Will Acute Kidney Injury directly affect heart function?
Pathophysiological interactions between kidney and heart in AKI are called “cardiorenal connectors,” which include immune modulation (both pro- and antiinflammatory cytokines and chemokines), sympathetic nervous system, RAAS activity, and activation of the coagulation cascade.
Circulating levels of tumor necrosis factor-alpha (TNFα), interleukin-1 (IL-1) and interleukin-6 (IL-6), increase immediately after experimental kidney ischemia and, together with other cytokines as well as interferon-alfa (IFN-α), have direct cardiodepressant effects, such as a reduction in the left ventricular EF and elevation of the left ventricular end diastolic and systolic volumes and areas.
Cytokines can decrease myocardial contractility directly or by interacting with the extracellular matrix to cause negative inotropic effects.
Cellular mechanisms involve secondary mediators, such as sphingolipids, arachidonic acid, and alterations in intracellular calcium.
Hyperactivity of the SNS with abnormal secretion of norepinephrine is found in AKI and impairs myocardial activity in several ways:
- • Direct norepinephrine effect
- • Impairment in Ca2+ metabolism
- • Increased myocardial oxygen demand with potential evolution to myocardial ischemia
- • β1-adrenergic mediated apoptosis of myocardial cells
- • Stimulation of α1 receptors
- • Activation of RAAS
- • Angiotensin II promotion of cellular hypertrophy and apoptosis.
Increased RAAS activity could be accountable for diminished coronary response to adenosine, bradykinin, and L-arginine. Other animal models exemplify how the inflammatory cascade of AKI can contribute to altered permeability of lung vessels, resulting in interstitial edema and micro-hemorrhage mediated by inflammatory mediators and altered expression of epithelial sodium channel and aquaporin-5.