Beneficial effect of short-term endurance training on glucose metabolism during rehabilitation after coronary bypass surgery.

AIMS: Our study was aimed at determining whether beneficial modification of carbohydrate metabolism can be obtained after a short-term training program and whether it is associated with an increase in binding and degradation of (125)I-insulin by erythrocyte receptors that suggests a decrease in insulin resistance. METHODS: The study was conducted in a group of 20 patients aged 56 +/- 1.9 years (mean +/- SEM), within 1 to 6 months after coronary bypass surgery. All patients completed 15 training sessions based on 30 min of cycling with a constant load. Before and after a 3-week training program, glucose, insulin, and C-peptide blood levels, as well as binding and degradation of (125)I-insulin by erythrocyte receptors, were determined. RESULTS: A statistically significant decrease was found in the blood glucose level, from 111.2 +/- 4.2 to 97.8 +/- 3.5 mg/dL (p < 0.01); this decrease was not accompanied by significant insulin concentration changes. There was also a significant increase in insulin binding, from 0.535 +/- 0.059 to 0.668 +/- 0.042 pg (125)I/10(11) RBCs (p < 0.01), and degradation from 7.64 +/- 0.54 to 9.49 +/- 0.58 pg (125)I/10(11) RBCs (p < 0.05). CONCLUSION: The results indicated that even short-term endurance training in patients rehabilitated after coronary bypass surgery induced favorable modification of glucose metabolism, presumably caused by a decrease in insulin resistance.

The influence of short-term endurance training on the insulin blood level, binding, and degradation of 125I-insulin by erythrocyte receptors in patients after myocardial infarction.

PURPOSE: This study was directed toward establishing whether and to what extent, short-term endurance training influences the insulin blood level, and the binding and degradation of 125I-insulin by erythrocyte receptors in patients undergoing rehabilitation after myocardial infarction. METHODS: The study was conducted in a group of 60 patients who had had myocardial infarction within the past 1.5 to 3 months and who did not have arterial hypertension and diabetes mellitus. All the patients took a symptom-limited cardiopulmonary exercise test. Before and after the test, venous blood was collected to determine lactic acid and insulin blood levels as well as the binding and degradation of 125I-insulin. The study group was randomized into two subgroups. One subgroup entered into a 3-week in-patient rehabilitation course. The control group was discharged from the hospital and was given no recommendations for physical exercise. The same investigation was repeated 3 weeks later. RESULTS: In the patients (50%) with hyperinsulinemia (insulin resistance index, > 10 microIU/mL), which was detected during the first investigation, insulin blood level decreased from 23.9 +/- 4.4 to 15.0 +/- 1.9 microIU/mL (P < 0.05) after rehabilitation, whereas insulin binding increased from 0.67 +/- 0.05 to 0.85 +/- 0.08 pg 125I/10(11) erythrocytes (P < 0.05). In the control group, which included normal subjects and those with hyperinsulinemia, the results obtained during the first and second investigations showed no statistically significant changes when compared. CONCLUSIONS: The results suggest that a 3-week endurance training period during rehabilitation after myocardial infarction reduces insulin resistance in patients with hyperinsulinemia.

Glucosamine in serum of patients after myocardial infarction subjected to rehabilitation training.

This paper presents results of 3 weeks physical training on glucosamine level in serum of male patients after myocardial infarction (MI) aged between 38 and 61. Patients were randomised in two groups: the training group (n = 21), staying in Cardiac Rehabilitation Department and the control group (n = 11), discharged home for 3 weeks. Each group received identical dietary instructions. The training group performed exercises every day: on bicycle ergometer during 30 minutes (5 times a week), overall-conditioning exercises for 30 minutes daily and 30 to 60 minutes of walking each day. Before administering of the therapy and 3 weeks later all MI patients performed the bicycle ergometer exercise test until the ventilatory threshold was reached. Before that test and 3 minutes after its termination capillary and venous blood samples were drawn. In the capillary blood samples indices of acid-base balance, lactate level, and glucose level were determined. In venous blood samples the serum levels of immunoreactive insulin, C-peptide and glucosamine were determined as well as binding of 125I-insulin to erythrocyte receptors. Obtained results show that administered therapy increased physical fitness and decreased of glucosamine concentration, insulinaemia and insulin resistance.

Exercise-induced increase in hydrogen peroxide plasma levels is diminished by endurance training after myocardial infarction.

We have investigated the influence of physical training on exercise-induced changes in free radical activity in patients after myocardial infarction. Seventeen patients admitted to the cardiac rehabilitation center performed a bicycle ergometry before and after a 3-week endurance training program. The oxygen consumption and carbon dioxide production were measured and the ECG and the systemic blood pressure were monitored during the tests. Blood samples for acid-base equilibrium, lactic acid levels and hydrogen peroxide concentrations were collected directly before and after each exercise test. Exercise-induced increases in systolic blood pressure, heart rate and rate-pressure product as well as lactic acid concentrations were significantly less marked during the bicycle ergometry performed after the rehabilitation program. During the initial exercise test hydrogen peroxide levels increased significantly from 7.15+/-0.74 micromol/l before to 9.09+/-1.04 micromol/l 3 min after the test (P=0.0229). In contrast, no significant changes in hydrogen peroxide concentrations were observed during the exercise test performed after the training (6.31+/-1.05 micromol/l before the test, 5.85+/-1.08 micromol/l after the test, P=0.201). These observations suggest that physical training may have a beneficial influence on free radicals' generation in patients after myocardial infarction.

Glucosamine levels in people with ischaemic heart disease with and without type II diabetes.

Glucosamine has a major influence on the impairment of some metabolic mechanisms in the human body. As shown in vitro experiments, it takes part in inducing mechanisms of insulin resistance. Therefore, the purpose of our study was to evaluate glucosamine levels in the serum of patients who suffered myocardial infarction (MI) and who either had or didn't have diagnosed type II diabetes in relation to healthy people. The levels of glucosamine, immunoreactive insulin, C-peptide, glucose and lipid indexes were measured in venous blood in investigated patients. In patients with MI without diabetes the highest concentrations of glucosamine, insulin and C-peptide were noted as compared to the results obtained from other groups of patients. In patients with diabetes, on the other hand, the highest glucose levels were noted as compared to the results of other patients. There were no statistically differences of lipid indexes between two groups of patients following MI. A negative correlation between glucosamine levels and glucose concentrations in patients without diabetes may suggest that glucose does not directly determine glucosamine levels. The returning of insulin levels to normal in patients with hyperinsulinemia (antidiabetic drugs) may play a role in the lowering of glucosamine induced peripheral insulin resistance.

The influence of oral glucose intake on binding and degradation of 125I-insulin by receptors on erythrocytes as well as on insulin and C-peptide serum levels in patients after myocardial infarction and healthy individuals.

In this study, we investigated the influence of glucose administration on binding and degradation of 125I-insulin by receptors on erythrocytes as well as on insulin and C-peptide serum levels in 15 patients after myocardial infarction and in 15 age-matched healthy persons. Venous blood samples were taken directly before and at 30, 60 and 120 minutes after oral administration of 75 g of glucose. In the collected blood samples serum glucose, insulin and C-peptide levels were determined. Binding and degradation of 125I-insulin by specific receptors on red blood cells were evaluated using the method described by Gambhir and modified by the authors. Serum insulin and C-peptide levels were significantly higher while binding of 125I-insulin to erythrocytes was decreased in patients after myocardial infarction. These results seem to support the hypothesis that insulin resistance and hyperinsulinism play a role in the pathogenesis of ischaemic heart disease. Impaired degradation of 125I-insulin during the oral glucose tolerance test in the patients after myocardial infarction indicates that insulin resistance is located at the receptor level.

The effect of antipyrine and rifampin on the metabolism of diazepam.

The elimination of diazepam and antipyrine and the urinary excretion of their metabolites were investigated in 21 healthy volunteers before and after 7 days of administration of antipyrine, 1200 mg, and rifampin, 600 or 1200 mg. After administration of antipyrine and rifampin in two doses, antipyrine total body clearance increased by 53% and 60% or 98%, respectively. The clearance to metabolite showed a preferential induction of the norantipyrine pathway with different proportions after antipyrine and rifampin; rifampin, 1200 mg, also enhanced the 4-hydroxyantipyrine pathway further. After antipyrine, diazepam total body clearance was increased by 102%, affecting all metabolic pathways to a similar extent. After rifampin in both doses, diazepam total body clearance rose equally to 300% and desmethyl- and 3-hydroxydiazepam metabolic clearance to 400%. Therefore rifampin preferentially affects norantipyrine or desmethyl- and 3-hydroxydiazepam metabolic formation, suggesting induction of different (iso)zymes of cytochrome P-450.

Bioavailability and elimination of nitrendipine in liver disease.

Twenty one patients with liver disease (cirrhosis 11, chronic hepatitis 5 and acute hepatitis 5) and 6 healthy volunteers were given a single i.v. dose of nitrendipine 5 mg. Afterwards nitrendipine 20 mg once daily were administered orally for seven days. With the intravenous injection a significant increase in the AUC and elimination half-life of nitrendipine was found in patients with cirrhosis as compared to the normal volunteers. After chronic oral dosing, the area under the plasma concentration-time curve, AUC (0-24), was 94.5 ng ml-1 h and the plasma clearance CL was 1380.6 ml/min in the healthy controls; in patients with cirrhosis the AUC (0-24) h was significantly greater at 309.4 ng ml-1 h and CL had fallen to 686.6 ml/min. Considerable accumulation of nitrendipine was also found in the patients with chronic hepatitis. Nitrendipine could not be detected in urine from any of the subjects. Blood pressure and heart rate were not significantly influenced by the treatment in the various groups investigated. Antipyrine clearance in the patients with cirrhosis was correlated with the nitrendipine plasma clearance. Thus, accumulation of nitrendipine has been demonstrated in the patients with cirrhosis and chronic hepatitis.

Effect of cisapride and metoclopramide on digoxin bioavailability.

Pharmacokinetics of digoxin were investigated in six healthy volunteers following one week of digoxin monotherapy 0.25 mg b.i.d., and during coadministration of metoclopramide 10 mg t.i.d. or cisapride 10 mg t.i.d.. Metoclopramide reduced the peak plasma concentration of digoxin from 1.5 +/- 0.2 ng/ml to 1.1 +/- 0.1 ng/ml (mean +/- SEM) (p = 0.05), cisapride lowered the peak concentration to 1.3 +/- 0.1 ng/ml (p = 0.14). Metoclopramide prolonged the time required to reach the peak concentration of digoxin from 2 hr to 2.7 hr (p = 0.17), cisapride did not. Digoxin AUC0-12 (743 +/- 79 ng/ml.min) was reduced by 12% on coadministration of cisapride (653 +/- 38 ng/ml.min, p = 0.22) and by 19% on coadministration of metoclopramide (605 +/- 34 ng/ml.min, p = 0.06). It is concluded that the gastrointestinal absorption of digoxin is reduced by both substances. Monitoring of the patient's clinical status should be recommended when metoclopramide and cisapride are coadministered.

Influence of nisoldipine on haemodynamic effects and plasma levels of digoxin.

In a placebo controlled double-blind study including 10 patients with heart failure the nisoldipine/digoxin interaction was studied. Nisoldipine was shown to elevate digoxin plasma concentrations significantly by about 15% (trough levels). During chronic combination therapy with nisoldipine trough levels and plasma concentrations 4 h after the morning dose of digoxin were 1.35 +/- 0.14 and 1.92 +/- 0.16 ng ml-1 respectively, whereas they averaged to 1.16 +/- 0.14 and 1.52 +/- 0.16 ng ml-1 with digoxin and placebo (P less than 0.05; mean +/- s.e. mean). Systolic time intervals were significantly altered by nisoldipine co-administration compared with digoxin plus placebo. In certain patients the elevation of digoxin plasma levels due to nisoldipine co-administration could be of clinical relevance.

Bioavailability and elimination of digitoxin in patients with hepatorenal insufficiency.

Following administration of digitoxin, 1 mg intravenously, the pharmacokinetics of this glycoside were studied in eight healthy volunteers and in eight patients with hepatorenal insufficiency (mean creatinine clearance 19.6 +/- 2.9 ml/min; antipyrine clearance 25.6 +/- 3.2 ml/min; means +/- SEM). Liver cirrhosis of the patients was confirmed by liver biopsy. Plasma protein binding of digitoxin (means +/- SEM) was 95.1 +/- 0.7% in the patients and 95.6 +/- 1.2% in the volunteers (NS). Total body clearance of digitoxin was 0.0530 +/- 0.0040 ml/min/kg of body weight in the patients and 0.0547 +/- 0.0043 ml/min/kg of body weight in the healthy subjects (NS). When elimination half-lives of the patients and the volunteers were compared, there was also no significant difference (7.0 +/- 0.77 days in the patient group and 7.8 +/- 0.8 days in the volunteers). Our data concerning digitoxin kinetics in patients with hepatorenal insufficiency do not indicate an accumulation of the drug in these patients.

Dose-dependence of the nifedipine/digoxin interaction?

The dose-dependence of the nifedipine/digoxin interaction was investigated in seven healthy volunteers. After an adequate loading dose of digoxin for two weeks, 0.25 mg digoxin was given alone orally twice daily. Afterwards, 0.25 mg digoxin was administered twice daily for three one week periods combined with capsules of nifedipine 5 mg, 10 mg or 20 mg (ADA-LAT) respectively on a three times daily basis. Subsequently the study was completed with a digoxin monotherapy phase lasting seven days. All three doses of nifedipine administered led to a significant increase of the digoxin plasma concentrations and of the area under the plasma concentration-time curve (AUC) compared with digoxin monotherapy. In conclusion, nifedipine causes a slight but significant increase of digoxin plasma concentrations and of its AUC (15%). This effect was not dependent on the nifedipine dose administered.

Dose-dependence of the nifedipine-digoxin interaction?

The dose-dependence of the nifedipine-digoxin interaction was investigated in seven healthy subjects. After an adequate loading dose of digoxin for 2 weeks, 0.25 mg digoxin b.i.d. was given by mouth by itself. Afterwards, 0.25 mg digoxin was given twice a day for three 1-week periods in combination with capsules of nifedipine, 5, 10, or 20 mg, respectively, given on a thrice-daily basis. The study ended with a digoxin monotherapy phase lasting 7 days. All three doses of nifedipine significantly increased digoxin plasma concentrations and AUC compared with digoxin monotherapy. Thus, for example, the AUC was 10.16 +/- 0.88 ng/ml . hr (mean +/- SE) when digoxin was given alone and 12.33 +/- 1.59 ng/ml . hr with concurrent nifedipine, 5 mg t.i.d. (P less than 0.05). Nifedipine causes a slight but significant increase (15%) in digoxin plasma concentrations and AUC. This effect did not depend on the nifedipine dose given in the range studied.