Simultaneous determination of the kinetics of cardiac output, systemic O2 delivery and lung O2 uptake at exercise onset in men.

We tested whether the kinetics of systemic O2 delivery (Q'aO2) at exercise start was faster than that of lung O2 uptake (V' O2), being dictated by that of cardiac output (Q'), and whether changes in Q' would explain the postulated rapid phase of the V'O2 increase. Simultaneous determinations of beat-by-beat (BBB) Q' and Q' aO2, and breath-by-breath V'O2 at the onset of constant load exercises at 50 and 100 W were obtained on six men (age 24.2 +/-3.2 years, maximal aerobic power 333 +/- 61 W). V'O2 was determined using Grønlund’s algorithm. Q' was computed from BBB stroke volume (Qst, from arterial pulse pressure profiles) and heart rate (fH, electrocardiograpy) and calibrated against a steadystate method. This, along with the time course of hemoglobin concentration and arterial O2 saturation (infrared oximetry) allowed computation of BBB Q'aO2. The Q', Q'aO2 and V'O2 kinetics were analyzed with single and double exponential models. fH, Qst, Q', and V'O2 increased upon exercise onset to reach a new steady state. The kinetics of Q'aO2 had the same time constants as that of Q'. The latter was twofold faster than that of V'O2. The V'O2 kinetics were faster than previously reported for muscle phosphocreatine decrease. Within a two-phase model, because of the Fick equation, the amplitude of phase I Q' changes fully explained the phase I of V'O2 increase. We suggest that in unsteady states, lung V' O2 is dissociated from muscle O2 consumption. The two components of Q' and Q'aO2 kinetics may reflect vagal withdrawal and sympathetic activation

Prolonged head down bed rest-induced inactivity impairs tonic autonomic regulation while sparing oscillatory cardiovascular rhythms in healthy humans.

Background. Physical inactivity represents a major risk for cardiovascular disorders, such as hypertension, myocardial infarction or sudden death; however, underlying mechanisms are not clearly elucidated. Clinical and epidemiological investigations suggest, beyond molecular changes, the possibility of an induced impairment in autonomic cardiovascular regulation. However, this hypothesis has not been tested directly. Methods. Accordingly, we planned a study with noninvasive, minimally intrusive, techniques on healthy volunteers. Participants were maintained for 90 days strictly in bed, 24 h a day, in head-down (S6-) position (HDBR). Physical activity was thus virtually abolished for the entire period of HDBR. We examined efferent muscle sympathetic nerve activity, as a measure of vascular sympathetic control, baroreceptor reflex sensitivity, heart rate variability (assessing cardiovagal regulation), RR and systolic arterial pressure and low-frequency and high-frequency normalized components (as a window on central oscillatory regulation). Measures. were obtained at rest and during simple maneuvers (moderate handgrip, lower body negative pressure and active standing) to assess potential changes in autonomic cardiovascular responsiveness to standard stimuli and the related oscillatory profiles. Results HDBR transiently reduced muscle sympathetic nerve activity,RR,heart ratevariabilityandbaroreceptor reflex sensitivity late during HDBR or early during the recovery phase. Conversely, oscillatory profiles of RR and systolic arterial pressure variability were maintained throughout. Responsiveness to test stimuli was also largely maintained

Phase I dynamics of cardiac output, systemic O2 delivery and lung O2 uptake at exercise onset in men in acute normobaric hypoxia.

We tested the hypothesis that vagal withdrawal plays a role in the rapid (phase I) cardiopulmonary response to exercise. To this aim, in five men (24.6+/-3.4 yr, 82.1+/-13.7 kg, maximal aerobic power 330+/-67 W), we determined beat-by-beat cardiac output (Q), oxygen delivery (QaO2), and breath-by-breath lung oxygen uptake (VO2) at light exercise (50 and 100 W) in normoxia and acute hypoxia (fraction of inspired O2=0.11), because the latter reduces resting vagal activity. We computed Q from stroke volume (Qst, by model flow) and heart rate (fH, electrocardiography), and QaO2 from Q and arterial O2 concentration. Double exponentials were fitted to the data. In hypoxia compared with normoxia, steady-state fH and Q were higher, and Qst and VO2 were unchanged. QaO2 was unchanged at rest and lower at exercise. During transients, amplitude of phase I (A1) for VO2 was unchanged. For fH, Q and QaO2, A1 was lower. Phase I time constant (tau1) for QaO2 and VO2 was unchanged. The same was the case for Q at 100 W and for fH at 50 W. Qst kinetics were unaffected. In conclusion, the results do not fully support the hypothesis that vagal withdrawal determines phase I, because it was not completely suppressed. Although we can attribute the decrease in A1 of fH to a diminished degree of vagal withdrawal in hypoxia, this is not so for Qst. Thus the dual origin of the phase I of Q and QaO2, neural (vagal) and mechanical (venous return increase by muscle pump action), would rather be confirmed

Cardiac output by model flow method from intra-arterial and finger tip pulse pressure profiles

Modelflow®, when applied to non-invasive fingertip pulse pressure recordings, is a poor predictor of cardiac output (Q’ litre· min-1). The use of constants established from the aortic elastic characteristics, which differ from those of finger arteries, may introduce signal distortions, leading to errors in computing Q’. We therefore hypothesized that peripheral recording of pulse pressure profiles undermines the measurement of Q’ withModelflow®, so we compared Modelflow® beat-by-beat Q’ values obtained simultaneously non-invasively from the finger and invasively from the radial artery at rest and during exercise. Seven subjects (age, 24.0 + - 2.9 years; weight, 81.2 + - 12.6 kg) rested, then exercised at 50 and 100 W, carrying a catheter with a pressure head in the left radial artery and the photoplethysmographic cuff of a finger pressure device on the third and fourth fingers of the contralateral hand. Pulse pressure from both devices was recorded simultaneously and stored on a PC for subsequent Q’ computation. The mean values of systolic, diastolic and mean arterial pressure at rest and exercise steady state were significantly (P < 0.05) lower from the finger than the intra-arterial catheter. The corresponding mean steady-state Q’ obtained from the finger (Q’porta) was significantly (P < 0.05) higher than that computed from the intra-arterial recordings (Q’pia). The line relating beat-by-beat Q’porta and Q’pia was y = 1.55x - 3.02 (r2 = 0.640). The bias was 1.44 litre · min-1 and the precision was 2.84 litre · min-1.The slope of this line was significantly higher than 1, implying a systematic overestimate of Q’ by Q’porta with respect to Q’pia. Consistent with the tested hypothesis, these results demonstrate that pulse pressure profiles from the finger provide inaccurate absolute Q’ values with respect to the radial artery, and therefore cannot be used without correction with a calibration factor calculated previously by measuring Q’ with an independent method

The effect of lower body negative pressure on phase 1 cardiovascular responses at exercise onset in healthy humans

We tested the hypothesis that vagal withdrawal and increased venous return interact in determining the rapid cardiac output response (Phase I) at exercise onset. We used lower body negative pressure (LBNP) to increase blood dislocation to the heart by muscle pump action and simultaneously reduce resting vagal activity. At exercise start, we expected larger response amplitude for stroke volume and smaller for heart rate at progressively stronger LBNP levels, so that the cardiac output response would remain unchanged. Ten subjects performed 50 W exercise supine in Control condition and during -45 mmHg LBNP exposure. On single beat basis, we measured heart rate (HR), stroke volume (SV), and we calculated cardiac output (CO). We computed Phase I response amplitudes (A1) using an exponential model. SV A1 was higher under LBNP than in Control (p &lt; 0.05). Conversely, the A1 of HR, was 23 ± 56 % lower under LBNP than in Control (although NS). Since these changes tended to compensate each other, the A1 for CO was unaffected by LBNP. The rapid SV kinetics at exercise onset is compatible with an effect of increased venous return, whereas the vagal withdrawal conjecture cannot be dismissed for HR kinetics. The rapid CO response may indeed be the result of two independent yet parallel mechanisms, as hypothesized, one acting on SV, the other on H

Radiological findings of complications after lung transplantation.

Complications following lung transplantation may impede allograft function and threaten patient survival. The five main complications after lung transplantation are primary graft dysfunction, post-surgical complications, alloimmune responses, infections, and malignancy. Primary graft dysfunction, a transient ischemic/reperfusion injury, appears as a pulmonary edema in almost every patient during the first three days post-surgery. Post-surgical dysfunction could be depicted on computed tomography (CT), such as bronchial anastomosis dehiscence, bronchial stenosis and bronchomalacia, pulmonary artery stenosis, and size mismatch. Alloimmune responses represent acute rejection or chronic lung allograft dysfunction (CLAD). CLAD has three different forms (bronchiolitis obliterans syndrome, restrictive allograft syndrome, acute fibrinoid organizing pneumonia) that could be differentiated on CT. Infections are different depending on their time of occurrence. The first post-operative month is mostly associated with bacterial and fungal pathogens. From the second to sixth months, viral pneumonias and fungal and parasitic opportunistic infections are more frequent. Different patterns according to the type of infection exist on CT. Malignancy should be depicted and corresponded principally to post-transplantation lymphoproliferative disease (PTLD). In this review, we describe specific CT signs of these five main lung transplantation complications and their time of occurrence to improve diagnosis, follow-up, medical management, and to correlate these findings with pathology results. KEY POINTS: • The five main complications are primary graft dysfunction, surgical, alloimmune, infectious, and malignancy complications. • CT identifies anomalies in the setting of unspecific symptoms of lung transplantation complications. • Knowledge of the specific CT signs can allow a prompt diagnosis. • CT signs maximize the yield of bronchoscopy, transbronchial biopsy, and bronchoalveolar lavage. • Radiopathological correlation helps to understand CT signs after lung transplantation complications

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Treating pulmonary hypertension in pediatrics.

INTRODUCTION: Pulmonary hypertension is a hemodynamic condition occurring rarely in pediatrics. Nevertheless, it is associated with significant morbidity and mortality. When characterized by progressive pulmonary vascular structural changes, the disease is called pulmonary arterial hypertension (PAH). It results in increased pulmonary vascular resistance and eventual right ventricular failure. In the vast majority of cases, pediatric PAH is idiopathic or associated with congenital heart disease, and, contrary to adult PAH, is rarely associated with connective tissue, portal hypertension, HIV infection or thromboembolic disease. AREAS COVERED: This article reviews the current drug therapies available for the management of pediatric PAH. These treatments target the recognized pathophysiological pathways of PAH with endothelin-1 receptor antagonists, prostacyclin analogs and PDE type 5 inhibitors. New treatments and explored pathways are briefly discussed. EXPERT OPINION: Although there is still no cure for PAH, quality of life and survival have been improved significantly with specific drug therapies. Nevertheless, management of pediatric PAH remains challenging, and depends mainly on results from adult clinical trials and pediatric experts. Further research on PAH-specific treatments in the pediatric population and data from international registries are needed to identify optimal therapeutic strategies and treatment goals in the pediatric population