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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe hypophosphatemia is associated in man with low intracellular stores of ATP and a set of specific cellular dysfunctions. To investigate whether hypophosphatemia affects myocardial performance, we measured cardiac output by thermodilution and calculated stroke work in seven patients with severe hypophosphatemia before, during and after repletion with an intravenous potassium phosphate solution. Mean left ventricular stroke work for these patients increased from 49.57 to 71.71 g-m per beat (P less than 0.01) at the same or higher afterload whereas pulmonary-artery wedge pressure fell from a mean value of 10.1 to 6.7 torr (P less than 0.02). Return of serum phosphate to normal, therefore, improved myocardial stroke work independently of the Starling effect. The mechanism of this improvement in contractile force is unknown but may be related to intracellular availability of ATP.
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PMID:Effect of hypophosphatemia on myocardial performance in man. 90 68

In 6 open chest dogs, regional myocardial function und metabolic changes (ATP, creatine phosphate, lactate) were studied during coronary flow reduction in LAD by ultrasonic dimension gauges and transmural biopsies. After reduction of the perfusion pressure from 108 to 50 mm Hg the ischemic segment showed a marked dyskinesis: the enddiastolic segment length increased by 7%, and segment shortening and segment stroke work decreased by 22% and 63% respectively. Left ventricular (LV) enddiastolic pressure rose from 5 to 8 mm Hg (p less than 0.05). Heart rate, LV systolic pressure, LV max dP/dt and Vpm did not change significantly.
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PMID:[Myocardial function and metabolism during local coronary flow reduction]. 91 15

To investigate correlations between energy supply and mechanical work in the frog's myocardium in true anoxia, the stroke volume, systolic and diastolic volumes and the parameters of velocity of contraction and relaxation of frog hearts were compared to the levels of high energy phosphates and the delivery of lactate. During perfusion with N2 saturated Ringer solution, stroke volume, systolic contractility and diastolic relaxation decrease till a contracture. High preload produces a dilatation growing up to the contracture after retarded and weakened relaxation. The ATP-content decreases during the first quarter of the experiment to 60%. CP decreases continuously to 15%, ADP and AMP remain constant. There is a production of lactate increasing considerably with the onset of contracture. The measured glycolysis is not sufficient for production of mechanical work. The effect of anoxia on the action potential and the reduction of the sequestration of Ca++ and of the break of actomyosin bridges following the decrease of ATP are considered as causing the series of the mechanical events.
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PMID:[Effect of anoxia on energy supply and isotonic work performance in the myocardium of the frog]. 102 37

Since the proposal and rapid acceptance of the sliding-filament theory in 1953-1954, numerous suggestions have been made for the cause of the sliding movement. When the amount of overlap is varied by altering the initial length, the maximum tension is directly proportional to, but the speed of shortening under zero load is independent of, the amount of overlap. This suggests strongly that a relative force between thick and thin filaments is produced by independent force-generators distributed within each overlap zone. These force-generators are identified with projections (cross-bridges) on the thick filament, each consisting of part of a myosin molecule. Measurements of the 'tension transients' when the length of a stimulated muscle fibre is suddenly altered show that the range of action of each cross-bridge is 10-15 nm. The travel within a single contraction may be many times greater, so each cross-bridge must act cyclically by attaching, exerting a force and detaching. Details of the tension transients suggest that each cross-bridge makes its movement in two or three steps, each with a potential energy change a few times kT. Each cross-bridge contains also an elastic element in series. It is sufficient, on present evidence, to postulate that the only action of ATP is to dissociate the cross-bridge from the thin filament after it has completed its stroke.
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PMID:The origin of force in skeletal muscle. 109 17

The permissible duration of brain ischemia without sustaining damage is short. Less clear are the mechanisms accounting for the vulnerability of brain to ischemic insults. Neurochemical factors implicated include impairment of energy synthesis by mitochondria and of energy-dependent processes such as synaptic transmission, ATPase activity, membrane conductance and altered protein and lipid synthesis. To clarify the vulnerability of energy metabolism, we investigated energy availability and synthesis in our model of global cerebral ischemia. Our studies evaluated in vitro mitochondrial ATP synthesis and the in vivo quantitation of the cortical adenylate pool. Results of our investigations support a growing body of evidence showing the energy state to be relatively stable to ischemia. We conclude that an energy-dependent process of brain is primarily vulnerable to ischemia.
Stroke
PMID:Energy metabolism during brain ischemia. Stability during reversible and irreversible damage. 119 33

Previous studies utilizing crude brain homogenates have shown that forebrain ischemia results in inhibition of calcium/calmodulin-dependent protein kinase II (CaM kinase II) activity without large-scale proteolysis of the enzyme. In this report, a monoclonal antibody (1C3-3D6) directed against the beta- (60-kDa) subunit of CaM kinase II that does not recognize ischemically altered enzyme was utilized to further investigate the ischemia-induced inhibition of CaM kinase II. Immunohistochemical investigations showed that the ischemia-induced decreased immunoreactivity of CaM kinase II occurred immediately following ischemic insult in ischemia-sensitive cells such as pyramidal cells of the hippocampus. No decrease in CaM kinase II immunoreactivity was observed in ischemia-resistant cells such as granule cells of the dentate gyrus. The decreased immunoreactivity was observed for CaM kinase II balanced for protein staining and calmodulin binding in vitro. In addition, autophosphorylation of CaM kinase II in the presence of low (7 microM) or high (500 microM) ATP did not alter immunoreactivity of the enzyme with 1C3-3D6. The data demonstrate the production of a monoclonal antibody that recognizes the beta-subunit of CaM kinase II in a highly specific manner, but does not recognize ischemic enzyme. Together with previous studies, the data support the hypothesis that rapid, ischemia-induced inhibition of CaM kinase II activity may be involved in the cascade of events that lead to selective neuronal cell loss in stroke.
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PMID:Global forebrain ischemia results in decreased immunoreactivity of calcium/calmodulin-dependent protein kinase II. 132 53

Evidence has been put forth that a number of human and experimental cardiomyopathies are associated with a lower myocardial carnitine content. This study was performed to test the hypothesis that the correction of carnitine derivative, propionyl-L-carnitine (PLC), may improve cardiac function. Repeated administration of PLC was compared to saline with respect to cardiac function in rats with pressure-overload cardiac hypertrophy and low myocardial carnitine levels. Cardiac hypertrophy was induced by abdominal aorta constriction in rats. Separate groups of rats were used for (a) determination of myocardial carnitine content, (b) evaluation of in vivo hemodynamics, and (c) evaluation of performance and metabolic state of Langendorff perfused hearts. Results showed the following: (i) The myocardial carnitine content was inversely correlated to cardiac hypertrophy (r = 0.68, p less than 0.05) and PLC treatment (50 mg/kg i.a. for 4 days) restored it to normal values (ii) The PLC effect on cardiac function was significantly and directly related to cardiac hypertrophy [correlations between heart weight and percent changes in cardiovascular parameters: cardiac output (CO), p less than 0.001; cardiac work (CW), p less than 0.01, stroke volume (SV) and stroke work (SW), p less than 0.02]. In animals with heart weight greater than 1,400 mg, the effect of PLC on CO, CW, SV, SW, and total peripheral resistance (TPR) was significantly different from that of saline (CO, CW, SV, and SW, p less than 0.005 each; TPR, p less than 0.05). The effect was observed 24 h after the first PLC administration and significantly diminished following a 4 day suspension of the treatment. (iii) Perfused hearts from PLC-treated rats displayed a significantly lower left ventricular end-diastolic pressure (p less than 0.01) and greater relaxation rate (p less than 0.05) than those from control rats. Moreover, in PLC-treated hearts, the content of creatine phosphate, ATP, and total adenine nucleotides (ATP+ADP+AMP; TAN) was significantly increased (CP, p less than 0.05; ATP and TAN, p less than 0.01 vs. control). These data show that PLC exerts a stimulatory activity on hearts with hypertrophy and low carnitine content, implying that carnitine deficiency may contribute to the depression of cardiac function in this model.
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PMID:Hemodynamic and metabolic activities of propionyl-L-carnitine in rats with pressure-overload cardiac hypertrophy. 138 36

The ability of an oxygenated perfluorochemical (Fluosol) to limit myocardial reperfusion injury following global hypothermic ischemic insult was investigated. Neonatal piglet hearts were arrested with cold crystalloid cardioplegia and stored for 12 hours in 2 degrees C saline. Reperfusion was carried out using an isolated, blood-perfused, working heart preparation. Hearts were initially reperfused (10 minutes) with either whole blood (WB, n = 6), unmodified perfluorochemical (PFC, n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (PFC+, n = 6), prior to institution of whole blood perfusion, functional evaluation and left ventricular biopsy. A control group (C, n = 7) was evaluated without an intervening period of ischemia. At a left ventricular diastolic pressure of 9 mm Hg WB hearts developed a left-ventricular stroke work index (SWI) of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under similar conditions, PFC-reperfused hearts achieved a SWI of 14.6 +/- 1.3 x 10(3), significantly greater than that of WB (p less than 0.001). SWI for PFC+ hearts was 19.8 +/- 1.6 x 10(3), significantly increased over that of PFC (p less than 0.01), and not different from values obtained for C (19.2 +/- 0.8 x 10(3)). In addition, PFC-reperfused hearts demonstrated superior maintenance (p less than 0.05) of ATP (2.08 +/- 0.16 umole/g), compared to WB (1.50 +/- 0.19), while preservation of ATP in PFC+ hearts (2.99 +/- 0.12), was significantly increased over that of PFC (p less than 0.001), and not significantly different from that for C (2.68 +/- 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Perfluorochemical reperfusion limits myocardial reperfusion injury after prolonged hypothermic global ischemia. 139 43

Focal brain ischemia was produced in halothane-anesthetized Mongolian gerbils by occluding the right common and the left external carotid artery. Ninety minutes after vascular occlusion the following regional hemodynamic and metabolic parameters were evaluated in adjacent cryostat sections taken from seven different coronal planes of each brain: cerebral blood flow (CBF), glucose utilization (CMRG), and the tissue content of ATP and glucose. NADH fluorescence was recorded from the surface of the cryostat block. In addition, tissue slices were taken from each brain to determine the rate of phosphorylation of 2-deoxyglucose in ischemic and nonischemic regions. Depending on the density of ischemia, the following metabolic disturbances were observed. At CBF values below 35 ml x 100 g-1 x min-1 CMRG increased and at values below 25 ml x 100 g-1 x min-1 it declined sharply. Glucose content declined when CBF was below 35 ml x 100 g-1 x min-1 and ATP fell at CBF below 20 ml x 100 g-1 x min-1. At 10 ml x 100 g-1 x min-1 ATP was completely depleted. NADH fluorescence was found elevated at flow rates that caused an increase of glucose utilization and was maximal when CBF stopped. The ischemic thresholds for the initial increase in CMRG and the complete depletion of ATP content represent the metabolic equivalent of the penumbra zone and provide a basis for the evaluation of therapeutic procedures for the treatment of stroke.
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PMID:Threshold relationship between cerebral blood flow, glucose utilization, and energy metabolites during development of stroke in gerbils. 139 69

We correlated the effects of high volumes of K+ cardioplegic solution on myocardial structure and function in 16 dogs following open-heart surgery. Eight animals received high volume potassium cardioplegic solution (25 cc/kg body weight, every 30 min) during 90 min of ischemic arrest (HVK-C group). The others received sufficient cardioplegic solution to maintain complete electrical arrest as defined by voltage monitoring criteria (VM group). Cardiac index (CI), left ventricular stroke work index (LVSWI), and myocardial contractility (dp/dt) were determined before arrest and after 90 min of ischemia and 45 min of reperfusion. Biopsies were taken for EM ultrastructure and ATP estimation. Morphometric analysis of EM micrographs found increased volume of damaged mitochondria (DMR) (p less than 0.025), damaged myofibrils (DMF) (p less than 0.001), intermyofibrilar edema (p less than 0.005), T-tubule and sarcoplasmic reticulum (p less than 0.05) in the HVK-C group. Left ventricular (LV) function was more depressed in animals receiving HVK-C. CI decreased by 1.8 +/- 0.4 l/min/square meter (p less than 0.01), LVSWS fell by 3.3 +/- 0.8 gm-m/beat/Kg (p less than 0.01), dp/dt decreased by 684 +/- 135 (p less than 0.0025). ATP decreased by 26% in HVK-C and by 12% in VM group (0.1 less than p less than 0.05). Structural damage (scores of injured volume of mitochondria and myofibrils) correlated with post-ischemic depression of LV function (Cardiac output and myocardial contractility), r = -0.72 and -0.66 (p less than 0.001 and 0.004).
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PMID:Morphometric analysis on myocardial injury related to the use of high volume potassium cardioplegic solution during ischemic arrest. 140 9


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