Benefits of short inspiratory muscle training on exercise capacity, dyspnea, and inspiratory fraction in COPD patients.

Abstract: Static lung hyperinflation has important clinical consequences in patients with chronic obstructive pulmonary disease (COPD). Given that most of these patients have respiratory and peripheral muscle weakness, dyspnea and functional exercise capacity may improve as a result of inspiratory muscle training (IMT). The present study is designed to investigate the benefits of a short outpatient program of IMT on inspiratory muscle performance, exercise capacity, perception of dyspnea, and the inspiratory fraction (IF). Thirty patients (24 males, 6 females) with significant COPD (forced expiratory volume in one second [FEV1] = 46.21% +/- 6.7% predicted, FEV1 = 33.6% +/- 8.04% predicted) were recruited for this study and had 3 months of IMT (30 minutes/day for 6 days/week) in an outpatient clinic. Following IMT, there was a statistically significant increase in inspiratory muscle performance (an increase of the maximal inspiratory pressure from 59% +/- 19.1% to 79% +/- 21.85% predicted; p = 0.0342), a decrease in dyspnea (from 5.8 +/- 0.78 to 1.9 +/- 0.57; p = 0.0001), an increase in the distance walked during the 6 minute walk test, from 245 +/- 52.37 m to 302 +/- 41.30 m, and finally an increase in the IF (the new prognostic factor in COPD) from 27.6 +/- 9.7% to 31.4% +/- 9.8%. The present study concludes that in patients with significant COPD, IMT results in improvement in performance, exercise capacity, sensation of dyspnea, and moreover an improvement in the IF prognostic factor.

Prenatal nicotine alters maturation of breathing and neural circuits regulating respiratory control.

While perinatal nicotine effects on ventilation have been widely investigated, the prenatal impact of nicotine treatment during gestation on both breathing and neural circuits involved in respiratory control remains unknown. We examined the effects of nicotine, from embryonic day 5 (E5) to E20, on baseline ventilation, the two hypoxic ventilatory response components and in vivo tyrosine hydroxylase (TH) activity in carotid bodies and brainstem areas, assessed at postnatal day 7 (P7), P11 and P21. In pups prenatally exposed to nicotine, baseline ventilation and hypoxic ventilatory response were increased at P7 (+48%) and P11 (+46%), with increased tidal volume (p<0.05). Hypoxia blunted frequency response at P7 and revealed unstable ventilation at P11. In carotid bodies, TH activity increased by 20% at P7 and decreased by 48% at P11 (p<0.05). In most brainstem areas it was reduced by 20-33% until P11. Changes were resolved by P21. Prenatal nicotine led to postnatal ventilatory sequelae, partly resulting from impaired maturation of peripheral chemoreceptors and brainstem integrative sites.

A study of experimental acute lung injury in pigs on zero end-expiratory pressure.

OBJECTIVES: Tidal expiratory flow limitation (EFL) has been reported in humans with acute lung injury (ALI) and assumed to be associated with small airway closure. Detection of EFL is important because by selecting positive end-expiratory pressure at such a level that EFL is no longer present in the tidal breath, the repeated opening and closure of small airways can be prevented. The objective of this study was to investigate the occurrence of EFL in two experimental models of ALI. ANIMALS: Ten female piglets. METHODS: Animals were anaesthetized, tracheotomized and mechanically ventilated on zero end-expiratory pressure. Acute lung injury was induced by oleic acid (OA) (n = 5) or saline lavage (SL) (n = 5). Tidal EFL was assessed by the negative expiratory pressure test. Lung and chest wall mechanics were partitioned using an oesophageal balloon. Resistance and static elastance were assessed by a rapid airway occlusion technique at baseline ventilatory settings. RESULTS: There was no EFL at any time before and after ALI in both models. This may be due to an increased elastance which promoted higher expiratory flow after ALI and to a decreased chest wall to lung static elastance ratio which could favour small airways patency. The similar increase in total lung resistance, in the two models, after ALI was mostly due to an increased airway resistance in the OA model and to the lung tissue resistance in the SL model. CONCLUSIONS AND CLINICAL RELEVANCE: Tidal EFL was not detected in experimental ALI. This finding casts some doubt about the usefulness of some experimental models of ALI to mimic some reported findings in human ALI.

Increased intra-abdominal pressure affects respiratory variations in arterial pressure in normovolaemic and hypovolaemic mechanically ventilated healthy pigs.

OBJECTIVE: To evaluate the effect of increased intra-abdominal pressure (IAP) on the systolic and pulse pressure variations induced by positive pressure ventilation in a porcine model. DESIGN AND SETTING: Experimental study in a research laboratory. SUBJECTS: Seven mechanically ventilated and instrumented pigs prone to normovolaemia and hypovolaemia by blood withdrawal. INTERVENTION: Abdominal banding gradually increased IAP in 5-mmHg steps up to 30 mmHg. MEASUREMENTS AND MAIN RESULTS: Variations in systolic pressure, pulse pressure, inferior vena cava flow, and pleural and transmural (LVEDPtm) left-ventricular end-diastolic pressure were recorded at each step. Systolic pressure variations were 6.1+/-3.1%, 8.5+/-3.6% and 16.0+/-5.0% at 0, 10, and 30 mmHg IAP in normovolaemic animals (mean+/-SD; p<0.01 for IAP effect). They were 12.7+/-4.6%, 13.4+/-6.7%, and 23.4+/-6.3% in hypovolaemic animals (p<0.01 vs normovolaemic group) for the same IAP. Fluctuations of the inferior vena cava flow disappeared as the IAP increased. Breath cycle did not induce any variations of LVEDPtm for 0 and 30 mmHg IAP. CONCLUSIONS: In this model, the systolic pressure and pulse pressure variations, and inferior vena cava flow fluctuations were dependent on IAP values which caused changes in pleural pressure swing, and this dependency was more marked during hypovolaemia. The present study suggests that dynamic indices are not exclusively related to volaemia in the presence of increased IAP. However, their fluid responsiveness predictive value could not be ascertained as no fluid challenge was performed.

Liver function during extracorporeal whole liver perfusion in a pig model of acute ischemic liver failure.

The shortage of livers for transplant has renewed interest in the potential of temporary liver support such as extra corporeal whole liver perfusion. In an ischemic induced liver failure model we perfused an extra corporeal liver through only a portal vein and assessed the function of this ex vivo liver by using hepatic tests to estimate elimination as well as synthesis capacities. Acute liver failure was performed in five control pigs by a hepatic devascularization associated to an end to side portocaval shunt. In a treated group, 5 to 6 h after this hepatic devascularization, animals were connected to an extra corporeal liver perfused via the portal vein with blood withdrawn from the ischemic liver animal from its portal vein. Devascularization of the liver induced an increase in liver enzymes and ammonia, a drop in the ratio of branched chain amino acids to aromatic amino acids, and a decrease in blood urea and indocyanine green and galactose clearances. In treated animals, urea, amino acid ratio, and clearances increased after the ex vivo liver perfusion. In this group, mean bile production and mean liver oxygen consumption were 13.7 +/- 3.6 ml/h and 16.1 +/- 7.7 ml/min, respectively. In an acute ischemic liver failure pig model, an extra corporeal whole liver perfusion demonstrated detoxification properties as well as synthesis capacities.

Effects of positive end-expiratory pressure on the sigmoid equation in experimental acute lung injury.

OBJECTIVES: To describe inflation and deflation volume-pressure (V-P) curves of the respiratory system by the sigmoidal equation at different levels of positive end-expiratory pressure (PEEP) in acute lung injury. DESIGN: Experimental study. SETTING: Physiological laboratory in a university setting. SUBJECTS: Six pigs of 25 kg each. INTERVENTIONS: Acute lung injury was induced by oleic acid. PEEP was applied from 0 to 15 cm H(2)O and from 15 to 0 cm H(2)O for 10 min in steps of 5 cmH(2)O. MEASUREMENTS AND RESULTS: Inflation and deflation V-P curves were constructed from an automated super-syringe that delivers a constant flow of 7 l/min in both inspiratory and expiratory directions. V-P curves were obtained at each level of PEEP without disconnecting the animal from the ventilator. The experimental data were fitted to the sigmoid equation which provided the true inflection point (c), the point of maximal compliance increase (Pmci) reflecting opening/closure and the point of maximal compliance decrease (Pmcd) reflecting end of recruitment/onset of de-recruitment. The sigmoid equation provided an excellent fit. The values of the coefficients of determination were greater than 0.970 (median 0.996, IQR 0.994-0.997 for the 84 determinations). Negative values of Pmci in the deflation limb of the V-P curve were recorded in five pigs, suggesting closure below the volume range studied. CONCLUSIONS: Inflation and deflation V-P curves at different PEEPs can be fitted by the sigmoid equation. However, further work is needed to investigate the meaning of negative values for Pmci.

Hepatic ischemia is associated with an increase in liver parenchyma nitric oxide that is in part enzyme-independent.

BACKGROUND: Nitric oxide (NO) might be involved in liver response to local ischemia-reperfusion injury. METHODS: A specific NO-sensitive electrode was inserted into liver parenchyma of anesthetized rabbits. After a 45-min period of stable NO signal, the vascular pedicle of the caudal lobe of the liver was clamped for 45 min, then the clamp was removed. Perfusion of the right upper lobe was left unchanged. The same procedure was applied in other animals after administration of a long-acting nonspecific NO synthase inhibitor NAPNA. RESULTS: Occlusion of the caudal pedicle was associated with a mean threefold increase in NO signal measured in the caudal lobe. After unclamping, this signal returned within 8 min to baseline value and remained stable for the next 6 h. In the right upper lobe, NO signal was unaffected by caudal lobe ischemia. By the end of the 6-h reperfusion period, administration of the NO inhibitor l-NAME led to a suppression of the NO signal, thus demonstrating the specificity of the measurement. Plasma nitrate and nitrite concentrations remained almost unchanged during the study period in all groups. In animals whose NO synthases had been previously inhibited by NAPNA, clamping the caudal pedicle for 45 min was still associated with a significant increase in caudal lobe NO signal. CONCLUSION: Nitric oxide is present in liver parenchyma, and its generation is dramatically affected by an ischemia injury. The increased NO generation during local ischemia is, at least in part, independent of NO synthases.

Effects of positive end-expiratory pressure and body position on pulmonary blood flow redistribution in mechanically ventilated normal pigs.

STUDY OBJECTIVES: To assess the respective effects of position and positive end-expiratory pressure (PEEP) on the distribution of regional pulmonary blood flow (PBF). DESIGN: Prospective randomized animal study. SETTING: Animal research facility in a university hospital. PARTICIPANTS: Normal pigs that were tracheostomized, anesthetized, and mechanically ventilated. INTERVENTIONS: PBF was measured in seven pigs in the supine position (SP) and the prone position (PP) at both zero end-expiratory pressure (ZEEP) and 10 cm H(2)O of PEEP. The regional PBF was assessed by the radioactive microsphere method. The lungs from each pig were sliced into 90 samples. The heterogeneity of PBF was estimated from its coefficient of variation. MEASUREMENTS AND RESULTS: The lung samples had a mean (+/- SD) weight of 1.60 +/- 0.39 g. Changing position from SP to PP at ZEEP redistributed PBF toward the anterior, superior, and peripheral regions and did not significantly reduce the coefficient of variation for regional PBF (reduction, 44.7 +/- 7% to 42.2 +/- 8%). Changing from the SP to PP position at PEEP induced a similar, but more marked, redistribution of PBF and a significant reduction in the coefficient of variation from 53 +/- 13% to 30.4 +/- 7% (p < 0.001). In the SP, PEEP redistributed PBF toward the posterior, inferior, and central regions without changing the heterogeneity of PBF. In the PP, PEEP had little effect on the PBF redistribution but significantly reduced the coefficient of variation of PBF from 42.2 +/- 8% to 30.4 +/- 7% (p < 0.05). CONCLUSIONS: Pigs in the PP had altered gravitational dependence of PBF compared to that observed when pigs were in the SP. This effect was enhanced by using a PEEP of 10 cm H(2)O.

Comparison of PET with radioactive microspheres to assess pulmonary blood flow.

UNLABELLED: Microsphere technique is the reference for assessment of pulmonary blood flow (PBF) but is destructive; PET, however, can determine PBF noninvasively. Comparisons of these 2 methods are scanty. Our study aimed at comparing these 2 techniques using a mathematic model taking into account the right ventricle in determining the transit time of a tracer through lung tissue. METHODS: Ten normal pigs were investigated at baseline, during dobutamine infusion, and during 10 cm H(2)O of positive end-expiratory pressure. Under each condition, PBF was successively measured with PET (PET-PBF) and radioactive microspheres (MS-PBF). For PET-PBF, 2 mCi (74 MBq) (15)O-labeled water were injected intravenously over 20 s and PET scanning was performed for 10 min. The input function was determined noninvasively from PET and invasively from mixed venous blood withdrawals. PET-PBF was computed using a mathematic model taking into account the right ventricle in determining the transit time of the tracer through lung tissue. For MS-PBF, 1 given isotope was injected under a given condition. PET-PBF and MS-PBF for 5 lung regions were compared. RESULTS: PET-PBF significantly correlated with MS-PBF both over all experimental points (PET-PBF = 0.79. MS-PBF + 1,538; r = 0.79; P < 0.001) and in separate lung regions. Invasive and noninvasive input functions also correlated significantly (r = 0.90; P < 0.001). Simulations stressed the crucial role of the right ventricle to the transit time of tracer through lung tissue in the determination of PET-PBF. CONCLUSION: PBF can accurately be assessed using PET and a mathematic model taking into account the right ventricle in determining the transit time of a tracer through lung tissue. Noninvasive determination of the input function of the right ventricle is accurate and can readily be used for clinical applications.