Negroni J A, Lascano E C, Barra J G, Crottogini A J, Pichel R H
Fundación Favaloro, Departamento de Investigación y Docencia, Buenos Aires, Argentina.
Cardiovasc Res. 1993 Aug;27(8):1449-61. doi: 10.1093/cvr/27.8.1449.
The aim was to construct a model linking a simplified interpretation of the contractile process at the myofilament level to the mechanical behaviour of the left ventricle to improve the ability of elastic-resistive models to represent the pumping response of the left ventricle. The mechanical model, consisting of an elastic component connected in series with a contractile component and an elastic component parallel to both the series elastic and contractile components, is able to develop pressure by the binding of a structural substance T to an excitatory substance C, the behaviour of which is a simplification of miofibrillar Ca2+ kinetics.
Theoretically, the model was validated for its ability to reproduce by computer simulation, experiments that described the pumping properties of the left ventricle--namely, elasticity, resistivity, deactivating and positive effect of ejection, and the behaviour of intracellular Ca2+. Experimentally, the model was tested to fit intraventricular pressure (P(t)) and volume (V(t)) of single ejective beats in nine open chest dogs fitted with a pressure microtransducer to measure intraventricular P(t) and an aortic flowprobe to measure ventricular outflow and calculate V(t). Parameters were estimated up to maximum negative dP/dt adjusting P(t) or V(t) data of the ejective beats, and the goodness of the fit was evaluated through the root mean square error normalised with respect to the corresponding mean P(t) or V(t) in the fitting interval (NE).
Descriptive validation of the model showed that the mean NE for the ejective P(t) fit was 0.03(SD 0.005) and for the V(t) fit 0.014(0.003). Predictive validation of P(t) and V(t) data of beats with partial occlusion of the aorta was performed up to end ejection, with parameters estimated from the P(t) or V(t) fit of the preceding ejective beat. Results gave a mean NE equal to 0.05(0.02) for predicted P(t) and 0.02(0.007) for predicted V(t), from either source of estimated parameters. Explanative validation showed that all the estimated parameters were in the same range used in simulation and that derived indexes [isovolumic maximum pressure (Pmax) = 166(13) mm Hg, time to maximum pressure (TPmax) = 0.186(0.012) s and the slope of the end systolic pressure volume relation (Emax) = 5.45(1.5) mm Hg.ml-1] were within reported experimental values. Finally, the model responded to increased inotropic state [dobutamine (5-35 micrograms.kg-1.min-1)] causing the estimated Pmax and Emax to increase by 33% and 25%, respectively, and TPmax to decrease by 10%.
This model represented an improvement over previous pump models because (1) the model was able to represent behaviours other than purely elastic-resistive ones, such as the deactivation and positive effect of ejection; (2) left ventricular properties were the response of model behaviour and not constitutive elements of its structure; and (3) it adequately fulfilled model validation procedures.
构建一个模型,将肌丝水平收缩过程的简化解释与左心室的力学行为联系起来,以提高弹性阻力模型表征左心室泵血反应的能力。该力学模型由一个与收缩成分串联的弹性成分以及一个与串联弹性成分和收缩成分均平行的弹性成分组成,它能够通过一种结构物质T与一种兴奋性物质C的结合来产生压力,其中物质C的行为是对肌原纤维Ca2+动力学的简化。
从理论上讲,通过计算机模拟验证该模型再现描述左心室泵血特性实验的能力,这些特性包括弹性、阻力、舒张和射血的正性作用以及细胞内Ca2+的行为。通过实验,在9只开胸犬身上测试该模型,这些犬配备有压力微传感器以测量心室内压力(P(t))和主动脉血流探头以测量心室流出量并计算V(t),以拟合单次射血搏动的心室内压力(P(t))和容积(V(t))。通过调整射血搏动的P(t)或V(t)数据,估计参数直至最大负dP/dt,并通过在拟合区间(NE)相对于相应平均P(t)或V(t)归一化的均方根误差来评估拟合优度。
该模型的描述性验证表明,射血P(t)拟合的平均NE为0.03(标准差0.005),V(t)拟合的平均NE为0.014(0.003)。对主动脉部分闭塞搏动的P(t)和V(t)数据进行预测性验证直至射血末期,参数根据前一次射血搏动的P(t)或V(t)拟合进行估计。无论从哪个估计参数来源,预测P(t)的平均NE等于0.05(0.02),预测V(t)的平均NE等于0.02(0.007)。解释性验证表明,所有估计参数均在模拟中使用的相同范围内,并且导出的指标[等容最大压力(Pmax) = 166(13)mmHg,达到最大压力的时间(TPmax) = 0.186(0.012)s,以及收缩末期压力-容积关系的斜率(Emax) = 5.45(1.5)mmHg.ml-1]均在报告的实验值范围内。最后,该模型对增强的心肌收缩状态[多巴酚丁胺(5 - 35微克.千克-1.分钟-1)]有反应,导致估计的Pmax和Emax分别增加33%和25%,TPmax降低10%。
该模型相较于先前的泵模型有改进,原因如下:(1)该模型能够表征除纯弹性阻力行为之外的其他行为,如舒张和射血的正性作用;(2)左心室特性是模型行为的响应,而非其结构的组成要素;(3)它充分完成了模型验证程序。