A modified intraventricular balloon method for functional assessment of hearts from donation after circulatory death.

Objective: Functional assessment of hearts during ex-vivo heart perfusion is not well-established. Conventional intraventricular balloon methods for large animals sacrifice the mitral valve. This study assessed the effectiveness of the modified intraventricular balloon method in comparison with other modalities used during working mode in juvenile pigs. Methods: Following asphyxia circulatory arrest, hearts were ischemic for 15 minutes and then reperfused on an ex-vivo device for 2 hours before switching to working mode. Left ventricular pressure was continuously measured during reperfusion by a saline-filled balloon fixated in the left atrium. Spearman Correlation Coefficients with linear regression lines with confidence intervals were analyzed. Results: Maximum dp/dt at 90 minutes of reperfusion and minimum dp/dt at 60 minutes of reperfusion showed a moderate positive correlation to that in working mode, respectively (Rs = 0.61, P = .04 and Rs = 0.60, P = .04). At 60 minutes of reperfusion, minimum dp/dt showed moderate positive correlation to tau (Rs = 0.52, P = .08). Myocardial oxygen consumption during reperfusion consistently decreased at least 30% compared to working mode (at 90 minutes as the highest during reperfusion, 3.3 ± 0.8; in working mode, 5.6 ± 1.4, mLO2/min/100 g, P < .001). Conclusions: Functional parameters of contractility and relaxation measured during reperfusion by the modified balloon method showed significant correlations to respective parameters in working mode. This mitral valve sparing technique can be used to predict viability and ventricular function in the early phase of ex-vivo heart perfusion without loading the heart during working mode.

Impact of Hemoglobin Level in Ex Vivo Heart Perfusion on Donation After Circulatory Death Hearts: A Juvenile Porcine Experimental Model.

BACKGROUND: Ex vivo heart perfusion (EVHP) of donation after circulatory death (DCD) hearts has become an effective strategy in adults; however, the small circulating volume in pediatrics poses the challenge of a low-hemoglobin (Hb) perfusate. We aimed to determine the impact of perfusate Hb levels during EVHP on DCD hearts using a juvenile porcine model. METHODS: Sixteen DCD piglet hearts (11-14 kg) were reperfused for 4 h in unloaded mode followed by working mode. Metabolism, cardiac function, and cell damage were compared between the low-Hb (Hb, 5.0-5.9 g/dL; n = 8) and control (Hb, 7.5-8.4 g/dL; n = 8) groups. Between-group differences were evaluated using 2-sample t-tests or Fisher's Exact tests. RESULTS: During unloaded mode, the low-Hb group showed lower myocardial oxygen consumption (P < 0.001), a higher arterial lactate level (P = 0.001), and worse systolic ventricular function (P < 0.001). During working mode, the low-Hb group had a lower cardiac output (mean, 71% versus 106% of normal cardiac output, P = 0.010) and a higher arterial lactate level (P = 0.031). Adjusted cardiac troponin-I (P = 0.112) did not differ between the groups. Morphological myocyte injury in the left ventricle was more severe in the low-Hb group (P = 0.028). CONCLUSIONS: Low-Hb perfusate with inadequate oxygen delivery induced anaerobic metabolism, resulting in suboptimal DCD heart recovery and declined cardiac function. Arranging an optimal perfusate is crucial to organ protection, and further endeavors to refine the priming volume of EVHP or the transfusion strategy are required.

Cardioprotective Actions of a Glucagon-like Peptide-1 Receptor Agonist on Hearts Donated After Circulatory Death.

Background Heart transplantation with a donation after circulatory death (DCD) heart is complicated by substantial organ ischemia and ischemia-reperfusion injury. Exenatide, a glucagon-like peptide-1 receptor agonist, manifests protection against cardiac ischemia-reperfusion injury in other settings. Here we evaluate the effects of exenatide on DCD hearts in juvenile pigs. Methods and Results DCD hearts with 15-minutes of global warm ischemia after circulatory arrest were reperfused ex vivo and switched to working mode. Treatment with concentration 5-nmol exenatide was given during reperfusion. DCD hearts treated with exenatide showed higher myocardial oxygen consumption (exenatide [n=7] versus controls [n=7], over 60-120 minutes of reperfusion, P<0.001) and lower cardiac troponin-I release (27.94±11.17 versus 42.25±11.80 mmol/L, P=0.04) during reperfusion compared with controls. In working mode, exenatide-treated hearts showed better diastolic function (dp/dt min: -3644±620 versus -2193±610 mm Hg/s, P<0.001; Tau: 15.62±1.78 versus 24.59±7.35 milliseconds, P=0.02; lateral e' velocity: 11.27 ± 1.46 versus 7.19±2.96, P=0.01), as well as lower venous lactate levels (3.17±0.75 versus 5.17±1.44 mmol/L, P=0.01) compared with controls. Higher levels of activated endothelial nitric oxide synthase (phosphorylated to total endothelial nitric oxide synthase levels: 2.71±1.16 versus 1.37±0.35, P=0.02) with less histological evidence of endothelial damage (von Willebrand factor expression: 0.024±0.007 versus 0.331±0.302, pixel/µm, P=0.04) was also observed with exenatide treatment versus controls. Conclusions Acute treatment of DCD hearts with exenatide limits myocardial and endothelial injury and improves donor cardiac function.

Flow-targeted pediatric ex vivo heart perfusion in donation after circulatory death: A porcine model.

BACKGROUND: The optimal blood flow and pressure to perfuse pediatric hearts from donation after circulatory death (DCD) on the ex vivo perfusion system has not been elucidated. This study sought to investigate the optimal perfusion strategy for pediatric DCD hearts by using a juvenile porcine model comparing pressure- vs flow-targeted strategy. METHODS: The hearts of the juvenile DCD pigs were explanted, and the coronary arteries were perfused for 2 hours by the ex vivo heart perfusion system with 2 different perfusion strategies; pressure-targeted perfusion (target coronary perfusion pressure: 40 mm Hg, group A) and flow-targeted perfusion (target coronary perfusion flow: 10 ml/kg/min, group B). The working model heart perfusion was used to assess systolic and diastolic myocardial performance. RESULTS: The body weight, warm and cold ischemic time, and ex vivo perfusion time were comparable between the groups. In the working model, group B showed significantly preserved cardiac output (A: 70.5 ± 15.3 ml/kg/min vs B: 113.8 ± 15.0 ml/kg/min, p < 0.01), stroke volume (A: 0.4 ± 0.1 ml/kg vs B: 0.7 ± 0.1 ml/kg, p < 0.01), and ejection fraction (A: 18.8% ± 5.9% vs B: 35.0% ± 10.6%, p < 0.01). E/e' and Tei index were also significantly preserved in group B. The percentage gain of heart weight after ex vivo (net increase of the heart weight divided by heart weight at baseline) was significantly smaller in group B (A: 20.0% ± 5.3% vs B: 11.6% ± 5.0%, p < 0.05). Troponin-I, myocardial hemorrhage, oxidative stress markers; myeloperoxidase and 8-hydroxy-2'-deoxyguanosine were also significantly lower after ex vivo perfusion in group B (p < 0.05). CONCLUSIONS: The tightly controlled flow-targeted myocardial perfusion strategy for DCD donor hearts achieved better myocardial performance by causing less myocardial edema and limiting myocardial reperfusion injury.

Antithrombin activity and heparin response in neonates and infants undergoing congenital cardiac surgery: a retrospective cohort study.

PURPOSE: The immature coagulation system during infancy has age-related physiological differences in proteins that contribute to significant variation in heparin responsiveness through alterations in heparin-enhanced thrombin inhibition. The primary aim of this study was to evaluate the relationship between preoperative antithrombin (AT) activity and heparin responsiveness in neonates and infants undergoing congenital cardiac surgery. METHODS: In this retrospective cohort study, neonates (aged 0-28 days) and infants (aged 29-365 days) undergoing congenital cardiac surgery in the 12-month period from October 2013 to 2014 were studied. The two age groups were compared for the primary endpoint of heparin response measured by the heparin sensitivity index (HSI), with heparin loading doses and heparin resistance being secondary endpoints. Multivariable linear regression analyses were used to explore the relationship between AT activity and heparin response measured by HSI. RESULTS: There were 122 infants and 19 neonates included in the study. After adjusting for low-molecular-weight heparin, unfractionated heparin, and platelet count, there was a significant relationship between AT activity and HSI (r = 0.44; P = 0.009). The median [interquartile range] HSI did not differ between neonates and infants (0.76 [0.69- 0.98] vs 0.89 [0.70-1.10] sec·unit(-1)·kg(-1), respectively; median difference, 0.08; 95% confidence interval [CI], -0.01 to 0.17; P = 0.182), despite the mean (standard deviation) AT activity differing between age groups [60 (16)% vs 84 (18)%, respectively; mean difference, 24; 95% CI, 15 to 32; P < 0.001]. CONCLUSIONS: There was a moderate relationship between AT activity and heparin response measured by HSI. Comparing neonates and infants, there was similar heparin responsiveness measured by HSI despite differing AT activity levels. These findings should help guide the perioperative administration of exogenous AT to neonates and infants and suggest that, outside the neonatal period, preoperative AT activity may be used to identify children at risk of decreased heparin responsiveness.