Abstract
A variety of animal models exist for the study of cardiovascular function using many approaches from surgically induced ischemia to genetic manipulation. A murine physiological model was recently proposed for the non-invasive study of peripheral circulation and was strengthened by the wavelet transform analysis (WA) of laser Doppler flowmetry (LDF) signals. WA allows the extraction of cardiac, respiratory, sympathetic, endothelial, and myogenic components from the raw LDF signal. The present study was designed to evaluate the discernment capacity of the model through an analysis of the short-term effects of the well-known hypotensive cardiovascular drug, atenolol. Six male C57/BL6 mice (16 weeks old) were included in the study, with each animal serving as its own control. Following anesthesia with ketamine-xylazine, skin perfusions were continuously assessed in both hindlimbs by LDF during baseline and after two sequential atenolol administrations (2.5 and 5.0 mg/kg, as commonly prescribed). Expected atenolol-induced hypotension was present, associated with a significantly increased heart rate and peripheral perfusion with both dosages. Through the application of WA to the LDF signal, we could detail the mechanisms of the atenolol-induced peripheral perfusion modulation: an immediate amplitude decrease of the cardiac LDF spectrum with an amplitude increase of the sympathetic component (p < 0.05) and the endothelial and myogenic components (non-significant). These data suggested a regulatory crosstalk between the peripheral (baroreceptors) and the microcirculatory units, which ultimately resulted in hypotension, inotropic reduction, and tachycardia. In conclusion, WA offered insight that simply could not be seen with only the perfusion curve and, thus, was an effective tool to investigate this cardiovascular mechanism of regulation.
Highlights
In vivo models, whether animal or human, provide useful information on both physiological mechanisms and pathophysiological processes leading to disease
The anesthetized mouse model measures perfusion in both hindlimbs with laser Doppler flowmetry (LDF) which has been applied in different experimental conditions with
The model utilizes the wavelet transform analysis (WA), a scale-independent tool used to obtain a spectral decomposition of the continuous, pulsatile, raw LDF signal [9,10,11,12]
Summary
Whether animal or human, provide useful information on both physiological mechanisms and pathophysiological processes leading to disease. For blood peripheral perfusion variables, including cardiac, respiratory, and peripheral (myogenic, neurogenic, and endothelial) components, the Morlet mother wavelet shows good localization both in time and frequency domains, in addition to an adequate correlation between time, width, and the corresponding frequency [9,14]. This analytical strategy, not common in experimental animals, was previously attempted in rats [13] and more recently in mice as part of the development of this model [14,15] using human component frequencies as a reference
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