干预犬下腔静脉脂肪垫对窦房结及房室结功能的影响

目的通过不同干预方法,观察犬下腔静脉脂肪垫对窦房结及房室结功能的影响。方法选择16只犬开胸暴露下腔静脉脂肪垫,首先以固定的输出频率(20Hz)连续电刺激下腔静脉脂肪垫30 s,测量刺激前和刺激时窦房结恢复时间(SNRT)、校正SNRT(cSNRT)及AH、HV、RR间期变化;然后在直视下心外膜射频消融脂肪垫,再测定迷走神经刺激前后上述指标的变化。结果:14只完成试验。当电刺激下腔静脉脂肪垫时,AH间期与刺激前比较明显延长(122.2±12.4 m s vs 82.5±10.3 m s,P<0.05),其余指标未发生明显变化。电刺激通常在2 s内起效,AH间期随刺激电压增加而延长,在刺激停止3 s内恢复。射频消融下腔静脉脂肪垫后,刺激左右颈部迷走神经,SNRT、cSNRT及RR间期与刺激前比较有明显变化(分别为696.4±54.9 m s vs 467.5±45.4 m s;296.3±20.5 m svs 164.5±20.1 m s,400.3±39.1 m s vs 210.1±14.5 m s,P均<0.05),但AH间期及HV间期未发生明显变化。结论:刺激下腔静脉脂肪垫可使房室传导延迟,而不影响窦房结功能。消融下腔静脉脂肪垫可以消除迷走神经对房室结的支配。     

左心交感神经切除术对长QT综合征患者U波的调节作用

目的为进一步理解T波和U波的关系及U波在长QT综合征(LQTS)中的病理生理学意义。方法对11例LQTS患者行左心交感神经切除(LCSD)手术,评价其手术前后及跟踪期间ECG上U波和T波变化。结果术后QTc(校正的QT间期:从0.50±0.05s到0.47±0.03s,P=0.02)、QTp(从QRS波起始到T波顶点的时间间隔:0.37±0.07s到0.33±0.06s,P=0.041)和QTpc(校正的QTp:从0.37±0.07s到0.34±0.05s,P=0.006)均显著缩短。同时QU间期(从QRS波起始到U波结束)、QUc(校正的QU间期)、QUp(从QRS波起始到U波顶点的时间间隔)、QUpc(校正的QUp)却无显著改变。TpTe(同一导联上T波顶点到T波结束点的时间间隔)无显著变化,但TpTe-max(12导联中最早的T波顶点到最晚的T波结束点的时间间隔,代表跨壁复极离散度:0.21±0.09s到0.18±0.07s,P=0.02)显著降低。U波幅度、T波幅度及U/T幅度比值均无显著变化,但TpUp(T波顶点到U波顶点的时间间隔:0.16±0.06s到0.19±0.05s,P=0.041)显著增加。手术后2天内,多数患者U波更明显并叠加于T波之上形成T-U融合现象;但随后融合程度逐渐减轻。结论LQTS患者的U波与T波具有不同的起源机制,因此在诊断LQTS测量QT间期时不应包含U波。     

Myostatin在小鼠腓肠肌失神经支配萎缩过程中的表达

目的:分析myostatin在腓肠肌失神经支配萎缩过程中的表达变化及其在肌萎缩过程中的作用。方法:采用坐骨神经横断术制备小鼠腓肠肌失神经支配模型,实时荧光定量PCR和Western印迹法分别检测失神经支配不同时段腓肠肌myostatin mRNA和蛋白表达水平,并对失神经前后肌肉湿重比、肌纤维横截面积进行比较。结果:失神经支配1 d时,腓肠肌myostatin mRNA迅速上升,3 d达到高峰,随后逐渐下降,而相应蛋白水平逐渐增高,7 d达到高峰继而逐渐下降,至56 d时mRNA和蛋白水平仍略高于正常水平。结论:腓肠肌失神经支配萎缩过程中myostatin的表达变化是一重要的分子事件。     

Acute sinoaortic denervation induces pre- and postsynaptic alpha-adrenergic subsensitivity in mesenteric arteries in the rat

Bilateral sinoaortic denervation induced a rapid increase in blood pressure and heart rate in the rat. Four hours after sinoaortic denervation, the dose-response curve to l-norepinephrine (NE) in perfused mesenteric arteries in vitro was shifted to the right and the maximal response reduced, compared with sham-operated controls. These changes were abolished in the presence of cocaine (10 μg/ml). Four hours after sinoaortic denervation, the dose-response curves to methoxamine and serotonin, but not to adenosine-5'-triphosphate (ATP), were significantly reduced and the muscular response induced by barium chloride was not modified. Vascular responses to stimulation with different frequencies of the sympathetic nerve were reduced 4hr after sinoaortic denervation. These changes in both the responses to l-NE and to nerve stimulation were reversed 24 hr after sinoaortic denervation. In the same preparation, 4 hr after sinoaortic denervation, the fractional release per pulse of [³H]-NE was significantly enhanced at 10 and 20 Hz frequencies of stimulation, whereas the blockade of the alpha-presynaptic receptors with phentolamine (3.1 μM) did not increase the release of [³H]-NE induced by nerve stimulation, as was observed in sham-operated controls. The results are compatible with the hypothesis that 4 hr after sinoaortic denervation, the pre- and postsynaptic alpha-adrenoceptors are desensitized. These changes could affect arterial sympathetic neurotransmission; the increase in blood pressure observed following sinoaortic denervation could therefore not be explained only by an increase in sympathetic tone.     

Innervation of dystrophic muscle after muscle stem cell therapy

Introduction: Duchenne muscular dystrophy (DMD) is caused by loss of the structural protein, dystrophin, resulting in muscle fragility. Muscle stem cell (MuSC) transplantation is a potential therapy for DMD. It is unknown whether donor‐derived muscle fibers are structurally innervated. Methods: Green fluorescent protein (GFP)–expressing MuSCs were transplanted into the tibials anterior of adult dystrophic mdx/mTR mice. Three weeks later the neuromuscular junction was labeled by immunohistochemistry. Results: The percent overlap between pre‐ and postsynaptic immunolabeling was greater in donor‐derived GFP⁺ myofibers, and fewer GFP⁺ myofibers were identified as denervated compared with control GFP^– fibers (P = 0.001 and 0.03). GFP⁺ fibers also demonstrated acetylcholine receptor fragmentation and expanded endplate area, indicators of muscle reinnervation (P = 0.008 and 0.033). Conclusion: It is unclear whether GFP⁺ fibers are a result of de novo synthesis or fusion with damaged endogenous fibers. Either way, donor‐derived fibers demonstrate clear histological innervation. Muscle Nerve 54 : 763–768, 2016     

Pharmacological analysis of the tachycardia produced by histamine and specific H1-and H2-receptor agonists in anesthetized dogs.

A study was designed to investigate the mechanism(s) of the tachycardia produced by histamine and specific H₁- and H₂-receptor agonists in anesthetized dogs. I.v. administration of histamine, 2-methylhistamine, and 4-methylhistamine caused a fall in blood pressure and an increase in heart rate. Prior administration of mepyramine, a histamine H₁-receptor antagonist, significantly antagonized the depressor and positive chronotropic effects of histamine and completely abolished the cardiovascular actions of 2-methylhistamine, whereas responses to 4-methylhistamine were not affected. Subsequent administration of metiamide, a specific H₂-receptor antagonist, completely abolished the remaining cardiovascular effects of histamine and the hypotension and tachycardia observed after 4-methylhistamine were also antagonized.In another series of experiments, bilateral vagotomy significantly attenuated the tachycardia and subsequent removal of cardiac sympathetic nerve supply completely abolished it without affecting the depressor effects of these agents. Pharmacological blockade of muscarinic receptors with atropine in another group of animals also significantly attenuated the positive chronotropic effect which was completely prevented by further treatment with propranolol. The hypotension produced by histamine agonists was not affected by atropine and propranolol. These results demonstrate that in pentobarbital-anesthetized dogs, the tachycardia produced by histamine and specific H₁- and H₂-receptor agonists are due to reciprocal alterations in cardiac autonomic activity as a result of the fall in the arterial pressure. Activation of cardiac histamine receptors does not seem to account for the positive chronotropic effects of these compounds in intact dogs.     

经皮肾动脉交感神经消融术中消融点位对顽固性高血压患者降压效果的影响

目的 探索不同消融位点对经皮肾动脉交感神经消融术治疗顽固性高血压降压效果的影响。方法 选择16例顽固性高血压患者,随机分为近中段消融组和全段消融组,每组8例。完善相关检查后行经皮肾动脉交感神经消融术治疗。术中记录消融参数（起始阻抗值、最低阻抗值、消融实际功率、消融实际温度）,术后即刻复查肾动脉造影。所有患者术后继续监测血压,随访至术后3个月。结果 全部16例患者均成功完成经皮肾动脉交感神经消融术。所有患者消融起始阻抗平均值为（180.0±12.3）Ω,消融最低阻抗平均值为（157.8±12.8）Ω,阻抗下降率平均为（12.4±2.6）%;实际消融温度为40～50℃,功率为5～18 W。术后肾动脉造影显示全段消融组2例发生肾动脉痉挛,近中段消融组无一例发生肾动脉痉挛,两组肾动脉痉挛发生率差异无统计学意义（P=0.08）。术后3个月随访,两组患者血压未见明显差异。结论 在肾动脉近中段进行消融,特别是在肾动脉开口处消融,可能不会影响经皮肾动脉交感神经消融术的降压效果,并可一定程度上减少肾动脉狭窄的发生率。     

The concept of crosstalk‐directed embryological target mining and its application to essential hypertension treatment failures

This review aims to introduce the novel concept of embryological target mining applied to interorgan crosstalk network genesis, and applies embryological target mining to multidrug‐resistant essential hypertension (a prototype, complex, undertreated, multiorgan systemic syndrome) to uncover new treatment targets and critique why existing strategies fail. Briefly, interorgan crosstalk pathways represent the next frontier for target mining in molecular medicine. This is because stereotyped stepwise organogenesis presents a unique opportunity to infer interorgan crosstalk pathways that may be crucial to discovering novel treatment targets. Insights gained from this review will be applied to patient management in a clinician‐directed fashion.