A novel heart failure model induced by sequential coronary artery occlusions and tachycardiac stress in awake pigs
A novel heart failure model induced by sequential coronary artery occlusions and tachycardiac stress in awake pigs
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DOI：
10.1152/ajpheart.1999.277.1.h388
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发表时间：
1999-07-01
影响因子：
4.8
通讯作者：
Wiedmann, RT
中科院分区：
文献类型：
--
作者：
Shen, YT;Lynch, JJ;Wiedmann, RT
使用有意识的猪建立了一种心力衰竭模型，这些猪先经历连续的心肌梗死，随后进行间歇性快速心室起搏。在15头猪体内植入主动脉和心房导管、左心室（LV）压力计、左心室维度晶体、升主动脉血流探头、起搏导线以及两个冠状动脉闭塞器。最初对左回旋支冠状动脉（LCX）远端进行闭塞，造成了适度的梗死，即占左心室的18±3%，48小时后对LCX近端进行第二次闭塞，使梗死面积扩大到左心室的33±2%，而左心室功能仅有适度变化。此后，这些猪以220次/分钟的频率进行心室起搏，持续7天，然后停止3天。这个起搏周期又重复了两次，导致左心室功能和全身血流动力学显著受损。例如，在第二次起搏周期后，左心室压力变化率（dP/dt，从2778±112 mmHg/s降低了 -41±4%）、周向纤维缩短速度（V - cf：从1.1±0.1 s⁻¹降低了 -53±6%）以及心脏指数（CI：从122±4 ml·min⁻¹·kg⁻¹降低了 -42±5%）都显著降低，而左心室舒张末期直径（EDD：从39±2 mm增加了 +34±6%）、总外周阻力（TPR：从0.79±0.05 U增加了 +75±16%）以及平均左心房压力（LAP）（从5±1 mmHg增加了 +21±1 mmHg）都显著增加。重要的是，在最后一次起搏周期停止3周后，左心室dP/dt（ -40±5%）、V - cf（ -48±9%）和CI（ -30±4%）仍然降低，而左心室EDD（ +39±5%）、TPR（ +43±9%）和LAP（ +13±4 mmHg）仍然升高。相比之下，6头仅进行起搏的有意识的猪在起搏停止后血流动力学损害并未持续。因此，该模型可为研究临床前治疗干预的效果以及心力衰竭发生的相关机制提供独特的机会。
A heart failure model was developed using conscious pigs subjected to serial myocardial infarctions followed by intermittent rapid ventricular pacing. Aortic and atrial catheters, left ventricular (LV) pressure gauge, LV dimension crystals, ascending aortic flow probe, pacing leads, and two coronary artery occluders were implanted in 15 pigs. The initial distal left. circumflex coronary artery (LCX) occlusion produced a modest infarct, i.e., 18 +/- 3% of LV, and the second proximal LCX occlusion, performed 48 h later, enlarged the infarct to 33 +/- 2% of the LV with only modest changes in LV function. Thereafter, the pigs were subjected to ventricular pacing at 220 beats/min, which was maintained for 7 days and terminated for 3 days. This pacing cycle was repeated two more times and resulted in significantly impaired LV function and systemic hemodynamics. For example, after the second cycle of pacing, LV rate of pressure change (dP/dt, -41 +/- 4% from 2,778 +/- 112 mmHg/s), velocity of circumferential fiber shortening (V-cf: -53 +/- 6% from 1.1 +/- 0.1 s(-1)), and cardiac index (CI: -42 +/- 5% from 122 +/- 4 ml . min(-1) . kg(-1)) were reduced significantly, whereas LV end-diastolic diameter (EDD: +34 +/- 6% from 39 +/- 2 mm), total peripheral resistance (TPR: +75 +/- 16% from 0.79 +/- 0.05 U), and mean left, atrial pressure (LAP) (+21 +/- 1 mmHg from 5 +/- 1 mmHg) were increased significantly. Importantly, 3 wk after cessation of the final pacing cycle, LV dP/dt (-40 +/- 5%), V-cf(-48 +/- 9%), and CI (-30 +/- 4%) remained depressed, whereas LV EDD (+39 +/- 5%), TPR (+43 +/- 9%), and LAP (+13 +/- 4 mmHg) were still increased. In contrast, hemodynamic impairment in six conscious pigs subjected to pacing only did not persist when pacing was terminated. Thus this model could provide a unique opportunity to study both the effects of preclinical therapeutic interventions and the mechanisms involved in the development of heart failure.