NASA Human Research Program Investigators' Workshop (2012) 4064.pdf EDOTHELIAL REPAIR AFTER LOW-DOSE IOIZIG RADIATIO IJURY Maggie M. Kuo1, Artin A. Shoukas1, Dan E. Berkowitz1,2 Departments of 1Biomedical Engineering, 2Anesthesiology and Critical Care Medicine Johns Hopkins Medical Institutions, Baltimore, MD Radiation exposure remains the primary concern for manned deep-space missions. Epidemiological and animal studies support that exposure to low doses of ionizing radiation results in endothelial dysfunction and increased risk of developing cardiovascular disease. Our vasoreactivity experiments in mice aorta show that radiation-induced endothelial injury is not permanent and support involvement of endothelial repair mechanisms. We continue to use ex vivo and in vivo methods to investigate the state of vascular repair mechanisms after low-dose heavy ion radiation exposure. We use iron ion as the model for the space radiation environment. AORTIC RIG VASOREACTIVITY Mice were exposed whole body to 1 Gy, 1 GeV iron. At 1 month after irradiation, 1 Gy mice exhibited decreased sensitivity to endothelial-dependent vasodilating drug, acetylcholine (Ach). At 4 months after exposure, Ach sensitivity of 1 Gy mice was the same as control mice. Ach response of control mice did not differ significantly between one and four months. Response to endothelial-independent vasodilating drug, sodium nitroprusside, did not change between cohorts or time points. These results show that initial endothelial injury due to radiation exposure is not sustained and support active endothelial repair mechanisms. OGOIG STUDIES We are using a targeted irradiation model and a hind limb ischemia model to study ionizing radiation effects on endothelial repair function. We are also using coronary flow reserve to evaluate endothelial function in vivo. Targeted irradiation To determine if radiation-induced vascular injury can be repaired by endogenous repair mechanisms, the femoral artery of one hind limb is exposed to 5Gy, 600 MeV iron. Repair mechanisms are intact in this model. Femoral arteries are harvested and the vasoreactivity behavior of the exposed vessel is compared to behavior of the unexposed vessel. Hind limb ischemia Long-term effects of radiation exposure on vascular repair are studied with the hind limb ischemia model. Mice are whole-body exposed to 1 Gy, 1GeV iron radiation. Two months after exposure, the femoral artery of the left hind limb is excised. Degree of angiogenesis in the ischemic limb is measured through amount of blood flow using a laser Doppler perfusion imaging system. Angiogenesis is tracked over 28 days. Coronary flow velocity reserve Endothelial function of coronary arteries in vivo is characterized using high-resolution ultrasound. A catheter is inserted into the tail vein for administration of vasodilating drugs. The left coronary artery is visualized with color Doppler. Flow velocity measurements are taken at the left main coronary artery. Coronary flow velocity reserve is calculated as the ratio of hyperemic to baseline flow. Conclusions from these studies will clarify if ionizing radiation exposure is detrimental to the cardiovascular health of astronauts.