title: Reversal of hypocalcemia and decreased afterload in sepsis. Effect on myocardial systolic and diastolic function.
abstract: Sepsis is a major cause of death in intensive care units. Clinically, sepsis induces a number of physiologic and metabolic abnormalities, including decreased myocardial contractility and decreased plasma ionized calcium. There is debate about the proper therapy of hypocalcemia in sepsis because calcium administration may worsen cell function by causing intracellular Ca2+ overload. We investigated the effect of Ca2+ administration on myocardial systolic and diastolic function in an extensively utilized rat model of sepsis, i.e., the cecal ligation and puncture model (CLP). Approximately 24 h after CLP or sham surgery, rats were anesthetized and myocardial function assessed in vivo by a left ventricular Millar catheter and simultaneous two-dimensional guided M-mode echocardiography. Septic rats had a 28% decrease in peak left ventricular developed pressure, a 30% decrease in +dP/ dt, and a 23% decrease in -dP/dt (p < 0.05). Plasma ionized Ca2+ was decreased in septic compared with that in sham rats: 4.9 +/- 0.9 and 5.6 +/- 0.01 mg/dl, respectively (p < 0.05). CaCl2 improved both systolic and diastolic function and there was no evidence of adverse effects of Ca2+ even at supraphysiologic levels. Surprisingly, correction of decreased afterload in septic rats, using the pure alpha-agonist phenylephrine, caused normalization of all indices of cardiac contractility, indicating that the presumed decrease in cardiac function was due entirely to an effect of the decreased afterload to "unload" the left ventricle. We conclude that Ca2+ administration is not detrimental to cardiac function in the rat CLP model. Although the rat CLP model is widely utilized and reproduces many of the clinical hallmarks of sepsis, it does not cause intrinsic myocardial depression and, therefore, it may not be an appropriate model to investigate the clinical cardiac dysfunction that occurs in patients with sepsis.
authors.affiliation: Divisions of Cardiovascular Disease and Metabolism, Department of Medicine, and the Department of Anesthesiology, Research Unit, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kovacs
authors.forename: M R
authors.initials: MR
authors.lastname: Courtois
authors.forename: B
authors.initials: B
authors.lastname: Barzilai
authors.forename: I E
authors.initials: IE
authors.lastname: Karl
authors.forename: P A
authors.initials: PA
authors.lastname: Ludbrook
authors.forename: R S
authors.initials: RS
authors.lastname: Hotchkiss
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use; D000818:Animals; D002118:Calcium / Q000097:blood / Q000627:therapeutic use; D006328:Cardiac Catheterization; D003971:Diastole; D004195:Disease Models, Animal; D004452:Echocardiography; D006321:Heart / Q000503:physiopathology*; D006996:Hypocalcemia / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D013318:Stroke Volume / Q000502:physiology; D013599:Systole; D016277:Ventricular Function, Left / Q000502:physiology; D017725:Ventricular Pressure / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D010656:Phenylephrine; D002118:Calcium