RESUMO
Background: In heart transplantation, the adoption of hearts from donation after circulatory death (DCD) is considered to be a promising approach to expanding the donor pool. Normothermic ex situ heart perfusion (ESHP) is emerging as a novel preservation strategy for DCD hearts. Therefore, pre-clinical animal models of ESHP are essential to address some key issues before efficient clinical translation. We aim to develop a novel, reproducible, and economical rat model of DCD protocol combined with normothermic ESHP. Methods: Circulatory death of the anesthetized rats in the DCD group was declared when systolic blood pressure below 30 mmHg or asystole was observed after asphyxiation. Additional 15 min of standoff period was allowed to elapse. After perfusion of cold cardioplegia, the DCD hearts were excised and perfused with allogenic blood-based perfusate at constant flow for 90 min in the normothermic ESHP system. Functional assessment and blood gas analysis were performed every 30 min during ESHP. The alteration of DCD hearts submitted to different durations of ESHP (30, 60, and 90 min) in oxidative stress, apoptosis, tissue energy state, inflammatory response, histopathology, cell swelling, and myocardial infarction during ESHP was evaluated. Rats in the non-DCD group were treated similarly but not exposed to warm ischemia and preserved by the normothermic ESHP system for 90 min. Results: The DCD hearts showed compromised function at the beginning of ESHP and recovered over time, while non-DCD hearts presented better cardiac function during ESHP. The alteration of DCD hearts in oxidative stress, apoptosis, tissue energy state, histopathological changes, cell swelling, and inflammatory response didn't differ among different durations of ESHP. At the end of 90-min ESHP, DCD, and non-DCD hearts presented similarly in apoptosis, oxidative stress, inflammatory response, myocardial infarction, and histopathological changes. Moreover, the DCD hearts had lower energy storage and more evident cell swelling compared to the non-DCD hearts. Conclusion: We established a reproducible, clinically relevant, and economical rat model of DCD protocol combined with normothermic ESHP, where the DCD hearts can maintain a stable state during 90-min ESHP.
RESUMO
BACKGROUND: Diabetes mellitus has been proved to be a potent, independent risk factor for mortality in patients with heart failure. However, the influence of diabetes on outcomes after continuous-flow left ventricular assist device (CF-LVAD) implantation is still under debate. This study sought to investigate the effect of preoperative diabetes on all-cause mortality and major postoperative complications among patients with contemporary CF-LVAD support. METHODS: A systematic literature search (PubMed, Embase, and ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials) was performed. The primary endpoint was hazard ratio for all-cause mortality. Secondary endpoints were postoperative complications, including infection, transient ischemia attack, intracranial hemorrhage, and pump thrombosis. A meta-analysis was conducted to generate pooled hazard ratio and 95% confidence interval (CI) for all-cause mortality and pooled odds ratio (OR) and 95% CI for postoperative complications. RESULTS: A total of 1120 patients (478 diabetic patients, 642 nondiabetic patients) from four studies were included in this study. Diabetes did not increase the risk for all-cause mortality among patients with CF-LVAD support (hazard ratio 1.33; 95% CI, 0.88 to 2.02; P = .18). Moreover, pooled analysis demonstrated no significant difference was found in the diabetes and nondiabetes groups in terms of infection (OR 1.18; 95% CI, 0.89 to 1.56; P = .24), transient ischemia attack (OR 1.30; 95% CI, 0.86 to 1.97; P = .21), intracranial hemorrhage (OR 1.86; 95% CI, 0.93 to 3.71; P = .08), and pump thrombosis (OR 1.01; 95% CI, 0.68 to 1.48; P = .97). CONCLUSIONS: The results of this meta-analysis demonstrate that diabetes does not increase all-cause mortality or rates of major adverse events during contemporary CF-LVAD support.