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.