Isoflurane-Dependent Heart Rate Modulation by Cardiac Focused Ultrasound

Focused ultrasound (FUS) is an emerging noninvasive neuromodulation technique, yet its effects vary across studies due to multiple factors, including subject physiology, targeting accuracy, FUS exposure conditions and anesthetic state. This study investigated whether isoflurane-induced anesthetic depth modulates heart rate (HR) responses to cardiac FUS (cFUS) in mice.

The acoustic field of a FUS transducer was characterized via hydrophone measurements and numerical simulations. Transthoracic cFUS was applied to adult C57BL/6 mice under 1% or 2% isoflurane, with continuous electrocardiogram (ECG) recording. In acoustic-parameter experiments, cFUS was delivered at 1.5 MHz with peak negative pressures (PNP) of 1.0-3.0 MPa, pulse repetition frequencies (PRF) of 100-1000 Hz and duty cycles (DC) of 3%-20%.

The cFUS transducer produced a well-defined focus, and murine ribs had minimal impact on transthoracic focusing. cFUS decreased HR under 1% isoflurane, whereas identical acoustic parameters increased HR under 2% isoflurane. Varying PRF (100, 500 and 1000 Hz), PNP (3, 2.5 and 1 MPa) and DC (20%, 10% and 3%) altered HR response magnitude but did not change the polarity. HR variability analysis suggested that isoflurane-induced anesthetic depth alterations in autonomic state may account for divergent HR responses.

The polarity reversal of cFUS-induced HR responses depended on isoflurane-induced anesthetic depth under the tested conditions, with acoustic parameters mainly affecting response magnitude. These findings highlight the need to control and report anesthetic state in cFUS studies.