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Pre-arrest administration of the cell-permeable free radical scavenger tempol reduces warm ischemic damage of lung function in non-heart-beating donors
D Hodyc, O Hnilickova, V Hampl, J Herget
Language English Country United States
NLK
ScienceDirect (archiv)
from 1999-01-01 to 2009-12-31
- MeSH
- Anticoagulants pharmacology MeSH
- Time Factors MeSH
- Cyclic N-Oxides pharmacology MeSH
- Tissue Donors MeSH
- Financing, Organized MeSH
- Heparin MeSH
- Rats MeSH
- Lung physiology drug effects MeSH
- Pulmonary Ventilation MeSH
- Reperfusion Injury prevention & control MeSH
- Free Radical Scavengers pharmacology MeSH
- Spin Labels MeSH
- Heart Arrest MeSH
- Warm Ischemia adverse effects MeSH
- Lung Transplantation MeSH
- Organ Preservation methods MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
BACKGROUND: Lungs retrieved from non-heart-beating donors (NHBDs) may alleviate the shortage of suitable organs for transplantation. The critical point is the preservation of lungs during warm ischemia, when severe damage is caused by free radicals. We investigated the effect of ventilation, pre-arrest administration of heparin, and the cell-permeable free radical scavenger, tempol, on the function of NHBD grafts. METHODS: Six experimental and two control groups (n = 6 per group) were established. All experimental groups underwent a protocol of NHBD lung harvesting, which included 1 hour of warm ischemia after pentobarbital euthanasia followed by 90 minutes of cold ischemia. The groups were constructed as follows: Group An-non-ventilated during warm ischemia, no heparin; Group Av-room-air ventilated during warm ischemia, no heparin; Group Hn-non-ventilated, heparin added pre-arrest; Group Hv-ventilated, heparin; Group Tn-non-ventilated, heparin and tempol added pre-arrest; Group Tv-ventilated, tempol, heparin; Group Ac-control group, no warm and cold ischemia, lungs harvested immediately after euthanasia; and Group Tc-controls with tempol added pre-arrest. The lungs were then perfused ex vivo and the perfusion pressure, lung weight and arteriovenous difference in oxygen partial pressure were measured. RESULTS: We found that room-air ventilation during warm ischemia caused severe pulmonary edema during reperfusion. Heparinization prevented an increase in perfusion pressure and ameliorated the oxygen transport ability. Pre-arrest administration of tempol prevented edema formation after ventilation during warm ischemia and had a positive effect on the oxygen transport ability of the lungs. CONCLUSIONS: The free radical scavenger tempol, which has a very good ability to permeate biologic membranes, contributes to better preservation of lungs retrieved from NHBDs.
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- $a Pre-arrest administration of the cell-permeable free radical scavenger tempol reduces warm ischemic damage of lung function in non-heart-beating donors / $c D Hodyc, O Hnilickova, V Hampl, J Herget
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- $a Department of Physiology, Second Medical School, Charles University of Prague, Prague, Czech Republic. daniel.hodyc@lfmotol.cuni.cz
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- $a BACKGROUND: Lungs retrieved from non-heart-beating donors (NHBDs) may alleviate the shortage of suitable organs for transplantation. The critical point is the preservation of lungs during warm ischemia, when severe damage is caused by free radicals. We investigated the effect of ventilation, pre-arrest administration of heparin, and the cell-permeable free radical scavenger, tempol, on the function of NHBD grafts. METHODS: Six experimental and two control groups (n = 6 per group) were established. All experimental groups underwent a protocol of NHBD lung harvesting, which included 1 hour of warm ischemia after pentobarbital euthanasia followed by 90 minutes of cold ischemia. The groups were constructed as follows: Group An-non-ventilated during warm ischemia, no heparin; Group Av-room-air ventilated during warm ischemia, no heparin; Group Hn-non-ventilated, heparin added pre-arrest; Group Hv-ventilated, heparin; Group Tn-non-ventilated, heparin and tempol added pre-arrest; Group Tv-ventilated, tempol, heparin; Group Ac-control group, no warm and cold ischemia, lungs harvested immediately after euthanasia; and Group Tc-controls with tempol added pre-arrest. The lungs were then perfused ex vivo and the perfusion pressure, lung weight and arteriovenous difference in oxygen partial pressure were measured. RESULTS: We found that room-air ventilation during warm ischemia caused severe pulmonary edema during reperfusion. Heparinization prevented an increase in perfusion pressure and ameliorated the oxygen transport ability. Pre-arrest administration of tempol prevented edema formation after ventilation during warm ischemia and had a positive effect on the oxygen transport ability of the lungs. CONCLUSIONS: The free radical scavenger tempol, which has a very good ability to permeate biologic membranes, contributes to better preservation of lungs retrieved from NHBDs.
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