Isovelocity investigation of the lengthening behaviour of the erector spinae muscles

The purpose of this study was to investigate the force-velocity (F/) relationship for the erector spinae muscles in submaximal activation movements, with particular attention to their response during lengthening movements and at lower shortening contraction velocities. Dynamic models that predict lower back muscle forces require reasonable representations of the modulating effect of instantaneous velocity. Ten males were observed performing trunk flexion and extension in the sagittal plane under constant load. Contraction velocities were measured as the first derivative from a devise sensitive to changes in spine curvature, and controlled by a visual feedback system while a constant load was applied through a chest harness. The erector spinae exhibited a yielding phenomenon which causes an abrupt drop in force during constant velocity stretching under constant, submaximal, stimulation. The findings were consistent with previous isovelocity muscle lengthening experiments. Yielding appeared dependent on the level of load/activation supporting the theory of a state-variableF/ relationship. The eccentric behaviour of the lower erectors (L3) seemed independent of velocity and length, while that of the upper erectors (T9) showed a dependence on length. At lower concentric velocities, concavity in torque-velocity curves was noted after a threshold velocity. The findings of this study strongly reinforce the notion that theF/ length relationship is not a continuous hyperbolic relationship during muscle shortening and that the commonly modelled force augmentation effect of lengthening is incorrect, at least for submaximal activation of the extensors of the lower back.     

Evidence against a role of nitric oxide in the indirect negative inotropic-effect of M-cholinoceptor stimulation in human ventricular myocardium

Nitric oxide (NO) has been reported to mediate several effects in response to muscarinic cholinergic stimulation in cardiovascular tissues. Recently, an attenuation of guinea pig cardiac myocyte contraction by NO has been described. The aim of the present study was to determine whether the indirect negative inotropic effect of M-cholinoceptor stimulation in human myocardium is in part due to an effect of endogenous NO. Therefore, the effect of carbachol was studied under control conditions and during inhibition of NO-synthase by pretreatment with N^G-monomethyl-l-arginine (NMMA). Functional experiments were performed in isolated, electrically driven (1 Hz, 37°C) left ventricular papillary muscle strips of human myocardium. Since cytokines have been reported to be increased in the serum of patients with heart failure and could induce NO-synthase activity in failing myocardium, we compared samples from nonfailing and terminally failing (classified as NYHA IV) hearts. The indirect negative inotropic effect of carbachol (10 mol/l) was studied in the presence of the \-adrenoceptor agonist isoprenaline (0.03 mol/l).After stimulation with isoprenaline, carbachol significantly (P < 0.05) reduced force of contraction. This effect was diminished in failing myocardium compared to nonfailing, probably due to the diminished inotropic response most likely due to the lower cAMP levels in response to \-adrenoceptor stimulation in the former condition. Pretreatment with NMMA (100 mol/l) altered the antiadrenergic effect of carbachol neither in nonfailing nor in failing preparations. Furthermore, inhibition of guanylyl cyclase, the target enzyme of NO, by preincubation with methylene blue (10 mol/l) for 30 min had no effect on the carbachol-induced decrease in force of contraction. Basal force of contraction, as well as the positive inotropic effect of isoprenaline remained unaffected by NMMA or methylene blue.The present study provides evidence that the indirect negative inotropic effect of M-cholinoceptor agonists is not due to an effect of NO in the human myocardium. Furthermore, the well known enhancement of cGMP in response to M-cholinoceptor stimulation appears not to be involved in this antiadrenergic effect.     

SYMPOSIUM: Experimental Biology 1995 Role of Mesangial Cell Ion Transport in Glomerular Physiology and Disease: ANGIOTENSIN II-INDUCED TYROSINE PHOSPHORYLATION IN MESANGIAL AND VASCULAR SMOOTH MUSCLE CELLS

• 1 Angiotensin II (AngII)-induced, activation of phospholipase C (PLC) and Ca²⁺-dependent Cl^? channels is an important signal transduction pathway for the regulation of vascular smooth muscle cell (VSMC) and glomerular mesangial cell contraction and growth. While AT receptors are traditionally thought to be G-protein coupled to the β isoform of PLC, recent evidence suggests that in some tissues AT receptors may also activate the PLC-γ isoform via tyrosine phosphorylation.
• 2 By western analysis, we identified PLC-γ1 in the above cell types. We found that within 3 min of exposure to 10^?7 mol/L AngII, tyrosine phosphorylation of PLC-γ1 was observed; however, peak response (> 3-fold increase) occurred within 0.5 min. In addition, pre-incubation of these cells with the tyrosine kinase inhibitor genistein blocked the tyrosine phosphorylation of PLC-γ1 by AngII. In contrast, preincubation with the tyrosine phosphatase inhibitor sodium vanadate increased the levels of tyrosine phosphorylation of PLC-γ1. Similar results were found when intracellular levels of 1,4,5-IP₃ were measured after AngII exposure.
• 3 By using patch clamp techniques on cultured rat mesangial cells exposed to AngII, we found that the release of 1,4,5-IP₃-sensitive intracellular Ca²⁺ stores stimulated low conductance Cl^? channels. Preincubation with genistein, abolished the usual 10-fold increase in Cl^? channel activity observed with AngII.
• 4 Therefore, we conclude that in VSMC and glomerular mesangial cells (i) AngII transiently stimulates PLC activity via tyrosine phosphorylation of the γ1 isoenzyme, (ii) tyrosine phosphorylation of PLC-γ1 and production of 1,4,5-IP₃ in response to AngII is dramatically inhibited by tyrosine kinase inhibition and stimulated by tyrosine phosphatase inhibition, (iii) activation of Ca²⁺-dependent Cl^? channels by AngII-induced release of 1,4,5-IP₃-dependent intracellular Ca²⁺ stores is also abolished by tyrosine kinase inhibition. In summary, this AngII-induced signal transduction cascade provides a possible mechanism for both the contractile and growth-stimulating effects of AngII on VSMC and glomerular mesangial cells.

     

β-Adrenoceptor blocking agents as partial agonists in isolated heart muscle: Dissociation of stimulation and blockade

Summary The cardiac stimulant actions of nine -adrenoceptor blocking agents were examined in kitten papillary muscles and in isolated atria of kittens and guinea pigs to determine to what extent these drugs behaved as classical partial agonists. In many ways the agents do appear to comprise a spectrum of partial agonists with widely differing efficacies. However, in one respect the actions of some of the -blockers did not fit into the classical mold. Several -blockers were found to exert stimulant effects only in concentrations appreciably higher than those required for substantial -adrenoceptor blockade. These observations suggest that more than one type of -adrenoceptor may be involved in the production of sympathomimetic effects on cardiac muscle.     

Field stimulation-induced responses of circular smooth muscle from guinea-pig stomach

Summary Field stimulation of circular smooth muscle of guinea-pig stomach from the regions of the cardia and fundus caused contraction responses at low stimulation frequencies (0.25–1 Hz) with relaxation at higher frequencies (1–10 Hz), whilst tissues of the body and antrum responded with contraction throughout the frequency range. Atropine (10^–9–10^–8 M) antagonised the contraction responses of all tissues, with relaxation developing at higher concentrations (except for antral tissue). In contrast, metoclopramide (10^–8–10^–6 M) caused modest (cardia, fundus) or marked (body, antrum) enhancement of contractions to field stimulation, whilst domperidone (10^–8–10^–7 M), haloperidol (10^–8–10^–6 M), prazosin, propranolol and methysergide (10^–8–10^–6 M) failed to modify the contraction responses. However, whilst yohimbine and guanethidine failed to modify the contractions of the cardia, fundus and body tissues, those of the antral preparations were antagonised by nanomolar concentrations of yohimbine and by guanethidine (10^–6–5×10^–5 M). To optimise the relaxation responses for study, atropine was included in the physiological solution. Relaxation to field stimulation of preparations from the body and cardia, but not the fundus, was antagonised by reserpine pretreatment (5 mg/kg i.p., 24h), addition of guanethidine (10^–5–10^–4 M), phentolamine, prazosin or propranolol (10^–7–10^–6 M) (the effects of prazosin and propranolol being additive). Higher concentrations of haloperidol and domperidone antagonised the relaxation responses of the body preparations only. Metoclopramide, yohimbine and methysergide (10^–8–10^–6 M) were ineffective. Thus, it is concluded that the contractile effects of the 4 stomach areas to field stimulation reflects a major cholinergic involvement, with an additional ₂-adrenoceptor contractile component in antral tissue. Relaxation responses of cardia and body tissue involve ₂- and -adrenoceptors plus a further, unidentified, non-adrenergic component; the latter represents the total relaxation response of the fundic preparation.     

Effects of isoflurane and halothane on the calcium ion-tension curve in rat myocardium

In order to clarify the interaction of volatile anesthetics and extracellular calcium ion on the myocardial contraction, effects of both isoflurane (1.0%) and halothane (0.5%) on the extracellular calcium ion concentration ([Ca²⁺]_O)-tension curve were studied. Increasing [Ca²⁺]_O enhanced the myocardial contraction response, and the maximal response was obtained at [Ca²⁺]_O of 3.0mM. Halothane depressed the maximal value of the tension development in response to increasing [Ca²⁺]_O, while isoflurane did not (P 0.01). The probit response of the developed tension to the changes in [Ca²⁺]_O indicated that isoflurane increased the median effective concentration (EC₅₀) of [Ca²⁺]_O significantly from 0.484 ± 0.051 (mean ± SEM) to 0.870 ± 0.056mM (P = 0.001), but halothane did not (P = 0.018). Therefore, 1.0% isoflurane was concluded to move the [Ca²⁺]_O-tension curve to the right, while a downwards shift occurred with 0.5% halothane.(Saeki S, Hirakawa M, Shimosato S: Effects of Isoflurane and Halothane on the Calcium Ion-tension Curve in Rat Myocardium. J Anesth 6: 172–175, 1992)     

Detrusor sphincter dyssynergia,detrusor instability,and urethral sphincter spasticity as the urodynamic findings in the urethral syndrome: Role of treatment with a combined anticholinergic and alpha blocking agent,bladder drill,and antibiotics

The combined effect of isopropamide 5 mg plus trifluoperazine 1 mg (a combined anticholinergic and alpha-adrenergic antagonist) (Smith, Kline and French Canada Ltd, Ontario, Canada), antibiotics, and bladder drill was retrospectively assessed on 100 consecutive women, aged 16 to 47 years, presenting with the signs and symptoms of the urethral syndrome. Assessment included history, physical examination, routine bacterial and chlamydial cultures (cervical, urethral, vaginal, and urine), cystourethroscopy, and urodynamics. Urodynamic diagnoses included detrusor sphincter dyssynergia (n=84), detrusor instability (n =8), external urethral sphincter spasticity (n=4), and sensory urgency (n=1). Three patients with positive urine cultures were excluded. Urethrotrigonitis was visualized at cystourethroscopy in all patients. Only one case of chlamydial urethritis-cervicitis was identified by culture: 82% of patients had a history of prior antibiotic therapy for lower urinary tract symptoms and 21% were being treated with antibiotics at the time of their initial assessment.Following 1 month of treatment, 44 (45%) patients were cured of all symptoms, 49 (51%) were improved, 3 (3%) were unchanged and 1 (1%) was worse. Significant changes in uroflowmetry included a reduction in postvoid residual urine volume from 49 ± 28 ml to 14 ±21 ml (P=0.029) in the unstable bladder group and a conversion from intermittent to continuous uroflow patterns in the detrusor sphincter dyssynergia group (P <0.005, ²) and overall (P <0.005, ²). A statistically significant number of patients (P <0.025, ²) converted from increased to normal tracings on repeat perianal electromyography, suggesting that the pathophysiology of the urethral syndrome is urethral spasticity related to urethral inflammation rather than actual infection.We conclude that detrusor sphincter dyssynergia, bladder instability, and urethral sphincter spasticity are the common urodynamic findings in the urethral syndrome. A combination of anticholinergic and alpha blocking agent, antibiotics, and a bladder drill markedly improved (96%) symptoms in women with the urethral syndrome.     

PNS单体Rb_l对豚鼠心脏乳头肌动作电位和收缩力的影响

目的 :了解PNS单体Rbl对豚鼠心脏乳头肌动作电位和收缩力的影响。方法 :运用带有动作电位和收缩力分析软件控制的细胞内微电极技术 ,研究了三七皂苷 (PNS)单体Rbl对豚鼠正常心脏乳头肌动作电位 (AP)各特征参数及收缩力 (FC)的影响。结果 :Rb1 1 0～ 30 μmol·L- 1 分别使APD 2 0 ,APD 90明显缩短 ,FC显著下降 (P<0 .0 1 ,n =5) ,并可降低高钾诱发的豚鼠乳头肌慢反应动作电位的动作电位幅值 (APA)及零相最大上升速率(Vmax) (P <0 .0 5 ,n =5)。但对静息电位 (RP) ,APA ,Vmax及AP的超射值 (OS)无明显影响 (P >0 .0 5 ,n =5)。另外 ,Rbl可浓度依赖性地抑制乳头肌收缩力 (FC) ,RP ,APA不随Rbl剂量增加而产生明显变化 ,呈典型的兴奋 收缩脱藕联。结论 :其效应可能通过阻滞钙通道而产生     

蒙药广枣中3种黄酮类成分对离体心功能的影响

采用Langendorff灌流法,观察广枣中3种黄酮类成分对离体心功能的影响,为找到一种抗心律失常作用较强的主要化学单体或简单复合物打下基础.结果表明：样品1和样品2减慢心率作用在0.027g生药1/ml～0.22g生药/ml范围内,具有明显的浓度依赖性,当浓度大于0.22g生药/ml时,减慢心率作用反而随着剂量增加而减小;样品3减慢心率作用与剂量成反比.在0.027g生药1ml～1.72g生药/ml范围内,样品1、样品2和样品3使心肌收缩幅度的变化均无统计学意义.结论：广枣中3种黄酮类成分均可减慢心率,对心肌收缩力影响不明显.     

室性早搏的快速检测方法

提出一种利用相关性和RR间期比相结合的快速室性早搏的检测算法.该算法具有一定的病人自适应性.通过MIT-BIH心律失常数据库的验证,该方法对Normal和PVC有很高的识别率.