Effect of adenosine triphosphate-sensitive potassium channel openers on lung preservation.

Abstract

ATP-sensitive potassium channel (KATP) openers have been proven to be involved in ischemic preconditioning, which protects ischemic tissue. However, the effect of KATP openers on ischemia-reperfusion injury of the lungs remains unknown. We investigated whether a KATP opener, pinacidil, can attenuate ischemia-reperfusion injury using an ex vivo rat lung model. Heart-lung blocks were flushed and preserved with phosphate-buffered saline (control group) or with one of the solutions containing pinacidil (pinacidil group) or pinacidil + glibenclamide (a KATP blocker) (glibenclamide group). The control and glibenclamide groups showed significantly higher values with respect to shunt fraction, pulmonary arterial pressure, and peak inspiratory pressure than the pinacidil group. The concentrations of total adenine nucleotides and ATP in the lung after reperfusion became significantly lower in the control and glibenclamide groups than in the fresh group. Lipid peroxidation of the lungs increased significantly in the control and glibenclamide groups after reperfusion. State 3 mitochondrial respiration and State 3/4 ratios of mitochondrial respiration were significantly decreased in the lungs of the control and glibenclamide groups. These findings suggested that KATP openers would maintain the mitochondrial respiratory function during lung preservation, prevent lipid peroxidation after reperfusion, and attenuate ischemia-reperfusion injury.

• Authors: Tatsuo Fukuse, Toshiki Hirata, Mitsugu Omasa, Hiromi Wada
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 165 Issue 11 Pg. 1511-5 (Jun 01 2002) ISSN: 1073-449X [Print] United States
• PMID: 12045125 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channels
• Pinacidil
• Adenosine Triphosphate
• Glyburide

Topics

• Adenosine Triphosphate (analysis, metabolism)
• Animals
• Disease Models, Animal
• Glyburide (pharmacology)
• Hypertension, Pulmonary (physiopathology)
• Lung (drug effects, metabolism)
• Pinacidil (pharmacology)
• Potassium Channels (drug effects, metabolism)
• Pulmonary Wedge Pressure (drug effects)
• Random Allocation
• Rats
• Rats, Inbred Lew
• Reference Values
• Reperfusion Injury (prevention & control)
• Sensitivity and Specificity