Prolonged Ischemia Time Research Articles

In vivo multiparametric magnetic resonance imaging study for differentiating the severity of hepatic warm ischemia-reperfusion injury in a rabbit model

ObjectivesTo assess the value of multiparametric magnetic resonance imaging including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI) and blood oxygen level dependent (BOLD) MRI in differentiating the severity of hepatic warm ischemia-reperfusion injury (WIRI) in a rabbit model. MethodsFifty rabbits were randomly divided into a sham-operation group and four test groups (n = 10 for each group) according to different hepatic warm ischemia times. IVIM, DTI and BOLD MRI were performed on a 3 T MR scanner with 11 b values (0 to 800 s/mm2), 2 b values (0 and 500 s/mm2) on 12 diffusion directions, multiple-echo gradient echo (GRE) sequences (TR/TE, 75/2.57–24.25 ms), respectively. IVIM, DTI and BOLD MRI parameters, hepatic biochemical and histopathological parameters were compared. Pearson and Spearman correlation methods were performed to assess the correlation between these MRI parameters and laboratory parameters. Furthermore, receiver operating characteristic (ROC) curves were compiled to determine diagnostic efficacies. ResultsTrue diffusion (Dslow), pseudodiffusion (Dfast), perfusion fraction (PF), mean diffusivity (MD) significantly decreased, while R2* significantly increased with prolonged warm ischemia times, and significant differences were found in all of biochemical and histopathological parameters (all P < 0.05). Dslow, PF, and R2* correlated significantly with all of biochemical and histopathological parameters (all |r| = 0.381–0.746, all P < 0.05). ROC analysis showed that the area under the ROC curve (AUC) of IVIM across hepatic WIRI groups was the largest among IVIM, DTI and BOLD. ConclusionsMultiparametric MRI may be helpful with characterization of early changes and determination of severity of hepatic WIRI in a rabbit model.

EMBRYONIC EVENTS AND NOT UTERINE EVENTS ARE ASSOCIATED WITH PREGNANCY OUTCOMES IN A DECEASED DONOR UTERUS TRANSPLANT PROGRAM: PRELIMINARY RESULTS

Uterus transplantation is an emerging treatment for absolute uterine factor infertility. The majority of uterus transplants to date have utilized living donors (LDs). Only a few sporadic case reports exist with deceased/cadaveric donors (DDs), an approach with prolonged graft ischemia times. Our objective is to determine whether pregnancy rates are similar in DD to LD uterus transplantation.

Diazoxide preserves myocardial function in a swine model of hypothermic cardioplegic arrest and prolonged global ischemia

ObjectiveAdenosine triphosphate potassium sensitive channels provide endogenous myocardial protection via coupling of cell membrane potential to myocardial metabolism. Adenosine triphosphate potassium sensitive channel openers, such as diazoxide, mimic ischemic preconditioning, prevent cardiomyocyte swelling, preserve myocyte contractility after stress, and provide diastolic protection. We hypothesize that diazoxide combined with hyperkalemic cardioplegia provides superior myocardial protection compared with cardioplegia alone during prolonged global ischemia in a large animal model. MethodsTwelve pigs were randomized to global ischemia for 2 hours with a single dose of cold blood (4:1) hyperkalemic cardioplegia alone (n = 6) or with diazoxide (500 μmol/L) (n = 6) and reperfused for 1 hour. Cardiac output, myocardial oxygen consumption, left ventricular developed pressure, left ventricular ejection fraction, diastolic function, myocardial troponin, myoglobin, markers of apoptosis, and left ventricular infarct size were compared. ResultsFour pigs in the cardioplegia alone group could not be weaned from cardiopulmonary bypass. There were no differences in myoglobin, troponin, or apoptosis between groups. Diazoxide preserved cardiac output versus control (74.5 vs 18.4 mL/kg/min, P = .01). Linear mixed regression modeling demonstrated that the addition of diazoxide to cardioplegia preserved left ventricular developed pressure by 36% (95% confidence interval, 9.9-61.5; P < .01), dP/dt max by 41% (95% confidence interval, 14.5-67.5; P < .01), and dP/dt min by 33% (95% confidence interval, 8.9-57.5; P = .01). It was also associated with higher (but not significant) myocardial oxygen consumption (3.7 vs 1.4 mL O2/min, P = .12). ConclusionsDiazoxide preserves systolic and diastolic ventricular function in a large animal model of prolonged global myocardial ischemia. Diazoxide as an adjunct to hyperkalemic cardioplegia may allow safer prolonged ischemic times during increasingly complicated cardiac procedures.

Serial assessment of focal myocardial function after percutaneous coronary intervention for ST‐elevation myocardial infarction: Value of layer‐specific speckle tracking echocardiography

Ischemia-reperfusion injury (IRI) frequently follows successful PCI for STEMI and is recognized by multiple modalities. Multilayer speckle tracking echocardiography (STE) has the potential of detecting myocardial dysfunction in different myocardial layers. Our objective was to describe the changes in layer-specific myocardial function over the 24hours after successful PCI for ST-elevation myocardial infarction (STEMI). Patients (n=120) with STEMI and no prior myocardial infarction underwent echocardiography prior to PCI, immediately after and at 3- and 24-hours post-PCI. Worsening focal dysfunction (WFD) was defined as an immediate reduction, compared to the pre-PCI value, in the amplitude of endo-myocardial longitudinal strain (endo-MLS) within the infarction territory. Patients with WFD (52%) had further reductions in endo-MLS, mid-MLS, and epi-MLS in the infarction region immediately post-PCI; at 3hours strain began to improve and continued to improve at 24hours. Reductions of endo-MLS strain were more evident than those of global, mid-MLS, and epi-MLS. This same pattern was seen in each of the ischemic territories of the anterior descending, circumflex, and right coronary arteries. Immediate improvement in endo-MLS following PCI was seen in 48% of patients. The time from symptom onset to balloon time was markedly longer in those with WFD (P<.0001). Multilayer SPE is a sensitive method that identifies serial alterations in focal myocardial function following successful PCI for STEMI. Layer-specific reductions in endo-MLS appeared more evident than decreases in global LV strain. Prolonged total ischemic time prior to PCI was directly related to the incidence of WFD.

Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank

BackgroundDeceased organ donors represent an untapped source of therapeutic bone marrow (BM) that can be recovered in 3–5 times the volume of that obtained from living donors, tested for quality, cryopreserved, and banked indefinitely for future on-demand use. A challenge for a future BM banking system will be to manage the prolonged ischemia times that are inevitable when bones procured at geographically-dispersed locations are shipped to distant facilities for processing. Our objectives were to: (a) quantify, under realistic field conditions, the relationship between ischemia time and the quality of hematopoietic stem and progenitor cells (HSPCs) derived from deceased-donor BM; (b) identify ischemia-time boundaries beyond which HSPC quality is adversely affected; (c) investigate whole-body cooling as a strategy for preserving cell quality; and (d) investigate processing experience as a variable affecting quality.MethodsSeventy-five bones from 62 donors were analyzed for CD34+ viability following their exposure to various periods of warm-ischemia time (WIT), cold-ischemia time (CIT), and body-cooling time (BCT). Regression models were developed to quantify the independent associations of WIT, CIT, and BCT, with the viability and function of recovered HSPCs.ResultsResults demonstrate that under “real-world” scenarios: (a) combinations of warm- and cold-ischemia times favorable to the recovery of high-quality HSPCs are achievable (e.g., CD34+ cell viabilities in the range of 80–90% were commonly observed); (b) body cooling prior to bone recovery is detrimental to cell viability (e.g., CD34+ viability < 73% with, vs. > 89% without body cooling); (c) vertebral bodies (VBs) are a superior source of HSPCs compared to ilia (IL) (e.g., %CD34+ viability > 80% when VBs were the source, vs. < 74% when IL were the source); and (d) processing experience is a critical variable affecting quality.ConclusionsOur models can be used by an emerging BM banking system to formulate ischemia-time tolerance limits and data-driven HSPC quality-acceptance standards.

Risk factors and management of incisional hernia in the recipients of living donor liver transplant: A single institutional experience

AbstractAimIncisional hernia (IH) has a wide range of incidence after liver transplant (LT), with reported different risk factors. The aim of the study was to shed more light on the incidence, risk factors, and management of IH after living donor liver transplantation (LDLT).MethodsAdult recipients who underwent LDLT between April 2004 and December 2017 were retrospectively studied. The patients were divided into a group of post‐LDLT IH and another group without IH.ResultsA total of 239 recipients who underwent LDLT, 35 patients (14.6%) had post LT IH. The independent risk factors for post‐LDLT IH were, presence of hepatocellular carcinoma (HCC) pre‐transplant, small graft weight, prolonged warm ischaemia time (WIT), postoperative bile leak, postoperative surgical site infection (SSI), (all P values &lt;.05). The commonest site for hernia was the midline skin incision (65.7%). Eighteen recipients (51.4%) with IH underwent repair by mesh hernioplasty with no recurrence.ConclusionsThe following variables have been shown to be significant risk factors for the development of post‐LDLT IH: HCC indication for LDLT; small graft weight; prolonged WIT; and postoperative complications like bile leak and SSI. Mesh hernioplasty is the treatment of choice for this complication.

Interhospital Transfer versus Direct Admission in Patients with Acute ST-Segment Elevation Myocardial Infarction.

There is concern whether patients with ST-segment elevation myocardial infarction (STEMI) who admitted to a percutaneous coronary intervention (PCI) center from interhospital transfer is associated with longer reperfusion time compared with direct admission. We evaluated the reperfusion delays in patients with STEMI who admitted to a primary PCI center through interhospital transfer or direct admission. We retrospectively analyzed 6,494 consecutive STEMI patients admitted between 2011 and 2019. Compared with direct admission ( n = 4,121; 63%), interhospital transferred patients ( n = 2,373) were younger (55 ± 10 vs. 56 ± 10 years, p < 0.001), had similar gender (85.6 vs. 86% male, p = 0.67), greater proportion of off-hour admission (65.2 vs. 48.3%, p < 0.001), less diabetes mellitus (28 vs. 30.8%, p = 0.019), and received more primary PCI (70.5 vs. 48.7%, p < 0.001). Interhospital transferred patients who received primary PCI ( n = 3,677) or fibrinolytic ( n = 238) had longer symptom-to-PCI center admission time (median, 360 vs. 300 minutes, p < 0.001), shorter door-to-device (DTD) time for primary PCI (median, 74 vs. 87 minutes, p < 0.001), and longer total ischemic time (median, 465 vs. 414 minutes, p < 0.001). Logistic regression in interhospital transferred patients showed that delay in door-in-to-door-out (DI-DO) time at the first hospital was strongly associated with prolonged total ischemic time (adjusted odds ratio = 3.92; 95% confidence interval: 3.06-5.04, p < 0.001). This study suggests that although interhospital transferred patients received more primary PCI with shorter DTD time, interhospital transfer creates longer total ischemic time that associates with the delay in DI-DO time at the first hospital that should be improved.

Amputation of an unsalvageable post-traumatic limb in a young Haemophiliac: A multi-faceted clinical dilemma

A twenty-nine-year-old male presented to the emergency ward of our institute with a history of having been involved in a road traffic accident with a heavy motor vehicle (HMV), 18 hours ago, with trauma to his left lower limb. Arteriovenous Doppler evaluation of the affected limb confirmed devascularization, and radiographs showed fracture of the femur in supracondylar region and tibial diaphysis with significant soft tissue injury (Letts and Vincent type D floating knee). Due to the prolonged ischemia time of 18 hours, the Mangled Extremity Severity Score (MESS) of 10, and the contaminated nature of the wound, it was decided to proceed with Guillotine above-knee amputation. However, a detailed history-taking revealed the patient to be a sufferer of Hemophilia Type A (Coagulation factor VIII deficiency). The patient was stabilized hemodynamically, and supplemented with Factor VIII following which the amputation was done successfully. This case report documents his perioperative and postoperative course in the hospital, ending with his discharge with a small wound healing by secondary intention. Surgical procedures in hemophiliacs have always presented as clinical dilemmas, with increased blood loss, poor tissue perfusion, and infective events adding to the postoperative complications. Lower limb amputations in sufferers of hemophilia are very rare, with less that fifty cases being found in the global medical literature. A meta-analysis of said cases reveals the vast majority to have been due to infective indications or for management of hemophilic pseudo-tumours, and post-traumatic above knee amputations are virtually unheard of in such a clinical scenario. The presence of a traumatic vascular insult in this case, provided a rare clinical predicament, and the successful management of this Catch-22 situation makes for a unique situation.

Características de los pacientes trasplantados renales con retraso de la función del injerto, asistidos en el servicio de terapia intensiva del Instituto de Cardiología de Corrientes entre 2016 y 2018.

This research was intended to describe the characteristics of renal transplant patients with delayed graft function. Descriptive, transversal and observational study. Population: assisted renal transplants at the Institute of Current Cardiology between 2016 and 2018 that met the inclusion criteria. Own form was used; the data were obtained from review of medical record.The information collected was scanned by computer Epidat_4.2. The institution's committee was endorsed. 61 transplantedpatients were studied; 43% belonged to living donors and 57% to cadaveric. 66% of cadaveric donors had delayed graft function, those from living donors did not present it. In terms of sex 48% of males had delayed function; women was 28%. In age of patients, the average was 40.6 years x 15.7; the increased frequency of function delays was observed in the age group of 31 to 50 years with 44%. As for nutritional status 17% who were overweight and 48% underweight were delayed graft function. Depending on the years on pre-transplant dialysis, 65% of those with 4 to 7 years of dialysis had delayed graft function. According to cold ischemia time of the transplanted organ, 52% had delayed graft function when the time was greater than 15 hours. At the request of postoperative dialysis, 66% had delayed graft function and belonged to cadaveric donors. In renal vascular resistance index in the first 24 hours, 65% with delay of graft function had pathological index. In conclusion, male sex, age group of 31 to 50 years, having altered nutritional status, having dialed pre transplant between 4 to 7 years, suffering a prolonged time of cold ischemia &gt; 15 hours and present a pathological renal vascular resistance index, are present characteristics; renal transplants with delayed graft function; and need to be taken into account when planning these surgeries.

Decreased Incidence of Hepatic Artery Thrombosis in Pediatric Liver Transplantation Using Technical Variant Grafts: Report of the Society of Pediatric Liver Transplantation Experience

To evaluate risk factors for hepatic artery thrombosis (HAT) and examine the long-term outcomes of graft and patient survival after HAT in pediatric recipients of liver transplantation. Using multicenter data from the Society of Pediatric Liver Transplantation, Kaplan-Meier and Cox regression analyses were performed on first-time pediatric (aged <18years) liver transplant recipients (n=3801) in the US and Canada between 1995 and2016. Of children undergoing their first liver transplantation, 7.4% developed HAT within the first 90days of transplantation and, of those who were retransplanted, 20.7% developed recurrent HAT. Prolonged warm ischemia times increased the odds of developing HAT (OR, 1.11; P=.02). Adolescents aged 11-17years (OR, 0.53; P=.03) and recipients with split, reduced, or living donor grafts had decreased odds of HAT (OR, 0.59; P<.001 compared with whole grafts). Fifty percent of children who developed HAT developed graft failure within the first 90days of transplantation (adjusted hazard ratio, 11.87; 95% CI, 9.02-15.62) and had a significantly higher post-transplant mortality within the first 90days after transplantation (adjusted hazard ratio, 6.18; 95% CI, 4.01-9.53). These data from an international registry demonstrate poorer long-term graft and patient survival in pediatric recipients whose post-transplant course is complicated by HAT. Notably, recipients of technical variant grafts had lower odds of HAT compared with whole liver grafts.

Evaluation of Renal Anionic Secretion Following Living-donor and Deceased-donor Renal Transplantation: A Clinical Pharmacokinetic Study of Cefoxitin Microdosing.

Background.Renal transplantation is the treatment of choice for patients with end-stage renal disease. Because kidneys are the primary excretory organs for various drugs/drug metabolites, changes in renal graft function would significantly alter the clearance and exposure of renally secreted drugs. Renal allografts from living and deceased donors normally undergo numerous insults, including injuries associated with prolonged cold ischemic time, reperfusion, and nephrotoxicity due to calcineurin inhibitors. These physiologic and pharmacologic stresses can alter the expression and functional capacity of renal organic anionic transporters (OATs).Methods.The objectives of this study were to assess the longitudinal changes in renal anionic secretion in kidney transplant patients, to study the effect of prolonged cold ischemic time on OAT secretion in kidney transplant patients (living- versus deceased-donor recipients), and to compare OAT secretory capacity of renal transplant recipients with healthy volunteers. Cefoxitin was used as a probe drug to assess OAT secretion. Cefoxitin pharmacokinetics was studied in 15 de novo renal transplant recipients following intravenous administration of 200 mg cefoxitin within 14 d and beyond 90 d posttransplantation.Results.No longitudinal changes in real OAT secretion in early posttransplant period were observed, and there were no differences in renal OAT secretion between living- and deceased-donor renal transplant recipients. Overall, cefoxitin exposure was 2.6-fold higher and half-life increased by 2.2-fold in renal transplant recipients when compared with historical healthy controls.Conclusions.These results suggest that OAT system is functioning well, but renal transplant recipients would need significantly lower dosage of drugs that are primarily secreted via the OAT system compared with normal subjects.

Tantangan Penatalaksanaan STEMI di Pandemi Covid-19

The necessity of timely management of ST-elevation myocardial infarction (STEMI) is now disrupted by the Covid-19 pandemic. This paper discussed the challenge to manage STEMI in Indonesia due to Covid-19. It also discussed the alternative strategies for solution. Challenge can occur in term of the healthcare safety as well as STEMI patient safety. Healthcare safety potentially impaired by the problem of STEMI mimicry due to cardiovascular complication of Covid-10, inaccuracy of Covid-19 screening, lack of effective personal protection equipment for the healthcare and appropriate catheterisation laboratory to anticipate virus contamination. The safety of STEMI patient is potentially impaired due to prolonged ischemia time, and the risk of cross-infection. Solution for this challenge should include mass screening, rapid and accurate test to rule-out Covid-19, dual system of hospital units - Covid and non-Covid, and algorithm for triage patients with STEMI and Covid-19.

Tantangan Penatalaksanaan STEMI di Pandemi Covid-19

The necessity of timely management of ST-elevation myocardial infarction (STEMI) is now disrupted by the Covid-19 pandemic. This paper discussed the challenge to manage STEMI in Indonesia due to Covid-19. It also discussed the alternative strategies for solution. Challenge can occur in term of the healthcare safety as well as STEMI patient safety. Healthcare safety potentially impaired by the problem of STEMI mimicry due to cardiovascular complication of Covid-10, inaccuracy of Covid-19 screening, lack of effective personal protection equipment for the healthcare and appropriate catheterisation laboratory to anticipate virus contamination. The safety of STEMI patient is potentially impaired due to prolonged ischemia time, and the risk of cross-infection. Solution for this challenge should include mass screening, rapid and accurate test to rule-out Covid-19, dual system of hospital units - Covid and non-Covid, and algorithm for triage patients with STEMI and Covid-19.

Lumbar Artery Perforator Flap: Initial Experience with Simultaneous Bilateral Flaps for Breast Reconstruction.

Background:The lumbar artery perforator (LAP) flap is a useful alternative for patients who are not a candidate for breast reconstruction using the deep inferior epigastric perforator flap. Due to the positioning and concerns for prolonged ischemia time, bilateral breast reconstruction using LAP flaps is frequently performed in separate stages. We present our early experience performing simultaneous LAP flaps for bilateral breast reconstruction.Methods:We performed a retrospective review of all patients who underwent breast reconstruction with LAP flaps from December 2018 to September 2019. Demographics, flap data, and complication data were collected. Surgical sequence is presented.Results:A total of 30 simultaneous bilateral breast reconstruction were performed with LAP. We experienced 1 flap loss in an undiagnosed hypercoagulable patient. The average patient age was 52.7 years, and the average body mass index was 26.9. Most patients had a surgically absent abdominal donor site (66.7%). The average operative time was 510 minutes and ischemia time was 90.3 minutes. All flaps were performed using a composite deep inferior epigastric arterial/venous graft.Conclusions:The LAP flap is an innovative, yet technically challenging, choice for autologous breast reconstruction. In our experience, simultaneous bilateral breast reconstruction using LAP flaps can be safely performed in a single surgical stage; however, we recommend caution and a coordinated team approach. With simultaneously performing bilateral LAP flaps, there is an inherent prolonged ischemia time and, thus, an increased possibility for vasospasm and intraoperative revisions. This experience represents the first series of bilateral LAP flaps performed simultaneously.

Neurologic complications after surgical management of complex elbow trauma requiring radial head replacement

Radial head arthroplasty (RHA) has become a successful procedure for addressing acute unreconstructible radial head fractures that compromise elbow stability in complex elbow trauma. The purpose of this study was to investigate the incidence of and risk factors for the development of neurologiccomplications after surgical treatment of complex elbow fractures that require an RHA. Sixty-two patients with an unreconstructible radial head fracture and complex elbow instability treated with RHA were included. There were 33 men and 29 women, with a mean age of 54 years (range, 22-87 years). The average follow-up period was 5.2 years (range, 3-16 years). All patients were neurologically intact before surgery. The arthroplasty was implanted through a Kocher approach in 55 cases, whereas a Kaplan approach was used in 7. An uncemented smooth stem arthroplasty (Evolve) was used in 27 patients, and an anatomic ingrowth system (Anatomic Radial Head), in 35. At the time of surgery, 23 patients underwent fixation of a coronoid fracture and 15 underwent plating of the proximal ulna. All patients were clinically examined immediately after surgeryand during follow-up to detect any degree of neurologic deficit. Radial and ulnar nerve injuries were classified according to the Hirachi and McGowan classifications, respectively. Functional outcomes were evaluated with the Mayo Elbow Performance Score. A complete posterior interosseous nerve palsy occurred postoperatively in 2 patients. Hand function had completely recovered in both at 2 months after surgery without sequelae. Nine patients complained of ulnar nerve symptoms (immediately after surgery in 6andasdelayed ulnar neuropathy in 3). Most patients with ulnar nerve deficits had undergone additional surgical procedures to address ulnar fractures. Among patients with ulnar neuropathies, only 3 complained of mild sensory symptoms at the latest follow-up. Nosignificant differences in range of motion and Mayo Elbow Performance Score were found between patients with and without neurologic complications. Associated olecranon or coronoid fixation and a prolonged tourniquet time were identified as risk factors for neurologic complications. This study shows that the incidence of neurologic complications associated with the surgical treatment of complex elbow fractures requiring implantation of a radial head prosthesis may be underestimated in the literature. Inappropriate retraction in the anterior aspect of the radial neck, a prolonged ischemia time, and concomitant coronoid or olecranon fracture fixation represent the main risk factors for the development of this complication. Although the great majority of patients have full recovery of their nerve function, they should be advised on the risk of this stressful complication.

Induction Therapy in Patients with Prolonged Ischemic Times May Be Protective for Early Graft Failure

Primary graft dysfunction (PGD) in heart transplantation (HTx) patients is the leading cause of death within the first 30 days of HTx. Ischemic time >4 hours has been associated with a significant increase in mortality at 30 days post-transplant and up to 6 years post-transplant. The optimal immunosuppression regimen including induction therapy to prevent allograft failure is unclear. Induction therapy may have a protective effect against ischemia-reperfusion injury, a main mechanism of allograft injury after HTx. We sought to evaluate the effect of induction therapy in heart transplant recipients with longer ischemic times in both early and long-term graft failure. This retrospective cohort study used the United Network for Organ Sharing (UNOS) and included adult (>21yr) heart transplant patients from Jun 30, 2004 to Mar 2015. The effect of induction therapy, either basiliximab (IL-2Rab) or ATG/ALG/thymoglobulin, on all-cause early and late graft failure was estimated by a logistic regression adjusted for the covariates ischemic time, age, African American race, serum creatinine >2.5, HLA mismatch > 4, and acute rejection episodes. The Inverse Probability Treatment Weighting (IPTW) was used to control for imbalanced propensity of receiving induction given the covariates. At 30 days, induction was shown to reduce graft failure OR 0.69 (95% CI, 0.57-0.82) in all comers with no additional benefit for patients with prolonged ischemic time OR 1.08 (95% CI 0.87-1.36). Induction had no effect on long term graft failure up to 5.6 years OR 0.96 (95% CI 0.88 -1.04), except in patients with prolonged ischemic time OR 0.88 (95%CI 0.79-0.98). Our results suggest that induction therapy may be protective against graft failure at 30 days, and late graft failure up to five years in a subset of patients with prolonged ischemic times.

Early Administration of Crystalloid Cardioplegia after Circulatory Death in a Porcine Model of Cardiac Resuscitation

Transplantation of hearts donated after circulatory death (DCD) remains challenging due to the risk myocardial injuries. These hearts are exposed to hypoxia and prolonged warm ischemic time (WIT). We hypothesize that administration of cardioplegia (CPG) after extended WIT could make DCD hearts suitable for transplantation without severe myocardial injury. A hypoxic cardiac arrest was induced in twelve piglets (40 kg). Since peripheral cannulation could not be considered, a normothermic regional perfusion (NRP) was established between the right atrium and the aortic arch, 5 min. after mechanical asystole. In the CPG group (n=6), a crystalloid solution (40 mL/kg, Celsior, IGL, Lyon, France) was administered after 15 min. of WIT, while no preservation solution was administrated in the control group (n=6). The aortic clamp was released after 35 min. and NRP withdrawal was attempted 60 min. after cardiac reperfusion. Pressure-volume loops were performed before and after cardiac resuscitation. Early ischemic changes were detected on Masson's trichrome staining and incorporated to a composite score. Agonal phase was 14 min. in the CPG group (9.5-14) vs. 12 min. (11-13) (P=1.0). Three (50%) piglets could be weaned from NRP in the CPG group, vs. 1 (16.7%) in the CTL group (P=0.55). Troponin I was not different between groups (53 vs. 49 µg/L, P=0.73). All resuscitated hearts had biventricular function impairment with marked decline in left ventricular end-systolic elastance. Left ventricular ischemic changes were less severe in CPG group (P=0.034), while multifocal myocardial injury of the right ventricle was observed in both groups (Figure 1). Early administration of crystalloid cardioplegia was associated with a 50% rate of heart resuscitation in our porcine model. The viability of DCD hearts after prolonged WIT was limited by right ventricular severe injury.

Development and Validation of a Risk Score to Predict One-Year Mortality after Bridge to Heart Transplantation with Contemporary Durable Left Ventricular Assist Devices

The purpose of this study was to develop and validate a risk score for patients bridged to orthotopic heart transplantation (OHT) with contemporary durable left ventricular assist devices (LVADs). The United Network for Organ Sharing database was queried to identify patients bridged to OHT with a HeartMate III (HM3) or HeartWare (HVAD) LVAD from January 2010 to December 2018. Multivariable logistic regression analysis was used to identify predictors of one year post-OHT mortality. A composite risk score was created by summing individual risk points that were assigned based on the absolute magnitude of the odds ratios in the multivariable model. Model discrimination was assessed using 10-fold cross-validation and area under receiver operating characteristic curves, or c-index. The study included 2,728 patients (2,331 HVAD and 397 HM3). One-year mortality was 7.8% (n=214). The risk score incorporated 5 independent predictors of one year mortality, which resulted in a total of 12 possible points (Table). The multivariable pre-transplant predictors included: age >60 years, total bilirubin >3 mg/dL, prolonged ischemic time >4 hours, body mass index >35 kg/m2, and pre-transplant dialysis dependence (Table). The predicted post-transplant 1-year survival was 92% in the low risk (score <3 points), 84% in the moderate risk (score 4-5 points), and 76% in the high risk (score >6 points) patients (p<0.001). The risk score was found to be predictive in 10-fold cross validation with a c-index of 0.76, indicating good overall discrimination. We developed and validated a risk score for patients being bridged to OHT with contemporary durable devices including the HVAD and HM3 LVADs. This risk score may have clinical utility in guiding timing, patient selection, and prognostication and counseling for OHT in patients being supported with contemporary LVADs.

Impact of Histidine-Tryptophan-Ketoglutarate Preservation Solution in Heart Transplantation with Extended Distance

In countries with such continental dimensions, and low rates of organs donations and recovery, strategies to shorten the waiting time in heart transplantation (HT) list are still required. A prolonged ischemic time (pISQT, >240 min) has been reported to be a significant factor leading to primary graft dysfunction (PGD). Thus, optimal heart preservation is mandatory for transplant procedures with pISQT. Use of Histidine-Tryptophan-Ketoglutarate (HTK) solution has been suggested to improve extended organ preservations up to 180 min. This study investigated the impact of the donor distance (DD) from transplantation center and pISQT on PGD after HT using preservation with HTK solution. Between January 2017 and December 2018, all 92 consecutive patients underwent HT at our institution after preservation with HTK solution were retrospectively evaluated divided into 2 groups according to the DD: (G1) 46 patients underwent HT with a DD <100km, and (G2) 46 patients after HT with a DD >100km. No significant differences were observed with regard to gender, age, diagnosis, donor inotropic support, and donor-recipient weight ratio among patients in G2 when compared with G1. The PGD was characterized using the ISHLT defined criteria. Descriptive analyses of the results are presented as mean values and standard deviations. The analytical studies were performed with the Fisher exact test. Kaplan-Meier and log-rank tests were performed to investigate survivals. All analyses were performed using R and p<0.05 was considered to be significant. The incidence of PGD was similar in both groups (p=0.81). After risk adjustment, longer DD were associated with a significantly lower risk of mortality at both 60 days (p=0.05, Figure 1). This study illustrates that HTK solution may help to expand donor acceptance criteria to include more distant donor heart locations and accepting longer allograft ischemic times without increase in PGD and mortality after transplantation.

Assessment of Cerebral Perfusion and Activity during Normothermic Regional Perfusion in a Porcine Model of Donation after Circulatory Death

To determine cerebral perfusion/activity during normothermic regional perfusion (NRP) in a model of donation after circulatory death (DCD). NRP is a resuscitation strategy used for DCD hearts involving in situ reperfusion of the donor excluding cerebral circulation. Ethical concerns have been raised regarding potential return of spontaneous cerebral activity due to collateral circulation METHODS: We induced circulatory arrest by stopping mechanical ventilation in 6 donor pigs. A 15-minute stand-off period followed before resuscitation with NRP. We performed NRP via central cannulation with the supra-aortic vessels clamped and anesthetic drugs suspended. We assessed cerebral activity using Bispectral Index (BIS) and tested the presence of brainstem reflexes (pupillaryresponse, oculocephalic and corneal reflex, and spontaneous respirations). Cerebral perfusion was assessed by continuous oximetry with Near-Infrared Spectroscopy (NIRS) and a cerebral angiography RESULTS: Brainstem reflexes were uniformly absent at all time points following DCD in all cases. NIRS decreased markedly during DCD induction and became absent during NRP. A slight increase in oxygenation was noted in Case 1 during NRP; however, this stabilized at non-viable oxygenation levels. This case also demonstrated flow through collateral circulation via internal mammary arteries on angiography, but no cerebral activity was detected. BIS monitoring demonstrated absence of cerebral activity during NRP CONCLUSION: Our findings suggest that, although occasional collateral brain flow may occur, there is no significant brain perfusion or return of function during NRP. NRP is safe to be performed clinically and can enhance DCD donor organ utilization, especially in heart transplantation. Future studies are required focusing on the impact of NRP over DCD organ functional recovery and clinical outcomes.