Noninvasive Biomarkers for Cardiovascular Dysfunction Programmed in Male Offspring of Adverse Pregnancy

Figures

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  Figure 1. Origins of arterial blood pressure (BP) and heart rate (HR) variability. Acute changes in BP are restored via the baroreflex. A change in BP is detected by arterial baroreceptors which signal to the medulla. This triggers a compensatory change in HR, and thus CO, via reciprocal modulation of sympathetic and vagal activity to the cardiac sinoatrial node. There is also a change in sympathetic outflow to peripheral arterioles, resulting in a compensatory change in total peripheral vascular resistance (TPR). Very low frequency (VLF, red box) blood pressure variability (BPV) occurs due to myogenic responses creating a VLF oscillation in peripheral arteriolar tone and thus TPR. The VLF BPV activates the baroreflex leading to compensatory VLF HRV. Low frequency (LF) BPV and HRV originate from baroreflex loop resonance (red box). At the resonant frequency, the time delay in this negative feedback loop means the input and output are in phase, generating self-sustained oscillations. High frequency (HF) BPV and HRV correspond to Respiration (red box). The mechanical changes during respiration lead to HF BP oscillations (inspiration lowers intrathoracic pressure, leading to increased venous…

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  Figure 2. Experimental design. Days gestational age (dGA) for the induction of prenatal hypoxia, and MitoQ intervention, weaning at 21 postnatal days (dPN), and cardiovascular assessment at 4.5 postnatal months (mPN).

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  Figure 3. Cardiovascular recording analysis. Representative LabChart recording of continuous, pulsatile arterial blood pressure (red trace) and femoral blood flow (blue trace) from a normoxic rat (A). Expanded section of the blood pressure trace (B); the peak height (systolic blood pressure) and inter-peak interval are noted. Values for systolic blood pressure and inter-peak interval were plotted against time, and fast Fourier transformed into the frequency domain to produce BPV (C) and HRV (D) power spectra, respectively.

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  Figure 4. Baseline cardiovascular function. Mean arterial pressure (MAP, A) and mean heart rate (HR, B) in male offspring from normoxic (N; white, n=8 and 10, respectively), hypoxic (H; grey, n=6 and 9, respectively), hypoxic+MitoQ (HM; red, n=6 and 8, respectively), and normoxic+MitoQ (NM; blue, n=4 and 6, respectively) pregnancies. Data are mean ± SEM. Two-way ANOVA for the effect of hypoxia (*, p <0.05) and the effect of MitoQ (†, p <0.05).

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  Figure 5. Blood pressure variability. Very low frequency (VLF, A) and low frequency (LF, B) blood pressure variability (BPV) in from male offspring from normoxic (N; white, n=8), hypoxic (H; grey, n=6), hypoxic+MitoQ (HM; red, n=6), and normoxic+MitoQ (NM; blue, n=4) pregnancies. Data are mean ± SEM. Two-way ANOVA for the effect of hypoxia (*p <0.05) and the effect of MitoQ (†p <0.05).

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  Figure 6. Heart rate variability. The standard deviation of the inter-beat intervals (SDNN, A), very low frequency (VLF) heart rate variability (HRV, B), low frequency/ high frequency ratio (LF/HF, C) in male offspring from normoxic (N; white, n=10), hypoxic (H; grey, n=9), hypoxic+MitoQ (HM; red, n=8), and normoxic+MitoQ (NM; blue, n=6) pregnancies, and normalised LF (black bars) and HF (white bars) HRV (D). Data are mean ± SEM. Two-way ANOVA for the effect of hypoxia (*, p <0.05) and the effect of MitoQ (†, p <0.05).