Although the myocardium contains progenitor cells potentially capable of regenerating tissue upon lethal ischaemic injury, their actual role in post-infarction heart healing is negligible. Therefore, transplantation of extra-cardiac stem cells is a promising therapeutic approach for post-infarction heart dysfunction. Paracrine cardiotropic factors released by the grafted cells, such as the cardiotropic hormone relaxin (RLX), may beneficially influence remodelling of recipient hearts. The current study was designed to address whether grafting of mouse C2C12 myoblasts, genetically engineered to express green fluorescent protein (C2C12/GFP) or GFP and RLX (C2C12/RLX), are capable of improving long-term heart remodelling in a rat model of surgically induced chronic myocardial infarction. One month after myocardial infarction, rats were treated with either culture medium (controls), or C2C12/GFP cells, or C2C12/RLX cells plus exogenous RLX, or exogenous RLX alone. The therapeutic effects were monitored for 2 further months. Cell transplantation and exogenous RLX improved the main echocardiographic parameters of cardiac function, increased myocardial viability (assessed by positron emission tomography), decreased cardiac sclerosis and myocardial cell apoptosis and increased microvascular density in the post-infarction scar tissue. These effects were maximal upon treatment with C2C12/RLX plus exogenous RLX. These functional and histopathological findings provide further experimental evidence that myoblast cell grafting can improve myocardial performance and survival during post-infarction heart remodelling and dysfunction. Further, this study provides a proof-of-principle to the novel concept that genetically engineered grafted cells can be effectively employed as cell-based vehicles for the local delivery of therapeutic cardiotropic substances, such as RLX, capable of improving adverse heart remodelling.
We report the use of extra-corporeal cardiopulmonary support (ECLS), in a case of complicating refractory severe cardiogenic shock, in a patient with Tako-tsubo cardiomyopathy (TC). Tako-tsubo cardiomyopathy syndrome is characterized by left ventricular (LV) wall motion abnormalities, usually without coronary artery disease, mimicking the diagnosis of acute coronary syndrome. This ventricular dysfunction is typically reversible in the acute phase, though it can progress into refractory cardiogenic shock with limited therapeutic options available. Here, we report for the first time in a Tako-tsubo patient with refractory cardiogenic shock, the use of ECLS treatment in order to unload the heart, sustain circulation and end-organ perfusion, and promote potential ventricular recovery. Extra-corporeal life support allowed inotropic drug weaning while maintaining end-organ function and supported the patient until myocardial recovery. The patient recovered completely, and a normal LV ejection fraction was documented by 2D echocardiography on day 7. From our experience, ECLS can be an appropriate treatment for severe refractory cardiogenic shock in patients with TC. Extra-corporeal life support was an effective ultimate solution.--
Pharmacologic challenge with sodium channel blockers is part of the diagnostic workout in patients with suspected Brugada syndrome. The test is overall considered safe but both ajmaline and flecainide detain well known pro-arrhythmic properties. Moreover, the treatment of patients with life-threatening arrhythmias during these diagnostic procedures is not well defined. Current consensus guidelines suggest to adopt cautious protocols interrupting the sodium channel blockers as soon as any ECG alteration appears. Nevertheless, the risk of life-threatening arrhythmias persists, even adopting a safe and cautious protocol and in absence of major arrhythmic risk factors. The authors revise the main published case studies of sodium channel blockers challenge in adults and in children, and summarize three cases of untreatable ventricular arrhythmias discussing their management. In particular, the role of advanced cardiopulmonary resuscitation with extra-corporeal membrane oxygenation is stressed as it can reveal to be the only reliable lifesaving facility in prolonged cardiac arrest.
OBJECTIVES Patients with mechanical circulatory support bridged to a heart transplant (HTx) are at higher risk of postoperative graft dysfunction. In this subset, a mode of graft preservation that shortens graft ischaemia should be beneficial. METHODS The outcomes of 38 patients on mechanical circulatory support (extracorporeal life support, left ventricular assist device and biventricular assist device) who received a HTx between 2015 and 2020 were analysed according to the method of graft preservation: cold storage (CS) group, 24 (63%) or ex vivo perfusion (EVP) group, 14 (37%). RESULTS The median age was 57 (range 30–73) vs 64 (35–75) years (P = 0.10); 88% were men (P = 0.28); extracorporeal life support was more frequent in the CS group (54% vs 36%; P = 0.27) versus left ventricular and biventricular assist devices in the EVP group (46% vs 64%; P = 0.27). Clamping time was shorter in the EVP group (P < 0.001) and ischaemic time >4 h was higher in the CS group (P = 0.01). Thirty-day mortality was 13% (0–27%) in the CS group and 0% (P = 0.28) in the EVP group. A significantly lower primary graft failure [7% (0–23%) vs 42% (20–63%); P = 0.03] was observed in the EVP group. Survival at 1 year was 79 ± 8% (63–95%) in the CS group and 84 ± 10% (64–104%) in the EVP group (P = 0.95). CONCLUSIONS Our results support the use of ex vivo graft perfusion in patients on mechanical circulatory support as a bridge to a HTx. This technique, by shortening graft ischaemic time, seems to improve post-HTx outcomes.
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