Platelets are believed to play a role in the pathogenesis of atherosclerosis and of the vascular obstruction that causes the acute complications of coronary artery disease. Since specific behavioral patterns appear to be related to the development of coronary artery disease and since emotional stress may predispose an individual to acute cardiovascular ischemia, it was hypothesized that platelet activation by catecholamines might be involved in these events. To study emotional stress, plasma samples were obtained from 61 senior medical residents immediately before they were to speak in public. There were significant increases in the plasma concentrations of the platelet-secreted proteins platelet factor 4 and ,B-thromboglobulin and epinephrine and norepinephrine immediately before speaking, which demonstrates that platelet activation and secretion occur in association with this type of emotional stress. Four trials were carried out to study the mechanism for this observed platelet secretion: (1) phenoxybenzamine, (2) propranolol, (3) 650 mg aspirin, and (4) 80 mg aspirin were given several hours before the public speaking engagement. Neither phenoxybenzamine nor propranolol in doses that blocked the hemodynamic effects of a,-and 3,1-adrenergic stimulation modified platelet secretion. Aspirin also did not block platelet secretion, which suggests that platelets were not being stimulated through a cyclooxygenase-dependent pathway. This study provides direct evidence of platelet secretion in vivo in association with emotional stress, and underscores the potential importance of platelet activation and secretion in the acute events that occur in patients with vascular disease.

A recent development in the treatment of obesity is the widespread use of very-low-calorie diets. This study assessed the response to refeeding (RF) after semistarvation (SS) in a rat model. Male Sprague-Dawley rats (440 g) were semistarved for 21 d, receiving a nutritionally complete defined formula diet at 23% of calories of control (C) rats fed ad libitum, and subsequently refed over 21 d (SS----RF). Organ weight, contents of protein and DNA, and the protein-DNA ratio were determined for the liver, pancreas, small intestine, and heart. Compared with C animals, SS----RF animals showed variable repletion of tissue protein but not of tissue DNA. The higher protein-DNA ratio shown in these organ systems suggests a cellular hypertrophic adaptive response to refeeding. A persistent reduced number of cells in ratio to protein concentration is evident despite refeeding over 21 d. Very-low-calorie diets as well as refeeding influence nitrogen economy of selected organ systems.

We evaluated cardiac response to weight loss induced by a very-low-energy (VLE) diet similar to commercially available protein-sparing diets. Such diets have been implicated in sudden death, and whether organ and tissue responses to them are untoward is not known. Rapid weight loss was induced in rats with weights ranging from obese to normal, and cardiac mass and myocardial histomorphometry were assessed. Over 3 wk body weight dropped from 544 +/- 12 to 417 +/- 21 g (P < 0.001). Heart weight was less in the VLE group than in obese controls (1246 +/- 115 vs 1625 +/- 179 mg, P < 0.001), as were the weights of the left ventricle (805 +/- 81 vs 1061 +/- 134 mg, P < 0.001) and right ventricle (198 +/- 27 vs 265 +/- 40 mg, P < 0.002). Reduction in heart weight was commensurate with loss of body weight (r = 0.89). Myocyte cross-sectional area was reduced in the VLE group (452.6 +/- 108.6 to 331.8 +/- 41.5 microns 2, P < 0.05), with no structural abnormalities. We conclude that weight loss in the weight range studied is accompanied by proportional reduction in cardiac mass and myocyte size. Myocardial regression is not accompanied by myocyte dropout or edema, and likely represents a simple adaptation to reduced body size.

Hepatic effects of very-low-energy diets (VLEDs) and refeeding were studied in dietary obese rats. Rats weighing 490-530 g (ages 72-119 d) were randomly assigned to control (C) and VLED groups. Control animals consumed a complete diet ad libitum whereas VLED animals consumed 20% of the energy intake of C animals for 7, 14, or 21 d, and some VLED animals were refed the C diet for 7 d. Hepatic weights, lipid, DNA, and total protein decreased in VLED animals. Observed hepatocytic lipid was high in C and progressively decreased in VLED rats. Hepatocytes from VLED rats lost cytoplasmic organelles, contained myelin figures, and became smaller. Decreased protein-DNA ratios and lipids in these same animals is consistent with atrophy. Other biochemical findings included reductions in blood urea nitrogen, albumin, triglycerides, total protein, and glucose, all of which are synthesized or metabolized by the liver. These observations suggest that attenuation of hepatic function is likely.

Effects of low-calorie semistarvation diets on gastrointestinal and cardiac organ systems were studied. Male Sprague Dawley rats were divided into two groups, Group I, control (C) and Group II, semistarvation (SS), and maintained on a diet designed after low-calorie modified-fasting regimens in popular use. C animals consumed this diet ad libitum; SS animals received 23% of the total calories of C but the same ratio of calories from protein, carbohydrate, and fat and the same quantity and quality of all essential nutrients. Final weights of total body, heart, liver, and small intestine were lower in SS than in C animals. Protein depletion in SS compared with C animals was evident for heart, pancreas, and intestinal mucosa. Unless aggressively supplemented, low-calorie SS diets may deplete protein stores of the gastrointestinal organs of digestion and absorption and contribute to decrease in body nitrogen stores, specifically cardiac muscle.