Lake Louise Consensus Conference on Cyclosporin Monitoring in Organ Transplantation: Report of the Consensus Panel

Oellerich, Michael; Armstrong, Victor W.; Kahan, Barry D.; Shaw, Les; Holt, D W; Yatscoff, R.; Lindholm, Annika; Halloran, Philip F.; Gallicano, Keith; Wonigeit, K.; Schütz, Ekkehard; Schran, Horst; Annesley, Thomas M.

doi:10.1097/00007691-199512000-00017

Cited by 223 publications

(74 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The cyclosporine doses and blood concentrations that produced significant reduction of the area of infarction are comparable with those obtained in/desired in patients after heart transplantation (Oellerich et al, 1995). In conclusion, cyclosporine, in a dose-dependent fashion, induced depression of the cardiac energy metabolism before occlusion and decreased infarct size in a rat coronary occlusion model.…”

Section: Cardiac Effects Of Cyclosporine 1127supporting

confidence: 74%

“…We also measured cyclosporine concentrations in the remote nonischemic myocardium, the area at risk, and the infarcted area by using a highly specific and sensitive, validated HPLC/MS assay. Since cyclosporine oral bioavailability is known to be erratic and variable (Oellerich et al, 1995), we also measured cyclosporine blood concentrations. Our study Fig.…”

Section: Csamentioning

confidence: 99%

See 1 more Smart Citation

Close Association Between the Reduction in Myocardial Energy Metabolism and Infarct Size: Dose-Response Assessment of Cyclosporine

Niemann

Saeed²,

Akbari³

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Cyclosporine protects the heart against ischemia/reperfusion injury, but its effect on cardiac metabolism is largely unknown. We assessed cyclosporine-induced metabolic changes in the rat heart prior to occlusion using magnetic resonance spectroscopy (MRS) and correlated effects with infarct size in a coronary occlusion/reperfusion model. The two study groups were cyclosporine and cyclosporine ϩ coronary occlusion (n ϭ 20/ group). Rats were pretreated with cyclosporine (5, 10, 15, and 25 mg/kg/day) or the vehicle by oral gavage for 3 days (n ϭ 4/dose). On day 4, hearts of rats in the cyclosporine group were excised, and extracted cell metabolites were measured using 1 H and 31 P MRS. The second group was subjected to 30 min of coronary artery occlusion followed by 24 h of reperfusion. Infarct size and area at risk were measured using a double staining method. In the cyclosporine group, cyclosporine reduced cardiac energy metabolism (ATP: r ϭ Ϫ0.89, P Ͻ 0.001) via depression of oxidative phosphorylation and the Krebs' cycle in a dose-dependent manner. The decrease of ATP levels was positively correlated with changes of NAD ϩ (r ϭ 0.89), glutamate (r ϭ 0.95), glutamine (r ϭ 0.84), and glucose concentrations (r ϭ 0.92, all P Ͻ 0.002). It was inversely correlated with lactate (r ϭ Ϫ0.93, P Ͻ 0.001). In the coronary occlusion group, cyclosporine dose dependently reduced the ratio [area of infarct/area of the left ventricle] (r ϭ Ϫ0.86, P Ͻ 0.01), with 15 mg/kg/day being the most effective cyclosporine dose. The reduction in infarct size correlated with the reduction in oxidative phosphorylation (ATP: r ϭ 0.97; NAD ϩ : r ϭ 0.82, P Ͻ 0.01). The reduction in cardiac energy metabolism before occlusion may be the cause of myocardial preservation during ischemia/ reperfusion.

show abstract

Section: Cardiac Effects Of Cyclosporine 1127supporting

confidence: 74%

Section: Csamentioning

confidence: 99%

Close Association Between the Reduction in Myocardial Energy Metabolism and Infarct Size: Dose-Response Assessment of Cyclosporine

Niemann

Saeed²,

Akbari³

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Even if some studies showed a relationship between those parameters and CsA efficacy, those correlations have been poor, and the pharmacokinetic approach in general is not well accepted (22,23).…”

mentioning

confidence: 99%

Whole blood flow cytometric measurement of NFATc1 and IL‐2 expression to analyze cyclosporine A‐mediated effects in T cells

et al. 2010

View full text Add to dashboard Cite

The calcineurin inhibitor Cyclosporine A (CsA) is one of the crucial immunosuppressive drugs given after organ transplantation. The small therapeutic window of CsA generates the dilemma that efficient and toxic drug doses differ only slightly. Moreover, these threshold concentrations differ considerably between individuals; therefore, functional assays are urgently needed. We explored whether the transcription factor NFATc1, a direct as well as indirect target of CsA, can be used as a potential biomarker to determine the individual immunosuppressive activity of CsA. First, in isolated human T cells we showed that flow cytometry is practicable to measure NFATc1, the most abundant NFATc isoform in activated T cells. Second, for whole blood we developed a flow cytometric assay to determine in parallel the inducible transcription factor NFATc1 and the cytokine IL-2 in stimulated T cells. We found that added CsA inhibits both the expression of NFATc1 and IL-2 in T cells of stimulated whole blood samples with IC 50 values of 200 and 150 nM, respectively. The intra-and inter-assay variability was low, and clinical practicability was good. Further experiments have to demonstrate whether the parallel cytometric measurement of NFATc1 and IL-2 in whole blood is a good predictor of individual CsA efficacy and toxicity in CsA-treated patients. '

show abstract

“…Currently four commercial companies are producing eight different immunoassay assay systems kidney transplant patients there was a six fold range in the concentrations considered effective and a three fold for the measurement of cyclosporin in whole blood (Table 1). In addition, a number of laboratories are using range in those considered toxic [94]. There was also considerable variation in the width of the therapeutic high performance liquid chromatography (h.p.l.c.)…”

Section: Assay Methodology the 'Therapeutic' Rangementioning

confidence: 99%

“…h.p.l.c. is specific for cyclosporin, the technique can given sample (Figure 2 accuracy do not seem to affect the clinical usefulness of the assays [103] but do add to variability of reported concentrations in the literature [105] and have an impact suffer from poor precision and can give spurious results on the local target ranges [94]. However, in clinical due to interference from other sources [102].…”

Section: Assay Methodology the 'Therapeutic' Rangementioning

confidence: 99%

Untitled

1999

Brit J Clinical Pharma

View full text Add to dashboard Cite

Lake Louise Consensus Conference on Cyclosporin Monitoring in Organ Transplantation: Report of the Consensus Panel

Cited by 223 publications

References 0 publications

Close Association Between the Reduction in Myocardial Energy Metabolism and Infarct Size: Dose-Response Assessment of Cyclosporine

Close Association Between the Reduction in Myocardial Energy Metabolism and Infarct Size: Dose-Response Assessment of Cyclosporine

Whole blood flow cytometric measurement of NFATc1 and IL‐2 expression to analyze cyclosporine A‐mediated effects in T cells

Untitled

Contact Info

Product

Resources

About