Sodium lactate reversal of electrophysiological effects of imipramine in guinea-pig ventricular myocardium

Overdose cardiac effects of imipramine are due to fast Na channel blockade and are clinically reversed by administration of sodium lactate which induces alkalosis (about pH 7.50) and hypernatremia (about 8 mM). The mechanisms of this beneficial effect of Na lactate were explored in vitro on guinea-pig ventricular myocardium using the microelectrode technique. The time-course effects of the clinically relevant concentration of 10 microM imipramine on action potential characteristics were examined at pH 7.20 and pH 7.50. To test whether alkalinisation per se is important or whether an increase in Na concentration plays a major role in the reversal effect, preparations were exposed to increasing concentrations (1, 3, 10, 30, 100 mM) of either Na lactate, bicarbonate or chloride in the absence or in the presence of 10 microM imipramine at pH 7.50. The influence of elevating osmolality was evaluated with equivalent concentrations of sucrose. Imipramine alone significantly depressed Vmax and shortened action potential duration at all phases of repolarisation. All three high sodium solutions reversed imipramine effects. However the reversal effect was already obvious with 10 mM Na lactate and 10 mM NaHCO3 but not 10 mM NaCl. Osmolality did not reverse the imipramine-induced Vmax depression. The results suggest that at the clinically relevant 10 mM concentration, sodium lactate and bicarbonate may displace imipramine from its receptor site on the Na channel by causing alkalosis at the membrane level without profoundly affecting the driving force of the Na current, whereas at the upper concentrations, the increase in Na ion concentrations is predominantly involved in the reversal of imipramine effects.     

“钾异心”停搏液对培养心肌细胞缺血损伤的保护作用

目的 研究“钾异心”停搏液对缺血心肌的保护作用并探讨其机理，方法 用原代培养的乳鼠心肌细胞为材料，缺糖缺氧处理３ｈ造成缺血损伤，以培养液中乳酸脱氢酶（ＬＤＨ）活性及细胞含钙量为指标，比较高钾，钾异心停搏液对缺血心肌的保护作用。结果 “钾异心”停搏液能显著降低缺血处理的心肌细胞培养液的ＬＤＨ活性及细胞含钙量，与高钾停搏液相比效果显著。结论 “钾异心”停搏液保护缺血心肌的效果优于高钾液，其机理与降低细     

Simultaneous multi-site EPR spectroscopy in vivo

A gradient technique to measure electron paramagnetic resonance spectra simultaneously at several different locations is described. The technique is based on the use of point probes containing paramagnetic centers. The value of the magnetic field gradient is chosen to be sufficient to separate the EPR signals from the different paramagnetic probes yet at the same time small enough to change only minimally the shape of individual signals. The conditions to apply this technique are considered in detail. When experimental data have a high signal-to-noise ratio, the lineshape distortion induced by the gradient can be corrected with the aid of a known distribution function of paramagnetic centers within the probe. The maximum entropy deconvolution algorithm is successfully applied for the correction of significantly distorted lines. The technique is experimentally tested and applied to measure the concentration of oxygen in hypertrophied rat myocardium and normal rat kidney in vivo by low frequency EPR (L-band, 1.2 GHz). No types of EPR oxygen-sensitive probes-lithium phthalocyanine crystals and synthetic carbohydrate chars-were used.     

Stunning: A radical re-view

Summary The recovery from trauma, whether ischemia or some other form of tissue injury, is never instantaneous; time is always required for repair and the return of normal metabolism and function. To what extent the delay in recovery of contractile activity (stunning) after a brief period of ischemia represents convalescence from ischemia-induced injury, as opposed to the expression of reperfusion-induced injury, is perhaps not as clear as the proponents of stunning would hope. Definitive evidence for a distinct reperfusion-induced pathology, which compromises the recovery of contractile function from the depressed state induced by ischemia, is elusive. If reperfusion-induced injury accounts for a significant proportion of stunning, then the molecular mechanisms responsible for initiating the event and those responsible for orchestrating the event at the level of the contractile protein are far from clear. Perturbations of calcium homeostasis are frequently cited as responsible for the depressed contractile state, however, some metabolic derangement must precede any pathologically induced ionic disturbance. In this connection, evidence indicates that free-radical-induced oxidant stress, during the early moments of reperfusion, may modify the activity of a number of thiol-regulated proteins that are directly, or indirectly, responsible for controlling the movement of calcium. Sarcolemmal sodium-calcium exchange and the calcium release channel of the sarcoplasmic reticulum may be activated. whereas the sarcolemmal calcium pump and sodium-potassium ATPase, together with the calcium pump of the sarcoplasmic reticulum, may be inhibited. Under the conditions prevailing during ischemia and reperfusion, this would be expected to promote an early intracellular calcium overload. It is difficult to reconcile such a change with the decreased inotropic state that characterizes stunning; however, it seems likely that the calicum overload is transient and that the stunned myocardium rapidly reestablishes normal levels of intracellular calcium. It is still difficult to explain adequately the reduced inotropic state; clearly, the mechanism of stunning is not quite as simple as its definition.     

缺血心肌细胞钙分布变化的细胞化学研究

本文报道用细胞化学的磷酸盐—焦锑酸盐(PPA)法观察大鼠心肌缺血时心肌细胞钙分布变化。用PPA法显示正常心肌细胞钙定位在肌膜包括T管及闰盘的肌膜。钙沉淀物分布在肌膜的胞质面,沉淀物大小不超过20nm。在冠状动脉结扎30min后,肌膜的结合钙沉淀物减少甚至消失。当缺血超过60min,心肌细胞损伤严重,肌膜结合钙消失,细胞内肿胀线粒体的基质内积聚了丝团状的钙沉淀物。说明肌膜和钙结合能力是心肌细胞生存的重要特性。     

On the cooperativity of ouabain-binding to intact myocardium

A theoretical concept is presented which proposes that binding of ouabain to intact myocardium should be positive cooperative. It is based on the assumption that the myocardial Na/K-ATPases expose the ouabain-binding site only at a particular conformation adopted during a turnover cycle. The turnover rate and thus the ouabain-binding properties are regulated by the cytosolic Na-ion-concentration Nai. Any occupation of cellular Na/K-ATPases should affect the ouabain-binding properties of the unoccupied Na/K-ATPases, because their turnover rate is increased via an elevated Nai. A computer model which takes into account the interrelationships of the Na/K-ATPases both with Nai and with the ouabain-concentration predicts that ouabain-binding should proceed in a concentration-proportional fashion as long as the Na-load can be counterbalanced by non-occupied Na/K-ATPase molecules. The concentration-proportional binding reflects a positive cooperativity. Experimental results reveal that (3H)ouabain-binding to Na/K-ATPase of electrically stimulated guinea-pig left atria was in fact concentration-proportional under certain experimental conditions. The biological significance of the proposed concept remains to be elucidated.     

Clinical usefulness of iodine 123-labeled fatty acid imaging in patients with acute myocardial infarction

Background  Iodine 123-labeled 15-(p-iodophenyl)-3R,S-methylpentadecanoic acid (BMIPP) has recently been developed, since normal myocardium metabolizes free fatty acids. This study investigated the clinical usefulness of BMIPP imaging in patients with acute myocardial infarction (MI), particularly in the detection of stunned myocardium in patients who underwent acute coronary revascularization. Methods  The subjects were 41 patients with acute MI who had undergone emergency coronary revascularization. Both BMIPP and thallium-201 images at rest were obtained during the subacute phase. The myocardial distribution of radiotracers was quantified by generating circumferential count-distribution profile analysis. Initial 201 Tl imaging, delayed 201Tl imaging, and BMIPP imaging were performed, and the mean count densities in the infarct region (initial 201Tl images [TL1], delayed 201Tl images [TL2], and BMIPP images in the infarct region [BM], respectively) were obtained. The differences between mean count densities (TL1-BM: BM subtracted from TL1; TL2-BM: BM subtracted from TL2) were also calculated. Results  BM showed a higher correlation with wall motion data by echocardiography (WM) in the acute phase than other nuclear imaging tests, whereas TL2 showed the highest correlation with WM in the chronic phase. Acute to chronic WM improvement showed a good correlation with TL2-BM. Conclusion  Single photon emission computed tomography imaging with BMIPP is a candidate for providing the “memory image” of ischemic damage, whereas TL2 reflects all viable tissue. The mismatch between the tracers can serve as an indicator of myocardial stunning.     

NITRIC OXIDE SYNTHESIS IN MYOCARDIUM FOLLOWING BURN INJURY IN RATS

The nitric oxide and cyclic GMP production in myocardium early after burn injury in tats were investigated. Nitric oxide synthase activity was measured in cytosols from the left ventricular wall of burned rats.Cytosols from the control group animals were shown to contain mainly Ca^2 dependent nitric oxide synthase (cNOS) with small amount of Ca^2 independent nitric oxide synthase (iNOS). Following burn injury,there was a marked increase in iNOS activity with a peak at 8h post-butyl, however, myocardial cNOS activity was found to decline obviously. Parallel to iNOS induction there was a significant increase in myocardial nitric oxide and cyelic GMP production. All these chenges were alleviated by treatment of the rats with dexamethasone. Since increases in cyclic GMP levels in the heart were associated with reduced myocardial contractility, it is possible that enhanced production of nitric oxide by a Ca^2 independent NO synthase accounts, at least in part, for the depression of myocardial contractility seen in burn animals and patients.     

天然心房肽的制备及其对心肌滋养保护作用的研究

 参照deBold方法制备心房肽，体外培养心肌细胞实验观察到本制剂可减少细胞内乳酸脱氢酶漏出，使细胞存活期延长10d以上。动物实验观察到本制剂具有预防和对抗氯仿、氯化钡诱发的严重心律失常效应，从而揭示了心房肽对心肌的滋养保护作用。     

乳清酸对急性心肌梗塞非梗塞区心肌线粒体的有益作用

结扎大鼠冠状动脉前降支造成急性心肌梗塞（ＡＭＩ），分成乳清酸治疗组（ＡＭＩＯＡ），生理盐水治疗组（ＡＭＩＮＳ）和假手术组（ＳＯＮＳ）。观察非梗塞区心肌线粒体功能、结构及心肌纤维的改变。在ＡＭＩ后２４，７２ｈ，ＡＭＩＮＳ组Ｒ３，Ｐ／Ｏ，ＲＣＲ，ＯＰＲ有意义降低，ＡＭＩＯＡ组则明显增加（Ｐ＜０．０１），且与ＳＯＮＳ组相似（Ｐ＞０．０５）。ＡＭＩＮＳ组非梗塞区心肌超微结构，特别是边缘区表现为线粒体基质减