bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanochemistry of Cardiac Muscle
Authors: POOL PETER E. , CHANDLER BRIAN M. , SEAGREN SHIRLEY C. , SONNENBLICK EDMUND H.
Published: June 2012

The aim of this study was to evaluate utilization of chemical energy in relation to myocardial mechanics in variably afterloaded contractions of cardiac muscle by determining total energy utilization (∼P) in the absence of energy production. Right ventricular papillary muscles of cats were equilibrated at 26°C in a myograph in Krebs' solution while contracting isometrically (12/min). Following treatment with iodoacetate and N
2
to inhibit completely ATP production from glycolytic and aerobic metabolism, the muscles were stimulated to contract isotonically 20 to 75 times with varying after loads. They were then rapidly frozen in liquid N
2
-cooled isopentane, and concentrations of ATP, creatine phosphate, inorganic phosphate and creatine were measured.

The efficiency of energy utilization for the performance of internal work was 0.0067 µmoles ∼P/g-cm of work and for external work was 0.0031 µmoles ∼P/g-cm. In addition, resting energy utilization was 0.662 µmoles/g/min and activation energy was estimated to be 0.040 µmoles/g/contraction. These findings provide a demonstration of the Fenn effect in cardiac muscle and explain the well-known discrepancy in energy cost when cardiac work is increased by increasing pressure load as opposed to increasing volume load.
Influence of Pituitary, Thyroid, and Adrenal Hormones on Norepinephrine Turnover and Metabolismin the Rat Heart
Authors: LANDSBERG LEWIS , AXELROD JULIUS
Published: June 2012

Norepinephrine turnover was estimated in the rat heart from the rate of release of tracer
3
H-norepinephrine and the depletion of endogenous norepinephrine after inhibition of synthesis. Cardiac norepinephrine turnover was markedly increased in chronically hypophysectomized rats. Thyroidectomy and adrenalectomy were also associated with increased cardiac norepinephrine turnover, whereas ovariectomy was not. Chronic treatment of hypophysectomized rats with thyroxine and ACTH restored the turnover to normal, the replacement of thyroxine being quantitatively more significant.

Cardiac atrophy and decreased blood pressure occurred concomitantly with increased norepinephrine turnover in the hypophysectomized rat and were restored to normal with thyroid treatment. Ganglionic blockade of the hypophysectomized rat also restored the turnover toward normal. The metabolites of
3
H-norepinephrine were shifted with a decrease in O-methylated metabolites and an increase in deaminated products.

This evidence suggests that thyroid deficiency and, to a lesser extent, adrenal deficiency are associated with an increase in cardiac norepinephrine turnover mediated by an increase in sympathetic nervous activity. The role of the increased turnover in relation to the hormonal deficiencies is discussed.
Effect of Graded Reduction of Umbilical Blood Flow on Right and Left Ventricular Outputs in the Fetal Lamb
Authors: GOODWIN JAMES W. , MAHON WILLIAM A. , REID DAVID W. J.
Published: June 2012

Right and left ventricular outputs were measured by a dye dilution technique in fetal lambs before and during graded reduction of umbilical blood flow by constriction of the abdominal portion of the umbilical vein. P
o
2
, P
co
2
and pH were measured on blood samples taken from the carotid artery and the ductus arteriosus. Oxygen saturation values were estimated from oxygen dissociation curves for fetal lambs' blood. With slight constriction of the umbilical vein, both ventricular outputs fell, but there was no significant difference between them for umbilical flows exceeding 150 ml/kg per min. With further reduction of umbilical flow, the output of the right ventricle fell more than that of the left. When flow was reduced to less than 120 ml/kg per min, right ventricular output was significantly higher than that of the left (
P
<0.001). Oxygen saturation of blood from both the carotid artery and the ductus arteriosus fell with reduction of umbilical flow, but the difference between these values was not significantly altered. These observations show that major reduction of venous return may change the proportion in which various blood streams mix as they pass through the fetal heart.
Influences of Corticosteroids on Cardiac Glycogen Concentration in the Rat
Authors: DAW J. CHARLES , Lefer Allan M. , Berne Robert M.
Published: June 2012

Bilateral adrenalectomy resulted in a decrease (4.97 to 2.79 mg/g) in cardiac glycogen concentration in pentobarbital-anesthetized rats. Similar differences were observed at 10 to 14 days and at 27 days after adrenalectomy. Sham-adrenalectomized rats had normal cardiac glycogen concentration (4.98 mg/g). Total phosphorylase and phosphorylase α activities and glucose-6-phosphate concentrations in hearts obtained from adrenalectomized rats were not significantly different from controls. Total glycogen transferase activity was decreased in adrenalectomized rats and for any given glycogen concentration, the percent of the glycogen transferase in the independent form (percent transferase I) was significantly lower in the adrenalectomized rats than in the intact controls. The glucocorticoid dexamethasone (40 µg/day) prevented the decreases in cardiac glycogen concentration and percent transferase I in adrenalectomized rats. In the intact rat dexamethasone (40 µg/day) increased cardiac glycogen concentration and total transferase activity to above control levels as did larger doses in both adrenalectomized and control rats. The mineralocorticoid deoxycorticosterone acetate (DOCA), had relatively little effect on cardiac glycogen concentration. Conclusion: glucocorticoids exert a regulatory role in cardiac glycogen metabolism.
Inert Gas Diffusion Method for Measurement of Blood Flow Using Saturation Techniques
Authors: SEJRSEN PER , TØNNESEN KNUD H.
Published: June 2012

The isolated gastrocnemius muscle of the cat was used to study the relation between the desaturation of
133
xenon measured by external monitoring, and blood flow measured directly by a dropcounter.

The metered blood flow agreed with that calculated from the initial slope of the desaturation curve from tissue equilibrated by prolonged intra-arterial infusion and also by atraumatic gas labelling of a local area of the muscle (approximately 0.15% of the muscle weight). In this sense the concept of uniform distribution of blood flow in skeletal muscle has received substantial support. The identity of the results obtained by local gas labelling and by intra-arterial equilibration of the whole muscle with gas implies that there is, at least initially, diffusion equilibrium between tissue and blood in both.

However, the clearance curves could in no instance be fitted by a single exponential function. This indicates that the diffusion equilibrium is not maintained after the initial phase. It is suggested that this is not due to the presence of anatomical arteriovenous shunts or other types of uneven perfusion, but to counter current exchange of inert gas through the walls of vessels, i.e. shunting by diffusion explains the shape of the desaturation curves.
On the Genesis of the Absolute Ventricular Arrhythmia Associated with Atrial Fibrillation
Authors: YAMADO KAZUO , OKAJIMA MITSUHARU , HORI KAZUHIKO , FUJINO TETSURO , MURAKI HIROSHIGE , HISHIDA HITOSHI , KOBAYASHI TOSIJI
Published: June 2012

Genetic factors in the formation of the long R-R interval in ventricular arrhythmia associated with atrial fibrillation were investigated in the isolated rabbit heart which was perfused using Langendorff's technique. The trans-membrane action potentials recorded from a single cell within the A-V node or within its vicinity were analyzed, and contiguous bipolar-lead electrograms simultaneously recorded from the right atrium and ventricle. Atrial fibrillation was induced by the combined application of acetylcholine solution and electrical stimulation. Atrial excitation was mainly blocked in the right atrium and in the anterior half of the A-V node.

To clarify further the time-correlation between the right atrial electrogram and the A-V nodal responses, the pattern of atrio-ventricular conduction was studied by applying only the electrical stimulation at high frequency without acetylcholine. The conduction was mainly blocked in the same sites as in the above experiment and the pattern of the conduction block in Wenckebach rhythm was observed. The conduction block within the anterior half of the A-V node may be the most important factor in producing the long R-R interval in atrial fibrillation. It was shown that the pattern of the conduction block can be explained by the Wenckebach rhythm.
Cardiac Performance in Experimental Adrenal Insufficiency in Cats
Authors: LEFER ALLAN M. , VERRIER RICHARD L. , CARSON WALTER W.
Published: June 2012

Cardiac function was evaluated by ventricular function curves during the cardiovascular collapse observed in acute and chronic adrenal insufficiency. A progressive decline in peak cardiac work was observed in the acutely adrenalectomized cat (30% decrease at 1.8 hours and 50% at 3.5 hours after adrenalectomy). This impairment in cardiac work paralleled the decrease in mean arterial blood pressure which reached 50 mm Hg 3.5 hours after adrenalectomy. Cortisol and
d
-aldosterone, and the volume-expander, dextran, prevented a significant fall in mean arterial blood pressure and in peak cardiac work. When the mean arterial blood pressure of nonadrenalectomized cats was adjusted to follow the changes seen in adrenalectomized cats, a 49% depression in cardiac work resulted 3.5 hours after the initial decline in arterial blood pressure. The data suggest that the time course of the hypotension and presumed reduction in coronary perfusion pressure is sufficient to account for the large impairment in peak cardiac work observed. Cardiac work was reduced 56% in chronically adrenalectomized cats 8 to 10 days after adrenalectomy. Dexamethasone and deoxycorticosterone acetate, administered separately, prevented significant myocardial impairment. Since the mean arterial blood pressure of conscious, chronically adrenalectomized cats was normal, the myocardial depression was not secondary to inadequate coronary perfusion in chronic adrenal insufficiency and thus represents direct impairment of myocardial performance.
Segmental Responses of Dog Paw Vasculature
Authors: HAMMOND MARY C. , DAVIS D. L. , DOW PHILIP
Published: June 2012

The production of constrictive responses limited to either arterial or venous segments of the vasculature of the dog paw was tested by stimulating various peripheral nerves of the hind leg. Resistance changes of the total vasculature of the paw, and of three of its component series-coupled segments (arterial, small vessel, and venous) were studied sequentially before and during stimulation of the sciatic nerve and of three of its branches (tibial, deep, and superficial fibular nerves). Stimulation characteristics (15 to 90 volts, 1-3 msec duration, 25/sec, and 30-second stimulation periods) were chosen to produce maximum vasoconstrictive responses. Tibial and deep fibular nerve stimulations produced constriction of the arterial segment but not of the venous segment. Superficial fibular nerve stimulation produced constriction of the venous segment but not of the arterial segment. All nerve stimulations produced constriction of small blood vessel segments. Thus, responses could be limited to either arterial (plus small vessel) or venous (plus small vessel) segments. Inability to localize response within small-vessel segments made it impossible to determine whether any peripheral nerve produced constrictive responses limited strictly to either pre- or postcapillary segments. No relationship was evident between control resistance values and the subsequent changes in resistance occurring in response to the standard stimulations.
Ribonucleic Acid Synthesis in Experimental Cardiac Hypertrophy in Rats
Authors: FANBURG BARRY L. , POSNER BARRY I.
Published: June 2012

Cardiac hypertrophy was induced in rats by constriction of the aortic arch. Hearts from rats with aortic constriction increased in weight about 50% above those of control rats by 7 days after operation. RNA concentration increased between 24 and 48 hours after constriction and, thereafter, returned toward the control level. DNA concentration of hearts from rats with aortic constriction remained unchanged from that of sham-operated rats. Labeling of heart RNA with
32
P was increased relative to that of sham-operated rats within the first 4 hours after aortic constriction. However, RNA labeling, relative to the labeling of AMP derived from ATP, increased above that of sham-operated rats only after 4 hours of aortic constriction and rose to maximum or near maximum values by 8 hours after operation.

Various methods of extraction of RNA showed that the increase in labeling involved all the major species of RNA (28S, 18S, and 4S), and no evidence was found for the selective stimulation of a minority species. The nucleotide base composition of the various species of heart RNA of rats with aortic constriction was not significantly different from that of normal rats during the 4- to 8-hour period after operation. There was no terminal labeling of sRNA in hearts of either normal animals or those with aortic constriction.
Hemodynamics of Collateral Vasodilatation following Femoral Artery Occlusion in Anesthetized Dogs
Authors: ROSENTHAL STANLEY L. , GUYTON ARTHUR C.
Published: June 2012

Dilatation of collateral blood vessels was studied following occlusion of the femoral artery in anesthetized dogs. This was achieved by measuring pressure and flow in the anterior tibial artery distal to the occlusion and pressure in the femoral artery proximal to the occlusion. Dilatation of the collateral vessels to the anterior tibial artery was estimated by the increase in the conductance of the collaterals from the minimum value measured 8 to 10 seconds following onset of the occlusion. Conductance rose 277 ± 67 (SEM)% during the first 70 seconds following occlusion and an additional 178 ± 66% during the ensuing hour. When the femoral artery was reopened after a 2-minute period of occlusion, the collaterals reconstricted to their preocclusion size in 12 to 14 minutes. Elimination of circulatory reflexes by total spinal anesthesia did not alter the course of collateral vasodilatation. However, when systemic arterial pressure was lowered to approximately 45 mm Hg for 8 minutes prior to occlusion, the collaterals dilated almost completely even before the occlusion was instituted, indicating that tissue ischemia is in some way related to collateral vasodilatation.
Pharmacologic Actions of Tetrodotoxin Studied by Direct Perfusion of the Sinus Node
Authors: TOMLINSON JOHN C. , JAMES THOMAS N.
Published: June 2012

The effects of tetrodotoxin on sinus node activity were studied by direct perfusion through its nutrient artery. Tetrodotoxin suppresses action potentials by blocking sodium entry into the cell. In the open-chest anesthetized dog, direct perfusion of the sinus node artery with tetrodotoxin, 1.0 µg/ml, caused immediate sinus slowing lasting 12 to 60 minutes. This slowing was not affected by intranodal atropinization. Tetrodotoxin also produced complete blockade of sinus node response to vagal stimulation. Blockade of sinus node responses to stellate stimulation was less profound. Tetrodotoxin had no effect on chronotropic responses to intranodal acetylcholine and norepinephrine. These findings suggest that blockade of transmembrane sodium transport (or the rapid entry channel) has a negative chronotropic effect which is not cholinergic and during which response to neurotransmitter substances is normal. Concomitant with this effect there is blockade of neurotransmitter release (or synthesis) in the sinus node.
Renal Excretion of Renin in the Rat
Authors: RAPPELLI ALESSANDRO , PEART W. STANLEY
Published: June 2012

The renal excretion of renin infused intravenously was studied in anesthetized rats. The renin in the urine was adsorbed onto DEAE cellulose and selectively eluted for separate assay on the rat blood pressure preparation. The influence of saline loading, furosemide, mercuric chloride, and maleic acid was determined by following the changes in renin excretion. Both mercuric chloride and maleic acid led to a sixfold increase in the amount of renin appearing in the urine. Among the various factors which might have led to this result, an effect on renal tubular reabsorption after glomerular filtration of the renin is the most likely.
Mechanism of Cardiovascular Action of Tetrodotoxin in the Cat
Authors: FEINSTEIN MAURICE B. , PAIMRE MARVE
Published: June 2012

Tetrodotoxin given to cats in doses of 1 to 10 µg/kg iv caused profound cardiovascular depression characterized by decreases in systolic and diastolic blood pressures, pulse pressure, heart rate, force of myocardial contraction, cardiac output and peripheral resistance. These effects were associated with marked inhibition of the responses to stimulation of nerves to the adrenal medulla and the sympathetic nerves to heart and blood vessels. Sinus bradycardia due to toxin did not occur after acute cardiac sympathetic denervation. In isolated sympathetic nerve-right atrium preparations, tetrodotoxin at 1 to 2 x 10
-8
g/ml abolished the positive inotropic and chronotropic responses to nerve stimulation without effect on spontaneous rate or force, or transmitter release by tyramine. Toxin-produced vasodilation in perfused hindlimbs was associated with marked inhibition of the normal vasoconstrictor responses to sympathetic vasomotor nerve stimulation. Vasodilation was not due to a direct action on vascular smooth muscle, since it was not seen after α-receptor blockade with phenoxybenzamine, after sympathetic denervation, or after blockade of adrenergic transmitter release by guanethidine or β-TM 10 accompanied by adrenalectomy. Vasodilators such as acetylcholine, histamine and isoproterenol consistently produced additional vasodilation under these conditions. The hypotensive effect of the toxin was also observed in spinal cats. It is concluded that the potent hypotensive action of tetrodotoxin, in the cat, is primarily due to blockade of conduction in peripheral sympathetic nerves and nerve fibers innervating the adrenal medulla.
Systemic and Regional Hemodynamic Changes during Food Intake and Digestion in Nonanesthetized Dogs
Authors: FRONEK K. , STAHLGREN L. H.
Published: June 2012

In nine dogs under pentobarbital anesthesia, electromagnetic flow transducers were implanted around the ascending aorta, brachiocephalic artery, superior mesenteric artery, and iliac artery. A catheter to measure arterial pressure was implanted into the thoracic aorta. After full recovery, hemodynamic variables were measured daily in conscious dogs in five sets of recordings: control, during anticipation of food, during actual food intake, and 1 hour and 3 hours after completion of ingestion. During food intake there was a generalized sympathomimetic stimulation characterized by a significant increase in cardiac output with a peak of 142%, heart rate (176%), arterial blood pressure (147%), while the ratio of flow in the superior mesenteric artery to cardiac output decreased from 8.9% to 7.6% (
P
<0.05). Flow in the brachiocephalic artery increased during food intake to 196% and that in the iliac artery dropped to 75.4%. The possibility was discussed that a certain level of sympathomimetic stimulation may signal the diminishing or ending of ingestion. During digestion (at 1 and 3 hours after ingestion), there were no significant changes in cardiac output, heart rate, and mean arterial blood pressure, whereas the flow in the superior mesenteric artery increased to 133% and mesenteric regional resistance decreased to 82%, and flows in the brachiocephalic and iliac arteries decreased to 86.5% and 74.6%, respectively. The ratio of flow in the superior mesenteric artery to cardiac output increased to 8.9% and 12.5% in the third hour. These results indicate that a redistribution of blood flow occurs during digestion with a preference for the vascular bed of the superior mesenteric artery.
Uptake and Metabolism of
14
C-Labeled Oleic Acid by Atherosclerotic Lesions in Rabbit Aorta
Authors: DAY ALLAN J. , WAHLQVIST MARK L.
Published: June 2012

The uptake of
14
C-labeled oleic acid and its incorporation into combined lipids by aortic intimas from normal and cholesterol-fed rabbits has been investigated in vitro. More than five times as much oleic acid was taken up by the atherosclerotic intima as by the normal intima. About twice as much oleic acid was incorporated into phospholipid, and twenty times as much into cholesterol ester by the atherosclerotic intima as by the normal. Lecithin was the major phospholipid synthesized from oleic acid in both normal and atherosclerotic intimas.

Radioautographs of the atherosclerotic vessels show that the
14
C-labeled oleic acid and its metabolic derivatives, principally phospholipid and cholesterol ester, were localized in sudanophilic cells in the intima in both early and advanced lesions. It is concluded that intimal foam cells are primarily responsible for the lipid synthesis that occurs in the atherosclerotic lesion.
Activation of Adenyl Cyclase by Glucagon in Cat and Human Heart
Authors: LEVEY GERALD S. , EPSTEIN STEPHEN E.
Published: June 2012

The purpose of this investigation was to determine the direct effects of glucagon on adenyl cyclase activity in cat and human heart particles and to elucidate the role of the beta receptor in any glucagon-mediated activation of adenyl cyclase. At the peak of its dose-response curve, crystalline glucagon increased the conversion of AT
32
P to cyclic 3', 5'-AM
32
P in particulate fractions of both cat and human heart homogenates by approximately 70%. The activation of adenyl cyclase was dose-related over a concentration ranging from 1 x 10
-7
M to 1 x 10
-5
M. Half maximal activity was observed at 8 x 10
-7
M. DL-propranolol, 1 x 10
-5
M, did not block the activation of adenyl cyclase produced by glucagon, 1 x 10
-6
M or 1 x 10
-5
M. However, the same concentration of propranolol blocked adenyl cyclase activation induced by norepinephrine, 1 x 10
-6
M and 1 x 10
-5
M. Combined maximal doses of glucagon and norepinephrine did not produce additive effects on the activation of adenyl cyclase. The failure of DL-propranolol to block the glucagon-mediated activation of adenyl cyclase suggests that there are at least two receptor sites in myocardial tissue responsible for the activation of adenyl cyclase, one responsive to glucagon and one to norepinephrine. Moreover, since combined maximal doses of glucagon and norepinephrine failed to produce an additive response, it appears that in the heart there is probably only a single adenyl cyclase enzyme responsive to these hormones.
Effect of Prolonged Cold Storage on the Contractile Response of Strips of Rabbit Aorta to Various Agents
Authors: SHIBATA SHOJI , Timmerman D.D.
Published: June 2012

After 2 days in cold storage (2.0 ± 0.5°C), the contractile response of spiral strips of rabbit aorta to low concentrations (10
-9
to 10
-10
) of epinephrine and of norepinephrine was potentiated; after storage for 4 to 7 days, an increased contractile response to high concentrations (10
-8
to 10
-6
M) of these catecholamines was also observed. Reserpine-pretreated strips showed potentiation of epinephrine- and norepinephrine-induced contractions, but only after 2 to 7 days in cold storage. Another result of several days of cold storage was a decrease or loss of contractile response to nicotine (10
-5
to 10
-6
M), tyramine (10
-4
to 10
-6
M), and potassium (10 to 40 mM). Potentiation of the contractile response to epinephrine and to norepinephrine was also observed in potassium depolarized strips at low temperature (19°C). After incubation of the depolarized or cold-stored strips in the Ca-free medium, no potentiation of epinephrine- or norepinephrine-induced contractions was observed. These results indicate that cold storage, up to 7 days, does not interfere with the activation system related to epinephrine- or norepinephrine-induced contractions. However, such treatment does affect the membrane system involved in potassium-induced contraction. The decreased response to nicotine and tyramine after several days of cold storage may be due to the unavailability of tissue catecholamine. No significant histopathologic changes were observed in any layer of the aorta after cold storage up to 7 days.
Mechanochemistry of Cardiac Muscle
Authors: POOL PETER E. , CHANDLER BRIAN M. , SPANN JAMES F. , SONNENBLICK EDMUND H. , BRAUNWALD EUGENE
Published: June 2012

This investigation was designed to determine whether a defect in energy utilization exists in heart failure. Accordingly, the direct conversion of chemical energy to mechanical work was studied in right ventricular papillary muscles from normal cats and cats with experimental right ventricular failure secondary to pulmonary artery constriction. Energy production was inhibited by iodoacetic acid and N
2
. After resting or performing variable amounts of internal contractile element work under isometric conditions, muscles were instantly frozen, and the total amount of chemical energy (∼ P = creatine phosphate + ATP) used was correlated with work performed and the number of contractions. The contractile properties of papillary muscles from cats with heart failure were severely depressed. There was a significant depression in initial ∼P stores in muscles from cats with heart failure, but there was no significant change in the resting rate of ∼P utilization. Although the muscles from cats with heart failure performed, on the average, 13% as much work and were activated 64% as many times, the average amount of energy used was only 7% of that used by normal muscles. It is concluded that in this form of experimentally produced heart failure the utilization of ∼P is reduced but only in relation to the reduction in contractile element work and that the direct conversion of chemical energy to mechanical work is not an inefficient process in this state.
Range of the Sympathetic Control of the Dog Femoral Artery
Authors: GEROVÁ MÁRIA , GERO JÁN
Published: June 2012

Femoral arterial diameter and pressure were measured in anesthetized dogs. Immediately after section of the ipsilateral lumbar sympathetic chain the artery dilated, reaching a maximum of 122.0% (±0.56
sem
) of resting diameter within 30 to 40 seconds. Later the diameter diminished, stabilizing at 104.3% (±1.8
sem
) of resting diameter within 15 minutes. Stimulation of the peripheral stump of the sympathetic chain induced frequency-dependent constriction, the frequency-response curve being hyperbolic. The average maximal response was 13.42% (± 1.19
sem
) of the resting diameter. These changes were not dependent on suprarenal secretion, blood flow, or changes in distal vascular bed resistance. The contraction of the artery was slow. The half-time of stabilized contraction was 21.6 seconds at a stimulus frequency of 1/sec and 36.8 seconds at 25/sec. The half-time of relaxation was shorter (10.7 seconds and 21.5 seconds, respectively) and also frequency-dependent. A significant dilatation, after stimulation, inversely proportional to the stimulation frequency, occurred after low-frequency stimulations. The time course of contraction suggests the activation of individual smooth muscle layers successively more remote to the nerve endings, possibly due to diffusion of transmitter liberated at the nerve endings by stimulation.
Influence of Sympathetic Nerve Stimulation on Right Ventricular Outflow-Tract Pressures in Anesthetized Dogs
Authors: PACE JOHN B. , KEEFE WILLIAM F. , ARMOUR J. ANDREW , RANDALL WALTER C.
Published: June 2012

Stellate ganglion stimulation in the anesthetized, open-chest dog consistently resulted in the generation of pressure differences which averaged 20 mm Hg across the infundibular region of the right ventricle. Before stimulation, peak systolic pressures in the sinus and conus were closely matched. Peak sinus pressure showed an average increase of 184 and 162% during stimulation of the left and right stellate ganglia, respectively. Simultaneously, peak conus pressure showed average increases of 88 and 61% during left and right stellate ganglion stimulation, respectively. In addition, the maximal rate of intrasinus pressure development (dP/dt) was usually elevated above conus dP/dt, and this change contributed to the generation of early systolic pressure differences. Cervical vagosympathetic nerve stimulation following atropine administration also resulted in the generation of infundibular pressure differences, but the latter were less marked than those elicited during stellate ganglion stimulation. Elevations in main pulmonary arterial resistance abolished the induced pressure differences by allowing peak conus pressure to rise to the same extent as peak intrasinus pressure. Simultaneous electromagnetic flow recordings of pulmonary arterial blood flow during stellate ganglion stimulation revealed two- to five-fold increases in maximum flow acceleration with relatively little change in stroke volume. Infundibular pressure gradients which developed in early systole were associated with maximum flow changes in the pulmonary artery.
Inotropic Effects of Electric Currents
Authors: WOOD EARL H. , HEPPNER RICHARD L. , WEIDMANN SILVIO
Published: June 2012

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.
Effect of Exogenous Adenosine Triphosphate on the Metabolic State of the Excised Hypothermic Dog Heart
Authors: FEDELEŠOVÁ MARGITA , ZIEGELHÖFFER ATTILA , KRAUSE ERNST-GEORG , WOLLENBERGER ALBERT
Published: June 2012

Solutions of adenosine triphosphate (ATP) were injected into the left coronary artery of isolated nonperfused dog hearts kept for 30 to 180 minutes at temperatures varying from 4 to 34°C. The amount of ATP administered varied from 0.5 to 7 µmoles/g heart. The left ventricles of the ATP-treated hearts had a higher content of adenine nucleotides and of phosphocreatine than did the left ventricles of control hearts not exposed to ATP. This effect was temperature-dependent and was maximal at 14°C. Glycogen disappearance in the hypothermic myocardial tissue was markedly slowed in a dose-dependent fashion by the administration of ATP. Injections of adenine and adenosine were without effect.

An analysis of the intra- and extracellular distribution of simultaneously administered adenosine-8
-14
C-triphosphate and adenosine triphosphate-α-
32
P shows that the injected ATP was mainly split into ADP, AMP, adenosine, and inorganic phosphate and indicates that a minor percentage of these fission products entered the myocardial cells, some of the ADP and AMP being rephosphorylated there to ATP. The results suggest that intravascular introduction of ATP into the arrested hypothermic heart might help in the survival of the organ.
Electrophysiological Actions of Lidocaine on Canine Ventricular Muscle and Purkinje Fibers
Authors: DAVIS L. D. , TEMTE J. V.
Published: June 2012

Isolated canine papillary muscles with attached false tendons were perfused with Tyrode's solution containing lidocaine. Transmembrane action potentials of ventricular muscle fibers and Purkinje fibers were recorded with glass microelectrodes. Repolarization of Purkinje fibers was accelerated by lidocaine but that of ventricular muscle fibers was unaffected. The maximum rate of rise of the action potential of Purkinje fibers decreased only at 50.0 mg/liter lidocaine; that of ventricular muscle fibers was unchanged by any concentration. The curve relating rate of rise of premature responses to level of membrane potential for Purkinje fibers was unchanged with 5.0 mg/liter but shifted down and to the right with 10.0 and 50.0 mg/liter. The effective refractory period of Purkinje fibers shortened at 5.0 and lengthened at 50.0 mg/liter. The level of membrane potential needed to elicit premature propagated responses in Purkinje fibers with a standardized test stimulus increased and the earliest responses obtained in the presence of lidocaine were relatively large. Duration of the effective refractory period of ventricular muscle fibers was unchanged with 5.0 mg/liter but lengthened progressively with 10.0 and 50.0 mg/liter. Lidocaine impaired the ability of both fibers to respond to rapid frequencies of stimulation, slowed the rate of inherent diastolic depolarization of driven Purkinje fibers, decreased the rate of discharge of spontaneously beating preparations, and minimized the increase in rate and magnitude of diastolic depolarization caused normally by epinephrine. The possible role of these effects of lidocaine in regard to its antiarrhythmic actions was discussed.
Endotoxin-Induced Regional Circulatory Changes in the Unanesthetized Monkey
Authors: WYLER FELIX , FORSYTH RALPH P. , NIES ALAN S. , NEUTZE JOHN M. , MELMON KENNETH L.
Published: June 2012

Endotoxin in eight unanesthetized monkeys produced a small decrease in cardiac output, a marked fall in blood pressure, and a decrease in total peripheral vascular resistance. The distribution of cardiac output was measured by injecting nuclide-labeled radioactive microspheres (50µ in diameter) into the left ventricle, and blood flow and vascular resistance were calculated for each organ. All vascular beds except that of the spleen reacted with variable degrees of vasodilation, and the most pronounced decreases in resistance were observed in the coronary, gastrointestinal, and adrenal vasculature. Cerebral flow was reduced, but flow was maintained in the brain stem and cerebellum. In contrast to studies in other species, both the gastrointestinal tract and the kidneys showed vasodilation and no significant decrease in flow during the early phase of endotoxemia.

There is some similar evidence in humans of decreased total systemic peripheral resistance without abnormal myocardial function or pooling of blood during the early phase of endotoxemia. The acute regional circulatory changes we have found appear to indicate that endotoxin either directly or through secondary biochemical reactions initiates and maintains a generalized (except for the spleen) vasodilation that reflex compensatory mechanisms cannot overcome. This vasodilation is particularly critical in preventing maintenance of adequate blood flow to the cerebral hemispheres.
Partition of Blood Flow to the Cutaneous and Muscular Beds of the Forearm at Rest and during Leg Exercise in Normal Subjects and in Patients with Heart Failure
Authors: ZELIS ROBERT , MASON DEAN T. , BRAUNWALD EUGENE
Published: June 2012

The purpose of this study was to determine the relative effects of various levels of exercise on blood flow to skin and muscle of the resting extremity of normal subjects and the manner in which this distribution is modified by congestive heart failure. Blood flow to the skin and muscle of the forearm was determined plethysmographically with the aid of epinephrine iontophoresis at rest and during supine leg exercise in 12 normal subjects and in 9 patients with failure. In normal resting subjects, forearm blood flow averaged 6.30 ml/min/100 ml, 52% partitioned to muscle and 48% to skin. In the patients, forearm blood flow averaged 2.94 ml/min/100 ml, with 48% to muscle and 52% to skin. In normal subjects performing mild exercise, forearm muscle flow was not significantly changed, but during moderate and strenuous activity it was significantly reduced. Cutaneous blood flow, however, declined early at all levels of exertion. In the normal subjects, cutaneous hyperemia occurred late during moderate exercise but with strenuous exercise, was delayed until after exercise had been discontinued. In contrast, in the patients, forearm muscle blood flow decreased strikingly during leg exercise, cutaneous flow fell and remained depressed during the entire period of exercise, and no postexercise hyperemia occurred. Thus, in congestive heart failure, both the cutaneous and muscle beds of the forearm are abnormally constricted at rest, there is excessive vasoconstriction in both beds during leg exercise, and postexercise cutaneous vasodilation is abolished.
Propagation of Blood Flow Pulse in the Normal Human Pulmonary Arterial System: ANALYSIS OF THE PULSATILE CAPILLARY FLOW
Authors: KARATZAS NICHOLAS B. , DE J. LEE GRANT
Published: June 2012

We studied a number of dynamic events associated with the pulsatile flow of blood in the pulmonary arterial system of six healthy men in the supine position. We used the nitrous oxide-body plethysmograph method to record the pulmonary capillary blood flow pulse and the phonocardiogram to determine the time of opening and closing of the pulmonary valve. The pattern of right ventricular ejection was modified by administration of atropine and isoproterenol and by exercise.

The time of conduction of the flow pulse from the pulmonary valve to the lung capillaries averaged 120 msec. Acceleration of capillary blood during systole averaged 8.2 ml/sec/msec. The fraction of stroke volume which distended the pulmonary arterial system during systole averaged 67.2%. The peak flow rate averaged 186 ml/sec. Tachycardia resulted in a decrease in the fraction of the stroke volume stored in the arterial tree during systole. Isoproterenol and exercise resulted in an increase in average capillary blood acceleration. Conduction time is accounted for by pulmonary arterial distensibility, which also allows storage of the ejected blood during systole, which in turn helps to maintain continuity of blood flow in the capillaries. Despite these modifying effects of the pulmonary arterial system upon the flow wave, changes in the pattern of inflow pulse were detectable in the capillary flow pulse.
Decreased Affinity of Blood for Oxygen in Patients with Low-Output Heart Failure
Authors: METCALFE JAMES , DHINDSA DHARAM S. , EDWARDS MILES J. , MOURDJINIS ATHANASIOS
Published: June 2012

Oxygen affinity of blood was measured in 16 patients (nonsmokers) without anemia and with clinical evidence of low cardiac output. Of these patients, 12 were catheterized and showed an arteriovenous oxygen concentration difference across the lungs greater than 5 ml/100 ml. The partial pressure of oxygen required to half-saturate their blood with oxygen (P
50
) averaged 29.4 mm Hg (SD ± 1.9). Blood from normal subjects (nonsmokers) had an average P
50
of 27.3 mm Hg (SD ± 0.9). The decreased oxygen affinity found in blood of patients with low levels of cardiac output is considered as a compensatory adjustment to poor tissue blood flow, promoting the diffusion of oxygen from blood in tissue capillaries to intracellular sites of utilizaton.
Effects of Ouabain on Insulin Secretion in the Dog
Authors: TRINER L. , PAPAYOANOU J. , KILLIAN P. , VULLIEMOZ Y. , CASTANY R. , NAHAS G. G.
Published: June 2012

The mechanism of the previously reported hypoglycemic effect of ouabain was studied in dogs. Ouabain (1.0 µg/kg/min infused intravenously for 60 minutes) combined with insulin or propranolol caused a greater and more prolonged decrease in blood glucose than either of the drugs administered separately. In intact dogs, ouabain changed significantly portohepatic venous differences in plasma glucose from +6.6 to -13.6 mg/100 ml and in K
+
from -0.03 to -0.4 mEq/liter. In pancreatectomized animals, ouabain did not cause any significant decrease in peripheral glucose level, and the portohepatic differences in plasma glucose changed from +5.3 to +30.2 mg/100 ml and the differences in K
+
from -0.01 to +0.2 mEq/liter. These changes, indicating an increased release of glucose and K
+
by the liver in the pancreatectomized dog, were also observed in isolated rat liver perfused with ouabain 10
-6
M. Glucose uptake of the hindlimb increased significantly during the infusion of ouabain in normal dogs, but did not change in pancreatectomized dogs. Ouabain caused a significant increase in plasma insulin in portal blood (+155%). These results demonstrate that the observed metabolic effects of ouabain in the dog are mainly mediated by insulin and that ouabain increases the secretion of insulin in intact dogs.
Hypertrophied Non-Failing Rat Heart: PARTIAL BIOCHEMICAL CHARACTERIZATION
Authors: Dart Charles H. , Holloszy John O.
Published: June 2012

Cardiac hypertrophy was induced in rats by constructing an arteriovenous fistula. Heart weights approximately doubled in 7.5 weeks. The levels of activity, expressed per gram of heart, of a variety of enzymes of the mitochondrial respiratory chain and of the citric acid cycle, as well as the concentrations of cytochrome c and of mitochondrial protein, were the same in the hypertrophied and control hearts. Similarly, the capacity of whole heart homogenate to oxidize pyruvate was unaltered in hypertrophy.

There was also no change in the levels of activity of cytochrome oxidase and malate dehydrogenase, or in the concentration of cytochrome c in early hypertrophy (3 to 10 days after construction of an A-V fistula). These results suggest that cardiac mitochondria increase in parallel with the other components of the myocardial cell.

The levels of activity, per gram of heart, of creatine phosphokinase and adenylate kinase, and of the rate-limiting enzymes of glycolysis and glycogenolysis, were the same in the hypertrophied and the control hearts.

The above findings suggest that the capacity, per gram of heart, for regenerating ATP, both aerobically and anaerobically, is unchanged in the non-failing, hypertrophied heart.
Positive and Negative Inotropic Responses of the Atria and Ventricles to Vagosympathetic Stimulation in the Isovolumic Canine Heart
Authors: Priola Donald V. , Fulton Robert L. , Anagnostelis Constantine
Published: June 2012

The responses of the paced, isovolumic atria and ventricles to cervical vagosympathetic stimulation were examined in eight normal and seven sympathectomized dogs under chloralose anesthesia. Before atropine, stimulation usually caused decreases in both atrial and ventricular contractility but with significant quantitative and qualitative variation from animal to animal. The right atrium showed the greatest average decrease (>30%), followed by the left atrium (12%), right ventricle (4% to 12%), and the left ventricle (1% to 10%). After atropine, 0.5 mg/kg, all chambers responded positively to stimulation. The right ventricle was most responsive (about 30%), and the other chambers showed increases of 10% to 20%. These positive inotropic responses were eliminated by propranolol, 0.5 mg/kg, or by pentolinium tartrate, 0.5 mg/kg. In the sympathectomized animals, negative inotropic responses were usually greater and positive responses were reduced or eliminated. The data demonstrate that fibers exist in the cervical vagosympathetic trunks which have both negative and positive inotropic effects on all chambers of the heart. The net effect of vagosympathetic stimulation on a chamber's contractility reflects the relative numbers of the two fiber types which supply it. The fibers mediating the positive effects are probably preganglionic with significant postganglionic stations in the caudal cervical and stellate ganglia and perhaps in the heart itself.
Turnover and Synthesis of Norepinephrine in Experimental Hypertension in Rats
Authors: de Champlain Jacques , Mueller Robert A. , Axelrod Julius
Published: June 2012

The turnover of norepinephrine and the enzymes responsible for the synthesis of catecholamines were studied in various organs of rats made hypertensive by DOCA and NaCl. After inhibition of tyrosine hydroxylase by α-methyl-
p
-tyrosine, an increase in the rate of disappearance of endogenous norepinephrine in the heart, intestine, and spleen of hypertensive rats indicated an increased norepinephrine turnover rate in these organs: Similarly, the rate of decline of
3
H-norepinephrine endogenously formed from
3
H-dopamine seemed to be increased in the same organs from hypertensive animals. In contrast, the salivary glands showed no change in turnover of norepinephrine.

The conversion of tyrosine to catecholamines was normal in the hearts of the hypertensive rats but it was increased in the adrenal glands. The β-hydroxylation of dopamine to norepinephrine was normal or slightly increased in the heart, spleen, intestine, and salivary glands of hypertensive animals. The phenylethanolamine N-methyl transferase activity was normal in the adrenal glands. It thus seems that in hypertension produced by DOCA and NaCl the turnover of norepinephrine is increased in various organs without any detectable change in the synthesis rate, with the exception of the adrenal gland, in which it was increased. This might explain the reduction of the endogenous norepinephrine levels observed in many tissues of animals made hypertensive by DOCA and sodium.