External pressure-blood flow relations during limb compression in man

The effect of increased tissue pressure on blood flow in subcutaneous and skeletal muscle tissue was studied in 8 healthy humans resting in horizontal position. Blood flow was measured by the local ¹³³Xe washout technique in the mid-calf region. Tissue pressure in the depot area was increased by inflating a compression cuff, 50 cm wide (knee to ankle). Blood flow rates were obtained from compressed tissues with normal vasomotor tone, at papaverine-induced vasoparalysis and during distension of the compressed vessels. The latter was achieved by inflating a proximal (extra) compression cuff on the thigh 10 or 20 mmHg above the pressure level in the more distally placed compression cuff. Increased tissue pressure was a potent stimulus for arteriolar dilatation (autoregulation) in both tissues. The autoregulatory response was to some extent counteracted by an increase in local vascular resistance in the postcapillary section as evidenced by the results of simultaneous venous stasis. Blood flow ceased in vasoparalysed tissues as well as in tissues with normal vasomotor tone, when the compression cuff was inflated to the level of the local diastolic blood pressure. Maintaining external compression at the diastolic blood pressure level, blood flow reappeared in both tissues, when the compressed vessels were distended by adding the proximal (extra) compression. It is concluded, that blood flow cessation in compressed tissues is caused by a widespread arterial-arteriolar collapse in diastole, as the volume of blood injected during the systolic peak is too small to expand also the distal sections of the precapillary vessels.     

Roles of inositol trisphosphate and protein kinase C in the spontaneous outward current modulated by calcium release in rabbit portal vein

We examined the effects of heparin, guanosine nucleotides, protein kinase C (PKC) modulators, such as phorbol 12,13-dibutylate (PDBu) and H-7 on Ca²⁺-dependent K⁺ currents in smooth muscle cells of the rabbit portal vein using the whole-cell patch-clamp technique, to explore the effects of PKC on the oscillatory outward current (I _oo). Neomycin (30 M), an inhibitor of phospholipase C, and intracellular applications of heparin (10 g/ml) and guanosine 5-O-(2-thiodiphosphate) (GDP[S]; 1 mM) partly but consistently inhibited the generation of I _oo, whereas a higher concentration of heparin (100 g/ml) transiently enhanced then suppressed the generation of I _oo. Inhibition of I _oo generation by heparin was more powerful at the holding potential of + 20 mV than at –20 mV. Inositol 1,4,5-trisphosphate (InsP ₃; 30 M) continuously generated I _oo at holding potentials more positive than –60 mV. Noradrenaline (10 M) and caffeine (3–20 mM) transiently augmented, then reduced the generation of I _oo. Heparin (10 g/ml) completely inhibited responses induced by InsP ₃ and noradrenaline, but not those induced by caffeine. Intracellular application of guanosine 5-triphosphate (GTP; 200 M) or low concentrations of guanosine 5-O-(3-thiotriphosphate) (GTP[S]; 3 M) continuously augmented the generation of I _oo. High concentrations of GTP[S] (10 M) transiently augmented, then inhibited I _oo. Neither GTP[S] nor noradrenaline induced the transient augmentation or the subsequent inhibition of I _oo when applied in the presence of GDP[S] (1 mM), neomycin (30 M) or heparin (10 g/ml). PDBu (0.1 M) reduced the generation of I _oo but failed to produce an outward current following application of caffeine (3–5 mM). This action of PDBu was inhibited by pretreatment with H-7 (20 M). In the presence of H-7, GTP[S] continuously enhanced the generation of I _oo. The suppression of the generation of I _oo during application of noradrenaline (10 M) was reduced by pretreatment with H-7. Thus both InsP₃ and protein kinase C contribute to the generation of I _oo in smooth muscle cells of the rabbit portal vein and heparin is not a specific InsP ₃ antagonist on the InsP ₃-induced Ca²⁺-release channel (PIRC). InsP ₃ opens PIRC and protein kinase C may deplete the stored Ca²⁺ by either inhibiting the reuptake of Ca²⁺ or by enhancement of the releasing actions of InsP ₃.     

Activities of creatine kinase isoenzymes in single skeletal muscle fibres of trained and untrained rats

Biochemical changes in the creatine kinase isoenzyme compositions in single muscle fibres of different types in rats were induced by endurance running training. Single muscle fibres were dissected from the soleus and extensor digitorum longus muscles of Wistarstrain male rats trained on a motor-driven treadmill for 16 weeks. Each fibre was typed histochemically (SO, slow-twitch oxidative; FOG, fast-twitch oxidative glycolytic; FG, fast-twitch glycolytic), and the activities of total creatine kinase and its four isoenzymes (CK-MM, -MB,-BB, and mitochondrial creatine kinase) were measured. The endurance training did not affect the total creatine kinase activity, but resulted in significantly increased activities of CK-MB and CK-BB in SO and FOG fibres, and the mitochondrial enzyme activity in FOG and FG fibres. Endurance training induced biochemical changes in the isoenzyme compositions, specifically in FOG fibres. These results suggest that changes in creatine kinase isoenzymes with endurance training reflect changes in the energy metabolism in the different muscle fibres, supporting the hypothesis that the different isoenzymes play different roles in energy transduction.     

Effect of arm-cranking on leg blood flow and noradrenaline spillover during leg exercise in man

Controversy exists whether recruitment of a large muscle mass in dynamic exercise may outstrip the pumping capacity of the heart and require neurogenic vasoconstriction in exercising muscle to prevent a fall in arterial blood pressure. To elucidate this question, seven healthy young men cycled for 70 minutes at a work load of 5540%VO_2max. At 30 to 50 minutes, arm cranking was added and total work load increased to (mean ± SE) 82 ± 4% of Vo_2max. During leg exercise, leg blood flow average 6.15 4.511 minutes^-1, mean arterial blood pressure 137 ± 4 mmHg and leg conductance 42.3 ± 2.2 ml minutes^-1 mmHg^-1. When arm cranking was added to leg cycling, leg blood flow did not change significantly, mean arterial blood pressure increased transiently to 147 ± 5 mmHg and leg vascular conductance decreased transiently to 33.5 ± 3.1 ml minutes^-1 mmHg^-1. Furthermore, arm cranking doubled leg noradrenaline spillover. When arm cranking was discontinued and leg cycling continued, leg blood flow was unchanged but mean arterial blood pressure decreased to values significantly below those measured in the first leg exercise period. Furthermore, leg vascular conductance increased transiently, and noradrenaline spillover decreased towards values measured during the first leg exercise period. It is concluded that addition of arm cranking to leg cycling increases leg noradrenaline spillover and decreases leg vascular conductance but leg blood flow remains unchanged because of a simultaneous increase in mean arterial blood pressure. The decrease in leg vascular conductance observed when arm cranking increased mean arterial blood pressure could be regarded more as a measure to prevent overperfusion than a measure to maintain arterial blood pressure.     

Differential effects of neonatal denervation on intrafusal muscle fibers in the rat

The response of developing muscle spindles to denervation was studied by sectioning the nerve to the medial gastrocnemius muscle of rats at birth. The denervated spindles were examined daily throughout the first postnatal week for changes in ultrastructure and expression of several isoforms of myosin heavy chain (MHC). Each of the three different types of intrafusal muscle fiber exhibited a different response to denervation. Within 5 days after the nerve section nuclear bag₂ fibers degenerated completely; nuclear bag₁ fibers persisted, but ceased to express the spindle-specific slow-tonic MHC isoform and thereby could not be differentiated from extrafusal fibers; nuclear chain fibers did not form. The capsules of spindles disassembled, hence spindles or their remnants could no longer be identified 1 week after denervation. Neonatal deefferentation has little effect on these features of developing spindles, so removal of afferent innervation is presumably the factor that induces the loss of spindles in denervated muscles. Degeneration of the bag₂ fiber, but not bag₁ or extrafusal fibers, reflects a greater dependence of the bag₂ fiber than the bag₁ fiber on afferent innervation for maintenance of its structural integrity. This difference in response of the two types of immature bag fiber to denervation might reflect an origin of the bag₂ fibers from a lineage of myogenic cells distinct from that giving rise to bag₁ or extrafusal fibers, or a difference in the length of contact with afferents between the two types of bag fiber prior to nerve section.     

Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening

Objectives  We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes. Background  We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening. Methods  Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 ± 1 years, n = 20) and older (61 ± 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR⁺/CD34⁺ and KDR⁺/CD133⁺) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival. Results  We observed thicker IMT in older as compared to younger subjects (0.68 ± 0.03 mm Vs. 0.48 ± 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = −0.466 P < 0.05; r = −0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R ² = 0.58). Conclusion  Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance. Returned for 1. Revision: 13 December 2007 1. Revision received: 16 June 2008 Returned for 2. Revision: 20 June 2008 2. Revision received: 17 July 2008     

Critical roles of VEGF-C-VEGF receptor 3 in reconnection of the collecting lymph vessels in mice

Molecular mechanisms of reconnection of collecting lymph vessels were analyzed by using murine popliteal prenodal lymph vessels. At 1 and 2 weeks after being divided by cutting the lymph vessel, lymphatic reconnection was frequently observed accompanied by mesh-like lymphatic channels. Electron microscopic study also showed a monolayer of endothelial cells in the newly developed lymph vessels. Smooth muscle markers were immunofluorescently demonstrated in the wall of the new vessels. At 1 week after the procedure of cutting, augmented expressions of VEGF receptors 1, 2 and 3 were found immunohistochemically at the site of the reconnected lymph vessels. The expression of mRNA for VEGF receptor 3 was enhanced at 5 days and 1 week in small pieces of the tissues containing the reconnected lymph vessels, compared with that in the corresponding tissues obtained with sham operated ones. The administration of VEGF-C at the cutting site of the collecting lymph vessel significantly increased the rate of the reconnected lymph vessels, whereas additional treatment with Flt4/Fc chimera protein significantly reduced the rate of the reconnected ones. These results suggest that activation of VEGF-C-VEGF receptor 3 has critical roles in reconnection of the collecting lymph vessels in adult mice.     

点阵Er:YAG激光对光老化豚鼠皮肤胶原纤维和弹性纤维的影响

目的 探讨点阵Er:YAG激光照射对紫外线所致豚鼠光老化皮肤胶原纤维和弹性纤维的影响.方法 随机数字表法将60只豚鼠分为无处理组10只和模型组50只,中波紫外线(UVB)和长波紫外线(UVA)照射模型组豚鼠皮肤构建光老化模型,随机选择10只作为光老化模型组,余40只豚鼠分为2周、4周、8周、12周治疗组.点阵Er:YAG激光连续多脉冲照射治疗组豚鼠左侧背部(治疗侧)皮肤,HE染色、Masson染色、Weigert-van Gieson染色和碱水解-分光光度法比较照射后,治疗侧和对照侧皮肤组织学改变、胶原纤维、弹性纤维和羟脯氨酸含量.结果 UVA和UVB的最小红斑量4224 mJ/cm2和504 mJ/cm2隔日照射豚鼠背部皮肤,累积照射UVA 459.36 J/cm2和UVB 54.81 J/cm2,成功获得光老化模型.HE染色显示,治疗组治疗侧皮肤真皮浅层激光刺激区新生的胶原纤维和弹性纤维增加、排列致密.12周组Masson染色胶原面积比值治疗侧(0.70±0.12)较对照侧(0.63±0.08)均有增加,差异有统计学意义(f=1.18,P＜0.05);羟脯氨酸含量治疗侧[(4.73±0.39) mg/g]较对照侧[(3.66±0.85) mg/g]亦有增加,差异有统计学意义(t=3.40,P＜ 0.05).结论 点阵Er:YAG激光连续多脉冲照射可以刺激光老化豚鼠皮肤真皮浅层胶原纤维含量增加,纤细的弹性纤维新生.     

盆底肌肉功能锻炼对中青年女性糖尿病卵巢切除术后性功能的影响

目的:探讨盆底肌肉功能锻炼对中青年女性糖尿病卵巢切除术后性功能的影响。方法:选择2013年1月至2015年3月本院收治的糖尿病且实施双侧卵巢切除术中青年性生活活跃患者80例,按照随机数字法分两组,各40例,观察组实施本研究盆底功能锻炼方法,对照组未针对盆底肌肉功能进行特殊干预,比较术后3d和术后3个月两组盆底肌电压、盆底肌力变化情况、术后3个月两组FSFI评分情况及两组存在性功能相关障碍情况。结果:术后3d两组盆底肌电压、盆底肌力差异无统计学意义(P>0.05),术后3个月两组盆底肌电压高于术后3d(P<0.05),盆底肌肌力高于术后3d(P<0.05);且术后3个月观察组盆底肌电压高于对照组(P<0.05),盆底肌肌力高于对照组(P<0.05)。术后3个月观察组FSFI评分中性欲、性唤起、性高潮及性心理的评分均显著高于对照组(P<0.05)。术后3个月观察组发生阴道干涩、性交痛、性欲低下及性高潮缺失的比例显著低于对照组(P<0.05)。结论:有效的盆底肌肉功能锻炼能显著改善中青年女性糖尿病患者实施卵巢切除术后盆底肌肉功能,提高患者性功能,改善患者生活质量。