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

The involvement of prostaglandins in the redistribution of renal cortical blood flow to inner cortical nephrons during hemorrhagic hypotension was studied in the pentobarbital-anesthetized dog. Total renal blood flow and distribution of renal cortical flow were determined with the radioactive microsphere technique by dividing the cortex into four zones of equal thickness, zone 1 being outermost and zone 4 being juxtamedullary. Two inhibitors of prostaglandin synthesis were used: indomethacin 8 mg/kg and aspirin 100 mg/kg. The inhibitor or the vehicle was given intravenously prior to a control period which was followed by a hemorrhage sufficient to decrease arterial pressure by about one-third. The distribution of cortical flow was determined before hemorrhage, during hemorrhagic hypotension, and after transfusion. In the vehicle-treated dogs, total renal blood flow was well maintained, but flow redistributed to favor the inner cortical nephrons. This vasodilation in the inner cortex was blocked by both inhibitors of prostaglandin synthesis resulting in a decrease in total renal blood flow and relative ischemia of the juxtamedullary nephrons. Salicylate levels required to accomplish blockage of inner cortical vasodilaton were less than 7 mg/100 ml. These studies indicate that prostaglandins are responsible for the decreased vascular resistance of the inner cortical nephrons which results in the redistribution of blood flow during hemorrhage, and when prostaglandin synthesis is blocked, the kidney vasculature constricts during hemorrhage.
 ...
PMID:Alteration of canine renal vascular response to hemorrhage by inhibitors of prostaglandin synthesis. 81 11

To elucidate the pathophysiological role of the hydroxyl radical (.OH) during the postischemic reperfusion of the heart, we measured the .OH product in the coronary effluent from isolated perfused rat heart during a 30-minute reperfusion period after various ischemic intervals of 5, 10, 15, 20, 30, and 60 minutes. Salicylic acid was used as the probe for .OH, and its derivative, 2,5-dihydroxybenzoic acid (2,5-DHBA), was quantified using high-performance liquid chromatography with ultraviolet detection. 2,5-DHBA was negligible in the effluent from nonischemic hearts, but a significant amount was detected from the hearts rendered ischemic for 10 minutes or longer. The peak of 2,5-DHBA was seen within 90 seconds after the onset of reperfusion in every group. The accumulated amount of 2,5-DHBA was maximal in the group with 15-minute ischemia (6.73 +/- 1.04 nmol/g wet heart wt after 30 minutes of reperfusion); it decreased as the ischemic time was prolonged and was 2.38 +/- 0.84 nmol/g wet wt after 30 minutes of reperfusion in the group with 60-minute ischemia. In the model of 15-minute ischemia/30-minute reperfusion, there was no correlation between the accumulated amount of 2,5-DHBA and functional recovery (+/- dP/dt, heart rate, and coronary flow), lactate dehydrogenase release, and morphological damage. Although treatment with 0.5 mM deferoxamine, an iron chelator, significantly decreased 2,5-DHBA (from 6.73 +/- 1.04 to 2.29 +/- 0.80 nmol/g wet wt after 30 minutes of reperfusion, p less than 0.01), it failed to reduce the postischemic myocardial injury in the group with 15-minute ischemia. The results suggest that .OH production is influenced by the preceding ischemic interval and that .OH does not exert an immediate direct effect on postischemic damage during early reperfusion in the isolated perfused rat heart, although a possibility remains that the small portion of .OH trapped by salicylic acid may not be intimately associated with myocardial injury.
 ...
PMID:Quantification of hydroxyl radical and its lack of relevance to myocardial injury during early reperfusion after graded ischemia in rat hearts. 131 98

To elucidate the significance of hydroxyl radical (.OH) in postischemic reperfusion injury, we measured the .OH production in the coronary effluent collected from isolated perfused rat hearts during reperfusion period of 15 minutes after various ischemic intervals ranging from 5 to 60 minutes. Salicylic acid was used as a probe for .OH formation, and its derivative, 2,5-dihydroxybenzoic acid (2,5-DHBA), was quantified using high performance liquid chromatography. A significant amount of 2,5-DHBA was detected from the hearts rendered ischemic for 10 minutes and longer. The peak of 2,5-DHBA was seen within 90 seconds after the onset of reperfusion in every group, and the accumulated amount of 2,5-DHBA was maximal in 15 minutes ischemia group (3.97 +/- 0.49 nmol/g/15 minutes reperfusion) in contrast to 1.22 +/- 0.30 nmol/g/15 minute in 60 minutes ischemia. This study demonstrated an ischemic time-dependent .OH production during reperfusion, and no direct effect of .OH was observed on the post-ischemic injury related to myocardial function.
 ...
PMID:Hydroxyl radical production during early reperfusion after different periods of ischemia in rat hearts and its effect on myocardial function. .OH in postischemic heart. 132 89

Recent studies have shown the ability of salicylic acid (SA) to trap hydroxyl radicals (OH.) generated during reperfusion in ischemic myocardium. Since OH. is implicated in the pathogenesis of reperfusion injury, we examined the effect of SA on reperfusion-induced arrhythmias and postischemic ventricular dysfunction. Isolated rat hearts perfused by the Langendorff technique were preperfused with Krebs-Henseleit buffer containing SA for 10 min. Hearts were then made ischemic for 30 min, followed by 30 min of reperfusion. In a separate group, SA was administered only at the onset of reperfusion. The left ventricular contractile functions, left ventricular developed pressure (LVDP) and its first derivative (LV dP/dt), coronary flow (CF), and creatine kinase (CK) release were determined before and after ischemia. Epicardial electrocardiogram (ECG) was also recorded to analyze the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF). SA improved LVDP, LV dp/dt, and CF recovery and reduced CK release compared to the control group. The incidence of VT and VF during reperfusion was also significantly reduced by SA. Analysis of tissue thiobarbituric acid-reactive products indicates that SA decreased oxidative stress during reperfusion. In conclusion, these results suggest that SA reduces myocardial reperfusion injury and attenuates ventricular arrhythmias by trapping OH. radicals upon reperfusion in isolated rat hearts.
 ...
PMID:Salicylate reduces ventricular dysfunction and arrhythmias during reperfusion in isolated rat hearts. 137 90

The present report describes a method suitable for the indirect assay of hydroxyl radical (OH.), which is likely to be produced during reperfusion of ischemic myocardium. Isolated rat heart perfused by the Langendorff technique was subjected to 30 min of ischemia, followed by 30 min of reperfusion. Salicylic acid (2 mM) was added to the perfusion circuit to trap any OH. radical generated during the experiment. 2,5- and 2,3-dihydroxybenzoic acids (hydroxylated products of salicylic acid) were identified by authentic standards as well as by pure OH.-generating system using high-performance liquid chromatography with electrochemical detection. In addition to serving as a chemical trap for the detection of OH., salicylate attenuated myocardial reperfusion injury as evidenced by reduced formation of creatine kinase, decreased lipid peroxidation, and improved myocardial contractile functions during reperfusion. These results thus provide direct evidence for the presence of OH. in heart and link it to the myocardial reperfusion injury.
 ...
PMID:High-performance liquid chromatographic detection of hydroxylated benzoic acids as an indirect measure of hydroxyl radical in heart: its possible link with the myocardial reperfusion injury. 164 29

The pathophysiology of cold injury was examined by cooling a hind leg of an anesthetized New Zealand white rabbit. A flow probe and a thermocouple were placed in the leg to be cooled to monitor the blood flow and tissue temperature. After baseline measurements, the leg was cooled with a freezing mixture up to 0 degrees C, which was followed by rewarming. The other leg served as control. In the experimental group, liposome-bound superoxide dismutase and catalase were infused through the femoral vein 15 minutes prior to putting the freezing mixture on the leg. Salicylic acid was injected through the femoral vein at the end of some experiments to assay hydroxy radical (OH). Our results demonstrated reduction of local blood flow in cold-exposed leg, indicating development of ischemia. Creatine kinase and lactage dehydrogenase were increased during rewarming in conjunction with hydroxyl radical formation, phospholipid breakdown, and lipid peroxidation. Treatment with superoxide dismutase and catalase reduced OH formation, prevented phospholipid degradation, and decreased creatine kinase, lactate dehydrogenase, and malonaldehyde formation. These results indicate that rewarming of cooled tissue is associated with "rewarming injury" similar to "reperfusion injury", and that oxygen-derived free radicals play a significant role in the pathophysiology of such injury.
 ...
PMID:Reduction of cold injury by superoxide dismutase and catalase. 164 16

The formation of hydroxyl radical in the post-ischemic reperfused heart was measured with high performance liquid chromatography and ultraviolet detection using salicylic acid. Hydroxyl radicals react with salicylic acid yielding 2,3- and 2,5-dihydroxybenzoic acid, which can be separated by the liquid chromatography. Isolated rat hearts were perfused with 1 mM salicylic acid and were subjected to 30 mins of global ischemia followed by aerobic or anaerobic reperfusion at 37 degrees C. The effluent from the hearts was collected at various intervals, extracted with ether, and injected into the high performance liquid chromatography unit. 2,5-dihydroxybenzoic acid was present only after aerobic reperfusion and was not detected before ischemia. The liquid chromatography peak of 2,3-dihydroxybenzoic acid was too small for quantitation. The concentration of 2,5-dihydroxybenzoic acid was the highest within 300 s of reperfusion. 2,5-dihydroxybenzoic acid was not detected in the ischemic hearts during anaerobic reperfusion. In ischemic hearts perfused with mannitol, the amount of 2,5-dihydroxybenzoic acid after reperfusion was reduced. These data suggest that hydroxyl radicals are produced in the post-ischemic reperfused heart and that the present method is useful and reliable for the measurement of hydroxyl radicals in the heart.
 ...
PMID:Detection of hydroxyl radicals in the post-ischemic reperfused heart using salicylate as a trapping agent. 165 47

Salicylic acid was used as a probe for .OH formed during reperfusion of the ischemic myocardium. .OH adds to the phenolic ring of salicylate to yield dihydroxybenzoic acid species. The two principal dihydroxybenzoic acids formed are the 2,3- and 2,5-derivatives and can be isolated and quantitated using HPLC combined with electrochemical detection. In these experiments, dihydroxybenzoic acids were detectable in the f molar range. Rat hearts were perfused in the Langendorff mode with Krebs-Henseleit buffer containing 100 microM salicylate. Following 20 min of global ischemia a 173% increase in tissue content of 2,5-dihydroxybenzoic acid was detected after 2.5 min of reperfusion. The duration of ischemia did not significantly affect tissue content of 2,5-dihydroxybenzoic acid peaked at 250 to 300% of control within 2.5 min of reperfusion. The inclusion of 100 microM salicylate in the perfusion buffer had no effect on myocardial function during the duration of the experiments. The results indicate that salicylate can be used as a very sensitive probe for .OH in the isolated ischemic heart.
 ...
PMID:Use of salicylate as a probe for .OH formation in isolated ischemic rat hearts. 217 99

Early thrombolytic therapy has been shown to reduce hospital mortality after myocardial infarction by 20-50%. This is achieved through reperfusion of the ischemic myocardium, which leads to limitation of infarct size by 15-30% and preservation of regional and global left ventricular function. Thrombolysis and reperfusion can be achieved by intravenous administration of streptokinase, urokinase, APSAC, or rt-PA, or by intracoronary administration of streptokinase or urokinase. Thrombolytic therapy is most effective in patients with extensive myocardial ischemia (large infarction) treated early after the onset of symptoms, but also patients with smaller infarcts may benefit from the therapy. It is uncertain whether treatment later than six hours after the onset of symptoms is beneficial, and if so, in which patients. Thrombolytic therapy leads to bleeding complications in a minority of patients. The risk of intracranial bleeding is approximately 0.5%. However, in several large trials the rate of cerebrovascular accidents (bleeding plus embolism) was not higher after thrombolytic therapy with streptokinase or rt-PA than after placebo. In order to prevent rethrombosis, additional treatment with acetyl salicylic acid and heparin is recommended. Nitrates and antiarrhythmic drugs are not recommended as routine practice. Immediate PTCA does not improve patient outcome. At present angiography and subsequent angioplasty or bypass surgery is recommended in patients with recurrent ischemia (spontaneous or upon exercise) after the infarct.
 ...
PMID:Thrombolytic therapy in acute myocardial infarction. 252 93

Although the presence of free radicals has been indicated in ischemic-reperfused heart, the exact nature and source of these free radicals are not known. The present study utilized a chemical trap, salicylic acid, to trap hydroxyl radical which could be detected as hydroxylated benzoic acid using high pressure liquid chromatography. Since the hydroxylated product is extremely stable, heart was subjected to subcellular fractionation after ischemia and reperfusion, and each fraction was separately examined for the presence of hydroxyl radical. The results indicated for the first time the presence of hydroxyl radical in the mitochondrial fraction during early reperfusion, which decreased in intensity as the reperfusion progressed.
 ...
PMID:Detection of hydroxyl radical in the mitochondria of ischemic-reperfused myocardium by trapping with salicylate. 255 44


1 2 3 4 5 Next >>