Juan C. Grignola

Hemodynamic assessment of pulmonary hypertension

There has been significant progress in our understanding of the pathobiology, epidemiology and prognosis of pulmonary vascular disease and, over the past few years, there has been an explosion of clinical therapeutic trials for pulmonary arterial hypertension (PAH). The increasing number of different conditions now associated with PAH and the appearance of new diagnostic techniques have led to a need for a systematic diagnostic approaches and a new disease classification, which has resulted in notable improvements in the quality and efficacy of clinical care. We appreciate traditional resting right heart catheterization techniques (which still remain the gold standard for diagnosing PAH and managing patients on therapy) and look forward to novel invasive techniques (e.g. intravascular ultrasound) that add greatly to our understanding of right ventricle and pulmonary circulation, and for the interpretation of data from clinical trials as well.

Acute absolute vasodilatation is associated with a lower vascular wall stiffness in pulmonary arterial hypertension

BACKGROUND Acute vasoreactivity testing (VT) is considered mandatory in the diagnostic work-up of patients with pulmonary arterial hypertension (PAH). We studied the relation between the acute absolute arterial vasodilatation and the severity of vascular remodeling estimated by intravascular ultrasound (IVUS) in patients with idiopathic PAH. METHODS Simultaneous right heart catheterization and IVUS of the pulmonary artery (PA) were performed both in basal conditions and during short-term intravenous epoprostenol infusion in nineteen idiopathic PAH patients. Pulmonary vascular resistance (PVRi) and capacitance indexes (stroke volume/pulse pressure, Cp), were calculated. Local pulsatility was estimated by IVUS (IVUSp) (systolic-diastolic lumen area/diastolic lumen area×100; sA-dA/dA) and PA stiffness was assessed by the elastic modulus (E: pulse pressure/IVUSp). RESULTS Epoprostenol infusion (11±2ng/kg/min) determined a real vasodilatation (increment of dA>10%) in six patients. This vasodilation group presented on average significantly higher cardiac index, stroke volume index and Cp, and lower PVRi and IVUSp (P<0.05), with a lower E (P=0.08). Three patients were responders according to the actual criteria, but only one showed a real vasodilator response. Baseline E below the median value (≤190mm Hg) was able to differentiate patients with an acute vasodilator response (sensibility 83%, specificity 73%, area under ROC 0.81; P<0.05). Neither E nor vasodilator response is correlated with delta mean PA pressure and PVRi. CONCLUSIONS Patients with higher IVUSp and lesser E displayed an absolute PA vasodilation during VT with epoprostenol. The patients with a positive VT according to actual criteria do not necessarily have a real vasodilatation on intravascular ultrasound.

Hipertensión pulmonar aguda: función protectora de la activación del músculo liso vascular

Aim. To characterize the buffering function of the pulmonary artery in vivo and to determine the role of vascular smooth muscle (VSM) activation in vessel wall elasticity. Material and method. Pulmonary artery pressure and diameter were measured in 9 anesthetized sheep. Pulmonary artery hypertension was induced by mechanical occlusion of the pulmonary artery and by phenylephrine infusion (5 µg/kg/min) (PHE). Once the pressure-diameter loop was obtained, hysteresis was reduced to a minimum by increasing the modulus of viscosity. Elasticity was calculated as the first derivative of mean diastolic pressure assuming a purely elastic relation. Pulse wave velocity (PWV) and time constant (τ) were also obtained. Results. Systolic, diastolic, mean and pulse pressures were similar during pulmonary artery hypertension and PHE infusion, but significantly higher in comparison to baseline conditions. Elasticity and diameter of the pulmonary artery increased significantly. In contrast, during VSM activation elasticity remained unchanged and diastolic diameter was reduced. PWV increased during both pulmonary artery hypertension and PHE infusion (p < 0.05); however, the increase during PHE infusion was smaller (15%) than during induced hypertension (33%). τ was significantly reduced during hypertension, but did not change during VSM activation. Conclusions. VSM activation may offset the deleterious effect of pulmonary artery hypertension on arterial wall stiffness by reducing elasticity and PWV. The VSM may modulate the Windkessel function in the pulmonary artery, preserving elasticity indexes during pulmonary artery hypertension.

Improved pulmonary artery buffering function during phenylephrine-induced pulmonary hypertension

The goal of this study was to determine the in vivo pulmonary arterial buffering function (BF) during acute and moderate pulmonary hypertension achieved by phenylephrine-induced smooth muscle activation.Pulmonary pressure (Konigsberg P7) and diameter (sonomicrometry) were measured in nine anesthetized sheep. Transit pulmonary arterial hypertension was induced by mechanical occlusion of the pulmonary artery (HP) and by phenylephrine infusion (5 μg/kg/min) (PHE). A viscoelastic Kelvin-Voigt model was used. By increasing the values of the viscous modulus, the pressure-diameter hysteresis area was reduced to a minimum in order to obtain the purely elastic pressure-diameter relationship. The elastic index (E) was calculated as the first derivative of the exponential model of the purely elastic pressure-diameter relationship at the mean pressure point.Systolic, diastolic, mean and pulse pressures were similar during HP and PHE, but significantly higher with regard to control steady state. In HP, E and arterial diameter (both its minimum and maximum values) increased significantly. In contrast, when pulmonary hypertension was induced by VSM activation, E was maintained concomitantly with pulmonary artery vasoconstriction.Pulmonary hypertension produced by occlusion of the pulmonary artery increases elasticity. Smooth muscle activation may offset the deleterious effect of pulmonary hypertension on arterial wall elasticity by reducing E and impeding arterial dilatation and collagen recruitment, maintaining BF during pulmonary hypertension.

Interrater Reliability and Diagnostic Performance of Subjective Evaluation of Sublingual Microcirculation Images by Physicians and Nurses: A Multicenter Observational Study.

ABSTRACT Introduction: This was a cross-sectional multicenter study to investigate the ability of physicians and nurses from three different countries to subjectively evaluate sublingual microcirculation images and thereby discriminate normal from abnormal sublingual microcirculation based on flow and density abnormalities. Methods: Forty-five physicians and 61 nurses (mean age, 36 ± 10 years; 44 males) from three different centers in The Netherlands (n = 61), Uruguay (n = 12), and Japan (n = 33) were asked to subjectively evaluate a sample of 15 microcirculation videos randomly selected from an experimental model of endotoxic shock in pigs. All videos were first analyzed offline using the A.V.A. software by an independent, experienced investigator and were categorized as good, bad, or very bad microcirculation based on the microvascular flow index, perfused capillary density, and proportion of perfused capillaries. Then, the videos were randomly assigned to the examiners, who were instructed to subjectively categorize each image as good, bad, or very bad. An interrater analysis was performed, and sensitivity and specificity tests were calculated to evaluate the proportion of A.V.A. score abnormalities that the examiners correctly identified. Results: The &kgr; statistics indicated moderate agreement in the evaluation of microcirculation abnormalities using three categories, i.e., good, bad, or very bad (&kgr; = 0.48), and substantial agreement using two categories, i.e., normal (good) and abnormal (bad or very bad) (&kgr; = 0.66). There was no significant difference between the &kgr; three and &kgr; two statistics. We found that the examiner’s subjective evaluations had good diagnostic performance and were highly sensitive (84%; 95% confidence interval, 81%–86%) and specific (87%; 95% confidence interval, 84%–90%) for sublingual microcirculatory abnormalities as assessed using the A.V.A. software. Conclusions: The subjective evaluations of sublingual microcirculation by physicians and nurses agreed well with a conventional offline analysis and were highly sensitive and specific for sublingual microcirculatory abnormalities.

In vivo assessment of pulmonary arterial wall fibrosis by intravascular optical coherence tomography in pulmonary arterial hypertension: a new prognostic marker of adverse clinical follow-up.

Background: The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hypertension (PAH) with clinical follow-up. Histology of PA specimens is also performed. Methods: 19 patients, aged 54±16 (4 men), functional class II-III were studied with right heart catheterization, PA Intravascular Ultrasound and optical coherence tomography (OCT) in inferior lobe segment. PA wall fibrosis was obtained by OCT ( area of fibrosis/PA cross sectional area × 100). Patients follow-up was blind to OCT. Events were defined as mortality, lung transplantation, need of intravenous prostaglandins or onset of right ventricular failure. Results: OCT measurements showed high intra- and interobserver agreement. There was a good correlation between OCT and histology in PA fibrosis from explanted lungs. Area of fibrosis was 1.4±0.8 mm2, % fibrosis was 22.3±8. Follow-up was 3.5 years (2.5-4.5). OCT %Fib was significantly correlated with PA capacitance (r=-0.536) and with pulmonary vascular rsistance (r=0.55). Patients were divided according to the median value of PA fibrosis. There were 10 patients with a high (≥ 22%) and 9 with a low fibrosis (<22%). Events occurred in 6 (1 death, 1 lung transplantation, 2 intravenous prostaglandins, 2 right heart failure) out of 10 patients with high and in 0 out of 9 patients with low fibrosis (p<0.01). Conclusions: In PAH, the severity of PA remodeling assessed by OCT wall fibrosis was significantly predictive of severely unfavorable clinical outcome. In vivo assessment of pulmonary arterial wall fibrosis by intravascular OCT in PAH is a promising new prognostic marker of adverse clinical outcome.

The increase of vasomotor tone avoids the ability of the dynamic preload indicators to estimate fluid responsiveness

BackgroundThe use of vasoconstrictor can affect the dynamic indices to predict fluid responsiveness. We investigate the effects of an increase of vascular tone on dynamic variables of fluid responsiveness in a rabbit model of hemorrhage, and to examine the ability of the arterial pressure surrogates dynamic indices to track systolic volume variation (SVV) during hypovolemia under increased vasomotor tone.MethodsEighteen anesthetized and mechanically ventilated rabbits were studied during normovolemia (BL) and after blood progressive removal (15 mL/kg, BW). Other two sets of data were obtained during PHE infusion with normovolemia (BL + PHE) and during hypovolemia (BW + PHE). We measured central venous and left ventricular (LV) pressures and infra diaphragmatic aortic blood flow (AoF) and pressure. Pulse pressure variation (PPV), systolic pressure variation (SPV) and SVV were estimated manually by the variation of beat-to-beat PP, SP and SV, respectively. We also calculated PPVapnea as 100 × (PPmax-PPmin)/PP during apnea. The vasomotor tone was estimated by total peripheral resistance (TPR = mean aortic pressure/mean AoF), dynamic arterial elastance (Eadyn = PPV/SVV) and arterial compliance (C = SV/PP). We assessed LV preload by LV end-diastolic pressure (LVEDP). We compared the trending abilities between SVV and pressure surrogate indices using four-quadrant plots and polar plots.ResultsBaseline PPV, SPV, PPVapnea, and SVV increased significantly during hemorrhage, with a decrease of AoF (P < 0.05). PHE induced significant TPR and Eadyn increase and C decrease in bled animals, and a further decrease in AoF with a significant decrease of all dynamic indices. There was a significant correlation between SVV and PPV, PPVapnea and SPV in normal vasomotor tone (r2 ≥ 0.5). The concordance rate was 91%, 95% and 76% between SVV and PPV, PPVapnea and SPV, respectively, in accordance with the polar plot analysis. During PHE infusion, there was no correlation between SVV and its surrogates, and both four-quadrant plot and polar plot showed poor trending.ConclusionIn this animal model of hemorrhage and increased vasomotor tone induced by phenylephrine the ability of dynamic indices to predict fluid responsiveness seems to be impaired, masking the true fluid loss. Moreover, the arterial pressure surrogates have not the reliable trending ability against SVV.

Características propias de las fases del ciclo cardíaco del ventrículo derecho

Objetivos. El proposito de este trabajo fue definir, en condiciones fisiologicas, la existencia o no de una fase isovolumetrica de relajacion en el ventriculo derecho y las caracteristicas de su fase eyectiva. Material y metodos. Se registraron simultaneamente las presiones del ventriculo derecho, arteria pulmonar, ventriculo izquierdo, aorta, flujo pulmonar, y diametros ventriculares por sonomicrometria, en 9 ovejas anestesiadas. Se obtuvo off-line la primera derivada de las presiones ventriculares, los volumenes ventriculares, y las curvas de presionvolumen de ambos ventriculos. Se obtuvo una reduccion abrupta de precarga por oclusion de la vena cava posterior. Resultados. El ventriculo derecho presento una fase de eyeccion en dos etapas (temprana y tardia), cuya finalizacion quedo establecida por la coincidencia temporal del flujo pulmonar 0, el valor sistolico minimo del volumen ventricular derecho y un valor de presion diastolica de dicho ventriculo de 0–4 mmHg. El tiempo entre el inicio de la fase de eyeccion y: a) el fin de sistole, b) el pico negativo de la primera derivada de la presion ventricular, y c) el fin de eyeccion, resultaron diferentes para el ventriculo derecho (67 ± l5 ms, 274 ± 30 ms y 4l2 ± 33 ms, respectivamente), en tanto que el ventriculo izquierdo presento los siguientes valores: 204 ± 33 ms, 262 ± 23 ms y 266 ± 24 ms, respectivamente. Conclusiones. El ventriculo derecho presenta una fase de eyeccion prolongada, que puede dividirse en dos fases, y que se extiende hasta el inicio del llenado siguiente. Esto nos permite afirmar que el ventriculo derecho carece de una fase de relajacion isovolumetrica como la existente en el ventriculo izquierdo.

Sincronización de la contracción del ventrículo derecho frente a un aumento agudo de su poscarga. «Izquierdización» del comportamiento mecánico del ventrículo derecho

Objetivo El proposito de este trabajo fue demostrar la sincronizacion de la contraccion del ventriculo derecho durante un aumento agudo y moderado de su poscarga. Material y metodo En 7 ovejas anestesiadas se registraron simultaneamente las presiones de ambos ventriculos, arteria pulmonar, aorta, flujo pulmonar, y los volumenes ventriculares por sonomicrometria. Se provoco hipertension arterial pulmonar mediante la inyeccion intravenosa de endotoxina de Escherichia coli . Resultados El aumento agudo de poscarga del ventriculo derecho, medido a traves del aumento de la presion media de la arteria pulmonar (11,9 ± 1,3 a 24 ± 3,6 mmHg) produjo las siguientes modificaciones sobre el ventriculo derecho sin cambios de precarga ni de contractilidad: a) la elastancia maxima se aproximo al fin de la eyeccion (127,5 ± 18,5 ms) y el tiempo de eyeccion se acorto (57,5 ± 20,3 ms), de modo que el pico negativo de la primera derivada de la presion ventricular coincidio con el fin de la eyeccion; b) el bucle presion-volumen adopto una forma rectangular, apareciendo ambas fases isovolumetricas, y c) la eyeccion puso de manifiesto una unica fase. Conclusiones La contraccion del ventriculo derecho asincronica o secuencial con poscarga normal adopta un patron sincronico –similar al del ventriculo izquierdo– durante un aumento agudo y moderado de su poscarga. Esta «izquierdizacion» del comportamiento mecanico del ventriculo derecho constituye un mecanismo de compensacion propio del ventriculo derecho, dado que le permite mantener su funcion sistolica en situacion de poscarga aumentada, independiente de la precarga y de la contractilidad.

The distribution of the obstruction in the pulmonary arteries modifies pulsatile right ventricular afterload in pulmonary hypertension

a Heart Failure, Heart Transplantation and PulmonaryHypertensionUnit, Department of Cardiology, 12 deOctubre University Hospital,Madrid, Spain, and Cardiovascular ResearchNetwork (RIC), Spain b Department of Pulmonary Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona Spain and Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain c Department of Pneumonoloy, Hospital Universitario, Leon, Spain d Department of Cardiology, Hospital Virgen Salud, Toledo, Spain