inotropics in heart failure

BACKGROUND: Angiotensin-(1-12) [Ang-(1-12)] is a chymase-dependent source for angiotensin II (Ang II) cardiac activity. The direct contractile effects of Ang-(1-12) in normal and heart failure (HF) remain to be demonstrated. We assessed the hypothesis that Ang-(1-12) may modulate [Ca2+ ]i regulation and alter cardiomyocyte contractility in normal and HF rats. METHODS AND RESULTS: We compared left ventricle (LV) myocyte contractile and calcium transient ([Ca2+ ]iT ) responses to angiotensin peptides in 16 SD rats with isoproterenol-induced HF and 16 age-matched controls...

Left ventricular dysfunction triggers the activation of the sympathetic nervous system, providing inotropic support to the failing heart and concomitantly increasing the risk of atrial fibrillation (AF). The cardiovascular effects of cannabis have been characterized as biphasic on the autonomic nervous system with an increased sympathetic effect at low doses and an inhibitory sympathetic activity at higher doses. It is unknown if the autonomic effect of cannabis impacts the occurrence of AF in patients with heart failure (HF)...

We previously reported that uridine 5'-triphosphate (UTP), a pyrimidine nucleoside triphosphate produced a concentration- and time-dependent increase in the contraction force in isolated right atrial preparations from patients undergoing cardiac bypass surgery due to angina pectoris. The stimulation of the force of contraction was sustained rather than transient. In the present study, we tried to elucidate the underlying receptor and signal transduction for this effect of UTP. Therefore, we measured the effect of UTP on force of contraction, phosphorylation of p38 and ERK1/2, in human atrial preparations, atrial preparations from genetically modified mice, cardiomyocytes from adult mice and cardiomyocytes from neonatal rats...

Cardiovascular disease, including congestive heart failure, pericardial disease, and atherosclerosis, is becoming increasingly better recognized in companion birds, small mammals, and reptiles. A wide range of medications is available to treat these conditions, including diuretics, vasodilators, positive and negative inotropes, antiarrhythmic agents, and pentoxifylline. This review systematically discusses each of these drug classes and their potential applications in exotic species. Although treatment approaches remain largely empirical and extrapolated from small animal and human medicine, the management strategies presented here have the potential to both maintain quality of life and extend survival time for the exotic cardiac patient...

Introduction: Ultrafast tracking of anesthesia (UFTA) is practiced routinely, whereas immediate on-table extubation after off-pump coronary artery bypass (OPCAB) grafting surgery has many concerns. The purpose of our study was to evaluate the safety and feasibility of immediate extubation (IE) versus UFTA. Methods: Sixty patients were enrolled who underwent OPCAB surgery. The two groups IE and UFTA had thirty patients each. Inclusion criteria were patients for OPCAB surgery including left main stenosis...

We present the case of a patient with acute necrotizing eosinophilic myocarditis (ANEM) who rapidly recovered after receiving high-dose corticosteroid therapy. A previously healthy 29-year-old woman presented to our hospital with abdominal pain, nausea, and fever that had lasted for two days. Her clinical condition progressively declined and she ultimately presented with cardiogenic shock due to fulminant heart failure and atrioventricular dissociation due to sinus bradycardia, which required inotropic and ventilatory support...

RATIONALE: Ca/calmodulin-dependent protein kinase II (CaMKII) was shown to increase diastolic sarcoplasmic reticulum (SR) Ca leak, which can result in delayed afterdepolarizations and triggered arrhythmias. Since increased CaMKII expression and activity has been mechanistically linked to arrhythmias in human heart failure (HF) and atrial fibrillation (AF), specific strategies aimed at CaMKII inhibition may have therapeutic potential. OBJECTIVE: We tested the antiarrhythmic and inotropic effects of a novel selective and ATP-competitive CaMKII inhibitor (GS-680)...

BACKGROUND: There are data suggesting that free hemoglobin (Hb), heme, and iron contribute to infection, thrombosis, multiorgan failure, and death in critically ill patients. These outcomes may be mitigated by haptoglobin. STUDY DESIGN AND METHODS: 164 consecutively treated children undergoing surgery for congenital heart disease were evaluated for associations between free Hb and haptoglobin and clinical outcomes, physiologic metrics, and biomarkers of inflammation RESULTS: Higher perioperative free Hb levels (and lower haptoglobin levels) were associated with mortality, nosocomial infection, thrombosis, hours of intubation and inotropes, increased interleukin-6, peak serum lactate levels, and lower nadir mean arterial pressures...

BACKGROUND: Levosimendan is a calcium sensitizer drug causing increased contractility in the myocardium and vasodilation in the vascular system. It is mainly used for the therapy of acute decompensated heart failure. Several studies on animals and humans provided evidence of the cardioprotective properties of levosimendan including preconditioning and anti-apoptotic. In view of these favorable effects, levosimendan has been tested in patients undergoing cardiac surgery for the prevention or treatment of low cardiac output syndrome...

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many organs, but multisystem dysfunction is rare. Here, we report a case of a 29-year-old woman who was initially diagnosed with SLE complications including lupus nephritis, lupus encephalopathy, renal hypertension, thrombocytopenia, anaemia and hyperkalaemia. She recovered following treatment with high dose methylprednisolone, intravenous immunoglobulin (IVIG) and continuous renal replacement therapy (CRRT). However, a few days after hospital discharge, she developed gastrointestinal bleeding...

Myocardial PDE2 activity increases in terminal human heart failure and after isoprenaline infusion in rat heart. PDE2 inhibitors do not potentiate the murine sinoatrial tachycardia produced by noradrenaline. We investigated whether isoprenaline infusion induces PDE2 to decrease the chronotropic and inotropic effects of catecholamines in rat heart. Sprague-Dawley rats were infused with isoprenaline (2.4 mg kg-1  day-1 ) for 3 days. We used spontaneously beating right atria, paced right ventricular strips and left ventricular papillary muscles...

OBJECTIVES: To validate the EAHFE-3D scale, based on the Acute Heart Failure in Emergency Departments registry, in a cohort of patients attended for acute heart failure. MATERIAL AND METHODS: Study of a multipurpose cohort of patients with acute heart failure in 3 hospitals in the Basque Country between 2011 and 2013. We extracted age, baseline New York Heart Association functional class, systolic blood pressure, baseline arterial oxygen saturation, sodium level in blood, and emergency department treatments (noninvasive mechanical ventilation, use of inotropic agents and vasopressors) in order to calculate each patient's EAHFE-3D score...

BACKGROUND: Caloric restriction (CR) has been described to have cardioprotective effects and improve functional outcomes in animal models and humans. Chronic ischemic heart failure (HF) is associated with reduced cardiac sympathetic innervation, dysfunctional β-adrenergic receptor signaling, and decreased cardiac inotropic reserve. We tested the effects of a long-term CR diet, started late after myocardial infarction on cardiac function, sympathetic innervation, and β-adrenergic receptor responsiveness in a rat model of postischemic HF...

The apelinergic system is an important player in the regulation of both vascular tone and cardiovascular function, making this physiological system an attractive target for drug development for hypertension, heart failure and ischemic heart disease. Indeed, apelin exerts a positive inotropic effect in humans whilst reducing peripheral vascular resistance. In this study, we investigated the signaling pathways through which apelin exerts its hypotensive action. We synthesized a series of apelin-13 analogs whereby the C-terminal Phe13 residue was replaced by natural or unnatural amino acids...

Sepsis is the leading cause of death in critically ill patients, and its incidence continues to rise. Sepsis was defined as a systemic inflammatory response syndrome with an identifiable focus of infection, but therapeutic strategies aimed at eliminating the inflammatory response have only modest clinical benefit. The development of a failure of one or more organs poses a major threat to the survival of patients with sepsis, and mortality in sepsis is most often attributed to multiple organ dysfunction. Accordingly, sepsis has been recently redefined as life-threatening organ dysfunction due to a dysregulated host response to infection...

Currently, there are no tailored therapies available for the treatment of right ventricular (RV) hypertrophy, and the cellular mechanisms that underlie the disease are poorly understood. We investigated the cellular changes that occur early in the progression of the disease, when RV hypertrophy is evident, but prior to the onset of heart failure. Intracellular Ca2+ ([Ca2+ ]i ) handling was examined in a rat model of monocrotaline (MCT)-induced pulmonary hypertension and subsequent RV hypertrophy. [Ca2+ ]i and stress production were measured in isolated RV trabeculae under baseline conditions (1-Hz stimulation, 1...

To test whether remote ischaemic conditioning (RIC) as adjuvant to standard of care (SOC) would prevent progression towards heart failure (HF) after ST-elevation myocardial infarction (STEMI). Single-centre parallel 1:1 randomized trial (computerized block-randomization, concealed allocation) to assess superiority of RIC (3 cycles of intermittent 5 min lower limb ischaemia) over SOC in consecutive STEMI patients (NCT02313961, clinical trials.gov). From 258 patients randomized to RIC or SOC, 9 and 4% were excluded because of unconfirmed diagnosis and previously unrecognized exclusion criteria, respectively...

BACKGROUND: Right ventricular (RV) failure due to pulmonary embolism (PE) increases morbidity and mortality and contributes to prolonged hospital length of stay and higher costs of care. RV mechanical circulatory support (MCS) including Impella RP devices have been increasingly used in hemodynamically compromised PE patients who are refractory to intravascular volume expansion and inotropic therapy. However, effectiveness and safety of Impella RP, in hemodynamically unstable PE patients is unknown...

Heart transplant has become an increasingly important option for patients with end-stage nonobstructive hypertrophic cardiomyopathy (HC). However, clinical details related specifically to the overall HC transplant experience remain sparse. We assessed outcomes of HC heart transplants, from 2002 to 2016, at Tufts Medical Center. Fifty-two nonobstructive severely symptomatic patients underwent evaluation at 47 ± 13 years; 11 (21%) declined or failed to qualify, most commonly because of co-morbidities (n = 7)...

BACKGROUND AND OBJECTIVE: Diltiazem is a nondihydropyridine calcium channel blocker that is used to control rapid ventricular response in patients who have atrial fibrillation or flutter. Diltiazem has a negative inotropic effect and may cause hemodynamic decompensation in patients with reduced ejection fraction. This study evaluated outcomes in patients who had low ejection fraction and were treated with diltiazem. METHODS: This was a retrospective chart review in 635 patients who were hospitalized because of rapid atrial fibrillation and who were treated with intravenous diltiazem...