Quantitative measurement of local cerebral blood flow in the anesthetized mouse using intraperitoneal [C-14]iodoantipyrine injection and final arterial heart blood sampling

Autoradiographic measurement of local cerebral blood flow (CBF) with [C-14] iodoantipyrine (IAP) is limited in mice by the difficulty in cannulating ve ssels and the blood loss for repeated blood sampling. The authors modified and validated the method to measure local CBF with [C-14]IAP in mice by com bining intraperitoneal tracer application with a single blood sampling from the heart at the end of the experiment. Experiments were carried out in ma le SV129 mice under halothane anesthesia. After intraperitoneal administrat ion of 15 mu Ci [C-14]IAP, arterial blood samples were collected repeatedly and anesthetized animals were immersed in liquid nitrogen. In addition, fr ozen blood from the heart was sampled to obtain the final blood [C-14]radio activity. Correlation analysis between the sampling time and [C-14] radioac tivity of the arterial blood revealed a highly significant linear relations hip (P < 0.001, r = 0.978) and a lag time of the [C-14]tracer in arterial b lood of 3.3 +/- 0.6 seconds. [C-14]radioactivity of the final arterial bloo d sample (444 +/- 263 nCi/mL) was almost equal to that of the heart blood ( 453 +/- 242 nCi/mL), and the absolute difference in each animal was 3.3 +/- 4.2% (mean +/- SD). The convolution integrals for the CBF calculation were determined either by integrating the radioactivity of individual arterial blood samples or by assuming a linear rise from [C-14]tracer lag time after intraperitoneal [C-14]IAP injection to the value measured in the blood sam ple from the frozen heart. Regional flow values calculated by the two metho ds differed by less than 11% (not significant). This method allows the quan titative measurement of local CBF in anesthetized mice without any vessel c atheterization and will make mutant mice a more powerful tool to elucidate the molecular mechanisms of brain injuries by combining flow studies with m olecular-biological methods.