Co-transplantation of Mesenchymal Stem Cell Derived Exosomes and Autologous Mitochondria for Patients...
Myocardial InfarctionMyocardial Ischemia1 moreHeart failure (HF) and acute myocardial infarction that often follows are among the main causes of disability and death worldwide. As such, new treatments and biological drugs are needed to protect the heart against the harmful effects of ischemia and also reperfusion injury (IRI), preserve cardiac function, reduce the zone of myocardial infarction (MI), and improve patient outcomes. In this regard, it has been shown that mitochondrial dysfunction has a key role in the pathogenesis of heart ischemia, cardiomyopathy, and reperfusion injury. in this study which includes 4 groups of intervention, we try to minimize the damage by transplantation of mitochondria and administration of MSC-derived exosomes. MSC-derived exosomes limit inflammatory damage while fresh autologous exosomes limit oxidative stress.
Is Myocardial Stunning Induced by Continuous Renal Replacement Therapy a Reality in Critically Ill...
Acute Kidney Injury KDIGO 3Continuous Renal Replacement Therapy Initiated by the Clinician in Charge Without Emergency1 moreMyocardial stunning during chronic intermittent hemodialysis is a well-described phenomenon. Little case series of patients presenting myocardial stunning during renal replacement therapy for acute kidney injury in critically ill patients are reported, with intermittent hemodialysis and continuous renal replacement therapy. However, the small sample sizes and the absence of a control arm limit their interpretation, mainly whether the myocardial stunning may be related to cardiac loading conditions variations and whether it may impact the hemodynamic. The investigator hypothesize that myocardial stunning induced by renal replacement therapy is frequent, independent from cardiac loading conditions and associated with peripheral hypoperfusion.
Intracoronary Administration of Levosimendan in Cardiac Surgery Patients
Myocardial StunningIncomplete recovery from ischemia causes stunned myocardium. Ischemia may be due to coronary artery disease or aortic cross-clamping during surgery. Stunning leads to myocardial dysfunction. It has been suggested that the mechanism responsible for the contractile depression in stunned myocardium is a decreased sensitivity of the myofibrils to calcium. Levosimendan is a calcium sensitizer, which has been shown to improve the function of stunned myocardium without obvious impairment of diastolic function. Systemic vasodilation and need of vasoconstrictive medication is usually apparent after administration of levosimendan. Colucci et al have demonstrated that with intracoronary administration of milrinone, another inodilator, systemic vasodilation could be excluded. If this is true with levosimendan, it may be possible to improve left ventricular hypo/dyskinesia without afterload reduction by adding levosimendan into cardioplegia solution. The investigators hypotize that levosimendan, delivered together with cardioplegia, can improve LV dysfunction after opening of aortic cross-clamp in patients undergoing aortic valve and coronary artery bypass operation. Our primary endpoint is a change in cardiac output 15 min after separation from cardiopulmonary bypass compared to the baseline. Secondary endpoints are a change in LV ejection fraction from baseline to 5 min after sternal closure and cTnT/CK-MB on the first postoperative morning.
Immunomodulatory Biomimetic Device to Treat Myocardial Stunning in End-stage Renal Disease Patients...
End Stage Renal DiseaseAcute Kidney Injury1 moreHemodialysis is a therapy that filters waste, removes extra fluid and balances electrolytes. In hemodialysis, blood is removed from the body and filtered through a man-made membrane called a dialyzer, and then the filtered blood is returned to the body. Hemodialysis is associated with injury to the heart muscle called myocardial stunning. This may occur for many reasons, including removal of fluid during dialysis or low blood pressure. Initial ischemia and subsequent white blood cell infiltration into the injured myocardium play a critical role in the degree of myocardial ischemia reperfusion injury. In this study an additional man made membrane (selective cytopheretic device) and tubing will be added to the dialysis circuit. The device shifts the circulating white blood cells pool to a less inflammatory phenotype. Researchers believe the selective cytopheretic device will alter the phenotype of circulating white blood cells which play a role in myocardial stunning. The purpose of this study is to evaluate whether the selective cytopheretic device will reduce myocardial stunning events in hemodialysis patients. It will also report the rate of adverse events.
The Success of Opening Single CTO Lesions to Improve Myocardial Viability Study (SOS-comedy)
HibernationMyocardial1 moreThe purpose of this study is to investigate the effect of percutaneous coronary intervention (PCI) on myocardial viability in coronary artery disease patients with single coronary total occlusion (CTO) lesions.
Exercise-induced Changes in Cardiac Function & Morphology
Myocardial IschemiaExercise3 moreUntil now it has been assumed that regular endurance training has a positive influence on cardiac function and that the positive effect increases with increasing intensity. However, little is known about the effects of intense endurance stress on the heart. According to current knowledge repeated exposure to strenuous endurance activity may lead to minor but possibly irreversible damage to the heart with resultant scarring of the heart's muscle. Within this study we attempt to find out by different analytical methods - in particular magnetic resonance imaging (MRI) and ultrasound of the heart - to what extent the heart muscle is affected by an intense endurance exercise, i.e. the "Jungfrau-Marathon", and which changes can possibly be found. Due to repeated measurements we will obtain further information on the short-term course of possible changes. Hypotheses: A single bout of prolonged strenuous exercise (PSE) leads to transient alteration in cardiac function accompanied by the appearance of biomarkers for myocardial damage.
Ranolazine a Potential New Therapeutic Application
Myocardial StunningDespite surgical and medical innovation have reduced mortality rates in cardiac surgery, the disease severity and operative procedural complexity have increased and morbidity rate is still high. Ischemia-reperfusion (I/R) injury, redefined in cardiac surgery "post-cardioplegic injury" (2) as a whole of ischemia-reperfusion, cardiopulmonary bypass and surgical trauma, has been recognized as a significant contributor to mortality and morbidity. I/R injury is classified as reversible or irreversible. Reversible injury includes arrhythmias, edema, vascular dysfunction and contractile stunning expressed as low output syndrome without cell death and without apparent signs of infarction or other serum injury markers. Irreversible reperfusion injury includes apoptosis and necrosis. I/R injury is a complex process associated with increase of radical, oxidant and cytokines production, complement and neutrophil activation and endothelial activation leading to microvascular dysfunction and deterioration of coronary flow reserve. In the hypoxic heart increase anaerobic lactate production, K+ efflux and membrane depolarization. The intracellular Na+ concentration rises as a consequence of slow Na+ channels inactivation and the induction of voltage-gated Na+ channel late current component (late INA). Intracellular Na++ accumulation enhanced activity of reversed-mode Na+-Ca++ exchanger causing intracellular Ca++ overload and ventricular dysfunction. Therefore inhibition of late INA has been shown to be cardioprotective. Ranolazine, an FDA-approval antianginal and anti-ischemic agent, high selective blocker of late INA, inhibits the late sodium current in myocardial ischemia, decreases Na+ and Ca2+ overload and improves left ventricular function in experimental animal models. For this reason it was also adjuncted to cardioplegia improving diastolic function in isolate Langerdoff-perfused rat hearts. The authors test the hypothesis that ranolazine improve myocardical protection in patients undergoing coronary artery surgery with cardiopulmonary by-pass (CPB).
Safety and Efficacy of IV Diazoxide as an Additive to Hyperkalemic Cardioplegia in Patients Undergoing...
Myocardial StunningThis study aims to confirm the safety and efficacy of diazoxide as an additive to hyperkalemic cardioplegia in patients undergoing cardiac surgery with cardiopulmonary bypass. The investigators hypothesize that diazoxide combined with hyperkalemic cardioplegia provides superior myocardial protection and reduced myocardial stunning compared with standard cardioplegia alone. The investigators will randomize 30 patients in a 2:1 fashion to treatment vs control. Safety will be assessed by comparing mean arterial blood pressure measurements, glucose levels and incidence of adverse events between the two groups. Efficacy will be assessed by comparing right and left ventricular function in pre-operative vs post-operative transesophageal echocardiograms, need for mechanical circulatory support, ease of separation from bypass and Vasoactive Inotrope Score (VIS) between the two groups. The information gained could pave the way for the use of Katp (Potassium-atp) channel openers to prevent stunning, improve patient outcomes, and reduce health care costs related to myocardial stunning that requires inotropic and mechanical support following cardiac surgery.
Myocardial Stunning During Hemodialysis: Role of Dialyste Calcium Concentration
Myocardial StunningEnd-stage Renal DiseaseChronic kidney disease (CKD) is linked to elevated mortality rate, and cardiovascular disease is the main cause related to this outcome. The cardiovascular mortality among patients on conventional hemodialysis (CHD) is high, achieving up to 30 times more risk of death when comparing to individuals of same age on general population. Congestive heart failure can develop in 25% to 50% of patients, leading to a worse prognosis. CKD patients present anatomic and functional abnormalities on peripheral bed vases and also cardiovascular abnormalities that can cause myocardial ischemia. This last usually is transitory and lead to left ventricular dysfunction that can persist even after the end of dialysis session despite normal coronary perfusion. The prolonged dysfunction is called myocardial stunning (MS). Patients on CHD are subject to hemodynamic instability, myocardial ischemia and development of regional abnormalities of myocardial wall (ARPM´s). MS induced by intradialytic ischemia is a complication that can be minimized by applying techniques associated to more stability during the CHD, as cool dialysate or increasing the length of the therapy. The goal of the present study is to evaluate the behavior of cardiovascular system (trough hemodynamic performance during CHD, accessing MS by echocardiography technique, and biomarkers associated to MS). Finally, the investigators aimed to investigate the role of two different dialysate calcium concentration (2,5 and 3,5 mEq/l) in the genesis of MS during CHD. The elucidation of pathogenesis of MS during CHD might help us modified hemodialysis technique in order to prevent MS, and reduce the high cardiovascular mortality among CKD patients.
Evaluation of Myocardial Viability by Means of Low-dose Dobutamine Gated SPECT (the DOGS Study)...
Coronary ArteriosclerosisHeart Failure4 moreViability assessment remains a clinical challenge in patient with coronary artery disease and left ventricular dysfunction. Several imaging modalities are available for evaluating myocardial viability, based either on perfusion or on contractile reserve analysis. Briefly, perfusion analysis is highly sensitive and contractile reserve highly specific. A combined analysis of both perfusion and contractile reserve has been proposed to improve the diagnostic accuracy in patient referred for a revascularization procedure. However, the value of this combined analysis has not been validated in unselected patients referred for viability assessment. The patients enrolled in the study will undergo a nitrate enhanced rest gated SPECT using a Tc-99m labeled tracer (sestamibi or tetrofosmine) followed by a second gated SPECT acquired during a low-dose dobutamine infusion (10 mcg/kg/mn). All patients will have a 6-month clinical and imaging follow-up, including physical examination and a nitrate enhanced rest gated SPECT using the same radiopharmaceutical. All treatments received during this 6-month period will be recorded, including medical therapy and coronary revascularization (angioplasty, stenting and CABG). Finally, the value of baseline perfusion and contractile reserve analysis in predicting left ventricular ejection fraction changes at 6-month follow-up will be evaluated.