Action Points

Explain to interested patients that these early findings suggest a way to prevent or mitigate the damage of a heart attack but will require further study in animal models as well as patients.

CINCINNATI, Jan. 7 -- Brief periods of ischemia may prepare the heart to survive a heart attack, an effect that appears to be transferable, according to early findings from an animal study.

Rat hearts transfused with blood preconditioned by mini "stress tests" from reduced blood flow had significantly better reperfusion after heart attack-like ischemia than those that received a transfusion from donors that were not subjected to stress beforehand (P<0.05), reported Karyn L. Butler, M.D., of the University of Cincinnati here, and colleagues in the January issue of the American Journal of Physiology: Heart and Circulatory Physiology.

Preconditioning activated a protective pathway -- Janus kinase (JAK)-signal transducers and activators of transcription (STAT) -- known to play a role in heart health, the researchers said.

This adaptive response to ischemia has been suggested as the reason for lower mortality rates among heart attack patients with angina, Dr. Butler said.

While this does not suggest patients should ignore angina symptoms, she said, the findings do imply the JAK-STAT pathway could offer a therapy against the damage of a heart attack.

"We would hope that the molecules that are important in allowing the heart to adapt would be something that we could perhaps duplicate pharmacologically," she said.

She and colleagues exposed freshly dissected rat hearts to brief ischemic conditions, coronary effluent from hearts exposed to brief ischemia, or control conditions. Ischemic preconditioning consisted of three cycles of five minutes of ischemia followed by five minutes of reperfusion.

They then subjected the hearts to 30 minutes of ischemia and measured subsequent reperfusion over 40 minutes.

End-reperfusion was no different between hearts that had ischemic preconditioning and hearts that received effluent from them (4304 and -1847 versus 3637 and -1692 mmHg/s for +dP/dtmax and -dP/dtmin, respectively).

Developed pressure was likewise better for hearts that were preconditioned or received effluent from preconditioned donor hearts (both P<0.05).

The transfer of protection suggested that the effect was mediated by a soluble molecule released during brief periods of stress, Dr. Butler and colleagues said.

Whatever this molecular mediator is, it likely activates the JAK-STAT pathway, they said.

Hearts that received effluent from preconditioned hearts but were treated with the JAK 2 inhibitor AG-490 recovered less than any other group.

Increased STAT-3 activation, reduced STAT-1 activation, and decreased expression of the pro-apoptotic protein Bax were associated with the protective effect.

Further study is needed in animal models before human studies or pharmacological development could begin, the researchers cautioned.

One important question to be answered is how long the cardioprotective effect lasts after a brief period of ischemia, Dr. Butler said.

"It is unlikely that a 'silver bullet' will be identified to support at-risk myocardium," she and colleagues wrote.

However, "translating this phenomenon into a clinically useful tool may protect the myocardium from potential injury in a variety of settings," they said, "including acute myocardial infarction, cardiac revascularization surgery, supply/demand imbalance in congestive heart failure, and ischemia/reperfusion challenge following shock."

The study was supported by the National Institutes of Health. One of the researchers reported support from a training grant from the National Institutes of Health. Dr. Butler reported no conflicts of interest.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine