Denis Chemla

Haemodynamic evaluation of pulmonary hypertension

Pulmonary hypertension is characterised by the chronic elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) leading to right ventricular enlargement and hypertrophy. Pulmonary hypertension may result from respiratory and cardiac diseases, the most severe forms occurring in thromboembolic and primary pulmonary hypertension. Pulmonary hypertension is most often defined as a mean PAP >25 mmHg at rest or >30 mmHg during exercise, the pressure being measured invasively with a pulmonary artery catheter. Doppler echocardiography allows serial, noninvasive follow-up of PAPs and right heart function. When the adaptive mechanisms of right ventricular dilatation and hypertrophy cannot compensate for the haemodynamic burden, right heart failure occurs and is associated with poor prognosis. The haemodynamic profile is the major determinant of prognosis. In both primary and secondary pulmonary hypertension, special attention must be paid to the assessment of pulmonary vascular resistance index (PVRI), right heart function and pulmonary vasodilatory reserve. Recent studies have stressed the prognostic values of exercise capacity (6-min walk test), right atrial pressure, stroke index and vasodilator challenge responses, as well as an interest in new imaging techniques and natriuretic peptide determinations. Overall, careful haemodynamic evaluation may optimise new diagnostic and therapeutic strategies in pulmonary hypertension.

Pulmonary artery pulse pressure and wave reflection in chronic pulmonary thromboembolism and primary pulmonary hypertension

OBJECTIVES The purpose of this time-domain study was to compare pulmonary artery (PA) pulse pressure and wave reflection in chronic pulmonary thromboembolism (CPTE) and primary pulmonary hypertension (PPH). BACKGROUND Pulmonary artery pressure waveform analysis provides a simple and accurate estimation of right ventricular afterload in the time-domain. Chronic pulmonary thromboembolism and PPH are both responsible for severe pulmonary hypertension. Chronic pulmonary thromboembolism and PPH predominantly involve proximal and distal arteries, respectively, and may lead to differences in PA pressure waveform. METHODS High-fidelity PA pressure was recorded in 14 patients (7 men/7 women, 46 +/- 14 years) with CPTE (n = 7) and PPH (n = 7). We measured thermodilution cardiac output, mean PA pressure (MPAP), PA pulse pressure (PAPP = systolic - diastolic PAP) and normalized PAPP (nPAPP = PPAP/MPAP). Wave reflection was quantified by measuring Ti, that is, the time between pressure upstroke and the systolic inflection point (Pi), deltaP, that is, the systolic PAP minus Pi difference, and the augmentation index (deltaP/PPAP). RESULTS At baseline, CPTE and PPH had similar cardiac index (2.4 +/- 0.4 vs. 2.5 +/- 0.5 l/min/m2), mean PAP (59 +/- 9 vs. 59 +/- 10 mm Hg), PPAP (57 +/- 13 vs. 53 +/- 13 mm Hg) and nPPAP (0.97 +/- 0.16 vs. 0.89 +/- 0.13). Chronic pulmonary thromboembolism had shorter Ti (90 +/- 17 vs. 126 +/- 16 ms, p < 0.01) and higher deltaP/PPAP (0.26 +/- 0.01 vs. 0.09 +/- 0.07, p < 0.01). CONCLUSIONS Our study indicated that: 1) CPTE and PPH with severe pulmonary hypertension had similar PA pulse pressure, and 2) wave reflection is elevated in both groups, and CPTE had increased and anticipated wave reflection as compared with PPH, thus suggesting differences in the pulsatile component of right ventricular afterload.

Mechanics and crossbridge kinetics of tracheal smooth muscle in two inbred rat strains

The aim of the study was to determine whether the nonspecific in vivo airway hyperresponsiveness of the inbred Fisher F‐344 rat strain was associated with differences in the intrinsic contractile properties of tracheal smooth muscle (TSM) when compared with Lewis rats. Isotonic and isometric contractile properties of isolated TSM from Fisher and Lewis rats (each n=10) were investigated, and myosin crossbridge (CB) number, force and kinetics in both strains were calculated using Huxleys equations adapted to nonsarcomeric muscles. Maximum unloaded shortening velocity and maximum extent of muscle shortening were higher in Fisher than in Lewis rats (∼46% and ∼42%, respectively), whereas peak isometric tension was similar. The curvature of the hyperbolic force/velocity relationship did not differ between strains. Myosin CB number and unitary force were similar in both strains. The duration of CB detachment and attachment was shorter in Fisher than in Lewis rats (∼−46% and −34%, respectively). In Fisher rats, these results show that inherited, genetically determined factors of airway hyperresponsiveness are associated with changes in crossbridge kinetics, contributing to an increased tracheal smooth muscle shortening capacity and velocity.