Frank's Windkessel model described the hemodynamics of the arterial system in terms of resistance and compliance. It explained aortic pressure decay in diastole, but fell short in systole. Therefore characteristic impedance was introduced as a third element of the Windkessel model. Characteristic impedance links the lumped Windkessel to transmission phenomena (e.g., wave travel). Windkessels are used as hydraulic load for isolated hearts and in studies of the entire circulation. Furthermore, they are used to estimate total arterial compliance from pressure and flow; several of these methods are reviewed. Windkessels describe the general features of the input impedance, with physiologically interpretable parameters. Since it is a lumped model it is not suitable for the assessment of spatially distributed phenomena and aspects of wave travel, but it is a simple and fairly accurate approximation of ventricular afterload.

After PAH-targeted therapy, RV function can deteriorate despite a reduction in PVR. Loss of RV function is associated with a poor outcome, irrespective of any changes in PVR.

In pulmonary hypertension, the right ventricle adapts to the increasing vascular load by enhancing contractility ("coupling") to maintain flow. Ventriculoarterial coupling implies that stroke volume changes little while preserving ventricular efficiency. Ultimately, a phase develops where ventricular dilation occurs in an attempt to limit the reduction in stroke volume, with uncoupling and increased wall stress as a consequence. With pressure-volume analysis, we separately describe the changing properties of the pulmonary vascular system and the right ventricle, as well as their coupling, as important concepts for understanding the changes that occur in pulmonary hypertension. On the basis of the unique properties of the pulmonary circulation, we show how all relevant physiological parameters can be derived using an integrative approach. Because coupling is maintained by hypertrophy until the end stage of the disease, when progressive dilation begins, right ventricular volume is the essential parameter to measure in follow-up of patients with pulmonary hypertension.

Background-Type 2 diabetes (DM-2) and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease risk. In nondiabetic individuals, increased arterial stiffness is an important cause of cardiovascular disease. Associations between DM-2 and IGM and arterial stiffness have not been systematically investigated. Methods and Results-In a population-based cohort (nϭ747; 278 with normal glucose metabolism, 168 with IGM, and 301 with DM-2; mean age, 68.5 years), arterial stiffness was ultrasonically estimated by distensibility and compliance of the carotid, femoral, and brachial arteries and by the carotid elastic modulus. After adjustment for age, sex, and mean arterial pressure, DM-2 was associated with increased carotid, femoral, and brachial stiffness, whereas IGM was associated only with increased femoral and brachial stiffness. .63) for femoral compliance. The brachial artery followed a pattern similar to that of the femoral artery. Increases in stiffness indices were explained by decreases in distension, increases in pulse pressure, an increase in carotid intima-media thickness, and, for the femoral artery, a decrease in diameter. Hyperglycemia or hyperinsulinemia explained only 30% of the arterial changes associated with glucose tolerance. Adjustment for conventional cardiovascular risk factors did not affect these findings. Conclusions-IGM and DM-2 are associated with increased arterial stiffness. An important part of the increased stiffness occurs before the onset of DM-2 and is explained neither by conventional cardiovascular risk factors nor by hyperglycemia or hyperinsulinemia.

Abstract-Impaired glucose metabolism (IGM) and type 2 diabetes (DM-2) are associated with high cardiovascular disease risk. Increases in peripheral and central artery stiffness may represent pathophysiologic pathways through which glucose tolerance status leads to cardiovascular disease. Peripheral artery stiffness increases with deteriorating glucose tolerance status, whereas this trend remains unclear for central artery stiffness. Therefore, we investigated the associations between glucose tolerance status and estimates of central arterial stiffness. We performed a population-based study of 619 individuals (normal glucose metabolism, nϭ261; IGM, nϭ170; and DM-2, nϭ188) and assessed central artery stiffness by measuring total systemic arterial compliance, aortic pressure augmentation index, and carotid-femoral transit time. After adjustment for sex, age, heart rate, height, body mass index, and mean arterial pressure, DM-2 was associated with decreased total systemic arterial compliance, increased aortic augmentation index, and decreased carotid-femoral transit time. IGM was borderline significantly associated with decreased total systemic arterial compliance. Respective regression coefficients (95% confidence intervals) for IGM and DM-2 compared with normal glucose metabolism were Ϫ0.05 (Ϫ0.11 to 0.01) and Ϫ0.13 (Ϫ0.19 to Ϫ0.07) mL/mm Hg for total systemic arterial compliance; 1.1 (Ϫ0.2 to 2.5) and 1.

I diopathic pulmonary arterial hypertension (PAH) is a rare but fatal disease with a survival rate of 58% at 3 years. Present therapy is unable to normalize pulmonary arterial pressures, and PAH patients ultimately develop right heart failure. Editorial see p 1999 Clinical Perspective on p 2025Previous studies have demonstrated that PAH patients have reduced systolic function as measured by right ventricular Background-The role of right ventricular (RV) diastolic stiffness in pulmonary arterial hypertension (PAH) is not well established. Therefore, we investigated the presence and possible underlying mechanisms of RV diastolic stiffness in PAH patients. Methods and Results-Single-beat RV pressure-volume analyses were performed in 21 PAH patients and 7 control subjects to study RV diastolic stiffness. Data are presented as mean±SEM. RV diastolic stiffness (β) was significantly increased in PAH patients (PAH, 0.050±0.005 versus control, 0.029±0.003; P<0.05) and was closely associated with disease severity. Subsequently, we searched for possible underlying mechanisms using RV tissue of PAH patients undergoing heart/lung transplantation and nonfailing donors. Histological analyses revealed increased cardiomyocyte cross-sectional areas (PAH, 453±31 μm 2 versus control, 218±21 μm 2 ; P<0.001), indicating RV hypertrophy. In addition, the amount of RV fibrosis was enhanced in PAH tissue (PAH, 9.6±0.7% versus control, 7.2±0.6%; P<0.01). To investigate the contribution of stiffening of the sarcomere (the contractile apparatus of RV cardiomyocytes) to RV diastolic stiffness, we isolated and membrane-permeabilized single RV cardiomyocytes. Passive tension at different sarcomere lengths was significantly higher in PAH patients compared with control subjects (>200%; P interaction <0.001), indicating stiffening of RV sarcomeres. An important regulator of sarcomeric stiffening is the sarcomeric protein titin. Therefore, we investigated titin isoform composition and phosphorylation. No alterations were observed in titin isoform composition (N2BA/N2B ratio: PAH, 0.78±0.07 versus control, 0.91±0.08), but titin phosphorylation in RV tissue of PAH patients was significantly reduced (PAH, 0.16±0.01 arbitrary units versus control, 0.20±0.01 arbitrary units; P<0.05). In addition, these measures are highly sensitive to the confounding effects of increased preload and afterload and are therefore not reliable in the setting of PAH. 4 On the other hand, the gold standard of measuring load-independent diastolic stiffness by pressure-volume (PV) analysis is not without risk in PAH patients because it requires temporal preload reduction. Conclusions-RV3 In left heart failure, this was circumvented by the development of single-beat analyses of diastolic PV relationship. 5,6 However, it is unclear whether this analysis could also be used for the RV in PAH.There are several possible contributing factors explaining RV diastolic stiffness in PAH. Hypertrophy and fibrosis are known to increase ventricular stiffness.7 However, RV diastolic stiffn...

In earlier studies we found that the three-element windkessel, although an almost perfect load for isolated heart studies, does not lead to accurate estimates of total arterial compliance. To overcome this problem, we introduce an inertial term in parallel with the characteristic impedance. In seven dogs we found that ascending aortic pressure could be predicted better from aortic flow by using the four-element windkessel than by using the three-element windkessel: the root-mean-square errors and the Akaike information criterion and Schwarz criterion were smaller for the four-element windkessel. The three-element windkessel overestimated total arterial compliance compared with the values derived from the area and the pulse pressure method ( P = 0.0047, paired t-test), whereas the four-element windkessel compliance estimates were not different ( P = 0.81). The characteristic impedance was underestimated using the three-element windkessel, whereas the four-element windkessel estimation differed marginally from the averaged impedance modulus at high frequencies ( P = 0.0017 and 0.031, respectively). When applied to the human, the four-element windkessel also was more accurate in these same aspects. Using a distributed model of the systemic arterial tree, we found that the inertial term results from the proper summation of all local inertial terms, and we call it total arterial inertance. We conclude that the fourelement windkessel, with all its elements having a hemodynamic meaning, is superior to the three-element windkessel as a lumped-parameter model of the entire systemic tree or as a model for parameter estimation of vascular properties.

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