Monitoring haemodynamic changes in rodent models to better inform safety pharmacology: Novel insights from in vivo studies and waveform analysis

Figures

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  Figure 1.. General set-up of a radiotelemetry study. Animals are generally co-housed with either an un-instrumented 'buddy' or, in more recent multi-channel systems, with another instrumented rodent. Created with Biorender.com.

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  Figure 2.. Surgical implantation of Doppler flow probes. Rat in supine position showing a schematic arterial network, with the positioning of Doppler flow probes around the superior mesenteric and left renal arteries and descending abdominal aorta (highlighted in green, yellow and blue, respectively). Created with BioRender.com.

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  Figure 3.. Cuff development of the miniaturised pulsed Doppler flow probe. Schematic representation of the miniaturised Pulsed Doppler flow probe made in-house based around the design given in (Haywood et al., 1981). 37 (A) A 1 mm diameter 20 MHz piezoelectric crystal with insulated copper wires is housed inside silastic tubing, designed to sit at a 45o angle to the blood vessel lumen. (B) The back and sides around the crystal are covered with an acoustic baffle to prevent interference from surrounding blood vessels. A soft silastic cuff is created with the aid of a section of stainless steel tubing to encase the probe and allow the creation of a lumen for the vessel to sit in. Adapted from Haywood et al. 1981. 37 Figure created with BioRender.com.

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  Figure 4.. Doppler flowmetry experimental set-up. Single-housed rats, instrumented with Doppler flow probes around the superior mesenteric and left renal arteries, and descending abdominal aorta (highlighted in green, yellow and blue, respectively). Additional intravascular catheters, including intravenous catheters for drug administration and an arterial catheter which is connected to the blood pressure (BP) transducer for measurement of heart rate and mean arterial pressure are also present. Amplified signals are digitalised and recorded using an IdeeQ data acquisition system. Figure created with BioRender.com.

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  Figure 5.. Example and derivation of Doppler waveforms. (A) Example recording of BP in distal abdominal aorta (red trace) and Doppler shift in renal (blue), mesenteric (green) and aortic (yellow) vascular beds in IdeeQ. (B) The algorithm shows how peak systolic (Ps = SBP) and peak end-diastolic BP (Ped = DBP) are measured for one cycle of the signal. (C) Equations used to calculate mean arterial pressure (1), Doppler shift (2) and vascular conductance (3). Figure 5B created with BioRender.com.

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  Figure 6.. Analysis of waveform morphology changes. Pulse pressure (PP) and pulse pressure amplification (PPA), augmentation index (AIx), the position of the dicrotic notch and the slope of the upstroke segment can be used to assess changes in blood pressure waveform morphology. Created with BioRender.com.