Mechanical parameters determined in dispersed ventricular heart cells

A high-resolution laser diffraction system suitable for studying the basic mechanical properties of small contractile single cells has been developed. This method was used to establish the mechanical behavior of 95 ventricular cells isolated from adult guinea pig hearts. During contraction, the sarcomere length shortened from 1828 +/- 43 nm (mean +/- SD) to 1518 +/- 99 nm. The maximal velocities were 1.98 +/- 0.64 micron/s for shortening and 1.93 +/- 0.54 micron/s for re-lengthening. The twitch duration from 20% shortening to 80% re-lengthening was 622 +/- 120 ms.     

Über den Nukleinsäuregehalt des normalen und hypertrophischen Kaninchenherzens

Summary In left ventricular myocardium of 9 hypertrophic (artificial aortic insufficiency) and 12 normal rabbit hearts, ribonucleic and desoxyribonucleic acids were determined. In hypertrophy DNA-P was significantly reduced, where-as RNA-P was higher than in normal myocardium. The RNA-P/DNA-P ratio was 2·9 in normal as compared to 4·0 in hypertrophic heart muscle.

---

---

Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Myocardial function and energy metabolism in carnitine-deficient rats

Carnitine is essential for mitochondrial metabolism of long-chain fatty acids and thus for myocardial energy production. Accordingly, carnitine deficiency can be associated with cardiomyopathy. To better understand this disease, we determined myocardial function and energy metabolism in a rat model of carnitine deficiency. Carnitine deficiency was induced by a 3- or 6-week diet containing N-trimethyl-hydrazine-3-propionate, reducing cardiac and plasma carnitine by 70-85%. Myocardial function was investigated in isolated isovolumic heart preparations. Carnitine-deficient hearts showed left ventricular systolic dysfunction, reduced contractile reserve, and a blunted frequency-force relationship independently of the substrate used (glucose or palmitate). After glycogen depletion, palmitate could not sustain myocardial function. Histology and activities of carnitine palmitoyl transferase, citrate synthase, and cytochrome c oxidase were unaltered. Thus, as little as 3-6 weeks of systemic carnitine deficiency can lead to abnormalities in myocardial function. These abnormalities are masked by endogenous glycogen and are not accompanied by structural alterations of the myocardium or by altered activities of important mitochondrial enzymes.     

Failure of opioids to affect excitation and contraction in isolated ventricular heart muscle

The opioid agonists morphine (selective for mu-receptors) and ethylketocyclazocine (selective for kappa-receptors), at concentrations evoking strong effects in neuronal structures, did not significantly affect the configuration of the intracellularly recorded action potential and the force of contraction in ventricular heart muscle isolated from guinea pigs, rabbits and man. These results suggest that any changes of heart functions in vivo in response to opioid-like drugs are probably not mediated postsynaptically at the myocardial cell membrane but rather presynaptically, influencing the release of noradrenaline and/or acetylcholine from the nerve terminals.     

Interarterielle koronare Anastomosen

Summary Wax spheres with a diameter of 35–45 µ and 75–90 µ were injected into one coronary artery of 73 human hearts. The finding of spheres in the opposite coronary artery was considered as evidence for the presence of interarterial coronary anastomoses. In hearts with occlusive coronary sclerosis or ventricular hypertrophy anastomoses were found in approximately 70% of the cases. Of the 15 normal hearts only 1 (7%) was found to have anastomoses.     

Mechanical and biochemical characterization of the contraction elicited by a calcium-independent myosin light chain kinase in chemically skinned smooth muscle

The contraction induced by a Ca2+-independent myosin light chain kinase (MLCK-) was characterized in terms of isometric force (Fo), immediate elastic recoil (SE), unloaded shortening velocity (Vus), shortening under a constant load and ATPase activity of chemically skinned smooth muscle preparations. These parameters were compared to those measured in a Ca2+ -induced contraction to assess the nature of cross bridge interaction in the MLCK-induced contraction. Fo developed in chicken gizzard fibers as well as SE were similar in contractions elicited by either agent. Vus in the contraction induced by MLCK-(0.36 mg/ml) was similar though averaged 39.3 +/- 8.9% less than Vus induced by Ca2+ (1.6 X 10(-6) M) in the control fibers. Addition of Ca2+ (1.6 X 10(-6) M) to a contraction induced by MLCK-resulted in small increases in both Fo and Vus. Shortening under a constant load was similar for both types of contractions. The contraction induced by MLCK-was accompanied by an increased rate of ATP hydrolysis. The MLCK-induced contraction is thus kinetically similar though not identical to a contraction induced by Ca2+. We conclude that with respect to actin-myosin interaction, MLCK-and Ca2+ -induced contractions are similar.     

Failure of opioids to affect excitation and contraction in isolated ventricular heart muscle

Summary The opioid agonists morphine (selective for -receptors) and ethylketocyclazocine (selective for kappa-receptors), at concentrations evoking strong effects in neuronal structures, did not significantly affect the configuration of the intracellularly recorded action potential and the force of contraction in ventricular heart muscle isolated from guinea pigs, rabbits and man. These results suggest that any changes of heart functions in vivo in response to opioid-like drugs are probably not mediated postsynaptically at the myocardial cell membrane but rather presynaptically, influencing the release of noradrenaline and/or acetylcholine from the nerve terminals.     

Thermoadaptive influence on reactivity pattern of vasopressinergic neurons in the guinea pig

Summary In cold-adapted guinea pigs, increased amounts of arginine-vasopressin (AVP) immunoreactive material could be visualized in neurons of the supraoptic and paraventricular nucleus, in fibers projecting to the neurohypophysis and in fiber terminals in the ventral lateral septum and in the amygdala. In warm-adapted animals the reactivity to AVP antiserum was poor in all neuronal structures examined. High AVP-immunoreactivity was accompanied by a reduced febrile response to bacterial pyrogen in cold-adapted guinea pigs.     

聚焦超声辐照豚鼠慢性湿疹模型的超微结构变化

目的探讨聚焦超声辐照豚鼠慢性湿疹模型豚鼠的皮肤超微结构改变。方法豚鼠32只，以2，4-二硝基氯苯（DNCB）为抗原，小剂量多次刺激豚鼠背部皮肤制备慢性湿疹模型。随机分为辐照组3组和对照组，辐照组以频率10MHz、声功率3W的连续波直接辐照模型皮肤真皮层，3组分别于辐照后1、7和14天取材，对照组不辐照立即取材，做透射电镜观察．结果辐照前可见表皮角质层增厚明显，成纤维细胞线粒体肿胀、粗面内质网扩张，细胞间隙加大；辐照后第1天和7天可见血管内皮细胞线粒体肿胀、微吞饮小泡数量多，成纤维细胞线粒体肿胀、粗面内质网扩张，但细胞间隙变小；第14天基本恢复正常。结论聚焦超声可用于治疗湿疹，有利于微血管和胶原纤维的增生与修复，可使患处上皮细胞及真皮组织的超微结构趋于恢复正常。     

Isoprenaline, modifications of the turnover of ATP in the perfused rat heart]

5 hrs after a single sub-cutaneous injection of the drug in a dose of 5 mg/kg, the ATP concentration was reduced by 15%, the incorporation of 14C adenine was augmented by 20% and the turnover of ATP was accelerated: the reduction of specific radioactivity attained 16%, 75 mn after the period of marquage, instead of 7% in the control hearts. When the drug was added to the perfusion fluid, there was no supplementary reduction of the ATP concentration and the action on the nucleotide turnover only existed if the ATP level was reduced by a pretreatment: the reduction of specific radioactivity then attained 24% after 75 min. of perfusion.     

Na, K-ATPase in the salivary gland of the ixodid tick Amblyomma hebraeum (Koch) and its relation to the process of fluid secretion.

Total and ouabain-sensitive ATPase activities were determined in the salivary glands of ticks throughout the feeding cycle. Activities were very low in unfed specimens. In the glands of feeding females, the activities rose until a maximum was reached for both ATPase components at approximately 200 mg. The activities remain low in males throughout the feeding period. These findings are discussed in relation to the fluid secretory process of the salivary glands.     

Mechanical and biochemical characterization of the contraction elicited by a calcium-independent myosin light chain kinase in chemically skinned smooth muscle

Summary The contraction induced by a Ca²⁺-independent myosin light chain kinase (MLCK-) was characterized in terms of isometric force (F_o), immediate elastic recoil (SE), unloaded shortening velocity (V_us), shortening under a constant load and ATPase activity of chemically skinned smooth muscle preparations. These parameters were compared to those measured in a Ca²⁺-induced contraction to assess the nature of cross bridge interaction in the MLCK-induced contraction. F_o developed in chicken gizzard fibers as well as SE were similar in contractions elicited by either agent. V_us in the contraction induced by MLCK-(0.36 mg/ml) was similar though averaged 39.3±8.9% less than V_us induced by Ca²⁺ (1.6x10^–6M) in the control fibers. Addition of Ca²⁺ (1.6x10^–6M) to a contraction induced by MLCK-resulted in small increases in both F_o and V_us. Shortening under a constant load was similar for both types of contractions. The contraction induced by MLCK-was accompanied by an increased rate of ATP hydrolysis. The MLCK-induced contraction is thus kinetically similar though not identical to a contraction induced by Ca²⁺. We conclude that with respect to actin-myosin interaction, MLCK- and Ca²⁺-induced contractions are similar.     

The effect of ascorbic acid on cadmium accumulation in guinea pig tissues

Accumulation of cadmium in organs of guinea pigs after subchronic oral cadmium treatment (1 mg Cd/animal/24 h) was in the following order: kidneys > liver > heart > testes > brain. The preventive effects of high doses of ascorbic acid (AA) against cadmium deposition were more pronounced in the testes, heart and brain, and in the kidney only after short-term cadmium treatment. Ascorbic acid had no protective effect on cadmium accumulation in the liver.     

Enhanced toxicity of the immunosuppressant ovalicin upon application to the skin

Summary The non-myelotoxic immunosuppressive sesquiterpene ovalicin, of fungal origin, is much more toxic when applied to the skin of animals than when injected i.v., the LD-50 in guinea pigs being 0.2 in the first case and 7 mg/kg in the second. It elicits aphagia and adipsia. It is assumed that ovalicin effects are due to slow, tissue-specific, metabolic toxification.     

The effect of ascorbic acid on cadmium accumulation in guinea pig tissues.

Accumulation of cadmium in organs of guinea pigs after subchronic oral cadmium treatment (1 mg Cd/animal/24 h) was in the following order: kidneys > liver > heart > testes > brain. The preventive effects of high doses of ascorbic acid (AA) against cadmium deposition were more pronounced in the testes, heart and brain, and in the kidney only after short-term cadmium treatment. Ascorbic acid had no protective effect on cadmium accumulation in the liver.     

Disruption of mitochondrial function as the basis of the trypanocidal effect of trifluoperazine on Trypanosoma cruzi.

The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes of Trypanosoma cruzi, at concentrations lower than 100 microM, and motility and infectivity of the bloodstream trypomastigote form at 200 microM. Electron microscopy of TFP-treated epimastigotes showed that the major effect was at the mitochondrial level, with gross swelling and disorganization. The oligomycin-sensitive, mitochondrial ATPase was completely inhibited by 20 microM TFP, and the same drug concentration caused a 60% decrease in intracellular ATP content. The results suggest that the trypanocidal effect of TFP may be related more to mitochondrial damage than to the well-known anticalmodulin effect of the drug.     

The ATP synthase (F0−F1) complex in oxidative phosphorylation

The transmembrane electrochemical proton gradient generated by the redox systems of the respiratory chain in mitochondria and aerobic bacteria is utilized by proton translocating ATP synthases to catalyze the synthesis of ATP from ADP and P_i. The bacterial and mitochondrial H⁺-ATP synthases both consist of a membranous sector, F₀, which forms a H⁺-channel, and an extramembranous sector, F₁, which is responsible for catalysis. When detached from the membrane, the purified F₁ sector functions mainly as an ATPase. In chloroplasts, the synthesis of ATP is also driven by a proton motive force, and the enzyme complex responsible for this synthesis is similar to the mitochondrial and bacterial ATP synthases. The synthesis of ATP by H⁺-ATP synthases proceeds without the formation of a phosphorylated enzyme intermediate, and involves co-operative interactions between the catalytic subunits.     

Energetics and regulation of crossbridge states in mammalian smooth muscle

Conclusion On the basis of measurements of the high energy phosphate usage associated with different mechanical states, as well as the degree of myosin light chain phosphorylation and mechanical properties, information has been gained concerning the existence and regulation of different crossbridge states in smooth muscle. Although incomplete, a general operational scheme is shown in figure 5. At very low intracellular calcium concentrations, actin and myosin are dissociated, as shown by a loss of resistance to stretch in resting muscles. At somewhat higher intracellular calcium concentrations in atonic, resting muscles, crossbridges can attach and be manifest mechanically as an increased resistance to stretch without ATP-driven crossbridge cycling and active force production. When the muscle is activated, intracellular calcium increases further, the light chains of myosin are phosphorylated through the calcium-calmodulin activation of myosin light chain kinase, actin-activated myosin ATPase activity increases and crossbridges cycle. Calcium also appears to modulate the ATPase activity and the rate of cycling of the phosphorylated crossbridge. The crossbridge cycling rate is highest during force development and slows with time as maximum isometric force is maintained reflecting a change in the rate at which phosphorylated crossbridges cycle. This may result from a decrease in the intracellular free calcium concentration with continued stimulation. During relaxation, the intracellular calcium concentration decreases, there is net dephosphorylation of the myosin light chains, the rate at which phosphorylated crossbridges cycle slows further with a gradual return to the attached, but non-cycling state or the detached state.     

Effects of nitric oxide on the contraction of skeletal muscle

A review of the literature suggests that the effects of nitric oxide (NO) on skeletal muscles fibers can be classified in two groups. In the first, the effects of NO are direct, due to nitrosation or metal nitrosylation of target proteins: depression of isometric force, shortening velocity of loaded or unloaded contractions, glycolysis and mitochondrial respiration. The effect on calcium release channels varies, being inhibitory at low and stimulatory at high NO concentrations. The general consequence of the direct effects of NO is to ‘brake’ the contraction and its associated metabolism. In the second group, the effects of NO are mediated by cGMP: increase of the shortening velocity of loaded or unloaded contractions, maximal mechanical power, initial rate of force development, frequency of tetanic fusion, glucose uptake, glycolysis and mitochondrial respiration; decreases of half relaxation time of tetanus and twitch, twitch time-to-peak, force maintained during unfused tetanus and of stimulus-associated calcium release. There is negligible effect on maximal force of isometric twitch and tetanus. The general consequence of cGMP-mediated effects of NO is to improve mechanical and metabolic muscle power, similar to a transformation of slow-twitch to fast-twitch muscle, an effect that we may summarize as a ‘slow-to-fast’ shift.