[Preclinical study of anti-arrhythmia agents. Classification].
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Biomedical subjects
Publications and source records attributed to B Dupuis.
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Cardioprotection is a new concept proposed for clinical situations as myocardial infarction and cardiac surgery. Cardioprotective effects are mainly evaluated in patients by enzymatic, electrocardiographic and sometimes histological findings. The aim of this work was to study the effects of trimetazidine on guinea-pig ventricular myocardium submitted in vitro to conditions mimicking ischaemia. A three step procedure was used: a period of stabilization of 180 minutes under control conditions, then a period of 60 minutes under ischaemic conditions, and last a replacement into control conditions perfusion (30 minutes). Trimetazidine was added in the superfusion during the last hour of stabilization and maintained during the ischaemic and the reperfusion periods. Electrical activities (micro-electrodes) and creatine phosphokinase activity in the effluent were monitorized. Trimetazidine (10(-6) M) prolonged during the ischaemic phase the duration of decremental response and improved electrical recovery during reperfusion. Moreover, trimetazidine (10(-6) M) reduced creatine phosphokinase leakage during ischaemia. The effects of trimetazidine were compared to those observed with calcium channel antagonists in the same model. Thus slowing of enzyme leakage and electrical improvement observed under trimetazidine are compatible with a so-called cardioprotective effect.
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Biphasic contractions were produced in guinea pig papillary muscle by inducing partial depolarization in a K+ -rich solution (22 mM) containing 10(-6) M isoproterenol. However, when the same conditions were applied to frog and rat, monophasic contractions were obtained. In the case of guinea pig, an increase in the beating frequency produced an increase in amplitude of the first component and a reduction of the second, while in frog and rat, only a decrease in the amplitude of contractions was recorded. Caffeine (10(-3) M) eliminated the first component and increased the second in guinea pig, while in the case of rat and frog it decreased the amplitude of contractions. Procaine (10(-3) M) suppressed the first component and decreased the second one. The contraction in frog appears to be similar to the second component of contraction in guinea pig, while in rat, the contraction is comparable with the first component in guinea pig. It is suggested that the calcium ions which activate the two components of contraction in guinea pig under the given experimental conditions may arise from two different sources.
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There are relatively few reported studies of continuous electrocardiographic recordings by the Holter method in children. We report our experience of 296 24-hour recordings in 160 patients (average age 10.5 years), investigated for suspected or known cardiac arrhythmias. One hundred and ten patients (68.75%) had no organic heart disease and 6 patients (3.75%) had acquired lesions. Eighty-three patients (52%) were symptomatic. Sixty-three patients (39%) had normal recordings; 97 patients (61%) had a total of 126 arrhythmias. There were 45 cases of atrioventricular block, 24 cases of sinus node dysfunction, 39 cases of supraventricular arrhythmias and 18 cases of ventricular arrhythmias. Overall, 47.6% of these rhythm disturbances were diagnosed by Holter monitoring. This technique was particularly valuable in the diagnosis of arrhythmias in symptomatic patients, patients with arrhythmogenic cardiac lesions and in the detection and surveillance of postoperative arrhythmias in congenital heart disease, of pacemakers, of congenital atrioventricular block and of the chronic arrhythmias of childhood.
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Amberlite XAD 4 resin hemoperfusion was studied in the treatment of massive digitoxin overdosage. In vitro experiments using 4 hour resin hemoperfusion showed that digitoxin is removed 100 percent from an isotonic saline reservoir, 83 +/- 14 percent from plasma, and 42 +/- 7 percent from whole blood. In dogs, serum level reduction is fast: 50 +/- 12 percent in 15 minutes, 71 +/- 6 percent in 180 minutes; mean plasma clearance is 24 +/- 6.5 ml/min for a 150 ml/min plasma flow rate. Eleven patients with massive digitoxin overdosage recovered with resin hemoperfusion. Serum level reduction was 32 +/- 14 percent with a 325 g resin column, 59 +/- 6 percent with two 325 g resin columns in series as compared with a 4.5 +/- 1.7 percent reduction without perfusion. Hemoperfusion increased the rate of spontaneous removal of digitoxin 8.6 +/- 3.3 times with a 325 g resin column, and 14 +/- 7.4 times with two 325 g resin columns.
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Diisopyramide overdose induces an early and severe cardiogenic shock; hemoperfusion on resin (Amberlite XAD 4) is the most efficient treatment. In vitro, 92% of the drug is adsorbed in 240 min. In dog, the plasmatic epuration is 66% with a mean plasma clearance of 74% plasmatic flow. A woman who had absorbed 4.50 g diisopyramide showed an idioventricular rhythm. The cardiac electrical stimulation and positive inotrope drugs were inefficient. Hemoperfusion on resin Amberlite XAD 4 corrected hemodynamic and ECG disturbances in 4 h. The epuration was proved by the decrease of diisopyramide plasma level: 24.4 micrograms/mL before epuration, 1.9 micrograms/mL after epuration, and a mean plasma clearance of 107.8 mL/min (61% of the plasmatic flow). Hemoperfusion of resin (Amberlite XAD 4) is more efficient than hemodialysis (cuprophan) and hemofiltration (polyacrylonitrile). The system that we have used is well tolerated and of low cost.
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The electrical activity of the sino-atrial node was studied after the selective cannulation of its artery in the intact open-chest dog. After tetrodotoxin infusion and despite cardiac arrest, a slow rhythmic activity was recorded from the sinus epicardial electrode.
The cells of the SA node (SAN) are very resistant to the action of tetrodotoxine (TTX), a drug which. paradoxically, blocks depolarisation of the outer myocardial cells. Injection of TTX into the artery of the SAN brings about asystole; bur regular electrical activity, consisting of a slow wave of 200 to 300 ms duration, can still be picked up by an electrode placed on the SAN. This electrical activity, which can only be picked up over the SAN, and is resistant to TTX but blocked by acetylcholine, is interpretated as being the electrogram of the SAN. After the artery has been washed out by normal saline, the effect of TTX becomes progressively less; under these conditions, all degrees of sino-atrial block can be observed. Arising from a study of the phenomena of capture of the SA and AV nodes, of the effect of artrial stimulation, and of the time relationships between the various electrical events recorded, some hypotheses of the electrophysiology of the SAN and the sino-atrial conduction are put forward.
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