| Summary: | 碩士 === 國防醫學院 === 生理學研究所 === 95 === Introduction
Hereditary myopathic Syrian hamster (Biobreeders strain Bio 14.6) had been frequently used as an experimental model for the study of congestive heart failure (CHF). Recently, there is an increase in AF prevalence in patients afflicted with more advance CHF. The pulmonary veins (PVs) are an important source of ectopic beats, initiating frequent paroxysms of AF. These foci respond to treatment with radio-frequency ablation. Previous studies in multiple cells or single cell from dogs and rabbits have shown that PVs contain cardiomyocytes with or without spontaneous activities. It is not clear whether CHF alters the arrhythmogenic activity of PVs.
Aim
The aim of the present experiments was to study alternations in the ionic currents and action potential (AP) of the myopathic versus healthy left atrial (LA)-PV.
Material and Methods
A. ECG recording
Male myopathic Syrian hamsters (Bio 14.6, 41-57 week-old) and
age-matched male healthy hamsters (Biobreeders strain F1B) were
anesthetized with pentobarbital and the heart and lungs quickly
removed and immersed in Tyrode solution. ECG was recorded by
using Hugo Sachs Elektronik-Harvard apparatus GmbH (Germany)
B. Preparation of hamster LA-PV tissues :
The animals preparation were the same in ECG recording. LA-PV tissue were perfused in vitro at 37℃. Action potentials were recorded by microelectrode techniques and twitch force by a transducer.
C. Isolation of PV cardiomyocytes After getting the heart, PVs were perfused in a retrograde manner via polyethylene tube connected through the aorta and left ventricular into the left atrium. The free end of the polyethylene tubing was connected to a Langendorff perfusion column for perfusion with Tyrode solution at 37℃. The perfusate was replaced with Ca2+-free Tyrode solution containing collagenase (1 mg/ml) and protease (0.01 mg/ml) for 30-40 min. The piece of tissue was cut into fine pieces and gently shaken in 5-10 ml of high-K+ storage solution until single cardiomyocytes were obtained.
D. Electrophysiology study
The isolated cells were placed in a 1-ml chamber mounted on the stage of an inverted microscope and superfused ( at 3 mL/min ) with extracellular solution appropriate to each patch-clamp experiment. The LA-PV cardiomyocytes obtained from 14 myopathic hamsters and 16 healthy hamsters were used for experiments on the following ionic currents and membrane potentials by means of whole-cell patch-clamp techniques.
Results
1. The myopathic hamster was easier inducing arrhythmia by using isoproterenol.
2. The LA tissue has a longer APD in myopathic hamster.
3. But, PV tissue APD in myopathic hamster is shorter than healthy.
4. The densities of the INa and INCX in PV cardiomyocytes were smaller in myopathic hamster than the healthy control. But in IK1 have no significant differences. The densities of the INCX in myopathic hamster and failing human heart ventricular myocytes were small. Conclusion
In addition to previous findings from our Lab that myopathic hamsters had smaller ICa,L but no difference in IK and IK1, the present experiments show that the myopathic hamsters have smaller INa,and INCX. Change of these currents could lead to shorter APD in myopathic hamster PVs than in healthy PVs. In contrast, myopathic hamsters LAs have longer APD. Thus our results suggest that CHF can promote LA-PV and ventricle ionic remodeling.
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