Sepsis-induced cardiomyopathy (SIC), which is a common morbid condition, occurs in patients with severe sepsis and septic shock. The clinical characterization of SIC has been largely concept-driven. Heart function has traditionally been evaluated according to two basic conceptual models: a hydraulic pump system, whereby the output from the heart is entirely dependent on its input, or a hemodynamic pump, whereby the cardiac output is a function of preload, global ventricular performance, and afterload. Minimal attention has been given to the intrinsic contractile function of the heart or to the interaction between the peripheral circulation and the intrinsic myocardial function in sepsis. Currently, SIC is assumed to be the result of the interaction of microorganisms that activate the physiopathological pathways and cellular signaling mechanisms that lead to intrinsic myocardial dysfunction. However, the animal models used to study SIC exhibit multiple limitations. This review addresses the conceptual background, historical perspectives, physiologic mechanisms, current evidence, and limitations of SIC characterization. It also highlights potential future directions for the hemodynamic assessment of the intrinsic contractile function of the heart to overcome current methodological limitations. Finally, the present review recommends the exploration of additional potential mechanisms underlying SIC.

Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central in the pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI based on its role in decreasing oxidative stress, cytokine release, leukocyte endothelial-adhesion and hepatic apoptosis. This review will highlight the influence of endogenous NO on hepatic IRI, role of inhaled NO in ameliorating IRI, modes of delivery, donor drugs and potential side effects of exogenous NO.

Halogens are widely used, highly toxic chemicals that pose a potential threat to humans because of their abundance. Halogens such as bromine (Br2) cause severe pulmonary and systemic injuries; however, the mechanisms of their toxicity are largely unknown. Here, we demonstrated that Br2 and reactive brominated species produced in the lung and released in blood reach the heart and cause acute cardiac ultrastructural damage and dysfunction in rats. Br2-induced cardiac damage was demonstrated by acute (3–24 h) increases in circulating troponin I, heart-type fatty acid-binding protein, and NH2-terminal pro-brain natriuretic peptide. Transmission electron microscopy demonstrated acute (3–24 h) cardiac contraction band necrosis, disruption of z-disks, and mitochondrial swelling and disorganization. Echocardiography and hemodynamic analysis revealed left ventricular (LV) systolic and diastolic dysfunction at 7 days. Plasma and LV tissue had increased levels of brominated fatty acids. 2-Bromohexadecanal (Br-HDA) injected into the LV cavity of a normal rat caused acute LV enlargement with extensive disruption of the sarcomeric architecture and mitochondrial damage. There was extensive infiltration of neutrophils and increased myeloperoxidase levels in the hearts of Br2- or Br2 reactant-exposed rats. Increased bromination of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and increased phosphalamban after Br2 inhalation decreased cardiac SERCA activity by 70%. SERCA inactivation was accompanied by increased Ca2+-sensitive LV calpain activity. The calpain-specific inhibitor MDL28170 administered within 1 h after exposure significantly decreased calpain activity and acute mortality. Bromine inhalation and formation of reactive brominated species caused acute cardiac injury and myocardial damage that can lead to heart failure. NEW & NOTEWORTHY The present study defines left ventricular systolic and diastolic dysfunction due to cardiac injury after bromine (Br2) inhalation. A calpain-dependent mechanism was identified as a potential mediator of cardiac ultrastructure damage. This study not only highlights the importance of monitoring acute cardiac symptoms in victims of Br2 exposure but also defines calpains as a potential target to treat Br2-induced toxicity.

AbsractEnd-stage liver disease (ESLD) is a multisystemic disease that adversely and mutually aggravates other organs such as the heart. Cardiac dysfunction in ESLD encompasses a spectrum of disease that could be aggravated, precipitated or be occurring hand-in-hand with coexisting aetiological factors precipitating cirrhosis. Additionally and more complexly, liver transplantation, the curative modality of ESLD, is responsible for additional intra-and postoperative short-and long-term cardiac morbidity. The phenotypic distinction of the different forms of cardiac dysfunction in ESLD albeit important prognostically and therapeutically is not allowed by the current societal recommendations, due to conceptual, and methodological limitations in the appraisal of cardiac function and structure in ESLD and in designing studies that are based on this appraisal. This review comprehensively discusses the spectrum of cardiac dysfunction in ESLD, discusses the limitations of the current appraisal of cardiac dysfunction in ESLD, and proposes a hypothetical approach for studying cardiac dysfunction in liver transplant candidates.

Victims of chlorine (Cl2) inhalation that die demonstrate significant cardiac pathology. However, a gap exists in the understanding of Cl2-induced cardiac dysfunction. This study was performed to characterize cardiac dysfunction occurring after Cl2 exposure in rats at concentrations mimicking accidental human exposures (in the range of 500 or 600 ppm for 30 min). Inhalation of 500 ppm Cl2 for 30 min resulted in increased lactate in the coronary sinus of the rats suggesting an increase in anaerobic metabolism by the heart. There was also an attenuation of myocardial contractile force in an ex vivo (Langendorff technique) retrograde perfused heart preparation. After 20 h of return to room air, Cl2 exposure at 500 ppm was associated with a reduction in systolic and diastolic blood pressure as well echocardiographic/Doppler evidence of significant left ventricular systolic and diastolic dysfunction. Cl2 exposure at 600 ppm (30 min) was associated with biventricular failure (observed at 2 h after exposure) and death. Cardiac mechanical dysfunction persisted despite increasing the inspired oxygen fraction concentration in Cl2-exposed rats (500 ppm) to ameliorate hypoxia that occurs after Cl2 inhalation. Similarly ex vivo cardiac mechanical dysfunction was reproduced by sole exposure to chloramine (a potential circulating Cl2 reactant product). These results suggest an independent and distinctive role of Cl2 (and its reactants) in inducing cardiac toxicity and potentially contributing to mortality.