Impact of minimal invasive extracorporeal circulation on systemic inflammatory response - a randomized trial.

BACKGROUND: Extracorporeal circulation causes a systemic inflammatory response, that may cause postoperative haemodynamic instability and end-organ dysfunction. This study aimed to investigate the impact of minimal invasive extracorporeal circulation (MiECC) on the systemic inflammatory response compared with conventional extracorporeal circulation (CECC). METHODS: Patients undergoing coronary artery bypass grafting were randomized to MiECC (n = 30) and CECC (n = 30). Primary endpoint was tumor necrosis factor-α. Secondary endpoints were other biochemical markers of inflammation (IL1ß, IL6 and IL8, C-reactive protein, leukocytes), and markers of inadequate tissue perfusion and tissue damage (lactate dehydrogenase, lactate and creatine kinase-MB). In addition, we registered signs of systemic inflammatory response syndrome, haemodynamic instability, atrial fibrillation, respiratory dysfunction, and infection. RESULTS: Patients treated with MiECC showed significantly lower levels of tumor necrosis factor-α than CECC during and early after extracorporeal circulation (median: MiECC 3.4 pg/mL; CI 2.2-4.5 vs. CECC 4.6 pg/mL; CI 3.4-5.6; p = 0.01). Lower levels of creatine kinase-MB and lactate dehydrogenase suggested less tissue damage. However, we detected no other significant differences in any other markers of inflammation, tissue damage or in any of the clinical outcomes. CONCLUSIONS: Lower levels of TNF-α after MiECC compared with CECC may reflect reduced inflammatory response, although other biochemical markers of inflammation were comparable. Our results suggest better end-organ protection with MiECC compared with CECC. Clinical parameters related to systemic inflammatory response were comparable in this study. CLINICAL REGISTRATION NUMBER: NCT03216720.

Development of a human heart-sized perfusion system for metabolic imaging studies using hyperpolarized [1-13 C]pyruvate MRI.

PURPOSE: Increasing worldwide demand for cardiac transplantation has spurred new developments to increase the donor pool. Normothermic preservation of heart grafts for transplantation is an emerging strategy to improve the utilization of marginal grafts. Hyperpolarized MR using metabolic tracers such as [1-13 C]pyruvate, provide a novel means of investigating metabolic status without the use of ionizing radiation. We demonstrate the use of this methodology to examine ex vivo perfused porcine heart grafts. METHODS: Hearts from three 40-kg Danish domestic pigs were harvested and subsequently perfused in Langendorff mode under normothermic conditions, using an MR-compatible perfusion system adapted to the heart. Proton MRI and hyperpolarized [1-13 C]pyruvate were used to investigate and quantify the functional and metabolic status of the grafts. RESULTS: Hearts were perfused with whole blood for 120 min, using a dynamic contrast-enhanced perfusion experiment to verify successful myocardial perfusion. Hyperpolarized [1-13 C]pyruvate MRI was used to assess the metabolic state of the myocardium. Functional assessment was performed using CINE imaging and ventricular pressure data. High lactate and modest alanine levels were observed in the hyperpolarized experiment. The functional assessment produced reduced functional parameters. This suggests an altered functional and metabolic profile compared with corresponding in vivo values. CONCLUSION: We investigated the metabolic and functional status of machine-perfused porcine hearts. Utilizing hyperpolarized methodology to acquire detailed myocardial metabolic information-in combination with already established MR methods for cardiac investigation-provides a powerful tool to aid the progress of donor heart preservation.

Graft assessment of the ex vivo perfused porcine kidney using hyperpolarized [1-13 C]pyruvate.

PURPOSE: Normothermic perfusion is an emerging strategy for donor organ preservation and therapy, incited by the high worldwide demand for organs for transplantation. Hyperpolarized MRI and MRS using [1-13 C]pyruvate and other 13 C-labeled molecules pose a novel way to acquire highly detailed information about metabolism and function in a noninvasive manner. This study investigates the use of this methodology as a means to study and monitor the state of ex vivo perfused porcine kidneys, in the context of kidney graft preservation research. METHODS: Kidneys from four 40-kg Danish domestic pigs were perfused ex vivo with whole blood under normothermic conditions, using an MR-compatible perfusion system. Kidneys were investigated using 1 H MRI as well as hyperpolarized [1-13 C]pyruvate MRI and MRS. Using the acquired anatomical, functional and metabolic data, the state of the ex vivo perfused porcine kidney could be quantified. RESULTS: Four kidneys were successfully perfused for 120 minutes and verified using a DCE perfusion experiment. Renal metabolism was examined using hyperpolarized [1-13 C]pyruvate MRI and MRS, and displayed an apparent reduction in pyruvate turnover compared with the usual case in vivo. Perfusion and blood gas parameters were in the normal ex vivo range. CONCLUSION: This study demonstrates the ability to monitor ex vivo graft metabolism and function in a large animal model, resembling human renal physiology. The ability of hyperpolarized MRI and MRS to directly compare the metabolic state of an organ in vivo and ex vivo, in combination with the simple MR implementation of normothermic perfusion, renders this methodology a powerful future tool for graft preservation research.