Functional abnormalities of experimental autogenous vein graft neoendothelium.

When a vein is grafted into the arterial circulation, the endothelium of the graft is damaged. Regeneration of an intact neoendothelium occurs, but the functional properties of this surface have not been clarified. In this study, the functional integrity of the neoendothelium of veins grafted into the carotid artery of the rabbit was assessed through the use of acetylcholine and histamine to stimulate the production of the important endothelium-derived relaxing factor (EDRF). Control veins, precontracted with norepinephrine [10(-5) M], relaxed after exposure to acetylcholine [( 10(-7) M], 42.4% +/- 6.4%, p = 0.008) and histamine [( 10(-6) M], 30.6% +/- 4.3%, p = 0.03). This relaxation response was abolished after mechanical removal of the endothelium. By contrast, neither acetylcholine nor histamine caused an endothelium-dependent relaxation in the vein grafts, even though scanning electron microscopy demonstrated the presence of a morphologically intact endothelium. However, addition of stabilized EDRF purified from cultured endothelial cells induced relaxation of the vein grafts (35.8% +/- 3.6%, p = 0.002). These data indicate that vein graft endothelium is unable to produce EDRF in response to exposure to acetylcholine or histamine. The inability to produce this potent smooth muscle cell relaxing factor and anti-aggregatory substance may be a predisposition to vein graft failure.     

The Association of Different Measures of Insulinaemia with Vascular Risk Factors in Healthy Normoglycaemic Normotensive Non-obese Men and Women

Hyperinsulinaemia is said to be a risk factor for cardiovasculardisease, but the extent to which different insulinaemic measuresare associated with vascular risk factors in ostensibly healthyindividuals, and whether they operate independently in men andwomen, remains uncertain. The association between risk factors and various insulinaemicmeasures was examined in 148 men and 118 women who were normoglycaemic,normotensive, and non-obese (body mass index in men <27,in women <25). A 75 g glucose tolerance test was administeredafter blood sampling for fibrinogen, lipids, lipoproteins andinsulin. Insulin was also measured after 1 and 2 hours. Significantunivariate correlations (p<0.01) were most consistently recordedbetween insulinaemic measures and fasting serum triglyceridesin men and women, whilst systolic blood pressure only correlatedwith insulinaemia in women, and diastolic blood pressure correlatedwith fasting and 2 hour insulinaemic measures in men and women.Inconsistent associations were noted with total serum cholesterolin men and women, with high density lipoprotein cholesterol,body mass index, apoprotein B and A1 in men, and with fibrinogenin women. Age was not correlated with any insulinaemic measurein men or women. Differences in vascular risk factors between quintiles of theinsulinaemic measures were examined, after correction for bodymass index. The dominant association with fasting and post-glucoseload insulinaemic measures was with triglycerides, especiallyin women, with less frequent graded differences between quintilesobserved for total cholesterol, and diastolic and systolic bloodpressures in men and women. The incidence of other risk factors often only differed in thelowest or highest quintile in comparison to other quintiles,suggesting a threshold rather than a graded effect. Furthermore,differences in HDL cholesterol and apoprotein B were only recordedfor top quintiles of post-glucose challenge/integrated insulinaemicmeasures in men, whilst serum fibrinogen concentrations onlydiffered significantly in women in the top insulinaemic areaunder the curve quintile. In the absence of additional risk factors such as diabetes,hypertension and obesity, insulinaemic measures are not consistentlyrelated to blood pressure and measures of lipid metabolism andcoagulation, and are thus a weak predictor of other cardiovascularrisk factors. The vascular risk profile associated with insulinappears somewhat different in apparently healthy men and women.     

Asynchronous blepharospasm, facial and cervical dystonia, and bilateral asynchronous hemifacial spasm.

We present a patient with a facial movement disorder that has characteristics of both blepharospasm and bilateral asynchronous hemifacial spasm. Because of the increased incidence of blepharospasm in patients with hemifacial spasm, our patient's clinical presentation is probably not a chance occurrence, but rather a manifestation of some predisposition for these two movement disorders. This unusual constellation of signs and symptoms challenges the current diagnostic criteria and suggests that some of these facial movement disorders may lie on a spectrum, rather than represent distinct entities.     

Haloperidol-sensitive (+)[3H]SKF-10,047 binding sites (sigma sites) exhibit a unique distribution in rat brain subcellular fractions

The distribution of haloperidol-sensitive (+)[3H]N-allylnormetazocine ((+)[3H]SKF-10,047) binding sites (sigma sites) in subcellular fractions of rat brain homogenates was extensively characterized. In synaptosomal fractions, enriched in choline acetyltransferase activity, sigma sites were present in lower concentrations than in whole brain homogenates. On the other hand, microsomal and myelin fractions were found to be enriched in sigma sites. A similar pattern of enrichment was seen for 5'-nucleotidase activity, a general plasma membrane marker. However, subsequent experiments in which microsomes were subfractionated on linear sucrose gradients led to the recovery of sigma sites over a significantly lower density range than 5'-nucleotidase activity or ATP-stimulated [3H]ouabain binding, an additional plasma membrane marker. In addition, previously reported distributions of a number of other subcellular markers, including those for endoplasmic reticulum, were found to contrast with the observed distribution of sigma sites. It is concluded that rat brain sigma sites are not concentrated at synaptic regions of plasma membrane. However, the possibility that sigma sites are localized to specialized areas of nonsynaptic plasma membrane cannot be excluded.     

Comparative inotropic effect of calcium, endothelin-1, and forskolin on ferret papillary muscles during acidosis

Summary— Acidosis affects multiple steps in the excitation-contraction coupling pathway of myocardium, producing decreased calcium sensitivity of myofibrils and modification of the function of the sarcoplasmic reticulum. Our aim was to evaluate the effectiveness of three different classes of inotropic agents under acidotic conditions: 1) forskolin, an adenylate cyclase activator that enhances cellular cyclic AMP concentrations, 2) elevated extracellular Ca²⁺ and 3) endothelin-1, an activator of the inositol triphosphate, diacylglycerol pathway. Ferret papillary muscles were mounted in organ baths containing normal physiological solution (pH = 7.4). After baseline tension was measured, the muscles were bathed in an acidotic solution (pH = 6.98) that decreased tension to 40% of the control; subsequently, the muscles were washed with normal physiological solution until they returned to baseline. Each inotropic agent was added to the bathing solution in a concentration sufficient to increase tension by 40% above the baseline. Then the solution was made acidotic (pH = 6.98) in the continuous presence of that concentration of inotropic agent and the resultant steady-state developed tension measured. The increases in tension induced by each inotropic agent at normal pH were adjusted to be similar; in contrast, the response to each drug in acidosis was significantly different. Under acidotic conditions, endothelin-1 was the most effective inotropic agent in restoring the depressed developed tension. This was possibly due to enhancement of the myofilament sensitivity to Ca²⁺, which was more effective than increasing [Ca²⁺]_i through elevating extracellular Ca²⁺ or the addition of forskolin which increased [Ca²⁺]_i but desensitized the myofilaments to Ca²⁺.