Energetically wasteful wave reflections due to impedance mismatching in hypertension and their reversal with vasodilator: Time and frequency domain evaluations.

BACKGROUND: Increased pulse wave reflections in hypertension arise due to impedance mismatching and the effective energy transmission to the vasculature is compromised. Their quantification in the time and the frequency domains are compared and the beneficial effect of vasodilator is evaluated in the study. METHODS: A simple, fast time domain method for the resolution of aortic pressure and flow pulses into their forward and reflected components is presented, together with frequency domain reflection coefficient and impedance calculations. Both steady and pulsatile energy components are quantified during induced hypertension (HBP) and subsequent vasodilator (VSD, nitroprusside) treatment in experimental mongrel dogs. Corresponding power generation and usage are also analyzed. RESULTS: Characteristic impedance and peripheral resistance were not statistically different between the methods (p > 0.05). Time domain reflection coefficient identified significant differences among control, HBP and VSD groups (p < 0.05) while the frequency domain method did not adequately differentiate the control and the HBP groups. Impedance calculations were similar between the two methods. Frequency domain calculations of total, mean and pulsatile power were, on average, 32.6 mW higher, 12.8 mW lower and 45.4 mW higher than their respective time domain calculations (p < 0.05). Hypertension increased energy consumption, on average, by 88.8 mJ (p < 0.05) and subsequent VSD decreased the energy consumption, on average, by 99.4 mJ (p < 0.05). CONCLUSION: Impedance mismatching in hypertension which leads to increased wave reflections and significantly increased pulsatile work, could be effectively alleviated through vasodilator therapy. This can be quantified through the time-domain method, which is fast and equally accurate as the time-consuming frequency domain approach. The time domain method to quantify crucial parameters such as stroke work cannot be readily determined using the frequency domain methods.

A novel compliance-pressure loop approach to quantify arterial compliance in systole and in diastole.

Arterial compliance has been recognized as a critical parameter in governing pulsatile flow dynamics. It has traditionally been assumed constant throughout the cardiac cycle and its computation has been based either on the classic Windkessel model (C) in diastole or the stroke volume over pulse pressure (Cv) method in systole. Other methods using area (Cam) or two-area (Ctam) and exponential (C(P)exp1) methods were used for the cardiac cycle. We proposed a novel compliance-pressure loop (CPP loop) approach for the quantification of arterial compliance and compared it to existing linear and nonlinear methods. Experimental data were gathered in 5 dogs and blood pressure levels were varied (systolic pressure of 100 mmHg-185 mmHg) with induced hypertension and vasodilation. Results showed the limited regime of validity of C (Control:0.4681 ±â€¯0.1270 ml/mmHg, MTX:0.3015 ±â€¯0.1264 ml/mmHg and NTP:1.8323 ±â€¯0.7207 ml/mmHg) and Cv (Control:0.3583 ±â€¯0.0158 ml/mmHg, MTX:0.2602 ±â€¯0.1275 ml/mmHg and NTP:0.4131 ±â€¯0.0589 ml/mmHg), Cam (Control:0.4175 ±â€¯0.0505, MTX:0.3086 ±â€¯0.1568 and NTP:1.4181 ±â€¯0.4812) and Ctam (Control: 0.2064 ±â€¯0.0228 ml/mmHg, MTX:0.1967 ±â€¯0.0884 ml/mmHg, NTP:0.0881 ±â€¯0.0375 ml/mmHg) and that C(P)exp1 underestimates the arterial compliance compared to our method (Control:0.2233 ±â€¯0.0168 ml/mmHg vs 0.4481 ±â€¯0.0515 ml/mmHg, MTX:0.1976 ±â€¯0.0964 ml/mmHg vs 0.3273 ±â€¯0.1443 ml/mmHg and NTP: 0.2177 ±â€¯0.0273 ml/mmHg vs 1.9990 ±â€¯1.8221 ml/mmHg at mean arterial pressure). The CPP method based on the exponential method is superior, as it provides continuous compliance variations and CPP loop area can be readily visualized from hypotension to hypertension conditions. We conclude that the concept of using compliance-pressure loop is advantageous as it can afford continuous and accurate tracking of the dynamic arterial behavior despite greatly varying blood pressure levels.

Circulating Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Kidney Dysfunction and Arterial Stiffness.

BACKGROUND: Large artery stiffening is increased in advanced chronic kidney disease (CKD) but likely develops progressively in earlier stages of CKD. Active matrix Gla-protein (MGP) is a potent vitamin K-dependent inhibitor of vascular calcification. A recent animal model demonstrated intrinsic abnormalities in vitamin K metabolism even in early CKD, but whether early human CKD is associated with vascular vitamin K deficiency is unknown. METHODS: We enrolled 137 adults without HF with varying degrees of renal function: normal estimated glomerular filtration rate (eGFR; >90 ml/min; n = 59), mildly reduced eGFR (stage 2 CKD: eGFR = 60-89 ml/min; n = 53) or at least moderately reduced eGFR (stage 3-5 CKD; eGFR < 60 ml/min; n = 25). Carotid-femoral pulse wave velocity (CF-PWV) was measured with carotid and femoral tonometry. Dephospho-uncarboxylated matrix gla-protein (dp-ucMGP) was measured with enzyme-linked immunosorbent assay (ELISA) (VitaK; Maastricht University; The Netherlands). RESULT: Dp-ucMGP levels were progressively increased with decreasing renal function (eGFR ≥ 90: 247 pmol/l; eGFR 60-89: 488 pmol/l; eGFR < 60: 953 pmol/l; P < 0.0001). These differences persisted after adjustment for multiple potential confounders (eGFR ≥ 90: 314 pmol/l; eGFR 60-89: 414 pmol/l; eGFR < 60: 770 pmol/l; P < 0.0001). In a multivariable model adjusted for various confounders, dp-ucMGP was a significant independent predictor of CF-PWV (ß = 0.21; P = 0.019). In formal mediation analyses, dp-ucMGP mediated a significant relationship between eGFR and higher CF-PWV (ß = -0.16; P = 0.005), whereas no significant dp-ucMGP-independent relationship was present (ß = -0.02; P = 0.80). CONCLUSIONS: CKD is associated with increased (inactive) dp-ucMGP, a vitamin K-dependent inhibitor of vascular calcification, which correlates with large artery stiffness. Further studies are needed to assess whether vitamin K2 supplementation represents a suitable therapeutic strategy to prevent or reduce arterial stiffening in CKD.