Evolution de la prise en charge péri-opératoire en anesthésie pour chirurgie bariatrique de 2006 à 2009 au CHU de Caen

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Proarrhythmic effects of DL- and D-sotalol on the "border zone" between normal and ischemic regions of isolated ventricular myocardium and antiarrhythmic effects on reperfusion

Considering the Survival With ORal D-sotalol (SWORD) study results, in which mortality was higher in patients treated by the pure class III agent D-sotalol, we tested DL- and D-sotalol (5 and 10 mu M) in an in vitro model of "border zone" arrhythmias. Isolated guinea-pig ventricular strips were partly exposed to normoxia ("Normal Zone," NZ) and partly to modified Tyrode's solution ("Ischemic Zone," IZ) for 15 or 30 min ("ischemia"), followed by return to normoxia for 30 min ("reperfusion"). Resting membrane potential, action potential (AP) amplitude, and maximal upstroke velocity of AP were not significantly modified. Dr- And D-sotalol, 5 and 10 mu M, length ened AP duration 90% (APD(90)) in NZ (p < 0.05), whereas these drugs were unable to prevent ischemia-induced APD shortening. By using the accelerated failure time Weibull's model, and a large number of reference experiments to control random variability of analyzed covariates, Dr-and D-sotalol increased significantly the incidence of spontaneous arrhythmias during ischemia (chi(2) = 24.79; p = 0.0367): 83 (5 mu M D- and DL-sotalol), 86, and 62% (10 mu M D-and DL-sotalol, respectively) versus 32% of controls. During reperfusion, 10 mu M DL-sotalol prevented the occurrence of spontaneous arrhythmias (chi(2) = 46.74; p = 0.0001) similar to what seen with the beta-blocking agent propranolol (10 mu M). These data, providing evidence for proarrhythmic effects of DL- and D-sotalol on border-zone arrhythmias, concomitant with differential class III actions on NZ versus IZ, might be considered for understanding the SWORD study results

K(ATP) channels and ‘border zone' arrhythmias: role of the repolarization dispersion between normal and ischaemic ventricular regions

1. In order to investigate the role of K(ATP) channel activation and repolarization dispersion on the ‘border zone' arrhythmias induced by ischaemia-reperfusion, the effects of glibenclamide and bimakalim, agents modifying action potential (AP) duration, were studied in an in vitro model of myocardial ‘border zone'. 2. The electrophysiological effects of 10 μM glibenclamide and 1 μM bimakalim (n=8 each), respectively K(ATP) channel blocker and activator, were investigated on guinea-pig ventricular strips submitted partly to normal conditions (normal zone, NZ) and partly to simulated ischaemic then reperfused conditions (altered zone, AZ). 3. By preventing the ischaemia-induced AP shortening (P<0.0001), glibenclamide reduced the dispersion of AP duration 90% (APD(90)) between NZ and AZ (P<0.0001), and concomitantly inhibited the ‘border zone' arrhythmias induced by an extrastimulus (ES), their absence being significantly related to the lessened APD(90) dispersion (χ(2)=8.28, P<0.01). 4. Bimakalim, which also reduced the APD(90) dispersion (P<0.005) due to differential AP shortening in normal and ischaemic tissues, decreased the incidence of myocardial conduction blocks (25% of preparations versus 83% in control, n=12, P<0.05) and favoured ‘border zone' spontaneous arrhythmias (75% of preparations versus 25% in control, P<0.05). 5. During reperfusion, unlike bimakalim, glibenclamide inhibited the ES-induced arrhythmias and reduced the incidence of the spontaneous ones (12% of preparations versus 92% in control, P<0.05), this latter effect being significantly related (χ(2)=6.13, P<0.02) to the lessened ischaemia-induced AP shortening in the presence of glibenclamide (P<0.0001). 6. These results suggest that K(ATP) blockade may protect the ischaemic-reperfused myocardium from ‘border zone' arrhythmias concomitantly with a reduction of APD(90) dispersion between normal and ischaemic regions. Conversely, K(ATP) channel activation may modify the incidence of conduction blocks and exacerbate the ischaemia-induced ‘border zone' arrhythmias