Introduction
Materials and methods
Ethical approval of the study protocol
Animal management
Experimental phases
Animal survival, fluid requirements and blood losses
Hemodynamic parameters, tissue blood flow, organ function and blood gases
Coagulationfunction
Statistical analyses
Results
Blood loss, fluid requirements and animal survival
Blood loss
Fluid requirements
Animal survival
Hemodynamics, blood gases, tissue blood flow, and vital organ function
Hemodynamics
Group | Baseline | End of phase I | End of phase II | End of phase III | End of phase IV |
---|---|---|---|---|---|
6 weeks old
| |||||
Female
| |||||
No treatment | 103.2 ± 10.2 | 39.6 ± 3.5 | 37.5 ± 1.8 | 35.6 ± 1.7 | 33.8 ± 1.6 |
40 mmHg | 104.5 ± 11.2 | 41.2 ± 3.6 | 42.4 ± 2.1 | 83.6 ± 4.1** | 82.8 ± 4.1** |
50 mmHg | 102.8 ± 8.5 | 39.5 ± 3.5 | 50.2 ± 2.7 | 85.5 ± 4.8** | 90.6 ± 4.7*# |
60 mmHg | 104.6 ± 9.5 | 40.2 ± 3.5 | 62.8 ± 3.1 | 80.7 ± 4.0** | 79.8 ± 3.9** |
70 mmHg | 106.3 ± 11.0 | 41.0 ± 3.6 | 71.5 ± 3.7 | 81.7 ± 3.6** | 70.9 ± 3.5** |
80 mmHg | 108.3 ± 12.0 | 40.2 ± 3.5 | 71.4 ± 3.5 | 82.7 ± 3.1** | 62.1 ± 3.0** |
Male
| |||||
No treatment | 104.2 ± 8.6 | 39.6 ± 3.5 | 37.5 ± 1.8 | 35.6 ± 1.7 | 33.9 ± 1.6 |
40 mmHg | 105.2 ± 8.6 | 41.6 ± 3.7 | 42.5 ± 2.1 | 78.0 ± 3.8** | 76.0 ± 3.7** |
50 mmHg | 102.3 ± 5.9 | 43.2 ± 3.8 | 51.6 ± 2.7 | 89.1 ± 4.4** | 86.8 ± 4.3**# |
60 mmHg | 100.8 ± 6.8 | 41.5 ± 3.7 | 62.8 ± 3.1 | 85.5 ± 4.2** | 79.7 ± 3.9** |
70 mmHg | 104.3 ± 9.4 | 42.2 ± 3.7 | 70.5 ± 3.7 | 76.0 ± 3.8** | 70.8 ± 3.5** |
80 mmHg | 102.3 ± 10.2 | 38.9 ± 3.4 | 71.4 ± 3.5 | 76.5 ± 3.3** | 62.0 ± 3.0**# |
14 weeks old
| |||||
Female
| |||||
No treatment | 107.8 ± 11.3 | 42.2 ± 3.7 | 40.0 ± 1.9 | 38.0 ± 1.8 | 36.1 ± 1.7 |
40 mmHg | 108.6 ± 9.4 | 39.6 ± 3.5 | 42.4 ± 2.1 | 81.8 ± 3.5** | 72.5 ± 3.6** |
50 mmHg | 106.3 ± 10.2 | 43.6 ± 3.9 | 50.8 ± 2.7 | 85.8 ± 4.8** | 96.7 ± 4.8**## |
60 mmHg | 107.5 ± 9.2 | 41.1 ± 3.6 | 62.7 ± 3.1 | 86.8 ± 4.4** | 90.7 ± 4.5**## |
70 mmHg | 108.9 ± 9.5 | 43.6 ± 3.8 | 69.2 ± 3.6 | 86.3 ± 4.3** | 77.6 ± 3.9** |
80 mmHg | 109.8 ± 8.6 | 40.1 ± 3.5 | 81.4 ± 4.0 | 75.5 ± 3.7** | 67.9 ± 3.3** |
Male
| |||||
No treatment | 110.2 ± 10.2 | 40.9 ± 3.6 | 38.7 ± 1.9 | 36.8 ± 1.8 | 34.9 ± 1.7 |
40 mmHg | 109.8 ± 11.2 | 40.1 ± 3.5 | 42.4 ± 2.1 | 76.0 ± 3.2** | 71.8 ± 3.5** |
50 mmHg | 110.3 ± 8.8 | 40.2 ± 3.5 | 49.5 ± 2.6 | 85.1 ± 4.4** | 95.7 ± 4.8**## |
60 mmHg | 107.5 ± 8.2 | 41.2 ± 3.6 | 62.9 ± 3.1 | 82.6 ± 4.1** | 89.7 ± 4.4**# |
70 mmHg | 108.6 ± 9.1 | 41.0 ± 3.6 | 72.5 ± 3.8 | 82.1 ± 4.1** | 80.6 ± 4.0**# |
80 mmHg | 110.2 ± 9.6 | 42.0 ± 3.7 | 81.3 ± 4.0 | 81.9 ± 3.5** | 70.5 ± 3.5** |
1.5 years old
| |||||
Female
| |||||
No treatment | 123.3 ± 11.2 | 39.6 ± 3.5 | 37.5 ± 1.8 | 35.7 ± 1.7 | 33.9 ± 1.6 |
40 mmHg | 122.1 ± 11.5 | 38.5 ± 3.4 | 42.5 ± 2.1 | 84.9 ± 2.7** | 53.1 ± 2.6* |
50 mmHg | 119.5 ± 12.6 | 40.3 ± 3.6 | 51.6 ± 2.7 | 83.3 ± 3.6** | 70.8 ± 3.5**## |
60 mmHg | 118.5 ± 13.2 | 40.2 ± 3.5 | 62.8 ± 3.1 | 81.6 ± 3.7** | 76.1 ± 3.7**## |
70 mmHg | 132.2 ± 8.0 | 40.7 ± 3.6 | 71.4 ± 3.7 | 78.4 ± 3.9** | 84.9 ± 3.9**## |
80 mmHg | 129.6 ± 8.2 | 41.2 ± 3.6 | 81.4 ± 4.0 | 78.6 ± 3.4** | 69.1 ± 3.4*## |
Male
| |||||
No treatment | 130.2 ± 10.2 | 41.0 ± 3.6 | 38.8 ± 1.9 | 36.9 ± 1.8 | 35.0 ± 1.7 |
40 mmHg | 127.5 ± 7.2 | 39.6 ± 3.5 | 42.5 ± 2.1 | 85.7 ± 2.2** | 56.3 ± 2.8* |
50 mmHg | 125.6 ± 6.8 | 40.3 ± 3.6 | 52.3 ± 2.8 | 80.9 ± 3.0** | 75.1 ± 3.7**## |
60 mmHg | 126.9 ± 8.6 | 40.2 ± 3.5 | 62.9 ± 3.1 | 83.0 ± 3.6** | 73.3 ± 3.6**## |
70 mmHg | 130.2 ± 6.2 | 39.6 ± 3.5 | 72.5 ± 3.8 | 81.7 ± 3.8** | 79.1 ± 3.8 **## |
80 mmHg | 129.4 ± 9.2 | 39.6 ± 3.5 | 81.4 ± 4.05 | 84.3 ± 3.3** | 66.5 ± 3.3**# |
Group | Baseline | End of phase I | End of phase II | End of phase III | End of phase IV |
---|---|---|---|---|---|
6 weeks old
| |||||
Female
| |||||
No treatment | 132.9 ± 15.3 | 71.8 ± 8.1 | 68.0 ± 4.9 | 64.4 ± 4.6 | 61.1 ± 4.4 |
40 mmHg | 133.7 ± 15.2 | 72.4 ± 8.2 | 81.9 ± 5.9 | 106.0 ± 7.6** | 137.7 ± 9.8** |
50 mmHg | 134.6 ± 20.2 | 73.4 ± 9.6 | 86.7 ± 13.8 | 105.4 ± 9.8** | 129.6 ± 11.9** |
60 mmHg | 130.3 ± 14.8 | 72.9 ± 8.3 | 87.6 ± 6.3 | 106.5 ± 7.0** | 121.4 ± 8.7** |
70 mmHg | 128.7 ± 22.8 | 70.2 ± 6.8 | 89.5 ± 13.5 | 104.2 ± 18.6** | 101.9 ± 15.2** |
80 mmHg | 130.9 ± 14.9 | 72.9 ± 8.3 | 92.0 ± 5.9 | 106.3 ± 6.2** | 93.4 ± 6.7**# |
Male
| |||||
No treatment | 131.9 ± 15.0 | 66.4 ± 7.5 | 62.9 ± 4.5 | 59.6 ± 4.2 | 56.4 ± 4.0 |
40 mmHg | 130.8 ± 14.8 | 65.8 ± 7.4 | 85.5 ± 6.1 | 107.3 ± 8.4** | 130.7 ± 9.4** |
50 mmHg | 132.2 ± 13.6 | 65.4 ± 5.8 | 90.5 ± 11.9 | 108.5 ± 14.5** | 123.8 ± 11.6** |
60 mmHg | 129.8 ± 14.7 | 64.2 ± 7.3 | 87.4 ± 6.2 | 106.4 ± 7.0** | 116.7 ± 8.4** |
70 mmHg | 127.1 ± 11.6 | 62.9 ± 8.1 | 90.5 ± 9.8 | 104.6 ± 9.9** | 100.9 ± 10.2** |
80 mmHg | 130.7 ± 14.8 | 63.6 ± 7.2 | 93.7 ± 5.3 | 107.3 ± 5.7* | 92.5 ± 6.6**# |
14 weeks old
| |||||
Female
| |||||
No treatment | 135.6 ± 15.4 | 70.4 ± 8.0 | 66.7 ± 4.8 | 63.2 ± 4.5 | 59.9 ± 4.3 |
40 mmHg | 133.9 ± 15.2 | 69.9 ± 7.9 | 86.0 ± 6.1 | 114.1 ± 8.2** | 106.1 ± 7.6** |
50 mmHg | 128.2 ± 20.1 | 69.9 ± 9.0 | 91.1 ± 12.7 | 125.2 ± 17.7** | 116.8 ± 16.2** |
60 mmHg | 133.9 ± 15.2 | 72.3 ± 8.2 | 96.1 ± 6.9 | 122.6 ± 8.8** | 114.3 ± 8.2** |
70 mmHg | 134.7 ± 16.5 | 73.4 ± 7.6 | 107.4 ± 16.8 | 116.5 ± 16.6** | 108.8 ± 16.2** |
80 mmHg | 132.9 ± 15.1 | 73.0 ± 8.3 | 98.3 ± 7.0 | 106.5 ± 7.8** | 99.7 ± 7.1** |
Male
| |||||
No treatment | 132.5 ± 15.0 | 74.4 ± 7.3 | 61.0 ± 4.3 | 57.8 ± 4.1 | 54.7 ± 3.9 |
40 mmHg | 131.2 ± 14.9 | 75.2 ± 7.4 | 96.3 ± 6.9 | 105.7 ± 7.5** | 98.7 ± 7.11* |
50 mmHg | 129.9 ± 9.7 | 74.3 ± 8.0 | 101.8 ± 13.0 | 115.1 ± 17.0** | 108.6 ± 13.3** |
60 mmHg | 130.9 ± 14.8 | 68.8 ± 7.6 | 98.7 ± 7.1 | 113.4 ± 8.1** | 107.0 ± 7.7** |
70 mmHg | 135.3 ± 25.1 | 69.9 ± 4.2 | 99.4 ± 12.5 | 107.9 ± 15.3** | 103.6 ± 13.9** |
80 mmHg | 131.4 ± 14.9 | 68.0 ± 7.4 | 98.8 ± 6.0 | 98.7 ± 7.1** | 95.0 ± 6.8** |
1.5 years old
| |||||
Female
| |||||
No treatment | 143.8 ± 15.9 | 76.8 ± 8.7 | 72.8 ± 5.2 | 68.9 ± 4.9 | 65.3 ± 4.7 |
40 mmHg | 148.7 ± 15.7 | 77.8 ± 8.8 | 98.6 ± 7.1 | 104.7 ± 7.4** | 105.8 ± 7.6** |
50 mmHg | 141.9 ± 19.3 | 77.4 ± 3.8 | 104.4 ± 11.4 | 115.5 ± 13.2** | 116.4 ± 10.1** |
60 mmHg | 145.7 ± 16.0 | 78.0 ± 8.8 | 104.8 ± 7.5 | 118.2 ± 8.5** | 117.7 ± 8.4** |
70 mmHg | 146.1 ± 20.0 | 79.7 ± 7.6 | 106.5 ± 16.0 | 126.4 ± 14.9** | 120.5 ± 11.7** |
80 mmHg | 145.7 ± 16.1 | 78.3 ± 8.9 | 107.0 ± 7.1 | 115.3 ± 8.2** | 110.5 ± 7.6** |
Male
| |||||
No treatment | 145.4 ± 16.2 | 78.2 ± 8.9 | 74.1 ± 5.3 | 70.2 ± 5.0 | 66.5 ± 4.7 |
40 mmHg | 148.9 ± 16.9 | 77.2 ± 8.7 | 82.6 ± 8.1 | 98.2 ± 7.0* | 102.6 ± 7.4** |
50 mmHg | 146.3 ± 23.4 | 79.8 ± 6.5 | 89.3 ± 10.3 | 108.5 ± 11.4** | 113.4 ± 11.4** |
60 mmHg | 145.7 ± 16.5 | 76.9 ± 8.7 | 90.9 ± 7.9 | 112.4 ± 8.1** | 116.7 ± 8.4** |
70 mmHg | 148.6 ± 9.7 | 81.0 ± 7.8 | 92.5 ± 9.4 | 122.9 ± 15.8** | 124.9 ± 11.7** |
80 mmHg | 147.8 ± 16.8 | 79.0 ± 8.9 | 94.8 ± 6.1 | 111.2 ± 8.0** | 114.7 ± 8.2** |
Group | Baseline | End of phase I | End of phase II | End of phase III | End of phase IV |
---|---|---|---|---|---|
6 weeks old
| |||||
Female
| |||||
No treatment | 5,454.1 ± 717.6 | 2,474.2 ± 325.5 | 2,371.1 ± 311.9 | 2,272.3 ± 298.9 | 2,177.6 ± 286.5 |
40 mmHg | 5,461.8 ± 718.6 | 2,477.2 ± 325.9 | 3,400.0 ± 578.9** | 4,569.5 ± 601.2** | 5,045.9 ± 663.9** |
50 mmHg | 5,905.4 ± 1,362.2 | 2,314.5 ± 1,114.4 | 4,663.8 ± 918.0**# | 4,777.2 ± 903.7** | 5,275.2 ± 601.9** |
60 mmHg | 5,476.4 ± 720.5 | 2,482.9 ± 326.7 | 4,602.1 ± 605.5**# | 4,453.3 ± 585.9** | 4,878.6 ± 641.9** |
70 mmHg | 5,410.0 ± 788.7 | 2,456.9 ± 645.3 | 4,776.7 ± 1,111.0**# | 4,420.9 ± 1,015.7** | 4,821.9 ± 932.0** |
80 mmHg | 5,547.3 ± 729.9 | 2,510.8 ± 330.3 | 4,525.3 ± 595.4**# | 4,188.2 ± 551.0** | 4,568.2 ± 601.0**# |
Male
| |||||
No treatment | 5,417.0 ± 712.7 | 2,118.5 ± 278.7 | 2,030.2 ± 267.1 | 1,945.7 ± 256.0 | 1,864.6 ± 245.3 |
40 mmHg | 5,424.8 ± 713.7 | 2,121.2 ± 279.1 | 3,519.6 ± 528.9** | 4,404.9 ± 579.6** | 4,943.3 ± 650.4** |
50 mmHg | 5,938.1 ± 833.1 | 2,013.5 ± 681.6 | 4,278.2 ± 538.1** | 4,605.2 ± 398.8** | 5,168.0 ± 459.9** |
60 mmHg | 5,439.4 ± 715.7 | 2,126.1 ± 279.7 | 4,251.1 ± 559.3** | 4,525.9 ± 595.5** | 4,842.5 ± 637.1** |
70 mmHg | 5,372.7 ± 638.0 | 2,103.5 ± 522.0 | 4,328.0 ± 386.0** | 4,518.0 ± 499.0** | 4,796.0 ± 558.0** |
80 mmHg | 5,510.8 ± 725.1 | 2,150.3 ± 282.9 | 4,100.2 ± 539.5** | 4,280.2 ± 563.1** | 4,543.5 ± 597.8** |
14 weeks old
| |||||
Female
| |||||
No treatment | 5,925.4 ± 779.6 | 2,750.0 ± 361.8 | 2,635.4 ± 346.7 | 2,525.6 ± 332.3 | 2,420.3 ± 318.4 |
40 mmHg | 5,933.7 ± 780.7 | 2,753.5 ± 362.3 | 3,491.2 ± 590.9** | 5,068.1 ± 666.8** | 4,898.9 ± 644.6** |
50 mmHg | 6,369.5 ± 1,402.5 | 2,654.6 ± 1,147.7 | 4,232.5 ± 731.3** | 5,298.4 ± 930.4** | 5,121.6 ± 268.0** |
60 mmHg | 5,949.4 ± 782.8 | 2,760.0 ± 363.1 | 4,852.7 ± 638.5** | 4,943.2 ± 650.4** | 4,932.7 ± 649.0** |
70 mmHg | 5,877.8 ± 927.1 | 2,730.2 ± 758.5 | 4,392.3 ± 1,007.3** | 4,907.7 ± 1,578.3** | 4,905.7 ± 1,407.8** |
80 mmHg | 6,026.0 ± 792.8 | 2,791.9 ± 367.3 | 4,161.1 ± 547.5** | 4,649.4 ± 611.7** | 4,647.5 ± 611.5** |
Male
| |||||
No treatment | 6,689.7 ± 880.2 | 2,321.2 ± 305.4 | 2,224.5 ± 292.7 | 2,131.8 ± 280.5 | 2,042.9 ± 268.8 |
40 mmHg | 6,698.2 ± 881.3 | 2,324.1 ± 305.8 | 3,379.9 ± 576.3** | 4,696.6 ± 617.9** | 4,592.4 ± 604.2** |
50 mmHg | 6,495.3 ± 1,417.3 | 2,231.5 ± 660.0 | 4,660.1 ± 413.9**# | 4,910.0 ± 910.3** | 4,801.1 ± 645.3** |
60 mmHg | 6,714.2 ± 883.4 | 2,329.6 ± 306.5 | 4,814.1 ± 633.4**# | 4,674.9 ± 615.1** | 4,693.2 ± 617.5** |
70 mmHg | 6,641.3 ± 849.6 | 2,304.5 ± 695.1 | 4,224.5 ± 944.6** | 4,651.4 ± 823.9** | 4,677.8 ± 563.1** |
80 mmHg | 6,792.3 ± 893.7 | 2,356.4 ± 310.0 | 4,002.1 ± 526.6** | 4,406.6 ± 579.8** | 4,431.6 ± 583.1** |
1.5 years old
| |||||
Female
| |||||
No treatment | 6,664.3 ± 876.8 | 2,777.2 ± 365.4 | 2,661.5 ± 350.2 | 2,550.6 ± 335.6 | 2,444.3 ± 321.6 |
40 mmHg | 6,672.2 ± 877.9 | 2,780.9 ± 365.9 | 3,398.3 ± 447.1**# | 4,711.4 ± 619.9** | 5,625.3 ± 740.1** |
50 mmHg | 6,002.8 ± 1,707.0 | 2,803.2 ± 1,397.9 | 4,230.9 ± 594.2**## | 5,104.0 ± 1,121.5** | 6,094.0 ± 931.6** |
60 mmHg | 6,687.0 ± 879.8 | 2,787.8 ± 366.8 | 4,492.9 ± 591.1**## | 5,208.6 ± 685.3** | 6,307.0 ± 829.8** |
70 mmHg | 6,619.5 ± 1,166.2 | 2,756.3 ± 954.1 | 4,710.4 ± 827.6**## | 5,295.4 ± 1,312.6** | 6,483.7 ± 1,638.6** |
80 mmHg | 6,759.1 ± 889.3 | 2,821.5 ± 371.2 | 4,462.5 ± 587.1**## | 5,016.7 ± 660.1** | 6,142.5 ± 808.2** |
Male
| |||||
No treatment | 5,961.5 ± 784.4 | 2,618.5 ± 344.5 | 2,509.4 ± 330.2 | 2,404.9 ± 316.4** | 2,304.7 ± 303.2** |
40 mmHg | 5,969.8 ± 785.5 | 2,622.0 ± 345.0 | 3,418.3 ± 449.7** | 4,787.5 ± 629.9** | 5,711.2 ± 751.4** |
50 mmHg | 6,400.8 ± 1,410.1 | 2,654.6 ± 1,154.0 | 4,445.3 ± 761.2** | 5,186.4 ± 1,559.6** | 6,187.1 ± 1,311.6** |
60 mmHg | 5,985.6 ± 787.5 | 2,628.6 ± 345.8 | 4,719.6 ± 621.0**# | 5,197.9 ± 683.9** | 6,296.6 ± 828.5** |
70 mmHg | 5,913.7 ± 1,381.5 | 2,598.7 ± 1,130.8 | 4,947.3 ± 1,040.2**# | 5,207.4 ± 781.8** | 6,387.5 ± 1,125.5** |
80 mmHg | 6,062.6 ± 797.7 | 2,660.5 ± 350.0 | 4,686.9 ± 616.7**# | 4,933.3 ± 649.1** | 6,051.3 ± 796.2** |
Blood gases
Blood flow in vital organs
Liver and kidney function
Coagulation function
Discussion
Conclusion
Key messages
-
The target resuscitation pressure for uncontrolled hemorrhagic shock is different in different ages of rats.
-
Older rats need a higher target resuscitation pressure (70 mmHg) than reproductive-age rats (50 to 60 mmHg) during uncontrolled hemorrhagic shock.