In patients with mechanical heart valves (MHVs), transcranial Doppler methods commonly detect high intensity transient signals (HITS) representing microemboli. These microemboli, which are presumably gaseous, may cause stroke and cognitive deterioration. A bovine model was therefore developed for studying the relationship between mitral MHV induced HITS and potential etiogenic factors. We placed an 18 mm, 4 MHz Doppler probe in the brachiocephalic artery to detect MHV induced microbubbles at baseline (rest) and under 9 other conditions. To elucidate the gas composition (CO2 or N2) of the microbubbles, we administered 1%, 3%, and 5% CO2, and 100% O2. To determine effect of the heart rate, we paced the heart at 120, 160, and 180 bpm. To alter the myocardial contractility, we gave dobutamine and esmolol. Two independent, blinded observers counted the HITS from recorded doppler spectra. HITS were defined by an initial unidirectional spectral deviation, a signal power of >8 dB relative to the background power, and lack of a cyclic appearance. The electrocardiogram, aortic and LV pressures, and LV dP/dt were obtained telemetrically. The calves were studied 4 to 6, 8 to 10, and 12 to 14 weeks postoperatively, after which the animals were sacrificed at an approximate 4 month study duration, and a postmortem evaluation of the heart and the main viscera was performed. In all, 27 HITS recordings were made in 10 calves. Myocardial contractility was the only factor to significantly affect HITS frequency; the heart rate and blood gas concentrations had minimal effect on HITS frequency. Our bovine model will be useful for assessing valve designs, as well as the mechanism of HITS, the composition of the microemboli, and their possible pathophysiologic effects on the kidneys and brain.