A prospective evaluation of a simplified captopril test for the detection of renovascular hypertension.

Renovascular hypertension is potentially curable but of low prevalence. A previous retrospective study has demonstrated the use of a potentiated increase in plasma renin activity after captopril administration as a diagnostic test for renovascular hypertension; this requires two blood samples for plasma renin activity determination and three inclusive criteria for a positive test result. We applied this test prospectively to screen 100 hypertensive patients for renovascular hypertension. We evaluated 29 patients with renovascular hypertension; the remainder were diagnosed as having essential hypertension. In our patient population, a postcaptopril plasma renin activity of 5.7 ng of angiotensin per milliliter per hour (ngAl.mL-1.h-1) or greater had a 100% sensitivity and an 80% specificity for renovascular hypertension. An absolute increase in plasma renin activity with captopril of 4.7 ngAl.mL-1.h-1 or greater had a lower sensitivity of 90% and a specificity of 87%, whereas a fractional increase in plasma renin activity after captopril of 150% or higher had the lowest sensitivity of 69% and a specificity of 86%. A subgroup analysis of 38 patients who were receiving diuretic therapy demonstrated that the test sensitivity was unchanged but the specificity was reduced. In conclusion, a single postcaptopril plasma renin activity value of 5.7 ngAl.mL-1.h-1 or greater is a simplified screening test for renovascular hypertension, with excellent sensitivity and acceptable specificity. This test is well tolerated, inexpensive, and easy to perform.

Cardiac rate and rhythm changes with atropine and methscopolamine.

The effects of methscopolamine bromide (MSB) and atropine were compared in patients prior to elective surgery. After administration of the second dose of MSB (total dose 1.5 mug/kg) all patients exhibited at least 20% increase in heart rate. In contrast, three doses of atropine (total dose 5.3 mug/kg) were required for most patients to attain a 20% increase in heart rate while 2 patients did not attain this heart rate with a dose of 10.6 mug/kg of atropine. Comparison if single injections of MSB and atropine in normal subjects also demonstrated a more reliable dose-response relationship with MSB. Electrocardiographic changes recorded were typical of those reported with anticholinergic agents. Sinus and atrial arrhythmias were more common with atropine and nodal arrhythmias and conduction disturbances were more common with MSB. This study demonstrated that MSB can be reliably substituted for atropine when an anticholinergic drug is needed to increase heart rate. Since MSB has a limited ability to cross the blood-brain barrier, it may be the more desirable drug in patients in whom the central nervous system effects of atropine may be deleterious.

Prospective payment for nursing homes increased therapy provision without improving community discharge rates.

OBJECTIVES: To determine the impact of the prospective payment system (PPS) for skilled nursing facilities (SNFs) on therapy use and community discharge rates. DESIGN: Quasi-experimental study examining the predemonstration (1994) to demonstration (1997) change in amount of therapy provided, and in community discharge rates at PPS participating and nonparticipating facilities. SETTING: Eighteen PPS participating and 17 nonparticipating SNFs in five states. PARTICIPANTS: Two thousand sixty-seven admissions to 18 PPS participating and 17 nonparticipating SNFs in five states. MEASUREMENTS: We compared changes in number of physical and occupational therapy visits per stay for patients receiving therapy and likelihood of being located in the community 60 days after admission between 1994 and 1997. Analyses were stratified by functional category and risk adjusted using multivariate methods. RESULTS: Demographics and percentage of patients in each stratum were similar in participating and nonparticipating sites and between 1994 and 1997. Amount of therapy received by the highest-functioning patients increased in participating sites (19.3 to 26.5 visits per stay, P = .005), but not in nonparticipating sites (23.3 to 18.2, P = .98). After adjusting for covariates, likelihood of community discharge for the highest-functioning patients did not change between participating and nonparticipating sites. CONCLUSIONS: The highest-functioning patients treated under the SNF PPS demonstration experienced great increases in therapy, without any improvement in rate of community discharge.

Diagnostic uses of angiotensin-converting enzyme inhibitors in renovascular hypertension.

The response to angiotensin-converting enzyme inhibitors (ACEIs) can be of considerable help in the diagnosis of human renovascular hypertension (RVH) in three settings. First, a particularly dramatic antihypertensive response or a decline in glomerular filtration rate (GFR), as indexed by a rise in serum creatinine or blood urea nitrogen concentrations, are useful clues to the presence of renovascular hypertension. Second, an exaggerated rise in plasma renin activity (PRA) after short-term captopril administration is a very promising screening test for this condition. Third, ACEI-induced changes in single-kidney hemodynamics (assessed by renography) may be helpful in confirming the diagnosis and offers the prospect of localizing the ischemic kidney.

The captopril glomerular filtration rate renogram in renovascular hypertension.

Administration of captopril to animals with two-kidney, one clip, renovascular hypertension (RH) lowers the glomerular filtration rate (GFR) in the clipped kidney. The authors therefore tested the hypothesis that a decrease in GFR after captopril administration would identify patients with RH. Total GFR was measured by the plasma disappearance of Tc-99m-diethylenetriaminepentaacetic acid (DTPA) after bolus injection and single-kidney GFR from renal uptake of DTPA assessed by renography. The authors studied six patients with arteriosclerotic RH who had strongly lateralizing renal vein renin levels and greater than 80% stenosis of the renal artery to that kidney. Results were contrasted with those of six patients with essential hypertension (EH) with a similar mean arterial blood pressure (MABP). Captopril (50 mg orally) increased total GFR (ml/min) in all patients with EH (102 +/- 8 to 120 +/- 12, P less than 0.005). However, GFR decreased in patients with RH (73 +/- 8 to 61 +/- 9, P less than 0.05) after captopril. Although the single-kidney GFR of patients with RH decreased in all six stenotic kidneys (27 +/- 4 to 21 +/- 5, P less than 0.02), it did not change consistently in the contralateral kidneys (45 +/- 8 to 40 +/- 6, N.S.). Clonidine (0.3 mg) also lowered MABP in patients with RH but, unlike captopril, it did not reduce total kidney GFR (75 +/- 10 to 79 +/- 11, N.S.). In conclusion, short-term captopril administration increases GFR in patients with EH, but decreases it in those with RH. This action is unrelated to its depressor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia and the porphyrias.

A simplified classification of the porphyrias is given which is thought to be advantageous to the anesthesiologist in determining those patients who are predisposed to acute attacks. These acute attacks may be precipitated by the administration of barbiturates, but may also be spontaneous. The current theory for the precipitation of the acute attack is described, with the probable mechanism being a decrease in uroporphyrinogen synthetase levels and the resultant interference in heme production. Increased formation of cytochrome P-450 with barbiturates also produces increased levels of delta aminolevulinic acid, which may be a cause of the acute attack. The significance in anesthesia and suggested means of anesthetic management are discussed.

Effect of DA1 receptor blockade with SCH 23390 on the renal response to electrical stimulation of the renal nerves.

To evaluate the existence of functional renal dopaminergic innervation in the dog, we studied the effects of direct electrical stimulation of the renal nerves (RNS) with and without blockade of the dopamine receptor (DA1) that mediates the vasodilating and natriuretic response to intrarenal infusion of DA. Before infusion of the DA1 receptor antagonist, SCH 23390, RNS at 1 Hz did not change renal blood flow (RBF) but caused decreased urinary sodium excretion (-53 +/- 9%, P less than 0.01) and fractional excretion of sodium (-47 +/- 10%, P less than 0.01). Stimulation at 4 and 12 Hz elicited marked renal vasoconstriction (delta RBF = -37 +/- 12%, P less than 0.05 and -57 +/- 12%, P less than 0.01, respectively). When RNS (1 Hz) was performed during DA1 receptor blockade with SCH 23390, 0.5 microgram . kg-1 . min-1 iv, the responses were not different than those before SCh 23390 infusion (urinary sodium excretion: -54 +/- 7%, P less than 0.01 and fractional excretion of sodium: -46 +/- 5%, P less than 0.01). Renal vasoconstriction was also not influenced by SCH 23390 (delta RBF = -35 +/- 11%, P less than 0.05 during 4 Hz RNS and -58 +/- 12%, P less than 0.01 at 12 Hz RNS). Thus, the present study does not support the concept of functional dopaminergic innervation of the canine kidney.

Blockade of renal effects of dopamine in the dog by the DA1 antagonist SCH 23390.

Dopamine (DA) acts on two receptor subtypes, DA1 and DA2. The purpose of this study was to determine which subtype is involved in the increments in renal blood flow (RBF) and electrolyte excretion produced by DA. Mongrel dogs were anesthetized with pentobarbital sodium. Phenoxybenzamine (10 mg X kg-1 ia) and propranolol (5 mg X kg-1 iv) were administered to exclude effects mediated by alpha- and beta-adrenoceptors. DA was infused into the renal artery before and after administration of either the selective DA1 antagonist SCH 23390 or the selective DA2 antagonist domperidone. With DA alone, RBF increased by 52 +/- 7%, Na+ excretion increased by 35 +/- 8%, and K+ excretion increased by 35 +/- 5%. Infusion of SCH 23390 (0.5 micrograms X kg-1 X min-1) completely blocked DA-induced increase in RBF and electrolyte excretion. Intravenous infusion of domperidone (1 microgram X kg-1 X min-1) did not attenuate the responses to DA. Neither SCH 23390 nor domperidone affected base-line RBF or electrolyte excretion, suggesting that in these experiments endogenous DA was not active. In conclusion, these data indicate that the effects of DA to increase RBF and electrolyte excretion are the result of action on DA1 receptors.

Power spectrum of the respiratory system.

Spectrum analysis is proposed as a method for analyzing biologic time series data that arise in the study of respiration. A mechanical model of the respiratory system is used to provide a theoretical basis for the interpretation of the air flow spectrum in terms of a physically defined energy concept. We show that under certain conditions the flow variance is proportional to the mechanical work of breathing, and indicate how this new parameter is related to conventional measures of respiratory function. An example is presented to describe the computational procedure and to illustrate the graphical aspects of cross-spectrum analysis.

Clinical investigation of a new intravenous anesthetic--etoxadrol hydrochloride (CL-1848; U-37862A).

Twenty-eight patients were anesthetized with etoxadrol as primary agent. The anesthesia produced was characterized by profound analgesia and amnesia, while pharyngeal and laryngeal reflexes, as well as swallowing and lid reflexes, remained active. Systolic, diastolic, and pulse pressure were slightly increased, with associated tachycardia and tachypnea. A dose of 0.75 mg/kg produced anesthesia for an average of 26 (14 to 53) minutes. Alternating nystagmus was present for several hours and associated with dreams and/or visions that were pleasing to most patients. Six patients, however, had unpleasant dreams for up to 24 hours. One patient given an excessive dose (4.65 mg/kg) was cataleptic, amnesic, and analgesic for 6 days. The occurrence of unpleasant dreams and aberrations in over 20% of the patients suggests that the drug probably has little usefulness in anesthesia. However, the extreme safety of the drug (an LD50 equal to some 20 to 40 times the ED50) and the prolonged analgesia justified clinical testing. There was no evidence of metabolic or systemic organ system change from any of the clinical laboratory studies.

Effect of halothane on isometric twitch and tetanus response and the associated heat production in striated muscle of frogs.

The purpose of these investigations was to determine the effect of halothane on isometric contraction of striated muscle and to measure the associated heat production. This basic information is necessary before studies more directly relating to malignant hyperthermia are undertaken. Sartorius muscles were isolate from Rana pipiens during winter and summer months. It appears from these experiments that there is a prolongation of the relaxation phase of the twitch and tetanus responses with low concentrations of halothane, with a more diffuse effect on the contractile process evident at higher administered concentrations. The results of heat measurements, using a sensitive thermopile-galvanometer system, are compatible with the hypotheses that this effect on relaxation could result from either an interference with calcium reuptake by the sarcoplasmic reticulum or an increased affinity of the troponintropomyosin complex for available calcium.

Intraoperative patient monitoring: a method of analyzing esophageal phonocardiograms.

The value of esophageal phonocardiography as a noninvasive monitor during anesthesia was studied in dogs. Esophageal phonocardiograms were analyzed using fast Fourier transform and least squares linear regression technics. This method has demonstrated that it is feasible to estimate two parameters of cardiac contractility--1/(PEP)2 and stroke power--and one parameter that demonstrates the state of the vasculature--total peripheral resistance. A continuous time (analog) processor that will accomplish this task is described.

Effect of halothane and pentobarbital anesthesia on the dispersion of indicator particles passing through the central circulation of the dog.

To investigate the effect of different anesthetics on the flow properties of the central circulation, curves were obtained by the multiple indocyanine-green indicator-dilution technic from 7 dogs anesthetized with halothane or pentobarbital. The width of the curve provided a measure of the dispersion of indicator particles during passage through the central circulation. The vascular resistance of the animals was altered by the administration of methoxamine and sodium nitroprusside. The authors found that dispersion in the central circulation is linearly related to the total peripheral resistance (TPR). For any value of TPR, the amount of dispersion of indicator particles passing through the central circulation was greater with halothane plus pentobarbital anesthesia than with pentobarbital only. The study indicates that the type of anesthesia influences the dispersion of indicator particles passing through the central circulation. A better under standing of this process will be helpful in interpreting the results of indicator-dilution cardiac-output determinations performed in persons under general anesthesia.

Plasma heparin activity and antagonism during cardiopulmonary bypass with hypothermia.

Plasma heparin activity in 11 patients undergoing open-heart surgery was measured by comparing thrombin time of patient plasma to thrombin time of plasma containing known heparin concentrations. Although all patients received 300 units/kg of heparin, their initial plasma heparin levels varied significantly, from 1.8 units/ml in lighter petients to 3 units/ml in heavier patients. During hypothermia (25 degrees C), heparin decay was insignificant. At 37 degrees C, heparin decayed at a rate between 0.37 and 2.01 units/ml/hr. This decay was significantly faster in those patients with higher initial posthypothermia plasma heparin levels. When heparin was reversed with a protamine dose based on circulating plasma heparin levels, the mean difference between the predicted and the actual residual heparin activity was 0.025 units/ml. Heparin levels vary widely becuase of the influence of temperature on decay rates and because the space into which heparin is distributed is not simply proportional to weight. Evaluation and reversal of plasma heparin activity require ongoing analysis rather than any 1 dosage protocol.

The effect of total peripheral resistance on indicator-dilution curves from the central circulation of the dog.

The influence of total peripheral resistance on the dispersion of indicator particles passing through the central circulation was studied in five dogs. The standard deviation of indocyanine green indicator-dilution curves provided a measure of dispersion. The peripheral vascular resistance of the dog was altered during the experiment by the intravenous administration of sodium nitroprusside and methoxamine. We calculated the area of each curve by fitting the first portion of the curve to a random walk function and the cardiac output and the total peripheral resistance were calculated in the usual manner. The mean, standard deviation and area of each of the curves were calculated from the least squares estimate of the random walk function. The relationship of the cardiac output, mean arterial pressure, and total peripheral resistance to the mean and the standard deviation were compared in a multiple stepwise linear regression. For each dog there was a definite linear relationship between total peripheral resistance and standard deviation (p less than 0.01). These results indicate that the dispersion of particles passing through the central circulation is directly related to the total peripheral resistance.