An experimental model to study blood and inflammatory neutrophils.

We sought to develop an experimental animal model in order to study the effects of hypothermia on host defences under conditions which were similar to those used for humans. We required a large animal which could tolerate arterial and venous catheters and serial blood sampling without significantly altering its blood volume and blood pressure. The animal should be intubated and ventilated to control blood gases and fluid and electrolyte balance. Finally the model should have anatomic, metabolic and physiologic similarities to humans. We describe an experimental pig model which appears to fulfill these criteria and provide important information relevant to man.

Elevated plasma vasopressin in cardiomyopathic hamsters.

Hamsters of the BIO 14.6 strain characteristically develop cardiomyopathy as they age, and hamsters of this strain have overt signs of heart failure by 11 months of age. Plasma levels of the posterior pituitary hormone arginine-vasopressin (AVP) were found to be elevated (approximately 2-fold) in 11 month old BIO 14.6 hamsters, compared to age-matched hamsters of a control strain. AVP appeared inappropriately elevated in these animals, since they were neither hyperosmotic nor markedly hypotensive. The elevated levels of AVP observed in these animals appears to contribute to vasomotor tone, since intravenous administration of a specific antagonist of the vasoconstrictor action of AVP [d(CH2)5Ome(TYR)AVP] elicited a fall in arterial pressure (9 +/- 2 mm Hg, n = 6, p less than 0.05). The AVP antagonist had no effect on arterial pressure in hamsters of a control strain, and vehicle administration had no effect on arterial pressure in either strain. These data indicate that inappropriately elevated levels of AVP contribute to the cardiovascular state of myopathic hamsters. Since elevated plasma AVP has been noted in human congestive heart failure, these results suggest that AVP may contribute to the cardiovascular status during congestive heart failure.

Adiposity, anthropometric measures, and plasma insulin levels of rhesus monkeys.

In order to characterize spontaneous adult-onset obesity in a non-human primate model, we have studied a group of twenty-four obese and non-obese male rhesus monkeys (Macaca mulatta). The monkeys, ranging in age from 12 to 27 years, were defined as obese on the basis of tritiated water estimates of body fat content exceeding 25 percent of body weight. Although the obese and non-obese monkeys had similar crown-rump lengths, they differed significantly not only in body weight (17.0 +/- 3.2 vs 11.7 +/- 1.8 kg, X +/- s.d., P less than 0.001), and average body fat content (37.8 +/- 6.6 vs 13.2 +/- 5.4 percent, P less than 0.001) but also in midgirth circumferences (57.5 +/- 8.4 vs 34.8 +/- 6.2 cm, P less than 0.001) and abdominal (but not triceps or scapular) skinfold thicknesses (22.74 +/- 5.8 vs 9.82 +/- 1.82 mm, P less than 0.001), thus, indicating the predominantly abdominal distribution of the fat mass. A new Obesity Index Rh, for rhesus monkeys, defined as body weight divided by the square of the crown-rump length, was developed as an adaptation of obesity indices used for humans and rats. The high correlation of the Obesity Index Rh with percent body fat and its relative independence of height make possible future identification of obese rhesus monkeys on the basis of anthropometric measurements. There were slight, but not significant, differences between the obese and the non-obese groups in lean body mass (10.9 +/- 2.8 vs 8.8 +/- 1.8 kg) and in fasting plasma glucose levels (87.1 +/- 31.8 vs 63.2 +/- 7.5 mg/dl). Obese monkeys had significantly larger average fat cell sizes (1.29 +/- 0.54 vs 0.61 +/- 0.29 microgram lipid/cell, P less than 0.05) and significantly greater fat cell numbers (6.1 X 10(9) vs 2.2 X 10(9), P less than 0.01). Fat cell numbers were better correlated with body weight and total body fat parameters than fat cell size, while fat cell size was more closely associated with the log of fasting plasma insulin levels than was fat cell number. The similarities to studies in humans indicate the importance of the spontaneously obese adult rhesus monkey as an animal model in the study of obesity.

Can pseudomonas infection in experimental animals mimic Kawasaki's disease?

Experiments aimed at producing a model of Kawasaki's disease by injecting animals intraperitoneally with Pseudomonas bacilli are described. Injection of large numbers of bacilli into mice caused rapidly fatal sepsis. With appropriate numbers of organisms, some mice died within 3 days, most remained healthy, while in some an inapparent chronic disease developed. Positive blood cultures were occasionally obtained 4-17 weeks after the slow infection. An alcohol-precipitable polysaccharide, which could be measured by Roe's procedure for levan, was found in 20% of the experimentally infected mice. We suggest that this substance was partly responsible for the course of the infection. Severe vasculitis with little acute inflammatory reaction and carditis with coronary aneurysms were often obtained by injecting mice and guinea-pigs with supraliminal doses of bacilli at the same time as their immune system was impaired by treatment with either nitrogen-mustard or cyclophosphamide. We suggest that pseudomonas infection in immunologically deficient animals may mimic Kawasaki's disease and that a similar mechanism may operate in the natural form of the disease in children.