Supinski G S, DiMarco A F, Gonzalez J, Altose M D
Pulmonary Division, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio 44109.
J Appl Physiol (1985). 1990 Dec;69(6):2019-28. doi: 10.1152/jappl.1990.69.6.2019.
Recent studies have shown that diaphragm fatigue can be reversed by mechanical augmentation of phrenic arterial flow. The purpose of the present experiment was to determine whether it was possible to pharmacologically augment diaphragm blood flow and reverse fatigue by the administration of norepinephrine. Four groups of studies were performed, all employing our previously described in situ isometric canine diaphragm strip preparation (Supinski et al., J. Appl. Physiol. 60: 1789-1796, 1986). Group I studies examined the effects of norepinephrine on the contractility of the nonfatigued diaphragm in normotensive dogs, group II studies examined the effects of this drug on the contractility of the fatigued diaphragm in normotensive animals, and group III studies examined the effect of this drug on the contractility of the fatigued diaphragm in hypotensive animals. Group IV studies examined the effect of norepinephrine in normotensive animals in which the phrenic artery was cannulated and pump perfused at constant flow. Fatigue was induced in group II, III, and IV studies by rhythmically stimulating the diaphragm via intramuscular electrodes. Norepinephrine had no effect on the contractility of the nonfatigued diaphragm (group I). In normotensive (group II) and hypotensive animals (group III), norepinephrine elicited dramatic increases in arterial blood pressure and phrenic arterial flow and produced a significant upshift in the force-frequency curve of the fatigued diaphragm. However, when phrenic flow was held constant (group IV experiments), norepinephrine failed to augment the contractility of the fatigued diaphragm. These results indicate that 1) norepinephrine can increase phrenic blood flow and augment the contractility of the fatigued diaphragm in both normotensive and hypotensive conditions and 2) this effect of norepinephrine to partially reverse fatigue is secondary to its action to augment diaphragmatic blood flow.
最近的研究表明，通过机械增加膈动脉血流量可使膈肌疲劳得到逆转。本实验的目的是确定是否有可能通过给予去甲肾上腺素在药理学上增加膈肌血流量并逆转疲劳。进行了四组研究，均采用我们先前描述的犬原位等长膈肌条制备方法（Supinski等人，《应用生理学杂志》60：1789 - 1796，1986）。第一组研究检测了去甲肾上腺素对正常血压犬非疲劳膈肌收缩力的影响，第二组研究检测了该药物对正常血压动物疲劳膈肌收缩力的影响，第三组研究检测了该药物对低血压动物疲劳膈肌收缩力的影响。第四组研究检测了在正常血压动物中膈动脉插管并以恒定流量进行泵灌注时去甲肾上腺素的作用。在第二、三、四组研究中，通过肌肉内电极有节奏地刺激膈肌来诱导疲劳。去甲肾上腺素对非疲劳膈肌的收缩力没有影响（第一组）。在正常血压（第二组）和低血压动物（第三组）中，去甲肾上腺素引起动脉血压和膈动脉血流量显著增加，并使疲劳膈肌的力 - 频率曲线显著上移。然而，当膈血流量保持恒定时（第四组实验），去甲肾上腺素未能增强疲劳膈肌的收缩力。这些结果表明：1）去甲肾上腺素在正常血压和低血压情况下均可增加膈血流量并增强疲劳膈肌的收缩力；2）去甲肾上腺素这种部分逆转疲劳的作用是其增加膈肌血流量作用的继发效应。
