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1.
Arch Intern Med ; 158(12): 1340-5, 1998 Jun 22.
Article in English | MEDLINE | ID: mdl-9645829

ABSTRACT

BACKGROUND: It is expected that the treatment of hypertension in patients with renal disease decreases the risk of cardiovascular events, but the evidence in these patients is lacking. OBJECTIVE: To assess the effect of diuretic-based treatment on cardiovascular events in patients with isolated systolic hypertension and renal dysfunction. METHODS: A total of 4336 persons aged 60 years and older with systolic blood pressures of 160 mm Hg and higher and diastolic blood pressures of less than 90 mm Hg were randomly assigned to receive either placebo or chlorthalidone (12.5-25.0 mg/d), with the addition of atenolol (25-50 mg/d) or reserpine (0.05-0.10 mg/d) if needed, and observed for 5 years. The risk of first-occurring cardiovascular events, including stroke, transient ischemic attack, myocardial infarction, heart failure, coronary artery bypass surgery, angioplasty, aneurysm, endarterectomy, sudden death, or rapid death, was stratified according to baseline serum creatinine levels (35.4-84.0, 84.1-101.6, 101.7-119.3, and 119.4-212.2 micromol/L [0.4-0.9, 1.0-1.1, 1.2-1.3, and 1.4-2.4 mg/dL]). RESULTS: Systolic blood pressure reduction was not affected by baseline serum creatinine levels. Active treatment did not affect the risk of serum creatinine levels becoming elevated during follow-up. The risk of hypokalemia with active treatment decreased significantly with increasing baseline serum creatinine levels. In the 4 baseline serum creatinine groups, the relative risk (95% confidence interval) of cardiovascular events developing with active treatment was 0.73 (0.54-0.97), 0.63 (0.49-0.82), 0.62 (0.44-0.87), and 0.59 (0.38-0.91). The results were similar for the outcomes of stroke or coronary artery events and in analyses stratified by sex or age. CONCLUSION: Diuretic-based treatment of patients with isolated systolic hypertension prevents the development of cardiovascular events in older persons with mild renal dysfunction.


Subject(s)
Cardiovascular Diseases/prevention & control , Creatinine/blood , Diuretics/therapeutic use , Hypertension/complications , Hypertension/drug therapy , Kidney Failure, Chronic/complications , Aged , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Female , Humans , Hypertension/blood , Kidney Failure, Chronic/blood , Male , Middle Aged , Odds Ratio , Potassium/blood , Severity of Illness Index , Systole , Treatment Outcome
2.
Osteoarthritis Cartilage ; 3(3): 157-67, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8581745

ABSTRACT

This investigation describes the development and validation of a test battery for evaluating physical activity restrictions (PAR) in patients with knee osteoarthritis (OA). The tasks on the final version of the PAR include (a) a 6-min walk; (b) a stair climb; (c) a lifting and carrying task; and (d) getting into and out of a car. Data from patients with knee OA revealed that the four tasks loaded highly on a single unrotated principal component yielding an alpha internal consistency reliability of 0.92. These data suggest that investigators may choose to use an aggregate score and/or responses from individual tasks. Two week test-retest reliabilities for the four tasks were all in excess of 0.85 and there was support for their concurrent and convergent validity. Specifically, performance on the tasks correlated with time on treadmill, difficulty with self-reported ADLs, and ratings of difficulty following the performance of each task. Additional research is needed on the predictive validity of the measure and its sensitivity to change.


Subject(s)
Disability Evaluation , Knee Joint , Osteoarthritis/classification , Activities of Daily Living/classification , Aged , Cohort Studies , Exercise Test/statistics & numerical data , Female , Humans , Male , Middle Aged , Osteoarthritis/diagnosis , Osteoarthritis/rehabilitation , Reproducibility of Results , Work Capacity Evaluation
3.
J Am Geriatr Soc ; 42(1): 11-5, 1994 Jan.
Article in English | MEDLINE | ID: mdl-8277105

ABSTRACT

OBJECTIVE: To determine if diagnostic classification is associated with different outcomes from treatment on a geriatric assessment unit (GAU) compared with usual care for elderly patients with acute illnesses. STUDY DESIGN: Reanalysis after post-hoc diagnostic classification of a randomized clinical trial with one year follow up. SETTING: Community hospital with rehabilitation facility. SUBJECTS: A total of 155 subjects, mean age 78 years and 78% female, of whom 58 subjects had a rehabilitation classification of their diagnoses and 97 had a medical or surgical classification. OUTCOME MEASURES: Mortality, nursing home use, activities of daily living, and charges for subsequent medical services. RESULTS: Mortality was decreased in persons with a rehabilitation classification who had received the GAU intervention. The GAU increased point-prevalence residence in the community for persons with a rehabilitation classification. For persons with a medical-surgical classification, the GAU intervention was associated with decreased cumulative use of nursing homes. However, GAU intervention was also associated with trends for increased charges in both diagnostic classification groups, even when adjusted for differential survival. CONCLUSION: Greater benefit from the GAU intervention on mortality and maintenance of residence in the community was observed in a group with a rehabilitation classification when compared with a group with a medical-surgical classification. These improved outcomes in the rehabilitation group were not accompanied by decreased charges for later medical services that could compensate for initial rehabilitation charges.


Subject(s)
Diagnosis-Related Groups/classification , Fees and Charges , Geriatric Assessment , Outcome Assessment, Health Care , Rehabilitation Centers/organization & administration , Activities of Daily Living , Aged , Female , Follow-Up Studies , Health Services Research , Homes for the Aged/statistics & numerical data , Humans , Male , Nursing Homes/statistics & numerical data , Rehabilitation Centers/economics , Survival Rate
5.
Arch Intern Med ; 152(6): 1162-6, 1992 Jun.
Article in English | MEDLINE | ID: mdl-1599343

ABSTRACT

BACKGROUND: Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults, surprisingly little data exist to confirm the efficacy of these interventions in older persons. METHODS: We conducted a randomized, controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg. The experimental arm was a nonpharmacologic intervention combining weight reduction, sodium restriction, and increased physical activity. The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase, followed by four monthly group sessions during the maintenance phase. The control group received no treatment during the study. Blood pressure was assessed by certified technicians (blinded to group assignment) using random zero sphygmomanometers. RESULTS: Of 56 participants randomized, 47 completed the entire 6-month trial (21 in the intervention group and 26 in the control group). Attendance at the intervention sessions was excellent. The intervention group lost more weight (-2.1 kg) over 6 months than the control group (+0.3 kg). Trends for decreasing 24-hour urine sodium excretion in both the intervention and control groups, with greater trend in the intervention group, were not statistically significant. The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group (mean differences between groups at 6 months, 4.2/4.9 mm Hg, respectively). CONCLUSIONS: Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure.


Subject(s)
Hypertension/therapy , Aged , Aged, 80 and over , Diet, Reducing , Diet, Sodium-Restricted , Exercise , Female , Humans , Male , Middle Aged , Patient Compliance
6.
Am J Hypertens ; 5(1): 16-21, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1736929

ABSTRACT

Agreements between auscultatory blood pressure measurements and recordings of the Suntech Accutracker II ambulatory blood pressure monitor (ABPM) were examined in 103 participants ages 23 through 91 to estimate influence of age on accuracy of automated recordings. Simultaneous auscultation by two technicians and recording by the ABPM were compared. Technicians demonstrated close agreement in auscultation of blood pressure. Mean systolic blood pressure measured by ABPM was 5.6 mm Hg lower and mean ABPM diastolic blood pressure was 6.3 mm Hg lower than average auscultatory blood pressure measured by technicians (P less than .0001). Discrepancies in systolic blood pressure measurements between technicians and ABPM were associated with age and systolic blood pressure. The age effect, controlled for gender and race, was a 0.15 mm Hg increase in systolic blood pressure discrepancy per year of age. Discrepancies in diastolic blood pressure measurements were associated with race but not with age or body size measurements. Automated recordings of blood pressure by this ABPM may have systematic bias compared to auscultation which exceeds current standards for ABPM instrumentation. For systolic blood pressure, this bias increases with age and may affect interpretation of ABPM recordings in elderly persons.


Subject(s)
Aging/physiology , Blood Pressure Determination/instrumentation , Blood Pressure/physiology , Hypertension/epidemiology , Adult , Aged , Aged, 80 and over , Ambulatory Care/methods , Bias , Blood Pressure Monitors , Female , Humans , Hypertension/physiopathology , Male , Middle Aged , Racial Groups , Sex Factors
7.
Am J Public Health ; 81(10): 1302-6, 1991 Oct.
Article in English | MEDLINE | ID: mdl-1928529

ABSTRACT

BACKGROUND: In a recent randomized controlled trial assessing the efficacy of an inpatient geriatric assessment unit (GAU), we demonstrated that patients assigned to the unit were less likely than those in the usual care group to be admitted to a nursing home and more likely to remain living in the community. Despite evidence of benefits of GAU care, questions remain about its cost. We examine the impact of GAU treatment on subsequent health care charges. METHODS: Sequential referrals of elderly disabled patients considered at risk for institutionalization or likely to improve with rehabilitation were randomized to the GAU or to usual care. Charge data were collected on utilization of a wide variety of health care services starting at the point of randomization. RESULTS: The group randomized to the GAU experienced significantly higher rehabilitation charges per participant ($10,583 vs $2066, P = .0001), but lower mean nursing home charges ($1798 vs $3426, P = .004). Total health care charges per participant over the 1 year follow-up were greater for the GAU group ($28,406 vs $16,444, P = .004). When charges were adjusted per year of life survived, the GAU group still showed a substantial (but nonsignificant, P = .10) increase in total charges. However, when charges were adjusted per day subsequently spent residing in the community, adjusted total charges were similar between the two groups. CONCLUSIONS: Our results indicated that improved outcomes from GAU care require an investment in rehabilitation that is not totally offset by decreased institutional charges in the following year.


Subject(s)
Geriatric Assessment/statistics & numerical data , Health Services for the Aged/economics , Hospital Units/statistics & numerical data , Rehabilitation/economics , Aged , Fees and Charges , Female , Health Policy , Health Services for the Aged/trends , Hospital Units/economics , Humans , Male , Random Allocation , Tennessee
8.
Am J Public Health ; 81(9): 1127-30, 1991 Sep.
Article in English | MEDLINE | ID: mdl-1951822

ABSTRACT

BACKGROUND: Important clinical decisions often hinge on patients' functional status. Previous studies have shown disagreement among sources of ratings of patients' functional status. This study compared patient self-ratings, family member ratings, and physician ratings of patient function to performance-based functional testing criteria. METHODS: Five activities of daily living of 73 older patients were studied at admission to a rehabilitation unit following discharge from an acute care community hospital. Data were collected from patients, family members, and physicians and were compared with performance-based function testing. RESULTS: Patient ratings were significantly more accurate than physician ratings for walking, transferring, and telephoning. Patients were significantly more accurate than family members for rating walking and telephoning, but patients were not significantly more accurate than family members or physicians for rating eating or dressing. CONCLUSIONS: We conclude that decisions about patients' functional level should be based on performance testing. If performance testing is unavailable, patients' own ratings are most accurate, followed by family ratings. Physicians' ratings are least accurate.


Subject(s)
Activities of Daily Living , Frail Elderly , Geriatric Assessment , Aged , Aged, 80 and over , Family , Female , Humans , Male , Middle Aged , Physicians , Self-Assessment
9.
N Engl J Med ; 322(22): 1572-8, 1990 May 31.
Article in English | MEDLINE | ID: mdl-2186276

ABSTRACT

We conducted a randomized trial in a community rehabilitation hospital to determine the effect of treatment in a geriatric assessment unit on the physical function, institutionalization rate, and mortality of elderly patients. Functionally impaired elderly patients (mean age, 78.8 years) who were recovering from acute medical or surgical illnesses and were considered at risk for nursing home placement were randomly assigned either to the geriatric assessment unit (n = 78) or to a control group that received usual care (n = 77). The two groups were similar at entry and were stratified according to the perceived risk of an immediate nursing home placement. After six months, the patients treated in the geriatric assessment unit had significantly more functional improvement in three of eight basic self-care activities (P less than 0.05). Those in the lower-risk stratum had significantly more improvement in seven of eight self-care activities. Both six weeks and six months after randomization, significantly more patients treated in the geriatric assessment unit than controls (79 vs. 61 percent after six months) were residing in the community. During the year of follow-up, the control patients had more nursing home stays of six months or longer (10 vs. 3; P less than 0.05). However, there was no difference between the groups in the mean number of days spent in health care facilities (acute care hospital, nursing home, or rehabilitation hospital). Survival analysis showed a trend toward fewer deaths among the patients treated in the geriatric assessment unit, and mortality was significantly reduced in the patients considered to be at lower risk of immediate nursing home placement (P less than 0.05). We conclude that the treatment of selected elderly patients in a specialized geriatric rehabilitation unit improves function, decreases the risk of nursing home placement, and may reduce mortality. The beneficial effects on mortality and function appear greatest for patients at a moderate rather than high risk of nursing home placement.


Subject(s)
Geriatric Assessment , Rehabilitation Centers/organization & administration , Rehabilitation , Follow-Up Studies , Hospital Units , Humans , Institutionalization , Length of Stay , Mortality , Nursing Homes/statistics & numerical data , Randomized Controlled Trials as Topic , Rehabilitation Centers/statistics & numerical data , Self Care , Survival Rate , Tennessee
10.
J Gerontol ; 45(2): M40-4, 1990 Mar.
Article in English | MEDLINE | ID: mdl-2179391

ABSTRACT

Patients with cataracts and coincident retinal disease are at increased risk for unsuccessful cataract surgery. We developed a method for estimating probabilities of surgical success for older cataract patients with retinal disease. Using data from a prospective study of cataract surgery outcomes, 36 patients with both cataracts and retinal disease were identified, 13 of whom attained surgical success with 20/40 or better vision 4 months after surgery. Age, presurgical Snellen letter acuity, location of retinal lesions, and presurgical visual function in everyday life (newspaper reading or television viewing) were all reliable correlates of surgical outcome. These data were analyzed using multiple logistic regression to develop a clinical index combining presurgical Snellen letter acuity, location of retinal lesions, and age to predict surgical success. The resulting index demonstrated 83% sensitivity and 85% specificity in sample data, correctly predicting 83% of patients (predictive value positive: 73%; predictive value negative: 90%).


Subject(s)
Cataract Extraction/statistics & numerical data , Cataract/complications , Retinal Diseases/complications , Activities of Daily Living , Aged , Female , Follow-Up Studies , Humans , Lenses, Intraocular/statistics & numerical data , Male , Newspapers as Topic , Probability , Reading , Regression Analysis , Sensitivity and Specificity , Television , Vision, Ocular , Visual Acuity
11.
South Med J ; 82(1): 9-12, 1989 Jan.
Article in English | MEDLINE | ID: mdl-2911768

ABSTRACT

Inner-city adults (n = 108) with a chronic disease (sickle cell disease or asthma) and their unaffected siblings (n = 50) were interviewed and ratings of health perceptions and opinions about medical care were compared. Persons with a chronic disease reported unfavorable ratings of their health (P less than .001). Their siblings reported moderately favorable health perceptions but much worry and concern about their health. When compared with the asthma subgroup, persons with sickle cell disease reported more adverse ratings of health outlook susceptibility to illness, sickness orientation, humaneness of medical care, and satisfaction with medical care (P less than .05). These observations demonstrate low health perceptions in adults with two chronic medical conditions and more negative perceptions in persons with sickle cell disease. They indicate possible opportunities for improving medical care for patients with these conditions to achieve better perceptions of health, outlook, and medical services.


Subject(s)
Anemia, Sickle Cell/psychology , Asthma/psychology , Attitude to Health , Health , Quality of Health Care , Urban Health , Adolescent , Adult , Attitude , Family , Health Services Needs and Demand , Humans , Middle Aged
12.
J Gerontol ; 43(5): M122-6, 1988 Sep.
Article in English | MEDLINE | ID: mdl-3418032

ABSTRACT

We conducted a prospective study of 164 patients aged 70 and over who had undergone cataract removal and intraocular lens implantation to determine variables which predicted change in physical function experienced by the patients one year after cataract surgery. Path analysis was used to estimate direct and indirect effects of ADL change. Direct effects were estimated for mental status (-.35), mental status change (.51), binocular visual disability (-.39), binocular visual disability change over one year (.51), and baseline ADL (.36), with 45% of variance explained. Age and baseline mental status had important indirect effects through mental status change, and presurgical visual disability had important indirect effects through both visual disability change and mental status change. In summary, change in level of function one year after cataract surgery was not explained solely by change in vision, but was conditional on baseline function and baseline mental status and mediated in part by change in mental status.


Subject(s)
Activities of Daily Living , Cataract Extraction , Aged , Cataract Extraction/psychology , Educational Status , Female , Humans , Male , Marriage , Mental Status Schedule , Postoperative Period , Prospective Studies , Surveys and Questionnaires , Visual Acuity
13.
Ophthalmology ; 95(8): 1125-9, 1988 Aug.
Article in English | MEDLINE | ID: mdl-3231453

ABSTRACT

To determine how well visual outcomes of cataract surgery can be predicted from acuity estimations by visual instruments and an ophthalmologist, the authors compared predictions of postsurgical visual acuity with the measured acuity at 4 months in 82 elderly persons. Comparisons were made between the potential acuity meter (PAM), laser interferometer (LI), and an ophthalmologist, who predicted the final vision before surgery using screening visual information, including PAM, LI data, and results of the patient's examination. Neither instrument alone was successful in predicting postsurgical acuity +/- 1 contiguous Snellen chart line (bivariate correlation [r] = 0.03 for PAM and 0.07 for LI). The ophthalmologist was the most accurate predictor of acuity within 1 line (r = 0.41, p less than or equal to 0.001). These results indicate that the PAM and LI did not independently predict postsurgical vision in elderly cataract patients, but results of a clinical examination markedly improved the accuracy of predictions.


Subject(s)
Cataract Extraction , Aged , Female , Humans , Interferometry , Male , Prognosis , Prospective Studies , Visual Acuity
14.
Am J Ophthalmol ; 105(5): 460-5, 1988 May 15.
Article in English | MEDLINE | ID: mdl-3369514

ABSTRACT

We developed a clinical index for predicting postoperative visual acuity of cataract patients and cross-validated it using data from 182 patients aged 70 years and older. The index consisted of four statistically combined indicators: age, preoperative visual acuity, frequency of reading, and comorbidity. Validation of the index included comparisons to two standard technical instruments for measurement of retinal visual acuity. For the clinical index, 72% of predictions were accurate within one Snellen line of postoperative visual acuity compared to 37% using a laser interferometer and 33% using a potential acuity meter. Testing of the clinical index's external validity using data from 111 patients in a different ophthalmology clinic disclosed 61% of predictions accurate within one Snellen line.


Subject(s)
Cataract Extraction , Models, Theoretical , Visual Acuity , Aged , Forecasting , Humans , Interferometry/instrumentation , Interferometry/methods , Lasers , Ophthalmology/instrumentation , Postoperative Period
15.
JAMA ; 257(8): 1064-6, 1987 Feb 27.
Article in English | MEDLINE | ID: mdl-3806895

ABSTRACT

We conducted a prospective study of 293 elderly patients undergoing cataract surgery with intraocular lens implantation to determine the impact of the surgery on vision and on subjective and objective measures of patient function. Visual acuity in the surgical eye improved from a mean of 20/100 before surgery to 20/40 four months after surgery; improvement was maintained at one year. Positive changes occurred in some subjective measures of patient function, such as reported activities of daily living and patient report of vision-dependent activities, but these changes were modest. The most marked changes in patient function occurred in objective measures of function. Mental status had improved not quite significantly at four months but significantly at one year. Timed manual performance improved dramatically and significantly at four months and one year. Cataract surgery was associated with improved vision and improved objective function in most patients by four months after surgery, and these improvements were maintained at one year.


Subject(s)
Activities of Daily Living , Cataract Extraction , Lenses, Intraocular , Vision, Ocular , Aged , Aged, 80 and over , Cataract Extraction/psychology , Female , Health Status , Humans , Male , Time Factors , Visual Acuity
16.
Clin Geriatr Med ; 3(1): 145-54, 1987 Feb.
Article in English | MEDLINE | ID: mdl-3815240

ABSTRACT

This paper presents process and outcome data for a geriatric assessment unit in a rehabilitation hospital whose focus is on short-term rehabilitation. While the results presented here are positive, they are descriptive and do not prove a cause and effect relationship between the geriatric assessment and rehabilitation unit care and the outcomes described. This unit is currently being evaluated by a prospective randomized controlled clinical trial.


Subject(s)
Health Services for the Aged/organization & administration , Hospital Units , Rehabilitation Centers , Aged , Hospital Bed Capacity, 500 and over , Humans , Outcome and Process Assessment, Health Care , Tennessee
17.
J Cardiovasc Pharmacol ; 7(5): 833-40, 1985.
Article in English | MEDLINE | ID: mdl-2413289

ABSTRACT

The pulmonary vascular effects of a subarrhythmic dose of digoxin (60 micrograms/kg i.v.) were examined in the canine in situ perfused lung. Digoxin produced an increase in pulmonary vascular resistance (66.1%) and pulmonary arterial pressure (8.2 mm Hg) at 70 min after injection in the constant-flow, blood-perfused lung preparation. The digoxin-treated group exhibited higher plasma levels of norepinephrine compared with control dogs. The pulmonary vasoconstrictor response to digoxin was abolished by prior treatment with the alpha-adrenergic antagonists phenoxybenzamine and phentolamine. This vasoconstriction does not involve inhibition of synthesis or action of vasodilator prostaglandins by digoxin, as pretreatment with indomethacin did not attenuate, and even tended to increase, the pressor response to digoxin. The response was prevented by prior treatment with blockers of nonneuronal uptake of catecholamines normetanephrine and hydrocortisone, but not with cocaine, a blocker of neuronal uptake. In the lung preparation perfused with Krebs buffer solution, digoxin failed to produce vasoconstriction when administered intravenously (60 micrograms/kg) or in the perfusate at a concentration of 8 ng/ml, the blood level at the peak of the pressor response. Sodium-pump activity (ouabain-sensitive 86Rb+ uptake) of intralobular pulmonary arteries excised after 90 min of exposure to digoxin was the same as activity in arteries from control dogs. In conclusion, digoxin produces a pulmonary vasoconstriction through an alpha-adrenergic mechanism. Since the pressor response was observed only in the blood-perfused lung, blood-borne catecholamines are apparently involved.


Subject(s)
Digoxin/pharmacology , Pulmonary Circulation/drug effects , Vasoconstriction/drug effects , Anesthesia , Animals , Blood Pressure/drug effects , Cocaine/pharmacology , Dogs , Epinephrine/blood , Female , Heart Rate/drug effects , In Vitro Techniques , Indomethacin/pharmacology , Male , Norepinephrine/blood , Normetanephrine/pharmacology , Phenoxybenzamine/pharmacology , Phentolamine/pharmacology , Time Factors
18.
Eur J Pharmacol ; 94(3-4): 185-92, 1983 Oct 28.
Article in English | MEDLINE | ID: mdl-6140173

ABSTRACT

The specificity of the alpha-adrenergic vascular blockade by quinidine was tested in the intact dog, in rabbit isolated aortic strips, and in rats under ganglionic blockade. Quinidine did not affect the pressor response of angiotensin II in dogs, the contractile response of histamine nor angiotensin II in aortic strips, nor the dose-pressor response curve of the alpha-agonist, B-HT 933 in the rat. However, the pressor effect of adrenaline and noradrenaline (NA) were significantly reduced in dogs, and the dose-response curves to NA in aortic strips and to the alpha-agonist, phenylephrine in rats was shifted to the right in a parallel manner by quinidine. In the rat, quinidine is at least 14 times more potent in antagonizing the vasopressor effect of an alpha 1-vs. and alpha 2-adrenoceptor agonist.


Subject(s)
Adrenergic alpha-Antagonists , Muscle, Smooth, Vascular/drug effects , Quinidine/pharmacology , Angiotensin II/pharmacology , Animals , Aorta, Thoracic/drug effects , Azepines/pharmacology , Blood Pressure/drug effects , Dogs , Female , Hexamethonium Compounds/pharmacology , Histamine/pharmacology , In Vitro Techniques , Male , Norepinephrine/pharmacology , Phenylephrine/pharmacology , Rabbits , Rats , Rats, Inbred Strains , Vasoconstriction/drug effects
19.
J Pharmacol Exp Ther ; 226(1): 65-70, 1983 Jul.
Article in English | MEDLINE | ID: mdl-6864551

ABSTRACT

We studied the metabolism and cardiac actions of a polar aminocardenolide, 3-beta-O-(4-amino-4,6-dideoxy-beta-D-galactopyranosyl) digitoxigenin (ASI-222), in conscious, chronically instrumented dogs and compared the cardiac actions of this compound with those of digoxin. Chloroform-soluble metabolites and the excretion patterns of ASI-222 in urine and feces were identified and measured using thin-layer chromatography. The deaminated metabolite of ASI-222 appeared both in the urine and the feces together with the genin, digitoxigenin and the parent drug which constituted the majority of the radioactivity excreted. There was a secondary rise in the plasma concentration of ASI-222 starting 2 hr after the i.v. administration, which strongly suggests its enterohepatic recycling. The secondary increase in the plasma concentration was not seen in the dogs receiving digoxin. ASI-222 produced increases in cardiac contractility and systolic blood pressure which were more rapid in onset and shorter in duration than those produced by an equimolar dose of digoxin. Amplitudes of these physiologic responses to these two compounds in conscious dogs were approximately 2 times higher than the effects previously reported to similar doses in anesthetized dogs.


Subject(s)
Digitoxigenin/analogs & derivatives , Heart/drug effects , Animals , Blood Pressure/drug effects , Digitoxigenin/metabolism , Digitoxigenin/pharmacology , Digitoxigenin/urine , Digoxin/pharmacology , Dogs , Feces/analysis , Female , Heart Rate/drug effects , Kinetics , Male , Myocardial Contraction/drug effects
20.
Eur J Pharmacol ; 63(2-3): 159-66, 1980 May 02.
Article in English | MEDLINE | ID: mdl-6103815

ABSTRACT

In the anesthetized dog, quinine HCl (50 mg/kg, i.v.) infused over a 20 min period produced 1 22% maximum decrease in diastolic blood pressure, a 53% increase in pulse pressure and a 52% increase in myocardial contractile force. The initial positive inotropic response was maximal in the first 5--15 min of the quinine infusion and decreased to near control levels 40 min following the quinine infusion. Quinine caused a marked reduction in the noradrenaline (NA) pressor response, blockade of the adrenaline (A) pressor response, partial blunting of the angiotensin II (AII) pressor effect but no change in the depressor effect of isoprenaline (I). The positive inotropic effects of CaCl2 were reduced and the duration of contractile action to both I and CaCl2 was significantly prolonged by quinine. In isolated rabbit thoracic aortic strips, quinine produced a parallel, dose-related shift of the concentration-response curve for NA to the right but did not affect the maximum responses. A pA2 of 4.91 was estimated by the method of Schild. The determined line had a slope of -0.84 which is similar to a theoretical slope of -1.0 and indicates a direct relationship between the number of receptors occupied and the contractile response. The responses to AII and histamine (H) were not altered by quinine. These results suggest that quinine HCl produces alpha-adrenergic blockade; additionally, quinine modifies catecholamine- and calcium-induced myocardial contractile force responses.


Subject(s)
Adrenergic alpha-Antagonists , Cardiovascular System/drug effects , Quinine/pharmacology , Angiotensin II/physiology , Animals , Aorta/drug effects , Blood Pressure/drug effects , Calcium/metabolism , Dogs , Dose-Response Relationship, Drug , Epinephrine/antagonists & inhibitors , Female , Heart Rate/drug effects , In Vitro Techniques , Isoproterenol/pharmacology , Male , Muscle Contraction/drug effects , Myocardial Contraction/drug effects , Norepinephrine/antagonists & inhibitors , Quinidine/pharmacology , Rabbits , Vascular Diseases/drug therapy , Vasoconstrictor Agents/antagonists & inhibitors
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