EPR oximetry in the beating heart: Myocardial oxygen consumption rate as an index of postischemic recovery

Abstract

Oxygen plays a critical role in the pathophysiology of myocardial injury during both ischemia and subsequent reperfusion (I/R). Thus, oxygen concentration is an important variable to measure during I/R. In the present work, electron paramagnetic resonance (EPR)-based oximetry was used to measure the oxygen concentration during a series of I/R episodes and oxygenation levels were correlated with the contractile and hemodynamic functions of the heart. A custom-developed electronically tunable surface coil resonator working at 1.1 GHz was used to determine tissue pO 2 in the beating heart. Microcrystalline particulate of lithium phthalocyanine was used as an EPR oximetry probe. Isolated and perfused rat hearts were subjected to 1 or 3 hr durations of preischemic perfusion, followed by 15-min I/R cycles. In hearts perfused for 3 hr prior to 15-min I/R cycles, the myocardial pO 2 decreased gradually on subsequent reperfusions of three successive I/R cycles. However, in hearts perfused for 1 hr there was almost 100% recovery of myocardial pO 2 in all three I/R cycles. The extent of oxygenation recovered in each reperfusion cycle correlated with the recovery of hemodynamic and contractile function. The results also showed that the oxygen consumption rate of the heart at the end of each I/R episode decreased in direct proportion to the functional recovery. In summary, it was observed that the amount of myocardial oxygen consumption during I/R could provide a reliable index of functional impairment in the heart. Magn Reson Med 51:835-842, 2004.

Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion

“…In the setting of low-flow ischemia, ROS production occurs continuously (97). Even during stop flow ischemia in the isolated perfused heart, tissue oxygen remains detectable by sensitive electron paramagnetic resonance measurement at least during the initial 10 min of ischemia (68). The production of ROS monitored online increases during global ischemia, which is consistent with the presence of oxygen during the evolution of ischemic injury (71,77,116,129).…”

“…Early research led to the belief that during cardiac ischemia, oxygen content would rapidly decrease to complete anoxia, with all oxygen consumed by cytochrome oxidase. However, during the initial progression of myocardial ischemia, oxygen remains available (68). During simulated ischemia in cardiomyocytes, under conditions of oxygen depletion, the ROS generation actually increases (15,142).…”

Hypoxic reperfusion of the ischemic heart and oxygen radical generation

“…The LiNc-BuO probe yields a single sharp EPR line, the width of which is highly sensitive to oxygen tension. Decreased oxygen tension results in sharpening of the EPR spectrum, which yields a linear PO 2 response from 0 to 760 Torr (14). The isolated perfused hearts were placed in the active volume of a reentrant resonator of an L-band (1.2 GHz) EPR spectrometer that was controlled using custom-designed software (14,17).…”

“…Decreased oxygen tension results in sharpening of the EPR spectrum, which yields a linear PO 2 response from 0 to 760 Torr (14). The isolated perfused hearts were placed in the active volume of a reentrant resonator of an L-band (1.2 GHz) EPR spectrometer that was controlled using custom-designed software (14,17). This gives continuous online measurement of localized myocardial oxygen tension throughout ischemia and reperfusion.…”

Evaluation of oxygen-response times of phthalocyanine-based crystalline paramagnetic spin probes for EPR oximetry

“…Since a good signal-to-noise ratio (SNR) is essential to keep the acquisition time reasonable, particulate probes that have high densities of unpaired spins and a single narrow peak are generally preferred over soluble probes for EPR spectroscopy. The particulate probes are particularly suited for in vivo applications because of their ease of implantation and capability of local, reproducible, and repetitive measurements [7][8][9][10]. However, the response time (temporal response) of the particulate probes to oxygen is limited due to the need for the oxygen molecules to diffuse into the solid.…”