Heart Center, Semmelweis University, Budapest 1122, Hungary.
J Cardiovasc Pharmacol. 2009 Oct;54(4):341-7. doi: 10.1097/FJC.0b013e3181b7674b.
Intrapericardial (IP) administration of certain cardioactive agents allows investigation of local pharmacological actions on the heart and may carry potential benefit to influence myocardial function. The cardioprotective adenosine (ADO) and inosine (INO) may be the most representative candidates. Elimination and cardiovascular effects of IP and intravenously (IV) applied ADO and INO were compared on anesthetized dogs. Their pericardial and systemic concentrations were measured after consecutive administration of increasing ADO and INO doses. In the case of IP administration at the end of the incubation period, pericardial concentrations of adenine nucleosides significantly exceeded the control values. However, the IV applied ADO and INO were rapidly metabolized in the systemic plasma. As characteristic hemodynamic effects, small but sustained decrease in heart rate (IP ADO) and increase in myocardial contractility (IP INO) were observed. During IV administration, ADO and INO exerted remarkable effects on all hemodynamic variables, which then gradually disappeared in 15 minutes. In summary, the elimination of ADO and INO was significantly slower in the pericardial fluid than in the plasma. Considering the balanced cardiac actions and lack of strong systemic hemodynamic effects, IP administration of adenine nucleosides may suggest a promising approach in the local treatment of the diseased heart.
心包内（IP）给予某些心脏活性药物可研究局部药理作用于心脏，并可能对影响心肌功能具有潜在益处。具有心脏保护作用的腺苷（ADO）和肌苷（INO）可能是最具代表性的候选药物。在麻醉犬上比较了 IP 和静脉内（IV）给予的 ADO 和 INO 的消除和心血管作用。在连续给予递增剂量的 ADO 和 INO 后，测量其心包和全身浓度。在孵育期结束时进行 IP 给药的情况下，嘌呤核苷的心包浓度显著超过对照值。然而，IV 给予的 ADO 和 INO 在全身血浆中迅速代谢。作为特征性的血液动力学效应，观察到心率（IP ADO）略有但持续降低和心肌收缩力（IP INO）增加。在 IV 给予期间，ADO 和 INO 对所有血液动力学变量均产生显著影响，然后在 15 分钟内逐渐消失。总之，ADO 和 INO 在心包液中的消除明显比在血浆中慢。考虑到心脏作用平衡且无强烈的全身血液动力学作用，心包内给予嘌呤核苷可能提示局部治疗患病心脏的一种很有前途的方法。
