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)

A man of 68, who died from a second heart stroke had neurogenic atrophy of the legs. The anterior tibial muscle showed abundant target and targetoid fibres. Half a year prior to death he had increasing weakness and wasting of the legs. The morphometric evaluation of the target and targetoid fibres showed a considerable independence of the plane size of the single zones from the total gauge of the fibres on cross section. Only a small part of the variation in size of zone 2 (4%) depended on the size of the target, indicating that zone 2 cannot just be a passive product of a shrinkage and disappearance of the target, but that there must be an active process, which leads to the change in zone 2. The regressive development of the centrally demarcated fibrillar bundle (target) is regarded as secondary degeneration following interruption of the nutritional supply.
 ...
PMID:Considerations on the morphogenesis of target and targetoid fibres based on morphometric investigations. 93 76

The pathogenesis of reflex sympathetic dystrophy is controversial, but the condition can result from a major or seemingly minor injury to a limb, or even an insult to an organ, such as stroke or myocardial infarction. Onset can be sudden or insidious. The syndrome is characterized primarily by localized, deep, burning pain in a limb--pain that may not follow any logical distribution. Nonpitting edema, skin hyperesthesia, and guarding of the limb usually accompany the pain. If treatment is not instituted, deformity, contracture, and wasting of the limb can eventually occur. With appropriate therapy, the process can be stopped and often reversed. The keys are a high index of suspicion, early diagnosis, and aggressive treatment.
 ...
PMID:Burning pain in an extremity. Breaking the destructive cycle of reflex sympathetic dystrophy. 186 41

Inotropic support for the dilated, failing ventricle results in complex hemodynamic changes affecting preload, afterload, contractility, and heart rate, each of which affects myocardial oxygen consumption. Appreciation of a hierarchy of hemodynamic determinants of myocardial oxygen consumption may be helpful to the clinician trying to balance oxygen demands and hemodynamic performance. We tested the hypothesis that epinephrine alters the hierarchy of hemodynamic determinants of myocardial oxygen consumption in a canine model of dilated cardiomyopathy created by rapid ventricular pacing. Dogs (n = 10) were instrumented to record left ventricular pressure and dimension, and a modified right heart bypass preparation was used to control left ventricular workload. Coronary sinus effluent was quantitatively collected and analyzed for oxygen content and used to calculate myocardial oxygen consumption. Epinephrine administration significantly increased myocardial oxygen consumption in the empty, beating heart; however, when the relationships of multiple determinants of left ventricular work and load were compared before and after epinephrine administration, no oxygen wasting effect was observed. Using multivariate linear regression analysis, a hierarchy of hemodynamic determinants of myocardial oxygen consumption was created. In the untreated heart, stroke work and cardiac output were the primary hemodynamic determinants of oxygen consumption; epinephrine significantly altered the determinants such that wall stress became the dominant hemodynamic determinant of myocardial oxygen consumption. Focused manipulation of wall stress in the treated, failing heart may limit the potentially deleterious effects of inotropic stimulation in this setting.
 ...
PMID:Inotropic stimulation and oxygen consumption in a canine model of dilated cardiomyopathy. 192 25

Hyponatremia is common following aneurysmal subarachnoid hemorrhage and has been linked to the syndrome of inappropriate secretion of antidiuretic hormone. However, the demonstration of volume depletion and natriuresis in some patients has suggested that salt wasting is a more likely etiology. Atrial natriuretic factor appears to play a role in both central and peripheral regulation of sodium homeostasis. To investigate the behavior of circulating atrial natriuretic factor following subarachnoid hemorrhage, we studied 25 patients with intracranial aneurysms: 21 after acute subarachnoid hemorrhage and four without evidence of recent rupture. Atrial natriuretic factor was measured by radioimmunoassay of extracted plasma (normal value, 20.8 +/- 24.6, mean +/- 3 SD). Mean +/- SEM plasma atrial natriuretic factor concentration was elevated to 84 +/- 25 pg/ml on Day 1, rose to 134 +/- 29 pg/ml on Day 3, and fell to 86 +/- 17 pg/ml by Day 7 after subarachnoid hemorrhage (p less than 0.01). In two patients (9.5%) who developed hyponatremia after aneurysm rupture, plasma concentrations were no different from that in the group as a whole; concentrations in patients with no evidence of recent subarachnoid hemorrhage were not elevated. Neither fluid administration nor timing of surgery could account for the elevated concentrations. We conclude that concentrations of circulating atrial natriuretic factor are elevated after subarachnoid hemorrhage but do not solely account for the accompanying hyponatremia.
Stroke 1988 Sep
PMID:Plasma atrial natriuretic factor and subarachnoid hemorrhage. 297 Jul 2

The diltiazem serum concentration and the magnitude and time course of systemic and coronary hemodynamic and ECG responses to intravenous diltiazem (250 micrograms/kg intravenous bolus plus 1.4 micrograms/kg/min infusion) were investigated in 14 patients with chronic stable angina pectoris. After 3, 8, and 15 minutes this dosing schedule produced serum concentrations of 570 +/- 259, 199 +/- 62, and 136 +/- 30 ng/ml, respectively (mean +/- SD). These drug levels were associated with a small, transient increase in heart rate (6 bpm, mean) at 3 minutes, which occurred during the nadir of the blood pressure response. But at 8 and 15 minutes, heart rate was unchanged compared to control rates, although blood pressure remained decreased (19%, p less than 0.01 at 15 minutes). Pressure-rate product was significantly reduced as left ventricular end-diastolic pressure and dP/dT remained unchanged. Systemic resistance decreased 17% (p less than 0.05) and stroke index increased 10% (p less than 0.01). Coronary flow was maintained as coronary resistance declined (14%, p less than 0.01). PR interval prolongation (14%, p less than 0.01) occurred at 15 minutes. Correlations between changes in systolic, diastolic, and mean pressures and drug concentration were significant (r = -0.59, -0.80, and -0.78, respectively, all p less than 0.05). The intercept for each regression line was approximately 96 ng/ml diltiazem concentration, suggesting that this represents the minimum effective diltiazem serum concentration. These results indicate that intravenous diltiazem is well tolerated and promptly reduces blood pressure and both systemic and coronary resistances without oxygen-wasting effects of an increase in heart rate.
 ...
PMID:Pharmacodynamic aspects of intravenous diltiazem administration. 394 59

Neither stroke volume nor external cardiac work (the integral of pressure times flow during ejection) has been considered an important correlate of myocardial oxygen consumption. An initial set of experiments re-examined this question of independently varying heart rate, systolic blood pressure, and stroke volume in seven closed-chest, anesthetized dogs. This was achieved by cardiac pacing, a pressure control reservoir, phenylephrine infusion, and adjustment of arteriovenous shunts. Propranolol was used to minimize changes in contractility which might affect myocardial oxygen consumption. Stroke volume in the form of external work had a significant effect on oxygen consumption. From these results, a new pressure-work index of myocardial oxygen consumption was devised, and fitting parameters for the following indexes were determined: systolic pressure-rate product, estimated wall tension, external left ventricular work, triple product, mean pressure-rate product, Et (Bretschneider), and tension-time index. These indexes were prospectively applied to a second set of experiments in 11 closed-chest, anesthetized dogs given norepinephrine, isoproterenol, dobutamine, Nembutal, and propranolol to alter myocardial contractility. Inotropic oxygen wasting was observed with the tension-time, mean pressure-rate, triple product, and estimated wall tension indexes, but not with the pressure-work or systolic pressure-rate indexes. It is concluded that stroke work is an important correlate of myocardial oxygen consumption, and that the pressure-work of systolic pressure-rate indexes can account for catecholamine-induced, changes in myocardial oxygen consumption without postulating an oxygen-wasting effect.
 ...
PMID:Work as a correlate of canine left ventricular oxygen consumption, and the problem of catecholamine oxygen wasting. 612 48

In an open controlled trial with 6 male human volunteers Mg and K intake was reduced to 32-35% of normal during a 5- and 4-day period, respectively and 80 mg Furosemide/day was coadministered during the second period in order to induce Mg and K wasting. After each testing period an intravenous infusion of 27.87 mEq Mg and K was administered as K, Mg-D,L-aspartate during 2 h. Electrolyte and fluid balance were analysed before, during and after the testing period. Moreover, impedance cardiographic measurements were carried out in order to determine changes of cardiovascular function, and 24-hour ECGs were recorded simultaneously. It could be shown that reduced Mg and K intake induces depletion of the intracellular stores which was furthermore enhanced by coadministration of the loop diuretic Furosemide. Whereas Mg renal elimination amounted only to 60-54% of intake, K elimination exceeded intake to a considerable extent, a fact that could be explained by the lack of Mg. Changes of cardiovascular function, such as stroke volume, cardiac output and end-diastolic volume, expressed by alterations of total resistivity ZO, were less pronounced, but could be inverted at least partly by a single intravenous infusion of K,Mg-D,L-aspartate. Heart rate and 24-h ECG did not reveal any detectable change. The testing procedure described here can be considered a reliable model for tests in clinical pharmacology.
 ...
PMID:Influence of magnesium and potassium deficiency on renal elimination and cardiovascular function demonstrated by impedance cardiography. 653 36

The influence of cardiac stunning on the oxidation of fatty acids and the oxidative phosphorylation in mitochondria was investigated. Rat hearts were perfused for 15 min according to the working mode with a Krebs-Henseleit buffer containing glucose (11 mM). The hearts were then maintained in normoxic conditions (C group) or subjected to a 15-min global no-flow normothermic ischemia followed by a 30-min reperfusion (R group). Throughout the perfusion, the aortic and coronary flows, and the heart rate and oxygen consumption were monitored. At the end of the perfusion procedure, a bolus of 1-14C palmitate was injected in the coronary arterial bed to evaluate the fatty acid oxidation. Two sub-populations of mitochondria were isolated from each heart by either mechanical (ME mitochondria) or enzymic (EE mitochondria) extraction and their respiration properties were evaluated. Furthermore, the mitochondrial energy production (ATP and creatine phosphate) was assessed. During ischemia, the aortic flow was suppressed and recovered only to approximately 50% of the preischemic value during reperfusion. This mechanical stunning was associated with an important reduction of the stroke volume (-37%, p < 0.01) and a slight decrease in heart rate (-20%, p < 0.001). At the end of reperfusion, the beta-oxidation rate constituted 55 +/- 1.7% of the cell palmitate and was similar to that assessed in the C group. The oxygen consumption was decreased to 216 +/- 31.0 microL O2/min/gww and the venous O2 concentration increased to 5.1 +/- 0.572 microL O2/mL (instead of 2.9 +/- 0.342 microL O2/mL in the C group), although due to large SD, only the latter was statistically significant. A decrease in metabolic efficiency (42 +/- 14.4 vs 106 +/- 16.8 mL/microL O2 in the C group) and an increase in palmitate oxidation to oxygen consumption ratio (77 +/- 10.1 vs 47.6 +/- 4.25% beta-oxidized palmitate/microL O2 in the C group) were observed. This increased fatty acid contribution in the oxidation metabolism could be responsible for some oxygen wasting and could contribute to decrease the energy available for the contraction despite the normal cardiac oxygen uptake. Furthermore, the respiration parameters of the mitochondria were similar in the C and R groups when glutamate (20 mM) or palmitoylcarnitine (25 microM) were used as substrate. ME mitochondria of R group displayed a reduced rate of ATP production (118 +/- 29.5 vs 180 +/- 14.5 nmoles/min/mg proteins in the C group) without altered creatine phosphate production. The presence of calcium in the medium (10(-5) M) provoked a decrease in ATP production.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Cellular and mitochondrial energy metabolism in the stunned myocardium. 782 5

It is not known why alcohol ingestion poses a risk for development of hypertension, stroke and sudden death. Of all drugs, which result in body depletion of magnesium (Mg), alcohol is now known to be the most notorious cause of Mg-wasting. Recent data obtained through the use of biophysical (and noninvasive) technology suggest that alcohol may induce hypertension, stroke, and sudden death via its effects on intracellular free Mg2+ ([Mg2+]i), which in turn alter cellular and subcellular bioenergetics and promote calcium ion (Ca2+) overload. Evidence is reviewed that demonstrates that the dietary intake of Mg modulates the hypertensive actions of alcohol. Experiments with intact rats indicates that chronic ethanol ingestion results in both structural and hemodynamic alterations in the microcirculation, which, in themselves, could account for increased vascular resistance. Chronic ethanol increases the reactivity of intact microvessels to vasoconstrictors and results in decreased reactivity to vasodilators. Chronic ethanol ingestion clearly results in vascular smooth muscle cells that exhibit a progressive increase in exchangeable and cellular Ca2+ concomitant with a progressive reduction in Mg content. Use of 31P-NMR spectroscopy coupled with optical-backscatter reflectance spectroscopy revealed that acute ethanol administration to rats results in dose-dependent deficits in phosphocreatine (PCr), the [PCr]/[ATP] ratio, intracellular pH (pHi), oxyhemoglobin, and the mitochondrial level of oxidized cytochrome oxidase aa3 concomitant with a rise in brain-blood volume and inorganic phosphate. Temporal studies performed in vivo, on the intact brain, indicate that [Mg2+]i is depleted before any of the bioenergetic changes. Pretreatment of animals with Mg2+ prevents ethanol from inducing stroke and prevents all of the adverse bioenergetic changes from taking place. Use of quantitative digital imaging microscopy, and mag-fura-2, on single-cultured canine cerebral vascular smooth muscle, human endothelial, and rat astrocyte cells reveals that alcohol induces rapid concentration-dependent depletion of [Mg2+]i. These cellular deficits in [Mg2+]i seem to precipitate cellular and subcellular disturbances in cytoplasmic and mitochondrial bioenergetic pathways leading to Ca2+ overload and ischemia. A role for ethanol-induced alterations in [Mg2+]i should also be considered in the well-known behavioral actions of alcohol.
 ...
PMID:Role of magnesium and calcium in alcohol-induced hypertension and strokes as probed by in vivo television microscopy, digital image microscopy, optical spectroscopy, 31P-NMR, spectroscopy and a unique magnesium ion-selective electrode. 784 86

Cardiopulmonary bypass results in a "euthyroid sick" state. Recently, interest has focused on the relationship between low serum triiodothyronine levels and postoperative cardiovascular hemodynamics. The present study was undertaken to more clearly define the acute effects of triiodothyronine on myocardial mechanics and energetics after hypothermic global ischemia using an ex-vivo canine heart preparation to model the clinical condition. Experiments were performed on isolated hearts subjected to hyperkalemic arrest with 90 minutes of hypothermic (10 degrees C) ischemia. Isolated hearts were cross-perfused by euthyroid support dogs in which triiodothyronine levels spontaneously decreased by 65% to 75% (p < 0.01) after the initiation of cross-perfusion. In nine heart preparations, triiodothyronine (Triostat) was given as a bolus dose (0.2 micrograms/kg) after 1 hour of baseline data collection with a subsequent measurable rise in serum triiodothyronine levels (p < 0.01). In six postischemic hearts, reverse triiodothyronine was given as a 0.2 micrograms/kg bolus. Triiodothyronine was also administered to a group of eight nonischemic, continuously perfused isolated hearts. Intrinsic myocardial contractility was assessed by analysis of the preload recruitable stroke work area, energetic efficiency from the myocardial oxygen consumption-pressure-volume area relationship, and coronary vascular resistance from analysis of coronary flow and perfusion pressure. Acute administration of triiodothyronine to postischemic hearts improved the preload recruitable stroke work area from 9.5 +/- 1.42 to 14.9 +/- 2.03 x 10(7) erg/ml, a 56% increase from baseline (p < 0.001), but had no effect on the preload recruitable stroke work area of the nonischemic hearts. The inotropic response resulting from triiodothyronine treatment did not alter the myocardial oxygen consumption-pressure-volume area relationship. Triiodothyronine treatment was associated with significantly decreased coronary resistance and increased coronary flow through a range of diastolic loading conditions in the postischemic hearts. The biologically inactive thyroid hormone metabolite reverse triiodothyronine was without effect on any of the measured parameters. On the basis of these results, we conclude that the low triiodothyronine state of cardiopulmonary bypass can be reproduced in this isolated heart model and that acute triiodothyronine treatment results in a unique inotropic action manifest only in the postischemic reperfused myocardium and is accomplished without oxygen wasting effects.
 ...
PMID:Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia. 787 6


1 2 3 4 Next >>