(Boston) – When patients are placed on cardiopulmonary bypass (CPB) during cardiac surgery, a series of chemicals known as complement are activated, which results in an inflammatory response that can contribute to increased mortality and morbidity. TP10, a potent inhibitor of complement activation during CPB, has been previously shown to decrease mortality in high-risk male patients undergoing cardiac surgery.
However, the effects of TP10 have not been extensively studied in women. Researchers from Boston University School of Medicine now report that the benefits of TP10 appear to be gender related and that women may have special mechanisms that protect them from complement activation during open-heart surgery.
The study, reported in the recent issue of Circulation, involved 300 female patients undergoing high-risk cardiac surgical procedures. Half of the patients received TP10 during surgery; the other half received no drug. TP10 was not associated with any adverse events and resulted in a significant reduction in complement levels during surgery. However, there was no statistical difference in mortality between the two groups (1 percent for TP10 vs. 3 percent for non-TP10).
The lead author, Harold L. Lazar, M.D., director of cardiothoracic surgical research and professor of cardiothoracic surgery at Boston University School of Medicine and attending cardiothoracic surgeon at Boston Medical Center, offered several explanations for these findings. “Although we were disappointed that the beneficial effects of TP10 seen in our earlier study in high-risk males were not found in this study in females, we were happy to see that the mortality rate in the non-TP10 group was only three percent,” said Lazar. “In previous studies looking at mortality in high-risk women undergoing cardiac surgical procedures, the death rate has been five percent to 10 percent. We attribute the lower mortality in the non-TP10 group to better protection of the heart during surgery, and more widespread use of medications, such as aspirin, beta-blockers, ACE inhibitors, statins, and insulin, which have been shown to decrease mortality immediately following surgery. Almost all of the patients in this study received a combination of these drugs, which may have masked the beneficial effect of complement suppression with TP10.”
Researchers further suggest that complement activation may not be as detrimental to female patients during CPB. Researchers also hope to study the mechanisms by which females are protected from complement activation in the hope of developing new strategies to reduce the side effects associated with CPB during cardiac surgery in all patients.
“Sometimes a study such as this raises more questions than it answers,” said Lazar. “This study adds further proof that female patients react differently during periods of cardiac ischemia. Finding out more about these differences may help to reduce the mortality in both sexes during high-risk cardiac surgical procedures.”
Journal
Circulation