Armstrong P W, Moe G W, Howard R J, Grima E A, Cruz T F
Department of Medicine, Samuel Nunenfeld Research Institute, University of Toronto, Ontario.
Can J Cardiol. 1994 Mar;10(2):214-20.
Rapid ventricular pacing in the dog produces severe congestive cardiac failure in association with neurohumoral activation and marked depression of cardiac function. This syndrome is associated with left ventricular dilation, significant wall thinning, assumption of a more globular shape and disruption of the cardiac collagen infrastructure, given that the fibrillar collagen network is a major determinant of cardiac architecture. The purpose of the present study was to investigate whether there was evidence of increased activity of matrix metalloproteinases. The authors speculated that it could play an important permissive role in myocyte realignment, thereby resulting in the changes in cardiac size and shape.
Twenty-one male mongrel dogs underwent ventricular pacing and were allocated into one of three groups: early heart failure (n = 6), severe heart failure (n = 7) and recovered heart failure (n = 8). Measurements included echocardiographic and hemodynamic parameters, plasma noradrenaline levels, left ventricular noradrenaline levels and matrix metalloproteinase activity.
The study showed gelatinase activity present in normal left ventricular tissue predominantly attributable to a 72 kDa gelatinase (85%) and, to a much lesser extent, by a 92 kDa gelatinase (15%). Levels of 92 kDa gelatinase increased slightly within one week and reached maximal levels with severe heart failure, where it represented over one-half of the total gelatinase activity. In animals allowed to recover for four weeks, 92 kDa gelatinase decreased significantly to approximately 50% of the levels observed at severe heart failure. The levels of 72 kDa gelatinase did not change significantly during any experimental condition. Significant correlations between 92 kDa percentage activity and systolic and diastolic left ventricular areas across all time-points were evident (r = 0.59 and 0.63, respectively, P < 0.05 for both).
The association of 92 kDa gelatinase with changes in left ventricular area suggests a possible modulating role for this matrix metalloproteinase in disruption of the fibrillar components of the left ventricular extracellular matrix.
犬快速心室起搏可导致严重充血性心力衰竭，并伴有神经体液激活和心功能显著下降。鉴于纤维状胶原网络是心脏结构的主要决定因素，该综合征与左心室扩张、显著的室壁变薄、更接近球形的形态以及心脏胶原结构的破坏有关。本研究的目的是调查是否有基质金属蛋白酶活性增加的证据。作者推测它可能在心肌细胞重新排列中起重要的促成作用，从而导致心脏大小和形状的改变。
21只雄性杂种犬接受心室起搏，并被分为三组之一：早期心力衰竭组（n = 6）、严重心力衰竭组（n = 7）和心力衰竭恢复组（n = 8）。测量指标包括超声心动图和血流动力学参数、血浆去甲肾上腺素水平、左心室去甲肾上腺素水平和基质金属蛋白酶活性。
研究表明，正常左心室组织中存在明胶酶活性，主要归因于一种72 kDa的明胶酶（85%），在较小程度上归因于一种92 kDa的明胶酶（15%）。92 kDa明胶酶的水平在一周内略有升高，并在严重心力衰竭时达到最高水平，此时它占总明胶酶活性的一半以上。在恢复四周的动物中，92 kDa明胶酶显著下降至严重心力衰竭时观察到水平的约50%。在任何实验条件下，72 kDa明胶酶的水平均无显著变化。在所有时间点，92 kDa活性百分比与左心室收缩和舒张面积之间均存在显著相关性（r分别为0.59和0.63，两者P均<0.05）。
92 kDa明胶酶与左心室面积变化之间的关联表明，这种基质金属蛋白酶可能在破坏左心室细胞外基质的纤维成分中起调节作用。
