Left ventricular hypertrophy is prevalent in sprague-dawley rats.
Left ventricular hypertrophy is prevalent in sprague-dawley rats.
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发表时间：
2011-02
影响因子：
0.8
通讯作者：
C. Clifford;K. Pritchett-Corning;Guy B. Mulder
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作者：
C. Clifford;K. Pritchett-Corning;Guy B. Mulder
尊敬的编辑：McAdams及其同事最近在《比较医学》上发表的一篇文章6声称，在来自Charles River和哈兰Sprague-Dawley的Sprague-Dawley大鼠中发现左心室肥大的高患病率。作者进一步推断，这种心脏异常是其实验室内接受麻醉和大脑中动脉闭塞的大鼠的高死亡率的原因，即使在刘易斯大鼠中观察到类似的死亡率，他们得出的结论是心室肥大的发生率要低得多。他们没有发现心肌细胞增殖或心肌纤维化的证据。在两个长期分离的系（来源）远交大鼠的主要器官中明显发现了普遍和相应的异常，数百万人在研究中使用，包括使用Sprague-Dawley大鼠作为对照的实验诱导的心脏肥大的研究，3，5应该需要大量的证据。我们同情作者在研究期间所经历的困难，但不同意他们关于大鼠左心室肥大的结论。McAdams及其同事的研究结果是由于方法不当造成的。McAdams及其同事基于他们对死亡大鼠左心室壁厚度、心肌细胞横截面积和左心室管腔面积减少的测量结果提出了他们的主张。然而，这些参数不足以诊断心脏肥大，并且都可以由正常的死后心肌收缩产生。正如Diwan和多恩最近解释的那样，4 "人类心脏的肥厚[来自希腊语hyper（过度）和trophy（生长）]是一种由心肌质量增加定义的形态学临床诊断。死前，诊断通常是基于计算超声心动图或磁共振成像估计左心室质量。死后，病理诊断是基于心脏重量的直接测量。值得注意的是，心脏肥大的诊断没有功能方面，它可以发生在心脏正常，超常或抑郁的心脏性能。McAdams及其同事没有对心脏进行称重，也没有通过其他方法评估体内心室质量，例如在各种哺乳动物物种中使用的超声心动图，包括人类，大鼠和小鼠，1，2等。麦克亚当斯及其同事未能称量心脏的重量是有问题的，因为死后肌肉收缩，僵硬，导致左心室收缩。事实上，左心室的正常死后收缩应该基本上排出所有的血液，类似于McAdams及其同事论文中图1和图2所示的"肥大"心脏。为了进一步强调这一过程的正常性，也就是说，死后左心室的收缩足以排出大部分血液，如果发现左心室中残留有血块，甚至可以认为这是病理过程的一些证据。在缺乏确证数据的情况下，明显较小的左心室腔不应被视为心室肥大的证据，在这种情况下，这是正常的死后发现此外，心肌细胞横截面积的增加仅仅是收缩的结果;收缩的心肌细胞比伸展的心肌细胞厚。自然地，这种心室收缩导致心室壁比放松的心脏更厚，即使心室肌的总质量没有增加。这就是为什么心脏重量是必要的，以及为什么在没有心脏重量的情况下考虑心室厚度测量可能会产生误导。在新化合物的安全性评估研究中，任何心脏疾病的证据都是一个重要的发现，称重心脏是标准的，心脏的大小通常表示为器官与体重的比值。器官与体重的比值随体型的不同而正常化。例如，Sprague-Dawley大鼠的体型比刘易斯大鼠大，这至少可以部分解释为什么McAdams和同事发现Sprague-Dawley大鼠的心室壁比刘易斯大鼠厚。因此，死后心肌收缩可能导致McAdams及其同事报告的心肌增厚的所有证据。心肌的死后收缩可能是为什么在麻醉期间或麻醉后死亡的大鼠，其中直到尸检的时间可能比专门用于尸检的安乐死大鼠更长，其心脏比安乐死时收集的心脏更厚的原因。我们的结论是，McAdams及其同事没有提出任何证据支持Sprague-Dawley大鼠左心室肥大的说法。此外，McAdams及其同事在麻醉期间注意到的死亡率并不典型。例如，查尔斯河进行外科手术的老鼠作为一个有偿服务的客户。麻醉相关的死亡没有单独追踪，但手术和恢复期间所有原因的失败，包括麻醉，解剖变异的发现和医源性死亡，如心肌梗死诱导期间的死亡，仅占最近100，000例大鼠手术的2%。因此，McAdams及其同事不仅未能证明心室肥大，而且我们的经验也不支持任何类型的心脏异常可能增加麻醉相关死亡。诚挚的Charles B Clifford，DVM，PhD，DACVP病理学和技术服务总监Charles River研究模型和服务总监Kathleen Pritchett-Corning，DVM，DACLAM，MRCVS研究和专业服务总监Charles River研究模型和服务Guy B Mulder，DVM，MS，DACLAM专业服务总监Charles River研究模型和服务
Dear Editor: A recent article in Comparative Medicine by McAdams and colleagues6 claimed to find a high prevalence of left ventricular hypertrophy in Sprague–Dawley rats originating from both Charles River and from Harlan Sprague–Dawley. The authors further theorized that this cardiac abnormality was responsible for high mortality in rats within their laboratory that underwent anesthesia and middle cerebral artery occlusion, even though similar mortality was observed in Lewis rats which they concluded had a much lower incidence of ventricular hypertrophy. They found no evidence of cardiomyocyte proliferation or myocardial fibrosis. The apparent discovery of a prevalent and consequential anomaly in a major organ in 2 long-separated lines (sources) of outbred rats, used by the millions in research, including studies of experimentally-induced cardiac hypertrophy that use Sprague–Dawley rats as controls,3,5 should require substantial evidence. We sympathize with the difficulties experienced by the authors during their studies, but disagree with their conclusion that the rats had left ventricular hypertrophy. The findings of McAdams and colleagues result from inadequate methodology. McAdams and colleagues base their claim on their measurement of the thickness of the left ventricular wall, cross-sectional area of cardiomyocytes, and decreased lumen area of the left ventricle, as measured in dead rats. However, these parameters are not sufficient for a diagnosis of cardiac hypertrophy and can all be produced by normal postmortem constriction of the myocardium. As recently explained by Diwan and Dorn,4 “Hypertrophy [from the Greek hyper (over) and trophy (growth)] of the human heart is a morphological clinical diagnosis defined by increased myocardial mass. Premortem, the diagnosis is usually based on calculated echocardiographic or magnetic resonance imaging estimates of left ventricular mass. Postmortem, the pathologic diagnosis is based on direct measurements of gravimetric heart weight. Notably, there is no functional aspect to the diagnosis of cardiac hypertrophy, and it can occur in hearts with normal, supernormal, or depressed cardiac performance.” McAdams and colleagues did not weigh the hearts, nor did they assess ventricular mass in vivo by other methods such as echocardiography that have been used in various mammalian species, including humans, rats and mice,1,2 and others. The failure of McAdams and colleagues to weigh the hearts is problematic because postmortem muscle contraction, rigor mortis, causes contraction of the left ventricle. In fact, normal postmortem contraction of the left ventricle should expel essentially all blood, similar to the “hypertrophic” heart shown in Figures 1 and 2 in the paper by McAdams and colleagues. To further emphasize the normality of this process, that is, postmortem contraction of the left ventricle sufficient to expel most blood, if a blood clot is found remaining in the left ventricle it might even be considered as some evidence of a pathologic process.7 Thus, the apparently smaller left ventricular lumen should not be considered evidence of ventricular hypertrophy in the absence of corroborating data and in this case is likely a normal postmortem finding. Furthermore, the increased cross-sectional area of the cardiomyocytes is merely a consequence of contraction; contracted myocytes are thicker than stretched myocytes. Naturally, this ventricular constriction results in the wall appearing thicker than in a relaxed heart, even though the total mass of the ventricular muscle is not increased. This is why heart weights are necessary and why ventricular thickness measurements considered without the context of heart weights can be misleading. In safety assessment studies of novel compounds, where any evidence of cardiac disease is an important finding, weighing hearts is standard, and the size of the heart is often expressed as organ-to-body weight ratios. Organ-to-body weight ratios normalize for differences in body size. For example, differences in body size, Sprague–Dawley rats are larger than Lewis rats, may at least partly explain why McAdams and colleagues found that the Sprague–Dawley rats had thicker ventricular walls than the Lewis rats. Postmortem contraction of the myocardium thus could have caused all of the evidence of myocardial thickening reported by McAdams and colleagues. Postmortem contraction of the myocardium could be why rats that died during or after anesthesia, where the time until necropsy was perhaps longer than rats euthanized specifically for necropsy, more often had hearts which appeared thick than did those collected at euthanasia. We conclude that McAdams and colleagues have presented no evidence to support a claim of left ventricular hypertrophy in Sprague–Dawley rats. In addition, the mortality noted by McAdams and colleagues during anesthesia is not typical. For example, Charles River conducts surgical procedures on rats as a paid service for clients. Anesthetic-related deaths are not tracked separately, but failures for all reasons during surgery and recovery combined, including anesthesia, discovery of anatomic variations, and iatrogenic deaths, such as death during induction of myocardial infarctions, accounted for only 2% of the last 100,000 surgical procedures in rats. Thus, not only do McAdams and colleagues fail to demonstrate ventricular hypertrophy, but our experience does not support the possibility of any type of cardiac anomaly that could increase anesthetic-related deaths. Sincerely, Charles B Clifford, DVM, PhD, DACVP Director, Pathology and Technical Services Charles River Research Models and Services Kathleen Pritchett-Corning, DVM, DACLAM, MRCVS Director, Research and Professional Services Charles River Research Models and Services Guy B Mulder, DVM, MS, DACLAM Director, Professional Services Charles River Research Models and Services