Prone Positioning Attenuates Lung Injury During Warm Ischemia in a Large Animal Controlled Donation after Cardiac Death Model

Background Prone ventilation redistributes lung inflation along the gravitational axis; however, localized, nongravitational effects of body position are less well characterized. The authors hypothesize that positional inflation improvements follow both gravitational and nongravitational distributions. This study is a nonoverlapping reanalysis of previously published large animal data. Methods Five intubated, mechanically ventilated pigs were imaged before and after lung injury by tracheal injection of hydrochloric acid (2 ml/kg). Computed tomography scans were performed at 5 and 10 cm H2O positive end-expiratory pressure (PEEP) in both prone and supine positions. All paired prone–supine images were digitally aligned to each other. Each unit of lung tissue was assigned to three clusters (K-means) according to positional changes of its density and dimensions. The regional cluster distribution was analyzed. Units of tissue displaying lung recruitment were mapped. Results We characterized three tissue clusters on computed tomography: deflation (increased tissue density and contraction), limited response (stable density and volume), and reinflation (decreased density and expansion). The respective clusters occupied (mean ± SD including all studied conditions) 29.3 ± 12.9%, 47.6 ± 11.4%, and 23.1 ± 8.3% of total lung mass, with similar distributions before and after lung injury. Reinflation was slightly greater at higher PEEP after injury. Larger proportions of the reinflation cluster were contained in the dorsal versus ventral (86.4 ± 8.5% vs. 13.6 ± 8.5%, P < 0.001) and in the caudal versus cranial (63.4 ± 11.2% vs. 36.6 ± 11.2%, P < 0.001) regions of the lung. After injury, prone positioning recruited 64.5 ± 36.7 g of tissue (11.4 ± 6.7% of total lung mass) at lower PEEP, and 49.9 ± 12.9 g (8.9 ± 2.8% of total mass) at higher PEEP; more than 59.0% of this recruitment was caudal. Conclusions During mechanical ventilation, lung reinflation and recruitment by the prone positioning were primarily localized in the dorso-caudal lung. The local effects of positioning in this lung region may determine its clinical efficacy. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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Prolonged Warm Ischemia Prevents Lung Allograft Acceptance in Lung Transplantation from Donation after Cardiac Death in the Mouse

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2016.01.396 ◽

2016 ◽

Vol 35 (4) ◽

pp. S143-S144

Author(s):

Y. Hirano ◽

S. Sugimoto ◽

T. Kurosaki ◽

S. Otani ◽

K. Miyoshi ◽

...

Keyword(s):

Lung Transplantation ◽

Cardiac Death ◽

Warm Ischemia ◽

Donation After Cardiac Death

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Prolonged warm ischemia time leads to severe renal dysfunction of donation-after-cardiac death kidney grafts

Scientific Reports ◽

10.1038/s41598-021-97078-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Peter Urbanellis ◽

Laura Mazilescu ◽

Dagmar Kollmann ◽

Ivan Linares-Cervantes ◽

J. Moritz Kaths ◽

...

Keyword(s):

Renal Function ◽

Serum Creatinine ◽

Renal Dysfunction ◽

Serum Potassium ◽

Urine Output ◽

Cardiac Death ◽

Elevated Serum ◽

Graft Function ◽

Donation After Cardiac Death ◽

Large Animal

AbstractKidney transplantation with grafts procured after donation-after-cardiac death (DCD) has led to an increase in incidence of delayed graft function (DGF). It is thought that the warm ischemic (WI) insult encountered during DCD procurement is the cause of this finding, although few studies have been designed to definitely demonstrate this causation in a transplantation setting. Here, we use a large animal renal transplantation model to study the effects of prolonged WI during procurement on post-transplantation renal function. Kidneys from 30 kg-Yorkshire pigs were procured following increasing WI times of 0 min (Heart-Beating Donor), 30 min, 60 min, 90 min, and 120 min (n = 3–6 per group) to mimic DCD. Following 8 h of static cold storage and autotransplantation, animals were followed for 7-days. Significant renal dysfunction (SRD), resembling clinical DGF, was defined as the development of oliguria < 500 mL in 24 h from POD3-4 along with POD4 serum potassium > 6.0 mmol/L. Increasing WI times resulted in incremental elevation of post-operative serum creatinine that peaked later. DCD120min grafts had the highest and latest elevation of serum creatinine compared to all groups (POD5: 19.0 ± 1.1 mg/dL, p < 0.05). All surviving animals in this group had POD4 24 h urine output < 500 cc (mean 235 ± 172 mL) and elevated serum potassium (7.2 ± 1.1 mmol/L). Only animals in the DCD120min group fulfilled our criteria of SRD (p = 0.003), and their renal function improved by POD7 with 24 h urine output > 500 mL and POD7 serum potassium < 6.0 mmol/L distinguishing this state from primary non-function. In a transplantation survival model, this work demonstrates that prolonging WI time similar to that which occurs in DCD conditions contributes to the development of SRD that resembles clinical DGF.

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