The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Abstract

Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage, which all reduce cellular energy production. In order to reduce the risk of major cell death and a diminished likelihood of recovery, adaptive changes appear to be activated. As a result, cells and organs may survive in a non-functioning hibernation-like condition. Sepsis-induced cardiac dysfunction may represent an example of such functional shutdown. Sepsis-induced myocardial dysfunction is common, corresponds to the severity of sepsis, and is reversible in survivors. Its mechanisms include the attenuation of the adrenergic response at the cardiomyocyte level, alterations of intracellular calcium trafficking and blunted calcium sensitivity of contractile proteins. All these changes are mediated by cytokines. Treatment includes preload optimization with sufficient fluids. However, excessive volume loading is harmful. The first line vasopressor recommended at present is norepinephrine, while vasopressin can be started as a salvage therapy for those not responding to catecholamines. During early sepsis, cardiac output can be increased by dobutamine. While early administration of catecholamines might be necessary to restore adequate organ perfusion, prolonged administration might be harmful. Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine reduces myocardial oxygen expenditure and ameliorates diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. All these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice. While early administration of catecholamines might be necessary to restore adequate organ perfusion and pressure, prolonged administration might be harmful.Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine will reduce myocardial oxygen expenditure and ameliorate diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. However, all these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice.-3 -Alain Rudiger & Mervyn Singer: The heart in sepsis

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

“…Due to the severe inflammatory response and mitochondrial dysfunction during severe pneumonia, at least 30% of patients develop left ventricular dilatation with reduced ejection fraction that usually takes 7-10 days to recover (i.e., sepsis-induced cardiomyopathy) (37,38). In addition, Corrales-Medina et al showed recently in a cohort study that 10-30% of adults (without clinical history of cardiac disease) admitted for 16 CAP, developed clinically relevant heart failure, arrhythmias, or acute coronary syndromes, up to 10 years after hospitalization (6-8).…”

Improved Survival in a Long-Term Rat Model of Sepsis Is Associated With Reduced Mitochondrial Calcium Uptake Despite Increased Energetic Demand

“…Reduced ATP supply from dysfunctional mitochondria has been proposed as a mechanism underlying septic cardiomyopathy (41). However, most of the available evidence originates from measurements of phosphate intermediates or biochemical assays of respiratory complex activity.…”

Cardiac Effects of Echinocandins in Endotoxemic Rats

“…The mechanisms of sepsis-induced cardiac dysfunction include the attenuation of the adrenergic response on the cardiomyocyte level, alterations of intracellular calcium trafficking, and blunted calcium sensitivity of contractile proteins (15). Hypothesizing an echinocandin-induced aggravation of cardiac impairment in patients already suffering from septic shock, we performed in vivo hemodynamic measurements in endotoxemic rats.…”