A Non Invasive Estimate of Dead Space Ventilation from Exercise Measurements

Rationale

During exercise, heart failure patients (HF) show an out-of-proportion ventilation increase, which in patients with COPD is blunted. When HF and COPD coexist, the ventilatory response to exercise is unpredictable.

Objectives

We evaluated a human model of respiratory impairment in 10 COPD-free HF patients and in 10 healthy subjects, tested with a progressive workload exercise with different added dead space. We hypothesized that increased serial dead space upshifts the VE vs. VCO₂ relationship and that the VE-axis intercept might be an index of dead space ventilation.

Measurements

All participants performed a cardiopulmonary exercise test with 0, 250 and 500 mL of additional dead space. Since DS does not contribute to gas exchange, ventilation relative to dead space is ventilation at VCO₂ = 0, i.e. VE-axis intercept. We compared dead space volume, estimated dividing VE-axis intercept by the intercept on respiratory rate axis of the respiratory rate vs. VCO₂ relationship with standard method measured DS.

Main results

In HF, adding dead space increased VE-axis intercept (+0 mL = 4.98±1.63 L; +250 mL = 9.69±2.91 L; +500 mL = 13.26±3.18 L; p<0.001) and upshifted the VE vs.VCO₂ relationship, with a minor slope rise (+0 mL = 27±4 L; +250 = 28±5; +500 = 29±4; p<0.05). In healthy, adding dead space increased VE-axis intercept (+0 mL = 4.9±1.4 L; +250 = 9.3±2.4; +500 = 13.1±3.04; p<0.001) without slope changes. Measured and estimated dead space volumes were similar both in HF and healthy subjects.

Conclusions

VE-axis intercept is related to dead space ventilation and dead space volume can be non-invasively estimated.     

Effects of Slow Deep Breathing at High Altitude on Oxygen Saturation,Pulmonary and Systemic Hemodynamics

Slow deep breathing improves blood oxygenation (Sp_O2) and affects hemodynamics in hypoxic patients. We investigated the ventilatory and hemodynamic effects of slow deep breathing in normal subjects at high altitude. We collected data in healthy lowlanders staying either at 4559 m for 2–3 days (Study A; N = 39) or at 5400 m for 12–16 days (Study B; N = 28). Study variables, including Sp_O2 and systemic and pulmonary arterial pressure, were assessed before, during and after 15 minutes of breathing at 6 breaths/min. At the end of slow breathing, an increase in Sp_O2 (Study A: from 80.2±7.7% to 89.5±8.2%; Study B: from 81.0±4.2% to 88.6±4.5; both p<0.001) and significant reductions in systemic and pulmonary arterial pressure occurred. This was associated with increased tidal volume and no changes in minute ventilation or pulmonary CO diffusion. Slow deep breathing improves ventilation efficiency for oxygen as shown by blood oxygenation increase, and it reduces systemic and pulmonary blood pressure at high altitude but does not change pulmonary gas diffusion.     

Rationale and design of the Edwards SAPIEN-3 periprosthetic leakage evaluation versus Medtronic CoreValve in transfemoral aortic valve implantation (ELECT) trial

Background and objectives

Periprosthetic aortic regurgitation (PPR) after transcatheter aortic valve implantation (TAVI) remains an important issue associated with impaired long-term outcomes. The current randomised study aims to evaluate potential differences between the balloon-expandable Edwards SAPIEN-3 and the self-expanding Medtronic CoreValve system with the main focus on post-TAVI PPR by means of novel imaging endpoints, and an additional focus on other clinical endpoints.

Endpoints

The primary endpoint of this study is quantitative assessment of the severity of post-procedural PPR using cardiac magnetic resonance imaging. Several other novel imaging modalities (X-ray contrast angiography, echocardiography) are used as secondary imaging modalities for the assessment of PPR following TAVI. Secondary objectives of the study include clinical outcomes such as cerebral and kidney injury related to TAVI, and quality of life.

Methods and design

The ELECT study is a single-centre, prospective, two-armed randomised controlled trial. For the purpose of this study, 108 consecutive adult patients suitable for transfemoral TAVI will be randomly allocated to receive the SAPIEN-3 (n = 54) or the CoreValve system (n = 54).

Discussion

The ELECT trial is the first randomised controlled trial to quantitatively compare the extent of post-TAVI PPR between the SAPIEN-3 and CoreValve. Furthermore, it will evaluate potential differences between the two prostheses with regard to mid-term clinical outcome and quality of life.

     

Breastfeeding duration, milk fat composition and developmental indices at 1 year of life among breastfed infants

The associations of breastfeeding duration and milk fat composition with the developmental outcome at 1 year of age were measured within 44 infants exclusively breastfed for 3 months, out of 95 recruited at birth. Pooled breast milk (hindmilk) of the mothers was analysed at colostrum, 1, 3, 6, 9, and 12 months for total fat and fatty acid content. Infants were examined at 12 months by means of the Bayley test. There was a progressive reduction of the number of breastfed babies after the introduction of solids to 29 (6 months), 17 (9 months) and 10 (12 months). After adjusting for major confounders, infants breastfed for 6 months or longer showed a trend to have an advantage at the Bayley psychomotor developmental index compared to those breastfed >3 and <6 months (95% CI for difference: - 0.6, 13.8; P= 0.07) while the Bayley mental developmental index (MDI) was just 2.1 points higher. Among the milk fat components considered for each time-point, the total fat content at 6 months showed the strongest association with the MDI at 12 months (r=0.59, P=0.001). Prolonging breastfeeding during the weaning process may result in a better developmental performance at 12 months, possibly due to the supply of fats affecting brain composition.     

Pleural pressure between diaphragm and rib cage during inspiratory muscle activity

We measured the changes in pleural surface pressure (delta Ppl) in the area of apposition of the rib cage to the diaphragm (Aap) in anesthetized dogs during spontaneous breathing, inspiratory efforts after airway occlusion at functional residual capacity, and phrenic stimulation. Intact dogs were in supine or lateral posture; partially eviscerated dogs were in lateral posture. delta Ppl,ap often differed significantly from changes in abdominal pressure (delta Pab); sometimes they differed in sign (except during phrenic stimulation). Changes in transdiaphragmatic pressure in Aap (delta Pdi,ap) could be positive or negative and were less in eviscerated than in intact dogs. delta Pdi,ap could differ in sign among respiratory maneuvers and over different parts of Aap. Hence average delta Pdi,ap should be closer to zero than delta Pdi,ap at a given site. Since delta Ppl,ap = delta Prc,ap, where Prc,ap represents rib cage pressure in Aap, delta Pdi,ap = delta Pab - delta Prc,ap. Hence, considering that delta Pab and delta Prc depend on different factors, delta Pdi,ap may differ from zero. This pressure difference seems related to the interaction between two semisolid structures (contracted diaphragm and rib cage in Aap) constrained to the same shape and position.     

Exercise response after rapid intravenous infusion of saline in healthy humans.

Patients with chronic heart failure have an abnormal pattern of exercise ventilation (Ve), characterized by small tidal volumes (Vt), increased alveolar ventilation, and elevated physiological dead space (Vd/Vt). To investigate whether increased lung water in isolation could reproduce this pattern of exercise ventilation, 30 ml/kg of saline were rapidly infused into nine normal subjects, immediately before a symptom-limited incremental exercise test. Saline infusion significantly reduced forced vital capacity, 1-s forced expiratory volume, and alveolar volume (P < 0.01 for all). After saline, exercise ventilation assessed by the Ve/Vco(2) slope increased from 24.9 +/- 2.4 to 28.0 +/- 2.9 l/l, (P < 0.0002), associated with a small decrease in arterial Pco(2), but without changes in Vt, Vd/Vt, or alveolar-arterial O(2) difference. A reduction in maximal O(2) uptake of 175 +/- 184 ml/min (P < 0.02) was observed in the postsaline infusion exercise studies, associated with a consistent reduction in maximal exercise heart rate (8.1 +/- 5.9 beats/min, P < 0.01), but without a change in the O(2) pulse. Therefore, infusion of saline to normal subjects before exercise failed to reproduce either the increase in Vd/Vt or the smaller exercise Vt described in heart failure patients. The observed increase in Ve can be attributed to dilution acidosis from infusion of the bicarbonate-free fluid and/or to afferent signals from lung and exercising muscles. The reduction in maximal power output, maximal O(2) uptake, and heart rate after saline infusion may be linked to accumulation of edema fluid in exercising muscle, impairing the diffusion of O(2) to muscle mitochondria.