Effects of diltiazem compared with nicardipine on diaphragmatic fatigability in vivo.

نویسنده

  • Y Fujii
چکیده

Fatigue of the diaphragm may contribute to the development of respiratory failure [1]. The cause is thought to be an alteration in transmembrane calcium transport [2]. We have previously shown that the calcium channel blocker nicardipine intensifies diaphragmatic fatigue [3]. We compared the effects of diltiazem, another calcium channel blocker, on diaphragm fatigability in vivo with those of nicardipine when both were given at the same dose of 5 μg kg 1min 1. After approval by the University of Tsukuba Animal Care and Use Committee, 16 healthy mongrel dogs (12 males, 4 females, 10–15 kg) were prepared as described previously [3]. Briefly, anaesthesia was maintained with pentobarbital 2 mg kg 1h 1 intravenously (i.v.). No muscle relaxant was used. Each animal’s trachea was intubated and the lungs ventilated with O2 in air (FiO2 0.4) to maintain PaO2 13.3 kPa, PaCO2 4.7–5.3 kPa and pHa 7.35–7.45. Arterial blood-gas tensions were measured every 30 min. Transdiaphragmatic pressure (Pdi) was measured with two thin-walled latex balloons – one positioned in the stomach, the other in the middle third of the oesophagus – connected to a differential pressure transducer and an amplifier. The phrenic nerves were exposed bilaterally at the neck and the stimulating electrodes connected. Supramaximal electrical stimuli (10–15 V, 0.1 ms, 20 or 100 Hz) were applied for 2 s. Diaphragmatic contractility was evaluated by measuring maximal Pdi during airway occlusion at functional residual capacity. Electrodes placed through a midline laparotomy recorded the electrical activity of the crural and costal portions of the diaphragm. The signal was rectified and integrated to yield diaphragmatic electromyographical activity (Edi-cru and Edi-cost, respectively). The dogs were randomly divided into two groups of eight. After measuring baseline values of heart rate (HR), mean arterial pressure (MAP), Pdi, Edi-cru and Edi-cost, diaphragmatic fatigue was induced by intermittent supramaximal bilateral 20 Hz phrenic stimulation applied for 30 min (low-frequency fatigue) with alternating 2 s cycles of stimulation and rest [4]. During this fatigue-inducing period, the dogs in Group 1 received nicardipine 5 μg kg 1min 1 i.v. and those in Group 2 received diltiazem 5 μg kg 1min 1 i.v. The dose of the study drugs was chosen based on our previous study [3]. At the end of the fatigueinducing period, the phrenic nerves were stimulated again with 20 and 100 Hz and the diaphragm responses measured. Edi-cru and Edi-cost were calculated as the percentage of baseline (%Edi-cru, %Edicost). Statistical analysis was performed by ANOVA for repeated measurement with Bonferroni corrections for multiple comparisons and a t-test, where appropriate. P 0.05 was considered as statistically significant. Data were given as mean SD. The results are shown in Table 1. After the fatigueinducing period, HR had increased (P 0.05) and MAP decreased (P 0.05) in Group 1 (nicardipine). Transdiaphragmatic pressure decreased from baseline values after 20 Hz stimulation (P 0.05), but not after 100 Hz stimulation. Edi was not affected by either stimulation frequency. Heart rate and MAP decreased in Group 2 (diltiazem) (P 0.05). Pdi was decreased at both stimulation frequencies (P 0.05), but Edi only decreased after 100 Hz stimulation (P 0.05). The decrease of Pdi and Edi was larger in Group 2 than in Group 1 (P 0.05). Selective loss of force at 20 Hz stimulation was closely related to the impairment of excitation– contraction coupling [5], and selective loss of force and electromyographical activity at 100 Hz stimulation indicates the failure of neuromuscular transmission [6]. Pdi was decreased in Group 1 at 20 Hz stimulation but not at 100 Hz. Edi was unchanged at both frequencies. This was in agreement with our previous report [3]. The mechanism by which nicardipine intensifies diaphragmatic fatigability remains unclear but may be Correspondence

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عنوان ژورنال:
  • European journal of anaesthesiology

دوره 20 7  شماره 

صفحات  -

تاریخ انتشار 2003