惡性癌症的常見表現之一的消瘦症不僅與體重減輕有關，還與嚴重的心臟萎縮和心臟功能受損有關。在這裡，我們比較研究了ACM-001（0.3或3mg/kg/d）與卡维地洛（3或30mg/kg/d）、美托洛尔（50或100mg/kg/d）、奈必洛（1或10mg/kg/d）和特塔洛尔（0.5或5mg/kg/d）對大鼠癌症消瘦模型的心臟質量和功能的影響。年輕的Wistar Han大鼠被接種108個Yoshida肝瘤AH-130細胞，並每天透過灌胃進行治療，以進行verum或安慰劑療法。透過超聲心動圖來測試心臟功能，以NMR掃描來評估體重和體組成。動物的心臟在第11天時被安樂死，並用於進行信號研究。阻滯劑對腫瘤負擔沒有影響。ACM-001減輕體重減輕（安慰劑：-34±2.4g vs 3mg/kg/d ACM-001：-14.8±8.4g，p = 0.033）。降解的精益質量被減緩（安慰劑：-16.5±2.34g vs 3mg/kg/d ACM-001：-2.4±6.7g，p = 0.037），而脂肪損失在第11天時是相似的（p = 0.4）。安慰劑組動物失去LVmass（-101±14mg），只有3mg/kg/d ACM-001防止了這種情況（7±25mg，0 <0.01 vs安慰劑）。ACM-001改善了EF（ΔEF：安慰劑：-24.3±2.6，3mg/kg/d ACM-001：0.1±2.9，p <0.001）。安慰劑組的心輸出量比基線低了50％（-41±4mL/min），而3mg/kg/d ACM-001保持了心輸出量（-5±8，p <0.01）。分子機制涉及蛋白質降解的抑制和蛋白質合成途徑的激活。該研究表明，3mg/kg/d ACM-001恢復了心肌的分解/合成平衡，從而改善了功能。此外，并非所有的阻遏劑都具有相似的效果。本文受版權保護。 版權所有。

Cachexia, a common manifestation of malignant cancer, is not only associated with weight loss, but also with severe cardiac atrophy and impaired cardiac function. Here, we investigated the effects of ACM-001 (0.3 or 3mg/kg/d) in comparison to carvedilol (3 or 30mg/kg/d), metropolol (50 or 100mg/kg/d), nebivolol (1 or 10mg/kg/d) and tertatolol (0.5 or 5 mg/kg/d) on cardiac mass and function in a rat cancer cachexia model.Young male Wistar Han rats were inoculated with 108 Yoshida hepatoma AH-130 cells ip and treated once daily with verum or placebo by gavage. Cardiac function (echocardiography), body weight and body composition (NMR-Scans) were assessed. The hearts of animals were euthanized on day 11 (placebo and 3 mg/kg/d ACM-001) were used for signaling studies.Beta-blockers had no effect on tumour burden. ACM-001 reduced body weight loss (placebo: -34±2.4g vs 3mg/kg/d ACM-001: -14.8±8.4g, p=0.033). Lean mass wasting was attenuated (placebo: -16.5±2.34g vs 3mg/kg/d ACM-001: -2.4±6.7g, p=0.037), while fat loss was similar (p=0.4) on day 11. Placebo animals lost LVmass (-101±14mg), which was prevented only by 3mg/kg/d ACM-001 (7±25mg, 0<0.01 vs placebo). ACM-001 improved the EF (ΔEF: placebo: -24.3±2.6, 3mg/kg/d ACM-001: 0.1±2.9, p<0.001). Cardiac output was 50% lower in the placebo group (-41±4mL/min) compared to baseline, while 3mg/kg/d ACM-001 preserved cardiac output (-5±8, p<0.01). The molecular mechanisms involve inhibition of protein degradation and activation of protein synthesis pathways.This study shows that 3mg/kg/d ACM-001 restores the anabolic/catabolic balance in cardiac muscle leading to improved function. Moreover, not all beta-blockers have similar effects. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.