To investigate cardiovascular changes in experimental acromegaly, a growth hormone-secreting tumour (MtT-W-15) was implanted in adult female rats. Somatic and tumour growth occurred steadily during the 8 week study period, as did an increase in serum growth hormone titre. Weight of left ventricle and right ventricle increased directly with tumour growth, both on an absolute basis and when compared with normal rats of equal body weight. Atrial weight also increased substantially. Haematocrit declined sharply at first, and more slowly later with increasing tumour weight. Haemodynamic measurements were made on these animals at two stages of tumour growth using an anaesthetised open-chest preparation. Cardiac index (per g body wt), stroke index, stroke work, left ventricle +dP/dtmax, and dF/dtmax of aortic flow were greatly elevated in rats with the largest tumours (longer duration), and to a lesser extent in those with smaller tumours (shorter duration). Systemic peripheral resistance and heart rate were depressed. Ventricular weight increased non-linearly with increases in cardiac index. Cardiac output, stroke volume, stroke work and dF/dtmax normalised per g left ventricle weight were also elevated. Splenomegaly accompanied tumour growth; however, splenectomy of tumour-bearing animals failed to prevent development of anaemia and cardiomegaly. While a direct effect of elevated growth hormone provides the best explanation for development of cardiomegaly in this model, volume work overloading due to anaemia and water retention may be a contributory cause.

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To explore the effect of persistent cardiomegaly on cardiovascular function, groups of newborn rats inhaled up to 500 ppm CO for 33 days, after which development continued in ambient air. In the first two experiments hemodynamics were assessed by use of an anesthetized open-chest preparation; in the third experiment heart rate (HR) and arterial systolic blood pressure (BP) were monitored by auscultation in the conscious state. In all three experiments weights of left ventricle (LV) plus interventricular septum (S), both ventricles (2V), and right ventricle (RV) were significantly greater by prediction on the basis of body weight (BW) than for normal rats at 87-97, 166-176, and 337-339 days of age in females and 98-108, 177-183, and 337-339 days of age in males. 2V/BW ratio was significantly greater than littermate controls in all six instances. In all but one case (male, 177-183 days) the RV/(LV+S) weight ratios were significantly greater than the respective control groups. In experiments 1 and 2 unconscious HR was significantly elevated in females at 87-97 days and in males at 98-108 and 177-183 days. The first derivative of LV pressure rise was also increased. There was no significant change in BP or other hemodynamic parameters. In experiment 3 awake HR was elevated above controls in previously CO-treated males and females at six monitoring points between 78 and 200 days, whereas BP was not altered. BW of previously CO-exposed males was depressed and returned to normal only after 290 days. A similar decrement in BW was not seen in females. Neonatal CO inhalation and cardiomegaly causes persistent cardiomegaly and tachycardia, lasting a significant fraction of the maximal life span of the rat in both sexes.