BackgroundTo compare continuous cardiac output obtained by simulation of an aortic input impedance model to bolus injection thermodilution (TDCO) in critically ill patients with septic shock.MethodsIn an open study, mechanically ventilated patients with septic shock were monitored for 1 (32 patients

Continuous cardiac output in septic shock by simulating a model of the aortic input impedance: a comparison with bolus injection thermodilution.

The proper understanding of the cardiovascular mechanisms involved in complaints of short-lasting dizziness and the evaluation of unexplained recurrent syncope requires continuous monitoring of cardiac stroke volume (SV) in addition to blood pressure and heart rate. The primary aim of the present study was to evaluate a pulse wave analysis method that calculates beat-to-beat flow from non-invasive arterial pressure by simulating a non-linear, time-varying model of human aortic input impedance (Modelflow; MF), by comparing MF stroke volume (SVMF) to Doppler ultrasound (US) flow velocity SV (SVUS). A second purpose was to compare the two methods under two different conditions: the supine and head-up tilt (30°) position. SVUS and SVMF with non-invasive arterial pressure (Finapres) as input to the aortic model were measured beat-to-beat during spontaneous supine breathing and in the passive 30° head-up tilt (HUT30) position in six normotensive healthy humans [three females, mean age 24 (21–26) years]. There were variations in supine SV track between the two methods with zero difference and a SD of the beat-to-beat difference (MF−US) of 4.2%. HUT30 induced a systematic difference of 10.5% and an increase in SD to 6.9%, which was reproducible. Beat-to-beat changes in SV in the supine resting condition were equally well assessed by both methods. Systematic differences appear during HUT30 and show opposite signs. The difference between the two methods upon a change in body position may be attributed to limitations in each method.

Beat-to-beat noninvasive stroke volume from arterial pressure and Doppler ultrasound.

Mechanisms involved in the control of arterial pressure during postural changes were studied by analysis of the dynamic time course of cardiovascular changes during head-up tilt (HUT) and tilt back to supine position (TB). Beat-to-beat values of cardiovascular variables were recorded continuously before, during, and after passive HUT to 30° in seven healthy humans. Left cardiac stroke volume (SV, Doppler ultrasound), mean arterial blood pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral conductance (TPC) were recorded. During HUT, MAP at the level of the carotid baroreceptors decreased by ∼5 mmHg. There was a striking asymmetry between the time courses of cardiovascular changes on HUT and on TB. Adjustments generally took up to 30 s after HUT, whereas most changes were completed during the first 10 s after TB. Cardiovascular reflex adjustments of HR and TPC were more symmetrical. After HUT, SV was maintained during the first 4–6 s and then decreased steadily during the next 30 s to...

Dynamic time course of hemodynamic responses after passive head-up tilt and tilt back to supine position

The hypoxia-inducible factors (HIFs; isoforms HIF-1α, HIF-2α, HIF-3α) mediate many responses to hypoxia. Their regulation is principally by oxygen-dependent degradation, which is initiated by hydroxylation of specific proline residues followed by binding of von Hippel-Lindau (VHL) protein. Chuvash polycythemia is a disorder with elevated HIF. It arises through germline homozygosity for hypomorphic VHL alleles and has a phenotype of hematological, cardiopulmonary, and metabolic abnormalities. This study explores the phenotype of two other HIF pathway diseases: classic VHL disease and HIF-2α gain-of-function mutation. No cardiopulmonary abnormalities were detected in classic VHL disease. HIF-2α gain-of-function mutations were associated with pulmonary hypertension, increased cardiac output, increased heart rate, and increased pulmonary ventilation relative to metabolism. Comparison of the HIF-2α gain-of-function responses with data from studies of Chuvash polycythemia suggested that other aspects of the Chuvash phenotype were diminished or absent. In classic VHL disease, patients are germline heterozygous for mutations in VHL, and the present results suggest that a single wild-type allele for VHL is sufficient to maintain normal cardiopulmonary function. The HIF-2α gain-of-function phenotype may be more limited than the Chuvash phenotype either because HIF-1α is not elevated in the former condition, or because other HIF-independent functions of VHL are perturbed in Chuvash polycythemia.—Formenti, F., Beer, P. A., Croft, Q. P. P., Dorrington, K. L., Gale, D. P., Lappin, T. R. J., Lucas, G. S., Maher, E. R., Maxwell, P. H., McMullin, M. F., O'Connor, D. F., Percy, M. J., Pugh, C. W., Ratcliffe, P. J., Smith, T. G., Talbot, N. P., Robbins, P. A. Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2α gain-of-function mutation.

Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2alpha gain-of-function mutation.

We present a theoretical evaluation of a cardiovascular system identification method that we previously developed for the analysis of beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure, and instantaneous lung volume. The method provides a dynamical characterization of the important autonomic and mechanical mechanisms responsible for coupling the fluctuations (inverse modeling). To carry out the evaluation, we developed a computational model of the cardiovascular system capable of generating realistic beat-to-beat variability (forward modeling). We applied the method to data generated from the forward model and compared the resulting estimated dynamics with the actual dynamics of the forward model, which were either precisely known or easily determined. We found that the estimated dynamics corresponded to the actual dynamics and that this correspondence was robust to forward model uncertainty. We also demonstrated the sensitivity of the method in detecting small changes in parameters characterizing autonomic function in the forward model. These results provide confidence in the performance of the cardiovascular system identification method when applied to experimental data.

A forward model-based validation of cardiovascular system identification.

An existing ultrasound Doppler method for measuring cardiac output has been improved and refined, partly by locating the sampling volume higher up in the aorta while still using the aortic ring size as the effective transverse flow area. The basis for using this technique is the approximately rectangular systolic velocity profile in the aortic orifice in physiologically and anatomically normal subjects, and the fact that this profile velocity is conserved as the maximum velocity in the ascending aorta for some 3 to 4 cm above the valves. This higher location of the sampling volume improves Doppler signal quality, and does not reduce the accuracy of the method, as can be confirmed in each experimental subject. Together with automatic computer-based online signal analysis, the technique employed enables us to make continuous long-term beat-to-beat measurements of cardiac output in subjects without aortic valve disease or grossly deforming disease of the aortic root.

L. Walløe

Papers

Improved method for cardiac output determination in man using ultrasound Doppler technique