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)

Reperfusion injury remains the most uncontrolled phenomenon during cardiac surgery. Potential myocardial protection by trimetazidine was tested in a double blind placebo controlled study on 19 patients undergoing aorto-coronary bypass surgery. The trimetazidine group was composed of 10 patients and the placebo group of 9 patients. Pretreatment was started three weeks before surgery with 1 tablet (trimetazidine 20 mg) t.i.d. and the same drug was added to the cardioplegic solutions (trimetazidine: 10(-6) M). The cross clamping time was 41.1 +/- 3.8 minutes in the trimetazidine group and 39.8 +/- 2.3 minutes in the placebo group. Metabolic measurements showed that the increase of malondialdehyde measured in the coronary sinus 20 minutes after reperfusion was significantly (p = 0.014) less in the trimetazidine group (from 1.60 +/- 0.11 to 1.79 +/- 0.2 mumol/L-1) than in the placebo group (from 1.17 +/- 0.11 to 2.84 +/- 0.58 mumol/L-1). Myosin was present 4 hours after surgery in all patients in the placebo group and in 5 of the 10 of the trimetazidine group (p = 0.036). Haemodynamic measurements showed that patients pretreated with trimetazidine had a better ventricular function, as assessed by the stroke work index (SWI) significantly (p = 0.01) higher in the trimetazidine group (0.0391 +/- 0.0029 g/min/m2/beta) than in the placebo group (0.0282 +/- 0.0026 g/min/m2/beat), the evolution of SWI during surgery was not significantly different between the two groups. Thus trimetazidine seems to reduce ischaemia-reperfusion damage during cardiac surgery; moreover pretreatment with trimetazidine allows the patient to face the operation with better ventricular function.
 ...
PMID:Cardioprotective effect of trimetazidine during coronary artery graft surgery. 152 57

The purpose of this study was to determine the extent to which functional demand regulates the biochemical character and enzyme capacities of the rat myocardium. Hearts from donor rats were heterotopically transplanted onto the abdominal aorta and inferior vena cava of isogenic recipients. The procedure results in a perfused but nonpumping heart that has a reduced heart rate (HR) and performs essentially no stroke work (SW). After 30 days, metabolic enzyme activities (phosphorylase, 6-phosphofructokinase, citrate synthase, and 3-hydroxyacyl-CoA dehydrogenase) were significantly lower (40-60%) in the nonworking heart. Specific sarcoplasmic reticulum Ca2(+)-adenosinetriphosphatase (ATPase) activity was unchanged, but activity per gram of heart was 41% lower. Myosin isozymes were 58% V1, 21% V2, and 21% V3 in the nonworking heart compared with 100% V1 in the working heart. Myosin and myofibrillar ATPase activities each decreased by 28%. These findings suggest that both HR and SW play major and specific roles in regulating myocardial biochemical capacities and determining the myosin phenotype.
 ...
PMID:Role of cardiac work in regulating myocardial biochemical characteristics. 214 21

The purpose of this study was to determine whether a chronic swimming program could reverse the decreased cardiac function and altered myosin biochemistry found in hearts of rats with established renal hypertension. Ten wk after the onset of hypertension [midpoint (m)], hearts from normotensive controls (C) and hypertensives (H) were studied in an isolated working heart apparatus, and myosin biochemistry was analyzed. Half of the control and hypertensive animals were then subjected to a 10-wk swimming program (Sw) and their hearts were compared with those from age-matched sedentary rats. Body weight was no different at the midpoint of the study between Cm and Hm or at the end point (e) of the study among Ce, Swe, He, or H-Swe. Swimming had no effect on blood pressure in either normotensive or hypertensive rats. Dry heart weight was increased by 46% in Hm compared with Cm and by 36% in He, 21% in Swe, and 61% in H-Swe when compared with Ce. Hypertension was associated in both the mid- and end-point studies, with decreases in coronary flow, stroke work (both per gram left ventricle), ejection fraction, and midwall fractional shortening. In addition, actin-activated myosin adenosinetriphosphatase (ATPase) activity was decreased in Hm and He associated with an increase in the content of the V3 myosin isoenzyme. Although the coronary deficit was not corrected in H-Swe, stroke work, ejection fraction, and fractional midwall shortening were normalized compared with control hearts. Myosin ATPase activity and the myosin isoenzyme distribution were similarly restored in H-Swe.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Chronic swimming reverses cardiac dysfunction and myosin abnormalities in hypertensive rats. 293 53

To determine whether a prior chronic swimming program would alter the heart's response to chronic hypertension, female rats were made to swim for 10 wk, and then the left renal artery was stenosed. Heart perfusions were performed 10 wk later. The five groups studied were: control (C), normotensive swimmers (Sw), sedentary hypertensives (H), swimming rats made hypertensive and then allowed to be sedentary (Sw-H-Sd); and swimming animals made hypertensive and continued in a swimming program (Sw-H-Sw). Total heart and left ventricular weights were increased in increasing degrees in the sequence Sw, H, Sw-H-Sd, and Sw-H-Sw. Right ventricular weight was only increased in Sw and Sw-H-Sw. Swimming before the onset of hypertension enhanced total cardiac output and stroke work. Ejection fractions and mean velocity of circumferential fiber shortening (Vcf) were increased in Sw-H-Sd or Sw-H-Sw vs. controls. Myocardial O2 extraction was increased and coronary flow and myocardial O2 consumption were diminished in all hypertensive groups. However, lactate production was similar in all groups. Myosin adenosinetriphosphatase activity was increased in Sw but decreased in the three H groups. The percent of V1 myosin isozyme was greater and the percent of V3 less in Sw than in C; V1 was diminished and V3 increased in H and Sw-H-Sd; isozymes were normal in Sw-H-Sw.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of hypertension on hearts of rats trained by swimming. 295 61

The goal was to describe the metabolic profile of ganglionic and cortical arteries and arterioles in aging normotensive male rats. Five enzymes indicative of key metabolic pathways in the vessel walls were semiquantitatively evaluated using bright-field histochemical microscopy. Lactate dehydrogenase showed significant reactivity which increased with vessel diameter in cortical and ganglionic vessels in all age groups tested. Succinate dehydrogenase and cytochrome oxidase showed little reactivity in both cortical and ganglionic vessels, suggesting a reduced role for aerobic metabolic pathways. Myosin ATPase reactivity was high in cortical and ganglionic vessels. Only this enzyme showed an increased reactivity that was correlated with the age and diameter of the vessel. Glucose-6-phosphate dehydrogenase reactivity was more pronounced in cortical than ganglionic vessels, suggesting that the hexose-monophosphate-shunt may be more active in the cortical vessels. There were no regional differences in enzyme reactivity throughout the caudatoputamen. In conclusion, both the cortical and ganglionic vessels are metabolically active, with significant anaerobic glycolysis, and reduced, but observable capacity for aerobic metabolism. The decreased myosin ATPase reactivity and the low level of glucose-6-phosphate dehydrogenase reactivity in the ganglionic arterioles of senescent rats may contribute to the susceptibility of these vessels to cerebrovascular accidents.
Stroke
PMID:A histochemical study of cerebral cortical vessels and ganglionic vessels of the caudatoputamen in aging normotensive rats. 315 35

To explore the interactions of physiologic and pathologic hypertrophy, four groups of hearts were studied in an isolated working rat heart apparatus. Cardiac contractile proteins were also evaluated. The groups were hearts of female control sedentary rats; rats subjected to a 10-week swimming programme; rats with renal hypertension; and hypertensive rats subjected to a 10-week swimming programme. The swimming programme in normotensive female rats caused a 30% cardiac hypertrophy, in hypertensive animals 46% hypertrophy, and in combined hypertension and swimming 70% hypertrophy. Ca2+-myosin ATPase activity and actin-activated myosin ATPase were elevated in hearts of swimmers, depressed in hearts of hypertensive sedentary animals and similar to control values in hearts of hypertensive swimmers. Myosin V1 isoenzyme content was increased in hearts of swimmers, depressed in hearts of hypertensives, but normal in hearts of hypertensive swimmers. Reciprocal relationships were seen with the V3 isoenzyme. Stroke work, mean velocity of circumferential fibre shortening, and per cent fractional shortening at the midwall showed increased values for hearts of swimmers, depressed values for hearts of hypertensives, and normal values or values above the control for hearts of hypertensive swimmers. Myocardial flow measured with microspheres was increased in the left ventricle of swimmers, depressed in hearts of hypertensives and still depressed in hypertensive swimmers, but significantly higher than in the hypertensives alone. The correlation of actin-activated ATPase activity and of fractional shortening was linear among the four groups. These studies demonstrate that physiologic and pathologic hypertrophy in the rat have distinctly opposite effects on contractile proteins and contractile performance. When one type of hypertrophy is superimposed on the other the effects are additive.
 ...
PMID:Correlation of myosin isoenzyme alterations with myocardial function in physiologic and pathologic hypertrophy. 624 4

We performed a chronologic investigation of left (LV) and right (RV) ventricular myosin ATPase activity and hemodynamics in newborn lambs. We found an elevation in myosin ATPase activity for the LV, which was achieved by 6 to 8 weeks of age and which correlated directly with increasing ventricular stroke work. Myosin ATPase activity did not increase with age for the RV, a finding which was associated with a postnatal decrease in ventricular stroke work. These findings may represent an important postnatal adaptation of newborn myocardium to the demands of extrauterine life.
 ...
PMID:Maturational changes in cardiac muscle myosin adenosine triphosphatase activity relative to hemodynamic alterations in newborn lambs. 646 50

Myosin couples ATP hydrolysis to the translocation of actin filaments to power many forms of cellular motility. A striking feature of the structure of the muscle myosin head domain is a 9-nm long "lever arm" that has been postulated to produce a 5-10-nm power stroke. This motion must be coupled to conformational changes around the actin and nucleotide binding sites. The linkage of these sites to the lever arm has been analyzed by site-directed mutagenesis of a conserved glycine residue (G699) found in a bend joining two helices containing the highly reactive and mobile cysteine residues, SH1 and SH2. Alanine mutagenesis of this glycine (G699A) dramatically alters the motor activity of skeletal muscle myosin, inhibiting the velocity of actin filament movement by > 100-fold. Analysis of the defect in the G699A mutant myosin is consistent with a marked slowing of the transition within the motor domain from a strong binding to a weak binding interaction with actin. This result is interpreted in terms of the role of this residue (G699) as a pivot point for motion of the lever arm. The recombinant myosin used in these experiments has been produced in a unique expression system. A shuttle vector containing a regulated muscle-specific promoter has been developed for the stable expression of recombinant myosin in C2C12 cells. The vector uses the promoter/enhancer region, the first two and the last five exons of an embryonic rat myosin gene, to regulate the expression of an embryonic chicken muscle myosin cDNA. Stable cell lines transfected with this vector express the unique genetically engineered myosin after differentiation into myotubes. The myosin assembles into myofibrils, copurifies with the endogenous myosin, and contains a complement of muscle-specific myosin light chains. The functional activity of the recombinant myosin is readily analyzed with an in vitro motility assay using a species-specific anti-S2 mAb to selectively assay the recombinant protein. This expression system has facilitated manipulation and analysis of the skeletal muscle myosin motor domain and is also amenable to a wide range of structure-function experiments addressing questions unique to the muscle-specific cytoarchitecture and myosin isoforms.
 ...
PMID:Glycine 699 is pivotal for the motor activity of skeletal muscle myosin. 876 15

The myocardium's response to increased stress or load is not stereotyped. Differences have been observed in the heart's molecular composition and performance characteristics when exposed to stress. Myosin isoforms gradually change during development of hypertrophy, whereas collagen levels change only during the chronic phase of hypertrophy. Cardiac hypertrophy can regress if treated with antihypertensive drugs, but the myocardium of the post-hypertrophic heart no longer has the same composition as it did before hypertrophy. In rat studies of the effects of antihypertensive drugs on cardiac functional reserve, captopril showed a regression of hypertrophy associated with a lower baseline stroke volume and, after dobutamine stress, a dose-dependent rise in stroke volume. In untreated rates captopril showed no change in stroke volume. In hydralazine-treated rats, there was no change in reserve after dobutamine stress, whereas propranolol treatment resulted in partial regression and a slight change in stroke volume. Overall, our data suggests that development of hypertension and hypertrophy plays a role in changes in the molecular structure of the myocardium, especially during the chronic phase of hypertrophy and heart failure. This complex process cannot be explained by one factor but involves a combination of factors. Identification of each factor would be of importance for the development of appropriate therapeutic agents.
 ...
PMID:Myocardial response to stress in cardiac hypertrophy and heart failure: effect of antihypertensive drugs. 1041 26

We have used polyethylene glycol (PEG) to perturb the actomyosin interaction in active skinned muscle fibers. PEG is known to potentiate protein-protein interactions, including the binding of myosin to actin. The addition of 5% w/v PEG (MW 300 or 4000) to active fibers increased fiber tension and decreased shortening velocity and ATPase activity, all by 25-40%. Variation in [ADP] or [ATP] showed that the addition of PEG had little effect on the dissociation of the cross-bridge at the end of the power stroke. Myosin complexed with ADP and the phosphate analog V(i) or AlF(4) binds weakly to actin and is an analog of a pre-power-stroke state. PEG substantially enhances binding of these states both in active fibers and in solution. Titration of force with increasing [P(i)] showed that PEG increased the free energy available to drive the power stroke by about the same amount as it increased the free energy available from the formation of the actomyosin bond. Thus PEG potentiates the binding of myosin to actin in active fibers, and it provides a method for enhancing populations of some states for structural or mechanical studies, particularly those of the normally weakly bound transient states that precede the power stroke.
 ...
PMID:The effect of polyethylene glycol on the mechanics and ATPase activity of active muscle fibers. 1065 5


1 2 3 4 5 6 Next >>