Blagova O V, Nedostup A V
Ter Arkh. 2006;78(8):30-8.
To characterize actions of beta-blockers and Ca antagonists (verapamil and diltiazem) on the rate, structure and parameters of ventricular rhythm variability in constant cardiac fibrillation (CCF) and to evaluate validity of monotherapy with these drugs.
Thirty patients with CCF (mean age 64.5 +/- 9.5 years) received beta-blockers (n = 10, atenolol in a dose 50.0 +/- 23.2 mg/day or metoprolol in a dose 45.0 +/- 20.9 mg/day), verapamil (n = 10, 192.0 +/- 83.9 mg/day) and diltiazem (n = 10, 286.6 +/- 107.2 mg/day). The patients were studied with Holter ECG monitoring (Schiller MT-100, Switzerland) and high resolution ECG (electrocardioanalyser Cardis, Geolink-electronics, RF) with construction of periodograms of ff waves and interval histograms RR (IHrr), estimation of the rhythm variability (SDRR, rMSSD, PNN50).
Beta-blockers (atenolol, metoprolol), verapamil and diltiazem had no significant effect on the period of ff waves. The degree of a mean heart rate lowering decreased in the following order: beta-blockers-verapamil-diltiazem (30.1 +/- 12.5, 25.0 +/- 18.8 and 22.0 +/- 23.6 beat/min, differences are insignificant), this corresponded to the degree of Rrmin increase (0.12 +/- 0.04, 0.08 +/- 0.07 and 0.07-0.08). In CCF the inhibiting effect of beta-blockers and verapamil is substrate-dependent: the shorter baseline Rrmin (and higher heart rate), the more potent is the effect due to action of beta-blockers and verapamil (r = -0.58 and r = -0.57, p < 0.05) and reduction of a mean heart rate (r = -0.74 and r = -0.84, p < 0.05). Dependence of diltiazem effect on initial Rrmin is inverse. In contrast to Ca antagonists (verapamil, diltiazem), beta-blockers increased latent conduction manifesting in a significant rise of Rrmax, range of RR intervals (the difference between Rrmax and Rrmin) and in increased latent conduction (Rrmax/Rrmin) by 0.4 versus 0 and 0.1 in the groups on verapamil and diltiazem). In addition to insufficient shift RRmod, there appeared non-optimal rhythm structure--combination of a large number of short and long RR in small number of middle ones. Verapamil and diltiazem improved the rhythm pattern due to proportional increase of RRmin shift RRmod (r = 0.72 and r = 0.71, p < 0.05) and absence of a distinct effect on latent conduction. The between groups differences by SDRR, RMSSD and PNN50 dynamics were insignificant. Diltiazem in doses 360-480 mg/ day moderately increased latent conduction, but was low effective in the presence of early peak RR (0.28-0.46 s).
Monotherapy with AB-blocking drugs was possible only in patients with moderate tachycardia, no waves of fibrillation of large and middle periods (0.15 s and higher) and should be conducted under Rrmin control. In the other cases, the above drugs are either low effective or promote non-optimal rhythm structure. Therefore, combined therapy with AB-blocking drugs and cardiac glycosides is indicated for CCF patients.
明确β受体阻滞剂和钙拮抗剂(维拉帕米和地尔硫䓬)对持续性心房颤动(CCF)时心室率、节律结构及变异性参数的作用,并评估这些药物单一疗法的有效性。
30例CCF患者(平均年龄64.5±9.5岁)接受β受体阻滞剂(n = 10,阿替洛尔剂量为50.0±23.2mg/天或美托洛尔剂量为45.0±20.9mg/天)、维拉帕米(n = 10,192.0±83.9mg/天)和地尔硫䓬(n = 10,286.6±107.2mg/天)治疗。采用动态心电图监测(瑞士席勒MT - 100)和高分辨率心电图(俄罗斯杰林克电子公司的Cardis心电分析仪)对患者进行研究,构建f波周期图和RR间期直方图(IHrr),评估节律变异性(SDRR、rMSSD、PNN50)。
β受体阻滞剂(阿替洛尔、美托洛尔)、维拉帕米和地尔硫䓬对f波周期无显著影响。平均心率降低程度依次为:β受体阻滞剂>维拉帕米>地尔硫䓬(分别为30.1±12.5、25.0±18.8和22.0±23.6次/分钟,差异无统计学意义),这与Rrmin增加程度相对应(分别为0.12±0.04、0.08±0.07和0.07 - 0.08)。在CCF中,β受体阻滞剂和维拉帕米的抑制作用依赖于底物:基线Rrmin越短(心率越高),β受体阻滞剂和维拉帕米作用导致的效果越强(r = - 0.58和r = - 0.57,p<0.05),平均心率降低越明显(r = - 0.74和r = - 0.84,p<0.05)。地尔硫䓬的作用与初始Rrmin呈负相关。与钙拮抗剂(维拉帕米、地尔硫䓬)不同,β受体阻滞剂增加了隐匿性传导,表现为Rrmax显著升高、RR间期范围(Rrmax与Rrmin之差)增大以及隐匿性传导增加(Rrmax/Rrmin),维拉帕米组和地尔硫䓬组分别为0、0.1,β受体阻滞剂组为0.4。除RRmod偏移不足外,还出现了非最优节律结构——少量中等RR间期与大量短RR间期和长RR间期并存。维拉帕米和地尔硫䓬通过RRmin和RRmod成比例增加改善了节律模式(r = 0.72和r = 0.71,p<0.05),且对隐匿性传导无明显影响。SDRR、RMSSD和PNN50动态变化的组间差异无统计学意义。剂量为360 - 480mg/天的地尔硫䓬适度增加了隐匿性传导,但在RR早期峰值(0.28 - 0.46秒)存在时效果不佳。
仅在中度心动过速、无大周期和中周期(0.15秒及以上)颤动波的患者中,β受体阻滞剂单一疗法可行,且应在Rrmin控制下进行。在其他情况下,上述药物要么效果不佳,要么会导致非最优节律结构。因此,CCF患者适合β受体阻滞剂与强心苷联合治疗。