Endotoxin-induced heart dysfunction in rats: Assessment of myocardial perfusion and permeability and the role of fluid resuscitation

OBJECTIVE:The pathophysiology of sepsis-induced myocardial dysfunction is still controversial. Whether microcirculatory hypoperfusion together with capillary leakage can occur in the heart wall also remains a matter of debate.The objective was to evaluate the impact of fluid resuscitation on endotoxin-induced myocardial dysfunction. DESIGN:Adult rats were given intraperitoneal injection of endotoxin (lipopolysaccharide, Escherichia coli, 10 mg/kg) or phosphate-buffered solution, followed up by echocardiography and acetate micro-positron emission tomography scan imaging, together with final hemodynamic, biochemical, and pathologic evaluations up to 48 hrs. SETTING:University laboratory. SUBJECTS:Pathogen-free male Wistar rats (350 g). INTERVENTIONS:Influence of isovolumic fluid infusion type (saline vs. pentastarch) on these variables was assessed in 11 groups of six animals including an unchallenged control one. MEASUREMENTS AND MAIN RESULTS:Endotoxin injection induced a) myocardial dysfunction (decrease of ∼15–20% in left ventricular ejection fraction); b) ventricular enlargement (∼1.5- to 1.7-fold increase in left ventricular systolic volume); c) cardiac output increase (10–15%); d) myocardial hypoperfusion (∼1.5- to 2-fold decrease in acetate k1 constant rate); e) increased oxygen consumption (k2); and f) interstitial wall increase. Endotoxin injection also enhanced levels of arterial lactates and troponin I. Colloid (pentastarch) over crystalloid (saline) fluid resuscitation significantly reversed echocardiographic changes, some positron emission tomography imaging alterations, and lactate and troponin I levels without further enhancing interstitial spaces. CONCLUSION:Endotoxin can induce reversible myocardial alterations with evidence of coronary hypoperfusion and heart wall enlargement/damage, some of which can be prevented by fluid resuscitation. The use of crystalloids is less beneficial than pentastarch.