Preconditioning with Porphyromonas gingivalis lipopolysaccharide may confer cardioprotection and improve recovery of the electrically induced intracellular calcium transient during ischemia and reperfusion.
OBJECTIVE
Porphyromonas gingivalis lipopolysaccharide (LPS) is a ligand for cell surface toll-like receptors (TLR), TLR2 and TLR4 while stimulation of either leads to cardioprotection. We hypothesized that: (1) pretreatment with P. gingivalis LPS at appropriate concentrations would induce cardioprotection against injury induced by ischemia and reperfusion; and (2) P. gingivalis LPS pretreatment at cardioprotective concentrations may reduce Ca(2+) overload, which is a precipitating cause of injury, and improve recovery of contractile function.


METHODS
Male Sprague-Dawley rats were randomly selected to receive intraperitoneal saline or hot phenol-water-extracted P. gingivalis LPS at 0.2, 0.5, 1.0, 2.0 or 4.0 mg/kg 24 h before the experiment. The hearts were isolated and subjected to regional ischemia by coronary artery ligation followed by reperfusion. In isolated rat ventricular myocytes, the cytosolic Ca(2+) level and the electrically induced intracellular calcium (E[Ca(2+)](i)) transient, which reflects contractile function, were determined after pretreatment with a cardioprotective dose of P. gingivalis LPS.


RESULTS
Pretreatment with 0.5 mg/kg P. gingivalis LPS significantly reduced, while pretreatment with 1.0-4.0 mg/kg significantly increased infarct size. The Ca(2+) overload induced by ischemia-reperfusion was attenuated in myocytes from rats pretreated with 0.5 mg/kg P. gingivalis LPS. Pretreated myocytes also showed an increased amplitude of the E[Ca(2+)](i) transient, no prolongation of the time to reach the peak E[Ca(2+)](i) transient and shorter 50% decay time during reperfusion.


CONCLUSIONS
At a dosage of 0.5 mg/kg, P. gingivalis LPS confers cardioprotection against ischemia-reperfusion-induced injury and improved intracellular E[Ca(2+)](i) transient recovery, hence improving myocyte contractile recovery.
Fan
M H M
MH
Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Wong
K L
KL
Wu
S
S
Leung
W K
WK
Yam
W C
WC
Wong
T M
TM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000032:analysis; D015220:Calcium Channels / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003600:Cytosol / Q000187:drug effects; D006352:Heart Ventricles / Q000473:pathology; D007274:Injections, Intraperitoneal; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000187:drug effects; D016966:Porphyromonas gingivalis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D012508:Sarcolemma / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000187:drug effects; D013997:Time Factors
D015220:Calcium Channels; D002316:Cardiotonic Agents; D008070:Lipopolysaccharides; D002118:Calcium