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Does Cyclosporine Protect Against Myocardial Reperfusion Injury?

Findings from a small pilot study support intervention for a complication of arterial reperfusion that may impair patient outcomes after MI.

Some laboratory evidence suggests that arterial reperfusion can cause mitochondrial dysfunction by increasing membrane permeability, leading to the loss of the membrane potential. Cyclosporine is known to inhibit this mitochondrial dysfunction. Investigators performed this pilot study to test whether cyclosporine would improve outcomes after reperfusion therapy. They randomized patients with acute ST-segment–elevation MI to receive cyclosporine (30 patients) or normal saline (28 patients) before undergoing reperfusion by percutaneous coronary intervention. All patients had presented within 12 hours of symptom onset and had a completely occluded artery at the time of catheterization. The primary endpoint was the size of the infarction as measured by biomarker levels.

Mean patient age was 58, and nearly 80% were men. The area under the curve for serum creatine kinase release was significantly lower in the cyclosporine group than in the control group (138,053 and 247,930 arbitrary units, respectively), amounting to a reduction of about 40%. The area under the curve for troponin I release was also lower in the cyclosporine group than in the control group (112,312 and 129,320 arbitrary units, respectively), but the difference was not statistically significant. In a subgroup of 27 patients who underwent magnetic resonance imaging, randomization to cyclosporine was associated with a 20% reduction in the area of hyperenhancement, compared with randomization to normal saline.

Comment: Concerns about myocardial reperfusion injury have been around for as long as we have had the capability to open blocked arteries in patients suffering acute MI. These results suggest that reperfusion injury does mitigate the benefits of acute reperfusion therapy, and they provide enough evidence to support further study of cyclosporine as adjunctive therapy in these patients.

— Harlan M. Krumholz, MD, SM

THE JW EMERGENCY MEDICINE PERSPECTIVE

Although clearly preliminary, this "proof of concept" study yielded two important pieces of information about acute myocardial infarction care: (1) infarct size can be reduced by an agent that affects membrane permeability, and (2) such reduction in infarct size strongly supports the concept that reperfusion, although beneficial, may itself usher in a phase of ongoing myocardial damage. These results might bring about the birth of yet another adjunct to reperfusion, and cyclosporine might one day find its way into the emergency department armamentarium of pre-PCI drugs.

— J. Stephen Bohan, MD, MS, FACP, FACEP

Published in Journal Watch Emergency Medicine July 30, 2008

Citation(s):

Piot C et al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 2008 Jul 31; 359:473.

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