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

We have examined the effect of atrial natriuretic factor (ANF) administered with and without mannitol on renal function following ischemic injury in both the isolated erythrocyte-perfused rat kidney and in the rat in vivo. ANF, administered alone after 25 min ischemia in the isolated kidney, reversed postischemic vasoconstriction but did not improve glomerular filtration rate (GFR). Mannitol alone had no effect on either renal vascular resistance or GFR. However, in isolated kidneys treated with the combination of both ANF and mannitol following reflow, GFR (0.65 +/- 0.04 ml.min-1.g-1) was markedly improved compared with GFR in the untreated ischemia group (0.20 +/- 0.04 ml.min-1.g-1) and was not different from GFR in the nonischemic controls (0.68 +/- 0.05 ml.min-1.g-1). Comparable results were obtained in studies performed in vivo. In rats subjected to 45 min ischemia, GFR (0.15 +/- 0.05 ml/min) was reduced compared with the GFR in sham-operated animals (0.95 +/- 0.07 ml/min). ANF or mannitol administered alone following ischemia and reflow did not improve GFR compared with the untreated ischemic group. However, in rats subjected to ischemia and treated with a combination of ANF and mannitol postreflow, GFR (0.69 +/- 0.10 ml/min) was 4.6-fold higher than GFR in the untreated ischemic group. Thus the combination of ANF and mannitol appear to act synergistically to improve GFR following ischemic injury.
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PMID:Protective effect of atrial natriuretic factor and mannitol following renal ischemia. 214 16

Experiments were performed on rats to examine the cause of the vascular congestion that accompanies renal ischemia, and the potential role of cell swelling in its generation. Renal function and gross morphology were examined after reflow, whereas tissue morphometry was performed both before and after reflow in kidneys. Small doses of mannitol applied into the renal artery just before ischemia greatly reduced the incidence of vascular congestion and the depression of renal function. During ischemia the outwardly directed swelling of the proximal tubule depleted the interstitial and vascular space of the cortex and outer medullary outer stripe and the inwardly directed swelling of the thick ascending limb occluded the lumen. Mannitol reduced cell swelling, lessened the depletion of the interstitial and vascular space and eliminated the occlusion of the thick ascending limb. It is proposed that the loss of interstitial and vascular fluid during ischemia is the cause of the vascular congestion, which, in turn, is responsible for the poor perfusion and impaired renal function seen after ischemia.
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PMID:Vascular congestion in ischemic renal failure: the role of cell swelling. 249 26

This study tests the hypothesis that metabolic support of remote "nonischemic" myocardium during acute infarction will reverse the trend toward cardiogenic shock. Thirty-seven dogs underwent ligation of the left anterior descending coronary artery and 50% stenosis of the circumflex coronary artery. Irreversible ventricular fibrillation developed in 11 of them. The 26 survivors were observed for up to 6 hours; global and regional left ventricular function (cardiac index, stroke work index, ultrasonic crystals) and regional blood flow (radioactive microspheres) were measured. After 2 hours, eight dogs received an intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, coenzyme Q10, and 2-mercapto-propionyl-glycine for 4 hours. Five dogs received the mannitol infusion to raise serum osmolarity 30 mOsm. Four additional dogs received the intravenous substrate infusions over 4 hours without undergoing ischemia. The substrate infusion for 4 hours caused no change in regional or global cardiac function in the four control dogs. Three of nine untreated dogs died of cardiogenic shock, and progressive left ventricular power failure occurred in the six others (40% decrease in cardiac index, 50% decrease in stroke work index, p less than 0.05) because of persistent dyskinesia in the left anterior descending region (-40% of systolic shortening, p less than 0.05) and hypocontractility in the circumflex region (48% of control systolic shortening, p less than 0.05), despite normal transmural blood flow in the posterior left ventricular wall (76 ml/100 gm/min). In contrast, in treated dogs, hypercontractility recovered in the circumflex segment (138% of systolic shortening) and stroke work index rose to control levels (91%) without a change in regional blood flow. Mannitol infusion did not improve hemodynamics or avoid the development of progressive left ventricular power failure. We conclude that cardiogenic shock after myocardial infarction is due, in large part, to impaired ability of "nonischemic" myocardium to maintain hypercontractility. This limitation can be prevented by metabolic support of viable muscle, and the data imply that intravenous substrate infusions may be helpful before definitive treatment (i.e., coronary artery bypass grafting) is undertaken.
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PMID:Studies on prolonged acute regional ischemia. V. Metabolic support of remote myocardium during left ventricular power failure. 250 26

Abdominal aortic aneurysmectomy (AAA) results in thromboxane (Tx)A2 generation, a rise in mean pulmonary artery pressure (MPAP), leukopenia, and noncardiogenic pulmonary edema. This study tests whether mannitol, a hydroxyl radical scavenger, modifies these events. Patients received mannitol 0.2 g/kg (n = 14) or saline (n = 12) intravenously before infrarenal aortic clamping. With saline, 30 minutes after clamping, plasma TxB2 levels rose from 124 to 290 pg/mL (p less than 0.01), and MPAP rose from 19 to 27 mmHg (p less than 0.01). Aortic clamp release led to further increases in plasma TxB2 to 378 pg/mL (p less than 0.01) and MPAP to 34 mmHg (p less than 0.01). The white blood count (WBC) fell from 9800 to 4400/mm3 (p less than 0.01). Four to eight hours after surgery, physiologic shunting (Q[sc]S[xsc]/Q[sc]T[xsc]) rose from 9% to 20% (p less than 0.01) and peak inspiratory pressure (PIP) increased from 22 to 32 cmH2O (p less than 0.01). Chest radiography demonstrated pulmonary edema while the pulmonary wedge pressure was 12 mmHg, excluding left ventricular failure. By 24 hours pulmonary edema resolved and the PIP and PaO2 returned to baseline. Mannitol treatment relative to saline, during and after aortic clamping reduced plasma TxB2 levels to 155 and 198 pg/mL, respectively (p less than 0.01); MPAP to 21 and 26 mmHg (p less than 0.01); minimized the decline in WBC to 5850/mm3 (p less than 0.01), and the postoperative rise in Q[sc]S[xsc]/Q[sc]T[xsc] to 12%, and PIP to 28 cmH2O (both p less than 0.01). Chest radiography showed no pulmonary edema. Finally in vitro studies documented that mannitol 1 to 10(-4)M, but not dextrose, in a dose-dependent manner inhibited Tx synthesis by ADP-activated platelets. These data indicate that mannitol maintains pulmonary function after AAA by limiting ischemia-induced thromboxane synthesis.
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PMID:Pulmonary edema after aneurysm surgery is modified by mannitol. 1257 26

Energy reserves (TAN) and anaerobic substrates (glucose, glycogen) are lower in renal than in myocardial tissue. Euro-Collins-solution contains nearly 200 mmol/l glucose, while the HTK-solution of Bretschneider contains none. Therefore the influence of glucose on kidney lactate production, on energy reserves (TAN), intrarenal pH and on morphology during the protection of ischemic kidneys was analysed using either Euro-Collins-solution, or modified "Euro-Collins-solution", containing mannitol instead of glucose, or HTK-solution with and without the addition of 5, 10 and 20 mmol/l glucose. Glucose content changed during kidney perfusion with Euro-Collins-solution from about 60 to 800 mumol/gdw. While intrarenal pH decreased from 7.1 to 5.1 in Euro-Collins-kidneys during 420 min of ischemia at 25 degrees C, pH decreased to 6.7 with the modified, mannitol containing "Euro-Collins-solution". In HTK-protected kidneys intrarenal pH decreased with increasing glucose addition to the solution. Although Total Adenine Nucleotides are highest at the end of ischemia with Euro-Collins-solution, structural protection after the same ischemic stress was best in HTK-protected kidneys without glucose addition. We conclude that glucose stimulated lactate production, reduced interstitial pH in the kidney even in combination with a highly buffered solution and that it might cause greater membrane permeability leading to a structural deterioration. Mannitol seemed more appropriate than glucose in this respect, although other substances, which provide energy substrate and prevent structural damage, may exist.
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PMID:Effects of glucose in protected ischemic kidneys. 311 45

Isolated rat hearts (n = 15/group) were subjected to regional ischemia (10 min) and reperfusion (3 min). Mannitol (5, 11, 25, 50, 55, 61, or 75 mM included in the perfusate throughout) reduced reperfusion-induced sustained ventricular fibrillation (VF) from its control incidence of 93% (14/15) to 80, 80, 40, 27, 47, 80, and 80%, respectively. Addition of glucose (11 mM) potentiated this effect, VF now fell to 87, 47, 33, 7, 7, 7, 13, and 13%, respectively. However, 11 mM glucose alone exerted no antiarrhythmic effects. When hearts (n = 15/group) were perfused with identical osmotic loads of mannitol plus glucose (11 + 50, 50 + 11, 61 + 0, or 0 + 61 mM, respectively), very different antiarrhythmic effects were observed. When given throughout the experimental period, glucose alone (0, 11, 25, 50 or 61 mM) had no effect on the incidence of VF (93, 87, 47, 53, and 20%, respectively), but when glucose was added 2 min before reperfusion, improved protection was observed (VF: 93, 87, 40, 27, and 13%, respectively). Our results suggest that the osmotic and free-radical scavenging properties of hexoses are relatively unimportant in relation to their antiarrhythmic effects. The metabolic effects are complex, suggesting that low concentrations of glucose may be beneficial, whereas high concentrations may be detrimental.
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PMID:Reperfusion-induced arrhythmias: mechanisms of protection by glucose and mannitol. 312 50

Mannitol has been shown to exert a dose-dependent, antiarrhythmic effect in the rat heart during reperfusion following a brief period of regional myocardial ischemia. Isolated perfused rat hearts were used to determine whether this protective effect is direct (ie, operative during reperfusion) or indirect (ie, due to an action during ischemia). Hearts (12 in each group) were subjected to 5, 10, 20, 30 or 40 mins of regional ischemia which was induced by ligation of the left anterior descending coronary artery. Upon reperfusion 25%, 100%, 83%, 33% and 17%, respectively, of the hearts fibrillated and 8%, 92%, 58%, 17% and 17% remained in irreversible fibrillation for the duration of the reperfusion period. Addition of mannitol (50 mM, the optimal antiarrhythmic dose) to the perfusion fluid throughout the experiment (early administration) caused a shift of this 'bell-shaped' time-vulnerability curve to the right such that the highest incidence of arrhythmias occurred after 20 mins rather than 10 mins of ischemia. Similar shifts were seen in other indices of electrical instability. Regional ischemia caused a 40 to 45% reduction in coronary flow in all groups of hearts, with no significant difference between the control and the mannitol-treated series. Heart rate fell by a mean of 10 to 15% in all control hearts and by a similar extent in mannitol-treated hearts. In additional studies, mannitol (50 mM) was administered 2 mins before reperfusion and throughout the reperfusion period (late administration studies). In the mannitol-free control group 100% of the hearts exhibited fibrillation and 92% remained in fibrillation for the duration of the reperfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mannitol and reperfusion-induced arrhythmias: possible mechanisms of action in the isolated rat heart. 314 Oct 24

A study was made of protective effect of several drugs (mannitol, phenytoin, vitamin E and dexamethasone) against the deprivation of both glucose and oxygen from the bathing medium on electrical activities of guinea-pig hippocampal neurons in vitro. Using guinea-pig hippocampal slice, we recorded antidromic field potentials in the granular cell layer of the dentate gyrus with stimulating mossy fibers. "Ischemia" of a slice was achieved by substracting both glucose and oxygen from the perfusing medium. In standard medium, after 10 minutes of ischemia, field potentials had minimum recovery with an amplitude of 5% of control after 60 minutes in the standard medium. Mannitol treatment had no protective effect, but phenytoin, vitamin E and dexamethasone had clear dose-dependent effect. The protective effect was evaluated by recovery of field potential amplitude of the 60 minutes postischemic response and histological examination of the brain slice tissue. The degree of the histological damage was correlated with recovery of field potential. In this experiment we have demonstrated that phenytoin and vitamin E obviously have the protective action against ischemic neuronal damage in the guinea-pig hippocampal slice and the combined application of these drugs were more effective.
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PMID:[Protective effect of various agents against ischemic neuronal damage in guinea pig hippocampal neurons studied in vitro]. 314 4

The purpose of this study was to evaluate the effect of hyperosmolality on the performance of, and the collateral blood flow to, ischemic myocardium. The myocardial response to mannitol, a hyperosmolar agent which remains extracellular, was evaluated in anesthetized dogs. Mannitol was infused into the aortic roots of 31 isovolumic hearts and of 15 dogs on right heart bypass, before and during ischemia. Myocardial ischemia was produced by temporary ligation of either the proximal or mid-left anterior descending coronary artery. Mannitol significantly improved the depressed ventricular function curves which occurred with left anterior descending coronary artery occlusion. Mannitol also significantly lessened the S-T segment elevation (epicardial electrocardiogram) occurring during myocardial ischemia in the isovolumic hearts and this reduction was associated with significant increases in total coronary blood flow (P < 0.005) and with increased collateral coronary blood flow to the ischemia area (P < 0.005).THUS, INCREASES IN SERUM OSMOLALITY PRODUCED BY MANNITOL RESULT IN THE FOLLOWING BENEFICIAL CHANGES DURING MYOCARDIAL ISCHEMIA: (a) improved myocardial function, (b) reduced S-T segment elevation, (c) increased total coronary blood flow, and (d) increased collateral coronary blood flow.
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PMID:Improvement in myocardial function and coronary blood flow in ischemic myocardium after mannitol. 464 Sep 43

The effectiveness of postischemic reperfusion with mannitol has been well documented in previous studies. Mannitol, a hyperosmolar agent, is also an effective scavenger of the cytotoxic hydroxyl radical. If mannitol acts solely as a hyperosmolar agent, hyperosmolar reperfusion with its isomer, glucose, should be equally effective. To elucidate the beneficial effect of mannitol, 24 isolated rabbit heart preparations were subjected to 60 min of hypothermic (27 degrees C) cardioplegic arrest and normothermic reperfusion. There were three study groups with eight hearts in each. Group I hearts were reperfused with an unmodified isosmolar solution. Group II hearts were reperfused with a hyperosmolar (350 mOsm/liter) solution containing glucose, and group III hearts had hyperosmolar (350 mOsm/liter) reperfusion with mannitol. Left ventricular function (developed pressure and maximum positive dP/dt) was measured isovolumically before and after ischemia. Coronary flow was measured volumetrically during reperfusion, and myocardial edema formation was determined after 45 min of reperfusion. Reperfusion with mannitol resulted in significant improvement in recovery of developed pressure (77.3 +/- 2.8% of control vs 65.5 +/- 2.9% in group I and 62.6 +/- 2.2% in group II; p less than .05). Mannitol-treated hearts also had significantly greater coronary flow throughout the reperfusion period and significantly less marked myocardial edema formation compared with hearts treated with isosmolar and hyperosmolar glucose. These data confirm the particular usefulness of mannitol in improving postischemic ventricular function, maintaining coronary blood flow during early reflow, and reducing myocardial edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The mechanism of mannitol in reducing ischemic injury: hyperosmolarity or hydroxyl scavenger? 608 78


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