Regionalization Patterns for Children with Serious Trauma in California (2005-2015): A Retrospective Cohort Study.

OBJECTIVE: Trauma centers provide coordinated specialty care and have been demonstrated to save lives. Many states do not have a comprehensive statewide trauma system. Variable geography, resources, and population distributions present significant challenges to establishing an effective uniform system for pediatric trauma care. We aimed to identify patterns of primary (field) triage and transfer of serious pediatric trauma throughout California. We hypothesized that pediatric primary triage to trauma center care would be positively associated with younger age, increased injury severity, and local emergency medical service (EMS) regions with increased resources. We hypothesized that pediatric trauma transfer would be associated with younger age, increased injury severity, and rural regions with decreased resources. Methods: We conducted a retrospective cohort study of the California Office of Statewide Health Planning and Development emergency department and inpatient discharge data (2005-2015). All patients with serious injury, defined as Injury Severity Score (ISS) >9 were included. Demographic, injury, hospital, and regional characteristics such as distances between patient residence and destination hospitals were tabulated. Univariate and multinomial logit analyses were conducted to analyze individual, hospital, and regional characteristics associated with the outcomes of location of primary triage and transfer. Estimates were converted into predicted probabilities for ease of data interpretation. Results: Primary triage to was to either a pediatric trauma center (37.8%), adult level I/II trauma center (35.0%), adult level III/IV trauma center (1.9%), pediatric non-trauma hospital (3.4%), or an adult non-trauma hospital (21.9%).Younger age, private non-HMO insurance, motor vehicle mechanism, and rural areas were the major factors influencing primary triage to any trauma hospital. Younger age, private non-HMO insurance, higher ISS, fall mechanism, <200 bed hospital, and rural areas were the major factors influencing transfer from a non-trauma hospital to any trauma center. Conclusions: We demonstrate statewide primary triage and transfer patterns for pediatric trauma in a large and varied state. Specifically we identified previously unrecognized individual, hospital, and EMS system associations with pediatric trauma regionalization. Knowledge of these de facto trauma care access patterns has policy and process implications that could improve care for all injured children in need.

Comparing Percutaneous to Open Access for Extracorporeal Membrane Oxygenation in Pediatric Respiratory Failure.

OBJECTIVES: Evaluate trends in method of access (percutaneous cannulation vs open cannulation) for pediatric extracorporeal membrane oxygenation and determine the effects of cannulation method on morbidity and mortality. DESIGN: Retrospective cohort study. SETTING AND SUBJECTS: The Extracorporeal Life Support Organization's registry was queried for pediatric patients on extracorporeal membrane oxygenation for respiratory failure from 2007 to 2015. INVERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3,501 patients identified, 77.2% underwent open cannulation, with the frequency of open cannulation decreasing over the study period from approximately 80% to 70% (p < 0.001). Percutaneous cannulation patients were more commonly male (24.2% vs 21.5%; p = 0.01), older (average 7.6 vs 4.5 yr; p < 0.001), and heavier (average 33.0 vs 20.2 kg; p < 0.001). Subset analysis of patients on venovenous extracorporeal membrane oxygenation revealed higher rates of mechanical complications due to blood clots (28.9% vs 22.6%; p = 0.003) or cannula problems (18.9% vs 12.7%; p < 0.001), cannula site bleeding (25.3% vs 20.2%; p = 0.01) and increased rates of cannula site repair in the open cannulation cohort. Limb related complications were not significantly different on subset analysis for venovenous extracorporeal membrane oxygenation patients stratified by access site. Logistic regression analysis revealed that method of access was not associated with a difference in mortality. CONCLUSIONS: The proportion of pediatric patients undergoing percutaneous extracorporeal membrane oxygenation cannulation is increasing. Mechanical and physiologic complications occur with both methods of cannulation, but percutaneous cannulation appears safe in this cohort. Further analysis is needed to evaluate long-term outcomes with this technique.

The impact of perianal disease in young patients with inflammatory bowel disease.

BACKGROUND: Perianal disease is a potentially significant source of morbidity for patients with inflammatory bowel disease (IBD). We sought to identify the impact of perianal disease on IBD outcomes in children, adolescents, and young adults. METHODS: We studied 12,465 inpatient admissions for patients ≤20 years old with IBD in 2009 using the Kids' Inpatient Database (KID). Patients were stratified by their principal diagnosis of ulcerative colitis (UC) or Crohn's disease (CD). Perianal disease (perianal abscess, anal fissure, or anal fistula), complex fistulas (rectourethral, rectovaginal, or enterovesical), and growth failure were defined by ICD-9 codes. Logistic regression was performed adjusting for CD or UC, gender, age, need for surgical intervention, fistulas, or growth failure. RESULTS: Of the 511 (4.1%) patients with perianal disease, 480 had CD (94%, p < 0.001). Girls were less likely to suffer perianal disease (OR = 0.63, CI 0.52-0.76, p < 0.001). Those with perianal disease were more likely to suffer complex fistulas (OR = 3.5, CI 1.98-6.20, p < 0.001) but less likely to suffer enteroenteral fistulas (OR = 0.30, CI 0.15-0.63, p = 0.001) than those without perianal disease. Perianal disease did not increase the incidence of growth failure (p = 0.997) but doubled the likelihood of an operation of any type during admission (p < 0.001). Additionally, patients with perianal disease spent on average 1.29 more days in the hospital (7.45 vs. 6.16 days, p < 0.001) and accrued $5838 extra in hospital charges (p = 0.005). CONCLUSIONS: Perianal disease in younger patients is associated with a longer length of stay, higher hospital charges, and increased rates of both perineal and abdominal operative procedures. These data support the notion that, similar to adults, the presence of perianal disease in pediatric Crohn's patients is associated with a more severe course.

Evaluation of preparatory psychosocial counselling for medically assisted reproduction.

BACKGROUND: This study evaluated couples' perceptions of preparatory psychosocial counselling prior to participation in medically assisted reproduction (MAR). METHODS: Eighty-three couples about to undergo IUI treatment were asked about their expectations regarding a subsequent single psychosocial counselling session and assessed in terms of their levels of infertility-specific stress, anxiety and depressive symptoms. Afterwards, participants rated their satisfaction with different elements of the session. RESULTS: Almost two-thirds of women and one-half of men expected counselling to be important, and the majority anticipated that the session would be helpful and informative. Views of preparatory counselling were significantly more positive afterwards, indicating that a focused session addressing issues of treatment concerns, goal setting and managing infertility stress was more beneficial than anticipated. Those experiencing higher levels of infertility-specific stress expected the counselling session to be more important, and elevated stress and greater utilization of social support were predictive of post-counselling satisfaction. CONCLUSIONS: Preparatory psychosocial counselling provided with a specific and practical focus appears to be a potentially important and helpful service prior to MAR. Clinics should not assume that patients can accurately judge the benefits of counselling before actually engaging in the session. Identifying patients most likely to benefit and providing a clear rationale may further increase receptivity to this proactive counselling service. While patients characterize this intervention as beneficial, it is not yet known if these benefits translate into improved management of treatment procedures.

Universal Level Designations for Hospitalized Pediatric Patients in Evacuation.

Children comprise approximately 22% of the population in the United States.1 In a widespread disaster such as a hurricane, pandemic, wildfire or major earthquake, children are at least proportionately affected to their share of the population, if not more so. They also have unique vulnerabilities including physical, mental, and developmental differences from adults, which make them more prone to adverse health effects of disasters.2-4 There are about 5000 pediatric critical care beds and 23 000 neonatal intensive care beds out of 900 000 total hospital beds in the United States.5 While no mechanism exists to consistently track pediatric acute care beds nationally (especially in real time), a previous study6 showed a 7% decline in pediatric medical-surgical beds between 2002 and 2011. This study also estimated there are about 30 000 acute care pediatric beds nationally. Finding appropriate hospital resources for the provision of care for pediatric disaster victims is an important concern for those charged with triaging patients in a major event.

The inability of B-type natriuretic protein to predict short-term risk of death or myocardial infarction in non-heart-failure patients with marginally increased troponin levels.

STUDY OBJECTIVE: We want to know whether a low B-type natriuretic peptide (BNP) level, obtained shortly after presentation and independent of information provided by other clinical findings and laboratory tests, would affect management decisions for emergency department (ED) patients with nondiagnostic troponin levels. Previous studies have generally been retrospective or inclusive of patients with heart failure. METHODS: We prospectively studied patients evaluated for possible acute coronary syndromes who had nondiagnostic levels of serum troponin, nondiagnostic ECGs, and no clinical heart failure within 4 hours of presentation. BNP levels were obtained but results not provided to clinical staff. The primary outcome was the composite of acute myocardial infarction or death within 30 days. The secondary outcome was the composite of the primary outcome, percutaneous coronary intervention, or coronary artery bypass grafting. RESULTS: Almost half of the patients screened for but excluded from the study had known heart failure or a history of heart failure. The resulting cohort was composed of 348 patients, with a median age of 64 years and 51% women. The primary outcome occurred in 16.1% of patients; the secondary outcome, in 27.6%. At a standard cutoff of BNP greater than or equal to 80 pg/mL, the negative predictive value for the primary outcome was 80% (95% confidence interval 73% to 86%). The negative predictive value for the secondary outcome was 69% (95% confidence interval 61% to 75%). Multivariable analyses supported these findings. CONCLUSION: A single, low BNP level obtained shortly after presentation to the ED could not identify patients at low risk for 30-day acute myocardial infarction or death.

Erratum: 2-C-Hydro-xymethyl-2,3-O-iso-propyl-idene-d-ribono-1,5-lactam. Corrigendum.

The name of one of the authors in the paper by Newton et al. [Acta Cryst. (2004), E60, o909-o910] is corrected.[This corrects the article on p. o909 in vol. 60.].

Patient, hospital and regional characteristics associated with undertriage of injured children in California (2005-2015): a retrospective cohort study.

BACKGROUND/OBJECTIVE: Trauma centers save lives, but they are scarce and concentrated in urban settings. The population of severely injured children in California who do not receive trauma center care (undertriage) is not well understood. METHODS: Retrospective observational study of all children (0-17 years) hospitalized for severe trauma in California (2005-2015). We used the California Office of Statewide Health Planning and Development linked Emergency Department and Inpatient Discharge data sets. Logistic regression models were created to analyze characteristics associated with undertriage. The model was clustered on differential distance between distance from residence to primary triage hospital and distance from residence to nearest trauma center. We controlled for body part injured, injury type, intent and year. The a priori hypothesis was that uninsured and publicly insured children and hospitals and regions with limited resources would be associated with undertriage. RESULTS: Twelve percent (1866/15 656) of children with severe injury experienced undertriage. Children aged >14 years compared with 0-13 years had more than 2.5 times the odds of undertriage (OR 2.58; 95% CI 2.1 to 3.16). Children with private Health Maintenance Organization (HMO) insurance compared with public insurance had 13 times the odds of undertriage (OR 12.62; 95% CI 8.95 to 17.79). Hospitals with >400 compared with <200 beds had more than three times the odds of undertriage (OR 3.64; 95% CI 2.6 to 5.11). Urban versus suburban residence had 1.3 times increased odds of undertriage (OR 1.31; 95% CI 1.02 to 1.67) Undertriage volume was largest in urban areas. CONCLUSION: Undertriage is associated with private HMO insurance, primary triage to large hospitals and urban residence. Understanding the characteristics associated with undertriage can help improve trauma systems. LEVEL OF EVIDENCE: Level III (non-experimental retrospective observational study).

Hepatocyte growth factor, hepatocyte growth factor activator and arginine in a rat fulminant colitis model.

INTRODUCTION: Dextran sodium sulfate (DSS) is commonly used to induce a murine fulminant colitis model. Hepatocyte growth factor (HGF) has been shown to decrease the symptoms of inflammatory bowel disease (IBD) but the effect of its activator, HGFA, is not well characterized. Arginine reduces effects of oxidative stress but its effect on IBD is not well known. The primary aim is to determine whether HGF and HGFA, or arginine will decrease IBD symptoms such as pain and diarrhea in a DSS-induced fulminant colitis murine model. METHODS: A severe colitis was induced in young, male Fischer 344 rats with 4% (w/v) DSS oral solution for seven days; rats were sacrificed on day 10. Rats were divided into five groups of 8 animals: control, HGF (700 mcg/kg/dose), HGF and HGFA (10 mcg/dose), HGF and arginine, and high dose HGF (2800 mcg/kg/dose). Main clinical outcomes were pain, diarrhea and weight loss. Blinded pathologists scored the terminal ileum and distal colon. RESULTS: DSS reliably induced severe active colitis in 90% of animals (n = 36/40). There were no differences in injury scores between control and treatment animals. HGF led to 1.38 fewer days in pain (p = 0.036), while arginine led to 1.88 fewer days of diarrhea (P = 0.017) compared to controls. 88% of HGFA-treated rats started regaining weight (P < 0.001). DISCUSSION/CONCLUSION: Although treatment was unable to reverse fulminant disease, HGF and arginine were associated with decreased days of pain and diarrhea. These clinical interventions may reduce associated symptoms for severe IBD patients, even when urgent surgical intervention remains the only viable option.

Dextran modulates microvascular permeability: effect in isotonic and hypertonic solutions.

Hypertonic saline solutions with Dextran (HSD) have been advocated for rapid restoration of intravascular volume. Dextran is thought to increase the duration of action of hypertonic saline (HS) by selectively partitioning the water in the vascular space that has been drawn out of cells by HS. The goal of this study was to define the microvascular permeability modulating activity of Dextran in both isotonic and hypertonic solutions. We hypothesized that Dextran would decrease hydraulic permeability (Lp). Using the modified Landis micro-occlusion technique, single rat mesenteric venules were perfused with either normal Ringers (NR) with 135 mM NaCl or HS with 185 mM NaCl. In sequential cannulations of the venules, 1%, 2%, and 3% of Dextran was added to the NR perfusion (n = 6) and the HS perfusion (n = 6). The Lp was measured at baseline and after perfusion with each Dextran concentration. Baseline Lp measurements for NR and HS solutions were 1.01 +/- 0.034 and 5.14 +/- 1.02, respectively. In the NR group, the 2% and 3% Dextran decreased permeability below baseline levels to 0.79 +/- 0.028 (P < 0.0001) and 0.66 +/- 0.028 (P < 0.0001), respectively. In the HS group, the 2% and 3% Dextran decreased permeability to 1.65 +/- 0.53 (P < 0.0001) and 0.99 +/- 0.2 (P < 0.0001), respectively. All values for Lp are x10(-7) cm s(-1) x cm H2O(-1). The addition of Dextran to isotonic and hypertonic solutions results in a decrease in microvessel permeability. This effect is more pronounced with the perfusion of hypertonic solutions. The results demonstrate the oncotic potential of Dextran and its ability to hold water in the vascular space. Dextran may have a beneficial effect when used for resuscitation with HS by decreasing microvascular permeability and augmenting intravascular volume.

The impact of albumin on hydraulic permeability: comparison of isotonic and hypertonic solutions.

Hypertonic saline, Dextran, and albumin have been advocated for rapid restoration of intravascular volume. The goal of this study was to define how albumin impacts the effects of hypertonic saline and Dextran on hydraulic permeability. We hypothesized that albumin would decrease the hydraulic permeability (L(p)) of isotonic and hypertonic solutions containing Dextran. Using the modified Landis micro-occlusion technique, single rat mesenteric venules were perfused with either Ringer's + 1% albumin (RA) or hypertonic saline + 1% albumin (HSA). In sequential cannulations of the venules, 1%, 2%, and 3% Dextran was added to the RA perfusion (n = 6) and the HSA perfusion (n = 6). These results were compared with similar studies completed without albumin. Albumin significantly decreased L(p) with all HS solutions studied compared with HS without albumin. Baseline L(p) measurements for RA and HSA solutions were 1.08 +/- 0.07 and 0.51 +/- 0.03, respectively. In the RA group, 2% and 3% Dextran was associated with a lower L(p) of 0.83 +/- 0.04 (P = 0.002) and 0.67 +/- 0.05 (P = 0.002), respectively. In the HSA group, 2% and 3% Dextran was associated with a lower L(p) of 0.37 +/- 0.02 (P = 0.001) and 0.32 +/- 0.02 (P < 0.0001), respectively. All values for L(p) are x 10(-7) cm x s(-1) x cmH2O(-1). Albumin maintains low hydraulic permeability levels during perfusion with hypertonic saline. In the setting of sufficient of endothelial albumin levels, hypertonic saline and Dextran may be advantageous when used for resuscitation by decreasing trans-endothelial fluid flux and augmenting intravascular volume.

Angiotensin II type 1 receptor activation increases microvascular hydraulic permeability.

BACKGROUND: In addition to its vasoconstricting effects, angiotensin II (Ang II) has also demonstrated the ability to modulate microvessel permeability. We hypothesized that activation of the angiotensin II type 1 receptor (AT1) would increase hydraulic permeability. METHODS: Hydraulic permeability (L(p)) was measured in rat mesenteric venules using the Landis micro-occlusion technique. Paired measures of L(p) were obtained at baseline and after perfusion with the AT1 agonist, [Sar(1)]-angiotensin II, at 10 micromol/L (n=6) and 100 micromol/L (n=6). Activation of the AT1 receptor was also achieved by perfusion with 20 nmol/L Ang II plus the angiotensin II type 2 receptor (AT2) antagonist, PD123319. In these studies, 30 micromol/L (n=6) and 300 micromol/L (n=6) of PD123319 were used. RESULTS: [Sar(1)]-angiotensin II increased L(p) 2-fold with the 10 micromol/L dose (P=.04) and 4-fold with the 100 micromol/L dose (P < .001). The L(p) peak due to [Sar(1)]-angiotensin II occurred sooner than the peak observed with Ang II. PD123319 (30 micromol/L) plus 20 nmol/L Ang II increased L(p) 5-fold (P=.003), while PD123319 (300 micromol/L) plus 20 nmol/L Ang II increased L(p) 20-fold (P < .0001). The magnitude of the effect due to PD123319 (300 micromol/L) plus Ang II (20 nmol/L) was approximately twice the summation of effects due to PD123319 (300 micromol/L) alone and Ang II (20 nmol/L) alone. CONCLUSIONS: We conclude that endothelial cell Ang II receptors play an important role in modulating transendothelial fluid flux. Activating the AT1 receptor increases L(p); the AT2 receptor may operate to oppose this action. Pharmacologic manipulation of Ang II receptors may be beneficial during shock states to limit intravascular fluid loss.

The effect of race on outcomes for appendicitis in children: a nationwide analysis.

BACKGROUND: We sought to examine the impact of race on the management and outcomes of appendicitis in children aged 20 years or younger. METHODS: We studied 96,865 inpatient admissions for children undergoing an appendectomy for acute appendicitis in 2009 using the Kids' Inpatient Database. RESULTS: Perforation at presentation was more common among African-Americans and Hispanics than Caucasians (27.5% and 32.5%, respectively, vs 23.9%, P < .001). African-Americans were less likely to have a laparoscopic procedure (odds ratio [OR]: .839, P < .001) and more likely to experience a complication (OR: 1.753, P < .001). Hispanics were also more likely to have a complication (OR: 1.123, P = .001). African-Americans and Hispanics remained in the hospital for .73 more days than Caucasians (3.07 vs 2.34 days, P < .001). CONCLUSIONS: African-American and Hispanic children present more often with perforation. Adjusting for perforation, they were more likely to have a complication and longer hospital stays. Access to care and delayed presentations may be potential explanations.

Laparoscopy utilization and outcomes for appendicitis in small children.

PURPOSE: To examine the trends in laparoscopic appendectomy (LA) utilization and outcomes for children 5 years or younger. METHODS: We studied 16,028 inpatient admissions for children 5 years of age or less undergoing an appendectomy for acute appendicitis in 2000, 2003, and 2006 using the Kids' Inpatient Database (KID). Laparoscopy frequency, hospital length of stay, and complications were reviewed. RESULTS: In 2000, 2003 and 2006 appendectomies were done laparoscopically 11.4%, 18.7% and 31.3% of the time, respectively. Children were more likely to undergo LA at a children's hospital (P<0.001). LA complications were less likely overall (OR: 0.80, CI: 0.70-0.92, P=0.002) and in perforated cases (OR: 0.78, CI: 0.67-0.91, P=0.001). LA decreased hospital length of stay by 0.54 days for all patients and 0.70 days for perforated cases (P<0.001). CONCLUSIONS: Open appendectomy has historically been the standard in children 5 years of age and younger. Laparoscopic appendectomy has slowly gained acceptance for the treatment of appendicitis in smaller children. The use of laparoscopy has increased significantly at all facilities. Furthermore, laparoscopic appendectomy in this age group has a comparatively low complication rate and short hospital length of stay, and is safe in complicated perforated appendicitis cases.

The increasing incidence of adolescent bariatric surgery.

BACKGROUND: Morbid obesity continues to be a significant problem within the United States, as overweight/obesity rates are nearing 33%. Bariatric surgery has had success in treating obesity in adults and is becoming a viable treatment option for obese adolescents. METHODS: We studied 1615 inpatient admissions for children ≤20 years of age undergoing a bariatric procedure for morbid obesity in 2009 using the Kids' Inpatient Database (KID). Patients had a principal diagnosis of obesity and a bariatric procedure listed as one of their first 5 procedures. Procedures (open gastric bypass, laparoscopic gastric bypass, sleeve gastrectomy, laparoscopic gastroplasty, and laparoscopic gastric band) and complications were defined by ICD-9 codes. RESULTS: There were 90 open gastric bypasses, 906 laparoscopic gastric bypasses, 150 sleeve gastrectomies, 18 laparoscopic gastroplasties, and 445 laparoscopic gastric bandings. The length of stay for each procedure was 2.44, 2.20, 2.33, 1.10, and 1.02 days, respectively (P<0.001). The complication rates were 3.3%, 3.5%, 0.7%, 0.0%, 0.2%, respectively (P=0.004). CONCLUSIONS: Bariatric surgery is an increasingly utilized option for the treatment of morbid obesity among adolescents. The procedures can be performed safely as evidenced by low complication rates. Additional long-term follow-up is necessary.

Anxiety and sexual stress in men and women undergoing infertility treatment.

OBJECTIVE: To better understand the specific nature of the relationship between anxiety and sexual infertility-related stress in men and women. DESIGN: Prospective study. SETTING: University-affiliated teaching hospital. PATIENT(S): Consecutively referred patients referred for in vitro fertilization and intrauterine insemination (306 women, 295 men). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertility Problem Inventory (FPI), Beck Anxiety Inventory (BAI). RESULT(S): Women reported greater anxiety and sexual infertility stress than men. However, men and women showed a similar pattern in the way anxiety symptoms were related to sexual infertility stress, with subjective anxiety and autonomic anxiety having the strongest relationship. Anxiety symptoms accounted for a significant proportion of the variance in sexual infertility stress for both sexes and predicted sexual stress to a considerable degree in men. CONCLUSION(S): Although this study found that there is more similarity than difference in how men and women experience anxiety and sexual infertility stress, the strong linkage between anxiety and sexual stress in men was surprising, because men tend to report less sexual stress and also less anxiety. Sexual stress among infertile men may be more closely tied to performance anxiety rather than to a more general deterioration in sexual satisfaction associated with infertility.

Factors affecting patients' attitudes toward single- and multiple-embryo transfer.

OBJECTIVE: To identify factors that influence patient decision making concerning embryo transfer. DESIGN: Prospective analysis. SETTING: In vitro fertilization unit at a tertiary-care, university-affiliated teaching hospital. PATIENT(S): Seventy-nine women and 53 men who were referred consecutively for IVF treatment. INTERVENTION(S): Provision of risk information about complications of twin pregnancy. MAIN OUTCOME MEASURE(S): Rated desirability of different transfer options and twin pregnancy, together with standardized measures of depression and infertility stress. RESULT(S): Women's initial preference for two-embryo transfer (2ET) was related to beliefs that the chance of pregnancy was higher with 2ET vs. elective single-embryo transfer and that the personal chance of twins was relatively likely with 2ET but was not related to a specific desire for twins. Providing risk information increased the desirability of elective single-embryo transfer and decreased the desirability of twin pregnancy among both men and women. CONCLUSION(S): Cautious patients, preferring transfer of fewer embryos, balance desires to maximize the chance of pregnancy with acceptance of risks associated with twins. Less-cautious patients may be motivated by beliefs about the influence of age, desires for, and likelihood of twin pregnancy. Information about risks may affect these groups differently and diverse patient motivations may require tailored information to ensure informed consent.

The relationship between coping and depression in men and women referred for in vitro fertilization.

This study examined coping with infertility and how coping is related to depression for men and women. Results showed that both men and women who engage in a disproportionate degree of escape/avoidance behavior and acceptance of responsibility for infertility were more vulnerable to symptoms of depression.

Angiotensin II type 1 receptor activation increases microvascular permeability via a calcium dependent process.

BACKGROUND: Elevated serum angiotensin II (Ang II) has been implicated in the endothelial barrier dysfunction associated with shock. We hypothesized that the increase in microvascular permeability seen with activation of the type 1 (AT1) receptor is a calcium dependent process. MATERIALS AND METHODS: Microvascular hydraulic permeability (Lp) was measured in rat mesenteric venules using the Landis micro-occlusion model. A 100 mm KCl (HK) solution was used to negate the electrochemical potential of calcium influx, and measures of Lp were obtained before and after 20 ng/ml Ang II plus HK solution (n = 5). Intracellular calcium dependence on AT1 activation was evaluated two ways: 1) Lp changes were measured in response to 10 microm of the type 1 receptor agonist [SAR] [1]-angiotensin II in HK solution (n = 6), and 2) Lp changes were measured in response to 25 microg/ml of the type 2 (AT2) receptor blocker PD-123319 (PD) plus 20 ng/ml Ang II in HK solution (n = 6). RESULTS: As expected, HK perfusion (P < 0.08) and Ang II plus HK solution (P < 0.42) did not affect Lp. Although perfusion of [SAR] [1]-angiotensin II in HK solution (P < 0.001) and PD plus Ang II in HK solution (P < 0.003) both significantly increased Lp, the magnitude of this response was less than that observed with Ang II alone. CONCLUSIONS: Abrogation of intracellular calcium influx during AT1 activation blunted the known Ang II induced increase in microvascular permeability. Although the effect observed during AT1 activation was blunted by the HK solution, a significant elevation of Lp was still observed. This suggests that Ang II activation of the AT1 receptor increases microvascular permeability primarily, but not exclusively, via modulation of endothelial intracellular calcium ion levels.