MXPA97004374A - Solutions for organ transplants and method to transplant an org - Google Patents

Abstract

Cardioplegic solutions are provided to contain an organ that is intended to be transplanted and preservation solutions to perfuse and store an organ while waiting for transplantation, cardioplegic solutions include, per liter of solution, a balanced isotonic solution of ions and sodium bicarbonate, potassium, calcium and magnesium in a physiologically acceptable amount, at least 0.5æM of a compound containing amyloride, and enough water to make a liter of solution, preservation solutions include, per liter of solution, a balanced isotonic solution of ions and bicarbonate of sodium, potassium, calcium and magnesium in a physiologically acceptable amount, from about 1.0æM to about 5.0æM of a compound containing amyloride, and water to make a liter of solution, in addition, the preservation solution may contain other components such as EDTA, a small amount of adenosine, and at least one antioxidant the amiloride-containing compound can be amiloride, hexamethylene-phyllid, dimethylamyloride, ethylisopropyl-amyloride or methylisobutylamilide; a method is also provided to contain an organ, store an organ and transplant an entire organism at room temperature for at least 24 hours.

Description

SOLUTIONS FOR ORGAN TRANSPLANTS AND RETARDANT TO TRANSPLANT AN ORGAN BACKGROUND OF THE INVENTION FIELD OF THE INVENTION The present invention relates to orthodoxy solutions, to solutions for organ preservation a methods for transplanting organs. In particular, the present invention relates to cardioplegic solutions for stopping the operation of an organ for transplantation, for storage solutions for perfusion and for the storage of an organ while awaiting implantation, and for m all par'a u + iJirar the cardioplegic and conservation solutions during the transplantation of an organ.

PREVIOUS TECHNIQUE 0 A great deal of progress has been made in research for several years in the understanding of cellular mechanisms, as well as in the development of new transplanto techniques to keep viable organs not only during storage but afterwards of the reperfusion of them. As a result, organ transplantation, including heart transplantation, is an established elective operation. A significant factor that limits the clinical application of organ transplantation is the deviation of the viability of the organ after its removal from the donor. At the same time, the two most commonly used for heart transplantation are simple hypothermic storage and pulsating contiguous perfusion. With simple hypothermic storage, the operation of the heart is stopped with a logical solution, then it is removed from the donor and cooled rapidly. This is achieved by a combination of activation and a short period of perfusion to lower the heart temperature as quickly as possible to a temperature between 0 ° C and ° C, where it can be maintained for up to 6 hours. While cold storage of the organs to be transplanted, the time during which the organ is viable is short. Cold storage decreases the rate at which the intracellular enzymes, essential components of the cells necessary for the viability of the organ, reduce but do not stop the metabolism. The second method of organ preservation that has been subjected to extensive research, continuous pulsatile perfusion, includes the following steps: (1) pulsatile flow, (2) hypothermia, (3) oxygenation of the membrane, (4) a liquid of per-fusion containing albumin and lipids. The advantages of using continuous pulsatile perfusion instead of simple hypothermia, although technically more complex and costly, include the long-term viability of the organ and the test of plantability viability. The compositions of numerous cardioplegic and preservation solutions have been extensively studied. For example, Gal ñanes et al. (M. Gal inanes, í.) Murashita and DJ Hear (iqcJL) The Journal of Heart and Lung Transplantation (10) 975-985, compared the protective properties of three car dioplegic solutions where the solutions of Cold storage limits the storage time of the organs.A storage solution for keeping organs that can be used at temperatures from 0 ° C to 37 ° C but that had a limited storage time is described in the US patent No 5,145,771 issued to ernasters et al. [The solution requires the use of the hydroxyethyl starch colloid for support against the appearance of interstitial edema In the present invention, edema is not a problem because there are no free radicals derived from oxygen that injure The organ preservation on a temperature scale between 0 ° C and 4 ° C results in damage to the organism during storage and after reperfusion with a calcium solution. reperfusion entity. The injury to the organ occurs through the loss of endothelial cells due to dissolved oxygen in the reperfusion solution. Although some of the prior art solutions have been useful to extend the donor's organ storage time and reduce the injury? 1 organ after the reperfusion, the cell injury still happens. Therefore, it is desirable to extend the life of the viable organ and improve the quality of the transplanted organ. Extending the viability of the organ provides sufficient time to test the compatibility of the donor and the recipient and an increased availability of the organ. The recovery of cardiac function is also greatly influenced by the lapse of time in or removal of the donor-and reperfusion as well as the effectiveness of protective interventions used during that period. To overcome the harmful effects of ischemia, techniques such as intermittent or continuous perfusion have been used. Finally, reperfusion itself, although necessary for tissue survival, can initiate a series of events known as reperfusion-induced injury, which, if it occurs, limits the extent or speed of recovery. Thus, modification of the nature of reperfusion is desired to improve myocardial recovery i squern i co / repe rfundi do. More particu- larly, as a result of the deprivation of circulation and, therefore, oxygen (eg, ischemia) during transplantation, the sodium pump, which normally maintains the high-potassium, magnesium and magnesium composition. phosphate and low sodium and chlorine, stops working- due to lack of energy, resulting in a flow of sodium and chlorine into the cells and a flow of potassium and to a lesser extent a flow of magnesium towards force of the cells. The result of these rapid changes in the distribution of Na + - H + in the cell is a net gain, not merely an exchange, of ionic r-acellular ions followed by water and a profound loss of potassium and magnesium which results in the damage to the organ., not fat, et al. (MP rio f fat and N. Karmazyn, (1993), J. Iolec, Cell Cardiol (25), 959-971) studied the protective effects of Na / H exchange inhibitors, including arn lóp and its analogues in It is therefore the general object of the present invention to provide conservation solutions for pulsing and storing organs while awaiting their implantation which inhibits the exchange of ions, extends the vitality of the organ. and reduce the damage to the cells. Another object of the present invention is to provide a method for stopping function and for conserving organs which extends the maximum life of the organ during transplantation. Still another object of the present invention is to provide a method of organ transplantation in which the storage of the organ can be carried out at room temperature for at least 24 hours without significant damage to the organ.

Other objects, aspects and advantages of the present invention will be apparent from the following details of the invention as described more fully.

BRIEF DESCRIPTION OF THE INVENTION In accordance with these objects and the principles of the present invention, cardioplegic solutions and preservation solutions are described for their use in organ transplantation and methods for organ transplantation using the solution in combination with eardioplegic solutions, whose methods increase storage times and reduce injury to the organ. It has been found that a cardioplegic solution with a compound containing arniiopda is effective to achieve the objectives of the present invention. In one aspect of this invention, the cardioplegic solution includes a balanced isotonic solution that includes sodium, potassium, calcium and magnesium ions and bicarbonate in a physiologically acceptable amount, at least 0.5 μn, preferably from 1.0 μn to 5.0 μn and preferably from l.Oμn to 3.0 μ of a compound containing ilópda and enough water to make a liter of solution. The cardioplegic solution also contains glucose to increase the preservation of the organ, adenosine to prevent fibrillation of the organ prior to its removal from the donor and EDTA as a chelating agent. Optionally, the cardiological solution contains hepapna and therefore an antioxidant. The conservation solution, while similar to the cardioplegic solution in the composition of r > ar? l, in that it is based on a balanced isotonic solution that includes ions of sodium, potassium, calcium and magnesium and bicarbonate in a physiologically acceptable amount, also includes from l.Ojín to 5.0 of a compound that Contain ai I nda. The preservation solution preferably includes at least one antioxidant, such as di-thiourea (DnTU), catalase as a scavenger of hydrogen peroxide and apoferptma to decrease the iron content within the conservation solution. Since the function of the organ has been stopped by the eardyopic solution, the preservation solution includes less adenosm and normme hepapne is not needed. In addition, conservation solutions may optionally include hormones, such as insulin and prostagline and antibiotics. The inclusion of a compound containing arnilopda in the isothelial solution of both cardioplegic and preservation solutions can be from the same arniloride or ainiloride analogs, such as hexarnetilene amiopiopda (HMA), d met ii arniloride (DMA), ethyl isopropyl arniiopda (EIPA ) or net ii isobutyl amylópda (niA), all of which inhibit the Na + / H + exchange in organ cells. C? ~ Í pre iere í dimot i 1 amilopda. The invention also provides a method for transplanting an organ that includes steps to stop the function of an organ and remove it from the donor, and to conserve and store the organ that is to be implanted. The method of the present invention includes stopping the function of the organ that will be donated with an oplegic cardiac solution. The organ is removed and connected to a perfusion unit where it is maintained at a <-. temperature between 0 ° C and 37 ° C, preferably from 15 ° C to 25 ° C while perfusing with the preservation solution. Thus, novel aspects of the present invention include storing the organism at cool temperatures, e.g., up to room temperature, while it is perfused. It is believed that the ability to store the organ at or near ambient temperature prevents mechanical damage that can result from cold storage and that continuous perfusion with the preservation solution maintains the metabolic requirements of the organ and prevents potential etabolic blockages. As a result, storage times for the organ can be increased up to at least 24 hours.

DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to new cardiobic solutions to stop the function of an organ that is desired to be transplanted and to new preservation solutions to store and per fundi organs that are desired to implant in a patient that requires such an implant. The suitable organs on which the solutions can be used include, for example, blood, kidney, kidney and pancreas. All the individual components of the present invention are non-toxic and have been found to be stable during storage. While some of the components of the present invention are similar to those of other cardioplegic and preservative solutions, it has been surprisingly found that the addition of aniury or a compound containing aryloride to a balanced isotonic solution including ions of sodium, potassium, calcium, magnesium and bicarbonate in a physiologically acceptable amount to form a cardioplegic solution and its use with the preservation solution of the present invention allows the organs to be stored at room temperature for at least 24 hours without significant damage to the organ. Both cardioplegic and preservative solutions of the present invention are based on a balanced isotonic solution that includes sodium, potassium, calcium and magnesium ions as well as glucose and sodium bicarbonate in a Physiologically acceptable amount. Certain of these types of solutions are well known, such as the one described below, known < the solution of Krebs-Henseleí ~ bicarbonate, which has the following composition: TABLE 1 Fsc l s concentration in a l tro NaCl B5.0 inH at 145 n KCl 3.0 mN at 'SO mM KH2 POA 0, .7 n at 1.3 rnn Mg O * 0.9 mn at .8 mM NaHC03 15.0 ml at 35 inM Glucose 1.0 mM at 50 ini The cardioplegic solution The cardioplegic solution is made starting with the balanced isotonic solution described above. The amount of potassium chloride in the cardiac optic solution is preferably from 20 minutes to 30 minutes. To the isotonic solution is added a compound containing the ylide in an amount of at least 0.5 μm, preferably from 1.0 μM to 5.0 μm and preferably from 1 μM to 3.0 μM. The term "arniloride-containing compound" is intended to include arnilopda and arnilopide analogues. It has been found that the addition of amiiopda, n chemically designated as 3,5-d? ammonium hydrochloride? no-h -cloro-N- (diarn nomet i len) ?? razi nc rbo x the ida inhibits the exchange Na + - M +. Other compounds < What do you hear about? < or its analogs that can be used in the cardioplegic solution include, for example, hexarnet Lien to iloride (Hnn) chemically designated as 5- (N, N-hexame i len) amilopda, dirnetyl arniloride (DÍ1ñ) designated chemically as 5- (N, Nd? Met? L) -amilori da, ethyl isopropyl arni lopda (ETPD) , designated as 5 - (N- ot 11 - N- i sopropí 1) -ami Ion da yr ?? + 11 isobutyl amilopda (nifl), designated as 5- (N-met i I -I I isob? T? I) -ai? Ii Ion da. (Merel- 'harpe &Doh e, St Point, Pa) To be effective, the cardioplegic solution needs to prevent fibrillation of the organ in a relatively short time, e.g., from 2 minutes to 5 minutes or less. For that purpose, adenosm is added to the solution in an amount d < > 5μM to 15μ per liter, preferably 10μn per liter. The adenosi a quickly stops the function of cor z n r n seconds), improves the preservation properties and increases the glucose level. The cardioplegic solution also preferably includes ethyl diamine tetraacetic acid (EDTA) in a quantity of O.drnM at 1.5 mM as a chelating agent. The solution may optionally contain other ingredients, such as at least one antioxidant and, for example, catalase, in an amount which is effective to inhibit the generation of oxygen-derived free radicals via hydrogen peroxide. Heparin is used to carry out the method of the present invention, and can be included directly in the cardioplegic solution or can it be administered to the donor organ separately,? >It requires the addition of hepapna in an amount of 500 units to 1500 units, preferably 1000 units to prevent the formation of blood or dentinal blood clusters during the cardiopulp function and prior excision. to the stamping and implantation of the organ.

The preservation solution The preservation solution is designed to prevent various mechanisms that cause organ injury and thus must be a composition that (1) prevents or restricts intracellular acidosis, (2) prevents the expansion • of the space int racelular, (3) prevent injury from free radicals derived from oxygen, especially during reperfusion, (4) allow the regeneration of high-energy phosphate compounds during reperfusion, (5) sustain a metabolic requirement adequate and (6) prevent rapid changes in Na + -H + -Ca ++ nt racelulares after reperfusion. While the cardioplegic solution and the conservation solution start with the balanced isotonic solution described above, there are significant differences in the final compositions. For example, the preservation solution begins with isotonic solution, wherein the potassium concentration is preferably maintained at 3"0rnM to fl.QmM. Magnesium chloride LO can be used instead of c 1 o u of po s s or. A compound containing amilopda is added to the balanced isotonic solution in an amount of 1.0 μM to 5.0 μM, preferably 1.5-3.0 μM. By compound containing amiloride it is meant that it includes arylilide and analogues of amino acid. It has been found that the addition of ami lop da, chemically designated as the 3'-5-d-arn-i-n-6-chloro-N- (diane nornet iien) -pyrazi ncarbox lamida, monohydrochloride, inhibits Na + exchange. - H +. Ot ros comf > Positions or analogues which have arni lopda that can be used in the cardioplegic solution include, for example, hexarnet len am lopda (HMA) des? gn < Chemically labeled 5- (N, M-hexarnet i len) amiloride, dirnetii amilopda (DMA) chemically designated co or 5- (N, Nd? met ii) -arnilopda, ethyl isopropyl a iloride (EIPA), designated 5 - (N-et? L-N-isopropyl 1) -an loi-ida and ethyl isobutyl amilopda (MTA), designated as 5- (N-met il -Ni sobut? L) -anilópda. (MercL- Sharpe &Dohme, Uest Point, Pa). While the adenosm is included in the conservation solution, the amount of adenosm is considerably less than the amount of adenosm present in the cardioplegic solution because the functions of the organ have been previously stopped. The amount of adenosine in the preservation solution is usually from 0.7 μM to 2.0 μM, preferably l.QuM. The preservation solution also preferably includes diaminetetraacetic acid (EDTA) in an amount of 0.5μn to 1.5μn as a chelating agent. It has also been found desirable to add from 10 to 100 nTl of cappolic acid which helps the solution to divert the use of blocked fatty acids and from 10 μg / L to 100 μg / L of apoforp, which serves to remove iron ( Fe ++) which LC) causes the decomposition of cells. Defernoxyamine can also be used to chelate the iron. The dichloroacetic acid can be used to reduce lactate. Suitable anti oxidants include, but are not limited to, allophenol, glotation, bet-charcoal, catalase, superoxide disrnutase, dunthyl thiourea (DMTU), di feni 1 phenylenediamine (DPPD), mannitol or ciamdanol in an amount effective to inhibit the generation of free radicals derived from oxygen. Antioxidants are present in an amount of 1 n to 10 nn. Antibiotics can be added to transplant organs, but they are usually not added during acute studies.

Method of use The method of transplantation of the present invention is to stop the functions of the organ using the cardioplegic solution, store and store the organ with the preservation solution and reperfuse with the preservation solution In a preferred method, it is injected sufj (icn) "cardioplegic solution to stop the functions of, for example, the heart and prevent its fibulation, the surgeon then removes the organ and connects the heart to a device d <; 5 perfusion comprising tubing and pumps. The conservation solution is then perfused to heart birds while it is saturated with oxygen and carbon dioxide while awaiting its implantation in a patient. It has been found that 1 > Perfusion rate of 50ml / hour at 1"0 ° C is effective. The heart perfusion method can be either a constant flow or the solution can be used at all temperatures within the 0 ° C scale at normal temperature. of the body, 37 ° C. At temperatures of 12 ° C to 37 ° C, the solution protects more than other preservation solutions and, unlike other storage solutions, this protects its protective function of 10 ° C during at least 4 hours The following examples are provided to further illustrate the present invention and not to be considered limiting of the invention in any way.

IB EXAMPLE 1 One liter of cardioplogy solution having the same composition is prepared.

NaCl 118 mn KCl 30 mM CaCl2 1., 75 inM KH2 PO4 L. rnM M OA 1.2 rnn MaHC03 25 ipM Glucose 11 inM no yes 10 μM ÜTA 1.0 inr DMA 1.0 μp Hepap at 1000 units Water destined for water , za < -the c .. s " Add the Krebs-Henselei solution and double-distilled water to a 1000 ml volumetric flask to make a liter while stirring. The rest of the components are added one at a time. After all the components were added, the pH was adjusted to 7.3 with NaOH and the mixture was saturated with O2 / CO2: 5/5%. The solution is stirred for thirty minutes and filtered to remove any undissolved particles (5.0 μ porosity filter). After sterile filtration the solution is ready to be used.

EXAMPLE 2 One liter of preservation solution is prepared which has the following composition NaC 1 118 rnM KCl 4.7 mM CaCl2 1.7 b mM KH2 PO * 1"2 rnM g OA 1.2 rnM MaHC03 25 mli Glucose 11 mM Adeno ina 1.0 μM EDTA 1.0 rnM Apoterpt i at 100 μg / l Catal sa 10 μg / l_ DMTU 10 nM DPPD 1 nM Capric Acid 50 DnA 3.0) JM Insul ma 200.0 units / rnL Distilled, deionized water c. s. ,.

The preservation solution is prepared very similarly to the cardioplegic solution of Example I, that is, by adding Krebs-Henseleite solution to a 1000-in. Volumetric flask with double-distilled water to make a lipo while undergoing agitation. n. The rosto of the components are added one by one and the p is adjusted to 7.3 with NaOH and saturated with 95% oxygen plus 5% carbon dioxide. The solution is stirred for about thirty minutes and filtered to remove any undissolved particles (5.0μ porosity filter). After sterilizing by filtration the solution is ready to be used.

EXAMPLE 3 A mestizo bitch weighing approximately 20 kg was anaesthetized. An IV moisturizing solution of 5% dexose was administered in 0.45% saline at 75 cc / hr throughout the procedure. The heart was exposed by ester-notomy. The cardioprotective solution of Example 1 was administered to stop the functions of the heart, which was then removed. The heart was placed on ice and quickly transferred to the laboratory by placing it in a perfusion apparatus at room temperature where the aorta was adhered to a tube for continuous perfusion with the preservation solution of Example 2. After 2-3 minutes the heart began to beat at a pulsation speed of 50 beats per minute. The excess of the preservation solution was allowed to fill the container until the heart was covered to prevent its flotation and thus not ion the or + a. The perfusion with the solution of Example 2 continued through the storage time. The heart continued to beat for 24 hours. This experiment demonstrates that the cardioplegic and conservation solutions and methods of the present invention increase the conservation time between the collection of an organ and its transplantation and allow it to remain at room temperature without serious degeneration of the organism. The present invention has been described in detail and with particular reference to the preferred embodiments. Those skilled in the art will appreciate that changes can be made without departing from the spirit and scope thereof. Accordingly, the present invention is defined by the following indications with their equivalents included herein.

Claims (1)

1. NOVELTY OF THE INVENTION CLAIMS 1"- A cardioplegic solution to stop the function of an organ selected from the group consisting of heart, liver, kidney and pancreas destined for transplantation, characterized because it comprises, per liter of solution: (a) a balanced isotonic solution comprising sodium, potassium, calcium, magnesium and bicarbonate ions in a physiologically acceptable amount; (b) at least 0.5μM of a compound containing arniloride; and (c) water 2. The cardioplegic solution according to claim 1, further characterized in that said compound containing anilophore is a compound selected from the group consisting of arnilopda, hexarnet ilen arniloride, dimet and 1 ainilopda. , et isopropyl 1 arylilide and isobutyl ether. 3. The cardioplegic solution according to claim 1, further characterized in that the compound containing arnilonda is dirnethyl amylópda. 4. The cardioplegic solution according to claim 1, further characterized in that it comprises 0.5? Nn to 1.5 mM EDTA., 5. The cardioplegic solution according to claim 1, further characterized in that it comprises 5.0 μM. to 15 μn of adenosine. &.- The cardiophoretic solution according to claim 1, further characterized in that it comprises from 500 uni ades to 1500 units of hepapna. 7. The cardioplegic solution according to claim 1, further characterized in that it comprises an antioxidant in an amount effective to inhibit the generation of free radicals derived from oxygen. 8. - A cardioplegic solution to stop the function of an organ selected from the group that consisted? heart, liver, kidney and pancreas destined for transplantation, characterized because it comprises, per liter of solution: NaCl from 85 mM to 145 KCl from 20 rnM to 30 rnM CaCl2 from 0.5 inM to 2.5 rnn KH2 POA from 0.7 p to 1.3 rnn M O? 0.9 mM to 4.8 mM NaHCO3 from 15.0 rnM to 35 n 1.0 mn to 50 inli EDTA 0.5 rnM to 1.5 mM EDTA distilled, deionized water q.s. and from 0.5 μM to 5.0 μM of a compound containing arnilopda. 9. The cardioplegic solution according to claim 8, further characterized in that said compound containing aryllopda is a compound selected from the group consisting of amiloride, hexarnetiene amiloride, 7 > dirnetyl arnilopda, ethyl isopropyl 1 amylopide and rnet 11 isobutyl aryl p da. 1. The cardioplegic solution according to claim 8, further characterized in that said compound is dimeth ii ainiloride. 11. The cardioplegic solution according to claim 8, further characterized by being from 5.0 μM to 15 μM of denosin. 12. The cardioplegic solution according to claim 8, further characterized in that it comprises from 500 units to 1500 units of hepapna. 13. The cardioplegic solution according to claim 8, further characterized in that it comprises an antioxidant in an amount effective to inhibit the generation of free radicals derived from oxygen. 14 »- A cardioplegic solution for stopping the function of an organ selected from the group consisting of heart, liver, kidney and pcreas destined for transplantation, characterized in that it comprises, per liter of solution: 118 mM NaCl KCl 30 inf CaCl2 1.75 rnM KH2PO4 1.2 rnM MgSO * 1.2 rnM NaHC? 3 25 rnM Glucose 11 rnn Adenosma 10 JJIÍ Dirnetil arnilopda 1.0 μM He pa p na 1000 a 11 s 5 Distilled water, deioni ada cs 15. A preservation solution for the storage and reperfusion of diseased organs to implantation characterized in that it comprises, per liter of solution: (a) a balanced isotonic solution comprising LC) ions of sodium, potassium, calcium, magnesium and bicarbonate in a physiologically acceptable amount; (b) from 0.7 μM to 2.0 jiM of adeno a; (c) from 1.0 μM to 5.0 μM of a compound containing amilopda; and (d) water. 16. The preservation solution according to claim 15, further characterized in that said arniloride-containing compound is a compound selected from the group consisting of arnilopda, hexameth and L'en amilopda, dimetil amilopda, ethyl isopropyl arniionda and metii i obu il amilorida. 17. The preservation solution according to claim 15, further characterized in that said compound is dimethyl amilopda. 18. The preservation solution according to claim 15, further characterized in that it comprises an antioxant in an amount effective to inhibit the generation of free radicals derived from oxygen. 19. - The preservation solution according to claim 15, further characterized in that from 10 nM to 100 nM caprylic acid. 20. The conservation solution according to claim 8, further characterized in that it comprises 100 μg / ml to 500 units / ml of insulin. 21.- A conservation solution useful for preserving organs for storage and for the reperfusion of organs intended for implantation characterized because it comprises, per liter of solution: NaCl from 85 mM to 145 inM KCl from 3.0 rnn to 8.0 mn CaCl2 from 1.0 inM to 2.0 rnn KH2 PO4 from 0.7 M to 1.3 mM Mg 0 «from 0.9 rnn to 4.0 rnn NaHC03 from 15.0 rnM to 35 rnn Glucose from 1.0 to 50 inM EDTA from 0.5 inM to 1. rnn Adeno ina from 0.7 μn a 1.5 Apoferritma from Iμg / L to 100 μg / L Catalase from Iμg / L to 10 μg / L Caprylic acid from 10 nM to 100 nM DMTU from 1 nM to 10 nM DPPD from InM to 10 nM Dirnetil arniloride from 1 μM to 5.0 μ Distilled water, desiomzada cs 22. - A conservation solution useful for preserving organs for storage and for the reperfusion of organs destined for implantation, characterized because I understood them), because of their use: NaCl 118? Ntt KCl 4.7 rnn CaCl2 1 5 mn KH2 PO4 1.2 rnM ng O .; 1.2 rnn NaHC03 25 mM Glucose 11 inM A de oi na 1.0 μM FDTA LO mM Apoferritma 100 μg / L Catalase 10 μg / L DMTU 10 nM DPPD 10 nM Dirnetil to ilopda 3.0 μM Insulin 200.0 μm / rnl Caustic acid 50 nM Water distilled, deionized cs 2. 3,. - The use of a cardioplegic solution comprising, per liter of solution: (a) a balanced isotonic solution comprising sodium, potassium, calcium, magnesium and bicarbonate ions in a physiologically acceptable amount; (b) at least 0.5 μM of a compound containing amilunate; and (c) water; to stop the function of the heart of a mammal, prior to its removal from a donor, in order to implant said heart in a mammal that requires said implantation. 24. The use of the cardioplegic solution according to claim 23, further characterized in that said compound containing aryllopda is a compound selected from the group consisting of a ilópda, hexa etiien arnilonda, di motil arnilópda, ethyl isopropil arnilópda and methyl isobu i] aniLoride. The use of the cardioplegic solution according to claim 23, further characterized in that said compound is di ethyl arnilopda. 26. The use of the cardioplegic solution according to claim 23, further characterized in that said solution comprises 0.5 mM to 1.5 EDTA. 27. The use of the cardioplegic solution according to claim 23, further characterized in that said solution comprises from 5.0 μM to 15 μM of adenosm. 28. The use of the cardioplegic solution according to claim 23, further characterized in that said solution comprises from 500 units to 1500 units of hepapna. 29. The use of the cardioplegic solution according to claim 23, further characterized in that said solution comprises an antioxidant in an amount effective to inhibit the generation of free radicals derived from oxygen. 30.- The use of an ophthalmic cardi solution comprising, per liter of solution: NaCl from 85 rnM to 145 rnn KCl from 3.0 mn to 30 inM CaCl2 from 0.5 mn to 2.5 rnn KH2PO4 from 0.7 rnM to 1.3 rnn MgS0 «from 0.9 ml at 4.8 rnn NaHCO3 from 15.0 rnM to 35? T »M Glucose from mM LO to 50 ml EDTA from 0.5 inM to 1.5 rnM Distilled, deionized water cs and at least 0.5 μM of a compound containing amyloride, to stop the heart function of a mammal, prior to its removal from a donor, for the purpose of implanting said heart in a mammal that requires such implantation. 31. The use of the cardioid solution according to claim 30, further characterized in that said compound containing arnylori is a compound selected from amiloride, hexa etiien a ilórida, dihydryl dihydryl, ethyl eopropyl arniloride and rnethyl isobutyl arnylori a. 32. The use of the cardioplegic solution according to claim 30, further characterized in that said amilopda-containing compound is dimethylene arnide. 33.- The use of the cardioplegic solution according to claim 30, further characterized in that said solution compresses from 5μn to 15μn of adenosm. 34. The use of the cardtographic solution according to claim 30, further characterized in that said solution comprises from 500 units to 1500 units of hepap na. 35.- The use of the cardioplegic solution according to claim 30, further characterized in that said solution comprises at least one antipoxant in an amount effective to inhibit the generation of oxygen-derived free radicals. 36.- The use of the cardioplegic solution comprising, per liter of solution: KCl 30 rnn CaCl2 1.75 inM KH2PO4 1.2 rnn MgSO * 1.2 mM NaHC03 25 rnM 11 mM Glucose Adenosine 10 μn EDTA 1. 0 rnn Dimeti l arni lóri da 1. 0 μn Heparin 1000 units Distilled, deionized water c.s to stop the heart function of a mammal, prior to its removal from a donor, in order to implant said heart in a mammal that requires such implantation. 37.- A method for the conservation, storage and reperfusion of organs that are intended to be transplanted, said method comprising: perfusing said organ with a solution comprising, per liter of the solution: (a) a balanced isotonic solution comprising ions of sodium, potassium, calcium, magnesium and bicarbonate in a physiologically acceptable amount; (b) from 0.7 n to 2.0 μM of adenosine; (c) from 1.0 μn to 5.0 μn of a compound containing aryllopda; and (d) water. 38.- The method of compliance with the claim 37, further characterized in that said arnilopda-containing compound is a compound selected from the group consisting of amylópda, hexarnetilen amilopda, dimetii amilopda, eti] isopropyl 1 aryuloride and rnethylbutyl arnilopda. 39. A method according to claim 37, further characterized in that said compound containing amylopda is annealed dirnetii. The method according to claim 37, further characterized in that said solution comprises at least one antioxidant in an amount effective to inhibit the generation of oxygen-derived free radicals. 41.- The method in accordance with the claim 37, further characterized in that said solution comprises from 100 μu / ml to 500 μ / n of insulin. 42. The method according to claim 37, further characterized in that said organ is a heart. 43. The method according to claim 37, further characterized in that it comprises preserving and storing said organ in a solution of from about 0 ° C to about 37 ° C. 44. The method according to claim 37, further characterized in that said temperature is from 15 ° C to 37 ° C. 45.- A method for the conservation, storage and per-fusion of an organ that is intended to be transplanted, said method comprising: perfusing said organ with a solution comprising, per liter of the solution: NaCl from 85 rnn to 145 rnn KC1 from 3.0 rnn to 8.0 rnn KH2 PO4 from 0.7 nm to 1.3 m MgSO .; from 0.9 rnM to 4.8 rnM NaHC? 3 from 15.0 rnM to 35 mM Glucose from 1.0 mM to 50 rnn EDTA from 0.5 rnM to 1.5 rnM Apoferptin from Iμg / L to 100 μg / L Catalase from Img / L to 10 mg / L Acid caprylic from 10 nM to 100 nM DMTU from 1 nM to 10 nM DPPD from InM to 10 nM Dirnetil arniloride from 1 μM to 5.0 μM Distilled water, desiomado cs 46. The method according to claim 45, further characterized in that said solution comprises from about 0.7 μM to about 2.0 μM of adenosm. 47. The method according to claim 45, further characterized in that said solution comprises at least one antioxidant in an amount effective to inhibit the generation of free radicals derived from oxygen. 48. The method according to claim 45, further characterized in that said organ is a heart. 49. The method according to claim 45, further characterized in that it comprises preserving and storing said organ in a solution of from about 0 ° C to about 37 ° C. 50.- The method according to claim 45, further characterized in that said temperature is from 15 ° C to 37 ° C. 51.- A method for the conservation, storage and perfusion of an organ that is intended to be transplanted, said method comprising: permeating said organ with a solution comprising, per liter of the solution: NaCl 118 ml KCl 4.7 M CaCl2 1.75 mn KH2P0 «1.2 rnn MgSO« 1.2 rnn NaHC03 25 inM Glucose 11 inM Adenosine 1.0 μM EDTA 1.0 mn Apoferritma 100 μg / l Catalase 10 μg / L Dmu? n nn DPPD 10 nM Cappolic acid 50 nn Dirnetii nylon 3.0 μn Insulin 200.0 μ units / rnl Distilled water, deionized cs 52.- A method for making a cardioplegic solution characterized p > or which comprises, per liter of solution: (a) formulating a balanced isotonic solution comprising sodium, potassium, calcium, magnesium and bicarbonate ions in a pharmaceutically acceptable amount; (b) incorporating - at least 0.5 μn of a compound containing arnyloride; and (c) adding water. 53.- A method for making a conservation solution for storing and reperfusing organs destined for transplantation, characterized in that it comprises, per liter of solution: (a) formulating a balanced isotonic solution comprising sodium, potassium, calcium, magnesium and bicarbonate ions in a pharmaceutically acceptable amount; (b) incorporating from 1.0 μM to 5.0 μM of a compound containing ilopda; and (c) adding water.