Correspondence
Exercise and Coronary Endothelial Function
N Engl J Med 2000; 343:147-148July 13, 2000
- Article
To the Editor:
Hambrecht and colleagues (Feb. 17 issue)1 report that exercise training improves endothelial function in the coronary circulation. In their discussion of the potential mechanisms involved, the authors correctly point out that the recruitment of collateral vessels may enhance coronary blood flow in ischemic areas of the myocardium. However, they state that although there is evidence that exercise training improves collateral circulation in animals, such angiographic evidence is lacking in humans.
The authors fail to mention that there is angiographic evidence of improvement in the collateral circulation after exercise training in patients with coronary artery disease. We recently showed that moderate exercise training increases thallium uptake by 30 percent.2 Coronary angiography demonstrated a substantial improvement in the collateral circulation, explaining in part the improvement in myocardial perfusion. Hambrecht et al. did not measure myocardial perfusion. Furthermore, exercise training improved the endothelial response to acetylcholine but did not restore it to normal levels, suggesting that the improvement in endothelial function alone may not explain the increase in myocardial perfusion. Thus, the study by Hambrecht et al. does not provide direct evidence that the increase in myocardial perfusion is the result of the improvement in endothelial function.
A decrease in myocardial ischemia was reported by the same authors3 in patients with progression of stenotic lesions, suggesting that collateral circulation may be responsible in part for the increase in myocardial perfusion. Thus, the mechanism of the increased perfusion is likely to be the formation of collateral vessels, as detected by conventional angiography. However, small collateral vessels may not always be visible on conventional angiography, a limitation that may lead to the erroneous conclusion that there is no evidence of collateralization.
3 ReferencesDemetrios Georgiou, M.D.
Columbia University, New York, NY 10010Romualdo Belardinelli, M.D.
Lancisi Institute, 60100 Ancona, Italy1
Hambrecht R ,Wolf A ,Gielen S , et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med 2000;342:454-460
Full Text | Web of Science | Medline2
Belardinelli R ,Georgiou D ,Ginzton L ,Cianci G ,Purcaro A . Effects of moderate exercise training on thallium uptake and contractile response to low-dose dobutamine of dysfunctional myocardium in patients with ischemic cardiomyopathy. Circulation 1998;97:553-561
Web of Science | Medline3
Schuler G ,Hambrecht R ,Schlierf G , et al. Regular physical exercise and low-fat diet: effects on progression of coronary artery disease. Circulation 1992;86:1-11
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: In our article, we reported that a four-week period of high-intensity exercise training has the potential to improve endothelial dysfunction associated with nonstenotic coronary atherosclerosis. Georgiou and Belardinelli point out that an increase in collateral circulation represents the most important mechanism responsible for the improvement in myocardial perfusion after exercise training in patients with occlusive coronary artery disease and exercise-induced ischemia. Until now, however, there has been no evidence that exercise training in patients with stable coronary artery disease and preserved left ventricular function improves coronary collateral circulation. As correctly mentioned, we previously investigated the effect of a low-fat diet in combination with a vigorous exercise-training program lasting one year on the progression of coronary artery disease.1 This intervention retarded the progression of coronary atherosclerosis; however, the intervention improved myocardial perfusion even in patients with progression of coronary artery disease. To prove the hypothesis that increases in the formation of coronary collateral vessels are responsible for improved myocardial perfusion, we screened all the angiograms for coronary collateral vessels. However, we were unable to detect any beneficial effect of exercise training on myocardial collateralization.2
In contrast to our own experience, Belardinelli et al. reported that only eight weeks of moderate exercise training in 46 patients with ischemic cardiomyopathy was sufficient to enhance both myocardial thallium uptake and the contractile response of dysfunctional myocardium to low doses of dobutamine.3 A subgroup analysis of 12 patients who trained and underwent repeated coronary angiography revealed an increase in coronary collaterals, which were visually classified. We acknowledge that this study provides some evidence that collateral growth may also occur in humans with ischemic cardiomyopathy in response to exercise training. However, to the best of our knowledge, such angiographic evidence is still lacking in patients with coronary artery disease and normal left ventricular function.
An important reason the detection of collaterals is an angiographic challenge is that they are recruited mainly in response to ischemia — for instance, during physical exercise. We have therefore initiated a study in which coronary angiography (by the Sones technique) is performed during cycle ergometry in patients with chronic coronary occlusions before and after exercise training. In our opinion, the data currently available from clinical trials are not convincing enough to establish that exercise training reduces exercise-induced myocardial ischemia by an increase in collateralization. However, we share with Georgiou and Belardinelli the hypothesis that the recruitment of new or existing intramyocardial collaterals in response to exercise may contribute to improved myocardial perfusion in patients with symptomatic coronary artery disease.
3 ReferencesRainer Hambrecht, M.D.
Stephan Gielen, M.D.
Gerhard Schuler, M.D.
University of Leipzig Heart Center, 04289 Leipzig, Germany1
Schuler G ,Hambrecht R ,Schlierf G , et al. Regular physical exercise and low-fat diet: effects on progression of coronary artery disease. Circulation 1992;86:1-11
Web of Science | Medline2
Niebauer J ,Hambrecht R ,Marburger C , et al. Impact of intensive physical exercise and low-fat diet on collateral vessel formation in stable angina pectoris and angiographically confirmed coronary artery disease. Am J Cardiol 1995;76:771-775
CrossRef | Web of Science | Medline3
Belardinelli R ,Georgiou D ,Ginzton L ,Cianci G ,Purcaro A . Effects of moderate exercise training on thallium uptake and contractile response to low-dose dobutamine of dysfunctional myocardium in patients with ischemic cardiomyopathy. Circulation 1998;97:553-561
Web of Science | Medline
