A study on optimal temperature for isolated lung preservation

doi:10.1016/0003-4975(92)90766-W

The Annals of Thoracic Surgery

Volume 53, Issue 1, January 1992, Pages 101-108

https://doi.org/10.1016/0003-4975(92)90766-W Get rights and content

Abstract

Fifty-two heart-lung blocks (grafts) of New Zealand white rabbits were used for determining optimal temperature in lung preservation. Grafts were inflated with room air and preserved by simple surface cooling at arbitrarily determined temperatures for 18 hours. Graft function was assessed by nonrecirculated perfusion with autologous blood. Segmented regression models between functional parameters and preservation temperature (T) were applied for determining optimal temperature. Graft ability was also assessed from the point of view of pulmonary circulation by indocyanine green dilution rate of effluent and histological distribution of carbon particles. Significant segmented regression curves and lines between parameters of effluent oxygen tension (PO₂) and wet-dry weight ratio (W/D), and T were obtained as follows: PO₂ = 150/(1 + 3208.1[e^−1.17T]), p < 0.01; PO₂ = −13.8T + 222.6, p < 0.05; W/D = 5.0 + 1.5/(1 + 0,0028[e^0.94T]), p < 0.01; W/D = 0.075T + 4.52, p < 0.05. Optimal temperature for lung preservation by topical cooling was calculated as 8 ° to 9 ° C from each intersecting point of regression equations. Analysis of regression curves suggested that the most common hypothermic ischemic injury during preservation by topical cooling is pulmonary vascular obstruction, which might be induced at temperatures lower than the critical temperature of 6 ° to 7 ° C. Indocyanine green dilution rate and histological findings supported the results of graft functional parameters.

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Cited by (17)

Lungs Preserved on Ice or in a Refrigerator? Prolonged Static Lung Storage at 10 °C
2023, Annals of Thoracic Surgery
Overcoming the Limits of Lung Transplantation: 10 °C Static Cold Preservation
2023, Archivos de Bronconeumologia
Evaluation of 10°C as the optimal storage temperature for aspiration-injured donor lungs in a large animal transplant model
2022, Journal of Heart and Lung Transplantation
Citation Excerpt :
During 10°C storage, metabolomic analysis showed that the lungs were actively metabolizing cytoprotective molecules during the 12-hour period, while lungs stored at 4°C had minimal changes in metabolic changes occurring. Results of our study also showed that injured lungs stored at 10°C for a 12-hour period had superior physiologic performance post-transplantation in comparison to lungs stored using the current standard methods which is consistent with previously published literature examining 10°C lung preservation for the storage of healthy lungs.9,21–23 Post-transplant lung tissue also showed reduced histological damage and had lower concentrations of the potent inflammatory mediator IL-1β.
Our recent work has challenged 4°C as an optimal lung preservation temperature by showing storage at 10°C to allow for the extension of preservation periods. Despite these findings, the impact of 10°C storage has not been evaluated in the setting of injured donor lungs.
Aspiration injury was created through bronchoscopic delivery of gastric juice (pH: 1.8). Injured donor lungs (n = 5/group) were then procured and blindly randomized to storage at 4°C (on ice) or at 10°C (in a thermoelectric cooler) for 12 hours. A third group included immediate transplantation. A left lung transplant was performed thereafter followed by 4 hours of graft evaluation.
After transplantation, lungs stored at 10°C showed significantly better oxygenation when compared to 4°C group (343 ± 43 mm Hg vs 128 ± 76 mm Hg, p = 0.03). Active metabolism occurred during the 12 hours storage period at 10°C, producing cytoprotective metabolites within the graft. When compared to lungs undergoing immediate transplant, lungs preserved at 10°C tended to have lower peak airway pressures (p = 0.15) and higher dynamic lung compliances (p = 0.09). Circulating cell-free mitochondrial DNA within the recipient plasma was significantly lower for lungs stored at 10°C in comparison to those underwent immediate transplant (p = 0.048), alongside a tendency of lower levels of tissue apoptotic cell death (p = 0.075).
We demonstrate 10°C as a potentially superior storage temperature for injured donor lungs in a pig model when compared to the current clinical standard (4°C) and immediate transplantation. Continuing protective metabolism at 10°C for donor lungs may result in better transplant outcomes.
Commentary: Long-distance relationships work well in lung transplantation
2021, Journal of Thoracic and Cardiovascular Surgery
Combined use of prostacyclin and higher perfusate temperatures further enhances the superior lung preservation by Celsior solution in the isolated rat lung
1999, Journal of Heart and Lung Transplantation
Background: The poor tolerance of the lung to ischemia and reperfusion (IR) still represents one of the limitations in clinically successful lung transplantation. Modified Euro-Collins (EC) is routinely used in lung preservation, but alternative solutions have been developed for improvement of pulmonary preservation. Celsior is an extracellular solution that has significantly reduced the IR-induced pulmonary damage in animal studies. So far, no extensive experimental studies exist concerning the influence of Celsior on pulmonary gas exchange following IR.
In an extracorporeal rat lung model 10 lungs, each, were preserved with Celsior (CE) and Celsior/prostacyclin (CEPC, 6 μg/100 ml) at 4° and 15°C, each, and compared to low-potassium Euro-Collins (EC-40, 40 mmol/liter potassium). After 2 hours of ischemia lungs were reventilated and reperfused using a roller pump. Oxygenation in terms of oxygen partial tension in the left atrial effluent, pulmonary vascular resistance (PVR), peak inspiratory pressure, and wet/dry ratio were monitored for 50 minutes. Furthermore, edema formation was evaluated by light microscopy. Statistical analysis was performed using ANOVA models.
Compared to the EC-40 group, oxygenation was increased and amount of edema was reduced in most Celsior-preserved organs (p < 0.032) with exception of the CEPC group at 4°C (p = 0.06). Additional application of prostacyclin did not have any significant effect on oxygenation in the Celsior group. However, after temperature elevation of the CEPC perfusate to 15°C, a superior partial tension of oxygen was observed (p < 0.023) in contrast to the 4°C groups CE and CEPC. The lowest PVR was found in the CE 4°C group (p < 0.02).
Celsior provides better lung preservation than EC-40 solution. Application of prostacyclin at higher perfusate temperatures results in additional functional improvement. In vivo experiments and ultrastructural analysis are warranted for further evaluation of Celsior in lung preservation.
External cooling of warm ischemic rabbit lungs after death
1996, Annals of Thoracic Surgery
If lungs could be retrieved for transplantation after circulatory arrest, the shortage of donors might be significantly alleviated. However, in such nonheart-beating donors, there is great concern that even a short period of warm ischemia will be deleterious for lung tissue, jeopardizing the transplant recipient. It was the purpose of this study to look for the efficacy of different methods of lung cooling inside a cadaver after circulatory arrest.
New Zealand white rabbits were sacrificed with an intravenous overdose of pentobarbital and left at room temperature. Subcutaneous, rectal, lung core, lung surface, and endobronchial temperatures were measured at intervals after death. Cooling of the lung during ischemia differed between groups (n = 6 in each group): lungs left deflated at room temperature (24°C) (group 1 = control non-heart-beating donors), lungs ventilated with cooled (4°C) room air (group 2), lungs left deflated plus topical cooling (1°C) of both the cadaver and its lungs (group 3), and lungs flushed in situ immediately after circulatory arrest with a cold (4°C) crystalloid solution followed by ex vivo deflated storage in cold (1°C) saline solution (group 4 = control heart-beating donors).
There was a slow decline in lung core, lung surface, and endobronchial temperatures toward room temperature in group 1 (1.5° ± 0.0°C/h, 1.8° ± 0.2°C/h, and 1.9° ± 0.1°C/h, respectively). In contrast, all three lung temperatures immediately (<5 minutes) dropped to less than 10°C in group 4. Hypothermic ventilation (group 2) decreased endobronchial temperature (p < 0.05 at 30 minutes) but not lung surface, rectal, or subcutaneous temperature when compared with group 1. Cooling rate for lung surface and endobronchial temperatures during the first 4 hours after death was faster (p < 0.01) in group 3 (6.6° ± 0.3°C/h and 6.1° ± 0.⇌gC/h, respectively) when compared with group 2 (2.5° ± 0.3°C/h and 3.9° ± 0.1°C/h, respectively), but slower (p < 0.001) when compared with group 4 (9.2° ± 0.1°C/h and 8.7° ± 0.1°C/h, respectively).
These data demonstrate that in the non-heart-beating donor, (1) in situ cold flush will result in immediate cooling of the lung, (2) ventilation with cooled air will only accelerate the decline in endobronchial temperature but has no effect on lung surface temperature, and (3) topical cooling of the cadaver is more efficacious in decreasing lung temperature than hypothermic ventilation.

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Original articleA study on optimal temperature for isolated lung preservation

Abstract

Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Unilateral lung transplantation for pulmonary fibrosis

N Engl J Med

Lung transplantation

Curr Probl Surg

Technique of clinical double-lung transplantation

J Heart Transplant

Preservation of the lung. Comparison of topical cooling and cold crystalloid pulmonary perfusion

J Thorac Cardiovasc Surg

Successful 4-hour hypothermic lung storage with Euro-Collins solution: a simplified model assessing preservation

Heart Transplant

The measurement of edema in heartlung preparation

Am J Physiol

Nomograms for correction of blood PO2, PCO2, pH and base excess for time and temperature

J Appl Physiol

Original article
A study on optimal temperature for isolated lung preservation

Nomograms for correction of blood PO₂, PCO₂, pH and base excess for time and temperature