Sepsis-Induced Cardiac Dysfunction


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Sepsis-Induced Cardiac Dysfunction

  1. 1. Mechanism of Sepsis-induced cardiac dysfunction Ricardo Riveros M.D. Cleveland Clinic CCM 2007 Vol. 35,N. 6
  2. 2. Objetives <ul><li>To provide a detailed overview on sepsis-induced cardiac dysfunction in general and on intrinsic myocardial depression in particular. </li></ul>
  3. 3. Patient Studies <ul><li>Frequency remains unknown. </li></ul><ul><li>No consensus exist for a suitable definition. </li></ul><ul><li>Survivors from septic shock have lower EF and higher end-diastolic volumes compared with nonsurvivors (protective role). </li></ul><ul><li>The decrease in EF is reversible </li></ul>
  4. 4. Patient Studies. <ul><li>By Echocardiography: Initial Hyperdynamic LV function during initial resucitation is an independent predictor of sepsis. </li></ul><ul><li>In septic shock Low EF with High Lv end diastolic volume </li></ul>
  5. 5. Patient Studies <ul><li>BIOMARKERS: </li></ul><ul><li>Troponins I- T: elevated in 31-85%. Associated with higher catecolamines requirement, lower stroke work index, LVEF and higher mortality. </li></ul><ul><li>BNP: Afected by age, renal function,gender. High levels are correlated with adverse otcomes </li></ul>
  6. 6. Animal Models <ul><li>Variability on LV assessment, type and duration of insult, species,duration of study, volume resucitation, anesthesia: </li></ul><ul><li>The physiologic and immunologic response will vary and will affect outcome </li></ul>
  7. 8. Circulatory and microvascular <ul><li>Intravascular volume depletion- underfilling on the heart- reduced cardiac output - oxygen supply-demand imbalance. </li></ul><ul><li>Myocardial edema, pulmonary HTN, Intrinsic cardiac contractility </li></ul><ul><li>Endothelial Cell activation: Nitric oxide (Isometric contraction), endotelin and prostaglandins </li></ul>
  8. 9. Autonomic dysregulation <ul><li>Apoptosis in cardiovascular autonomic centers. </li></ul><ul><li>Tachycardia: Restricted diastolic filling, increase oxygen requirement, cardiomyopathy </li></ul>
  9. 10. Metabolic Changes <ul><li>Increase lactate extraction, decrease ketones, fatty acids and glucose intake. </li></ul><ul><li>Septic patients with organ dysfunction can tolerate lower values of oxygen delivery but also reduce cellular oxygen utilization. </li></ul><ul><li>>90% oxygen consumption is used for mitochondria for ATP production. </li></ul>
  10. 11. Mitochondrial Dysfunction
  11. 12. Mitochondrial dysfunction <ul><li>Elevated production of NO and superoxide. </li></ul><ul><li>Increase expression of mitochondrial uncoupling proteins (UCP) </li></ul><ul><li>Permeability transition pore (PTP): Swelling, proton gradient collapse and cytochome c (Apoptosis) </li></ul>
  12. 13. Cell Death <ul><li>Hypoxia and Dysoxia. </li></ul><ul><li>Myocardial cell death is a rare event during sepsis and insufficient to account for the functional depression observed. </li></ul><ul><li>Reversibility: more functional than anatomical abnormalities. </li></ul>
  13. 14. Inflammatory Signaling <ul><li>Endotoxin induced cardiac dysfunction depend on the presence of the cell wall receptors Toll-like receptor 4 and CD14. </li></ul><ul><li>Toll-like receptor 2 in sepsis by Gram positive. </li></ul><ul><li>TNFa, IL 1B, Interleulin 6. </li></ul>
  14. 15. Inflammatory Signaling <ul><li>Nitric Oxide (NO): Direct effect on vascular tone, depression on mitochondrial respiration, release of proinflamatory citokines, Antiapoptotic, mitochondrial biogenesis, free radical scanvenger. </li></ul><ul><li>All three isoforms of NOS are found in cardiomyocytes: NOS1-3 regulate homeostasis and function; NOS2 depress cardiac function. </li></ul>
  15. 16. Adrenergic signaling <ul><li>Studies in patients and animals have documented elevated levels of cathecolamines. </li></ul><ul><li>Prolong and excess stimulation can lead to myocardial damage by calcium overload and cell necrosis </li></ul><ul><li>Down-regulation of B adrenergic response is associated with high levels of NO </li></ul>
  16. 17. Calcium Trafficking
  17. 18. Calcium Trafficking <ul><li>Reductions in Cytosolic calcium levels reduce contractility </li></ul><ul><li>Is linked with mitochondrial function and integrity </li></ul><ul><li>To determine time-dependent changes in NO, B adrenergic response and protective effect during prolong sepsis </li></ul>
  18. 19. Conclusions <ul><li>40%-50% of pt with septic shock develop myocardial depression </li></ul><ul><li>Cytokines and NO </li></ul><ul><li>Myocardial depression could protect the heart reducing energy expenditure </li></ul><ul><li>Further investigation is needed. </li></ul>