| Objiective: Atrial fibrillation (AF) and rapid atrial pacing resulted in atrial electrical and gap junction(GJ) remodeling. These changes are involved in the creation of a substrate for episode and maintenance of AF. All previous experimental work on electrical and GJ remodeling has been performed in normal animals. Clinical AF commonly occurs in the presence of atrial pathology, and rapid atrial activation could have different electrophysiological effects in pathological compared with normal atria.Atrial fibrillation is one of the common arrhythmias associated with hyperthyroidism. Between 10% and 15% of hyperthyroid patients develop AF. Although serum thyrotropin becomes normal in these patients,AF may be maintained for three months. The longer time course of maintenance of AF, strongly suggest that substrate for these arrhythmias is involved. It is unclear that a candidate for such substrate is GJ remodeling or electrical remodeling. Although L-type Ca2+ current was unaffected by acute exposure to thyroid hormone, which increases intracellular Ca2+ in atrial myocytes. In addition, hyperthyroidism enhances sarcoplasmic reticulum (SR) Ca2+ release and results in [Ca2+L over- load. The mRNA-level of the a1c - subunit of L-type Ca2+ channel was reduced byt high level of hyroid hormone on the study about the effects of thyroid hormone (T3) on mRNA expression and currents of ionic channels. In the light of these, high level of thyroid hormone may directly lead to atrial electrical remodeling. However, there is no evidence to support this speculation.In the atrium, GJs are mainly consisted of Cx43 and Cx40. Changes in expression of this gap junction protein and its distribution patterns have clear impact on impulse propagation, creating a situation that supports microreentry, which could lead to arrhythmias. Connexin 43 in rat liver cells increases by 4-5 fold after two days of incubation with T3 and T4. Thyroid hormones can alter the localization of gap junctional protein connexin 43 in the testis and the epididymis of the rat. There is no report about the impacts of thyroid hormone on the expression of Cx40 in atrium and the effects of atrial rapid pacing on the gap junctional protein and its distribution in the condition of the high level of thyroid hormones.Recent clinical studies have demonstrated that AF can be caused by a rapidly firing focus in PVs. Verheule reported that PVs in the dog had myocardial sleeves extending into the veins, myocytes in which similar to normal atrial myocytes. The circumferential orientation ofthese myocytes may provide a substrate for rapid circular reentry. Chen YC reported that thyroid hormone changes the electrophysiological activity of the PV cardiomyocytes with a higher incidence of triggered activity. Increased automaticity and enhanced triggered activity may increase the arrhythmogenic activity of PVs in hyperthyroidism. The effect of thyroid hormone and rapid atrial pacing on the GJ in the PVs is unknown.This study was conducted to investigate the effects of thyroid hormone on the electrophysiological characteristics of atrium and GJs of atrium and pulmonary veins, and test the hypothesis that in the presence of hyperthyroidism the effects of short-term rapid atrial pacing on the electrophysiological characteristics of atrium and GJs in the atrium and PVs are different from those in normal hearts. MethodsForty-six adult rabbits were randomly divided into 4 groups: normal control group (A group, n=10) , pacing group (B group, n=10) , hyperthyroid group (C group, n=14) , hyperthyroidism/pacing group (D group, n=12) . The former two groups received intraperitoneal injection of 0. 45mg/kg L-Thyroxin in a day for four weeks. According to loss of weight, hoist of temperature, acceleration of heart rate and hoist of serum T3 and T4, hyperthyroid rabbit models were established successfully. Rabbit was anesthetized and fixed on the operation table. The internal jugular vein and external jugular vein were isolated, and two Cordis electrode catheters were inserted into the right atrium vi... |
PDF Full Text Request