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)

The effects of fenoldopam, a dopamine-1 (DA-1) receptor agonist, were studied in two groups of anesthetized dogs before and after induction of splanchnic ischemia by way of hemorrhage. During the first portion of the experiment, both groups received fenoldopam (1.5 microg x kg(-1) x min(-1)) for 45 min followed by a 45-min washout. During the second portion, hemorrhage (10 ml/kg) was induced, followed by no intervention in group I (controls) and restarting of the fenoldopam infusion in group II. Prehemorrhage, fenoldopam increased composite portal blood flow by 33% (P < 0.01). After hemorrhage-induced splanchnic ischemia, fenoldopam restored portal vein blood flow to near baseline, maintained the splanchnic fraction of cardiac output, and attenuated the rise in gut mucosal PCO(2). DA-1 receptor stimulation increased portal blood flow and redistributed blood flow away from the serosal layer in favor of the mucosa during basal conditions and after hemorrhage, suggesting a more concentrated distribution of splanchnic DA-1 receptors within the mucosal layer vasculature. Fenoldopam maintained splanchnic blood flow during hypoperfusion and attenuated the splanchnic vasoconstrictive response to hemorrhage.
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PMID:Dopamine-1 receptor stimulation attenuates the vasoconstrictive response to gut ischemia. 1145 70

Effects of a dopamine-1 (DA-1) receptor agonist on systemic and intestinal oxygen delivery (Do(2))-uptake relationships were studied in anesthetized dogs during sequential hemorrhage. Control (group 1) and experimental animals (group 2) were treated similarly except for the addition of fenoldopam (1.0 microg x kg(-1) x min(-1)) in group 2. Both groups had comparable systemic critical Do(2) (Do(2crit)), but animals in group 2 had a higher gut Do(2crit) (1.12 +/- 1.13 vs. 0.80 +/- 0.09 ml. kg(-1) x min(-1), P < 0.05). At the mucosal level, a clear biphasic delivery-uptake relationship was not observed in group 1; thus oxygen consumption by the mucosa may be supply dependent under physiological conditions. Group 2 demonstrated higher peak mucosal blood flow and lack of supply dependency at higher mucosal Do(2) levels. Fenoldopam resulted in a more conspicuous biphasic relationship at the mucosa and a rightward shift of overall splanchnic Do(2crit) despite increased splanchnic blood flow. These findings suggest that DA-1 receptor stimulation results in increased gut perfusion heterogeneity and maldistribution of perfusion, resulting in increased susceptibility to ischemia.
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PMID:Dopamine-1 receptor stimulation impairs intestinal oxygen utilization during critical hypoperfusion. 1239 58

Delayed renal allograft function (DGF) is a factor for acute rejection and chronic allograft nephropathy. Cold ischemia time (CIT) is associated with an increased in DGF. Twenty patients receiving allografts with CIT>12 were enrolled in a double-blinded, randomized (1:1), placebo-controlled study to assess vasodilatation with fenoldopam (Abbott; dopamine-1 receptor agonist) on DGF. Fenoldopam infusion began at arterial anastomosis at 0.025 microg/kg/min and titrated to 0.1 microg/kg/min continued for 48 h postop (PO). Immunosuppression included steriods, MMF, and calcinurin inhibitors begun 36 h PO. Antibody induction (AI) using antithymocyte globulin (rabbit) (AT-G(r); Sangstat) was added halfway through the study to African-Americans and for PRA>40%. The need for dialysis, cumulative urine output (UOP), and creatinine (Cr) at PO day 7, 14, and 30 were compared. Eighteen patients completed the study drug infusion. Demographics of groups were not different. There was no difference between fenoldopam and controls for dialysis, UOP at 48 and 72 h, or Cr at 7, 14, or 30 days. There was a difference in UOP when AI (n=7) was compared to non-AI (n=11). At 48 h non-AI UOP 4796+/-3284 ml compared to AI UOP 8960+/-5130 ml (p=0.050). At 72 h, non-AI patients had UOP of 6824+/-4547 ml compared to AI patients with UOP of 12196+/-5868 ml (p=0.044). There was a trend to a lower Cr at day 7 for AI 2.7+/-2.1mg/dl compared to 4.9+/-3.0 mg/dl in non-AI (p=0.11). There was no difference in dialysis or Cr at day 14 and 30 between the AI and non-AI patients. AI with AT-G(r) significantly increases UOP in allografts with CIT>12 h, whereas vasodilatation did not. Therapy for DGF may include AT-G(r) AI.
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PMID:Vasodilatation vs. immunotherapy to prevent delayed graft function: delayed graft function as an indication of immune activation. 1558 64

Low dose of dopamine is commonly used after kidney transplantation as a reno-protective agent, although its benefits are controversial. Dopamine may increase renal blood flow, decrease resistive index (RI), and induce urine output in normal kidneys. Many authors hypothesized that the vasculature of a denervated renal transplant may not respond to dopamine in the same fashion as healthy native kidneys, which led us to find other drugs to attenuate the ischemia-reperfusion (I/R) injury. Fenoldopam is a selective dopamine1 (DA1) receptor agonist, most of the activity of which resides in the R-enantiomer, which also shows weaker alpha 2-adrenoceptor antagonist activities. Fenoldopam produces a vasidilatory effect in vascular beds that are rich in vascular DA1 receptors, producing increased renal blood flow at doses that do not affect blood pressure. In addition to its renal vasodilator activity, fenoldopam is natriuretic, possibly resulting from a direct effect of DA1 receptors on the proximal convoluted tubule. In animals with spontaneous or drug-induced renal failure, fenoldopam improves renal function. The aim of this study was to investigate the possible effects of fenoldopan mesylate in recent kidney transplants. Creatinine, blood urea nitrogen, urine output, and renal vascular resistive index (IR) were measured using Doppler ultrasound. Two groups of patients with no statistical differences in demographic data were treated with dopamine or fenoldopan, showing no significant difference but a trend favoring the fenoldopan group.
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PMID:Dopamine "renal dose" versus fenoldopam mesylate to prevent ischemia-reperfusion injury in renal transplantation. 1618 14

Ischaemia-reperfusion injury (IRI) is a frequent event in kidney transplantation, particularly when the kidney comes from a deceased donor. The brain death is usually associated with generalized ischaemia due to a hyperactivity of the sympathetic system. In spite of this, most donors have profound hypotension and require administration of vasoconstrictor agents. Warm ischaemia after kidney vessels clamping and the cold ischaemia after refrigeration also reduce oxygen and nutrients supply to tissues. The reperfusion further aggravates the state of oxidation and inflammation created by ischaemia. IRI first attacks endothelial cells and tubular epithelial cells. The lesions may be so severe that they lead to acute kidney injury (AKI) and delayed graft function (DGF), which can impair the graft survival. The unfavourable impact of DGF is worse when DGF is associated with acute rejection. Another consequence of IRI is the activation of the innate immunity. Danger signals released by dying cells alarm Toll-like receptors that, through adapter molecules and a chain of kinases, transmit the signal to transcription factors which encode the genes regulating inflammatory cells and mediators. In the inflammatory environment, dendritic cells (DCs) intercept the antigen, migrate to lymph nodes and present the antigen to immunocompetent cells, so activating the adaptive immunity and favouring rejection. Attempts to prevent IRI include optimal management of donor and recipient. Calcium-channel blockers, l-arginine and N-acetylcysteine could obtain a small reduction in the incidence of post-transplant DGF. Fenoldopam, Atrial Natriuretic Peptide, Brain Natriuretic Peptide and Dopamine proved to be helpful in reducing the risk of AKI in experimental models, but there is no controlled evidence that these agents may be of benefit in preventing DGF in kidney transplant recipients. Other antioxidants have been successfully used in experimental models of AKI but only a few studies of poor quality have been made in clinical transplantation with a few of these agents and we still lack of unambiguous demonstration that pre-treatment with these antioxidants can attenuate the impact of IRI in kidney transplantation. Interference with the signals leading to activation of innate immunity, inactivation of complement or manipulation of DCs is a promising therapeutic option for the near future.
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PMID:Ischaemia-reperfusion injury: a major protagonist in kidney transplantation. 2433 82