Realizing the potential of clinical judgment: a real-time strategy for predicting outcomes and cost for medical inpatients.

PURPOSE: We sought to determine whether illness severity and anticipated level of function, as evaluated at the time of admission, were associated with outcomes and costs of care for patients admitted to the medical service. METHODS: All 1,759 patients admitted to the medical service at a large urban academic medical center between July 1, 1997, and September 30, 1997 (excluding those admitted directly to the intensive care units or for protocol chemotherapy), were evaluated and categorized by the admitting intern by illness severity (not ill, mildly ill, moderately ill, severely ill, or moribund) and anticipated level of function at discharge (excellent, good, fair, or poor) as part of their routine sign-out process. Interns' ratings were always available within 24 to 28 hours of admission. In-hospital mortality, length of stay, cost of hospitalization, and anticipated billing revenue were evaluated. RESULTS: Patients who were more severely ill had significantly greater in-hospital mortality. For example, mortality was 1.1% (11 of 972) among those who were not ill or mildly ill, 3.6% (26 of 724) among those who were moderately ill, and 15% (9 of 60) among those who were severely ill. Illness severity (P = 0.003) and anticipated functional status (P < 0.01) were significant predictors of in-hospital mortality. Illness severity and function were also significant predictors of greater length of stay and greater costs of hospitalization (all P < 0.0001). The 389 patients who were moderately ill with fair or poor anticipated function were associated with the largest cumulative losses (about $330,000 during the 3-month period), whereas the 798 mildly ill patients with good or excellent function were associated with the largest cumulative profits ($550,000). CONCLUSION: Physicians' estimates of patients' illness severity and anticipated function at the time of discharge, as made by interns using a system designed to help them sign out to their colleagues, predict outcomes and costs of hospitalization. Such a system may be useful in developing new approaches to management strategies based on prognosis.

Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects.

Although beta-adrenergic-blocking drugs suppress the renin system (RAAS), plasma angiotensin II (Ang II) responses during beta-blockade have not been defined. This study quantifies the effects of beta-blockade on the RAAS and examines its impact on prorenin processing by measuring changes in the ratio of plasma renin activity (PRA) to total renin. In normotensive (N = 14) and hypertensive (N = 16) subjects, blood pressure (BP), heart rate, PRA, plasma prorenin, plasma total renin (prorenin + PRA), ratio of PRA to total renin (%PRA), plasma Ang II, and urinary aldosterone were measured before and after 1 week of beta-blockade. Plasma renin activity, Ang II, and urinary aldosterone levels were similar for normotensive and hypertensive subjects. Plasma renin activity correlated with Ang II. Total renin, which is proportional to (pro)renin gene expression, was lower in hypertensive subjects and was inversely related to BP. Beta-blockade decreased BP and heart rate in both groups, with medium- and high-renin hypertensive subjects responding more frequently than those with low renin. Beta-blockade consistently suppressed PRA, Ang II, and aldosterone. Total renin was unchanged, thus, %PRA fell. These results indicate that beta-blockers suppress plasma angiotensin II levels, in parallel with the marked reductions in PRA and urinary aldosterone levels in normotensive and hypertensive subjects. The suppression of Ang II levels was comparable to that produced during angiotensin converting enzyme (ACE) inhibition. However, by reducing prorenin processing to renin, beta-blockers do not stimulate renin secretion, unlike ACE inhibitors and Ang II receptor antagonists. This unique action of beta-blockers has important implications for the treatment of cardiovascular disease.

Control of blood pressure and end-organ damage in maturing salt-loaded stroke-prone spontaneously hypertensive rats by oral angiotensin II receptor blockade.

OBJECTIVE: To study the effects of renin-angiotensin system blockade by a novel non-peptide angiotensin II receptor antagonist, losartan, on development of hypertension and acceleration of end-organ damage in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). DESIGN AND METHODS: One hundred and eighty-one male SHRSP were fed a 4% sodium diet from 6 to 18 weeks of age. Seventy-eight SHRSP were treated orally with losartan, 30 mg/kg per day. One hundred and three rats constituted untreated controls. Blood pressure, plasma renin activity (PRA), renal function and end-organ damage were monitored during the transition to malignant hypertension. RESULTS: Losartan prevented a blood pressure rise during the first 4 weeks of salt loading. Thereafter, blood pressure rose slowly in losartan-treated rats; however, at each time-point studied blood pressure was significantly lower in losartan-treated rats than in control rats. Losartan treatment increased PRA during the first 4 weeks, but this effect was not sustained. Thereafter, PRA decreased to control (week 0) levels. In contrast, 2 weeks after high-sodium feeding started, untreated SHRSP failed to suppress PRA appropriately; thereafter, PRA rose significantly. Losartan affected renal pathophysiology by blunting the decline in glomerular filtration rate, controlling proteinuria and preventing or delaying the appearance of malignant nephrosclerosis. Losartan treatment significantly increased survival and completely prevented cerebrovascular infarcts. CONCLUSIONS: The results indicate that angiotensin II blockade markedly reduces both hypertension and end-organ damage in chronically salt-loaded SHRSP and that the renin-angiotensin system may play an important role in the development of hypertensive cardiovascular disease in SHRSP.

DuP 753 increases survival in spontaneously hypertensive stroke-prone rats fed a high sodium diet.

We studied the effects of the nonpeptide angiotensin II receptor antagonist, DuP 753, on blood pressure, body weight, plasma renin activity, sodium excretion, and mortality in male stroke-prone spontaneously hypertensive rats (SHRsp) fed a 4% NaCl diet for 12 weeks. The rise in blood pressure, due to high sodium intake, was blunted in the first 8 weeks of the study in the DuP 753-treated group; however, it started slowly to rise in the following weeks. In the untreated group, blood pressure rose steadily and it was significantly higher than that of the treated group during the whole experimental period. DuP 753-treated rats gained weight continuously during the study in contrast to the untreated group, where weight gain was arrested after 4 weeks. Plasma renin activity rose significantly after 4 weeks of treatment with DuP 753; by week 6 its values returned to baseline values and remained at these lower values until week 12. In the untreated group, plasma renin activity was not suppressed by high sodium intake after 4 weeks; it continued to rise and it was significantly elevated by 8 and 12 weeks. Survival at 12 weeks was 84% in DuP 753-treated group and 26% in the untreated group. The data demonstrate that DuP 753 decreased mortality and dramatically blunted the blood pressure rise in SHRsp fed a high sodium diet.

Characterization of auscultatory gaps with wideband external pulse recording.

Three types of auscultatory gaps, called G1, G2, and G3, that occur during blood pressure measurement have been identified by using wideband external pulse recording. We have previously shown that the wideband external pulse recorded during cuff deflation can be separated into three components (K1, K2, and K3), one of which (K2) is closely related to the Korotkoff sound. G1 occurs with cuff pressure just below systolic and is characterized by the presence of K1 and K2 with intermittent disappearance of K2. G1 gaps are related to a phasic decrease of arterial (systolic) pressure and were exhibited by 13 of 60 hypertensive patients. G2 gaps are related to a phasic increase of arterial (diastolic) pressure, occur when cuff pressure is just above diastolic, and are characterized by the presence of K1, K2, and K3 with intermittent disappearance of K2. Seven of 60 hypertensive patients exhibited a G2 gap. G3 gaps occur with cuff pressure between systolic and diastolic and are characterized by an underdeveloped or blunted K2 signal. Three of 60 hypertensive patients exhibited a G3 gap. The identification of auscultatory gaps in relation to the wideband external pulse provides a qualitative measure of their existence, can be of significant value in better understanding aspects of the auscultatory blood pressure measurement technique, and provides an objective basis with which to better understand the mechanisms that cause them.

Dietary salt and blood pressure. A perspective.

Although dietary salt restriction is often valuable as sole or adjunctive therapy of hypertensive disorders, it is abundantly clear that hypertensive patients comprise a heterogeneous group with regard to salt sensitivity of blood pressure. This is apparent despite the many methodological obstacles to defining salt sensitivity in an individual patient. Currently, dietary trial is the only sure means of defining a given patient as responsive to salt restriction. Easily definable markers of salt sensitivity would allow appropriate targeting of this rather ponderous therapy. Promising leads include the assessment of membrane ion transporters such as sodium-lithium exchange and of the activity of the renin-angiotensin system, including the phenomenon of "non-modulating" hypertension and other volume regulatory hormones such as atrial natriuretic factor. Although less intensively studied than in hypertensive patients, the blood pressure response of normal subjects to salt restriction is also marked by great variability. Given the possibility of deleterious consequences of population-wide salt restriction for at least some people in a setting such as the United States, it seems imprudent to recommend such a policy before its proven worth has been demonstrated by clinical trial. Pending such evidence and the development of markers, salt restriction should be reserved for those in whom it is of demonstrated efficacy.

Diurnal and postural variations in plasma atrial natriuretic factor, plasma guanosine 3':5'-cyclic monophosphate and sodium excretion.

1. We studied diurnal patterns of plasma atrial natriuretic factor, plasma guanosine 3':5'-cyclic monophosphate and urinary sodium excretion in normal subjects after 3 days on a 200 mmol of sodium/60 mmol of potassium diet. On the fourth day blood samples and urine were collected every 3 h. 2. Two studies were performed. In study 1, normal subjects (n = 8) were recumbent for 23 h from 09.00 hours to 08.00 hours the next day. In study 2, normal subjects (n = 10) were permitted to ambulate from 09.00 hours to 23.00 hours and then were recumbent until 08.00 hours the next day. 3. In study 1, assumption of the recumbent posture was associated with increases in plasma atrial natriuretic factor (P less than 0.01), plasma guanosine 3':5'-cyclic monophosphate (P less than 0.05) and urinary sodium excretion (P less than 0.05). 4. In contrast, in study 2 there were no significant changes in plasma atrial natriuretic factor during the day; instead, plasma atrial natriuretic factor increased overnight, reaching a peak at 24.00 hours after 1 h of recumbency (P less than 0.01). A smaller rise in plasma guanosine 3':5'-cyclic monophosphate (P less than 0.05) occurred; urinary sodium excretion decreased markedly (P less than 0.01) and there was no change in creatinine clearance. 5. In both studies, recumbency was associated with an initial drop, followed by a rise, in packed cell volume. 6. These data demonstrate that assumption of the supine position induces a rise in plasma atrial natriuretic factor and accounts for most of the observed variation.(ABSTRACT TRUNCATED AT 250 WORDS)

A validation study of the instromedix Baro-Graf QD home blood pressure monitor.

The purpose of this study was to assess the accuracy of the Instromedix Baro-Graf QD home blood pressure monitor. Forty subjects were divided among three blood pressure (BP) groups: low (BP less than 110/70, N = 11); medium (BP 110/70 to 140/90, N = 17) and high (BP greater than 140/90, N = 12). Five seated readings were taken per subject. We examined the differences between simultaneous auscultatory and machine readings and assessed the machine's accuracy using ANOVA and correlation analysis. The results show that the device, while highly accurate, tended to become less so as pressure increased. However, its accuracy was superior compared to most other devices we have tested, and because of features, such as a computer memory that stores events and blood pressure over time, this monitor will likely be a useful tool for clinical trials of long term blood pressure change.

Relation of plasma renin to end organ damage and to protection of K+ feeding in stroke-prone hypertensive rats.

We studied the effects of regular diet (0.35% NaCl/1.1% potassium), high sodium diet (4% NaCl/0.75% potassium), or high sodium and high potassium diet (4% NaCl/2.11% potassium) on blood pressure, plasma renin activity, renal and cerebrovascular lesions, and incidence of stroke and mortality in male stroke-prone spontaneously hypertensive rats (SHRSP). In the first 4 weeks, the rise in blood pressure was higher in high NaCl than in high NaCl/high potassium or regular diet groups. However, by 8 and 12 weeks, the blood pressure in all three groups was similar. After 4 weeks of diet, plasma renin activity was similar in the three groups (3.4 +/- 0.8, 4.1 +/- 0.9, and 5.2 +/- 1.6 ng/ml/hr, in high NaCl, high NaCl/high potassium, and regular diet groups, respectively) and were not related to sodium excretion. After 8 weeks, plasma renin activity was significantly increased only in the high NaCl group (13.7 +/- 3.7 ng/ml/hr), and by 12 weeks plasma renin activity was significantly higher in the high NaCl group (25.3 +/- 3.6 ng/ml/hr) than in the high NaCl/high potassium (11.1 +/- 2.9 ng/ml/hr) or in the regular diet (7.8 +/- 4.6 ng/ml/hr) groups. Moderate to severe renal vascular lesions were first detected in the high NaCl group by 8 weeks of diet. At 12 weeks, renal vascular damage index (RVDI), estimated histologically, was significantly higher in the high NaCl group (RVDI = 79 +/- 14) than in the high NaCl/high potassium (RVDI = 40 +/- 11) and regular diet (RVDI = 7.8 +/- 4.6) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma atrial natriuretic factor in essential hypertension: relation to cardiac size, function and systemic hemodynamics.

To evaluate determinants of elevated plasma atrial natriuretic factor levels in patients with hypertension, immunoreactive plasma atrial natriuretic factor in 54 normal subjects and 40 untreated hypertensive patients was compared with echocardiographic measurements of cardiac size, function and systemic hemodynamics. In normal subjects, plasma atrial natriuretic factor was related to age, systolic blood pressure and left atrial and ventricular chamber sizes, but only age and ventricular size were independent predictors. In untreated hypertensive patients, atrial natriuretic factor was directly related to age, atrial size, systolic pressure, peripheral resistance and ventricular systolic performance; age, atrial size and peripheral resistance were independent predictors. Eight patients with elevated atrial natriuretic factor values (greater than 25 fmol/ml) were significantly (p less than 0.01) older and had greater atrial and ventricular size and higher systolic pressure and function than normal subjects or patients with normal natriuretic factor levels. Plasma atrial natriuretic factor was inversely related to peak diastolic filling rate in normal subjects (r = -0.59; p less than 0.001), whereas it was positively related to the proportional contribution of atrial systole to left ventricular filling in hypertensive patients (r = 0.77; p less than 0.001). These findings suggest that in normal subjects, impairment of ventricular relaxation with age may contribute to atrial natriuretic factor secretion by increasing left atrial afterload; the correlation with left ventricular size may reflect physiologic fluctuations in plasma volume. In patients with uncomplicated hypertension, left atrial enlargement and consequent stronger atrial contraction contributed to increased atrial natriuretic factor release, whereas no independent relation existed with left ventricular hypertrophy or systolic function. Because ventricular relaxation was normal and ventricular size and systolic performance were increased in hypertensive patients with high atrial natriuretic factor levels, the observed increase in left atrial size and atrial contribution to ventricular filling might reflect a primary increase in venous return in this subset of hypertensive patients.

Increased plasma atrial natriuretic factor and reduced plasma renin in patients with poorly controlled diabetes mellitus.

1. To investigate atrial natriuretic factor (ANF) and its relationship to the renin system in diabetes, we measured plasma immunoreactive ANF and plasma renin activity (PRA) in 27 non-ketotic diabetic patients without evidence of cardiac or overt renal disease, and compared them with 26 age- and sex-matched normal subjects. 2. Diabetic patients were divided prospectively into poor (PGC, n = 14) or moderate (MGC, n = 13) glycaemic control depending on their concurrent plasma glycohaemoglobin (HbA1) levels (greater than 9% or less than 9%, respectively). Plasma ANF was elevated in PGC diabetic patients (15.7 +/- 1.8 fmol/ml, mean +/- SEM) compared with MGC diabetics (9.9 +/- 0.8 fmol/ml, P less than 0.001) and normal subjects (10.1 +/- 1.3 fmol/ml, P less than 0.05). 3. In contrast, PRA was lower in the PGC diabetic patients (1.3 +/- 0.3 pmol of angiotensin 1 h-1 ml-1) compared with the other groups (2.5 +/- 0.5 and 2.1 +/- 0.2 pmol of angiotensin I h-1 ml-1, P less than 0.05). Diabetic groups had proportionally more patients with high prorenin values (over 30 ng h-1 ml-1) than the normal group, but there was no difference between the diabetic groups. 4. Among the diabetic patients, ANF was directly related to HbA1 (r = 0.49, P less than 0.005) and urinary albumin excretion (r = 0.40, P less than 0.02), and was inversely related to PRA (r = 0.36, P less than 0.04) and plasma creatinine (r = -0.42, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

On the renal basis for essential hypertension: nephron heterogeneity with discordant renin secretion and sodium excretion causing a hypertensive vasoconstriction-volume relationship.

We propose herein that there are two functionally abnormal nephron populations in essential hypertension: (1) a group of ischemic nephrons with impaired sodium excretion which chronically hypersecrete renin. Numerically, these ischemic nephrons comprise a minor subgroup since most patients with essential hypertension exhibit no overt evidence of renal insufficiency. (2) In reaction to this, a more numerous group of normal nephrons appears in adaptive hypernatriuresis. They have an increased distal sodium supply and consequently, a chronically suppressed renin secretion. One difference between patients with renovascular hypertension and those with essential hypertension is the intermingling of these two populations of nephrons. In our hypothesis, the adapting hyperfiltering normal nephrons accomplish the hypernatriuresis in response to saline infusion, that is characteristic of all essential hypertension. However, the unsuppressed secretion of renin, that arises from the ischemic nephron population attenuates this compensatory natriuresis in the following ways: (1) by inappropriately acting on the hyperfiltering nephrons to enhance proximal tubular sodium reabsorption; (2) by activating TGF-mediated afferent constriction in these nephrons, and (3) simultaneously, the reactive secretion of renin from ischemic nephrons is diluted by non-participation of the adapting hypernatriuretic nephrons so that plasma renin settles at a level which is insufficient to fully compensate GFR in the ischemic nephrons. These adaptive responses provide a basis for the observation that the inhibition of renin activity with converting enzyme inhibitors in essential hypertension increases renal blood flow and sodium excretion. They also explain why converting enzyme inhibitors can effectively reduce blood pressure, even when renin levels are not absolutely elevated, since any circulating renin imposed upon the adapting hypernatriuretic nephrons inappropriately impairs their sodium excretion. In addition, the theory explains why basal renin secretion is either not suppressed or inadequately suppressed in patients with essential hypertension. As a result, whole kidney homeostatic function is compromised because individual nephrons are responding to their individual stimuli to fulfil their individual need, rather than acting in concert with other nephrons. The net effect of this uncoordinated response is to shift total renal function so that systemic arterial hypertension is sustained by abnormal sodium retention for the inappropriately high plasma renin level, or vice versa.(ABSTRACT TRUNCATED AT 400 WORDS)

Wideband external pulse recording during cuff deflation: a new technique for evaluation of the arterial pressure pulse and measurement of blood pressure.

Analysis of the external brachial pulse recorded during standard blood pressure cuff deflation with use of a transducer with a wide frequency response has revealed a reproducible pattern with three distinct components that we have labeled K1, K2, and K3. K1 is a low-amplitude, low-frequency signal that is present with cuff pressures above systolic pressure. K2 is a triphasic signal appearing at systolic pressure and disappearing at diastolic pressure, which approximately corresponds to the audible Korotkoff sound. K3 appears with cuff pressure between systolic and diastolic pressure and continues to be present below diastolic pressure. Intra-arterial pressure recordings made with a high-fidelity Millar catheter-tip manometer revealed K2 and K3 analogs. K3 resembles the intra-arterial pressure waveform and when calibrated according to the pulse pressure, noninvasive dK3/dt determinations correlated well with intra-arterial dP/dt measurements. The appearance/disappearance property of K2 was designated as the "K2 algorithm" and represents a new, objective noninvasive method for measurement of blood pressure. The K2 algorithm compares favorably with intra-arterial measurements, is more accurate than the auscultatory technique, and may be especially useful in clinical situations in which the auscultatory technique does not work well.

A longitudinal study of urinary creatinine and creatinine clearance in normal subjects. Race, sex, and age differences.

The purpose of this study was to examine the variability of 24-hour urinary and serum creatinine levels and creatinine clearance in normal subjects and to develop nomograms for assessing the adequacy of 24-hour urine collections. The data were from a longitudinal research program examining biochemical, hormonal, and hemodynamic parameters in normal subjects. Bloods and 24-hour urine specimens were collected at yearly intervals from 144 people over 9 years, and from an additional 110 over 4 years. The subjects were originally distributed equally by sex, race (black, white), blood pressure (three groups within the normal range), and age (three groups). Men had 33% higher urine creatinines per weight than females (P less than 0.001). Because they only had 8% higher creatinine clearance per weight they also exhibited 21% higher serum creatinine. Blacks had 5% higher urine creatinine per weight than whites, perhaps reflecting greater muscle mass, but their serum creatinines were not different from those of whites, reflecting a 5% higher creatinine clearance by weight than whites (P less than 0.01). Interestingly, older black men (age greater than 60 years) had 12% lower urine creatinine/weight than younger black men (P less than 0.001). They also had 13% lower creatinine clearance by weight, resulting in no net difference in serum creatinine. The intraindividual variability in urine creatinine excretion averaged 15% and did not differ between blacks and whites and men and women. The within individual variability in serum creatinine and creatinine clearance averaged 14 and 20%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated levels of plasma prorenin (inactive renin) in diabetic and nondiabetic patients with autonomic dysfunction.

We measured plasma inactive renin (prorenin) levels in 46 diabetic patients, 4 nondiabetic patients with idiopathic autonomic dysfunction, and 115 normal subjects. Plasma inactive renin levels were normal in the diabetic patients who had no complications (n = 6) and in those with microvascular disease (n = 8) who did not have coexistent autonomic dysfunction. Plasma inactive renin was either grossly elevated or in the upper limit of the normal range in diabetic patients with autonomic dysfunction (n = 18). No correlation was found between plasma inactive renin and glycemic control, as measured by hemoglobin A1c. High plasma inactive renin levels were also found in the 4 nondiabetic patients with idiopathic autonomic dysfunction. These data suggest that increased plasma inactive renin levels in diabetic patients are a consequence of coexistent autonomic dysfunction. This finding is consistent with other evidence that suggests autonomic regulation of the processing of prorenin to renin within the kidney.

Effect of norepinephrine and cyclic AMP on intracellular sodium ion activity and contractile force in canine cardiac Purkinje fibers.

The effect of norepinephrine on the Na+-K+ pump was investigated by simultaneously measuring intracellular sodium ion activity (aiNa) and contractile force of canine cardiac Purkinje fibers driven at 1.0 Hz in K+-free solution, high K+ solution, and in the presence of tetrodotoxin. In Tyrode solution containing 5.4mM [K+]o, 10(-6) M norepinephrine decreased aiNa, whereas in K+-free solution 10(-6) M norepinephrine did not lower aiNa. 16.2 mM [K+]o decreased aiNa from 8.8 +/- 0.9 mM to 6.5 +/- 0.5 mM (mean +/- SD, n = 5). Exposure to 10(-6) M norepinephrine in the presence of high [K+]o further decreased aiNa by 0.7 +/- 0.4 mM. This further decrease was prevented by exposure to 2.5 X 10(-6) M strophanthidin (n = 4). Blockade of the fast sodium channel with 5 X 10(-6) M tetrodotoxin lowered aiNa from 8.5 +/- 1.3 mM to 7.4 +/- 1.1 mM (n = 4). Exposure to 10(-6) M norepinephrine in the presence of tetrodotoxin further lowered aiNa by 0.9 +/- 0.2 mM. We also studied the effects of the analogues of adenosine 3':5'-cyclic monophosphate, N6, 2'-0-dibutyryladenosine 3':5'-cyclic monophosphate, and 8-(4-chlorophenylthiol)-adenosine 3':5'-cyclic monophosphate on aiNa and twitch tension. Both analogues lowered to aiNa and increased twitch tension mimicking the effects of norepinephrine. Our results support the hypothesis that norepinephrine lowers aiNa by stimulating the Na+-K+ pump in this tissue. This stimulation appears to be mediated by adenosine 3':5'-cyclic monophosphate and does not appear to be due to intercellular K+ accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

The captopril test for identifying renovascular disease in hypertensive patients.

To develop a screening test for identifying renovascular hypertension, the blood pressure and plasma renin activity responses to an oral test dose of captopril were studied in 246 quietly seated hypertensive patients. The following criteria were developed that exploit the hyperresponsiveness of renin secretion in renovascular hypertensive patients: a 60-minute post-captopril plasma renin activity of 12 ng/ml per hour or more and an absolute plasma renin activity increase of 10 ng/ml per hour or more, along with a 150 percent increase in plasma renin activity (or a 400 percent increase if the baseline plasma renin activity was below 3 ng/ml per hour). Retrospectively, the test identified, among 200 hypertensive patients without evidence of renal dysfunction, all 56 patients with proved renovascular disease. In this group, false-positive results occurred only in two of 112 patients with essential hypertension and in six with secondary hypertension. Nine untreated patients had blood pressure levels of less than 160/100 mm Hg. The test was neither as sensitive nor specific in the 46 patients with renal insufficiency. This study demonstrates that the renin response to oral captopril is a useful screening test for identifying patients with unilateral or bilateral renovascular disease. Since the test also characterizes the renin dependency of the hypertension, it may have other diagnostic and therapeutic uses.

Strophanthidin inotropy: role of intracellular sodium ion activity and sodium-calcium exchange.

The relation among the ratio of extra- and intra-cellular sodium ion activities (aoNa/aiNa), contractile force and action of strophanthidin was studied in cardiac Purkinje fibers when transmembrane Na+ and Ca2+ gradients were changed. The aiNa, contractile force and action potential were simultaneously measured. Simultaneous reduction of [Na+]o and [Ca2+]o to 80.8 and 1.08 mM respectively, decreased aiNa from 8.0 +/- 1.1 mM (mean +/- S.D., n = 17) to 6.0 +/- 0.9 mM (n = 17) whereas contractile force transiently increased and then recovered toward the level similar to that in Tyrode solution. Reduction of [Ca2+]o alone increased aiNa by 1.7 +/- 0.4 mM (n = 5) and decreased contractile force by 87 +/- 5% (n = 5). Raising osmolarity of Tyrode solution with sucrose increased both aiNa and contractile force. Substitution of sucrose with Na+ (high [Na+] solution) increased aiNa by 1.2 +/- 0.3 mM (n = 5) and decreased contractile force by 31 +/- 9% (n = 5). Strophanthidin (2 X 10(-7) M) increased aiNa by 0.4 +/- 0.1 mM (n = 6) and contractile force by 24 +/- 8 (n = 6) in a low [Na+] - [Ca2+] solution. These changes were smaller than those in Tyrode solution (1.1 +/- 0.3 mM); 96 +/- 32%, n = 6). On the other hand, strophanthidin increased aiNa and contractile force more in a low [Ca2+] (2.7 +/- 0.5 mM; 220 +/- 24%, n = 5) or a high [Na+] (2.3 +/- 0.9 mM; 164 +/- 37%, n = 5) solution than in Tyrode solution. In the solutions containing the altered [Na+]o and/or [Ca2+]o, the increases in aiNa and force by strophanthidin were parallel. Therefore, the parallel increase in aiNa and contractile force due to strophanthidin depends on the initial level of aiNa, suggesting the dependence of digitalis inotropy on the rate of Na+ extrusion by the Na+ -K+ pump. The results also indicate that the ratio of aoNa/aiNa is an important and powerful factor in the control of contractile force. Presumably this is mediated through the Na+ -Ca2+ exchange.