Rossing T H, Shannon K, Miller M J
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Am Rev Respir Dis. 1987 Oct;136(4):841-4. doi: 10.1164/ajrccm/136.4.841.
We studied the effects of the phosphodiesterase inhibitor, milrinone, on isometric force production in the isolated, directly stimulated rat diaphragm. Milrinone (500 micrograms/ml) significantly increased force during twitch stimulation and submaximal tetanic stimulation (p less than 0.05); force during maximal tetanic stimulation was significantly reduced by milrinone (p less than 0.05). The force-augmenting effects of milrinone were not abolished by pretreatment with indomethacin (10(-5)M). Baseline force production decreased when diaphragmatic strips were placed in a calcium-free bathing solution; force potentiation by milrinone, however, persisted in this medium. Pretreatment with milrinone more than doubled the mean time to fatigue (10.8 +/- 1.0 versus 5.1 +/- 0.6 min) during repetitive submaximal stimulation (p less than 0.01). In diaphragmatic strips fatigued by repetitive submaximal stimulation until force production was 60% of baseline, milrinone promptly improved force production; the magnitude of force potentiation after milrinone was quite similar in fresh and fatigued muscle. In conclusion, milrinone enhances diaphragmatic contractility during the most forms of direct stimulation, and delays and reverses diaphragmatic fatigue.
我们研究了磷酸二酯酶抑制剂米力农对离体直接刺激的大鼠膈肌等长力产生的影响。米力农（500微克/毫升）在单收缩刺激和次最大强直刺激期间显著增加了力量（p<0.05）；米力农使最大强直刺激期间的力量显著降低（p<0.05）。米力农的力量增强作用不会因用吲哚美辛（10⁻⁵M）预处理而消除。当膈肌条带置于无钙的浴液中时，基线力量产生下降；然而，米力农在这种培养基中仍能持续增强力量。在重复次最大刺激期间，用米力农预处理使平均疲劳时间增加了一倍多（10.8±1.0对5.1±0.6分钟）（p<0.01）。在因重复次最大刺激而疲劳直至力量产生降至基线的60%的膈肌条带中，米力农能迅速改善力量产生；新鲜肌肉和疲劳肌肉在使用米力农后力量增强的幅度相当相似。总之，米力农在大多数形式的直接刺激期间增强膈肌收缩力，并延迟和逆转膈肌疲劳。
