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

Several different edible oils were compared for their ability to modify eicosanoid biosynthesis following experimentally-induced myocardial ischemia and reperfusion in the rat. Two types of palm oil [neutralized, bleached, and deodorized (NBDPO) and refined, bleached, and deodorized (RBDPO)] and partially hydrogenated soybean oil (SBO) were tested against a diet supplemented with sunflower seed oil (SSO) rich in n-6 polyunsaturated fatty acids (PUFA). Fish oil (FO) rich in n-3 PUFA, with its known cardioprotective actions, served as an internal reference point for the study. Test oils were fed as a 12% (w/w) supplement for nine months before the induction of myocardial ischemia and reperfusion. Palm oil diets exerted effects indistinguishable from the SBO group against cardiac arrhythmia, which occurred following alterations to coronary blood flow. Arrhythmic potentials, as expressed by a hierarchical scale (0-9) of arrhythmia score, were: SSO, 1.5 +/- 0.5; FO, 0.9 +/- 0.4; SBO, 3.1 +/- 0.5*; NBDPO, 3.2 +/- 0.5*; RBDPO, 3.3 +/- 0.6*; *P < 0.05 vs. SSO. Following ischemia and reperfusion, both SSO and RBDPO groups tended to show an increase in myocardial prostacyclin, with the effect being more prominent in the RBDPO group (SSO, 10%; RBDPO, 25%). Thromboxane production was reduced in the FO group. Interestingly, cardiac muscle from both FO and palm oil groups displayed a reduced capacity to produce 12-hydroxyeicosatetraenoic acid SSO, 591 +/- 95.8; SBO, 375.5 +/- 48.9; NBDPO, 287.2 +/- 64.7*; RBDPO, 230.9 +/- 80.2**; FO, 203.7 +/- 81.4** (ng/g dry wt, *P < 0.05, **P < 0.01). No clear relationship was seen between the availability of 20:4n-6 in myocardial phospholipids and eicosanoid profile. Data suggests that fatty acid composition of edible oils is not the only determinant of arrhythmic vulnerability and eicosanoid production.
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PMID:Dietary lipid modification of myocardial eicosanoids following ischemia and reperfusion in the rat. 861 6

After a transient ischemic attack of the cardiac vascular system, reactive oxygen-derived free radicals, including the superoxide (O2-.) and hydroxyl (.OH) radicals can be easily produced during reperfusion. These free radicals have been suggested to be responsible for reperfusion-induced cardiac stunning and reperfusion-induced arrhythmia. Hydrogen peroxide (H2O2) is often used as an experimental source of oxygen-derived free radicals. Using freshly dissociated single rat cardiac myocytes and the rat cardiac myoblast cell line, H9c2, we have shown, for the first time, that an intriguing pHiota acidification (approximately 0.24 pH unit) is induced by the addition of 100 micromol/L H2O2 and that this dose is without effect on the intracellular free Ca2+ levels or viability of the cells. Using H9c2 as a model cardiac cell, we have shown that it is the intracellular production of .OH, and not O2-. or H2O2, that results in this acidification. We have excluded any involvement of (1) the three known cardiac pHi regulators (the Na+-H+ exchanger, the Cl--HCO3 exchanger, and the Na+-HCO3 co-transporter), (2) a rise in intracellular Ca2+ levels, and (3) inhibition of oxidative phosphorylation. However, we have found that H2O2-induced acidosis is due to inhibition of the glycolytic pathway, with hydrolysis of intracellular ATP and the resultant intracellular acidification. In cardiac muscle and in skinned cardiac muscle fiber, it has been shown that a small intracellular acidification may severely inhibit contractility. Therefore, the sustained pHi decrease caused by hydroxyl radicals may contribute, in some part, to the well-documented impairment of cardiac mechanical function (ie, reperfusion cardiac stunning) seen during reperfusion ischemia.
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PMID:Mechanism of hydrogen peroxide and hydroxyl free radical-induced intracellular acidification in cultured rat cardiac myoblasts. 863 13

Prolonged tissue ischemia and subsequent reperfusion results in significant tissue injury due to the ischemic-reperfusion (IR) syndrome. Ischemic preconditioning (IPC) or adenosine (ADO) pretreatment are known to protect IR injury in cardiac muscle. Our aim was to determine whether IPC or ADO pretreatment attenuates and protects against ischemic tissue reperfusion injury in skeletal muscle. Rats were anesthetized and global hindlimb ischemia was induced by 60 min of suprarenal aortic clamping followed by 30 min of reperfusion period. The degree of skeletal muscle dysfunction was determined by decreases in maximum contractile force, and adenosine triphosphate (ATP) and creatine phosphate (CP) levels of extensor digitorum longus (EDL) muscle. The distal tendon of the EDL was attached to a force transducer for maximum isometric force measurement. Samples were taken from the EDL for measurement of ATP and CP levels. The following were protective protocols prior to the IR challenge: (1) four consecutive 5-min periods of ischemia separated by 5-min reperfusion periods (PC/I) or (2) i.v. adenosine infusion (350 microg/kg/min x 10 min, PC/A). Our data suggest that pretreatment with brief periods of ischemia or systemic ADO infusion attenuates ischemic tissue reperfusion injury in skeletal muscle. [Table: see text]
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PMID:Preconditioning with ischemia or adenosine protects skeletal muscle from ischemic tissue reperfusion injury. 866 Nov 67

Rabbit, rat, and pigeon are species representative of three cardiac muscle mitochondrial ATPase regulatory classes, a, b and c, respectively. Class a species contain a full complement of higher affinity ATPase inhibitor subunit, IF1, in their cardiac muscle mitochondria and show marked IF1-mediated mitochondrial ATPase inhibition during myocardial ischemia. Class b species contain low levels of higher affinity IF1 and show very little IF1-mediated ATPase inhibition during ischemia. Class c species contain a full complement of a lower affinity form of IF1 and show a low-to-moderate level of IF1- mediated ATPase inhibition during ischemia. In the present study we perfused hearts of a member of each regulatory class through the coronary arteries with the uncoupler, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), before making them ischemic. We then compared net rates of cell ATP depletion during ischemia in the FCCP-treated hearts to identically treated FCCP-free hearts. Thus, we tested the relative capacities of cardiac muscle mitochondria of the three species to avert a potentially greatly increased net rate of cell ATP depletion due to ATP hydrolysis by the fully uncoupled mitochondrial ATPase. We found that FCCP-uncoupling in situ had a relatively small effect on ATP depletion during ischemia in rabbit hearts, that it dramatically accelerated ATP depletion in ischemic rat hearts, and that it had an intermediate effect on ATP depletion in ischemic pigeon hearts. These results demonstrate for the first time the relative extents to which IF1-mediated mitochondrial ATPase inhibition can slow cell ATP depletion due to the fully uncoupled mitochondrial ATPase in these three classes of hearts. They show that, in contrast to the situation in rabbit hearts, the low level of higher affinity IF1 present in the cardiac muscle mitochondria of the rat is, under these conditions, essentially nonfunctional, while the full complement of the lower affinity form of IF1 present in the cardiac muscle mitochondria of the pigeon is partially functional in that it appeared to provide an intermediate level of protection against rapid cell ATP depletion.
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PMID:IF1 function in situ in uncoupler-challenged ischemic rabbit, rat, and pigeon hearts. 879 81

A study was made of effects of transcardiac galvanization (TCG) on activities of a panel of oxidation-reduction enzymes as well as on the cardiac muscle content of high energy substrates, and size of the lesion area, in experimental myocardial infarction (EMI) in 50 albino male rats. After two TCG procedures, and at 24-h EMI, augmentation was found of activities of succinic dehydrogenase, lactate dehydrogenase, NADH-dehydrogenase, beta-hydroxybutyrate dehydrogenase, both in the area of profound ischemia and peri-infarction myocardium, this being accompanied with an increase in myocardial content of adenosine triphosphate, creatine phosphate, and glycogen, and reduction of the developing mass of necrosis. Stimulation of enzyme activity in the course on the enzyme complex and membrane-stabilizing action of this preformed physical factor.
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PMID:[The effect of transcardiac galvanization on energy metabolism and the size of the area of the heart muscle lesion in experimental myocardial infarct]. 884 53

The role of ischaemia in the pathogenesis of acute pancreatitis is unknown. Some experimental studies have shown that ischaemia has little effect on the pancreas, while others have found an association with pancreatic injury. Ischaemia-reperfusion damage has been well documented in other sites such as the intestine, cardiac muscle, and skeletal muscle. However, in the pancreas, injury is usually seen only after complete ischaemia, which is uncommon clinically. Experimental chronic pancreatitis is characterized by low pancreatic blood flow, low interstitial pH, and impaired pancreatic tissue oxygenation, which are all findings consistent with the ischaemia-reperfusion mechanisms. Acute pancreatitis is also associated with a reduction in pancreatic blood flow and evidence of free radical generation, similarly suggesting the possibility of ischaemia-reperfusion injury. Ethanol ingestion, which is commonly associated clinically with both chronic and acute pancreatitis, may itself contribute to an ischaemic-reperfusion injury. We have shown that administration of ethanol to cats decreases pancreatic blood flow and may also directly activate neutrophils. Further investigation is needed to determine whether or not these findings are also associated with an ischaemia-reperfusion injury.
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PMID:Ischaemia-reperfusion mechanisms in acute pancreatitis. 886 66

Prolonged tissue ischemia and subsequent reperfusion result in significant tissue injury due to the ischemic-reperfusion syndrome. Although skeletal muscle has significant tolerance to ischemic-reperfusion injury (IRI), compared to other organ systems, IRI of skeletal muscle does occur when there is a prolonged ischemic period. In many reconstructive surgical procedures involving microsurgery and prolonged tissue ischemia time, IRI-induced skeletal-muscle injury is a serious clinical concern. Specifically, there are significant vascular complications (venous thrombosis and arteriolar no-reflow) and loss of transplanted muscle function on reperfusion with prolonged ischemia. Ischemic preconditioning (IPC) or adenosine (ADO) pretreatment applied prior to the ischemic period are known to protect against IRI in cardiac muscle. Recent data from basic science research suggest that IPC or ADO pretreatment may be employed to protect skeletal muscle against IRI. This review summarizes the basic mechanisms and potential clinical relevance of ischemia- and reperfusion-induced skeletal muscle injury and describes how skeletal muscle can be protected against IRI with IPC or ADO pretreatment.
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PMID:Protection against ischemic-reperfusion injury of skeletal muscle: role of ischemic preconditioning and adenosine pretreatment. 886 78

The heart is known for its ability to produce energy from fatty acids (FA) because of its important beta-oxidation equipment, but it can also derive energy from several other substrates including glucose, pyruvate, and lactate. The cardiac ATP store is limited and can assure only a few seconds of beating. For this reason the cardiac muscle can adapt quickly to the energy demand and may shift from a 100% FA-derived energy production (after a lipid-rich food intake) or any balanced situation (e.g., diabetes, fasting, exercise). These situations are not similar for the heart in terms of oxygen requirement because ATP production from glucose is less oxygen-consuming than from FA. The regulation pathways for these shifts, which occur in physiologic as well as pathologic conditions (ischemia-reperfusion), are not yet known, although both insulin and pyruvate dehydrogenase activation are clearly involved. It becomes of strategic importance to clarify the pathways that control these shifts to influence the oxygen requirement of the heart. Excess FA oxidation is closely related to myocardial contraction disorders characterized by increased oxygen consumption for cardiac work. Such an increased oxygen cost of cardiac contraction was observed in stunned myocardium when the contribution of FA oxidation to oxygen consumption was increased. In rats, an increase in n-3 polyunsaturated FA in heart phospholipids achieved by a fish-oil diet improved the recovery of pump activity during postischemic reperfusion. This was associated with a moderation of the ischemia-induced decrease in mitochondrial palmitoylcarnitine oxidation. In isolated mitochondria at calcium concentrations close to that reported in ischemic cardiomyocytes, a futile cycle of oxygen wastage was reported, associated with energy wasting (constant AMP production). This occurs with palmitoylcarnitine as substrate but not with pyruvate or citrate. The energy wasting can be abolished by CoA-SH and other compounds, but not the oxygen wasting. Again, the calcium-induced decrease in mitochondrial ADP/O ratio was reduced by increasing the n-3 polyunsaturated FA in the mitochondrial phospholipids. These data suggest that in addition to the amount of circulating lipids, the quality of FA intake may contribute to heart energy regulation through the phospholipid composition. On the other hand, other intervention strategies can be considered. Several studies have focused on palmitoylcarnitine transferase I to achieve a reduction in beta-oxidation. In a different context, trimetazidine was suggested to exert its anti-ischemic effect on the heart by interfering with the metabolic shift, either at the pyruvate dehydrogenase level or by reducing the beta-oxidation. Further studies will be required to elucidate the complex system of heart energy regulation and the mechanism of action of potentially efficient molecules.
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PMID:Fatty acid oxidation in the heart. 889 66

The recirculation fraction (RF) of the activator Ca2+ of the cardiac muscle is an index of the fraction of the internally released Ca2+ sequestered by the sarcoplasmic reticulum during each contraction-relaxation cycle. Estimates of the RF were obtained by the slope method during the decline of the post-rest potentiation in the isolated aorta-perfused rat heart. Normalized contractile force P(max) of the second post-interval beat, B2, was plotted as a function of the first post-interval beat, B1, and fitted by a linear regression line. The correlation coefficient (r2) and the slope of the line were computed. Under the control experimental perfusion with oxygenated (95% O2-5% CO2) Krebs-Henseleit buffer ([Ca2+]0 1.25 mM, 34 degrees C, ph 7.40), the slope of the line, representing the RF of the rat left ventricle, was 0.73 +/- 0.01 (mean +/- SE) (r2 0.95 +/- 0.01). Increasing the stimulation frequency from 1 to 3.3 Hz produced a negative inotropic effect and significantly reduced the RF, to 0.17 +/- 0.02. Positive inotropic interventions significantly increased the RF, to 0.95 +/- 0.05 with [Ca2+]0 4 mM and to 0.92 +/- 0.04 with a 30% reduction in [Na+]0, whereas inhibition of Ca2+ release from the sarcoplasmic reticulum by ryanodine (1 microM) perfusion significantly reduced the RF, to 0.68 +/- 0.05 from the control ([Ca2+]0 2.5 microM) value of 0.81 +/- 0.05. These findings indicate that RF is a good index of the inotropic status of the rat heart. The time course of changes in RF after graded ischemia-reperfusion indicated a significant increase in the reperfusion RF between 30 and 60 min of ischemia accompanied by a significant rise in left ventricular end-diastolic pressure (LVEDP) and a significant fall in P(max), indicating an irreversible phase of the injury. During the reversible phase ( < 30 min) of the ischemia-reperfusion injury, no significant changes in RF were detected. It was concluded that RF, as derived from the simple interval-force relationship, is a good predictor of the reversible and irreversible phases of the myocardial ischemia-reperfusion injury and index of the extent of Ca2+ loading of the sarcoplasmic reticulum.
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PMID:Recirculation fraction of the activator Ca2+: index of the extent of Ca2+ loading of rat myocardium during ischemia-reperfusion. 896 47

The present study evaluates the activity of the Na/H antiport during cold ischemia and aims to determine its influence on cellular sodium. pH and volumes. Cellular parameters; volumes, sodium, pH and high energy phosphates, were measured by multinuclear NMR spectroscopy in rat hearts during 12 h of storage at 4 degrees C and reperfusion, along with functional parameters. Cell volumes were measured by 1H and 59Co NMR using the extracellular marker cobalticyanide, pH and energetics by 31P NMR and sodium compartmental distribution by 23Na NMR spectroscopy using the shift reagent Dy(TTHA)-3. Three storage solutions were applied: Krebs-Henseleit (containing 144 mM sodium, KH), a solution supplemented with 0.20 mM amiloride (KH-ami) and a solution containing 23 mM sodium and 242 mM mannitol (KH-man). Inhibition of the Na/H antiport with amiloride reduced the cellular sodium accumulation by 56%. The end-ischemic concentrations were 45 mM (KH-ami) and 77 mM (KH). Amiloride also reduced the extent of cell swelling by 53% from an end-ischemic volume of 3.56 ml/gdw (KH) to 2.97 ml/gdw (KH-ami), however cell swelling persisted in both groups at reperfusion (33% increase in cell water). The molar ratio of sodium and water cellular accumulation was constant: Na/H2O approximately 3.7 x 10(-3) throughout the whole storage period. Inhibition of the antiport was protective for the high energy phosphates during ischemia and reperfusion. In KH-ami the pH acidified after 6 h of storage to an end-ischemic value of 6.35 (pH = 6.50 in KH): this difference persisted after 60 min of reperfusion, pH = 6.98 in KH-ami and pH = 7.1 in KH. Storage in the low-sodium solution was disadvantageous for the high energy phosphates during ischemia and reperfusion with a recovery of pH to 6.92 when reperfused with KH. Hearts stored with amiloride or mannitol solution failed to resume contraction at reperfusion. It is concluded: (a) the antiport is active at 4 degrees C; (b) during ischemia it mediates sodium influx and contributes to cell swelling with minor effects on the cytosolic pH; (c) at reperfusion the antiport is active it participates in the extrusion of excess protons, but has a minor impact on sodium and water homeostasis; (d) inhibition of the antiport does not protect the cardiac muscle at low temperatures.
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PMID:The relation between cellular sodium, pH and volumes and the activity of Na/H antiport during hypothermic ischemia: multinuclear NMR studies of rat hearts. 901 42


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