Prevention of Cold-Preservation Injury of CulturedEndothelial Cells by Catecholamines and Related Compounds

Yard, Benito A.; Beck, Grietje; Schnuelle, Peter; Braun, Claude; Bechtler, Mathias; Göttmann, Uwe; Xiao, Yang; Breedijk, Annette; Wandschneider, Silke; Lösel, Ralf; Sponer, G.; Wehling, Martin; Woude, Fokko J. van der

doi:10.1046/j.1600-6143.2003.00268.x

Cited by 61 publications

(87 citation statements)

References 44 publications

(61 reference statements)

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“…Alternatively, redox imbalance might increase the membrane permeability for Ca 2+ directly. Although, the protective effect of dopamine is strictly redox dependent [22] This study does not argue against an important role for iron in cold preservation injury. In fact, a number of studies already have shown the importance of iron in this respect.…”

Section: Discussionmentioning

confidence: 56%

“…Furthermore, it does not explain why Ca 2+ release from the intracellular stores can overcome the protective effect of dopamine. The protective effect of dopamine is strictly redox dependent [22], however, we can not exclude that oxidation of dopamine impairs the ability to chelate iron. Unpublished findings also have shown that protection mediated by dihydroxy phenolic compounds, was only observed when the hydroxyl groups were in ortho-or para-but not in meta-position.…”

Section: Discussionmentioning

confidence: 82%

“…A decreased ox-phos [16], the expression of uncoupling proteins in brown adipose tissue [17], as well as an increased Ca 2+ uptake in the sarco-/ endoplasmic reticulum [18,19] are amongst mechanisms used by hibernating mammals to adapt to long periods of hypothermia and reduced oxygen pressure. We and others have demonstrated that dihydroxy-phenolic compounds [20][21][22] and iron chelators [23,24] can protect endothelial-and tubular epithelial cells against hypothermia mediated cell death. In the present study we hypothesized that these compounds mediate protection by balancing the mitochondrial Ca 2+ -ATP -ROS love-hate triangle during hypothermia.…”

Section: Introductionmentioning

confidence: 93%

“…Like dopamine, BAPTA-AM prevented mitochondrial Ca Respiratory chain inhibitors A consequence of mitochondrial Ca 2+ accumulation is MPT and loss of mitochondrial membrane potential (ΔΨ). During hypothermia, dopamine prevents the loss of ΔΨ [22]. We tested if respiratory chain inhibitors (myxothiazol, Na-azide), an inhibitor of ATP synthase (oligomycin) and an uncoupler (CCCP), all of which are known to generate mitochondrial ROS, were able to overcome the protective effect of dopamine or EDTA.…”

Section: +mentioning

confidence: 99%

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Hypothermic Injury: the Mitochondrial Calcium, ATP and ROS Love-Hate Triangle out of Balance

Brinkkoetter

Song²,

Lösel³

et al. 2008

Cell Physiol Biochem

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Background/Aims: Catecholamines prevent hypothermic cell death which accounts for severe tissue damage and impaired allograft function after prolonged organ preservation. Here, we identified cellular processes which govern hypothermia-mediated cell death in endothelial cells and how they are influenced by dopamine. Methods: Lactate dehydrogenase assay, intracellular ATP, reactive oxygen species and reduced thio-group measurement, intracellular calcium measurement and mitochondrial calcium staining were performed in the study. Results: Intracellular ATP was almost completely depleted within 12 hrs of hypothermic preservation in untreated human umbilical vein endothelial cells (HUVEC), while dopamine pre-treatment significantly delayed ATP depletion. 4 hrs after hypothermia a redox imbalance was observed in untreated cells, which increased with the duration of hypothermia. The redox imbalance was primarily caused by depletion of SH reduction equivalents and was significantly inhibited by dopamine. In addition, hypothermia-induced Ca²⁺ influx and mitochondrial Ca²⁺ accumulation were both prevented by dopamine. The protective effect of dopamine was abrogated by ionomycin and sodium azide and partly by oligomycin and CCCP. Conclusions: Our data demonstrated that loss of intracellular ATP, generation of a redox imbalance and accumulation of intracellular Ca²⁺ underlie cold preservation injury. Dopamine improves the redox balance, prevents intracellular Ca²⁺ accumulation and delays ATP depletion.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 93%

Section: +mentioning

confidence: 99%

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Hypothermic Injury: the Mitochondrial Calcium, ATP and ROS Love-Hate Triangle out of Balance

Brinkkoetter

Song²,

Lösel³

et al. 2008

Cell Physiol Biochem

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“…In addition, catecholeamines may prevent cold-induced damage to endothelial cells by scavenging reactive oxygen species (ROS) or by inhibition of ROS production. 133 Volatile anesthetics (sevoflurane, isoflurane, and desflurane) have, in several experimental and clinical settings, been shown to protect the heart from I/R injury. [134][135][136][137] Recently, isoflurane was demonstrated to have a similar effect on the rat liver, 138 and sevoflurane, in a prospective randomized study, protected the human liver from I/R injury during liver resection.…”

Section: Pulmonary Carementioning

confidence: 99%

Brain death and its implications for management of the potential organ donor

Bugge

2009

Acta Anaesthesiol Scand

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The systemic physiologic changes that occur during and after brain death affect all organs suitable for transplantation. Major changes occur in the cardiovascular, pulmonary, endocrine, and immunological systems, and, if untreated may soon result in cardiovascular collapse and somatic death. Understanding these complex physiologic changes is mandatory for developing effective strategies for donor resuscitation and management in such a way that the functional integrity of potentially transplantable organs is maintained. This review elucidates these physiological changes and their consequences, and based on these consequences the rationale behind current medical management of brain-dead organ donors is discussed.

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Effects of Donor Pretreatment With Dopamine on Graft Function After Kidney Transplantation

Schnuelle¹,

Göttmann²,

Hoeger³

et al. 2009

JAMA

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231

159

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Context Kidney graft function after transplantation can be improved through pharmacological donor pretreatment to limit organ injury from cold preservation. Objective To determine whether pretreatment of brain-dead donors with lowdose dopamine improves early graft function in human renal transplant recipients. Design, Setting, and Patients Randomized, open-label, multicenter, parallelgroup trial of 264 deceased heart-beating donors and 487 subsequent renal transplants performed at 60 European centers between March 2004 and August 2007 (final follow-up, December 31, 2008). Eligible donors were stable under low-dose norepinephrine with a normal serum creatinine concentration on admission. Interventions Donors were randomized to receive low-dose dopamine (4 µg/kg/min). Main Outcome Measures Dialysis requirement during first week after transplantation. Results Dopamine was infused for a median of 344 minutes (IQR, 215 minutes). Dialysis was significantly reduced in recipients of a dopamine-treated graft. Fewer recipients in the treatment group needed multiple dialyses (56/227; 24.7%; 95% CI, 19.0%-30.3%; vs 92/260; 35.4%; 95% CI, 29.5%-41.2%; P=.01). The need for multiple dialyses posttransplant was associated with allograft failure after 3 years (HR, 3.61; 95% CI, 2.39-5.45; PϽ.001), whereas a single dialysis was not (HR, 0.67; 95% CI, 0.21-2.18; P=.51). Besides donor dopamine (OR, 0.54; 95% CI, 0.35-0.83; P=.005), cold ischemic time (OR, 1.07; 95% CI, 1.02-1.11 per hour; P=.001), donor age (OR, 1.03; 95% CI, 1.01-1.05 per year; PϽ.001), and recipient body weight (OR, 1.02; 95% CI, 1.01-1.04 per kg; P=.009) were independent explanatory variables in a multiple logistic regression model. Dopamine resulted in significant but clinically meaningless increases in the donor's systolic blood pressure (3.8 mm Hg; 95% CI, 0.7-6.9 mm Hg; P=.02) and urine production before surgical recovery of the kidneys (29 mL; 95% CI, 7-51 mL; P=.009) but had no influence on outcome. Conclusion Donor pretreatment with low-dose dopamine reduces the need for dialysis after kidney transplantation.

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Prevention of Cold-Preservation Injury of CulturedEndothelial Cells by Catecholamines and Related Compounds

Cited by 61 publications

References 44 publications

Hypothermic Injury: the Mitochondrial Calcium, ATP and ROS Love-Hate Triangle out of Balance

Hypothermic Injury: the Mitochondrial Calcium, ATP and ROS Love-Hate Triangle out of Balance

Brain death and its implications for management of the potential organ donor

Effects of Donor Pretreatment With Dopamine on Graft Function After Kidney Transplantation

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