Electroanatomic mapping the interrelation of intracardiac electrical activation with anatomic locations has become an important tool for clinical assessment of complex arrhythmias. Optical mapping of cardiac electrophysiology combines high spatiotemporal resolution of anatomy and physiological function with fast and simultaneous data acquisition. If applied to the clinical setting, this could improve both diagnostic potential and therapeutic efficacy of clinical arrhythmia interventions. The aim of this study was to explore this utility in vivo using a rat model. To this aim, we present a single-camera imaging and multiple light-emitting-diode illumination system that reduces economic and technical implementation hurdles to cardiac optical mapping. Combined with a red-shifted calcium dye and a new near-infrared voltage-sensitive dye, both suitable for use in blood-perfused tissue, we demonstrate the feasibility of in vivo multi-parametric imaging of the mammalian heart. Our approach combines recording of electrophysiologically-relevant parameters with observation of structural substrates and is adaptable, in principle, to trans-catheter percutaneous approaches.
Background
Survival after sudden cardiac arrest is limited by post-arrest myocardial dysfunction but understanding of this phenomenon is constrained by lack of data from a physiological model of disease. In this study, we established an in vivo model of cardiac arrest and resuscitation, characterized the biology of the associated myocardial dysfunction, and tested novel therapeutic strategies.
Methods
We developed rodent models of in vivo post-arrest myocardial dysfunction using extra-corporeal membrane oxygenation (ECMO) resuscitation followed by invasive hemodynamics measurement. In post-arrest isolated cardiomyocytes, we assessed mechanical load and Ca2+ induced Ca2+ release (CICR) simultaneously using the micro-carbon-fiber technique and observed reduced function and myofilament calcium sensitivity. We used a novel-designed fiber optic catheter imaging system, and a genetically encoded calcium sensor GCaMP6f, to image CICR in vivo.
Results
We found potentiation of CICR in isolated cells from this ECMO model and also in cells isolated from an ischemia-reperfusion Langendorff model perfused with oxygenated blood from an arrested animal, but not when reperfused in saline. We established that CICR potentiation begins in vivo. The augmented CICR observed post-arrest was mediated by the activation of Ca2+/calmodulin kinase II (CaMKII). Increased phosphorylation of CaMKII, phospholamban and ryanodine receptor 2 (RyR2) was detected in the post-arrest period. Exogenous adrenergic activation in vivo recapitulated Ca2+ potentiation but was associated with lesser CaMKII activation. Since oxidative stress and aldehydic adduct formation were high post arrest, we tested a small molecule activator of aldehyde dehydrogenase type 2, Alda-1, which reduced oxidative stress, restored calcium and CaMKII homeostasis, and improved cardiac function and post-arrest outcome in vivo.
Conclusions
Cardiac arrest and reperfusion lead to CaMKII activation and calcium long-term potentiation which support cardiomyocyte contractility in the face of impaired post-ischemic myofilament calcium sensitivity. Alda-1 mitigates these effects, normalizes calcium cycling and improves outcome.
OBJECTIVES
Coronavirus disease 2019 is a new contagious disease that has spread rapidly across the world. It is associated with high mortality in those who develop respiratory complications and require admission to intensive care. Extracorporeal membrane oxygenation (ECMO) is a supportive therapy option for selected severely ill patients who deteriorate despite the best supportive care. During the coronavirus disease 2019 pandemic, extra demand led to staff reorganization; hence, cardiac surgery consultants joined the ECMO retrieval team. This article describes how we increased service provisions to adapt to the changes in activity and staffing.
METHODS
The data were collected from 16 March 2020 to 8 May 2020. The patients were referred through a dedicated Web-based referral portal to cope with increasing demand. The retrieval team attended the referring hospital, reviewed the patients and made the final decision to proceed with ECMO.
RESULTS
We reported 41 ECMO retrieval runs during this study period. Apart from staffing changes, other retrieval protocols were maintained. The preferred cannulation method for veno-venous ECMO was drainage via the femoral vein and return to the right internal jugular vein. There were no complications reported during cannulation or transport.
CONCLUSIONS
Staff reorganization in a crisis is of paramount importance. For those with precise transferrable skills, experience can be gained quickly with appropriate supervision. Therefore, the team members were selected based on skill mix rather than on roles that are more traditional. We have demonstrated that an ECMO retrieval service can be reorganized swiftly and successfully to cope with the sudden increase in demand by spending cardiac surgeons services to supplement the anaesthetic-intensivist roles.
Metastatic heart tumours are rare. Most arise from lung, breast and renal cancerous primaries, soft-tissue sarcoma and malignant melanoma. We report the case of a 32-year-old policeman who presented to the emergency department very short of breath with a five-week history of weight loss and malaise. He was noted to have a mass in his right testicle, numerous 2-3 cm round shadows on chest X-ray (CXR) and a large mass within the right ventricular cavity. After much informed debate, the patient was treated solely with chemotherapy with the expectation of cure. We set out this argument and recommendations for future patients with this unusual problem.
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