Characterization of the withdrawal phase in a swine controlled intestinal donation after circulatory death model

Abstract

Purpose: Transplantation of donation after cardiac death (DCD) intestine has higher rates of organ failure and complications. Fortunately, this is less grievous in a subclass of DCD called controlled (CDCD), those with irreversible but incomplete brain injury. The aim of the paper is to establish a CDCD porcine model which is closely mimicking human CDCD scenario, and investigate the physiologic changes from withdrawal of ventilatory support to circulatory arrest. Method: Ten domestic crossbred pigs were anesthetized and ventilated with room air. Once all baseline data was taken, atracurium besilate (0.9 mg/kg, 3×ED95) was administered and the ventilator was discontinued while the animal was under deep anesthesia to establish the porcine CDCD model. Meanwhile, heparin (150~200 U/kg) was administered after discontinuation of the ventilator. The time to death and the changes of arterial blood gases and hemodynamic parameters were monitored every 5 minutes until circulatory arrest. In addition, histopathology, ultrastructures (via electron microscope) and expression of tight junction proteins of intestinal mucosa were observed at the baseline and the time of death. Result: The mean time to death was approximately (21.8±3.12 min. Within 5 minutes of removal of the ventilator, there was a hyperdynamic period. Systolic blood pressure and heart rate quickly increased to 118.5±10.4 mmHg and 108.2±4.94 bpm, respectively. Blood pressure and heart rate then reduced rapidly until circulatory arrest. Moreover, the PaO2 quickly dropped to 17.4±3.13 mmHg, the blood gases throughout the apneic time showed a rapid hypercapnia and acidosis. In addition, warm ischemia damaged intestinal mucosa and reduced TJ proteins expression. Conclusion: A new swine CDCD model, simulating three stages of “withdrawal of ventilation, systemic anticoagulation and determination of death”, which closely mimics the human DCD scenario and can thus be used in studies related to organ transplantation, was successfully established.

Does DCD Donor Time-to-Death Affect Recipient Outcomes? Implications of Time-to-Death at a High-Volume Center in the United States

“…One possible mechanism for this may be that, unlike brain death, organ damage during circulatory arrest is mediated by inflammatory changes (e.g. cytokines and damage‐associated molecular patterns), acidosis, and hypoxia affecting the graft prior to recovery, all processes that may take place in the peri‐withdrawal period .…”

Physiologic Changes in the Heart Following Cessation of Mechanical Ventilation in a Porcine Model of Donation After Circulatory Death: Implications for Cardiac Transplantation

“…Following WLST, the donor heart is forced to function in an increasingly hypoxic environment while attempting to maintain systemic oxygen delivery. Previous studies have suggested that this process is associated with a catecholamine‐mediated period of hyperdynamic circulation and ventricular distention that may exacerbate the severity of injury suffered by DCD hearts ; however, a systematic description of the physiologic response to WLST in the donor heart has not been previously reported. A greater understanding of this process may inform the creation of resuscitation protocols tailored specifically to the DCD heart and evaluation strategies that identify organs suitable for transplantation.…”

Intestinal Conditioning After Cardiac Arrest: The Use of Normothermic Extracorporeal Membrane Oxygenation in the Non‐Heart‐Beating Animal Model

“…CA was produced by intravenous injection of atracurium besilate (0.9 mg/kg, 3 × ED95, HR Co. Ltd, Jiangsu, China) and discontinuing both propofol and mechanical ventilation as previously described . The time of circulatory arrest was determined when a pulse pressure of zero, determined by arterial line, was observed after a 5‐min “no‐touch” period.…”