Citations

Simple plastic constricting devices for producing experimental arterial stenosis may be prepared from formalinized polyvinyl alcohol (surgical ivalon) sponge. Not a single instance of arterial rupture, a common sequel of stenosis produced by rigid devices, was encountered in 56 experiments.

The indicator-dilution method was used in the dog in an attempt to define the proportion of the "central" blood volume contained in the lung vessels. When injections were made into the pulmonary artery with sampling from the femoral artery only half or even less of the calculated blood volume could be accounted for by the lungs. When a venous injection site was used, the proportion in the lungs was reduced to a third or less. Thus when peripheral sites are used for the inscription of indicator-dilution curves few deductions can be made about either the actual volume or even relative changes in the volume of blood in the lungs.

Potential changes attending excitation of the atrioventricular node, the common bundle, the bundle branches, and initial ramifications of the conducting tissue in the subendocardium of the bovine heart beating in situ have been recorded from unipolar exploring electrodes. Correlations between the form of nodal deflection and the location in the node of the electrode tip have been established. From right bundle branch and subendocardial action potentials, data were derived indicating a rate of transmission through the right branch of 2.02 M/sec. Certain observations on the effects of acute injury and severe hypoxia are recorded. The character of nodal deflections attending retrograde excitation is reviewed. In studies on canine hearts beating in situ , electrograms have been made from the regions in which the atrioventricular node, the common bundle, and bundle branches are believed to lie. Deflections comparable to those recorded in bovine experiments were encountered and, by analogy with those bovine studies, certain morphologic correlations postulated. In general, canine nodal deflections are smaller than their bovine counterparts and lack the variety of form ascribed to potential changes in the several portions of the bovine node. In canine studies, deflections of atrial, atrionodal, and nodal type coexisted in recordings from a single needle electrode suggesting a degree of proximity between the sources of these potential changes not encountered in bovine experiments.

Vasodilating agents were tested on smooth-muscle strips of small arterial blood vessels of dog and rabbit skin and mesentery, and two patterns of reaction were demonstrated. The type 1 Vasodilating agents, for example nicotinate, caused relaxation of contracted strips or blocked their contraction. The type 2 Vasodilating compounds, histamine, choline esters, and bradykinin, either caused contraction or had no effect on the vascular smooth-muscle preparation. Responses that were species specific and region specific characterize the action of type 2 vasodilators and must be accounted for in any in-vitro testing procedure for vasodilator drugs.

The lateral saphenous vein of the dog was perfused with homologous blood at constant flow. Changes in driving pressure were used to measure active changes in venous tone. Administration of tranylcypromine greatly reduced the activity of monoamine oxidase in the vein and increased its response to electric stimulation of the lumbar sympathetic chain and to norepinephrine infusions. Administration of pyrogallol (a catechol-O-methyl transferase inhibitor) also increased the response of the vein to adrenergic stimulation. These chemicals did not alter the increase in the sensitivity of the venous smooth muscle to sympathetic nerve impulses and infused norepinephrine produced by cooling the perfusate. Thus, the potentiating effect of local cooling on the response of the cutaneous veins to adrenergic stimulation cannot be explained by interference with the local enzymatic inactivation of catecholamines.

Acetylstrophanthidin, 0.3 to 10 µg/ml, caused contraction of helical strips of the dog cutaneous vein in an organ bath at 37°C. A latent period of 12 to 60 minutes preceded the contraction. During this time, the vein exhibited a progressive increase in response to transmural electric stimulation and added norepinephrine. As the dose of acetylstrophanthidin was increased, the latent period shortened and the increased response during the latent period was potentiated. When the contraction caused by 10 µg/ml was maximal, no additional contraction occurred with electric stimulation; the response to electric stimulation was only partially restored by the repeated washing out of the drug, despite relaxation of the strip to almost base-line tension. Since transmural electric stimulation causes contraction by release of tissue catecholamines, these experiments demonstrate that digitalis glycosides sensitize the cutaneous veins of the dog to adrenergic stimulation. This was confirmed in dogs anesthetized with pentobarbital. Intravenous injections of acetylstrophanthidin and digoxin, in doses too small (12.5 to 15.5 µ/kg) to cause direct constriction of the lateral saphenous vein, potentiated the constriction of this vein caused by electric stimulation of the lumbar sympathetic chain.

Studies were performed in dogs to determine if inhibition of neuronal reuptake of norepinephrine was the cause of the enhanced response to sympathetic nerve impulses seen in the cutaneous veins when the temperature of the blood perfusing them was decreased. Changes in driving pressure of the saphenous vein perfused with blood at constant flow were used to measure venomotor responses. The increases in venoconstrictor response to norepinephrine infusion caused by cooling the perfusate were similar in both hindlegs, one subjected to acute and the other to chronic sympathectomy. Blocking the reentry of norepinephrine into the sympathetic nerve endings by treating the vein with cocaine did not affect the augmentation by local cooling of the constrictor response to norepinephrine or electric stimulation of the lumbar sympathetic chain. The venoconstrictor responses to norepinephrine, epinephrine, 5-hydroxytryptamine, and molar potassium chloride were all augmented by local cooling. The results suggest that the sensitizing effect of cold on the smooth muscle of the veins cannot be explained by inhibition of norepinephrine re-uptake by the nerve terminals.

I. Tension was recorded from a segment of a thin bundle of calf or sheep ventricular fibers in which the membrane potential could be changed electrically, using a sucrose-gap technique. After reversal of membrane potential and consequent contracture for 2 to 3 seconds, a positive inotropic effect 2 to 12 times that which occurred during paired-pulse stimulation was obtained. The decay of this potentiated state was slow in resting preparations (average half-life, 95 seconds), but was determined by the number of beats in driven preparations (about eight beats to return to control amplitude). Lengthening consecutive action potentials by subthreshold constant depolarizing currents or 5-mv shifts in the membrane potential by 50-msec current pulses during the plateau phase of successive action potentials caused positive inotropic effects, attaining a steady state in about eight beats. Reversing the polarity of such currents (hyperpolarization) caused negative inotropic effects with the same phase dependency as for depolarizing currents. These negative inotropic effects attained a steady state in six to eight beats. The first action potential after cessation of these currents was close to normal, whereas return to control tension required six to eight beats. The half-life of decay of these negative inotropic states at rest was similar to that of positive inotropic states. Decay of inotropic states in contracting preparations was phase dependent, occurring only during the rapid depolarization and plateau phases of the action potential. II. These and other strength-interval effects on cardiac contractility in a constant chemical and physical environment are consistent with two hypotheses. (1) The presystolic level of intracellular calcium bound to specific (rapid release) sites on the sarcoplasmic reticulum, the inner surfaces of the sarcolemma and T tubules, is a major determinant of the level of [Ca 2+ ] 1 attained during the initial phase of an action potential and hence the tension developed by mammalian cardiac muscle (that is, its inotropic state) at that particular instant. (2) The amount of intracellular calcium present at these sites at any instant after an action potential (that is, the moment-to-moment inotropic state of the muscle) is predetermined in the inverse direction of the intersystolic intervals of prior systoles and in the positive direction by the duration and magnitude of the plateau phases of prior action potentials and (for rest periods as long as 10 seconds) the elapsed time, in an exponentially decreasing fashion, since termination of the last absolute refractory period.

Ten intact dogs were subjected to hemodialysis against a solution of low-sodium content to determine the influence of sodium depletion on myocardial binding of digoxin- 3 H. Serial determinations of serum sodium, potassium, chloride, bicarbonate, pH, and osmolality, of cardiac output, and of cardiac rhythm were obtained in these and in 10 control dogs dialyzed against the standard solution. A dose of digoxin- 3 H (0.05 mg/kg) was given intravenously after start of the dialysis and the animals were killed 1 hour afterward for measurement of myocardial radioactivity, potassium, and sodium. Significant depletion of serum sodium and chloride and myocardial sodium ( P < 0.001) occurred in all animals dialyzed against the low-sodium solution. No significant changes occurred in other serum electrolytes or pH; osmolality was maintained constant by a slow intravenous drip of 25% urea or mannitol. Myocardial radioactivity was reduced in sodium-depleted animals by 50% ( P < 0.001). The Na-K ratio was 0.40 in the myocardium of control animals and 0.26 in sodium-depleted animals. It was concluded that depletion of body sodium inhibits binding of digitalis glycosides to the myocardium during the first hour after injection of the dose.

The cutaneous veins of the dog constrict and dilate with local cooling and warming, respectively. This response, which is dependent on the integrity of the adrenergic nerves, might be explained by an altered response of the smooth muscle to a given frequency of sympathetic nerve impulses or by local temperature receptors that initiate alterations in sympathetic nerve activity. In the lateral saphenous vein perfused at 42°, 27°, and 17°C, the constriction caused by stimulation of lumbar sympathetic nerves was 40%, 160%, and 200%, respectively, of that at 37°C; the constriction caused by norepinephrine at the same temperatures was 70%, 187%, and 318% of that at 37°C. Division of the dorsal spinal roots from L-1 to S-1 made no difference to the veno-constrictor response to local cooling. It is concluded that an alteration in the sensitivity of the smooth muscle to arriving sympathetic nerve impulses accounts for the venous responses to local temperature changes seen in the intact dog.