Cardiac sensitivity and responsiveness to beta-adrenergic stimulation in experimental cancer and undernutrition

We have previously reported that the heart retains its pumping performance despite loss of contractile mass during tumor disease and malnutrition. This adaptation is associated with increased agonist affinity of the beta-receptor. The present study was undertaken to evaluate if increased beta-receptor agonist affinity has a physiologic counterpart which may contribute to the remained function in hypotrophic hearts. The isolated, perfused, working rat heart was used as a model. Hearts from tumor-bearing rats showed an increased sensitivity and reactivity to graded isoproterenol stimulation compared to freely-fed control animals. Starved and protein-calorie malnourished (PCM) control animals had a similar response of heart rate, left ventricular peak pressure and contractility as the tumor-bearing group. This increased response to beta-adrenergic stimulation thus seems to be a general adaptation to loss of contractile mass and not to a tumor-specific reaction. Tumor-bearing animals had lower myocardial content of norepinephrine and epinephrine compared to starved, PCM and freely-fed control rats. Oxygen consumption was higher in hearts from tumor-bearing animals compared to freely-fed controls during all experimental conditions. Starved and PCM rats, in contrast, had decreased oxygen consumption compared to the freely-fed controls. The heart might thus be one of the organs contributing to the increased energy expenditure seen in malignant tumor disease possibly due to a changed adrenergic regulation in the tumor state compared to uncomplicated undernutrition.