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Organ preservation and/or perfusionRelated Patent Categories: Chemistry: Molecular Biology And Microbiology, Differentiated Tissue Or Organ Other Than Blood, Per Se, Or Differentiated Tissue Or Organ Maintaining; Composition ThereforOrgan preservation and/or perfusion description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070148628, Organ preservation and/or perfusion. Brief Patent Description - Full Patent Description - Patent Application Claims
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 .epsilon. (PKC .epsilon.). 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 transplants have a higher frequency of success when performed immediately after excision from their hosts. [0003] Recent advances have increased the rate of successful organ transplants and organ surgery, such as coronary bypass surgery. The first includes organ preservation and organ perfusion solutions. The second is improved methods and devices for the delivery of organ perfusion solutions to an organ. [0004] Short-term myocardiac preservation is currently provided by cold storage after cardioplegic arrest. A variety of processes exist however differing by the composition of the solution used, the preservation temperature and the administration protocol. Different solutions for arresting and preserving the heart have been developed to protect the myocardium in cardiac surgery. Examples of these solutions include Krebs-Henseleit solution, UW solution, St. Thomas II solution, Collins solution and Stanford solution. (See, e.g., U.S. Pat. Nos. 4,798,824 and 4,938,961; Southard and Belzer, Ann. Rev. Med. 46:235-247 (1995); and Donnelly and Djuric, Am. J. Hosp. Pharm. 48:2444-2460 (1991)). 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. [0005] Restoration of blood flow is the primary objective for treatment of organ tissue experiencing prolonged ischemia, e.g., during transplant. However, reperfusion of blood flow induces endothelium and myocyte injury, resulting in organ dysfunction (Buerke et al., Am J Physiol 266: HI128-136,1994; Lucchesi and Mullane, Ann Rev Pharmacol Toxicol 26: 2011-2024, 1986; and Lucchesi et al., J Mol Cell Cardiol 21: 1241-1251, 1989). The sequential events associated with reperfusion injury are initiated by endothelial dysfunction which is characterized by a reduction of the basal endothelial cell release of nitric oxide (NO) within the first 2.5-5 min post-reperfusion (Tsao and Lefer, Am J Phyiol 259: H1660-1666, 1990). The decrease in endothelial derived NO is associated with adhesion molecule up-regulation on endothelial and polymorphonuclear (PMN) leukocyte cell membranes (Ma et al., Circ Res 72: 403-412, 1993; and Weyrich et al., J Leuko Biol 57: 45-55, 1995). This event promotes PMN/endothelial interaction, which occurs by 10 to 20 min post-reperfusion, and subsequent PMN infiltration into the myocardium is observed by 30 min post reperfusion (Lefer and Hayward, In The Role of Nitric Oxide in Ischemia-Reperfusion: Contemporary Cardiology, Loscalzo et al. (Eds.), Humana Press, Totowa, N.J., pp. 357-380, 2000; Lefer and Lefer, Cardiovasc Res 32: 743-751, 1996; Tsao et al., Circulation 82: 1402-1412, 1990; and Weyrich et al., J Leuko Biol 57: 45-55, 1995). [0006] Chemotactic substances released from reperfused tissue and plasma factors activate PMNs that augment PMN release of cytotoxic substances (i.e. superoxide anion) and contribute to organ dysfunction following ischemia/reperfusion (Lucchesi et al. J Mol Cell Cardiol 21: 1241-1251, 1989; Ma et al., Circ Res 69: 95-106, 1991; Tsao et al., Circulation 82: 1402-1412, 1990; and Tsao et al., Am Heart J 123: 1464-1471, 1992). Superoxide combines with NO to produce peroxynitrite anion thus reducing the bioavailability of NO and promotes endothelial dysfunction and PMN infiltration after myocardial ischemia/reperfusion (Clancey et al., J Clin Invest 90: 1116-1121, 1992; Hansen, Circulation 91: 1872-85, 1995; Lucchesi et al., J Mol Cell Cardiol 21: 1241-1251, 1989; Rubanyi and Vanhoutte, Am J Physiol 250: H815-821, 1986; Tsao et al., Am Heart J 123: 1464-1471, 1992; and Weiss, New Eng JMed 320: 365-375, 1989). [0007] Therefore, there remains a need for a solution of improved quality that can extend the preservation time of an organ for transplantation and protect the organ from reperfusion injury after ischemia, so that the organ can resume proper function after restoration of blood flow. SUMMARY OF THE INVENTION [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 .epsilon. (PKC .epsilon.). 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 .epsilon. can exert protective effects in organs undergoing ischemia/reperfusion. [0009] In an embodiment, the solution contains about 1-10 .mu.M, preferably about 1-5 .mu.M, of the peptide inhibitor of PKC .epsilon. dissolved in a solution, preferably a saline solution. [0010] The solution of the present invention can be used as a perfusion solution or a preservation solution. As a perfusion solution, it is pumped into the vasculature of the organ to protect the organ tissues and cells. As a preservation solution, it serves as a bathing solution into which the organ is submerged. Preferably, the organ is perfused with and submerged in the present solution. Further, the present solution also serves as a reperfusion solution upon restoration of blood flow to the organ after ischemia. [0011] The present invention also include methods of using the solution of the present invention. These include methods for preserving an organ for transplantation, for protecting an ischemic organ from damage, for attenuating organ dysfunction after ischemia, and for protecting an organ from damage when isolated from the circulatory system. BRIEF DESCRIPTION OF THE DRAWINGS [0012] FIG. 1 is a graph showing the time course of LVDP (left ventricular developed pressure=left ventricular end systolic pressure (LVESP)-left ventricular end diastolic pressure (LVEDP)) in sham I/R, I/R, I/R+PMNs and I/R+PMN+PKC .epsilon. peptide inhibitor (5 .mu.M) perfused rat hearts. [0013] FIG. 2 is a graph showing LVEDP timecourse in sham I/R, I/R, I/R+PMN and I/R+PMN+PKC .epsilon. peptide inhibitor (5 .mu.M) groups. [0014] FIG. 3 is a graph showing initial and final LVDPs expressed in mmHg from isolated perfused rat hearts before ischemia (I) (Initial) and after 45 min post reperfusion (Final). Hearts were perfused in the presence or absence or PMNs. PMNs induced a significant contractile dysfunction, which was attenuated by the PKC .epsilon. peptide inhibitor. All values are expressed as mean.+-.SEM. Numbers of hearts examined are at the bottom of the bars. [0015] FIG. 4 is a graph showing initial and final maximal rates of LVDP (+dP/dt max) expressed in mmHg/s in isolated perfused rat hearts before ischemia (Initial) and after reperfusion (Final). Hearts were perfused in the presence or absence of PMNs. PMNs induced a significant contractile dysfunction, which was attenuated by the PKC .epsilon. peptide inhibitor. All values are expressed as means.+-.SEM. Numbers of hearts examined are at the bottom of the bars. [0016] FIG. 5 is a graph showing coronary flows among the seven groups in the cardiac function experiments (sham I/R, sham I/R+PKC .epsilon. peptide inhibitor (5 .mu.M), I/R, I/R+PKC .epsilon. peptide inhibitor (5 .mu.M), I/R+PMNs, and I/R+PMN+PKC .epsilon. peptide inhibitor (1 and 5 .mu.M)). [0017] FIG. 6 is a graph showing heart rates among the seven groups in the cardiac function experiments (sham I/R, sham I/R+PKC .epsilon. peptide inhibitor (5 .mu.M), I/R, I/R+PKC .epsilon. peptide inhibitor (5 .mu.M), I/R+PMNs, and I/R+PMN+PKC .epsilon. peptide inhibitor (1 and 5 .mu.M)). [0018] FIG. 7 is a graph showing NO release from rat aortic endothelium in untreated (basal) segments compared to PKC .epsilon. peptide inhibitor treated segments (1, 5, and 10 .mu.M). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT [0019] The present invention provides a solution for the preservation, perfusion, and/or reperfusion of an organ, especially the heart. The solution contains peptide inhibitor(s) of protein kinase .epsilon. (PKC .epsilon.). Preferably, the peptide inhibitor of PKC .epsilon. is present in the solution in an amount of about 1-10 .mu.M, more preferably about 1-5 .mu.M. Continue reading about Organ preservation and/or perfusion... Full patent description for Organ preservation and/or perfusion Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Organ preservation and/or perfusion patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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