Measurement of aortic input impedance in mice: effects of age on aortic stiffness

Mice are used with increasing frequency as models of human cardiovascular diseases, but significant gaps exist in our knowledge of vascular function in the aging mouse. We determined aortic input impedance spectra, pulse wave velocity, and augmentation index in adult (8-mo-old) and old (29-mo-old) mice to determine whether arterial stiffening occurred with age in mice as it does in humans. Pressure and blood velocity signals measured simultaneously from the same location in the ascending aorta were used to determine input impedance spectra (0–10 harmonics). The first minimum of the impedance modulus occurred at the second harmonic in adult mice but shifted to the fourth harmonic in old mice. Characteristic impedance (average of 2nd–10th harmonic) was 57% higher in old mice: 471 ± 62 vs. 299 ± 10 (SE) dyn · s · cm–3 ( P < 0.05). Pulse pressure and augmentation index, determined from the aortic pressure signals, were also higher in old mice: 42 ± 2.2 vs. 29 ± 4.9 mmHg ( P < 0.05) and 37 ± 5 vs. 14 ± 2% ( P < 0.005). Aortic pulse wave velocity measured from the timing of upstrokes of the Doppler velocity signals was 45% higher in old mice: 416 ± 22 vs. 286 ± 14 cm/s ( n = 3, P < 0.01). These results reproduce age-related findings reported in humans and confirm that mice may be used as models of age-related vascular stiffening.

Fumonisin-induced blockade of ceramide synthase in sphingolipid biosynthetic pathway alters aortic input impedance spectrum of pigs

The sphingolipid signaling pathway appears to play an important role in regulating vascular tone. We examined the effect of fumonisin B1, a fungal toxin in corn that blocks ceramide synthase in the sphingolipid signaling pathway, on the ascending aortic impedance spectrum of pigs. Sixteen pigs were fed culture material containing fumonisin B1 (20 mg/kg body wt) ( n = 7) or a control diet ( n = 9) daily for 3 days and then instrumented under α-chloralose anesthesia for measurement of ascending aortic pressure and flow. Fumonisin ingestion increased serum sphinganine and sphingosine concentrations. Fumonisin ingestion also decreased cardiac output and characteristic impedance and increased the frequency of the first minimum impedance modulus, systemic vascular resistance, and the terminal, first, and second harmonic reflection coefficients, without changing mean arterial pressure. Thus blockade of ceramide synthase is accompanied by decreased vascular tone in systemic conduit arteries and increased vascular tone in systemic resistance vessels. The results indicate that the sphingolipid signaling pathway influences vascular tone in α-chloralose-anesthetized pigs.

Effects of Diabetes and Gender on Mechanical Properties of the Arterial System in Rats: Aortic Impedance Analysis1

We determined the effects of diabetes and gender on the physical properties of the vasculature in streptozotocin (STZ)-treated rats based on the aortic input impedance analysis. Rats given STZ 65 mg/kg i.v. were compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured and were then subjected to Fourier transformation for the analysis of aortic input impedance. Wave transit time was determined using the impulse response function of the filtered aortic input impedance spectra. Male but not female diabetic rats exhibited an increase in cardiac output in the absence of any significant changes in arterial blood pressure, resulting in a decline in total peripheral resistance. However, in each gender group, diabetes contributed to an increase in wave reflection factor, from 0.47 ± 0.04 to 0.84 ± 0.03 in males and from 0.46 ± 0.03 to 0.81 ± 0.03 in females. Diabetic rats had reduced wave transit time, at 18.82 ± 0.60 vs 21.34 ± 0.51 msec in males and at 19.63 ± 0.37 vs 22.74 ± 0.57 msec in females. Changes in wave transit time and reflection factor indicate that diabetes can modify the timing and magnitude of the wave reflection in the rat arterial system. Meanwhile, diabetes produced a fall in aortic characteristic impedance from 0.023 ± 0.002 to 0.009 ± 0.001 mmHg/min/kg/ml in males and from 0.028 ± 0.002 to 0.014 ± 0.001 mmHg/min/kg/ml in females. With unaltered aortic pressure, both the diminished aortic characteristic impedance and wave transit time suggest that the muscle inactivation in diabetes may occur in aortas and large arteries and may cause a detriment to the aortic distensibility in rats with either sex. We conclude that only rats with male gender diabetes produce a detriment to the physical properties of the resistance arterioles. In spite of male or female gender, diabetes decreases the aortic distensibility and impairs the wave reflection phenomenon in the rat arterial system.