Functional, morphologic, and molecular characterization of cold storage injury

ObjectiveCold storage is used to preserve tissue for later transplantation. There is particular interest in prolonging cold storage time for transplantation purposes. To date, the mechanisms that contribute to vascular dysfunction in response to cold storage are poorly understood. The present study aims to characterize cold storage injury of blood vessels on functional and molecular levels.MethodsTo assess vessel function of mouse aorta, isometric force measurements were performed in a Mulvany myograph after cold storage at 4°C for various intervals. Morphologic changes were judged by histologic analysis of aortic cross-sections. To characterize cold storage-induced alterations on RNA levels, microarray analysis with subsequent polymerase chain reaction analysis was performed.ResultsCold storage for 2 days revealed significant impairment of vessel function with respect to potassium-induced vessel tone development and acetylcholine-induced vessel relaxation. Detailed analysis of acetylcholine-mediated vascular response using specific pharmacologic blockers revealed that calcium-activated potassium channels seem to be impaired after 2 days of cold storage. At this point, no severe histologic changes (eg, elastic fiber disruption) were visible. RNA expression of 24 genes was significantly changed due to cold storage even after 2 hours. These include genes associated with vessel tone development (prostaglandin E3 receptor), cardiovascular function (adiponectin), electron transport chain (uncoupling protein 1), or calcium signaling (protein kinase A regulatory subunit 2b).ConclusionsLong-term cold storage impairs vascular function, especially with respect to potassium signaling by calcium-dependent potassium channels. Microarray analysis confirmed impairment of pathways that are involved in calcium signaling and vascular function. Furthermore, various genes were significantly altered even after 2 hours, significantly before functional impairment was observed.Clinical RelevanceIn bypass surgery, vessels are stored ex situ for <2 hours and for vessel banking for up to 48 hours during decontamination before cryopreservation. We investigated the onset of storage-induced alterations. The experiments reveal various genes were altered significantly, even within the first 2 hours of cold storage. This is of major importance, because of the time delay between regulation of messenger RNA and protein level and functional consequences. The alterations described here on the molecular level occur before any alterations on morphologic or functional levels are obvious. These molecular alterations, however, may affect later graft function

Comparison of external and intravascular cooling to induce hypothermia in patients after CPR

Objective: Hypothermia has been shown to reduce neurologic deficits in patients after cardiopulmonary resuscitation (CPR). It was not clear if intravascular cooling is superior to standard external cooling in inducing hypothermia. Goal of this study was to compare intravascular cooling with an automated cooling device with external cooling in everyday practice on a cardiac-care ICU (intensive care unit)

Remote Ischemic Preconditioning Neither Improves Survival nor Reduces Myocardial or Kidney Injury in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI)

BACKGROUND: Peri-interventional myocardial injury occurs frequently during transcatheter aortic valve implantation (TAVI). We assessed the effect of remote ischemic preconditioning (RIPC) on myocardial injury, acute kidney injury (AKIN) and 6-month mortality in patients undergoing TAVI. METHODS: We performed a prospective single-center controlled trial. Sixty-six patients treated with RIPC prior to TAVI were enrolled in the study and were matched to a control group by propensity-score. RIPC was applied to the upper extremity using a conventional tourniquet. Myocardial injury was assessed using high-sensitive troponin-T (hsTnT), and kidney injury was assessed using serum creatinine levels. Data were compared with the Wilcoxon-Rank and McNemar tests. Mortality was analysed with the log-rank test. RESULTS: TAVI led to a significant rise of hsTnT across all patients (p < 0.001). No significant inter-group difference in maximum troponin release or areas-under-the-curve was detected. Medtronic CoreValve and Edwards Sapien valves showed similar peri-interventional troponin kinetics and patients receiving neither valve did benefit from RIPC. AKIN occurred in one RIPC patient and four non-RIPC patients (p = 0.250). No significant difference in 6-month mortality was observed. No adverse events related to RIPC were recorded. CONCLUSION: Our data do not show a beneficial role of RIPC in TAVI patients for cardio- or renoprotection, or improved survival