Adaptation of the growing lung to increased VO2. I. IDPN as inducer of hyperactivity

This paper is the first part of a study aiming to further analyse the hypothesis that in growing animals an increased VO2 due to a high physical activity leads to a quantitative adaptation of the gas exchange apparatus. Trying to avoid the tedious treadmill exercises we tested the applicability of the drug IDPN (imino-beta,beta'-dipropionitrile) as an inducer of increased VO2. Three intraperitoneal injections of IDPN permanently transform normal white mice into 'waltzing mice'. In our experiments ten male mice were injected with IDPN at the age of 20, 21 and 23 days. A control group was simultaneously injected with saline. The typical 'IDPN' hyperkinetic syndrome' appeared within five days from the first injection. The treated mice lost weight and grew at a slower rate than the controls. Their physical activity, as measured by Animex activity meters, was about twice that of the controls and was accompanied by a 50% increase in specific VO2 (VO2/body weight). At the age of about 4 months all animals were killed, their lungs fixed by intratracheal instillation of glutaraldehyde for a complete morphometric analysis. The body weights and the weights of heart, liver, kidneys, viscera, skin and carcass as well as the skin surface area were determined. IDPN mice were significantly lighter than the controls (-16%). All the other parameters cited above were reduced in about the same proportions, so that, when related to body weight, no significant changes could be detected. Specific lung volumes (VL/body weight) of IDPN mice were however up by 23%. These findings confirm that IDPN treatment represents a suitable way to increase VO2 in mice and may therefore allow to avoid more cumbersome methods of enforced exercise. The complete morphometric analysis will be published in a following paper.