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

We have investigated the early effects of hypothyroidism on cardiac function and tolerance to hypothermic ischemia. Hypothyroidism was induced by thyroidectomy. Five days after operation, sham-operated and thyroidectomized rats were anesthetized and cardiac function was assessed. At this time, the plasma levels of triiodothyronine and thyroxine had fallen by eightfold and threefold, respectively, in thyroidectomized rats compared with the values in sham-operated rats. In vivo pump function was assessed by measuring mean arterial pressure, cardiac index, and stroke volume index: all were reduced by thyroidectomy (respectively 95 +/- 5 mmHg, 22 +/- 2 ml/min/100 gm body weight and 67 +/- 7 microliters/beat/100 gm body weight versus 112 +/- 4 mm Hg, 35 +/- 1 ml/min/100 gm body weight and 85 +/- 4 microliters/beat/100 gm body weight in the sham-operated group; p < 0.05 in each instance). Systemic vascular resistance index was higher in thyroidectomized than in sham-operated rats (4.4 +/- 0.4 versus 3.1 +/- 0.2 mmHg/ml/min/100 gm body weight; p < 0.05). In vivo indices of contractile function were also reduced by thyroidectomy: maximum rate of left ventricular pressure development fell by almost 50% (5190 +/- 790 versus 9600 +/- 900 mmHg/sec; p < 0.05) and left ventricular developed pressure and heart rate also fell (respectively 92 +/- 8 mmHg and 340 beats/min versus 129 +/- 6 mmHg and 398 +/- 6 beats/min; p < 0.05 in each instance). After excision, hearts were blood-perfused and ex vivo function assessed with intraventricular balloons. Systolic and diastolic functions were significantly impaired in the thyroidectomized group and the myocardial Na(+)-K(+)-adenosinetriphosphatase activity was reduced from a control value of 8.3 +/- 0.3 to 5.8 +/- 0.4 mean integrated extinction x 100. The hearts were then subjected to 2 minutes of cardioplegic infusion, 6 hours of hypothermic (4 degrees C) ischemia, and 40 minutes of reperfusion. In control hearts, left ventricular developed pressure (at an end-diastolic pressure of 8 mm Hg) recovered to 76% of its preischemic value (131 +/- 8 versus 173 +/- 8 mmHg; p < 0.05); in hearts from thyroidectomized rats, left ventricular developed pressure recovered to 81% of its preischemic value (110 +/- 8 versus 136 +/- 12 mmHg; p = not significant), an absolute value that was not significantly different from that in the sham-operated group. Diastolic function recovered to the same extent in both groups.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Early effects of hypothyroidism on the contractile function of the rat heart and its tolerance to hypothermic ischemia. 812 12

The protective effect of ATP-MgCl2 on ischemia-reperfusion lung injury has been reported in kidney, liver, heart, and muscle but has not been examined in lungs. The aim of this study was to determine whether ATP or ATP-MgCl2 pretreatment would attenuate ischemia-reperfusion-induced acute lung injury and to identify the possible mechanisms for such protection. Typical acute lung injury was successfully induced in Sprague-Dawley rats by 10 min of hypoxia followed by 75 min of ischemia and 50 min of reperfusion. Pretreatment with ATP-MgCl2 (or adenosine) but not ATP or MgCl2 (all at 10(-6) M) significantly attenuated the acute lung injury. All the protective effects of ATP-MgCl2 were nearly undetectable when promazine (an ecto-adenosinetriphosphatase inhibitor) or 3,7-dimethyl-1-propargylxanthine (an A2-receptor antagonist) was added before ATP-MgCl2 pretreatment. These observations support our hypothesis that the protective effect of ATP-MgCl2 is in part mediated through adenosine, the degradation product of ATP, which is produced by the Mg(2+)-dependent ecto-adenosinetriphosphatase on the surface of neutrophils and reacts with neutrophil A2 receptors to inhibit the production of O2 radicals.
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PMID:Ischemia-reperfusion lung injury attenuated by ATP-MgCl2 in rats. 817 61

We have previously demonstrated using immunocytochemical, histochemical, and biochemical techniques that ischemia in vivo and ATP depletion in vitro result in dissociation of Na(+)-K(+)-adenosinetriphosphatase (ATPase) from the actin cytoskeleton and redistribution to the apical domain in renal proximal tubule cells. To directly evaluate whether apical Na(+)-K(+)-ATPase retained Na+ pumping activity, a rapidly reversible model of cellular ATP depletion in confluent LLC-PK1 cells grown on semipermeable membranes was utilized. Tight-junction integrity, monitored by electrical resistance, was lost during ATP depletion and reestablished during 2 h of ATP repletion. Total cellular Na(+)-K(+)-ATPase activity and total surface membrane [3H]ouabain binding remained constant, but specific apical [3H]ouabain binding increased (7 vs. 26 fmol/filter, P < 0.01). Apical [3H]ouabain binding returned to baseline during 5 h of ATP repletion. Apically applied ouabain was then used to selectively inhibit apical Na(+)-K(+)-ATPase. It had no effect on apical-to-basolateral Na+ flux under physiological conditions (1.3 +/- 0.61 vs. 1.27 +/- 0.46 meq.filter-1.30 min-1), but it increased the apical-to-basolateral flux in ATP-depleted and then repleted monolayers (0.39 +/- 0.12 vs. 0.83 +/- 0.27 meq.filter-1.30 min-1, P < 0.01), implying that apical Na(+)-K(+)-ATPase retained Na+ pumping activity. Together, these data imply that ATP depletion induces loss of surface membrane polarity resulting in redistribution of functional proteins to the alternate domain.
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PMID:Na(+)-K(+)-ATPase that redistributes to apical membrane during ATP depletion remains functional. 823 49

Pressure overload left ventricular (LV) hypertrophy (LVH) induces ventricular dysfunction during stress, which is commonly attributed to diminished myocardial capillary density and ischemia. Immature hearts with LVH have a normal coronary flow reserve and capillary density. The purpose of this study was to determine 1) whether young lambs with LVH had an abnormal response to chronotropic stress, 2) whether nonischemic mechanisms contributed to the abnormal response, and 3) whether the age at which LVH was induced affected the response. We assessed LV endomyocardial function, perfusion, and Ca(2+)-adenosinetriphosphatase (ATPase) mRNA levels in chronically instrumented lambs with and without LVH and adult sheep with and without LVH. Rapid pacing induced diastolic dysfunction, increased time constant of isovolumic relaxation using an iterative fit (tM), and elevated LV diastolic pressures in young lambs and adult sheep with LVH. During pacing, tM was greater in the adult sheep with LVH than in the young lambs with LVH. Ca(2+)-ATPase mRNA levels were 79% less in adult sheep with LVH than in those without. Ca(2+)-ATPase mRNA levels in lambs with and without LVH and adult sheep without LVH were similar. Diastolic dysfunction occurred in the absence of subendomyocardial hypoperfusion, suggesting a nonischemic mechanism. In adult sheep with LVH diastolic dysfunction was associated with a marked reduction in Ca(2+)-ATPase mRNA levels.
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PMID:Response of the hypertrophied left ventricle to tachycardia: importance of maturation. 845 97

The present study aims to determine the volume-related activities of sodium ion transporters in the rat heart. Intracellular volumes were measured in isolated hearts by 1H of water and 59Co nuclear magnetic resonance (NMR) of the extracellular marker cobalticyanide. Inhibition of the Na-K-adenosinetriphosphatase pumps with 50 microM ouabain did not affect the extent of cellular swelling during 30 min of ischemia: cells swelled by 0.37 ml/g dry wt compared with the controls (0.38 ml/g dry wt). After perfusion with 400 microM ouabain or 200 microM iodoacetate, the cells shrank during ischemia (from 2.50 +/- 0.06 to 2.20 +/- 0.09 and 2.28 +/- 0.07 ml/g dry wt, respectively). Inhibition of passive sodium ion transporters reduced cellular swelling during ischemia: pretreatment (10 min) with 100 microM furosemide (Na-K-2Cl cotransport), 1.5 microM ethylisopropylamiloride (Na/H antiport), and 50 microM lidocaine (sodium channels) led to swelling of 0.27, 0.21, and 0.13 ml/g dry wt, respectively. The extent of cellular water accumulation was apparently correlated with the onset and maximal force of the ischemic contracture, unlike the data of hearts treated with ouabain and iodoacetate. The blockage of each of the passive sodium transporters improved the recovery of intracellular volumes at reperfusion, indicating that in the heart these pathways are responsible for the sustained reperfusion cellular edema. It is concluded that acute cellular swelling during myocardial ischemia is not caused by insufficiency of the Na-K pumps but is partially mediated by systems that transport sodium into the cells.
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PMID:Volume-related activities of sodium ion transporters: multinuclear NMR studies of isolated rat hearts. 876 Jan 63

We studied the effects of acidic reperfusion on 1) the incidence of ventricular fibrillation (VF) and 2) sarcolemmal Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity. Isolated rat hearts (n = 12/group) were subjected to independent perfusion (15 min) of left and right coronary beds with pH 7.4 buffer followed by zero-flow ischemia (10 min) of the former bed. This was then reperfused for 5 min, with acidic (pH 6.6) buffer for the first 0 (control), 0.5,1,2, or 4 min and with pH 7.4 buffer thereafter. In the control group, 92% of hearts developed VF within 20 s of reperfusion and remained in VF. In the 0.5-, 1-, 2-, and 4-min acidic reperfusion groups, only 17, 17, 42, and 25% of hearts (P < 0.05 vs. control for all groups), respectively, exhibited VF during acidic reperfusion. However, on switching to pH 7.4, VF occurred in a further 50, 58, 0, and 0% of hearts, respectively; thus the overall incidences of VF were 67, 75, 42 (P < 0.05 vs. control), and 25% (P < 0.05 vs. control), respectively. Additional hearts (n = 8/group) were used for cytochemical determination of sarcolemmal Na(+)-K(+)-ATPase activity in both the ischemic/reperfused left ventricular (LV) and the nonischemic right ventricular (RV) free walls. Ischemia (10 min) reduced LV Na2(+)-K(+)-ATPase activity from 110 +/- 8 to 25 +/- 3% of the RV value. After 0.5, 1, 2, 3, and 4 min of acidic reperfusion, LV Na(+)-K(+)-ATPase activity was 24 +/- 3, 29 +/- 3, 37 +/- 5, 55 +/- 6, and 70 +/- 4, respectively (P < 0.05 vs. 10-min ischemia). No significant recovery of LV Na(+)-K(+)-ATPase activity occurred following up to 4 min of pH 7.4 reperfusion. In conclusion, 1) at least 2 min of acidic reperfusion is required to achieve sustained protection against VF and 2) the protective mechanism may involve enhanced recovery of Na(+)-K(+)-ATPase activity as well as inhibition of Na+ influx.
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PMID:Effects of acidic reperfusion on arrhythmias and Na(+)-K(+)-ATPase activity in regionally ischemic rat hearts. 878 Jan 91

Mitochondrial F1F0 adenosinetriphosphatase (ATPase) is responsible for the majority of ATP synthesis during normoxic conditions, but under ischemic conditions it accounts for significant ATP hydrolysis. A previous study showed that preconditioning in isolated rat hearts is mediated by inhibition of this ATPase during ischemia. We tested this hypothesis in our isolated rat heart model of preconditioning. Preconditioning was accomplished by three 5-min periods of global ischemia separated by 5 min of reperfusion. This was followed by 20 min of global ischemia and 30 min of reperfusion. Preconditioning significantly enhanced reperfusion contractile function and reduced lactate dehydrogenase release but paradoxically reduced the time to onset of contracture during global ischemia. Myocardial ATP was depleted at a faster rate during the prolonged ischemia in preconditioned than in sham-treated hearts, which is consistent with the reduced time to contracture. ATP during reperfusion was repleted more rapidly in preconditioned hearts, which is consistent with their enhanced contractile function. Preconditioning significantly reduced lactate accumulation during the prolonged ischemia. We were not able to demonstrate that mitochondrial F1F0 ATPase (measured in submitochondrial particles) was inhibited by preconditioning before or during the prolonged ischemia. The mitochondrial ATPase inhibitor oligomycin significantly conserved ATP during ischemia and increased the time to the onset of contracture, which is consistent with inhibition of the mitochondrial ATPase. Our results show that preconditioning in rat hearts can be independent of mitochondrial ATPase inhibition as well as ATP conservation.
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PMID:Preconditioning in rat hearts is independent of mitochondrial F1F0 ATPase inhibition. 945 56


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