Propofol is cardioprotective in a clinically relevant model of normothermic blood cardioplegic arrest and cardiopulmonary bypass

The general anesthetic propofol has been shown to be cardioprotective. However, its benefits when used in cardioplegia during cardiac surgery have not been demonstrated. In this study, we investigated the effects of propofol on metabolic stress, cardiac function, and injury in a clinically relevant model of normothermic cardioplegic arrest and cardiopulmonary bypass. Twenty anesthetized pigs, randomized to propofol treatment (n = 8) and control (n = 12) groups, were surgically prepared for cardiopulmonary bypass (CPB) and cardioplegic arrest. Doses of warm blood cardioplegia were delivered at 15-min intervals during a 60-min aortic cross-clamped period. Propofol was continuously infused for the duration of CPB and was therefore present in blood cardioplegia. Myocardial biopsies were collected before, at the end of cardioplegic arrest, and 20 mins after the release of the aortic cross-clamp. Hemodynamic parameters were monitored and blood samples collected for cardiac troponin I measurements. Propofol infusion during CPB and before ischemia did not alter cardiac function or myocardial metabolism. Propofol treatment attenuated the changes in myocardial tissue levels of adenine nucleotides, lactate, and amino acids during ischemia and reduced cardiac troponin I release on reperfusion. Propofol treatment reduced measurable hemodynamic dysfunction after cardioplegic arrest when compared to untreated controls. In conclusion, propofol protects the heart from ischemia-reperfusion injury in a clinically relevant experimental model. Propofol may therefore be a useful adjunct to cardioplegic solutions as well as being an appropriate anesthetic for cardiac surgery.     

Interstitial cells from the atrial and ventricular sides of the bovine mitral valve respond differently to denuding endocardial injury

Summary The mitral valve has atrial and ventricular sides, each lined by endocardial cells. The valve stroma contains α smooth muscle actin positive interstitial cells, collagen, glycosaminoglycans, and elastic tissue. To eliminate the effect of endocardium on wound repair in bovine mitral valve organ culture, the endocardium was removed from both sides of the valve. At 6 days, organ cultures of these preparations revealed surface cells on the ventricular side but not on the atrial side. Ventricular surface cells were negative for Factor VIII-related antigen, and positive for α smooth muscle actin. Immuno-peroxidase staining for proliferating cell nuclear antigen/cyclin, a marker for cell proliferation, revealed a positive labeling index of (mean ± standard deviation) 0.08 ± 0.16% for interstitial cells from the atrial side and 0.14 ± 0.19% for ventricular side interstitial cells in uncultured preparations (not significant), and 0.44 ± 0.69% for atrial side interstitial cells and 2.25 ± 1.64% for ventricular side interstitial cells in the cultured preparations (significant,P<0.0006). The results suggest that in organ culture, interstitial cells from the ventricular side of the mitral valve respond to a denuding endocardial injury by proliferating and migrating onto the adjacent surface whereas interstitial cells from the atrial side do not. This difference in the response to injury of interstitial cells from the atrial and ventricular sides of the valve may reflect differences in phenotype or may be due to effects of extracellular matrix on interstitial cell behavior. The latter is possible because of differences in the extracellular matrix of the atrial and ventricular sides of the valve.     

Murine Isolated Heart Model of Myocardial Stunning Associated with Cardioplegic Arrest

The following protocol is of use to evaluate impaired cardiac function or myocardial stunning following moderate ischemic insults. The technique is useful for modeling ischemic injury associated with numerous clinically relevant phenomenon including cardiac surgery with cardioplegic arrest and cardiopulmonary bypass, off-pump CABG, transplant, angina, brief ischemia, etc. The protocol presents a general method to model hypothermic hyperkalemic cardioplegic arrest and reperfusion in rodent hearts focusing on measurement of myocardial contractile function. In brief, a mouse heart is perfused in langendorff mode, instrumented with an intraventricular balloon, and baseline cardiac functional parameters are recorded. Following stabilization, the heart is then subject to brief infusion of a cardioprotective hypothermic cardioplegia solution to initiate diastolic arrest. Cardioplegia is delivered intermittently over 2 hr. The heart is then reperfused and warmed to normothermic temperatures and recovery of myocardial function is monitored. Use of this protocol results in reliable depressed cardiac contractile function free from gross myocardial tissue damage in rodents.     

Ethane: a marker of lipid peroxidation during cardiopulmonary bypass in humans

The goals of this study were to (1) determine the utility of quantification of ethane as a marker of ischemia-reperfusion during human cardiopulmonary bypass (CPB); and (2) determine, using an animal model for this surgical procedure, whether the mode of surgical approach produced increases the quantity of exhaled ethane. Human CPB was initiated following standard anesthetic and monitoring regimens. Samples of gas were collected at baseline and at multiple defined time points throughout the studies. Ethane was determined using cryogenic concentration and gas chromatography. Sternotomy increased exhaled ethane compared to baseline (p < .007; 5.8 ± 1.7 vs. 3.0 ± 0.7 nmol/m² · min); ethane returned to baseline levels prior to the initiation of CPB. Aortic unclamping produced ethane elevation (p < .05; 2.3 ± 0.8 vs. 1.5 ± 0.4 nmol/m² · min) with the levels being related to a lower cardiac index and a higher systemic vascular resistance post aortic unclamping. Termination of CPB significantly increased ethane levels compared to baseline (p < .002; 4.8 ± 1.7 vs. 3.0 ± 0.7 nmol/m² · min). Independent variables that correlated with increased ethane measurements included a higher arterial blood pH on bypass and the change in hemoglobin pre- and post-CPB. Electrocautery, but not scalpel, incision of the porcine abdominal wall increased ethane levels significantly (p < .02). These results indicate that exhaled ethane may be a valuable marker of lipid peroxidation during and following CPB.     

The importance of myocardial amino acids during ischemia and reperfusion in dilated left ventricle of patients with degenerative mitral valve disease

Taurine, glutamine, glutamate, aspartate, and alanine are the most abundant intracellular free amino acids in human heart. The myocardial concentration of these amino acids changes during ischemia and reperfusion due to alterations in metabolic and ionic homeostasis. We hypothesized that dilated left ventricle secondary to mitral valve disease has different levels of amino acids compared to the right ventricle and that such differences determine the extent of amino acids' changes during ischemia and reperfusion. Myocardial concentration of amino acids was measured in biopsies collected from left and right ventricles before cardioplegic arrest (Custodiol HTK) and 10 min after reperfusion in patients undergoing mitral valve surgery. The dilated left ventricle had markedly higher (P < 0.05) concentrations (nmol/mg wet weight) of taurine (17.0 ± 1.5 vs. 10.9 ± 1.5), glutamine (20.5 ± 2.4 vs. 12.1 ± 1.2), and glutamate (18.3 ± 2.2 vs. 11.4 ± 1.5) when compared to right ventricle. There were no differences in the basal levels of alanine or aspartate. Upon reperfusion, a significant (P < 0.05) fall in taurine and glutamine was seen only in the left ventricle. These changes are likely to be due to transport (taurine) and/or metabolism (glutamine). There was a marked increase in the alanine to glutamate ratio in both ventricles indicative of ischemic stress which was confirmed by global release of lactate during reperfusion. This study shows that in contrast to the right ventricle, the dilated left ventricle had remodeled to accumulate amino acids which are used during ischemia and reperfusion. Whether these changes reflect differences in degree of cardioplegic protection between the two ventricles remain to be investigated.     

The role of bronchial epithelial cell apoptosis in the pathogenesis of COPD

There is an increased airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD), and it has been suggested that there may also be problem in the apoptosis and renewal of cells. However, there are limited human airway cell studies, in particular those from larger airways such as bronchi. We cultured primary human bronchial epithelial cells (HBECs) from bronchial explants of smokers (n = 6) without COPD and smokers with COPD (n = 8). Apoptosis was studied by fluorescence activated cell sorting. qRT-PCR was used to assess mRNA expression for proteins involving apoptosis including p21^CIP1/WAF1, p53, caspase-8 and caspase-9. Although there was no difference in the rate of viable cells between cells from smokers and COPDs, the level of early apoptotic cells was significantly increased in COPD cells [mean ± standard error of mean (SEM) = 4.86 ± 3.2 %, p = 0.015] as compared to smokers (mean ± SEM = 2.71 ± 1.62 %). In contrast, the rate of late apoptotic cells was significantly decreased in COPD cells (mean ± SEM = 9.82 ± 5.71 %) comparing to smokers (mean ± SEM = 15.21 ± 5.08 %, p = 0.003). Although expression of mRNA for p21^CIP1/WAF1 and caspase-9 was similar in both groups, p53 and caspase-8 mRNA expression was significantly greater in COPD cells. These findings suggest that HBEC apoptosis is increased in COPD, and that this involves p53 and caspase-8 pathways.     

Atrial fibrillation pacing decreases intravascular shear stress in a New Zealand white rabbit model: implications in endothelial function

Atrial fibrillation (AF) is characterized by multiple rapid and irregular atrial depolarization, leading to rapid ventricular responses exceeding 100 beats per minute (bpm). We hypothesized that rapid and irregular pacing reduced intravascular shear stress (ISS) with implication to modulating endothelial responses. To simulate AF, we paced the left atrial appendage of New Zealand White rabbits (n = 4) at rapid and irregular intervals. Surface electrical cardiograms were recorded for atrial and ventricular rhythm, and intravascular convective heat transfer was measured by microthermal sensors, from which ISS was inferred. Rapid and irregular pacing decreased arterial systolic and diastolic pressures (baseline, 99/75 mmHg; rapid regular pacing, 92/73; rapid irregular pacing, 90/68; p < 0.001, n = 4), temporal gradients ( ${\partial\tau/\partial t}$ from 1,275 ± 80 to 1,056 ± 180 dyne/cm² s), and reduced ISS (from baseline at 32.0 ± 2.4 to 22.7 ± 3.5 dyne/cm²). Computational fluid dynamics code demonstrated that experimentally inferred ISS provided a close approximation to the computed wall shear stress at a given catheter to vessel diameter ratio, shear stress range, and catheter position. In an in vitro flow system in which time-averaged shear stress was maintained at ${{\tau_{\rm avg}} = 23 \pm 4\, {\rm dyn}\, {\rm cm}^{-2} {\rm s}^{-1}}$ , we further demonstrated that rapid pulse rates at 150 bpm down-regulated endothelial nitric oxide, promoted superoxide (O ₂ ^.? ) production, and increased monocyte binding to endothelial cells. These findings suggest that rapid pacing reduces ISS and ${\partial\tau/\partial t}$ , and rapid pulse rates modulate endothelial responses.     

p53蛋白在周期调节蛋白A1变异引起的雄性小鼠生殖细胞凋亡中的作用

为研究p5 3蛋白在周期调节蛋白A1(cyclinA1)变异引起的雄性小鼠生殖细胞凋亡中的作用 ,以p5 3基因敲除的小鼠和周期调节蛋白A1基因敲除的小鼠杂交 ,获取同胎生单基因变异和双基因同时变异的雄性后代共 4组 12只 .比较它们的性腺和生殖细胞发育 ,并用TUNEL染色法观察和比较生殖细胞的凋亡情况 .在睾丸最大横切面上观察到 :周期调节蛋白A1变异组凋亡细胞最多 (348± 10 4个 ) ,明显高于p5 3 周期调节蛋白A1双基因变异组 (12 1± 38个 ) ,t=3 2 5 79,P =0 0 4 72 .p5 3变异组凋亡细胞最少 (45± 2 4个 ) ,配对t检验显示有非常显著性差异 ,t=8 4 0 13,P =0 0 0 35 .这一研究结果提示 ,p5 3基因可能在雄性生殖细胞的发育中起监视作用 ,并在周期调节蛋白A1变异引起发育异常时启动p5 3途径造成异常细胞的凋亡 .     

Effects of bile salts on cholestan-3β,5α,6β-triol-induced apoptosis in dog gallbladder epithelial cells

Oxysterols are cytotoxic agents. The gallbladder epithelium is exposed to high concentrations of oxysterols, and so elucidating the mechanisms of cytotoxicity in this organ may enhance our understanding of the pathogenesis of biliary tract disorders. We investigated the cytotoxic effects of the oxysterol cholestan-3β,5α,6β-triol (TriolC) on dog gallbladder epithelial cells. Apoptosis was the major form of cytotoxicity, as determined by analysis of nuclear morphologic changes and by multiparameter flow cytometry. Hydrophobic bile salts are known to have cytotoxic effects, whereas hydrophilic bile salts have cytoprotective effects. We therefore examined whether the hydrophobic bile acid taurodeoxycholic acid (TDC) and the hydrophilic bile acid tauroursodeoxycholic acid (TUDC) had modifying effects on oxysterol-induced cytotoxicity. TriolC caused an increase in the number of apoptotic cells from 14±11% (control) to 48±12% of total cells (P<0.01). After combining TriolC with TDC, cell apoptosis increased to 63±16% (P<0.05), whereas after addition of TUDC, the number of apoptotic cells decreased to 31±12% (P<0.05) of total cells. In summary, oxysterols such as TriolC induce apoptosis. Hydrophobic bile salts enhance TriolC-induced apoptosis, whereas hydrophilic bile salts diminish TriolC-induced apoptosis. These results suggest that interactions between oxysterols and bile salts play a role in the pathophysiology of biliary tract disorders.     

SMAD‐proteins as a molecular switch from hypertrophy to apoptosis induction in adult ventricular cardiomyocytes

Heart failure development goes along with a transition from hypertrophic growth to apoptosis induction. In adult cardiomyocytes SMAD proteins are only activated under apoptotic, but not under hypertrophic conditions and are increased at the transition to heart failure. Therefore, SMADs could be candidates that turn the balance from hypertrophic growth to apoptosis resulting in heart failure development. To test this hypothesis we infected isolated rat ventricular cardiomyocytes with adenovirus encoding SMAD4 (AdSMAD4) and investigated the impact of SMAD4 overexpression on the development of apoptosis and hypertrophy under stimulation with phenylephrine (PE). Infection of cardiomyocytes with AdSMAD4 significantly enhanced SMAD‐binding activity while apoptosis after 24 and 36 h infection did not rise. But when SMAD4 overexpressing cardiomyocytes were incubated with PE (10 µM), the number of apoptotic cells increased (Ctrl: 94.97 ± 6.91%; PE: 102.48 ± 4.78% vs. AdSMAD4 + PE: 118.64 ± 3.28%). Furthermore expression of caspase 3 as well as bax/bcl2 ratio increased in SMAD4 overexpressing, PE‐stimulated cardiomyocytes. In addition, the effects of SMAD4 overexpression on PE‐induced hypertrophic growth were analyzed. Protein synthesis 36 h after AdSMAD4 infection was comparable to control cells, whereas the increase in protein synthesis stimulated by phyenylephrine was significantly reduced in SMAD4 overexpressing cells (134.28 ± 10.02% vs. 100.57 ± 8.86%). SMAD4 triggers the transition from hypertrophy to apoptosis in ventricular cardiomyocytes. Since SMADs are increased under several pathophysiological conditions in the heart, it can be assumed that it triggers apoptosis induction and therefore contributes to negative remodeling and heart failure progression. J. Cell. Physiol. 220: 515–523, 2009. © 2009 Wiley‐Liss, Inc.     

Granulocyte Colony Stimulating Factor Reduces Brain Injury in a Cardiopulmonary Bypass-Circulatory Arrest Model of Ischemia in a Newborn Piglet

Ischemic brain injury continues to be of major concern in patients undergoing cardiopulmonary bypass (CPB) surgery for congenital heart disease. Striatum and hippocampus are particularly vulnerable to injury during these processes. Our hypothesis is that the neuronal injury resulting from CPB and the associated circulatory arrest can be at least partly ameliorated by pre-treatment with granulocyte colony stimulating factor (G-CSF). Fourteen male newborn piglets were assigned to three groups: deep hypothermic circulatory arrest (DHCA), DHCA with G-CSF, and sham-operated. The first two groups were placed on CPB, cooled to 18 °C, subjected to 60 min of DHCA, re-warmed and recovered for 8–9 h. At the end of experiment, the brains were perfused, fixed and cut into 10 µm transverse sections. Apoptotic cells were visualized by in situ DNA fragmentation assay (TUNEL), with the density of injured cells expressed as a mean number ± SD per mm². The number of injured cells in the striatum and CA1 and CA3 regions of the hippocampus increased significantly following DHCA. In the striatum, the increase was from 0.46 ± 0.37 to 3.67 ± 1.57 (p = 0.002); in the CA1, from 0.11 ± 0.19 to 5.16 ± 1.57 (p = 0.001), and in the CA3, from 0.28 ± 0.25 to 2.98 ± 1.82 (p = 0.040). Injection of G-CSF prior to bypass significantly reduced the number of injured cells in the striatum and CA1 region, by 51 and 37 %, respectively. In the CA3 region, injured cell density did not differ between the G-CSF and control group. In a model of hypoxic brain insult associated with CPB, G-CSF significantly reduces neuronal injury in brain regions important for cognitive functions, suggesting it can significantly improve neurological outcomes from procedures requiring DHCA.     

Semi-automated program for analysis of local Ca2+ spark release with application for classification of heart cell type

Local Ca²⁺ spark releases are essential to the Ca²⁺ cycling process. Thus, they play an important role in ventricular and atrial cell contraction, as well as in sinoatrial cell automaticity. Characterizing their properties in healthy cells from different regions in the heart can reveal the basic biophysical differences among these regions. We designed a semi-automatic Matlab Graphical User Interface (called Sparkalyzer) to characterize parameters of Ca²⁺ spark release from any major cardiac tissue, as recorded in line-scan mode with a confocal laser-scanning microscope. We validated the algorithm on experimental images from rabbit sinoatrial, atrial, and ventricular cells loaded with Fluo-4 AM. The program characterizes general image parameters of Ca²⁺ transients and sparks: spark duration, which indicates for how long the spark provides Ca²⁺ to the closed intracellular mechanisms (typical value: 25 ± 1, 23 ± 1, 26 ± 1 ms for sinoatrial, atrial, and ventricular cells, respectively); spark amplitude, which indicates the amount of Ca²⁺ released by a single spark (1.6 ± 0.1, 1.6 ± 0.2, 1.4 ± 0.1 F/F₀ for sinoatrial, atrial, and ventricular cells, respectively); spark length, which is the length of the Ca²⁺ wavelets fired out of a row of ryanodine receptors (5 ± 0.1, 5 ± 0.2, 3.4 ± 0.3 μm for sinoatrial, atrial, or ventricular cells, respectively) and number of sparks (0.14 ± 0.02, 0.025 ± 0.01, 0.02 ± 0.01 for 1 μm in 1 s for sinoatrial, atrial, and ventricular cells, respectively). This method is reliable for Ca²⁺ spark analysis of sinoatrial, atrial, or ventricular cells. Moreover, by examining the average value of Ca²⁺ spark characteristics and their scattering around the mean, atrial, ventricular and sinoatrial cells can be differentiated.     

Atrial electrogram quality in single-pass defibrillator leads with floating atrial bipole in patients with permanent atrial fibrillation and cardiac resynchronization therapy

Many patients receiving cardiac resynchronization therapy (CRT) suffer from permanent atrial fibrillation (AF). Knowledge of the atrial rhythm is important to direct pharmacological or interventional treatment as well as maintaining AV-synchronous biventricular pacing if sinus rhythm can be restored. A single pass single-coil defibrillator lead with a floating atrial bipole has been shown to obtain reliable information about the atrial rhythm but has never been employed in a CRT-system. The purpose of this study was to assess the feasibility of implanting a single coil right ventricular ICD lead with a floating atrial bipole and the signal quality of atrial electrograms (AEGM) in CRT-defibrillator recipients with permanent AF.

Changes of ghrelin and brain natriuretic peptide levels in systemic vascular resistance after cardiopulmonary bypass

The application of cardiopulmonary bypass (CPB) using a heart-lung machine in open heart surgery is associated with numerous pathophysiological changes in the vascular system and the neurohormonal environment. In this study our purpose was to investigate whether the hormones brain natriuretic peptide (BNP) and ghrelin are involved in changes in the systemic vascular resistance index (SVRI) after CPB, using data from 20 patients who had undergone coronary artery by pass grafting accompanied by CPB. Hemodynamic measurements were obtained using a thermodilution catheter and included cardiac index and systemic vascular resistance index. Blood samples were taken before CPB, after CPB, and at 0 and 24 h postoperatively. The blood levels of total and acylated ghrelin were quantified by radioimmunoassay. Blood levels of BNP were measured by a fluorescence immunoassay kit. The SVRI was significantly higher at the end of CPB and at 0 h postoperatively than before CPB (end of CPB: 4282±1035 dyne·s·cm^?5·m^?2, 0 h postoperatively: 3239±635 dyne·s·cm^?5·m^?2 vs. before CPB: 2289±330 dyne·s·cm^?5·m^?2, p<0.05). Total and acylated ghrelin levels decreased until 0 h postoperatively but the change was not statistically significant. However, at 24 h after surgery, they showed a statistically significant increase over the initial ghrelin values (total before CPB: 1413.71±287.93 pg/ml vs. 24 h postoperatively: 1736.85±236.89 pg/ml; acylated ghrelin before CPB: 55.85±25.53 pg/ml vs. 24 h postoperatively: 106.28±30.86 pg/ml; p<0.05 for both). BNP values were markedly lower after than before CPB (before CPB: 69.07±48 pg/ml vs. after CPB: 21.96±13 pg/ml, p<0.05) and reached a maximum value 24 h postoperatively (before CPB: 56.3±42 vs. after CPB: 454.7±229 pg/ml, p<0.05). There was a weak negative correlation between the changes in SVRI and total and acylated ghrelin levels after the CPB period, but this was not statistically significant. However, there was a statistically significant negative correlation between SVRI and BNP after CPB and at 24 h postoperatively (r:?0.709, p<0.01 and r:?0.649, p<0.03, respectively). Taken together, our results show that the observed initial increases in ghrelin and/or BNP in the postoperative period (at 24 h) might be causally related to the decrease in the SVRI in the same period. However, further investigations are needed to clarify the significance of this observation with respect to that of SVRI.     

Cardioprotective Efficacy of a Novel Antioxidant Mix VitaePro Against Ex Vivo Myocardial Ischemia–Reperfusion Injury

Circumstantial evidence frequently implicates oxygen-derived free radicals and oxidative stress as mediators of myocardial ischemia/reperfusion (I/R) injury. Therefore, external supplementation of natural antioxidants plays a main role as cardioprotective compounds. This study was designed to evaluate the cardioprotective effect of VitaePro (70 mg/kg body weight, 21 days), a novel antioxidant mix of astaxanthin, lutein and zeaxanthin in a rat ex vivo model of ischemia/reperfusion injury. The cardioprotective effect of VitaePro was also compared with vitamin E (70 mg/kg body weight, 21 days) treatment. Rats were randomized into control I/R (CIR), VitaePro I/R (VPIR) and Vitamin E I/R (VEIR). After 21 days of oral treatment, isolated hearts from each group were subjected to 30 min of ischemia followed by 2 h of reperfusion. In the VPIR group compared to CIR and VEIR groups at 2 h of reperfusion, increased left ventricular functional recovery, such as left ventricular developed pressure (92.7 ± 0.7 vs. 85.3 ± 0.3 and 89.4 ± 1.2 mm Hg), dp/dt _max (2518.7 ± 77.9 vs. 1962.5 ± 24 and 2255.7 ± 126.6 mm Hg/s), and aortic flow (21.5 ± 1.36 vs. 4.4 ± 0.6 and 13.2 ± 1.02 ml/min) were observed. The infarct size (27.68 ± 1.7 vs. 45.4 ± 1.8 and 35.4 ± 0.6%), apoptotic cardiomyocytes (61.7 ± 10.6 vs. 194.1 ± 14.8 and 118.7 ± 15.4 counts/100 HPF) and thiobarbituric acid reactive substances levels (80 ± 3 vs. 127 ± 5 and 103 ± 2 nM/mg tissue) also were decreased in VPIR group when compared to CIR and VEIR. As evidenced by the data, administration of vitamin E offered substantial cardioprotection to I/R injury, but VitaePro enhanced cardioprotection significantly more than vitamin E treatment. Taken in concert, the results of this study suggests that the oral ingestion of VitaePro protects myocardium from ischemia/reperfusion injury by decreasing oxidative stress and apoptosis, which may be of therapeutic benefit in the treatment of cardiovascular complications. However, further in vivo animal and human intervention studies are warranted before establishing any recommendations about usage of VitaePro for human cardiovascular complications.     

右室Tei指数与血清醛固酮水平对COPD患者发生房颤的预测价值研究

摘要 目的：探讨右室Tei指数、血清醛固酮水平对慢性阻塞性肺病(COPD)患者发生房颤的预测价值。方法：根据房颤的发生情况,将200例COPD患者分为房颤发生组和无房颤发生组。比较两组的病程、COPD严重程度、血清醛固酮(ALD)水平及右室Tei指数、肺动脉压、右心室横径的差异,分析右室Tei指数和ALD预测房颤发生的ROC曲线下面积、截断值、灵敏度及特异度。结果：房颤发生组病程(8.48±1.3和7.59±1.75)、右心室横径(40.52±2.74和36.27±2.4)、血清ALD(137.64±42.77和98.61±15.39)、右室Tei指数(0.37±0.12和0.31±0.07)、COPD、肺动脉高压的严重程度与无房颤发生组比较差异都有统计学意义(P<0.05)。logistic回归分析结果显示ALD、右室Tei指数、病程、和肺动脉高压程度为影响COPD患者发生房颤的独立影响因素。右室Tei指数预测房颤发生的ROC曲线下面积AUC=0.645,截断值为0.420,灵敏度为38.0%,特异度达到93.33%;ALD预测房颤发生的ROC曲线下面积为0.792,截断值为122.72 pg/mL,灵敏度为66.0%,特异度可达到98.0%。结论：右室Tei指数和血清醛固酮水平可作为慢性阻塞性肺病患者发生房颤的预测参考指标。     

Presence of factors that activate platelet aggregation in mitral stenotic patients' plasma

Background

In high-risk coronary artery bypass patients; off-pump versus on-pump surgical strategies still remain a matter of debate, regarding which method results in a lower incidence of perioperative mortality and morbidity. We describe our experience in the treatment of high-risk coronary artery patients and compare patients assigned to on-pump and off-pump surgery.

Methods

From March 2002 to July 2004, 86 patients with EuroSCOREs > 5 underwent myocardial revascularization with or without cardiopulmonary bypass. Patients were assigned to off-pump surgery (40) or on-pump surgery (46) based on coronary anatomy coupled with the likelihood of achieving complete revascularization.

Results

Those patients undergoing off-pump surgery had significantly poorer left ventricular function than those undergoing on-pump surgery (28.6 ± 5.8% vs. 40.5 ± 7.4%, respectively, p < 0.05) and also had higher Euroscore values (7.26 ± 1.4 vs. 12.1 ± 1.8, respectively, p < 0.05). Differences between the two groups were nonsignificant with regard to number of grafts per patient, mean duration of surgery, anesthesia and operating room time, length of stay intensive care unit (ICU) and rate of postoperative atrial fibrillation

Conclusion

Utilization of off-pump coronary artery bypass graft (CABG) does not confer significant clinical advantages in all high-risk patients. This review suggest that off-pump coronary revascularization may represent an alternative approach for treatment of patients with Euroscore ≥ 10 and left ventricular function ≤ 30%.     

A Matched-Filter-Based Algorithm for Subcellular Classification of T-System in Cardiac Tissues

In mammalian ventricular cardiomyocytes, invaginations of the surface membrane form the transverse tubular system (T-system), which consists of transverse tubules (TTs) that align with sarcomeres and Z-lines as well as longitudinal tubules (LTs) that are present between Z-lines in some species. In many cardiac disease etiologies, the T-system is perturbed, which is believed to promote spatially heterogeneous, dyssynchronous Ca²⁺ release and inefficient contraction. In general, T-system characterization approaches have been directed primarily at isolated cells and do not detect subcellular T-system heterogeneity. Here, we present MatchedMyo, a matched-filter-based algorithm for subcellular T-system characterization in isolated cardiomyocytes and millimeter-scale myocardial sections. The algorithm utilizes “filters” representative of TTs, LTs, and T-system absence. Application of the algorithm to cardiomyocytes isolated from rat disease models of myocardial infarction (MI), dilated cardiomyopathy induced via aortic banding, and sham surgery confirmed and quantified heterogeneous T-system structure and remodeling. Cardiomyocytes from post-MI hearts exhibited increasing T-system disarray as proximity to the infarct increased. We found significant (p < 0.05, Welch’s t-test) increases in LT density within cardiomyocytes proximal to the infarct (12 ± 3%, data reported as mean ± SD, n = 3) versus sham (4 ± 2%, n = 5), but not distal to the infarct (7 ± 1%, n = 3). The algorithm also detected decreases in TTs within 5° of the myocyte minor axis for isolated aortic banding (36 ± 9%, n = 3) and MI cardiomyocytes located intermediate (37 $\pm$ 4%, n = 3) and proximal (34 ± 4%, n = 3) to the infarct versus sham (57 ± 12%, n = 5). Application of bootstrapping to rabbit MI tissue revealed distal sections comprised 18.9 ± 1.0% TTs, whereas proximal sections comprised 10.1 ± 0.8% TTs (p < 0.05), a 46.6% decrease. The matched-filter approach therefore provides a robust and scalable technique for T-system characterization from isolated cells through millimeter-scale myocardial sections.     

Mentha piperita as a pivotal neuro-protective agent against gamma irradiation induced DNA fragmentation and apoptosis

Ionizing radiation is classified as a potent carcinogen, and its injury to living cells, in particular to DNA, is due to oxidative stress enhancing apoptotic cell death. Our present study aimed to characterize and semi-quantify the radiation-induced apoptosis in CNS and the activity of Mentha extracts as neuron-protective agent. Our results through flow cytometry exhibited the significant disturbance and arrest in cell cycle in % of M1: SubG1 phase, M2: G0/1 phase of diploid cycle, M3: S phase and M4: G2/M phase of cell cycle in brain tissue (p < 0.05). Significant increase in % of apoptosis and P53 protein expression as apoptotic biomarkers were coincided with significant decrease in Bcl₂ as an anti-apoptotic marker. The biochemical analysis recorded a significant decrease in the levels of reduced glutathione, superoxide dismutase, deoxyribonucleic acid (DNA) and ribonucleic acid contents. Moreover, numerous histopathological alterations were detected in brain tissues of gamma irradiated mice such as signs of chromatolysis in pyramidal cells of cortex, nuclear vacuolation, numerous apoptotic cell, and neural degeneration. On the other hand, gamma irradiated mice pretreated with Mentha extract showed largely an improvement in all the above tested parameters through a homeostatic state for the content of brain apoptosis and stabilization of DNA cycle with a distinct improvement in cell cycle analysis and antioxidant defense system. Furthermore, the aforementioned effects of Mentha extracts through down-regulation of P53 expression and up-regulation of Bcl₂ domain protected brain structure from extensive damage. Therefore, Mentha extract seems to have a significant role to ameliorate the neuronal injury induced by gamma irradiation.     

Aortic Pulse Wave Velocity is Associated with Measures of Subclinical Target Organ Damage in Patients with Mild Hypertension

We evaluated the temporal association between aortic arterial stiffness and subclinical target organ damage, including renal function decline, left ventricular geometric remodeling, and left ventricular diastolic dysfunction in patients with mild hypertension. Automatic pulse wave velocity (PWV) measuring system was applied to examine carotid-femoral PWV (CFPWV) reflecting aortic arterial stiffness in 644 essential hypertensive patients. Clinical data were collected, and cardiac structure and function were assessed by echocardiography. CFPWV was significantly and positively associated with left ventricular mass index (r = 0.153, P = 0.018), relative wall thickness (r = 0.235, P < 0.001), and left atrial diameter (r = 0.192, P = 0.003), and negatively with E/A ratio (r = ?0.361, P < 0.001) and creatinine clearance (r = ?0.248, P < 0.001). Logistic regression analysis demonstrated that CFPWV remained significantly correlated with renal function decline (P = 0.011), left ventricular diastolic dysfunction (P = 0.009) and left ventricular geometric remodeling (P = 0.020). Higher CFPWV was independently associated with greater burden of subclinical disease in renal impairment, left ventricular geometric remodeling and diastolic dysfunction.