Role of the liver in splanchnic extraction of atrial natriuretic factor in the rat

Mesenteric, hepatic and splanchnic extraction of C-terminal and N-terminal atrial natriuretic factor was investigated in male Sprague-Dawley rats. Plasma concentrations (mean ± S.E.M.) of C-terminal atrial natriuretic factor were 55.0 ± 6.1 fmol/ml, 31.2 ± 4.0 fmol/ml and 23.5 ± 3.3 fmol/ml (n = 12) in the abdominal aorta, the portal vein and the hepatic vein, respectively. N-terminal atrial natriuretic factor plasma levels in these vessels were 3031 ± 756 fmol/ml, 2264 ± 661 fmol/ml and 1618 ± 496 fmol/ml (n = 6), respectively. Although the mesenteric extraction ratio was higher (p < 0.05) for C-terminal atrial natriuretic factor (42% ± 6%) than for N-terminal atrial natriuretic factor (28% ± 4%), there were no significant differences in the hepatic extraction ratio (41% ± 5% vs. 39% ± 6%) and the splanchnic extraction ratio (56% ± 5% vs. 50% ± 7%). These data suggest a major role of the liver in the splanchnic extraction of C-terminal and of N-terminal atrial natriuretic factor in the rat. (HEPATOLOGY 1992;16:790-793

Atrial natriuretic factor (ANF) and renin-aldosterone in volume regulation of patients with cirrhosis

The role of the atrial natriuretic factor and of the main counteracting sodium-retaining principle, the renin-aldosterone system, in acute volume regulation of cirrhosis of the liver has been investigated. Central volume stimulation was achieved in 21 patients with cirrhosis, 11 without and 10 with ascites, and 25 healthy controls by 1-hr head-out water immersion. Immersion prompted a highly significant (p<0.001) increase of atrial natriuretic factor plasma concentrations in cirrhotic patients without ascites from 8.5 ± 1.3 fmoles per ml to 16.5 ± 2.6 fmoles per ml, comparable to the stimulation in control subjects (6.0 ± 0.6 fmoles per ml to 13.6 ± 2.6 fmoles per ml). In cirrhotic patients with ascites, atrial natriuretic factor increase (from 7.7 ± 1.3 fmoles per ml to 11.4 ± 2.3 fmoles per ml) was blunted (p<0.05). Plasma renin activity and plasma aldosterone concentration were elevated in cirrhotic patients, especially in the presence of ascites. Following immersion, plasma renin activity and plasma aldosterone concentration were reduced similarly in all groups. Water immersion induced a more pronounced natriuresis and diuresis in control subjects than in cirrhotic patients. Neither atrial natriuretic factor nor plasma renin activity nor plasma aldosterone concentration alone correlated to sodium excretion. However, atrial natriuretic factor to plasma aldosterone concentration ratios were closely correlated to basal and stimulated natriuresis in cirrhotic patients, particularly in those with ascites. These data suggest that atrial natriuretic factor and the renin-aldosterone system influence volume regulation in patients with cirrhosis

Estradiol and testosterone levels in patients undergoing partial hepatectomy - A possible signal for hepatic regeneration?

In five adult male patients undergoing a 40-60% partial hepatectomy, serum sex hormone levels before and after hepatic resection were determined. Blood was drawn immediately prior to each surgical procedure and at specified time points postoperatively. Compared to hormone levels found prior to surgery, following major hepatic resection, estradiol levels increase at 24 and 48 hr, while testosterone levels decline, being significantly reduced at 96 and 144 hr. These data demonstrate that adult males who undergo a 40-60% partial hepatectomy experience alterations in their sex hormone levels similar to those observed in male rats following a 70% hepatectomy. These changes in sex hormone levels have been associated in animals with an alteration of the sex hormone receptor status of the liver that is thought to participate in the initiation of the regenerative response. These studies suggest, but do not prove, that in man, as in the case of the rat, sex hormones may participate in the initiation of or at least modulate in part the regenerative response that occurs following a major hepatic resection. © 1989 Plenum Publishing Corporation

Indication Alerts Intercept Drug Name Confusion Errors during Computerized Entry of Medication Orders

Background: Confusion between similar drug names is a common cause of potentially harmful medication errors. Interventions to prevent these errors at the point of prescribing have had limited success. The purpose of this study is to measure whether indication alerts at the time of computerized physician order entry (CPOE) can intercept drug name confusion errors. Methods and Findings: A retrospective observational study of alerts provided to prescribers in a public, tertiary hospital and ambulatory practice with medication orders placed using CPOE. Consecutive patients seen from April 2006 through February 2012 were eligible if a clinician received an indication alert during ordering. A total of 54,499 unique patients were included. The computerized decision support system prompted prescribers to enter indications when certain medications were ordered without a coded indication in the electronic problem list. Alerts required prescribers either to ignore them by clicking OK, to place a problem in the problem list, or to cancel the order. Main outcome was the proportion of indication alerts resulting in the interception of drug name confusion errors. Error interception was determined using an algorithm to identify instances in which an alert triggered, the initial medication order was not completed, and the same prescriber ordered a similar-sounding medication on the same patient within 5 minutes. Similarity was defined using standard text similarity measures. Two clinicians performed chart review of all cases to determine whether the first, non-completed medication order had a documented or non-documented, plausible indication for use. If either reviewer found a plausible indication, the case was not considered an error. We analyzed 127,458 alerts and identified 176 intercepted drug name confusion errors, an interception rate of 0.14±.01%. Conclusions: Indication alerts intercepted 1.4 drug name confusion errors per 1000 alerts. Institutions with CPOE should consider using indication prompts to intercept drug name confusion errors

THE EFFECT OF PROPRANOLOL ON PLASMA RENIN ACTIVITY AND BLOOD PRESSURE IN MILD ESSENTIAL HYPERTENSION

Fourteen male patients with mild to moderate essential hypertension have been studied with regard to plasma renin activity (PRA) after acute and prolonged Β-adrenergic blockade with propranolol. Initial PRA was determined after four weeks of placebo treatment. Before propranolol was given PRA rose in response to 10 min of 45° head-up tilt from 151.7 ng/100 ml/h to 248.7 ng/100 ml/h ( p <0.01). After acute administration of propranolol 0.22 mg/kg b.wt. i.v. and following repeated tilt for 10 min PRA only rose to 204.7 ng/100 ml/h (n.s.). Following four weeks of oral propranolol treatment at 160–320 mg daily PRA after tilt was 39.0 ng/100 ml/h. Thus a significant reduction of PRA had taken place ( p < 0.005) to a level constituting only 15% of the initial PRA after tilt. The reduction of blood pressure (BP) after four weeks of propranolol treatment was also significant. Diastolic BP was reduced by 19 mmHg( p < 0.001). The changes in BP and tilted PRA were not significantly correlated ( r =0.449, p <0.10). These results indicate that propranolol causes a marked reduction of PRA in addition to its hypotensive effect. However, this does not necessarily imply that there is a direct causal relationship between the effect of propranolol on PRA and its effect on BP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73325/1/j.0954-6820.1974.tb08159.x.pd

VALUE trial: Long-term blood pressure trends in 13,449 patients with hypertension and high cardiovascular risk

Background: The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study compares cardiovascular outcomes in 15,314 eligible patients from 31 countries randomized to valsartan or amlodipine-based treatment. Methods: The blood pressure (BP) trends are analyzed in 13,449 of VALUE study patients who had baseline BP and 24 months BP and treatment data. Results: In a cohort of 12,570 patients, baseline 24 and 30 months BP, but not 30 months treatment data, were available. Of 13,449 patients, 92% (N = 12,398) received antihypertensive therapy at baseline. The baseline BP was 153.5/86.9 mm Hg in treated compared to 168.1.8/95.3 mm Hg in 1051 untreated patients. After 6 months both groups had indistinguishable BP values. At 12 months the BP decreased to 141.2/82.9 mm Hg (P < .0001 for systolic BP and diastolic BP versus baseline), at 24 months to 139.1/80 mm Hg (P < .0001 v 12 months), and to 138/79 mm Hg at 30 months (P < .0001 v 24 months). The systolic BP control (<140 mm Hg) at 30 months increased from 21.9% at baseline to 62.2%, the diastolic BP (< 90 mm Hg) from 54.2% to 90.2% and the combined control (<140 and <90 mm Hg) from 18.9% to 60.5%. At 24 months 85.8% of patients were on protocol drugs: monotherapy = 39.7%, added hydrochlorothiazide = 26.6%, add-on drugs = 15.1%, and protocol drugs in nonstandard doses = 4.3%. Conclusions: The achieved BP control exceeds values reported in most published large-scale trials. The VALUE study is executed in regular clinical settings and 92% of the patients received antihypertensive drugs at baseline. When an explicit BP goal is set, and a treatment algorithm is provided, the physicians can achieve better control rates than in their regular practice. Am J Hypertens 2003;16: 544-548 @ 2003 American Journal of Hypertension, Lt

Atrial natriuretic factor

The discovery of the first well-defined natriuretic hormone, the Atrial Natriuretic Factor (ANF), has prompted research on its impact on volume regulation in health and disease. The natriuretic, diuretic, and smooth muscle-relaxing properties suggest an important role of this novel hormone in pathophysiological states with sodium or volume retention, such as congestive heart failure or cirrhosis of the liver. Investigations on the implications of ANF in liver disease have been performed for little more than 1 year, and results are still controversial in many respects. At present, it seems very likely that there is no absolute deficiency of plasma ANF in patients with cirrhosis. Moreover, elevated plasma levels in cirrhotics with ascites have been reported by several groups. However, as yet, a molecular characterization of this increased immunoreactivity is still lacking. There is disagreement on the reduced release of and renal response to ANF in subgroups of cirrhotics; however, stimulus-response-coupling might be impaired. Further studies are needed to elucidate the pathophysiological implications and therapeutical potential of ANF in patients with chronic liver disease

Prediction of Primary vs Secondary Hypertension in Children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91106/1/j.1751-7176.2012.00603.x.pd