Metabolomics Analysis Identifies Differential Metabolites as Biomarkers for Acute Myocardial Infarction.

Myocardial infarction (MI), including ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI), is still a leading cause of death worldwide. Metabolomics technology was used to explore differential metabolites (DMs) as potential biomarkers for early diagnosis of STEMI and NSTEMI. In the study, 2531 metabolites, including 1925 DMs, were discovered. In the selected 27 DMs, 14 were successfully verified in a new cohort, and the AUC values were all above 0.8. There were 10 in STEMI group, namely L-aspartic acid, L-acetylcarnitine, acetylglycine, decanoylcarnitine, hydroxyphenyllactic acid, ferulic acid, itaconic acid, lauroylcarnitine, myristoylcarnitine, and cis-4-hydroxy-D-proline, and 5 in NSTEMI group, namely L-aspartic acid, arachidonic acid, palmitoleic acid, D-aspartic acid, and palmitelaidic acid. These 14 DMs may be developed as biomarkers for the early diagnosis of MI with high sensitivity and specificity. These findings have particularly important clinical significance for NSTEMI patients because these patients have no typical ECG changes.

Metabolomics and Biomarkers for Paroxysmal and Persistent Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common type of arrhythmia worldwide and is associated with serious complications. This study investigated the metabolic biomarkers associated with AF and the differences in metabolomics and associated metabolic biomarkers between paroxysmal AF (AFPA) and persistent AF. METHODS AND RESULTS: Plasma samples were prospectively collected from patients with AF and patients in sinus rhythm with negative coronary angiography. The patients were divided into 3 groups: AFPA, persistent AF, and sinus rhythm (N=54). Metabolomics (n=36) using ultra-high-performance liquid chromatography mass spectrometry was used to detect differential metabolites that were validated in a new cohort (n=18). The validated metabolites from the validation phase were further analyzed by receiver operating characteristic. Among the 36 differential metabolites detected by omics assay, 4 were successfully validated with area under the curve >0.8 (P<0.05). Bioinformatics analysis confirmed the enrichment pathways of unsaturated fatty acid biosynthesis, glyoxylate and dicarboxylate metabolism, and carbon metabolism. Arachidonic acid was a potential biomarker of AFPA, glycolic acid and L-serine were biomarkers of AFPA and persistent AF, and palmitelaidic acid was a biomarker of AFPA. CONCLUSIONS: In this metabolomics study, we detected 36 differential metabolites in AF, and 4 were validated with high sensitivity and specificity. These differential metabolites are potential biomarkers for diagnosis and monitoring of disease course. This study therefore provides new insights into the precision diagnosis and management of AF.

Homocysteine impairs the anticontractile/vasorelaxing activity of perivascular adipose tissue surrounding human internal mammary artery.

OBJECTIVES: Perivascular adipose tissue (PVAT) surrounding human internal mammary artery (IMA) possesses anticontractile property. Its function under pathological conditions is barely studied. We previously reported that homocysteine impairs the vasodilator function of IMA through endothelium and smooth muscle-dependent mechanisms. This study investigated the effect of homocysteine on the function of PVAT and the associated mechanisms. METHODS: Residual IMA tissues were collected from patients undergoing coronary artery bypass grafting. Vasoreactivity was studied using myograph. Adiponectin was measured by ELISA. Expressions of adiponectin receptors (AdipoRs), eNOS and p-eNOS were determined by RT-qPCR and Western blot. RESULTS: Exposure to homocysteine augmented the contractile responses of PVAT-intact IMA to U46619 and potassium chloride, regardless with or without endothelium. Such augmentation was also observed in skeletonized IMA with transferred, homocysteine-exposed PVAT. Homocysteine attenuated the relaxant response of PVAT-intact while endothelium-denuded vessels to acetylcholine. Homocysteine lowered adiponectin content in the PVAT, downregulated the expression of AdipoR1 and AdipoR2 as well as eNOS and p-eNOS in skeletonized IMA. The relaxant response of skeletonized IMA to AdipoR agonist AdipoRon was blunted by homocysteine or eNOS inhibitor, and homocysteine significantly attenuated the inhibitory effect of eNOS inhibitor on AdipoRon-induced relaxation. CONCLUSIONS: Homocysteine impairs the anticontractile/vasorelaxing activity of PVAT surrounding the IMA through inhibiting adiponectin/AdipoR/eNOS/nitric oxide signalling pathway.

Identification and Functional Verification of CITED2 Gene Promoter Region in Patients with Patent Ductus Arteriosus.

Patent ductus arteriosus (PDA) is a common congenital heart disease. CITED2 plays an important role in the development of the heart, and genetic variants in its coding region are significantly associated with cardiac malformations. However, the role of variants in the promoter region of CITED2 in the development of PDA remains unclear. We extracted the peripheral blood of 646 subjects (including 353 PDA patients and 293 unrelated healthy controls) for sequencing. We identified 13 promoter variants of the CITED2 gene (including 2 novel heterozygous variants). Of the 13 variants, 10 were found only in PDA patients. In mouse cardiomyocytes (HL-1) and rat cardiac myocytes (RCM), the transcriptional activity of the CITED2 gene promoter was significantly changed by the variants (p < 0.05). The results of the experiments of electrophoretic mobility indicated that these variants may affect the transcription of the CITED2 gene by influencing the binding ability of transcription factors. These results, combined with the JASPAR database analysis, showed that the destruction/production of transcription factor binding sites due to the variants in the promoter region of the CITED2 gene may directly or indirectly affect the binding ability of transcription factors. Our results suggest for the first time that variants at the CITED2 promoter region may cause low expression of CITED2 protein related to the formation of PDA.

Establishment and application of cricothyrotomy in vivo.

BACKGROUND: Cricothyrotomy is a procedure performed to establish an airway in critical airway events. It is performed only rarely and anesthesiologists are often unprepared when called upon to perform it. This study aimed to simulate cricothyrotomy using pig larynx and trachea models to help anesthesiologists master cricothyrotomy and improve the ability to establish cricothyrotomy quickly. METHODS: The porcine larynx and trachea were dissected and covered with pigskin to simulate the structure of the anterior neck of a human patient. An animal model of cricothyrotomy was established. Forty anesthesiologists were randomly divided into four groups. Each physician performed three rounds of cricothyrotomy, and recorded the time to accomplish each successful operation. After training the cricothyrotomy procedure, a questionnaire survey was conducted for the participating residents using a Likert scale. The participants were asked to score the utility of the training course on a scale of 1 ((minimum) to 5 ((maximum). RESULTS: Through repeated practice, compared with the time spent in the first round of the operation (67 ± 29 s), the time spent in the second round of the operation (47 ± 21 s) and the time spent in the third round of the operation (36 ± 11 s) were significantly shortened (P < 0.05). Results of the survey after training were quite satisfied, reflecting increased the ability of proficiency in locating the cricothyroid membrane and performing a surgical cricothyrotomy. CONCLUSION: The porcine larynx and trachea model is an excellent animal model for simulating and practicing cricothyrotomy, helping anesthesiologists to master cricothyrotomy and to perform it proficiently when required.

Lysine crotonylation of SERCA2a correlates to cardiac dysfunction and arrhythmia in Sirt1 cardiac-specific knockout mice.

Protein post-translational modifications (PTMs) are important regulators of protein functions and produce proteome complexity. SIRT1 has NAD+-dependent deacylation of acyl-lysine residues. The present study aimed to explore the correlation between lysine crotonylation (Kcr) on cardiac function and rhythm in Sirt1 cardiac-specific knockout (ScKO) mice and related mechanism. Quantitative proteomics and bioinformatics analysis of Kcr were performed in the heart tissue of ScKO mice established with a tamoxifen-inducible Cre-loxP system. The expression and enzyme activity of crotonylated protein were assessed by western blot, co-immunoprecipitation, and cell biology experiment. Echocardiography and electrophysiology were performed to investigate the influence of decrotonylation on cardiac function and rhythm in ScKO mice. The Kcr of SERCA2a was significantly increased on Lys120 (1.973 folds). The activity of SERCA2a decreased due to lower binding energy of crotonylated SERCA2a and ATP. Changes in expression of PPAR-related proteins suggest abnormal energy metabolism in the heart. ScKO mice had cardiac hypertrophy, impaired cardiac function, and abnormal ultrastructure and electrophysiological activities. We conclude that knockout of SIRT1 alters the ultrastructure of cardiac myocytes, induces cardiac hypertrophy and dysfunction, causes arrhythmia, and changes energy metabolism by regulating Kcr of SERCA2a. These findings provide new insight into the role of PTMs in heart diseases.

The effect of preoperative sleep quality on the target plasma concentration of propofol and postoperative sleep in patients undergoing painless gastroscopy.

BACKGROUND: This study aims to investigate the effect of preoperative sleep quality on the target plasma concentration of propofol and postoperative sleep in patients undergoing painless gastroscopy. METHODS: Ninety-three outpatients aged 45 to 64 years with body mass index (BMI) of 18.5-30 kg/m2 and ASA grades of I or II, who underwent painless gastroscopy, were selected. All patients were evaluated by the Athens insomnia scale (AIS) before the painless gastroscopy. The patients were divided into two groups according to the AIS score evaluated before painless gastroscopy: normal sleep group (group N, AIS score < 4 points, 47 cases) and sleep disorder group (group D, AIS score > 6 points, 46 cases). The target-controlled infusion (TCI) of propofol (Marsh model) was used for general anesthesia, the Bispectral index (BIS) was used to monitor the depth of anesthesia, and the BIS was maintained between 50 and 65 during the painless gastroscopy. The target plasma concentration (Cp) of propofol was recorded when the patient's eyelash reflex disappeared (T1), before the painless gastroscopy (T2), at the time of advancing the gastroscope (T3) and during the painless gastroscopy (T4), and the infusion rate per body surface area of propofol was calculated. The patient's AIS score was followed up by telephone at day 1, day 3, 1 week, and 1 month after the painless gastroscopy to assess the postoperative sleep of the patient. The occurrence of adverse reactions during the painless gastroscopy was recorded; the patient's satisfaction and the endoscopist's satisfaction with the anesthesia effect were compared between the two groups. RESULTS: Compared with group N, the Cp at each time point and the infusion rate per body surface area of propofol in group D was increased significantly (P < 0.05); compared with the AIS scores before the painless gastroscopy, the AIS scores of the two groups of patients were significantly increased day 1 after the painless gastroscopy (P < 0.05); there were no significant differences in the AIS scores of the two groups at day 3, 1 week, and 1 month after the painless gastroscopy (P > 0.05). There were no statistically significant differences in the occurrence of adverse reactions and the patient's satisfaction and the endoscopist's satisfaction with the anesthesia effect between the two groups (P > 0.05). CONCLUSION: The preoperative sleep disturbance will increase the Cp and the infusion rate per body surface area of propofol in patients undergoing painless gastroscopy. Propofol only affects the patients' sleep for day 1 after the painless gastroscopy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100045332) on 12/04/2021.

Antispastic Effect of Fasudil and Cocktail of Fasudil and Nitroglycerin in Internal Thoracic Artery.

BACKGROUND: Spasm of arterial grafts in coronary artery bypass grafting is a clinical problem and can occasionally be lethal. Perioperative spasm in the internal thoracic artery (ITA) and coronary arteries occurs in 0.43% of patients. This study aimed to investigate the antispastic effect of a RhoA/Rho-kinase (Rho-associated coiled-coil-containing protein kinase [ROCK]) inhibitor (fasudil) with and without nitroglycerin in combination in the ITA. METHODS: Isolated human ITA rings taken from 68 patients who were undergoing coronary bypass were studied in a myograph. Cumulative concentration-relaxation curves for fasudil (-9 to -3.5 log M) were established in the ITA, which was precontracted with potassium chloride or U46619. The inhibitory effect of fasudil (-6.3 or -5.3 log M) or fasudil in combination with nitroglycerin were also tested. The ROCK2 protein was measured by Western blot. RESULTS: Fasudil caused similar relaxation in ITA rings contracted by potassium chloride or U46619. Pretreatment with -5.3 log M fasudil significantly depressed contraction induced by potassium chloride (P = .004 vs control; P = .017 vs -6.3 log M) and U46619 (P = .010 vs control; P = .041 vs. -6.3 log M). Fasudil in combination with nitroglycerin had more effect and more rapid and sustained relaxation than either vasodilator alone. Fasudil caused a decrease of ROCK2 protein content (P = .014). CONCLUSIONS: Fasudil fully relaxes some vasoconstrictor-induced contraction and decreases ROCK2 protein content in the ITA. The combination of fasudil and nitroglycerin has a superior effect than either vasodilator alone. The new cocktail solution composed of fasudil and nitroglycerin (pH 7.4) has effective antispastic action and may prove to be a new antispastic method for arterial conduits during coronary bypass surgery.

Pathophysiological Role of Variants of the Promoter Region of CITED2 Gene in Sporadic Tetralogy of Fallot Patients with Cellular Function Verification.

Tetralogy of Fallot (TOF) is a common congenital heart malformation. Genetic variants in the CITED2 coding region are known to be significantly associated with cardiac malformation, but the role of variants in the CITED2 promoter region in the development of TOF remains unclear. In this study, we investigated CITED2 promoter variants in the DNA of 605 subjects, including 312 TOF patients and 293 unrelated healthy controls, by Sanger sequencing. We identified nine CITED2 gene promoter variants (including one novel heterozygous variant). Six were found only in patients with TOF and none in the control group. The transcriptional activity of the CITED2 gene promoter in mouse cardiomyocyte (HL-1) cells was significantly altered by the six variants (p < 0.05). The results of the electrophoretic mobility change assay and JASPAR database analysis showed that these variants generated or destroyed a series of possible transcription factor binding sites, resulting in changes in the CITED2 protein expression. We conclude that CITED2 promoter variants in TOF patients affect transcriptional activity and may be involved in the occurrence and progression of TOF. These findings may provide new insights into molecular pathogenesis and potential therapeutic insights in patients with TOF.

Genetic Variants of CITED2 Gene Promoter in Human Atrial Septal Defects: Case-Control Study and Cellular Functional Verification.

Atrial septal defect (ASD) is one of the most common forms of congenital heart disease (CHD). Genetic variants in the coding region of the CITED2 gene are known to be significantly correlated with CHD, but the role of variants in the promoter region of CITED2 is unknown. We investigated variants in the promoter of the CITED2 gene in 625 subjects (332 ASD and 293 healthy controls) through Sanger sequencing. Four variants in the CITED2 gene promoter were found only in eight ASD patients with zero occurrence in the control subjects (one case of g.4078A>C(rs1165649373), one case of g.4240C>A(rs1235857801), four cases of g.4935C>T(rs111470468), two cases of g.5027C>T(rs112831934)). Cellular functional analysis showed that these four variants significantly changed the transcriptional activity of the CITED2 gene promoter in HEK-293 and HL-1 cells. Electrophoretic mobility change assay results and JASPAR database analysis demonstrated that these variants created or destroyed a series of possible transcription factor binding sites, resulting in changes in the expression of CITED2 protein. We conclude that the variants of CITED2 promoter in ASD patients affect the transcriptional activity and are likely involved in the occurrence and development of ASD. These findings provide new perspectives on the pathogenesis and potential therapeutic insights of ASD.

The effects of morning/afternoon surgeries on the early postoperative sleep quality of patients undergoing general anesthesia.

OBJECTIVE: This study aimed to investigate the effects of morning and afternoon surgeries on the early postoperative sleep function in patients undergoing general anesthesia. METHODS: Fifty nine patients, aged 18-60 years, American society of anaesthesiologists (ASA) grade I or II, Body mass index of 18.5-28 kg/m2, undergoing laparoscopic myomectomy under total intravenous anesthesia, were included in the study. These patients were divided into two groups according to the start time of anesthesia: morning surgery group (group A, 8:00-12:00) and afternoon surgery group (group P, 14:00-18:00). The sleep conditions of the two groups of patients were evaluated by the Athens Insomnia Scale (AIS) one day before and one day after the operation. A total score of > 6 was regarded as postoperative sleep disturbance. The incidences of sleep disturbance one day after the operation in two groups were compared. The bispectral Index assessed the patient's total sleep duration, sleep efficiency, and overall quality of sleep from 21:00 to 6:00 on the first night after surgery. Plasma concentrations of melatonin and cortisol at 6:00 am 1 day before surgery, 1 day after surgery were measured by ELISA, and rapid random blood glucose was measured. RESULTS: The total AIS score, overall quality of sleep, total sleep duration, and final awakening earlier than desired scores of the two groups of patients on the first night after surgery were significantly increased compared with preoperative scores (P < 0.01). In group P, the sleep induction and the physical and mental functioning during the day scores increased significantly after surgery compared with preoperative scores (P < 0.05). The postoperative AIS scores in group P increased significantly compared with those in group A (P < 0.01). The incidence of postoperative sleep disturbances (70.0%) in group P was significantly higher than that in group A (37.9%) (P < 0.05). Compared with group A, the total sleep duration under BIS monitoring in group P was significantly shorter, the sleep efficiency and the overall quality of sleep was significantly reduced (P < 0.01). Compared with those in group A, the level of melatonin on 1 d after surgery in group P was significantly decreased, and the level of cortisol in group P was significantly increased. There were no significant differences between the two groups in the levels of postoperative blood glucose and pain. CONCLUSION: Both morning and afternoon surgeries have significant impacts on the sleep function in patients undergoing general anesthesia, while afternoon surgery has a more serious impact on sleep function. TRIAL REGISTRATION: ClinicalTrials, NCT04103528. Registered 24 September 2019-Retrospectively registered, http://www. CLINICALTRIALS: gov/ NCT04103528.

Identification of novel rare copy number variants associated with sporadic tetralogy of Fallot and clinical implications.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Highly penetrant copy number variants (CNVs) and genes related to the etiology of TOF likely exist with differences among populations. We aimed to identify CNV contributions to sporadic TOF cases in Han Chinese. Genomic DNA was extracted from peripheral blood in 605 subjects (303 sporadic TOF and 302 unaffected Han Chinese [Control] from cardiac centers in China) and analyzed by genome-wide association study (GWAS). The GWAS results were compared with existing Database of Genetic Variants. These CNVs were further validated by qPCR. Bioinformatics analyses were performed with protein-protein interaction (PPI) network and KEGG pathway enrichment. Across all chromosomes 119 novel "TOF-specific CNVs" were identified with prevalence of CNVs of 21.5% in chromosomes 1-20 and 37.0% including Chr21/22. In chromosomes 1-20, CNVs on 11q25 (encompasses genes ACAD8, B3GAT1, GLB1L2, GLB1L3, IGSF9B, JAM3, LOC100128239, LOC283177, MIR4697, MIR4697HG, NCAPD3, OPCML, SPATA19, THYN1, and VPS26B) and 14q32.33 (encompasses genes THYN1, OPCML, and NCAPD3) encompass genes most likely to be associated with TOF. Specific CNVs found on the chromosome 21 (6.3%) and 22(11.9%) were also identified in details. PPI network analysis identified the genes covering the specific CNVs related to TOF and the signaling pathways. This study for first time identified novel TOF-specific CNVs in the Han Chinese with higher frequency than in Caucasians and with 11q25 and 14q32.33 not reported in TOF of Caucasians. These novel CNVs identify new candidate genes for TOF and provide new insights into genetic basis of TOF.

Endoplasmic reticulum stress mediates homocysteine-induced hypertrophy of cardiac cells through activation of cyclic nucleotide phosphodiesterase 1C.

Although the association of elevated homocysteine level with cardiac hypertrophy has been reported, the molecular mechanisms by which homocysteine induces cardiac hypertrophy remain inadequately understood. In this study we aim to uncover the roles of cyclic nucleotide phosphodiesterase 1 (PDE1) and endoplasmic reticulum (ER) stress and their relationship to advance the mechanistic understanding of homocysteine-induced cardiac cell hypertrophy. H9c2 cells and primary neonatal rat cardiomyocytes are exposed to homocysteine with or without ER stress inhibitor TUDCA or PDE1-specific inhibitor Lu AF58027, or transfected with siRNAs targeting PDE1 isoforms prior to homocysteine-exposure. Cell surface area is measured and ultrastructure is examined by transmission electron microscopy. Hypertrophic markers, PDE1 isoforms, and ER stress molecules are detected by q-PCR and western blot analysis. Intracellular cGMP and cAMP are measured by ELISA. The results show that homocysteine causes the enlargement of H9c2 cells, increases the expressions of hypertrophic markers ß-MHC and ANP, upregulates PDE1A and PDE1C, promotes the expressions of ER stress molecules, and causes ER dilatation and degranulation. TUDCA and Lu AF58027 downregulate ß-MHC and ANP, and alleviate cell enlargement. TUDCA decreases PDE1A and PDE1C levels. Silencing of PDE1C inhibits homocysteine-induced hypertrophy, whereas PDE1A knockdown has minor effect. Both cAMP and cGMP are decreased after homocysteine-exposure, while only cAMP is restored by Lu AF58027 and TUDCA. TUDCA and Lu AF58027 also inhibit cell enlargement, downregulate ANP, ß-MHC and PDE1C, and enhance cAMP level in homocysteine-exposed primary cardiomyocytes. ER stress mediates homocysteine-induced hypertrophy of cardiac cells via upregulating PDE1C expression Cyclic nucleotide, especially cAMP, is the downstream mediator of the ER stress-PDE1C signaling axis in homocysteine-induced cell hypertrophy.

Plasma Concentrations of Trace Elements Selenium and Cobalt During and After Coronary Artery Bypass Grafting Surgery.

Trace elements selenium (Se) and cobalt (Co) are essential in the human body, and a correlation between Se and cardiac surgery has been suggested. We investigated the plasma concentrations of Se and Co during and after coronary artery bypass grafting (CABG) surgery under cardiopulmonary bypass (CPB). From December 2019 to January 2020, preoperative plasma samples from isolated first-time CABG patients (n=20; 10 males, 10 females) were prospectively collected post-anesthesia and before CPB (T1), 45 min after CPB started (T2), 90 min after CPB started (T3), and postoperative days 1 (T4), and day 4 (T5). The plasma concentrations of Se and Co were measured. The Se concentration was significantly decreased at T2 (105.24±4.08 vs. 68.56±2.42 µg/L, p<0.001) and T3 (105.24±4.08 vs. 80.41±3.40 µg/L, p<0.001). The Co concentration was significantly decreased at T4 (0.35±0.19 vs. 0.26±0.13 µg/L, p<0.01) and T5 (0.35±0.19 vs. 0.23±0.11 µg/L, p<0.001). Five patients developed atrial fibrillation (AF); there was no other operative mortality or major morbidity. This is the first report of alterations of plasma Se and Co concentrations during and after CABG surgery. Our results may indicate that Se supplementation before or during CABG and Co supplementation after CABG may become necessary for patients undergoing CABG.

Construction of integrative transcriptome to boost systematic exploration of Bougainvillea.

Members of the genus Bougainvillea are rich sources of natural dyes, pigments, and traditional medicines. They are also commonly used as ornamentals in roadside landscape construction. However, the horticultural development of Bougainvillea flowers with extended growth periods and coloration is not always feasible. One reason is limited molecular knowledge and no genomic information for Bougainvillea. Here, we compiled an integrative transcriptome of all expressed transcripts for Bougainvillea × buttiana Miss Manila by integrating 20 Illumina-sequencing RNA transcriptomes. The integrative transcriptome consisted of 97,623 distinct transcripts. Of these, 47,006 were protein-coding, 31,109 were non-coding, and 19,508 were unannotated. In addition, we affirmed that the integrative transcriptome could serve as a surrogate reference to the genome in aiding accurate transcriptome assembly. For convenience, we curated the integrative transcriptome database for Bougainvillea, namely InTransBo, which can be freely accessed at http://www.bio-add.org/InTransBo/index.jsp . To the best of our knowledge, the present study is the most comprehensive genomic resource for Bougainvillea up-to-date. The integrative transcriptome helps fill the genomic gap and elucidate the transcriptional nature of Bougainvillea. It may also advance progress in the precise regulation of flowering in horticulture. The same strategy can be readily applied toward the systematic exploration of other plant species lacking complete genomic information.

del Nido cardioplegia better preserves cardiac diastolic function but histidine-tryptophan-ketoglutarate is better for endothelial function.

OBJECTIVES: The effectiveness of myocardial protection of cardioplegia has been a matter of debate for decades. This study was designed to compare cardiac and endothelial protection of 3 clinically used cardioplegias: del Nido cardioplegia (DNC), histidine-tryptophan-ketoglutarate (HTK) and blood cardioplegia (BC) followed by HTK (BC + HTK) in a rat model of ischaemia/reperfusion (I/R). METHODS: Sixty male Wistar rats were subjected to either 120 min of global ischaemia at 4°C followed by 90 min of reperfusion (I/R) at 37°C or no I/R (control) in a Langendorff apparatus and were randomly allocated to 5 groups: control, I/R, DNC, HTK and BC + HTK. Cold cardioplegia solutions were administered at doses of 20 ml/kg for DNC and HTK or 10 ml/kg for BC followed by HTK. Haemodynamic parameters were continuously recorded using an intraventricular balloon. The endothelium-dependent relaxation to acetylcholine was measured in the left anterior descending artery using a myograph. Protein expression of cardiac troponin T (cTnT) and creatine kinase MB was determined by western blot. RESULTS: During reperfusion, HTK had higher left ventricular systolic pressure whereas DNC had lower left ventricular end-diastolic pressure, better left ventricular developed pressure and best +dp/dtmax and -dp/dtmax than the other 2 groups but the differences disappeared at the end of the reperfusion. HTK or BC + HTK preserves the acetylcholine-induced endothelium-dependent relaxation better than DNC (Emax = 48.2 ± 8.0% in DNC vs 75.0 ± 8.0% in HTK, P < 0.05; vs 96.9 ± 3.5% in BC + HTK, P < 0.001). The protein levels of cTnT and creatine kinase MB were downregulated in the 3 groups. CONCLUSIONS: All 3 cardioplegias prevented myocardial damage against I/R injury at the end of reperfusion. DNC demonstrated better preserved diastolic function of the left ventricle whereas HTK or BC + HTK showed better preserved coronary endothelial function. These findings may suggest that currently no 'perfect' cardioplegia exists and that exploration for the 'perfect' cardioplegia is needed.

Effect of Forced-Air Warming Blanket on Perioperative Hypothermia in Elderly Patients Undergoing Laparoscopic Radical Resection of Colorectal Cancer.

The study aimed to evaluate the effect of forced-air warming blanket combined with conventional thermal insulation measures on inadvertent perioperative hypothermia (IPH) in elderly patients undergoing laparoscopic radical resection of colorectal cancer. A total of 70 elderly patients undergoing laparoscopic radical resection of colorectal cancer with general anesthesia were included, and divided into conventional warming treatment (CT) group or forced-air warming treatment (FT) group. In the FT group, based on the conventional warming strategy, patients received prewarming with the forced-air warming blanket (38°C) for ≥20 minutes before induction of anesthesia, and received this treatment continuously during operation. The core body temperature, recovery time from anesthesia, extubating time, and length of stay in the postanesthesia care unit were recorded. The incidence of IPH and postoperative shivering was observed. The incidence of IPH was significantly lower, and average minimum body temperature during the operation was significantly higher in the FT group than that in the CT group (5.7% vs. 22.8% and 36.23°C vs. 35.89°C, respectively). The intraoperative body temperature decreased less (0.32°C vs. 0.69°C), the recovery time from anesthesia was faster (12.8 minutes vs. 17.1 minutes), and the incidence of postoperative shivering was less (2.8% vs. 28.6%) in the FT group than the CT group. In elderly patients undergoing laparoscopic radical resection of colorectal cancer, use of forced-air warming blankets combined with conventional warming measures is more effective to maintain normal body temperature during the perioperative period and reduce the incidence of IPH.

Homocysteine alters vasoreactivity of human internal mammary artery by affecting the KCa channel family.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for atherosclerotic heart disease. We previously demonstrated that disruption of calcium-activated potassium (KCa) channel activity is involved in homocysteine-induced dilatory dysfunction of porcine coronary arteries. Recently we reported that the KCa channel family, including large-, intermediate-, and small-conductance KCa (BKCa, IKCa, and SKCa) subtypes, are abundantly expressed in human internal mammary artery (IMA). In this study, we further investigated whether homocysteine affects the expression and functionality of the KCa channel family in this commonly used graft for coronary artery bypass surgery (CABG). METHODS: Residual IMA segments obtained from patients undergoing CABG were studied in a myograph for the role of KCa subtypes in both vasorelaxation and vasoconstriction. The expression and distribution of KCa subtypes were detected by Western blot and immunohistochemistry. RESULTS: Both the BKCa channel activator NS1619 and the IKCa/SKCa channel activator NS309 evoked significant IMA relaxation. Homocysteine exposure suppressed NS1619-induced relaxation whereas showed no influence on NS309-induced response. Blockade of BKCa but not IKCa and SKCa subtypes significantly suppressed acetylcholine-induced relaxation and enhanced U46619-induced contraction. Homocysteine compromised the vasodilating activity of the BKCa subtype in IMA, associated with a lowered protein level of the BKCa ß1-subunit. Homocysteine potentiated the role of IKCa and SKCa subtypes in mediating endothelium-dependent relaxation without affecting the expression of these channels. CONCLUSIONS: Homocysteine reduces the expression of BKCa ß1-subunit and compromises the vasodilating activity of BKCa channels in IMA. Unlike BKCa, IKCa and SKCa subtypes are unessential for IMA vasoregulation, whereas the loss of BKCa functionality in hyperhomocysteinemia enhances the role of IKCa and SKCa subtypes in mediating endothelial dilator function. Targeting BKCa channels may form a strategy to improve the postoperative graft performance in CABG patients with hyperhomocysteinemia who receive IMA grafting.