UMLS:C0022116 - FACTA Search

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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preconditioning may find ready applicability in humans facing scheduled global cardiac ischemia-reperfusion (IR) during bypass or transplantation, where such a maneuver is feasible before arrest. Our objective was to delineate and exploit the endogenous preconditioning mechanism triggered by transient ischemia (TI) and thereby attenuate myocardial postischemic mechanical dysfunction by clinically acceptable means. Preconditioning by 2 minutes of TI followed by 10 minutes of normal perfusion protected isolated rat left ventricle function assessed after 20 minutes of global, 37 degrees C ischemia and 40 minutes of reperfusion. Final recovery of developed pressure (DP) was improved (91.5 +/- 1.9% of equilibration DP versus unconditioned IR control, 57.4 +/- 2.4%, P < .01) and was accompanied by increased contractility (+/- dP/dt). Norepinephrine release increased after TI, and reserpine pretreatment abolished TI preconditioning. This suggests that endogenous norepinephrine mediates functional preconditioning in rat. Brief pretreatment (2 minutes) with exogenous norepinephrine reproduced the protection (89.1 +/- 1.4%) of postischemic function. Functional protection persisted after the hemodynamic effects had resolved. Norepinephrine-induced preconditioning was simulated by phenylephrine and blocked by alpha 1-adrenergic receptor antagonist. TI preconditioning was similarly lost after selective alpha 1-adrenergic receptor blockade. We conclude that transient ischemic preconditioning is mediated by the sympathetic neurotransmitter release and alpha 1-adrenergic receptor stimulation. Although the postreceptor mechanism remains unclear, functional protection after IR does not seem related to the magnitude of ATP depletion and elevation of resting pressure during ischemia. Rather, the endogenous mechanisms facilitate both recovery of mechanical function and ATP repletion during reperfusion.
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PMID:Preconditioning against myocardial dysfunction after ischemia and reperfusion by an alpha 1-adrenergic mechanism. 839 3

Hepatic surgery in man often requires a transient interruption of the blood flow to the liver. After the vascular declamping the hepatic reperfusion induces a group of phenomena commonly called "reperfusion injuries." The aim of this study was to evaluate the presence and effect of vasoactive agents that could induce the acute pulmonary arterial hypertension which contributes to reperfusion injury. Wistar rats were used. The hepatic ischemia was induced by crossclamping the whole hepatic hilus for 20, 40, and 60 min. In control experiments a sham operation was performed. Blood samples were collected from the suprahepatic inferior vena cava. Strips of the main pulmonary artery were set up in an isolated organ bath and tested for the response to noradrenaline, adrenaline, KCl, and plasma samples. Plasma levels of catecholamines were determined by high-performance liquid chromatography. Plasma concentration of noradrenaline significantly increased from 1.6 +/- 0.4 (control) to 10.8 +/- 2.9 ng.ml-1 and adrenaline concentration rose from 2.7 +/- 0.7 to 38.7 +/- 7.6 ng.ml-1 after ischemia. Noradrenaline potency, compared to control values, significantly increased after prolonged liver ischemia. The plasma samples collected after prolonged liver ischemia caused a greater contraction of the pulmonary artery than from control plasma. This contraction is partially inhibited by phentolamine. We conclude that hepatic ischemia modifies the response of the pulmonary artery to exogenous noradrenaline. At the same time it induces an increase in the plasma levels of adrenaline and noradrenaline. The resulting combined effect may cause the pulmonary hypertension which has been observed in reperfusion injury.
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PMID:Evaluation of the reperfusion syndrome after liver ischemia in the rat. 863 32

Norepinephrine, that has been released from sympathetic nerve endings in response to myocardial ischemia, may have either a beneficial or a harmful effect on the ischemic heart. If the duration of ischemia is short, the release of norepinephrine may be favorable for the production of energy and for protection of the heart against ischemic damage. If the duration of ischemia is prolonged, there is a marked increase in number of both alpha 1 and beta-adrenoceptors located in the sarcolemmal membrane, as well as an excessive increase in release of norepinephrine. These events during the prolonged period of ischemia can produce an imbalance between oxygen supply and demand, which is harmful to the heart. The anti-ischemic effect of alpha 1- and beta-adrenoceptor antagonists is not attributed merely to improvement of oxygen balance, but reduction of phospholipase activity or stabilization of membrane may also be important as an underlying mechanism.
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PMID:Role of the sympathetic nervous system in the ischemic and reperfused heart. 880 1

We recently reported that pretreatment with the type IV phosphodiesterase inhibitor Ro 20-1724 attenuates the development of endotoxin-induced acute renal failure in rats. Norepinephrine is an important therapeutic agent in human endotoxemia, but its efficacy is limited by its deleterious side effect of potent renal and mesenteric vasoconstriction. In this study we examined whether posttreatment with Ro 20-1724 after endotoxin infusion 1) attenuates increased renal vascular resistance and the development of acute renal failure in the absence and presence of norepinephrine infusion, 2) improves mesenteric blood flow in the presence of norepinephrine and 3) improves survival rates in the absence and presence of norepinephrine infusion. Forty-eight rats were anesthetized and instrumented, and eight 20-min clearance periods were performed. Endotoxin (20 mg/kg i.v.) was administered after the first period, and a constant-rate i.v. infusion of either Ro 20-1724 (10 micrograms/kg/min) or vehicle was initiated after period 3, in the absence and presence of norepinephrine infusion (1 microgram/kg/ min, begun after period 4). Urinary cAMP excretion in the Ro 20-1724-treated groups was 2- to 3-fold (P < .001) higher, compared with the vehicle-treated groups. Ro 20-1724 markedly attenuated endotoxin-induced (P < .01) increases in renal vascular resistance and attenuated norepinephrine-induced (P < .05) increases in renal vascular resistance in rats pretreated with endotoxin. Moreover, Ro 20-1724 reduced endotoxin-induced decreases in renal blood flow (P < .05) and glomerular filtration rate (P < .01) in the absence and presence of norepinephrine. In animals pretreated with endotoxin, Ro 20-1724 attenuated norepinephrine-induced increases in mesenteric vascular resistance (P = .054) and decreases in mesenteric blood flow (P < .01). Ro 20-1724 also improved survival rates for endotoxin-treated rats, whether or not the rats were administered norepinephrine (P < .01). Type IV-specific phosphodiesterase inhibitors warrant further study as selective therapeutic agents that protect against endotoxin/vasopressor-induced renal and mesenteric ischemia and death.
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PMID:Treatment with the type IV phosphodiesterase inhibitor Ro 20-1724 protects renal and mesenteric blood flow in endotoxemic rats treated with norepinephrine. 896 41

The objective of the present study was to determine norepinephrine release, functional recovery, and incidence of arrhythmias following multiple episodes of brief (5 min) ischemia and to compare these variables with those obtained after continuous ischemia (30 min) in isolated rat hearts perfused with modified Krebs-Henseleit solution. Left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and cardiac rhythm were continuously recorded. The amount of norepinephrine in perfusate was measured by high-performance liquid chromatography. The data showed no increases in LVEDP during the six successive 5-min periods of ischemia interrupted by 5-min reperfusion. The six repetitive periods of reperfusion after repetitive 5-min periods of ischemia were associated with a restoration of left ventricular diastolic function and preservation of reactive hyperemia (23.3 +/- 1.5 mL/min vs. baseline 16.5 +/- 1.3 mL/min; p < 0.05). The incidences of ventricular fibrillation (VF) (10/10) and ventricular tachycardia (VT) (10/10) upon reperfusion in the continuous ischemia group were higher than those in the repetitive ischemia group (VF, 2/10; VT, 3/10; p < 0.05). Norepinephrine washout upon reperfusion after 30-min continuous ischemia was 58.2 +/- 17.4 ng/g of heart, but no increase in norepinephrine washout was observed after brief repetitive ischemic episodes (11.2 +/- 2.4 ng/g of heart) (p < 0.05). Our results show a substantial release of norepinephrine only after 30 min of continuous ischemia, in the isolated rat heart.
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PMID:Brief repetitive ischemia: effect on norepinephrine release, arrhythmias, and functional recovery in isolated perfused rat heart. 904 46

Manipulations of plasma catecholamine concentrations influence outcome from ischemic brain insults. It has been suggested that these effects are mediated by influences on brain catecholamine concentrations. This study examined whether major changes in brain norepinephrine concentrations can alter outcome from severe forebrain ischemia. Sprague-Dawley rats were administered 50 mg/kg i. p. N-(chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) or were left untreated (control). One week later, these rats were subjected to either 7 or 8 min of normothermic forebrain ischemia (bilateral carotid occlusion and MABP=30 mmHg) and allowed to recover for 4 days. Histologic damage was then evaluated. In other control and DSP-4-treated animals, hippocampal microdialysate norepinephrine concentrations were measured before, during and after 8 min of forebrain ischemia. Norepinephrine concentrations were also determined in brain homogenates from non-ischemic DSP-treated and control rats. A 95% depletion of norepinephrine was observed in brain homogenates from non-ischemic DSP-4-treated rats compared with control. During ischemia, microdialysate norepinephrine concentrations increased in control but not in DSP-4-treated rats (P=0.002). For plasma, intra-ischemic epinephrine concentrations increased 8-10-fold and returned to baseline values post-ischemia with no differences between groups. Plasma norepinephrine values remained unchanged in both groups. Histologic damage resulting from either 7 or 8 min of ischemia in hippocampal structures, caudoputamen, and neocortex was similar between DSP-4-treated and control groups. This study could not identify any effect of major changes in brain norepinephrine concentrations on ischemic brain damage. These data indicate that peripheral catecholamine effects on near-complete forebrain ischemic outcome are unlikely to be mediated by effects on central catecholamine concentrations.
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PMID:Effect of intracerebral norepinephrine depletion on outcome from severe forebrain ischemia in the rat. 1057 96

The aim of the study was to use the isolated blood-perfused rat heart to: (i) determine whether brief intermittent rapid pacing and ventricular fibrillation are able to mimic preconditioning by ischemia and thereby protect the isolated blood-perfused heart against ischemia-induced injury and (ii) characterize the effects of these interventions on cardiac metabolism. To this end, isolated, blood-perfused (2.4 ml/min), paced (360 beats/min) rat hearts (n = 6/group), were aerobically perfused for 20 min. Hearts were then randomized to four groups: (i) a further 16 min aerobic perfusion (UC, untreated controls), (ii) ischemic preconditioning (IP, 3 min ischemia + 3 min reperfusion followed by 5 min ischemia + 5 min reperfusion), (iii) electrically induced ventricular fibrillation (VF, 3 min fibrillation + 3 min sinus rhythm followed by 5 min fibrillation + 5 min sinus rhythm) and (iv) rapid pacing at > or = 600 beats/min (RP, 3 min rapid pacing + 3 min normal heart rate followed by 5 min rapid pacing + 5 min normal heart rate). Hearts were then subjected to 35 min of zero-flow, global ischemia (37 degrees C) and 40 min reperfusion. In parallel studies, blood samples were collected during the first 3 min of treatment and plasma taken for the analysis of noradrenaline. The hearts were then immediately frozen and assayed for high energy phosphates and noradrenaline content. Time-to-50% contracture during ischemia was 13.2 +/- 0.8 min in controls; this was reduced to 6.3 +/- 1.1 min by IP but was unaffected by VF or RP (12.4 +/- 1.1 and 12.8 +/- 1.2 min respectively). Post-ischemic left ventricular developed pressure (LVDP) in untreated controls recovered to only 19.9 +/- 8.4% of its pre-ischemic value whereas with IP, VF and RP substantial and similar improvements were observed (60.3 +/- 7.4, 56.2 +/- 5.7 and 45.3 +/- 10.3%, respectively, P < 0.01). This protection was achieved without any significant depletion of high energy phosphates during VF or RP. Noradrenaline was essentially unchanged in controls and with RP, but VF caused a loss from tissue and a large elevation in the plasma. Our results suggest that both RP and VF are as effective as brief ischemia in protecting the heart against injury during ischemia and reperfusion. In contrast to IP, this protection can be achieved without the exacerbation of ischemic contracture and without inducing ischemia during the preconditioning period.
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PMID:Cardioprotection: intermittent ventricular fibrillation and rapid pacing can induce preconditioning in the blood-perfused rat heart. 1059 Oct 23

The ischemia induced vasospasm of the renal arterial blood vessels mediated by alpha1-adrenoceptors is of importance for the loss of kidney function. This is based on reduced perfusion of the kidney cortex occurring in kidney transplant and organ preserving surgery. The present study considered the intracellular mechanism of the norepinephrine (NE) induced renal artery vasospasm by using swine renal artery smooth muscle ring. Norepinephrine and phenylephrine (PE) induced dose-dependent and fully reversible isometric contractions with a threshold concentration of 10 nM (n = 7) and 10 nM (n = 4), and an EC50 of 0.3 microM and 1 microM, respectively. The receptor was identified as alpha1A-subtype. The contraction was completely inhibited by verapamil (IC50 = 1.51 microM; n = 11) and diltiazem (IC50 = 9.49 microM; n = 8) and 85% by nifedipine (IC50 = 0.13 microM; n = 21). Blockade of the intracellular inositol- 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store by thapsigargin (1 microM, n = 7) or suppression of Ca2+ release from the intracellular Ca2+-sensitive Ca2+ store by ryanodine (100 microM, n = 4) inhibited the PE induced contraction by 39.5% and 47.6%, respectively. The results suggest a key role of voltage-dependent Ca2+ channels and intracellular Ca2+ stores in the alpha1A-adrenoceptor induced contraction of the renal artery.
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PMID:Regulation of renal artery smooth muscle tone by alpha1-adrenoceptors: role of voltage-gated calcium channels and intracellular calcium stores. 1085 Jun 35

Impaired right ventricular (RV) function may be caused by pulmonary hypertension or myocardial ischemia. It is characterized by a dilation of the RV, which is followed by an increase of wall tension and O2-consumption and a decrease of RV ejection fraction (RV 'dysfunction'). If a drop of arterial pressure occurs this my precipitate RV failure and shock (RV 'insufficiency'). Diagnosis of RV failure and monitoring of RV function is difficult. Sometimes, even a severe impairment of RV function goes undetected or is misinterpreted. Patients in the operating room or on intensive care units seem to be especially prone to RV dysfunction and failure. Since a causative therapy often is not readily available, adequate symptomatic therapy is of utmost importance. Four basic principles have to be considered: 1) Optimizing preload: The failing RV requires adequate filling for preservation of stroke volume. On the other hand, overdistension of the RV may result in RV ischemia, thereby further deteriorating RV function Hence, volume loading is important, but requires continuous monitoring. 2) Maintenance of aortic pressure: Vasopressors are indicated if there is a critical drop of coronary perfusion pressure. Norepinephrine presently is the drug of choice for this purpose. 3) Reduction of RV afterload: Whereas intravenous vasodilators are limited in their efficacy in dilating pulmonary vessels due to systemic side effects, inhaled vasodilators result in selective pulmonary vasodilation and may improve RV function. 4) Increase of RV contractility: In RV failure and shock, norepinephrine and epinephrine are the drugs of choice. Inodilators are well suited for reducing pulmonary vascular resistance due to their positive inotropic and vasodilating effects. Since systemic vasodilation may occur, these drugs must only be used in hemodynamically stable patients.
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PMID:[Acute right heart failure. Etiology--pathophysiology--diagnosis--therapy]. 1107 67

Cardioprotection by K(ATP) channel openers during ischemia is well documented although ill understood. Proarrhythmic effects may be an important drawback. K(ATP) channel modulation influences neurotransmitter release during ischemia in brain synaptosomes. Therefore, we studied the effects of K(ATP) channel modulation on myocardial noradrenaline release and arrhythmias in ischemic rabbit hearts. Isolated rabbit hearts were perfused according to Langendorff and stimulated. Local electrograms were recorded and K+-selective electrodes were inserted in the left ventricular free wall. Cromakalim (3 microM) or glibenclamide (3 microM) was added 20 min prior to induction of global ischemia. After 15, 20, or 30 min of ischemia, hearts were reperfused and noradrenaline content of the first 100 ml of reperfusate was measured. Cromakalim (n = 16) prevented the second rise of extracellular [K(+)] in accordance with its cardioprotective effect. Cromakalim significantly reduced noradrenaline release after 15 min (mean, 169 +/- SEM 97 pmol/gr dry weight vs. control 941 +/- 278; p < 0.05) and 20 min of ischemia (230 +/- 125 pmol/gr dry wt vs. control 1,460 +/- 433; p < 0.05), but after 30 min of ischemia, the difference in noradrenaline release was no longer significant (cromakalim 2,703 +/- 1,195 pmol/gr dry wt vs. control 5,413 +/- 1,310; p = 0.08). Ventricular fibrillation or ventricular tachycardia occurred in 10 of 13 control hearts (77%) (n = 19), in six of 10 glibenclamide-treated hearts (60%) (n = 15), and in six of 14 cromakalim-treated hearts (43%) (p = NS). Cromakalim significantly accelerated onset of ventricular tachycardia or fibrillation (mean +/- SEM onset after 12.5 +/- 1.6 min ischemia vs. control 16.2 +/- 0.7 min; p < 0.05). Noradrenaline release occurred only in cromakalim-treated hearts with early-onset arrhythmias whereas no noradrenaline release was observed in cromakalim-treated hearts without ventricular tachycardia or fibrillation. Our results show that activation of the K(ATP) channel by cromakalim during ischemia reduces myocardial noradrenaline release and postpones the onset of irreversible damage, contributing to the cardioprotective potential of K(ATP) openers during myocardial ischemia.
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PMID:K(ATP) channel opening during ischemia: effects on myocardial noradrenaline release and ventricular arrhythmias. 1148 45

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