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No significant differences were observed in the body temperatures of animals in the S group, VF-C group and VF-I group at each time point (Table 1). At a MAP > 90 mmHg, the heart rates of the animals in the VF-C group and VF-I group after ROSC were significantly higher than those in the S group. The heart rates in the two groups of animals reached their peak 1 h after ROSC and then decreased over time. At 6 h after ROSC, these values remained significantly higher than those in the S group.
Table 1. Comparison of the body temperatures of the three groups of animals at different time points
Item Baseline ROSC immediate ROSC 30 min ROSC 1 h ROSC 2 h ROSC 4 h ROSC 6 h Sham operation 35.97 ± 1.11 36.30 ± 0.67 36.48 ± 0.33 36.55 ± 0.42 36.75 ± 0.33 36.58 ± 0.64 36.67 ± 0.52 VF control 35.65 ± 1.36 35.91 ± 1.17 36.55 ± 1.63 36.54 ± 1.69 36.85 ± 2.03 36.58 ± 2.50 36.49 ± 2.46 654-1 group 36.75 ± 1.54 36.11 ± 1.36 35.98 ± 1.85 36.29 ± 1.88 35.90 ± 1.97 35.91 ± 2.21 35.40 ± 2.48 Note. The unit is degrees Celsius. ROCS, recovery of spontaneous circulation. At 0.5 h after ROSC, the VF-I group began to receive 654-1 intravenously, and the infusion lasted approximately 1.5 h. The heart rates of animals in the VF-I group were significantly higher than those in the VF-C group at 1 h after ROSC (0.5 h after medication); the heart rates then decreased starting 2 h after ROSC. From baseline until 6 h after ROSC, the heart rates in the VF-I group did not significantly differ from those in the VF-C group (Figure 1).
Figure 1. Comparison of the heart rates in the three groups of animals at different time points. The yellow curve represents the S group, the blue curve represents the VF-C group, and the red curve represents the VF-I group, *P < 0.05. The heart rates in the post-ROSC VF-C group and the VF-I group were significantly higher than those in the S group, reaching a peak at 1 h after ROSC. These rates remained significantly higher than those in the S group at 6 h after ROSC. The VF-I group began to receive 654-1 at 0.5 h after ROSC, and the infusion time was approximately 1.5 h. The heart rates in the VF-I group were significantly higher than those in the VF-C group at ROSC 1 h (0.5 h after medication). From 2 h after ROSC (1.5 h after medication) to 6 h after ROSC, the heart rates in the VF-I group did not significantly differ from those in the VF-C group. ROSC, return of spontaneous circulation; CPR, cardiopulmonary resuscitation.
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No significant difference was observed in Pv-aCO2 and lactic acid levels among the S groups, VF-C group and VF-I group at baseline and immediately after ROSC. However, at various time points after ROSC, the levels of Pv-aCO2 and lactic acid in the VF-C group were significantly higher than those in the S group. Pv-aCO2 peaked at 1 h after ROSC, then slowly decreased until 6 h after ROSC but remained significantly higher than that in the S group. Lactic acid peaked at 0.5 h after ROSC. Although it decreased significantly afterward, it remained significantly higher than that in the S group at 6 h after ROSC.
The Pv-aCO2 level in the VF-I group decreased rapidly at 0.5 h after ROSC after 654-1 administration and was significantly lower than that in the VF-C group at 1 h ROSC. It was also significantly lower than that in the VF-C group at each subsequent time point. No significant difference was observed with respect to that in the S group. After initiation of the 654-1 intervention, the blood lactic acid level also changed rapidly. At 1 h after ROSC and various time points thereafter, the indicators in the VF-I group were significantly lower than those in the VF-C group.
The cardiac ejection capacity of experimental animals significantly decreased after ROSC. The cardiac index (CI) in the VF-C group and VF-I group was significantly lower than that in the S group, and this effect persisted until 6 h after ROSC. However, the VF-I group began to receive 654-1 0.5 h after ROSC, and the CI was significantly higher than that in the VF-C group at each subsequent time point, although it remained lower than that in the sham operation group.
The small vessel resistance (SVR) of experimental animals in the VF-C group and VF-I group after ROSC was significantly higher than that in the S group. The SVR level in the VF-C group peaked 1 h post-ROSC, then slowly decreased, and remained significantly higher than that in the S group 6 h after ROSC. The SVR in the VF-I group did not differ from that in the VF-C group at the time of ROSC until 0.5 h afterward, but after administration of 654-1 at 0.5 h, the SVR level was significantly lower than that in the VF-C group; the SVR level was not significantly different from that in the S group at 6 h after ROSC (Figure 2).
Figure 2. Comparison of lactic acid levels, Pv-aCO2, CI and SVR indicators at different time points in the three groups of animals. The yellow curve represents the S group, the blue curve represents the VF-C group, and the red curve represents the VF-I group, *P < 0.05. At various time points after ROSC, the levels of Pv-aCO2 and LAC in the VF-C group were significantly higher than those in the S group, then slowly decreased thereafter. These levels remained significantly higher than those in the S group at 6 h ROSC. After administration of 654-1, the blood lactic acid level and Pv-aCO2 were significantly lower than those in the VF-C group. The ejection capacity of the heart after ROSC was significantly diminished and remained significantly lower than that in the S group 6 h after ROSC. After administration of 654-1, the CI at each time point was significantly higher than that in the VF-C group but remained lower than that in the S group, whereas the SVR level was significantly lower than that in the VF-C group. No difference with respect to the S group was observed at 6 h ROSC. CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation; CI, cardiac index; SVR, small vessel resistance; LAC, Lactic acid.
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At baseline, the visceral microcirculation monitoring parameters in the three groups of experimental animals, including MFI, TVD, PPV and PVD, showed no significant differences. Although the experimental animals maintained a MAP > 90 mmHg after ROSC, no significant difference was observed with respect to the S group values, although the microcirculation indices after ROSC remained significantly lower than those in the S group until 6 h after ROSC.
After the 654-1 intervention at 0.5 h after ROSC, the MFI, TVD, PPV and PVD in the VF-I group were significantly higher than those in the VF-C group at all subsequent time points, although they remained significantly lower than those in the S group at 6 h post-ROSC (Figure 3).
Figure 3. Comparison of microcirculation indices of the three groups of animals at different time points. The yellow curve represents the S group, the blue curve represents the VF-C group, and the red curve represents the VF-I group, compare VF-C and the VF-I group, *P < 0.05. After ROSC, the experimental animals maintained a MAP > 90 mmHg; however, the microcirculation indices (MFI, TVD, PPV and PVD) in the experimental group were significantly lower than those in the S group at ROSC and for 6 h thereafter. The MFI, TVD, PPV, and PVD after 654-1 intervention were significantly higer than those in the VF-C group at all subsequent time points, but remained significantly lower than those in the S group at 6 h after ROSC. MFI, microcirculation flow index; TVD, total vessel density. PPV, perfusion pressure of valve; PVD, perfusion vessel density; CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation.
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No significant differences were observed in TNF-α among the three groups of animals at baseline, and its level increased significantly after CPR. The level in the VF-C group remained significantly higher than that in the S group until 6 h after ROSC. The level in the VF-I group was higher than that in the S group at 1 h, 2 h, and 4 h after ROSC, but was significantly lower than that in the VF-C group. At 6 h after ROSC, no significant difference was observed with respect to the S group.
The SDC-1 of the three groups of animals showed no significant differences at baseline, and its level increased significantly after CPR. The VF-C group level peaked at 4 h after ROSC, then decreased thereafter, but remained significantly higher than that in the S group after 6 h. No significant difference was observed between the VF-I group and VF-C group at 1 h ROCS, and the level was significantly lower than that in the VF-C group at each subsequent time point. No significant difference was observed at 6 h after ROSC with respect to the S group (Figure 4).
Figure 4. Comparison of TNF-α and SDC-1 levels in the three groups of animals at different time points. The yellow curve represents the S group, the blue curve represents the VF-C group, and the red curve represents the VF-I group, *P < 0.05. No significant difference was observed in the levels of TNF-α and SDC-1 in the three groups at baseline, and the levels significantly increased after ROSC. The VF-C group level was significantly higher than that in the S group at 6 h after ROSC. The levels of the two indicators were significantly lower than those in the VF-C group at simultaneous time points, and no significant difference with respect to the S group was observed at 6 h after ROSC. CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation.
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At 6 h post-ROSC, the levels of TNF-α and SDC-1 in the myocardial tissue of the VF-C group were significantly higher than those in the S group and the VF-I group, whereas the TNF-α level in the VF-I group did not significantly differ from that in the S group. Although the SDC-1 level in the VF-I group was higher than that in the S group, it was significantly lower than that in the VF-C group (Figure 5).
Figure 5. Comparison of TNF-α and SDC-1 levels in myocardial tissues of the three groups of animals 6 h after ROSC. The green bar represents the S group, the red bar represents the VF-C group, and the blue bar represents the VF-I group. *Significant difference with respect to the S group, #significant difference with respect to the VF-C group. At 6 h post-ROSC, the levels of TNF-α and SDC-1 in the myocardial tissue of the VF-C group were significantly higher than those in the S group. No significant difference was observed in TNF-α levels between the VF-I group and the S group. The SDC-1 level was higher than that in the S group but significantly lower than that in the VF-C group. ROSC, recovery of spontaneous circulation.
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Under a light microscope, the myocardial myofilaments of samples from the VF-I group appeared to be arranged neatly, whereas those in the VF-C group samples were disordered. Under an electron microscope, the myocardial muscle fibers of samples from the VF-I group appeared mildly damaged, with relatively complete and neatly arranged myofilament structures, whereas those in the VF-C group were severely damaged, showing a damaged, broken and disordered myofilament structure (Figure 6).
Figure 6. Electron microscopy and histopathological (H&E-stained samples) light microscopy of myocardial tissue from the VF-I group and the VF-C group. Pictures of the VF-I group: 0.5 μm transmission electron microscopy (A); 2 μm transmission electron microscopy (B); 400× magnification of histopathologic (H&E-stained) samples (C). Pictures of the VF-C group: 0.5 μm transmission electron microscopy (D); 3 µm transmission electron microscopy (E); 400× magnification of histopathologic (H&E-stained) samples (F). The results of electron microscopy and light microscopy of histopathologic (H&E-stained) tissue samples revealed that the myocardial myofilament structure in the VF-I group was nearly complete and neatly arranged, and showed minimal muscle fiber damage; in contrast, the myocardial fibers in the VF-C group were severely damaged, as indicated by myofilament structures with clear damage and disordered arrangement.
doi: 10.3967/bes2022.044
Influence of Microcirculatory Dysfunction on Myocardial Injury after Cardiopulmonary Resuscitation
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Abstract:
Objective This study aimed to examine the effects of microcirculatory dysfunction and 654-1 intervention after cardiopulmonary resuscitation on myocardial injury. Methods Landrace pigs were divided into a sham operation group (S group, n = 6), ventricular fibrillation control group (VF-C group, n = 8) and 654-1 intervention group (VF-I group, n = 8). Hemodynamics was recorded at baseline, at recovery of spontaneous circulation (ROSC), and 1 h, 2 h, 4 h and 6 h thereafter. Sidestream dark field (SDF) technology was used to evaluate and monitor the microcirculation flow index, total vessel density, perfusion vessel ratio, De-Backer score, and perfusion vessel density in animal viscera at various time points. Results After administration of 654-1 at 1.5 h post-ROSC, the hemodynamics in the VF-I group, as compared with the VF-C group, was significantly improved. The visceral microcirculation detected by SDF was also significantly improved in the VF-I group. As observed through electron microscopy, significantly less myocardial tissue injury was present in the VF-I group than the VF-C group. Conclusion Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation. -
Figure 1. Comparison of the heart rates in the three groups of animals at different time points. The yellow curve represents the S group, the blue curve represents the VF-C group, and the red curve represents the VF-I group, *P < 0.05. The heart rates in the post-ROSC VF-C group and the VF-I group were significantly higher than those in the S group, reaching a peak at 1 h after ROSC. These rates remained significantly higher than those in the S group at 6 h after ROSC. The VF-I group began to receive 654-1 at 0.5 h after ROSC, and the infusion time was approximately 1.5 h. The heart rates in the VF-I group were significantly higher than those in the VF-C group at ROSC 1 h (0.5 h after medication). From 2 h after ROSC (1.5 h after medication) to 6 h after ROSC, the heart rates in the VF-I group did not significantly differ from those in the VF-C group. ROSC, return of spontaneous circulation; CPR, cardiopulmonary resuscitation.
Figure 2. Comparison of lactic acid levels, Pv-aCO2, CI and SVR indicators at different time points in the three groups of animals. The yellow curve represents the S group, the blue curve represents the VF-C group, and the red curve represents the VF-I group, *P < 0.05. At various time points after ROSC, the levels of Pv-aCO2 and LAC in the VF-C group were significantly higher than those in the S group, then slowly decreased thereafter. These levels remained significantly higher than those in the S group at 6 h ROSC. After administration of 654-1, the blood lactic acid level and Pv-aCO2 were significantly lower than those in the VF-C group. The ejection capacity of the heart after ROSC was significantly diminished and remained significantly lower than that in the S group 6 h after ROSC. After administration of 654-1, the CI at each time point was significantly higher than that in the VF-C group but remained lower than that in the S group, whereas the SVR level was significantly lower than that in the VF-C group. No difference with respect to the S group was observed at 6 h ROSC. CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation; CI, cardiac index; SVR, small vessel resistance; LAC, Lactic acid.
Figure 3. Comparison of microcirculation indices of the three groups of animals at different time points. The yellow curve represents the S group, the blue curve represents the VF-C group, and the red curve represents the VF-I group, compare VF-C and the VF-I group, *P < 0.05. After ROSC, the experimental animals maintained a MAP > 90 mmHg; however, the microcirculation indices (MFI, TVD, PPV and PVD) in the experimental group were significantly lower than those in the S group at ROSC and for 6 h thereafter. The MFI, TVD, PPV, and PVD after 654-1 intervention were significantly higer than those in the VF-C group at all subsequent time points, but remained significantly lower than those in the S group at 6 h after ROSC. MFI, microcirculation flow index; TVD, total vessel density. PPV, perfusion pressure of valve; PVD, perfusion vessel density; CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation.
Figure 4. Comparison of TNF-α and SDC-1 levels in the three groups of animals at different time points. The yellow curve represents the S group, the blue curve represents the VF-C group, and the red curve represents the VF-I group, *P < 0.05. No significant difference was observed in the levels of TNF-α and SDC-1 in the three groups at baseline, and the levels significantly increased after ROSC. The VF-C group level was significantly higher than that in the S group at 6 h after ROSC. The levels of the two indicators were significantly lower than those in the VF-C group at simultaneous time points, and no significant difference with respect to the S group was observed at 6 h after ROSC. CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation.
Figure 5. Comparison of TNF-α and SDC-1 levels in myocardial tissues of the three groups of animals 6 h after ROSC. The green bar represents the S group, the red bar represents the VF-C group, and the blue bar represents the VF-I group. *Significant difference with respect to the S group, #significant difference with respect to the VF-C group. At 6 h post-ROSC, the levels of TNF-α and SDC-1 in the myocardial tissue of the VF-C group were significantly higher than those in the S group. No significant difference was observed in TNF-α levels between the VF-I group and the S group. The SDC-1 level was higher than that in the S group but significantly lower than that in the VF-C group. ROSC, recovery of spontaneous circulation.
Figure 6. Electron microscopy and histopathological (H&E-stained samples) light microscopy of myocardial tissue from the VF-I group and the VF-C group. Pictures of the VF-I group: 0.5 μm transmission electron microscopy (A); 2 μm transmission electron microscopy (B); 400× magnification of histopathologic (H&E-stained) samples (C). Pictures of the VF-C group: 0.5 μm transmission electron microscopy (D); 3 µm transmission electron microscopy (E); 400× magnification of histopathologic (H&E-stained) samples (F). The results of electron microscopy and light microscopy of histopathologic (H&E-stained) tissue samples revealed that the myocardial myofilament structure in the VF-I group was nearly complete and neatly arranged, and showed minimal muscle fiber damage; in contrast, the myocardial fibers in the VF-C group were severely damaged, as indicated by myofilament structures with clear damage and disordered arrangement.
Table 1. Comparison of the body temperatures of the three groups of animals at different time points
Item Baseline ROSC immediate ROSC 30 min ROSC 1 h ROSC 2 h ROSC 4 h ROSC 6 h Sham operation 35.97 ± 1.11 36.30 ± 0.67 36.48 ± 0.33 36.55 ± 0.42 36.75 ± 0.33 36.58 ± 0.64 36.67 ± 0.52 VF control 35.65 ± 1.36 35.91 ± 1.17 36.55 ± 1.63 36.54 ± 1.69 36.85 ± 2.03 36.58 ± 2.50 36.49 ± 2.46 654-1 group 36.75 ± 1.54 36.11 ± 1.36 35.98 ± 1.85 36.29 ± 1.88 35.90 ± 1.97 35.91 ± 2.21 35.40 ± 2.48 Note. The unit is degrees Celsius. ROCS, recovery of spontaneous circulation. -
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