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

Cerebral hypoxia-oligemia was produced by lowering of the arterial PO2 to 30 mm Hg and by right common carotid artery occlusion in rats who were pretreated with intravenous Krebs' solution, gamma-hydroxybutyrate (GHB) (500 mg/kg) or gamma-butyrolactone (GBL) (300 mg/kg). At 0.5 h exposure the right cerebral hemisphere of animals receiving Krebs', GHB or GBL showed equivalent decreases of ATP and phosphocreatine and increase of ADP, AMP and lactate which indicated that these depressant drugs had no beneficial effect on the energy metabolism of the acutely hypoxic-oligemic brain. In a second series of rats in which Krebs' solution, GHB or GBL were administered to animals during the early recovery period from 0.5 h hypoxic-oligemic exposure, the brain metabolic patterns of the right hemisphere indicated that GHB retarded the restitution of energy phosphates and the oxidation of the accumulated lactate; whereas, GBL led to a delayed metabolic deterioration. It is concluded that GHB and GBL do not beneficially alter cerebral energy metabolism during acute hypoxia-oligemia and that their administration during restitution may result in metabolic alterations which suggest an unfavorable effect.
Stroke
PMID:Effects of gamma-hydroxybutrate and gamma-butyrolactone on cerebral energy metabolism during exposure and recovery from hypoxemia-oligemia. 739 64

The hemodynamic changes which occur when clamping and unclamping the aorta during reconstructive surgery might be a threat to the elderly patient with concomitant cardiac disease. In addition, the cross-clamping induces a temporary ischemia of the legs, with severe metabolic derangement after the release of the aortic clamp. We have studied the effect of a intraoperative adrenergic block (phenoxybenzamine plus metoprolol) on the central circulation and the skeletal metabolism in 14 patients undergoing aortic reconstruction to treat occlusive arteriosclerotic disease. Cardiac output, heart rate, arterial and pulmonary artery pressures, and cardiac filling pressures, as well as femoral venous blood flow were studied. Biopsy specimens of the lateral vastus muscle and blood samples from the radial artery and iliac vein were taken before aortic clamping, and before, 30 minutes, four and 16 hours after the aorta was unclamped, as well as five days postoperatively. In addition, intramuscular temperature and pH were measured. Glycogen, glucose, lactate, pyruvate, ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) contents of the muscle and lactate and pyruvate concentrations in iliac venous and radial arterial blood were determined using enzymatic fluorometric techniques. Mean arterial blood pressure (MAP) averaged 80 mmHg before clamping, chiefly because of the low systemic vascular resistance (SVR), and left ventricular stroke work (LVSW) was normal. At clamping MAP, SVR, LVSW, remained unchanged. MAP and LVSW were unaffected even though SVR decreased slightly after the aorta was unclamped and resulted in an increased cardiac output, mainly due to a higher stroke volume. No major change in the pulmonary circulation was observed. During clamping the muscle lactate/pyruvate ratio increased, intramuscular pH and femoral venous blood flow decreased indicating insufficient tissue perfusion. Energy charge (EC), the adenylate (ATP + ADP + AMP) and creatine (PCr + Cr) pools were, however, unchanged. In spite of a restored blood flow to the legs, a severe metabolic derangement of the muscle was observed after declamping, with lowered EC, ATP + ADP + AMP and PCr + Cr indicating cellular damage. No improvement in the condition of the cells was observed 16 hours after operation. In conclusion, we found that by using neurolept anesthesia and an intraoperative adrenergic block in combination with a differentiated fluid therapy the central circulation stabilized and was largely unaffected by the clamping and unclamping procedures. In spite of the improved central hemodynamics no favorable effect on the skeletal muscle metabolism was observed.
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PMID:Temporary incomplete ischemia of the legs induced by aortic clamping in man: effects on central hemodynamics and skeletal muscle metabolism by adrenergic block. 745 55

Recent results have demonstrated that the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) reduces infarct size due to middle cerebral artery occlusion (MCAO), even when given after ischemia. The objective of the present study was to explore whether PBN influences recovery of energy metabolism. MCAO of 2-hr duration was induced in rats by an intraluminal filament technique. Brains were frozen in situ at the end of ischemia and after 1, 2, and 4 hr of recirculation. PBN was given 1 hr after recirculation. Neocortical focal and perifocal ("penumbra") areas were sampled for analyses of phosphocreatine (PCr), creatine, ATP, ADP, AMP, glycogen, glucose, and lactate. The penumbra showed a moderate-to-marked decrease and the focus showed a marked decrease in PCr and ATP concentrations, a decline in the sum of adenine nucleotides, near-depletion of glycogen, and an increase in lactate concentration after 2 hr of ischemia. Recirculation for 1 hr led to only a partial recovery of energy state, with little further improvement after 2 hr and signs of secondary deterioration after 4 hr, particularly in the focus. After 4 hr of recirculation, PBN-treated animals showed pronounced recovery of energy state, with ATP and lactate contents in both focus and penumbra approaching normal values. Although an effect of PBN on mitochondria cannot be excluded, the results suggest that PBN acts by preventing a gradual compromise of microcirculation. The results justify a reevaluation of current views on the pathophysiology of focal ischemic damage and suggest that a therapeutic window of many hours exists in stroke.
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PMID:N-tert-butyl-alpha-phenylnitrone improves recovery of brain energy state in rats following transient focal ischemia. 776 48

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system were examined. When PACAP-38 (270 or 420 pmol/kg body weight) was administered intravenously to the anesthetized dogs, both mean arterial pressure and left ventricular systolic pressure increased within 2 min after a temporal depression. Pulmonary arterial systolic pressure increased promptly. These hemodynamic values and heart rates (HR) 5 min after injection were significantly higher than the corresponding values in physiological saline injected dogs, and some effects were still sustained over 15 min. Cardiac output and stroke volume also increased and the values at 5 min were significantly higher than those in controls. The high dose of PACAP-38 (420 pmol/kg) evoked greater responses than those induced by the low dose (270 pmol/kg). Plasma adrenaline, but neither noradrenaline nor dopamine concentration significantly increased 15 min after injection of 420 pmol/kg PACAP-38. Moreover, PACAP-38 clearly stimulated cyclic AMP production in rat cardiac myocytes with EC50 of 1.5 x 10(-9) M and plasma cAMP levels significantly and dose-dependently increased in dogs 5 min after administration. These results first demonstrated that PACAP has inotropic and chronotropic actions on the heart possibly by a direct stimulation of adenylate cyclase in cardiac myocytes and also that the cardiovascular functions may be possibly modified by an evoked adrenaline secretion in vivo.
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PMID:Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system. 790 74

Glucagon has been reported to be one of the most effective treatments for severe beta-blocker poisoning. Recently, amrinone was suggested as an alternative therapeutic choice for beta-blocker poisoning. Milrinone, a derivative of amrinone, acts independently of beta-adrenoceptors and increases cyclic AMP. Therefore milrinone may also be effective in the treatment of beta-blocker poisoning. In the present study, we compared the effect of glucagon and milrinone in treating severe beta-blocker poisoning. Following the administration of 10 mg/kg propranolol i.v. over 10 min, heart rate, cardiac output, mean arterial pressure, stroke volume, and end tidal CO2 were depressed, while central venous pressure, and pulmonary capillary wedge pressure increased significantly (p < 0.05). Following the administration of saline (Group S, N = 3), glucagon 20 micrograms/kg (Group G, N = 5), and milrinone 300 micrograms/kg (Group M, N = 5), hemodynamic parameters were observed for 30 min. In group M, mean arterial pressure, cardiac output and stroke volume recovered to their baseline values, while central venous pressure and pulmonary capillary wedge pressure decreased. Although there were no significant differences between groups G and M, the heart rate, central venous pressure and pulmonary capillary wedge pressure, mean arterial pressure and stroke volume did not return to baseline values in group G. Milrinone administration produced a significant hemodynamic improvement without increasing the heart rate in the canine model of severe heart failure caused by propranolol. In the glucagon treatment group, central venous pressure and pulmonary capillary wedge pressure improved less than the milrinone group. Although more data are needed before a clinical recommendation, milrinone might be an effective drug to treat beta-blocker poisoning.
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PMID:Milrinone versus glucagon: comparative hemodynamic effects in canine propranolol poisoning. 800 35

The relaxant effects of calcitonin gene-related peptide (CGRP) on the 3rd branches of renal arteries obtained from stroke-prone spontaneously hypertensive rats (SHRSP), and Wistar-Kyoto rats (WKY) were investigated in vitro. CGRP elicited concentration-dependent relaxation, and the relaxant response was not affected by the mechanical removal of endothelium in either SHRSP or WKY. The CGRP-induced relaxant response was markedly greater in SHRSP than in WKY, whereas there was no significant difference in acetylcholine-induced relaxation, which was endothelium-dependent, between the two groups. Additionally, significantly enhanced reactivity to CGRP was also shown in spontaneously hypertensive rats compared to WKY; however, this reactivity was less than that observed in SHRSP. There were also no significant differences between WKY and SHRSP in the relaxation induced by forskolin, dibutyryl cyclic AMP, and 3-isobutyl-1-methylxanthine (IBMX). CGRP-induced relaxation was significantly potentiated in similar manner by the pretreatment with IBMX in both WKY and SHRSP. Incubation with glibenclamide (10(-6) M) had no effect on CGRP-induced relaxation in either group, the WKY or the SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the small renal arteries in the rat, and that the increased CGRP-induced relaxant response found in SHRSP may not be associated with the altered vasodilation mediated by cyclic AMP, or with functional changes in ATP-sensitive potassium channels.
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PMID:Relaxant effects of calcitonin gene-related peptide on isolated small renal arteries in stroke-prone spontaneously hypertensive rats. 804 80

We investigated the effects of VA-045, an apovincaminic acid derivative, on isolated blood vessels. VA-045 (10(-7)-10(-5) M) and vinpocetine (10(-7)-10(-5) M) inhibited the 64 mM KCl-induced and 10(-6)M norepinephrine (NE)-induced contraction of rat aortic strips. VA-045 (10(-7)-10(-4) M) and vinpocetine (10(-7)-10(-4) M) inhibited the activity of cyclic AMP and cyclic GMP phosphodiesterase in porcine coronary artery. VA-045 (3 x 10(-9-3 x 10(-6) M) relaxed the 64 mM KCl-induced contraction of the canine basilar artery without affecting the peripheral arteries. These results indicate that VA-045 selectively dilates canine cerebral artery, and that it may be a useful agent for the treatment of cerebrovascular diseases such as stroke.
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PMID:Effects of VA-045, a novel apovincaminic acid derivative, on isolated blood vessels: cerebroarterial selectivity. 838 30

Defibrotide, a polydeoxyribonucleotide, has been found to modulate endothelial cell function, causing an increase in tissue plasminogen activator (t-PA) levels, a decrease in plasminogen activator inhibitor (PAI) levels, and an increase in prostaglandin I2 (PGI2) formation in humans. Defibrotide has no direct anticoagulant effect but has a synergistic action with heparin. A strong antithrombotic effect has been observed in animal models. Thus, defibrotide has a beneficial effect in cases of deep venous thrombosis (DVT), peripheral obliterative vascular disorder (POVD), stroke, vasculitis, and thromboembolism. Defibrotide also inhibits platelet function and activation. A significant decrease in platelet aggregate formation on the suture line in microarterial anastomosis in rats is one way defibrotide can inhibit platelet function and activation. In humans, a slight prolongation' of the lag period in collagen-induced aggregation has been observed. In addition, a slight decrease in the maximum amplitude of the secondary wave of ADP and adrenalin-induced aggregations was also found. Platelet adhesion is diminished, the platelet differential count on formvar membrane is altered, and platelet aggregate formation is significantly inhibited. With an increase in platelet cyclic AMP (cAMP) content and a decrease in malonyl dialdehyde (MDA) and thromboxane B2 (TXB2) formation, the levels of platelet secretion products such as PF-4 and beta-thromboglobulin (beta-TG) in plasma decreased progressively. It was also demonstrated that the 14C-glucose transport defect of the platelet membrane of atherosclerotic patients was partially corrected with defibrotide treatment.
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PMID:Effect of defibrotide on platelet function. 880 24

1. The relaxant responses to calcitonin gene-related peptide (CGRP) of the 3rd order branches of the superior mesenteric arteries (SMA) from 6 month old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats were studied in vitro. 2. Cumulative addition of CGRP (10(-11)-10(-7) mol/L) caused endothelium-independent relaxation of arterial rings precontracted with noradrenaline (10(-6) mol/L). A markedly increased response to CGRP was observed in SHRSP. 3. There was no significant difference between SHRSP and WKY in relaxation produced by forskolin, dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine. 4. Pretreatment with glibenclamide (10(-6) mol/L) did not affect CGRP-induced relaxation in either SHRSP or WKY. 5. These results indicated that CGRP-induced vasodilation was increased in the small branches of SMA from SHRSP, and that this increase did not seem to be associated with an augmented response to cyclic AMP or with increased involvement of ATP-sensitive potassium channels.
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PMID:Calcitonin gene-related peptide-induced relaxation in isolated small superior mesenteric arteries from adult stroke-prone spontaneously hypertensive rats. 907 16

1. The relaxant effects of dopamine (DA) on the intrarenal arteries obtained from 6 month old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats were pharmacologically investigated in vitro. 2. DA (10(-7)-3 x 10(-5) mol/L) produced endothelium-independent relaxation on the arterial rings which had been incubated with phenoxybenzamine (2 x 10(-6) mol/L) and precontracted with KCl. 3. DA-induced relaxation was greater in the arterial rings from SHRSP than in those from WKY. SKF 38393 (10(-8)-10(-6) mol/L) partially mimicked DA-produced relaxation in both groups. SCH 23390 dose-dependently inhibited DA-induced relaxation with pD'2 value of 9.33 for SHRSP and of 9.26 for WKY. 4. There were no significant differences between SHRSP and WKY in the relaxation caused by forskolin, dibutyryl cyclic AMP, or 3-isobutyl-1-methylxanthine. 5. These results suggested that DA1 receptor-mediated relaxation was increased in the intrarenal arteries from SHRSP, and this increase might not be associated with altered vasodilation mediated by cyclic AMP.
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PMID:Dopamine-induced relaxation in isolated intrarenal arteries from adult stroke-prone spontaneously hypertensive rats. 907 59


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