RESUMEN
BACKGROUND: We evaluated the effect of warm (37 degrees C) versus cold (4 degrees C) solutions as the initial flush for liver preservation from non-heart beating donors in rats. METHODS: An initial flush was performed just before donor hepatectomy with cold or warm University of Wisconsin solution (UW), UW without hydroxyethyl starch, sodium lactobionate sucrose solution, or lactated Ringer's solution as the control group. A separate group also used as control received no initial flushing. Liver transplantation was performed, and the graft function was determined by survival and assessment of enzyme release. The viscosity of each solution and the vascular resistance of the graft were measured. RESULTS: The 7-day survival rate was 83% and 100% in the warm and cold sodium lactobionate sucrose solution groups and 60% and 50% in the warm and cold lactated Ringer's solution groups, respectively. In the no-initial-flush group, rats did not survive. The 7-day survival rate was 67% and 0% in the warm and cold UW groups, respectively. Eliminating the hydroxyethyl starch from the cold UW improved the survival to 67%. Serum alanine aminotransferase levels 1 day after transplantation in the no-initial-flush and the cold UW groups were significantly higher than those of the remaining groups. At 4 degrees C the viscosity was higher in the UW (86.2 cp) compared to hydroxyethyl starch-free UW solution (30.9 cp), lactated Ringer's solution (24.5 cp), and sodium lactobionate sucrose solution (32.7 cp). The viscosity of UW at 37 degrees C was 34.7 cp. Vascular resistance correlated well with the viscosity. Livers flushed with solutions with a low viscosity showed lower vascular resistance than those flushed with cold UW and led to better survival. CONCLUSIONS: These data suggest that the viscosity of the initial flushing solution may play an important role in determining the outcome of organ procurement from non-heart beating donors.
Asunto(s)
Supervivencia de Injerto , Trasplante de Hígado/métodos , Hígado/efectos de los fármacos , Soluciones Preservantes de Órganos , Preservación de Órganos/métodos , Soluciones/farmacología , Temperatura , Viscosidad , Adenosina/farmacología , Alanina Transaminasa/sangre , Alopurinol/farmacología , Animales , Clorpromazina/farmacología , Disacáridos/farmacología , Glutatión/farmacología , Supervivencia de Injerto/efectos de los fármacos , Derivados de Hidroxietil Almidón/farmacología , Insulina/farmacología , Soluciones Isotónicas/farmacología , Ácido Láctico/farmacología , Hígado/patología , Trasplante de Hígado/mortalidad , Trasplante de Hígado/patología , Masculino , Rafinosa/farmacología , Ratas , Ratas Wistar , Solución de Ringer , Sacarosa/farmacología , Tasa de Supervivencia , Resistencia Vascular/efectos de los fármacosAsunto(s)
Trasplante de Corazón/fisiología , Corazón , Soluciones Preservantes de Órganos , Preservación de Órganos/instrumentación , Perfusión/instrumentación , Adenosina , Alopurinol , Bicarbonatos , Cloruro de Calcio , Soluciones Cardiopléjicas , Glutatión , Humanos , Insulina , Magnesio , Preservación de Órganos/métodos , Perfusión/métodos , Cloruro de Potasio , Rafinosa , Estudios Retrospectivos , Cloruro de SodioAsunto(s)
Paro Cardíaco Inducido , Corazón , Soluciones Preservantes de Órganos , Preservación de Órganos/métodos , Adenosina , Alopurinol , Animales , Bicarbonatos , Cloruro de Calcio , Gasto Cardíaco , Soluciones Cardiopléjicas , Glutatión , Corazón/fisiología , Insulina , Magnesio , Reperfusión Miocárdica , Cloruro de Potasio , Conejos , Rafinosa , Cloruro de Sodio , Factores de TiempoRESUMEN
Although cardioplegia is limited to 4 hours of ice storage, University of Wisconsin solution has successfully extended this period to approximately 12 hours. In this study we have substituted polyethylene glycol for hydroxyethyl starch in a simplified University of Wisconsin solution (Cardiosol). Rabbit hearts were ice stored for 24 hours at 0 degrees C in either University of Wisconsin solution or Cardiosol (containing either 5% or 10% polyethylene glycol). Fresh control hearts were tested immediately after cardiectomy. Function was evaluated in an in vitro working heart model for 1 hour with aortic afterload at 100 cm H2O. Total cardiac output or the proportion of hearts reaching 100 cm H2O were compared. Hearts stored in University of Wisconsin solution for 24 hours functioned at 6% of control levels at 15 minutes of observation. None reached 100 cm H2O or deteriorated further with time (p < 0.05). By contrast, hearts stored in 5% Cardiosol showed progressive recovery during the 1-hour observation. Of the 13 hearts, 11 reached 100 cm H2O with a mean cardiac output of 51% of the control value. Increasing the concentration of polyethylene glycol to 10% improved cardiac output at all observation times, reaching 80% of control heart performance at 1 hour (control > 10% > 5% > University of Wisconsin solution [p < 0.05]). We concluded that 10% polyethylene glycol significantly improved 24-hour ice storage and, hence, viability to a functional level that matched our previously reported microperfusion results.
Asunto(s)
Soluciones Cardiopléjicas/uso terapéutico , Criopreservación , Trasplante de Corazón/fisiología , Soluciones Preservantes de Órganos , Polietilenglicoles/uso terapéutico , Conservación de Tejido , Adenosina/administración & dosificación , Adenosina/uso terapéutico , Alopurinol/administración & dosificación , Alopurinol/uso terapéutico , Animales , Aorta/fisiología , Presión Sanguínea/fisiología , Gasto Cardíaco/fisiología , Soluciones Cardiopléjicas/administración & dosificación , Circulación Coronaria/fisiología , Glutatión/administración & dosificación , Glutatión/uso terapéutico , Derivados de Hidroxietil Almidón/uso terapéutico , Hielo , Insulina/administración & dosificación , Insulina/uso terapéutico , Modelos Cardiovasculares , Reperfusión Miocárdica , Polietilenglicoles/administración & dosificación , Conejos , Rafinosa/administración & dosificación , Rafinosa/uso terapéutico , Factores de TiempoRESUMEN
The use of polyethylene glycol (PEG) in preservation solutions has been associated with a decreased incidence of rejection in clinical and experimental organ transplantation. In this study, we examined the effect of PEG with different molecular configurations on rejection of small bowel allografts in the rat. Male ACI and LEW rats were used as donors and recipients, respectively. Orthotopic small bowel transplantation was performed using the following preservation solutions: lactated Ringer's solution (n = 7), University of Wisconsin solution (n = 7), University of Wisconsin solution without hydroxyethyl starch (sUW; n = 7), sUW with PEG20M (n = 9), sUW with PEG8000 (n = 6), and sUW with PEG20L (n = 7). No immunosuppression was given. In orthotopic small bowel transplantation, only groups with a high molecular weight PEG, PEG20M and PEG20L, demonstrated longer survival (P < 0.01 and P < 0.001, respectively) and delayed onset of unkempt appearance (P < 0.05 and P < 0.001, respectively). In heterotopic small bowel transplantation, sUW was compared with sUW with PEG20L. Rejection occurred later and its progression was slower in the sUW with PEG20L than in the sUW alone. Our observations suggest that the onset and progression of rejection after small bowel transplantation were influenced by the molecular weight and configuration of the PEG molecule. The mechanism is unclear, but high molecular weight PEG appears to reduce or change the immunogenicity of the small bowel allograft.
Asunto(s)
Rechazo de Injerto/prevención & control , Intestino Delgado/trasplante , Polietilenglicoles/farmacología , Animales , Intestino Delgado/inmunología , Masculino , Peso Molecular , Polietilenglicoles/química , Ratas , Ratas Endogámicas ACI , Ratas Endogámicas LewRESUMEN
This investigation was designed to examine the role of glutathione and other reduced sulfhydryl amines during reperfusion of the ischemic rabbit heart. To identify the biochemical features of reduced sulfhydryl amines contributing toward improved myocardial function, we investigated several chemical agents sharing a common property with glutathione (L-leucine, L-glycine, ascorbate, oxidized glutathione, L-cysteine). After a period of 24-hour hypothermic storage of the rabbit heart in a modified University of Wisconsin solution containing polyethylene glycol, the hearts were functionally evaluated on a Langendorff working heart model. The agents were then injected as a bolus (60 mumol/L) during reperfusion, and coronary flow and aortic output were measured. Control hearts were untreated. Reduced sulfhydryl amines (glutathione, L-cysteine) significantly improved coronary flow (p < 0.005) and cardiac output (p < 0.005). Ascorbate, L-leucine, L-glycine, and oxidized glutathione all failed to influence cardiac function.
Asunto(s)
Cardiotónicos/farmacología , Glutatión/farmacología , Corazón/efectos de los fármacos , Reperfusión Miocárdica , Preservación de Órganos , Animales , Aorta/fisiología , Ácido Ascórbico/farmacología , Gasto Cardíaco/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Criopreservación , Cisteína/farmacología , Glutatión/análogos & derivados , Disulfuro de Glutatión , Glicina/farmacología , Leucina/farmacología , Conejos , Volumen Sistólico/efectos de los fármacosAsunto(s)
Hígado , Soluciones Preservantes de Órganos , Preservación de Órganos/métodos , Adenosina , Alopurinol , Animales , Clorpromazina , Disacáridos , Glutatión , Insulina , Soluciones Isotónicas , Masculino , Rafinosa , Ratas , Ratas Wistar , Lactato de Ringer , Sacarosa , Factores de TiempoRESUMEN
A terminal rinse (TR) is standard practice in liver preservation with University of Wisconsin solution (UW) to avoid a potassium load. The fact that sodium lactobionate sucrose solution (SLS) is an effective organ preservation solution with a low potassium provided an opportunity to evaluate rat liver preservation without the TR step. Its importance was investigated in 122 rat liver preservation experiments. In study 1, UW and a hydroxyethyl starch-free, modified UW (UWm) were used for 20-hr liver preservation followed by either no TR or Ringer's lactate TR. The 1-week survival was: UW-TR, 2/14; UW-no TR, 1/6; UWm-TR, 0/6; UWm-no TR, 5/5 (P < 0.01). In study 2, livers were stored for 30 hr in SLS, UW, UWm, and UWm + chlorpromazine 5 mg/L, all without a TR. Nine of 11 rats survived 7 days after SLS, but there were no survivors in the other groups (P < 0.05). Study 3 compared no TR with TR with SLS, Ringer's lactate (RL), or a modified Carolina rinse (CRm) after 30-hr SLS preservation. Survival, serum aspartate aminotransferase and alanine aminotransferase, and histology were assessed. One-week survival of 9/11 rats in no TR was significantly better than in the other groups (3/14 in TR-SLS, 0/8 in TR-RL, and 0/14 in TR-CRm, P < 0.01). The values of aspartate aminotransferase (mean +/- SE) 3 hr after transplantation were 1862 +/- 439 U/L, 3334 +/- 817 U/L, 6591 +/- 1944 U/L, and 7028 +/- 1704 U/L, respectively, in no TR, TR-SLS, TR-RL, and TR-CRm. There were significant differences both in aspartate aminotransferase and alanine aminotransferase between no-TR and each of TR-RL and TR-CRm (P < 0.05). Liver specimens from rats killed 3 hr after OLT showed only mild injury in the no TR group and severe injury in the remaining groups. We conclude that a terminal rinse is harmful in rat liver preservation.
Asunto(s)
Hígado , Soluciones Preservantes de Órganos , Preservación de Órganos/métodos , Adenosina , Alopurinol , Animales , Clorpromazina , Disacáridos , Estudios de Evaluación como Asunto , Glutatión , Supervivencia de Injerto , Insulina , Hígado/lesiones , Hígado/patología , Hígado/fisiología , Trasplante de Hígado/patología , Trasplante de Hígado/fisiología , Masculino , Preservación de Órganos/efectos adversos , Rafinosa , Ratas , Ratas Wistar , SacarosaAsunto(s)
Supervivencia de Injerto , Trasplante de Riñón/fisiología , Soluciones Preservantes de Órganos , Preservación de Órganos/métodos , Adenosina , Adulto , Alopurinol , Animales , Cadáver , Clorpromazina , Creatinina/sangre , Disacáridos , Perros , Glutatión , Humanos , Soluciones Hipertónicas , Insulina , Trasplante de Riñón/patología , Necrosis Tubular Aguda/patología , Rafinosa , Soluciones , Sacarosa , Factores de Tiempo , Donantes de TejidosAsunto(s)
Gasto Cardíaco , Soluciones Cardiopléjicas , Endotelio Vascular/fisiología , Corazón/fisiología , Soluciones Preservantes de Órganos , Preservación de Órganos , Soluciones , Adenosina , Alopurinol , Animales , Endotelio Vascular/patología , Glucosa , Glutatión , Insulina , Manitol , Contracción Miocárdica , Cloruro de Potasio , Procaína , Conejos , RafinosaAsunto(s)
Inmunosupresores/farmacología , Trasplante de Hígado/inmunología , Soluciones Preservantes de Órganos , Polietilenglicoles/farmacología , Adenosina , Alopurinol , Animales , Glutatión , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Insulina , Masculino , Preservación de Órganos/métodos , Rafinosa , Ratas , Ratas Endogámicas ACI , Ratas Endogámicas Lew , Soluciones/farmacologíaRESUMEN
In 1969 we described a method for kidney preservation that used a brief flush with a new "intracellular" solution followed by ice storage. This paper stimulated research into optimizing solution composition culminating in the UW solution which is now the accepted standard. Further developments in the design of solutions for hypothermic organ preservation have proceeded along several paths, including: (1) modification and simplification of UW solution, (2) investigation of organ specific requirements, (3) addition of pharmacologic agents particularly calcium antagonists to flush solutions, (4) the concept of "microperfusion" for control of acidosis, (5) the use of solutions containing polyethylene glycol, and (6) the use of a terminal rinse solution. Broadly speaking, the results of these studies have shown that it is possible to improve upon the UW solution by simplification, eliminating several of the components, and that sodium variants, and pharmacological additives, such as chlorpromazine, may yield better results in experimental and clinical trials. It has also been found that there are special requirements for individual organs, rendering the concept of a universal solution unlikely. Of the promising new ideas, microperfusion and polyethylene glycol have been found to be very effective for heart preservation yielding for the first time virtually perfect 24-hour preservation. The concept of a terminal rinse to diminish reperfusion injury has strong experimental support and awaits clinical evaluation.
Asunto(s)
Soluciones Preservantes de Órganos , Preservación de Órganos , Adenosina , Adulto , Anciano , Alopurinol , Animales , Glutatión , Humanos , Insulina , Persona de Mediana Edad , Perfusión , Polietilenglicoles , Rafinosa , SolucionesAsunto(s)
Rechazo de Injerto , Intestino Delgado/trasplante , Soluciones Preservantes de Órganos , Polietilenglicoles , Soluciones , Trasplante Homólogo/inmunología , Adenosina , Alopurinol , Animales , Glutatión , Insulina , Preservación de Órganos/métodos , Rafinosa , Ratas , Ratas Endogámicas ACI , Ratas Endogámicas LewRESUMEN
The effects of the calcium antagonists, chlorpromazine (CPZ), nisoldipine (NIS), trifluoperazine (TFP), and nicardipine (NIC) were compared in rat livers following either 20- or 30-hr ice storage in sodium lactobionate sucrose solution (SLS). Survivals beyond 7 days after orthotopic liver transplantation following 20-hr cold storage were 1/14 in the University of Wisconsin solution, 4/14 in SLS, 4/8 in UW+CPZ, 7/8 in SLS+CPZ. Survivals beyond 7 days after OLT following 30-hr cold storage were 3/8 in SLS+CPZ, 3/8 in SLS+NIS, 2/8 in SLS+TFP, 0/8 in SLS+NIC, and 0/8 in SLS alone. Survival rates were significantly (P less than 0.05) better in both SLS+CPZ and SLS+NIS than in UW and SLS alone. The effluent lactate dehydrogenase (LDH) levels and pH changes were measured at the time of OLT. After 20 hr, LDH levels were 525 +/- 78 IU/L (mean +/- SEM) in UW, 492 +/- 44 in SLS, 322 +/- 35 in UW+CPZ, and 290 +/- 39 in SLS+CPZ. After 30 hr, LDH values were 416 +/- 40 in SLS+CPZ, 450 +/- 25 in SLS+NIS, 448 +/- 21 in SLS+TFP, 573 +/- 18 in SLS+NIC, and 614 +/- 68 in SLS. The LDH levels for SLS+CPZ and SLS+NIS were significantly lower than those of SLS and UW (P less than 0.01). The pH changes in the effluent were significantly less in both the CPZ and NIS groups (P less than 0.01). This study demonstrated improved liver preservation by the use of a simplified colloid-free lactobionate solution containing sodium as the principal cation. The addition of CPZ or NIS to the solution demonstrated the same potency for significant improvement in efficacy of this solution, while NIC was ineffective.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Disacáridos/farmacología , Trasplante de Hígado , Soluciones Preservantes de Órganos , Preservación de Órganos/métodos , Sacarosa/farmacología , Adenosina , Alopurinol , Animales , Calcio/metabolismo , Clorpromazina/farmacología , Glutatión , Insulina , Masculino , Rafinosa , Ratas , Ratas Endogámicas , Soluciones , Trifluoperazina/farmacologíaRESUMEN
We investigated the effect of the addition of chlorpromazine to a new, simplified organ preservation solution, sodium lactobionate sucrose (SLS), for 20-hour hypothermic rat liver preservation. Survival beyond 7 days after orthotopic transplantation of the stored liver was eight of eight rats in control groups (immediate transplantation, less than 1-hour preservation), one of 14 rats with the University of Wisconsin (UW) solution, four of 14 rats with SLS, seven of eight rats with SLS + chlorpromazine, 1 mg/L, and seven of eight rats with SLS + chlorpromazine, 10 mg/L. The differences is survival between UW and SLS and between SLS and SLS + chlorpromazine were significant (p less than 0.05). Lactic dehydrogenase levels in the effluent after reflushing through the portal vein at the time of transplantation were 145 +/- 20 IU/L (mean +/- SEM) in the controls, 525 +/- 78 IU/L in UW, 492 +/- 44 IU/L in SLS, 290 +/- 39 IU/L in SLS + chlorpromazine, 1 mg/L, 290 +/- 11 IU/L in SLS + chlorpromazine, 10 mg/L. The values for the SLS + chlorpromazine were significantly lower than for SLS and UW (p less than 0.05). The pH of the effluent was 7.10 +/- 0.10 in controls, 6.42 +/- 0.12 in UW, 6.64 +/- 0.18 in SLS, and 7.07 +/- 0.02 in SLS + chlorpromazine, 1 mg/L and 10 mg/L. The pH drop was significantly greater in the groups without chlorpromazine (p less than 0.01). This study shows that superior rat liver preservation was achieved with a simplified lactobionate solution containing sodium as the principal cation, sucrose in place of raffinose, and omitting the colloid and several of the other UW components. The addition of low concentrations of chlorpromazine further enhanced the effectiveness of this solution, without the need for donor pretreatment.