78.0% of the basic cycle, hence occuring shortly after phase 3 of the MAP. In the ventricle, a phase of supernormal conduction was present in 52.4% of cases, starting at 66.1% and ending at 77.9% of the basic cycle. After ajmaline, the supernormal conduction was moved towards the end of the cycle. The mechanism of supernormal conduction, and its implications in the study of arrhythmias are discussed.

[Cardiac toxicity of bupivacaine and diazepam. Experimental study in the anesthetized dog]. / Toxicité cardiaque de la bupivacaïne et diazépam. Etude expérimentale chez le chien anesthésié.

The use of diazepam has been suggested for the treatment of convulsions resulting from accidental high plasma levels of local anaesthetics. However, it has been reported that this drug may increase the cardiac effects of bupivacaine in dogs. The present study aimed to assess the effects of diazepam on the electrophysiological signs of a high-dose intravenous bolus of bupivacaine in fourteen dogs, divided into two groups, and anaesthetized with thiopentone and ventilated. All the animals were given a bolus dose of 4 mg.kg-1 bupivacaine. Immediately afterwards, group I (n = 7) received 0.8 ml.kg-1 normal saline solution and group II (n = 7) was given 4 mg.kg-1 diazepam over 1 min. The parameters measured on lead II of the electrocardiogram were: cycle length (R-R interval), QRS length (QRS) and QT interval corrected for heart rate (cQT). Intranodal (AH) and His-Purkinje (HV) conduction times were measured with recording bipolar stimulation electrodes (USCI 6F). Mean aortic pressure (Pao) was measured via a femoral arterial line. In the two groups, the parameters were recorded before and 2, 5, 10 and 15 min after the bupivacaine bolus. Arterial blood samples for measurement of bupivacaine and diazepam serum levels were obtained before and 3, 15 and 30 min after the bupivacaine bolus. There was no significant difference between the two groups in the electrophysiological or haemodynamic parameters at any time. However, the increase in HV and QRS length was a little higher in group I than in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

[Do beta adrenergic receptor blockaders increase bupivacaine cardiotoxicity?]. / Les bêta-bloquants aggravent-ils la cardiotoxicité de la bupivacaïne?

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.

[Cardiotoxicity of local anesthetics]. / Cardiotoxicité des anesthésiques locaux.

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.

[The role of neoadjuvant treatment prior to radical prostatectomy]. / Rôle du traitement néoadjuvant avant la prostatectomie radicale.

Preoperative hormonal therapy has been recently advocated, but remain controversial. The aim purpose is to achieve downstaging, downgrading and improvement of the surgical results. In the last 80 patients undergoing radical retropubic prostatectomy, 28 had preoperative androgen deprivation, for a period ranging from 2 to 12 months with a mean treatment time of 3 months. Medical castration was obtained with total androgen deprivation. Return to normal value of PSA level in 90% cases and to undetectable level (< 0.25) in 39% of cases, expressing probably reduction of the tumor activity. Total prostatic volume is reduced by 30-50% after three months of treatment. The operative procedure was facilitated by an easier dissection, reducing operative time and blood loss. Recovery of postoperative continence was achieved in a significantly shorter period of time (3 months) as compared with the untreated patients (9 months). Immediate continence was obtained in 70% of patients treated preoperatively. No tumor was found in one specimen but no change was observed in the histological grading of the tumor in all the patients. This present study indicates the interest of a large scale randomized study, in order to show the real benefits of neoadjuvant hormonal treatment in prostate cancer patients.

[Value of PSA in the staging of prostatic cancer]. / La valeur du PSA dans le staging du cancer prostatique.

The clinical value of Serum Prostate Specific Antigen (PSA) in the staging of prostatic carcinoma was evaluated in 62 patients who underwent radical retropubic prostatectomy. Preoperative levels of PSA were compared with the final pathological stage obtained from all surgical specimens examined for capsular penetration, seminal vesical invasion and lymph node involvement. PSA level was closely correlated with the volume and the stage of the prostatic carcinoma. 93% of the patients with PSA < or = 10 ng/ml had tumor confined to the gland. All patients with PSA > 20 ng/ml had extraprostatic tumor extension (stage C or D). Patients with histologically proved prostatic carcinoma, PSA > 20 ng/ml and negative bone scan can be assumed to have extraprostatic disease and/or lymphatic involvement. Patients with PSA (drawn in the requested conditions) < or = 10 ng/ml can be considered to have organ confined disease, and can be spared a bone scintigraphy. Our study indicate an increasing role of PSA in the clinical staging of patients with prostatic carcinoma.