Human adipose tissue in culture. VIII. Studies on the insulin-antagonistic effect of glucocorticoids.

Biopsies of human adipose tissue were maintained for 1 wk in vitro with physiologic (1.5-30 X 10(-8) M) or pharmacologic (300 X 10(-8) M) concentrations of hydrocortisone or 1000 muU/ml insulin, or both. After this period, the explants were washed and incubated for 2 hr according to techniques generally used to study fat cell metabolism. Physiologic concentrations of hydrocortisone mainly exert an insulin antagonistic effect. Thus, the long-term effects of insulin in increasing lipolysis, as well as glucose metabolism to triglycerides, were reduced, as were the acute effects of insulin on these parameters. At these concentrations, the glucocorticoid itself did not influence the basal metabolic rates when due consideration was given to simultaneous changes in mean fat cell size. At higher concentrations, which may easily be reached during nonspecific glucocorticoid therapy, the glucose metabolism was reduced. Hydrocortisone decreased the number of insulin receptors. However, this cannot solely explain the insulin-antagonistic effect, since it was not overcome by a supramaximal concentration of insulin. Insulin and hydrocortisone together increased the lipoprotein lipase (lpl) activity several times. The resultant changes in LPL appear to depend upon the insulincorticosteroid ratio.     

Relationship between electrocardiographically and enzymatically estimated size in anterior myocardial infarction

In 179 patients with anterior myocardial infarction the electrocardiographically estimated infarct size was related to serum enzyme activity. A precordial map containing 24 precordial positions and the peak activity of heat stable dehydrogenase (LD; EC 1.1.1.27) were used. A positive correlation was found between the area at risk (initial sum of ST-elevation) and the peak LD activity (r = 0.48 - 0.55; p less than 0.001). When the final Q-and R-wave amplitude were related to peak enzyme activity a better correlation was observed (r = 0.56 - 0.68; p less than 0.001). The sum of R-waves (sigma R) and the sum of Q-waves (sigma Q) in the 24 precordial leads were related to sigma R and sigma Q in five precordial standard leads. A good correlation was found between the two ECG methods (r = 0.75 - 0.83; p less than 0.001), indicating that an increased number of precordial leads gives information regarding the extent of infarction similar to that obtained with the routinely used standard leads. It is concluded that in the individual patient, serum enzyme activity and the final Q-and R-wave changes can give different information about infarct size. If, however, these two independent methods are used in a large number of patients in intervention studies they will probably give similar information about relative influence of the intervention on the mean infarct size.     

Peripheral insulin in response to the sight and smell of food

Twenty-five obese and 23 reference women were compared with respect to their peripheral insulin concentrations in response to the sight and smell of food. An additional 21 obese women were examined for different control purposes. The women were examined after fasting for approximately 16 hr. Venous blood samples for determination of glucose and insulin were drawn 20, 10, and 1 min prior to the demonstration of food for 5 min. After the food had been presented to the subjects, samples were drawn at 1, 2, 3, 4, 5, 6, 10, 15, and 20 min. The response was calculated in two different ways: method I--the difference between meal basal insulin values and mean insulin values during and/or after stimulation, and method II--the "insulin area" over the mean basal concentration was calculated for 0-20 min after start of food presentation. Both methods resulted in significantly higher insulin responses in obese as compared to reference subjects. However, when performing duplicate experiments in the same subjects only method II resulted in reproducible results and even with this method the error was as high as 60%-90%. The high error of the method was partly expected since the insulin elevation is most likely not only a function of controlled external cues but also dependent on unknown sensorimotor and cognitive-affective alterations. No insulin response was observed when obese women were exposed to an external cue that was not food related. Atropine completely blocked the insulin elevation in response to food related external stimuli indicating that this insulin response is mediated via vagus.     

Adipocyte precursor cells in obese and nonobese humans

Adipose precursors isolated from the stromal-vascular fraction of omental and subcutaneous adipose tissue, from defined hyperplastic obese and nonobese human adults were cultured in order to measure and compare replication rates. After multiplication to confluence these cells were also cultured in an enriched viscous suspension medium to optimize the expression of these cells to adipocytes, allowing an estimation of the number of cells having the ability to express an adipocyte phenotype. No difference in replication rate was seen between obese and nonobese donors or when adipocyte precursors from different depots were compared. When cells were allowed to develop fully in the enriched medium, approximately 6.5% of the original inoculated cell population exhibited an adipocyte morphology. Thus, these results suggest that environmental rather than genetic factors may be responsible for the hyperplasia seen in certain massively obese humans. Furthermore, the results indicate that fat-free cells found within the stromal-vascular fraction of adipose tissue have the ability to develop into adipocytes. However, it is suggested that the relatively low yield in obtaining fully differentiated fat cells under these conditions may be due to the heterogeneity of adipose related cells within the original stromal-vascular fraction from which these cultures were initially derived.     

Fat cell number,resting metabolic rate,mean heart rate,and insulin elevation while seeing and smelling food as predictors of slimming

The explanatory value of total fat cell number, resting metabolic rate, mean heart rate during sleep, and peripheral insulin while seeing and smelling food were examined in relation to weight reduction in 19 obese women on a 1100-kcal/day diet. The insulin response while seeing and smelling food was expressed as the insulin area (mU · min · 1^?1) over the baseline level. Food was presented in front of the patient for 5 min. Insulin was determined in short intervals 20 min before and 20 min after start of food presentation. Fat cell number, resting metabolic rate, and mean heart rate during sleep were determined with standard techniques. All patients went through a period of weight loss, a plateau phase, and a period of weight regain. Body weight, fat cell number, resting metabolic rate, and/or heart rate correlated significantly with degree and rate of weight loss, duration of plateau phase, and rate of regain. In multiple regression analysis fat cell number and resting metabolic rate explained 81% of the variance for weight loss, 66% for rate of regain, and 29% for duration. For duration, only fat cell number contributed significantly. The variance of rate of weight loss was explained up to 49% by metabolic rate and insulin response while seeing and smelling food. The possibility of predicting weight reduction to a certain target weight is of great practical importance since the patients can obtain a realistic goal for their efforts to reduce body weight. Hopefully systematic investigations of factors associated with the inability of obese subjects to maintain weight reduction will improve treatment in the future.     

Influence of fat-rich versus carbohydrate-rich diets on bile acid kinetics,biliary lipids,and net steroid balance in hyperlipidemic subjects

Altogether, 14 patients with hyperlipoproteinemia type IIa (n = 3), IIb (n = 4), or IV (n = 7) were maintained on diets in which 60% of the energy was supplied as fat or carbohydrates. The switch from the fat-rich to the carbohydrate-rich diet resulted in elevation of the plasma triglyceride levels. Although not consistent in all instances, the change of diet also resulted in an enhanced formation of both cholic acid and chenodeoxycholic acid and a higher contribution of deoxycholic acid in duodenal bile. Due to a reciprocal decrease in the excretion of neutral steroids in feces, the mean steroid balance remained unchanged. In all but four patients this switch of diets was associated with a decreased molar cholesterol concentration in duodenal bile obtained in the postabsorptive state.     

Size distribution of ribosomes in biopsy specimens of human skeletal muscle during starvation

The changes in the poly- and monoribosome distribution and in the total ribosome concentration in muscle during short term starvation were investigated. Transcutaneous muscle biopsies of 50 mg wet wt were taken from healthy human subjects, nonstarved and after one, two, and three days of total starvation. The percentage amount of polyribosomes was significantly lower (P less than 0.02) on days 2 and 3 of starvation than on day 0 (nonstarved). No significant sex-dependent differences were observed between the group of five females and six males. Ribosome concentration per g wet wt of muscle tissue was significantly lower on day 3 than on each preceding day (P less than 0.05). The reproducibility of the polyribosome analyses, together with the changes observed, suggest a future application of this method for evaluation of the effects of nutritional support in patients with posttraumatic and septic conditions.     

Effect of physical training on insulin uptake by the perfused rat liver

Hepatic uptake of insulin by the in situ perfused rat liver has been measured in rats subjected for 9 wk to physical training (T rats) on a treadmill. Three sedentary groups, one food-restricted (FR) to have the same weight as T rats, one freely-eating (FE), and one sucrose-fed (SF) were also studied. Each liver was cyclically perfused for 30 min with three different insulin concentrations in the medium (～80, ～500, and ～2000 μU/ml). Plasma insulin concentrations in T rats were 50 and 17, in FR 55 and 20, in FE 71 and 30 and in SF 84 and 42 μU/ml in portal and peripheral venous plasma, respectively. Insulin decay curves followed first order kinetics. Taking FE rats as controls physical training enhanced hepatic clearance (expressed in ml/g/min) by 37%–60% whereas sucrose feeding reduced it by 15%–31% during the three perfusion periods. Food restriction in the FR rats caused only minor changes. Similar results were obtained with respect to hepatic extraction ratio and insulin removal. There was a significant negative correlation between portal insulin concentration and hepatic clearance rate. The results indicate that the hepatic extraction of insulin depends on portal insulin concentration. The mean net insulin uptake of the liver was similar in the groups, utilizing portal insulin concentrations and the hepatic clearance rate for calculations. As previously shown, the low peripheral plasma insulin levels after physical training are due mainly to a decreased insulin secretion from the pancreas. This is thus magnified by the efficient trapping of insulin in the liver.     

Effects of long-term physical training on body fat, metabolism, and blood pressure in obesity.

Twenty-seven women with varying degrees of obesity were physically trained for 6 mo on an ad lib. diet. Body fat changes were positively correlated with the number of fat cells in adipose tissue. Obese women with fewer fat cells decreased in weight during training whereas women with severe obesity and an increased number of fat cells even gained weight. Blood pressure decreased consistently after training. Blood pressure elevation was not associated with body fat mass, nor was a decrease in blood pressure associated with a decrease in body fat or with pretraining blood pressure level. There were, instead, correlations between decreases in blood pressure on the one hand and initial concentrations and decreases in plasma insulin and triglycerides and blood glucose on the other. These results suggest an association between elevated blood pressure and metabolic variables. The possibility of treating and preventing early essential hypertension with methods that also correct the metabolic derangement, such as diet and exercise, should be given high priority in further research.     

Expansion of adipose tissue storage capacity at different ages in rats

The expansion of adipose tissue storage capacity with growth and with dietary, fat-induced obesity was studied in Sprague-Dawley and Osborne-Mendel rats by a combination of techniques. Mature adipocytes were counted and measured morphometrically. All heavy cells were counted after collagenase liberation, and then subjected to different culture procedures. An aliquot part was cultured in a suspension medium which prevented cellular multiplication, and was asssumed to allow an estimation of in vivo determined, non-filled precursor cells to adipocytes (preadipocytes) by their filling with lipid in this system. Simple purification steps allowed another aliquot of the heavy cells to multiply and form, essentially quantitatively, adipocytes or preadipocytes in a confluent monolayer in a substrate-rich culture-medium. Before confluence these cells are not determined to cells in the adipocyte series and were therefore called adipoblasts. Their rate of multiplication was determined by measurement of rate of incorporation of labelled thymidine into DNA. The results obtained are compatible with the following integrated picture. Adipose tissue of the young rat is growing by an increased multiplication of adipoblasts, which after determination to preadipocytes fill up to adipocytes until the tissue is full-grown. Cells other than adipocytes continue to increase in number with age. In the adult rat fat-feeding results in expansion of adipose depots, first by increase in fat cell size. Formation of adipoblasts and cells for supply and support of adipocytes is triggered early. This “readiness” of the precursor pool of cells, not yet recruited to adipocytes, is a generalized phenomenon. When the increased demand for triglyceride storage can no longer be met by an expansion of available adipocytes, which now have reached a “critical size” and are “full”, then cells from the adipoblast precursor pool are recruited and are determined to become preadipocytes, which are rapidly filled with triglycerides to mature adipocytes. This determination is presumably triggered by a local signal and is associated with the degree of cellular expansion. Sprague-Dawley rats are less sensitive to fat-feeding than Osborne-Mendel rats and showed only part of this development.     

The antilipolytic effect of insulin in human adipose tissue in obesity,diabetes mellitus,hyperinsulinemia, and starvation

The antilipolytic effect of insulin in vitro was investigated in conditions known to be associated with resistance to the effect of insulin on glucose metabolism. Human subcutaneous adipose tissue was obtained from 14 obese subjects before and during starvation for 7 days, 12 untreated non-insulin dependent diabetics (NIDDM), 6 untreated insulin dependent diabetics (IDDM), and 10 nonobese control subjects. The tissue was incubated with and without insulin in concentration ranging from 1–10.000 μU/ml. Responsiveness (maximum effect) and sensitivity to insulin were determined under basal induction conditions, since insulin had a bimodal effect on noradrenaline stimulated lipolysis. Under normal conditions both insulin sensitivity and insulin responsiveness were positively correlated with the basal rate of lipolysis. In obesity, IDDM and NIDDM there were no change in insulin sensitivity or in insulin responsiveness. When the obese subjects were divided into one hyperinsulinemic group (6 individuals) and one group with normal fasting serum insulin levels (7 individuals) a similar antilipolytic effect of insulin was observed in the two groups. During starvation there was a 20-fold increase in insulin sensitivity (p < 0.01) but no change in insulin responsiveness in femoral fat and only a decrease in responsiveness (p < 0.01) in abdominal fat. The present data supports the view that antilipolysis in human fat cells is not involved in the insulin resistance seen in obesity, starvation, diabetes and hyperinsulinemia.     

Whole-body tyrosine flux in relation to energy expenditure in weight-losing cancer patients

Whole-body tyrosine flux was measured in seven weight-losing cancer patients and compared with that of seven noncancer patients with malnutrition. L[U-14C] tyrosine was infused intravenously (IV) after an overnight fast under resting conditions and flux rates, oxidation, and incorporation into proteins of tyrosine were calculated from plateau values of specific activity of tyrosine in plasma and of labeled expired carbon dioxide. Rates of protein synthesis were calculated from the flux rate of tyrosine after subtracting the proportion oxidized. Simultaneous measurements of whole-body carbon dioxide production and oxygen uptake were also performed in each subject. Cancer patients had elevated whole-body tyrosine flux, protein synthesis, and energy expenditure when expressed in relation to body weight and whole-body potassium while the differences in tyrosine kinetics became of borderline significance when expressed in relation to energy expenditure. Tyrosine incorporation into whole-body proteins corresponded to a synthesis rate of 2.70 +/- 0.17 protein/kg/d in cancer patients and 2.18 +/- 0.17 in control patients (P less than 0.025). The results show that elevated protein synthesis in weight-losing cancer patients may explain not more than one third of the elevated energy expenditure. Therefore, other systems that utilize energy must increase in activity.     

Increased insulin binding to adipocytes and monocytes and increased insulin sensitivity of glucose transport and metabolism in adipocytes from non-insulin-dependent diabetics after a low-fat/high-starch/high-fiber diet

Nine non-insulin-dependent diabetics were studied before and after 3 weeks on an isoenergetic high-fiber/high-starch/low-fat diet (alternative diet), and nine non-insulin-dependent diabetics were studied on their usual diet. In the group that ate the alternative diet, the intake of fiber and starch increased 120% and 53%, whereas fat intake decreased 31%. Diabetes control improved as demonstrated by decreased fasting plasma glucose (P < 0.05) and 24-hour urinary glucose excretion (P < 0.05). The in vivo insulin action increased (K_IVITT increased, P < 0.05) with no change in fasting serum insulin levels. In fat cells obtained from patients in the alternative-diet group, insulin receptor binding increased (P < 0.05) after the change of diet. Insulin binding to purified monocytes (more than 95% monocytes) also increased (P < 0.05), whereas no change was found in insulin binding to erythrocytes. When lipogenesis was studied at a tracer glucose concentration at which glucose transport seems to be rate limiting, insulin sensitivity increased (P < 0.02). This is the predicted consequence of increased receptor binding. Moreover, when CO₂ production and lipogenesis were studied at a higher glucose concentration, where steps beyond transport seem to be rate limiting for glucose metabolism, increased insulin sensitivity was also observed. In contrast, no change was found in maximal insulin responsiveness. Fat and blood cells from the patients who continued on their usual diet showed no changes of the mentioned quantities. In the total group of non-insulin-dependent diabetics, fat cell insulin binding as well as rates (both basal and maximal insulin-stimulated rates) of glucose transport, CO₂ production, and lipogenesis were very heterogeneous, but when results from the first and second fat biopsy from the same patient were compared, these values varied only slightly. We conclude that the beneficial effect of a high-fiber/high-starch/low-fat diet on metabolic control in diabetics may in part be mediated through an increased insulin-binding ability of target cells for insulin, which causes an increased insulin sensitivity in these cells.     

Thyrotropin and prolactin responses to thyrotropin-releasing hormone: influence of fasting- and insulin-induced changes in glucose metabolism

It has been reported that prolonged fasting inhibits the response of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) in normal persons. To explore possible mechanisms behind this reduced TSH responsiveness and also to see whether dietary factors influence prolactin (PRL) responsiveness, six nonobese volunteers were intravenously injected with a small dose of TRH (25 μg) after three different fasting periods: an 8-hour overnight fast, a 56-hour fast supplemented with oral administration of glucose (4 g/kg/56 h yielding 16 kcal/kg/56 h), and a 56-hour fast supplemented with oral administration of an equicaloric amount of an amino acid (AA) mixture (4 g/kg/56 h) containing 17 different amino acids. The dose of TRH raised the PRL level from 14 ± 2 to 58 ± 8 ng/ml after the overnight fast. Similar PRL responses were obtained after the two prolonged fasting periods. The TRH also raised the TSH level from 1.0 ± 0.0 to 5.2 ± 0.8 μU/ml after the overnight fast. Prolonged fasting with glucose supplementation had no significant effect on this TSH responsiveness, nor did it change the basal blood glucose level. In contrast, prolonged fasting with AA supplementation not only reduced TSH responsiveness by 47 ± 7% (P < 0.002), it also lowered the basal blood glucose level from 4.2 ± 0.1 to 3.5 ± 0.2 mmol/L (P < 0.002). In an additional six normal subjects who fasted overnight, 25 μg TRH was injected intravenously on two occasions: after intravenous infusion of insulin, and after intravenous infusion of saline. The insulin induced market hypoglycemia (1.8 ± 0.1 mmol/L) in 30 ± 3 minutes, whereas saline, infused over a similar time period, had no significant influence on the blood glucose level. When PRL responsiveness was measured during the insulin-induced hypoglycemia, it was found to be increased by 56 ± 15% (P < 0.02). The corresponding TSH responsiveness was decreased by 18 ± 6% (P < 0.05). These results imply that an adequate glucose delivery to pituitary thyrotrophs might be a prerequisite for normal TSH responsiveness. They also show that changes in glucose utilization affect lactotrophs and thyrotrophs differently.     

Effects of age, sex, and clinical conditions on adipose tissue cellularity in man

Methods for measurements of fat cell size in man are now available. Total fat cell number is more difficult to measure, and the numbers reported should probably so far be regarded as estimates of fat-containing fat cells. The first years of life seem to be critical for adipose tissue development in man. Nonobese adult women probably have more fat cells than men. Fat cell size increases with age.Obese children and adults show increases in both fat cell size and number. Division of obese subjects into different subgroups according to adipose tissue cellularity must take into consideration the age and sex variations in the nonobese population. Attempts to such subdivision seem to give one group with an increased number of fat cells, early debut of obesity, and increased body cell mass. These patients are difficult to treat successfully by conventional methods. Adult onset obesity seems to be characterized by enlarged fat cells.All data presently available are transsectional and do not allow any definite conclusions about possible fat cell division. Thus, there might well be adult obese subjects who, like certain genetically obese rodents, have fat cells which multiply during an abnormally long period of life.Fat cell size has been found to correlate with plasma insulin and triglyceride concentrations. Patients with endogenous hypertriglyceridemia and possibly adult onset diabetes mellitus before debut of the diabetes have enlarged fat cells, while patients with juvenile, insulin-requiring diabetes mellitus have small fat cells.Thus, the subgrouping of obesity according to the cellularity of adipose tissue has given associations with clinical observations such as age at debut of obesity, disturbances of carbohydrate and lipid metabolism, and with prognosis for treatment. These relationships seem to justify the adipose cellularity measurements as they are now performed, although only a fairly rough estimate of the total cell number is obtained.     

Glucose tolerance,plasma insulin,and lipids in intermittent claudication with reference to muscle metabolism

Sixteen nondiabetic patients with intermittent claudication (IC) due to peripheral arterial insufficiency had as low plasma insulin values after a peroral glucose tolerance test as healthy, well-trained, middle-aged men, and both these groups had considerably lower values than controls. The low plasma insulin concentrations were more pronounced in IC patients with a high arterial stenosis than in those with a low stenosis. There was also a lower plasma triglyceride concentration in the former group than in the latter. Together with the normal glucose tolerance the low plasma insulin values in the IC patients and in the well-trained men indicate a high insulin sensitivity in the periphery. Succinic oxidase activity as well as the incorporation rate in vitro of glucose carbon into glycogen, lipids, and carbon dioxide were elevated above controls in muscle specimens from the IC patients and the well-trained men. This finding indicates that the adaptation of muscle metabolism might be of importance for insulin sensitivity after physical training, because the IC patients are physically inactive. This supposition seems to be considerably strengthened by the fact that a quantitative factor could be introduced in the comparisons. Higher arterial stenoses, with presumably a larger mass of adapted muscle tissue, showed the most pronounced increase in insulin sensitivity.     

Physical training in human hyperplastic obesity. IV. Effects on the hormonal status.

Severly obese subjects and sex- and age-matched controls underwnet physical training during a 6-wk period. Evidence of training was shown in all subjects by increased aerobic power. Before training the obese subjects were characterized by the following abberations: decreased glucose tolerance, hyperinsulinemia, elevated blood glycerol and plasma free fatty acids, and a blunted plasma growth hormone response during glucose tolerance. Noradrenaline output was elevated, a finding of potential interest for the explanation of increased lipolysis, blood pressure, and heart size in obesity. With training the following changes were found:In the controls there was evidence for the beginning of a decrease of adipose tissue mass. In the obese, however, body weight, body fat, or fat cell size did not decrease during training. Plasma insulin decreased, and a corresponding increase of plasma glycerol was seen. Glucose tolerance was not changed, and this, together with decreased plasma insulin, indicated an increase insulin sensitivity of the periphery. Changes in noradrenaline or growth hormone during training could not explain this increased sensitivity. Urinary cortisol output was found to decrease after training in the obese; this might be interpreted as a decrease in cortisol secretion allowing a more effective insulin action on the periphery.     

Daily variations of plasma glucose and insulin in physically-trained and sedentary subjects

The variations in plasma glucose and insulin levels were measured at 30-minute intervals throughout the day in physically trained and in sedentary subjects. The subjects exercised for 75 minutes at 65% of VO2max in the first experiment and refrained from heavy exercise in the second experiment. In all situations the physically trained subjects overall had lower plasma glucose and insulin levels than the nontrained subjects. In addition, the positive correlation between plasma glucose and plasma insulin levels observed in the physically trained subjects was significantly smaller than that note in the nontrained subjects, indicating reduced insulin requirements in physically-trained persons. During the period of exercise, glucose levels increased significantly in the trained subjects only. In the period that followed exercise, that is between 1:30 PM and 9:00 PM, the physically trained subjects had plasma glucose levels that were higher than those noted during the comparable hours not preceded by exercise; no comparable difference were found with insulin. Calculation of the total area for insulin indicated a reduction of insulin requirement of about 40% associated with physical training.     

Thyroid hormones and lipolysis in physically trained rats

In rats a single bout of exercise resulted in increased triiodothyronine (T3), thyroxine (T4), and triiodothyronine/reverse triiodothyronine ($\text{T3}\text{rT3}$) ratio 20 hr after exercise. The effect of norepinephrine on lipolysis in vitro was potentiated.In trained rats no changes were found in T4, T3 or rT3 concentrations. The $\text{T3}\text{rT3}$ ratio as well as basal and stimulated TSH concentrations decreased in comparison with sedentary, freely eating rats. Moderate food restriction to produce a body weight similar to that of trained animals caused no changes in T4, T3 or rT3 concentrations but caused a decrease in $\text{T3}\text{rT3}$ and in TSH levels. Training and moderate food restriction groups were not different. T3 in vitro caused a potentiation of catecholamine induced lipolysis in trained and food-restricted animals. With aging the serum concentration of T3 decreased and that of rT3 increased.Acute and chronic exercise both exert an effect on peripheral hormonal responses of lipolysis, while they have different and opposite effects on thyroid hormone concentrations. Physical training seems to have effects in this regard similar to those of moderate energy intake restriction. The results suggest that changes in peripheral effects of thyroid hormones during training should attract more attention.     

The relationship between electrocardiographic changes and early mortality rate in acute myocardial infarction

In 587 patients with acute myocardial infarction (AMI) and no previous MI, electrocardiographically estimated infarct size was related to three-month mortality. Mortality was found to be higher in patients with transmural MI (Q or R-wave changes in standard ECG) than in patients with subendocardial infarction (ST-T wave changes in standard ECG). In patients with anterior MI, precordial mapping with 24 chest electrodes was analyzed four days after arrival in hospital (n = 197). Neither the sum of R-waves, the sum of Q-waves, nor the number of Q-waves correlated significantly with early mortality, although there was a trend towards higher mortality among patients with more pronounced ECG changes. Finally, in patients with inferior AMI (n = 230), neither the sum of R-waves nor the sum of Q-waves in leads II, III and aVF on the fourth day influenced three-month mortality. However, when subtracting the sum of Q-waves from the sum of R-waves, there was a significant correlation between the estimated infarct size and the early mortality.