Hypothermic ex vivo perfusion (HEVP) is a novel preservation alternative to cold static storage (CSS) of donor hearts for transplantation (HTx). Unlike CSS, HEVP may safely extend donor heart preservation time without the penalty of primary graft dysfunction. We sought to determine the impact of increasing preservation time on post-HTx cardiac injury, contractility, mitochondrial function following donor heart preservation by CSS (2 hrs) or HEVP (2 and 8 hrs).
Purpose Cold static storage (CSS) is the standard method for heart preservation during transplantation (HTx). However, CSS beyond 4 hours increases the risk of primary graft dysfunction (PGD). Hypothermic ex vivo perfusion (HEVP) of donor hearts allows oxygen delivery during preservation, and may facilitate extended donor preservation without increasing PGD risk. We compared post-HTx survival, systemic inflammation and cardiac function following donor heart preservation by CSS (2 hrs) versus HEVP (2 and 8 hrs). Methods Brain death was induced in donor sheep for 24 hrs. Donor hearts were preserved by a) CSS for 2 hrs (n=7), b) HEVP for 2 hrs (n=4), or c) HEVP for 8 hrs (n=4). Orthotopic HTx was performed in matched recipients. Recipients were weaned from cardiopulmonary bypass and monitored for 6 hrs. Recipient blood was collected and assayed for inflammatory cytokines and cardiac markers. Cardiac function was assessed by echocardiography. Results Six-hour survival was 71% following CSS, and 100% following 2 and 8 hrs HEVP, respectively. Recipients systemic interleukin-6 and 8 levels were reduced using HEVP vs CSS. Post-HTx haemodynamic function was no different between groups, but HEVP reduced the requirement for vasoactive support compared to CSS (2 hrs CSS: 1.57±0.7; 2 hrs HEVP: 0.35±0.09; 8 hrs HEVP: 0.35±0.05 mmHg−1). HEVP was associated with reduced post-HTx lactate (2 hrs CSS: 11.4±1.8; 2 hrs HEVP: 5.2±0.7; 8 hrs HEVP: 6.7±1.3 mmol/L), more stable base excess and physiological pH in blood. Post-HTx cardiac function was no different between groups. Cardiac troponin I levels were comparable between CSS vs. 8 hrs HEVP, but reduced with 2 hrs HEVP. Conclusion Preliminary data on donor heart preservation by HEVP shows promising outcomes in comparison to CSS. Heart preservation by HEVP can be extended up to 8 hours, without compromising post-HTx recipient survival. HEVP may assist in overcoming limitations in preservation time associated with HTx, without increasing PGD risk.
We aimed to evaluate cardiac function by trans-epicardial echocardiography in a pioneering ovine model of severe cardiopulmonary failure (CPF). Six healthy female sheep (weight 61±6.5 kg) were anesthetized, tracheally intubated and mechanically ventilated. An arterial catheter was placed for blood sampling and pressure monitoring. Left femoral artery and right jugular vein were cannulated and veno-arterial extracorporeal membrane oxygenation support commenced at a rate of 1.57±0.60 L/min. A left mini-thoracotomy was performed to access the pericardial sac. Heart failure was developed through intra-myocardial ethanol injections in the left ventricle. Ventilatory support was substantially decreased to concomitantly develop pulmonary failure. Cardiac function pre and post-development of CPF was evaluated by trans-epicardial echocardiography (Philips IE-33, North Ryde, Australia) and analysed by dedicated software (TOMTEC Imaging Systems GmbH, Germany). CPF caused a drop in mean arterial pressure and oxygenation, which resulted in an upsurge of lactate. Corresponding with a drop of mean arterial pressure, LV systolic function including left ventricular (LV) fractional area change, global circumferential strain and global radial strain also significantly decreased. In an innovative animal model of CPF, epicardial echocardiography is a reliable and feasible mean to follow-up dynamics of cardiac dysfunction.
In heart transplantation (HTx), cold static storage (CSS) is the standard method used to preserve donor hearts. However, CSS beyond 4 hours increases the risk of primary graft dysfunction (PGD) in the recipient. Hypothermic ex vivo perfusion (HEVP) of donor hearts allows continued oxygen delivery during heart preservation and may thus facilitate extended donor heart preservation without increasing the risk of PGD. We sought to compare cardiac function post-transplant following donor heart preservation using CSS versus HEVP.
BD appears to trigger cardiac mitochondrial uncoupling. This may be a protective mechanism against higher amino-acid utilisation and glucose accumulation, in order to maintain adequate mitochondrial function for cell survival. HTx following CSS, particularly from BD donors, induces significant mitochondrial dysfunction, which occurs in response to upstream metabolic impairments. Strategies that improve cardiac mitochondrial function or metabolism (eg. HEVP) may assist to improve HTx outcomes.
Hypothermic ex vivo perfusion (HEVP) of donor hearts for transplantation (HTx) may provide superior preservation to cold static storage (CSS). Extended donor heart ischemic time increases the risk of primary graft dysfunction and decreases patient survival. We examined post-HTx survival, systemic inflammation and cardiac function following donor heart preservation by HEVP.
Aim: Extended life plasma (ELP) is fresh frozen plasma (FFP) that has been thawed and intended for extended storage at 2-6 C beyond 24 hours and up to 5 days (120 hours). This extended shelf life provides an opportunity to reduce wastage, given that there is more time to utilise the product before expiry; as well as provide the product promptly for patients in emergency or retrieval settings, with the potential to develop trauma induced coagulopathy or coagulopathy from haemorrhage to improve survival.