Effect and mechanism of propofol on myocardial contractile dysfunction in sepsis

To investigate the effect and mechanism of propofol on myocardial systolic dysfunction in sepsis.

Cecal ligation and puncture（CLP）was used to induce a septic rat model. Twenty-four adult SD rats were randomly divided into sham group, sepsis group（the samples were taken 12 h after CLP modeling）and propofol group（10 mg/kg propofol was injected intraperitoneally in 0 and 12 h after CLP modeling, and the samples were taken 3 h after the second injection of propofol）. Sarcomere length and intracellular calcium fluorescence intensity of myocardial cells were measured by cell microtensiometer. Further, acute isolated cardiomyocytes from the propofol group were incubated with inositol 1,4,5-triphosphate receptor（IP₃R）inhibitor 2-aminoethyl diphenylborinate（2-APB）, sarco/endoplasmic reticulum Ca²⁺-ATPase（SERCA）inhibitor 2, 5-di-t-butyl-1, 4-benzohydroquinone（BHQ）, ryanodine receptor（RyRs）inhibitor azumolene, and large conductance calcium-activated potassium channel（BKCa）inhibitor paxiline, respectively. Then sarcomere length and intracellular calcium fluorescence intensity of myocardial cells were measured again.

Compared with the sham group, the contractile function and calcium transient amplitude of myocardial cells were significantly decreased in the sepsis group, while propofol treatment obviously restored the contractile function and calcium release ability of myocardial cells in sepsis, with a maximum contractile amplitude restoration of 27.6%（P<0.05）and a maximum calcium transient amplitude restoration of 41.2%（P<0.05）. However, 2-APB and BHQ notably suppressed the improvement of contractile function of cardiomyocytes induced by propofol, with an inhibitory rate of 62.61%（P<0.05）and 42.15%（P<0.05）, respectively. However, azumolene had no significant effect on contractile function. Further studies showed that azumolene, 2-APB and BHQ had inhibitory effects on calcium transients with different extent. Among the 3 inhibitors, azumolene showed the mildest inhibitory effect, with a rate of 46.94%（P<0.05）, and the rate was 65.28%（P<0.05）and 65.33%（P<0.05）, respectively for 2-APB and BHQ. Paxiline had no statistical effect on propofol improving myocardial contractile function and calcium transients.

Propofol improves the contractile function of myocardial cells in sepsis, which may be related to the regulation of calcium concentration through IP₃R and SERCA.