Pentostatin-augmented interstitial adenosine prevents postcardioplegia injury in damaged hearts.
This study tests the hypothesis that the adenosine deaminase inhibitor pentostatin (2-deoxycoformycin), when given before ischemia or during infusions of blood cardioplegia, augments interstitial adenosine levels and prevents postcardioplegia dysfunction in hearts with antecedent ischemia. Twenty-one anesthetized dogs were placed on cardiopulmonary bypass, and the hearts were made globally ischemic for 30 minutes. Dogs received blood cardioplegia with no pentostatin (BCP group, n = 6), pretreatment pentostatin (0.2 mg/kg) infused 5 minutes before global ischemia (PS-PTx group, n = 7), or pentostatin included only in the blood cardioplegia without pretreatment (PS-BCP group, n = 8). Microdialysate myocardial adenosine levels (an index of interstitial fluid levels) increased only modestly in the BCP group (from 0.55 +/- 0.13 microM to 2.64 +/- 0.50 microM) and the PS-BCP group (from 0.55 +/- 0.18 microM to 1.08 +/- 0.48 microM) during normothermic ischemia, but interstitial adenosine levels were not augmented further during cardioplegic arrest in either group. In contrast, the adenosine level in the PS-PTx group was significantly (p < 0.05) augmented during global ischemia (from 0.50 +/- 0.13 microM to 63.16 +/- 28.08 microM) and cardioplegia infusion (to 15.26 microM +/- 5.61 microM). Relative to baseline, postischemic left ventricular performance (end-systolic pressure-volume relation) was depressed in both the BCP (from 5.5 +/- 1.2 mm Hg/mL to 3.8 +/- 0.4 mm Hg/mL) and PS-BCP groups (from 7.1 +/- 0.9 mm Hg/mL to 3.8 +/- 0.7 mm Hg/mL). In contrast, PS-PTx restored postischemic performance (from 6.2 +/- 0.5 mm Hg/mL to 7.5 +/- 0.9 mm Hg/mL).(ABSTRACT TRUNCATED AT 250 WORDS)
Hudspeth
D A
DA
Department of Cardiothoracic Surgery, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27157-1096.
Williams
M W
MW
Zhao
Z Q
ZQ
Sato
H
H
Nakanishi
K
K
McGee
D S
DS
Hammon
J W
JW
Vinten-Johansen
J
J
Van Wylen
D G
DG
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000097:blood / Q000187:drug effects; D004285:Dogs; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D017551:Microdialysis; D008954:Models, Biological; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015649:Pentostatin / Q000494:pharmacology / Q000627:therapeutic use*; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011292:Premedication; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects; D019820:Xanthine; D014970:Xanthines / Q000378:metabolism
D007042:Hypoxanthines; D007773:Lactates; D014970:Xanthines; D019820:Xanthine; D019271:Hypoxanthine; D019344:Lactic Acid; D015649:Pentostatin; D007288:Inosine; D009195:Peroxidase; D003402:Creatine Kinase; D000241:Adenosine