Nrg1β Released in Remote Ischemic Preconditioning Improves Myocardial Perfusion and Decreases Ischemia/Reperfusion Injury Via ErbB2-Mediated Rescue of Endothelial Nitric Oxide Synthase and Abrogation of Trx2 Autophagy Venkatesh Kundumani-Sridharan, Jaganathan Subramani, Cade Owens, Kumuda C. Das OBJECTIVE: Remote ischemic preconditioning (RIPC) is an intervention process where the application of multiple cycles of short ischemia/reperfusion (I/R) in a remote vascular bed provides protection against I/R injury. However, the identity of the specific RIPC factor and the mechanism by which RIPC alleviates I/R injury remains unclear. Here, we have investigated the identity and the mechanism by which the RIPC factor provides protection. APPROACH AND RESULTS: Using fluorescent in situ hybridization and immunofluorescence, we found that RIPC induces Nrg1β expression in the endothelial cells, which is secreted into the serum. Whereas, RIPC protected against myocardial apoptosis and infarction, treatment with neutralizing-Nrg1 antibodies abolished the protective effect of RIPC. Further, increased superoxide anion generated in RIPC is required for Nrg1 expression. Improved myocardial perfusion and nitric oxide production were achieved by RIPC as determined by contrast echocardiography and electron spin resonance. However, treatment with neutralizing-Nrg1β antibody abrogated these effects, suggesting Nrg1β is a RIPC factor. ErbB2 (Erb-B2 receptor tyrosine kinase 2) is not expressed in the adult murine cardiomyocytes, but expressed in the endothelial cells of heart which is degraded in I/R. RIPC-induced Nrg1β interacts with endothelial ErbB2 and thereby prevents its degradation. Mitochondrial Trx2 (thioredoxin) is degraded in I/R, but rescue of ErbB2 by Nrg1β prevents Trx-2 degradation that decreased myocardial apoptosis in I/R. CONCLUSIONS: Nrg1β is a RIPC factor that interacts with endothelial ErbB2 and prevents its degradation, which in turn prevents Trx2 degradation due to phosphorylation and inactivation of ATG5 (autophagy-related 5) by ErbB2. Nrg1β also restored loss of eNOS (endothelial nitric oxide synthase) function in I/R via its interaction with Src.
Effect of remote ischemic preconditioning on cerebral vasospasm, biomarkers of cerebral ischemia, and functional outcomes in aneurysmal subarachnoid hemorrhage (ERVAS): A randomized controlled pilot trial R. P. Sangeetha, Ramesh J. Venkatapura, Sriganesh Kamath, Rita Christopher1 , Dhananjaya Ishwar Bhat2 , H. R. Arvinda3 , Dhritiman Chakrabarti Abstract BACKGROUND: Cerebral vasospasm can complicate aneurysmal subarachnoid hemorrhage (aSAH), contributing to cerebral ischemia. We explored the role of remote ischemic preconditioning (RIPC) in reducing cerebral vasospasm and ischemia and improving outcomes after aSAH. MATERIALS AND METHODS: Patients with ruptured cerebral aneurysm undergoing surgical clipping and meeting the trial criteria were randomized to true RIPC (n = 13) (inflating upper extremity blood pressure cuff thrice to 30 mmHg above systolic pressure for 5 min) or sham RIPC (n = 12) (inflating blood pressure cuff thrice to 30 mmHg for 5 min) after ethical approval. A blinded observer assessed outcome measures‑cerebral vasospasm and biomarkers of cerebral ischemia. We also uated the feasibility and safety of RIPC in aSAH and Glasgow Outcome Scale‑Extended (GOSE). RESULTS: Angiographic vasospasm was seen in 9/13 (69%) patients; 1/4 patients (25%) in true RIPC group, and 8/9 patients (89%) in sham RIPC group (P = 0.05). Vasospasm on transcranial Doppler study was diagnosed in 5/25 (20%) patients and 1/13 patients (7.7%) in true RIPC and 4/12 patients (33.3%) in sham RIPC group, (P = 0.16). There was no difference in S100B and neuron‑specific enolase (NSE) levels over various time‑points within groups (P = 0.32 and 0.49 for S100B, P = 0.66 and 0.17 for NSE in true and sham groups, respectively) and between groups (P = 0.56 for S100B and P = 0.31 for NSE). Higher GOSE scores were observed with true RIPC (P = 0.009) unlike sham RIPC (P = 0.847) over 6‑month follow‑up with significant between group difference (P = 0.003). No side effects were seen with RIPC. CONCLUSIONS: RIPC is feasible and safe in patients with aSAH and results in a lower incidence of vasospasm and better functional outcome. Keywords: Biomarkers of cerebral ischemia, cerebral vasospasm, delayed cerebral ischemia, Glasgow outcome scale extended, remote ischemic preconditioning, transcranial Dopple
普通的血压计绑在手臂上不可以作为远程缺血预适应训练。水银血压计不适合是因为缺血训练在临床上有明确的禁忌症和适用人群,在训练时很多重要参数把握不好,训练效果适得其反。电子血压计不适合改装成为远程缺血预适应训练仪不仅不能产生有益物质(缓激肽、一氧化氮、腺苷、应激蛋白、蛋白激酶A、超氧化物歧化酶),还可能导致身体出现皮下出血,渗血,血管受损等等危害。
远程缺血预适应训练(RIPC)是对人体肢体进行短暂、安全的加压、释放、再加压再释放反复无危害的缺血刺激,激发人体内产生内源性保护物质:腺苷,缓激肽,一氧化氮,应激蛋白,蛋白激酶A,超氧化物歧化酶SOD。这些物质的对心脏、脑缺血产生保护及提高耐受能力,一旦心、脑出血或缺血,它就会对缺血产生耐受,有效地避免人发生脑梗死、脑中风、脑溢血、心脏猝死等疾病。 缺血预适应(RIPC)经过全球临床医学30年的实践,迄今为止还没有发现比RIPC更好的内源性心肌保护手段,被医学界认为是一种最安全有效的内源性物理疗法。
RIPC训练5分钟的效果肯定比训练3分钟的效果更好,能产生更多的内源性物质,但具体的能增加多少无法进行具体的量化试验,也就没有具体的数据。所以我们建议,在正常情况下,每次进行双臂训练5分钟。每天建议训练两次,如果有时间每天训练3-5次也是可以的,倘若当天没有时间,训练1次也行。禁止在进行整个疗程治疗训练时,连续中断2天及以上不进行训练。
答:正常的大气压为760毫米汞柱(101.325kpa),也就是日常生活中我们空气中的大气压力,这个大气压力随着海拔高度升高而下降,因为空气密度越来越稀薄。RIPC训练治疗加压200毫米汞柱相当于加压了0.263个标准大气压。而1hpa=100pa,因此产品储存压力就相当于0.8-1个标准大气压下,储存压力大概相当于在0.5-1个标准大气压下,这几乎适应全国范围内,因此不必担心。(标准大气压是海平面为0的压力值)
我们建议在进行上肢(单臂、双臂)训练时尽可能的少穿衣服进行RIPC训练,尤其是穿羽绒服和毛线进行训练,可能导致加压了却未能有效阻断血流,导致训练无效。冬天训练时可以在有暖气或者空调和有热源的地方,最多穿两件较为薄的衣服进行训练。
主机自动放气有两种原因,第一种是由于臂带绑的太松,导致RIPC主机检测不到手臂反给气囊的压力,从而自动进行停机的保护功能,这类情况只要将臂带重新绑好即可。第二种原因是在进行RIPC训练治疗时,上臂肌肉用力过大,简单说就是在训练时,手臂拿重物或者饶痒痒的时候动作过大,导致主机检测到手臂反给气囊的压力过大,从而使机器进行了一种停机保护。出现这类情况的解决方法就是按两次双臂键重新进行训练,且在训练治疗过程中注意手臂的动作不要太大,以免再次出现自动放气导致训练失败。
RIPC缺血预适应产品的使用对有心脏起搏器的人是没有影响的,如果还有疑问可在使用前咨询专业医生。
这个训练或者治疗效果因人而异,毕竟每个人的体质不一样,对不同的疾病起效不同。我们只能提供一个参考:正常人使用产品起效在7-15天左右,每个人的自我感觉也会有些许不同。对于身体有不同病症的患者,病情不同也会不同。我们坚信,您在训练或者治疗后,只要持久使用,身体会恢复的越来越好。
本公司生产研发设计的产品外观简洁,功能强大;操作简便,实用性强;价格高中低档俱全,可以满足各个价位阶层的需要。更重要的是本产品属于医疗器械,经过几千例的临床使用数据经验,产品质量和疗效都能得到保障,不是一般的保健品所能比拟的。
本公司产品在功能上和使用效果上军用和民用都没有区别,由于和军队医院有合作研发关系,军队可以利用产品对部队在高原或者海上进行抗高原反应和晕船等训练,部队曾大量采购使用。外观上面民用的比较简洁,海军版的RIPC产品是迷彩的,满足部队对隐蔽效果的需要。另外,不仅是军队和民用,喜欢登山的驴友初次进行登山时也可使用本产品进行适应性训练,以免登高缺氧出现不适。
有的。尤其是第一次、第二次使用本产品,或多或少都会感觉训练的单臂或者双臂压的难受,而且使用后可能会有臂带的压痕和血液的积痕。但是请放心,这都是正常现象,时间一久会自动消退,对身体皮肤没有任何影响。而且请务必坚持下去,本产品由于是物理性治疗训练,没有任何副作用。坚持使用肯定会有很好的效果的。
预防、康复为主。产品训练的效果较为缓和,一般最快15天见效。所以安全性特好,无副作用。对有中风前兆的小中风患者,有积极的治疗效果,能有效的避免中风。简单来说,该产品训练的原理是在保证绝对安全的情况下,让身体部分器官适应缺血状况,以防身体一旦出现心、脑缺血,身体器官能够适应并延长适应时间,避免发生脑梗死及心脏猝死的意外,而且能够为使用者赢得更多治疗时间,保障生命安全。
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