Perioperative Medicine  |   December 2016
Transient Receptor Potential Ankyrin 1 Activation within the Cardiac Myocyte Limits Ischemia–reperfusion Injury in Rodents
Author Notes
  • From the Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California.
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    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site www.anesthesiology.org.×
  • Submitted for publication April 13, 2016. Accepted for publication August 29, 2016.
    Submitted for publication April 13, 2016. Accepted for publication August 29, 2016.×
  • Address correspondence to Dr. Gross: Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, 300 Pasteur Drive, Grant Building Room S268b, Stanford, California 94305. ergross@stanford.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Basic Science / Cardiovascular Anesthesia / Pain Medicine
Perioperative Medicine   |   December 2016
Transient Receptor Potential Ankyrin 1 Activation within the Cardiac Myocyte Limits Ischemia–reperfusion Injury in Rodents
Anesthesiology 12 2016, Vol.125, 1171-1180. doi:10.1097/ALN.0000000000001377
Anesthesiology 12 2016, Vol.125, 1171-1180. doi:10.1097/ALN.0000000000001377
Abstract

Background: Recent evidence suggests that cross talk exists between cellular pathways important for pain signaling and ischemia–reperfusion injury. Here, the authors address whether the transient receptor potential ankyrin 1 (TRPA1) channel, important in pain signaling, is present in cardiac myocytes and regulates cardiac ischemia–reperfusion injury.

Methods: For biochemical analysis of TRPA1, techniques including quantitative polymerase chain reaction, Western blot, and immunofluorescence were used. To determine how TRPA1 mediates cellular injury, the authors used an in vivo model of rat cardiac ischemia–reperfusion injury and adult rat–isolated cardiac myocytes subjected to hypoxia–reoxygenation.

Results: The authors’ biochemical analysis indicates that TRPA1 is within the cardiac myocytes. Further, using a rat in vivo model of cardiac injury, the TRPA1 activators ASP 7663 and optovin reduce myocardial injury (45 ± 5%* and 44 ± 8%,* respectively, vs. control, 66 ± 6% infarct size/area at risk; n = 6 per group; mean ± SD; *P < 0.001). TRPA1 inhibition also blocked the infarct size–sparing effects of morphine. In isolated cardiac myocytes, the TRPA1 activators ASP 7663 and optovin reduce cardiac myocyte cell death when given during reoxygenation (20 ± 3%* and 22 ± 4%* vs. 36 ± 3%; percentage of dead cells per field, n = 6 per group; mean ± SD; *P < 0.05). For a rat in vivo model of cardiac injury, the infarct size–sparing effect of TRPA1 activators also occurs during reperfusion.

Conclusions: The authors’ data suggest that TRPA1 is present within the cardiac myocytes and is important in regulating myocardial reperfusion injury. The presence of TRPA1 within the cardiac myocytes may potentially explain why certain pain relievers that can block TRPA1 activation, such as cyclooxygenase-2 inhibitors or some nonsteroidal antiinflammatory drugs, could be associated with cardiovascular risk.