低分子肝素对缺血再灌注大鼠肾组织核因子-κB表达的影响

探讨低分子肝素对缺血再灌注大鼠肾组织核因子-κB（NF-κB）表达的影响。建立大鼠IRI模型，健康WistaI大鼠80只随机分为正常对照组、假手术组、模型未治疗组、LMWH治疗组，后两组又分别分为术后1、3、6、24h组。检测各组血清肌酐（Scr）水平及中性粒细胞（PMNs）细胞间黏附分子-1（ICAM-1）表达；通过光镜和免疫组织化学方法观察各组大鼠肾组织形态学及趋化因子NF-κB表达变化。结果表明：（1）肾缺血再灌注未治疗组造模后1h，Scr水平虽然没有明显变化，但ICAM-1、NF-κB表达增多，肾小管坏死积分值亦较假手术组明显增加（P〈0．01）；（2）缺血再灌注6h以后，两组Scr浓度明显增高（P〈0．01），但LMWH治疗组SCr、ICAM-1、NF-κB表达水平及肾小管坏死积分值均明显低于模型未治疗组（P〈0．05）；（3）肾组织中NF-κB表达与肾小管损伤积分值呈现良好的相关性（r=0．71，P〈0、01）；而NF-κB与ICAM-1间则呈现显著正相关（r=0．62，P〈0．05）。由此说明：（1）ICAM-1、NF-κB在肾缺血再灌注早期的瞬时表达，可能参与了炎症早期的白细胞迁移与浸润，与肾损伤的发生密切相关；（2）LMWH可通过减少ICAM-1及NF-κB的表达，阻抑炎症反应过程，减轻肾组织损伤。     

Peroxisomal fatty acid oxidation capacity is more resistant to ischaemic and reperfusion injury than mitochondrial fatty acid oxidation capacity in feline hearts

We investigated ischaemic and postischaemic mitochondrial and peroxisomal fatty acid oxidation capacity, ATP levels and regional function in 40 anaesthetized open chest cats subjected to 10 or 40 min of regional myocardial ischaemia with or without 3 h of reperfusion (n=10 in each situation). Following 10 min of ischaemia, the mitochondrial fatty acid oxidation capacity measured in tissue extracts from ischaemic tissue (nmol min^-1 mg protein^-1) was reduced in both subepi- and subendocardium, but was normalized in reperfused tissue extracts from both wall layers (0.29±0.03 and 0.30±0.04 vs. 0.57±0.05 and 0.59±0.05, P<0.05). Peroxisomal fatty acid oxidation capacity in tissue extracts was unaffected by ischaemia and reperfusion. ATP levels and regional function measured in the LAD region was partly restored transmurally. After 40 min of LAD occlusion, mitochondrial fatty acid oxidation capacity was reduced, with higher activity in subepi- than in subendocardium (0.27±0.05 vs. 0.19±0.04, P<0.05). Reperfusion did not restore mitochondrial fatty acid oxidation capacity. Peroxisomal fatty acid oxidation capacity was increased in the ischaemic subendocardium compared with levels in non-ischaemic subendocardium (0.53±0.02 vs. 0.45±0.03, P<0.05), with normalization at the end of reperfusion. ATP levels were non-uniformly reduced during ischaemia and not repleted during reperfusion. Regional function recovered in circumferential segments but not in longitudinal segments following 40 min of ischaemia. In conclusion fatty acid oxidation enzymes seem to be more resistant to ischaemia in peroxisomes than in mitochondria. Mitochondrial fatty acid oxidation is fully reversible following shortlasting ischaemia, but remains depressed following prolonged ischaemia and reperfusion.     

Three-dimensional modeling of the anatomy of the heart and great vessels

Summary The anatomic constraints imposed on a total artificial heart (TAH) require specific anatomic studies. A thoracic anatomic study was performed with a scanning device equipped with three-dimensional (3-D) reconstruction software on 15 male patients, between the ages of 41 to 63 years (52 ± 6 years). All were candidates for heart transplantation. The 3-D reconstructions of the cardiovascular structures obtained from surgical anatomy data specific to TAH implantation allowed a volumetric measurement of these structures. A modeling diagram of these structures permitted reproducible quantitative measurements of the 35 geometrical parameters which characterized shape, orientation, and position of these structures within the thorax. Most of the measured parameters were characterized by low variability (coefficient of variation from 10 to 25%).

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Modélisation tridimensionnelle de l'anatomie du cur et des gros vaisseaux

Résumé Les contraintes anatomiques imposées au cur artificiel total (CAT) nécessitent des études anatomiques spécifiques. Une étude anatomique thoracique a été réalisée avec un scanner doté d'un logiciel de reconstruction tridimensionnelle (3-D) chez 15 patients, tous de sexe masculin, agés de 41 à 63 ans (52 ± 6 ans), et candidats à une transplantation cardiaque. Les reconstructions 3-D des structures cardio-vasculaires réalisées selon les données de l'anatomie chirurgicale propre à l'implantation du CAT ont permis la mesure volumétrique de ces structures. Un schéma de modélisation de ces structures a permis des mesures quantitatives reproductibles de 35 paramètres géométriques caractéristiques de la forme, de l'orientation, de la position de ces structures dans le thorax. Les résultats de ces mesures ont pu être exprimés en termes statistiques. La plupart des paramètres mesurés étaient caractérisés par une faible variabilité (coefficients de variations de 10 à 25%).

     

Mathematical Modeling of the Human Body During Water Replacement and Dehydration: Body Water Changes

A model of the human body that integrates the variables involved in temperature regulation and blood gas transport within the cardiovascular and respiratory systems is presented here. It expands upon previous work to describe the competition between skin and muscles when both require increased blood flows during exercise and/or heat stress. First, a detailed study of the control relations used to predict skin blood flow was undertaken. Four other control relations employed in the model were also examined and modified as indicated by empirical results found in literature. Internal responses to exercise and/or heat stress can affect both thermoregulation and the cardiorespiratory system. Dehydration was studied in addition to complete water replacement during similar environmental and exercise situations. Control relations for skin blood flow and evaporative heat loss were modified and a water balance was added to study how the loss of water through sweat can be limiting. Runoff from sweating as a function of relative humidity was introduced along with evaporation, and these results were compared to data to validate the model. © 2000 Biomedical Engineering Society. PAC00: 8719Pp, 8719Uv, 8719Ff, 8710+e     

Effects of Crowding on the Thermal Stability of Heterogeneous Protein Solutions

Crowding can substantially affect the transition of a protein between its native (N) and unfolded (U) states via volume exclusion effects. Also, it influences considerably the aggregation (A) of unfolded proteins. To examine the details, we developed an approach for computing the kinetic rates of the process N ↔ U → A in which the concentration of the protein is explicitly taken into account. We then compute the relative change with temperature of the protein denaturation for various fractional volume occupancies and partition of proteins in solution. The analysis indicates that, in protein solutions in which the average distance between proteins is comparable with the radius of gyration of an unfolded protein, steric effects increase the stability of the proteins which are in compact, native states. In heterogeneous protein solutions containing various types of proteins with different thermal stabilities, the unfolding of the most thermolabile proteins will increase the stability of the other proteins. The results shed light on the way proteins change the thermal stability of a cell as they unfold and aggregate. This study may be valuable in questions related to the dynamics of thermal injuries.     

In-vivo quantification of myocardial Na-K pump rate during β-adrenergic stimulation of intact pig hearts

Maintenance of adequate electrical activity of the heart depends critically on the ability of the Na-K pump to compensate for normal passive sodium and potassium fluxes. Using sudden injections of [³H]ouabain into the left coronary artery in anaesthetized open-chest pigs, we monitored transient changes in myocardial potassium balance by PVC-valinomycin mini-electrodes. When related to the number of pumps blocked and fractional inhibition, these data provided estimates of total Na-K pump capacity as well as actual pump rate and perturbations of the Na-K balance. Experiments were performed in hearts with and without intracoronary isoprenaline infusion (2.5 nmol min^-1). After injection of 120 nmol [³H]ouabain into the left coronary artery, myocardial [³H]ouabain concentrations were 118 (74–178) and 103 (76–145) pmol g^-1 and total concentrations of [³H]oubain binding sites were 893 (752–1076) and 785 (691–877) pmol g^-1 (median, 95% confidence interval) in isoprenaline-treated and control hearts respectively (differences not significant). The [³H]ouabain injection caused a net potassium release of 81 (56–132) and 43 (23–75) μcool 100 g^-1 (median, 95% confidence interval) in isoprenaline-treated and control hearts respectively (n= 6–8; significance of difference, P= 0.03). Na–K pump rate estimated from mono-exponential release curves was 6363 (3942–10,858) K⁺ ions min^-1 site^-1 during β-adrenoceptor stimulation and 2514 (1380–4322) in control (significance of difference, P= 0.03). This corresponds to 40 and 16%, respectively, of the maximum possible pump rate determined from ATP hydrolysis. Comparison of accumulated potassium release and relative Na-K pump rate indicates that catecholamines enhance the sensitivity of the Na-K pump for intracellular sodium.     

Influence of vascular parameters on the effectiveness of intra-aortic balloon pumping: A model study

The intra-aortic balloon pump has been widely used as a temporary heart-assist device. In this investigation, a nonlinear mathematical model of the arterial system and intra-aortic balloon pump was studied analytically. Thus, the influences of a number of vascular parameters on the effectiveness of intra-aortic balloon pumping (IABP) were determined. The effects of changes in vascular parameters of the model on a number of performance indexes were investigated. These performance indexes (aortic mean diastolic pressure, aortic end diastolic pressure, cardiac output, coronary flow and phase differences between the fundamental Fourier components of aortic root pressure and flow) were used as the criterion for an evaluation of the effectiveness of the assist pump. The following vascular parameters were perturbed by four steps (±10%, ±20%) from the values in the standard model: heart rate, peripheral resistance, left ventricular pressure, aortic elastance, aortic radius, arterial wall thickness, and aortic length. This model was evaluated for a wide range of balloon-pump phase-control settings (assisted case) and for the unassisted case (when the pump is disabled). It is concluded that changes in heart rate, peripheral resistance and left ventricular pressure cause the most significant changes in pump performance. Dr. Ohley is with the Datascope Corporation Dr. Kao is with the Technicare Corporation     

Relationship between chamber mechanical properties and mean pressure-mean flow diagram of the left ventricle

We undertook a theoretical analysis of the source resistance of the left ventricle represented in a mean pressure-mean flow diagram, using the chamber properties established in terms of the pressure-volume relationship. This analysis showed that pairs of points should lie above the linear function proposed by Elzinga and Westerhof. A third-order polynomial function would theoretically explain better than a linear relation or a parabolic fit the curved shape of experimentally obtained relationships. The analysis resolves the discrepancy between Elzinga and Westerhof's theoretical concept of linear source resistance and the actual nonlinear relationship.