Abstract
Objective: Damage to the circulatory system resulting from ischemia–reperfusion injury (I/R injury) occurs during heart attacks and hemorrhagic shock. The authors report a method for mitigating microcirculatory injury, using diagnostic frequency continuous-mode ultrasound and how effects are influenced by nitric oxide production impairment.
Methods: Five groups of hamsters were studied using the dorsal skin fold window chamber: (1) I/R; (2) I/R + ultrasound during ischemia; (3) I/R + ultrasound after ischemia; (4) I/R + Nω-nitro-l-arginine methyl ester (l-NAME); and (5) I/R + l-NAME + ultrasound. Functional capillary density (FCD) and microvascular diameter, flow velocity, and flow were monitored. During the exposures 2.49 MHz continuous ultrasound was used.
Results: Significant improvements in animals exposed to ultrasound after ischemia were found at 24 h of reperfusion in FCD, arteriolar diameter, and arteriolar and venular flow velocity and flow. Animals exposed to ultrasound during ischemia showed significantly improved FCD. l-NAME treatment reduced the improvement of microvascular function, compared to animals exposed after ischemia.
Conclusions: The use of continuous-mode diagnostic frequency ultrasound is beneficial in preventing long-term ischemia–reperfusion effects in the microcirculation as shown by the return of microvascular parameters to baseline values, an effect not attained in the absence of ultrasound treatment. The effects may be in part due to the production of nitric oxide consequent to locally induced shear stress effects by ultrasound exposure.
The authors thank Froilan P. Barra and Cynthia Walser for the surgical preparation of the animals. The authors also gratefully acknowledge Dustin E. Kruse (University of California, Davis) for his discussion on and assistance with ultrasonics and the calibration of our ultrasound transducer. This work has been supported by the NIH Grant HL 40696.