Effect of Central Muscarine Receptor Blockade with DKJ-21 on the Blood Pressure and Heart Rate in Stress-Induced Hypertensive Rats

Da-Nian Zhu, Long-Mei Xue, Peng Li. Effect of central muscarine receptor blockade. with DKJ-21 on the blood pressure and heart rote in stress-induced hypertensive rats.

The experiments were performed on Wistar or Sprague-Dawley rats of both sexes divided at random into stress and control groups. The rats in the stress groups were put into cages and subjected to electric foot-shocks and noises for 9-15 days, which caused an increase in blood pressure (BP) and heart rate (HR). In hypertensive rats DKJ-21 (4mg/lml) was injected intravenously (i.v.), and 0.5-1.0h after administration the BP and HR dropped from the high level to normotensive level. In normotensive rats, however, administration of DKJ-21 had no effect on BP or HR. In separate groups of normotensive rats, pretreatment of DKJ-21 (4 mg/l ml, i.v.) blocked the pressor and tachycardiac effect induced by microinjection of physostigmine (0.4μg/0.1 /μl/site), corticosterone (40μg/0.1μl/site) or aldosterone (40 μg/0.1 μl/site) into the rostral ventrolateral medulla (rVLM). Furthermore, DKJ-21 also attenuated the enhancement of the pressor response to stimulation of the defense area in the midbrain, which was induced by microinjection of drugs (mentioned above) into the rVLM. These results indicate that i.v. DKJ-21 can selectively block the muscarinic receptors in the rVLM in stress-induced hypertensive rats, which suggests that abnormal enhancement of cholinergic mechanism in the rVLM may be related to hypertensive effects of corticoids in this area.     

Simultaneous measurement of intracellular pH and contraction in uterine smooth muscle

Changes in intracellular pH (pH_i) are thought to produce large changes in force production in the uterus. There have however, been no simultaneous measurements of pH_i and force in the uterus and therefore no direct information is available about the relation between the two. We have used carboxy-SNARF (a pH-sensitive fluorophore) in small strips of longitudinal myometrium and obtained simultaneous measurements of pH_i and force. SNARF did not alter contractile function, and continuous measurements of pH_i could be made for 2 hours. The mean resting pH_i (7.16) was similar to that reported previously. Application of weak bases rapidly raised pH_i, in a concentration-dependent manner, followed by a gradual restoration of pH_i to resting levels. Alkalinization greatly increased the frequency of contractions, often accompanied by a small increase in their amplitude. Removal of base produced a rebound acidification which transiently abolished contractions. Direct acidification of the cytoplasm, by application of weak acid, also abolished contractions. However the alkalinization which accompanied removal of acid, produced variable effects on force.Supported by the M.R.C.     

汞对人体必需元素干扰的研究

对42例汞吸收、2例汞中毒者(尿汞>99.7nmol/L),采用原子吸收光谱法,检测了汞对人体必需五种金属元素代谢的干扰。研究发现,汞时人体必需元素镁、铜具有拮抗作用。汞吸收者血清镁极显著低于对照组(P>0.01)。经驱汞治疗后,血清镁、铜自然上升与对照组无统计学差异(P>0.05),镁离子低下,可出现神经肌纤维兴奋性增高。由此推测,汞引起肌肉震颤的毒理,可能由汞拮抗镁离子低下引起。设想,对汞中毒者采用补镁制剂治疗,是否具有驱汞作用值得探讨。     

Quality of life on treatment with Metoprolol in Dilated Cardiomyopathy: Results from the MDC trial

Summary Quality of life in heart failure patients is receiving increased attention as a reflection of a treatment's potential secondary benefit of general well-being and daily functioning. The Metoprolol in Dilated Cardiomyopathy (MDC) trial was conducted as a large, multicenter trial to establish the effects of metoprolol on mortality and need for heart transplantation in patients with symptomatic idiopathic cardiomyopathy. It was found that metoprolol was well tolerated, improved symptoms and cardiac function, and prevented clinical deterioration in patients with symptomatic idiopathic dilated cardiomyopathy. Quality of life was evaluated as a secondary endpoint in 345 out of 383 randomized patients using a disease-specific questionnaire, the Quality of Life in Heart Failure Questionnaire, depicting physical activity, somatic symptoms, emotions, and life satisfaction. In a comparison of patients treated with metoprolol or placebo, patients treated with metoprolol noted a significantly more favorable response than those treated with placebo in terms of the overall treatment evaluation (p<0.05). Additionally, an analysis of the changes from baseline to 18 months, using 95% confidence intervals, revealed that patients treated with metoprolol showed a significant improvement from baseline to 18 months in life satisfaction, physical activity, and the total score, while patients treated with placebo did not change at all. The improvement in quality of life was supported by the correlations with improvement in traditional clinical parameters.     

The effect of ionic strength on the kinetics of rigor development in skinned fast-twitch skeletal muscle fibres

 Recent atomic 3-D reconstructions of the acto-myosin interface suggest that electrostatic interactions are important in the initial phase of cross-bridge formation. Earlier biochemical studies had also given strong evidence for the ionic strength dependence of this step in the cross-bridge cycle. We have probed these interactions by altering the ionic strength (Γ/2) of the medium mainly with K⁺, imidazole⁺ and EGTA^2– to vary charge shielding. We examined the effect of ionic strength on the kinetics of rigor development at low Ca²⁺ (experimental temperature 18–22°C) in chemically skinned single fast-twitch fibres of mouse extensor digitorum longus (EDL) muscle. On average the delay before rigor onset was 10 times longer, the maximum rate of rigor tension development was 10 times slower, the steady-state rigor tension was 3 times lower and the in-phase stiffness was 2 times lower at high (230 mM) compared to low (60 mM) ionic strength. These results were modelled by calculating ATP depletion in the fibre due to diffusional loss of ATP and acto-myosin Mg.ATPase activity. The difference in delay before rigor onset at low and high ionic strength could be explained in our model by assuming a 15 times higher Mg.ATPase activity and a threefold increase in K _m in relaxing conditions at low ionic strength. Activation by Ca²⁺ induced at different time points before and during onset of rigor confirmed the calculated time course of ATP depletion. We have also investigated ionic strength effects on rigor development with the activated troponin/tropomyosin complex. ATP withdrawl at maximum activation by Ca²⁺ induced force transients which led into a ”high rigor” state. The peak forces of these force transients were very similar at low and high ionic strength. The subsequent decrease in tension was only 10% slower and steady-state ”high rigor” tension was reduced by only 27% at high compared to low ionic strength. Addition of 10 mM phosphate to lower cross-bridge attachment strongly suppressed the transient increases in force at high ionic strength and reduced the steady-state rigor tension by 17%. A qualitatively similar but smaller effect of phosphate was observed at low ionic strength where steady-state rigor force was reduced by 10%. The data presented in this study show a very strong effect of ionic strength on rigor development in relaxed fibres whereas the ionic strength dependence of rigor development after thin filament activation was much less. The data confirm the importance of electrostatic interactions in cross-bridge attachment and cross-bridge-attachment-induced activation of thin filaments. Received: 3 September 1997 / Received after revision and accepted: 12 December 1997     

Unsteady Fluid Dynamics of Several Mechanical Prosthetic Heart Valves Using a Two Component Laser Doppler Anemometer System

Abstract: Five typical mechanical heart valves (Starr-Edwards, Björk-Shiley convexo-concave (c-c), Björk-Shiley monostrut, Bicer-Val, and St. Jude Medical) were tested in the mitral position under the pulsatile flow condition. The test program included measurements of velocity and turbulent stresses at 5 downstream locations. The study was carried out using a sophisticated cardiac simulator in conjunction with a highly sensitive 2 component laser Doppler anemometer (LDA) system. The continuous monitoring of parametric time histories revealed useful details about the complex flow and helped to establish the locations and times of the peak parameter values. Based upon the nondimensional presentation of data, the following general conclusions can be made. First, all the 5 valve designs created elevated turbulent stresses during the accelerating and peak flow phases, presenting the possibility of thromboembolism and perhaps hemolysis. Second, the difference in valve configuration seemed to affect the flow characteristics; third, the bileaflet design of the St. Jude valve appeared to create a lower turbulence stress level.     

Plastic surgical treatment of a chronic thoracic duct fistula using a sternocleidomastoid muscle flap — a case report

Thoracic duct fistula is a rare but potentially serious complication of head and neck surgery. Such fistulae may be difficult to treat, and several techniques, both operative and non-operative, have been advocated. A case of successful surgical treatment of a chronic thoracic duct fistula is presented. The fistula occurred in a 51-year-old female following treatment of a solitary supraclavicular breast metastasis by local excision and radiotherapy. The divided duct was ligated and the area was covered with the clavicular head of the sternocleidomastoid muscle.     

西雅图心绞痛调查量表对冠心病患者机体功能及生活质量的评估研究

目的对冠心病患者机体功能状态及生活质量进行评估。方法采用Ｓｐｅｔｕｓ等设计的ＳｅａｔｔｌｅＡｎｇｉｎａＱｕｅｓｔｉｏｎｎａｉｒｅ问卷对１００例冠心病患者躯体活动受限程度、心绞痛稳定状态及发作情况、治疗满意程度和疾病认识程度进行测评研究。结果重复测定显示该量表有良好的重复性，心理疗法配合药物治疗组的评分明显优于单纯药物治疗组（Ｐ＜０．０５）。结论该量表用于我国冠心病患者有较满意的信度，同时也证实了心理疗法在冠心病治疗中的重要地位。     

Life satisfaction in patients with chest pain subsequently diagnosed as coronary heart disease – connection through depressive symptoms?

The aim of this study was to investigate factors associated with life dissatisfaction in symptomatic patients (n = 144) with chest pain subsequently diagnosed as coronary heart disease (CHD) by coronary angiography. Life dissatisfaction was assessed with a four-item life satisfaction scale (LS), depression with the 21-item Beck Depression Inventory (BDI) and other psychiatric symptoms with the symptom check list (SCL). DSM-III-R Axis I and Axis II psychiatric diagnoses were performed by means of the Structured Clinical Interview. All assessments took place one day before angiography. Twenty-four per cent of CHD patients were dissatisfied with their lives. Life dissatisfaction was associated with being unmarried. Dissatisfied patients had Axis I mental disorders and Axis II personality disorders more frequently than others. Psychiatric and depressive symptoms according to the SCL and BDI, respectively, were also higher among dissatisfied patients. In multiple logistic regression analyses, mental disorders were related to life dissatisfaction when age, sex, employment status, New York Heart Association class, duration of chest pain symptoms and work load were controlled in the model. Married subjects had a lower probability of being dissatisfied with their lives than other subjects (Odds Ratio, OR: 0.23). When BDI scores were included in the model, the only factor independently associated with life dissatisfaction was the severity of depressive symptoms (OR: 1.81). To conclude, life dissatisfaction is not primarily determined by the severity of CHD but by the existence of depressive symptoms.     

Can a Single Muscle Fiber Model the Features of Myocardial Stunning?

The exact mechanisms that cause myocardial stunning are still unclear. We previously utilized a computer model of the ventricle that was effective in modeling the dominant observable features of stunning, but it was not simple to implement. This led to the design of a single muscle fiber model. The mathematical model of a muscle fiber consisted of three elements: a contractile element, a series elastic element, and a parallel elastic element. The model created length waveforms based on time-dependent force and contractile stiffness functions. This model was initially evaluated by entering the same regional parameter values used in the global dual region ventricular model. First a reduction of the contractile stiffness function was applied by reducing the peak stiffness by 30%, and then the rates of activation and deactivation were reduced by 20% while maintaining the peak values constant. The three-element model produced results very similar to the canine and ventricular model. Thus, it is concluded that the simpler three-element model provides an accurate model of the myocardial tissue and its deficiencies during stunning.