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首页> 外文期刊>American Journal of Physiology >PPAR-gamma agonist rosiglitazone ameliorates ventricular dysfunction in experimental chronic mitral regurgitation.
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PPAR-gamma agonist rosiglitazone ameliorates ventricular dysfunction in experimental chronic mitral regurgitation.

机译：PPAR-γ激动剂罗格列酮可改善实验性慢性二尖瓣反流中的心室功能障碍。

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Previously we reported that the beneficial effects of beta-adrenergic blockade in chronic mitral regurgitation (MR) were in part due to induction of bradycardia, which obviously affects myocardial energy requirements. From this observation we hypothesized that part of the pathophysiology of MR may involve faulty energy substrate utilization, which in turn might lead to potentially harmful lipid accumulation as observed in other models of heart failure. To explore this hypothesis, we measured triglyceride accumulation in the myocardia of dogs with chronic MR and then attempted to enhance myocardial metabolism by chronic administration of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist rosiglitazone. Cardiac tissues were obtained from three groups of dogs that included control animals, dogs with MR for 3 mo without treatment, and dogs with MR for 6 mo that were treated with rosiglitazone (8 mg/day) for the last 3 mo of observation. Hemodynamics and contractile function (end-systolic stress-strain relationship, as measured by K index) were assessed at baseline, 3 mo of MR, and 6 mo of MR (3 mo of the treatment). Lipid accumulation in MR (as indicated by oil red O staining score and TLC analysis) was marked and showed an inverse correlation with the left ventricular (LV) contractility. LV contractility was significantly restored after PPAR therapy (K index: therapy, 3.01 +/- 0.11*; 3 mo MR, 2.12 +/- 0.34; baseline, 4.01 +/- 0.29; ANOVA, P = 0.038; *P < 0.05 vs. 3 mo of MR). At the same time, therapy resulted in a marked reduction of intramyocyte lipid. We conclude that 1) chronic MR leads to intramyocyte myocardial lipid accumulation and contractile dysfunction, and 2) administration of the PPAR-gamma agonist rosiglitazone ameliorates MR-induced LV dysfunction accompanied by a decline in lipid content.
机译：先前我们曾报道β-肾上腺素能阻滞在慢性二尖瓣关闭不全（MR）中的有益作用部分是由于心动过缓的诱发，这显然会影响心肌能量需求。根据这一观察，我们假设MR的部分病理生理可能涉及错误的能量底物利用，这反过来可能导致潜在的有害脂质积聚，如在其他心力衰竭模型中所观察到的。为了探索这一假设，我们测量了患有慢性MR的犬心肌中的甘油三酸酯积累，然后尝试通过长期施用过氧化物酶体增殖物激活受体（PPAR）-γ激动剂罗格列酮来增强心肌代谢。从三组狗中获取心脏组织，其中包括对照组动物，未经治疗的MR持续3个月的MR犬和经过6个月的罗格列酮治疗的MR持续6个月的MR犬。在基线，MR 3 mo和MR 6 mo（治疗3 mo）时评估血流动力学和收缩功能（通过K指数测量的收缩末期应力-应变关系）。标记了MR中的脂质蓄积（如油红色O染色评分和TLC分析所示），并显示出与左心室（LV）收缩力成反比。 PPAR治疗后左室收缩力显着恢复（K指数：治疗3.01 +/- 0.11 *; MR 3个月，2.12 +/- 0.34;基线，4.01 +/- 0.29;方差分析，P = 0.038; * P <0.05 vs MR的3个月）。同时，治疗导致肌内脂质的明显减少。我们得出的结论是：1）慢性MR导致心肌细胞内心肌脂质积聚和收缩功能障碍，以及2）PPAR-γ激动剂罗格列酮的给药改善了MR引起的LV功能障碍，并伴有脂质含量下降。

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