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)

This double-blind randomized trial assessed the effect of adding an intravenous continuous infusion of ketorolac to a patient-controlled analgesia (PCA) morphine regimen on analgesia, heart rate, arterial blood pressure, and postoperative myocardial ischemia. Patients having elective total hip or knee replacement were randomized to receive ketorolac 30 mg bolus, followed by an infusion of 5 mg/h for 24 h or placebo. All patients had access to PCA morphine (20 microg/kg bolus, with a lockout of 6 min). Patients were monitored for pain visual analog scale, blood pressure, heart rate, and ST segment depression via a continuous Holter monitor. ST depression of 1 mm 60 ms after the J point was considered significant if it lasted more than 1 min. There was no difference in demographics, risk factors, or cardiac medications between the groups. Ketorolac-treated patients had significantly better pain control at 2, 6, and 24 h. There was significant morphine sparing at all times after 3 h. There was no difference in the number of ischemic events between the groups. The ischemic episodes of the patients who received ketorolac occurred at slower heart rates (97 +/- 15 vs 114 +/- 16 bpm, P = 0.001) than those of patients in the placebo group. The duration of ST depression was shorter in ketorolac-treated patients (24 +/- 35 vs 76 +/- 95 min, P < 0.05). All ST depressions were clinically silent. Logistic regression of factors predicting ischemia included the use of calcium channel blockers and low pain score. These results suggest that analgesia with ketorolac reduces the duration of ischemic episodes in the first 24 h postoperatively.
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PMID:The addition of continuous intravenous infusion of ketorolac to a patient-controlled analgetic morphine regime reduced postoperative myocardial ischemia in patients undergoing elective total hip or knee arthroplasty. 908 43

The eicosanoids, leukotriene B4 (LTB4) and thromboxane A2 (TXA2), contribute to neutrophil adhesion and arteriole vasoconstriction, important microcirculatory events in ischemia-reperfusion (I-R) injury. The purpose of this study was to evaluate the effect of ketorolac on I-R injury of skeletal muscle. A videomicroscopic preparation of gracilis muscle in male Wistar rats (n=7) in two experimental groups was evaluated: Group 1-4 hr global ischemia only (19 arterioles, 19 venules), and Group 2-4 hr ischemia plus ketorolac (13 arterioles, 14 venules). Ketorolac (0.86 mg/kg, i.m.) was given 30 min prior to reperfusion. The number of neutrophils, rolling and adherent, was counted in 100-micron venular segments, and arteriole diameters were measured at 5, 15, 30, 60 and 120 min of reperfusion. The I-R-induced increase in neutrophil adhesion was significantly reduced by ketorolac, which significantly increased arteriolar vasodilation in the first 30 min of reperfusion and significantly reduced the I-R-induced vasoconstriction in arterioles at 30 min; this effect was lost at 1 hr of reperfusion. Although ketorolac augments immediate arteriole vasodilation and blocks subsequent vasoconstriction, this effect appears to be transient. These findings suggest that ketorolac may have potential as a treatment for I-R injury.
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PMID:Effect of ketorolac tromethamine (Toradol) on ischemia-reperfusion injury in skeletal muscle. 959 Jun 20

Animal studies suggest that prostaglandins in skeletal muscles stimulate afferents and contribute to the exercise pressor reflex. However, human data regarding a role for prostaglandins in this reflex are varied, in part because of systemic effects of pharmacological agents used to block prostaglandin synthesis. We hypothesized that local blockade of prostaglandin synthesis in exercising muscles could attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing exercise. Blood pressure (Finapres), heart rate, and MSNA (microneurography) were assessed in 12 young healthy subjects during static handgrip and postexercise muscle ischemia (PEMI) before and after local infusion of 6 mg of ketorolac tromethamine in saline via Bier block (regional intravenous anesthesia). In the second experiment (n = 10), the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased the prostaglandins synthesis to approximately 33% of the baseline. After ketorolac Bier block, the increases in MSNA from the baseline during the fatiguing handgrip was significantly lower than that before the Bier block (before ketorolac: Delta502 +/- 111; post ketorolac: Delta348 +/- 62%, P = 0.016). Moreover, the increase in total MSNA during PEMI after ketorolac was significantly lower than that before the Bier block (P = 0.014). Saline Bier block had no similar effect. The observations indicate that blockade of prostaglandin synthesis attenuates MSNA responses seen during fatiguing handgrip and suggest that prostaglandins contribute to the exercise pressor reflex.
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PMID:The role of the cyclooxygenase products in evoking sympathetic activation in exercise. 1760 32

Passive muscle stretch performed during a period of post-exercise muscle ischemia (PEMI) increases muscle sympathetic nerve activity (MSNA), and this suggests that the muscle metabolites may sensitize mechanoreceptors in healthy humans. However, the responsible substance(s) has not been studied thoroughly in humans. Human and animal studies suggest that cyclooxygenase products sensitize muscle mechanoreceptors. Thus we hypothesized that local cyclooxygenase inhibition in exercising muscles could attenuate MSNA responses to passive muscle stretch during PEMI. Blood pressure (Finapres), heart rate, and MSNA (microneurography) responses to passive muscle stretch were assessed in 13 young healthy subjects during PEMI before and after cyclooxygenase inhibition, which was accomplished by a local infusion of 6 mg ketorolac tromethamine in saline via Bier block. In the second experiment, the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased prostaglandin synthesis to approximately 34% of the baseline. Before ketorolac Bier block, passive muscle stretch evoked significant increases in MSNA (P < 0.005) and mean arterial blood pressure (P < 0.02). After ketorolac Bier block, passive muscle stretch did not evoke significant responses in MSNA (P = 0.11) or mean arterial blood pressure (P = 0.83). Saline Bier block had no effect on the MSNA or blood pressure response to ischemic stretch. These observations indicate that cyclooxygenase inhibition attenuates MSNA responses seen during PEMI and suggest that cyclooxygenase products sensitize the muscle mechanoreceptors.
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PMID:Cyclooxygenase inhibition attenuates sympathetic responses to muscle stretch in humans. 1844 Nov 94

We and others have demonstrated a rapid and dramatic increase in brain prostanoids upon decapitation-induced brain global ischemia and injury. However, the mechanism for this induction, including the cell types involved, are unknown. In the present study, we have validated and applied a pharmacological approach to inhibit prostanoid synthesis in the blood-brain barrier including endothelial cells. Our results indicate that a nonspecific cyclooxygenase (COX) inhibitor, ketorolac, does not pass the blood-brain barrier and does not enter red blood cells but penetrates endothelial cells. Ketorolac treatment did not affect basal prostanoid levels but completely prevented prostanoid induction upon global ischemia. These data indicate that basal prostanoids are synthesized in brain parenchyma cells, while inducible prostanoids are synthesized in the blood-brain barrier, most likely in endothelial cells. However, future studies with cell and COX isoform-specific gene ablation are needed to further validate this conclusion. These findings identify endothelial cells as a possible target for the development of pharmacological approaches to selectively attenuate inducible prostanoid pools without affecting basal levels under brain ischemia, trauma, surgery, and other related conditions.
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PMID:Blood-Brain Barrier Is the Major Site for a Rapid and Dramatic Prostanoid Increase upon Brain Global Ischemia. 3181 37