One- and two-compartment minimal models detect similar alterations of glucose metabolism indexes in hypertension.

A standard intravenous glucose tolerance test (IVGTT) was performed in 10 nondiabetic patients with essential hypertension (H group) and 9 normotensive control subjects (N group). A 2-compartment minimal model (2CMM) of glucose kinetics was applied to estimate indexes of glucose effectiveness, S2G and insulin sensitivity, S2I, by means of a maximum a posteriori (MAP) bayesian estimation technique. These estimates were contrasted to the S1G and S1I indexes provided by the classic minimal model (1CMM). In both the N group and the H group, the 2CMM underestimated the glucose effectiveness and overestimated the insulin sensitivity. In the H group, S2G was, on average, 63% of S1G (P > .05) and S2I was 137% of S1I (P > .05). In the N group S2G was 67% of S1G (P > .05) and S2I was 134% of S1I (P > .05). The 2CMM detected a reduction of approximately 40% (P > .05) and approximately 48% (P > .05) in S2G and S2I estimates, respectively, from the N group to the H group. Despite its reduced complexity, the 1CMM also detected a reduction of approximately 35% (P < .05) and approximately 49% (P < .05) in the S1G and in S1I indexes, respectively. Thus, the 1CMM and 2CMM showed a substantial equivalence in detecting a severe reduction in insulin sensitivity and impaired glucose effectiveness in hypertensive patients compared with normal.

Insulin sensitivity and glucose effectiveness estimated by the minimal model technique in spontaneously hypertensive and normal rats.

This study was performed to compare glucose metabolism in anaesthetised spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) in an attempt to clarify whether this animal model of hypertension approximates the insulin-resistant state seen in human hypertension. With this aim the minimal model of glucose kinetics was applied to glucose and insulin data derived from a 12-sample, 120 min intravenous glucose tolerance test (IVGTT) performed in ten SHR and nine WKY rats under pentobarbital anaesthesia. This method provided two metabolic indices: the glucose effectiveness, S(G), which quantifies the ability of glucose per se to enhance its rate of disappearance and to inhibit hepatic glucose production, and the insulin sensitivity, S(I), which measures the ability of insulin to enhance plasma glucose disappearance and to inhibit hepatic glucose production. Systolic and diastolic arterial pressures in the SHR group were significantly higher (P < 0.0005) than in the WKY group. Mean S(G) and S(I) estimates from the SHR group (S(G) = 16.2 (+/- 2.0) x 10(-2) dl x min(-1) x kg(-1) and S(I) = 12.5 (+/- 1.9) x 10(-4) dl x min(-1) x kg(-1) (microU ml(-1))(-1)) were not significantly different (P > 0.05) from mean estimates that characterised the WKY group (S(G) = 13.1 (+/- 1.5) x 10(-2) dl x min(-1) x kg(-1) and S(I) = 15.8 (+/- 4.3) x 10(-4) dl x min(-1) x kg(-1) (microU ml(-1))(-1)). This result is in contrast with reported findings from humans in which insulin sensitivity is significantly reduced in the presence of hypertension.

Viscoelasticity modulates resonance in the terminal aortic circulation.

We used an inertance-viscoelastic windkessel model (IVW) to interpret aortic impedance patterns as seen in the terminal aortic circulation of the dog, and to explain evident oscillatory phenomena in flow measurements. This IVW model consists of an inertance, L, connected in series with a viscoelastic windkessel (VW) where the peripheral resistance, Rp, is connected in parallel with a Voigt cell (a resistor, Rd, in series with a capacitor, C) to account for viscoelasticity. Pressure and flow measurements were taken from the terminal aorta, just downstream of the origin of renal arteries, in three anaesthetised open-chest dogs, under a variety of haemodynamic conditions induced by administering a vasoconstrictor agent (methoxamine) and a vasodilator (sodium nitroprusside). Mean pressure ranged from 40 to 140 mm Hg. The resistance Rp was calculated as the ratio of mean pressure to mean flow. Parameters L, C and Rd were estimated by fitting measured to model predicted flow waves. We found that prominent oscillations observed in flow waves, from midsystole to diastole, are related to resonance that occurs at a frequency, f(o), where reactance of inertance of blood motion matches the reactance of arterial compliance. Estimates of f(o) increased from 2.4 to 10 Hz with increasing pressure and showed a correlation with values of static elastic moduli plotted against mean pressure of dogs' peripheral arteries previously reported by others. Viscous losses, Rd, of arterial wall motion limited the amplitude of resonance peak. We conclude that viscoelasticity, rather than pure elasticity, is a key issue to interpret terminal aortic impedance as it relates to resonance.

Complex and frequency-dependent compliance of viscoelastic windkessel resolves contradictions in elastic windkessels.

Based on simulated data, recent studies by others showed that fitting measured pulse pressure with the pulse pressure predicted by the two-element windkessel (W2-based pulse pressure method, PPM) yielded estimates of total arterial compliance closer to simulated values than other estimation methods that use either the W2 model or the three-element windkessel (W3). A later experimental application of the PPM, made by us, however, yielded relatively non pressure dependent estimates of compliance that were in contradiction with pressure dependent estimates obtained from the W2 model by fitting to the full aortic pressure wave (full pressure method, FPM). To explain these contradictory findings, in the present study we interpreted the aortic input impedance in terms of a viscoelastic windkessel (VW), where total peripheral resistance is connected in parallel to a complex and frequency dependent compliance, Cc(j omega), described by the Voigt cell. Using ascending aortic pressure and flow taken from four dogs, under a variety of haemodynamic states, we compared the estimates of compliance obtained from the W3 and VW models and from different W2-based estimation methods: the FPM (Cw2), the PPM (Cpp), the decay time method, DTM (Cdt), and the area method, AM (C(am)). The VW-based estimates of complex compliance resolved contradictions in the W2-based estimates. Static compliance of VW-model, Cvw = Cc(0), showed a good correlation (p = 0.999) with Cw2. Correlation of static compliance with C(am) and Cdt estimates was affected by distortions in diastolic pressure decay. The modulus of VW model's dynamic compliance, ¿Cc(omega(h))¿, at the heart pulsation omega(h), was well correlated (p = 0.975) with Cpp. Analysis of data fit and compliance estimates indicated that the VW model yields an improvement over the W3 in the physical interpretation of the overall arterial properties.