Optical pacing of the adult rabbit heart

Abstract

Optical pacing has been demonstrated to be a viable alternative to electrical pacing in embryonic hearts. In this study, the feasibility of optically pacing an adult rabbit heart was explored. Hearts from adult New Zealand White rabbits (n = 9) were excised, cannulated and perfused on a modified Langendorff apparatus. Pulsed laser light (λ = 1851 nm) was directed to either the left or right atrium through a multimode optical fiber. An ECG signal from the left ventricle and a trigger pulse from the laser were recorded simultaneously to determine when capture was achieved. Successful optical pacing was demonstrated by obtaining pacing capture, stopping, then recapturing as well as by varying the pacing frequency. Stimulation thresholds measured at various pulse durations suggested that longer pulses (8 ms) had a lower energy capture threshold. To determine whether optical pacing caused damage, two hearts were perfused with 30 µM of propidium iodide and analyzed histologically. A small number of cells near the stimulation site had compromised cell membranes, which probably limited the time duration over which pacing was maintained. Here, short-term optical pacing (few minutes duration) is demonstrated in the adult rabbit heart for the first time. Future studies will be directed to optimize optical pacing parameters to decrease stimulation thresholds and may enable longer-term pacing.

Keywords: (140.3460) Lasers; (170.3890) Medical optics instrumentation.

Figures

Fig. 1

Experimental setup. Hearts of male New Zealand White rabbits weighing 2.9-4 kg were extracted, cannulated, and perfused on a modified Langendorff apparatus. A: Photograph of heart 1. Electrodes (yellow wires) are attached to the left ventricle of the heart. Pulsed laser light (λ = 1.851 μm) was directed toward the epicardial surface of the left or right atrium through a multimode optical fiber. The black arrow indicates the optical fiber. A pad directly behind the heart diminishes swinging motion. B: Diagram of the setup. A computer simultaneously recorded both the trigger pulse from the laser and an ECG signal to determine when capture was achieved.

Fig. 2

Optical pacing of an adult rabbit heart (Media 1). Pacing was captured, stopped, then recaptured to demonstrate 1:1 pacing of the heart. Top left panel: A photograph of heart 1, identical to Fig. 1(a), indicating the position of the optical fiber and electrodes. Top right panel: a video recording of heart 1 beating, while optical pacing is captured, stopped and recaptured. Bottom panel: The blue (lower) trace represents the ECG recording, while the red (upper) trace is the trigger output from the laser.

Fig. 3

Frequency modulation. The heart rate was modulated from 2.5 to 2.76 to 2.5 Hz using OP. When the laser pulse rate was changed, the heart rate quickly tracked the new pacing frequency. The trigger pulse from the laser is shown in red (upper trace) and the ECG recording in blue (lower trace). The laser did not smoothly transition between frequencies and pacing lapsed during these short periods (dotted ovals).

Fig. 4

Propidium iodide (PI) staining. To assay for cell membrane disruption caused by OP, the heart was perfused with 30 µM of PI solution. Positive staining indicated permeation Out of the two hearts tested neither showed PI staining at the lowest stimulation threshold (6.3 J/cm2). One out of two hearts at the mid (7.9 J/cm2) and highest thresholds (9.7 J/cm2) exhibited a low level of PI staining. PI staining was found on the epicardial side of the atrium near the position of the optical fiber. The white arrows indicate the stimulation fiber direction. A: Positive control. B: Light staining was evident in one of the hearts when 8 ms pulses containing 7.9 J/cm2 per pulse were directed to the heart for one minute (dashed circle). C: Pulses containing 6.3 J/cm2 under similar conditions resulted in no apparent damage.

Fig. 5

Extended pacing. The heart was paced for extended periods (1-5 minutes) in three hearts. The TTL trigger signal from the laser (red) and the ECG recording (blue) show OP at 2.5 Hz for over 90 seconds without skipping a beat. The dotted lines delineate a region that was expanded and shown directly above the traces to clearly visualize the synchronization of the laser pulses and ECG traces. Extended pacing beyond 5 minutes was not be reliably maintained.