Troponin T Concentrations Research Articles

Remifentanil and sevoflurane based anesthesia combined with bilateral erector spinae plane block in patients undergoing off-pump coronary artery bypass graft surgery.

IntroductionWorking on the institutional Enhanced Recovery After Surgery (ERAS Cardio) protocol for off-pump coronary artery bypass graft surgery (OP-CABG) we have noticed that patients treated according to the modified anesthesia protocol had not only significantly shorter time of respiratory support and intensive care unit stay but also lower postoperative troponin T concentration than patients who had standard fentanyl/sevoflurane-based anesthesia.AimTo compare the perioperative course of patients undergoing OP-CABG surgery and receiving standard fentanyl/sevoflurane anesthesia and those anesthetized according to the institutional ERAS Cardio protocol with remifentanil, sevoflurane, and bilateral extensor spinae plane (ESP) block.Material and methodsDesign: a prospective, open-label, observational study performed in a tertiary health center. Participants: 30 consecutive patients undergoing off-pump coronary bypass graft surgery. Interventions: 15 patients had standard anesthesia with etomidate, fentanyl, and rocuronium for induction and fentanyl/sevoflurane for maintenance (standard group); 15 others had bilateral single shot ESP block, then etomidate, remifentanil and rocuronium for induction, and remifentanil/sevoflurane for maintenance of anesthesia.ResultsMedian time to extubation was 7.6 (5.5–12.5) h and 1.7 (1–3.25) h in “standard care” and ERAS groups, respectively (p = 0.00002). Length of stay in the intensive care unit was also shorter for patients in the ERAS group 20.5 (18–24) vs. 48 (42–48) h (p = 0.00001). Troponin concentration increased to a lesser extent in patients from the ERAS group: an increase of 151.8 (71.9–174.3) ng/ml vs. 253.8 (126.6–373.1) ng/ml, p = 0.008.ConclusionsRemifentanil/sevoflurane anesthesia combined with bilateral ESP block shortens mechanical ventilation time and ICU stay, and decreases postoperative troponin-T concentration in patients undergoing off-pump coronary bypass graft surgery.

Microvascular spasm in non-ST-segment elevation myocardial infarction without culprit lesion (MINOCA).

Up to 30% of patients with acute coronary syndrome have no culprit lesion. Coronary microvascular spasm is an alternative cause for such a clinical presentation. However, this has rarely been investigated systematically. The aim of our study was to assess the frequency of coronary microvascular spasm in patients with NSTEMI without culprit lesion (MINOCA) by intracoronary acetylcholine testing (ACH-test). Between 2014 and 2017, 940 patients with NSTEMI underwent coronary angiography and 125 (13%) had no culprit lesion (< 50% stenosis on visual assessment). Of the latter, 29 patients had other causes for the clinical presentation (e.g. tako-tsubo-syndrome or myocarditis). The remaining 96 patients were recruited for the study and underwent ACH-testing according to a standardized protocol. The ACH-test was normal in 40 (42%) and abnormal in the remaining 56 (58%) patients. Of the latter, 26 patients (46%) had epicardial spasm (epicardial narrowing ≥ 90%, reproduction of symptoms and ischemic ST-segment changes) and 30 (54%) microvascular spasm (ischemic ST-shifts and angina without epicardial vasoconstriction ≥ 90%). The peak high-sensitive troponin-T concentration was 113 (42-255)pg/ml. Patients with coronary spasm had more often a positive family history compared to those without and patients with epicardial compared to microvascular spasm were more often smokers. Coronary microvascular spasm is frequently found in patients with NSTEMI without culprit lesion and represents a likely cause of myocardial injury. ACH-testing is useful for detection of vasomotor disorders allowing tailored treatment with calcium antagonists and/or nitrates in addition to secondary prevention to improve symptoms and prognosis. Microvascular spasm in non-ST-segment elevation myocardial infarction without culprit lesion (MINOCA) .

AT1Rknockdown confers cardioprotection against sepsis-induced myocardial injury by inhibiting the MAPK signaling pathway in rats.

Myocardial dysfunction is an important manifestation of sepsis. In addition, inactivation of the mitogen-activated protein kinase (MAPK)signaling pathway has been reported to be beneficial in sepsis. The current study used gene expression profiling to demonstrate the overexpression of angiotensin II type 1 receptor (AT1R) and activation of the MAPK signaling pathway in sepsis. In this study, we used a rat model of sepsis established by cecal ligation and puncture to explore the mechanism of AT1R silencing in relation to the MAPK signaling pathway on myocardial injury. Various parameters including blood pressure, heart rate, and cardiac function changes were observed. Enzyme-linked immunosorbent assay was used to measure the concentration of cardiac troponin T (TnT), cardiac troponin I (cTnI), and creatine kinase isoenzyme muscle/brain (CK-MB). Myocardial enzyme, tissue antioxidant capacity, mitochondria swelling, and membrane potential were also detected. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labelingstaining was applied to measure cell apoptosis, andmessenger RNAand protein levels of apoptosis-related proteins (Fas ligand [Fasl], B-cell CLL/lymphoma [Bcl-2], p53) were also detected. Initially, sepsis rats exhibited decreased survival rate, but increased ejection fraction (EF), heart rate, and concentrations of TnT, cTnI, and CK-MB. Furthermore, decreased AT1R expression inactivated the MAPK signaling pathway (shown as decreased extracellular signal-regulated kinase and cyclic adenosine 3',5'-monophosphate response element binding protein expression), decreased EF, heart rate, and concentrations of TnT, cTnI, and CK-MB, but increased sepsis rat survival rate. Eventually, decreased AT1R expression inhibited myocardial cell apoptosis (shown as decreased apoptosis rate and p53 and Fasl expression as well as increased Bcl-2 expression). These findings indicated that AT1R silencing plays an inhibitory role in sepsis-induced myocardial injury by inhibiting the MAPK signaling pathway.

Protective effect of scutellarin on myocardial infarction induced by isoprenaline in rats.

Objective(s):Scutellarin (Scu) is the main effective constituent of Erigeron breviscapus which has anti-oxidant, anti-apoptotic, anti-inflammatory and other therapeutic properties. The purpose of this study was to investigate the protective effect of Scu on myocardial infarction (MI) induced by isoprenaline (ISO).Materials and Methods:The rats were subcutaneously injected with ISO (45 mg/kg) on the first day, then single tail-intravenously injected with different doses of Scu (10 mg/kg, 20 mg/kg, 40 mg/kg) for 7 consecutive days. The protective effect of Scu on ISO-induced MI was evaluated by measuring markers of heart injury in serum, levels of lipid peroxidation, and antioxidants in heart tissue, observing pathological changes of tissue, and detecting quantified expression of apoptotic-related family members and inflammation.Results:Compared with the model group, the concentration of troponin T (CTn-T) and troponin I (CTn-I), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the serum all decreased in the Scu high dose group. The activities of superoxide dismutase (SOD), catalase (CAT), and the content of reduced glutathione (GSH) in heart increased, and the content of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) decreased. In addition, the histopathologic aspects showed that pathological heart change was found in the model group, and was reduced to varying degrees in the Scu group. Moreover, the expression of Bax, P53, Caspase3, Caspase9, cytochrome C, NGAL, NFκB, IL-1β and IL-6 in the heart decreased, while the expression of Bcl2 increased.Conclusion:Scu could reduce the degree of MI induced by ISO by improving the antioxidant, anti-apoptotic, and anti-inflammatory capacities of the body.

Prognostic Value of High-Sensitivity Versus Conventional Cardiac Troponin T Assays Among Patients With Type 2 Diabetes Mellitus Undergoing Maintenance Hemodialysis

Mortality is high among patients undergoing hemodialysis for whom cardiac troponin concentration is a strong predictor of outcome. Modern troponin assays allow measurement of very low concentrations. Using data from a randomized controlled trial, a cohort analysis to evaluate the prognostic value of very low cardiac troponin T (TnT) concentrations. 1,255 patients with end-stage renal disease and type 2 diabetes mellitus undergoing maintenance hemodialysis from the German Diabetes and Dialysis Study (4D) who had a median follow-up of 4 years. Cardiac TnT was measured using a high-sensitivity assay (hs-TnT) and a conventional assay (conventional TnT) in a subpopulation (n=1,034) with valid measurements for both assays. Outcome measures were all-cause mortality and a composite cardiovascular end point including cardiac death, myocardial infarction, or stroke. Among the 1,034 study participants, 505 died and 377 had a cardiovascular event.Both hs-TnT and conventional TnT concentrations were associated with mortality and cardiovascular events in models adjusted for cardiovascular risk factors and dialysis-associated variables. 455 (44%) patients with very low TnT concentrations (hs-TNT< 50ng/L) would have been classified as normal by the conventional TnT assay. Among these patients, hs-TnT concentrations were also associated with mortality. The study of patients with type 2 diabetes may limit generalizability. These findings have not been externally validated. In patients with type 2 diabetes mellitus receiving hemodialysis, cardiac TnT is associated with long-term mortality and cardiovascular outcomes. Concentrations of TnT not measurable with acceptable precision using a conventional TnT assay were associated with a poor prognosis when measured using a high-sensitivity assay.

A Risk Assessment Score and Initial High-sensitivity Troponin Combine to Identify Low Risk of Acute Myocardial Infarction in the Emergency Department.

Early discharge of patients with presentations triggering assessment for possible acute coronary syndrome (ACS) is safe when clinical assessment indicates low risk, biomarkers are negative, and electrocardiograms (ECGs) are nonischemic. We hypothesized that the Emergency Department Assessment of Chest Pain Score (EDACS) combined with a single measurement of high-sensitivity cardiac troponin (hs-cTn) could allow early discharge of a clinically meaningful proportion of patients. We pooled data from four patient cohorts from New Zealand and Australia presenting to an emergency department with symptoms suggestive of ACS. The primary outcome was major adverse cardiac events (MACE) within 30 days of presentation. In patients with a nonischemic ECG we evaluated the sensitivity for MACE and percentage low risk of every combination of high-sensitivity cardiac troponinT (hs-cTnT) concentration and high-sensitivity cardiac troponinI (hs-cTnI) concentration with EDACS. We used a standard smoothing technique on the probability density function for hs-cTn and EDACS and applied bootstrapping to determine the optimal threshold combinations, namely, the combination that maximized the percentage low risk with ≥98.5% sensitivity for MACE. From 2,536 patients, 2,258 presented without an ischemic ECG of whom 272 (12.1%) had a MACE within 30 days. The optimal threshold for hs-cTnI was 7 ng/L combined with an EDACS threshold of 16 (36.8% patients low risk). The optimal thresholds for hs-cTnT were 8ng/L combined with an EDACS threshold of 15 (30.2% patients low risk). Single measurements of both hs-cTnI and hs-cTnT at presentation combined with EDACS to identify over 30% of patients as low risk and therefore eligible for safe early discharge after only one blood draw.

Troponin-T as a biomarker in neonates with perinatal asphyxia.

Troponin-T is a commonly used cardiac biomarker, which could be useful in perinatal asphyxia. We aimed to analyze troponin-T concentrations in asphyxiated neonates and to correlate the concentrations with clinical outcomes. Data were collected from electronic medical records of neonates diagnosed with perinatal asphyxia over a period of four years. There were 63 neonates with moderate to severe encephalopathy, in whom serial troponin-T concentrations had been done on days 1, 3, and 7. 53 (84%) asphyxiated infants had troponin-T concentration >100 pg/ml at 2-4 h of life.The difference in troponin-T concentrations between moderate and severe encephalopathy was not statistically significant (173 vs. 263 pg/ml, p value 0.40). The difference in the concentrations at 72 hours between cooled and non-cooled neonates was not significant (48.5 vs. 62.5 pg/ml, p value 0.22). Troponin-T concentration was significantly higher in babies with hypotensive shock and hepatic injury, but not acute kidney injury. There was no significant correlation between troponin-T and the extent of resuscitation needed.Troponin-T concentration on day 1 of life was significantly higher in babies who died than who survived (407 vs. 168 pg/ml, p value 0.03). ROC curve for troponin-T to predict mortality had an area under the curve (AUC) of 0.803; the best cut-off value (190 pg/ml) had 82% sensitivity and 80% specificity. There was no significant difference in troponin-T concentrations between cooled and non-cooled neonates. Troponin-T concentration had a good predictive accuracy for mortality before discharge.

Diosmin prevents left ventricular hypertrophy, adenosine triphosphatases dysfunction and electrolyte imbalance in experimentally induced myocardial infarcted rats

Currently, there has been an increased interest globally to identify natural compounds that are pharmacologically potent and have low or no adverse effects for use in preventive medicine. Myocardial infarction is a vital pathological feature resulting in high levels of mortality and morbidity. Left ventricular hypertrophy (LVH), adenosine triphosphatases (ATPases) dysfunction and electrolyte imbalance play a vital role in the pathogenesis of myocardial infarction. This study aims to evaluate the preventive effects of diosmin on LVH, ATPases dysfunction and electrolyte imbalance in isoproterenol induced myocardial infarcted rats. Male albino Wistar rats were pretreated orally with diosmin (10mg/kg body weight) daily for a period of 10 days. After pretreatment, isoproterenol (100mg/kg body weight) was injected subcutaneously into the rats twice at an interval of 24h to induce myocardial infarction. Isoproterenol induced myocardial infarcted rats showed increased LVH, altered levels/ concentrations of serum cardiac troponin-T, heart ATPases, heart sodium ion, calcium ion and potassium ion, and increased myocardial infarct size. Pretreatment with diosmin revealed preventive effects on LVH, and all the above mentioned biochemical parameters evaluated in isoproterenol induced myocardial infarcted rats. The 2, 3, 5-triphenyl tetrazolium chloride staining on myocardial infarct size confirmed the prevention of myocardial infarction. Further, the 1, 1 diphenyl-2- picryl-hydrazyl (DPPH) radical in vitro study revealed a potent DPPH free radical scavenging action of diosmin. Thus, the observed effects of diosmin are due to its antihypertrophic and free radical scavenging activities in isoproterenol induced myocardial infarcted rats.

On/off-switchable LSPR nano-immunoassay for troponin-T

Regeneration of immunosensors is a longstanding challenge. We have developed a re-usable troponin-T (TnT) immunoassay based on localised surface plasmon resonance (LSPR) at gold nanorods (GNR). Thermosensitive poly(N-isopropylacrylamide) (PNIPAAM) was functionalised with anti-TnT to control the affinity interaction with TnT. The LSPR was extremely sensitive to the dielectric constant of the surrounding medium as modulated by antigen binding after 20 min incubation at 37 °C. Computational modelling incorporating molecular docking, molecular dynamics and free energy calculations was used to elucidate the interactions between the various subsystems namely, IgG-antibody (c.f., anti-TnT), PNIPAAM and/or TnT. This study demonstrates a remarkable temperature dependent immuno-interaction due to changes in the PNIPAAM secondary structures, i.e., globular and coil, at above or below the lower critical solution temperature (LCST). A series of concentrations of TnT were measured by correlating the λLSPR shift with relative changes in extinction intensity at the distinct plasmonic maximum (i.e., 832 nm). The magnitude of the red shift in λLSPR was nearly linear with increasing concentration of TnT, over the range 7.6 × 10−15 to 9.1 × 10−4 g/mL. The LSPR based nano-immunoassay could be simply regenerated by switching the polymer conformation and creating a gradient of microenvironments between the two states with a modest change in temperature.

Does therapeutic hypothermia during extracorporeal cardiopulmonary resuscitation preserve cardiac function?

BackgroundExtracorporeal cardiopulmonary resuscitation (E-CPR) is increasingly used as a rescue method in the management of cardiac arrest and provides the opportunity to rapidly induce therapeutic hypothermia. The survival after a cardiac arrest is related to post-arrest cardiac function, and the application of therapeutic hypothermia post-arrest is hypothesized to improve cardiac outcome. The present animal study compares normothermic and hypothermic E-CPR considering resuscitation success, post-arrest left ventricular function and magnitude of myocardial injury.MethodsAfter a 15-min untreated ventricular fibrillation, the pigs (n = 20) were randomized to either normothermic (38 °C) or hypothermic (32–33 °C) E-CPR. Defibrillation terminated ventricular fibrillation after 5 min of E-CPR, and extracorporeal support continued for 2 h, followed by warming, weaning and a stabilization period. Magnetic resonance imaging and left ventricle pressure measurements were used to assess left ventricular function pre-arrest and 5 h post-arrest. Myocardial injury was estimated by serum concentrations of cardiac TroponinT and Aspartate transaminase (ASAT).ResultsE-CPR resuscitated all animals and the hypothermic strategy induced therapeutic hypothermia within minutes without impairment of the resuscitation success rate. All animals suffered a severe global systolic left ventricular dysfunction post-arrest with 50–70% reductions in stroke volume, ejection fraction, wall thickening, strain and mitral annular plane systolic excursion. Serum concentrations of cardiac TroponinT and ASAT increased considerably post-arrest. No significant differences were found between the two groups.ConclusionsTwo-hour therapeutic hypothermia during E-CPR offers an equal resuscitation success rate, but does not preserve the post-arrest cardiac function nor reduce the magnitude of myocardial injury, compared to normothermic E-CPR. Trial registration FOTS 4611/13 registered 25 October 2012Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1099-y) contains supplementary material, which is available to authorized users.

Incidence, Risk Factors, and Outcome of Life-Threatening Ventricular Arrhythmias in Giant Cell Myocarditis.

Ventricular tachyarrhythmias are characteristic of giant cell myocarditis, but their true incidence, predictors, and outcome are unknown. Our work involved 51 patients with giant cell myocarditis (35 women) aged 52±12 years. Their medical records were reviewed for history, results of laboratory and imaging studies, and occurrence of serious cardiac events, including life-threatening ventricular tachyarrhythmias. Sudden cardiac death (fatal or aborted) was the primary end point of our analyses, whereas the composite of sudden cardiac death and ventricular tachycardia requiring treatment constituted the secondary end point. Giant cell myocarditis presented as nonfatal ventricular tachyarrhythmia in 10 patients and as a fatal cardiac arrest in 1 patient. Overall, 14 of 50 patients suffered a sudden cardiac death during follow-up, with a cumulative incidence of 22% at 1 year and 26% at 5 years from presentation. The composite incidence of sudden cardiac death or ventricular tachycardia was 41% at 1 year and 55% at 5 years. The incidence of arrhythmias was associated with high plasma concentrations of troponin-T and N-terminal brain natriuretic propeptide, as well as with moderate-to-severe fibrosis on myocardial biopsy and history of ventricular tachyarrhythmias at presentation (P<0.05 for all). An intracardiac cardioverter defibrillator was implanted in 31 patients, of whom 17 had altogether 114 appropriate antiarrhythmic therapies by the device and none suffered an arrhythmic death. In giant cell myocarditis, the risk of life-threatening ventricular arrhythmias exceeds 50% at 5 years from admission, being related to the presenting clinical manifestation and markers of myocardial injury and scarring.

Factors influencing troponin T concentration in patients with obstructive sleep apnea syndrome

Introduction. Obstructive sleep apnea syndrome (OSAS) is strongly associated with adverse cardiovascular outcomes, however the relation between OSAS severity and troponin T (TnT) remain unclear. Material and methods. Diagnosis and assessment of OSAS severity was based on non-supervised, overnight screening polysomnography (PSG) performed without an adaptation night. The study group consisted of 72 patients diagnosed with OSAS (including 31 with mild, 10 with moderate and 31 patients with severe OSAS), whereas the control group contained 16 individuals. PSG was performed with equipment fulfilling the criteria of type III diagnostic devices according to the American Academy of Sleep Medicine. Results. Revealed significant differences in troponin T levels between patients with severe OSAS and controls (p = 0.02) as well as in patients with severe and with mild OSAS (p = 0.04). The factors substantially affecting TnT concentrations were found to be apnea–hypopnea index (AHI), apnea index (AI), hypopnea index (HI) and minimum nocturnal saturation. Conclusions. The relationship between sleep apnea syndrome and the level of serum TnT confirms that OSAS predisposes to myocardial damage in a manner dependent on the severity of sleep apnea. The increase in troponin level is mainly associated with AHI and minimum nocturnal saturation. This suggests that early treatment of OSAS patients may protect against myocardial injury.

Protective effect of right coronary artery ischemic preconditioning on myocardial ischemia reperfusion injury in rabbit heart

To explore the protective effects of right coronary artery ischemic preconditioning and post-conditioning on myocardial ischemia reperfusion injury in rabbit heart. Methods: A total of 30 rabbits were randomly divided into 4 groups: a control group (n=7), an ischemia reperfusion group (IR group, n=8), an ischemic preconditioning group (IPC group, n=8) and an ischemic post-conditioning group (IPO group, n=7). Venous blood samples were taken at pre-operation, 1 and 6 h post-operation, and the concentration of serum creatine kinase isoenzyme (CK-MB) and cardiac troponin-T (cTn-T) were measured. The infarct area of cardiac muscle was calculated. Results: Compared with the IR group, the levels of CK-MB and cTn-T at 1 and 6 h post-operation in the IPC group and the IPO group were reduced (all P<0.05). Compared with the IR group, the infarct size in the IPC group and the IPO group was significantly decreased, with significant difference (both P<0.05) . Conclusion: Right coronary artery ischemic preconditioning and post-conditioning exert significant protective effects on the myocardial ischemia reperfusion injury in New Zealand rabbits.

High-density lipoprotein cholesterol values independently and inversely predict cardiac troponin T and I concentration.

This retrospective study was planned to establish potential associations between circulating values of cardiac troponins and those of conventional blood lipids. The study population consisted of patients attending an inpatient clinic of the University Hospital of Verona during the year 2015 as part of routine cardiovascular risk assessment. No exclusion criteria were applied. Serum lipids including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were measured using reference enzymatic techniques, whereas troponin T (TnT) was measured using a high-sensitivity (HS) immunoassay. A second analysis was also performed in the General Hospital of Verona, extracting data from the local laboratory database of all patients in whom troponin I (TnI) and blood lipids were simultaneously measured during the same year. In univariate analysis, HS-TnT was found to be associated with age, sex, TC, LDL-C, HDL-C, but not with TG. In multivariate linear regression analysis, age (positive correlation; P<0.001) and HDL-C (negative correlation; P=0.032) remained significantly associated with HS-TnT. The frequency of HS-TnT values >50 ng/L was higher in subjects with HDL-C <1 mmol/L than in those with HDL-C ≥1 mmol/L [odds ratio (OR), 1.84; 95% confidence interval (CI), 1.03-3.32]. The frequency of HS-TnT values >50 ng/L was also higher in elderly subjects than in younger ones (OR, 2.10; 95% CI, 1.15-3.84). The combination of age and HDL-C explained 35% of overall variability of TnT concentration. In the second analysis, HDL-C was also found to be an independent and negative predictor of TnI in multivariate linear regression analysis (P=0.010). The combination of age and HDL-C explained approximately 28% of the overall variability of TnI concentration. Our study suggests that HDL-C values inversely predict cardiac troponins concentration irrespective of age, sex and other blood lipids.

Effect of hydromorphone postconditioning on myocardial ischemia-reperfusion injury in isolated rat hearts and the role of mitochondrial permeability transition pore

Objective To investigate the effect of hydromorphone postconditioning on ischemia-reperfusion(I/R)injury in isolated rat hearts and the role of mitochondial permeability transition pore(mPTP). Methods Male Sprague-Dawley rats, aged 2–3 months, weighing 250–320 g, were used in the study.The rats were heparinized and anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg.The hearts were excised, and perfused in a Langendorff apparatus with K-H solution saturated with 95% O2-5% CO2 at 36.5–37.5 ℃.Forty isolated rat hearts were randomly divided into 4 groups(n=10 each)using a random number table: control group(group C), group I/R, hydromorphone postconditioning group(group H), and hydromorphone postconditioning + mPTP opener lonidamine group(group HL). Group C was continuously perfused with K-H solution for 120 min.Group I/R was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group I/R was perfused with K-H solution for another 30 min.Group H was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group H was perfused with K-H solution containing 0.3 μmol/L hydromorphone for 10 min, and then with K-H solution for 50 min.Group HL was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group HL was perfused with K-H solution containing 0.3 μmol/L hydromorphone and 30 μmol/L lonidamine for 10 min, and then with K-H solution for 50 min.At 30 min of equilibration(T0), and 30 and 60 min of reperfusion(T2, 3), left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVEDP), left ventricular developed pressure(LVDP), ±dp/dtmax, heart rate(HR), and coronary flow(CF)were measured.The concentrations of lactic dehydrogenase(LDH), creatine kinase-MB(CK-MB), and troponin-T(Tn-T)in the coronary effluent were determined at T0 and T3.The coronary effluent was collected at T0 and 15 min of reperfusion(T1), nicotinamide-adenine dinucleotide(NAD+ )concentrations were measured using enzyme-linked immunosorbent assay to reflect the degree of mPTP opening.The myocardial infarct size was determined at T3 by TTC staining. Results Compared with group C, LVDP, HR, ±dp/dtmax and CF were significantly decreased, and LVEDP was increased at T2, 3, and the concentrations of LDH, CK-MB and Tn-T in the coronary effluent, myocardial infarct size at T3, and NAD+ concentrations in the coronary effluent at T1 were increased in group I/R(P<0.05). Compared with I/R and HL groups, LVDP, ±dp/dtmax, CF and HR were significantly increased, and LVEDP was decreased at T2, 3, and the concentrations of LDH, CK-MB and Tn-T in the coronary effluent, myocardial infarct size at T3, and NAD+ concentrations in the coronary effluent at T1 were decreased in group H(P<0.05). Conclusion Hydromorphone postconditioning can reduce myocardial I/R injury in isolated rat hearts, and the mechanism is related to inhibition of mPTP opening. Key words: Hydromorphone; Myocardial reperfusion injury; Mitochondrial membrane transport proteins; Postconditioning

Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition.

BackgroundHalf a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition.ObjectiveTo determine malnutrition-induced echocardiographic disturbances and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model.Methods and ResultsFive-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet (AGE-REF, n = 12) for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8). Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased markedly in MAIZE relative to AGE-REF during week 5–7 (p≤0.001). There was overall no difference in plasma cardiac troponin-T between groups. However, further analysis revealed that release of cardiac troponin-T in plasma was more frequent in AGE-REF compared with MAIZE (OR: 4.8; 95%CI: 1.2–19.7; p = 0.03). However, when release occurred, cardiac troponin-T concentration was 6.9-fold higher (95%CI: 3.0–15.9; p<0.001) in MAIZE compared to AGE-REF. At week 7, the mean body weight in MAIZE was lower than AGE-REF (8.3 vs 32.4 kg, p<0.001), whereas heart-weight relative to body-weight was similar across the three groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (p<0.001) and 27% higher in MAIZE vs WEIGHT-REF (p = 0.025).ConclusionsMalnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide and it associates with cardiac injury by elevated cardiac troponin-T. Clinical studies are needed to see if the same applies for children suffering from malnutrition.

Serial measurement of N-terminal pro–B-type natriuretic peptide and cardiac troponin T for cardiovascular disease risk assessment in the Multi-Ethnic Study of Atherosclerosis (MESA)

N-terminal-pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (TnT) predict cardiovascular disease (CVD) risk in a variety of populations. Whether their predictive value varies by ethnicity is unknown. We sought to determine whether NT-proBNP and TnT improve prediction of incident coronary heart disease (CHD) and CVD, independent of CVD risk factors, in a multiethnic population; whether NT-proBNP improves prediction compared with the Framingham Risk Score or the Pooled Cohort Risk Equation; and whether a second NT-proBNP further improves prediction. Both NT-proBNP and TnT were measured in 5,592 MESA white, black, Hispanic, and Chinese participants (60% nonwhite; mean age 62.3 ± 10.3 years) in 2000 to 2002 and 2004 to 2005. We evaluated adjusted risk of incident CHD and CVD based on baseline and change in biomarker concentration. Participants were followed up through 2011 and incurred 370 CVD events (232 CHD). Concentrations of NT-proBNP and TnT varied by ethnicity. Both NT-proBNP and TnT were associated with an increased risk of events (adjusted hazard ratio [HR] for CHD [95% CI] for fifth quintile vs other 4 quintiles of NT-proBNP, 2.03 [1.50-2.76]; HR for CHD for detectable vs undetectable TnT, 3.95 [2.29-6.81]). N-terminal-pro-B-type natriuretic peptide improved risk prediction and classification compared with the Framingham Risk Score and the Pooled Cohort Risk Equation. Change in NT-proBNP was independently associated with events (HR for CHD per unit increase in ΔlogNT-proBNP, 1.95 [1.16-3.26]). None of the observed associations varied by ethnicity. Both NT-proBNP and TnT are predictors of incident CHD, independent of established risk factors and ethnicity, in a multiethnic population without known CVD. Change in NT-proBNP may add additional prognostic information.

Trastuzumab Induces an Immediate, Transient Volume Increase in Humans: A Randomised Placebo-Controlled Trial

BackgroundThe exact extent of and the mechanism by which trastuzumab causes cardiac side effects are not completely unravelled. We investigated the (cardiotoxic) side effects of trastuzumab in a relatively large homogeneous population. MethodsHealthy male volunteers (n=54) with a left ventricle ejection fraction (LVEF) >55% were administered 6mg/kg trastuzumab (n=46) IV in 90min in a placebo-controlled, parallel study. Placebo consisted of 0·9% NaCl (n=8). Assessments included body weight, routine and cardiac laboratory markers and serial echocardiographic examinations (8 placebo and 9 trastuzumab treated participants) up to 63days after dosing. Statistical analysis was done using repeated measurements of variance. FindingsFollowing trastuzumab infusion, fluid retention was observed: mean body weight increased over the first 4days post-administration with 0·4kg (95%-confidence interval: −0·2, 0·9, p=0·2261) compared to placebo, mean haemoglobin concentration decreased with 0·3mM (−0·6, −0·1; p=0·0043), as did haematocrit (−0·013L/L [−0·024, −0·002], p=0·0216), and protein (−2g/L [−4, −0], p=0·0443) and albumin (−2g/L [−3, −1], p<0·0001) concentrations. Elevations in NT-proBNP levels, parallel to the weight increase, were observed in individual cases, but not on a group level. Troponin-T concentrations did not increase.The only echocardiographic parameter that changed significantly at all studied dose levels was E/A-ratio, a load-dependent parameter: from 1·81 (SD 0·42) to 1·98 (0·31) 3–5days after administration, contrast to placebo of 0·57 (90%-CI: 0·21–0·93, p=0·0034). Ejection fraction and pulsed-wave Doppler recorded parameters remained unchanged. InterpretationSingle dose administration of trastuzumab in humans is associated with an immediate, transient extracellular volume increase, either as a primary or secondary (compensatory) response, which can be detected easily using routine clinical assessments. Echocardiographic changes, both short and long term, could not be found after single dose administration to drug-naive patients.

Biological variation of high sensitivity cardiac troponin-T in stable dialysis patients: implications for clinical practice.

Changes in high sensitivity cardiac troponin-T (hs-cTnT) concentrations may reflect either acute myocardial injury or biological variation. Distinguishing between these entities is essential to accurate diagnosis, however, the biological variation of hs-cTnT in dialysis population is currently unknown. We sought to estimate the within- and between-person coefficients of variation of hs-cTnT in stable dialysis patients, and derive the critical difference between measurements needed to exclude biological variation with 99% confidence. Fifty-five prevalent haemo- and peritoneal-dialysis patients attending two metropolitan hospitals were assessed on 10 consecutive occasions; weekly for 5 weeks then monthly for 4 months. Assessments were conducted at the same dialysis cycle time-point and entailed hs-cTnT testing, clinical review, electrocardiography, and bioimpedance spectroscopy. Patients were excluded if they developed clinical or physiological instability. In total 137 weekly and 114 monthly hs-cTnT measurements from 42 stable patients were analysed. Respective between- and within-person coefficients of variation were 83% and 7.9% for weekly measurements, and 79% and 12.6% for monthly measurements. Within-person variation was unaffected by dialysis modality or cardiac co-morbidity. The bidirectional 99% reference change value was -25% and +33% for weekly measurements, and -37% and +58% for monthly measurements. The between-person variation of hs-cTnT in the dialysis population is markedly greater than within-person variation indicating that hs-cTnT testing is best applied in this population using a relative change strategy. An increase of 33% or a reduction of 25% in serial hs-cTnT concentrations measured at weekly intervals excludes change due to analytical and biological variation alone with 99% confidence.

Left ventricular end-diastolic pressure and ejection fraction correlate independently with high-sensitivity cardiac troponin-T concentrations in stable heart failure

BackgroundCardiac troponin is widely accepted as a biomarker of myocyte injury in patients with myocardial ischemia. Patients with congestive heart failure are also associated with elevated cardiac troponin and it is a very sensitive prognostic marker. However, the mechanisms of troponin elevation in patients with heart failure are not fully understood. Decompensated state itself is suggested as a factor contributing to elevated cardiac troponin-T. However comparison between invasive hemodynamic parameters and cardiac troponin-T is insufficient. MethodsData were collected from 167 patients in stable, chronic HF, without acute coronary syndrome, recent revascularization, mitral stenoses, hemodialysis, or clinically significant right HF. We evaluated the correlations and 95% confidence intervals (CI) between invasive hemodynamic measurements and serum high-sensitivity (hs) concentrations of cTnT. ResultsThe serum cTnT concentration was equal to or more than the detection threshold (0.003ng/ml) in all patients. The serum cTnT concentration was equal to or more than the cut-off value of 0.014ng/ml in 46% of patients. By multiple variable analysis, left ventricular (LV) end-diastolic pressure (EDP; adjusted coefficient=0.014; 95% CI 0.0003–0.029; P=0.046) was positively correlated, while hemoglobin (adjusted coefficient=−0.079; 95% CI −0.140 to −0.018; P=0.012), estimated glomerular filtration rate (adjusted coefficient=−0.008; 95% CI −0.013 to −0.003; P=0.004), and LV ejection fraction (EF; adjusted coefficient=−0.011; 95% CI −0.018 to −0.003; P=0.004) were negatively correlated with hs-cTnT concentrations. ConclusionIn patients with stable chronic HF, LVEDP and LVEF correlate with the serum concentrations of hs-cTnT, independently of other correlates of elevated plasma concentrations of hs-cTnT.