| Background: Clinical atrial fibrillation (AF) and congestive heart failure (CHF) frequently occur together. Atrial structural remodeling creates a substrate for AF, but the underlying mechanism and the molecular basis are unclear. This study observed atrial structural remodeling and assessed the effects of tetramethylpyrazine(TMP) on a dog model of CHF by ventricular tachypacing(VTP). Futher more, to discuss the molecular mechanism of atrial structural remodeling and prevention of TMP during CHF, the mRNA expression of matrix metalloproteinases-2(MMP-2), tissue inhibitor of metalloproteinase 2 and l(TIMP-2, TIMP-1), type I collagen(Col I), type IV collagen(Col IV) and Transforming growth factor- (TGF) were detected by RT-PCR technique. Methods and ResultsPart I: To search the substratal factors of AF during CHF, we had compared the mechanism of AF induced by atrial tachypacing (ATP) with VTP model. Seven control dogs, 7 atrial tachypacing (ATP) dogs (400 bpm for 5 weeks), 7 CHF dogs (VTP induced, 240 bpm for 5 weeks) were studied for evaluation of atrial electrical remodeling, atrial dilation and fibrosis. Burst atrial pacing was used to induce AF. After 5 weeks tachypacing: l.Compared with control and ATP group, Left ventricular ejection fraction (LVEF) decreased significantly in CHF dogs. LVEF decreased but it is also in normal range in ATP group. 2.Compared with control group, AF and sustained AF(SAF) incidence increased, duration of AF (DAF) prolonged significantly in ATP and CHF group. ATP strongly decreased the effective refractory period (ERP) and abolished ERP rate adaptation (ERP-RA) at various basic cycle lengthes (BCLs), and DAF has a positive correlation with ERPs. 3.ERP and ERP-RA had no chang in CHF group. Atrial fibrous tissue content and atrial size of CHF group were significantly greater than the controls and ATP dogs. And DAF has a positive correlation with LA systolic area, LA systolic volume and LA fibrosis during CHF, whereas ATP atrial were dilated mildly due to ventricular rate and had no fibrous hyperplasia. 4.The serum levels of angiotensin II(Ang), aldosterone (ALD), procollagen type III N-terminal peptide (PNP), hyaluronate(HA) except for laminin (LN) were significantly higher in CHF than in controls, and these serum levels of ATP group had no change.Part II: To examine the prevention effect on AF and structural remodeling by TMP and the molecular mechanism of AF during CHF, twenty-one mongrel dogs weresubjected to CHF group (induced by VTP, 240bpm, 5weeks), TMP prevention group(deal with TMP simultaneously by intramascular injection during VTP ) and control group, 7 dogs each group. Burst atrial pacing was used to induce AF. ERP, atrial area and volume, fibrosis and the serum levels of Ang, ALD, PNP, HA and LN were measured. And the mRNA level of MMP-2, TIMP-1, TIMP-2 , Col I, Col IV and TGF in left and right atrial were detected by RT-PCR technique. l.Compared with CHF group, TMP group LVEF increased from 29.2% to 40.7%, SAF markedly decreased 50% and DAF reduced from 462.1 seconds to 340.6 seconds but has no statistics signification, and we did not see ERPs reduction and ERP-RA attenuation. 2.Compared with CHF group, RA systolic area, LA systolic area and volume, LA diastolic area and volume, fibrosis reduced significantly in TMP group although the area, volume and fibrosis were greater than controls. 3.Compared with CHF group, the serum levels of Angll and PIIINP in TMP decreased markedly whereas ALD, LN and HA did not. There were no significantly difference of all the serum levels between TMP and controls. 4.The mRNA expression in RA: The mRNA expression of MMP-2, Col I, TGF from CHF were 65.7%,34.7% and 62.9% more than that from controls, respectively, and the ratio of MMP-2/TIMP-2 increased 106.1% although the TIMP-2 expression has no changed in CHF. The expression of TIMP-1 and Col IV decreased 33.3% and 27.0% respectively in CHF, but then there was no statistics difference in Col IV. No significant difference was found in the ex...
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