Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The [3H]-verapamil binding activity of rat cardiac sarcolemmal fragments was studied, using membranes harvested from non-perfused, aerobically-perfused and ischaemic hearts. Glass-fibre filters were found to contain specific, high affinity--(KD 38 +/- 3.1 nM) [3H]-verapamil binding sites--making them unsuitable for use in [3H]-verapamil binding studies. Incubation of membranes from non-perfused hearts in a medium containing 150 mM NaCl, 1 mM CaCl2 and 50 mM Tris revealed two populations of [3H]-verapamil binding sites. When centrifugation instead of filtration was used to separate bound and free [3H]-verapamil, high affinity sites with a KD of 0.57 +/- 0.19 microM and a Bmax of 38 +/- 5.2 pmol mg-1 protein, and low affinity sites with a KD of 78 +/- 27.5 microM and a Bmax of 2.9 +/- 1.3 nmol mg-1 protein were detected. However, only low affinity binding sites could be detected in membranes which had been incubated in a cation-free medium containing 50 mM Tris. [3H]-verapamil binding to the low and high affinity sites was saturable, reversible, stereospecific and displaceable by D600 greater than diltiazem greater than Ca2+ but not by nifedipine, nitrendipine, nisoldipine or prazosin. The two populations of binding sites survived aerobic perfusion and 60 min ischaemia at 37 degrees C. Ischaemia reduced the Bmax and KD but selectivity was maintained.
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PMID:[3H]-verapamil binding to rat cardiac sarcolemmal membrane fragments; an effect of ischaemia. 302 61

The relation between adenine nucleotide liver concentrations and the viability of liver allografts after cold preservation and warm ischemia was studied. A rat model was used with storage times defined in terms of allograft viability. Livers were excised and stored for 4 hr at 4 degrees C or 1 hr at 37 degrees C (viable if transplanted) or for 8 hr at 4 degrees C or 2 hr at 37 degrees C (not viable if transplanted) in a solution containing 0.9% NaCl and 2 mM CaCl2. Adenine nucleotide, malondialdehyde, and glutathione concentrations were measured in liver biopsies at the end of the storage periods and in control livers. During cold preservation, ATP concentrations decline, but degradation is largely halted at AMP, and this is independent of the length of storage or viability of the allograft. Graft failure is not due to lack of availability of intramitochondrial substrate (AMP) for rephosphorylation to adenosine triphosphate (ATP), nor is it likely that provision of such substrate will be helpful. On the other hand, with warm ischemia, degradation to inosine, hypoxanthine and xanthine occurs and nonviable livers develop higher levels of xanthine than viable ones; in fact, xanthine concentrations provide 100% discrimination between viable and nonviable warm preserved livers. Malondialdehyde concentrations were also significantly greater in the warm preserved nonviable livers, indicating that some lipid peroxidation may occur even before reperfusion of allografts. Glutathione concentrations were similar in all experimental groups.
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PMID:Adenine nucleotide tissue concentrations and liver allograft viability after cold preservation and warm ischemia. 328 45

Following detailed investigation and definition of some of the critical factors relating to the composition and use of cardioplegic protective solutions, we have formulated the St. Thomas' Hospital cardioplegic solution number 2. This cardioplegic solution (NaCl 110.0 mM, NaHCO3 10.0 mM, KCl 16.0 mM, MgCl2 16.0 mM, CaCl2 1.2 mM, pH 7.8) is designed for routine clinical use combining optimal protection with simplicity of formulation and administration/infusion. In order to characterize the efficacy of this modified solution, experiments have been carried out in two species: the isolated rat heart and the in-situ dog heart. In parallel protocols, hearts were subjected to ischemic arrest of up to 4 hours. Multidose (every 40 minutes) cardioplegic infusion of the St. Thomas' solution combined with topical hypothermia extended the tolerable period of ischemia from less than 30 minutes to about 120 minutes in the rat and from less than 60 minutes to more than 180 minutes in the dog. These conclusions were based on the measurement of functional indices together with biochemical, cellular chemical and ultrastructural assessments. The studies confirmed the additive protective properties of hypothermia and chemical cardioplegia and the utility of the rat heart model in the assessment of protective interventions.
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PMID:The St. Thomas' hospital cardioplegic solution: a characterization in two species. 627 81

OUr study was designed to evaluate and compare the effects of three structurally different calcium channel blocking drugs, verapamil (10 and 100 ng/ml), diltiazem (1 and 10 micrograms/ml) and nifedipine (10 and 100 ng/ml), and altering calcium concentration on two models of heart damage, hypoxia/reoxygenation and ischemia/reperfusion (60 min/15 min) of isolated rat hearts. The increase in creatine phosphokinase release by hypoxia and reoxygenation was significantly decreased by treatment with all three drugs. Reoxygenation-induced enzyme efflux was enhanced by a 3-fold elevation in external CaCl2 and depressed by a two-thirds calcium reduction. In contrast, elevation of calcium concentration had no significant effect on postischemia reperfusion-induced creatine phosphokinase efflux whereas "low calcium" decreased release during reperfusion. Two drugs which effectively reduced reperfusion- (nifedipine) or reoxygenation- (diltiazem) induced enzyme release as well as reducing calcium concentration were evaluated to determine during which phase of perfusion these treatments exerted their beneficial effect. The reduction of creatine phosphokinase release during reoxygenation by diltiazem was dependent on the drug's presence during the hypoxia phase of perfusion whereas low calcium (either reoxygenation or reperfusion) or nifedipine treatment (reperfusion) was protective irrespective of whether the treatment was present during hypoxia/ischemia or reoxygenation/reperfusion. The reduction in enzyme release was associated with an enhanced mechanical recovery and a reduction in arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of calcium channel blocking agents and varying extracellular calcium concentration on hypoxia/reoxygenation and ischemia/reperfusion-induced cardiac injury. 670 24

The conversion of L-[3H]arginine to L-[3H]citrulline in the absence of calcium can be used to assay selectively the activity of inducible nitric oxide synthase (NOS) in rat spleen homogenates 6 h after lipopolysaccharide administration. Using similar assay conditions, changes in inducible NOS activity were measured within ischemic brain tissue between 2 h and 7 days following permanent middle cerebral artery (MCA) occlusion in Sprague-Dawley rats and SV-129 mice. Total (constitutive and inducible) NOS activity was measured in the presence of 0.5 mM CaCl2. Whereas total NOS activity in rat decreased dramatically to 16% and 6% of baseline 6 and 12 h after MCA occlusion, inducible NOS activity remained undetectable before 2 days after occlusion, became maximal at 3 days, and decreased to less than 10% of maximal iNOS activity at 7 days. In the mouse, total NOS activity decreased after MCA occlusion but inducible NOS activity was undetectable from 2 h to 4 days after occlusion. Sustained NO production by inducible NOS activity does not contribute to ischemic injury within 24 h after MCA occlusion, but may contribute to infarct maturation 2-4 days after ischemia in some but not all species.
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PMID:Induction of nitric oxide synthase activity in rodent brain following middle cerebral artery occlusion. 747 41

New indexes for evaluation of isometric myocardial relaxation were proposed. In fully isometric and physiologically sequenced twitches, the time course of isometric force decline fitted well with Gompertz's double-exponential curve (r > or = 0.9995). We conformed the original equation to suit myocardial mechanics, i.e., F(t) = gamma 0 - gamma.exp [-alpha.exp (-beta t)] (t = 1, 2, ..., n), where F(t) denotes force as a function of time t. The gamma 0 and gamma relate to upper asymptote and force amplitude, respectively. Phase-plane analysis of F(t) revealed that alpha [3.56 +/- 0.67 (SD)] related to the phasic delay of relaxation onset but did not affect the F(t) vs. dF(t)/dt relation. The beta (0.127 +/- 0.021) and gamma were linearly related to negative dF(t)/dtmax; however, the terminal slope of the phase-plane diagram was governed by beta alone. The tau beta (0.081 +/- 0.017 s), a reciprocal of beta multiplied by sampling time, was practically independent of preload, total load, and muscle shortening. In isometric twitches, tau beta was substantially decreased by global ischemia, isoproterenol, and CaCl2 but increased by reperfusion. The alpha was independent of inotropic interventions but fell significantly during ischemia and was increased by reperfusion.
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PMID:Double-exponential curve fitting of isometric relaxation: a new measure for myocardial lusitropism. 876 78

Whether calcium chloride (CaCl2) should be used to reverse myocardial dysfunction during cardiac operations remains a controversial issue. Calcium chloride may reduce, rather than increase, myocardial contractility and may produce exaggerated vasoconstriction in postischemic vessels in which the endothelium has been damaged. These possibilities were investigated in an open-chest porcine model that allowed control of systemic hemodynamics. Incremental doses of CaCl2 (1, 3, and 10 mg/min) were infused directly into a coronary artery before and after 10 or 15 minutes of ischemia followed by 15 minutes of reperfusion. Calcium chloride increased regional contraction, coronary blood flow, and oxygen consumption before ischemia, whereas oxygen and lactate extraction were unchanged. After ischemia and reperfusion, contraction was impaired and lactate extraction was reduced, but a similar response to CaCl2 was observed. Contraction returned to baseline values promptly after CaCl2. Thus, CaCl2 exerts a positive inotropic effect both in normal and in postischemic myocardium. Calcium chloride does not cause direct coronary constriction nor does it worsen myocardial stunning after a short period of normothermic myocardial ischemia.
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PMID:Effects of intracoronary calcium chloride on the postischemic heart in pigs. 777 23

Liver endothelial cells appear to be particularly vulnerable to cold ischemia reperfusion. However, their function has not yet been evaluated, except using electron microscopic changes and trypan blue exclusion (an index of cell death). Hyaluronic acid is a polysaccharide highly extracted by normal liver endothelial cells. We thus evaluated liver endothelial cell function by measuring hyaluronic acid elimination in a model of ischemia-reperfusion injury using isolated perfused Wistar rat livers. We compared the effects of two preservation solutions during cold ischemia (4 degrees C): normal saline with 2 mM CaCl2 (4 h and 8 h ischemia) and the University of Wisconsin solution (8 h and 24 h ischemia). Eliminations were measured during two 40-min periods before and after ischemia; during each period, hyaluronic acid (150 ng/ml) and also, to evaluate hepatocyte function, propranolol (100 ng/ml) were infused into the reservoir. We show that, whatever the preservation solution or time used, liver endothelial cell function is altered to a larger extent than hepatocyte function. University of Wisconsin solution does not appear to protect liver endothelial cells during preservation, particularly after 24 h of cold ischemia. Hyaluronic acid elimination can be a useful tool in the investigation of an ideal preservation solution to protect liver endothelial cells from ischemia-reperfusion damage.
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PMID:Metabolism of hyaluronic acid by liver endothelial cells: effect of ischemia-reperfusion in the isolated perfused rat liver. 807 37

Local vasodilation in response to hypoxia or ischemia improves perfusion and O2 supply of the affected tissue. This local vasodilation thus constitutes the most important mechanism in the prevention of ischemic cell injury. The regulation of vascular tone has mainly been attributed to changes of cytoplasmatic Ca2+ ((Ca2+)i) concentrations in vascular smooth muscle cells. The mechanism underlying these changes has not, however, been elucidated so far. Using aortic strips of guinea pigs (transversally cut in spirals; normal Tyrode, in mM: NaCl 150, KCl 4.5, MgCl2 2, CaCl2 2.5, glucose 10; buffered with 10 mM HEPES at pH 7.4; equilibrated with 100% O2 at 31 degrees C) the authors could show that metabolic blockade (glucose replaced by 10 mM 2-deoxyglucose (DOG) led to a relaxation of the preparation. Thus, in four experiments, resting tension decreased from 0.75 g by 27% +/- 12% within two hours (% of maximal contractile force developed by each preparation when depolarized with 43 mM KCl and 101.5 mM NaCl). When the same experiment was carried out in the presence of 1 mM tolbutamide (a known blocker of ATP-dependent K+ channels) in vascular smooth muscle no such relaxation could be seen (n = 4). Furthermore, in the same type of preparation, similar results have been obtained upon hypoxic relaxation (100% O2 replaced by 100% N2), where 1 mM tolbutamide also prevented vasodilation. Thus, hypoxic/ischemic vasodilation in response to glycolytic inhibition (DOG) and hypoxia (N2) is based upon the opening of K+ ATP channels and hence can be prevented by sulfonylureas (the opening of K+ ATP channels would lead to hyperpolarization (increased K+ conductance, Goldmann equation), thus diminishing the open probability of voltage-gated Ca2+ channels with subsequent vasodilation). This inhibition by sulfonylureas of vasodilative response to ischemia may also constitute the so far unknown cause of the increased cardiovascular mortality seen under sulfonylurea treatment.
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PMID:Vasodilative response to hypoxia and simulated ischemia is mediated by ATP-sensitive K+ channels in guinea pig thoracic aorta. 844 33

We have studied the effects of adding 0.5 mmol/L CaCl2 to University of Wisconsin solution (0.08 mmol/L free Ca++) on hypothermic heart preservation. Isolated pig hearts were subjected to 8 hours of preservation at 12 degrees C; eight hearts were arrested with Ca++ free University of Wisconsin solution, and seven hearts were arrested with Ca(++)-containing University of Wisconsin solution. The recovery of contractile function was evaluated by measuring isovolumic ventricular pressure development. 31P nuclear magnetic resonance spectroscopy was used to monitor the changes in high-energy phosphates. Compared to the hearts arrested with the Ca(++)-free University of Wisconsin solution, the heart arrested with the Ca(++)-containing University of Wisconsin solution showed significantly improved (p < 0.001) contractile functional recovery. No "stone heart" or loss of high-energy phosphates was observed on reperfusion. The hearts showed an increase in diastolic pressure during infusion of the Ca(++)-containing University of Wisconsin solution, however, to show the relationship between the addition of calcium and the increase in diastolic pressure, a second protocol was performed. A 30-minute period of ischemia was induced in thirteen hearts that were arrested at 12 degrees C with either Ca(++)-containing University of Wisconsin solution (n = 8) or Ca(++)-free University of Wisconsin solution (n = 5). Diastolic pressure was monitored during ischemia while ventricular volume was maintained constant with a balloon. The hearts arrested with the Ca(++)-containing University of Wisconsin solution showed a mean rise of 5 mm Hg in diastolic pressure and a rapid decline of phosphocreatine (p < 0.001). Our results suggest that, although 0.08 mmol/L free Ca++ improves functional recovery after 8 hours of heart preservation with University of Wisconsin solution at 12 degrees C, it can increase diastolic pressure during ischemia and accelerate breakdown of the high-energy phosphate stores in the myocardium, suggesting that use of University of Wisconsin solution containing 0.5 mmol/L CaCl2 may result in a significant increase in the intracellular calcium level.
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PMID:The effects of Ca++ on the preservation of myocardial energy and function with University of Wisconsin solution. A 31P nuclear magnetic resonance study of isolated blood perfused Langendorff pig hearts. 844 6


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