硫化氢及其外源性供体对心血管疾病治疗潜力的研究进展

硫化氢(H2S)被认为是继一氧化碳、一氧化氮后的第3大内源性气体信号分子,可在哺乳动物组织中合成,并能自由地穿过细胞膜,在包括心血管系统在内的多系统中发挥多种生物作用。心血管疾病是世界范围内死亡的主要原因,其具体发病机制尚未完全明确。近年来,越来越多的研究支持内源性H2S和外源性H2S供体化合物对动脉粥样硬化、心肌肥厚、心力衰竭和缺血/再灌注损伤等心血管疾病发挥保护作用,本文综述了此方面的研究进展,重点介绍了H2S以及各种外源性H2S供体在治疗心血管疾病中的潜力。     

贝那普利联用氨氯地平对高血压患者血压、左室肥厚和心功能的影响

目的探讨贝那普利联用氨氯地平的降压效果以及逆转左心室肥厚、改善心功能的作用。方法将140例原发性高血压伴左心室肥厚患者随机分为贝那普利组（46例）、氨氯地平组（47例）、贝那普利联用氨氯地平组（47例）,分别接受贝那普利、氨氯地平、贝那普利加氨氯地平治疗12个月,观察期间定期测量血压,服药前后做超声心动图检查。结果用药后三组血压、超声心动图各指标较用药前变化显著（P〈0．05）,两单用药组比较各指标差异无显著性（P〉0．05）,联合用药组与单用药组比较各指标差异有显著性意义（P〈0．05）。结论贝那普利联合应用氨氯地平治疗原发性高血压降压效果好,逆转左室肥厚效果好,改善心功能作用明显,不良应少。     

早期干预钙磷代谢对慢性肾脏病左室肥厚的影响

目的 探讨早期干预钙磷代谢对改善慢性肾脏病患者左室肥厚的影响.方法 将住院治疗的116例非透析慢性肾脏病3、4期患者随机分为干预组和对照组,对干预组患者进行早期钙磷代谢干预,观察两组患者的血钙、血磷和左室心肌质量指数的变化情况.结果 干预组患者干预后的血磷、钙磷乘积、血全段甲状旁腺素均显著低于对照组,差异有统计学意义（P＜0.05）;干预组的LVMI显著低于干预前,也显著低于对照组,差异有统计学意义（P＜0.05）.结论 对慢性肾脏病患者进行早期钙磷代谢干预能有效改善患者的左室肥厚症状,有利于患者整个病情的改善.     

经口鼻内镜下腺样体切除术与传统腺样体刮除术的疗效比较

目的比较经口鼻内镜下腺样体切除术与传统腺样体刮除术的治疗效果。方法分析本院2009年6月到2010年6月间采用两种术式所治疗的42例腺样体肥大患儿病例资料,比较两种术式的优缺点。结果采用经口鼻内镜下腺样体切除术组无腺样体残留且止血彻底。采用传统腺样体刮除术组中有3例腺样体残留且出血较多。结论经口鼻内镜下腺样体切除术腺样体切除术式优于传统腺样体刮除术。     

厄贝沙坦联合左旋氨氯地平治疗高血压合并左心室肥厚的疗效观察

目的探讨厄贝沙坦联合左旋氨氯地平对高血压合并左室肥厚患者的血压及心室肥厚的影响及作用机制。方法318例原发性高血压合并左心室肥厚患者,随机分成2组。I组（n=159）予以厄贝沙坦联合左旋氨氯地平治疗,Ⅱ组（n=159）只用左旋氨氯地平治疗。2组均在给药前和给药6个月后分别监测收缩压（SBP）、舒张压（DBP）、心率（HR）、左心室舒张末期室间隔厚度（IVST）、左心室后壁厚度（LV冈盯）、左心室舒张末期内径（LVDd）及左心室重量指数（LVMI）。结果治疗6个月后,2组SBP、DBP,IVST、LVPwT、LVDd、LVMI明显低于治疗前,且I组低于Ⅱ组,差异均有统计学意义（P〈0．05）。结论厄贝沙坦和左旋氯地平联合用药具有协同作用,不仅能很好的控制高血压,而且能够逆转左心室肥厚。     

Vasodilator therapy with hydralazine induces angiotensin AT2 receptor-mediated cardiomyocyte growth in mice lacking guanylyl cyclase-A

Background and purpose:

Recent clinical guidelines advocate the use of the isosorbide dinitrate/hydralazine combination in treatment for heart failure. However, clinical and laboratory evidence suggest that some vasodilators may induce cardiac hypertrophy under uncertain conditions. This study investigated the effects and underlying mechanism of action of the vasodilator hydralazine on cardiac growth.

Experimental approach:

Wild-type mice and animals deficient in guanylyl cyclase-A (GCA) and/or angiotensin receptors (AT₁ and AT₂ subtypes) were treated with hydralazine (≈24 mg·kg⁻¹·day⁻¹ in drinking water) for 5 weeks. Cardiac mass and/or cardiomyocyte cross-sectional area, fibrosis (van Giessen-staining) and cardiac gene expression (real-time RT-PCR) were measured.

Key results:

Hydralazine lowered blood pressure in mice of all genotypes. However, this treatment increased the heart and left ventricular to body weight ratios, as well as cardiomyocyte cross-sectional area, and cardiac expression of atrial natriuretic peptide mRNA in mice lacking GCA. Hydralazine did not affect cardiac hypertrophy in wild-type mice and mice lacking either AT₁ or AT₂ receptors alone. However, the pro-hypertrophic effect of hydralazine was prevented in mice lacking both GCA and AT₂, but not GCA and AT₁ receptors. However, hydralazine did decrease cardiac collagen deposition and collagen I mRNA (signs of cardiac fibrosis) in mice that were deficient in GCA, or both GCA and AT₂ receptors.

Conclusions and implications:

The vasodilator hydralazine induced AT₂ receptor-mediated cardiomyocyte growth under conditions of GCA deficiency. However, attenuation of cardiac fibrosis by hydralazine could be beneficial in the management of cardiac diseases.     

Acquired cardiac hypertrophy with outflow tract obstruction in a patient with severe Takayasu arteritis

Takayasu arteritis with coronary artery involvement is rare and its association with secondary cardiac hypertrophy with severe outflow tract obstruction is not common. We describe a case of Takayasu arteritis, diagnosed 10 years ago, whose coronary artery involvement and obstructive cardiac hypertrophy are ascertained after our investigations.     

Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

Cardiotrophin-1 (CT-1) produces longitudinal elongation of neonatal cardiomyocytes, but its effects in adult cardiomyocytes are not known. Recent observations indicate that CT-1 may be involved in pressure overload left ventricular hypertrophy (LVH). We investigated whether the hypertrophic effects of CT-1 are different in cardiomyocytes isolated from adult normotensive and spontaneously hypertensive rats (SHR). Hypertrophy was evaluated by planimetry and confocal microscopy, contractile proteins were quantified by Western blotting and real-time RT-PCR, and intracellular pathways were analyzed with specific chemical inhibitors. CT-1 increased c-fos and ANP expression (p<0.01) and cell area (p<0.01) in cardiomyocytes from both rat strains. In Wistar cells, CT-1 augmented cell length (p<0.01) but did not modify either the transverse diameter or cell depth. In SHR cells, CT-1 increased cell length (p<0.05), cell width (p<0.01) and cell depth, augmented the expression of myosin light chain-2v (MLC-2v) and skeletal alpha-actin (p<0.01) and enhanced MLC-2v phosphorylation (p<0.01). The blockade of gp130 or LIFR abolished CT-1-induced growth in the two cell types. All distinct effects observed in cardiomyocytes from SHR were mediated by STAT3. Baseline angiotensinogen expression was higher in SHR cells, and CT-1 induced a 1.7-fold and 3.2-fold increase of angiotensinogen mRNA in cardiomyocytes from Wistar rats and SHR respectively. In addition, AT1 blockade inhibited the specific effects of CT-1 in SHR cells. Finally, ex vivo determinations revealed that adult SHR exhibited enhanced myocardial CT-1 (mRNA and protein, p<0.01), increased cell width (p<0.01) and concentric LVH compared with pre-hypertensive SHR. These findings reveal a specific cell-broadening effect of CT-1 in cardiomyocytes from adult SHR and suggest that the hypertensive phenotype of these cells may influence the hypertrophic effects of CT-1, probably by means of an exaggerated induction of angiotensinogen expression. We suggest that CT-1 might facilitate LVH in genetic hypertension through a cross-talk with the renin-angiotensin system.     

A SERCA2 pump with an increased Ca2+ affinity can lead to severe cardiac hypertrophy, stress intolerance and reduced life span

Abnormal Ca(2+) cycling in the failing heart might be corrected by enhancing the activity of the cardiac Ca(2+) pump, the sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) isoform. This can be obtained by increasing the pump's affinity for Ca(2+) by suppressing phospholamban (PLB) activity, the in vivo inhibitor of SERCA2a. In SKO mice, gene-targeted replacement of SERCA2a by SERCA2b, a pump with a higher Ca(2+) affinity, results in cardiac hypertrophy and dysfunction. The stronger PLB inhibition on cardiac morphology and performance observed in SKO was investigated here in DKO mice, which were obtained by crossing SKO with PLB(-/-) mice. The affinity for Ca(2+) of SERCA2 was found to be further increased in these DKO mice. Relative to wild-type and SKO mice, DKO mice were much less spontaneously active and showed a reduced life span. The DKO mice also displayed a severe cardiac phenotype characterized by a more pronounced concentric hypertrophy, diastolic dysfunction and increased ventricular stiffness. Strikingly, beta-adrenergic or forced exercise stress induced acute heart failure and death in DKO mice. Therefore, the increased PLB inhibition represents a compensation for the imposed high Ca(2+)-affinity of SERCA2b in the SKO heart. Limiting SERCA2's affinity for Ca(2+) is physiologically important for normal cardiac function. An improved Ca(2+) transport in the sarcoplasmic reticulum may correct Ca(2+) mishandling in heart failure, but a SERCA pump with a much higher Ca(2+) affinity may be detrimental.