Prolonged immunodepression after trauma and hemorrhagic shock

OBJECTIVE: To define and discuss the cytologic findings in six cases of nodular pseudoangiomatous stromal hyperplasia (PASH) of the breast. STUDY DESIGN: Retrospective evaluation of the medical records, cytologic and histologic material from six patients with palpable mammary PASH. Cases in which PASH was associated with other predominant mammary lesions were not included in the study. RESULTS: A total of six patients with histologically proven PASH underwent aspiration in nine occasions (three patients studied twice). Clinically, five patients were diagnosed as having fibroadenoma or another benign lesion, and in one patient carcinoma was suspected. In two patients, mammography disclosed rapid growth of the lesion. Seven aspirations, performed on five patients, were diagnosed as fibroadenoma (n = 5) or fibroadenomatous lesion (n = 2). An eighth aspiration was cystic and reported as fibrocystic disease. The last case was erroneously diagnosed as suspicious for carcinoma. Even after revision, the cytologic similarities of PASH with fibroadenoma were remarkable. Most smears were less cellular than those of conventional fibroadenomas. Epithelial clusters showed variable size, with a predominance of medium to small groups. Stromal elements were minimal or absent. Background cellularity was composed of round to oval naked nuclei and others with spindle shapes. Occasional epithelial clusters showed cellular dissociation and slight atypia. CONCLUSION: Due to the absence of specific cytologic features and similarities to fibroadenoma, a precise diagnosis of PASH cannot be made on cytologic material. However, the majority of cases can be diagnosed correctly as benign, allowing appropiate treatment.     

Liver injury as a model of uncontrolled hemorrhagic shock: resuscitation with different hypertonic regimens

OBJECTIVE: To study if metabolic stress modifies the thermogenic effect of dobutamine. DESIGN: Prospective, increasing dose, pharmacologic study. SETTING: Laboratory of the Department of Intensive Care Unit at a university hospital. SUBJECTS: Twelve normal volunteers. INTERVENTIONS: Dobutamine hydrochloride was infused to 12 healthy male volunteers starting at a dose of 2 micrograms/min/kg and gradually increased to 4 and 6 micrograms/min/kg. Each dose of dobutamine was infused for 20 mins. Metabolic stress was induced in six of the 12 volunteers using a triple hormone infusion (epinephrine, cortisol, and glucagon) before dobutamine, and was continued at a constant rate during the dobutamine infusion. The remaining six volunteers served as the control group and received only dobutamine. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption (VO2) was measured using a metabolic monitor. Arterial blood pressure was measured noninvasively, and cardiac output was monitored by Doppler echocardiography. Plasma concentrations of dopamine, norepinephrine, and epinephrine were measured in both groups. In the triple hormone group, blood was sampled to measure concentrations of insulin, glucagon, cortisol, free fatty acids, and glycerol to ensure the presence of a metabolic stress reaction. At the maximum dose, dobutamine induced a 19% increase (from 140 +/- 17 to 166 +/- 17 mL/min/m2) in VO2 in the control group and an 11% increase (from 167 +/- 10 to 184 +/- 13 mL/min/m2) in the triple hormone group (p < .05 between the two groups) compared with baseline. No change in the respiratory exchange ratio was seen. The triple hormone infusion alone induced hypermetabolism, a marked hemodynamic response, and increased lipolysis. CONCLUSIONS: Stress, induced by a triple hormone infusion, diminishes the thermogenic effect of dobutamine. In the clinical setting, a > 10% to 15% increase in VO2 in response to dobutamine may not be explained just by the thermogenic effect of the drug.     

Soluble P-selectin is released into the coronary circulation after coronary spasm

BACKGROUND: The glycoprotein P-selectin is an adhesion molecule involved in the property change of leukocytes at the initiation of the inflammatory process. The purpose of the present study was to determine whether acute myocardial ischemia induced by coronary spasm causes an acute inflammatory response in the coronary circulation. METHODS AND RESULTS: We examined plasma soluble P-selectin levels in the coronary sinus and the aortic root simultaneously in 16 patients with coronary spastic angina before and after left coronary artery spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Ten control patients with chest pain but normal coronary arteries and no coronary spasm also received intracoronary acetylcholine. Plasma soluble P-selectin levels were increased significantly in the coronary sinus (32.8 +/- 3.6 to 52.8 +/- 5.9 ng/mL, P < .001) and in the aortic root (34.6 +/- 3.7 to 41.9 +/- 4.4 ng/mL, P < .05) after the attacks in the coronary spastic angina group but remained unchanged in the stable exertional angina group after the attacks and in the control group after the administration of acetylcholine. Furthermore, the coronary sinus-arterial difference of soluble P-selectin increased significantly after the attacks in the coronary spastic angina group (-1.8 +/- 2.2 to 10.9 +/- 2.7 ng/mL, P < .001). CONCLUSIONS: Our data indicate that soluble P-selectin is released into the coronary circulation after coronary artery spasm. We conclude that coronary artery spasm may induce the leukocyte adhesion in the coronary circulation and may lead to myocardial damage.     

Alveolar liquid clearance is increased by endogenous catecholamines in hemorrhagic shock in rats

The primary objective of this study was to test the hypothesis that hemorrhagic shock would stimulate alveolar liquid clearance by a catecholamine-dependent mechanism. Anesthetized rats were hemorrhaged to a mean arterial pressure of 30 mmHg for 90 min, but they were not resuscitated. Alveolar liquid clearance was measured by the concentration of labeled and unlabeled protein over 2 h in an isosmolar physiological solution of 5% albumin that had been instilled into one lung. Hemorrhaged rats developed a severe metabolic acidosis that was associated with a 5- to 10-fold rise in plasma epinephrine levels. There was a 60% increase in alveolar liquid clearance in the hemorrhaged rats compared with control rats (55 +/- 6 vs. 34 +/- 7%; P < 0.05). Amiloride (10(-4) M) or propranolol (10(-4)M) inhibited the increase in alveolar liquid clearance. Thus the endogenous release of catecholamines associated with hemorrhagic shock markedly stimulates alveolar fluid clearance by a beta-adrenergic-mediated stimulation of active sodium transport. These data suggest a new, previously unrecognized mechanism that may protect against alveolar flooding in the acute phase of hemorrhagic shock.     

Serotonin is involved in the ACTH-induced reversal of hemorrhagic shock in anesthetized rats

In a rat model of volume-controlled hemorrhagic shock (mean arterial pressure = 20-24 mm Hg) causing the death of all saline-treated animals within 30 min, the i.v. bolus injection of ACTH-(1-24) (160 micrograms/kg) produced an almost complete and sustained reversal of the shock condition, with recovery of arterial blood pressure, pulse pressure and respiratory rate, and with 100% survival at the end of the experiment (2 h). The serotonin-depleting agent p-chlorophenylalanine (316 mg/kg i.p., administered 66-70 h before hemorrhage) almost completely prevented the effect of ACTH. The 5-HT1/5-HT2 receptor antagonist, methysergide, prevented the effect of ACTH completely when injected i.v. (5 mg/kg), but only in part when injected into a brain ventricle (i.c.v.) (15 micrograms/rat); the 5-HT2 antagonist, ketanserin, prevented the effect of ACTH completely when injected i.c.v. (1.5 micrograms/rat), but only in part when injected i.v. (0.5 mg/kg); the 5-HT3 antagonist, MDL 72222, largely prevented the effect of ACTH when injected i.c.v. (10 micrograms/rat), but had no influence at all when injected i.v. (3 mg/kg); finally, the 5-HT4 antagonist, GR 125487, had no effect when injected i.v. (5 micrograms/kg) or when injected i.c.v. (30 ng/rat). Overall, these data indicate that both CNS and peripheral serotonin play an important role in the complex mechanism of the ACTH-induced hemorrhagic shock reversal.     

Effect of hypertonic saline solution and dextran on ventricular blood flow and heart-lung interaction after hemorrhagic shock

BACKGROUND: Hypertonic saline solutions may have beneficial hemodynamic effects in the resuscitation of hemorrhagic shock. The effects on cardiac function and potential interaction with lung function are controversial and served as the basis for this study. METHODS: Domestic swine were resuscitated from hemorrhagic shock with equivalent sodium loads of lactated Ringer's solution (LR) or 7.5% NaCl plus 10% dextran (HSD). Hemodynamic data were obtained at baseline, shock, and after resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time (dP/dt) were used to index contractility. Regional myocardial blood flow was determined with microspheres. Lung water was determined gravimetrically. RESULTS: There were no differences in the ability to restore hemodynamic parameters with equivalent sodium loads of LR and HSD resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time were only transiently affected by shock and resuscitation. Regional myocardial blood flow was increased above baseline values after HSD. The total resuscitation volumes were 1958 +/- 750 mL and 140 +/- 31 mL with LR and HSD, respectively. CONCLUSIONS: Although LR and HSD were equally effective in the early resuscitation of hemorrhagic shock, this occurred at the expense of significantly greater volume requirements for resuscitation with LR. This may contribute to cardiac dysfunction in this setting. Enhanced regional myocardial blood flow after HSD resuscitation may be beneficial against ongoing myocardial stress.     

Hepatic Kupffer cell blockade reduces mortality of acute hemorrhagic pancreatitis in mice

BACKGROUND: Recovery of upper aerodigestive tract function after reconstruction of segmental oromandiblectomy defects is frequently incomplete. The purpose of this study was to quantitate postreconstruction function and define variables that predict functional outcome in this population. METHODS: A prospective study of 21 patients who underwent microvascular free tissue transfer reconstruction of segmental oromandibular defects was performed. Measures of swallowing, speech, bite, and oral intake were performed preoperatively and at 1, 3, 6, and 12 months postoperatively or until plateau. Preoperative versus maximal postoperative measures were compared and correlated with nine potentially predictive variables. Univariate and multivariate analyses were performed to determine the most significant predictive factors. RESULTS: Baseline function in the study population was abnormal. Postoperative bite force improved, but swallowing, speech, and oral intake were worse than preoperative. Significant (univariate) predictors of outcome included diagnosis of cancer, tongue resection, pharynx resection, and flap skin paddle area. Only tongue resection remained significant in multivariate analysis. CONCLUSIONS: Increasing need for oropharyngeal lining replacement, especially after tongue resection, is the most important predictor of functional outcome in reconstruction of segmental mandible defects.     

Immunohistochemical study of myoglobin deletion from myocardium in hemorrhagic shock

Myoglobin (MB) deletion from myocardium in the case of hemorrhagic shock was firstly studied by immunohistochemical and morphometry technique. The results showed that there were different degrees of segmental deletion of MB from myocardium in each case of hemorrhagic shock which has continued over an hour. The significance of these changes in forensic medicine are discussed.     

Plasma endotoxin and cytokine concentrations in patients with hemorrhagic shock

OBJECTIVES: The roles of cytokines and endotoxin in hemorrhagic shock, particularly the translocation of endotoxin and bacteria during hemorrhagic shock, were investigated. DESIGN: Prospective study. SETTING: Critical care and emergency center of a university hospital. PATIENTS: Twenty-nine patients with hemorrhagic shock and 20 healthy controls. INTERVENTIONS: Serial blood samples were collected from both study and control patients. Standard resuscitation techniques were used. MEASUREMENTS AND MAIN RESULTS: Plasma levels of endotoxin and various cytokines were determined repeatedly during hemorrhagic shock. Endotoxin was measured using an endotoxin-specific assay in addition to a new perchloric acid method for pretreatment of plasma. Cytokines were measured by commercial enzyme-linked immunosorbent assays. Plasma endotoxin concentrations remained within the normal range for 7 days after admission. Although levels of tumor necrosis factor-alpha and several interleukins increased slightly in some patients, these cytokines did not reach the levels seen in septic shock. CONCLUSIONS: Translocation of bacteria or endotoxin from the gastrointestinal tract into the bloodstream has been noted in animal experiments; however, translocation was not detected in our patients with hemorrhagic shock.     

Increased skeletal muscle Na+, K+-ATPase activity as a cause of increased lactate production after hemorrhagic shock

BACKGROUND: Lactate production after hemorrhagic shock may be produced by aerobic glycolysis, which has been linked to activity of the Na+/K+ pump in smooth muscle and other tissues. We tested whether increased muscle Na+/K+ pump activity after shock was linked to increased lactate production. METHODS: Male Sprague-Dawley rats were subjected to 1 or 2 hours of hemorrhagic shock and then resuscitated with shed blood and normal saline. After 24 hours, pairs of extensor digitorum longus muscles were preincubated for 30 minutes in Krebs buffer (95:5, O2:CO2) with 10 mmol/L glucose. One muscle served as a control and was incubated in buffer alone; the other was incubated in buffer with 1 mmol/L ouabain, an inhibitor of the Na+, K+-ATPase. Lactate, ADP, ATP, glycogen, and creatinine-phosphate were determined. RESULTS: Under these well-oxygenated conditions, muscles from shocked rats produced about twice as much lactate as sham muscles. Inhibition of the Na+/K+ pump by ouabain significantly reduced lactate production. CONCLUSIONS: Hypoxia is unlikely to account for increased muscle lactate production after resuscitated hemorrhagic shock, because high lactate production persists under well-oxygenated incubation conditions. Inhibition of shock-induced lactate production by ouabain indicates energetic coupling of glycolysis to the Na+, K+-ATPase.     

Safety of anticoagulation after hemorrhagic infarction

Cerebral hemorrhagic infarction visualized on CT, secondary to embolic stroke in an anticoagulated individual, is usually associated with clinically stable or improving neurologic signs; fear of transforming the hemorrhagic infarction into a hematoma, however, usually prompts cessation of anticoagulation until the blood has cleared on CT, despite the recognized risk of recurrent embolism during this non-anticoagulated period. We now report our experience with 12 patients with hemorrhagic infarction who remained anticoagulated. Eleven men and one woman, ages 33 to 77, developed hemorrhagic infarction while on heparin, warfarin, or both, for prevention of recurrent embolism. Patients were either continued on uninterrupted anticoagulation from stroke onset (n = 6), or anticoagulation was withheld for several days and then resumed (n = 4), or it was withheld for 5 and 14 days (n = 2) after stroke onset and then continued uninterrupted despite the CT appearance of hemorrhagic infarction. Eleven patients had a definite cardioembolic source for stroke (atrial fibrillation, seven; ventricular thrombus, two; and ventricular dyskinesia, two). One patient had carotid occlusion with local intra-arterial embolism. Hemorrhagic infarcts varied in size and were located in the middle cerebral artery territory in 11 patients and posterior cerebral artery territory in one. All patients remained clinically stable or improved on anticoagulation. Serial CTs showed fading hemorrhagic areas. When the risk of recurrent embolism is high, anticoagulation may be safely used in some patients with hemorrhagic infarction.     

Function of the liver reticuloendothelial system in hemorrhagic shock in dogs

The function of hepatic reticulo-endothelial system at normal circulation and during hemorrhagic shock was examined in 13 dogs. The results were as follows:1.198Au-colloid liver scintigraphy demonstrated no essential alterations by shock. A trifling diminution caused by the diminished blood amount in the liver was found at heavy blood loss. The spleen was opcified in no case. 2. The elimination rate, resp. the blood clearance, of 198Au-colloid remained constant during the first 2 hours, proving that the vital clearance function of hepatic reticulo-endothelial system is completely maintained in this phase of hemorrhagic shock. After longer duration of hypovolemic shock (5 hours) elimination rate decreased. 3. It can be concluded that hepatic circulation at first alters according to the blood volume. 4. Consequently, functional testing of hepatic reticulo-endothelial system is not fit for early diagnosis of shock.     

Dopexamine improves liver oxygenation during crystalloid resuscitation from experimental hemorrhagic shock

OBJECTIVE: To evaluate the effects of dopexamine administration on hemodynamic variables and tissue oxygen tensions during crystalloid resuscitation from hemorrhagic shock. DESIGN: Randomized, control trial. SETTING: An animal laboratory at a university center. SUBJECTS: Twelve piglets, mean weight 22 kg. INTERVENTIONS: The animals were anesthetized and bled to a state of hemorrhagic shock and resuscitated, using a crystalloid solution infused at a rate of approximately 2.6 mL/min/kg (total amount 208 mL/kg). Cardiac output and mean arterial pressure (MAP were measured as indicators of volume filling during the 20- to 30-min resuscitation period and during the follow-up period until 80 mins from the start of resuscitation. Dopexamine was administered by infusion at 6 micrograms/kg-min from the start of volume replacement (dopexamine group, n = 6). The rest of the animals (control group, n = 6) were given volume replacement only. MEASUREMENTS AND MAIN RESULTS: Systemic oxygen transport variables were calculated. Tissue oxygen tensions were continuously recorded from the liver, conjunctival layer, and via subcutaneous and transcutaneous electrodes in the abdominal region. MAP decreased from 119 +/- 2 (SEM) to 44 +/- 2 mm Hg and cardiac output decreased by 77% during the shock period. During resuscitation, cardiac output was restored in both groups. MAP increased close to the baseline during the early resuscitation period and decreased slowly during follow-up. Oxygen delivery remained at 46% of baseline, whereas systemic oxygen consumption was restored during resuscitation in both groups. Liver tissue oxygen tension increased well above baseline during resuscitation in the dopexamine group, and liver tissue oxygen tension was significantly higher than in the control group. After 60 mins of resuscitation, the liver oxygen tension decreased to control group values. None of the other tissue oxygen tensions showed any differences between groups. CONCLUSIONS: Dopexamine administration during crystalloid resuscitation from hemorrhagic shock was well tolerated and resulted in significant and specific, although transient, improvement in liver oxygenation.     

The effects of bacterial overgrowth and hemorrhagic shock on mucosal immunity

Impairment in systemic and mucosal immune function is noted after hemorrhagic shock (HS). Overgrowth of gut microflora is common after shock insults and may act as a reservoir for intensive care unit-acquired infections and subsequent remote organ failure. Secretory immunoglobulin A (IgA), the principle immunoglobulin in intestinal secretions, is the first line of defense of mucosal surfaces. Although HS and gut bacterial overgrowth are often temporarily related, their combined effect on IgA is unknown and served as the basis for this study. After sham or HS, self-filling blind loops (SFBL) were created to affect bacterial overgrowth. Intestinal secretions were obtained 7 days later from SFBL and jejunal segments for quantitative culture. Gut washings were also obtained and secretory IgA levels determined by enzyme-linked immunosorbent assay. Bacterial overgrowth in the SFBL was associated with significant increases in IgA levels in the sham group only. IgA levels were depressed in both jejunal and SFBL segments in the HS group. Impaired humoral mucosal defense may be important mechanistically in the development of nosocomial infections and organ failure after HS, particularly with concurrent gut bacterial overgrowth.