Endotoxemic myocardial dysfunction: subendocardial collagen deposition related to coronary driving pressure.

Sepsis impairs the autoregulation of myocardial microcirculatory blood flow, but whether this impairment is correlated with myocardial remodeling is unknown. This study investigated the role of coronary driving pressure (CDP) as a determinant of microcirculatory blood flow and myocardial fibrosis in endotoxemia and sepsis. The study is composed of two parts: a prospective experimental study and an observational clinical study.

Effects of a potent peroxynitrite decomposition catalyst in murine models of endotoxemia and sepsis.

Excessive free-radical production due to various bacterial components released during bacterial infection has been linked to cell death and tissue injury. Peroxynitrite is a highly reactive oxidant produced by the combination of nitric oxide (NO) and superoxide anion, which has been implicated in cell death and tissue injury in various forms of critical illness. Pharmacological decomposition of peroxynitrite may represent a potential therapeutic approach in diseases associated with the overproduction of NO and superoxide.

Pathomechanisms of myocardial dysfunction in sepsis.

Sepsis remains one of the leading causes of death in intensive care units. Progressive cardiovascular failure is an important cause of the mortality. Septic patients with myocardial dysfunction have significantly higher mortality compared with patients without cardiovascular impairment.

Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents.

Objective: To synthesize novel inhibitors of the nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) synthetase (PARS), also known as poly(ADP-ribose) polymerase (PARP), and to test them in in vitro models of oxidant-induced cytotoxicity and in endotoxin and splanchnic occlusion-reperfusion-induced shock.

Design: Randomized, prospective laboratory study.

Setting: Research laboratory.