Stand-off Period Research Articles

Right Ventricular Distension in Donor Hearts Following Cardiocirculatory Death: Implications for Post-Transplant Function

<h3>Purpose</h3> Donation after cardiocirculatory death (DCD) may expand the donor pool for heart transplantation; however, right ventricular (RV) dysfunction has been observed in resuscitated DCD hearts and the cause of this is not well understood. We sought to characterize changes in RV pressure and volume following withdrawal of life-sustaining therapy (WLST) in a large animal model of DCD. <h3>Methods and Materials</h3> Thirteen pigs were anesthetized and mechanically ventilated with room air. Mechanical ventilation was discontinued, hypoxic cardiac arrest ensued, and a 10-minute standoff period was observed. Changes in RV pressure and volume were monitored using a conductance catheter and magnetic resonance imaging (MRI). <h3>Results</h3> The arterial partial pressure of oxygen decreased rapidly and reached its nadir after 2 minutes (Figure 1). This corresponded with an increase in RV systolic pressure (baseline RVSP 24.1±0.9 vs. 35±2 mmHg, p<0.01), diastolic function (baseline dPdt_min −172±24 vs. −267±24 mmHg/s, p<0.01), and systolic function (baseline dPdt_max 254±32 vs. 378±32 mmHg/s, p=0.01) compared to baseline. Subsequent RV function progressively declined leading to an 18±6% (p<0.01) increase in RV end-diastolic volume and an increase in RV end diastolic pressure (baseline 4.2±0.5 vs. 7.3±0.4 mmHg, p<0.01). MRI confirmed an 18±12% increase in RV end diastolic volume compared to baseline. <h3>Conclusions</h3> Following WLST the RV experiences significant distension that may exacerbate myocardial injury. Assessment of RV function prior to transplantation of the DCD heart is essential, highlighting the need for an <i>ex vivo</i> perfusion device capable of biventricular functional assessment.

Abstract 255: A Normokalemic Nondepolarizing Cardioplegia Minimizes Myocardial Injury and Improves Cardiac Function in a Large Animal Model of Donation After Cardiocirculatory Death

Background: Procurement of donor hearts is typically preceded by delivery of a cold hyperkalemic cardioplegia (CP) that achieves arrest by depolarization of the membrane potential. This method has no intrinsic cardioprotective properties and may exacerbate ischemia-reperfusion (IR) injury. A tepid adenosine-lidocaine (AL) non-depolarizing CP has been shown to limit IR injury and improve myocardial functional recovery in a small animal model of orthotopic heart transplantation. We sought to determine the impact of AL CP on myocardial injury and function, in a porcine model of donation after cardio-circulatory death (DCD). Methods: Female Yorkshire pigs (60 kg) were subjected to a hypoxic cardiac arrest. Following a 15-minute standoff period donor hearts were procured, resuscitated ex-vivo, and transplanted into a recipient animal. Hearts in group 1 (N=7) were protected with a cold blood-Plegisol CP, perfused with a blood-crystalloid solution during ex-vivo assessment, and arrested with a cold blood-Plegisol CP prior to transplantation. Hearts in group 2 (N=5) were protected with a tepid AL-STEEN CP and perfused with a blood-STEEN solution in a continuous fashion during ex-vivo assessment and transplantation. Results: Animals in group 2 had a significantly longer ex-vivo perfusion time compared to those in group 1 (174±29 vs. 135±45 min, p&lt;0.05), yet they demonstrated significantly less weight gain (14±4 vs. 25±8 grams/hour, p&lt;0.05). Further, animals in group 2 exhibited less troponin I release during ex-vivo perfusion and had significantly better diastolic function following wean from cardiopulmonary bypass (left ventricular end-diastolic pressure volume relationship 0.115±0.052 vs. 0.508±0.223, p&lt;0.05). However, there was no significant difference in level of calpain activity between groups (171.3±68.6 vs. 140.12±50.6, p=0.36). Conclusion: A tepid non-depolarizing AL CP results in less myocardial edema during ex-vivo perfusion, minimizes myocardial injury, and improves diastolic function following transplantation of DCD hearts, but fails to eliminate the activation of calcium-dependent proteases. Further studies should investigate if a calpain inhibitor delivered at reperfusion could further minimize IR injury in DCD hearts.

Preliminary results of transplantation with kidneys donated after cardiocirculatory determination of death: a French single-centre experience

Donation after circulatory determination of death (DCDD), formerly non-heart-beating donation and donation after cardiac death, has been re-introduced into clinical practice in France since June 2006 as a potential solution to organ shortage, but this kidney transplantation programme is not popular yet, mainly because of logistical concerns and uncertainty about the long-term warm ischaemia impact on transplanted kidneys. Our institution started the DCDD programme in January 2007, following the national 'BioMedicine Agency' protocol. We only considered uncontrolled donors with an initial no-flow period (i.e. delay between collapse and external cardiac massage start) <30 min. A 5-min stand-off period was observed before declaring the death and performing in situ cold perfusion, and since January 2010, normothermic subdiaphragmatic extracorporeal membrane oxygenation. All kidneys were machine-perfused using the hypothermic pulsatile preservation system before transplantation. Morphologic assessment and perfusion indexes were used to assess the suitability for transplantation. From January 2007 to December 2010, our team performed 58 kidney transplantations from uncontrolled Maastricht Category I and II donors. Mean recipient age was 47 ± 9 years. Male/female ratio was 45/13. Mean waiting time on transplantation registry was 30 months (4-180). Mean cold ischaemia time was 13 h 40 min (7-18) and pulsatile perfusion time 8 h (1-16). We had three cases (5%) of primary non-function (PNF) and 95% of delayed graft function. There was no increase in biopsy-proven acute rejection incidence (12.7%). Patient and graft survivals were 98 and 91.4%, respectively, at 1 year and 98 and 88%, respectively, at last follow-up. Estimated glomerular filtration rate ( Modification of Diet in Renal Disease formula) was 48 ± 16 mL/min/1.73 m(2) at 1 year and 48 ± 15 mL/min/1.73 m(2) at the last follow-up. DCDD kidneys are a valuable additional source of organs for transplantation. Our results show encouraging outcomes, which give rise to further interest in this donor pool. Respecting the national protocol is crucial to prevent PNF and deleterious warm ischaemia effect on transplanted kidney.

Single-Center Experience With Liver Transplantation From Controlled Non-Heartbeating Donors

To increase the number of livers available for transplantation a non-heartbeating donor (NHBD) liver transplant program was started after obtaining hospital ethical committee approval. Controlled donors with a warm ischemia of <30 minutes were considered. A 5-minute stand-off period was observed from asystole to skin incision. A super-rapid technique was used for the retrieval. Methods used to assess the suitability for transplantation included liver function tests, morphologic and histologic assessment, and hepatocyte viability testing. Sixty livers were retrieved from NHBDs. Of these, 33 were judged suitable for transplantation. Of these one was exported and transplanted, and one could not be matched to a suitable recipient. A further 27 were not used because of liver appearance in 21, prolonged hypoxia and hypotension in 4, poor perfusion in 1, and donor malignancy in 1. Mean donor age was 39.4 years (range, 0.75-67 years). Causes of death were head trauma in 10 donors, intracranial bleed in 24, and anoxic/ischemic brain injury in 26. Mean warm ischemia time was 14.7 minutes (range, 7-40 minutes). Thirty-two patients were transplanted (one split liver), and the mean age of the recipients was 38.4 years (range, 0.7-72 years). All grafts had good early function except one right lobe split. There were 4 deaths resulting from ischemic brain injury, chronic rejection, biliary sepsis, and multiorgan failure following retransplantation for primary nonfunction. Overall patient and graft survival is 87% and 84%, respectively, at a median follow-up of 15 months. Early results suggest that controlled NHBDs are a significant new source of grafts, but careful donor selection and short cold ischemia are mandatory.

The effects of surface type on lying behaviour and stress responses of dairy cows during periodic weather-induced removal from pasture

In some dairy cow grazing systems, during wet weather, the cows are removed from the pasture to a separate area for most of the day, in order to minimise treading damage to the soil. The objective of this study was to compare the effects of four surfaces commonly used for this “stand-off” procedure, in terms of cow lying behaviour, bodyweight, dirtiness, locomotion, and faecal concentrations of stress-induced hormones. In a replicated 4×4 Latin square design, 32 non-lactating Friesian cows were allocated in groups of four to either a specially constructed wood chip pad, a concrete yard, a gravel-surfaced farm laneway or a small paddock. The cows were held on the stand-off areas for 4 days, apart from a 3 h period each day spent grazing at pasture. Both the farm laneway and the small paddock became extremely muddy. The total time spent lying per day was greater ( P<0.001) for cows on the wood chip pad (11.9 h), than for cows on the concrete yard (7.0 h), farm laneway (5.7 h), or small paddock (6.9 h). These effects were driven by differences in the frequency of lying down on the stand-off surfaces, as there were no treatment effects on mean lying bout duration during stand-off. Cows on stand-off treatments where lying was reduced attempted to compensate by lying down to a greater extent during the 3 h period at pasture. Cows on the concrete yard had lower bodyweights and higher faecal glucocorticoid metabolite concentrations at the end of the 4-day stand-off period than cows on the wood chip pad and the small paddock. Similarly, cows on the concrete yard had a reduced gait length at the end of the stand-off period compared with cows on the farm laneway and the small paddock. The cows on the wood chip pad were less dirty than cows on the other surfaces. These results highlight the importance of providing a well drained and comfortable surface for cows to rest upon during periodic weather-induced removal from the pasture.