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Purpose Although heart donation after circulatory death (DCD) is a promising option to increase graft availability, hearts undergo warm, global ischemia prior to procurement, which is a concern for graft quality. In clinical DCD, hearts are commonly procured and subjected to cold, static storage (CSS) prior to ex-situ normothermic machine perfusion for transport and graft evaluation. Cold ischemia induced by CSS and reoxygenation at normothermic temperatures, however, may aggravate graft injury, especially in endothelial cells. We hypothesized that replacing CSS with hypothermic, oxygenated perfusion (HOPE) provides cardioprotection by preserving the vasculature through the production of nitric oxide. Methods Following anaesthesia, diaphragm transection and circulatory arrest in male Wistar rats to simulate DCD conditions, hearts underwent 21 min of warm, in-situ ischemia. Hearts were then subjected to either 30 min of CSS, HOPE, or HOPE with the presence of L-NAME (nitric oxide synthase inhibitor). Afterwards, hearts were reperfused ex-situ for 60 min under oxygenated, normothermic conditions. Results Compared to CSS, HOPE hearts demonstrated higher cardiac function (determined by cardiac output, left ventricular work, as well as contraction and relaxation rates) after 60 min of reperfusion. Furthermore, preliminary results indicate a higher coronary vascular resistance at the end of the hypothermic perfusion period in hearts with L-NAME compared to HOPE alone. Early reperfusion coronary flow, an indicator of vascular function, tended to be higher in hearts subjected to HOPE compared to hearts treated with L-NAME or to the current clinical scenario (CSS). Conclusion Preservation of vascular and contractile function with HOPE appears superior to the current clinical protocol (CSS). The increase in coronary flow during early reperfusion in HOPE hearts was abolished with the addition of L-NAME, indicating that the beneficial vascular effects of HOPE could be mediated by the production of nitric oxide. Consequently, we believe that HOPE holds great potential for preservation of cardiac grafts obtained with DCD.

BACKGROUND Use of the Freedom SOLO (FS) stentless aortic bioprosthesis is limited by a unique and as yet unexplained severe decrease in postoperative platelet count in the absence of FS-related excess bleeding or thromboembolism. We investigated whether anticoagulant-associated pseudothrombocytopaenia could explain this complication. METHODS Thirty consecutive patients (mean age 75.4±7.7 years, 11 [36.7%] female) underwent elective aortic valve replacement (AVR) with either the stented bovine Mitroflow (MF, n=18) or the stentless bovine FS (n=12) aortic valve bioprostheses. Serial platelet counts were performed simultaneously with sampling tubes containing tripotassium (K3-)-EDTA, trisodium (Na3)-citrate, or novel alternative magnesium sulfate (MgSO4, ThromboExact™)-based anticoagulant, respectively. RESULTS Postoperative platelet counts decreased compared with preoperative values in all patients (p

Purpose Donation after circulatory death (DCD) could substantially improve donor heart availability. In DCD, the heart is not only exposed to a period of warm ischemia, but also to a damaging pre-ischemic phase after withdrawal of life support. We investigated the effects of different pre-ischemic lactate levels on post-ischemic recovery using an isolated rat heart model of DCD. Methods Isolated, working rat hearts underwent 20’ aerobic perfusion, 28.5’ global ischemia, and 60’ reperfusion. In addition to 11 mM glucose and 1.2 mM palmitate, three pre-ischemic lactate levels were tested: no lactate (0 Lac), physiologic lactate (0.5 mM; 0.5 Lac), or DCD-relevant lactate (1 mM; 1 Lac). Contractile function, mitochondrial integrity and potential mediators of injury were evaluated. Results During reperfusion, left ventricular work (heart rate-developed pressure product) was significantly greater in 0.5 Lac hearts compared to 0 Lac or 1 Lac. In 0.5 Lac vs 0 Lac hearts, in parallel with increased function, cytochrome c release and carbonylated protein levels were significantly reduced, indicating less mitochondrial damage and oxidative stress, respectively. In 1 Lac vs 0.5 Lac hearts, in parallel with decreased function, cytochrome c release tended to increase, but carbonylated protein levels tended to decrease. Conclusion DCD-relevant levels of pre-ischemic lactate (1 mM) reduce contractile recovery during reperfusion compared to physiologic levels. Although increased pre-ischemic lactate tends to lower oxidative stress during reperfusion; this, alone, is insufficient to maintain functional recovery at DCD-relevant levels. Further investigations are ongoing to clarify underlying mechanisms.

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.

OBJECTIVES Use of the Freedom SOLO (SOLO) stentless aortic bioprosthesis is associated with a unique, and as yet unexplained, observation of postoperative low platelet count. Potential causes include the valve design, tissue and chemicals used for anticalcification treatment. This study compares the platelet response associated with the SOLO to mechanical, stented, sutureless and stentless valve prostheses. METHODS In total, 1587 patients receiving mechanical ATS (n = 199), stented Perimount Magna (Perimount, n = 911), sutureless 3f Enable (n = 34) and Perceval S (n = 48), stentless Pericarbon Freedom (n = 29) or SOLO (n = 366) valves were analysed. The primary end-point was defined as maximum decrease in platelet count expressed as % reduction from baseline within 5 days of aortic valve replacement. RESULTS The smallest decrease in platelets was observed for mechanical valves (44 ± 12%), followed by stented Perimount (50 ± 11%) and sutureless 3f Enable (53 ± 12%) bioprostheses. Compared with these valves, significantly greater reductions in platelets of 61 ± 14%, 60 ± 10% and 64 ± 12% were observed for the Pericarbon Freedom, Perceval S and SOLO, respectively. Multivariable linear regression analysis identified combined procedures, female gender, body surface area, date of operation and longer extracorporeal circulation time, but neither age nor valve size, as significant independent predictors for postoperative low platelet count. After adjustment, Sorin valves caused 13% (95% confidence interval 11-14) greater decrease in platelet counts compared with non-Sorin valves, but were associated with lower need for red blood cell [OR 0.56 (CI 0.41-0.75), P