Development of cardiac dysfunction in sepsis‐surviving rats

Abstract

ObjectivesSepsis is a life‐threatening syndrome induced by an infection and is associated with physiological, pathological and biochemical systemic changes. It is one of the major causes of death in critical care units and a public health concern around the world. A particular occurrence in sepsis is the development of cardiovascular dysfunction. Notably, cardiovascular diseases have been described as an important risk factor among those who survived sepsis (ANNANE et al., 2007; YENDE et al., 2014). We have hypothesized that depressed cardiac function is one of the long‐lasting effects in sepsis.Material and methodsTo investigate our hypothesis, we evaluated the cardiac function from male Wistar rats subjected to the cecal ligation puncture (CLP) model at 6, 24, 72 h, and 30 days after the surgery. Age matched sham‐operated animals were used as control. For this, the animals were maintained under anesthesia and a pressure‐volume catheter was inserted into the left ventricle chamber through the carotid artery. This approach allowed the assess of thirteen volume dependent cardiac parameters: cardiac output, CO; heart rate, HR; stroke volume, SV; end diastolic volume, EDV; end diastolic pressure, EDP; ventricular stroke work, SW; the rate of ventricle pressure rise and decrease, dP/dtmax and dP/dtmin, respectively; the pressure at dP/dtmax, P@dP/dtmax, relaxation time constant, TAU; ejection fraction, EF; the rate of ventricle volume rise, dV/dtmax; and end systolic volume; ESV. These parameters were analyzed before and after intravenous injection of 30 nmol/Kg dobutamine.ResultsAt 6 h and 24 h after the CLP surgery, the CO, EF, and SW were significantly reduced in the CLP groups when compared with control animals. For instance, the CO, EF, and SW were reduced from 30.4 ± 1.9 mL/min, 43.6 ± 2.2%, and 6097 ± 469 mmHg*μl in sham‐operated animals to 12.4 ± 1.2 mL/min, 24.4 ± 3.1%, and 2561 ± 597 mmHg*μl in the CLP 24 h group, respectively. Importantly, as measured under basal condition, all cardiac parameters at 72 h after the CLP were back to levels found in sham‐operated animals or even increased (i.e. both dV/dtmax and SW were around 70 and 57% higher in the CLP group). Nevertheless, when evaluated at 30 days after the CLP, the sepsis‐surviving animals presented decreased CO (20.85 ± 5.01 mL/min), EF (41.3 ± 4.8%), SW (6481 ± 1252 mmHg*μl), and EDV (169.3 ± 7.7 μl), compared with control animals (38.4 ± 4.1 mL/min, 57.8 ± 2.3%, 10551 ± 725 mmHg*μl, and 226.6 ± 12.0 μl, respectively). On the other hand, both EDP and Tau were increased in sepsis‐surviving rats around 57 and 70% respectively, compared with control animals. In addition, dobutamine, an inotropic adrenergic agent, had its effect on intraventricular pressure of sepsis‐surviving animals reduced aroud 58% compared with control animals.DiscussionAltogether these data indicate that cardiac injury, characterized by both diastolic and systolic dysfunction is present in early (6 and 24 h), but not late (72 h) sepsis, and reappeared in the sepsis‐surviving rats at 30 days after the CLP surgery. The translation of our results for humans may allow the development of new strategies for the management of cardiac function in those who survived the septic insult.Support or Funding InformationFAPESC, SC, Brazil (TR2012000367) and CNPq, Brazil (448738/2014)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.