Reversal of hypocalcemia and decreased afterload in sepsis: Effect on myocardial systolic and diastolic function

Attila Kovacs, Michael R. Courtois, Benico Barzilai, Irene E. Karl, Philip A. Ludbrook, Richard S. Hotchkiss

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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 α-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.

Original languageEnglish
Pages (from-to)1990-1998
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Issue number6
StatePublished - 1998


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