Masanori Sato1, Hiroo Yamanaka2, Mitsuo Iwasaki1, Yuka Miyata3, Takahiko Kamibayashi1, Yuji Fujino1, Yukio Hayashi4. 1. Department of Anesthesiology, Osaka University Medical School, Osaka, Japan. 2. Department of Anesthesia, Kansai Rosai Hospital, Osaka, Japan. 3. Anesthesiology Service, Sakurabashi-Watanabe Hospital, Osaka, Japan. 4. Department of Anesthesiology, Osaka University Medical School, Osaka, Japan; Anesthesiology Service, Sakurabashi-Watanabe Hospital, Osaka, Japan. Electronic address: yhayashi@anes.med.osaka-u.ac.jp.
Abstract
BACKGROUND: Phosphatidylinositol 3-kinase is involved in myocardial function, including contractility. To date, myocardial regulation by phosphatidylinositol 3-kinase after brain death has not been investigated. The present study using a brain death model was designed to examine the role of phosphatidylinositol 3-kinase in myocardial function after brain death. METHODS: After anesthesia with sevoflurane, a Fogarty catheter was placed intracranially for induction of brain death. A conductance catheter was inserted into the left ventricle for measurement of myocardial function. Rats were assigned to the following groups: one group undergoing sham operation (with catheter placement but no brain death introduction); one group receiving saline before brain death; and one group receiving wortmannin, an inhibitor of phosphatidylinositol 3-kinase, before brain death. Various measurements, including mean blood pressure, heart rate, maximal rate of rise of left ventricular pressure, and ejection fraction, were obtained every 30 minutes for 6 hours after brain death. The phosphorylation status of Akt and phospholamban was determined 360 minutes after brain death. RESULTS: After induction of brain death, rats showed significant decreases in blood pressure, maximal rate of rise of left ventricular pressure, and ejection fraction. Inhibition of phosphatidylinositol 3-kinase using wortmannin significantly improved these measurements, resulting in increased survival. Western blot analysis demonstrated that brain death increased Akt phosphorylation and decreased phospholamban phosphorylation; these effects were abolished by wortmannin. CONCLUSIONS: Inhibition of phosphatidylinositol 3-kinase prevented myocardial dysfunction after brain death in association with inhibition of the decrease in phosphorylation of myocardial phospholamban, characteristic of brain death.
BACKGROUND: Phosphatidylinositol 3-kinase is involved in myocardial function, including contractility. To date, myocardial regulation by phosphatidylinositol 3-kinase after brain death has not been investigated. The present study using a brain death model was designed to examine the role of phosphatidylinositol 3-kinase in myocardial function after brain death. METHODS: After anesthesia with sevoflurane, a Fogarty catheter was placed intracranially for induction of brain death. A conductance catheter was inserted into the left ventricle for measurement of myocardial function. Rats were assigned to the following groups: one group undergoing sham operation (with catheter placement but no brain death introduction); one group receiving saline before brain death; and one group receiving wortmannin, an inhibitor of phosphatidylinositol 3-kinase, before brain death. Various measurements, including mean blood pressure, heart rate, maximal rate of rise of left ventricular pressure, and ejection fraction, were obtained every 30 minutes for 6 hours after brain death. The phosphorylation status of Akt and phospholamban was determined 360 minutes after brain death. RESULTS: After induction of brain death, rats showed significant decreases in blood pressure, maximal rate of rise of left ventricular pressure, and ejection fraction. Inhibition of phosphatidylinositol 3-kinase using wortmannin significantly improved these measurements, resulting in increased survival. Western blot analysis demonstrated that brain death increased Akt phosphorylation and decreased phospholamban phosphorylation; these effects were abolished by wortmannin. CONCLUSIONS: Inhibition of phosphatidylinositol 3-kinase prevented myocardial dysfunction after brain death in association with inhibition of the decrease in phosphorylation of myocardial phospholamban, characteristic of brain death.