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Biomedical subjects

R Hambrecht

Publications and source records attributed to R Hambrecht.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: A randomized trial.

CONTEXT: Exercise training in patients with chronic heart failure improves work capacity by enhancing endothelial function and skeletal muscle aerobic metabolism, but effects on central hemodynamic function are not well established. OBJECTIVE: To evaluate the effects of exercise training on left ventricular (LV) function and hemodynamic response to exercise in patients with stable chronic heart failure. DESIGN: Prospective randomized trial conducted in 1994-1999. SETTING: University department of cardiology/outpatient clinic in Germany. PATIENTS: Consecutive sample of 73 men aged 70 years or younger with chronic heart failure (with LV ejection fraction of approximately 0.27). INTERVENTION: Patients were randomly assigned to 2 weeks of in-hospital ergometer exercise for 10 minutes 4 to 6 times per day, followed by 6 months of home-based ergometer exercise training for 20 minutes per day at 70% of peak oxygen uptake (n=36) or to no intervention (control group; n=37). MAIN OUTCOME MEASURES: Ergospirometry with measurement of central hemodynamics by thermodilution at rest and during exercise; echocardiographic determination of LV diameters and volumes, at baseline and 6-month follow-up, for the exercise training vs control groups. RESULTS: After 6 months, patients in the exercise training group had statistically significant improvements compared with controls in New York Heart Association functional class, maximal ventilation, exercise time, and exercise capacity as well as decreased resting heart rate and increased stroke volume at rest. In the exercise training group, an increase from baseline to 6-month follow-up was observed in mean (SD) resting LV ejection fraction (0.30 [0.08] vs 0.35 [0.09]; P=.003). Mean (SD) total peripheral resistance (TPR) during peak exercise was reduced by 157 (306) dyne/s/cm(-5) in the exercise training group vs an increase of 43 (148) dyne/s/cm(-5) in the control group (P=.003), with a concomitant increase in mean (SD) stroke volume of 14 (22) mL vs 1 (19) mL in the control group (P=.03). There was a small but significant reduction in mean (SD) LV end diastolic diameter of 4 (6) mm vs an increase of 1 (4) mm in the control group (P<.001). Changes from baseline in resting TPR for both groups were correlated with changes in stroke volume (r=-0.76; P<.001) and in LV end diastolic diameter (r=0.45; P<.001). CONCLUSIONS: In patients with stable chronic heart failure, exercise training is associated with reduction of peripheral resistance and results in small but significant improvements in stroke volume and reduction in cardiomegaly. JAMA. 2000.

Aged↗
PubMed2000

Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation.

OBJECTIVES: The aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium-dependent vasodilation in patients with chronic heart failure (CHF). BACKGROUND: Endothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg. and regular physical exercise. METHODS: Forty patients with severe CHF (left ventricular ejection fraction 19 +/- 9%) were randomized to an L-arg. group (8 g/day), a training group (T) with daily handgrip training, L-arg. and T (L-arg. + T) or an inactive control group (C). The mean internal radial artery diameter was determined at the beginning and after four weeks in response to brachial arterial administration of acetylcholine (ACh) (7.5, 15, 30 microg/min) and nitroglycerin (0.2 mg/min) with a transcutaneous high-resolution 10 MHz A-mode echo tracking system coupled with a Doppler device. The power of the study to detect clinically significant differences in endothelium-dependent vasodilation was 96.6%. RESULTS: At the beginning, the mean endothelium-dependent vasodilation in response to ACh, 30 microg/min was 2.54 +/- 0.09% (p = NS between groups). After four weeks, internal radial artery diameter increased by 8.8 +/- 0.9% after ACh 30 microg/min in L-arg. (p < 0.001 vs. C), by 8.6 +/- 0.9% in T (p < 0.001 vs. C) and by 12.0 +/- 0.3% in L-arg. +/- T (p < 0.005 vs. C, L-arg. and T). Endothelium-independent vasodilation as assessed by infusion of nitroglycerin was similar in all groups at the beginning and at the end of the study. CONCLUSIONS: Dietary supplementation of L-arg. as well as regular physical exercise improved agonist-mediated, endothelium-dependent vasodilation to a similar extent. Both interventions together seem to produce additive effects with respect to endothelium-dependent vasodilation.

Acetylcholine↗
PubMed2000

Effect of exercise on coronary endothelial function in patients with coronary artery disease.

BACKGROUND: Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease. METHODS: We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography. RESULTS: In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group). CONCLUSIONS: Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.

Acetylcholine↗
PubMed2000

The revival of surgical treatment for isolated proximal high grade LAD lesions by minimally invasive coronary artery bypass grafting.

BACKGROUND: Percutaneous coronary angioplasty (PTCA) and stent implantation have become the first-line intervention for patients with isolated proximal LAD-lesions. Minimally invasive direct coronary artery bypass surgery (MIDCAB) has recently been developed to reduce surgical invasiveness for single LAD revascularization. This study focus on the question whether MIDCAB could be an alternative treatment for isolated proximal LAD lesions. METHODS: Starting in 1996, MIDCAB was performed in 618 patients. Angiography was performed before discharge and repeated after 6 months at follow-up examination. In an ongoing randomized trial 150 patients with an indication for treatment of a LAD lesion have been included to compare the mid-term outcome after PTCA (n=79) vs. MIDCAB (n=71). RESULTS: In 618 MIDCAB procedures 30-day mortality was 0.6%, perioperative myocardial infarction rate was 1.6%. The conversion rate to sternotomy was 3.4%. The learning curve was demonstrated by a patency rate of 96.0% in 1997, 98.0% in 1998 and 99.1% in 1999, respectively. At 6 months patency rate was 94.4% in 1997 and 97.0% in 1998. The rate of severe stenosis >75% dropped from 5.4% in 1997 to 3.4% in 1998. The over all rate of reinterventions was 5.6%. The preliminary result of the randomized trial revealed a difference in the number of perioperative adverse events, 11.4% in the MIDCAB group vs. 6.3% in the PTCA group (P<0.05). At 6 months follow-up 88. 7% of the MIDCAB patients were free from angina vs. 58.2% of the PTCA patients (P<0.02). Restenosis and a positive stress test was diagnosed in 27.9% of the PTCA patients vs. 8.4% of the MIDCAB patients (P<0.02). Reintervention was necessary in 27.9% of the patients after PTCA vs. 8.4% of the patients after MIDCAB. CONCLUSION: MIDCAB is a safe and effective but technically demanding procedure. Perioperative adverse events may be expected, but early as well as mid-term patency rate are good. When compared to PTCA, the freedom from angina and the need for additional revascularization procedures after 6 months is statistically better for patients having MIDCAB surgery. Thus, MIDCAB is considered a valuable alternative for isolated proximal high grade LAD lesions.

Adult↗
PubMed1999

Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance.

OBJECTIVES: The purpose of the study was to investigate if apoptosis occurs in skeletal muscle myocytes and its relation to exercise intolerance in patients with chronic heart failure (CHF). BACKGROUND: Intrinsic abnormalities of skeletal muscle frequently limit exercise tolerance in CHF patients. Recently, apoptosis has been detected in cardiac myocytes of patients with CHF, suggesting that apoptosis may contribute to the reduced contractile force. The presence and regulation of apoptosis in skeletal myocytes of patients with CHF remains to be defined. METHODS: Skeletal muscle biopsies (m. vastus lateralis) of 34 CHF patients (New York Heart Association functional class II-III) and eight age-matched healthy control subjects were analyzed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling for the presence of apoptosis, and by immunohistochemistry and videodensitometrical quantification for inducible nitric oxide synthase (iNOS) and Bcl-2 expression. Maximal oxygen consumption (VO2max) was determined by ergospirometry. RESULTS: Apoptosis was detected in 16/34 (47%) patients with CHF and in none of the healthy subjects. Patients with apoptosis-positive skeletal muscle myocytes exhibited a significantly lower VO2max (12.0 +/- 3.7 vs. 18.2 +/- 4.4 ml/kg/min; p = 0.0005), a higher iNOS expression (6.8 +/- 3.6 vs. 3.7 +/- 2.6% iNOS-positive stained tissue area; p = 0.015) and a lower Bcl-2 expression (1.0 +/- 0.3 vs. 1.4 +/- 0.4% Bcl-2-positive tissue area; p = 0.03) as compared with patients with apoptosis-negative biopsies. CONCLUSIONS: These results indicate that apoptosis is frequently found in skeletal muscle obtained from CHF patients, which is associated with significant impairment of functional work capacity. In skeletal muscle of these patients, iNOS and Bcl-2 are possibly involved in the regulation of apoptosis.

Adult↗
PubMed1999

Physical training as an adjunct therapy in patients with congestive heart failure: patient selection, training protocols, results, and future directions.

Exercise intolerance in patients with chronic heart failure (CHF) shows no correlation to the degree of left ventricular dysfunction. This surprising finding has directed attention to peripheral changes in CHF: reduced endothelium-dependent vasodilation and altered skeletal muscle metabolism. Physical exercise training has evolved as an important therapeutic approach to influence these noncardiac causes of exercise intolerance. It has been shown to enhance the oxidative capacity of the working skeletal muscle, to attenuate ergoreflex activity, to correct endothelial dysfunction, and to improve ventilation. All exercise-induced adaptations converge to increase peak oxygen uptake by up to 2 mL/kg.min(-1). Uncertainty remains concerning optimal patient selection, training protocol, and long-term effects on cardiac function. For patients experiencing stable CHF while on optimal cardiac medication, a combination of in-hospital and home-based aerobic endurance training in combination with local muscle strength training seems most promising. Although exercise training offers no causal treatment of CHF, it has great potential as an adjunct therapy directed at improving exercise tolerance and expanding the physical limits of CHF patients.

Arrhythmias, Cardiac↗
PubMed1999

Exercise intolerance in patients with chronic heart failure and increased expression of inducible nitric oxide synthase in the skeletal muscle.

OBJECTIVES: This study was designed to analyze the effect of iNOS on mitochondrial creatine kinase (mi-CK) expression and exercise capacity in chronic heart failure (CHF). BACKGROUND: The molecular mechanisms underlying exercise intolerance in CHF are still unclear. Expression of inducible nitric oxide synthase (iNOS) and reduced phosphocreatine resynthesis have been described in skeletal muscle of patients with CHF. However, it is unknown whether these phenomena are causally related to each other and to exercise tolerance. METHODS: Thirty-eight patients with CHF and 8 healthy controls (C) underwent bicycle ergospirometry and biopsy of the vastus lateralis muscle. Expression of iNOS was quantified by immunohistochemistry and reverse-transcriptase polymerase chain reaction, mi-CK by Western-blot. Intracellular presence of NO was confirmed by immunohistochemical quantification of nitrotyrosine (NT). To corroborate clinical findings, L6 rat skeletal myoblasts were incubated with sodium nitroprusside (SNP). RESULTS: Expression of iNOS was significantly increased in CHF (4.0+/-2.8 vs. 0.8+/-0.7% iNOS positive tissue area, p < 0.001 vs. C) and inversely correlated to maximal oxygen uptake (r=-0.65, p < 0.001). Intracellular NO-accumulation was confirmed by increased NT levels (13.5+/-8.5 vs. 2.0+/-1.7% NT-positive tissue area, p < 0.001 vs. C). Mi-CK was decreased in CHF (0.84+/-0.36 vs. 1.57+/-0.60, p < 0.001 vs. C). The inverse correlation seen between iNOS and mi-CK expression in patients (r=-0.68, p < 0.001) was reproduced in incubation experiments with SNP. CONCLUSIONS: Increased expression of iNOS in skeletal muscle of patients with CHF was inversely correlated with mi-CK expression and exercise capacity. Cell experiments confirmed a causal relationship via NO. These findings extend our knowledge of the pathophysiology of exercise intolerance in CHF.

Aged↗
PubMed1998

Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure.

BACKGROUND: The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure (CHF). Endothelial dysfunction is a key feature of CHF, contributing to increased peripheral vasoconstriction and impaired exercise capacity. Local handgrip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF. METHODS AND RESULTS: Twenty patients were prospectively randomized to a training group (n=10, left ventricular ejection fraction [LVEF] 24+/-4%) or a control group (n=10, LVEF 23+/-3%). At baseline and after 6 months, peak flow velocity was measured in the left femoral artery using a Doppler wire; vessel diameter was determined by quantitative angiography. Peripheral blood flow was calculated from average peak velocity (APV) and arterial cross-sectional area. After exercise training, nitroglycerin-induced endothelium-independent vasodilation remained unaltered (271% versus 281%, P=NS). Peripheral blood flow improved significantly in response to 90 microg/min acetylcholine by 203% (from 152+/-79 to 461+/-104 mL/min, P<0.05 versus control group) and the inhibiting effect of L-NMMA increased by 174% (from -46+/-25 to -126+/-19 mL/min, P<0.05 versus control group). Peak oxygen uptake increased by 26% (P<0.01 versus control group). The increase in peak oxygen uptake was correlated with the endothelium-dependent change in peripheral blood flow (r=0.64, P<0. 005). CONCLUSIONS: Regular physical exercise improves both basal endothelial nitric oxide (NO) formation and agonist-mediated endothelium-dependent vasodilation of the skeletal muscle vasculature in patients with CHF. The correction of endothelium dysfunction is associated with a significant increase in exercise capacity.

Blood Flow Velocity↗
PubMed1998

Complete coding sequence of inducible nitric oxide synthase from human heart and skeletal muscle of patients with chronic heart failure.

The presence of the inducible nitric oxide synthase (iNOS) has previously been reported in heart and skeletal muscle of patients with chronic heart failure, where it is thought to be involved in the pathogenesis of dilated cardiomyopathy or of exercise intolerance observed in patients with chronic heart failure. To identify the iNOS of these human tissues the cDNA sequence was determined using reverse transcription polymerase chain reaction (RT-PCR). The deduced amino acid sequence of human heart and skeletal muscle shows a 99% identity between each other. The amino acid sequence was distinct from the constitutively expressed nitric oxide synthases. A 98% identity at the protein level was detected to rat vascular smooth muscle iNOS, whereas the homology to human hepatocyte iNOS was only 79%. The cofactor binding sites in the reported iNOS from human heart and skeletal muscle are highly conserved. The iNOS sequence described in this report is the first one isolated directly from human tissue expressing iNOS in the circumstances of chronic heart failure.

Amino Acid Sequence↗
PubMed1998

Sensing lead insulation defect resulting in a damage of the ICD pulse generator case.

Eight months after ICD implantation with an electrically active case the patient presented with ICD system sensing failure. Upon reoperation, we found an insulation defect of the proximal sensing lead and the generator case showed arc marks suggesting a short circuit between the sensing lead and case. The generator was replaced, the original sensing lead insulated, and a new sensing lead inserted. Bench testing of the explanted generator showed a damaged internal circuitry. Proximal lead insulation defects combined with electrically active cases may result in damage of the case. The potential damage of internal circuitry warrants generator replacement.

Defibrillators, Implantable↗
PubMed1997

Attenuated progression of coronary artery disease after 6 years of multifactorial risk intervention: role of physical exercise.

BACKGROUND: It was the aim of this study to assess the long-term effects of physical exercise and low-fat diet on the progression of coronary artery disease. At the beginning of the study, 113 male patients with coronary artery disease were randomized to an intervention group (n=56) or a control group (n=57); 90 patients (80%) could be reevaluated after 6 years. METHODS AND RESULTS: Patients in the intervention group (n=40) showed a reduction in total serum cholesterol (6.03+/-1.03 versus 5.67+/-1.01 mmol/L; P<.03) and triglyceride levels (1.94+/-0.8 versus 1.6+/-0.89 mmol/L; P<.005) and maintained their initial body mass index (26+/-2 versus 27+/-2 kg/m2; P=NS), but results were not statistically different from the control group (n=50) (total serum cholesterol, 6.05+/-1.02 versus 5.79+/-0.88 mmol/L; triglycerides, 2.25+/-1.28 versus 1.85+/-0.96 mmol/L [both P=NS]; body mass index, 26+/-2 versus 28+/-3 kg/m2 [P<.0001]). In the intervention group, there was a significant 28% increase in physical work capacity (166+/-59 versus 212+/-89 W; P<.001), whereas values remained essentially unchanged in the control group (165+/-51 versus 170+/-60 W; P=NS; between groups, P<.05). In the intervention group, coronary stenoses progressed at a significantly slower rate than in the control group (P<.0001). Energy expenditure during exercise was assessed in a subgroup; patients with regression of coronary stenoses spent an average of 1784+/-384 kcal/wk (approximately 4 hours of moderate aerobic exercise per week). Multivariate regression analysis identified only physical work capacity as independently contributing to angiographic changes. CONCLUSIONS: After 6 years of multifactorial risk intervention, there is significant and persistent improvement in lipoprotein levels and physical work capacity, which results in a significant retardation of disease progression. These beneficial effects appear to be largely due to chronic physical exercise.

Adult↗
PubMed1997

Increased inducible nitric oxide synthase in skeletal muscle biopsies from patients with chronic heart failure.

In addition to left ventricular pump failure and low cardiac output, structural and metabolic alterations of skeletal muscle are thought to contribute to exercise intolerance seen in patients with CHF. Studies using cardiac myocytes have implicated nitric oxide elaborated by inducible nitric oxide synthase (iNOS) as a potential agent associated with the genesis of dilated cardiomyopathy. The present study was designed to locate iNOS in the working skeletal muscle of patients with congestive heart failure. Specific antibodies were used to detect iNOS by immunohistochemistry in skeletal muscle biopsies (m. vastus lateralis) of 37 patients with left ventricular pump failure and 8 normal controls. The expression was restricted to skeletal muscle myocytes and was increased five- to ninefold in patients with chronic heart failure. There was no statistically significant difference in iNOS expression between patients with dilated cardiomyopathy and those with ischemic cardiomyopathy. The finding of a locally increased expression of iNOS and the experimental evidence that NO attenuates the contractile performance of the skeletal muscle suggest that the expression of iNOS may be responsible for the exercise intolerance seen in patients with chronic heart failure.

Adult↗
PubMed1997

[Comparative studies of the rate of restenosis after implantation of Palmaz-Schatz and AVE-Micro stents].

Late results of interventional procedures utilizing coronary stents are largely determined by the rate of restenosis. So far few data are available addressing the effect of stent design, implantation pressure and morphologic factors on this crucial variable. Therefore we analyzed the coronary angiograms obtained in 259 patients before, immediately after and at 3 to 6 months following stent implantation for obstructive coronary disease. A total of 196 AVE-Micro-Stents and 142 Palmaz-Schatz-Stents were implanted into 307 stenoses. In 126 stenoses there were implanted only Palmaz-Schatz-Stents, in 170 only AVE-Micro-Stents and in 11 stenoses there were implanted Palmaz-Schatz- as well as Micro-Stents. Restenosis was defined as an over 50% stenosis at follow up. No significant difference was detected with regard to global restenosis rate at an average of 4 months following implantation (Palmaz-Schatz 33%, Micro-Stent 27%). If results were analyzed according to implantation pressure however, there was a significantly lower restenosis rate for AVE-Micro-Stents implanted with > 10 atm (17%) as compared to < or = 10 atm (35%, p < 0.02) and as compared to Palmaz-Schatz-Stents (34%, p < 0.02), which were also implanted with high pressure over 10 atm. In addition to implantation pressure, vessel segment and morphology of stenosis proved to be important determinants of late results. In this series of patients the AVE-Micro-Stent compared favourably to the Palmaz-Schatz-Stent not only with respect to a significantly lower restenosis rate, when implanted with pressures > 10 atm, but also with regard to its superior flexibility and handling characteristics.

Aged↗
PubMed1997

Effects of endurance training on mitochondrial ultrastructure and fiber type distribution in skeletal muscle of patients with stable chronic heart failure.

OBJECTIVES: The present study was designed to evaluate the effects of an ambulatory training program in patients with chronic heart failure (CHF) on the ultrastructural morphology of mitochondria and fiber type distribution of skeletal muscle and its relation to peripheral perfusion. BACKGROUND: Recent studies in patients with CHF have suggested that intrinsic abnormalities in skeletal muscle can contribute to the development of early lactic acidosis and fatigue during exercise. METHODS; Patients were prospectively randomized to either a training group (n = 9; mean [+/- SD] left ventricular ejection fraction [LVEF] 26 +/- 10) participating in an ambulatory training program or to a physically inactive control group (n = 9; LVEF 28 +/- 10%). At baseline and after 6 months, patients underwent symptom-limited bicycle exercise testing with measurement of central and peripheral hemodynamic variables as well as percutaneous needle biopsies of the vastus lateralis muscle. The mitochondrial ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry; cytochrome c oxidase activity was visualized by histochemistry and subsequently quantitated by morphometry. The fiber type distribution was determined by adenosine triphosphatase staining. RESULTS: After 6 months of exercise training there was a significant increase of 41% in the surface density of cytochrome c oxidase-positive mitochondria (SVMOcox+) (p < 0.05 vs. control) and of 43% in the surface density of mitochondrial cristae (SVMC) (p < 0.05 vs. control). Furthermore, exercise training induced a 92% increase in the surface density of the mitochondrial inner border membrane (p < 0.05 vs. control). In contrast, the total number of cytochrome c oxidase-positive mitochondria remained essentially unchanged. Exercise-induced improvement in peak oxygen uptake was closely linked to changes in SVMOcox+ (p < 0.01, r = 0.66). After exercise training, changes in submaximal femoral venous lactate levels were not related to changes in submaximal leg blood flow (r = -0.4), but were inversely related to changes in the volume density of mitochondria (p = 0.01; r = -0.6) as well as to changes in SVMC (p < 0.05; r = -0.5). After exercise training there was a "reshift" from type II to type I fibers (p < 0.05 vs. control). CONCLUSIONS: Patients with CHF who engage in regular physical exercise show enhanced oxidative enzyme activity in the working skeletal muscle and a concomitant reshift to type I fibers. These exercise-induced changes in oxidative capacity appear to be unrelated to changes in peripheral perfusion.

Electron Transport Complex IV↗
PubMed1996

Predictive value of lipid profile for salutary coronary angiographic changes in patients on a low-fat diet and physical exercise program.

In this study, 113 patients with modestly elevated levels of low-density lipoprotein cholesterol (<210 mg/dl) and coronary artery disease were randomized to an intervention group (n=56) or a control group (n=57). The intervention program consisted of daily exercise and a low-fat diet according to the American Heart Association's recommendation phase III; patients in the control group received "usual care" rendered by their private physician. After 1 year, complete data were available for all 92 patients (intervention: n=40; control: n=52) who underwent repeat coronary angiography. During the study course, patients in the intervention group showed an increase in apolipoprotein A-I(123 +/- 18 vs 129 +/- 20 mg/dl; p < 0.02) and apolipoprotein A-I/B (1.3 +/- 0.4 vs 1.5 +/- 0.4; p <0.01) and a decrease in apolipoprotein B (99 +/- 20 vs 89 +/- 18 mg/dl; p < 0.01), while apolipoprotein A-II remained unchanged (38 +/- 6 vs 38 +/- 6 mg/dl; p=NS). In the control group, there were no significant changes (apolipoprotein A-I, 124 +/- 17 vs 128 +/- 13 mg/dl; apolipoprotein A-II, 38 +/- 6 vs 39 +/- 6 mg/dl; apolipoprotein B, 100 +/- 21 vs 99 +/- 16 mg/dl; apolipoprotein A-I/B, 1.3 +/- 0.3 vs 1.4 +/- 0.5; all p=NS). As previously reported, there was a significant retardation of progression in patients in the intervention group (progression 23%, no change 45%, regression 32%) compared with the control group (progression 48%, no change 35%, regression 17%) (p < 0.05). Although retardation of progression was significantly associated with an increase in apolipoprotein A-I/B and a decrease in apolipoprotein B (p < 0.05), these gave way in multivariate analysis to changes in total cholesterol/high-density lipoprotein cholesterol, absolute levels of low-density lipoprotein cholesterol, and, in a subgroup of patients, to leisure-time physical activity (all p < 0.05). These data demonstrate that an intervention based on a low-fat diet and intensive physical exercise is capable of improving apolipoprotein levels, associated with retardation of progression of coronary artery disease. However, total cholesterol/high-density lipoprotein cholesterol and low-density lipoprotein cholesterol appear superior to apolipoproteins as metabolic markers for effective treatment in patients with coronary artery disease.

Adult↗
PubMed1996

Regression and non-progression of coronary artery disease with exercise.

Metabolic interventions using low-fat diets and lipid level-lowering drugs were successful in controlling the progression rate of coronary artery disease and reduced the number of clinical events. Only a few studies have examined the role of regular physical exercise as a therapeutic instrument to enhance these beneficial effects. The design of the available studies did not permit differentiation among the effects of physical exercise, lowering of serum cholesterol level and stress management. The decrease in total serum cholesterol level ranged from 10 to 24%, the change in high-density lipoprotein cholesterol level from -3 to +12%. There was predominant regression of coronary artery lesions in one study (the Lifestyle trial); in the other two trials, progression was either halted (in the Heidelberg trial) or reduced (in the Stanford trial). In contrast, significant progression was noted in all of the control groups. In addition to the beneficial effects on progression of coronary artery disease, patients taking regular physical exercise experienced significant improvements in their physical work capacity (+25%) and in myocardial perfusion, and reduction in anginal pain. There were fewer clinical events in the intervention group in the Stanford study only, whereas clinical events tended to be more frequent in the other studies because of exercise-induced arrhythmias.

Coronary Disease↗
PubMed1996

[Physical training of patients with high grade compromise of heart pumping function].

Regular exercise is regarded as a mainstay of physical fitness and endurance; it remains to be determined, however, whether patients with severe impairment of left ventricular performance derive profit from this treatment to the same extent as patients with normal myocardial contractility. Irrespective of the underlying cause profound changes are initiated by heart failure with respect to neurohumoral factors, ultrastructure of skeletal muscle, and peripheral vascular resistance. Initially these changes are set in motion by the inability of the heart to provide sufficient flow to the peripheral organs; eventually, however, they attain a role of their own and contribute to the disease independently. Intolerance of physical exercise, in particular, is not so much the result of pulmonary congestion and low cardiac output. Reduction of oxidative capacity of skeletal muscle, excessive peripheral vascular resistance, and impairment of vasodilatation in response to metabolic needs seem to contribute more to this incapacitating symptom. Until recently, physical exercise was regarded as harmful in patients with severe impairment of left ventricular performance; in order to prevent further deterioration patients were frequently treated by bedrest. Controlled trials, however, have shown that regular physical exercise in these patients may favourably influence the course of this disease, or even reverse some harmful changes. The following results were obtained in a group of 12 patients with depressed left ventricular ejection fraction (LV-EF 25 +/- 10%) participating in an ambulatory training program: 1) Left ventricular end-diastolic dimension was significantly reduced from 70 +/- 5 mm to 66 +/- 3 mm (p < 0.05). 2) There was significant improvement of skeletal muscle perfusion and oxygen uptake during submaximal and maximal exercise resulting in delayed onset of anaerobic metabolism and increased exercise capacity. 3) Intrinsic change of skeletal muscle ultrastructure were in part corrected; mitochondrial volume density increased significantly. There was a close correlation between changes in maximal oxygen uptake and changes of cytochrome-C-oxidase positive mitochondrial volume density. 4) Cardiac output and left ventricular ejection fraction in response to exercise, however, remained unchanged, indicating that no significant central effects were achieved by regular exercise.

Cardiac Output↗