Cardiovascular Response in Anemia
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《美国医学杂志》
1 Departments of Cardiology, Christian Medical College, Ludhiana, Punjab, India
2 Department of Pediatrics, Christian Medical College, Ludhiana, Punjab, India
Abstract
Objective: To study the functional consequences of nutritional anemia by evaluating the exercise performance in these children. Methods: The study was conducted on 30 each of anemic and normal children of both sexes aged between 7 and 14 years. Relevant history was taken, and detailed examination was done. These children were classified according to severity of anemia based on hemoglobin estimation as mild (10-11.9 g/dl), moderate (7-9.9 g/dl) and normal (>12g/dl). Children with severe anemia (Hb <7g/dl), heart disease, non-nutritional anemia, acute febrile or respiratory illness were excluded. The subjects were tested on Mortara X Scribe colour stress treadmill using the modified Bruce protocol. Continuous computerised electrocardiographic analysis was done. The parameters studied included heart rate, systolic blood pressure, double product (DP = HRxSBP), ECG changes, metabolic equivalents (METS) and exercise duration. The end point of the test was a HR of 170/min (non-fatigue group) or inability to perform further (fatigue group). Statistical analysis was done by appropriate tests. Results: Fifteen children each with mild and moderate anemia and 30 age-matched controls were enrolled in the study. There was no significant difference in the resting HR, exercise duration or DP between the cases and controls. Thirty-one children reached the target HR (non-fatigue group). The end-point HR was significantly lesser among the anemic children in the fatigue group (P 0.04). The percent gain of SBP, at peak exercise (P 0.0007) and recovery SBP as percent of resting SBP (p 0.006) were significantly more in the anemic children, more so in the mildly anemic ones. Lesser METS was achieved by anemics as compared to controls (P 0.04). ECG changes occurred significantly more often in anemic children, 53.8% of those with changes being moderately anemic, the main abnormality being ST depression. None developed arrhythmia during exercise testing. Conclusion: The cardiovascular response to physical exercise is compromised in children with nutritional anemia and hence these children may never attain their full potential in various school activities. Prevention of anemia should be a priority in school going children.
Keywords: Anemia; Cardiovascular ; Children; Exercise test
Anemia is a worldwide problem, especially in developing countries where it is mainly multifactorial in origin.[1] A high incidence of anemia has been reported in India not only in the lower socioeconomic class but also in the affluent urban areas. The functional consequences of anemia in the human especially in children are of particular concern in view of its high prevalence in this age group.[2]
Anemia has a negative impact on physical work capacity in different age groups as measured by changes in maximal oxygen uptake and other metabolic parameters.[3]-[5] Exercise testing is a common physiological stress used to elicit cardiovascular abnormalities not present at rest and to determine adequacy of cardiac function.[6] The changes in heart rate, blood pressure, respiration and perceived levels of exertion provide data that permit quantitative estimation of cardiovascular functioning and conditioning.[7]
The treadmill has been used widely in the testing of exercise fitness in children in various congenital heart defects.[8]-[9] It is easy to use in children since only the ability to walk is required, numerous gradations of exercise level can be achieved and extensive standards have been developed.[7] Several studies have been done on exercise tolerance in normal children in western countries and occasional ones in India.[7],[10]-[12] The present study was undertaken to evaluate the exercise performance in Punjabi children with nutritional anemia.
Material and methods
The present study was conducted on 30 children with nutritional anemia and 30 normal children of both sexes aged between 7-14 years who attended the outpatient pediatric clinic of a teaching hospital. Relevant history was taken and detailed physical examination was done. The diagnosis of anemia was made by clinical assessment, hemoglobin estimation and peripheral smear. Children were classified according to the severity of anemia as mild (10-11.9g/dl), moderate (7-9.9 g/dl) and severe (<7 g/dl) as per WHO criteria.[1] Normal children with a hemoglobin value of 12 g/dl and above were enrolled as controls. Children with acute illness, cardiovascular, respiratory or musculoskeletal disorders, and with non-nutritional anemia or severe anemia were excluded. The cases included 15 each with mild and moderate anemia, enrolled by quota sampling. The subjects were tested on Mortara X Scribe colour stress treadmill. The TMT was done on an empty stomach after obtaining an informed consent from the guardian. A 12 lead electrode system was applied. The subjects were tested according to modified Bruce protocol wherein the Bruce protocol was modified by 2-3 minute warm up stages at 0% grade with 1.7mph and 5% grade with 1.7mph. Continuous computerised electrocardiographic analysis was done. Blood pressure and heart rate were measured in each stage. The end point of the test was any one of the following - heart rate of 170/min (non-fatigue group); inability to perform further (fatigue group); or significant ECG changes. The following parameters were measured and studied: heart rate, systolic blood pressure, double product (HRxBP), exercise duration, metabolic equivalents (METS), and ECG changes. Statistical analysis was done by ANOVA , chi square and Fisher's exact method as applicable.
Results
Thirty anemic children, 15 each with mild and moderate anemia and 30 age matched controls without anemia were studied. The resting HR in these three groups of children was similar being 97.6, 94.7 and 93.1 per minute respectively. The total duration of exercise before reaching the end point of the test was longer in the controls (13.5 min) compared to the mildly anemic (12.8 min) and moderately anemic (12.1) children, but these differences were not significant.
The target HR of 170/min in the non-fatigue group was achieved in 18(60%) controls, but in lesser number of anemics being 7 (46.7%) and 6 (40%) in the mildly and moderately anemic children respectively although the difference was not significant. The fatigue group consisted of the remaining twenty-nine children including 17 (56%) of anemics, who stopped exercise before achieving the target heart rate. In this group, lesser number (64.7%) of anemic children attained a HR >150/min compared to the controls (83.3%). The gain in HR at peak exercise as a percentage of the resting HR is shown in Table 1. In both the fatigue and the non-fatigue groups the gain of 3 75% occurred in lesser number of cases than controls, although the difference was not statistically significant probably on account of the small number of children in each sub group.
Blood pressure responses differed significantly between the groups table2. Mildly anemic children had higher resting systolic BP, more gain in BP at peak exercise and a higher percentage of recovery systolic BP at 1 minute after exercise as compared to the moderately anemic and controls. There were no significant differences in the double product (DP) at rest, gain in DP or recovery DP between cases and controls.
The METS achieved during peak exercise was significantly higher in normal children compared to the anemic group Figure1. Among those who developed significant ECG changes with exercise, 53.8% were moderately anemic Figure2. ST depression (>=1mm) was seen mainly in the moderately anemic subjects (P 0.0015). ST elevation of 1mm or more or changes in T wave morphology were not significantly different in the three groups, but among the 4 children who developed significant ST elevation, 3 were anemic. None of the children developed arrhythmias during exercise or during recovery.
Discussion
In the present study, heart rate limited exercise test was used which is more sensitive than symptom limited exercise test. We observed that anemic children exercised for relatively lesser duration (12.4 min) than normal children (13.4 min) although the difference was not statistically significant. This was comparable to an earlier study by Bhatia et al in which the average endurance time was observed to be significantly lesser in anemic children (8.8 minutes) compared to 11.8 minutes in normal children.[2]
Resting HR in healthy subjects indicates the state of physical conditioning. The lower the resting HR, the better the physical conditioning. In the present study, the mean resting HR was more in mildly and moderately anemic children (97.6 and 94.7 respectively) than in controls (93.1) similar to the observation by Kapoor et al.[13] Heart rate response to exercise in anemic children was less than in controls. Fifty-six percent of the anemic children became fatigued before reaching the maximum HR as compared to only 40% of the controls. Larger proportion (83.3%) of controls were able to attain a HR of more than 150/min compared to the anemics (64.7%). Rapid exhaustion of compensatory mechanisms such as increased cardiac output could result in earlier fatigue which is demonstrated in anemic subjects. We also studied the gain in HR as a percentage of resting HR and this was observed to be lesser in anemic children, table1. These findings are also similar to those by Kapoor et al.[13] The cardiac reserve, which is, depleted in anemic children results in higher resting HR, less gain in HR and prolonged recovery time.
Systolic blood pressure usually increases during exercise. Increasing level of SBP signifies physical adaptations namely increasing stroke volume and cardiac output. [11], [14] The authors observed that the resting SBP and gain in SBP at end point were significantly more in anemic children, being more in the mildly anemic when compared to moderately anemic and the control group. table2, similar to the report by Kapoor et al.[13] The recovery of BP was also significantly slower in anemic children than in the normal. In mildly anemic children the increase in cardiac output as a compensatory mechanism can cause the increase in BP. However in the moderately anemic children there is a failure to do so which can be explained by the decompensation of the myocardium in these children.
The myocardial oxygen uptake reflecting myocardial oxygen consumption is estimated during exercise testing by the product of HR and SBP, the Double Product, also called modified tension time index (MTTI).[15] No significant difference was observed in the DP of patients and controls, but in the report by Kapoor et al the mean values of gain in DP were significantly lesser in anemic children, probably due to decreased cardiac reserve in these children.[7]
Metabolic equivalents (METS) during exercise testing estimate the number of times the maximal oxygen usage under aerobic conditions (V O2 max) is above the basal level. Majority of children who achieved less than 5 METS were moderately anemic while majority of those who achieved more than 12 METS were normal. (p=0.04, Fig 1), the observation being similar to that of other authors.[2],[13],[16] The lower degree of METS achieved by anemic children may be related to skeletal muscle exhaustion rather than reduced cardiac reserve.
Decrease in QRS amplitude, T wave flattening, minor degrees of AV conduction disturbances and ST - T wave changes have been described in the ECG in anemic patients.[17] Significant ECG changes in (33.3%) cases were observed more so in the moderately anemic (46.7%) than in the controls (10%) (p = 0.019). ST depression was the most common evidence of electrical instability Figure2. Anemia is reported to be a common non-coronary cause of ST depression.[6] Among four children who developed ST elevation during exercise, three were anemic. The development of > 1 mm of persistent elevation is considered an abnormal response during exercise.[6] But several authors have found no electrical instability in their study of anemic children.[7],[18]
Conclusion
The duration of exercise, resting heart rate, gain in heart rate as a percentage of resting HR and the double product in anemic children undergoing submaximal treadmill test did not show any significant difference from that of normal children. However, the resting SBP was significantly higher and the recovery of systolic blood pressure was slower in anemic children compared to controls. There were significant ECG changes in anemics as compared to controls. Anemic school-going children may not be able to perform adequately in various school activities. Prevention of anemia and its treatment will go a long way in realising the full potential of these children.
References
1. DeMaeyer EM. Preventing and controlling iron deficiency anaemia through primary health care. Geneva, World Health Organisation. 1989
2. Bhatia D, Seshadiri S. Anemia, undernutrition and physical work capacity of young boys. Indian Pediatr 1987; 24: 133-139.
3. Gopaldas T, Kale M, Bhardwaj P. Prophylactic iron supplementation for underprivileged schoolboys. III. Impact on submaximal work capacity. Indian Pediatr 1985; 22: 745-752.
4. Gardner GW, Edgerton VR, Senewirathne B, Bernard RJ, Ohina Y: Physical work capacity and metabolic stress in subjects with iron deficiency anemia. Am J Clin Nutr 1977; 30: 910-917.
5. Viteri FE, Torun B. Anemia and physical work capacity. Clin Hematol 1974; 3: 609-626.
6. Chaitman B. Exercise stress testing. In Braunwald E, Zipes DP, Lippy P, eds. Heart Disease - A Text Book of Cardiovascular Medicine; 6th edn, Philadelphia; WB Saunders Co, 2001; 129-159.
7. Kapoor RK, Kumar A, Chandra M, Misra PK, Sharma B, Awasthi S. Cardiovascular responses to treadmill exercise testing in anemia. Indian Pediatr 197; 34: 607- 612.
8. Joshi VM, Carey A, SimpsonP, Paridon SM. Exercise performance following repair of hypoplastic left heart syndrome: A comparison with other types of Fontan patients. Pediatric Cardiol 1997; 18: 357-360
9. Mulla N, Simpson P, Sullivan NM, Paridon SM. Determinants of aerobic capacity during exercise following complete repair of tetralogy of Fallot with a transannular patch. Pediatric Cardiol 1997; 18: 350-356.
10. Riopel DA, Taylor AB, Hohn AR. Blood pressure, heart rate, pressure rate product and electrocardiographic changes in healthy children during treadmill exercise. Am J Cardiol 1979; 44: 697-704.
11. Bhave S, Phervani AV, Desai AG, Dattani KK. Cardiorespiratory response to stress test in normal Indian boys and adolescents. Indian Pediatr 1989; 26: 882-887.
12. Swaminathan S, Vijayan VK, Venkatesan P, Kuppurao KV. Aerobic capacity and cardiopulmonary response to exercise in healthy south Indian children. Indian Pediatr 1997; 34: 112-118.
13. Kapoor RK, Singh L, Mehrotra A, Mishra BK, Chandra M. Demasking of subclinical left ventricular dysfunction in anemic children. Indian Pediatr 1999; 36: 991-998.
14. Naughton JP. Physiological versus abnormal response to exercise. In Chung EK, ed. Exercise Electrocardiography - Practical Approach. Baltimore, Williams and Wilkins Co. 1982; 146-155.
15. Ellstead MH. General consideration of stress testing. In Ellstead MH, Davis FA, eds. Stress Testing . Philadelphia 1976; 122-145.
16. Satyanarayanan K, Raj Pradhan D, Ramnath T, Prahlad RN. Anemia and physical fitness of school children of rural Hyderabad. Indian Pediatr 1990; 27: 715-721.
17. Varat MA, Adolf RJ, Fowler NO. Cardiovascular effects of anemia. Am Heart J 1972; 83: 415-426.
18. Alpert BS, Gilman PA, Strong WB et al. Hemodynamic and ECG responses to exercise in children with sickle cell anemia. Am J Dis Child 1981; 135: 362-366.(Mani A, Singh T, Calton R)
2 Department of Pediatrics, Christian Medical College, Ludhiana, Punjab, India
Abstract
Objective: To study the functional consequences of nutritional anemia by evaluating the exercise performance in these children. Methods: The study was conducted on 30 each of anemic and normal children of both sexes aged between 7 and 14 years. Relevant history was taken, and detailed examination was done. These children were classified according to severity of anemia based on hemoglobin estimation as mild (10-11.9 g/dl), moderate (7-9.9 g/dl) and normal (>12g/dl). Children with severe anemia (Hb <7g/dl), heart disease, non-nutritional anemia, acute febrile or respiratory illness were excluded. The subjects were tested on Mortara X Scribe colour stress treadmill using the modified Bruce protocol. Continuous computerised electrocardiographic analysis was done. The parameters studied included heart rate, systolic blood pressure, double product (DP = HRxSBP), ECG changes, metabolic equivalents (METS) and exercise duration. The end point of the test was a HR of 170/min (non-fatigue group) or inability to perform further (fatigue group). Statistical analysis was done by appropriate tests. Results: Fifteen children each with mild and moderate anemia and 30 age-matched controls were enrolled in the study. There was no significant difference in the resting HR, exercise duration or DP between the cases and controls. Thirty-one children reached the target HR (non-fatigue group). The end-point HR was significantly lesser among the anemic children in the fatigue group (P 0.04). The percent gain of SBP, at peak exercise (P 0.0007) and recovery SBP as percent of resting SBP (p 0.006) were significantly more in the anemic children, more so in the mildly anemic ones. Lesser METS was achieved by anemics as compared to controls (P 0.04). ECG changes occurred significantly more often in anemic children, 53.8% of those with changes being moderately anemic, the main abnormality being ST depression. None developed arrhythmia during exercise testing. Conclusion: The cardiovascular response to physical exercise is compromised in children with nutritional anemia and hence these children may never attain their full potential in various school activities. Prevention of anemia should be a priority in school going children.
Keywords: Anemia; Cardiovascular ; Children; Exercise test
Anemia is a worldwide problem, especially in developing countries where it is mainly multifactorial in origin.[1] A high incidence of anemia has been reported in India not only in the lower socioeconomic class but also in the affluent urban areas. The functional consequences of anemia in the human especially in children are of particular concern in view of its high prevalence in this age group.[2]
Anemia has a negative impact on physical work capacity in different age groups as measured by changes in maximal oxygen uptake and other metabolic parameters.[3]-[5] Exercise testing is a common physiological stress used to elicit cardiovascular abnormalities not present at rest and to determine adequacy of cardiac function.[6] The changes in heart rate, blood pressure, respiration and perceived levels of exertion provide data that permit quantitative estimation of cardiovascular functioning and conditioning.[7]
The treadmill has been used widely in the testing of exercise fitness in children in various congenital heart defects.[8]-[9] It is easy to use in children since only the ability to walk is required, numerous gradations of exercise level can be achieved and extensive standards have been developed.[7] Several studies have been done on exercise tolerance in normal children in western countries and occasional ones in India.[7],[10]-[12] The present study was undertaken to evaluate the exercise performance in Punjabi children with nutritional anemia.
Material and methods
The present study was conducted on 30 children with nutritional anemia and 30 normal children of both sexes aged between 7-14 years who attended the outpatient pediatric clinic of a teaching hospital. Relevant history was taken and detailed physical examination was done. The diagnosis of anemia was made by clinical assessment, hemoglobin estimation and peripheral smear. Children were classified according to the severity of anemia as mild (10-11.9g/dl), moderate (7-9.9 g/dl) and severe (<7 g/dl) as per WHO criteria.[1] Normal children with a hemoglobin value of 12 g/dl and above were enrolled as controls. Children with acute illness, cardiovascular, respiratory or musculoskeletal disorders, and with non-nutritional anemia or severe anemia were excluded. The cases included 15 each with mild and moderate anemia, enrolled by quota sampling. The subjects were tested on Mortara X Scribe colour stress treadmill. The TMT was done on an empty stomach after obtaining an informed consent from the guardian. A 12 lead electrode system was applied. The subjects were tested according to modified Bruce protocol wherein the Bruce protocol was modified by 2-3 minute warm up stages at 0% grade with 1.7mph and 5% grade with 1.7mph. Continuous computerised electrocardiographic analysis was done. Blood pressure and heart rate were measured in each stage. The end point of the test was any one of the following - heart rate of 170/min (non-fatigue group); inability to perform further (fatigue group); or significant ECG changes. The following parameters were measured and studied: heart rate, systolic blood pressure, double product (HRxBP), exercise duration, metabolic equivalents (METS), and ECG changes. Statistical analysis was done by ANOVA , chi square and Fisher's exact method as applicable.
Results
Thirty anemic children, 15 each with mild and moderate anemia and 30 age matched controls without anemia were studied. The resting HR in these three groups of children was similar being 97.6, 94.7 and 93.1 per minute respectively. The total duration of exercise before reaching the end point of the test was longer in the controls (13.5 min) compared to the mildly anemic (12.8 min) and moderately anemic (12.1) children, but these differences were not significant.
The target HR of 170/min in the non-fatigue group was achieved in 18(60%) controls, but in lesser number of anemics being 7 (46.7%) and 6 (40%) in the mildly and moderately anemic children respectively although the difference was not significant. The fatigue group consisted of the remaining twenty-nine children including 17 (56%) of anemics, who stopped exercise before achieving the target heart rate. In this group, lesser number (64.7%) of anemic children attained a HR >150/min compared to the controls (83.3%). The gain in HR at peak exercise as a percentage of the resting HR is shown in Table 1. In both the fatigue and the non-fatigue groups the gain of 3 75% occurred in lesser number of cases than controls, although the difference was not statistically significant probably on account of the small number of children in each sub group.
Blood pressure responses differed significantly between the groups table2. Mildly anemic children had higher resting systolic BP, more gain in BP at peak exercise and a higher percentage of recovery systolic BP at 1 minute after exercise as compared to the moderately anemic and controls. There were no significant differences in the double product (DP) at rest, gain in DP or recovery DP between cases and controls.
The METS achieved during peak exercise was significantly higher in normal children compared to the anemic group Figure1. Among those who developed significant ECG changes with exercise, 53.8% were moderately anemic Figure2. ST depression (>=1mm) was seen mainly in the moderately anemic subjects (P 0.0015). ST elevation of 1mm or more or changes in T wave morphology were not significantly different in the three groups, but among the 4 children who developed significant ST elevation, 3 were anemic. None of the children developed arrhythmias during exercise or during recovery.
Discussion
In the present study, heart rate limited exercise test was used which is more sensitive than symptom limited exercise test. We observed that anemic children exercised for relatively lesser duration (12.4 min) than normal children (13.4 min) although the difference was not statistically significant. This was comparable to an earlier study by Bhatia et al in which the average endurance time was observed to be significantly lesser in anemic children (8.8 minutes) compared to 11.8 minutes in normal children.[2]
Resting HR in healthy subjects indicates the state of physical conditioning. The lower the resting HR, the better the physical conditioning. In the present study, the mean resting HR was more in mildly and moderately anemic children (97.6 and 94.7 respectively) than in controls (93.1) similar to the observation by Kapoor et al.[13] Heart rate response to exercise in anemic children was less than in controls. Fifty-six percent of the anemic children became fatigued before reaching the maximum HR as compared to only 40% of the controls. Larger proportion (83.3%) of controls were able to attain a HR of more than 150/min compared to the anemics (64.7%). Rapid exhaustion of compensatory mechanisms such as increased cardiac output could result in earlier fatigue which is demonstrated in anemic subjects. We also studied the gain in HR as a percentage of resting HR and this was observed to be lesser in anemic children, table1. These findings are also similar to those by Kapoor et al.[13] The cardiac reserve, which is, depleted in anemic children results in higher resting HR, less gain in HR and prolonged recovery time.
Systolic blood pressure usually increases during exercise. Increasing level of SBP signifies physical adaptations namely increasing stroke volume and cardiac output. [11], [14] The authors observed that the resting SBP and gain in SBP at end point were significantly more in anemic children, being more in the mildly anemic when compared to moderately anemic and the control group. table2, similar to the report by Kapoor et al.[13] The recovery of BP was also significantly slower in anemic children than in the normal. In mildly anemic children the increase in cardiac output as a compensatory mechanism can cause the increase in BP. However in the moderately anemic children there is a failure to do so which can be explained by the decompensation of the myocardium in these children.
The myocardial oxygen uptake reflecting myocardial oxygen consumption is estimated during exercise testing by the product of HR and SBP, the Double Product, also called modified tension time index (MTTI).[15] No significant difference was observed in the DP of patients and controls, but in the report by Kapoor et al the mean values of gain in DP were significantly lesser in anemic children, probably due to decreased cardiac reserve in these children.[7]
Metabolic equivalents (METS) during exercise testing estimate the number of times the maximal oxygen usage under aerobic conditions (V O2 max) is above the basal level. Majority of children who achieved less than 5 METS were moderately anemic while majority of those who achieved more than 12 METS were normal. (p=0.04, Fig 1), the observation being similar to that of other authors.[2],[13],[16] The lower degree of METS achieved by anemic children may be related to skeletal muscle exhaustion rather than reduced cardiac reserve.
Decrease in QRS amplitude, T wave flattening, minor degrees of AV conduction disturbances and ST - T wave changes have been described in the ECG in anemic patients.[17] Significant ECG changes in (33.3%) cases were observed more so in the moderately anemic (46.7%) than in the controls (10%) (p = 0.019). ST depression was the most common evidence of electrical instability Figure2. Anemia is reported to be a common non-coronary cause of ST depression.[6] Among four children who developed ST elevation during exercise, three were anemic. The development of > 1 mm of persistent elevation is considered an abnormal response during exercise.[6] But several authors have found no electrical instability in their study of anemic children.[7],[18]
Conclusion
The duration of exercise, resting heart rate, gain in heart rate as a percentage of resting HR and the double product in anemic children undergoing submaximal treadmill test did not show any significant difference from that of normal children. However, the resting SBP was significantly higher and the recovery of systolic blood pressure was slower in anemic children compared to controls. There were significant ECG changes in anemics as compared to controls. Anemic school-going children may not be able to perform adequately in various school activities. Prevention of anemia and its treatment will go a long way in realising the full potential of these children.
References
1. DeMaeyer EM. Preventing and controlling iron deficiency anaemia through primary health care. Geneva, World Health Organisation. 1989
2. Bhatia D, Seshadiri S. Anemia, undernutrition and physical work capacity of young boys. Indian Pediatr 1987; 24: 133-139.
3. Gopaldas T, Kale M, Bhardwaj P. Prophylactic iron supplementation for underprivileged schoolboys. III. Impact on submaximal work capacity. Indian Pediatr 1985; 22: 745-752.
4. Gardner GW, Edgerton VR, Senewirathne B, Bernard RJ, Ohina Y: Physical work capacity and metabolic stress in subjects with iron deficiency anemia. Am J Clin Nutr 1977; 30: 910-917.
5. Viteri FE, Torun B. Anemia and physical work capacity. Clin Hematol 1974; 3: 609-626.
6. Chaitman B. Exercise stress testing. In Braunwald E, Zipes DP, Lippy P, eds. Heart Disease - A Text Book of Cardiovascular Medicine; 6th edn, Philadelphia; WB Saunders Co, 2001; 129-159.
7. Kapoor RK, Kumar A, Chandra M, Misra PK, Sharma B, Awasthi S. Cardiovascular responses to treadmill exercise testing in anemia. Indian Pediatr 197; 34: 607- 612.
8. Joshi VM, Carey A, SimpsonP, Paridon SM. Exercise performance following repair of hypoplastic left heart syndrome: A comparison with other types of Fontan patients. Pediatric Cardiol 1997; 18: 357-360
9. Mulla N, Simpson P, Sullivan NM, Paridon SM. Determinants of aerobic capacity during exercise following complete repair of tetralogy of Fallot with a transannular patch. Pediatric Cardiol 1997; 18: 350-356.
10. Riopel DA, Taylor AB, Hohn AR. Blood pressure, heart rate, pressure rate product and electrocardiographic changes in healthy children during treadmill exercise. Am J Cardiol 1979; 44: 697-704.
11. Bhave S, Phervani AV, Desai AG, Dattani KK. Cardiorespiratory response to stress test in normal Indian boys and adolescents. Indian Pediatr 1989; 26: 882-887.
12. Swaminathan S, Vijayan VK, Venkatesan P, Kuppurao KV. Aerobic capacity and cardiopulmonary response to exercise in healthy south Indian children. Indian Pediatr 1997; 34: 112-118.
13. Kapoor RK, Singh L, Mehrotra A, Mishra BK, Chandra M. Demasking of subclinical left ventricular dysfunction in anemic children. Indian Pediatr 1999; 36: 991-998.
14. Naughton JP. Physiological versus abnormal response to exercise. In Chung EK, ed. Exercise Electrocardiography - Practical Approach. Baltimore, Williams and Wilkins Co. 1982; 146-155.
15. Ellstead MH. General consideration of stress testing. In Ellstead MH, Davis FA, eds. Stress Testing . Philadelphia 1976; 122-145.
16. Satyanarayanan K, Raj Pradhan D, Ramnath T, Prahlad RN. Anemia and physical fitness of school children of rural Hyderabad. Indian Pediatr 1990; 27: 715-721.
17. Varat MA, Adolf RJ, Fowler NO. Cardiovascular effects of anemia. Am Heart J 1972; 83: 415-426.
18. Alpert BS, Gilman PA, Strong WB et al. Hemodynamic and ECG responses to exercise in children with sickle cell anemia. Am J Dis Child 1981; 135: 362-366.(Mani A, Singh T, Calton R)