U p s a l a J M e d Sci 79: 84-89, 1974 Metabolic Aspects of Physical Training in Male Patients after Myocardial Infarction A R N E B J E R N U L F a n d J O N A S B O B E R G From the Departments of internal Medicine and Clinical Physiology, University Hospital, Uppsala, and the Depart- ment of Geriatrics, University of Uppsala, Sweden A B S T R A C T Twenty-six post infarct patients were selected and ad- mitted to hospital 3 months after the onset of the myocardial infarction for an investigation including lipid studies and glucose and fat tolerance tests. After this initial hospital stay the patients were randomly divided into a training (13 patients) and a reference (13 patients) group. During the following 3 months the first group of patients were physically trained (entirely in- doors, three sessions a week individually). Thereafter the patients of both groups were readmitted to hospital for a second investigation, identical with the initial one. The oral glucose tolerance (OGT)' was improved in the younger (less than or equal to 55 years) patients of the trained group. There were no significant changes of cholesterol or triglyceride levels after the training or reference periods measured 5 days after the last train- ing session. I N T R O D U C T I O N T h e risk f a c t o r s for ischaemic h e a r t disease ( I H D ) , n o w a d a y s well k n o w n , include c i g a r e t t e smoking, hyperlipidaemia, r e d u c e d g l u c o s e t o l e r a n c e a n d raised blood pressure ( I , 13, 17, 26, 39). A t t e m p t s at c o m b a t i n g t h e s e f a c t o r s h a v e included re- c o m m e n d a t i o n s for c h a n g e s i n diet, s m o k i n g with- d r a w a l , a n d different d r u g t h e r a p i e s . During r e c e n t y e a r s the interest in physical training as an addi- tional f o r m of t h e r a p y in primary prevention of IHD h a s increased. T h e e x p e c t e d benefits are a d e c r e a s e of s e r u m triglycerides ( T G ) a n d serum c h o l e s t e r o l (CHOL) c o n c e n t r a t i o n s (24, 27, 29, 34). P h y s i c a l training as secondary p r e v e n t i o n o f IHD has a l s o gained i n t e r e s t b e c a u s e of o t h e r benefits such as a c h i e v e m e n t of a higher physical w o r k c a p a c i t y , and i n c r e a s e d self-confidence of b o t h patient a n d his relatives ( 2 , 5, 33). The following abbreviations were used: OGT oral glu- cose tolerance, IVGT intravenous glucose tolerance. ?'his r e p o r t d e s c r i b e s e x p e r i e n c e s o f t h e effect o f physical training o n p l a s m a lipids a n d blood g l u c o s e metabolism in male p a t i e n t s r e c o v e r e d f r o m t h e i r first myocardial infarction. M A T E R I A L Selection of patients The material was selected from all male patients treated at the University Hospital, Uppsala during the period December 15, 1970-March 15, 1972 for their first myocar- dial infarction. Patients 70 years old or older were excluded, as well as all patients with the following conditions: treated dia- betes mellitus, diastolic blood pressure exceeding l 10 mmHg a t rest (indirect method), heart volume exceeding 600 ml/m2 body surface area (supine posture), cardiac arrhythmias (e.g. regularly recurring VES during exer- cise, or atrial fibrillation), a history of pain or aching in the back or the larger joints or pulmonary disease. No patients treated with digitalis, beta receptor blocking agents, or lipid lowering drugs were included in the study. The material is a subsample of the series previously described and compared with the whole infarct popula- tion treated at the hospital during a two-year period March 15, 1969-March IS, 1971 (2). After the above selections there remained 26 patients. who were assigned randomly to two groups, a so-called training group (13 patients) and a reference group (13 patients). The former group underwent a 3-month period of physical training (see below) while the reference group served as a control. Clinical characteristics of the material have been presented elsewhere (2, 3, 4). Drop-out of patients Three patients from the trained group and 5 patients from the reference group dropped out from the physical train- ing or were excluded for the following reasons: aggrava- tion of angina pectoris during training ( 1 patient), rein- , farction ( 1 patient) (not in connection with any training session), ulcerative proctitis ( 1 patient). One patient did not wish to take part in any follow-up investigations. Four patients dropped out for technical reasons: vaso- vagal reactions (2 patients), incomplete blood sampling (2 patients). Upsala J Med Sci 79 Infarction, physical training and metabolic changes 85 Table I. A g e , body weight, and blood plasma concentrations of triglycerides and cholesterol before and after the training and reference periods Plasma Trielvcerides” I < (mmole/l) Body weight Plasma cholesterol (kg)- - I I1 (mgil00 ml) Age (years) Before After Before After Before After Before After Trainedgroup Mean . 56 75.9 75.5 2.83 2.53 2.64 2.39 266 237 (0.421) (0.379) ( N = 10) S.E.M. 2.3 2.5 2.8 0.36 0.30 (-0.945) (-0.953) 13 9 h 2S.E.M. -0.4 k 0 . 7 -0.30 k0.25 (-0.042 k0.044) -29 + I 7 ns ns ns ns Reference group Mean 52 76.2 76.2 2.35 2.24 2.29 2.19 289 273 ( N =8) S.E.M. 3.0 3.3 3.5 0.21 0.17 (-0.962) (-0.965) 13 13 (0.359) (0.340) A i S . E . M . 0 -0.1 lk0.13 (-0.019k0.024) -16 *7 ns ns ns ns a Calculations made without (I) and with (11) logarithmic transfer of the values. The 10 logarithmic values are given within brackets. GENERAL PROCEDURE Three and six months after the onset of the acute my- ocardial infarction the patients were readmitted to hos- pital for investigations, which have been described pre- viously (2, 3). In addition during the last year of the study oral and intravenous glucose tolerance tests and also an intravenous fat tolerance test were performed on different days before and after the training or reference periods. Furthermore, adipose tissue biopsies were taken for determination of fat cell size. The patients of the trained group were then trained 3 times weekly as pre- viously described (3). Each session started with 10 min rest, and this was followed by 10 min of calisthenics under the leadership of a qualified physiotherapist. This was followed by three 10-min sessions of cycling on an ergometer bicycle with varying work loads. The training session ended with 10 min rest on a couch. It was con- sidered desirable that the work load should reach but not exceed the pain threshold for the patients with angina pectoris. N o instructions were given to the patients concerning dietary modifications. METHODS The patients came to the laboratory in the morning after fasting and refraining from smoking since the night be- fore. Teflon catheters (Stille Infart I . 15 mm, Stockholm) were inserted percutaneously in a cubital vein for blood sampling. Determinations of the plasma concentrations of cho- lesterol and triglycerides were made by an autoanalytical technique (32). The blood glucose concentrations were determined on venous blood plasma by the glucose oxidase method (2 1). The serum insulin concentration was determined by a “solid phase” radioimmunological technique (Phadebas Insulin Test, Pharmacia) based upon the method described by Wide & Porath (40). The serum uric acid was analysed by a method described by Sobel & Kim (36). The oral glucose tolerance (OGT) test was performed as follows: the patient drank about 200 ml water containing 100 g glucose. Blood samples for analysis of glucose and insulin concentrations were taken immediately before (O), 30, 60, and 120 min after inges- tion of the glucose. For the intravenous glucose tolerance (IVGT) test, 0.5 g glucose per kg body weight was given intrave- nously during 2 min in the form of a 50% solution. Blood samples were taken for determination of blood glucose before and 20, 30, 40, 50 and 60 rnin after, and of serum insulin before and 4, 6, 8, and 60 min after the start of the glucose injection. Early insulin response was cal- culated according to the method of Thorell et al. (38). The IVGT was expressed as the K value calculated from the formula 0.693 x loo/ glucose half time (25). The intravenous fat tolerance test (IVFTT) was ,per- formed in accordance with the method of Carlson & Rossner (16). The fat cell diameter was measured on cells obtained by adipose tissue biopsy according to the method of Sjo- strom et al. (35). Statistical concepts and methods as described by Hoe1 were used (22). RESULTS N o significant differences were found between the trained and the reference group with respect to age, height and body weight (Table I). In the 10 patients of the trained group the mean age was 56 years, the initial weight 75.9 and the final weight 75.5 kg, and the mean height 176 cm. In Upsala J Med Sci 79 86 A . Bjernulfand J . Boberg Table 11. A g e , body weight, and intravenous f a t tolerance and f a t cell diameter before and after the training and reference periods Intravenous fat Body weight tolerance, K Fat cell diameter (kg) (%/rnin) ( C L ) Age (years) Before After Before After Before After Trained group Mean 53.6 76.4 75.6 2.64 3.11 89.9 85.4 S.E.M. 2.1 3.2 3.8 0.66 0.83 6.58 4.00 Range 44-59 65.1-89.8 63.1-94.0 0.7-5.1 I . 1-7.7 61.5-108.0 67.8-93.6 N 7 7 7 6 Reference group Mean 58.7 75.4 75.2 3.53 4.05 89.4 89.0 S.E.M. 6.6 4.0 4.1 0.53 0.5 I 3.44 5.13 N 7 7 7 6 Range 49-66 63.4-94.6 61.6-95.2 2.2-6.0 2.6-6.0 72.8-99.0 66.0- 100.7 the 8 patients of the reference group the cor- reference period. In the training group there was responding figures were 52 years, 76.2 and 7 6 . 2 a reduction of 0.30-+0.25 mmoles/l ( 1 I % ) com- kg, and 174 cm. pared with 0.11kO.13 mmoles/l in the reference group (Table I ) . In the trained group 6 of the Effect o f training o n Lipid metabolism patients achieved a decrease i n plasma TG. Ail There were no significant changes of the mean these patients had initial TG values more than 1.90 plasma TG concentration after the training or mrnoles/l. Table 111. The effect of physical training on fasting blood glucose, and serum insulin, oral glucose tolerance, intravenous glucose tolerance and the serum insulin response after glucose given orally and intravenously Mean values 2 standard errors of the means (S.E.M.) are given Oral glucose test O G T (mg/100 ml) Insulin (microunits/ml) Age Body weight N (years) 0%) S u m N S u m 7rained group Total Before After Before After 6 5 years Reference group Total Before After Before After 6 5 5 years 80.8 23.7 81.0 24.2 8 52.4 23.1 81.1 2 5 . 4 82.1 2 6 . 0 5 4 7 . 0 2 2 . 3 77.3 2 2 . 6 9 5 4 . 4 2 3 . 0 76.1 5 3 . 1 78.2 2 4 . 4 76.8 25.6 5 4 8 . 4 2 3 . 3 0‘ 81 ?3 81 2 2 82 2 4 81 2 4 85 2 4 83 2 5 86 5 8 83 2 8 (0-60-120’) 328 2 2 2 298 2 1 5 350 +20 ** 5 294 2 16 8 349 2 3 3 374 2 2 5 3 14 2 3 2 354 2 4 2 7 5 0‘ 12 2 2 14 2 2 1 1 221 14 2 2 19 2 5 14 + 3 17 2 3 11 2 2 (Mo-120’) 175 2 3 9 151 2 2 8 146k32 134 2 3 3 228 2 9 3 178 2 5 7 131 2 2 7 108 2 1 7 * * P < 0.01 (significance for paired differences), N = n u m b e r of patients. The O G T test and IVGT test were performed a s described under Methods. O G T is expressed a s the fasting blood glucose (0 ) and the sum of the values for blood glucose concentration at 0, 60 and 120 min after the glucose intake. Serum insulin values during the O G T test are presented in the same way. IVGT is presented as the K value (25) and the serum insulin response during the IVGT test is expressed a s early response (38) (see under Methods) and the concentration 60 min after glucose injection. Uvsala J Med Sci 79 Infar Neither were there any significant changes of the mean plasma cholesterol concentration. In the trained group there was a reduction of I I % of the pretraining value, on the average, from 266 t o 237 mg/l00 ml. In the reference group the cholesterol value decreased from 289 to 273 mg/lOO ml (Ta- ble I ) . There were no significant changes in body weight after the training or reference period (Ta- ble I). As shown in Table I1 there were no significant changes of fractional removal rate of exogenous triglycerides (intravenous fat tolerance) after the training or reference periods. Neither were there any significant changes of the fat-cell diameter. Effects of training on carbohydrate metabolism In a sample of patients investigated during the last year of the study, oral and intravenous glucose tolerance and serum insulin were investigated be- fore and after the training and reference periods. Results of these investigations are presented i n Table 111. No changes in fasting blood glucose concentrations were obtained in any group, which is in agreement with results for the whole material presented elsewhere (4). A significant improve- Intravenous gliucose test [VGT Insulin (microunitslml) Y K-value N Early response 1.320.2 63213 34210 1.120. I 43 2 I7 3 2 2 10 7 4 1.420.3 1.220.2 4 1 .020. 1 103 248 392 10 1.120.1 97 248 3 3 4 5 1.120.2 0.920.1 8 4 vction, physical training and metabolic changes 87 ment in glucose tolerance (lower sum of glucose values 0-60-120 min (6) after the ingestion of glu- cose) was obtained in the younger patients (less than or equal to 5 5 years) of the trained group as measured by OGT. The sum decreased from 3 5 0 t 2 0 to 294216 mg/100 ml (P