Autoregulation of contractility in the myocardial cell

Summary An investigation was carried out on isolated cat's papillary muscle in order to study displacement effects upon the intensity and the time course of the contractile activity. Displacements occurring before or very early during a contractile cycle produce effects which can be entirely explained on the basis of the cardiac active length-tension relation. Displacements occurring later exhibit additional effects in so far as either stretches or releases induce a drop of contractile activation such that the course of the subsequent tension development is markedly below that of the same displacement applied earlier. In order to separate these effects from those based on the active length-tension correlation experiments were performed in which very short release-stretch or stretch-release operations were applied so that the muscle length was virtually the same at the beginning and at the end of the operation. The results obtained under these conditions can be summarized as follows.The extend to which contractile tension drops after a stretch-release or a release-stretch cycle has been applied depends upon (1) the stimulus intervention interval (2) the length change performed (3) the velocity of displacement during the intervention. It is not dependent on the initial muscle length. Increasing the extracellular Ca-concentration considerably reduces the displacement effects. The results are tentatively explained by assuming an internal feedback loop between a variable of the contractile machinary and the preceding mechanism of activation.This investigation was supported by the Deutsche Forschungsgemeinschaft (grant Ka 287, 1+3).     

Neuromuscular adaptations in rats trained by muscle stretch-shortening

The aim of this study was the analysis of neurophysiological, mechanical and histochemical parameters to demonstrate muscle adaptation with training. If the parameters studied were to show correlated changes, it would be possible to propose that the neural and the muscle components of motor units are both affected by the training programme used. The training consisted of repeated stretch-shortening cycles known to use extensively fast fibres. After the training period electromyographical reflex activities of the ankle plantar-flexors were recorded in awake rats and then mechanical and histochemical measurements were made on isolated soleus muscles of the control and trained rats. The reflexes studied were the H-response to electrical stimulation of the sciatic nerve and the T-response to an Achilles tendon tap. The H-response analysis indicated a decrease in reflex excitability of the trained muscles. The trained soleus muscle also presented a higher contractility as demonstrated by significantly smaller twitch contraction times and higher maximal velocities of shortening measured during tetanic contractions. The reflex and contractile muscle changes were accompanied by relative increases in the number of type II fibres. The T-response was not significantly modified by training despite the decrease in motoneuron excitability demonstrated by the decrease in H-response. This would suggest that the peripheral components of the reflex pathway such as tendon stiffness and/or spindle sensitivity might be modified by training. This would imply that both the motor and the sensory parts of a muscle are affected by training.     

Measurements of intracellular calcium and contractility in human ciliary muscle

Electromechanical and pharmacomechanical coupling was investigated in human ciliary muscle by measuring the intracellular free calcium in single cultured ciliary muscle cells and the contractility in meridional ciliary muscle strips. The basal resting calcium concentration was 75±8.7 nmol/l, n=23. Application of acetylcholine (0.1 mmol/l) and carbachol (0.1 mmol/l) resulted in an initial [Ca²⁺]_i peak followed by a recovery phase and a [Ca²⁺]_i plateau. The initial [Ca²⁺]_i peak was still observed in the absence of extracellular calcium and in the presence of verapamil (0.1 mmol/l). During its plateau [Ca²⁺]_i was decreased by withdrawal of extracellular calcium or application of verapamil (0.1 mmol/l). Depolarization induced by a high level of extracellular potassium yielded only a small transient [Ca²⁺]_i peak without a [Ca²⁺]_i plateau. In isolated ciliary muscle strips, muscarinic stimulation (carbachol 0.1 mmol/l) resulted in an initial phasic and a subsequent tonic contraction. Removal of external calcium reduced the phasic contraction to 30.6±4.4% (n=8) and completely abolished the tonic one. Verapamil (0.1 mmol/l) had only a slight relaxing effect when applied during the tonic contraction. We conclude that human ciliary muscle contraction is mediated by calcium release from intracellular stores and calcium entry through calcium channels, which are most probably receptor-operated. Depolarization of the muscle cell membrane and calcium entry through voltage-operated calcium channels do not contribute significantly to human ciliary muscle contraction.     

Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model

Most patients with hypertrophic cardiomyopathy and congenital heart diseases express the atrial essential myosin light chains (ALC-1) in their ventricles, partially replacing the ventricular essential light chains (VLC-1). This VLC-1/ALC-1 isoform shift is correlated with an increase in cross-bridge cycling kinetics as measured using skinned fibers from the hypertrophied ventricles of human hearts.To study the functional importance of hALC-1 in the intact perfused heart, we generated a transgenic rat model (TGR) overexpressing hALC-1 in the heart. Twelve-week-old TGR rats expressed 17±4 g hALC-1 per mg of whole SDS-soluble protein. Their perfused heart contractility parameters were evaluated using the Langendorff preparation. Expression of hALC-1 was accompanied by statistically significant improvements (P<0.001) in the contractile parameters of the hearts of the TGR compared to the age matched control (WKY) animals, represented by increases from 20.8±2.3 to 45.1±3.6 mmHg/g heart weight in the developed left ventricular pressure, 1,035.7±89.8 to 2,181±135.4 mmHg/s in the contraction rate, and 713±60.2 to 1,364±137.4 mmHg/s in the relaxation rate in the WKY and the TGR groups respectively. Characterizing the functional effects of hALC-1 at the whole organ level represents a step towards gene therapy of heart failure.     

芬太尼对离体大鼠心脏收缩力及心肌细胞钙离子移动的影响

目的　观察芬太尼对离体灌流心脏收缩力及心肌细胞钙离子移动的影响,研究其对心肌收缩力的作用。方法　（１） 以含不同浓度芬太尼的克汉二氏重碳酸盐缓冲液（ＫＨＢ） 灌流大鼠心脏,测定心率（ＨＲ） 、左室收缩压（ＬＶＳＰ） 、左室舒张压（ＬＶＤＰ）、左室收缩压上升最大速率（ ＋ ｄｐ／ｄｔｍａｘ）、左室舒张压下降最大速率（ － ｄｐ／ｄｔｍａｘ） ;（２） 用Ｆｌｕｏ３ＡＭ 钙荧光指示剂染色急性分离的大鼠心肌细胞,在激光共聚焦显微镜下动态观察用药前和用不同浓度芬太尼后,ＫＣｌ 诱发的细胞内钙离子浓度的变化。结果　１ ｎｇ／ｍｌ 和２０ ｎｇ／ｍｌ 的芬太尼对心肌收缩力和心肌细胞钙离子移动的影响较小,心肌收缩力的各项指标和钙荧光强度与对照组相比,差异无显著性（ Ｐ＞ ０．０５） 。而２００ ｎｇ／ｍｌ 芬太尼使心率减慢及＋ ｄｐ／ｄｔｍａｘ 、－ ｄｐ／ｄｔｍａｘ下降,且差异有显著性（ Ｐ＜０ ．０５） 。结论　芬太尼对心肌细胞钙离子的跨膜内流影响较小,而使心肌收缩力保持稳定。超临床使用浓度的芬太尼仍有抑制心肌的趋势。     

复方黄芩药效学研究Ⅰ

目的：观察复方黄芩对妊娠小鼠、正常小鼠离体子宫平滑肌的影响。方法：采用离体子宫平滑肌标本运动的实验方法。结果：复方黄芩能降低怀孕与正常小鼠离体子宫收缩力，在20，30min作用最明显；复方黄芩也能降低缩宫素诱导的子宫收缩作用，在20，30min作用最明显。结论：复方黄苓对小鼠的离体子宫有松弛作用。     

Ethanol Inhibits Contractility of Esophageal Smooth Muscle Strips

Acute ethanol (EtOH) in vivo decreases both the pressure of the lower esophageal sphincter (LES) and the amplitude of contractions of the smooth muscle of the lower esophageal body (LEB) in both man and cat. However, the mechanism of this inhibitory effect of EtOH is unclear. This inhibitory effect could be caused by a direct effect of EtOH on the esophagus or be secondary to known inhibitory effects of EtOH on the central nervous system. To this end, we evaluated the in vitro effect of EtOH on contractility of smooth muscle strips from both LES and LEB. Circular muscle strips from LES and LEB were isolated from cats. Changes in resting tension of LES strips and changes in stimulant-induced tension of LES or LEB strips were measured in the presence of up to five concentrations of EtOH (12.5–100 mM). Stimulants included electric field stimulation (EFS) and carbachol. EtOH at 75 mM significantly decreased resting LES tension. EtOH also decreased maximal contractile responses to carbachol in both LES and LEB and increased the EC₅₀ of carbachol for LES, but not LEB. EtOH also modulated EFS-induced esophageal contractility; EtOH potentiated EFS-induced "on-response relaxation" in LES and decreased EFS-induced "off-response contractions" in LEB. EtOH-induced inhibition of esophageal contractility seemed to be reversible. EtOH did not result in muscle fatigue. Thus, EtOH can directly inhibit contractility of the esophagus, and does so reversibly and at pharmacologically relevant concentrations.     

Protective Effects of Estradiol on Myocardial Contractile Function Following Hemorrhagic Shock and Resuscitation in Rats

Background:

Hemorrhagic shock (HS) results in myocardial contractile dysfunction. Studies showed that 17β-estradiol protects the myocardium against contractile dysfunction. The study investigated the cardioprotective effects of treatment with 17β-estradiol before resuscitation following 1 h of HS and resuscitation.

Methods:

Male Sprague-Dawley rats were assigned to 2 sets of experimental protocols: Ex vivo and in vivo treatment and resuscitation. Each set had three experimental groups (n = 6 per group): Normotensive (N), HS and resuscitation (HS-R) and HS rats treated with 17β-estradiol (E) and resuscitated (HS-E-R). Rats were hemorrhaged over 60-min to reach a mean arterial blood pressure of 40 mmHg. In the ex vivo group, hearts were resuscitated by perfusion in the Langendorff system. In the 17β-estradiol treated group, 17β-estradiol 280 µg/kg was added for the first 5 min. Cardiac function was measured. Left ventricular generated pressure (LVGP) and +dP/dt were calculated. In the in vivo group, rats were treated with 17β-estradiol 280 µg/kg s.c. after 60-min HS. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30-min to restore normotension.

Results:

Treatment with 17β-estradiol before resuscitation in ex vivo treated and resuscitated isolated hearts and in the in vivo treated and resuscitated rats following HS improved myocardial contractile function. In the in vivo treated group, LVGP and +dP/dt max were significantly higher in 17β-estradiol treated rats compared to the untreated group (LVGP 136.40 ± 6.61 compared to 47.58 ± 17.55, and +dP/dt 661.85 ± 49.88 compared to 88.18 ± 0.85). Treatment with 17β-estradiol improved LVGP following HS.

Conclusions:

The results indicate that treatment with 17β-estradiol before resuscitation following HS protects the myocardium against dysfunction.