Defibrotide Eases Heart Muscle Stiffening in Ischemic Rabbit Hearts

Berti and colleagues, writing in the European Journal of Pharmacology in 1987, studied Defibrotide, a polydeoxyribonucleotide made from mammalian lung tissue, in isolated rabbit hearts deprived of adequate blood flow. This is a laboratory pharmacology study, not a clinical trial, using excised rabbit heart preparations to model low-flow ischemia and subsequent reperfusion.

The researchers reduced blood flow to the heart to 0.2 ml/min to mimic ischemia, then restored it to 20 ml/min. Defibrotide lessened the muscle stiffening (contracture) that ischemia caused, in a dose-related way, and stopped irregular heart rhythms, helping the heart's mechanical activity recover once flow was restored. It also increased the heart's release of prostaglandin-like substances, without changing normal heart contraction. Two specific prostaglandins, PGE2 and PGI2, each partly reduced the ischemic stiffening when tested on their own in this preparation. When the researchers blocked prostaglandin production with indomethacin, Defibrotide's protective effects disappeared entirely, pointing to prostaglandins as a key part of how it works in this model — though the authors note other mechanisms, such as effects on cell membranes and calcium handling in mitochondria, may also play a role.

The study was confined to isolated rabbit heart tissue and cannot show whether these effects occur in a living animal, in humans, or in any skin or wound-healing context.