Regulators of Cardiac Cell Growth, Differentiation, and Apoptosis

The pathogenesis of heart hypertrophy and failure have been the focus of intense clinical and basic science investigation, yet the signal transduction pathways and molecular process that underlie the compensatory growth process that ultimately leads to heart failure remain enigmatic. Since ventricular myocytes have exited the cell cycle, growth of the myocardium in response to hemodynamic load occurs by cellular hypertrophy and not by hyperplasia. In this article, we document the potential involvement of tumor suppressor pocket proteins and cell cycle regulators that may impinge on the growth, differentiation, and apoptosis of cardiac muscle. This revised version was published online in August 2006 with corrections to the Cover Date.     

单侧门静脉栓塞诱导家兔肝细胞凋亡及对侧肝叶增生的实验研究

目的探讨家兔门静脉栓塞后同侧肝细胞凋亡及对侧肝叶增生的最佳时间。方法健康家兔40只,随机分成5组,每组8只。一组做对照,余剖腹细针穿刺行肝右叶选择性门静脉栓塞。分别于栓塞前、栓塞后第3、7、14、21天各处死1组,依次为A、B、C、D、E组。处死后测量肝左、右叶体积,右肝取病理切片观察肝细胞凋亡、坏死情况及肝功能改变。结果栓塞后肝右叶体积逐步减少,A到E组平均体积分别为46．4、46．0、44．4、42．0、39．7 cm~3。肝左叶体积逐步增大,A到E组平均体积分别为54．0、54．5、56．3、61．7、63．9 cm~3。剩余肝比例逐步增加,A到E组分别为53．8%、54．2%、55．9%、59．0%、61．0%。肝细胞凋亡指数A到E组分别为8．1%、12．2%、19．4%、20．1%、14．2%。结论选择性门静脉栓塞可引起同侧肝叶萎缩及诱导肝细胞凋亡和对侧肝叶体积代偿性增生,最佳时间为7～14 d。     

氯沙坦长期治疗对自发性高血压大鼠血管结构的影响

目的 :评价血管紧张素Ⅱ受体 1(AT1)拮抗剂氯沙坦 (Losartan)对自发性高血压大鼠 (SHR)血管结构的影响及在减缓高血压血管损害中的潜在作用 ,并探讨在高血压血管壁增厚的过程中醛固酮所起的作用。方法 :采用 10周龄SHR 16只 ,随机分为Losartan(SHRLOS)治疗组和对照组 (SHR) ,另选 10只同龄Wistar鼠作为正常对照。腹主动脉插管测定收缩压 ,应用计算机图像分析 ,计算血管中膜 /内径比 ,用光镜观察各组主动脉的结构变化 ;行肠系膜动脉离体灌注、反向高效液相 (HPLC)纯化和放免检测氯沙坦对血管局部合成醛固酮的影响。结果 :SHRLOS组收缩压 (SBP)与SHR组相比明显下降 (P =0 .0 0 1) ;其血管中膜 /内径比较SHR组显著降低 ,但仍高于Wistar组 ,血管壁结构接近Wistar组 ;SHRLOS组血管AngⅡ与SHR组无差异 ,醛固酮水平降至Wistar组。结论 :氯沙坦抑制血管合成醛固酮 ,逆转血管重构是其治疗高血压的机理之一。     

Effects of resistance training in humans on neck muscle performance, and electromyogram power spectrum changes

The purpose of this study was to quantify the neuromuscular cervical adaptations to an 8 week strength training programme. Seven healthy men, with no pathological conditions of the neck, performed a lateral flexion isometric resistance-training programme three times a week. The training sessions consisted of one set of ten contractions, each of 6 s duration, at 60% of the predetermined maximal voluntary isometric torque (MVT_im) (warm-up) and two sets of eight contractions, each of 6 s duration, at 80% MVT_im. The training effects were evaluated in three ways: muscle size, strength and fatigability. The cross-sectional areas (CSA) of the trapezius (TRP) and sternocleidomastoideus (SCM) muscles were determined using a computerised tomographic scanner. Results showed an increase in the CSA of TRP and SCM muscles after training, 8.8% at C5 level and 6.4% at C7 level for SCM muscle and 12.2% at C7 level for TRP muscle. Strength increased significantly under both isometric and isokinetic conditions (35% and 20%, respectively). Muscle fatigability in lateral flexion was quantified during a sustained isometric contraction at 50% of MVT_im. The shift of the mean power frequency of the electromyogram power spectrum density function of SCM muscle toward lower frequencies was less after training (14.6% compared to 6.8%). These results indicate the beneficial effect of a strength-training programme which increases neck muscle size and strength during lateral flexion, and decreases the fatigability of the superficial muscles of the neck. Electronic Publication     

Lactate dehydrogenase activity and isoform distribution in normal and hypertrophic smooth muscle tissue from the rat

The lactate dehydrogenase (LDH) activity and isoform distribution of LDH were investigated in tissue samples from the rat portal vein, aorta and urinary bladder. In addition, samples were obtained from hypertrophic urinary bladder. The total LDH activity per unit smooth muscle volume was higher in the urinary bladder compared to that in portal vein and aorta. Five LDH isoforms, reflecting different combinations of the two polypeptide chains denoted H and M, could be separated by agarose gel electrophoresis. The aorta contained more of the H form compared to the portal vein and urinary bladder. This difference suggests that the aorta, which is a slow smooth muscle, is more adapted for aerobic metabolism than the faster muscles of portal vein and urinary bladder. In the hypertrophic urinary bladder a shift in LDH isoform pattern towards less of the H form was found, which correlates with a better maintenance of contraction in anoxia in this type of hypertrophic smooth muscle.     

兔在体左室肥厚心肌跨室壁电异质性的实验研究

目的：探讨兔在体左室肥厚心肌单相动作电位跨室壁的不均一性变化。方法：以腹主动脉缩窄术制备家兔高血压左室肥厚模型，并设假手术组（仅游离腹主动脉未缩窄）作为对照。采用自制复合式电极在兔左心室前壁同步记录心内膜、心肌中层、心外膜在体3层心肌单相动作电位（MAP），比较两组间跨室壁复极离散度(TDR)等各项参数的差异。结果：腹主动脉缩窄组平均动脉压、全心重量及其与体重比率、左心室游离壁厚度均大于假手术组。缩窄组3层心肌MAPD100［内膜：(191±19)ms；中层：(244±24)ms;外膜：(196±15)ms］均长于对照组［内膜：(170±18)ms ;中层：(172±15)ms;外膜：(168±16)ms，P<0.01］，以中层心肌MAPD100延长最为明显，缩窄组TDR（65±10)ms较对照组（4±3)ms明显增大（P<0.01）。结论：兔在体左室肥厚心肌跨室壁电不均一性明显增大，可能是肥厚心肌心律失常发生增多的原因之一。     

阿托伐他汀对自发性高血压大鼠心肌组织PPARs表达的影响

目的： 探讨阿托伐他汀对自发性高血压大鼠心肌组织PPARs（peroxisome proliferator-activated receptors, PPARs）表达的影响及其对心肌肥厚的逆转作用与可能机制。方法: 自发性高血压大鼠分为阿托伐他汀灌胃治疗组（SHR-A，30 mg·kg-1·d-1）及模型组（SHR），治疗8周，同周龄Wistar-Kyoto 鼠为正常血压对照组。治疗前及治疗后2、4、8周测量大鼠尾动脉血压。治疗后测血浆血脂水平，以心脏组织病理分析判断心肌肥厚，Western blotting 检测心肌组织PPARα、PPARγ的表达水平。结果: 经过8周治疗， SHR-A组及SHR组血压及血脂水平无明显差异（P＞0.05）。SHR-A组左室重量指数低于SHR组（P＜0.01）。在SHR-A组，PPARα及PPARγ表达高于SHR组（P＜0.01）。结论: 阿托伐他汀显著改善自发性高血压大鼠心肌组织PPARs表达，有效逆转左室肥厚，可能与其降压及降脂作用无关。     

大鼠压力负荷性肥大心肌中TNF-α mRNA表达变化

目的：探讨大鼠压力负荷性肥大心肌中TNF-α mRNA表达的变化及卡托普利（captopril）对其的影响。方法：采用腹主动脉缩窄法复制压力超负荷心肌肥大模型，于术后42 d采血、摘取心脏，测定心肌肥大指数并采用酶联免疫法测定血清及左心室肌TNF-α含量；应用心肌原位杂交法结合图像分析系统检测心肌组织中TNF-α mRNA表达的变化，并观测TNF-α mRNA在心肌组织中的定位。结果：术后42 d心肌明显肥大，以左心室为主；主动脉缩窄（aorta-constriction, AC）组心室肌TNF-α含量比假手术（sham-operation, SO）组高98%（P<0.01）；卡托普利干预使心室肌TNF-α含量比AC组低64.14%（P<0.01），但未达到对照水平；心肌组织原位杂交显示TNF-α mRNA表达主要在心肌间质部位，假手术组心肌TNF-α mRNA表达水平极低，明显低于AC术后（P<0.01），captopril干预虽明显抑制AC术后心肌组织中TNF-α mRNA表达，但并未使其达到SO组水平。结论：心肌组织内源性TNF-α的表达增加在压力负荷性心肌肥大中具有重要的调控作用，其过表达可能与RAS激活促心肌间质TNF-α mRNA表达上调有关。     

Feinstrukturell-morphometrische Befunde an der Kammerwand hypertrophierter menschlicher linker Ventrikel

Zusammenfassung An den KammerwÄnden menschlicher linker Ventrikel, die auf Grund einer Aortenstenose, einer Aorteninsuffizienz oder eines kombinierten Aortenvitium hypertrophiert waren, wurden licht- und elektronenmikroskopisch morphometrische Untersuchungen angestellt. Die Ergebnisse wurden mit denen, die an nicht belasteten menschlichen linken Ventrikeln gewonnen wurden, verglichen.Lichtmikroskopisch unterscheiden sich die Anteile der Volumendichten des Interstitium und der Herzmuskelzellen am gesamten Herzmuskelgewebe nicht statistisch signifikant. Es konnte morphometrisch eine Zellvergrö\erung festgestellt werden, die aus der signifikanten Verringerung der Volumendichte der Zellkerne (P<0,001) und der Anzahl der Zellkerne pro TestflÄche (P<0,0001) gegenüber den beiden Normalkollektiven resultiert. Elektronenmikroskopisch ist eine Zunahme der Volumendichten der Myofibrillen (P<0,0001) auf Kosten des restlichen Cytoplasmas (P<0,001) festzustellen, wÄhrend die Volumendichte der Mitochondrien im Vergleich mit den jungen und alten Patienten abnahm (P<0,0001). Die OberflÄchendichte der Mitochondrien verringerte sich gegenüber den beiden Vergleichskollektiven (P<0,001) ebenso wie die der Cristae mitochondriales (P<0,0001). Diese Ergebnisse finden ihr morphologisches Korrelat in Mitochondriendestruktionen. Eine vermehrte Myolyse hat bei den hypertrophierten Herzen, die alle gewichtsmÄ\ig über dem kritischen Herzgewicht lagen, noch nicht eingesetzt. Bei allen Patienten wurde der herzchirurgische Eingriff mit Erfolg durchgeführt.

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Ultrastructural morphometric analysis of hypertrophied human myocardial left ventricles

Summary Biopsies of hypertrophied human myocardial left ventricles were investigated morphometrically. The diagnoses of the patients were stenosis of the aortic valve, aortic insufficiency or a combination of both lesions. The results were compared with those from normally loaded human left ventricles.There are no differences on light microscopical level between the volume densities of interstitial tissue and of heart muscle cells in the three groups of patients. A significant diminution of the volume density of the nuclei (P<0.001) and the number of nuclei per test area (P<0.0001) when compared with normal groups suggests an increase in volume of the single heart muscle cell. The ultrastructural study shows marked increase in volume density of myofibrils (P<0.0001), with accompanying decrease in the volume densities of mitochondria (P<0.0001) and the remaining cytoplasm (P<0.001). A gross decrease in the surface area of mitochondria (P<0.001) and of cristae mitochondriales (P<0.0001) is found. The morphological equivalents of this result are numerous stages of mitochondrial destruction including cristolysis. All myocardial weights were beyond the critical heart weight.

Mit dankenswerter Unterstützung der Deutschen Forschungsgemeinschaft über den Sonderforschungsbereich SFB 104