Aqueous fish extract increases survival in the mouse model of cytostatic toxicity

<p>Abstract</p> <p>Background</p> <p>Treatment of cancer patients with anthracycline antibiotic doxorubicin (DOX) may be complicated by development of acute and chronic congestive heart failure (CHF), malignant arrhythmias and death. The aim of this study was to test whether an aqueous low molecular weight (LMW) extract from cod muscle decreases acute mortality in the mouse model of acute CHF caused by DOX.</p> <p>Methods</p> <p>A LMW fraction (<500 Da) of the aqueous phase of cod light muscle (AOX) was used for treatment of male BALB/c mice (~25 g, n = 70). The animals were divided into four groups, DOX + AOX (n = 20), DOX + saline (NaCl) (n = 30), NaCl + AOX (n = 10) and NaCl only (n = 10). Echocardiography was performed in the separate subgroups (DOX treated n = 6 and controls n = 6) to verify the presence and the grade of acute CHF. The cod extract was delivered by subcutaneously implanted osmotic minipumps over the period of 2 weeks. High-dose injection of DOX was administered to randomly selected animals. The animals received single intraperitoneal injection of DOX (25 mg/kg) and were followed over two weeks for mortality.</p> <p>Results</p> <p>Mortality rate was 68% lower (p < 0.05) in the mice treated with the extract. The analyses of cod extract have shown strong antioxidative effect <it>in vitro</it>.</p> <p>Conclusion</p> <p>The aqueous LMW cod muscles extract decreases mortality in the mouse model of DOX induced acute CHF. This effect may be mediated by cardioprotection through antioxidative mechanisms.</p

Recovery and prognostic value of myocardial strain in ST-segment elevation myocardial infarction patients with a concurrent chronic total occlusion

Objectives: Global left ventricular (LV) function is routinely used to assess cardiac function; however, myocardial strain is able to identify more subtle dysfunction. We aimed to determine the recovery and prognostic value of featuring tracking (FT) cardiovascular magnetic resonance (CMR) strain in ST-segment elevation myocardial infarction (STEMI) patients with a concurrent chronic total occlusion (CTO). Methods: In the randomized EXPLORE trial, there was no significant difference in global LV functio

Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

<p>Abstract</p> <p>Background</p> <p>In the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events.</p> <p>Methods/Design</p> <p>The Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction (EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years.</p> <p>Discussion</p> <p>The ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome.</p> <p>Trial registration</p> <p>trialregister.nl NTR1108.</p

Myocardial metabolism in experimental infarction and heart failure

Abstract The heart is an organ heavily dependent on exogenous lipids for the oxidative production of adenosine-triphosphate (ATP) and therefore maintenance of normal cellular energy homeostasis. However, high energy flux organs such as the heart must closely match lipid import and utilization or otherwise lipids will accumulate in the cardiomyocytes. Intracellular lipid accumulation has detrimental effects on cardiomyocyte function and viability and results in development of lipotoxic cardiomyopathy. Different pathophysiological states such as congestive heart failure (CHF), myocardial ischemia and hypertrophy are associated with myocardial lipid accumulation. The heart, however, produces and secretes apolipoprotein B containing lipoproteins (apoB), which enables the cardiomyocyte to export lipids. It has been proposed that apoB may be involved in cardioprotection by means of elimination of toxic intracellular lipids. An important part of the patologic cardiac remodelling in CHF is disturbed myocardial energy metabolism. The failing myocardium contains low levels of creatine (Cr), phosphocreatine (PCr), and ATP. Cr depletion in the heart may result in disturbed energy production, transfer and utilisation of chemical energy and therefore compromised left ventricular function. Growth hormone (GH) has been shown to exert numerous positive effects on the failing and remodelled heart suggesting that GH may be an additional agent in the treatment of CHF and myocardial infarction (MI). The aims of this thesis were: I. To investigate in vivo the effects of Cr depletion in mice on left ventricular function and morphology, energy metabolism and myocardial lipids. II. To investigate importance of endogenous lipoproteins in the heart for cardiac function, morphology and survival in the settings of acute and chronic myocardial infarction and doxorubicine induced acute heart failure. III. To investigate the effects of Growth hormone on arrhythmogenesis IV. To evaluate the predictive value of native cardiac reserve on outcome after myocardial infarction in mice Using a mouse model of chemically-induced Cr depletion we show in vivo that myocardial Cr depletion leads to disturbed energy metabolism, left ventricular dysfunction, pathologic remodeling and accumulation of intracellular triglycerides. These alterations are reversible upon the normalization of the creatine levels suggesting that creatine metabolism may be an important target for pharmacological interventions. Using transgenic animals we show that myocardial apoB may be a cardioprotective system which is activated during ischemia, pathologic remodeling and heart failure and may be important for survival in myocardial infarction and heart failure. We show that GH possess novel antiarrhythmic properties in the setting of acute MI which adds further evidence to the concept of GH as an additional pharmacological agent in the treatment of CHF and MI. We demonstrate that native cardiac reserve is a predictor of post-MI survival

Comorbidities prior to out-of-hospital cardiac arrest and diagnoses at discharge among survivors

Background Out-of-hospital cardiac arrest (OHCA) has a dismal prognosis with overall survival around 10%. Previous studies have shown conflicting results regarding the prevalence and significance of comorbidities in OHCA, as well as the underlying causes. Previously, 80% of sudden cardiac arrest have been attributed to coronary artery disease. We studied comorbidities and discharge diagnoses in OHCA in all of Sweden.Methods We used the Swedish Registry of Cardiopulmonary Resuscitation, merged with the Inpatient Registry and Outpatient Registry to identify patients with OHCA from 2010 to 2020 and to collect all their comorbidities as well as discharge diagnoses (among those admitted to hospital). Patient characteristics were described using means, medians and SD. Survival curves were performed among hospitalised patients with acute myocardial infarction (AMI) as well as heart failure.Results A total of 54 484 patients with OHCA were included, of whom 35 894 (66%) were men. The most common comorbidities prior to OHCA were hypertension (43.6%), heart failure (23.6%), chronic ischaemic heart disease (23.6%) and atrial fibrillation (22.0%). Previous AMI was prevalent in 14.8% of men and 10.9% of women. Among women, 18.0% had type 2 diabetes, compared with 19.6% of the men. Among hospitalised patients, 30% were diagnosed with AMI, 27% with hypertension, 20% with ischaemic heart disease and 18% with heart failure as discharge diagnoses.Conclusion In summary, we find evidence that nowadays a minority of cardiac arrests are due to coronary artery disease and AMIs and its complications. Only 30% of all cases of OHCA admitted to hospital were diagnosed with AMI. Coronary artery disease is now likely in the minority with regard to causes of OHCA