The role of protein kinase C in lipopolysaccharide-induced myocardial depression in guinea pigs

UMMS Affiliation

Department of Anesthesiology; Department of Physiology; Department of Surgery

Publication Date


Document Type



Animals; Enzyme Activation; Female; Guinea Pigs; Heart; Injections, Intraperitoneal; Lipopolysaccharides; Male; Myocardial Contraction; Protein Kinase C; Sepsis


Amino Acids, Peptides, and Proteins | Anesthesiology | Biological Factors | Carbohydrates | Enzymes and Coenzymes | Lipids | Physiology


The effect of lipopolysaccharide (LPS) on cardiac protein kinase C (PKC) activation and cardiac depression was evaluated. Guinea pigs (n = 44) received intraperitoneal injections of saline or Escherichia coli LPS (2 mg/kg). Left atria were harvested 16 h later and suspended in oxygenated low calcium (1 mM) (n = 24) or high calcium (5 mM) (n = 20) 30 degrees C Krebs-Henseleit buffer. Atria were treated with H-7 (n = 23), a PKC inhibitor, or vehicle (n = 21). Contractile responses to changes in preload and stimulating frequency, in the resting and potentiated states, and to escalating doses of phenylephrine were measured. PKC activation in ventricular muscle was also determined. LPS activated ventricular PKC (p < .05) but treatment with H-7 failed to reverse LPS-induced atrial dysfunction in the low calcium buffer. Contractile function in the potentiated state indicated that LPS appears to interfere with calcium release from the sarcoplasmic reticulum (SR). The contractile response to phenylephrine was markedly attenuated in atria harvested from endotoxic animals. These data indicate that LPS-induced cardiac depression is mediated, in part, by alterations in SR calcium release. LPS activates cardiac PKC but a causal relationship among LPS, PKC, and cardiac dysfunction remains to be established.

DOI of Published Version



Shock. 1994 Jun;1(6):419-24.

Journal/Book/Conference Title

Shock (Augusta, Ga.)

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Link to Article in PubMed

PubMed ID