Norton Gavin R, Veliotes Demetri G A, Osadchii Oleg, Woodiwiss Angela J, Thomas D Paul
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown 2193, Johannesburg, South Africa.
Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H372-8. doi: 10.1152/ajpheart.01024.2007. Epub 2007 Nov 9.
We explored whether the hypertensive heart is susceptible to myocardial dysfunction in viable noninfarcted tissue post-myocardial infarction (MI), the potential mechanisms thereof, and the impact of these changes on pump function. Six to seven months after the ligation of the left anterior descending coronary artery, left ventricular (LV) myocardial systolic function, as assessed from the percent shortening of the noninfarcted lateral wall segmental length determined over a range of filling pressures (ultrasonic transducers placed in the lateral wall in anaesthetized, open-chest, ventilated rats) and the percent thickening of the posterior wall (echocardiography), was reduced in infarcted spontaneous hypertensive rats (SHR-MI) (P < 0.05) but not in normotensive Wistar-Kyoto (WKY-MI) animals compared with corresponding controls [SHR-sham operations (Sham) and WKY-Sham]. This change in the regional myocardial function in SHR-MI, but not in WKY-MI, occurred despite a similar degree of LV dilatation (increased LV end-diastolic dimensions and volume intercept of the LV end-diastolic pressure-volume relation) in SHR-MI and WKY-MI rats and a lack of difference in LV relative wall thinning, LV wall stress, apoptosis [terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL)], or necrosis (pathological score) between SHR-MI and WKY-MI rats. Although the change in regional myocardial function in the SHR-MI group was not associated with a greater reduction in baseline global LV chamber systolic function [end-systolic elastance (LV E(es)) and endocardial fractional shortening determined in the absence of an adrenergic stimulus], in the presence of an isoproterenol challenge, noninfarct-zone LV systolic myocardial dysfunction manifested in a significant reduction in LV E(es) in SHR-MI compared with WKY-MI and SHR and WKY-Sham rats (P < 0.04). In conclusion, these data suggest that with chronic MI, the hypertensive heart is susceptible to the development of myocardial dysfunction, a change that cannot be attributed to excessive chamber dilatation, apoptosis, or necrosis, but which in turn contributes toward a reduced cardiac adrenergic inotropic reserve.
我们探究了高血压心脏在心肌梗死（MI）后存活的非梗死组织中是否易发生心肌功能障碍、其潜在机制以及这些变化对泵功能的影响。在结扎左冠状动脉前降支6至7个月后，通过在一系列充盈压力下测定非梗死侧壁节段长度缩短百分比（将超声换能器置于麻醉、开胸、通气大鼠的侧壁）以及后壁增厚百分比（超声心动图）来评估左心室（LV）心肌收缩功能，结果显示，与相应对照组[自发性高血压大鼠假手术组（SHR - Sham）和WKY假手术组（WKY - Sham）]相比，梗死自发性高血压大鼠（SHR - MI）的左心室心肌收缩功能降低（P < 0.05），而正常血压的Wistar - Kyoto大鼠（WKY - MI）则未降低。尽管SHR - MI和WKY - MI大鼠的左心室扩张程度相似（左心室舒张末期内径增加以及左心室舒张末期压力 - 容积关系的容积截距增加），且SHR - MI和WKY - MI大鼠在左心室相对壁变薄、左心室壁应力、细胞凋亡[末端脱氧核苷酸转移酶生物素 - dUTP缺口末端标记法（TUNEL）]或坏死（病理评分）方面没有差异，但SHR - MI而非WKY - MI出现了局部心肌功能的这种变化。虽然SHR - MI组局部心肌功能的变化与基础整体左心室腔收缩功能[收缩末期弹性（LV E(es)）和在无肾上腺素能刺激情况下测定的心内膜分数缩短率]的更大降低无关，但在异丙肾上腺素刺激下，与WKY - MI以及SHR和WKY - Sham大鼠相比，SHR - MI中非梗死区左心室收缩性心肌功能障碍表现为LV E(es)显著降低（P < 0.04）。总之，这些数据表明，在慢性心肌梗死情况下，高血压心脏易发生心肌功能障碍，这种变化不能归因于过度的心室扩张、细胞凋亡或坏死，而反过来会导致心脏肾上腺素能变力储备降低。
