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)

Isolated, paced, isovolumetrically beating piglet hearts (n = 37) underwent retrograde aortic perfusion with a crystalloid solution during three periods: 1) baseline (coronary perfusion pressure 60 mm Hg), 2) ischemia (coronary flow 10% of baseline for approximately 80 min), and 3) reperfusion (perfusion pressure returned to baseline). In one group of hearts, glycolysis (using 3H2O formation from [3H]glucose) was assessed. During baseline, peak systolic pressure (PSP) was 101.1 +/- 5.0 mm Hg, end diastolic pressure (EDP) 4.4 +/- 0.5 mm Hg, glycolysis 970.5 +/- 65.3 nmol/min/gwet, and myocardial glycogen 234.8 +/- 12.0 mumol/gdry. During ischemia, PSP decreased to 23.3 +/- 2.7 mm Hg, EDP increased to 12.3 +/- 0.7 mm Hg, myocardial glycogen decreased to 181.5 +/- 30.3 mumol/gdry, and lactate (approximately 154 mumol/gwet) and glycerol (approximately 930 nmol/gwet) were released. Myocardial contracture correlated with a decrease in lactate release. Glycolysis decreased to approximately 400 nmol/min/gwet and remained stable, accounting for approximately 50% of the lactate produced. During reperfusion, PSP recovered to 79.8 +/- 3.5 mm Hg, EDP 6.6 +/- 1.7 mm Hg, and glycolysis 1103.9 +/- 81 nmol/min/gwet. In a second group of hearts, with similar mechanical responses, glucose oxidation (using 14CO2 formation from [14C]glucose) was evaluated. During baseline, glucose oxidation was 165.4 +/- 15.9 nmol/min/gwet and correlated closely (r = 0.957) with mechanical activity. With ischemia, glucose oxidation decreased to approximately 17 nmol/min/gwet, yet accounted for approximately 42% of the ATP produced. Upon reperfusion, glucose oxidation returned to baseline values, but now correlated poorly (r = 0.574) with mechanical activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanical and metabolic characterization of ischemic contracture in the neonatal pig heart. 747 21

Protein kinase C (PKC) and the ATP-dependent K+ channel (KATP channel) have been implicated in the mechanism of ischemic preconditioning in animal models. This study investigated the role of KATP channels and PKC in preconditioning in human myocardium and whether KATP channels are activated via a PKC-dependent pathway. Right atrial trabeculae were superfused with Tyrode's solution and paced at 1 Hz. After stabilization, muscles underwent one of nine different protocols, followed by simulated ischemia (SI) consisting of 90 minutes of hypoxic substrate-free superfusion paced at 3 Hz and then by 120 minutes of reperfusion. Preconditioning consisted of 3 minutes of SI and 7 minutes of reperfusion. The experimental end point was recovery of contractile function after SI, presented here as percentage recovery (%Rec) of baseline function. %Rec was significantly improved by preconditioning by the KATP channel opener cromakalim (CK), and by the PKC activator 1,2-dioctanoyl-sn-glycerol (DOG) compared with nonpreconditioned controls when these treatments were given before the SI insult (control group, 29.5 +/- 3.6%; preconditioned group, 63.5 +/- 5.4%, CK-treated group, 52.9 +/- 3.1%; and DOG-treated group, 48.0 +/- 3.5%; P < .01). The effects of CK could be blocked by the KATP channel blocker glibenclamide (%Rec, 17.8 +/- 3.5%). Preconditioning could be blocked by the PKC antagonist chelerythrine (%Rec, 24.1 +/- 5.0%) and the KATP blocker glibenclamide (%Rec, 24.8 +/- 3.1%). The effects of DOG could also be blocked by glibenclamide (%Rec, 23.1 +/- 2.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does ischemic preconditioning in the human involve protein kinase C and the ATP-dependent K+ channel? Studies of contractile function after simulated ischemia in an atrial in vitro model. 755 38

A recent study demonstrated biochemical and structural alterations of peroxisomes in rat kidney after ischemia/reperfusion. We examined whether peroxisomes play any role in the pathophysiology of myocardial ischemia/reperfusion injury. Isolated perfused rat heart was made ischemic for 30 min by terminating coronary flow (CF), followed by 30-min reperfusion. Experiments were divided into two groups; the experimental group received 1-O-hexadecyl-Sn-glycerol (chimyl alcohol) (25, 50, and 100 microM) before ischemia, and the control group received an equivalent amount of saline. Two of the experimental groups (50 and 100 microM) demonstrated improved postischemic myocardial performance, as demonstrated by accelerated recovery in left ventricular developed pressure (LVDP) and CF, as well as reduction in the incidence of ventricular fibrillation (VF). However, because the heart rate (HR) was significantly reduced in the 100-microM chimyl alcohol group, subsequent studies were performed with 50 microM chimyl alcohol as the optimal dose. Chimyl alcohol (50 microM) also reduced cellular injury, as evidenced by reduced creatine kinase (CK) release, and decreased development of oxidative stress, as evidenced by reduced formation of malonaldehyde (MDA). Peroxisomal catalase activity was decreased in the control group after ischemia/reperfusion, and chimyl alcohol treatment restored the activity of the enzyme. Our results indicate that chimyl alcohol, a precursor of ether-linked phosphoglyceride biosynthesis, can reduce myocardial ischemia/reperfusion injury, possibly by restoring catalase activity and reducing oxidative stress through synthesis of ether lipids, suggesting a possible role of peroxisomal disorder in ischemia/reperfusion injury.
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PMID:Myocardial salvage by 1-O-hexadecyl-Sn-glycerol: possible role of peroxisomal dysfunction in ischemia reperfusion injury. 779 44

Brain cell swelling is a consequence of seizure, ischemia or excitotoxicity. Changes in light reflectance from cortical surface are now used to monitor brain activity but these intrinsic signals are poorly understood. The objectives of this study were first, to show that changes in light transmittance were correlated with cell volume and second, to image increases in light transmittance as they related to neuronal activation. Transverse hippocampal slices from the rat were used for the study. Brief exposure (4-6 min) to hypo-osmotic artificial cerebrospinal fluid (-40 mOsm) elevated light transmittance consistently and reversibly in most regions of the slice and particularly in CA1 dendritic regions. Neither zero-Ca2+ artificial cerebrospinal fluid nor tetrodotoxin altered the transmittance increase and its subsequent reversal, suggesting that it was dependent on osmolality but independent of synaptic transmission and neuronal firing. The amplitude of the CA1 population spike evoked from Schaffer collaterals increased concomitantly with the hypo-osmotic increase in light transmittance, providing evidence that the extracellular tissue resistance increased. Hyper-osmotic artificial cerebrospinal fluid (+40 mOsm) containing impermeant mannitol consistently lowered light transmittance and the amplitude of the population spike. Glycerol (+40 mOsm), which is cell permeant, did not have an affect. Taken together these observations indicate that osmotic challenge alters light transmittance by inducing changes in cell volume. Transmittance increases induced by hypo-osmotic artificial cerebrospinal fluid or 10 microM kainate were small in the CA1 cell body region compared to dendritic regions. Similarly, orthodromic stimulation of axons terminating in stratum oriens or in stratum radiatum evoked transmittance increases only in their respective postsynaptic areas. In contrast, the cell body region and its adjacent proximal-apical dendrites (both sites of action potential initiation) could display dramatic increases in light transmittance upon brief exposure to 20 mM K+. The response, which may represent neuronal damage, was blocked in tetrodotoxin. Antidromic stimulation evoked a weak response in these same proximal areas. We conclude that activity-dependent increases in light transmittance across brain slices primarily reveal glial and neuronal swelling associated with excitatory synaptic input and action potential discharge. The signal can be imaged in real time to reveal neuronal activation, not only among hippocampal areas, but among neuronal regions. Cell swelling is a known consequence of excessive neuronal discharge. Therefore, the imaging of changes in light transmittance across brain slices should prove useful in monitoring epileptiform and excitotoxic states.
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PMID:Imaging cell volume changes and neuronal excitation in the hippocampal slice. 783 Aug 84

1. We investigated the effect of efonidipine hydrochloride (NZ-105) against acute renal failure (ARF) in male Wistar rats. ARF was produced by ischemia or glycerol. 2. Ischemia-induced ARF was produced by right nephrectomy and clamping of the left renal artery for 60 min, followed by reperfusion. NZ-105 (20 mg/kg) was orally administered twice a day for 3 days before ARF. The plasma creatinine and urea nitrogen concentrations were markedly elevated in the ischemia ARF group on the 1st day, but the elevation was significantly suppressed by NZ-105 treatment. 3. Glycerol-induced ARF was produced by intramuscular injection of 50% (v/v) glycerol (10 ml/kg) in rats which were restricted to drinking water for 24 hr. NZ-105 (20 mg/kg) was orally administered twice a day for 3 days before ARF. NZ-105 significantly attenuated the severe impairment of creatinine and urea nitrogen clearances and the elevated fractional sodium excretion (FENa) caused by ARF. 4. In the kidney homogenate, NZ-105 (10(-6)-10(-4) M) inhibited lipid peroxidation induced by ascorbic acid and Fe or by NADPH and the inhibitory effect of NZ-105 was stronger than alpha-tocopherol, an antioxidant agent. NZ-105 (10(-5)-10(-3) M) showed radical scavenging action against diphenyl-p-picrylhydrazyl and galvinoxyl induced radicals. 5. These findings suggest that NZ-105 prevents the renal damage caused by the two kinds of ARF. Moreover, the inhibitory effects of NZ-105 against lipid peroxidation and radical formation may be one of the mechanisms involved in the prevention of ARF.
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PMID:Effects of efonidipine hydrochloride (NZ-105), a new calcium antagonist, against acute renal failure in rats. 789 60

The rationale for these experiments is that administration of L-carnitine and/or short-chain acylcarnitines attenuates myocardial dysfunction 1) in hearts from diabetic animals (in which L-carnitine levels are decreased); 2) induced by ischemia-reperfusion in hearts from nondiabetic animals; and 3) in nondiabetic humans with ischemic heart disease. The objective of these studies was to investigate whether imbalances in carnitine metabolism play a role in the pathogenesis of diabetic peripheral neuropathy. The major findings in rats with streptozotocin-induced diabetes of 4-6 weeks duration were that 24-h urinary carnitine excretion was increased approximately twofold and L-carnitine levels were decreased in plasma (46%) and sciatic nerve endoneurium (31%). These changes in carnitine levels/excretion were associated with decreased caudal nerve conduction velocity (10-15%) and sciatic nerve changes in Na(+)-K(+)-ATPase activity (decreased 50%), Mg(2+)-ATPase (decreased 65%), 1,2-diacyl-sn-glycerol (DAG) (decreased 40%), vascular albumin permeation (increased 60%), and blood flow (increased 65%). Treatment with acetyl-L-carnitine normalized plasma and endoneurial L-carnitine levels and prevented all of these metabolic and functional changes except the increased blood flow, which was unaffected, and the reduction in DAG, which decreased another 40%. In conclusion, these observations 1) demonstrate a link between imbalances in carnitine metabolism and several metabolic and functional abnormalities associated with diabetic polyneuropathy and 2) indicate that decreased sciatic nerve endoneurial ATPase activity (ouabain-sensitive and insensitive) in this model of diabetes is associated with decreased DAG.
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PMID:Neural dysfunction and metabolic imbalances in diabetic rats. Prevention by acetyl-L-carnitine. 795 1

The effects of glycerol and mannitol, as well as urea, on delayed neuronal death (DND) in the gerbil hippocampus were investigated. 20% solution of glycerol, mannitol and urea were prepared, and 6.5 ml/kg of each agent, or saline, was administered to male Mongolian gerbils intraperitoneally 30 min before ischemia. The animals were subjected to transient forebrain ischemia for 5 min. Seven days after the ischemic insult, the brains were fixed and stained for histopathological analysis. The number of normal neurons (neuronal density, ND) in a 1 mm linear length of hippocampal CA1 region was counted. ND of sham-operated group (n = 6) was 275.3 +/- 16.7 (mean +/- SD). ND in the saline-treated group (n = 6) was 14.8 +/- 5.0. ND of groups treated with glycerol (n = 6), mannitol (n = 6) and urea (n = 4) was 68.2 +/- 56.7 (p < 0.01), 52.8 +/- 54.4 (p < 0.01) and 12.0 +/- 2.5 (NS), respectively. The present study demonstrates that glycerol and mannitol have some protective effects against DND in the gerbil hippocampus, whereas urea has no effect.
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PMID:Comparison of the effects of glycerol, mannitol, and urea on ischemic hippocampal damage in gerbils. 797 79

The effects of acetyl-L-carnitine (ALCAR) treatment on brain energy state recovery and lactic acid levels following 20 min ischemia and 2, 24 and 48 h reperfusion were investigated by 31P and 1H-NMR spectroscopy. Transient forebrain ischemia was induced by four-vessel occlusion method in fed 6-month-old Fischer rats. ALCAR or saline was administered by intraperitoneal route immediately after 20 min ischemia and again at 1, 4, 24 and 30 h during reperfusion. Twenty-min severe forebrain ischemia was associated with a marked decrease in phosphocreatine (PCr) and ATP levels and a corresponding increase in lactic acid, inorganic phosphate (Pi), AMP, creatine, glycerol 3-phosphate and alanine levels. Following reperfusion, a general tendency to restore pre-ischemic metabolite levels was observed. However, after 2 h reperfusion in saline-treated rats, lactic acid and Pi levels remained significantly higher, while ATP levels were still significantly lower than in non-ischemic controls. On the contrary, in ALCAR-treated animals a complete recovery of all metabolites including Pi and ATP was observed, while PCr levels were even more elevated compared with those in saline-treated rats. Furthermore lactic acid content was significantly lower than that in both saline-treated and non-ischemic control rats. It is concluded that a potential therapeutic role may be claimed for ALCAR in the treatment of cerebral ischemia through mechanisms that include faster recovery and improvement of brain energy production as well as a decreased lactic acid content during early post-ischemic reperfusion.
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PMID:Effect of acetyl-L-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat--study by 13P- and 1H-NMR spectroscopy. 803 36

The present study investigated whether protein kinase C (PKC) plays a role in ischemic preconditioning in the rat heart. Chelerythrine, a specific antagonist of PKC, and 1,2-dioctanoyl-sn-glycerol (DOG), a diacylglycerol analogue and specific antagonist of PKC, were used to determine whether preconditioning could be blocked or triggered, respectively. Sprague-Dawley rats were anesthetized and instrumented for coronary occlusion and reperfusion. All animals were subjected to 45 minutes of regional ischemia (ISC) followed by 2.5 hours of reperfusion. The preconditioning protocol consisted of 5 minutes of ischemia and then 10 minutes of reperfusion. There were six groups: (1) control (group C, n = 5), (2) preconditioned and ISC (group PC, n = 6), (3) chelerythrine given 2 minutes before ISC (group CC, n = 5), (4) preconditioned and chelerythrine given 2 minutes before ISC (group PCC, n = 6), (5) DOG (dissolved in dimethylsulfoxide [DMSO]) given 10 minutes before ISC (group CD, n = 5), and (6) DMSO given 10 minutes before ISC (group DMSO, n = 3). The end point was infarct size measured using triphenyl tetrazolium chloride and expressed as a percentage of the volume at risk (I/R), measured with fluorescent particles. I/R was significantly reduced by preconditioning (group C, 58.6 +/- 5.0%; group PC, 32.7 +/- 6.3%; P < .01) and by the PKC agonist DOG, which reduced I/R to a similar extent as preconditioning (group C, 58.6 +/- 5.0%; group CD, 28.0 +/- 7.0%; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein kinase C. Its role in ischemic preconditioning in the rat. 806 29

Myocardial protection in the rabbit induced by ischemic preconditioning is thought to be adenosine receptor linked, but the signaling pathway responsible for the protection has yet to be identified. This study tests whether protein kinase C could be involved. Either of two inhibitors of protein kinase C, staurosporine (50 micrograms/kg) or polymyxin B (24 mg/kg), were administered to rabbits subjected to 30 min regional myocardial ischemia followed by 180 min reperfusion. Half of the rabbits were preconditioned while the other half served as nonpreconditioned controls. Nonpreconditioned hearts without drug or treated with staurosporine or polymyxin B resulted in 37.8 +/- 3.1, 40.5 +/- 2.8, and 42.0 +/- 7.0% infarction of the risk zone, respectively. Preconditioning limited infarct size to 7.3 +/- 2.7%. Both inhibitors blocked protection in preconditioned hearts with 36.2 +/- 2.7 and 40.9 +/- 2.5% of the risk zone infarcted, respectively. Activation of protein kinase C with 4 beta-phorbol 12-myristate 13-acetate (PMA) or with 1-oleyl-2-acetyl glycerol (OAG) mimicked preconditioning in buffer-perfused hearts. PMA (0.01 nmol/min) or OAG (10 nmol/min) for 5 min was followed by 10 min of washout. Infarct size after 30 min regional ischemia was limited in the PMA and OAG groups (6.4 +/- 1.4 and 11.7 +/- 3.3 vs. 28.0 +/- 4.5% in untreated controls) and was equipotent with ischemic preconditioning (11.8 +/- 2.2%). Polymyxin B also blocked protection from ischemic preconditioning in the isolated heart (33.0 +/- 5.0%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preconditioning protects ischemic rabbit heart by protein kinase C activation. 816 Aug 17


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