Reduction of Hypercatecholaminemia Restores Vascular Endothelial Growth Factor Expression and Improves Tissue Repair after Lung Injury

Vol. 223, No. 4S1, October 2016

Scientific Forum Abstracts

Table. Cranial CT Scoring Tool vs Key Clinical Study Outcomes

Table.

Category CCTST < 2 CCTST 3-4 CCTST 5-6 CCTST 7+ Mortality, % 9.95 22.1 39.1 54.3 Morbidity, % 25.8 31.4 35.9 70.6 Glasgow Coma Scale, mean 13.1 11.0 8.92 8.00 Functional Independence Measure score, mean 15.7 14.1 12.4 10.4 Hospital LOS, d, mean 7.73 9.08 10.5 12.9 ICU LOS, d, mean 3.34 5.13 6.30 8.49 Ventilator days, mean 1.10 3.05 5.73 8.60 Step-down unit LOS, d, mean 0.64 1.43 1.98 3.14 Discharged to home, % 44.0 29.4 11.5 9.38

Variable

CONCLUSIONS: The number of discrete findings on CCT correlates with important TBI outcomes measures, including NSI and mortality. The CCTST is easy to calculate and this preliminary investigation supports further validation efforts of this novel scoring system. Reduction of Hypercatecholaminemia Restores Vascular Endothelial Growth Factor Expression and Improves Tissue Repair after Lung Injury Tyler J Loftus, MD, Ines Alamo, MD, Andrew J Thomson, Kolenkode B Kannan, PhD, Mc Harry N Ramos, Elizabeth M Whitley, DVM, PhD, Philip A Efron, MD, FACS, FCCM, Alicia M Mohr, MD, FACS University of Florida, Gainesville, FL INTRODUCTION: Previous animal work has shown that lung vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-1 (VEGFR-1) expression was increased after lung contusion (LC) alone, and lung tissue healed completely. Adding hemorrhagic shock (HS) and chronic stress (CS) to LC decreased expression of VEGF, VEGFR-1, and VEGFR-2, and injured lung tissue did not heal. We hypothesized that clonidine would reduce hypercatecholaminemia, increase VEGF and VEGF receptor expression, and promote lung healing after LCHS/CS. METHODS: Eight- to 9-week-old male Sprague-Dawley rats were allocated to 4 groups: naı¨ve, LC, LC followed by HS (LCHS), and LCHS with CS using a restraint cylinder for 2 hours daily (LCHS/ CS). Clonidine was administered 10 minutes after HS and daily after CS. Rats were sacrificed on day 7. Expression of lung VEGF, VEGFR-1, VEGFR-2 was determined by polymerase chain reaction. Lung Injury Score (LIS) was determined with a light microscopy scoring system evaluating inflammatory cell counts, interstitial edema, pulmonary edema, and alveolar integrity (0, normal; 8, severe injury). Groups were compared by 1-way analysis of variance and reported as mean
SD (Table). RESULTS: Clonidine restored VEGF expression to naı¨ve levels 7 days after LCHS and LCHS/CS. Clonidine significantly increased VEGFR-1 and R-2 expression 7 days after LCHS/CS. Clonidine decreased inflammatory cell counts and the overall severity of lung injury 7 days after LCHS/CS.

LCHS, mean
SD

LCHS + clonidine, mean
SD

LCHS/CS, mean
SD

S157

LCHS/CS + clonidine, mean
SD

VEGF (naı¨ve 113
8)

80
8

114
12*

80
19

VEGFR-1 (naı¨ve 80
9)

52
6

66
13

32
8

117
5* 98
9*

VEGFR-2 (naı¨ve 112
4)

79
8

76
8

69
13

102
9*

Inflammatory cells/high power field (naı¨ve 0.3
0.5)

3.3
0.5

3.0
1.3

3.8
0.4

2.4
0.9*

Lung Injury Score (naı¨ve 1.0
0.9)

6.5
1.0

7.3
2.1

8.2
0.8

5.4
2.2*

*p < 0.05 vs untreated counterpart. CONCLUSIONS: Clonidine significantly increased VEGF and VEGF receptor expression 7 days after severe trauma, especially when severe trauma was followed by CS. Increased VEGF, VEGFR-1, and VEGFR-2 expression correlated with decreased inflammatory cell infiltration and enhanced lung tissue healing.

Resuscitation with Lyophillized Plasma Is Safe and Provides Neuroprotection in a Long-Term Survival Model of Swine Subjected to Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma Vahagn C Nikolian, MD, Patrick E Georgoff, MD, Peter J Bruhn, Ihab Halaweish, MD, Kiril Chtraklin, DVM, Baihong Pan, Baoling Liu, MD, Yongqing Li, MD, PhD, Hasan B Alam, MD, FACS University of Michigan, Ann Arbor, MI INTRODUCTION: We have shown that fresh frozen plasma (FFP) and lyophilized plasma (LP) decrease brain lesion size within the first 6 to 8 hours in large-animal models of traumatic brain injury (TBI), hemorrhagic shock, and polytrauma. In this study, we examined the effects of these treatments on long-term functional outcomes. METHODS: Female Yorkshire swine were subjected to TBI (controlled cortical impact), hemorrhage (40% volume), grade III liver and splenic injuries, rib fracture, and rectus abdominis crush. The animals were maintained in a state of shock (mean arterial pressure 30-35 mmHg) for 2 hours and then randomized to resuscitation with normal saline (NS), FFP, or LP (n¼5/group). Two hours post-resuscitation, autologous packed red blood cells were administered and animals were recovered from anesthesia. Daily neurologic severity scores were calculated and congitive assessment performed using validated tools. Brain lesion sizes were measured via magnetic resonance imaging (MRI) on postoperative days (POD) 3 and 10. Animals were euthanized on POD 30. RESULTS: The severity of shock, response to resuscitation, and safety profile of resuscitative fluids were similar, but FFP- and LP-treated animals showed significantly less neurologic impairment (POD 1-5) and a faster return to baseline compared with the NS group. No statistically significant differences were noted in the brain lesion sizes measured by MRI. Although the final cognitive functional performance was similar, the NS animals showed significant delays due to neurologic impairment.