The change of the free energy of ATP hydrolysis during global ischemia and anoxia in the rat heart. Its possible role in the regulation of transsarcolemmal sodium and potassium gradients

The timecourse of change of the cytoplasmic free energy of ATP hydrolysis during acute global ischemia and during anoxic perfusion was determined in the isolated rat heart. The timecourse of change of transsarcolemmal Na+ and K+ gradients during anoxia, and of extracellular K+ during ischemia were measured. The free energy of ATP hydrolysis was calculated from the equilibrium of the creatinekinase reaction, taking into account the pH-dependence of the equilibrium constant, and intracellular inorganic phosphate. In control aerobic hearts the mean free energy of ATP hydrolysis was 55.2 kJ/mol. Both during ischemia and anoxia it declines biphasically. The first rapid phase terminates within 4 min into a plateau of about 46 kJ/mol. The duration of this plateau is shorter during anoxia than during ischemia. The second phase of decrease starts after 6 to 8 min during anoxia and after 15 to 20 min during ischemia. After 30 min of anoxia the free energy of ATP hydrolysis has decreased to 31 kJ/mol and after 30 min of ischemia a value of 35.5 kJ/mol is reached. The timecourses of change of measured intracellular Na+ and K during anoxia and of extracellular K+ during ischemia were also biphasic. During anoxia the loss of intracellular K+ was almost equal to the gain of intracellular Na+ at any point. Based on the assumption that the sodium pump is in thermodynamic equilibrium or near-equilibrium during anoxia and ischemia, the time-course of change of Na+ and K+ gradients during anoxia and of extracellular K+ during ischemia were calculated from the respective timecourses of change of the free energy of ATP hydrolysis. Good agreement was observed between calculated and measured changes of Na+ and K+ gradients. It is concluded that the magnitude and direction of change of transsarcolemmal ion-gradients during anoxia and ischemia may be under direct thermodynamic control of myocardial energy metabolism.     

探讨肝硬化测定肝静脉压梯度和门静脉血管阻力与食管静脉曲张再出血之关系

对有食管静脉曲张 (EV)出血后 ,肝硬化并门静脉高压之患者 2 1例 ,测定肝静脉压梯度 (HVPG)为 (2 2 6± 0 34)kPa;继之对其中之 18例又测门静脉血管阻力 (PVR)为 (0 2 3± 0 0 6 )kPa·ml 1·min·kg。治疗分两组 :手术组(n =10 )和介入组 (n =11) ,前者其HVPG和PVR之两值显著低于后者 ,随访 18个月内再出血率 ,手术组 (30 % )显然低于介入组 (5 4 6 % ) ,但两组之再出血例如以两值中位数相对比则无差异 ,均发生于高值者。再出血例与未再出血例就两值相对比 ,前者显著高于后者 ,差异非常显著 ,PVR尤著 (P <0 0 0 1)。本研究提示HVPG >2 33kPa ,PVR >0 2 2kPa·ml 1·min·kg是EV再出血危险的域值。HVPG与PVR呈正相关。     

A prospective follow-up of alcohol septal ablation for symptomatic hypertrophic obstructive cardiomyopathy--the Baylor experience (1996-2002)

BACKGROUND: There is a paucity of data on the long-term outcome of alcohol septal ablation (ASA) for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). HYPOTHESIS: The study was undertaken to evaluate the longer-term outcome of ASA therapy for symptomatic HOCM. METHODS: In all, 137 patients were enrolled consecutively (1996-1999) and 130 (95%) (74 men, 56 women, aged 51 +/- 17 years) underwent ASA and had serial prospective follow-up for up to 5 years (mean follow-up 3.6 +/- 1.4 years). Evaluation included angina (Canadian Cardiovascular Society [CCS] score), dyspnea (New York Heart Association [NYHA] class), duration of exercise on treadmill, and echocardiographic indices. RESULTS: Ethanol (3.5 +/- 1.5 cc), injected into 1.5 +/- 0.6 arteries, induced a mean peak plasma creatine kinase (CK) of 1676 +/- 944 units. Complications of procedures included death 1.5% (2/130), heart block requiring permanent pacemaker 13% (17/130), and coronary dissection 4.4% (6/130). Baseline versus last follow-up visit: NYHA class decreased from 3.0 +/- 0.4 to 1.2 +/- 0.6 (p < 0.01); CCS angina score from 2.0 +/- 0.8 to 0.08 +/- 0.4 (p < 0.01); and duration of exercise increased from 322 +/- 207 to 443 +/- 200 s (p < 0.01). Resting left ventricular outflow tract gradient at baseline versus last follow-up visit showed a decrease from 74 +/- 30 to 4 +/- 13 (p < 0.01), and the dobutamine-provoked gradient of 88 +/- 29 decreased to 21 +/- 21 (p < 0.01) mmHg. All-cause mortality over the duration of follow-up was 7.7% (10) giving an annual rate of 2.1%, and cardiac mortality was 2.3% (3) reflecting an annual rate of 0.6%. CONCLUSIONS: Alcohol septal ablation decreased symptoms and improved exercise performance, indicating that it is an effective procedure for symptomatic HOCM.     

Differential Improvement in Angina and Health-Related Quality of Life After PCI in Focal and Diffuse Coronary Artery Disease

BackgroundAn increase in fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is associated with improvement in angina. Coronary artery disease (CAD) patterns (focal vs diffuse) influence the FFR change after stenting and may predict angina relief.ObjectivesThe aim of this study was to investigate the differential improvement in patient-reported outcomes after PCI in focal and diffuse CAD as defined by the pullback pressure gradient (PPG).MethodsThis is a subanalysis of the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) randomized clinical trial. The 7-item Seattle Angina Questionnaire (SAQ-7) was administered at baseline and 3 months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks. The median PPG value was used to define focal and diffuse CAD. Residual angina was defined as an SAQ-7 score <100.ResultsA total of 103 patients were analyzed. There were no differences in the baseline characteristics between patients with focal and diffuse CAD. Focal disease had larger increases in FFR after PCI than patients with diffuse disease (0.30 ± 0.14 vs 0.19 ± 0.12; P < 0.001). Patients with focal disease who underwent PCI for focal CAD had significantly higher SAQ-7 summary scores at follow-up than those with diffuse CAD (87.1 ± 20.3 vs 75.6 ± 24.4; mean difference = 11.5 [95% CI: 2.8-20.3]; P = 0.01). After PCI, residual angina was present in 39.8% but was significantly less in those with treated focal CAD (27.5% vs 51.9%; P = 0.020).ConclusionsResidual angina after PCI was almost twice as common in patients with a low PPG (diffuse disease), whereas patients with a high PPG (focal disease) reported greater improvement in angina and quality of life. The baseline pattern of CAD can predict the likelihood of angina relief. (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve [TARGET-FFR]; NCT03259815)     

Denaturing gradient gel electrophoresis: a novel method for determining Rh phenotype from genomic DNA

Denaturing gradient gel electrophoresis (DGGE) was carried out on PCR products amplified from exons 2 and 5 of RHD and RHCE. Exon 2 of RHD and exon 2 of the C allele of RHCE have an identical sequence, which differs from that of the c allele of RHCE. One band representing D and/or C, and another representing c, could be distinguished by DGGE of exon 2 amplifications of genomic DNA from individuals with the appropriate Rh phenotype. C and c could only be distinguished in D-negative samples. Exon 5 of RHD and exon 5 of the E and e alleles of RHCE all have different nucleotide sequences. Bands representing D, E and e could be distinguished following DGGE of the products of exon 5 amplification of genomic DNA from individuals with red cells of the appropriate Rh phenotype. In samples from individuals with VS+ red cells (V+ or V?) there was a shift of the band representing e. Sequencing demonstrated that VS is associated with a RHCE e sequence with a single base change predicting a Leu245 → Val substitution in the Rh polypeptide. This substitution may be responsible for the VS and e^s antigens.     

Multipurpose A2 catheter approach to left heart catheterization in severe aortic stenosis

An approach has been presented for the performance of right and left heart catheterization, left ventriculography, supravalvular aortography, and coronary arteriography utilizing a #8 French, A2 multipurpose catheter. Using the manipulations described herein, the left ventricle was entered in 96% of the patients. The multipurpose catheter is an excellent catheter for left ventriculography, negating the need for catheter exchange once the left ventricle has been entered. Likewise, this catheter provides excellent supravalvular aortography and selective coronary arteriography supplemented as needed with preformed coronary arteriographic catheters. This method provides a very safe, efficient approach to the performance of complete heart catheterization in patients with clinically significant aortic stenosis.     

Constrained spherical deconvolution of nonspherically sampled diffusion MRI data

Constrained spherical deconvolution (CSD) of diffusion‐weighted MRI (DW‐MRI) is a popular analysis method that extracts the full white matter (WM) fiber orientation density function (fODF) in the living human brain, noninvasively. It assumes that the DW‐MRI signal on the sphere can be represented as the spherical convolution of a single‐fiber response function (RF) and the fODF, and recovers the fODF through the inverse operation. CSD approaches typically require that the DW‐MRI data is sampled shell‐wise, and estimate the RF in a purely spherical manner using spherical basis functions, such as spherical harmonics (SH), disregarding any radial dependencies. This precludes analysis of data acquired with nonspherical sampling schemes, for example, Cartesian sampling. Additionally, nonspherical sampling can also arise due to technical issues, for example, gradient nonlinearities, resulting in a spatially dependent bias of the apparent tissue densities and connectivity information. Here, we adopt a compact model for the RFs that also describes their radial dependency. We demonstrate that the proposed model can accurately predict the tissue response for a wide range of b‐values. On shell‐wise data, our approach provides fODFs and tissue densities indistinguishable from those estimated using SH. On Cartesian data, fODF estimates and apparent tissue densities are on par with those obtained from shell‐wise data, significantly broadening the range of data sets that can be analyzed using CSD. In addition, gradient nonlinearities can be accounted for using the proposed model, resulting in much more accurate apparent tissue densities and connectivity metrics.     

Combinatorial Approach for Fabrication of Coatings to Control Bacterial Adhesion

Abstract

Due to the high importance of bacterial infections in medical devices there is an increasing interest in the design of anti-fouling coatings. The application of substrates with controlled chemical gradients to prevent microbial adhesion is presented. We describe here the co-polymerization of poly(ethylene glycol) dimethacrylate with a hyperbranched multimethacrylate (H30MA) using a chemical gradient generator; and the resulting films were characterized with respect to their ability to serve as coating for biomedical devices. The photo-polymerized materials present special surface properties due to the hyperbranched structure of H30MA and phase separation at specific concentrations in the PEGDM matrix. This approach affords the investigation of cell response to a large range of different chemistries on a single sample. Two bacterial strains commonly associated with surgical site infections, Escherichia coli and Pseudomonas aeruginosa, have been cultured on these substrates to study their attachment behaviour. These gradient-coated samples demonstrate less bacterial adhesion at higher concentrations of H30MA, and the adhesion is substantially affected by the extent of surface phase segregation.     

Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular carcinoma via a reduction of the inflammatory load from the gut to the liver and inhibition of angiogenesis.     

人早孕绒毛细胞滋养层细胞培养方法的改良

目的 探索一种简便高纯度的早孕滋养细胞的体外培养方法。方法 采用完整早孕绒毛通过胰蛋白酶联合胶原酶消化法分离,Percoll梯度分离法提纯体外培养,应用光镜HE染色和免疫细胞化学法检测细胞纯度。 结果 CK-7表达阳性细胞数可以达到90%以上。结论 完整绒毛消化和Percoll纯化联合可在短期内获得高纯度、高产量的滋养细胞以供后期试验,方法更加简便。