Creatinine kinase-MB Research Articles

Dose and Time Dependent Protective Effects of Apocyanin and Curcumin Against Diclofenac-Induced Cardiotoxicity in Male Rats

This study explored the protective potential of apocyanin and curcumin in diclofenac-induced cardiotoxicity utilizing cardiac enzymes, pro-inflammatory markers, and along with histopathological endpoints. A total of 123 male Wistar rats were used for the study. 43 rats were used for the determination of the median lethal dose (LD50) of apocyanin and curcumin while 80 rats were randomly divided into 8 groups of 10 rats each. Group 1(control) received distilled water while others received orally, per mg/kg body weight of treatments as follows: group 2(1000, apocyanin, group 3(1000, curcumin), group 4(10, diclofenac), group 5(500, apocyanin and 10, diclofenac), group 6(1000, apocyanin and 10, diclofenac), group 7(500, curcumin and 10, diclofenac) and group 8(1000, curcumin and 10, diclofenac). The treatments were administered daily for 14 and 28 days. LD50 up to 5000mg/kg body weight of apocyanin and curcumin did not show any fatality in animals. Administration of diclofenac significantly (p < 0.05) elevated the activities of creatinine kinase-MB, lactate dehydrogenase, levels of troponin-T, and tumor necrosis factor. There was no alteration in the activities of Interleukin- 1β. The histological results also showed cardiac insults such as cardiac muscle having severe fibro collagenous stroma, reduced myocytes density, and thick wall blood vessels. However, pretreatment with 500 and 1000 mg/kg body weight of apocyanin or curcumin attenuated all biochemical alterations and histological lesions induced by diclofenac in a dose-dependent manner. Pretreatments with apocyanin and curcumin inhibitors of NADPH oxidases 2weres effective in ameliorating diclofenac-induced cardiotoxicity suppressing inflammation and restoring normal histological architecture, thus, highlighting the therapeutic potentials of apocyanin and curcumin in the management of diclofenac-mediated cardiotoxicity.

Cardiac Troponin-I, A Biomarker for Predicting COVID-Induced Myocardial Damage Prognosis.

To analyse the utility of cardiac Troponin-I as a prognostic marker in COVID-19-induced myocardial injury. A descriptive study. Place and Duration of the Study: COVID Intensive Therapeutic Unit (ITC) and Pathology Department, Combined Military Hospital (CMH), Malir, Karachi, from September 2021 to February 2022. Patients with chest pain, who tested positive for COVID-19 by real-time PCR, were inducted. Blood samples were screened for inflammatory and cardiac biomarkers. The levels of cardiac Troponin I (cTn-I) were categorised as normal (99th percentile = ≤0.01 ng/ml), raised (5 times the 99th percentile = >0.01 ng/ml), and markedly raised (>10 times the 99th percentile = >10 ng/ml) based on serial monitoring over a duration of 6-8 hours. Out of a total of 104 patients, the mean age was 48 ± 15.94 years; 78 (75%) were males and 26 (25%) were females. The mean levels of cardiac Troponin I (cTn-I) were 1.91 ng/ml, C-reactive protein (CRP) was 85 mg/l, Interleukin-6 (IL-6) was 43.3 ng/ml, Procalcitonin (PCT) was 1.40 ng/ml, Creatinine Kinase (CK) was 203 U/l, CK MB was 31 U/l, and Ferritin was 471 ng/ml. Forty-four (42.4%) had normal cTn-I levels, 38 (36.5%) had raised levels, and 22 (21.1%) had markedly raised levels. A persistent rising pattern of cTn-I with a maximum rise up to 30 ng/ml was observed in 16 patients (15.3%) labelled as myocarditis, while only 8 (7.6%) showed a rise-fall pattern. Cardiac Tn-I and CRP were significantly higher in patients with myocarditis (p <0.01). Six out of 104 patients (5.7%) died due to COVID- induced myocardial injury all having raised cTn-I. Cardiac Troponin-I is an effective biomarker for measuring myocardial injury in COVID-19 patients and can be an independent predictor to assess for severity of cardiac injury than other inflammatory markers in COVID-19. COVID-19, Cardiac Troponin I, Inflammatory markers, Myocardial injury, Prognosis.

PO-02-034 PULSED-FIELD ABLATION OF ATRIAL FIBRILLATION: KINETIC OF RELEASE OF MULTIPLE CARDIAC BIOMARKERS

Different studies have showed data on the variation of cardiac biomarkers after a thermal energy approach (i.e. cryoablation or radiofrequency) for the ablation of atrial fibrillation (AF). To date, when a non-thermal energy is used, such as electroporation obtained by means of a pulsed-field ablation (PFA), the kinetic of release of multiple cardiac biomarkers has not yet been clarified. We studied the pattern of release of 6 different biomarkers prior and after PFA of AF. All consecutive patients (pts) indicated for AF ablation who received a PFA treatment with the new PFA catheter (FARAWAVE) at our center were included. PVI was obtained using 2 kV with 8 applications per vein with additional lesions delivered at the operator’s discretion. Samples of cardiac troponin I (cTnI, ng/l), creatinine kinase-MB (CK-MB, ng/dl), fibrinogen (FB, mg/dl), myoglobin (MY, ng/ml), N-terminal (NT)-pro hormone B-type natriuretic peptide (NT-ProBNP, pg/ml) and C-reactive protein (CRP, mg/dl) were collected before PFA ablation (baseline) and at 3h, 24h and 48h after ablation. Data are reported as mean±SD. We analyzed data from a total of 25 pts (64±11 years, 52% male, 68% with paroxysmal AF). A total of 36±3 PFA deliveries was required to achieve PVI. In ten cases an additional set of PFA lesions was performed (25±6 PFA deliveries). No significant differences were found between baseline and 3h, 24h and 48h for both FB and NT-ProBNP (Panel a,b). On the contrary, MY level significantly increased from baseline at 3h and decreased at 24h and restored at 48h (Panel c). CRP values remained stable at 3h and significantly increased from baseline after 24h and 48h (Panel d). Kinetics of CK-MB and cTnI were similar: they both significantly increased after 3h and decreased after 24h and 48h (Panel e,f). No correlation was found between the total number of PFA deliveries and kinetics of different biomarkers after 3h, 24h and 48h. CK-MB, cTnI, and MY increased at 3h and have a recover towards lower values already after 24h. Cardiac enzyme elevations were not correlated with the number of PFA deliveries after AF ablation.

Metabolite profiling and Ameliorative effect of quince (Cydonia oblonga) leaves against doxorubicin induced cardiotoxicity in Wistar rats

Quince (Cydonia oblonga) leaves are traditionally reported to alleviate the risk of cardiovascular disease. The study envisaged to explore the in vitro and in vivo phytochemical and cardio protective potential of quince extract respectively. Different solvent extracts (Aqueous, Ethanolic, Hydroethanolic, Methanolic) of quince leaf obtained via two different extraction methods (Ultrasonication and Reflux) were evaluated for the phytochemical and antioxidant analysis. Among all the extracts, quince ethanolic extract, extracted via sonication was found to have the maximum phenolics (39.89 ± 0.67 mg GAE/g DW), flavonoids (21.51 ± 1.0 mgRE/g DW) and an anti-oxidant potential 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) with IC50 value of 168.88 ± 2.24 μg/ml. The High-performance thin layer chromatograph (HPTLC) and ultrahigh performance liquid chromatography mass spectrometry (UPLC-MS) analysis confirmed the presence of bio active compounds. Furthermore, the in vivo activity was ascertained against Doxorubicin (DOX) induced cardio toxicity in rats fed orally with the extract at 160 and 320 mg/kg body weight. The pre-treated groups significantly assuaged the changes induced by DOX in the electrocardiogram (ECG). Additionally, it mitigated the elevation in the blood serum parameters; aspartate transaminase (AST), lactate dehydrogenase (LDH), creatinine kinase-MB (CK- MB) and also repressed glutathione (GSH) depletion and rise in malondialdehyde (MDA) level induced by DOX. Furthermore, improvement in histopathological changes of the heart tissue concomitant to DOX induced toxicity was also observed such as, reduced degeneration, necrosis, inflammation and apoptosis. Thus, it could be concluded that cardioprotective activity of quince extract accredited to the occurrence of phytoconstituents prevented the DOX induced cardiotoxicity and helped to reinstate the cardiac damage in rats.

Del-Nido cardioplegia in cardiac surgery for elderly patients: a propensity score-matched analysis

ObjectivesTo compare the safety and efficacy of del-Nido cardioplegia (DNC) with traditional 4:1 cold blood cardioplegia (CBC) in coronary artery bypass grafting and/or valve surgeries in elderly patients.MethodsThe present study is a retrospective case-series study that included 302 consecutive patients aged 70 years and over who underwent on-pump valve surgery and/or coronary artery bypass graft (CABG). DNC was administered to 90 patients and CBC to 212 patients. After propensity-score matching, 89 pairs were compared. The safety and efficacy were analyzed between the two groups.ResultsThe DNC group had a similar mortality (3.4% vs. 5.6%, OR = 0.79, P = 0.720) and extracorporeal membrane oxygenation (ECMO) implantation rate (1.1% vs. 2.2%, OR = 0.75, P = 1.000) to the CBC group, a lower incidence of postoperative intra-aortic balloon pump (IABP) implantation (1.1% vs. 9.0%, OR = 0.54, P = 0.034) and a higher left ventricular ejection fraction (LVEF) at discharge (60 (56–64) % vs. 57 (51–62)%, P = 0.007). The estimated glomerular filtration rate (eGFR) in the DNC group was higher when the patient was transferred to the intensive care unit (79.4 (65.0-94.3) ml/min/1.73m2 vs. 77.2 (59.8–88.7) ml/min/1.73m2, P = 0.014), but no significant differences were identified after 24 h. The serum lactate values of the DNC group were significantly lower than those of the CBC group (0 h: 2.7 (2.0-3.2) vs. 3.2 (2.4–4.4), P = 0.001; 3 h: 3.2 (2.0-4.8) vs. 4.8 (2.8–6.6), P < 0.001; 6 h: 3.5 (2.2–5.4) vs. 5.8 (3.4–8.4), P < 0.001; 9 h: 3.4 (2.0–7.0) vs. 5.5 (2.9–8.3), P = 0.005). There were no differences between the two groups in respect of lactate levels at 12 h and thereafter. Postoperative creatinine kinase-MB concentrations were similar between the two groups.ConclusionsDel-Nido cardioplegia is safe and effective in elderly patients undergoing CABG and/or valve surgery.

Safety, tolerance, and pharmacokinetics of salvianolic acid B in healthy Chinese volunteers: A randomized, double-blind, placebo-controlled phase 1 clinical trial.

Background: Salvianolic acid B (Sal B) is one of the main active ingredients of Salvia miltiorrhiza Bunge. In China, many traditional Chinese medicines have been modified into injections for higher bioavailability and better efficacy. Salvianolic acid injection has been widely used in the clinic. Objective: This phase 1, randomized, double-blind, placebo-controlled, single-center study aimed to evaluate the safety, tolerance, and pharmacokinetics of Sal B injection in healthy Chinese volunteers. Methods: For the single-ascending-dose study, forty-seven healthy volunteers were randomly divided into 25, 75, 150, 200, 250, and 300mg groups. For the multiple-ascending-dose study, sixteen healthy volunteers were randomly divided into 150 and 300mg groups. In each group, volunteers were treated with Sal B or placebo randomly. Their safety was evaluated by a skin test, physical examination, vital sign, laboratory examination, 12-lead electrocardiogram, Holter, and clinical symptoms and signs. Blood samples were collected in 75, 150, and 300mg single-ascending-dose study groups and 150mg multiple-ascending-dose study groups to determine the concentration of salvianolic acid B. Results: In single-ascending-dose study groups, there were 41 adverse events in 24 cases (51.1%, 24/47). In multiple-ascending-dose study groups, there were 13 adverse events in eight cases (50.0%, 8/16). Sixty-six volunteers received the skin test, and three of them were excluded because of the positive result. Adverse events related to the treatment included increased alanine aminotransferase (4.0%), increased bilirubin (2.0%), increased creatinine kinase-MB (2.0%), increased brain natriuretic peptide (8.0%), increased urine N-acetyl-β-D-glucosidase (4.0%), dizziness (2.0%), and chest discomfort (2.0%). No serious adverse events occurred. No volunteers withdrew from the trial. Peak plasma concentration and the area under the plasma concentration-time curve of salvianolic acid B progressively increased in a dose-dependent manner in 75, 150, and 300mg single-ascending-dose study groups. There was no accumulation after 5 consecutive days of administration of 150mg salvianolic acid B. Conclusion: Salvianolic acid B injections administered up to 300mg in a single dose and 250mg for 5 consecutive days showed excellent safety and tolerability in healthy Chinese volunteers. Clinical Trial Registration: www.chinadrugtrials.org.cn, identifier CTR20192236.

Outcomes of del Nido cardioplegia after surgical aortic valve replacement and coronary artery bypass grafting.

The use of del Nido cardioplegia (DNC) was initially adopted in the field of pediatric cardiac surgery. Several studies in adult patients suggested there were no differences in early postoperative outcomes as compared to blood-based cardioplegia. We sought to evaluate the impact of DNC as compared to modified Buckberg cardioplegia (BC) on early postoperative outcomes in patients undergoing surgical aortic valve replacement with and without coronary artery bypass grafting (SAVR ± CABG). All SAVR ± CABG procedures were switched from BC to DNC at our institute in 2012. We compared outcomes of BC (November 2007-October 2012; n = 1037) with DNC (November 2012-December 2017; n = 1067). Significant baseline differences were observed between the two groups and such differences were adjusted via inverse propensity treatment weighting. After adjustment, SAVR ± CABG patients who received DNC required longer aortic cross-clamp times, while postoperative peak troponin I and creatinine kinase-MB isotype were significantly lower in the BC group. Length of hospital and intensive care unit stay were significantly shorter in the DNC group. The incidence of postoperative complications was lower in the DNC cohort. Thirty-day mortality rate was significantly lower in the DNC group (3.0% vs 4.9%, p = 0.002). The use of DNC cardioplegia in our cohort of adult patients who underwent SAVR ± CABG was safe and associated with improved postoperative outcomes. However, the use of DNC may be associated with higher degrees of myocardial injury.

Comparison of cardiac marker profiles in dengue myocarditis

Dengue patients may experience some grade of severity. Cardiac involvement is common in severe dengue, therefore cardiac markers could be used to ensure the diagnosis of dengue myocarditis. However, information of the cardiac marker profiles in patients with milder severity of dengue infection is limited. The study aimed to evaluate creatinine kinase (CK), creatinine kinase-MB (CK-MB) and troponin I (TnI) in dengue myocarditis against the spectrum severity of dengue infection in children. This cross-sectional study was conducted using secondary data from medical records of dengue myocarditis patients aged 1-18 yr in Dr. Sardjito General Hospital, Yogyakarta. Fisher’s Exact tests were performed to compare the increase in cardiac markers to the dengue severity. The increase of CK was observed in dengue fever/DF (6 or 75% of patients), dengue hemorrhagic fever/DHF (6 or 67%) and dengue shock syndrome/DSS (16 or 73%). Furthermore, the increase of CK-MB was also observed in DF (6 or 75%), DHF (8 or 87%), and DSS (21 or 95%). No significant difference in the increase of CK and CK-MB proportions was observed in DF compared to DHF groups and in DF compared to DSS (p&gt;0.05). The increase of Tn I was observed in DHF (2 or 22%) and DSS (10 or 45%) groups but not observed in DF group. Significant difference in the increase of Tn I proportion was observed in DF compared to DSS groups (p=0.022). In conclusion, cardiac involvement is common in all dengue severity level. The increment of Tn I corresponds to an increase in the dengue severity level. Further research by observing cardiac markers sequentially is needed.

Anti-inflammatory effect of omega-7 against doxorubicin-induced cardiotoxicity in male rats: An observational study

Background: Doxorubicin is a crucial anticancer medication, however, cardiotoxicity is a severe adverse effect of doxorubicin therapy. Various mechanisms, including inflammation, have been postulated to account for this negative effect. The omega-7 fatty acid is a polyunsaturated fatty acid with anti-inflammatory and antioxidant properties. Therefore, the study's objective was to see whether omega-7 had any possible protective benefits against doxorubicin-induced cardiotoxicity in male rats. Methods: 28 male Wister rats were split into four groups (seven per group). Group 1 (negative control): healthy animals received normal saline orally as the vehicle for eight successive days and were sacrificed on day nine. Group 2 (positive control): animals that received a single dose of doxorubicin hydrochloride (IP 15mg/kg) were sacrificed the next day. Group 3: the animals were administered omega-7 orally at a 100 mg/kg/day dose for eight days. A single injection of doxorubicin IP (15 mg/kg) was given on day nine. The animals were sacrificed on day 10. Group 4: the animal was administered omega-7 orally at a 300 mg/kg/day dose for eight days. A single injection of doxorubicin IP (15 mg/kg) was given on day nine. The animals were sacrificed on day 10. Serum was collected and used to measure lactate dehydrogenase, creatinine kinase-MB, tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta. Results: Lactate dehydrogenase and creatinine kinase-MB levels in group 3 (100mg/kg) were significantly lower than in group 2 (p&gt;0.05) and significantly lower in group 4 (300mg/kg) than in group 2. Tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta levels were considerably lower in the omega-7-treated groups (100 and 300mg/kg) than in the positive control group (p&lt;0.05). Conclusion: Through a mechanism involving the reduction of inflammation, omega-7 may preserve the cardiac tissue against doxorubicin-induced damage.

Clinical features of elderly patients with COVID-19 in Wuhan, China.

Elderly patients with coronavirus disease 2019 (COVID-19) who have comorbidities, frailty or profound disabilities experience poor outcomes. We analyzed the clinical characteristics of elderly patients from Wuhan who had COVID-19 during the early stages of the pandemic. To identify factors affecting the early mortality of elderly patients with COVID-19. The records of 234 patients who were 65-years-old or more and were hospitalized in Wuhan Huoshenshan Hospital from February 4 to March 4, 2020 were reviewed. All patients had confirmed COVID-19 and the final date of follow-up was April 4, 2020. There were 163 cases of mild disease (69.66%), 39 cases of severe disease (16.67%) and 32 cases of critical disease (13.68%). Twenty-nine patients died within 1 mo (12.40%), all of whom had critical disease. Surviving patients and deceased patients had no significant differences in age or chronic diseases. Overall, the most common symptoms were fever (65.4%), dry cough (57.3%), fatigue (47.4%) and shortness of breath (41%). The deceased patients had higher levels of multiple disease markers (C-reactive protein, D-dimer, lactate dehydrogenase, alanine amino transferase, aspartate aminotransferase, creatinine kinase and creatinine kinase-MB) and higher incidences of lymphocytopenia and hypoproteinemia. This single-center study of elderly patients from Wuhan, China who were hospitalized with COVID-19 indicated that age and chronic diseases were not associated with mortality. Hypertension, diabetes and cardiovascular disease were the most common comorbidities and the most common symptoms were fever, dry cough, fatigue and shortness of breath. Lymphocytopenia, increased levels of D-dimer and other markers indicative of damage to the heart, kidneys or liver were associated with an increased risk of death.

Efficacy of Off-Pump Coronary Artery Bypass Grafting with Concomitant Transcatheter Aortic Valve Replacement.

This study aimed to evaluate the early and intermediate-term outcomes of patients who underwent concomitant off-pump coronary artery bypass grafting (CABG) and transcatheter aortic valve replacement (TAVR). Between January 2014 and June 2021, 49 patients underwent concomitant off-pump CABG and TAVR via median sternotomy (TAVRCAB group) and 143 underwent concomitant on-pump CABG and surgical aortic replacement. Of the 143 patients who underwent on-pump surgery, 80 (SAVRCAB group) were eligible for comparison. The composite event included all-cause death, heart failure rehospitalisation, repeat revascularisation, brain infarction, and repeat aortic valve replacement. The Society of Thoracic Surgeons' predicted risk for mortality and age were higher in the TAVRCAB group than in the SAVRCAB group (7.1% vs 3.1% [p<0.001]; 81 years vs 75 years [p<0.001], respectively), while the surgical time was shorter (289 min vs 352 min; p<0.001). There was no conversion to on-pump surgery in the TAVRCAB group. The postoperative maximum creatinine kinase-MB value was lower in the TAVRCAB group. There was no deep sternal wound infection or repeat revascularisation in either group. Hospital death and brain infarction developed in one patient (1.3%) each in the SAVRCAB group, but in no patients in the TAVRCAB group. The rates of freedom from the composite event were similar between the two groups during the follow-up period. Concomitant off-pump CABG and TAVR would be a less-invasive alternative procedure for treating intermediate or high surgical risk patients with aortic stenosis and coronary artery disease unsuitable for percutaneous coronary intervention.

Evaluation of selected antidiabetics in cardiovascular complications associated with cancer cachexia.

So far, the cardio-protective potential of antidiabetics is proved, but their effect on cardiovascular complications associated with cancer cachexia is not explored until now. Insulin resistance and glucose intolerance along with systemic inflammation are prominent in cachexia but the potential effect of antidiabetic agents especially those belonging to biguanide, DPP4 inhibitors and SGLT2 on the heart are not studied till now. In present study, the effect of metformin, vildagliptin, teneligliptin, dapagliflozin and empagliflozin on cardiovascular complications associated with cancer cachexia by using B16F1 induced metastatic cancer cachexia and urethane-induced cancer cachexia was studied. These antidiabetic agents proved to be beneficial against cachexia-induced atrophy of the heart, preserved ventricular weights, maintained cardiac hypertrophic index, preserved the wasting of cardiac muscles assessed by HE staining, Masson trichrome staining, periodic acid Schiff staining and picro-Sirius red staining. Altered cardiac gene expression was attenuated after treatment with selected antidiabetics, thus preventing cardiac atrophy. Also, antidiabetic agents treatment improved the serum creatinine kinase MB, Sodium potassium ATPase and collagen in the heart. Reduction in blood pressure and heart rate was observed after treatment with antidiabetic agents. Results of our study show that the selected antidiabetics prove to be beneficial in attenuating the cardiac atrophy and helps in regulation of hemodynamic stauts in cancer cachexia-induced cardiovascular complications. Our study provides some direction towards use of selected antidiabetic agents in the management of cardiovascular complications associated with cancer cachexia and the study outcomes can be useful in desiging clinical trials.

Biometabolites of Tamarindus indica play a remarkable cardioprotective role as a functional food in doxorubicin-induced cardiotoxicity models

This research investigated the cardioprotective effects of Tamarindus indica extracts (TIEx) in doxorubicin (Dox)-induced cardiotoxicity model. TIEx was tested for phytochemical and antioxidative status followed by a randomized controlled intervention in Swiss albino models. The results were verified by in silico interactions of GC-MS characterized phytocompounds against AT1 (angiotensin II type 1) receptor antagonist complexed with PPARγ agonist. TIEx showed an excellent antioxidative effect and a significant (P < 0.05) decrease in C-reactive protein (CRP), Serum troponin I (STI), aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatinine kinase-MB (CKMB), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and increase high-density lipoprotein (HDL) in treatment groups in comparison with standard drug valsartan. The selected bioactive compounds especially Thymine, 4H-Pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl- showed the highest binding affinity with the human AT1 receptor antagonist complexed with PPARγ agonist. Results demonstrate that Tamarindus indica parts could be a food supplement for cardiac toxicity.

Lethal diquat poisoning manifests as acute central nervous system injury and circulatory failure: A retrospective cohort study of 50 cases

SummaryBackgroundThe mortality rate of patients with diquat (DQ) poisoning is extremely high due to insufficient understanding of DQ-induced injury. This study aimed to summarize the characteristics of DQ poisoning as well as analyse the correlation between plasma DQ concentration and patient outcomes, thus providing a new strategy for diagnosis and treatment.MethodsThis single-centre retrospective cohort study was conducted at the Emergency Department of the First Affiliated Hospital, Zhejiang University School of Medicine, China, between Oct 9, 2019 and March 10, 2022. 50 patients, whose plasma or urine samples tested positive for diquat and negative for paraquat by high performance liquid chromatography-tandem mass spectrometry, were included in the study.FindingsThe mortality rate of acute DQ poisoning was 25 (50%) of 50. Compared with the survival group, the death group presented significantly higher initial plasma DQ concentration (Cp1), aspartate aminotransferase, alanine aminotransferase, serum creatinine, and creatine kinase-MB (P < 0.05). We found that six (24.0%) patients died of central nervous system injury, six (24.0%) patients died of refractory circulatory failure, and 13 (52.0%) patients died of central nervous system injury combined with circulatory failure. Receiver operator characteristic curve analysis showed that the area under the curve of Cp1 was 0.967 (95% CI: 0.911, 1.000), and the cut-off value was 3516.885 ng/mL (sensitivity, 90.9%; specificity, 96.0%).InterpretationLethal DQ poisoning is primarily associated with serious brain and vascular injury, as well as a high rate of mortality. Further research into the mechanisms of refractory circulatory failure and central nerve system damage could help reduce mortality.FundingThere are no funding sources to declare.

Ferulic acid mitigates diabetic cardiomyopathy via modulation of metabolic abnormalities in cardiac tissues of diabetic rats.

Cardiovascular abnormalities have been reported as a major contributor of diabetic mortality. The protective effect of ferulic acid on diabetic cardiomyopathy in fructose-streptozotocin induced type 2 diabetes (T2D) rat model was elucidated in this study. Type 2 diabetic rats were treated by oral administration of low (150 mg/kg b.w) and high (300 mg/kg b.w) doses of ferulic acid. Metformin was used as the antidiabetic drug. Rats were humanely euthanized after 5weeks of treatment, and their blood and hearts were collected. Induction of T2D depleted the levels of reduced glutathione, glycogen, and HDL-cholesterol and the activities of superoxide dismutase, catalase, ENTPDase, and 5'nucleotidase. It simultaneously triggered increase in the levels of malondialdehyde, total cholesterol, triglyceride, LDL-cholesterol, creatinine kinase-MB as well as activities of acetylcholinesterase, angiotensin converting enzyme (ACE), ATPase, glucose-6-phopsphatase, fructose-1,6-bisphophatase, glycogen phosphorylase, and lipase. T2D induction further revealed an obvious degeneration of cardiac muscle morphology. However, treatment with ferulic acid markedly reversed the levels and activities of these biomarkers with concomitant improvement in myocardium structural morphology, which had favorable comparison with the standard drug, metformin. Additionally, T2D induction led to the depletion of 40%, 75%, and 33% of fatty acids, fatty esters, and steroids, respectively, with concomitant generation of eicosenoic acid, gamolenic acid, and vitamin E. Ferulic acid treatment restored eicosanoic acid, 2-hydroxyethyl ester, with concomitant generation of 6-octadecenoic acid, (Z)-, cis-11-eicosenoic acid, tridecanedioic acid, octadecanoic acid, 2-hydroxyethyl ester, ethyl 3-hydroxytridecanoate, dipalmitin, cholesterol isocaproate, cholest-5-ene, 3-(1-oxobuthoxy)-, cholesta-3,5-diene. These results suggest the cardioprotective potential of ferulic acid against diabetic cardiomyopathy.

Nigella sativa oil alleviates doxorubicin-induced cardiomyopathy and neurobehavioral changes in mice

Objective: To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice. Methods: Swiss strain of albino female mice were divided into 6 groups of 5 animals in each: Group I (control group), group II (doxorubicin, 10 mg/kg, i.v.), group III, IV, and V (Nigella sativa oil; 1.5, 3, and 6 mL/kg, respectively), group Ή (Nigella sativa oil per se; 6 mL/kg, p.o.). The duration of treatment was 15 d (10 days’ pre-treatment and 5 days’ post-treatment) and doxorubicin was administered on day 11th of the treatment schedule. Following Nigella sativa oil treatment, neurobehavioral tests, cardiac hypertrophy tests, and biochemical tests in serum and tissues were performed. Neurological tests included assessment of anxiety-like behavior in the elevated plus maze, spontaneous alternation behavior in the cross maze, and depression-like behavior in modified forced swim tests. Biochemical tests included serum lactate dehydrogenase and creatinine kinase-MB, malondialdehyde and reduced glutathione in tissues. Lastly, molecular docking was used to estimate the affinity of the phytoconstituents of Nigella sativa oil with histone deacetylases. Results: Nigella sativa oil treatment significantly (P&lt;0.001) restored doxorubicin-induced neurobehavioral changes, decreased lactate dehydrogenase and creatinine kinase-MB in the plasma, malondialdehyde contents in tissues, and increased reduced glutathione level. Besides, no significant alteration was observed in Nigella sativa oil per se group as compared to the control. Molecular docking showed that Nigella sativa oil components had appreciable binding affinitiy with the protein cavities of HDAC1 and HDAC6. Conclusions: The result shows that Nigella sativa oil exerts anxiolytic, antidepressant, and memory-enhancing effects in addition to cardioprotective effect against doxorubicin-induced cardiomyopathy in mice. The modulatory effect of Nigella sativa oil on oxidative stress could contribute to the cardioprotective effect and associated neurobehavioral changes in mice.

Cardiac Implications of COVID-19 in Deceased and Recovered Patients: A Systematic Review.

Background Patients infected with coronavirus disease 2019 (COVID-19) present with various clinical presentations with majority of them developing pulmonary complications. This study focuses on cardiac implications of COVID-19 which are less discussed and thus will help to address cardiac implications of COVID-19. Methods PubMed, PubMed Central, and Google Scholar were screened for articles which mentioned cardiac implications of COVID-19. NHLBI Study Quality Assessment Tools for the observational cohort and cross-sectional studies was used for assessing the risk of bias of our studies. Results All 14 studies selected were good and had score of ≥9 by NHLBI Study Quality Assessment Tools. Cardiac complications of COVID-19 are common. They are associated with significant mortality. Also, people infected with COVID-19 with premorbid conditions such as cardiovascular diseases and diabetes mellitus have poor prognosis as compared to those without premorbid conditions. Cardiac biomarkers such as highly sensitive troponin I, creatinine, and creatinine kinase-MB on admission are good prognostic markers. Conclusions Cardiac complications such as heart failure, myocardial injury, and arrhythmias are common among patients infected with COVID-19. Elevated cardiac markers and patients with cardiac complications require utmost care and continuous cardiac monitoring.

High Oxygenation During Normothermic Regional Perfusion After Circulatory Death Is Beneficial on Donor Cardiac Function in a Porcine Model.

Thoracoabdominal normothermic regional perfusion (NRP) is a new method for in situ reperfusion and reanimation of potential donor organs in donation after circulatory death by reperfusion of the thoracic and abdominal organs with oxygenated blood. We investigated effects of high oxygenation (HOX) versus low oxygenation (LOX) during NRP on donor heart function in a porcine model. Pigs (80 kg) underwent a 15-min anoxic cardiac arrest followed by cardiac reanimation on NRP using a heart-lung bypass machine with subsequent assessment 180 min post-NRP. The animals were randomized to HOX (FiO2 1.0) or LOX (FiO2 0.21 increased to 0.40 during NRP). Hemodynamic data were obtained by invasive blood pressure and biventricular pressure-volume measurements. Blood gases, biomarkers of inflammation, and oxidative stress were measured. Eight of 9 animals in the HOX group and 7 of 10 in the LOX group were successfully weaned from NRP. Right ventricular end-systole elastance was significantly improved in the HOX group compared with the LOX group, whereas left ventricular end-systole elastance was preserved at baseline levels. Post-NRP cardiac output, mean arterial, central venous, and pulmonary capillary wedge pressure were all comparable to baseline. Creatinine kinase-MB increased more in the LOX group than the HOX group, whereas proinflammatory cytokines increased more in the HOX group than the LOX group. No difference was found in oxidative stress between groups. All hearts weaned from NRP showed acceptable hemodynamic function for transplantation. Hearts exposed to LOX showed more myocardial damage and showed poorer contractile performance than hearts reperfused with high oxygen.

Early effect of extracorporeal membrane oxygenation and factors related to early outcome in adult patients with fulminant myocarditis

Objective: To evaluate the efficacy within the first 24 h post extracorporeal membrane pulmonary oxygenation (ECMO) and the impact of early efficacy on the prognosis of adult patients with fulminant myocarditis (FM). Methods: This retrospective case analysis study included hospitalized patients (age≥18 years) who were diagnosed with fulminant myocarditis from November 2016 to May 2021 in the First Affiliated Hospital of Zhengzhou University. Patients were divided into survival or non-survival groups according to treatment outcomes. The age, sex, treatments, drug use, ECMO use, clinical and laboratory data (before and 24 h after the use of ECMO) were analyzed. The change rate of clinical and laboratory data after 24 h use of ECMO was calculated to find differences between two groups. Multivariate logistic regression was used to analyze the related factors with in-hospital death and complication between the two groups. Results: A total of 38 FM patients treated with ECMO were included. There were 23 cases (60.5%) in the survival group, aged (39.6±13.7) years, and 17 (73.9%) cases were female. The total ECMO time was (134.4±71.3)h. There were 15 cases (39.5%) in non-survival group, aged (40.0±15.8) years, and there were 12(80.0%) female, the ECMO time was (120.1±72.4) h in this group. The proportion of tracheal intubation and continuous renal replacement therapy in the survivor group and dosage of norepinephrine within 24 h after ECMO implantation were significantly less than in non-survival group (all P<0.05). There was no significant difference in all efficacy related biochemical indexes between two groups before ECMO use. The levels of lactic acid, procalcitonin, creatinine, alanine aminotransferase, aspartate aminotransferase, creatine kinase-MB, cardiac troponin I and N-terminal B-type natriuretic peptide prosoma were significantly less in survival group than in non-survival group at 24 h after the use of ECMO (all P<0.05). Results of multivariate logistic regression analysis showed that the higher 24 h change rate of creatinine (OR=0.587, 95%CI 0.349-0.986, P=0.044) and creatine kinase-MB (OR=0.177, 95%CI 0.037-0.841, P=0.029) were positively correlated with reduced risk of in-hospital mortality. The central hemorrhage and acute kidney injury in survival group were less than in non-survivor group (P<0.05). Conclusions: After 24 h early use of ECMO in FM patients, the improvement of various efficacy related biochemical test indexes in the survival group was better than that in the non-survival group. Faster reduction of creatine kinase-MB and creatinine values within 24 h ECMO use is positively correlated with reduced risk of in-hospital mortality in adult patients with FM.

Cardioprotective Effect of Gossypin Against Myocardial Ischemic/Reperfusion in Rats via Alteration of Oxidative Stress, Inflammation and Gut Microbiota.

BackgroundMyocardial ischemic/reperfusion (I/R) injury is a key prognostic factor after the myocardial infarction. However, at the time of reperfusion, the myocardial tissue has undergone for the necrosis and initiated the induction of oxidative stress and inflammation. The current study was to scrutinize the cardioprotective effect of gossypin against ISO-induced I/R injury in myocardial tissue and explore the possible underlying mechanism.MethodsSprague Dawley (SD) was used in the current protocol and ISO was used for induction the I/R in rat. The rats were divided into different groups and received the oral administration of gossypin treatment before the reperfusion. The body weight, heart weight and heart body weight ratio were estimated. The antioxidant, cardiac injury parameters, inflammatory cytokines, inflammatory mediators, gut microbiota and lipid parameters were estimated. At the end, heart tissue histopathological study was carried out.ResultsISO-induced I/R rats received the gossypin treatment significantly (P < 0.001) enhanced the body weight and decreased the heart weight, along with suppressed the infarct size. Gossypin treatment significantly (P < 0.001) reduced the level of heart parameters, such as creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (CTn-I) and cardiac troponin T (CTn-T) in the serum. Gossypin treatment significantly (P < 0.001) altered the cardiac function, hepatic, antioxidant, inflammatory cytokines and inflammatory mediators. Gossypin significantly (P < 0.001) suppressed the MMP-2 and MMP-9 in ISO-induced I/R rats. Gossypin treatment considerably alleviated the gut dysbiosis through altered Firmicutes to Bacteroidetes (F/B) ratio and also maintained the relative abundance of Butyricicoccus, Clostridium IV, Akkermansia, Roseburia and Clostridium XIVs.ConclusionBased on result, we can conclude that gossypin is an alternative drug for the treatment of ISO-induced I/R in rats via alteration of oxidative stress, inflammatory reaction and gut microbiota.