The close-arterial infusion of free insulin-like growth factor-I (IGF-I; 1.1 nmol/min) for 6 h into the pudic artery supplying one mammary gland of lactating goats caused a 25 +/- 6% (mean +/- S.E.M., n = 6) increase in the rate of milk secretion of that gland. The increase in the rate of milk secretion in the adjacent noninfused gland (14 +/- 4%) was not significantly different from that observed during saline infusion (4 +/- 5%). Blood flow to the infused gland was increased from 378 +/- 26 ml/min 1 h before to 487 +/- 56 ml/min approximately 5 h after the start of the infusion of IGF-I, declining to 420 +/- 44 ml/min approximately 2 h after the end of the infusion. The total concentration of IGF-I (free and bound) in milk of the infused gland was significantly higher than that of the non-infused gland. The concentrations of IGF-I in carotid arterial plasma samples increased during IGF-I infusion from a mean value of 32 +/- 2 nmol/l before to a maximum of 49 +/- 3 nmol/l 5 h after the infusion commenced. Circulating concentrations of total IGF-I declined slowly after the infusion with an estimated half-life of 5 h. Infusion of saline alone did not alter mammary blood flow or the concentration of total IGF-I in milk or plasma. The results indicate that the infusion of free IGF-I into the mammary arterial supply enhances milk secretion and mammary blood flow in intact, conscious goats.(ABSTRACT TRUNCATED AT 250 WORDS)

5. It is suggested that the changes in milk composition, the decreases in mammary volume and in intramammary pressure after day 3 are due to the loss of integrity of the mammary epithelium.6. By about 7 weeks after the cessation of milking the udder volume was less than the empty udder volume before milking was stopped, indicating a loss of mammary tissue as well as the resorption of fluid.7. When milking of an autotransplanted gland was stopped, while milking of the control gland in situ was continued, the rate of secretion in the transplant fell while that of the control did not change.8. In goats milked normally but in which a volume of isosmotic lactose equal to the volume of milk removed at that milking was injected into the lumen of one gland at each milking, the rate of secretion of that gland, but not that of the other, decreased.

SUMMARY1. The volume of the udder and the composition of the secretion have been followed in five goats through pregnancy to the onset of lactation.2. During the middle of pregnancy udder volume was minimal and there was little or no fluid in the teats.3. Two stages of commencing secretary activity (lactogenesis) were defined. In the first, starting up to ten weeks pre-partum, udder volume increased and the fluid in the teats changed from an extracellular-fluid-like to a milk-like composition and acquired a high concentration of immunoglobulins. Four goats accumulated several litres of a pre-colostral fluid with a high [lactose] 6-7 weeks pre-partum.4. Comparison of the rate of increase in udder volume with previous data for the rate of increase in empty udder volume in pregnant goats showed that the rate of secretion, even in the last few days of pregnancy, was only a few per cent of the rate immediately after parturition.5. In the last 2-3 days of pregnancy there was a three to elevenfold increase in [citrate] in the secretion; this heralded the onset of copious secretion at about the time of parturition.6. The changes in mammary gland activities are discussed in relation to changes in plasma hormone concentrations during pregnancy.

Fegler showed in 1957 that the thermodilution method of measuring cardiac output 1 could be used also to measure the blood flow in the central veins of dogs. 2 Small quantities (0.4 to 1.0 ml) of saline at room temperature were rapidly injected through a three-holed needle into the vein, and the brief fall in temperature was recorded photographically from a thermocouple located 7 to 15 cm downstream. The blood flow was calculated from the concentration-time curve of the injected indicator ("cold"), the blood temperature and the temperature and volume of saline injected.The method was readily adapted to measure the venous flow from the udder of conscious goats, and with it were made the first direct measurements of mammary blood flow in conscious animals. These results agreed well with indirect estimates of blood flow calculated on the Fick principle from the transfer of plasma precursors into milk. 3 " 5 To ease the placement of the thermocouple and injection needles, and to reduce the chances of loss of indicator by heat exchange with the tissues, one mammary vein was exteriorized permanently as a skin covered loop, and was thus surrounded by air. Advantages of the method were chiefly that the injection and recording needles could be inserted and removed repeatedly for many months without disturbing the animal and without seriously damaging the exteriorized From the Agricultural Research Council, Institute of Animal Physiology, Babraham, Cambridge, England.Accepted for publication December 13, 1963. vessel, and since there was no recirculation of indicator and each response lasted about 5 sec, measurements could be made frequently. However, calculation of the flow from the area under each response was tedious and time consuming, and, although mean flow was fairly constant at a given stage of lactation (coefficient of variation 10% n ), single estimates could vary by as much as 50%, which may have been caused by extraneous factors influencing central venous pressure in the conscious animal.Modifications have been adopted to overcome these difficulties. Blood temperature is now recorded continuously on paper with a needle thermistor whilst saline is injected at a constant rate for 20 to 60 sec. The immediate measurement of the fall in blood temperature allows the flow to be calculated at once and the continuous record makes assessment of mean flow much easier. The validity of a constant rate infusion thermodilution method has been established in models in two laboratories, 0 -7 but not checked in vivo although Pavek, Boska and Selecky 7 showed that cardiac output can be measured by injecting cold saline for 6 to 10 sec into the right atrium and recording the fall of temperature in the pulmonary artery.The purpose of the present paper is to report that the technique has been further checked in vivo by three methods: 1) comparison with the single rapid injection technique, 2) comparison with mammary flow estimated on the Fick principle and 3) cannulation of the vessel and collection of blood in a measuring cylind...