Exercise Training and Bleed Viscosity in Patients With Ischemic Heart Disease

Abstract

Several studies have suggested that regular exercise in healthy persons improves blood viscosity.1.Letcher R.I. Pickering T.G. Chien S. Laragn J.H. Effects of exercise on plasma viscosity in athletes and sedentary normal subjects.Clin Cardiol. 1981; 4: 172-179Crossref PubMed Scopus (71) Google Scholar, 2.Charm S.E. Pax H. Kurland G.S. Reduced plasma viscosity among joggers compared with non-joggers.Biorheology. 1979; 16: 185-189Crossref PubMed Scopus (45) Google Scholar, 3.Ernst E. Matrai A. Aschembrenner E. Will V. Relationship between fitness and blood fluidity.Clin Hemorheol. 1985; 5: 507-510Google Scholar, 4.Dintenfass L. Lake B. Exercise fitness, cardiac work and blood viscosity factors in patients and normals.Eur Surg Res. 1976; 8: 174-184Crossref PubMed Scopus (29) Google Scholar, 5.Ernst E. Changes in blood rheology produced by exercise.JAMA. 1985; 253: 2962-2963Crossref PubMed Scopus (50) Google Scholar Regular exercise and exercise training have been shown to have several beneficial effects, including the prevention and modification of hypertension, hypercholesterolemia, diabetes mellitus, and obesity, and to have a role in both the primary and secondary prevention of coronary vascular events.6.Levine G.N. Balady G.J. The benefits and risks of exercise training: the exercise prescription.in: Advances in Internal Medicine. 38. Mosby Year Book, Boston1993: 57-79Google Scholar Whether exercise training, as prescribed in standard cardiac rehabilitation programs, can improve blood rheology has not been previously investigated. This study assesses whether a standard 10-week program of moderate-intensity aerobic exercise training had beneficial effects on whole blood viscosity and the factors that influence it among consecutive patients with ischemic heart disease who enrolled in cardiac rehabilitation. Several studies have suggested that regular exercise in healthy persons improves blood viscosity.1.Letcher R.I. Pickering T.G. Chien S. Laragn J.H. Effects of exercise on plasma viscosity in athletes and sedentary normal subjects.Clin Cardiol. 1981; 4: 172-179Crossref PubMed Scopus (71) Google Scholar, 2.Charm S.E. Pax H. Kurland G.S. Reduced plasma viscosity among joggers compared with non-joggers.Biorheology. 1979; 16: 185-189Crossref PubMed Scopus (45) Google Scholar, 3.Ernst E. Matrai A. Aschembrenner E. Will V. Relationship between fitness and blood fluidity.Clin Hemorheol. 1985; 5: 507-510Google Scholar, 4.Dintenfass L. Lake B. Exercise fitness, cardiac work and blood viscosity factors in patients and normals.Eur Surg Res. 1976; 8: 174-184Crossref PubMed Scopus (29) Google Scholar, 5.Ernst E. Changes in blood rheology produced by exercise.JAMA. 1985; 253: 2962-2963Crossref PubMed Scopus (50) Google Scholar Regular exercise and exercise training have been shown to have several beneficial effects, including the prevention and modification of hypertension, hypercholesterolemia, diabetes mellitus, and obesity, and to have a role in both the primary and secondary prevention of coronary vascular events.6.Levine G.N. Balady G.J. The benefits and risks of exercise training: the exercise prescription.in: Advances in Internal Medicine. 38. Mosby Year Book, Boston1993: 57-79Google Scholar Whether exercise training, as prescribed in standard cardiac rehabilitation programs, can improve blood rheology has not been previously investigated. This study assesses whether a standard 10-week program of moderate-intensity aerobic exercise training had beneficial effects on whole blood viscosity and the factors that influence it among consecutive patients with ischemic heart disease who enrolled in cardiac rehabilitation. Consecutive patients enrolling in the cardiac rehabilitation program at Boston University Medical Center Hospital who met study criteria were recruited. Entry criteria included: (1) existence of significant coronary artery disease, as established by either cardiac catheterization, documented past myocardial infarction, or positive exercise test results; (2) ability to perform aerobic exercise; and (3) willingness to participate in the study. Exclusion criteria consisted of: (1) concurrent use of pentoxifylline or any diuretic; (2) known liver, inflammatory, or infectious disease, or cancer; and (3) myocardial infarction within the preceding 3 weeks. At baseline, all patients underwent an initial history, physical examination, and symptom-limited treadmill exercise test. An exercise prescription was developed for each subject and consisted of 30 to 40 minutes of supervised dynamic exercise 3 times per week at a target heart rate range of 60% to 85% of the heart rate reserve, as determined from the exercise tolerance test. After approximately 10 weeks of exercise training, a symptom-limited exercise tolerance test was again performed. To assess the effect of exercise training on the heart rate response to matched levels of submaximal exercise, the heart rate was measured at the highest stage that was common to both initial and follow-up exercise tests. Peak MET levels were estimated based on published regression formulas for hand-held treadmill exercise.7.McConnell T.R. Clark B.A. Prediction of maximal oxygen consumption during handrail-supported treadmill exercise.J Cardiopulm Rehabil. 1987; 7: 324-331Crossref Google Scholar Blood samples were collected before and after the 10-week exercise training program. All blood samples were collected between 9 A.M. and noon, before patients had engaged in any exercise for that day. Plasma and whole blood viscosity were measured with a Brookfield RVT 0.4 coneplate viscometer. Blood and plasma samples were maintained at a temperature of 37.0 °C before and during viscosity measurements. Plasma viscosity was measured in triplicate at a shear rate of 1,500 s-1. Whole blood viscosity was measured in triplicate at shear rates of 15, 37.5, 75, 150, 300, and 750 s-1, representative of the shear rates in the coronary circulation.8.Aatabek H.B. Ling S.C. Patel D.J. Analysis of coronary flow fields in thoracotomized dogs.Ore Res. 1975; 37: 752-761Google Scholar,9.Most A.S. Ruocco N.A. Gewirtz H. Effect of a reduction in blood viscosity on maximal myocardial oxygen delivery distal to a moderate coronary stenosis.Circulation. 1986; 74: 1085-1092Crossref PubMed Scopus (109) Google Scholar Average whole blood viscosity was determined by averaging the viscosity at these 6 shear rates. Twenty patients were recruited for the study and underwent initial evaluation. Five patients did not complete exercise training, leaving 15 patients who were used in data analysis. These 15 subjects who completed training attended 86 ± 15% of scheduled sessions. No medication changes or cardiac events occurred during the training period. Exercise training in these subjects resulted in a marked training effect, as demonstrated by statistically significant increases in exercise time (497 ± 118 vs 648 ± 144 seconds, p < 0.001) and estimated peak MET level (6.8 ± 2.0 vs 9.0 ± 1.7 METs, p < 0.001), and a significant reduction in heart rate at matched submaximal work rates (118 ± 25 vs 102 ± 17 beats/min, p = 0.012). Rheologic measurements before and after exercise training are displayed in Table I. Values for hematocrit, fibrinogen, erythrocyte sedimentation rate, plasma viscosity, and average whole blood viscosity after exercise training were not significantly different from the corresponding values before exercise training.Table IParameters of Blood Rheology*p=NS for all values.Before TrainingAfter TrainingHematocrit (%)39.7 ± 2.5041.0 ± 3.50Fibrinogen (mg/dl)307 ± 55.4322 ± 89.5Sedimentation rate (mm/hr)26 ± 1524 ± 14Plasma viscosity (cP)1.41 ± 0.101.46 ± 0.09Whole blood viscosityAt 15 s-1 (cP)6.90 ± 1.137.98 ± 2.30At 37.5 s-1 (cP)5.80 ± 0.646.11 ± 1.15At 75 S·1 (cP)5.28 ± 0.565.47 ± 0.86At 150 s-1 (cP)4.57 ± 0.484.67 ± 0.70At 300 s-1 (cP)4.44 ± 0.454.57 ± 0.65At 750 s-1 (cP)4.03 ± 0.554.12 ± 0.55Average whole blood5.20 ± 0.585.46 ± 1.00viscosity (cP)Values are expressed as mean ± SD. cP = centipoise.* p = NS for all values. Open table in a new tab Values are expressed as mean ± SD. cP = centipoise. The importance of blood rheology in the pathogenesis of coronary artery disease was first recognized over 25 years ago.10.Dinlenfass L. Blood rheology in pathogenesis of the coronary heart diseases.Am Heart J. 1969; 77: 139-147Crossref PubMed Scopus (40) Google Scholar Blood viscosity is 1 of the 2 major determinants of flow resistance,11.Chien S. Hemorheology in clinical medicine.Clin Hemorheol. 1982; 2: 137-142Google Scholar and the pressure gradient across a coronary stenosis is directly proportional to whole blood viscosity.12.Lipscomb K. Hooten S. Effect of stenotic dimensions and blood flow on the hemodynamic significance of model coronary artery stenoses.Am J Cardiol. 1978; 42: 781-792Abstract Full Text PDF PubMed Scopus (36) Google Scholar Elevations in hematocrit have been shown to increase whole blood viscosity and result in increased coronary vascular resistance and decreased coronary blood flow.13.Kuramoto K. Matsushita S. Matsuda T. Junichiro M. Sakai M. Isawaki T. Shinagawa T. Moroki N. Murakami M. Effect of hematocrit and viscosity on coronary circulation and myocardial oxygen utilization.Jpn Ore J. 1980; 44: 443-448Google Scholar Increased degrees of red blood cell aggregation may lead to a displacement of platelets toward the endothelium, an enhancement of plateletadhesive properties, and subsequently better enable the formation of platelet aggregates.14.Lowe G.D.O. Blood rheology in arterial disease.Clin Sci. 1986; 71: 137-146Crossref PubMed Scopus (194) Google Scholar More viscous blood can lead to higher shear stresses on the coronary endothelium, which could lead to an increased incidence of plaque rupture. The manner in which abnormalities of blood viscosity lead to an increased incidence of clinical ischemic heart disease may thus be multifactorial. Several studies have demonstrated a positive correlation between regular exercise or physical fitness and blood fluidity. Two studies have found that those who jog regularly have lower blood viscocity than sedentary controls.1.Letcher R.I. Pickering T.G. Chien S. Laragn J.H. Effects of exercise on plasma viscosity in athletes and sedentary normal subjects.Clin Cardiol. 1981; 4: 172-179Crossref PubMed Scopus (71) Google Scholar,2.Charm S.E. Pax H. Kurland G.S. Reduced plasma viscosity among joggers compared with non-joggers.Biorheology. 1979; 16: 185-189Crossref PubMed Scopus (45) Google Scholar Physical fitness has been shown to be associated with lower whole blood and plasma viscosity, less red blood cell aggregation, and lower fibrinogen levels.3.Ernst E. Matrai A. Aschembrenner E. Will V. Relationship between fitness and blood fluidity.Clin Hemorheol. 1985; 5: 507-510Google Scholar,4.Dintenfass L. Lake B. Exercise fitness, cardiac work and blood viscosity factors in patients and normals.Eur Surg Res. 1976; 8: 174-184Crossref PubMed Scopus (29) Google Scholar These studies, along with 2 studies that have demonstrated improvements in blood viscosity after a period of exercise training,5.Ernst E. Changes in blood rheology produced by exercise.JAMA. 1985; 253: 2962-2963Crossref PubMed Scopus (50) Google Scholar,15.Ernst E. Matrai A. Intermittent claudication, exercise, and blood rheology.Circulation. 1987; 76: 1110-1114Crossref PubMed Scopus (166) Google Scholar provide reason to hypothesize that the exercise training that patients perform during cardiac rehabilitation may have beneficial effects on their blood rheology. However, despite exercise training sufficient to achieve a training effect, no significant changes in the in vitro measurements of whole blood viscosity and the rheologic factors that affect it were observed in this prospective study. This differs from results reported in other studies of exercise training in subjects without coronary artery disease. Ernst5.Ernst E. Changes in blood rheology produced by exercise.JAMA. 1985; 253: 2962-2963Crossref PubMed Scopus (50) Google Scholar investigated changes in blood rheology in a group of 12 previously sedentary persons who underwent 3 months of aerobic training, consisting of an average of 4 hours of intensive exercise for 7 days each week. Significant improvements in red blood cell deformation and significant decreases in whole blood viscosity were observed.5.Ernst E. Changes in blood rheology produced by exercise.JAMA. 1985; 253: 2962-2963Crossref PubMed Scopus (50) Google Scholar Ernst and Matrai15.Ernst E. Matrai A. Intermittent claudication, exercise, and blood rheology.Circulation. 1987; 76: 1110-1114Crossref PubMed Scopus (166) Google Scholar studied 42 patients with claudication, half of whom underwent treadmill exercise twice daily, 5 times per week, for 2 months. Although there were no changes in measured rheology parameters in the control group, the exercise group manifested favorable changes in blood and plasma viscosity, blood cell deformation, and red cell aggregation. These studies used a more intensive exercise training regimen than that used in standard cardiac rehabilitation; it may be that the exercise training regimen employed in cardiac rehabilitation centers is not of sufficient intensity to achieve beneficial effects on blood rheology. It is also possible that greater amounts of exercise are required to yield changes in rheologic parameters, although the 10-week duration in our study is similar to that of others in which a significant change was seen. Thus, the standard 10-week cardiac rehabilitation program of moderate-intensity dynamic exercise leads to a highly significant improvement in exercise tolerance, but does not have a beneficial effect on blood viscosity in patients with coronary artery disease.