ISSN:0304-324X    

DOI:10.1159/000212911

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

As a result of aging, a variety of structural and biochemical changes occur in arterial walls that result in hemodynamic adaptations. With age, there is a thickening of intima and media, together with an increase in the number of smooth muscle cells, synthesis of collagen and elastin, and deposition of calcium, glycosaminoglycans, free and esterified cholesterol, and sphingolipids. These changes are similar to those observed in atherosclerosis, which is accompanied by marked increases of intimal smooth muscle cells and connective tissue constituents. The net effects of both aging and atherosclerosis are a loss of elasticity and distensibility. This results in a decrease in arterial compliance or capacitance, which in turn means that with increasing age systolic blood pressure (SBP) tends to be higher, and diastolic blood pressure (DBP) lower. As a consequence of structural changes both in myocardium and vessels, cardiac output and renal and hepatic blood flow undergo adaptive alterations in order to meet the requirements of central hemodynamics and peripheral circulation. The implications of these processes of aging demand appropriate treatment of cardiovascular disorders, in particular hypertension, which occurs in 30–50% of patients above the age of 60 years. Appropriate treatment may demand dose adjustment and careful selection of antihypertensive drugs with a minimum of side effects, which additionally are capable of diminishing preload and afterloa

ISSN:0304-324X    

DOI:10.1159/000212912

出版商:S. Karger AG    

年代:1987

数据来源: Karger

ISSN:0304-324X    

DOI:10.1159/000212847

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The effects of age and physical exercise on synaptic function were studied in the neuromuscular junctions of three skeletal muscles of C57BL/6J mice subjected to a regimen of 10 weeks of physical training (30 min/day, 3.5 m/min). Synaptic function was found to be considerably reduced in old age, as revealed by the activity of the cholinergic enzymes choline acetyltransferase (CAT) and acetylcholinesterase (AChE). However, the number of acetylcholine receptors, as judged by specific bungarotoxin binding, was found to be unchanged with either age or exercise. The regimen of training employed did not further reduce CAT and AChE activities beyond the age-dependent changes observed. It is quite possible though that the age-associated decrement in enzyme activities can account for the reduced adaptability of the muscle to exercise in old age.

ISSN:0304-324X    

DOI:10.1159/000212848

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

A randomized, double-blind, placebo-controlled trial was conducted with 32 elderly patients (aged 75–97 years) with uncomplicated essential hypertension, to evaluate the efficacy and tolerance of enalapril, an angiotensin-converting enzyme inhibitor. It was given over an 8-week period in doses from 20 to 40 mg/day and was compared with an identical placebo. Enalapril caused a significant reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by the 2nd week, an effect that persisted through to the 8th week (190 ± 16/102 ± 7 to 151 ± 19/85 ± 11 mm Hg); 67% of patients had their pressures normalized ( < 160/95 mm Hg). BP was also significantly decreased by the 8th week under placebo (183 ± 16/101 ± 9 to 165 ± 21/91 ± 13 mm Hg), but only 35% of patients attained a normal pressure. Heart rate did not change with treatment. Enalapril caused an increase in plasma renin activity (1.22 ± 0.08 to 3.66 ± 2.50 ng/ml/h), whereas aldosterone levels remained unchanged. There was a mild, significant elevation of creatinine level with enalapril but other laboratory parameters, including serum potassium, were unaltered. Two deaths occurred in the enalapril group, but were not considered to be treatment-related. The drug was otherwise well tolerated. Serum enalapril concentration was assessed in 10 patients taking 20 mg/day over an 8-day period. At equilibrium, the level was 22.3 ± 5.0 ng/l and it correlated both with converting enzyme inhibition and with renal function. Enalapril is shown to be an effective and well-tolerated antihypertensive medication in elderly patients.

ISSN:0304-324X    

DOI:10.1159/000212913

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Creatine phosphokinase (CPK) has been shown to provide the initial ATP for muscle contraction. The effect of wheel running on CPK levels was compared in hindleg and cardiac muscles of young, intermediate-age and old outbred CW-1 and inbred C57BL mice. Short-term (5 weeks) and long-term (over 12 months) regimens were used in these studies. It was shown that as a function of age there was a 20–30% decrease of CPK activity in hindleg muscles of old sedentary animals. No change with age was observed in cardiac muscles of old animals. Short-term exercise of 5 weeks resulted in an increase in CPK levels in young running mice in both hindleg and cardiac muscles. In old animals there was a slight decrease in striated hindleg muscles, but no change in cardiac muscles. In the long-term exercise group, young (6-month-old) and intermediate-age (15-month-old) animals showed a 20–40 % increase in CPK specific activity in hindleg muscles over sedentary control mice. No such increase in CPK activity was observed in old trained mice. However, the long-term exercise regimen prevented the age-associated decline in CPK activity found in sedentary animals.

ISSN:0304-324X    

DOI:10.1159/000212849

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

If optimal dosage administration schedules are to be defined, the factors that influence the disposition of a drug in the population of patients who are likely to receive it should first be determined. Traditionally, separate groups of patients, each with different underlying disease, are given the drug and then detailed studies are performed to assess which groups have significantly different pharmacokinetic parameters and therefore require an adjustment in dose. An alternative approach, utilizing large groups of patients studied less intensively, will be described here. The analysis used the results of two multicenter trials of lisinopril: one in elderly ( > 65 years) hypertensive patients and one in a group of hypertensive patients with impaired renal function (creatinine clearance rate < 60 ml/min). Both protocols allowed for a stepwise increase in the dose of lisinopril until optimum control of BP was achieved. Required dosages ranged from 2.5 to 40 mg/day. During the course of therapy, regular trough concentrations were analyzed to assess compliance and a steady-state profile was determined during one dosage interval. Only patients who appeared to be compliant on the basis of multiple trough concentrations were used in the analysis. Data from a total of 53 patients were used, of whom 35 took part in the elderly study, and 18 in the renal study. There were 25 men and 28 women in this combined study group with ages ranging from 21 to 85 years (mean 65 years) and weights from 51 to 115 kg (mean 72 kg). Steady-state concentration-time profiles following at least 28 days of continuous therapy with a constant dose of lisinopril were analyzed simultaneously using the nonlinear, mixed-effect regression program NONMEM. A total of 336 measurements were available (mean six/patient). Preliminary results indicated that lisinopril clearance rate could be related to weight and renal function, but not to age per se.

ISSN:0304-324X    

DOI:10.1159/000212915

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Apical regions of the left ventricular myocardium of female C57BL/6J mice, aged between 6 and 27 months, that had been subjected to endurance running for 2, 10 or 15 months, were examined by light and electron microscopy. Focal degenerative changes were found in myocytes of these experimental mice, including loss of myofibrils, erosion of myo-cytes and changes in nuclei, lipofuscin content and mitochondria. The interstitial connective tissue showed an increase in collagen in aged myocardia. Endurance-trained runners frequently showed signs of platelet aggregation or microthrombi in small capillaries associated with myocytes. These were most common in endurance-trained middle-aged and very elderly mice, but were not found in sedentary age-matched controls. Our experiments indicate that running stress may be damaging to cardiac tissue in aged animals. Our findings may be of significance in helping the understanding of the development and the etiology of stress-induced cardiovascular damage in the elderly.

ISSN:0304-324X    

DOI:10.1159/000212850

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

One hundred seventy-four patients, 65 years of age or older, entered a double-blind, seven-center, 16-week, controlled study to compare the effects of enalapril and hydrochlorothiazide (HCTZ) in an elderly hypertensive population. Sixty-eight percent of the patients were men, 32% were women. Thirty-two percent of the patients had isolated systolic hypertension. Approximately 80% of the patients were white. After a 4-week placebo run-in period, patients with sitting diastolic BP (DBP) of 90–120 mm Hg or systolic BP (SBP) ≥ 160 mg Hg and DBP 140 mm Hg), the dose of the drug was doubled. If after successive 4-week intervals, their BPs were still not controlled, the other drug was added to their regimen and this was then doubled. The initial mean BPs were 167/94 mm Hg in both groups. By the end of the monotherapy phase at 8 weeks, the mean BPs had fallen significantly (p < 0.01) to 148/85 mm Hg in both groups. By 16 weeks, the mean BPs had again fallen similarly: in the enalapril group to 144/83 mm Hg, and in the HCTZ group to 145/83 mm Hg. Seventy-nine percent of the enalapril group and 85% of the HCTZ group had controlled BPs at this time (DBP < 85 or SBP < 140 mm Hg). White and nonwhite patients in both drug groups had similar falls in SBP and DBP both at the end of the monotherapy period and the overall study. The white patients experienced more rapid falls in BP with enalapril, the nonwhite patients with HCTZ. Three serious adverse experiences occurred in the enalapril group, none of which were considered likely to be due to the drug therapy. Overall, 49% of the enalapril group and 61% of the HCTZ group reported an adverse effect during the study (not significant). Laboratory adverse effects occurred 10% more frequently in the HCTZ group: enalapril, 22%; HCTZ, 32% (not significant); none was serious. Both drugs therefore appeared to be equally efficacious antihypertensive agents in these elderly patie

ISSN:0304-324X    

DOI:10.1159/000212916

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

During the course of an ultrastructural study on the apex region of the left ventricular myocardium of experimental female C57BL/6J mice, aged between 6 and 27 months, and that had been subjected to long-term daily enforced endurance running schedules, we encountered some instances of unusual giant mitochondria. These mitochondria showed degenerative changes including the disruption, disorganization and loss of cristae and the development of a very electron-lucent matrix. In many instances, these giant mitochondria showed dense inclusions within the matrix. The giant mitochondria appear to have developed as a result of fusion between adjacent hypertrophic mitochondria followed by a sequence of progressive degenerative changes. These giant mitochondria were most common in the myocardium of mice that had followed endurance training schedules for 10 or 15 months and were not encountered in age-matched nonrunning control mice.

ISSN:0304-324X    

DOI:10.1159/000212851

出版商:S. Karger AG    

年代:1987

数据来源: Karger