Surgical Research Laboratory, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
Am J Physiol Heart Circ Physiol. 2012 Apr 15;302(8):H1584-90. doi: 10.1152/ajpheart.00887.2011. Epub 2012 Feb 3.
Adrenomedullin (AM) used therapeutically reduces mortality in the acute phase of experimental myocardial infarction. However, AM is potentially deleterious in acute heart failure as it is vasodilative and inotropically neutral. AM and epinephrine (EPI) are cosecreted from chromaffin cells, indicating a physiological interaction. We assessed the hemodynamic and energetic profile of AM-EPI cotreatment, exploring whether drug interaction improves cardiac function. Left ventricular (LV) mechanoenergetics were evaluated in 14 open-chest pigs using pressure-volume analysis and the pressure-volume area-myocardial O(2) consumption (PVA-MVo(2)) framework. AM (15 ng·kg(-1)·min(-1), n = 8) or saline (controls, n = 6) was infused for 120 min. Subsequently, a concurrent infusion of EPI (50 ng·kg(-1)·min(-1)) was added in both groups (AM-EPI vs. EPI). AM increased cardiac output (CO) and coronary blood flow by 20 ± 10% and 39 ± 14% (means ± SD, P < 0.05 vs. baseline), whereas controls were unaffected. AM-EPI increased CO and coronary blood flow by 55 ± 17% and 75 ± 16% (P < 0.05, AM-EPI interaction) compared with 13 ± 12% (P < 0.05 vs. baseline) and 18 ± 31% (P = not significant) with EPI. LV systolic capacitance decreased by -37 ± 22% and peak positive derivative of LV pressure (dP/dt(max)) increased by 32 ± 7% with AM-EPI (P < 0.05, AM-EPI interaction), whereas no significant effects were observed with EPI. Mean arterial pressure was maintained by AM-EPI and tended to decrease with EPI (+2 ± 13% vs. -11 ± 10%, P = not significant). PVA-MVo(2) relationships were unaffected by all treatments. In conclusion, AM-EPI cotreatment has an inodilator profile with CO and LV function augmented beyond individual drug effects and is not associated with relative increases in energetic cost. This can possibly take the inodilator treatment strategy beyond hemodynamic goals and exploit the cardioprotective effects of AM in acute heart failure.
肾上腺髓质素（AM）在实验性心肌梗死的急性期被用作治疗药物，可以降低死亡率。然而，由于 AM 具有血管扩张和等力中性作用，因此在急性心力衰竭中可能具有有害作用。AM 和肾上腺素（EPI）从嗜铬细胞中共同分泌，表明存在生理相互作用。我们评估了 AM-EPI 共同治疗的血流动力学和能量特征，探讨了药物相互作用是否改善心脏功能。使用压力-容积分析和压力-容积面积-心肌耗氧量（PVA-MVo2）框架评估 14 只开胸猪的左心室（LV）机械能量。AM（15ng·kg-1·min-1，n=8）或生理盐水（对照组，n=6）输注 120min。随后，在两组中都添加了 EPI（50ng·kg-1·min-1）的同时输注（AM-EPI 与 EPI）。AM 使心输出量（CO）和冠状动脉血流量增加了 20±10%和 39±14%（平均值±标准差，P<0.05 与基线相比），而对照组则没有影响。AM-EPI 使 CO 和冠状动脉血流量增加了 55±17%和 75±16%（P<0.05，AM-EPI 相互作用），而 EPI 仅增加了 13±12%（P<0.05 与基线相比）和 18±31%（P=无显著意义）。LV 收缩期电容减少了-37±22%，LV 压力的峰值正导数（dP/dt(max)）增加了 32±7%（P<0.05，AM-EPI 相互作用），而 EPI 则没有观察到显著作用。AM-EPI 维持平均动脉压，而 EPI 则倾向于降低平均动脉压（+2±13%与-11±10%，P=无显著意义）。PVA-MVo2 关系不受所有治疗的影响。总之，AM-EPI 共同治疗具有扩张血管作用，CO 和 LV 功能增强，超出了单独药物的作用，并且与能量消耗的相对增加无关。这可能使扩血管治疗策略超越血流动力学目标，并利用 AM 在急性心力衰竭中的心脏保护作用。
