It is not known whether the reflex inhibition of the vasomotor centre exerted by the carotid sinus nerves is solely dependent on the mean systemic blood pressure, or whether pulsations about this mean pressure themselves modify this afferent inhibition. As the intact circulation is pulsatile it seems important to answer this question, and the present experiments were performed with this purpose. METHODSForty cats were used anaesthetized by intraperitoneal administration of chloralose and urethane (50 mg of chloralose + 250 mg of urethane/kg body weight) or of sodium pentobarbitone (60 mg/kg body weight). The trachea was cannulated. All animals were given heparin intravenously (5 mg/kg body weight).Three types of experiment were performed. Group 1. One common carotid was dissected clear of the surrounding tissues from the level of the superior thyroid artery to that of the subelavian artery. The superior thyroid artery and the r. musculus dorsalis were tied but not cut; the presence of these arteries served to 'splint' the peripheral end of the common carotid artery and thus prevented drag on the carotid sinus during later manipulations. A specially shaped Y cannula was inserted into the common carotid artery and connected to a 20 ml. syringe containing 5 ml. of blood and 10-15 ml. of air, as shown in Fig. 1 A. The syringe acted as an elasticity chamber; it could be excluded from the cannula system by means of a Halstead clip.The carotid sinus nerve on the same side was dissected and cut centrally. A peripheral twig containing a few or one active baroceptor fibre was placed on saline-wick electrodes. By means of a resistance-capacity coupled amplifier the baroceptor impulse activity was registered on a cathode-ray oscillograph. The ipsilateral external carotid artery was cannulated and the end-pressure in the artery recorded by means of a condenser-manometer (devised by H. W. Ead) coupled to a second cathode-ray tube. Simultaneous photographic records were taken of the electroneurogram, sinus blood pressure and time marker. As the connexion between artery and manometer was of lead tubing, care was taken to avoid any stretch of the sinus by the cannula
The carotid bodies from full-term fetal cats, 3- to 4-day-old neonates and adult cats were perfusion-fixed at normal arterial blood pressure with 3% phosphate-buffered glutaraldehyde. Serial 5-µm sections were cut and stained by the MSB method. Using an interactive image analysis system, determinations were made of the volumes of the carotid body and of its vascular and extravascular compartments. Compared to the fetus, the carotid body of the neonate increased in volume by 51% and by 286% in the adult cat. There was a proportional increase in the volumes of the vascular compartment and of the small vessels (5–12 µm diameter) in that compartment. The volume of the small vessels, expressed as a ratio of the total volume of the organ, remained constant in the three animal groups at 5–7%. The small vessel endothelial surface area, expressed as a ratio of the extravascular volume (which was assumed to consist largely of type 1 and type 2 cells) was the same in the neonate as in the full-term fetus. Thus, there were no apparent quantifiable morphological features of the carotid body and its vasculature which would account for the resetting of the hypoxic sensitivity of the organ from the fetal to the adult range within a few days of birth.
SUMMARY The haemodynamic effects of dobutamine (2.5 to 10 ug/min per kg) were determined in 5 patients without cardiac failure who were undergoing cardiac catheterisation for suspected coronary disease. Myocardial blood flow was determined by the coronary sinus thermodilution technique. Data were compared with those from two groups of 5 patients who received dopamine (4-8 ,ug/min per kg) and isoprenaline (0.005-0.025 ,ug/min per kg). Each drug was given in a lower and a higher dose, and all increased mean cardiac index (dobutamine, 18% and 39%; dopamine, 11% and 23%; isoprenaline, 15% and 44%). These increases were associated with significant increases in mean myocardial oxygen consumption (dobutamine, 38% and 61%; dopamine, 25% and 62%; isoprenaline, 20% and 45%). Mean myocardial blood flow was increased by each drug but mean myocardial oxygen extraction was decreased by isoprenaline, was increased by dopamine, and was unchanged by dobutamine. Each inotropic agent has a similar effect on myocardial oxygen consumption, but isoprenaline has a direct coronary vasodilator action while dopamine has a coronary vasoconstrictor action. Dobutamine has no direct effect upon coronary vascular tone.
The effects on coronary dynamics of propranolol and atenolol were studied in 12 patients undergoing cardiac catheterisation for suspected coronary artery disease. Myocardial blood flow was measured using the coronary sinus continuous thermodilution technique. Data were obtained immediately after drug administration and during rapid atrial pacing. The immediate effects were similar for both drugs. A significant reduction in heart rate was accompanied by a small reduction in myocardial oxygen consumption. Changes in coronary sinus flow induced by rapid pacing were closely related to changes in tension-time index. This relation was not modified by propranolol or atenolol. Neither propranolol nor atenolol therefore has significant coronary vasoconstrictor properties. Cardioselectivity appears to be unimportant with respect to beta-adrenergic blockade and the coronary circulation.
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