Bilinear correlation between tissue water content and diastolic stiffness of the ventricular myocardium

Summary In oedematous and dehydrated canine hearts a close bilinear correlation was demonstrated between myocardial water content and diastolic stiffness (characterized by the passive elastic modulus) with an optimal minimum of stiffness at normal myocardial water content.     

Effects of pertussis toxin on alpha 1-agonist-mediated phosphatidylinositide turnover and myocardial cell hypertrophy in neonatal rat ventricular myocytes

In neonatal rat ventricular myocytes pretreatment with pertussis toxin did not affect 1 microM (-)-norepinephrine stimulation of inositol phosphates or myocardial cell hypertrophy as measured either by protein radiolabelling or by myocardial cell protein content. Thus guanine nucleotide protein(s) ADP-ribosylated by pertussis toxin do not play a role in two alpha 1-adrenoceptor-mediated processes, phosphatidylinositide turnover and induction of myocardial cell hypertrophy.     

An electrophysiological study on the myocardium of dystrophic mice

Summary Decreased resting potential and prolonged duration of the action potential were observed in left ventricular muscles of dystrophic mice, while there was no change in myocardial potassium content.This study was supported in part by a Research Grant for Cardiomyopathy from the Ministry of Health and Welfare, Japan.     

K型偏心支撑钢框架抗震性能研究

为分析K型偏心支撑框架在低周往复荷载作用下的抗震性能,通过模型试验及仿真试验研究了K型偏心支撑框架的滞回性能、刚度退化现象以及在循环荷载作用下的能量耗散机理.结果表明K型偏心支撑框架在弹性阶段刚度大,在塑性阶段耗能能力强;不同的耗能梁段长度对结构各层的耗能能力有很大的影响,耗能梁段不宜过短也不宜过长;当耗能梁段出现剪切屈服后,刚度出现明显的退化现象,仿真试验验证了试验剪切型梁段的屈服现象.K型偏心支撑框架具有良好的滞回性能和耗能性能,分析结果可供工程设计和相关研究参考.     

Conduction of the impulse in the ischemic myocardium--implications for malignant ventricular arrhythmias

Ventricular arrhythmias occurring consequent to regional disturbances of myocardial perfusion are the most frequent cause of sudden cardiac death. They are related to marked changes of impulse propagation in the ischemic region, which consist of circulating excitation with re-entry. Mapping of the impulse during ventricular tachycardias and ventricular fibrillation shows that the circus movements change their shape and localization from beat to beat. Zones of tissue which block the impulse during one beat may conduct the impulse at a fast rate during the next beat. The main cause underlying this behavior is the depression of the ischemic action potential. This depression is caused by the partial inactivation and the prolonged recovery of the rapid sodium inward current. In addition to the decrease in resting potential, other factors, such as acidosis, contribute to the inactivation of the inward currents generating the upstroke of the action potential. An increase of coupling resistance between myocardial cells and/or an increase of extracellular resistance appear to be less important for explaining conduction disturbances in acute ischemia.     

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.     

Effects of pertussis toxin onα 1-agonist-mediated phosphatidylinositide turnover and myocardial cell hypertrophy in neonatal rat ventricular myocytes

Summary In neonatal rat ventricular myocytes pretreatment with pertussis toxin did not affect 1 M (–)-norepinephrine stimulation of inositol phosphates or myocardial cell hypertrophy as measured either by protein radiolabelling or by myocardial cell protein content. Thus guanine nucleotide protein (s) ADP-ribosylated by pertussis toxin do not play a role in two ₁-adrenoceptor-mediated processes, phosphatidylinositide turnover and induction of myocardial cell hypertrophy.     

Intramitochondrial inclusions in maturing and senescent muscle cells of rat myocardium

Summary Intramitochondrial myelin-like structures were found in ventricular myocardial cells of the rat heart. These inclusions were found in both the first 2 postnatal weeks and in senescent stages. The origin of such myelin-like structures could be related to an age-dependent metabolic change, specifically to an inability to oxidize long-chain fatty acids described in both periods.Acknowledgment. This work was supported by grant No. 801/82 of CAICYT.     

Tetrodotoxin slightly shortens action potential duration in ventricular but not in atrial heart muscle

Tetrodotoxin (TTX), at concentrations significantly decreasing maximal upstroke velocity (dV/dtmax) of the action potential, exerted variable effects on action potential duration (APD) in different myocardial preparations. APD was virtually unchanged by tetrodotoxin in the guinea pig atrium, but slightly shortened in the guinea pig ventricle at maximally effective concentrations. In the human ventricle, both dV/dtmax and APD were reduced in the same concentration range of TTX. These results suggest that a TTX-sensitive sodium current significantly contributes to the repolarization phase of the action potential in ventricular but not in atrial heart muscle.     

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.     

Conduction of the impulse in the ischemic myocardium — implications for malignant ventricular arrhythmias

Summary Ventricular arrhythmias occurring consequent to regional disturbances of myocardial perfusion are the most frequent cause of sudden cardiac death. They are related to marked changes of impulse propagation in the ischemic region, which consist of circulating excitation with re-entry. Mapping of the impulse during ventricular tachycardias and ventricular fibrillation shows that the circus movements change their shape and localization from beat to beat. Zones of tissue which block the impulse during one beat may conduct the impulse at a fast rate during the next beat. The main cause underlying this behavior is the depression of the ischemic action potential. This depression is caused by the partial inactivation and the prolonged recovery of the rapid sodium inward current. In addition to the decrease in resting potential, other factors, such as acidosis, contribute to the inactivation of the inward currents generating the upstroke of the action potential. An increase of coupling resistance between myocardial cells and/or an increase of extracellular resistance appear to be less important for explaining conduction disturbances in acute ischemia.     

Cardiovascular development: towards biomedical applicability

Regardless of erroneous claims by a minority of reports, adult cardiomyocytes are terminally differentiated cells which do not re-enter the cell-cycle under any known physiological or pathological circumstances. However, it has recently been shown that the adult heart has a robust myocardial regenerative potential, which challenges the accepted notions of cardiac cellular biology. The source of this regenerative potential is constituted by resident cardiac stem cells (CSCs). These CSCs, through both cell transplantation and in situ activation, have the capacity to regenerate significant segmental and diffuse myocyte losts, restoring anatomical integrity and ventricular function. Thus, CSC identification has started a brand new discipline of cardiac biology that could profoundly changed the outlook of cardiac physiology and the potential for treatment of cardiac failure. Nonetheless, the dawn of this new era should not be set back by premature attempts at clinical application before having accumulated the required scientifically reproducible data.     

Cell size of mammalian myocardia is not related to physiological demand

Morphological characteristics of myocardial ventricular myocytes have been evaluated from 5 mammalian orders with resting heart rates ranging from 51 to 475 bpm. The purpose was to determine if morphological characteristics of the myocardia are related to the functional demand imposed on the cell as represented by the resting heart rate. Cell size is a constant among mammals of different sizes which have different physiological demands. In contrast, there is more mitochondrial area and less myofibrillar area per cell in animals with rapidly beating hearts than in animals with slower heart rates. Additionally, the mean cross sectional area of individual myofibrils is 30% larger in the cow as compared to the mouse. These findings combined with our previous studies indicate that the different functional requirements of myocardia from different mammalian orders are satisfied by intracellular adaptations of both a structural and biochemical nature.     

Cell size of mammalian myocardia is not related to physiological demand

Morphological characteristics of myocardial ventricular myocytes have been evaluated from 5 mammalian orders with resting heart rates ranging from 51 to 475 bpm. The purpose was to determine if morphological characteristics of the myocardia are related to the functional demand imposed on the cell as represented by the resting heart rate. Cell size is a constant among mammals of different sizes which have different physiological demands. In contrast, there is more mitochondrial area and less myofibrillar area per cell in animals with rapidly beating hearts than in animals with slower heart rates. Additionally, the mean cross sectional area of individual myofibrils is 30% larger in the cow as compared to the mouse. These findings combined with our previous studies indicate that the different functional requirements of myocardia from different mammalian orders are satisfied by intracellular adaptations of both a structural and biochemical nature.     

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.     

Tetrodotoxin slightly shortens action potential duration in ventricular but not in atrial heart muscle

Summary Tetrodotoxin (TTX), at concentrations significantly decreasing maximal upstroke velocity (dV/dt_max) of the action potential, exerted variable effects on action potential duration (APD) in different myocardial preparations. APD was virtually unchanged by tetrodotoxin in the guinea pig atrium, but slightly shortened in the guinea pig ventricle at maximally effective concentrations. In the human ventricle, both dV/dt_max and APD were reduced in the same concentration range of TTX. These results suggest that a TTX-sensitive sodium current significantly contributes to the repolarization phase of the action potential in ventricular but not in atrial heart muscle.Supported by the Deutsche Forschungsgemeinschaft (Na 105/5-5) and by the Fonds der Chemischen Industrie. Author to whom reprint requests should be addressed. We thank Mrs. Johanna Rupp for expert technical help. We also thank one referee for suggesting the experiments depicted in figure 4.     

Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy

Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.     

Remodeling and dedifferentiation of adult cardiomyocytes during disease and regeneration

Cardiomyocytes continuously generate the contractile force to circulate blood through the body. Imbalances in contractile performance or energy supply cause adaptive responses of the heart resulting in adverse rearrangement of regular structures, which in turn might lead to heart failure. At the cellular level, cardiomyocyte remodeling includes (1) restructuring of the contractile apparatus; (2) rearrangement of the cytoskeleton; and (3) changes in energy metabolism. Dedifferentiation represents a key feature of cardiomyocyte remodeling. It is characterized by reciprocal changes in the expression pattern of “mature” and “immature” cardiomyocyte-specific genes. Dedifferentiation may enable cardiomyocytes to cope with hypoxic stress by disassembly of the energy demanding contractile machinery and by reduction of the cellular energy demand. Dedifferentiation during myocardial repair might provide cardiomyocytes with additional plasticity, enabling survival under hypoxic conditions and increasing the propensity to enter the cell cycle. Although dedifferentiation of cardiomyocytes has been described during tissue regeneration in zebrafish and newts, little is known about corresponding mechanisms and regulatory circuits in mammals. The recent finding that the cytokine oncostatin M (OSM) is pivotal for cardiomyocyte dedifferentiation and exerts strong protective effects during myocardial infarction highlights the role of cytokines as potent stimulators of cardiac remodeling. Here, we summarize the current knowledge about transient dedifferentiation of cardiomyocytes in the context of myocardial remodeling, and propose a model for the role of OSM in this process.     

Coronary perfusion pressure as a determinant of ventricular performance

Summary The results observed in this work support the view that coronary perfusion pressure affects ventricular performance independently of metabolic effects; a mechanism operating in beat-to-beat regulation is proposed.This work was carried out during the tenure of grants in aid from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP médicas 78/1392) and from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 2222, 1608/78).     

某古塔结构振动台试验研究

以模型试验的相似关系为基础,设计并制作一模型相似比为1/10的古塔模型结构,并对该模型进行了地震模拟振动台试验,测试其受震前后的动力特性变化,了解其刚度变化情况.同时测试了该模型结构在3种选定地震波作用下的加速度反应、位移反应;确定了相应的动力放大系数、最大加速度包络图、最大位移包络图;考察了相应的裂缝出现与发展情况以及薄弱部位的变形情况;最后根据试验结果,评判模型结构的地震反应机理和规律,评价结构的总体抗震性能,为古塔原型结构抗震保护提供了设计和构造建议.