Proteogenomics Research Institute for Systems Medicine, San Diego, California; and.
Am J Physiol Heart Circ Physiol. 2014 Jan 15;306(2):H270-8. doi: 10.1152/ajpheart.00818.2012. Epub 2013 Nov 8.
We describe a novel model of myocardial infarction (MI) in rats induced by percutaneous transthoracic low-energy laser-targeted photodynamic irradiation. The procedure does not require thoracotomy and represents a minimally invasive alternative to existing surgical models. Target cardiac area to be photodynamically irradiated was triangulated from the thoracic X-ray scans. The acute phase of MI was histopathologically characterized by the presence of extensive vascular occlusion, hemorrhage, loss of transversal striations, neutrophilic infiltration, and necrotic changes of cardiomyocytes. Consequently, damaged myocardium was replaced with fibrovascular and granulation tissue. The fibrotic scar in the infarcted area was detected by computer tomography imaging. Cardiac troponin I (cTnI), a specific marker of myocardial injury, was significantly elevated at 6 h (41 ± 6 ng/ml, n = 4, P < 0.05 vs. baseline) and returned to baseline after 72 h. Triphenyltetrazolium chloride staining revealed transmural anterolateral infarcts targeting 25 ± 3% of the left ventricle at day 1 with a decrease to 20 ± 3% at day 40 (n = 6 for each group, P < 0.01 vs. day 1). Electrocardiography (ECG) showed significant ST-segment elevation in the acute phase with subsequent development of a pathological Q wave and premature ventricular contractions in the chronic phase of MI. Vectorcardiogram analysis of spatiotemporal electrical signal transduction revealed changes in inscription direction, QRS loop morphology, and redistribution in quadrant areas. The photodynamically induced MI in n = 51 rats was associated with 12% total mortality. Histological findings, ECG abnormalities, and elevated cTnI levels confirmed the photosensitizer-dependent induction of MI after laser irradiation. This novel rodent model of MI might provide a platform to evaluate new diagnostic or therapeutic interventions.
我们描述了一种通过经皮经胸低能量激光靶向光动力照射诱导大鼠心肌梗死（MI）的新型模型。该方法不需要开胸手术，是现有手术模型的微创替代方法。要进行光动力照射的目标心脏区域是通过胸部 X 射线扫描进行三角定位的。MI 的急性期在组织病理学上表现为广泛的血管闭塞、出血、横纹消失、中性粒细胞浸润和心肌细胞坏死变化。因此，受损的心肌被纤维血管和肉芽组织取代。用计算机断层扫描成像检测梗死区的纤维化疤痕。心肌肌钙蛋白 I（cTnI）是心肌损伤的特异性标志物，在 6 小时（41 ± 6 ng/ml，n = 4，P < 0.05 与基线相比）显着升高，并在 72 小时后恢复基线。三苯基四唑氯化物染色显示，在第 1 天针对左心室 25 ± 3%的前外侧透壁梗死，在第 40 天减少至 20 ± 3%（每组 n = 6，P < 0.01 与第 1 天相比）。心电图（ECG）在急性期显示出明显的 ST 段抬高，随后在 MI 的慢性期出现病理性 Q 波和室性早搏。时空电信号转导的向量心电图分析显示，记录方向、QRS 环形态和象限区域分布发生变化。在 n = 51 只大鼠中，光动力诱导的 MI 与 12%的总死亡率相关。组织学发现、ECG 异常和升高的 cTnI 水平证实了激光照射后光敏剂依赖性诱导的 MI。这种新型的 MI 啮齿动物模型可能为评估新的诊断或治疗干预措施提供平台。
