Sepsis-Induced Cardiac Dysfunction

Mechanism of Sepsis-induced cardiac dysfunction Ricardo Riveros M.D. Cleveland Clinic CCM 2007 Vol. 35,N. 6

Objetives
To provide a detailed overview on sepsis-induced cardiac dysfunction in general and on intrinsic myocardial depression in particular.

Patient Studies
Frequency remains unknown.
No consensus exist for a suitable definition.
Survivors from septic shock have lower EF and higher end-diastolic volumes compared with nonsurvivors (protective role).
The decrease in EF is reversible

Patient Studies.
By Echocardiography: Initial Hyperdynamic LV function during initial resucitation is an independent predictor of sepsis.
In septic shock Low EF with High Lv end diastolic volume

Patient Studies
BIOMARKERS:
Troponins I- T: elevated in 31-85%. Associated with higher catecolamines requirement, lower stroke work index, LVEF and higher mortality.
BNP: Afected by age, renal function,gender. High levels are correlated with adverse otcomes

Animal Models
Variability on LV assessment, type and duration of insult, species,duration of study, volume resucitation, anesthesia:
The physiologic and immunologic response will vary and will affect outcome

Circulatory and microvascular
Intravascular volume depletion- underfilling on the heart- reduced cardiac output - oxygen supply-demand imbalance.
Myocardial edema, pulmonary HTN, Intrinsic cardiac contractility
Endothelial Cell activation: Nitric oxide (Isometric contraction), endotelin and prostaglandins

Autonomic dysregulation
Apoptosis in cardiovascular autonomic centers.
Tachycardia: Restricted diastolic filling, increase oxygen requirement, cardiomyopathy

Metabolic Changes
Increase lactate extraction, decrease ketones, fatty acids and glucose intake.
Septic patients with organ dysfunction can tolerate lower values of oxygen delivery but also reduce cellular oxygen utilization.
>90% oxygen consumption is used for mitochondria for ATP production.

Mitochondrial Dysfunction

Mitochondrial dysfunction
Elevated production of NO and superoxide.
Increase expression of mitochondrial uncoupling proteins (UCP)
Permeability transition pore (PTP): Swelling, proton gradient collapse and cytochome c (Apoptosis)

Cell Death
Hypoxia and Dysoxia.
Myocardial cell death is a rare event during sepsis and insufficient to account for the functional depression observed.
Reversibility: more functional than anatomical abnormalities.

Inflammatory Signaling
Endotoxin induced cardiac dysfunction depend on the presence of the cell wall receptors Toll-like receptor 4 and CD14.
Toll-like receptor 2 in sepsis by Gram positive.
TNFa, IL 1B, Interleulin 6.

Inflammatory Signaling
Nitric Oxide (NO): Direct effect on vascular tone, depression on mitochondrial respiration, release of proinflamatory citokines, Antiapoptotic, mitochondrial biogenesis, free radical scanvenger.
All three isoforms of NOS are found in cardiomyocytes: NOS1-3 regulate homeostasis and function; NOS2 depress cardiac function.

Adrenergic signaling
Studies in patients and animals have documented elevated levels of cathecolamines.
Prolong and excess stimulation can lead to myocardial damage by calcium overload and cell necrosis
Down-regulation of B adrenergic response is associated with high levels of NO

Calcium Trafficking

Calcium Trafficking
Reductions in Cytosolic calcium levels reduce contractility
Is linked with mitochondrial function and integrity
To determine time-dependent changes in NO, B adrenergic response and protective effect during prolong sepsis

Conclusions
40%-50% of pt with septic shock develop myocardial depression
Cytokines and NO
Myocardial depression could protect the heart reducing energy expenditure
Further investigation is needed.

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Sepsis-Induced Cardiac Dysfunction

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