1 Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
2 Department of Cardiology and Angiology, University Hospital Magdeburg, Otto-von-Guericke-Universitӓt Magdeburg, Saxony-Anhalt 39106, Germany.
Exp Biol Med (Maywood). 2019 Aug;244(11):915-922. doi: 10.1177/1535370219850786. Epub 2019 May 27.
Cardiac transplant outcomes can be compromised by the effects of global ischemia and associated reperfusion injury. In attempts to alleviate these phenomena, various pharmaceutical agents can be administered. Previous reports have shown that adenosine triphosphate (ATP) may act as either a postconditioning (PoC) or supplementary (Sup) therapy with cardiosupportive benefits. To further evaluate ATP’s relative effectiveness, we used an isolated swine heart four-chamber working model to monitor both hemodynamic and metabolic responses. We employed two strategies of ATP administration: (1) a postconditional (PoC) bolus just prior to reanimation, and (2) regular dosing throughout the assessment period (Sup). swine hearts in the Sup group elicited significantly higher left ventricular function during the 2 h monitoring period than controls. In contrast, PoC administration appeared to induce depressed cardiac function. The effects of ATP on cardiac function can have varied effects, dependent on when it is administered.
We employed an isolated swine heart four-chamber working model to investigate two potential strategies for adenosine triphosphate (ATP) administration as an therapy: (1) application of a single bolus dose during reperfusion (postconditioning or PoC), and (2) repeated bolus dosing throughout the experiment (supplementary or Sup). swine hearts in the Sup group elicited significantly higher left ventricular function during the 2 h experimental monitoring period. In contrast, ATP administration in the PoC group appeared to induce a degree of depressed hemodynamic function. These data suggest varied functional roles of ATP administration relative to their use in perfusion strategies. We consider that both treatment strategies, if appropriately administered and with further investigation of dosing paradigms, may eventually elicit value in various clinical scenarios, including heart transplantation and heart perfusion to assess potential organs for transplantation and potentially increase the pool of viable donor hearts.
心脏移植的结果可能会受到整体缺血和相关再灌注损伤的影响。为了减轻这些现象，可以使用各种药物。先前的报告表明，三磷酸腺苷（ATP）可以作为后处理（PoC）或补充（Sup）治疗，具有心脏支持作用。为了进一步评估 ATP 的相对有效性，我们使用了一个分离的猪心四腔工作模型来监测血液动力学和代谢反应。我们采用了两种 ATP 给药策略：（1）再灌注前即刻给予后处理（PoC）弹丸，（2）在评估期间定期给药（Sup）。Sup 组的猪心在 2 小时监测期间左心室功能明显高于对照组。相比之下，PoC 给药似乎会导致心脏功能抑制。ATP 对心脏功能的影响可能因给药时间而异。
我们使用了一个分离的猪心四腔工作模型来研究两种潜在的 ATP 给药策略作为心脏再灌注的治疗方法：（1）在再灌注期间（后处理或 PoC）应用单次弹丸剂量，（2）在整个实验过程中重复给予弹丸剂量（补充或 Sup）。Sup 组的猪心在 2 小时实验监测期间左心室功能明显提高。相比之下，PoC 组的 ATP 给药似乎会导致一定程度的血液动力学功能抑制。这些数据表明，ATP 给药的功能作用因给药方式的不同而不同。我们认为，如果给予适当的治疗策略，并进一步研究剂量方案，这两种治疗策略都可能在各种临床情况下产生价值，包括心脏移植和心脏灌注，以评估潜在的移植器官，并可能增加可用于移植的健康供心数量。
