[To lower blood pressure without medication].
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Alcohol Drinking↗
Biomedical subjects
H G Predel
Publications and source records attributed to H G Predel.
24-h blood pressure monitoring in normal tension glaucoma: night-time blood pressure variability.
Systemic arterial hypotension, hypertension and altered ocular blood flow are known risk factors in glaucoma. In this study, 24-h ambulatory blood pressure monitoring was performed in patients with normal tension glaucoma (NTG) and controls to evaluate blood pressure variability. In all, 51 patients with NTG and 28 age-matched controls were included in this prospective study. A 24-h ambulatory blood pressure monitoring (SpaceLabs Medical Inc., Redmond, USA) was performed and systolic, diastolic and mean arterial blood pressures were measured every 30 min during daytime (0800-2000) and night time (0000-0600). To evaluate blood pressure variability a variability index was defined as the s.d. of blood pressure measurements. Night-time blood pressure depression ('dip') was calculated (in percent of the daytime blood pressures). Patients with NTG exhibited higher night-time diastolic (P = 0.01) and mean arterial blood pressure values (P = 0.02) compared to controls, whereas systolic blood pressure data were not significantly different. The variability indices of night-time systolic, diastolic and mean arterial blood pressure measurements were significantly increased in patients with NTG compared to controls (P < 0.05). The night-time blood pressure depression of systolic (P = 0.47), diastolic (P = 0.11) and mean arterial blood pressures (P = 0.28) was not significantly different between patients with NTG and controls. In conclusion, patients with NTG showed increased variability of night-time blood pressure measurements compared to controls. Increased fluctuation of blood pressure may lead to ocular perfusion pressure fluctuation and may cause ischaemic episodes at the optic nerve head.
Aged↗
Efficacy of a comfrey root extract ointment in comparison to a diclofenac gel in the treatment of ankle distortions: results of an observer-blind, randomized, multicenter study.
In the treatment of minor blunt injuries several topical drugs are known to have anti-inflammatory and analgesic properties. They represent, however, two fundamentally different major pharmacological therapy approaches: the "chemical-synthetical" and the "phytotherapeutical" approach. The main objective of this trial (CODEC_2004) was to compare the efficacy and tolerability of an ointment of Comfrey extract (Extr. Rad. Symphyti) with that of a Diclofenac gel in the treatment of acute unilateral ankle sprain (distortion). In a single-blind, controlled, randomized, parallel-group, multicenter and confirmatory clinical trial outpatients with acute unilateral ankle sprains (n=164, mean age 29.0 years, 47.6% female) received either a 6 cm long ointment layer of Kytta-Salbe f (Comfrey extract) (n=82) or of Diclofenac gel containing 1.16 g of diclofenac diethylamine salt (n=82) for 7 +/- 1 days, four times a day. Primary variable was the area-under-the-curve (AUC) of the pain reaction to pressure on the injured area measured by a calibrated caliper (tonometer). Secondary variables were the circumference of the joint (swelling; figure-of-eight method), the individual spontaneous pain sensation at rest and at movement according to a Visual Analogue Scale (VAS), the judgment of impaired movements of the injured joint by the method of "neutral-zero", consumption of rescue medication (paracetamol), as well as the global efficacy evaluation and the global assessment of tolerability (both by physician and patient, 4 ranks). In this study the primary variable was also to be validated prospectively. It was confirmatorily shown that Comfrey extract is non-inferior to diclofenac. The 95% confidence interval for the AUC (Comfrey extract minus Diclofenac gel) was 19.01-103.09h*N/cm2 and was completely above the margin of non-inferiority. Moreover, the results of the primary and secondary variables indicate that Comfrey extract may be superior to Diclofenac gel.
Adolescent↗
[The PreFord Study. A prospective cohort study to evaluate the risk of a cardiovascular event (overall-collective) as well as a prospective, randomized, controlled, multicentre clinical intervention study (high-risk-collective) on primary prevention of cardiovascular diseases in the Ford Motor Company employees in Germany].
The PreFord Study is a multicenter prospective cohort study to evaluate guideline based risk management on primary prevention of cardiovascular diseases. Furthermore a randomised controlled trial (RCT) will be designed to analyse the effect of a special intervention program. 40,000 employees of the Ford Motor Company, Visteon Company and Deutz Company in Germany will be included, monitored for ten years and the following primary endpoints will be investigated: 1. evaluation and comparison of established and newly developed risk-scores, 2. the relative impact of single and combined cardiovascular risk factors on cardiovascular diseases, 3. the influence of a novel occupationally integrated ambulant rehabilitation program in combination with a guideline oriented optimal drug therapy within a high risk group on the primary endpoint: risk reduction by, 4. the influence of this intervention on secondary endpoints: death, myocardial infarction and stroke, combined appearance of angina pectoris and hospitalisation, occurrence of cerebral circulatory disorder and hospitalisation, occurrence of peripheral occlusive arterial disease and hospitalisation and single cardiovascular risk factors and cost-benefit-analysis. Beginning with an cross sectional study there will be a systemic screening of cardiovascular risk profiles, of anthropometric data and different lifestyle-factors. Based on these data participants will be differentiated into three risk-groups according to the risk score of the European Society of Cardiology (risk of a lethal primary acute cardiovascular event: I < or = 1%; II > 1-< 5% and III > or = 5%). In the following longitudinal study different strategies will be applied: Group I: low risk (< 0.5% per year): repetition of the investigation after five and ten years. Group II: middle risk, (0.6% to 1.4% per year), repetition of the investigation every two years, instruction of the patients general practitioner (GP) with respect to a risk factor oriented and evidence based treatment. Group III: high risk, (> 1.5% per year or >15% within the next 10 years) will be randomised into two interventional groups. The first one, the intervention-group "PreFord" will perform an occupational integrated rehabilitation program (2,5-3 hours twice a week, for 15 weeks according to the BAR guidelines) with a following engagement in heart-groups and an annual repetition of the check-ups. The second group, the "classic" intervention-group will be treated evidence based in cooperation with their GP. As a result of this long term interventional study efficient, area wide implementable and economically feasible prevention concepts with special regards to operational healthcare will be developed and evaluated. Core elements will be exercise- and lifestyle-oriented concepts as well as guideline-based pharmacotherapy.
Adult↗
Efficacy and tolerance of a comfrey root extract (Extr. Rad. Symphyti) in the treatment of ankle distorsions: results of a multicenter, randomized, placebo-controlled, double-blind study.
Comfrey (Symphytum officinale L.) is a medicinal plant with anti-inflammatory, analgesic and tissue regenerating properties. In a double-blind, multicenter, randomized, placebo-controlled, group comparison study on patients suffering from unilateral acute ankle sprains (n = 142, mean age 31.8 years, 78.9% male), the percutaneous efficacy of an ointment of comfrey extract (Kytta-Salbe f, four treatments per day for 8 days) was confirmed decisively. Compared to placebo, the active treatment was clearly superior regarding the reduction of pain (tonometric measurement, p<0.0001, as the primary efficacy variable) and ankle edema (figure-of-eight method, p = 0.0001). Statistically significant differences between active treatment and placebo could also be shown for ankle mobility (neutral zero method), and global efficacy. Under active treatment, no adverse drug reactions were reported. The good local and global tolerance of the trial medication could also be confirmed. The study results are consistent with the known pre-clinical and clinical data concerning comfrey.
Adolescent↗
Correlation between BMI, leisure habits and motor abilities in childhood (CHILT-project).
INTRODUCTION: The prevalence of childhood obesity is increasing with its negative medical and psychosocial consequences. This paper examines the association between body mass index (BMI), motor abilities and leisure habits of 668 children within the CHILT (Children's Health InterventionaL Trial) project. METHOD: A total of 668 children (51.0% boys; 49.0% girls) and their parents were questioned on sport and leisure behaviour of the children. The anthropometric data were measured. Motor abilities were determined by a body gross motor development test for children (Köperkoordinationstest für Kinder; KTK) and a 6-min run. RESULTS: The children were 6.70 +/- 0.42 y old, 122.72 +/- 5.36 cm tall and weighed 24.47 +/- 4.59 kg, the average BMI was 16.17 +/- 2.27 kg/m2. KTK showed an average motor quotient (MQ) of 93.49 +/- 15.01, the 6-min run an average of 835.24 +/- 110.87 m. Both tests were inversely correlated with BMI (KTK and BMI r=-0.164 (P<0.001); 6-min run and BMI r=-0.201 (P<0.001)); the group of overweight/obese children showed poorer results than the normal/underweight ones, even after adjustment for gender and age (in each case P<0.001). Children with the greatest extent of exercise achieve the highest MQ (P=0.035). SUMMARY: Overweight/obesity is associated with a poorer body gross motor development and endurance performance. On the other hand, an active lifestyle is positively correlated with a better gross motor development in first-grade children. Therefore, to prevent the negative consequences of physical inactivity and overweight/obesity early intervention to support exercise and movement is recommended.
Analysis of Variance↗
Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study.
OBJECTIVES: To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries. METHODS: This was a randomised, placebo controlled, double blind, multicentre study in 120 patients with traumatic blunt soft tissue injury. Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days. Patients were randomised (1:1) to two parallel groups. Tenderness produced by pressure was measured twice daily during the first 3 days after enrollment as well as at day 7. Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient. RESULTS: The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2 (95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group. CONCLUSIONS: A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries.
Acute Disease↗
[An exercise program for the hypertensive patient. Leaving hypertension behind].
Today, regular exercise is considered an important therapeutic principle in arterial hypertension. Apart from weight reduction, the positive effects of sports (moderately practiced) include a reduction in peripheral resistance, improvement of endothelial dysfunction, and an increase in insulin sensitivity of the skeletal muscles. Training programs should be tailored to the physical and mental status of the patient, in particular to the severity of the hypertension, where indicated, with consideration being given to the hypertensive drugs used. In the case of marked hypertension or already existing secondary complications, training should be started only when the patient's blood pressure has been brought under pharmacological control. Ideally, training should be applied as 20-60 minute sessions at least twice weekly, with exercise keeping within aerobic capacity.
Antihypertensive Agents↗
[Which antihypertensive drugs for physically active hypertensive patients?].
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Antihypertensive Agents↗
Integrated effects of the vasodilating beta-blocker nebivolol on exercise performance, energy metabolism, cardiovascular and neurohormonal parameters in physically active patients with arterial hypertension.
OBJECTIVE: The present study was designed to investigate the integrated effects of the beta-1-selective blocker with vasodilator properties, nebivolol, on systemic haemodynamics, neurohormones and energy metabolism as well as oxygen uptake and exercise performance in physically active patients with moderate essential hypertension (EH). DESIGN AND METHODS: Eighteen physically active patients with moderate EH were included: age: 46.9 +/- 2.38 years, weight: 83.9 +/- 2.81 kg, blood pressure (BP): 155.8 +/- 3.90/102.5 +/- 1.86 mm Hg, heart rate: 73.6 +/- 2.98 min(-1). After a 14-day wash-out period a bicycle spiroergometry until exhaustion (WHO) was performed followed by a 45-min submaximal exercise test on the 2.5 mmol/l lactate-level 48 h later. Before, during and directly after exercise testing blood samples were taken. An identical protocol was repeated after a 6-week treatment period with 5 mg nebivolol/day. RESULTS: Nebivolol treatment resulted in a significant (P < 0.01) decrease in systolic and diastolic BP and heart rate at rest and during maximal and submaximal exercise. Maximal physical work performance, blood lactate and rel. oxygen uptake (rel. VO(2)) before and after nebivolol treatment at rest and during maximal and submaximal exercise remained unaltered. Free fatty acid, free glycerol, plasma catecholamines, beta-endorphines and atrial natriuretic peptide (ANP) increased before and after treatment during maximal and submaximal exercise but remained unaltered by nebivolol treatment. In contrast, plasma ANP levels at rest were significantly higher in the presence of nebivolol, endothelin-1 levels were unchanged. CONCLUSIONS: Nebivolol was effective in the control of BP at rest and during exercise in patients with EH. Furthermore, nebivolol did not negatively affect lipid and carbohydrate metabolism and substrate flow. The explanation for the effects on ANP at rest remain elusive. This pharmacodynamic profile of nebivolol is potentially suitable in physically active patients with EH.
Adrenergic beta-Antagonists↗
ACE and angiotensinogen gene genotypes and left ventricular mass in athletes.
BACKGROUND: Genetic factors may be important in modifying heart size due to long-term athletic training. The significance of polymorphisms of genes of the renin-angiotensin system in myocardial mass in a population of athletes participating in different disciplines is not known. METHODS: The angiotensin I-converting enzyme gene insertion/deletion (I/D) polymorphism, angiotensinogen gene M235T polymorphism and angiotensin II type 1 receptor gene A1166C polymorphism were determined in 83 male Caucasian endurance athletes and associated with left ventricular mass. RESULTS: No association with left ventricular mass was found for the polymorphisms of angiotensin I-converting enzyme gene I/D, angiotensinogen gene M235T and angiotensin II type 1 gene A1166C when studied separately. However, combined analysis of the angiotensin I-converting enzyme gene I/D polymorphism and angiotensinogen gene M235T polymorphism genotypes suggested an association with left ventricular mass (g m(-2)) (P = 0.023). Athletes with the angiotensin I-converting enzyme gene DD/angiotensinogen gene TT genotype combination had greater left ventricular mass compared with all other genotype combinations (179.8 +/- 26.1 g m(-2) vs. 145.2 +/- 27.3 g m(-2), P = 0.003). CONCLUSIONS: These results suggest an association of combined angiotensin I-converting enzyme gene I/D polymorphism genotypes, and angiotensinogen gene M235T polymorphism genotypes with left ventricular hypertrophy due to long-term athletic training. A synergistic effect of angiotensin I-converting enzyme gene DD genotype and angiotensinogen gene TT genotype on left ventricular mass in endurance athletes appears to occur.
Adolescent↗
[Phase II ambulatory cardiac rehabilitation (Cologne model). 3 year results after conclusion of the intervention].
UNLABELLED: BASELINE: Of a total of 101 patients with CAD who participated in an ambulatory cardiac rehabilitation program (ACR) ("Cologne model") between 1992 and 1994, 76 (75.2%) were examined 36 months after concluding ACR. RESULTS: The significant improvement in exercise tolerance from 118.4 +/- 30.1 to 131.9 +/- 34.1 W achieved with the ACR was maintained at the 3-year examination. ACR also significantly decreased plasma cholesterol levels from 228.9 +/- 48.3 to 211.7 +/- 37.0 mg%; 3 years after ACR the corresponding figures were 219.1 +/- 39.3 mg%. In the high-risk group the significant reduction in plasma cholesterol levels from 265 +/- 43.6 to 231.9 +/- 35.4 mg% observed immediately after ACR was maintained over the three-year period (234.6 +/- 37.7 mg%). Similar patterns were observed for other parameters of lipid metabolism. Before the cardiac event 63.2% of the patients smoked; at the 3-year examination the percentage was 30.3%. Before ACR, 73.7% of the patients were gainfully employed. Within the first 6 months after ACR, 71.4% returned to work, and this percentage increased to 73.2% after one year. Three years later, 64.3% were still working. DISCUSSION: The results demonstrate that the lifestyle changes achieved with 4-weeks of ACR may, at least in part, be maintained over a period of 36 months.
Adult↗
[Ambulatory phase II cardiac rehabilitation (Cologne model). 3 year outcome after completion of the intervention].
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Adult↗
[Ambulatory cardiac phase II rehabilitation--"the Cologne model"--including 3-year-outcome after termination of rehabilitation].
From January 1992 until December 1994 the Cologne model of ambulant cardiac rehabilitation (ACR) in the greater area of Cologne, Germany, was performed and is still in progress. In Germany until 1992 the cardiac rehabilitation was exclusively performed stationary. The objective of the "Cologne model" was to evaluate, whether the transfer of the stationary cardiac rehabilitation programs into the ambulatory setting is achievable without deficits in efficiency, safety and overall quality. The results obtained are intended to serve for standardization and quality control of future ambulatory cardiac rehabilitation programs in Germany. From 1992 to 1994 108 patients (94 men, 14 women; 52.3 +/- 8.0 years old) with coronary artery disease (CAD) which were compatible with the criteria of the "Cologne model" (Table 1) participated in the 4-week ACR. The indications for inclusion into the ACR were in 74 cases a myocardial infarction (MI), in 34 cases CAD without MI, but with PTCA/stent-procedure (Table 3). Seven patients discontinued the ACR prematurely, 2 patients because of cardiovascular reasons. Reasons for the preference of the ambulatory over a stationary cardiac rehabilitation program were in 40.6% of the patients refusal of "hospital ambience", in 43.6% familiar or in 12.9% professional reasons. During the 4-week ACR patients participated in a mean of 72.9 +/- 6.7 hours of therapy (Table 4). As a result of the ACR exercise tolerance increased highly significantly (**) from 116.4 +/- 28.8 to 129.9 +/- 34.6 watt). This improvement was maintained at the 1- and 3-year control (128.7 +/- 35.8**) examinations (Tables 5 and 7). One year after ACR 77% of the patients stated to be physically active in ambulatory heart groups (AHG) (27.6%) or on their own (49.4%). Three years after ACR the rate of regularly physically active patients still was 59.2%. Furthermore, as a result of ACR the dietary behavior was changed significantly. There was a reduction in the consumption of lipids by 20.8%, saturated fatty acids by 30.7% and of cholesterol by 30.5%. The plasma concentrations of cholesterol decreased from 231 +/- 49.8 to 213.2 +/- 35.9 mg%**. Six (and 12) months after ACR they increased again to 225.6 +/- 39.4 mg%. Three years after ACR the mean cholesterol level was 219.1 +/- 39.3 mg%. In the high risk group (cholesterol at the initial visit > 220 mg%) cholesterol levels were reduced from 266 +/- 44 to 232 +/- 31.9 mg%**. Six and 12 months after ACR they were 239.7 +/- 35.8 mg% and 245.8 +/- 32.6 mg%, respectively, (Tables 6 and 7) and still significantly lower than before ACR, though only 19% of the patients were treated with lipid lowering agents. Three years after ACR cholesterol were 234.6 +/- 37.7 mg%** in the high-risk group. 34.2% of the patients received lipid lowering agents. Mean body weight remained unaltered over the 3-year period. Smoking behavior was not altered significantly during the 4-week ACR. However, before the cardiovascular event 67.3% of the patients had smoked cigarettes. At the beginning and at the end of ACR 20.8% of the patients still smoked. During the ACR the number of smoked cigarettes was reduced significantly from 32.4 +/- 15.2 to 6.9 +/- 5.2 cigarettes per day. One year after ACR 23% of the patients were smokers, 3 years after ACR the percentage of smokers increased to 30.3%. Before ACR 73.3% of the patients were still working. During the first 6 months after ACR 68.2% returned to work and the percentage increased to 73% in the following 6 months. The results demonstrate that it is achievable to transfer the contents of the established stationary cardiac rehabilitation programs into the ambulatory setting without loss of efficiency, safety and overall quality. It is further confirmed, that it is necessary to continuously evaluate the results of the cardiac rehabilitation program on a long-term basis. (ABSTRACT TRUNCATED)
Adult↗
[Clinical follow-up 6 months after ambulatory/partial inpatient after-care rehabilitation. Further results of the Cologne model of ambulatory cardiac phase II rehabilitation].
Three hundred and thirty patients with coronary artery disease (CAD) (288 men, 42 women, age of 55.5 +/- 10.0 years) participated in a 4-week ambulatory cardiac rehabilitation program (ACR) (Table 1). The cardiovascular indication for ACR was in 229 cases a myocardial infarction. In 101 patients a CAD with invasive revascularization but without a history of MI was present. In 92 patients with myocardial infarction additionally an invasive revascularization was performed. Eighty-three patients were included after a CABG-procedure (Tables 2 to 5). Six months after the ACR 290 (87.9%) patients presented for clinical reevaluation. In 235 (81.0%) of the 290 examined patients the cardiovascular diagnosis was unaltered. In the first 6 months after ACR in 76 (26.2%) patients a coronarography was performed, in 44 patients a restenosis was diagnosed. In 36 patients an additional invasive procedure (in 28 patients a PTCA, in 5 patients with additional stent-implantation, in 1 case with rotablation, in 8 patients CABG) was performed. In 1 patients a pace-maker was implanted. Since the ACR 1 patient experienced a myocardial infarction and 2 a recurrent myocardial infarction. In 1 patient myocardial fibrillation occurred. Totally, 70 patients (24.1%) required stationary-hospital treatment during the first 6 months after ACR (Table 6). In 11 cases an acute admission to hospital treatment because of cardiovascular reasons was documented. The majority of the hospital admission was elective, because of diagnostic or therapeutic procedures. In 6 patients a CABG-surgery was performed. In approximately 80% of the patients the cardiovascular status was stable during the first 6 months after ACR. Though 24.1% of the patients required stationary hospital treatment, the majority of the admissions was elective of interest, there was a high rate of hospital admissions in the PTCA-group in combination with recoronarographies and revascularization because of early reocclusion.
Adult↗
[Improvement of physical performance and aerobic capacity mediated by a novel 4--week ambulatory cardiac rehabilitation program].
During a 4-week ambulatory cardiac rehabilitation program, 262 patients with coronary artery disease (CAD), 235 men and 27 women, 53.6 +/- 10.2 years, performed 30.5 +/- 2.9 exercise units. Before and after the rehabilitation program exercise, capacity was assessed by bicycle ergometry. There was a significant (p < 0.001) increase in the maximum exercise capacity at the end of the program (105.3 +/- 32.3 vs. 121.9 +/- 37.3 W). Physical work capacity on the 2.0 mmol lactate level improved (p < 0.001) from 72.2 +/- 23.5 to 86.4 +/- 25.8 W, on the 2.5 mmol/l level (p < 0.001) from 83.5 +/- 23.2 to 97.4 +/- 26.4 W, and on the 3.0 mmol/l level (p < 0.001) from 93.1 +/- 23.0 to 106.6 +/- 26.1 W. Despite enhanced performance, heart rate remained unaltered on the 2.0, 2.5, and 3.0 mmol/l lactate level. Furthermore, ergometric performance on predefined heart rate levels was significantly (p < 0.001) increased: 85/min: from 56.0 +/- 24.1 to 65.8 +/- 24.5 W, 90/min: from 62.0 +/- 27.3 to 71.2 +/- 26 W; 95/min: from 67.2 +/- 26.4 to 77.5 +/- 27.6 W; 100/min: from 71.1 +/- 29.6 to 80.6 +/- 28.1 W; 105/min: from 69.8 +/- 26.2 to 81.9 +/- 28.2 W and 110/min: from 73.6 +/- 28.9 to 90.4 +/- 29.4 W. The results demonstrate that physical performance in patients with CAD was improved by our novel ambulatory cardiac rehabilitation program. This improvement included an increase in maximum as well as endurance work capacity; furthermore, this increase was accompanied by a decrease in resting and exercise heart rates. The results demonstrate an absolute increase of physical performance, more importantly an increase of physical performance at defined lactate levels in the presence of unchanged heart rates mediated by the rehabilitation program. Thus, this increase was independent of motivational factors in the patients and/or the investigators during the re-exercise test. On the contrary, our data demonstrate that it is based on an improvement of aerobic endurance capacity associated with a therapeutically beneficial significant decrease of heart rate for a defined workload. The effects were independent of pharmacological influences (e.g., beta-receptor antagonists). These findings are of clinical importance with respect to reduction of myocardial oxygen consumption in patients with CAD.
Coronary Disease↗
The exercise-induced increase in plasma levels of endothelin-1 is enhanced in patients with atherosclerotic coronary artery disease. Modulation by pentaerithrityltetranitrat (PETN).
BACKGROUND AND OBJECTIVE: Previous studies have suggested that endothelin (ET)-1 with its marked vasoconstrictive potency may play a role in the induction of coronary artery spasms. Furthermore, it was demonstrated using in-vitro vessel preparations that the secretion of ET-1 by the vascular endothelium is enhanced in the presence of atherosclerotic alterations. The objective of the present study was to investigate a) the effects of ergometric exercise on ET-1 plasma concentrations in 10 patients with coronary artery disease (CAD) as compared to an age and sex matched control group and b) the modulatory role of the orally administered organic nitrate, pentaerithrityltetranitrat (PETN), in patients with CAD. PATIENTS AND METHODS: 10 male patients with CAD confirmed by coronarography and 10 male healthy controls underwent a bicycle ergometry according to the WHO-standards upt to 125 watts. Venous blood samples for determination of ANP and ET-1 plasma concentrations were drawn in supine position directly before and 5 min after ergometric exercise. Subsequently, patients were randomized and treated for 3 days in a crossover design either with placebo or PETN (150 mg b.i.d.). RESULTS: Basal plasma levels of ET-1 were 6.1 +/- 0.7 pg/ml (patients) and 5.5 +/- 0.6 pg/ml (controls), resp. (n.s.). After ergometric exercise ET-1 plasma concentrations rose significantly (7.3 +/- 0.9 pg/ml; p < 0.05) in the placebo-treated patient group, whereas they remained constant (5.5 +/- 0.7 pg/ml) in the PETN-treated patient group. Blood pressure and heart rate were not modified by the PETN-treatment. ET-1 plasma levels remained unaffected by ergometric exercise in controls. DISCUSSION: In contrast to healthy controls ergometric exercise induced an increase in ET-1 plasma concentrations in patients with CAD that may be potentially harmful by promoting coronary vasospasms. The almost complete blunting of the ET-1-increase in the presence of PETN-therapy may result from local-hemodynamic effects of the organic nitrate; it may be hypothesized that the nitrate-induced rise in local NO-concentrations counteracts ET-secretion. The findings of the present study are in accordance with the beneficial clinical effects of organic nitrates in patients with CAD.
Administration, Oral↗
Exercise increases endothelin-1 plasma concentrations in patients with coronary artery disease: modulatory role of LDL cholesterol and of pentaerithrityltetranitrate.
Previous studies suggest that ET-1 plays a role in induction of coronary artery disease (CAD). It was shown that secretion of endothelin-1 (ET-1) by the vascular endothelium is enhanced in atherosclerotic alterations and may be antagonized by EDRF. The objective of the present study was to investigate the effects of ergometric exercise on plasma ET-1 concentrations, and the potential modulatory role of LDL cholesterol, and the effects of an orally administered nitrate, PETN, in patients with CAD. Ten men with CAD and 10 healthy men underwent bicycle ergometry according to the WHO-standards. Venous blood samples for determination of ET-1 concentrations were drawn directly before and 5 min after ergometric exercise. Patients were randomized and treated for 72 h in a crossover design either with placebo or pentaerithrityltetranitrate (PETN). After 72 h the identical ergometric protocol was repeated. Basal plasma levels of ET-1 were 6.1 +/- 0.7 pg/ml (patients) and 5.5 +/- 0.6 pg/ml (controls) (n.s.). After ergometric exercise ET-1 plasma concentrations rose significantly (7.3 +/- 0.9 pg/ml; p < 0.05) in the patient group under placebo treatment, whereas they remained constant (5.5 +/- 0.7 pg/ml) with PETN treatment. ET-1 levels remained unaffected by ergometric exercise in healthy controls. Mean LDL cholesterol plasma levels in patients with CAD were 156 +/- 8 mg% and 152 +/- 7 mg% in healthy controls. In the patient group there was a significant (p < 0.002) positive correlation between the exercise-induced increase in ET-1 and the LDL cholesterol plasma concentrations (r = 0.85). Blood pressure and heart rate were not modified by PETN treatment. In patients with CAD bicycle ergometry induced an increase in ET-1 plasma concentrations. The positive correlation with the LDL cholesterol plasma levels indicates that LDL cholesterol is involved in regulation of ET-1 secretion in vivo. PETN therapy completely abolished the exercise-induced increase in ET-1 plasma levels. This may result from local hemodynamic effects of the nitrate; hypothetically a nitrate-induced rise in the local NO concentrations can be considered. The clinical implications of these findings remain elusive. However, the findings of the present study are in accordance with the beneficial clinical effects of nitrates in patients with CAD.
Cholesterol, LDL↗