脓毒症休克心肌顿抑严重程度判断的临床研究

目的探讨脑钠肽（BNP）、心肌钙蛋白I（cTnI）、血乳酸及急性生理及慢性健康状况评分Ⅱ（APACHEⅡ评分）在脓毒症休克心肌顿抑严重程度判断中的应用价值。方法3l例确诊脓毒症休克患者,入院后1h内抽血查BNP、cTnI、血乳酸,并进行APACHElI评分,以后分别在开始治疗后6、24h监测上述指标。观察患者的最终预后,比较存活组和死亡组上述指标入院时的差异;分别比较不同预后组内各时间点上述指标的差异。结果3l例患者,死亡13例,存活18例,死亡率为41．9％。死亡组人院时各项指标数值均明显高于存活组[BNP：（3401．1±1710．2）pg／Lvs（1947．2±1319．5）pg／L,P=0．008;cTnI：（9．4±4．7）ng]L vs（5．1±4．4）．g／L,P=0．012;血乳酸：（10．8±4．9）mm01]L vs（7．1±4．5）mmol／L,P=0．027;APACHElI评分：29．4±5．7口s22．1-＋8．8,P：0．006]。死亡组患者中,治疗6h上述指标与入院时比较差异无统计学意义（P均〉0．05）,治疗后24hBNP[（4757．9-＋2044．4）pg／L vs（3401．1-＋1710．2）og／L,P=0．0111、血乳酸【（12．4-＋3．2）mmol／LVS（8．8±4．9）mmol／L,P=0．0311、APACHEII评分（34．6±6．1ws29．4±5．7,P=0．029）均明显高于人院时（P均〈0．05）,eTnI差异无统计学意义（P〉0．05）。存活组患者中．治疗6h[BNP：（1125．2＋563．3）pg／L vs（1947．2±l319．5）pgCL;eTnI：（2．1±1．4）ng／L vs（5．1＋4．4）nv4L;血孚L酸：（4．4±2．7）mmol／LVS（7．1±4．5）mmol／L;A．PACHEII评分：15．5±7．9vs22．1±8．81、24h]BNP：（578．1±345．5）pg／L vs（1947．2±l319．5）pz-／L;eTnI：（0．9±0．5）ng／L vs（5．1±4．4）ng／L;血乳酸：（2-4±1．3）mmol／Lvs（7．1±4．5）mmol／L;APACHEⅡ评分：10．4±2．8vs22．1±8．81各项指标均较入院时明显降低,差异有统计学意义（P均〈0．05）。结论BNP、eTnI、血乳酸和APACHEll评分可反映脓毒症休克患者心肌顿抑的严重程度,预测患者预后．进一步可据此建立相关的脓毒症休克患者心肌顿抑严重程度评估系统。     

乌司他丁对脓毒症大鼠早期心肌功能的保护作用

目的研究乌司他丁对脓毒症大鼠早期心肌功能的影响。方法72只SD大鼠,随机分成A组（假手术组,n=8）、B组（脓毒症组,n=32）和C组（乌司他丁组,n=32）,A组仅行盲肠探查术,B、C组采用盲肠结扎穿孔（CLP）制作大鼠脓毒症模型。A、B组术后即刻皮下注射生理盐水5ml,C组术后即刻皮下注射乌司他丁（105U／kg,溶于5ml生理盐水中）。B、C组均于术后3、6、12、24h时点经左侧颈总动脉插管至大鼠左心室,测量左室收缩峰压（LVSP）、左室压力最大上升速率（＋dp/dtmax）、左室压力最大下降速率（-dp／dtmax）,并采血检测肌钙蛋白I（cTnI）。A组术后行心肌力学和血清cTnI检测。结果盲肠结扎穿孔（CLP）造模后B、C组较A组LVSP、＋dp／dtmax、-dp／dtmax均明显降低（P〈0．05）,C组在各时点的LVSP、＋dp／dtmax、-dp／dtmax水平显著高于B组（P〈0．05）,C组血清cTnI在各时点均低于B组（P〈0．05）。结论脓毒症大鼠心肌早期即有损害,乌司他丁可明显改善心肌功能,对心肌具有一定保护作用。     

A review of troponins in ischemic heart disease and other conditions

Measuring cardiac troponin (cTn) I and T levels is currently considered to be a cornerstone for making the diagnosis of acute coronary syndrome (ACS).Based on current literature, cTnI and cTnT are known to be very sensitive and specific for myocardial damage, regardless of the underlying cause. Lately, it has been found that cTns can be elevated and reflect worse prognoses in many situations where ACS is excluded. Such information can affect the validity of cTns as markers for ACS without classic symptoms. This may call for a revision of the troponin cutoff values to make a diagnosis of ACS. Furthermore, it opens a new field of study to determine appropriate management of patients with elevated cTn levels in whom ACS has been excluded.     

Cardiac biomarker-based risk stratification algorithm in patients with severe COVID-19

Background and aimsCardiac biomarkers like cardiac troponins and natriuretic peptides are elevated in a substantial proportion of patients with coronavirus disease 2019 (COVID-19). We propose an algorithmic approach using cardiac biomarkers to triage, risk-stratify and prognosticate patients with severe COVID-19.MethodsWe systematically searched the PubMed and Google Scholar databases until May 31st, 2020, and accessed the available data on the role of cardiac biomarkers in patients with COVID-19.ResultsCOVID-19 is associated with acute cardiac injury in around 7–28% of patients, significantly increasing its associated complications and mortality. Patients with underlying cardiovascular disease are more prone to develop acute cardiac injury as a result of COVID-19. The use of cardiac biomarkers may aid in differentiating the cardiac cause of dyspnea in patients with severe COVID-19. Cardiac biomarkers may also aid in triaging, risk-stratification, clinical decision-making, and prognostication of patients with COVID-19. However, there are concerns that routine testing in all patients with COVID-19 irrespective of severity, may result in unnecessary downstream investigations which may be misleading. In this brief review, using an algorithmic approach, we have tried to rationalize the use of cardiac biomarkers among patients with severe COVID-19. This approach is also likely to lessen the infection exposure risk to the cardiovascular team attending patients with severe COVID-19.ConclusionIt appears beneficial to triage, risk-stratify, and prognosticate patients with COVID-19 based on the evidence of myocardial injury and the presence of underlying cardiovascular disease. Future research studies are, however, needed to validate these proposed benefits.     

Troponin phosphorylation and regulatory function in human heart muscle: dephosphorylation of Ser23/24 on troponin I could account for the contractile defect in end-stage heart failure

We made quantitative measurements of phosphorylation in troponin isolated from 6 non-failing donor hearts and 6 explanted hearts with end-stage heart failure in SDS-PAGE gels using Pro-Q Diamond phosphoprotein stain. The troponin T phosphorylation level was the same in troponin from failing and non-failing heart (3.1 mol Pi/mol). However, troponin I phosphorylation was significantly lower in failing (0.37+/-0.18 mol Pi/mol) compared with non-failing heart troponin (2.25+/-0.36 mol Pi/mol). Levels of troponin I PKA-dependent phosphorylation, measured with a phosphoserine 23/24-specific antibody, were also significantly lower in failing heart troponin (0.19+/-0.06 mol Pi/mol) compared to non-failing troponin (1.14+/-0.09 mol Pi/mol). We calculate that there is phosphorylation in addition to serine 23/24 of 1.11+/-0.34 mol Pi/mol in non-failing reduced to 0.18+/-0.17 mol Pi/mol in failing heart troponin, attributed to phosphorylation on the PKC sites. To test for the functional role of troponin I phosphorylation, the native troponin I from either non-failing or failing heart troponin was exchanged for a recombinant (unphosphorylated) human cardiac troponin I. Thin filament Ca(2+)-regulatory function was studied with the quantitative in vitro motility assay: thin filaments containing the replaced troponin I resulted in a failing phenotype of a 17-26% reduced sliding speed and an increased Ca(2+)-sensitivity relative to non-failing troponin (EC(50) TnI-exchanged/non-failing=0.57, p<0.001). When exchanged with troponin I phosphorylated with PKA motility parameters reverted to a pattern indistinguishable from non-failing troponin (p=0.35-0.75). We suggest that changes in troponin function can account for the contractile abnormality in failing heart muscle and that the functional changes in troponin are due to reduced phosphorylation of troponin I at the PKA sites.     

Independent FHC-related cardiac troponin T mutations exhibit specific alterations in myocellular contractility and calcium kinetics

Mutations in cardiac troponin T (cTnT) are linked to a severe form of Familial Hypertrophic Cardiomyopathy. Patients carrying mutations flanking the tropomyosin-binding domain of cTnT (R92L and Delta160E) develop distinct clinical syndromes. In order to better understand the cellular pathophysiology underlying these clinically relevant differences, we studied isolated adult left ventricular myocytes from independent transgenic cTnT mouse lines carrying either a 35% (Delta160E) or 50% (R92L) replacement of the endogenous cTnT with the mutant forms. Measurement of baseline myocellular contraction revealed that the Delta160E cells had significant decreases in the peak rate of contraction and percent shortening as compared to either R92L or Non-TG myocytes. In addition, while both Delta160E and R92L myocytes demonstrated a decrease in the peak rate of relaxation as compared to Non-TG, the magnitude of the difference was significantly greater in Delta160E cells. Concurrent myocyte [Ca2+](i) transient measurements revealed that while the alterations in the peak rates and times of the rise and decline of the [Ca2+](i) transient were similar to the changes in the respective measures of sarcomeric mechanics, R92L cells also exhibited reduced rates of the rise and decline of the [Ca2+](i) transient but did not exhibit these reductions in terms of sarcomeric mechanics. Of note, only Delta160E, and not R92L myocytes, demonstrated significant reductions in SR Ca2+ load and uptake, corresponding to the impairments seen in the [Ca2+](i) and mechanical transients. Finally, Western analysis revealed a significant Delta160E-specific reduction in the SERCA2a/PLB ratio, which may well underlie the observed alterations in Ca2+ homeostasis. Therefore, independent cTnT mutations result in significant mutation-specific effects in Ca2+ handling that may, in part, contribute to the observed clinical variability in cTnT-related FHC.     

无创正压通气对急性左心衰竭患者血浆高敏肌钙蛋白T水平的影响

目的 观察无创正压机械通气对急性左心衰竭患者血浆高敏肌钙蛋白T(hs-TnT)水平的影响.方法 选择急性左心衰竭患者46例随机分为两组:常规治疗组20例,正压通气组26例,两组患者分别给予高流量面罩吸氧+药物治疗及经面罩双水平无创正压通气+药物治疗,观察两组治疗后24 h的临床疗效以及血浆hs-TnT水平变化.结果正压通气组的临床疗效好于常规治疗组,差异有统计学意义( P ＜0.05).治疗后两组hs-TnT水平均较治疗前明显下降( P ＜0.05),且两组治疗后PaO2、SpO2、HR、呼吸频率、LVEF比较,差异均有统计学意义( P ＜0.05).结论 无创机械通气能够提高急性左心衰竭的治疗效果,并能进一步降低血浆hs-TnT水平.     

Significance of elevated cardiac troponin T levels in critically ill patients with acute respiratory disease

Background

Elevations in cardiac troponin have prognostic importance in critically ill patients. However, there are no data addressing the independent association between troponin levels and mortality, adjusted for the severity of the underlying disease, in patients hospitalized for acute respiratory disorders. We investigated whether troponin T (cTnT) elevations are independently associated with in-hospital mortality in patients in the intensive care unit (ICU) admitted for severe and acute respiratory conditions. After adjusting for the severity of disease measured by the Acute Physiology, Age, and Chronic Health Evaluation (APACHE) III prognostic system, we evaluated short-term (30 days) and long-term (3 years) mortality.

Methods

We studied the APACHE III database and cTnT levels from patients admitted consecutively to the ICU at Mayo Clinic, Rochester, Minnesota. Between January 2001 and December 2005, 2078 patients with respiratory conditions had cTnT measured at ICU admission. In-hospital, short-term (30 days) and long-term (3 years) all-cause mortality were determined.

Results

Of the study patients, 878 (42.3%) had elevated cTnT and 1200 patients (57.7%) had undetectable cTnT. During hospitalization, 1.1% of the patients with troponin T <0.01 ng/mL died compared to 21% of those with troponin T ≥0.01 ng/mL (P <.0001). At 30 days, mortality was 18.6% in patients with elevations of cTnT and 1.5% in patients without elevations of cTnT (P <.0001). The Kaplan-Meier probability of survival at 1-year follow-up was 71.0%, at 2-year follow-up was 48.3%, and 3-year follow-up was 39.4% with troponin T ≥0.01 ng/mL and at 1-year follow-up was 98.8%, at 2-year follow-up was 97.2%, and at 3-year follow-up was 95.5% with troponin T <0.01 μg/L (P <.0001). After adjustment for severity of disease and baseline characteristics, cTnT levels remained associated with in-hospital, short-term and long-term mortality (P <.0001).

Conclusions

In patients admitted to the ICU for respiratory disorders, cTnT elevations are independently associated with in-hospital, short-term and long-term mortality.     

(-)-Adrenaline elicits positive inotropic, lusitropic, and biochemical effects through β2-adrenoceptors in human atrial myocardium from nonfailing and failing hearts, consistent with Gs coupling but not with Gi coupling

Activation of either coexisting β₁- or β₂-adrenoceptors with noradrenaline or adrenaline, respectively, causes maximum increases of contractility of human atrial myocardium. Previous biochemical work with the β₂-selective agonist zinterol is consistent with activation of the cascade β₂-adrenoceptors→Gsα-protein→adenylyl cyclase→cAMP→protein kinase (PKA)→phosphorylation of phospholamban, troponin I, and C-protein→hastened relaxation of human atria from nonfailing hearts. However, in feline and rodent myocardium, catecholamines and zinterol usually do not hasten relaxation through activation of β₂-adrenoceptors, presumably because of coupling of the receptors to Gi protein. It is unknown whether the endogenously occurring β₂-adrenoceptor agonist adrenaline acts through the above cascade in human atrium and whether its mode of action could be changed in heart failure. We assessed the effects of (-)-adrenaline, mediated through β₂-adrenoceptors (in the presence of CGP 20712A 300 nM to block β₁-adrenoceptors), on contractility and relaxation of right atrial trabecula obtained from nonfailing and failing human hearts. Cyclic AMP levels were measured as well as phosphorylation of phospholamban, troponin I, and protein C with Western blots and the back-phosphorylation procedure. For comparison, β₁-adrenoceptor-mediated effects of (-)-noradrenaline were investigated in the presence of ICI 118,551 (50 nM to block β₂-adrenoceptors). The positive inotropic effects of both (-)-noradrenaline and (-)-adrenaline were accompanied by reductions in time to peak force and time to reach 50% relaxation. (-)-Adrenaline caused similar positive inotropic and lusitropic effects in atrial trabeculae from failing hearts. However, the inotropic potency, but not the lusitropic potency, of (-)-noradrenaline was reduced fourfold in atrial trabeculae from heart failure patients. Both (-)-adrenaline and (-)-noradrenaline enhanced cyclic AMP levels and produced phosphorylation of phospholamban, troponin I, and C-protein to a similar extent in atrial trabeculae from nonfailing hearts. The hastening of relaxation caused by (-)-adrenaline together with the PKA-catalyzed phosphorylation of the three proteins involved in relaxation, indicate coupling of β₂-adrenoceptors to Gs protein. The phosphorylation of phospholamban at serine16 and threonine17 evoked by (-)-adrenaline through β₂-adrenoceptors and by (-)-noradrenaline through β₁-adrenoceptors was not different in atria from nonfailing and failing hearts. Activation of β₂-adrenoceptors caused an increase in phosphorylase a activity in atrium from failing hearts further emphasizing the presence of the β₂-adrenoceptor–Gsα-protein pathway in human heart. The positive inotropic and lusitropic potencies of (-)-adrenaline were conserved across Arg16Gly- and Gln27Glu-β₂-adrenoceptor polymorphisms in the right atrium from patients undergoing coronary artery bypass surgery, chronically treated with β₁-selective blockers. The persistent relaxant and biochemical effects of (-)-adrenaline through β₂-adrenoceptors and of (-)-noradrenaline through β₁-adrenoceptors in heart failure are inconsistent with an important role of coupling of β₂-adrenoceptors with Giα-protein in human atrial myocardium.     

心肌型脂肪酸结合蛋白在钝性心脏损伤早期诊断中的价值

目的 探讨心肌型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)在钝性心脏损伤(blunt cardiac injury,BCI)早期诊断中的价值.方法前瞻性研究2007年1月至2008年6月间复旦大学附属上海市第五人民医院收治的42例钝性胸部损伤患者和同期本院健康体检中心42例健康体检者血清心肌标志物水平,采用双抗体夹心酶联免疫一步法定量检测42例健康体检者和42例钝性胸部损伤患者伤后3,6,12 h血清H-FABP、心肌肌钙蛋白Ⅰ(cardiac troponin Ⅰ,cTn Ⅰ)和肌红蛋白(Myoglobin,Myo)含量.以cTn Ⅰ作为诊断BCI的金标准,将42例钝性胸部损伤患者分为心肌损伤组(13例)和非心肌损伤组(29例).绘制H-FABP和cTn Ⅰ在胸部损伤患者伤后3,6,12 h诊断BCI的受试者特征曲线(receiver operating characteristic curve,ROC curve),并比较曲线下面积(area under the curve,AUC),分析伤后不同时间(3,6,12 h)血清H-FABP和cTn Ⅰ对BCI的诊断价值.多组均数间的差异性比较采用Kruskal Wallis检验,ROC曲线下面积比较采用delong.clarke-pearson检验.以P＜0.05为差异具有统计学意义.结果伤后3 h诊断BCI的AUCH-FABP和AUCcTnⅠ分别为0.9257和0.6844.AUCH-FABP大于AUCcTnⅠ,二者差异具有统计学意义(P=0.0125),伤后12 h诊断BCI的AUCH-FABP小于AUCcTn Ⅰ,差异具有统计学意义(0.9841 vs.0.8276,P=0.0278),二者对诊断伤后6 h BCI的ROC曲线下面积相比,差异无统计学意义(0.9655 vs.0.9125,P=0.2609).结论 H-FABP对BCI具有早期诊断价值,其伤后3 h的敏感性优于cTnⅠ.