Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that swim conditioning corrects the depressed mechanical function and myosin adenosinetriphosphatase (ATPase) activities associated with renovascular hypertension (HTN) in the rat. The present study was designed to assess the effects of swim conditioning on another form of systolic overload, subdiaphragmatic suprarenal aortic stenosis. Cardiac mechanics in an isolated working heart apparatus and myosin enzymology were studied in four groups of rats: controls (C), animals with chronic systolic overload secondary to aortic constriction (St), swim-conditioning animals (Sw), and animals exposed to a combined load (St-Sw). Heart weight was increased by 23% in St, 27% in Sw, and 36% in St-Sw. In contrast to HTN, cardiac pump and muscle function were not depressed in St. Sw was associated with improved cardiac output, stroke work, and velocity of circumferential fiber shortening. St-Sw showed improved mechanical cardiac performance relative to both C and St. The percent of ventricular myosin of the V1 type and Ca2+-activated myosin ATPase activity relative to C was unchanged in Sw but was depressed in St and St-Sw. These data demonstrate that the salutory mechanical effects of Sw can be superimposed on the systolic overload of St. However, the dissociation between mechanics and myosin enzymology suggests that factors in excitation-contraction coupling other than myosin isoenzyme shifts are responsible for this finding.
 ...
PMID:Effects of systolic overload and swim training on cardiac mechanics and biochemistry in rats. 296 13

A number of recent observations by probe and X-ray methods on the behaviour of crossbridges during contraction is considered in relation to the energetics of the process. It is shown that a self-consistent picture of the crossbridge cycle, compatible with these observations and involving strongly and weakly attached crossbridges, can be obtained providing that the tension-generating part of the crossbridge stroke is only about 40 A i.e. about one-third of the usually accepted value. The myosin head subunits in the tension-generating bridges could have a configuration close to that of rigor. A mechanism is suggested whereby rapid tension recovery after quick releases up to 120 A could still be produced by such a system.
 ...
PMID:Crossbridge behaviour during muscle contraction. 299 56

A model is presented to describe the inhibition of muscle fiber contraction by ligands that compete with MgATP. Two ligands, adenosine 5' (beta, gamma-imido) triphosphate (AMPPNP) and pyrophosphate (PPi), decrease the force developed in isometric contractions and act as weak competitive inhibitors of the maximum velocity of contraction (Pate & Cooke, 1985). These observations provide information on the energetics of actomyosin ligand states at the end of the power-stroke where MgATP dissociates the myosin cross-bridge from actin, and they are analysed in terms of a seven state model of cross-bridge kinetics. The model can reconcile the observations that these ligands bind tightly to fibers, Kd = 10(-4) M, while they are only weak inhibitors of fiber velocity, Ki = 2 X 10(-3) M. It provides a reasonable fit to the data and leads to several conclusions concerning the properties of the cross-bridge states. The states with bound ligand are shifted axially so that they occur earlier in the power-stroke than the nucleotide-free rigor state. This shift also explains the axial lengthening seen upon addition of ligands to rigor fibers. We can conclude that these ligands cause small perturbations in the cross-bridge configuration rather than large shifts. A second conclusion is that cross-bridges do not detach from actin during their power-strokes. Instead they traverse the entire length of the power stroke and are detached only at the end, leading to the suggestion that the cycling of bridges in isometric fibers is due to fluctuations in the relative positions of thick and thin filaments. With some further assumptions, the model also explains many of the rate constants and equilibrium constants of the actin-myosin-ligand interaction that have been measured in solution.
 ...
PMID:A model for the interaction of muscle cross-bridges with ligands which compete with ATP. 301 6

The structural and functional characteristics of the myocardium and coronary vessels are major determinants of cardiac function. Both can be influenced by long-term hemodynamic changes, such as sustained alterations of pressure and/or volume load on the heart. The diastolic pressure-volume relationship of the left ventricle (LV) was evaluated in arrested isolated hearts from spontaneously hypertensive rats (SHR), Wistar Kyoto normotensive rats (WKY), pregnant and hyperthyroid SHR and WKY. Such measurements of the LV dimensions were also performed after antihypertensive therapy by hydralazine, felodipine, metoprolol and alpha-methyldopa. Cardiac function was studied in a perfusion system in which external work could be measured at various pre- and afterloads. Coronary flow and O2-extraction could also be determined. LV function was examined in young and aged SHR and WKY, in metoprolol-felodipine treated SHR and in two-kidney, one clip hypertension before and after its reversal by renal artery unclipping. The SHR LV in early established primary hypertension mainly showed eccentric hypertrophy, with increased LV enddiastolic volume for a given filling pressure and a marginal reduction of wall to lumen ratio (w/ri). Hence, a higher stroke volume could be delivered for a given myocardial fibre shortening. Nevertheless, when challenged by high afterloads, LV function in SHR was considerably augmented compared with WKY. The antihypertensive drugs used reduce arterial pressure in different ways, which may differently affect cardiac design. Generally, the results suggest that wall thickness was structurally adapted to keep w/ri balanced to the prevailing blood pressure, while internal radius was adapted to long-term changes in diastolic filling. Thus sympatholytic drugs which lowered arterial pressure by reducing cardiac output, induced a reduction of wall thickness at a minor change of internal radius, while drugs which reduced pressure by systemic vasodilation increased internal radius, thus reducing w/ri. Further, the results stress the importance also to consider the type of load which causes LV hypertrophy, and how rapidly it is imposed. Thus, renal hypertension was associated with reduced LV performance, despite considerable hypertrophy. However, on reversal of renal hypertension by unclipping, cardiac function was soon enhanced to match the degree of LV hypertrophy as in SHR. This suggests that the renal hypertensive state per se adds some cardio-depressive influence, possibly by inducing reversible changes of cardiac myosin isoenzymes, which tends to offset the improved ventricular performance inherent in LV hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Structural and functional adaptation in the rat myocardium and coronary vascular bed caused by changes in pressure and volume load. 316 Dec 69

In our approach to dynamic cardiomyoplasty, which consists of wrapping a skeletal muscle around the heart and stimulating the former in synchrony with heart contractions to augment ventricular contractility, we have transferred a latissimus dorsi muscle flap to the heart by way of a partial resection of the second rib and subsequently suturing the muscle flap around the ventricles. The muscle flap is stimulated by a Cardio-Myostimulator burst-pulse generator (Medtronic SP 1005) connected to intramuscular electrodes. In preclinical animal research, the latissimus dorsi muscle flap was shown to maintain adequate contractile force and to increase its fatigue resistance by gradual conversion of glycolytic-fatigue-sensitive-to-oxidative-fatigue-resistant muscular fibers (100%). Histochemical and biochemical studies of chronically stimulated muscles showed a total transformation of muscle fast myosin to slow myosin with characteristics similar to those of myocardium. Electron microscopy showed preserved myofibrillar cytoarchitecture and increased mitochondrial density in the cell. At 9 months, cardiac output and ultrasonic Doppler studies showed a significant increase in ventricular function (cardiac output, +21%; peak blood velocity, +40% -80%; and stroke volume, +98% -102%) during muscle stimulation. In the clinical situation, long-term (range of follow-up interval, 4-42 months) beneficial cardiac effects of cardiomyoplasty have been documented in eight patients with various pathologies (ventricular tumor, left ventricular aneurysm, ischemic disease, and dilated cardiomyopathy). Our current understanding of this process is that dynamic cardiomyoplasty acts in two ways: 1) it promotes more vigorous systolic contraction, and 2) it appears to limit heart dilatation.
 ...
PMID:Effect of latissimus dorsi dynamic cardiomyoplasty on ventricular function. 318 Apr

We investigated the influence of testosterone on systolic blood pressure, heart weight, body weight, and ventricular myosin isoenzyme pattern of male spontaneously hypertensive stroke-prone rats (SHRSP). In two different study series (study 1, postpubertal; study 2, prepubertal), SHRSP were gonadectomized (HG), gonadectomized and replaced with dihydrotestosterone (HG-T), and sham-operated (H). Blood pressure was significantly higher in HG-T animals in both study series. Only prepubertal gonadectomy (study 2, HG group) led to a significantly decreased blood pressure. Heart weight and body weight were significantly diminished in the HG group when compared to the H group in study 2. Dihydrotestosterone (HG-T group) reversed this effect. In both study series gonadectomy shifted the myosin isoenzyme pattern to the V3 form while testosterone replacement led to a myosin isoenzyme pattern in favor of the V1 form. We conclude that the ventricular myosin isoenzyme pattern is under the dominant control of androgens and dissociates the expression of myosin isoenzyme from both blood pressure and cardiac hypertrophy in spontaneously hypertensive rats.
 ...
PMID:Gonadectomy and hormonal replacement changes systolic blood pressure and ventricular myosin isoenzyme pattern of spontaneously hypertensive rats. 319 74

We have performed thin-section electron microscopy on muscle fibers fixed in different mechanically monitored states, in order to identify structural changes in myosin crossbridges associated with force production and maintenance. Tension and stiffness of fibers from glycerinated Lethocerus flight muscle were monitored during a sequence of conditions using AMPPNP and then AMPPNP plus increasing concentrations of ethylene glycol, which brought fibers through a graded sequence from rigor relaxation. Two intermediate crossbridge forms distinct from the rigor or relaxed forms were observed. The first was produced by AMPPNP at 20 degrees C, which reduced isometric tension 60 to 70% below rigor level without reducing rigor stiffness. Electron microscopy of these fibers showed that, in spite of the drop in tension, no obvious change from the 45 degrees crossbridge angle characteristic of rigor occurred. However, the thick filament ends of the crossbridges were altered from their rigor positions, so that they now marked a 14.5 nm repeat, and formed four separate origins at each crossbridge level. The bridges were also less slewed and bent than rigor bridges, as seen in transverse sections. The second crossbridge form was seen in glycol-AMPPNP at 4 degrees C, just below the glycol concentration that produced mechanical relaxation. These fibers retained 90% of rigor stiffness at 40 Hz oscillation, but would not bear sustained tension. Stiffness was also high in the presence of calcium at room temperature under similar conditions. Electron microscopy showed crossbridges projecting from the thick filaments at an angle that centered around 90 degrees, rather than the 45 degree angle familiar from rigor. This coupling of relaxed appearance with persistent stiffness suggests that the 90 degree form may represent a weakly attached crossbridge state like that proposed to precede force development in current models of the crossbridge power stroke.
 ...
PMID:Two attached non-rigor crossbridge forms in insect flight muscle. 322 90

Evidence has been accumulating that muscle contraction may not be associated with the power stroke of the cross-bridges tightly coupled with ATP hydrolysis cycle. We have constructed a new contraction model which includes a number of basic properties of contraction processes not taken into consideration in the models hitherto reported. The basic assumption is that, when one head of a myosin molecule attaches to an actin monomer on thin filament, conformational changes take place in the neighbouring actin monomers to result in their non-symmetrical charge distribution to exert electrostatic force on the unattached head of the same myosin molecule in one direction. Thus, the unattached head moves along thin filament to attach to another actin monomer, while the already attached head detaches from thin filament. These steps are repeated to cause muscle contraction. The above contraction model can explain the results of our X-ray diffraction experiments as well as the results reported by other authors.
 ...
PMID:A self-induced translation model of myosin head motion along thin filament in muscle contraction. 340 24

Present evidence on crossbridge behaviour is reviewed from the viewpoint of the Eisenberg-Hill concepts. We conclude that a cartoon illustrating the operation of these ideas in practice should be drawn so as to include morphological changes in the body of the myosin molecule as part of the power-stroke. The bulk of structural evidence on the operation of crossbridges in intact muscle supports such a description.
 ...
PMID:Towards a molecular mechanism for the crossbridge cycle. 340 28

In our previous model, it was assumed that the two heads of myosin act co-operatively in producing force for the sliding of actin filaments relative to myosin filaments. We eliminate the assumption of co-operativity in the present model, following the conclusion by Harada and co-workers that a co-operative interaction between the two heads of myosin is not essential in producing actin filament movement. We assume that (1) a myosin head activated by ATP hydrolysis binds to the thin filament at a definite angle and does not do the power stroke, i.e. does not change its orientation during attachment, (2) a potential of force acting on the myosin head is induced around the thin filament when an ATP-activated myosin head binds to an actin molecule in the thin filament, and (3) the potential remains for a while after detachment of the myosin head and statistically controls the direction of thermal motion of the myosin head, so that the myosin head translates toward the Z-line as a statistical average. We did calculations on these assumptions with a mean tension approximation and got the following results. (a) The calculated force-velocity relation in muscle contraction is in fairly good agreement with experimental observation, including the give phenomenon that lengthening velocity becomes very large for a force about twice the isometric tension. (b) The calculated rate of energy liberation during muscle contraction as a function of load on muscle is in good agreement with experimental results. (c) The calculated distance over which a myosin molecule moves along the thin filament during one ATP hydrolysis can be more than 60 nm under unloaded conditions.
 ...
PMID:A self-induced translation model of myosin head motion in contracting muscle. I. Force-velocity relation and energy liberation. 341 Sep 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>