Christiansen Stefan, Stypmann Jörg J, Jahn Uli R, Redmann Klaus, Fobker Manfred, Gruber Achim D, Scheld Hans H, Hammel Dieter
Department of Cardiothoracic Surgery, University of Aachen, Aachen, Germany
J Heart Lung Transplant. 2003 Mar;22(3):301-8. doi: 10.1016/s1053-2498(02)00549-1.
The purpose of this study was to evaluate modified adriamycin-induced cardiomyopathy in the dog for research on partial left ventriculectomy (PLV).
An intracoronary catheter was introduced into the left main stem via the first marginal branch in a retrograde fashion in 12 adult foxhound dogs. The catheter was connected to a percutaneous access port that was used for weekly adriamycin administration (10 mg over a 1-hour period on 5 occasions). Follow-up examinations (transthoracic echocardiography, hemodynamic parameters, cardiopulmonary status, neurohormones) were done before, 1 week after the last adriamycin administration, and then 6 weeks later. This protocol was performed in 6 dogs (control group: Group 1). The other 6 dogs underwent PLV 1 week after the last adriamycin administration (Group 2). After the last measurements, all dogs were killed with saturated potassium chloride under general anesthesia and the hearts were excised for histologic examination. All data were calculated as mean and standard error of the mean. Differences were calculated by the Wilcoxon signed-rank test for paired and unpaired data. p < 0.05 was considered statistically significant.
One dog from each group died suddenly during adriamycin administration (probably due to ventricular arrhythmia). In addition, 1 dog from Group 2 suffered from a severe systemic inflammatory response syndrome after PLV and died 36 hours after surgery. Thus, 5 dogs from Group 1 and 4 from Group 2 underwent the entire study protocol. Adriamycin administration resulted in a severe dilated cardiomyopathy that was comparable in both groups (significant increase of central venous pressure, mean pulmonary artery pressure, pulmonary wedge pressure, left ventricular end-systolic and end-diastolic diameters, oxygen extraction, troponin I and anti-diuretic hormone, whereas cardiac output, ejection fraction and venous oxygen saturation decreased significantly). Deterioration of cardiac function continued after termination of adriamycin administration in Group 1 dogs, albeit not as progressively as during adriamycin administration. In contrast, cardiac function improved in Group 2 dogs after PLV, but did not reach baseline values. Cardiac index increased and oxygen extraction (p = 0.03) decreased, resulting in an enhanced venous oxygen saturation (p = 0.02). In particular, the distance of the papillary muscles at end diastole (p = 0.02) and at end systole (p = 0.02) at the mid-papillary level decreased significantly after PLV, resulting in reduced left ventricular diameter and volume (statistically significant for left ventricular end-systolic diameter and volume). All hearts had severe histologic alterations characteristic of adriamycin-induced toxicity, including cytoplasmic vacuolation, myocyte degeneration and increased fibrosis.
Modified adriamycin-induced cardiomyopathy in the dog may be suitable for research on PLV.
本研究旨在评估改良阿霉素诱导的犬心肌病，用于部分左心室切除术（PLV）的研究。
通过逆行方式，经第一边缘支将冠状动脉导管插入12只成年猎狐犬的左主干。导管连接至经皮接入端口，用于每周给予阿霉素（5次，每次1小时内给予10mg）。在末次给予阿霉素前、末次给药后1周及6周后进行随访检查（经胸超声心动图、血流动力学参数、心肺状态、神经激素）。该方案在6只犬中实施（对照组：第1组）。另外6只犬在末次给予阿霉素后1周接受PLV（第2组）。在最后一次测量后，所有犬在全身麻醉下用饱和氯化钾处死，取出心脏进行组织学检查。所有数据计算为均值和均值标准误差。通过Wilcoxon符号秩检验计算配对和非配对数据的差异。p < 0.05被认为具有统计学意义。
每组各有1只犬在给予阿霉素期间突然死亡（可能由于室性心律失常）。此外，第2组有1只犬在PLV后发生严重全身炎症反应综合征，术后36小时死亡。因此，第1组5只犬和第2组4只犬完成了整个研究方案。给予阿霉素导致严重扩张型心肌病，两组情况相当（中心静脉压、平均肺动脉压、肺楔压、左心室收缩末期和舒张末期直径、氧摄取、肌钙蛋白I和抗利尿激素显著增加，而心输出量、射血分数和静脉血氧饱和度显著降低）。第1组犬在停止给予阿霉素后心脏功能持续恶化，尽管不像给予阿霉素期间那样进行性恶化。相比之下，第2组犬在PLV后心脏功能改善，但未达到基线值。心脏指数增加，氧摄取（p = 0.03）降低，导致静脉血氧饱和度升高（p = 0.02）。特别是，PLV后乳头肌水平在舒张末期（p = 0.02）和收缩末期（p = 0.02）的距离显著减小，导致左心室直径和容积减小（左心室收缩末期直径和容积具有统计学意义）。所有心脏均有阿霉素诱导毒性的严重组织学改变，包括细胞质空泡化、心肌细胞变性和纤维化增加。
改良阿霉素诱导的犬心肌病可能适用于PLV研究。
