The Research Of QT Interval Affected By Isoflurane In Rabbits With Myocardial Injury Induced By Adriamycin

Objective To investigate the effects of isoflurane on QT interval in rabbits with myocardial injury induced by adriamycin and explore its mechanism. Methods Twenty-four 12-14 week-old healthy female Japanese white ear rabbits, weight 2.00-2.30kg, were randomly divided into 4 groups (n=6):control group (group C), isoflurane group (groupⅠ), adriamycin group (group A) and adriamycin isoflurane group (Group AI). To establish the models of primitive adriamycin cardiotoxicity as follows:group A and AI were injected with adriamycin via auricular vein of ears by 2mg/kg×1time/week×4weeks. In the same way, group C and I were injected with equivalent NS. Group I and AI were anesthetized by isoflurane. QT interval and RR interval were recorded and QTc interval (QTc) and QTc dispersion (QTcd) were calculated respectively before the establishment of the models of adriamycin cardiotoxicity (T1), before anesthesia (T2) and 30 min after anesthesia (T3) in group I and AI. At the same time, blood samples were taken in vein to measure the content of lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD). The above indexes were measured in group C and A only at T1, T2. The left ventricular myocardium was cut by thoracotomy under rapid sacrifice in 4 groups after T3. Then the Cx43 (connexin 43) fluorescent plaque area was analyzed by immunofluorescence under Laser scanning confocal microscope and the myocardial ultrastructure was observed under transmission electron microscope. Results (1) QTc and QTcd changes: Compared with group C at T1, QTc was extended and QTcd was increased in group I at T3 and group A at T2 (P＜0.05); compared with group I at T3 and group A at T2, QTc and QTcd were further extended in group AI at T3 (P＜0.05). (2) LDH changes:Compared with group C at T1, no significant change in LDH level was observed in group I at T3 (P＞0.05), while LDH was significantly increased in group A at T2 and group AI at T3 (P＜0.05); compared with group A at T2, there was no obvious change of LDH in group AI at T3 (P＞0.05). (3) MDA changes:The changes of MDA were consistent with those of LDH. (4) SOD changes:Compared with group C at T1, the statistical results showed no significant change of SOD in group I at T3 (P＞0.05), but SOD was significantly reduced in group A at T2 and group AI at T3 (P＜0.05); compared with group A at T2, there was no obvious change of SOD in group AI at T3 (P＞0.05). (5) Cx43 changes:Compared with group C, no significant change of Cx43 fluorescenc plaque area was observed in group I (P＞0.05), however, the size decreased in group A and AI (P＜0.05); compared with group A, the size unchanged in group AI (P＞0.05). (6) Myocardial ultrastructure under the Transmission Electron Microscopy:In group C and I, myofilaments was aligned, sarcomere was clear; intercalated disc was integral and clear, desmosomes, focal adhesions and side-side of the gap junction were visible; mitochondria showed a homogeneous sample, neat crest. In group A and AI, myocardial fiber arranged in a consecutive row; part of intercalated disc structure was fuzzy, side-side of the gap junctions increased and the gap slightly widened; the mitochondria were mild swelling.Conclusion (1) QTc and QTcd of rabbits can be extended and increased by isoflurane or adriamycin. (2) Adriamycin may lead to the reduction and disorder distribution of Cx43 in the left ventricular myocardium of rabbits. Therefore, Cx43 is involved in the mechanism of QT interval affected by adriamycin. (3) QTc and QTcd of rabbits with myocardial injury induced by adriamycin can be further extended and increased by isoflurane anesthesia. the mechanism of which may have relations with the function of the ion channel on myocardial cell membrane, and isoflurane can increase the probability of arrhythmia of rabbits with myocardial injury induced by adriamycin.