Effects Of KB-R7943on Oubain Induced Arrhythmia In Normal And Failing Hearts In Rabbits

Object:In this study，rabbit models of heart failure were established through destruction of theaortic valve combined with aortic ligation. Digitaloid drug like ouabain was used to inducearrhythmias in isolated normal and failing heart. Then the effects of KB-R7943, asodium-calcium exchanger inhibitor, on ouabain-induced arrhythmia were investigatedin isolatedrabbit normal and failing hearts.Methods:The adult rabbits weighing2.5±0.1kg were used and divided into three groups, includingnormal group (n=24), sham-operation group (n=8) and heart failure group (n=32). The heartfailure model was set up by aortic valve damaging and abdominal aorta ligating. After2monthsof operation, the rabbits of three groups were examined the ventricular septal diastolic thickness,interventricular septum systolic thickness, left ventricular diastolic thickness, left ventricularsystolic thickness, left ventricular posterior wall diastolic thickness, left ventricular wall systolicthickness, left ventricular ejection fraction and fractional shortening rate indicators usingultrasound separately. The hearts were harvested and perfused with Langendorff device, weobserved the left ventricular developed pressure, heart rate, maximal contraction rate, relaxationrate, and other indexes, Then arrhythmias was induced with ouabain (5μmol/L、4ml) andKB-R7943(1μmol/L、5μmol/L)s effect was observed.Results：1. Between normal and sham-operation groups, the ultrasonic results showed no significantdifference of interventricular septum diastolic thickness, interventricular septum systolicthickness, left ventricular diastolic thickness, left ventricular systolic thickness, left ventricularposterior wall diastolic thickness and left ventricular posterior wall systolic thickness after2months, meanwhile there is no significant difference of left ventricular ejection fraction andfractional shortening, either (P＞0.05).In the heart failure group, after2months of operation, Compared with the sham-operationand normal group, the interventricular septum diastolic thickness (3.2±0.4)mm, interventricularseptum systolic thickness (3.7±0.5) mm、left ventricular wall diastolic thickness (21.8±2.1) mm, left ventricular systolic wall thickness (13.0±1.70) mm, left ventricular posterior walldiastolic thickness (3.5±0.4) mm and left ventricular posterior wall systolic thickness (4.2±0.8)mm were all increased (P＜0.05).2. The isolated heart Langendorff perfusion results showed: there is no significantdifference between sham-operation group and normal group. in the sham-operation group, leftventricular developed pressure was (80.9±9.9) mmHg, heart rate was (168.1±13.7) beats/min,the maximum contraction rate was(1234.3±156.6) mmHg/s and maximum relaxation rate was(880.0±214.0) mmHg/s; in the normal group, left ventricular developed pressure was (79.8±7.4)mmHg, heart rate was(164.1±19.5) beats/min, maximum contraction rate was (1246.4±285.7)mmHg/s and maximum relaxation rate was (1010.4±235.0) mmHg/s.Compared with the normal and sham-operation groups the above heart function indexeswere all reduced (P＜0.05). the left ventricular developed pressure was (32.6±8.4) mmHg, heartrate was (70.7±15.4) beats/min, the maximum contraction rate was (353±140.9)mmHg/s andmaximal relaxation rate was (276.1±138.6) mmHg/s.,3. Between normal and sham-operation groups, There was no significant difference of thetotal arrhythmias time and Ventricular tachycardia(VT) time (P>0.05).When ouabain(5μmol/Ll、4ml) was gived, the total arrhythmias time(834.6±91.6s) and VT time(142.5±18.8s) wereincreased compared with before (P<0.05). After application of KB-R7943(5μmol/L、1ml), thetotal arrhythmias time (494.6±50.6s) and VT time (85.6±15.0s) were significantly reduced (P<0.05).4. In the heart failure group, After giving ouabain(5μmol/L、4ml) the total arrhythmiastime(27.5±8.6s) and VT time (10.1±7.4s) were significantly increased compared with before (P＜0.05). after aplication of ouabain(5μmol/L、４ml) combined with KB-R7943(1μmol/L、1ml)the total arrhythmias time(766.1±79.3s) and VT time (167.2±16.9s) were reduced compared withouabain group (P <0.05).5.Compared with normal group, the total arrhythmias time and VT time induced byouabain(5μmol/Ll、4ml) were longer in the heart failure group, The total arrhythmias time was(1427.3±77.3s) and VT time was(254.3±37.3s)(P<0.05) but in the normal group, was(834.6±91.6s) and (142.5±18.8s),Apication of KB-R7943(5μmol/L、1ml) reduced the totalarrhythmias time (9±11)%and VT time (32±18)%induced by ouabain. in normal group, but thesame dosage of KB-R7943reduced (75±6)%arrhythmias time and (82±5)%VT time (P <0.05).inouabain treated heart failure group.Conclusion：1.Sodium-calcium exchanger inhibitor KB-R7943could reduce arrhythmia induced byouabain in isolated rabbit normal or failing heart. 2.Ouabain could more easily induce arrhythmia on failured rabbit heart than normal heart,and KB-R7943could depress arrhythmia induced by ouabain more strongerly in failured heart.