Fibrin glue eliminates the need for packing after complex liver injuries.

Hemostasis after traumatic liver injury can be extremely difficult to obtain, particularly in coagulopathic patients who have suffered extensive liver damage. We determined the ability of a fibrin glue preparation (FG) to terminate ongoing bleeding using a new, clinically relevant porcine model of complex hepatic injury. Anesthetized swine (n = 6, 18 to 19 kg) received an external blast to the right upper abdomen and were immediately anticoagulated with intravenous heparin (200 u/kg). Uncontrolled hemorrhage from blast continued from time of injury (t = 0 minutes) to t = 15 minutes. Lactated Ringer's solution was infused to keep mean arterial pressure (MAP) > 80 mm Hg until the end of experiment (t = 90 minutes). Animals underwent routine surgical techniques to control bleeding, and FG was employed in the event these measures failed. Estimated blood loss and fluid resuscitation volume were measured. Serial MAP, arterial base excess, and temperature were recorded. Animals were severely injured with significant blood loss prior to laparotomy (26 +/- 6 cc/kg) and during routine surgical efforts to arrest hemorrhage (11 +/- 2 cc/kg). Bleeding could not be controlled with standard techniques in any animal. FG rapidly controlled hemorrhage and eliminated the need for packing. Re-bleeding was noted in only one animal (portal vein injury). FG can control severe hepatic hemorrhage when surgical techniques fail. Further work in the clinical arena is warranted to determine the potential benefits of FG in arresting hemorrhage in hemodynamically unstable coagulopathic patients with complex hepatic injuries.     

Fate of Diffusion Restricted Lesions in Acute Intracerebral Hemorrhage

Background

Diffusion-restricted lesions on diffusion-weighted imaging (DWI) are detected in patients with intracerebral hemorrhage (ICH). In this study, we aimed to determine the fate of DWI lesions in ICH patients and whether the presence of DWI lesions is associated with functional outcome in patients with ICH.

Methods

This prospective study enrolled 153 patients with acute ICH. Baseline MRI scans were performed within 2 weeks after ICH to detect DWI lesions and imaging markers for small vessel disease (SVD). Follow-up MRI scans were performed at 3 months after ICH to assess the fate of the DWI lesions. We analyzed the associations between the characteristics of DWI lesions with clinical features and functional outcome.

Results

Seventeen of the 153 patients (11.1%) had a total of 25 DWI lesions. Factors associated with DWI lesions were high initial systolic and mean arterial blood pressure (MAP) at the emergency room, additional lowering of MAP within 24 hours, and the presence of white matter hyperintensity and cerebral microbleeds. Thirteen of the 25 DWI lesions (52%) were not visible on follow-up T2-weighted or fluid-attenuated inversion recovery images and were associated with high apparent diffusion coefficient value and a sharper decease in MAP. The regression of DWI lesions was associated with good functional outcome.

Conclusions

More than half of the DWI lesions in the ICH patients did not transition to visible, long-term infarction. Only if the DWI lesion finally transitioned to final infarction was a poor functional outcome predicted. A DWI lesion may be regarded as an ischemic change of SVD and does not always indicate certain cerebral infarction or permanent tissue injury.     

Central hemodynamics of dogs in the early postresuscitation period and the outcome of resuscitation

Variations in central hemodynamics of dogs were compared with the outcome of resuscitation of 18 dogs subjected to 12-minute reversible circulatory arrest because of ventricular fibrillation. Nine survived dogs with completely recovered neurological status during the first 10 minutes after resuscitation had moderate hypertension, the mean arterial pressure (MAP) being 175.0 + 8.9 mm Hg. In the dogs who died within 24-48 hours after resuscitation, the MAP did not rise during this period as compared to the initial level; 2 dogs developed excessive hypertension (MAP about 200 mm Hg). There were also found certain differences in other parameters of central hemodynamics. Moderate hypertension in the first 10 minutes of the postresuscitation period leads to rapid restoration of the adequate level of peripheral blood flow in organs and tissues, thus favouring survival of animals subjected to a long circulatory arrest.     

重症肺炎患儿俯卧位与仰卧位机械通气的临床效果比较及其脱机结局的影响因素分析

摘要 目的：比较重症肺炎患儿俯卧位与仰卧位机械通气的临床效果,并分析其脱机结局的影响因素。方法：选择2020年5月~2021年12月期间在我院重症监护室（ICU）住院的重症肺炎患儿120例作为研究对象。根据机械通气体位方式的不同将患儿分为仰卧组（n=52）和俯卧组（n=68）,对比仰卧组、俯卧组的临床症状改善时间和血气分析指标[动脉血氧分压（PaO₂）、动脉血二氧化碳分压（PaCO₂）、平均动脉压（MAP）]。记录仰卧组、俯卧组的死亡例数、脱机成功和脱机失败例数,计算死亡率、脱机失败发生率。采用单因素及多因素Logistic回归分析脱机失败的影响因素。结果：俯卧组的发热消失时间、肺部啰音消失时间、呼吸改善时间短于仰卧组（P<0.05）。两组治疗5 d后 PaO₂、MAP较治疗前升高,PaCO₂较治疗前下降（P<0.05）;俯卧组的PaO₂、MAP高于仰卧组,PaCO2低于仰卧组（P<0.05）。两组患儿死亡率组间对比未见统计学差异（P>0.05）。俯卧组的脱机失败率低于仰卧组（P<0.05）。在120例患儿中,死亡7例,根据重症肺炎患儿脱机结局将剩余113例分为脱机成功组（n=72）和脱机失败组（n=41）,脱机失败组、脱机成功组在年龄、急性生理与慢性健康评分系统II（APACHE II）评分、病程、先天性病史、D-二聚体（D-D）、白蛋白（ALB）、血乳酸、脑尿钠肽（BNP）方面对比有统计学差异（P<0.05）。多因素Logistic回归分析结果显示：年龄偏小、APACHE II评分偏高、D-D偏高、ALB偏低、先天性病史均是重症肺炎患儿脱机结局的影响因素（P<0.05）。结论：与仰卧位相比,俯卧位机械通气用于重症肺炎患儿可获得更好的临床效果和脱机成功率,且患儿的脱机结局受到年龄、APACHE II评分、D-D、ALB、先天性病史的影响。     

Effect of carotid or aortic baroreceptor denervation on arterial pressure during hemorrhage in conscious dogs

We studied the effect of chronically denervating aortic baroreceptors (ABR; n = 6) or carotid baroreceptors (CBR; n = 7) on mean arterial pressure (MAP) and heart rate (HR) responses to hemorrhage in the dog. Neither denervation had a significant effect on basal MAP, the variability (standard deviation) of MAP, or resting HR. However, the breakpoint of MAP (defined as the volume of blood removed when MAP fell more than 10% below control and declined monotonically thereafter) was significantly reduced in dogs with only ABR functional (12.4 +/- 1.4 ml/kg) compared with the volume in the intact condition (18.9 +/- 1.8 ml/kg). In contrast, there was no difference in the breakpoint or the MAP at any time during hemorrhage in dogs with both CBR functional compared with their intact responses. In a different group of dogs (n = 6), responses were determined with both CBR operating and again after unilateral denervation, leaving only one CBR (1CBR) functional. Basal MAP and the variability of MAP were not altered in dogs with only 1CBR functional, but the breakpoint (11.7 +/- 1.4 ml/kg) during hemorrhage was significantly different compared with responses with two CBR (21.2 +/- 2.3 ml/kg), and MAP fell to much lower levels. These results indicate that the CBR can compensate fully for loss of ABR during hemorrhage but not vice versa; and bilateral CBR inputs are required for normal responses to hemorrhage.     

Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine

Previous studies have shown that the liver is the first organ to display signs of injury during hemorrhagic shock. We examined the mechanism by which pyruvate can prevent liver damage during hemorrhagic shock in swine anesthetized with halothane. Thirty minutes after the induction of a 240-min controlled arterial hemorrhage targeted at 40 mmHg, hypertonic sodium pyruvate (0.5 g. kg(-1). h(-1)) was infused to achieve an arterial concentration of 5 mM. The volume and osmolality effects of pyruvate were matched with 10% saline (HTS) and 0.9% saline (NS). Although the peak hemorrhage volume increased significantly in both the pyruvate and HTS group, only the pyruvate treatment was effective in delaying cardiovascular decompensation. In addition, pyruvate effectively maintained the NADH/NAD redox state, as evidenced by increased microdialysate pyruvate levels and a significantly lower lactate-to-pyruvate ratio. Pyruvate also prevented the loss of intracellular antioxidants (GSH) and a reduction in the GSH-to-GSSG ratio. These beneficial effects on the redox environment decreased hepatic cellular death by apoptosis. Pyruvate significantly increased the ratio of Bcl-Xl (antiapoptotic molecule)/Bax (proapoptotic molecule), prevented the release of cytochrome c from mitochondria, and decreased the fragmentation of caspase 3 and poly(ADP ribose) polymerase (DNA repair enzyme). These beneficial findings indicate that pyruvate infused 30 min after the onset of severe hemorrhagic shock is effective in maintaining the redox environment, preventing the loss of the key antioxidant GSH, and decreasing early apoptosis indicators.     

Acid-base disturbance during hemorrhage in rats: significant role of strong inorganic ions.

The present study tests the hypothesis that changes in the strong inorganic ion concentrations contribute significantly to the acid-base disturbance that develops during hemorrhage in the arterial plasma of rats in addition to lactate concentration ([Lac-]) increase. The physicochemical origins for this acid-base disorder were studied during acute, graded hemorrhage (10, 20, and 30% loss of blood volume) in three groups of rats: conscious, anesthetized with ketamine, and anesthetized with urethan. The results support the hypothesis examined: strong-ion difference (SID) decreased in the arterial plasma of all groups studied because of an early imbalance in the main strong inorganic ions during initial hemorrhagic phase. Moreover, changes in plasma [Lac-] contributed to SID decrease in a later hemorrhagic phase (after 10% hemorrhage in urethan-anesthetized, after 20% hemorrhage in ketamine-anesthetized, and after 30% hemorrhage in conscious group). Inorganic ion changes were due to both dilution of the vascular compartment and ion exchange with extravascular space and red blood cells, as compensation for blood volume depletion and hypocapnia. Nevertheless, anesthetized rats were less able than conscious rats to preserve normal arterial pH during hemorrhage, mainly because of an impaired peripheral tissue condition and incomplete ventilatory compensation.     

Renal inflammation and elevated blood pressure in a mouse model of reduced {beta}-ENaC

Previous studies suggest β-epithelial Na(+) channel protein (β-ENaC) may mediate myogenic constriction, a mechanism of blood flow autoregulation. A recent study demonstrated that mice with reduced levels of β-ENaC (β-ENaC m/m) have delayed correction of whole kidney blood flow responses, suggesting defective myogenic autoregulatory capacity. Reduced renal autoregulatory capacity is linked to renal inflammation, injury, and hypertension. However, it is unknown whether β-ENaC m/m mice have any complications associated with reductions in autoregulatory capacity such as renal inflammation, injury, or hypertension. To determine whether the previously observed altered autoregulatory control was associated with indicators of renal injury, we evaluated β-ENaC m/m mice for signs of renal inflammation and tissue remodeling using marker expression. We found that inflammatory and remodeling markers, such as IL-1β, IL-6, TNF-α, collagen III and transforming growth factor-β, were significantly upregulated in β-ENaC m/m mice. To determine whether renal changes were associated with changes in long-term control of blood pressure, we used radiotelemetry and found that 5-day mean arterial blood pressure (MAP) was significantly elevated in β-ENaC m/m (120 ± 3 vs. 105 ± 2 mmHg, P = 0.016). Our findings suggest loss of β-ENaC is associated with early signs of renal injury and increased MAP.     

The level of hypotension during hemorrhagic shock is a major determinant of the post-resuscitation systemic inflammatory response: an experimental study

Background

To evaluate whether the level of hypotension during hemorrhagic shock may influence the oxidative and inflammatory responses developed during post-ischemic resuscitation.

Methods

Fifteen rabbits were equally allocated into three groups: sham-operated (group sham); bled within 30 minutes to mean arterial pressure (MAP) of 40 mmHg (group shock-40); bled within 30 minutes to MAP of 30 mmHg (group shock-30). Shock was maintained for 60 min. Resuscitation was performed by reinfusing shed blood with two volumes of Ringer's lactate and blood was sampled for estimation of serum levels aminotransferases, creatinine, TNF-α, IL-1β, IL-6, malondialdehyde (MDA) and total antioxidant status (TAS) and for the determination of oxidative burst of polymorhonuclears (PMNs) and mononuclear cells (MCs).

Results

Serum AST of group shock-30 was higher than that of group shock-40 at 60 and 120 minutes after start of resuscitation; serum creatinine of group shock-30 was higher than group shock-40 at 120 minutes. Measured cytokines, MDA and cellular oxidative burst of groups, shock-40 and shock-30 were higher than group sham within the first 60 minutes after start of resuscitation. Serum concentrations of IL-1β, IL-6 and TNF-α of group shock-30 were higher than group shock-40 at 120 minutes (p < 0.05). No differences were found between two groups regarding serum MDA and TAS and oxidative burst on PMNs and MCs but both groups were different to group sham.

Conclusion

The level of hypotension is a major determinant of the severity of hepatic and renal dysfunction and of the inflammatory response arising during post-ischemic hemorrhagic shock resuscitation. These findings deserve further evaluation in the clinical setting.     

Detrimental effects of complement activation in hemorrhagic shock.

The complement system has been implicated in early inflammatory events and a variety of shock states. In rats, we measured complement activation after hemorrhage and examined the hemodynamic and metabolic effects of complement depletion before injury and worsening of complement activation after hemorrhage and resuscitation [with a carboxypeptidase N inhibitor (CPNI), which blocks the clearance of C5a]. Rats were bled to a mean arterial pressure of 30 mmHg for 50 min and were then resuscitated for 2 h. Shock resulted in significant evidence of complement consumption, with serum hemolytic activity being reduced by 33% (P < 0.05). Complement depletion before injury did not affect hemorrhage volume (complement depleted = 28 +/- 1 ml/kg, complement intact = 29 +/- 1 ml/kg, P = 0.74) but improved postresuscitation mean arterial pressure by 37 mmHg (P < 0.05) and serum bicarbonate levels (complement depleted = 22 +/- 3 meq/ml, complement intact = 13 +/- 8 meq/ml, P < 0.05). Pretreatment with CPNI was lethal in 80% of treated animals vs. the untreated hemorrhaged group in which no deaths occurred (P < 0.05). In this model of hemorrhagic shock, complement activation appeared to contribute to progressive hypotension and metabolic acidosis seen after resuscitation. The lethality of CPNI during acute blood loss suggests that the anaphylatoxins are important in the pathophysiological events involved in hemorrhagic shock.     

Pregnancy alters hemodynamic responses to hemorrhage in conscious rabbits

Pregnant animals are less able to maintain mean arterial pressure (MAP) during hemorrhage compared with nonpregnant animals, but the hemodynamic basis of this difference is unknown. The hypothesis that pregnancy attenuates responses of cardiac output, as well as total peripheral resistance (TPR) and femoral conductance, to hemorrhage was tested in conscious rabbits in both the pregnant and nonpregnant state (n = 10). During continuous slow blood loss (2% of the initial blood volume per minute), MAP was maintained initially in both groups. However, MAP then abruptly decreased to <45 mmHg in all animals after a smaller percentage of the initial blood volume was removed in pregnant compared with nonpregnant rabbits (43.6 +/- 1.7%, nonpregnant; 29.6 +/- 2.2%, pregnant; P < 0.005). The more rapid transition to hypotension exhibited by pregnant rabbits was associated with greater initial falls in cardiac output (-56 +/- 10 ml/min, nonpregnant; -216 +/- 33 ml/min, pregnant; P < 0.005) and stroke volume (0.8 +/- 0.1 ml/beat, nonpregnant; -1.3 +/- 0.1 ml/beat, pregnant; P < 0.05). In addition, the increase in TPR as a function of the decrease in cardiac output was markedly attenuated (P < 0.0001) during pregnancy. Whereas femoral conductance decreased in nonpregnant rabbits, it did not change significantly in pregnant animals. In conclusion, the lesser ability of conscious pregnant rabbits to maintain MAP during hemorrhage is due largely to a greater decrease in cardiac output but also to inadequate reflex increases in TPR, possibly in part in the femoral vascular bed.     

A Comparison of Vasopressin,Terlipressin, and Lactated Ringers for Resuscitation of Uncontrolled Hemorrhagic Shock in an Animal Model

Aim

The aim of this study is to compare the effect of lactated ringer (LR), vasopressin (Vaso) or terlipressin (Terli) on uncontrolled hemorrhagic shock (UHS) in rats.

Methods

48 rats were divided into four treatment groups for UHS study. Vaso group was given bolus vasopressin (0.8 U/kg); the Terli group was given bolus terlipressin (15 mcg/kg); LR group was given LR and the sham group was not given anything. Mean arterial pressure (MAP), serum lactate level, plasma cytokine levels, lung injury and mortality are investigated for these different treatment groups.

Results

Compared with LR group, vasopressin and terlipressin-treated groups were associated with higher MAP, lowered mortality rates, less lung injury, lowered serum lactate level, less proinflammatory and more anti-inflammatory cytokine production at certain time points. Comparing between vasopressin and terlipressin treated groups, there is no statistical difference in mortality rates, lung injury, serum lactate level and cytokine level. However, there is a difference in the length of time in maintaining a restored level of MAP (80 to 110 mmHg). The terlipressin treated rats can maintain this restored level of MAP for 45 minutes, but the vasopressin treated rats can only maintain this restored level of MAP for 5 minutes before decreasing gradually to the MAP observed in LR group (40 mmHg).

Conclusion

Early optimization of hemodynamics with terlipressin or vasopressin in an animal model of UHS was associated with improved hemodynamics and inflammatory cytokine profile than the LR control. Compared with vasopressin, terlipressin has the advantage of ease of use and sustained effects.     

Prognostic value of copeptin: one-year outcome in patients with traumatic brain injury

High plasma copeptin level has been associated with one-month mortality after traumatic brain injury. However, not much is known regarding its relation with long-term outcome. Thus, we investigated the ability of copeptin to predict 1-year outcome in patients with traumatic brain injury. One hundred and six healthy controls and 106 patients with acute severe traumatic brain injury were included. Plasma samples were obtained on admission. Its concentration was measured by enzyme-linked immunosorbent assay. Forty-eight patients (45.3%) suffered from unfavorable outcome (Glasgow Outcome Scale score of 1-3) and 31 patients (29.2%) died in 1 year after traumatic brain injury. Upon admission, plasma copeptin level in patients was substantially higher than that in healthy controls. A forward stepwise logistic regression selected plasma copeptin level as an independent predictor for 1-year unfavorable outcome and mortality of patients. A receiver operating characteristic curve analysis showed plasma copeptin level predicted 1-year unfavorable outcome and mortality obviously. The predictive value of the copeptin concentration was thus similar to that of Glasgow Coma Scale score for the prediction of unfavorable outcome and mortality after 1 year. In a combined logistic-regression model, copeptin improved the area under curve of Glasgow Coma Scale score for the prediction of unfavorable outcome and mortality after 1 year, but the differences were not significant. Thus, copeptin level is a useful, complementary tool to predict functional outcome and mortality 1 year after traumatic brain injury.     

Risk Evaluation of Selective Renal Arterial Embolization in the Treatment of Delayed Hemorrhage from Renal Artery Pseudoaneurysm After Partial Nephrectomy

Renal-artery pseudoaneurysm (RAP) is a well-described complication of partial nephrectomy. We aimed to evaluate the occurrence rate of delayed hemorrhage from RAP after partial nephrectomy, and to investigate the efficacy and safety of selective renal arterial embolization. Between January 2000 and December 2010, 426 partial nephrectomies were performed at our institution for treatment of small renal mass (SRMs). A retrospective review of these cases revealed that 14 patients developed a postoperative RAP (3.29 % incidence). We compared the clinical characteristics between the 14 patients with delayed renal hemorrhage and other 412 patients. RAP was diagnosed by renal angiography in 12 patients with delayed renal hemorrhage. Of the 12 patients, 10 patients were successfully treated with selective renal arterial embolization after presenting with symptoms postoperatively, 1 patient was treated with open surgery, and 1 patient was treated with nephrectomy. The other two patients showed no abnormalities in renal angiography, and the symptoms relieved by transfusion and hemostasis treatment. We found that tumor type, tumor size, tumor location, and surgical approach were significantly different between the 14 patients and other 412 patients. RAP showed a low incidence. The risk factors of RAP included renal cell carcinoma, tumor with large size, and tumor location. Most patients with delayed renal hemorrhage from RAP were successfully cured by selective renal arterial embolization. Therefore, selective renal arterial embolization can be used as the preferential therapy for RAP.     

‘Preconditioning’ with Low Dose Lipopolysaccharide Aggravates the Organ Injury / Dysfunction Caused by Hemorrhagic Shock in Rats

Methods

Male rats were ‘pretreated’ with phosphate-buffered saline (PBS; i.p.) or LPS (1 mg/kg; i.p.) 24 h prior to HS. Mean arterial pressure (MAP) was maintained at 30 ± 2 mmHg for 90 min or until 25% of the shed blood had to be re-injected to sustain MAP. This was followed by resuscitation with the remaining shed blood. Four hours after resuscitation, parameters of organ dysfunction and systemic inflammation were assessed.

Results

HS resulted in renal dysfunction, and liver and muscular injury. At a first glance, LPS preconditioning attenuated organ dysfunction. However, we discovered that HS-rats that had been preconditioned with LPS (a) were not able to sustain a MAP at 30 mmHg for more than 50 min and (b) the volume of blood withdrawn in these animals was significantly less than in the PBS-control group. This effect was associated with an enhanced formation of the nitric oxide (NO) derived from inducible NO synthase (iNOS). Thus, a further control group in which all animals were resuscitated after 50 min of hemorrhage was performed. Then, LPS preconditioning aggravated both circulatory failure and organ dysfunction. Most notably, HS-rats pretreated with LPS exhibited a dramatic increase in NF-κB activation and pro-inflammatory cytokines.

Conclusion

In conclusion, LPS preconditioning predisposed animals to an earlier vascular decompensation, which may be mediated by an excess of NO production secondary to induction of iNOS and activation of NF-κB. Moreover, LPS preconditioning increased the formation of pro-inflammatory cytokines, which is likely to have contributed to the observed aggravation of organ injury/dysfunction caused by HS.     

口腔黏膜二氧化碳分压与大鼠失血性休克程度的相关性研究

通过研究大鼠失血过程中口腔黏膜二氧化碳分压（PbuCO2）与失血性休克程度的相关性,证明PbuCO2可用于失血性休克早期救治过程中休克程度的评价.25只Wistar大鼠随机分成5组,用戊巴比妥钠麻醉后,除假手术组外,其余4组失血30min,失血量分别达到总血容量的25%,30%,35%和40%.用PbuCO2检测装置对大鼠口腔黏膜的PCO2进行连续、无创检测,并对动脉血压（ABP）、心输出量（CO）、心电（ECG）和呼吸（RES）进行实时或不间断的检测,另外不间断抽取动脉血进行血液检验.失血后30min时,除40%小组部分动物死亡外,其余存活动物的ABP,CO,ECG,RES,血气和电解质都没有显著差异,而仅失血15min后,相对上述生理指标,PbuCO2表现出极显著的差异性（P〈0.01）.实验证明,PbuCO2不仅能够检测失血后组织灌注的变化,而且与ABP,CO,血气和电解质等指标相比,在区分不同程度的休克时更具有一致性、准确性和灵敏性.结果显示,PbuCO2的连续无创检测可有效地评价失血性休克程度,指导早期救治.     

Erythropoietin responses to progressive blood loss over 10 days in the ovine fetus

Long-term loss of fetal blood can occur with fetomaternal hemorrhage, vasoprevia, or placental previa. Our objective was to determine the effects of progressive fetal blood loss over 10 days on fetal plasma erythropoietin (EPO) concentration and its relationship to arterial PO(2), hematocrit, and the volume of blood loss. Late-gestation fetal sheep (n = 8) were hemorrhaged daily at a rate of 1 ml/min over 10 days. The extent of hemorrhage differed in each fetus and ranged from 30 to 80 ml/day, with the cumulative volume removed ranging from 78 to 236 ml/kg estimated fetal weight. Four fetuses served as time controls. EPO concentration measurements were by radioimmunoassay. Statistical analyses included regression, correlation, and analysis of variance. We found that EPO and arterial PO(2) were unchanged until the cumulative hemorrhage volume exceeded 20-40 ml/kg. Once this threshold was exceeded, plasma EPO concentration increased progressively throughout the study and averaged 14.3 +/- 3.2 times basal values on day 10. EPO concentration, arterial PO(2), and hematocrit changes were related curvilinearly to cumulative hemorrhage volume (P < 0.01), whereas the relationship between plasma EPO and arterial PO(2) was log linear (P < 0.001). We conclude that 1) fetal plasma EPO concentration and arterial PO(2) are insensitive to a slow, mild-to-moderate blood loss over several days; 2) unlike the rapid return of EPO to normal within 48 h after acute hemorrhage, fetal EPO concentration undergoes a progressive increase with moderate-to-severe blood loss over several days; 3) the long-term hemorrhage-induced changes in EPO are best correlated with arterial PO(2); and 4) the fetal EPO response to hemorrhage does not appear to be limited by the fetus's ability to produce EPO.     

Blood pressure modifies retinal susceptibility to intraocular pressure elevation

Primary open angle glaucoma affects more than 67 million people. Elevated intraocular pressure (IOP) is a risk factor for glaucoma and may reduce nutrient availability by decreasing ocular perfusion pressure (OPP). An interaction between arterial blood pressure and IOP determines OPP; but the exact contribution that these factors have for retinal function is not fully understood. Here we sought to determine how acute modifications of arterial pressure will affect the susceptibility of neuronal function and blood flow to IOP challenge. Anaesthetized (ketamine:xylazine) Long-Evan rats with low (∼60 mmHg, sodium nitroprusside infusion), moderate (∼100 mmHg, saline), or high levels (∼160 mmHg, angiotensin II) of mean arterial pressure (MAP, n = 5–10 per group) were subjected to IOP challenge (10–120 mmHg, 5 mmHg steps every 3 minutes). Electroretinograms were measured at each IOP step to assess bipolar cell (b-wave) and inner retinal function (scotopic threshold response or STR). Ocular blood flow was measured using laser-Doppler flowmetry in groups with similar MAP level and the same IOP challenge protocol. Both b-wave and STR amplitudes decreased with IOP elevation. Retinal function was less susceptible to IOP challenge when MAP was high, whereas the converse was true for low MAP. Consistent with the effects on retinal function, higher IOP was needed to attenuated ocular blood flow in animals with higher MAP. The susceptibility of retinal function to IOP challenge can be ameliorated by acute high BP, and exacerbated by low BP. This is partially mediated by modifications in ocular blood flow.     

Development of a Fatal Noncompressible Truncal Hemorrhage Model with Combined Hepatic and Portal Venous Injury in Normothermic Normovolemic Swine

Noncompressible truncal hemorrhage and brain injury currently account for most early mortality of warfighters on the battlefield. There is no effective treatment for noncompressible truncal hemorrhage, other than rapid evacuation to a surgical facility. The availability of an effective field treatment for noncompressible truncal hemorrhage could increase the number of warfighters salvaged from this frequently-lethal scenario. Our intent was to develop a porcine model of noncompressible truncal hemorrhage with a ∼50% one-hour mortality so that we could develop new treatments for this difficult problem. Normovolemic normothermic domestic swine (barrows, 3 months old, 34–36 kg) underwent one of three injury types through a midline incision: 1) central stellate injury (N = 6); 2) excision of a portal vein branch distal to the main PV trunk (N = 6); or 3) hemi-transection of the left lateral lobe of the liver at its base (N = 10). The one-hour mortality of these injuries was 0, 82, and 40%, respectively; the final mean arterial pressure was 65, 24, and 30 mm Hg, respectively; and the final hemoglobin was 8.3, 2.3, and 3.6 g/dL, respectively. Hemi-transection of the left lateral lobe of the liver appeared to target our desired mortality rate better than the other injury mechanisms.