The Protective Effect Of Adenosine Precondition On Myocardium And Lung During Cardiopulmonary Bypass

Objective: To observe the effect of pharmacologic precondition of adenosine and nucleoside transport inhibitor Dipyridamole on myocardium and lung protection in cardiopulmonary bypass..Methods: 56 patients who would undergo cardiac valve replacement were randomized into four matched groups: group Dip, group Ado, group Ado+Dip, and group Cont. Group Dip(n=14) received Dipyridamole (adenosine transport inhibitor)only; group Ado(n=14) was pumped a little Adenosine before CPB; group Ado+Dip(n=14) received both; group Cont(n=14) received neither but the same volume of physiological saline. 1.Blood samples were taken to examine the serum concentrations of CK-MB, cTn-I and MDA before cardiopulmonary bypass, then at 2h, 6h and 16h after aorta opened, clinical data including spontaneous beating, duration of ventilator support, maximum dosage of dopamine in first 24 hours post-operation were also observed. 2. Blood samples of group Dip and group Ado+Dip were taken from left and right atrium for the measurements of PMN and PLT before CPB and at 10 min after the heart resuscitation respectively; blood samples were taken to examine the serum concentrations of TNF-α,IL-8,IL-10before cardiopulmonary bypass, and that at 2h,6h and 16h after aorta opened; Pulmonary compliance, airway pressure and the oxygen-nation index (OI) were also recorded.Results: 1.1 Maximum dosage of dopamine of group Ado and group Ado+Dip in first 24 hours post-operation was lower than that of group Dip and group Cont; the rate of spontaneous beating of group Ado and group Ado+Dip after aorta opened were higher than group Dip and group Cont whereas the difference was not significant; the duration of ventilator support of group Ado+Dip was less than others. 1.2 The levels of CK-MB, cTn-Ⅰand MDA before cardiopulmonary bypass were not prominently different among four groups. After aorta opened, the levels of CK-MB, cTn-Ⅰand MDA were significantly increased. The level of CK-MB peaked after 2h, then declined gradually; the level of cTn-Ⅰascended gently and got its peak after 16h; the level of MDA peaked after 6h, then declined gradually. 1.3 The levels of cTn-Ⅰafter surgery and CK-MB at 2h, MDA at 6h after aorta opened were significantly lower in the Ado group than that in the Cont group. All the levels of CK-MB, cTn-Ⅰand MDA of the Ado+Dip group after aorta opened were significantly lower compared with the Cont group and Dip group, especially the levels of CK-MB at 6h, cTn-Ⅰat 6h and 16h after aorta opened in the Ado+Dip group were significantly lower than that in the Ado group; compared with group Ado, group Ado+Dip, group Cont, the levels of that in group Dip didn't greatly change. 2.1 The level of pulmonary compliance, airway pressure and the oxygen- nation index (OI) of experiment group were significantly superior to that of Cont group. 2.2 PMN count and PLT count between left and fight atrium were not significantly different before CPB, but after the heart resuscitation, PMN count and PLT count of right atrium increased prominently, especially the Cont group. 2.3 The levels of TNF-α,IL-8,IL-10 before cardiopulmonary bypass were not significantly different between two groups, but after aorta opened, the levels of CK-MB, cTn-Ⅰand MDA increased greatly and peaked after 2h, then declined gradually. The level of TNF-α, IL-8 of Cont group after aorta opened was significantly higher than that of experiment group whereas the level of IL-10 was significantly lower than that of experiment group.Conclusion: Exogenous adenosine is effective in promoting myocardial protection that can also be enhanced by dipyridamole—the nucleoside transporter inhibitor. In contrast to that, the protective effect on myocardium of endogenous adenosine is likely ineffective. Exogenous adenosine has a protective effect on the lung injury by effectively enhancing the level of IL-10 and reducing the neutrophil sequestration in the lungs, the level of TNF-a, IL-8 and free oxygen molecules produced during CPB.