title: Endotoxaemic myocardial dysfunction: the role of coronary driving pressure in subendocardial perfusion.
abstract: OBJECTIVE
  To investigate the role of coronary driving pressure (CDP) in myocardial microcirculatory blood flow during sepsis. We hypothesised that in septic shock there is an impaired autoregulation of microcirculation, and blood flow is totally dependent on CDP. We analysed the effect of lipopolysaccharide (LPS)-induced shock on myocardial microcirculation, separating subendocardial and epicardial areas. We then studied the effect of CDP increases using noradrenaline (NOR) or metaraminol (Aramine [ARA]) on myocardial microcirculation and function, and we analysed the effect of volume infusion on CDP and myocardial function.
  
  
  METHODS
  Endotoxaemia was induced in male Wistar rats by an intraperitoneal injection of LPS 10 mg/kg. Animals were divided into a control (CT) group, an LPS-injected group, and an LPS-injected group treated with saline fluid, NOR or ARA.
  
  
  METHODS
  Ninety minutes later, a haemodynamic evaluation was performed. NOR or ARA were used to manage the mean arterial pressure (MAP) and CDP, and we inserted a catheter into the left ventricle to measure cardiac parameters. To measure blood flow in the myocardium and other organs, microspheres were introduced into the left ventricle using an infusion pump.
  
  
  RESULTS
  After LPS treatment, left ventricular (LV) systolic function (dP/dt max) and diastolic function (dP/dt min) decreased by 34% and 15%, respectively, and load-independent indices (LV contractility in ejection phase and dP/dt max÷end-diastolic volume) were reduced. The CDP was also reduced (by 58%) in the endotoxaemic rats. Myocardial blood flow was reduced (by 80%) in animals with an MAP≤65 mmHg. NOR increased the CDP (LPS, 38 mmHg [SEM, 2 mmHg]; LPS+NOR, 59 mmHg [SEM, 3 mmHg]) and microcirculatory perfusion (LPS, 2 mL/min/g tissue [SEM, 0.6 mL/min/g]; LPS+NOR, 6.2 mL/min/g [SEM, 0.8 mL/min/g]). ARA was also effective in improve microcirculation but saline volume infusion was ineffective in improving CDP or myocardial function. CDP showed a significant correlation with subendocardial blood flow.
  
  
  CONCLUSIONS
  Myocardial blood flow in the LV subendocardium and the right ventricle decreases in endotoxaemic rats. Increasing CDP improves myocardial blood flow and function. Thus, in endotoxaemia, microcirculatory blood flow is pressure dependent, suggesting that it may be beneficial to treat patients with sepsis using a higher CDP.
authors.affiliation: Institute of Orthopaedics and Traumatology, Clinical Hospital, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. gsoriano@usp.br.
authors.forename: Clara B
authors.initials: CB
authors.lastname: Lorigados
authors.affiliation: Discipline of Clinical Emergencies, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Suely K
authors.initials: SK
authors.lastname: Ariga
authors.affiliation: Discipline of Clinical Emergencies, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Tiago R
authors.initials: TR
authors.lastname: Batista
authors.affiliation: Discipline of Clinical Emergencies, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Irineu T
authors.initials: IT
authors.lastname: Velasco
authors.affiliation: Discipline of Clinical Emergencies, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Francisco G
authors.initials: FG
authors.lastname: Soriano
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000503:physiopathology*; D019446:Endotoxemia / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D008680:Metaraminol / Q000494:pharmacology; D008833:Microcirculation / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D008680:Metaraminol; D009638:Norepinephrine