Diaphragmatic fatigue assessed by ³¹P-magnetic resonance spectroscopy in vivo

We tested whether fatigue of the piglet diaphragm is associated with inadequate oxidative metabolism as measured by magnetic resonance spectroscopy (MRS). An MRS measured ratio of inorganic phosphate to phosphocreatine (P(i)/PCr) ≥1 was taken as evidence of inadequate oxidative metabolism. Piglets (n = 10) underwent phrenic nerve pacing for 90 min with stimulation frequency of 30 Hz and duty cycle of 0.33. In a separate group of six piglets PCr, P(i), ATP, and intracellular pH were measured by in vivo MRS, and diaphragmatic blood flow was measured with radioactive microspheres at control, 2, 10, 45, 60, and 90 min of pacing. Transdiaphragmatic pressure fell from 25 ± 3 to 15 ± 2 mmHg (61 ± 5%) at 2 min and remained depressed in a separate group of four piglets (P < 0.05). Conversely, compound action potential amplitude remained constant for the first 10 min of pacing and fell to 68 ± 5% of control at 45 min (P < 0.05). P(i)/PCr rose from a control value of 0.32 ± 0.06 to 0.92 ± 0.23 at 2 min and 0.79 ± 0.03 at 10 min (P < 0.05) before returning toward control at 45-90 min. O₂ delivery increased from 4.6 ± 1.2 to 24.7 ± 4.8 ml · min^-1 · 100 g^-1 at 2 min and 18.4 ± 2.2 ml · min^-1 · 100 g^-1 at 10 min (P < 0.05) but then fell to lower levels at 45-90 min. ATP and intracellular pH remained constant except for a decline in pH to 6.98 ± 0.09 at 45 min (P < 0.05) from the control value of 7.26 ± 0.06. We conclude that diaphragmatic fatigue after 2 min of pacing is associated with energy supply and/or demand imbalance manifested by P(i)/PCr approaching 1, whereas fatigue at 45-90 min was partly due to decreased activation of the diaphragm.