Effects of adenosine and defibrotide adjunct to a standard crystalloid cardioplegic solution.
OBJECTIVE
Adenosine has many actions potentially useful as adjunct to a cardioplegia. Defibrotide was recently shown to have protective effects during cardiac arrest. The aim of this study was to compare these 2 substances to delineate their profile of action in the setting of cardioplegic arrest.


METHODS
A Langendorff model for isolated rat hearts was employed: 3 groups of 8 hearts each were used, respectively with plain St. Thomas cardioplegia as control (group C), and the same solution added with adenosine (group A) or defibrotide (group D). The hearts had a baseline perfusion for 30 minutes with Krebs-Henseleit solution at 37 degrees C, cardioplegia administration for 3 minutes, then 30 minutes of ischemia without any perfusion and finally 30 minutes of reperfusion with Krebs-Henseleit solution at 37 degrees C.


RESULTS
The time to attain heart arrest was 20% shorter in group A, but this difference did not reach statistical significance (A: 13.6+/-1.5; D: 16.8+/-2.7; C: 17.3+/-2.2 s). The heart rate during reperfusion in group A was almost identical to baseline, while in both group C and D it was significantly lower (A: 101%, D: 93.4%, C: 82.4%, p<0.01).A and D decreased significantly the release of creatine phospokinase compared to group C (p=0.006). Lactate dehydrogenase release was lower in both treatment groups, although statistical significance was not reached. Peak positive dP/dT decreased more in controls during reperfusion (A: -23+/-6%, D: -17+/-5%, C: -31+/-5%, p=ns). Negative dP/dT was significantly worse in controls compared to both treatments (A: -19+/-6%, D: -12+/-5%, C: -34+/-7%, p=0.035).


CONCLUSIONS
Both adenosine and defibrotide have protective effects in an isolated model of cardioplegic arrest. Adenosine is significantly more active on heart rate while defibrotide is more active on contractily. Further studies are justified in order to test the combination of these 2 drugs.
Mantovani
V
V
Department of Cardiac Surgery, Ospedale di Circolo-Fondazione Macchi, University of Insubria, Varese, Italy. vitmantovani@hotmail.com
Mariscalco
G
G
Borsani
P
P
Tenconi
S
S
Bruno
V D
VD
Leva
C
C
Ferrarese
S
S
Sala
A
A
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology / Q000592:standards*; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004338:Drug Combinations; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006324:Heart Arrest, Induced / Q000379:methods*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D002314:Cardioplegic Solutions; D004338:Drug Combinations; D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; D014665:Vasodilator Agents; C036901:defibrotide; D000241:Adenosine