Michael P Kaye

A new concept for successful long-term pulmonary preservation in a dog model.

We developed a dextran-glucose-based extracellular perfusion solution (DGX) that supports limited aerobic metabolism to maintain cellular integrity of an inflated donor lung during long-term ischemia and a storage temperature of 10°C. In a dog model, we compared respiratory and hemodynamic function of or-thotopically transplanted left lungs preserved using this method (DGX, group I, n=6) with function of those preserved with EuroCollins solution (EC) stored at a temperature of 4°C (group II, n=6). All lungs were inflated with room air and stored for 12 hr. Pulmonary function was monitored for 5 hr of reperfusion. Values expressed below are group means with standard deviation. Statistical significance was calculated using a two-tailed t test. For PO2 (mmHg) (FiO2 = 0.4), group I (EC): control = 193±8, 30 min p.o. = 87±20*, 300 min p.o. = 174±13*; and group II (DGX): control = 217±28, 30 min p.o. = 184±46*, 300 min p.o. = 248±5*. For pulmonary vascular resistance (dynes), group I: control = 389±22, 30 min p.o. = 1209±301, 300 min p.o. = 1025±204*; and group II: control = 401 ±31, 30 min p.o. = 522±129, 300 min p.o. = 458±137* (*P<0.05 DGX vs. EC). Gas analysis performed on air samples taken from the ischemic donor lung immediately after harvest and after 12-hr storage showed (calculated as group means) a significant decrease of PO2 and a significant increase of PCO2, respectively. Histology of the lungs after 5 hr of reperfusion showed essentially normal-appearing lungs in the DGX group, whereas lungs in the EC group showed thickening of the intra-alveolar septi, marked cellular infiltration, and accumulation of protein-like material in the alveoli. In this study, preservation wih DGX resulted in satisfactory respiratory and hemodynamic function of the transplanted lung even after 12 hr of ischemia. It does not cause an increase of pulmonary vascular resistance as seen after preservation with EC. Data from the intrabronchial air analysis of the donor lung suggest that aerobic metabolism continues even under preservation conditions.

Relação entre tempo de isquemia e performance pós-operatória no transplante cardíaco

A presente dificuldade na obtencao de doadores adequados para o transplante cardiaco obriga a necessidade da utilizacao de orgaos removidos a distância, prolongando, assim, o tempo de isquemia total (TIT). Os efeitos do TIT sobre a funcao cardiaca no pos-operatorio imediato e a necessidade de agentes inotropicos ainda sao controversos, devendo os limites de seguranca serem determinados. As manifestacoes do TIT no indice cardiaco, durante os primeiros tres dias pos transplante cardiaco ortotopico (I/C 1-3), o periodo total do suporte inotropico (SIT), a dose total/kg de dopamina e dobutamina (D + D/kg), a necessidade inotropica maxima e picos dos niveis de CPK-MB (CPK-MB) foram medidos em 96 receptores de transplante cardiaco, na Universidade de Minnesota, para determinar a relacao destas variaveis com o TIT. O TIT variou entre 61 e 288 minutos (media 171,7, D.P. 51,9). A populacao foi dividida entre grupos representando intervalos de 30 minutos. Embora os niveis de CPK-MB fossem inferiores nos grupos de TIT menores, nao houve diferenca nos parâmetros de funcao cardiaca, tempo de suporte e necessidade inotropica. Concluimos que tempos de isquemia ate cinco horas sao bem tolerados e que outros fatores, como funcao cardiaca do doador previamente a remocao do orgao, ou possivel dano isquemico durante a remocao, sao mais importantes na determinacao da performance pos-operatoria imediata.

Canine Double-Lung Allotransplantation: Operative Technique and Results for 12-h Preservation Studies

A canine double-lung allotransplantation model was developed to study the effects of 12-h static pulmonary preservation. This model has not been used extensively for such experiments but allows a detailed evaluation of the quality of preservation. An operative technique is described in which cautery dissection and preliminary devascularization of the recipient right lung allows the period of cardiopulmonary bypass to be limited and reduces postoperative bleeding. Six double-lung blocks were successfully orthotopically transplanted and recipient animals were studied for 12 h postoperatively. All animals survived the study period and had a mean PO2 (FIO2 0.4) of 141 mm Hg, 12 h following reimplantation suggesting adequate pulmonary preservation. There was no evidence of pulmonary edema at any time following implantation, although airway pressures and pulmonary vascular resistance were elevated. The role of this model in lung preservation studies is discussed.

A desferoxamina e seu efeito protetor na preservação pulmonar

Ha recentes evidencias de que radicais livres derivados do oxigenio estao envolvidos na lesao tecidual decorrente de isquemia e subsequente reperfusao. A desferoxamina (DF), evitando a producao de radicais hidroxila e eliminando o ânion superoxido, pode atenuar este dano, sendo seus efeitos aqui avaliados apos quatro horas de preservacao pulmonar hipotermica. O auto-transplante pulmonar esquerdo foi realizado em 12 caes mesticos. O pulmao foi, inicialmente, perfurado com 1000 ml de solucao de Collins modificada e mantido insuflado, colocado sob refrigeracao (4 graus Celsius) em solucao salina durante quatro horas. Seis caes receberam 500 mg de DF administrados E.V. durante o periodo isquemico e imediatamente apos iniciar a reperfusao. Apos reimplante e ligadura da arteria pulmonar direita, os animais foram mantidos numa FiO(2) fixa (49 por cento) e monitorizados por quatro horas. Durante a primeira hora pos-reperfusao, o pO(2) arterial foi sifnificativamente superior no grupo tratado com DF (p

Transplantes cardiopulmonar e pulmonar com doador em localidade distante

In special situations, clinical heart-lung and lung transplantation are today established methods of therapy for end stage cardiopulmonary and pulmonary disease. Adequate donor availability remains a major problem and distant organ procurement is today a necessity. Although many methods of lung preservation can be used, for periods of up to 5 hours, hypothermic storage with cardioplegic arrest and pulmonary artery flush with modified Collins solution has proven to be a simple and reliable method of heart-lung preservation. We here describe our current method of heart-lung block protection, in which heart-lung and double lung transplantation were performed followed by excelent cardiac and pulmonary function.