Differential effects of ischemia/reperfusion on endothelial function and contractility in donation after circulatory death.

BACKGROUND: Donation after circulatory death (DCD) could significantly improve cardiac graft availability. However, DCD hearts undergo potentially deleterious warm ischemia/reperfusion (I/R). As endothelial damage is a key factor in cardiac I/R injury, we aimed to investigate the tolerance of cardiac and endothelial function after various durations of warm ischemia to improve the timing and choice of cardioprotective therapies. METHODS: Isolated, working rat hearts were perfused for 20 minutes aerobically, then underwent various periods of warm global ischemia and either 30 or 60 minutes of reperfusion. RESULTS: Compared with non-ischemic hearts, recovery of left ventricular work (heart rate-developed pressure product) was significantly reduced at 60 minutes of reperfusion with ≥27 minutes of ischemia (p <0.05 for all), but was unchanged after 21 or 24 minutes of ischemia. Markers of cell death and edema significantly increased with ≥27-minute ischemia compared with non-ischemic hearts (p <0.05 for all). Endothelial-dependent vasodilation was significantly impaired compared with non-ischemic hearts with ≥24 minutes of ischemia, whereas endothelial-independent vasodilation was impaired with ≥27 minutes of ischemia (p <0.05 for all). Furthermore, with ≥24 minutes of ischemia, superoxide production by nitric oxide synthase and peroxynitrite levels were significantly increased compared with non-ischemic hearts, suggesting endothelial nitric oxide synthase (eNOS) uncoupling (p <0.05 for both). CONCLUSIONS: The first signs of endothelial dysfunction after cardiac ischemia occur with less ischemia than cardiac functional alterations, and may result from increased eNOS uncoupling. Strategies aimed at improving eNOS coupling may thus help to optimize both endothelial and myocardial recovery, ultimately facilitating DCD heart transplantation.

Heart Transplantation With Donation After Circulatory Death.

Heart transplantation remains the preferred option for improving quality of life and survival for patients suffering from end-stage heart failure. Unfortunately, insufficient supply of cardiac grafts has become an obstacle. Increasing organ availability with donation after circulatory death (DCD) may be a promising option to overcome the organ shortage. Unlike conventional donation after brain death, DCD organs undergo a period of warm, global ischemia between circulatory arrest and graft procurement, which raises concerns for graft quality. Nonetheless, the potential of DCD heart transplantation is being reconsidered, after reports of more than 70 cases in Australia and the United Kingdom over the past 3 years. Ensuring optimal patient outcomes and generalized adoption of DCD in heart transplantation, however, requires further development of clinical protocols, which in turn require a better understanding of cardiac ischemia-reperfusion injury and the various possibilities to limit its adverse effects. Thus, we aim to provide an overview of the knowledge obtained with preclinical studies in animal models of DCD heart transplantation, to facilitate and promote the most effective and efficient advancement in preclinical research. A literature search of the PubMed database was performed to identify all relevant preclinical studies in DCD heart transplantation. Specific aspects relevant for DCD heart transplantation were analyzed, including animal models, graft procurement and storage conditions, cardioprotective approaches, and graft evaluation strategies. Several potential therapeutic strategies for optimizing graft quality are identified, and recommendations for further preclinical research are provided.

Mitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death-consequences of ischemic duration.

BACKGROUND: Cardioprotection and graft evaluation after ischemia-reperfusion (IR) are essential in facilitating heart transplantation with donation after circulatory death. Given the key role of mitochondria in IR, we aimed to investigate the tolerance of cardiac mitochondria to warm, global ischemia and to determine the predictive value of early reperfusion mitochondria-related parameters for post-ischemic cardiac recovery. METHODS: Isolated, working rat hearts underwent 0, 21, 24, 27, 30, or 33 minutes of warm, global ischemia, followed by 60 minutes of reperfusion. Functional recovery (developed pressure × heart rate) was determined at 60 minutes of reperfusion, whereas mitochondrial integrity was measured at 10 minutes of reperfusion. RESULTS: Functional recovery at 60 minutes of reperfusion decreased with ≥ 27 minutes of ischemia vs no ischemia (n = 7-8/group; p < 0.01). Cytochrome c, succinate release, and mitochondrial Ca2+ content increased with ≥ 27 minutes of ischemia vs no ischemia (p < 0.05). Ischemia at ≥ 21 minutes decreased mitochondrial coupling, adenosine 5'-triphosphate content, mitochondrial Ca2+ retention capacity, and increased oxidative damage vs no ischemia (p < 0.05). Reactive oxygen species (ROS) from reverse electron transfer increased with 21 and 27 minutes of ischemia vs no ischemia and 33 minutes of ischemia (p < 0.05), whereas ROS from forward electron transfer increased only with 33 minutes of ischemia vs no ischemia (p < 0.05). Mitochondrial coupling and adenosine 5'-triphosphate content correlated positively and cytochrome c, succinate, oxidative damage, and mitochondrial Ca2+ content correlated negatively with cardiac functional recovery (p < 0.05). CONCLUSIONS: Mitochondrial dysfunction occurs with shorter periods of ischemia than cardiac dysfunction. Mitochondrial coupling, ROS emission from reverse electron transfer, and calcium retention are particularly sensitive to early reperfusion injury, reflecting potential targets for cardioprotection. Indicators of mitochondrial integrity may be of aid in evaluating suitability of donation after circulatory death grafts for transplantation.

Cardioprotective reperfusion strategies differentially affect mitochondria: Studies in an isolated rat heart model of donation after circulatory death (DCD).

Donation after circulatory death (DCD) holds great promise for improving cardiac graft availability; however, concerns persist regarding injury following warm ischemia, after donor circulatory arrest, and subsequent reperfusion. Application of preischemic treatments is limited for ethical reasons; thus, cardioprotective strategies applied at graft procurement (reperfusion) are of particular importance in optimizing graft quality. Given the key role of mitochondria in cardiac ischemia-reperfusion injury, we hypothesize that 3 reperfusion strategies-mild hypothermia, mechanical postconditioning, and hypoxia, when briefly applied at reperfusion onset-provoke mitochondrial changes that may underlie their cardioprotective effects. Using an isolated, working rat heart model of DCD, we demonstrate that all 3 strategies improve oxygen-consumption-cardiac-work coupling and increase tissue adenosine triphosphate content, in parallel with increased functional recovery. These reperfusion strategies, however, differentially affect mitochondria; mild hypothermia also increases phosphocreatine content, while mechanical postconditioning stimulates mitochondrial complex I activity and reduces cytochrome c release (marker of mitochondrial damage), whereas hypoxia upregulates the expression of peroxisome proliferator-activated receptor-gamma coactivator (regulator of mitochondrial biogenesis). Characterization of the role of mitochondria in cardioprotective reperfusion strategies should aid in the identification of new, mitochondrial-based therapeutic targets and the development of effective reperfusion strategies that could ultimately facilitate DCD heart transplantation.

Development of a cardiac loading device to monitor cardiac function during ex vivo graft perfusion.

BACKGROUND: Ex vivo heart perfusion systems, allowing continuous perfusion of the coronary vasculature, have recently been introduced to limit ischemic time of donor hearts prior to transplantation. Hearts are, however, perfused in an unloaded manner (via the aorta) and therefore, cardiac contractile function cannot be reliably evaluated. OBJECTIVES: We aim to develop a ventricular loading device that enables monitoring of myocardial function in an ex vivo perfusion system. In this initial study, was to develop a prototype for rat experimentation. METHODS: We designed a device consisting of a ventricular balloon and a reservoir balloon, connected through an electronic check valve, which opens and closes in coordination with changes in ventricular pressure. All balloons were produced in our laboratory and their properties, particularly pressure-volume relationships, were characterized. We developed a mock ventricle in vitro test system to evaluate the device, which was ultimately tested in ex vivo perfused rat hearts. RESULTS: Balloon production was consistent and balloon properties were maintained over time and with use on the device. Results from in vitro and ex vivo experiments show that the device functions appropriately; hemodynamic function can be measured and compares well to measurements made in an isolated, working (loaded) rat heart preparation. CONCLUSIONS: Our cardiac loading device appears to reliably allow measurement of several left ventricular hemodynamic parameters and provides the opportunity to control ventricular load.

Prognostic Value of Early Postoperative Troponin T in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Cardiac troponin T (cTnT) is elevated after coronary artery bypass grafting surgery. The aim of this study was to determine the association between cTnT elevations between 6 and 12 hours after coronary artery bypass grafting and in-hospital outcome. METHODS AND RESULTS: We prospectively studied 1722 patients undergoing isolated coronary artery bypass grafting. We assessed the association between conventional cTnT (749 patients) and high-sensitivity cTnT (hs-cTnT; 973 patients) 6 to 12 hours postoperatively with in-hospital major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, or stroke. The prespecified secondary outcome was a safety composite of MACCE, resuscitation, intensive care unit readmission or admission ≥48 hours, inotrope or vasopressor use ≥24 hours, or new-onset renal insufficiency. Among patients with a conventional cTnT measurement, 92 experienced a MACCE (12%) and 146 experienced a safety composite event (19%). Likewise, for hs-cTnT, 114 experienced a MACCE (12%) and 153 experienced a safety composite event (16%). Compared with cTnT ≤200 ng/L, each 200-ng/L increment in cTnT was associated with a monotonous increase in the odds of MACCE and the safety composite outcome. Conventional and hs-cTnT demonstrated moderate discrimination for MACCE (areas under the fitted receiver operating characteristics curve, 0.72 and 0.77 for conventional and hs-cTnT, respectively) and the safety composite outcome (areas under the fitted receiver operating characteristics curve, 0.66 and 0.74 for conventional and hs-cTnT, respectively) and resulted in improved prognostic performance when added to the EuroSCORE. At a cutoff of 800 ng/L, conventional and hs-cTnT provided clinically relevant power to rule in MACCE and the safety composite outcome. CONCLUSIONS: cTnT levels assessed between 6 and 12 hours after coronary artery bypass grafting identify patients at increased risk of MACCE or other complications.

Myocardial infarction stabilization by cell-based expression of controlled Vascular Endothelial Growth Factor levels.

Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)-based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell-based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF-expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS-purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia.

Clinical Relevance of Troponin T Profile Following Cardiac Surgery.

Background: Peak post-operative cardiac troponin T (cTnT) independently predicts mid- and long-term outcome of cardiac surgery patients. A few studies however have reported two peaks of cTnT over the first 48-72 h following myocardial reperfusion. The aim of the current study was to better understand underlying reasons of these different cTnT profiles and their possible relevance in terms of clinical outcome. Methods: All consecutive adult cardiac surgical procedures performed with an extra-corporeal circulation during a >6 years period were retrospectively evaluated. Patients with a myocardial infarction (MI) < 8 days were excluded. cTnT profile of patients with at least one value ≥1 ng/mL value were categorized according to the time occurrence of the peak value. Univariable and multivariable analysis were performed to identify factors influencing early vs. late increase of cTnT values, and to verify the correlation of early vs. late increase with clinical outcome. Results: Data of 5,146 patients were retrieved from our prospectively managed registry. From 953 with at least one cTnT value ≥1 ng/mL, peak occurred ≤ 6 h (n = 22), >6 to ≤ 12 h (n = 366), >12 to ≤ 18 h (n = 176), >18 to ≤ 24 h (171), >24 h (218). Age (OR: 1.023; CI: 1.016-1.030) and isolated CABG (OR: 1.779; CI: 1.114-2.839) were independent predictors of a late increase of cTnT over a limit of 1 ng/ml (p < 0.05), whereas isolated valve procedures (OR: 0.685; CI: 0.471-0.998) and cross-clamp duration (OR: 0.993; CI: 0.990-0.997) independently predicted an early elevation (p < 0.05). Delayed elevation as opposed to early elevation correlated with a higher rate of post-operative complications including MI (19.8 vs. 7.2%), new renal insufficiency (16.3 vs. 6.7%), MACCE (32.0 vs. 15.5%), or death (7.4 vs. 4.4%). Conclusion: Profile of cTnT elevation following cardiac surgery depends on patients' intrinsic factors, type of surgery and duration of cross-clamp time. Delayed increase is of higher clinically relevance than prompt post-operative elevation.

High pre-ischemic fatty acid levels decrease cardiac recovery in an isolated rat heart model of donation after circulatory death.

RATIONALE: Donation after circulatory death (DCD) could improve cardiac graft availability. However, strategies to optimize cardiac graft recovery remain to be established in DCD; these hearts would be expected to be exposed to high levels of circulatory fat immediately prior to the inevitable period of ischemia prior to procurement. OBJECTIVE: We investigated whether acute exposure to high fat prior to warm, global ischemia affects subsequent hemodynamic and metabolic recovery in an isolated rat heart model of DCD. METHODS AND RESULTS: Hearts of male Wistar rats underwent 20min baseline perfusion with glucose (11mM) and either high fat (1.2mM palmitate; HF) or no fat (NF), 27min global ischemia (37°C), and 60min reperfusion with glucose only (n=7-8 per group). Hemodynamic recovery was 50% lower in HF vs. NF hearts (34±30% vs. 78±8% (60min reperfusion value of peak systolic pressure*heart rate as percentage of mean baseline); p<0.01). During early reperfusion, glycolysis (0.3±0.3 vs. 0.7±0.3µmol*min-1*g dry-1, p<0.05), glucose oxidation (0.1±0.03 vs. 0.4±0.2µmol*min-1*g dry-1, p<0.01) and pyruvate dehydrogenase activity (1.8±0.6 vs. 3.6±0.5U*g protein-1, p<0.01) were significantly reduced in HF vs. NF groups, respectively, while lactate release was significantly greater (1.8±0.9 vs. 0.6±0.2µmol*g wet-1*min-1; p<0.05). CONCLUSIONS: Acute, pre-ischemic exposure to high fat significantly lowers post-ischemic cardiac recovery vs. no fat despite identical reperfusion conditions. These findings support the concept that oxidation of residual fatty acids is rapidly restored upon reperfusion and exacerbates ischemia-reperfusion (IR) injury. Strategies to optimize post-ischemic cardiac recovery should take pre-ischemic fat levels into consideration.

A simple preoperative score including the surgeon's experience to predict the probability of a successful mitral valve repair.

OBJECTIVES: According to recent guidelines, mitral valve (MV) repair is preferable to replacement. However, replacement is sometimes inevitable. Aims of the study were to identify variables that predict the risk of an unsuccessful MV repair and to evaluate a score that could help in planning MV surgical procedures. METHODS: Clinical data of all consecutive adult mitral valve surgical procedures, performed during a 50-month period, were extracted from our clinical registry, and combined with echocardiographic variables. The variables identified by a univariable analysis, together with factors known from the literature as indicating a possible risk of an unsuccessful MV repair, were compiled in a multivariable logistic regression analysis. The surgeon's experience was also taken into account. RESULTS: Of 545 MV procedures, 162 (29.7%) were MV replacements. Seven variables were identified as independent predictors of MV replacement (odd ratio; 95% CI): endocarditis (7.8; 3.7-16.5), absence of annular dilatation (3.6; 2.2-5.9), leaflet calcification (6.1; 3.0-12.7), annular calcification (3.7; 1.9-7.3), mitral stenosis (29.6; 9.3-93.8), mitral sclerosis (3.0; 1.7-5.3), surgeon's limited experience (3.9; 1.4-11.0). The ability of this model to discriminate between repair and replacement was calculated, and an area under the ROC curve of 0.87 was shown. A score was calculated for each patient and distributed into four risk categories: low risk (0-6), moderate risk (7-10), high risk (11-16) and very high risk (>16) of MV replacement with, respectively, 10.2 vs 10.0%, 40.5% vs 38.9%, 66.7 vs 70.4% and 93.2 vs 93.2% observed vs predicted probability of MV replacement. CONCLUSIONS: Preoperative assessment of seven variables can accurately predict the risk of an unsuccessful MV repair.

Controlled Reperfusion Strategies Improve Cardiac Hemodynamic Recovery after Warm Global Ischemia in an Isolated, Working Rat Heart Model of Donation after Circulatory Death (DCD).

Aims: Donation after circulatory death (DCD) could improve cardiac graft availability, which is currently insufficient to meet transplant demand. However, DCD organs undergo an inevitable period of warm ischemia and most cardioprotective approaches can only be applied at reperfusion (procurement) for ethical reasons. We investigated whether modifying physical conditions at reperfusion, using four different strategies, effectively improves hemodynamic recovery after warm ischemia. Methods and Results: Isolated hearts of male Wistar rats were perfused in working-mode for 20 min, subjected to 27 min global ischemia (37°C), and 60 min reperfusion (n = 43). Mild hypothermia (30°C, 10 min), mechanical postconditioning (MPC; 2x 30 s reperfusion/30 s ischemia), hypoxia (no O2, 2 min), or low pH (pH 6.8-7.4, 3 min) was applied at reperfusion and compared with controls (i.e., no strategy). After 60 min reperfusion, recovery of left ventricular work (developed pressure*heart rate; expressed as percent of pre-ischemic value) was significantly greater for mild hypothermia (62 ± 7%), MPC (65 ± 8%) and hypoxia (61 ± 11%; p < 0.05 for all), but not for low pH (45 ± 13%), vs. controls (44 ± 7%). Increased hemodynamic recovery was associated with greater oxygen consumption (mild hypothermia, MPC) and coronary perfusion (mild hypothermia, MPC, hypoxia), and with reduced markers of necrosis (mild hypothermia, MPC, hypoxia) and mitochondrial damage (mild hypothermia, hypoxia). Conclusions: Brief modifications in physical conditions at reperfusion, such as hypothermia, mechanical postconditioning, and hypoxia, improve post-ischemic hemodynamic function in our model of DCD. Cardioprotective reperfusion strategies applied at graft procurement could improve DCD graft recovery and limit further injury; however, optimal clinical approaches remain to be characterized.

Rat Heterotopic Heart Transplantation Model to Investigate Unloading-Induced Myocardial Remodeling.

Unloading of the failing left ventricle in order to achieve myocardial reverse remodeling and improvement of contractile function has been developed as a strategy with the increasing frequency of implantation of left ventricular assist devices in clinical practice. But, reverse remodeling remains an elusive target, with high variability and exact mechanisms still largely unclear. The small animal model of heterotopic heart transplantation (hHTX) in rodents has been widely implemented to study the effects of complete and partial unloading on cardiac failing and non-failing tissue to better understand the structural and molecular changes that underlie myocardial recovery. We herein review the current knowledge on the effects of volume unloading the left ventricle via different methods of hHTX in rats, differentiating between changes that contribute to functional recovery and adverse effects observed in unloaded myocardium. We focus on methodological aspects of heterotopic transplantation, which increase the correlation between the animal model and the setting of the failing unloaded human heart. Last, but not least, we describe the late use of sophisticated techniques to acquire data, such as small animal MRI and catheterization, as well as ways to assess unloaded hearts under "reloaded" conditions. While giving regard to certain limitations, heterotopic rat heart transplantation certainly represents the crucial model to mimic unloading-induced changes in the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further improve our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients.

Efficacy of mechanical postconditioning following warm, global ischaemia depends on circulating fatty acid levels in an isolated, working rat heart model†.

OBJECTIVES: The number of heart transplantations is limited by donor organ availability. Donation after circulatory determination of death (DCDD) could significantly improve graft availability; however, organs undergo warm ischaemia followed by reperfusion, leading to tissue damage. Laboratory studies suggest that mechanical postconditioning [(MPC); brief, intermittent periods of ischaemia at the onset of reperfusion] can limit reperfusion injury; however, clinical translation has been disappointing. We hypothesized that MPC-induced cardioprotection depends on fatty acid levels at reperfusion. METHODS: Experiments were performed with an isolated rat heart model of DCDD. Hearts of male Wistar rats (n = 42) underwent working-mode perfusion for 20 min (baseline), 27 min of global ischaemia and 60 min reperfusion with or without MPC (two cycles of 30 s reperfusion/30 s ischaemia) in the presence or absence of high fat [(HF); 1.2 mM palmitate]. Haemodynamic parameters, necrosis factors and oxygen consumption (O2C) were assessed. Recovery rate was calculated as the value at 60 min reperfusion expressed as a percentage of the mean baseline value. The Kruskal-Wallis test was used to provide an overview of differences between experimental groups, and pairwise comparisons were performed to compare specific time points of interest for parameters with significant overall results. RESULTS: Percent recovery of left ventricular (LV) work [developed pressure (DP)-heart rate product] at 60 min reperfusion was higher in hearts reperfused without fat versus with fat (58 ± 8 vs 23 ± 26%, P < 0.01) in the absence of MPC. In the absence of fat, MPC did not affect post-ischaemic haemodynamic recovery. Among the hearts reperfused with HF, two significantly different subgroups emerged according to recovery of LV work: low recovery (LoR) and high recovery (HiR) subgroups. At 60 min reperfusion, recovery was increased with MPC versus no MPC for LV work (79 ± 6 vs 55 ± 7, respectively; P < 0.05) in HiR subgroups and for DP (40 ± 27 vs 4 ± 2%), dP/dtmax (37 ± 24 vs 5 ± 3%) and dP/dtmin (33 ± 21 vs 5 ± 4%; P < 0.01 for all) in LoR subgroups. CONCLUSIONS: Effects of MPC depend on energy substrate availability; MPC increased recovery of LV work in the presence, but not in the absence, of HF. Controlled reperfusion may be useful for therapeutic strategies aimed at improving post-ischaemic recovery of cardiac DCDD grafts, and ultimately in increasing donor heart availability.

Oxygen-transfer performance of a newly designed, very low-volume membrane oxygenator.

OBJECTIVES: Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. METHODS: The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature over flows of 5-60 ml × min(-1) were assessed. RESULTS: Twelve mini-oxygenators with a mean priming volume of 1.5 ± 0.3 ml were evaluated. With buffer, oxygen transfer reached a maximum of 14.8 ± 1.0 ml O2 × l(-1) (pO2: 450 ± 32 mmHg) at perfusate flow rates of 5 ml × min(-1) and decreased with an increase in perfusate flow to 7.8 ± 0.7 ml ml O2 × l(-1) (pO2: 219 ± 24 mmHg) at 60 ml × min(-1). Similarly, with blood perfusate, oxygen transfer also decreased as perfusate flow increased, ranging from 33 ± 5 ml O2 × l(-1) at 5 ml × min(-1) to 11 ± 2 ml O2 × l(-1) at 60 ml × min(-1). Furthermore, oxygen transfer capacity remained stable with blood perfusion over a period of at least 2 h. CONCLUSIONS: We have developed a new miniaturized membrane oxygenator with an ultra-low priming volume (<2 ml) and adequate oxygenation performance. This oxygenator may be of use in overcoming current limitations in equipment size for effective oxygenation in low-volume perfusion circuits, such as small animal extracorporeal circulation and ex vivo organ perfusion.

Supplemental Cardioplegia Immediately before Graft Implantation may Improve Early Post-Transplantation Outcome.

BACKGROUND: Preservation of cardiac grafts for transplantation is not standardized and most centers use a single administration of crystalloid solution at the time of harvesting. We investigated possible benefits of an additional dose of cardioplegia dispensed immediately before implantation. METHODS: Consecutive adult cardiac transplantations (2005-2012) were reviewed. Hearts were harvested following a standard protocol (Celsior 2L, 4-8°C). In 2008, 100 ml crystalloid cardioplegic solution was added and administered immediately before implantation. Univariate and logistic regression analyses were used to investigate risk factors for post-operative graft failure and mid-term outcome. RESULTS: A total of 81 patients, 44 standard ("Cardio(-)") vs. 37 with additional cardioplegia ("Cardio(+)") were analyzed. Recipients and donors were comparable in both groups. Cardio(+) patients demonstrated a reduced need for defibrillation (24 vs. 48%, p = 0.03), post-operative ratio of CK-MB/CK (10.1 ± 3.9 vs. 13.3 ± 4.2%, p = 0.001), intubation time (2.0 ± 1.6 vs. 7.2 ± 11.5 days, p = 0.05), and ICU stay (3.9 ± 2.1 vs. 8.5 ± 7.8 days, p = 0.001). Actuarial survival was reduced when graft ischemic time was >180 min in Cardio(-) but not in Cardio(+) patients (p = 0.033). Organ ischemic time >180 min (OR: 5.48, CI: 1.08-27.75), donor female gender (OR: 5.84, CI: 1.13-33.01), and recipient/donor age >60 (OR: 6.33, CI: 0.86-46.75), but not the additional cardioplegia or the observation period appeared independent predictors of post-operative acute graft failure. CONCLUSION: An additional dose of cardioplegia administered immediately before implantation may be a simple way to improve early and late outcome of cardiac transplantation, especially in situations of prolonged graft ischemia. A large, ideally multicentric, randomized study is desirable to verify this preliminary observation.