Creatine Kinase Myocardial Bound Research Articles

Blood C-peptide concentration as a proxy marker of cardiovascular disease: An observational cross-sectional study.

Cardiovascular diseases (CVDs) are among the leading causes of disability and early death in sub-Saharan Africa. Most of the current blood tests for CVD diagnosis involve performing about three test profiles; often at additional cost to patients. C-peptide, a cleavage product of proinsulin, is a promising marker that has the potential to serve as a proxy marker for diagnosing CVDs in resource-poor settings. The study was an observational cross-sectional one and involved 127 consenting persons diagnosed with CVD and 127 individuals without CVD. The socio-demographic and clinical characteristics of participants were obtained. Blood levels of C-peptide, fasting plasma glucose (FPG), total creatinine kinase (CK), creatine kinase myocardial bound (CKMB), lactate dehydrogenase (LDH), propeptide of brain natriuretic peptide (PBNP), Troponin T, lipids, and biomarkers of kidney and liver function were analyzed using ELISA and an automated analyzer. Insulin resistance was computed using the modified homeostatic model assessment (HOMA-IR). The CVD Group had significantly higher levels of C-peptide, CK, CKMB, troponin T, PBNP, FPG, HOMA-IR, and several selected kidney, liver, and lipid parameters compared to the non-CVD Group (p < 0.05 for all). Troponin T recorded a positive correlation (r = 0.34, p < 0.001) with C-peptide among the CVD Group. The sensitivity and specificity of C-peptide in identifying CVD were 96.1% and 91.3% respectively (area under the curve = 0.938, p < 0.001). C-peptide levels were higher in the CVD Group and appeared to be a valuable (high sensitivity and specificity) biomarker in detecting CVD.

Clinical Spectrum of Neonatal Encephalopathy and the Role of CK-MB Assay in Transient Myocardial Ischaemia in Neonates with Hypoxic Ischaemic Encephalopathy: A Prospective Cohort Study

Introduction: Significant advancements have been made in the field of perinatal medicine through the use of newer monitoring technologies. However, birth asphyxia continues to cause prolonged hospitalisation due to multiple organ dysfunction and unfortunately, sometimes results in death. An elevation of the serum Creatine Kinase Myocardial Bound (CK-MB) fraction in myocardial ischaemia could indicate exposure to asphyxia and shock in neonates. Aim: The aim of this study was to examine the clinical spectrum of Neonatal Encephalopathy (NE) and investigate Transient Myocardial Ischaemia (TMI) in neonates with Hypoxic Ischaemic Encephalopathy (HIE) using CK-MB assay at birth, 24 hours, and 72 hours. Materials and Methods: A prospective clinical study was conducted in the Neonatal Intensive Care Unit (NICU) at a Tertiary Care Hospital in Tamil Nadu, India. The study duration was eight months, from January 2014 to August 2014. A total of 70 term neonates admitted with NE symptoms were included. Among them, 65 babies with evidence of asphyxia, such as an Appearance, Pulse, Grimace,Activity and respiration (APGAR) score less than 3 at five minutes, heart rate less than 60 Beats Per Minute (bpm), meconium-stained amniotic fluid, or the need for positive pressure ventilation for more than one minute, were evaluated for TMI. Myocardial involvement was assessed through clinical evaluation, chest X-ray (CXR), Electrocardiogram (ECG), Echocardiography (ECHO), and CK-MB assay at birth, 24 hours, and 72 hours. Statistical analysis was performed using Epi Info software version 7.0. Results: The mean Gestational Age (GA) of the study participants was 38.97±1.31 weeks. During the study period, 70 babies were admitted with NE symptoms, and HIE was the cause of encephalopathy in 65 babies. Other causes included hypoglycaemia, intraventricular haemorrhage, and bilirubin encephalopathy. Meconium staining of amniotic fluid was the most common intrapartum event in HIE babies. The survival rate in encephalopathy cases was 28.57%. Shock and respiratory failure were common complications in HIE, representing 46.15% and 44.61% respectively. Cardiomegaly in CXR, ST depression in ECG, Tricuspid Regurgitation (TR) in ECHO, and elevated CK-MB were commonly detected in babies with TMI associated with HIE. Conclusion: NE caused by HIE has a high mortality and morbidity rate. 83.3% of asphyxiated babies with shock had elevated CK-MB levels at birth, but the CK-MB values at 24 hours and 72 hours were not significantly elevated.

Visfatin Amplifies Cardiac Inflammation and Aggravates Cardiac Injury via the NF-κB p65 Signaling Pathway in LPS-Treated Mice.

Background Visfatin is an adipocytokine that has been demonstrated to be involved in cardiovascular diseases. This study aims at determining the role of visfatin in sepsis-induced cardiac injury and identify its possible mechanisms. Methods Dynamic changes in visfatin expression in mice with lipopolysaccharide- (LPS-) induced septicemia were measured. Additionally, mice were pretreated with visfatin and further administered LPS to observe the effects of visfatin on cardiac injury. Finally, septic mice were also pretreated with JSH-23 to investigate whether visfatin regulates cardiac injury via the NF-κB p65 pathway. Results Visfatin expression levels in both the heart and serum were increased in LPS-treated mice and peaked at 6 hours, and visfatin was derived from cardiac macrophages. In septic mice, pretreatment with visfatin reduced the survival rate, worsened cardiac dysfunction, and increased the expression of cardiac injury markers, including creatine kinase myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Treatment with visfatin also increased the infiltration of CD3+ cells and F4/80+ cells, amplified the cardiac inflammatory response, and elevated myocardial cell apoptosis. Treatment with JSH-23 reversed the effects of visfatin in septic mice. Conclusions This study showed that visfatin amplifies the cardiac inflammatory response and aggravates cardiac injury through the p65 signaling pathway. Visfatin may be a clinical target for preventing cardiac injury in sepsis.

Cardiac Injury Biomarkers and the Risk of Death in Patients with COVID-19: A Systematic Review and Meta-Analysis.

Background Cardiac complications may develop in a proportion of patients with the novel coronavirus disease (COVID-19), which may influence their prognosis. Objectives To assess the role of cardiac injury biomarkers measured on admission and during hospitalization as risk factors for subsequent death in COVID-19 patients. Methods A systematic review and meta-analysis was carried out involving cohort studies that compared the levels of cardiac injury biomarkers in surviving and dead COVID-19 patients. Cardiac injury is defined as an elevation of the definitive markers (cardiac troponin (cTnI and cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) above the 99th percentile upper reference limit. Secondary markers included creatine kinase-myocardial bound (CK-MB), myoglobin, interleukin-6 (IL-6), and C-reactive protein (CRP). The risk of death and the differences in marker concentrations were analyzed using risk ratios (RRs) and standardized mean differences (SMDs), respectively. Results Nine studies met the inclusion criteria (1799 patients, 53.36% males, 20.62% with cardiac injury). The risk of death was significantly higher in patients with elevated cTn than those with normal biomarker levels (RR = 5.28, P < 0.0001). Compared to survivors, dead patients had higher levels of cTn (SMD = 2.15, P=0.001), IL-6 (SMD = 3.13, P=0.03), hs-CRP (SMD = 2.78, P < 0.0001), and CK-MB (SMD = 0.97, P < 0.0001) on admission and a significant rise of plasma cTnT during hospitalization. Conclusion COVID-19 patients with elevated cTn on admission, possibly due to immune-mediated myocardial injury, are at increased risk for mortality. This requires further radiographic investigations, close monitoring, and aggressive care to reduce the risk of severe complications and death.

Anti-Interleukin-16 Neutralizing Antibody Treatment Alleviates Sepsis-Induced Cardiac Injury and Dysfunction via the Nuclear Factor Erythroid-2 Related Factor 2 Pathway in Mice

Several interleukin (IL) members have been reported to participate in sepsis. In this study, the effects of IL-16 on sepsis-induced cardiac injury and dysfunction were examined, and the related mechanisms were detected. IL-16 expression in septic mice was first measured, and the results showed that both cardiac and serum IL-16 expression levels were increased in mice with sepsis induced by LPS or cecal ligation and puncture (CLP) compared with control mice. Then, IL-16 was neutralized, and the effects on lipopolysaccharide- (LPS-) induced cardiac injury were detected. The results showed that an anti-IL-16 neutralizing antibody (nAb) significantly reduced mortality and increased serum lactate dehydrogenase (LDH), creatine kinase myocardial bound (CK-MB), and cardiac troponin T (cTnT) levels while improving cardiac function in mice with LPS-induced sepsis. Neutralization of IL-16 also increased the activation of antioxidant pathways and the expression of antioxidant factors in septic mice while decreasing the activation of prooxidant pathways and the expression of prooxidants. Treatment with the anti-IL-16 nAb increased mitochondrial apoptosis-inducing factor (AIF) expression, decreased nuclear AIF and cleaved poly-ADP-ribose polymerase (PARP) expression, and decreased TUNEL-positive cell percentages in LPS-treated mice. Additionally, treatment with CPUY192018, the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway, significantly increased mortality and reversed the above effects in mice treated with LPS and the anti-IL-16 nAb. Our results showed that the anti-IL-16 nAb regulates oxidative stress through the Nrf2 pathway and participates in the regulation of cardiac injury in septic mice. Neutralization of IL-16 may be a beneficial strategy for the prevention of cardiac injury and dysfunction in sepsis patients.

Resolvin E1 protects against doxorubicin-induced cardiotoxicity by inhibiting oxidative stress, autophagy and apoptosis by targeting AKT/mTOR signaling

Doxorubicin (DOX)-induced cardiotoxicity impairs the quality of life of cancer patients during or after DOX treatment, and it is imperative to explore a novel strategy to address this problem. Resolvin E1 (RvE1) is derived from eicosapentaenoic acid (EPA), which has been reported to exert beneficial effects on DOX-induced oxidative stress in cardiomyocytes. This study was designed to investigate whether RvE1 protects against DOX-induced cardiotoxicity, and the underlying mechanism was explored. DOX (20 mg/kg, one injection, i.p.) was used to induce DOX-induced cardiotoxicity in C57BL/6 mice. At 5 days after DOX administration, the effect of RvE1 was assessed by measuring cardiac function, oxidative stress, autophagy and apoptosis in cardiac tissue. We used an AKT inhibitor and rapamycin to investigate the underlying mechanisms. Our results showed that RvE1 inhibited the DOX-induced decrease in body weight and heart weight, the reduction in left ventricular ejection fraction and fractional shortening, and the increase in lactate dehydrogenase, creatine kinase myocardial bound and cardiomyocyte vacuolization. Compared to the control group, the DOX group exhibited increased oxidative stress, autophagy and apoptosis in cardiac tissue, which were alleviated by treatment with RvE1. The AKT/mTOR signaling pathways were responsible for RvE1-mediated regulation of DOX-induced oxidative stress, autophagy and myocardial apoptosis. In conclusion, RvE1 protected against DOX-induced cardiotoxicity via the regulation of AKT/mTOR signaling.

The Anti-inflammatory Mediator Resolvin E1 Protects Mice Against Lipopolysaccharide-Induced Heart Injury.

BackgroundSepsis-induced cardiomyopathy (SIC) is a common severe complication of sepsis that contributes to mortality. SIC is closely associated with excessive inflammatory responses, failed inflammation resolution, and apoptotic damage. Resolvin E1 (RvE1), an omega-3 polyunsaturated fatty acid (PUFA)-derived metabolite, has been reported to exert anti-inflammatory or proresolving activity in multiple animal models of inflammatory disease. However, the therapeutic potential of RvE1 in SIC remains undetermined, which was, therefore, the aim of the present study.MethodsC57BL/6J mice were randomly divided into three groups: control, lipopolysaccharide (LPS), and LPS + RvE1. Echocardiography, Western blotting (WB), quantitative real-time (QRT)-PCR, histological analyses, and flow cytometry were used to evaluate cardiac function, myocardial inflammation, and the underlying mechanisms.ResultsThe RvE1-injected group showed improved left ventricular (LV) function and reduced serum lactate dehydrogenase (LDH) and creatine kinase myocardial bound (CK-MB) levels. Compared to LPS treatment alone, RvE1 treatment inhibited the infiltration of neutrophils and macrophages into the heart and spleen and suppressed the secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1, in the heart. We also observed that the activation of the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways was blocked by RvE1 treatment, and this inhibition contributed to the improvement in the inflammatory response induced by LPS. RvE1 inhibited LPS-induced M1 macrophage polarization and promoted macrophage polarization toward the M2-like phenotype in both the heart and spleen. In addition, LPS administration dysregulated cyclooxygenase (COX) and lipoxygenase (LOX) in the heart, which were rectified by RvE1 treatment. RvE1 also reduced myocardial apoptosis rate in response to LPS-induced heart injury.ConclusionRvE1 protects the heart against SIC possibly through the inhibition of the MAPK and NF-κB inflammatory signaling pathways, modulation of macrophage polarization, and reduction in myocardial apoptosis. RvE1 may be a novel lipid mediator for the treatment of SIC.

Cardioprotective effects of propofol-dexmedetomidine in open-heart surgery: A prospective double-blind study.

Background:Myocardial protection in cardiac surgeries is a must and requires multimodal approaches in perioperative period to decrease and prevent the increase of myocardial oxygen demand and consumption that lead to postoperative cardiac complications including myocardial ischemia, dysfunction, and heart failure.Study Design:Prospective, controlled, randomized, double-blinded study.Aims:This study aims to study the effect of propofol-dexmedetomidine continuous infusion cardioprotection during open-heart surgery in adult patients.Materials and Methods:Sixty adult patients of both sexes aged from 30 to 60 years old belonging to the American Society of Anesthesiologists III or IV undergoing open-heart surgery were randomly divided into two equal groups: Group P (control group) received continuous infusion of propofol at a rate of 2 mg/kg/h and 50 cc 0.9% sodium chloride solution infused at a rate of 0.4 μg/kg/h (used as a placebo) and Group PD received continuous infusion of propofol at a rate of 2 mg/kg/h and dexmedetomidine 200 μg diluted in 50 cc 0.9% sodium chloride solution infused at a rate of 0.4 μg/kg/h. Infusion for all patients started immediately preoperative till skin closure. Hemodynamic measurements of heart rate (HR), invasive mean arterial pressure, and oxygen saturation were recorded at baseline before induction of anesthesia, immediately after intubation, at skin incision, at sternotomy and every 15 min in the 1st h then every 30 min during the prebypass period then every 15 min in the 1st h then every 30 min after weaning from CPB till the end of the surgery. Serum biomarkers; cardiac troponin (cTnI) and creatine kinase-myocardial bound (CK-MB) samples were measured basally (T1), 15 min after unclamping of the aorta (T2), immediate postoperative (T3), and 24 h postoperative (T4). Intraoperative data were also recorded including the number of coronary grafts, aortic cross-clamping duration, duration of cardiopulmonary bypass (CPB), duration of surgery, and rhythm of reperfusion. Fentanyl requirement, extubation time, and length of intensive care unit (ICU) stay were also recorded for every case.Results:There was no statistically significant differences as regard to demographic data between the studied two groups. HR and blood pressure recorded was lower in the PD group than the control group, and this difference was noted to be statistically significant. Furthermore, the PD group showed lower levels of myocardial enzymes (cTnI and CK-MB), decreased total fentanyl requirement, earlier postoperative extubation, and shorter ICU stay than the P (control) group.Conclusion:The use of propofol-dexmedetomidine in CPB surgeries offers more cardioprotective effects than the use of propofol alone.

Involvement of neurotrophic signaling in doxorubicin‑induced cardiotoxicity

Dose dependent cardiotoxicity is the primary side effect of doxorubicin (DOX), but the underlying molecular mechanisms remain unclear. An increasing amount of evidence has demonstrated that neurotrophic signaling plays a pivotal role in both neurons and the heart, but the biological association between neurotrophic signaling and DOX-induced cardiotoxicity remains unknown. The present study determined the level of neurotrophins and their receptors in the heart of rats following DOX administration. DOX was administered 7 times at a dose of 2.5 mg/kg once every 2 days via intraperitoneal injection. The present study revealed that cardiac injury parameters, such as creatine kinase (CK), creatine kinase-myocardial bound, lactate dehydrogenase, troponin T and aspartate transaminase in serum were significantly increased in the DOX group. Both the gene and protein expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the heart were markedly decreased following DOX treatment. Notably, the protein level of BDNF in the serum was inhibited in DOX-treated rats, whereas DOX induced a significant increase in the protein level of NGF in the serum. DOX induced a significant decrease in the level of tropomyosin-associated kinase A (TrkA) and the ratio of pTrkA/TrkA and pTrkB/TrkB. Furthermore, the administration of DOX suppressed downstream protein kinase B and extracellular signal regulated kinase phosphorylation. The present study first demonstrated that BDNF/TrkB signaling and NGF/TrkA signaling were altered by DOX, which indicated that neurotrophic signaling was involved in DOX-induced cardiotoxicity.

MicroRNA-146a improves sepsis-induced cardiomyopathy by regulating the TLR-4/NF-κB signaling pathway.

The aim of the current study was to investigate the regulatory effect of miR-146a on the toll-like receptor 4 (TLR-4)/NF-κB pathway and therefore inflammation in septic cardiomyopathy. A total of 60 healthy male Sprague Dawley rats were equally divided into a control, LPS, miR-146a agonist and miR-146a inhibitor group. Blood samples were collected from rats 24 h after intraperitoneal lipopolysaccharide injection and myocardial tissues were subsequently collected. After hematoxylin and eosin staining of rat myocardial tissues, the degree of inflammatory cell infiltration and myocardial damage was observed. The content of certain myocardial injury markers were also observed, including cardiac troponin I (cTnI), B-type natriuretic peptide (BNP), creatine kinase myocardial bound (CK-MB) and myoglobin (Mb). Western blot analysis was performed to detect the expression of NF-κB/TLR-4, tumor necrosis factor (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) in myocardial tissues. Reverse transcription-quantitative (RT-q) PCR was used to detect the expression of miR-146a, TNF-α, interleukin (IL)-1α and IL-1β mRNA in myocardial tissues. In the LPS group, myocardial interstitial tissue edema occurred, with enlarged and loosely arranged cardiomyocytes. Compared with the sepsis model group, myocardial interstitial tissue edema was relieved in the miR-146a agonist group, but was aggravated in the miR-146a inhibition group. The serum levels of cTnI, BNP, CK-MB, Mb, NF-κB, TLR-4, TNF-α and ICAM-1 in the sepsis model group were higher than those in the control group. In the miR-146a agonist group, levels of myocardial injury markers were lower than those in the sepsis model group, but were higher in the miR-146a inhibition group. The results of RT-qPCR demonstrated that the expression of miR-146a, TNF-α, IL-1α and IL-1β in the sepsis model group were upregulated compared with the control group. In addition, miR-146a expression in the miR-146a agonist group and the miR-146a inhibition group was increased, but TNF-α, IL-1α and IL-1β mRNA was downregulated. miR-146a may regulate the TLR-4/NF-κB signaling pathway via negative feedback mechanisms, leading to the improvement of the inflammatory response and cardiac dysfunction in sepsis-induced cardiomyopathy.

β-Caryophyllene as a Potential Protective Agent Against Myocardial Injury: The Role of Toll-Like Receptors.

Myocardial infarction (MI) remains one of the major causes of mortality around the world. A possible mechanism involved in myocardial infarction is the engagement of Toll-like receptors (TLRs). This study was intended to discover the prospective cardioprotective actions of β-caryophyllene, a natural sesquiterpene, to ameliorate isoproterenol (ISO)-induced myocardial infarction through HSP-60/TLR/MyD88/NFκB pathway. β-Caryophyllene (100 or 200 mg/kg/day orally) was administered for 21 days then MI was induced via ISO (85 mg/kg, subcutaneous) on 20th and 21st days. The results indicated that ISO induced a significant infarcted area associated with several alterations in the electrocardiogram (ECG) and blood pressure (BP) indices and caused an increase in numerous cardiac indicators such as creatine phosphokinase (CPK), creatine kinase-myocardial bound (CK-MB), lactate dehydrogenase (LDH), and cardiac tropinine T (cTnT). In addition, ISO significantly amplified heat shock protein 60 (HSP-60) and other inflammatory markers, such as TNF-α, IL-Iβ, and NFκB, and affected TLR2 and TLR4 expression and their adaptor proteins; Myeloid differentiation primary response 88 (MYD88), and TIR-domain-containing adapter-inducing interferon-β (TRIF). On the other hand, consumption of β-caryophyllene significantly reversed the infarcted size, ECG and BP alterations, ameliorated the ISO elevation in cardiac indicators; it also notably diminished HSP-60, and subsequently TLR2, TLR4, MYD88, and TRIF expression, with a substantial reduction in inflammatory mediator levels. This study revealed the cardioprotective effect of β-caryophyllene against MI through inhibiting HSP-60/TLR/MyD88/NFκB signaling pathways.

Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis and Autophagy in Mice.

BackgroundRecent evidence has demonstrated that interleukin 12p35 knockout (IL-12p35 KO) is involved in cardiac diseases by regulating the inflammatory response. The involvement of inflammatory cells has also been observed in doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate whether IL-12p35 KO affects DOX-induced cardiac injury and the underlying mechanisms.MethodsFirst, the effect of DOX treatment on cardiac IL-12p35 expression was assessed. In addition, to investigate the effect of IL-12p35 KO on DOX-induced cardiac injury, IL-12p35 KO mice were treated with DOX. Because IL-12p35 is the mutual subunit of IL-12 and IL-35, to determine the cytokine that mediates the effect of IL-12p35 KO on DOX-induced cardiac injury, mice were given phosphate-buffered saline (PBS), mouse recombinant IL-12 (rIL-12) or rIL-35 before treatment with DOX.ResultsDOX treatment significantly increased the level of cardiac IL-12p35 expression. In addition, IL-12p35 KO mice exhibited higher serum and heart lactate dehydrogenase levels, higher serum and heart creatine kinase myocardial bound levels, and greater cardiac dysfunction than DOX-treated mice. Furthermore, IL-12p35 KO further increased M1 macrophage and decreased M2 macrophage differentiation, aggravated the imbalance of oxidants and antioxidants, and further activated the mitochondrial apoptotic pathway and endoplasmic reticulum stress autophagy pathway. Both rIL-12 and rIL-35 protected against DOX-induced cardiac injury by alleviating the inflammatory response, oxidative stress, apoptosis and autophagy.ConclusionsIL-12p35 KO aggravated DOX-induced cardiac injury by amplifying the levels of inflammation, oxidative stress, apoptosis and autophagy. (234 words).

Cyanobacteria as Nanogold Factories: Chemical and Anti-Myocardial Infarction Properties of Gold Nanoparticles Synthesized by Lyngbya majuscula

To the best of our knowledge, cyanobacterial strains from the Arabian Gulf have never been investigated with respect to their potential for nanoparticle production. Lyngbya majuscula was isolated from the AlOqair area, Al-Ahsa Government, Eastern Province, Kingdom of Saudi Arabia. The cyanobacterium was initially incubated with 1500 mg/mL of HAuCl4 for two days. The blue-green strain turned purple, which indicated the intracellular formation of gold nanoparticles. Prolonged incubation for over two months triggered the extracellular production of nanogold particles. UV-visible spectroscopy measurements indicated the presence of a resonance plasmon band at ~535 nm, whereas electron microscopy scanning indicated the presence of gold nanoparticles with an average diameter of 41.7 ± 0.2 nm. The antioxidant and anti-myocardial infarction activities of the cyanobacterial extract, the gold nanoparticle solution, and a combination of both were investigated in animal models. Isoproterenol (100 mg/kg, SC (sub cutaneous)) was injected into experimental rats for three days to induce a state of myocardial infarction; then the animals were given cyanobacterial extract (200 mg/kg/day, IP (intra peritoneal)), gold nanoparticles (200 mg/kg/day, IP), ora mixture of both for 14 days. Cardiac biomarkers, electrocardiogram (ECG), blood pressure, and antioxidant enzymes were determined as indicators of myocardial infarction. The results showed that isoproterenol elevates ST and QT segments and increases heart rate and serum activities of creatine phosphokinase (CPK), creatine kinase-myocardial bound (CP-MB), and cardiac troponin T (cTnT). It also reduces heart tissue content of glutathione peroxidase (GRx) and superoxide dismutase (SOD), and the arterial pressure indices of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP). Gold nanoparticles alone or in combination with cyanobacterial extract produced an inhibitory effect on isoproterenol-induced changes in serum cardiac injury markers, ECG, arterial pressure indices, and antioxidant capabilities of the heart.

In Vivo Protective Effects of Diosgenin against Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (DOX) induces oxidative stress leading to cardiotoxicity. Diosgenin, a steroidal saponin of Dioscorea opposita, has been reported to have antioxidant activity. Our study was aimed to find out the protective effect of diosgenin against DOX-induced cardiotoxicity in mice. DOX treatment led to a significant decrease in the ratio of heart weight to body weight, and increases in the blood pressure and the serum levels of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and creatine kinase myocardial bound (CK-MB), markers of cardiotoxicity. In the heart tissue of the DOX-treated mice, DOX reduced activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPx), were recovered by diosgenin. Diosgenin also decreased the serum levels of cardiotoxicity markers, cardiac levels of thiobarbituric acid relative substances (TBARS) and reactive oxygen species (ROS), caspase-3 activation, and mitochondrial dysfunction, as well as the expression of nuclear factor kappa B (NF-κB), an inflammatory factor. Moreover, diosgenin had the effects of increasing the cardiac levels of cGMP via modulation of phosphodiesterase-5 (PDE5) activity, and in improving myocardial fibrosis in the DOX-treated mice. Molecular data showed that the protective effects of diosgenin might be mediated via regulation of protein kinase A (PKA) and p38. Our data imply that diosgenin possesses antioxidant and anti-apoptotic activities, and cGMP modulation effect, which in turn protect the heart from the DOX-induced cardiotoxicity.

Ultrastructural changes, increased oxidative stress, inflammation, and altered cardiac hypertrophic gene expressions in heart tissues of rats exposed to incense smoke.

Incense smoke exposure has recently been linked to cardiovascular disease risk, heart rate variability, and endothelial dysfunction. To test the possible underlying mechanisms, oxidative stress, and inflammatory markers, gene expressions of cardiac hypertrophic and xenobiotic-metabolizing enzymes and ultrastructural changes were measured, respectively, using standard, ELISA-based, real-time PCR, and transmission electron microscope procedures in heart tissues of Wistar rats after chronically exposing to Arabian incense. Malondialdehyde, tumor necrosis alpha (TNF)-α, and IL-4 levels were significantly increased, while catalase and glutathione levels were significantly declined in incense smoke-exposed rats. Incense smoke exposure also resulted in a significant increase in atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain, CYP1A1 and CYP1A2 messenger RNAs (mRNAs). Rats exposed to incense smoke displayed marked ultrastructural changes in heart muscle with distinct cardiac hypertrophy, which correlated with the augmented hypertrophic gene expression as well as markers of cardiac damage including creatine kinase-myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Increased oxidative stress, inflammation, altered cardiac hypertrophic gene expression, tissue damage, and architectural changes in the heart may collectively contribute to increased cardiovascular disease risk in individuals exposed to incense smoke. Increased gene expressions of CYP1A1 and CYP1A2 may be instrumental in the incense smoke-induced oxidative stress and inflammation. Thus, incense smoke can be considered as a potential environmental pollutant and its long-term exposure may negatively impact human health.

Relationship of high sensitivity C-reactive protein with cardiac biomarkers in patients presenting with acute coronary syndrome.

To determine high sensitivity C-reactive protein (hsCRP) levels in patients with acute myocardial infarction (AMI) and its correlation with classical enzyme markers of myocardial damage. Observational study. Department of Emergency Medicine at King Khalid University Hospital, King Saud University, Riyadh and Department of Physiology, from August 2010 to December 2011. Consecutive eligible patients with either ST elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI) who were admitted to the Emergency Department of King Khalid University Hospital were recruited. A total of 71 subjects were finally selected for the study. The hsCRP, Troponin I (Trop I), creatine kinase myocardial bound (CK-MB), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) concentrations of all patients with an acute myocardial infarction (AMI) were measured. Among all patients 34 (47.9%) patients had diabetes mellitus, 21 (29.6%) were hypertensive, and 16 (22.5%) had no associated illness. Patients with STEMI had significantly higher levels of CKMB (p=0.0348), LDH (p=0.0471) and hsCRP (p=0.0231) compared to NSTEMI patients. While the differences were non-significant for Trop I (p=0.7022), AST (p=0.9729) and Lp(a) (p=0.5985). Spearman's correlations revealed that CRP correlated significantly with Trop I, CK-MB and LDH. There was a significant predictive relationship of hsCRP with Trop I, LDH and CK-MB while with AST it was nonsignificant. High sensitivity CRP levels is a significant predictor of standard markers for myocardial damage and it may be a useful prognostic marker in acute coronary syndromes.

Heat Shock Protein Expression During Cardiac Surgery

There has been a great deal of interest in a group of cellular proteins collectively called heat shock proteins (HSPs) to identify their role in the inflammatory and cell-mediated responses that occur during heart surgery [1]. Although most patients do fine after cardiopulmonary bypass (CPB), some develop an inflammatory response clinically resembling a sepsis-like state. At the cellular level, several stressrelated proteins, clustered as HSPs, participate in the inflammatory cascade mostly by acting as chaperons. Their basic role is to maintain the structural integrity of proteins under stress states by keeping them in their folded state, but their overexpression can lead to an inflammatory response. The ex vivo environment created during CPB exposes blood to nonendothelial circuitry, thereby triggering responses in the complement, coagulation, and humoral cascades. Chaperone HSPs play a significant role in inciting and modulating these triggers and responses. HSP-60, for example, is mostly intracellular; but in stress states it is overexpressed on endothelial cells. This protein is taken up by macrophages, which in turn cause it to trigger the immune system by signaling T and B lymphocytes. An HSP-60 lipopolysaccharide (LPS) complex then activates dendritic cells, causing release of interferon-c (INFc) and interleukin-12 (IL-12). This complex depends on toll-like receptors (TLRs) to gain entry into the cell via CD14 receptors. TLR 2, along with HSP-60, causes a T-cell response that down-regulates the secretion of tumor necrosis factor-a (TNFa) and INF c and up-regulates the secretion of transforming growth factor-b (TGFb) and IL-10. Intracellularly, the HSP60–LPS complex assembles nuclear factor jB (NF-jB) components, which in turn lead to initiation of cytokines, chemokines, and growth factor synthesis. This cascade leads to the hyperdynamic sepsislike syndrome sometimes seen following CPB. The HSP-70s are yet another complex set of proteins that include HSP-73, HSP-72, HSP-70 (which is stress inducible), and HSP70L1. This HSP family, however, is protective in nature. In stress states, HSP-70 enters the nucleus and activates poly (ADP-ribose) polymerase enzyme, involved in DNA repair. Overexpression of the latter enzyme can cause cellular energy depletion by overconsumption of ATP and NAD? often seen after rapid reperfusion. The deleterious effects of poly (ADP-ribose) polymerase can be neutralized by HSP-70 synthesized by inducing heat shock. This family of proteins also stabilizes the membranes of lysosomes, thereby preventing autolysis and apoptosis. HSP-70 is released into the extracellular compartment and also uses the CD-14 receptor along with TLR-2 and TLR-4 to stimulate nucleic synthesis of NK-jB, ultimately leading to monocyte stimulation. HSP70 is detected after cardiac surgery and more so during myocardial damage wherein high expression correlates with high creatine kinase, myocardial bound (CK-MB) and troponin-T levels. Its expression peaks 2 h after surgery and is fourfold lower during off-pump heart surgery compared to on-pump heart surgery. This is unlike HSP-60 levels, which seem to be unaffected regardless of whether CPB is used [2]. Other proteins that are increased during CPB include HSP-27, which prevents apoptosis by halting activation of caspase through sequestering cytochrome c and procaspase 3 and by stabilizing the cytoskeleton. Its levels rise with stress and decline when stress is attenuated; and it is increased twofold with use of CPB. HSP-90a is another A. Z. Chaudhry M. D. Diodato M. G. Massad (&) Division of Cardiothoracic Surgery, University of Illinois at Chicago, 840 S. Wood Street, CSB Suite 417(MC 958), Chicago, IL 60612, USA e-mail: mmassad@uic.edu

Evolution of Anticoagulant and Antiplatelet Therapy: Benefits and Risks of Contemporary Pharmacologic Agents and Their Implications for Myonecrosis and Bleeding in Percutaneous Coronary Intervention

Periprocedural myonecrosis, as evidenced by elevated creatine kinase-myocardial bound (CK-MB) levels, occurs in up to 25% of patients undergoing percutaneous coronary intervention (PCI) and has been linked with an increased risk of adverse short- and long-term clinical outcomes. Such myonecrosis arises from three main pathophysiological mechanisms: procedure-related complications, lesion-specific characteristics (e.g., large thrombus burden, plaque volume), and patient-specific characteristics (e.g., genetic predisposition, arterial inflammation). Periprocedural myonecrosis has not been definitively identified as the cause of postprocedural ischemic events, although agents that reduce or prevent thrombosis--including aspirin, thienopyridines, heparin, low-molecular-weight heparins, glycoprotein IIb/IIIa inhibitors, and direct thrombin inhibitors--have been shown to reduce the incidence of ischemic outcomes in this population, as have agents that reduce inflammation (aspirin, statins). At the same time, antithrombotic agents are known to increase the risk of bleeding and the use of transfusions, which have likewise been associated with worse outcomes in these patients. Thus, optimal management of patients undergoing PCI represents a balance between minimizing the risk of ischemic outcomes and simultaneously minimizing the risk of major bleeding. It may be that patients who have only minor, untreated postprocedural elevations in CK-MB level (with no clinical or angiographic signs of ischemia) might have a better prognosis than patients who have normal CK-MB levels but who suffer major bleeding complications.