title: Endotoxemic myocardial dysfunction: subendocardial collagen deposition related to coronary driving pressure.
abstract: 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. The experimental study was performed on male Wistar rats weighing 300 to 320 g. Endotoxemia was induced in rats by lipopolysaccharide (LPS) injection (10 mg·kg intraperitoneally). Hemodynamic evaluation was performed 1.5 to 24 h after LPS injection by measuring the mean arterial pressure, CDP, left ventricular end-diastolic pressure, dP/dtmax, and dP/dtmin. Microspheres were also infused into the left ventricle to measure myocardial blood flow, and myocardial tissue was histologically assessed to analyze collagen deposition. The CDP, mean arterial pressure, and myocardial blood flow were reduced by 55%, 30%, and 70%, respectively, in rats 1.5 h after LPS injection compared with phosphate buffer saline injection (P < 0.05). The CDP was significantly correlated with subendocardial blood flow (r = 0.73) and fibrosis (r = 0.8). Left ventricular function was significantly impaired in the LPS-treated rats, as demonstrated by dP/dtmax (6,155 ± 455 vs. 3,746 ± 406 mmHg·s, baseline vs. LPS; P < 0.05) and dP/dtmin (-5,858 ± 236 vs. -3,516 ± 436 mmHg·s, baseline vs. LPS; P < 0.05). The clinical study was performed on 28 patients with septic shock analyzed for CDP. The CDP data and histological slices were collected from septic patients. In addition, the clinical data demonstrated fibrosis and 45% CDP reduction in nonsurvivors compared with survivors. In conclusion, the left ventricular subendocardial blood flow was positively correlated with CDP, and higher CDP was negatively correlated with myocardial collagen deposition. Thus, early reductions in myocardial blood flow and CDP facilitate late myocardial fibrosis in rats and likely in humans.
authors: *Emergências Clínicas do Departamento de Clínica Médica, and †Departamento de Anatomia Patológica da Faculdade de Medicina da Universidade de São Paulo; ‡Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo-Instituto de Ortopedia e Traumatologia; and §Hospital Universitário da Universidade de São Paulo-Divisão de Clínica Médica-UTI, São Paulo, Brazil.
authors: Francisco Garcia
authors: FG
authors: Soriano
authors: Maria Carolina
authors: MC
authors: Guido
authors: Hermes Vieira
authors: HV
authors: Barbeiro
authors: Elia Garcia
authors: EG
authors: Caldini
authors: Clara Batista
authors: CB
authors: Lorigados
authors: Antonio Carlos
authors: AC
authors: Nogueira
mesh_terms: D000328:Adult; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003094:Collagen / Q000378:metabolism*; D003326:Coronary Circulation / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005355:Fibrosis; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D012772:Shock, Septic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D016207:Cytokines; D017392:Thiobarbituric Acid Reactive Substances; D003094:Collagen; D020778:Matrix Metalloproteinase 2