The National Grange: A Rural Community Resource to Increase the Reach of Health Promotion and Disease Prevention in the United States.

Our objectives were to review the Grange as a rural community organization with the potential to increase the reach of public health efforts. We examined seven years of Grange member newsletters and publications for content pieces that reflected a public health focus and organized our findings according to the Healthy People 2020 five determinant areas within the Social Determinants of Health. Results: We found ample evidence of overlap between the goal and objectives of public health and those of the Grange. The Grange currently operates programs of education or participation in all five of the determinant areas: (1) Health and Health Care Access; (2) Social and Community Context; (3) Education; (4) Economic Stability; and (5) the Neighborhood and the Built Environment. The Grange is a grass roots rural organization that is uniquely positioned to offer a rich and nuanced partnership with public health agencies. The Grange has been contributing towards rural health for over 150 years, but despite this predisposition to the mission of public health, the Grange remains an underused community resource capable of improving rural health and addressing a variety of rural public health issues.

Improved glycaemic control and treatment satisfaction with a simple wearable 3-day insulin delivery device among people with Type 2 diabetes.

AIM: To evaluate the PAQ® (CeQur SA, Horw, Switzerland), a wearable 3-day insulin delivery device that provides set basal rates and bolus insulin on demand, in people with Type 2 diabetes. METHOD: Adults with Type 2 diabetes with HbA1c concentrations ≥53 and ≤97 mmol/mol (7.0 and 11.0%) while treated with ≥2 insulin injections/day were enrolled in two single-arm studies comprising three periods: a baseline (insulin injections), a transition and a PAQ treatment period (12 weeks). Endpoints included HbA1c , seven-point self-monitored blood glucose, total daily dose of insulin and body weight. Safety was assessed according to examination, hypoglycaemic episodes and adverse device effects. RESULTS: A total of 28 adults were enrolled (age 63 ± 7 years, 86% men, BMI 32.3 ± 4.3kg/m2 , Type 2 diabetes duration 17 ± 8 years, HbA1c 70 ± 12 mmol/mol (8.6 ± 1.1%), total daily insulin dose 58.7 ± 20.7 U), of whom 24 completed the studies. When transitioned to PAQ, 75% of participants continued on the first basal rate selected. After 12 weeks of PAQ wear, significant improvements from baseline were seen [HbA1c -16 ± 9 mmol/mol (95% CI -20, -12) or -1.5 ± 0.9% (95% CI -1.8, -1.1) P<0.0001], and at all seven self-monitored blood glucose readings time points (P ≤0.03). Total daily insulin dose increased by 12.1 ± 19.5 U (95% CI 3.9, 20.4; P=0.0058), the number of meal time boluses increased by 0.9 ± 1.5/day (95% CI 0.3, 1.5; P=0.0081) and body weight remained stable. Six participants had mild to moderate catheter site reactions and one mild skin irritation occurred. No participant experienced severe hypoglycaemia. CONCLUSIONS: Adults with Type 2 diabetes were safely transitioned from insulin injections to the PAQ and had significantly improved glycaemic control and treatment satisfaction with insulin therapy. (ClinicalTrials.gov identifiers: NCT02158078 & NCT02419859).

Successful Lung Transplantation From Hepatitis C Positive Donor to Seronegative Recipient.

Lung transplantation using RNA+ hepatitis C (HCV+) donors to seronegative recipients is not currently performed due to the very high risk of transmission. Previous reports have shown poor survival when this practice was applied. The emergence of new direct-acting antiviral drugs (DAA) suggests a high chance of sustained virologic response in immunocompetent patients. We report here successful transplantation of lungs from HCV+ donor to HCV- recipient. The recipient was an HCV- patient with chronic lung allograft dysfunction. Viral transmission occurred early posttransplant but excellent clinical outcomes were observed including elimination of HCV after 12 weeks of treatment using DAAs.

Donor BMI >30 Is Not a Contraindication for Live Liver Donation.

The increased prevalence of obesity worldwide threatens the pool of living liver donors. Although the negative effects of graft steatosis on liver donation and transplantation are well known, the impact of obesity in the absence of hepatic steatosis on outcome of living donor liver transplantation (LDLT) is unknown. Consequently, we compared the outcome of LDLT using donors with BMI <30 versus donors with BMI ≥30. Between April 2000 and May 2014, 105 patients received a right-lobe liver graft from donors with BMI ≥30, whereas 364 recipients were transplanted with grafts from donors with BMI <30. Liver steatosis >10% was excluded in all donors with BMI >30 by imaging and liver biopsies. None of the donors had any other comorbidity. Donors with BMI <30 versus ≥30 had similar postoperative complication rates (Dindo-Clavien ≥3b: 2% vs. 3%; p = 0.71) and lengths of hospital stay (6 vs. 6 days; p = 0.13). Recipient graft function, assessed by posttransplant peak serum bilirubin and international normalized ratio was identical. Furthermore, no difference was observed in recipient complication rates (Dindo-Clavien ≥3b: 25% vs. 20%; p = 0.3) or lengths of hospital stay between groups. We concluded that donors with BMI ≥30, in the absence of graft steatosis, are not contraindicated for LDLT.

First-Degree Living-Related Donor Liver Transplantation in Autoimmune Liver Diseases.

Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.

N-acetyl-l-tryptophan, but not N-acetyl-d-tryptophan, rescues neuronal cell death in models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss. Evidence suggests that mitochondrial dysfunction, apoptosis, oxidative stress, inflammation, glutamate excitotoxicity, and proteasomal dysfunction are all responsible for ALS pathogenesis. N-acetyl-tryptophan has been identified as an inhibitor of mitochondrial cytochrome c release and therefore is a potential neuroprotective agent. By quantifying cell death, we demonstrate that N-acetyl-l-tryptophan (L-NAT) and N-acetyl-DL-tryptophan are neuroprotective in NSC-34 motor neuron-like cells and/or primary motor neurons, while their isomer N-acetyl-d-tryptophan has no protective effect. These findings are consistent with energy minimization and molecular modeling analysis, confirming that L-NAT generates the most stable complex with the neurokinin-1 receptor (NK-1R). L-NAT inhibits the secretion of Substance P and IL-1ß (Enzyme-Linked Immunosorbent Assay and/or dot blots) and mitochondrial dysfunction by effectively inhibiting the release of cytochrome c/Smac/AIF from mitochondria into the cytoplasm and activation of apoptotic pathways, including the activation of caspase-1, -9, and -3, as well as proteasomal dysfunction through restoring chymotrypsin-like, trypsin-like, and caspase-like proteasome activity. These data provide insight into the molecular mechanisms by which L-NAT offers neuroprotection in models of ALS and suggest its potential as a novel therapeutic strategy for ALS. We demonstrate that L-NAT (N-acetyl-l-tryptophan), but not D-NAT, rescues NSC-34 cells and primary motor neurons from cell death. L-NAT inhibits the secretion of Substance P and IL-1ß, and caspase-1 activation, the release of cytochrome c/Smac/AIF, and the activation of caspase -9, and -3, as well as proteasomal dysfunction. The data suggest the potential of L-NAT as a novel therapeutic strategy for amyotrophic lateral sclerosis (ALS). AIF, apoptosis-inducing factor.

Proposed management algorithm for severe hypoxemia after liver transplantation in the hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS) is defined as the triad of liver disease, intrapulmonary vascular dilatation, and abnormal gas exchange, and is found in 10-32% of patients with liver disease. Liver transplantation is the only known cure for HPS, but patients can develop severe posttransplant hypoxemia, defined as a need for 100% inspired oxygen to maintain a saturation of ≥85%. This complication is seen in 6-21% of patients and carries a 45% mortality. Its management requires the application of specific strategies targeting the underlying physiologic abnormalities in HPS, but awareness of these strategies and knowledge on their optimal use is limited. We reviewed existing literature to identify strategies that can be used for this complication, and developed a clinical management algorithm based on best evidence and expert opinion. Evidence was limited to case reports and case series, and we determined which treatments to include in the algorithm and their recommended sequence based on their relative likelihood of success, invasiveness, and risk. Recommended therapies include: Trendelenburg positioning, inhaled epoprostenol or nitric oxide, methylene blue, embolization of abnormal pulmonary vessels, and extracorporeal life support. Availability and use of this pragmatic algorithm may improve management of this complication, and will benefit from prospective validation.

Live donor liver transplantation: a valid alternative for critically ill patients suffering from acute liver failure.

We report the outcome of live donor liver transplantation (LDLT) for patients suffering from acute liver failure (ALF). From 2006 to 2013, all patients with ALF who received a LDLT (n = 7) at our institution were compared to all ALF patients receiving a deceased donor liver transplantation (DDLT = 26). Groups were comparable regarding pretransplant ICU stay (DDLT: 1 [0-7] vs. LDLT: 1 days [0-10]; p = 0.38), mechanical ventilation support (DDLT: 69% vs. LDLT: 57%; p = 0.66), inotropic drug requirement (DDLT: 27% vs. LDLT: 43%; p = 0.64) and dialysis (DDLT: 2 vs. LDLT: 0 patients; p = 1). Median evaluation time for live donors was 24 h (18-72 h). LDLT versus DDLT had similar incidence of overall postoperative complications (31% vs. 43%; p = 0.66). No difference was detected between LDLT and DDLT patients regarding 1- (DDLT: 92% vs. LDLT: 86%), 3- (DDLT: 92% vs. LDLT: 86%), and 5- (DDLT: 92% vs. LDLT: 86%) year graft and patient survival (p = 0.63). No severe donor complication (Dindo-Clavien ≥3 b) occurred after live liver donation. ALF is a severe disease with high mortality on liver transplant waiting lists worldwide. Therefore, LDLT is an attractive option since live donor work-up can be expedited and liver transplantation can be performed within 24 h with excellent short- and long-term outcomes.

Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series.

PURPOSE: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS: We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d'Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2-129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1-112.5) months. RESULTS: At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001). CONCLUSIONS: Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

Living vs. deceased donor liver transplantation provides comparable recovery of renal function in patients with hepatorenal syndrome: a matched case-control study.

Outcomes of living versus deceased donor liver transplantation in patients with chronic liver disease and hepatorenal syndrome (HRS) was compared using a matched pair study design. Thirty patients with HRS receiving a live donor liver transplantation (LDLT) and 90 HRS patients receiving a full graft deceased donor liver transplantation (DDLT) were compared. LDLT versus DDLT of patients with HRS was associated with decreased peak aspartate aminotransferase levels (339 ± 214 vs. 935 ± 1253 U/L; p = 0.0001), and similar 7-day bilirubin (8.42 ± 7.89 vs. 6.95 ± 7.13 mg/dL; p = 0.35), and international normalized ratio levels (1.93 ± 0.62 vs. 1.78 ± 0.78; p = 0.314). LDLT vs. DDLT had a decreased intensive care unit (2 [1-39] vs. 4 [0-93] days; p = 0.004), and hospital stay (17 [4-313] vs. 26 [0-126] days; p = 0.016) and a similar incidence of overall postoperative complications (20% vs. 27%; p = 0.62). No difference was detected between LDLT and DDLT patients regarding graft survival at 1 (80% vs. 82%), at 3 (69% vs. 76%) and 5 years (65% vs. 76%) (p = 0.63), as well as patient survival at 1 (83% vs. 82%), 3 (72% vs. 77%) and 5 years (72% vs. 77%) (p = 0.93). The incidence of chronic kidney disease post-LT (10% vs. 6%; p = 0.4) was similar between both groups. LDLT results in identical long-term outcome when compared with DDLT in patients with HRS.

Hepatitis C core Ag and its clinical applicability: potential advantages and disadvantages for diagnosis and follow-up?

Chronic hepatitis C virus (HCV) infection which is often a silent disease has resulted in a global epidemic. The diagnosis of hepatitis C virus often requires confirmation with molecular techniques such as the polymerase chain reaction for detection of HCV RNA. Following laboratory confirmation of the diagnosis, molecular techniques are routinely used to monitor HCV RNA levels, particularly in those undergoing treatment. Unfortunately, molecular tests are relatively expensive and their cost may be prohibitive in the developing world. Several studies have investigated the applicability of the hepatitis C core Ag (HCVcAg), as a substitute for measuring HCV RNA levels. In this review, we provide an overview of the major findings of these studies focused on the utility of measuring HCVcAg antigen levels in the clinical setting. Overall, measuring HCVcAg levels is associated with several advantages and disadvantages. It may be useful in different clinical settings for monitoring HCV patients after obtaining an initial baseline HCV RNA result.

Long-term outcomes of ablation, liver resection, and liver transplant as first-line treatment for solitary HCC of 3 cm or less using an intention-to-treat analysis: A retrospective cohort study.

Background: Curative-intent therapies for hepatocellular carcinoma (HCC) include radiofrequency ablation (RFA), liver resection (LR), and liver transplantation (LT). Controversy exists in treatment selection for early-stage tumours. We sought to evaluate the oncologic outcomes of patients who received either RFA, LR, or LT as first-line treatment for solitary HCC ≤ 3 cm in an intention-to-treat analysis. Materials and methods: All patients with solitary HCC ≤ 3 cm who underwent RFA, LR, or were listed for LT between Feb-2000 and Nov-2018 were analyzed. Cox regression analysis was then performed to compare intention-to-treat (ITT) survival by initial treatment allocation and disease-free survival (DFS) by treatment received in patients eligible for all three treatments. Results: A total of 119 patients were identified (RFA n = 83; LR n = 25; LT n = 11). The overall intention-to-treat survival was similar between the three groups. The overall DFS was highest for the LT group. This was significantly higher than RFA (p = 0.02), but not statistically significantly different from LR (p = 0.14). After multivariable adjustment, ITT survival was similar in the LR and LT groups relative to RFA (LR HR:1.13, 95%CI 0.33-3.82; p = 0.80; LT HR:1.39, 95%CI 0.35-5.44; p = 0.60). On multivariable DFS analysis, only LT was better relative to RFA (LR HR:0.52, 95%CI 0.26-1.02; p = 0.06; LT HR:0.15, 95%CI 0.03-0.67; p = 0.01). Compared to LR, LT was associated with a numerically lower hazard on multivariable DFS analysis, though this did not reach statistical significance (HR 0.30, 95%CI 0.06-1.43; p = 0.13). Conclusion: For treatment-naïve patients with solitary HCC ≤ 3 cm who are eligible for RFA, LR, and LT, adjusted ITT survival is equivalent amongst the treatment modalities, however, DFS is better with LR and LT, compared with RFA. Differences in recurrence between treatment modalities and equipoise in ITT survival provides support for a future prospective trial in this setting.

Improved survival after liver transplantation in patients with hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) is present in 10-32% of chronic liver disease patients, carries a poor prognosis and is treatable by liver transplantation (LT). Previous reports have shown high LT mortality in HPS and severe HPS (arterial oxygen (PaO(2)) < or =50 mmHg). We reviewed outcomes in HPS patients who received LT between 2002 and 2008 at two transplant centers supported by a dedicated HPS clinic. We assessed mortality, complications and gas exchange in 21 HPS patients (mean age 51 years, MELD score 14), including 11/21 (52%) with severe HPS and 5/21 (24%) with living donor LT (median follow-up 20.2 months after LT). Overall mortality was 1/21 (5%); mortality in severe HPS was 1/11 (9%). Peritransplant hypoxemic respiratory failure occurred in 5/21 (24%), biliary complications in 8/21 (38%) and bleeding or vascular complications in 6/21 (29%). Oxygenation improved in all 19 patients in whom PaO(2) or SaO(2) were recorded. PaO(2) increased from 52.2 +/- 13.2 to 90.3 +/- 11.5 mmHg (room air) (p < 0.0001) (12 patients); a higher baseline macroaggregated albumin shunt fraction predicted a lower rate of postoperative improvement (p = 0.045) (7 patients). Liver transplant survival in HPS and severe HPS was higher than previously demonstrated. Severity of HPS should not be the basis for transplant refusal.

Adult living liver donors have excellent long-term medical outcomes: the University of Toronto liver transplant experience.

Right lobe living donor liver transplantation is an effective treatment for selected individuals with end-stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow-up of 12 months (range 12-96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 +/- 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long-term follow-up may contribute to favorable donor outcomes.

Survival after liver transplantation for hepatitis C is unchanged over two decades in Canada.

Allograft failure secondary to recurrence of hepatitis C virus (HCV) infection is the most common cause of death and retransplantation among recipients with HCV infection. It has been suggested that patients transplanted for HCV have had worse outcomes in more recent years than in previous years (the 'era effect'). A Canadian transplantation registry database was analyzed to determine the outcomes of patients transplanted over the years for HCV. The results of the present analysis of 1002 patients show that the 'era effect' was not seen in liver transplantation recipients with HCV in Canada, because no survival difference was noted based on the year of transplantation. All groups had overall two-year and five-year survival rates of 76% to 83% and 69% to 72%, respectively. The present study's national results prove continued benefit to transplantation of HCV patients.

Enteral Feeding as an Adjunct to Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Withholding enteral feedings during hypothermia lacks supporting evidence. OBJECTIVES: We aimed to determine if minimal enteral nutrition (MEN) during hypothermia in patients with hypoxic-ischemic encephalopathy was associated with a reduced duration of parenteral nutrition, time to full oral feeds, and length of stay, but would not be associated with increased systemic inflammation or feeding complications. METHODS: We performed a pilot, retrospective, matched case-control study within the Florida Neonatal Neurologic Network from December 2012 to May 2016 of patients who received MEN during hypothermia (n = 17) versus those who were not fed (n = 17). Length of stay, feeding-related outcomes, and brain injury identified by MRI were compared. Serum inflammatory mediators were measured at 0-6, 24, and 96 h of life by multiplex assay. MRI were scored using the Barkovich system. RESULTS: MEN subjects had a reduced length of hospital stay (mean 15 ± 11 vs. 24 ± 19 days, p < 0.05), days receiving parenteral nutrition (7 ± 2 vs. 11 ± 6, p < 0.05), and time to full oral feeds (8 ± 5 vs. 18 ± 18, p < 0.05). MEN was associated with a significantly reduced serum IL-12p70 at 24 and 96 h (p < 0.05). Brain MRI scores were not significantly different between groups. CONCLUSION: MEN during hypothermia was associated with a reduced length of stay and time to full feeds, but did not increase feeding complications or systemic inflammation.

Symptomatic hypotension following the clonidine suppression test for pheochromocytoma.

A 42-year-old man with generalized atherosclerosis underwent surgery of the left carotid artery with eventual placement of a Dacron graft bypassing the left carotid sinus. Subsequently, symptoms suggestive of pheochromocytoma developed, and 24-hour urine catecholamine levels were elevated. Clonidine testing resulted in suppression of plasma norepinephrine levels but was complicated by severe hypotension and a transient ischemic attack. Baroreceptor dysfunction may have been involved. Caution is advised and recommendations are offered for future usage of the clonidine suppression test.

Neuroprotective agents target molecular mechanisms of disease in ALS.

Amyotrophic lateral sclerosis (ALS) is a debilitating disease characterized by progressive loss of voluntary motor neurons leading to muscle atrophy, weight loss and respiratory failure. Evidence suggests that inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and proteasomal dysfunction are all responsible for ALS pathogenesis. We review neuroprotective agents with the ability to reduce ALS-related bodyweight loss, summarize the various therapies tested on animal models targeting the proposed molecular mechanisms, compare their effects on bodyweight loss, muscle damage, disease onset, duration and survival, and analyze their structure-activity relationships, with the overall goal of creating a screening strategy for further clinical application.

Hyponatremia in congestive heart failure: implications for neurohumoral activation and responses to orthostasis.

To study the relationship between serum Na concentration and impairment of homeostatic mechanisms in advanced congestive heart failure (CHF), we evaluated the status of the sympathetic nervous system, renin-angiotensin system, and regional visceral blood flow in 26 patients with this syndrome. Compared with normal subjects, hyponatremic patients had marked stimulation of PRA (P = 0.012), norepinephrine (P less than 0.001), and epinephrine (P less than 0.001) with severe impairment of renal (P less than 0.001) and hepatic (P less than 0.003) plasma flows. In contrast, normonatremic patients, with an apparently similar degree of CHF, demonstrated less pronounced abnormalities in all of these parameters. Moreover, the responses of neurohormones and regional blood flow to orthostatic stress were greatly attenuated in the hyponatremic patients, whereas, the normonatremic subjects had more normal responses. We conclude that serum Na concentration serves as a useful index of activation of the sympathetic nervous system, renin-angiotensin system, and impairment of regional perfusion in patients with advanced CHF.

Relationship of cardiac chamber volume to baroreflex activity in normal humans.

The objectives of this study were to examine the effect of incremental lower body negative pressure (LBNP) on cardiac chamber volume and assess the relationship between cardiac chamber volume and baroreflex activation of the neurohormonal axis. Accordingly, echocardiographic determination of cardiac chamber volume and neurohormonal responses were studied in 14 normal subjects during incremental LBNP. LBNP -10 mm Hg decreased left atrial diameter and left ventricular systolic volume index, but did not alter heart rate, systolic or pulse pressure, or stroke volume. During LBNP -10 mm Hg, plasma norepinephrine levels increased, suggesting activation of the sympathetic nervous system. LBNP -40 mm Hg caused a significant decrease in left atrial diameter and left ventricular systolic, diastolic, and stroke volume indices. During LBNP -40 mm Hg, heart rate increased, and systolic and pulse pressure fell. With this more negative level of LBNP, norepinephrine, angiotensin II, aldosterone, and arginine vasopressin concentrations and PRA all increased. The findings that left atrial diameter decreased and plasma norepinephrine concentration increased during LBNP -10 mm Hg suggest that the sympathetic nervous system is sensitive to changes in atrial receptor activity. At higher levels of LBNP (-40 mm Hg), activation of the renin-angiotensin system and release of vasopressin were associated with a fall in left ventricular diastolic volume as well as a decrease in the pressure input to the arterial baroreceptors. Under this condition, the differential contribution of the cardiopulmonary and arterial baroreceptors to the regulation of the renin-angiotensin system and vasopressin release cannot be distinguished.