| Background: Cardiac contractile dysfunction associated with hemorrhagic shock(HS) has long been considered as an important contributor involved in microcirculation disturbance, multiple organ dysfunction and even death. Among causes of HS-induced cardiac contractile dysfunction, the calcium desensitization of myocardial cells plays a pivotal role in the pathogenesis of HS. It has been reported that the return of post-hemorrhagic shock mesenteric lymph(PHSML) is one of major factors that aggravates myocardial injury and recruit cardiac pump dysfunction. However, whether the return of PHSML is related to the myocardial contractile dysfunction and its mechanism is associated with the calcium desensitization of myocardial cells deserves to research.Objective: In order to clarify the possible mechanism of PHSML in cardiac contractile dysfunction, after establishing hemorrhagic shock model in rats, focused on the papillary muscles, using the mean of PHSML drainage, the study observed the effects of PHSML drainage on the contractile function and calcium sensitization of papillary muscles harvested from HS. Thus, taken shock mesenteric lymph as a target, the present experiment may provide an experimental evidence for the clinical interference of cardiac contractile dysfunction.Methods: Healthy Wistar rats were randomized to Sham, Shock and Shock+drainage groups. All of the animals were anesthetized with pentobarbital(50 mg/kg) generally. Bilateral femoral arteries and the right femoral vein were separated. The right femoral vein was cannulated for anticoagulation with 0.5% heparin sodium(500U/kg). A minimally heparinized polyethylene catheter was introduced into the right femoral artery used to continuously monitor the animals’ mean artery pressure(MAP) using a Power Lab data acquisition system. Another catheter was similarly inserted into the left femoral artery for bleeding by a syringe pump. In the shock and shock+drainage groups, after a 30-min stabilization period blood was withdrawn from the right femoral artery to a mean arterial pressure(MAP) of 40±2 mm Hg within 10 min at an even speed and was maintained at this level for 3 h by withdrawing or reinfusing shed blood as blood pressure required. In rats of shock + drainage group, the mesenteric lymph duct was cannulated and mesenteric lymph was drained continuously from 1h of hypertension up to 3h. In the sham group, the rats were performed same protocol as described above, but no blood was withdrawn. The papillary muscles were harvested at 3 h or corresponding time points after shock and were used to determine of cardiac contractile function. Two papillary muscle strips were prepared from one animal. The one was used to observe myocardial cell contractile response to isopropylarterenol(Iso)(final concentration 1×10-8, 1×10-7, 1×10-6, 1×10-5 mol/L) and the other was used to measure contractile response to calcium(final concentration 2.5×10-4, 5×10-4, 1.5×10-3, 2.5×10-3 mol/L)(calcium sensitivity).Results: The contractile response and +df/dt of papillary muscle strip to gradient Iso in shock and shock+drainage group is decreased when compared with that of sham group significantly. Moreover, the contractile response of papillary muscle strip to Iso at concentration of 1×10-7 and 1×10-6 mol/L in shock+drainage group is increased when compared with that of shock group significantly(P<0.05). The-df/dt of papillary muscle strip to Iso at concentration of 1×10-7 and 1×10-6 mol/L in shock group is decreased when compared with that of sham group significantly(P<0.05); the-df/dt of papillary muscle strip to Iso at concentration of 1×10-7 mol/L in shock+drainage group is increased when compared with that of shock group significantly(P<0.05). The contractile response of papillary muscle strip to gradient calcium(2.5×10-4, 5×10-4, 1.5×10-3 and 2.5×10-3 mol/L) in shock group is decreased when compared with that of sham group significantly(P<0.05). The contractile response of papillary muscle strip to calcium at concentration of 5×10-4, 1.5×10-3 and 2.5×10-3 mol/L in shock+drainage group is increased when compared with that of shock group significantly(P<0.05). The ±df/dt of papillary muscle strip to calcium at multiple concentration points of shock group is decreased when compared with that of sham group significantly(P<0.05), the ±df/dt at multiple concentration points of shock+drainage group is increased when compared with that of shock group significantly(P<0.05).Conclusion: PHSML drainage improves the reactivity of papillary muscle to Iso harvested from rats challenged by HS, its mechanisms may be related to the up-regulation of calcium sensitivity. Targeted shock mesenteric lymph, the present results provide a novel insight for the intervention of cardiac contractile dysfunction associated with hemorrhagic shock. |
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