The effects of hydrogen sulfide under sevoflurane administration against ischemia and reperfusion injury in isolated rat heart

Abstract

Background: Hydrogen sulfide (H(2)S) produces a protective effect against myocardial ischemia and reperfusion injury. Sevoflurane, which is used for anesthesia in cardiac problem patients, also has a protective effect. This study is designed to reveal the effects of H(2)S under sevoflurane using rat hearts.

Methods: The hearts were Langendorff-perfused, subjected to 30 minutes ischemia and 60 minutes reperfusion. Group I was a control group. The other groups were pretreated for 15 minutes before ischemia as follows: 1.6% sevoflurane for group S; 18.5 µM H(2)S S for group H; and 1.6% sevoflurane and 18.5 µM H(2)S simultaneously for group HS. Hemodynamics and the infarct size were measured.

Results: Group HS presented depressed hemodynamics during pretreatment. LV function in group HS achieved better recovery than group I after reperfusion. The infarct size of groups S, H and HS was smaller than group I, while there were no differences between groups S, H and HS.

Conclusions: Exogenous H(2)S did not enhance the preconditioning effects of sevoflurane. Rather, the results suggest that H(2)S under sevoflurane might depress hemodynamics.

Keywords: Heart; Hydrogen sulfide; In vitro; Ischemia; Reperfusion injury; Sevoflurane.

Fig. 1

Experimental protocol. After stabilization, each group was subjected to 30 minutes of global ischemia and 60 minutes of reperfusion. Before global ischemia, a 15 minute pre-treatment period was conducted and specific agents were applied to each group as follows: perfusate and mixed gas (95% O₂ + 5% CO₂) only for group I; mixed gas with 1.6% sevoflurane and perfusate without H₂S for group S; 18.5 µM H₂S mixed perfusate and mixed gas for group H; 1.6% sevoflurane and 18.5 µM H₂S for group HS. Hemodyamic variables were measured after stabilization, after pre-treatment and 5, 30, 60 minutes after reperfusion started (Arrows). After all processes were completed, triphenyl tetrazolium staining was performed to calculate infarct size.

Fig. 2

Left ventricular end systolic pressure. Group HS showed lower systolic pressure after pre-treatment than those after stabilization. Groups H and HS showed mostly higher pressures during the reperfusion period than groups I and S. St: after stabilization, Tx: pretreatment, R5: reperfusion 5 minutes, R30: reperfusion 30 minutes, R60: reperfusion 60 minutes. P < 0.05 is remarked as follows: ^*vs. after stabilization in the same group. ^†vs. Group I, ^‡vs. Group S, ^§vs. Group H at the same measurement time.

Fig. 3

Left ventricular diastolic pressure. During the reperfusion period, diastolic pressure in all groups initially increased, and then progressively decreased over time. In group H, diastolic pressure was sustained at a high rate until 30 minutes after reperfusion and then decreased toward the value of that after stabilization. Groups S and HS showed similar patterns in pressure changes. St: after stabilization, Tx: pretreatment, R5: reperfusion 5 minutes, R30: reperfusion 30 minutes, R60: reperfusion 60 minutes. P < 0.05 is remarked as follows: ^*vs. after stabilization and/or pretreatment in the same group, ^†vs. groups I and H at the same measurement time.

Fig. 4

Heart rate. Heart rates during the reperfusion period in all groups were lower than those prior to ischemia. Heart rates in groups H and HS were mostly lower than those in group S during the reperfusion period. St: after stabilization, Tx : pretreatment, R5: reperfusion 5 minutes, R30: reperfusion 30 minutes, R60: reperfusion 60 minutes. P < 0.05 is remarked as follows: ^*vs. after stabilization in the same group, ^†vs. groups I, ^‡vs. group S at the same measurement time.

Fig. 5

Maximum rate of change of left ventricular pressure (dP/dt max). 5 minutes after reperfusion, dP/dt max in groups I and S decreased rapidly. During the rest of reperfusion, dP/dt max of all groups remained low. St: after stabilization, Tx: pretreatment, R5: reperfusion 5 minutes, R30: reperfusion 30 minutes, R60: reperfusion 60 minutes. P < 0.05 is remarked as follows: ^*vs. after stabilization in the same group.

Fig. 6

Coronoary effluent flows measured in rate. During the reperfusion period, coronary effluent flow rates of all groups decreased with time. Primarily, group S showed higher rates than groups I, H and HS. St: after stabilization, Tx: pretreatment, R5: reperfusion 5 minutes, R30: reperfusion 30 minutes, R60: reperfusion 60 minutes. P < 0.05 is remarked as follows: ^*vs. after stabilization in the same group. At the same measuring time, ^†vs. groups I, ^‡vs. group S at the same measurement time.

Fig. 7

Infarct size measured in each group. Groups S, H and HS showed smaller infarct size than group I. There was no difference between infarct size of groups S, H and HS. P < 0.05 is remarked as follows: ^*vs. group I.