Citations

The exchanges of 125 I-labeled 4-iodoantipyrine (I-Ap), 14 C-labeled antipyrine ( 14 C-Ap), and tritiated water (THO) were studied in isolated blood-perfused, beating, nonworking dog hearts. From a first set of experiments, analysis of externally monitored myocardial clearance curves of I-Ap after its injection into coronary artery blood showed its washout to be flow limited at flows ranging from 0.8 to 3.8 ml. g -1 . min -1 . Therefore, these curves can be used for estimating coronary blood flow. In a second set of experiments, coronary sinus dilution curves of simultaneously injected I-Ap and THO were found to be indistinguishable in shape at high coronary flows. At low flows (<1.8 ml. g -1 . min -1 ), THO curves showed an earlier upslope and higher peak than antipyrine, indicating either a diffusional shunt for water or a larger volume of distribution for antipyrine. 14 C-Ap had a slightly faster washout than I-Ap. The differences are partially attributable either to differences in solubility of I-Ap, 14 C-Ap, and THO in erythrocytes or to differences in their volumes of distribution, and partially to diffusional shunting of water.

Indicator dilution techniques used for the estimation of flow (F), mean transit time (t), dispersion (σ), and mean transit time volume (V) in the circulation are subject to error when (1) flow is not steady and (2) concentrations are obtained by sampling at a constant rate (time averaging) rather than at rates proportional to the instantaneous flow past the sampling site (volume averaging). Using a simple descriptive model for indicator transport, the effects of simulated aortic flow or of sinusoidal flow of widely variable frequency were assessed. Errors in estimates of F, t, σ, and V are greater with bolus injections than with constant-rate injections. Errors are roughly proportional to the amplitude of variation in flow. They are maximal when the period of flow fluctuation is similar to the passage time of the dilution curve, which, for the human central circulation, is about the time for one respiratory cycle. With sinusoidal flow between 50% and 150% of the mean flow, errors were at worst up to 60% in F, 30% in t, 50% in σ, and 70% in V, with a bimodal distribution. Errors are minimal at cardiac frequencies. The troublesome lower frequencies can be avoided. Preliminary tests of a method for converting time- to volume-averaged concentrations gave encouraging results.

Acetylstrophanthidin, 1.0 to 10.0 µg/ml, caused contraction of strips of the lateral saphenous vein of the dog in an organ bath at 37°C. The superior mesenteric vein, which exhibited spontaneous activity in the organ bath, responded to acetylstrophanthidin with an almost immediate increase in tension and an increased frequency of contractions; this was followed by a sustained contraction which had the same time lag as the contraction of a saphenous vein strip from the same dog. In strips from both veins, the contraction was depressed by cooling and augmented by warming, an effect opposite to that seen with norepinephrine-induced contractions. A latent period of 10 to 60 minutes preceded the contraction of the saphenous vein; during this time, the vein showed increased reactivity to added norepinephrine, 5-hydroxytryptamine, acetylcholine, barium chloride, increased bath concentration of K + , and decreased bath concentration of Na + . The increased reactivity and contraction still occurred after catecholamine depletion of the vein by chronic lumbar sympathectomy and in umbilical veins, which are devoid of adrenergic nerves. In addition to its direct constrictor action on cutaneous and mesenteric veins, acetylstrophanthidin sensitized cutaneous veins to vasoactive agents and to changes in ionic environment. These actions did not depend on the presence of norepinephrine in the veins.

The possibility of sympathetic vasoconstrictor control of blood flow to active muscles was studied in dogs during graded exercise by comparing the blood flow in the normal with that in the Sympathectomized hind limb. Blood flow was measured by electromagnetic flow transducers around each external iliac artery, or inferred from the oxygen saturation of blood samples from the common iliac veins. The dogs either ran for successive periods of 3 minutes at 5.5 km/hr and grades of 0, 7, 14, 21, and 28% or ran each level of exercise separately. Unilateral lumbar sympathectomy (L-2 through L-7) was performed when the flow transducers were implanted or later by a snare technique. The latter allowed observations during exercise as early as 4 hours after sympathectomy. The magnitude of limb blood flow during exercise and the decline of exercise hyperemia were similar in the normal and the sympathectomized limb, as were the changes in the oxygen saturation of limb venous blood. However, electric stimulation of the lumbar sympathetic chain at the L-5 level in the conscious dog by a chronically implanted electrode reduced limb blood flow at all levels of exercise, the maximal flow of 1,000 ml/min was almost halved.

In anesthetized dogs, the vasoconstrictor nerves to the vessels of the hind limb left the spinal cord in the anterior spinal nerve roots from T-10 through L-4 levels. Maximal vasoconstrictor responses occurred on stimulation of the T-12, T-13, and L-l roots; none occurred on stimulation of roots caudal to L-4. The nerves first entered the lumbar paravertebral chain at or above L-1; the last point of entry was at the L-4, L-5 level. No fibers left the lumbar chain at L-1, L-2, and L-3 levels. The first point of exit was at L-4, and nerves continued to leave as far distal as S-1, The most caudal point examined. The maximal response to stimulation of the lumbar chain was at the L-4, L-5 level. With a single exception, the responses to electric stimulation of the anterior spinal nerve roots, lumbar chain, or sympathetic ganglia were confined to the vessels of the ipsilateral limb. In 22 dogs with unilateral sympathectomy (L-2 through L-7), changes in hind-limb vascular resistance were induced reflexly or by electric stimulation of the anterior spinal roots. The results indicated that sympathetic control of the resistance vessels of the hind limb was still absent 77 days after sympathectomy.

It has been suggested that the pressor effect of hypertonic solutions of sodium chloride on the Pulmonary circulation results from spasm of the pulmonary veins at their junction with the left atrium. These studies demonstrate that the increased resistance in the pulmonary vessels develops upstream to this site and that it may result primarily from mechanical blockage of vessels by clumped erythrocytes rather than from vasoconstriction.

Application of hemodialysis to dogs has been complicated by an acute reaction consisting of hypotension, bradycardia and respiratory depression followed by instability and a mortality rate of about 30 per cent. This reaction appears to be a response to homologous blood used to fill the dialyzers. Sensitization occurs in survivors, and accentuated reactions with marked hemolysis are noted on subsequent challenge. Cross matching the donor and recipient bloods has not permitted an adequate determination of compatibility under the conditions of hemodialysis. Satisfactory hemodialysis may be accomplished in dogs by using autogenous blood or blood substitutes to fill the dialyzers.

Preferential right-to-left shunting of inferior vena caval blood and left-to-right shunting of right-lung blood has been demonstrated to occur in experimental atrial septal defects in dogs as in the congenital defects in human beings. Existence of these preferential shunts proves that uniform mixing of blood does not occur in either atrium.

The possibility of measuring pulmonary blood flow in patients with central arteriovenous shunts utilizing the initial portion of indicator-dilution curves was explored in 16 patients by comparing these values for pulmonary blood flow with determinations by the direct Fick method. A good correlation between Fick and indicator-dilution values was obtained, and no systematic differences were demonstrated. The standard deviation of the differences between Fick and dye values was in the order of 20 to 25 per cent.

Central (aortic or subclavian), brachial, radial and femoral pressure pulses were recorded simultaneously in 12 healthy subjects during conditions of rest, exercise and 70 degree head-up tilt. Peripheral systolic pressure at rest uniformly exceeded the central systolic pressure generated by the same heartbeat. The average radial pulse pressure was 146, 146 and 165 per cent of central pulse pressure during rest, exercise and tilt while radial mean pressures were 94, 93 and 98 per cent of central mean pressures respectively. Summation of the incident pulse wave with reflected waves from the periphery and resonance effects in the peripheral arterial systems may produce these changes in pressure and contour.