Novel protection strategy for pulmonary transplantation

A. M. Vaida, D. G. Tang, C. Allen, R. M. Wise, Robert Higgins, N. M. Cohen

Research output: Contribution to journalArticle

Abstract

Background. Ischemia-reperfusion injury continues to represent a significant challenge to successful lung transplantation. Traditional pulmonary ischemic protection is performed using hypothermic hyperkalemic depolarizing solutions to reduce the metabolic demands of the ischemic organ. Measures to further reduce the effects of ischemic injury have focused on the reperfusion period. We tested the hypothesis that novel physiologic hyperpolarizing solutions - using ATP-dependent potassium channel (KATP) openers - given at the induction of ischemia, will reduce cellular injury and provide superior graft function even after prolonged periods of ischemia. Methods. An isolated blood-perfused ventilated rabbit lung model was used to study lung injury. Airway, left atrial, and pulmonary artery pressures were measured continuously during the 2-h reperfusion period. Oxygenation, as a surrogate of graft function, was measured using intermittent blood gas analysis of paired left atrial and pulmonary artery blood samples. Graft function was measured by oxygen challenge technique (FiO2 = 1.0). Wet-to-dry ratio was measured at the conclusion of the 2-h reperfusion period. Control (Group I) lungs were perfused with modified Euro-Collins solution (depolarizing) and reperfused immediately (no ischemia). Traditional protection lungs were perfused with modified Euro-Collins flush solution and stored for 4 h (Group II) or 18 h (Group III) at 4°C before reperfusion. Novel protection (Group IV) lungs were protected with a hyperpolarizing solution containing 100 nM Aprikalim, a specific KATP channel opener, added to the modified Euro-Collins flush solution and underwent 18 h of ischemic storage at 4°C before reperfusion. Results. Profound graft failure was measured after 18 h of ischemic storage with traditional protection strategies (Group III). Graft function was preserved by protection with hyperpolarizing solutions even for prolonged ischemic periods (Group IV). Wet-to-dry weight ratio, airway, left atrial, and pulmonary artery pressures were not significantly different between the groups. Conclusions. We have created a model of predictable lung injury. Membrane hyperpolarization with a KATP channel opener (PCO) provides superior prolonged protection from ischemia-reperfusion injury in an in vitro model of pulmonary transplantation.

Original languageEnglish (US)
Pages (from-to)8-15
Number of pages8
JournalJournal of Surgical Research
Volume109
Issue number1
DOIs
StatePublished - Jan 2003
Externally publishedYes

Fingerprint

Lung Transplantation
Reperfusion
Transplants
Lung
Pulmonary Artery
KATP Channels
Ischemia
Lung Injury
Reperfusion Injury
Pressure
Blood Gas Analysis
Potassium Channels
Wounds and Injuries
Adenosine Triphosphate
Oxygen
Rabbits
Weights and Measures
Control Groups
Membranes
Euro-Collins' solution

Keywords

  • ATP-dependent potassium channels
  • Graft protection
  • Hyperpolarization
  • Lung transplantation
  • Potassium channel openers

ASJC Scopus subject areas

  • Surgery

Cite this

Novel protection strategy for pulmonary transplantation. / Vaida, A. M.; Tang, D. G.; Allen, C.; Wise, R. M.; Higgins, Robert; Cohen, N. M.

In: Journal of Surgical Research, Vol. 109, No. 1, 01.2003, p. 8-15.

Research output: Contribution to journalArticle

Vaida, A. M. ; Tang, D. G. ; Allen, C. ; Wise, R. M. ; Higgins, Robert ; Cohen, N. M. / Novel protection strategy for pulmonary transplantation. In: Journal of Surgical Research. 2003 ; Vol. 109, No. 1. pp. 8-15.
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AU - Cohen, N. M.

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N2 - Background. Ischemia-reperfusion injury continues to represent a significant challenge to successful lung transplantation. Traditional pulmonary ischemic protection is performed using hypothermic hyperkalemic depolarizing solutions to reduce the metabolic demands of the ischemic organ. Measures to further reduce the effects of ischemic injury have focused on the reperfusion period. We tested the hypothesis that novel physiologic hyperpolarizing solutions - using ATP-dependent potassium channel (KATP) openers - given at the induction of ischemia, will reduce cellular injury and provide superior graft function even after prolonged periods of ischemia. Methods. An isolated blood-perfused ventilated rabbit lung model was used to study lung injury. Airway, left atrial, and pulmonary artery pressures were measured continuously during the 2-h reperfusion period. Oxygenation, as a surrogate of graft function, was measured using intermittent blood gas analysis of paired left atrial and pulmonary artery blood samples. Graft function was measured by oxygen challenge technique (FiO2 = 1.0). Wet-to-dry ratio was measured at the conclusion of the 2-h reperfusion period. Control (Group I) lungs were perfused with modified Euro-Collins solution (depolarizing) and reperfused immediately (no ischemia). Traditional protection lungs were perfused with modified Euro-Collins flush solution and stored for 4 h (Group II) or 18 h (Group III) at 4°C before reperfusion. Novel protection (Group IV) lungs were protected with a hyperpolarizing solution containing 100 nM Aprikalim, a specific KATP channel opener, added to the modified Euro-Collins flush solution and underwent 18 h of ischemic storage at 4°C before reperfusion. Results. Profound graft failure was measured after 18 h of ischemic storage with traditional protection strategies (Group III). Graft function was preserved by protection with hyperpolarizing solutions even for prolonged ischemic periods (Group IV). Wet-to-dry weight ratio, airway, left atrial, and pulmonary artery pressures were not significantly different between the groups. Conclusions. We have created a model of predictable lung injury. Membrane hyperpolarization with a KATP channel opener (PCO) provides superior prolonged protection from ischemia-reperfusion injury in an in vitro model of pulmonary transplantation.

AB - Background. Ischemia-reperfusion injury continues to represent a significant challenge to successful lung transplantation. Traditional pulmonary ischemic protection is performed using hypothermic hyperkalemic depolarizing solutions to reduce the metabolic demands of the ischemic organ. Measures to further reduce the effects of ischemic injury have focused on the reperfusion period. We tested the hypothesis that novel physiologic hyperpolarizing solutions - using ATP-dependent potassium channel (KATP) openers - given at the induction of ischemia, will reduce cellular injury and provide superior graft function even after prolonged periods of ischemia. Methods. An isolated blood-perfused ventilated rabbit lung model was used to study lung injury. Airway, left atrial, and pulmonary artery pressures were measured continuously during the 2-h reperfusion period. Oxygenation, as a surrogate of graft function, was measured using intermittent blood gas analysis of paired left atrial and pulmonary artery blood samples. Graft function was measured by oxygen challenge technique (FiO2 = 1.0). Wet-to-dry ratio was measured at the conclusion of the 2-h reperfusion period. Control (Group I) lungs were perfused with modified Euro-Collins solution (depolarizing) and reperfused immediately (no ischemia). Traditional protection lungs were perfused with modified Euro-Collins flush solution and stored for 4 h (Group II) or 18 h (Group III) at 4°C before reperfusion. Novel protection (Group IV) lungs were protected with a hyperpolarizing solution containing 100 nM Aprikalim, a specific KATP channel opener, added to the modified Euro-Collins flush solution and underwent 18 h of ischemic storage at 4°C before reperfusion. Results. Profound graft failure was measured after 18 h of ischemic storage with traditional protection strategies (Group III). Graft function was preserved by protection with hyperpolarizing solutions even for prolonged ischemic periods (Group IV). Wet-to-dry weight ratio, airway, left atrial, and pulmonary artery pressures were not significantly different between the groups. Conclusions. We have created a model of predictable lung injury. Membrane hyperpolarization with a KATP channel opener (PCO) provides superior prolonged protection from ischemia-reperfusion injury in an in vitro model of pulmonary transplantation.

KW - ATP-dependent potassium channels

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KW - Potassium channel openers

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