Perfusion and/or preservation solution for organs

Abstract

The present invention relates to a solution for preservation, perfusion, and / or reperfusion of an organ, especially the heart, for transplantation. The solution contains peptide inhibitor(s) of protein kinase C βII (PKC βII) and / or of protein kinase C ζ (PKC ζ) and / or peptide activator(s) of protein kinase C δ (PKCδ). Methods for using the inventive solution are also disclosed, including methods for preserving an organ for transplantation, for protecting an ischemic organ from damage, for attenuating organ dysfunction after ischemia, for maintaining nitric oxide release and / or inhibiting superoxide release in an ischemic organ, and for protecting an organ from damage when isolated from the circulatory system.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a solution for preservation, perfusion, and / or reperfusion of an organ, especially the heart, for transplantation. The solution contains peptide inhibitor(s) of protein kinase C beta II (PKC βII) and / or of protein kinase C zeta (PKC ζ) and / or peptide activator(s) of protein kinase C delta (PKC δ). BACKGROUND OF THE INVENTION [0002] Successful organ transplantation is often limited due to ischemic / reperfusion injury. Isolated human hearts deprived of oxygen for more than four hours progressively loose vigor and often do not survive in recipient hosts. Other organs such as the kidney, liver, pancreas and lung are also subject to tissue and cellular damage when removed from their hosts prior to transplantation. This damage is due to hypoxic conditions and a lack of circulation, which normally delivers physiological concentrations of oxygen and nutrients, and removes toxic compounds produced by an organ's cells. Organ transp...

AI Technical Summary

Benefits of technology

[0008] The present invention provides a solution for preservation, perfusion, and / or reperfusion of an organ, especially the heart, containing peptide inhibitor(s) of protein kinase C βII (PKC βII) and / or of protein kinase C ζ (PKC ζ) and / or peptide activator(s) of protein kinase C δ (PKC δ). The solution protects organ tissues and cells from damage while the organ is isolated from the circulatory system or is experiencing decreased blood flow (ischemia). The present inventor has discovered that the peptide inhibitors of PKC βII and / or PKC ζ, and / or peptide activator(s) of PKC δ enhance NO release or inhibit endothelial / PMN superoxide release, which can exert protective effect in organs undergoing ischemia / reperfusion.

Problems solved by technology

Successful organ transplantation is often limited due to ischemic / reperfusion injury.

Isolated human hearts deprived of oxygen for more than four hours progressively loose vigor and often do not survive in recipient hosts.

Other organs such as the kidney, liver, pancreas and lung are also subject to tissue and cellular damage when removed from their hosts prior to transplantation.

This damage is due to hypoxic conditions and a lack of circulation, which normally delivers physiological concentrations of oxygen and nutrients, and removes toxic compounds produced by an organ's cells.

Nevertheless, organ rejections still remains due to deterioration in the condition of the transplanted organ between the time of removal and the restoration of blood flow in the recipient.

However, reperfusion of blood flow induces endothelium and myocyte injury, resulting in organ dysfunction (Buerke et al., Am J Physiol 266: H128-136, 1994; Lucchesi and Mullane, Ann Rev Pharmacol Toxicol 26: 2011-2024, 1986; and Lucchesi et al., J Mol Cell Cardiol 21: 1241-1251, 1989).

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