Insulin Secretion in Cardiogenic Shock

A nearly complete suppression of insulin secretion was observed in four patients in circulatory shock following acute myocardial infarction. This may be due to intense sympathetic activity and raised catecholamine excretion associated with shock.     

The Acute Phase of Experimental Cardiogenic Shock Is Counteracted by Microcirculatory and Mitochondrial Adaptations

The mechanisms contributing to multiorgan dysfunction during cardiogenic shock are poorly understood. Our goal was to characterize the microcirculatory and mitochondrial responses following ≥10 hours of severe left ventricular failure and cardiogenic shock. We employed a closed-chest porcine model of cardiogenic shock induced by left coronary microembolization (n = 12) and a time-matched control group (n = 6). Hemodynamics and metabolism were measured hourly by intravascular pressure catheters, thermodilution, arterial and organ specific blood gases. Echocardiography and assessment of the sublingual microcirculation by sidestream darkfield imaging were performed at baseline, 2±1 and 13±3 (mean±SD) hours after coronary microembolization. Upon hemodynamic decompensation, cardiac, renal and hepatic mitochondria were isolated and evaluated by high-resolution respirometry. Low cardiac output, hypotension, oliguria and severe reductions in mixed-venous and hepatic O₂ saturations were evident in cardiogenic shock. The sublingual total and perfused vessel densities were fully preserved throughout the experiments. Cardiac mitochondrial respiration was unaltered, whereas state 2, 3 and 4 respiration of renal and hepatic mitochondria were increased in cardiogenic shock. Mitochondrial viability (RCR; state 3/state 4) and efficiency (ADP/O ratio) were unaffected. Our study demonstrates that the microcirculation is preserved in a porcine model of untreated cardiogenic shock despite vital organ hypoperfusion. Renal and hepatic mitochondrial respiration is upregulated, possibly through demand-related adaptations, and the endogenous shock response is thus compensatory and protective, even after several hours of global hypoperfusion.     

老年急性心肌梗死并心源性休克冠状动脉介入治疗的临床效果分析

目的:对比分析介入治疗和保守治疗对急性心梗合并心源性休克的老年患者的治疗效果。方法:回顾性分析急性心肌梗死并心源性休克患者,共入选230例,按照医生评估进行分组治疗,分为介入治疗组和非介入治疗组,介入组患者120例,接受冠脉介入治疗;非介入组患者110例,接受非介入治疗。对比分析危险因素以及治疗效果。结果:介入组中心肌梗死病史及心衰病史患者明显高于非介入组(24.2%vs 20%P<0.05;25%vs 17.3%,P<0.05),经皮冠状动脉介入治疗与非介入治疗相比能显著降低急性心梗合并心源性休克的老年患者住院病死率(40.8%vs 71.8%,P<0.05),非介入治疗组心律失常发生率高于介入治疗组(26.7%vs 21.8%,P<0.05),同时非介入治疗组肺部感染及肾衰的发病率较高(11.8%vs 5.8%P<0.05;8.2%vs 2.0%,P<0.05)。结论:针对急性心梗合并心源性休克的老年患者制定治疗方案时,虽然介入治疗存在更多的并发症,但是可以显著改善患者预后。     

Mild Electrical Stimulation with Heat Shock Ameliorates Insulin Resistance via Enhanced Insulin Signaling

Low-intensity electrical current (or mild electrical stimulation; MES) influences signal transduction and activates phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Because insulin resistance is characterized by a marked reduction in insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance. In addition, it was also previously reported that heat shock protein 72 (Hsp72) alleviates hyperglycemia. Thus, we applied MES in combination with heat shock (HS) to in vitro and in vivo models of insulin resistance. Here we show that 10-min treatment with MES at 5 V (0.1 ms pulse duration) together with HS at 42°C increased the phosphorylation of insulin signaling molecules such as insulin receptor substrate (IRS) and Akt in HepG2 cells maintained in high-glucose medium. MES (12 V)+mild HS treatment of high fat-fed mice also increased the phosphorylation of insulin receptor β subunit (IRβ) and Akt in mice liver. In high fat-fed mice and db/db mice, MES+HS treatment for 10 min applied twice a week for 12–15 weeks significantly decreased fasting blood glucose and insulin levels and improved insulin sensitivity. The treated mice showed significantly lower weight of visceral and subcutaneous fat, a markedly improved fatty liver and decreased size of adipocytes. Our findings indicated that the combination of MES and HS alleviated insulin resistance and improved fat metabolism in diabetes mouse models, in part, by enhancing the insulin signaling pathway.     

Impaired Glucose Tolerance: A Late Effect of Insulin Shock Treatment

Glucose tolerance tests were performed in a group of patients in a mental hospital who had been treated with insulin shock and in a matched control group. Five out of 31 (16%) patients in the insulin-treated group and 1 out of 22 (5%) controls had “diabetic” blood sugar curves. Median blood sugar values were significantly higher at 60 minutes and later in the insulin-treated group, as were mean blood sugar values when the “diabetic” patients were excluded. Small amounts of plasma insulin-binding antibody were found in two insulin-treated patients. In the absence of any other clear-cut explanation, it is suggested that in some patients massive doses of insulin by injection may leave diminished tissue responsiveness to insulin as a long-term after-effect.     

The Effectiveness of Inodilators in Reducing Short Term Mortality among Patient with Severe Cardiogenic Shock: A Propensity-Based Analysis

Background

The best catecholamine regimen for cardiogenic shock has been poorly evaluated. When a vasopressor is required to treat patients with the most severe form of cardiogenic shock, whether inodilators should be added or whether inopressors can be used alone has not been established. The purpose of this study was to compare the impact of these two strategies on short-term mortality in patients with severe cardiogenic shocks.

Methods and Results

Three observational cohorts of patients with decompensated heart failure were pooled to comprise a total of 1,272 patients with cardiogenic shocks. Of these 1,272 patients, 988 were considered to be severe because they required a vasopressor during the first 24 hours. We developed a propensity-score (PS) model to predict the individual probability of receiving one of the two regimens (inopressors alone or a combination) conditionally on baseline-measured covariates. The benefit of the treatment regimen on the mortality rate was estimated by fitting a weighted Cox regression model. A total of 643 patients (65.1%) died within the first 30 days (inopressors alone: 293 (72.0%); inopressors and inodilators: 350 (60.0%)). After PS weighting, we observed that the use of an inopressor plus an inodilator was associated with an improved short-term mortality (HR: 0.66 [0.55–0.80]) compared to inopressors alone.

Conclusions

In the most severe forms of cardiogenic shock where a vasopressor is immediately required, adding an inodilator may improve short-term mortality. This result should be confirmed in a randomized, controlled trial.     

IABP支持下急诊PCI治疗急性心肌梗死并心源性休克的疗效观察

目的:探讨主动脉内球囊反搏(IABP)支持下急诊经皮冠状动脉介入(PCI)治疗急性心肌梗死(AMI)并心源性休克(CS)的临床疗效。方法:选取急诊PCI治疗的AMI并CS的患者47例,24例接受IABP支持下急诊PCI治疗的患者为治疗组,23例直接急诊PCI治疗的患者为对照组。治疗一周后,检测两组患者平均动脉压(MAP)、尿量、心率、肺动脉楔压(PCWP)、心脏指数(CI)、左室射血分数(LVEF)、及N末端血浆B型尿钠肽前体(NT-pro BNP)指标的变化,多巴胺、速尿和硝酸酯类用量的比较及死亡率比较。结果:治疗前两组各项观察指标差异无统计学意义(P0.05);治疗后两组各项观察指标与治疗前比较,差异均有统计学意义(P0.05);治疗后两组各观察指标差值比较,差异有统计学意义(P0.05);治疗组多巴胺、速尿用量少于对照组,差异有统计学意义(P0.05);治疗组硝酸酯类用量少于对照组,但差异无统计学意义(P0.05);治疗后两组死亡率比较,差异有统计学意义(P0.05)。结论:急性心肌梗死并心源性休克患者在IABP支持下行急诊PCI,可明显改善患者的冠状动脉血流,改善心肌的血供,改善心功能,降低病死率。     

Intra-Aortic Balloon Pump Counterpulsation during Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction and Cardiogenic Shock: Insights from the British Columbia Cardiac Registry

Background

Cardiogenic shock complicating ST-elevation myocardial infarction (STEMI) is associated with significant morbidity and mortality. In the primary percutaneous coronary intervention (PPCI) era, randomized trials have not shown a survival benefit with intra-aortic balloon pump (IABP) therapy. This differs to observational data which show a detrimental effect, potentially reflecting bias and confounding. Without robust and valid risk adjustment, findings from non-randomized studies may remain biased.

Methods

We compared long-term mortality following IABP therapy in patients with cardiogenic shock undergoing PPCI during 2008–2013 from the British Columbia Cardiac Registry. We addressed measured and unmeasured confounding using propensity score and instrumental variable methods.

Results

A total of 12,105 patients with STEMI were treated with PPCI during the study period. Of these, 700 patients (5.8%) had cardiogenic shock. Of the patients with cardiogenic shock, 255 patients (36%) received IABP therapy. Multivariable analyses identified IABP therapy to be associated with increased mortality up to 3 years (HR = 1.67, 95% CI:1.20–2.67, p<0.001). This association was lost in propensity-matched analyses (HR = 1.23, 95% CI: 0.84–1.80, p = 0.288). When addressing measured and unmeasured confounders, instrumental variable analyses demonstrated that IABP therapy was not associated with mortality at 3 years (Δ = 16.7%, 95% CI: -12.7%, 46.1%, p = 0.281). Subgroup analyses demonstrated IABP was associated with increased mortality in non-diabetics; patients not undergoing multivessel intervention; patients without renal disease and patients not having received prior thrombolysis.

Conclusions

In this observational analysis of patients with STEMI and cardiogenic shock, when adjusting for confounding, IABP therapy had a neutral effect with no association with long-term mortality. These findings differ to previously reported observational studies, but are in keeping with randomized trial data.     

降纤酶治疗心源性脑栓塞

目的　探讨降纤酶治疗心源性脑栓塞病人的疗效和安全性。　方法　 2 6例心源性脑栓塞病人均有心房纤颤病史 ,男 1 0例 ,女 1 6例 ,年龄 4 0～ 78岁 ,平均 ( 5 1 .73± 1 1 .1 9)岁。给予降纤酶 1 0 u,每日 1次静滴 ,7天为 1疗程。用药期间监测血浆纤维蛋白原、血小板计数、出凝血时间及肝肾功能。　结果　降纤酶治疗心源性脑栓塞疗效确切 ,能改善神经功能 ,总有效率为 88.4 6 % ,早期应用效果更好。无任何不良反应。　结论　降纤酶是一种安全、有效的治疗心源性脑栓塞的药物 ,宜早期、足量、长疗程应用。     

Osmotic Shock Inhibits Insulin Signaling by Maintaining Akt/Protein Kinase B in an Inactive Dephosphorylated State

We have previously reported that insulin and osmotic shock stimulate an increase in glucose transport activity and translocation of the insulin-responsive glucose transporter isoform GLUT4 to the plasma membrane through distinct pathways in 3T3L1 adipocytes (D. Chen, J. S. Elmendorf, A. L. Olson, X. Li, H. S. Earp, and J. E. Pessin, J. Biol. Chem. 272:27401-27410, 1997). In investigations of the relationships between these two signaling pathways, we have now observed that these two stimuli are not additive, and, in fact, osmotic shock pretreatment was found to completely prevent any further insulin stimulation of glucose transport activity and GLUT4 protein translocation. In addition, osmotic shock inhibited the insulin stimulation of lipogenesis and glycogen synthesis. This inhibition of insulin-stimulated downstream signaling occurred without any significant effect on insulin receptor autophosphorylation or tyrosine phosphorylation of insulin receptor substrate 1 (IRS1). Furthermore, there was no effect on either the insulin-stimulated association of the p85 type I phosphatidylinositol (PI) 3-kinase regulatory subunit with IRS1 or phosphotyrosine antibody-immunoprecipitated PI 3-kinase activity. In contrast, osmotic shock pretreatment markedly inhibited the insulin stimulation of protein kinase B (PKB) and p70S6 kinase activities. In addition, the dephosphorylation of PKB was prevented by pretreatment with the phosphatase inhibitors okadaic acid and calyculin A. These data support a model in which osmotic shock-induced insulin resistance of downstream biological responses results from an inhibition of insulin-stimulated PKB activation.     

热激蛋白90与热激应答

热激蛋白90(heat shock protein 90,HSP90)作为机体重要的分子伴侣之一,主要是维持机体内环境的稳态.在机体遭受内外界刺激时,体内氧化-抗氧化平衡失调诱发机体热激应答,诱导HSP90高表达来抵御刺激对机体造成的损伤.     

热激蛋白70与热激反应

热激反应是细胞保护的最原始机制之一。近年来,越来越多的研究证明热激蛋白作为一种自然机制参与细胞保护,而热激蛋白70家族在其中起重要作用,从而成为恶劣条件、手术过程以及同病原体的斗争中器官保护的重要机制之一。