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.
One of the major medical advances of the twentieth century is the development of cardiac transplantation. Cardiac transplantation is the definitive treatment for end-stage heart disease. Cardiac transplantation relies on organs procured from Brain Dead Donors (DBD). Donation after Circulatory Death (DCD) organs are being increasingly used for renal, liver and lung transplantation. Hearts from DCD donors have not been utilized as there is a fear that they will have sustained irreversible myocardial injury post cardiac arrest. We have a limited understanding of Post cardiac arrest myocardial depression due to the lack of a good physiological model of the disease. Objective: To develop a model of in-vivo cardiac arrest and resuscitation in order to characterize the biology of the associated myocardial dysfunction and test potential therapeutic strategies. Methods and Results: We developed a rodent model of post arrest myocardial depression (DCD model) using extracorporeal membrane oxygenation for resuscitation, followed by invasive haemodynamic measurements. In isolated cardiomyocytes, we assessed mechanical load and Ca2+-induced Ca2+ release (CICR) simultaneously using the microcarbon fiber technique and observed reduced function and myofilament calcium sensitivity in the post arrest group. Additionally, in contrast with findings from Langendorff models of ischemia-reperfusion, there is a marked augmentation of CICR in isolated cells. This increase in calcium serves to maintain contraction in the face of myofilament dysfunction and, it seems to be mediated by autophosphorylation of calcium-calmodulin protein kinase II (CAMKII). It is further dependent on ryanodine receptor calcium but not PKA leading us to speculate that it is triggered by adrenergic activation but maintained by CAMKII. Finally, activation of aldehyde-dehydrogenase II by the small molecule Alda-1 dramatically improved whole animal and cellular contractile performance after arrest, and restored CICR to close to normal levels. Conclusions: Cardiac arrest and reperfusion lead to calcium cardiac memory, which support cardiomyocyte contractility in the face of post arrest myofilament calcium sensitivity. Alda-1 mitigates these effects and improves outcome.
Abstract Pulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be indicated to treat these residual vascular lesions. We compared whether patients post‐PEA (PP) treated by BPA derived similar benefit to those who had inoperable CTEPH (IC), and assessed predictors of BPA response after surgery. We treated 109 patients with BPA—89 with IC and 20 PP. Serial right heart catheterization performed at baseline (immediately before BPA) and 3 months after completing BPA, compared pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) as well as change in WHO functional class and 6‐minute walk distance. We also assessed the impact of total thrombus tail length (TTTL) from photographed PEA surgical specimens and PP computed tomography pulmonary angiography (CTPA)‐quantified residual disease burden on BPA response. PP and IC groups did not differ significantly in terms of demographics, baseline hemodynamics or procedural characteristics. However, IC derived greater hemodynamic benefit from BPA: ΔPVR (−27.9 ± 20.2% vs. −13.9 ± 23.9%, p < 0.05) and ΔmPAP (−17.1 ± 14.4% vs. −8.5 ± 18.0%, p < 0.05). There was a negative correlation between pre‐BPA PVR and TTTL ( r = −0.47, p < 0.05) which persisted post‐BPA. PVR, mPAP, WHO FC and 6MWD were not improved significantly post‐BPA in PP patients. BPA response was not related to TTTL terciles or CTPA‐quantified residual disease burden. Patients PP experienced inferior response to BPA, despite similar baseline and procedural characteristics to IC. BPA does not abolish the relationship between TTTL and postsurgical PVR in PP patients, suggesting that BPA is less effective in treating residual PH after surgery in an experienced surgical center.
Survival after sudden cardiac arrest is limited by postarrest myocardial dysfunction, but understanding of this phenomenon is constrained by a 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.We developed rodent models of in vivo postarrest myocardial dysfunction using extracorporeal membrane oxygenation resuscitation followed by invasive hemodynamics measurement. In postarrest isolated cardiomyocytes, we assessed mechanical load and Ca(2) (+)-induced Ca(2+) release (CICR) simultaneously using the microcarbon fiber technique and observed reduced function and myofilament calcium sensitivity. We used a novel fiberoptic catheter imaging system and a genetically encoded calcium sensor, GCaMP6f, to image CICR in vivo.We found potentiation of CICR in isolated cells from this extracorporeal membrane oxygenation model and 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 after arrest was mediated by the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Increased phosphorylation of CaMKII, phospholamban, and ryanodine receptor 2 was detected in the postarrest period. Exogenous adrenergic activation in vivo recapitulated Ca(2+) potentiation but was associated with lesser CaMKII activation. Because oxidative stress and aldehydic adduct formation were high after 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 postarrest outcome in vivo.Cardiac arrest and reperfusion lead to CaMKII activation and calcium long-term potentiation, which support cardiomyocyte contractility in the face of impaired postarrest myofilament calcium sensitivity. Alda-1 mitigates these effects, normalizes calcium cycling, and improves outcome.
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.
Abstract 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.
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