| Objectives:The goal of the present study was to determine weather the changes of P-wave duration, dispersion of P-wave effective refractory (ERP) period and dispersion of ERP in adult and aged normal canine. Explore the underling mechanism that aging-associated changes in the atrial actionpotential (AP) and atrial myocardial current of L-type calcium channel, provide a substrate for abnormal conduction and arrhythmogenesis, particularly atrial fibrillation (AF). Methods:1) Two groups of mongrels either sex weighing 18～26kg (19.6±5.8)kg were investigated:seven adult (2～2.5years) and ten old (> 8years). Animals were anesthetized with sodium pentobarbital (20mg/kgi.v.). Twelve-lead ECG measurements were made on conscious dogs resting quietly using electrocardiogram. Echocardiograms were performed to exclude the structural heart disease. Dual atrium and ventriaular size, the left ventricular ejection fraction (LVEF) were also measured by echocardiogram. A right cervical vein cutdown was then a 6-Fr quadripolar electrode catheter was inserted into the high right atria (HRA) and a multipolar catheters were placed at the coronary sinus (CS). The chest was opened through the fourth intercostal space. After left lateral thoracotomy, the pericardium was incised to expose the heart. A multielectrod catheters was secured to left atrial appendage (LAA), left superior pulmonary vein (LSPV) or left inferior pulmonary vein (LIPV), Similar electrode catheters were secured to right atrial appendage (RAA), right superior pulmonary vein (RSPV) and right inferior pulmonary vein (RIPV) through a right thoracotomy approach at the fourth intercostal space. The effective refractory period (ERP) of HRA, coronary sinus proximal (CSp), coronary sinus distal (CSd), LAA or RAA, LSPV, LIPV, RSPV, RIPV were measured in sequence at an atrial pacing of S1S2. The measurements were repeated 3 times and then averaged.To induce AF, atrial burst pacing was delivered through quadripolar electrode by a high-frequenc pacing in the RAA at a rate of 1000 bpm. If AF was not induced, a high-frequenc stimulats in the cervical vagosympathetic at a rate of 1000 bpm.We averaged the time of the duration of AF induced at 3 procedures in all dogs of each group.2) The current of L-type calcium channel was recorded by patch clamp technique in the whole cell mode. Action potential duration (APD), amplitude of action potential plateau, Ica-L peak current density were measurements.3) We measured the mRNA gene and protein expression levels of L-type Ca channelα1 subunit (CaV1.2), sarcoplasmic reticulum Ca+-ATPase (SECRA2), Calpain I, ryanodine receptor (RyR-2) in atrial myocardial tissue from two groups of 17 dogs. Results:1) P-wave duration and dispersion of P-wave were both longer in aged animals (P<0.05). The LVEF was significantly lower in aged than adult groupswhereas differences in left atrial dimensionLAD), right atrial dimension (RAD), left ventricular diastolic dimension (LVDd), right ventricular diastolicdimension (RVDd) between the two groups failed to achieve statistical significance.The ERP of RAA and CSp measured during atrial-programmed stimulation was significantly longer in the aged than in the adult dogs (P<0.05). However, the ERP of LAA and CSd was significantly shorter in the aged than in the adult dogs. Although significant shorter of ERP in LIPV, RSPV, RIPV was not observed, the ERP of LSPV was significantly shorter in the aged than in the adult dogs. Compared with adult dogs the dERP of different site of atrium and pulmonary veins (PVs) were increased in aged dogs (P<0.05). Compared with adult dogs a rate dependency of ERP in LAA, CSd and LSPV was significantly shorter in the aged dogs (P <0.05). Although shorter of rate dependency of ERP in LIPV, RSPV, RIPV was observed, but there are not significantly shorter in the aged than adult dogs. (P>0.05).2) Ica-L peak current density was (-14.04±0.82pA/pF), in adult group compared with (-8.11±0.54pA/pF, P<0.05) in the aged group and action potential duration to 90% repolarization (APD90) of aged group was significantly decreased. Left、right atrium transverse diameter gradually increased, but have no significant difference (P>0.05).3) The mRNA gene expression levels of CaV1.2 was significantly lower in the aged doges (0.9±0.35) than in the adult dogs (2.38±0.4, P<0.05), The mRNA gene expression levels of RYR2 was significantly higher in the aged doges (4.39±4.68) than in the adult dogs (1.49±1.69, P<0.05), There were not significantly different gene expression levels of SECRA2> PLN1 and Calpain I in two groups; The protein expression levels of CaV1.2 was significantly lower in the aged doges (0.13±0.10) than in the adult dogs (0.29±0.12, P<0.05), The prorein expression levels of RYR2 was significantly higher in the aged doges (0.18±0.21) than in the adult dogs (0.08±0.36, P<0.05), There were not significantly different protein expression levels of SECRA2, PLN1and Calpain I in two groups. Connclusions:The pesent study demonstrated the change of ERP, dERP.APD, Ica-L peak current density in two groups dogs. There are have a structural remodeling and electrical remodeling presented in aged doges. The gene and ion channel protein expression levels was different in two groups. These aging-related changes of atrial myocyte electrical and structural properties and molecular changes in aged dogs play a impotrant role in the predisposition to developing and maintaining AF due to aging. |
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