Florian Sonntag

Impairment of respiratory muscle function in pulmonary hypertension

It has been suggested that impaired respiratory muscle function occurs in patients with PH (pulmonary hypertension); however, comprehensive investigations of respiratory muscle function, including the application of non-volitional tests, needed to verify impairment of respiratory muscle strength in patients with PH have not yet been performed. In the present study, respiratory muscle function was assessed in 31 patients with PH (20 females and 11 males; mean pulmonary artery pressure, 51+/-20 mmHg; median World Health Organization class 3.0+/-0.5; 25 patients with pulmonary arterial hypertension and six patients with chronic thromboembolic PH) and in 31 control subjects (20 females and 11 males) well-matched for gender, age and BMI (body mass index). A 6-min walking test was performed to determine exercise capacity. Volitionally assessed maximal inspiratory (7.5+/-2.1 compared with 6.2+/-2.8 kPa; P=0.04) and expiratory (13.3+/-4.2 compared with 9.9+/-3.4 kPa; P<0.001) mouth pressures, sniff nasal (8.3+/-1.9 compared with 6.6+/-2.2 kPa; P=0.002) and transdiaphragmatic (11.3+/-2.5 compared with 8.7+/-2.5 kPa; P<0.001) pressures, non-volitionally assessed twitch mouth (1.46+/-0.43 compared with 0.97+/-0.41 kPa; P<0.001) and transdiaphragmatic (2.08+/-0.55 compared with 1.47+/-0.72 kPa; P=0.001) pressures during bilateral anterior magnetic phrenic nerve stimulation were markedly lower in patients with PH compared with control subjects. Maximal inspiratory mouth (r=0.58, P<0.001) and sniff transdiaphragmatic (r=0.43, P=0.02) pressures were correlated with the 6-min walking distance in patients with PH. In conclusion, the present study provides strong evidence that respiratory muscle strength is reduced in patients with PH compared with well-matched control subjects. Furthermore, the 6-min walking distance is significantly linked to parameters assessing inspiratory muscle strength.

New physiological insights into exercise-induced diaphragmatic fatigue.

Data on the dynamic process and time-point of manifestation of exercise-induced diaphragmatic fatigue (DF) are lacking. Therefore, this study was aimed assessing dynamic changes of diaphragmatic strength during exercise and determining the time-point of DF manifestation. Fourteen trained subjects (maximal oxygen uptake (VO2(max)) 59.3+/-5.5 ml/min/kg) performed standardized exercise protocols (maximal workload: 85% VO2(max)) followed by recovery (6 min). Ergospirometric data and twitch transdiaphragmatic pressure (TwPdi) were consecutively assessed. DF was induced (TwPdi-rest: 2.34+/-0.26 versus TwPdi-end-recovery 2.01+/-0.21 kPa, p<0.01). TwPdi progressively increased during exercise (TwPdi-rest: 2.34+/-0.26 versus TwPdi-maximal-workload: 3.28+/-0.38 kPa, p<0.001). DF was detectable immediately after exercise-termination (TwPdi-maximal-workload: 3.28+/-0.38 versus TwPdi-early-recovery 2.55+/-0.34 kPa, p<0.001). TwPdi during exercise was highly correlated to workload, VO2(max) and dyspnea (r=0.96/r=0.92/r=0.97; all p<0.0001). In conclusion, diaphragmatic strength progressively increases with increasing workload, and DF manifests after - rather than during - exercise. In addition, TwPdi is highly correlated to key-measures of ergospirometry, approving the physiological thesis that muscle strength is progressively enhanced and escapes fatiguing failure during high-intensity exercise performance.

Independence of exercise-induced diaphragmatic fatigue from ventilatory demands

Exercise-induced diaphragmatic fatigue (DF) manifests after - rather than during - exercise. This suggests that DF reflects post-exercise diaphragm-shielding. This study tested the physiological hypothesis that diaphragmatic force-generation undergoes similar regulations during either whole-body-exercise or controlled hyperventilation, but differs during recovery. Ten trained subjects (VO2(max) 60.3+/-6.4 ml/kg/min) performed: I, cycling exercise (maximal workload: 85% VO2(max)); II, controlled hyperventilation (exercise breathing pattern) followed by recovery. Ergospirometric data and twitch transdiaphragmatic pressure (TwPdi) were consecutively assessed. DF occurred following exercise, while hyperventilation enhanced diaphragmatic force-generation (TwPdi-rest 2.28+/-0.58 vs. 2.52+/-0.54, TwPdi-end-recovery: 1.94+/-0.32 kPa vs. 2.81+/-0.49 kPa, both p<0.05). TwPdi was comparable between the two protocols until recovery (p>0.05, RM-ANOVA) whereby it underwent a progressive increase. In conclusion, TwPdi progressively increases and is subject to similar regulations during exercise versus controlled hyperventilation, but differs markedly during recovery. Here, DF occurred after exercise while TwPdi increased subsequent to hyperventilation. Therefore, ventilatory demands regulate diaphragmatic force-generation during exercise, whereas DF must be attributed to non-ventilatory controlled feedback mechanisms.

Diaphragmatic fatigue is counterbalanced during exhaustive long-term exercise.

Based on externally paced (repetitive) short-term trials exercise-induced diaphragmatic fatigue has been shown to manifest after rather than during exercise. The current study aimed at investigating diaphragmatic contractility and diaphragmatic fatigue during self-paced long-term exhaustive exercise at maximally tolerated loading by the use of supramaximal twitch transdiaphragmatic pressure (TwPdi). Seven trained subjects (VO(2max) 63.3+/-13.9 ml kg(-1) min(-1)) performed self-paced long-term exhaustive exercise at maximally tolerated loading (45 min+endspurt, initial workload 85% VO(2max)) followed by recovery (9 min). TwPdi (every 45 s) and ergospirometric data (continuously) were assessed throughout the protocol. Diaphragmatic contractility tended to initially increase during the exercise protocol with a slight decline and final increase during endspurt. Diaphragmatic fatigue manifested only after exercise termination (TwPdi rest 2.6+/-0.8 kPa; TwPdi exercise start/mid/end 2.9+/-0.7 kPa vs. 2.6+/-0.8 kPa vs. 2.4+/-0.6 kPa; TwPdi endspurt/recovery 2.7+/-0.8 kPa vs. 1.9+/-0.6 kPa). In conclusion, diaphragmatic contractility tends to decrease but manifestation of diaphragmatic fatigue is counterbalanced during self-paced long-term exhaustive exercise at maximally tolerated loading.

Non-invasive ventilation applied for recovery from exercise-induced diaphragmatic fatigue.

Background: Exercise-induced diaphragmatic fatigue (DF) is conventionally considered to reflect impaired diaphragm function resulting from load imposed on the diaphragm during exercise and is known to be reduced by the application of non-invasive ventilation (NIV) during heavy-intensity exercise testing (HEET). On that physiological condition NIV applied for diaphragm unloading during recovery from exercise should be capable of accelerating recovery from DF and therewith prolonging exercise time to exhaustion and limiting the development of DF during a subsequent HEET compared to recovery during spontaneous breathing. Methods: Seven highly-trained subjects (V’O2max 62.7±7.8 ml/kg/min) performed four HEET at 85% V’O2max with 60 min of recovery during I spontaneous breathing and II NIV between two HEET. Results: Twitch transdiaphragmatic pressure (TwPdi) during supramaximal magnetic phrenic nerve stimulation decreased (p<0.04) following first HEET and subsequently completely recovered (p>0.2) during I and II. Following second HEET TwPdi comparably decreased (I 0.24±0.21 vs II 0.32±0.29 kPa; p=0.17). Exercise time to exhaustion during second HEET was equal during I and II (I 514±49 vs II 511±92 s; p=0.88). Conclusions: In conclusion, NIV applied for diaphragm unloading during recovery following HEET does neither affect recovery from DF nor subsequent exercise performance thereby providing further evidence that DF might reflect post-exercise diaphragm shielding rather than impaired diaphragm function.