bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of Vasopressin and the Baroreceptor Reflex System in the Regulation of Arterial Blood Pressure in the Dog
Authors: COWLEY ALLEN W. , MONOS EMIL , GUYTON ARTHUR C.
Published: June 2012

The hemodynamic effects of 1-hour intravenous infusions of vasopressin were evaluated in trained, unanesthetized dogs in the normal state and following sinoaortic baroreceptor denervation. Pressor sensitivity to vasopressin was greatly enhanced following baroreceptor denervation; threshold sensitivity was increased 11-fold and sensitivity at higher dose levels was increased 60-100-fold. Infusion of physiological levels of vasopressin caused an average increase in arterial blood pressure of 33 mm Hg in conscious, baroreceptor-denervated dogs compared with an increase of 5 mm Hg in normal dogs. In contrast, similar intravenous infusions of norepinephrine at physiological levels resulted in a 3-fold increase in pressor sensitivity with no change in threshold dose. Hy-pophysectomy of baroreceptor-denervated dogs did not significantly alter their pressor sensitivity to vasopressin in the conscious state. The arterial blood pressure response to intravenous vasopressin infusions was greatly depressed when a high background level of circulating vasopressin was present. Decapitated, spinal, anesthetized dogs maintained with a small continuous infusion of norepinephrine exhibited the greatest sensitivity to vasopressin; the threshold dose for a pressor response was similar to that in conscious baroreceptor-denervated dogs, but pressor sensitivity at physiological dose levels was increased nearly 8, 000-fold. The elevations in arterial blood pressure resulting from vasopressin infusions of less than 1.0 munits/kg min
-1
were large enough to implicate the direct pressor effect of vasopressin in the normal control of arterial blood pressure.
Estimating the Functional Capabilities of Sarcoplasmic Reticulum in Cardiac Muscle
Authors: SOLARO R. JOHN , BRIGGS F. NORMAN
Published: June 2012

A method was developed to estimate the amount of calcium which can be bound to the sarcoplasmic reticulum of the dog heart. Incubation conditions that permitted calcium oxalate uptake (steady-state filling or uptake rate) to be used as a marker for sarcoplasmic reticulum vesicles in homogenates and microsomal fractions were developed. By dividing the values for peak steady-state filling of a cardiac homogenate by those for peak steady-state filling of a sarcotubular-enriched fraction, we obtained a sarcoplasmic reticulum-homogenate ratio with units of mg sarcoplasmic reticulum x P/g wet heart, where P is the unknown fractional purity of the microsomal fraction. The mean value for the sarcoplasmic reticulum-homogenate ratio obtained from the steady-state filling studies was 6.9 mg sarcoplasmic reticulum x P/g wet heart. Similar values, 6.5 and 7.1 mg sarcoplasmic reticulum x P/g wet heart, were obtained when the rate of calcium oxalate uptake was used as the functional parameter for calculation of the sarcoplasmic reticulum-homogenate ratio. Evidence that sarcoplasmic reticulum vesicles in the homogenate are functionally the same as those in the isolated fraction was obtained. Calcium binding by the sarcotubule fraction was measured by either a spectrophotometric (murexide) or a Millipore filtration technique. Multiplication of the sarcoplasmic reticulum homogenate ratio by the amounts of calcium bound by sarcoplasmic reticulum vesicles (nmoles calcium/[mg sarcoplasmic reticulum x P]) provided an estimate of the ability of the cardiac sarcoplasmic reticulum to bind calcium. Application of this method indicated that the sarcoplasmic reticulum could bind 300-400 nmoles calcium/g wet heart at 10
-5
M free calcium and 170 nmoles calcium/g wet heart at 10
-6
M free calcium.
Norepinephrine Uptake, Smooth Muscle Sensitivity, and Metabolizing Enzyme Activity in Rabbit Veins
Authors: BEVAN JOHN A. , HOSMER DAVID W. , LJUNG BENGT , PEGRAM BARBARA L. , SU CHE
Published: June 2012

Some parameters of the adrenergic neuroeffector mechanism were measured in vitro in the central ear (near the base of the ear), common jugular, pulmonary, brachial, femoral, renal, superficial cervical, cephalic, and small saphenous veins, a branch of the deep circumflex iliac vein, the parietal branch of the internal iliac vein, branches of the anterior mesenteric vein, the inferior vena cava (immediately distal to the left renal vein), and a subcutaneous vein of the back. Although extraneuronal uptake of
3
H-norepinephrine was the same in all of the veins except the mesenteric, the neuronal uptake of norepinephrine varied widely. A number of veins, including the femoral and superficial cervical veins, showed no neuronal uptake, and the uptake of others, including the cephalic and mesenteric veins, was greater than that measured in any previously studied vascular tissue. The median effective dose for the contractile effect of norepinephrine on the veins was on the same order of magnitude as that for the aorta and the ear artery. Catechol-O-methyl transferase, but not monoamine oxidase, activity appeared to be related to innervation density. It is concluded that veins show a remarkable variation in the dimensions of their adrenergic parameters, particularly those related to innervation density.
Influence of Temperature on the Mechanical Properties of Cardiac Muscle
Authors: TEMPLETON GORDON H. , WILDENTHAL KERN , WILLERSON JAMES T. , REARDON WILLIAM C.
Published: June 2012

The influence of temperature on contractile performance, total myocardial stiffness, and the elastic and viscous components of stiffness was studied in intact hearts (dog) and isolated cardiac muscle (cat). In 12 dogs on whole-heart bypass, stiffness (Δ
P
/Δ
V
) was determined by inducing sinusoidal 0.5-ml volume changes in paced, isovolumically contracting left ventricles and measuring the resultant pressure changes (Δ
P
). In eight cat papillary muscles contracting isometrically at Lmax, stiffness (Δ
T
/Δ
L
) was similarly determined from the changes in tension and length during sinusoidal length changes of 0.25%
L
max. Total stiffness was linearly related to ventricular pressure or muscular tension during both contraction and rest. As the temperature rose from 33° to 40°C in vivo and from 22° to 40°C in vitro, the slopes of the stiffness-pressure and stiffness-tension relationships and the intercept of the latter declined; therefore, stiffness is inversely related to temperature. Since both preparations responded as linear second-order systems, stiffness could be separated into its elastic and viscous components. The moduli of both components varied in the same direction as total stiffness during temperature changes; however, the viscous component was more sensitive to the influence of temperature.
Regional Coronary Venous Oxygen Saturation and Myocardial Oxygen Tension following Abrupt Changes in Ventricular Pressure in the Isolated Dog Heart
Authors: GAMBLE WALTER J. , LAFARGE C. GRANT , FYLER DONALD C. , WEISUL JONATHAN , MONROE R. GRIER
Published: June 2012

Regional coronary venous oxygen saturation and myocardial oxygen tension (PO
2
) in isolated dog hearts were measured using two different methods--a new technique of microscopic oximetry and an improved oxygen electrode. Both methods yielded similar results. In studies of the isolated perfused dog heart developing a constant left ventricular systolic pressure, mean coronary venous oxygen saturation of blood in the subendocardial veins of the left ventricle was significantly lower than that in the subepicardial veins. Following abrupt increases in systolic pressure, subendocardial coronary venous saturations fell to even lower levels. Following abrupt decreases in systolic pressure, the mean subendocardial coronary venous oxygen saturation increased to levels above those in the blood of the subepicardial veins. These findings agree with the hypothesis that transient underperfusion and overperfusion of the subendocardial layers of the left ventricle occur with abrupt increases and decreases in ventricular pressure, respectively.
Nature of the Gap Phenomenon in Man
Authors: WU DELON , DENES PABLO , DHINGRA RAMESH , ROSEN KENNETH M.
Published: June 2012

The atrioventricular (AV) gap phenomenon occurs when the effective refractory period of a distal site is longer than the functional refractory period of a proximal site and when closely coupled stimuli are delayed enough at the proximal site to allow distal site recovery. According to previous studies, in type 1 gap, the distal site of block is distal to the His bundle (ventricular specialized conduction system) and the proximal site of block is in the AV node. In type 2 gap, both the proximal and the distal sites of conduction block are within the ventricular specialized conduction system. Using His bundle recordings and atrial extra-stimulus techniques in man, we observed three previously undescribed types of gaps between (1) the AV node (distal) and the atrium (proximal), (2) the His bundle (distal) and the AV node (proximal), and (3) the ventricular specialized conduction system or a bundle branch (distal) and the His bundle (proximal). The delays at the His bundle in the second and third types of gaps seen in this study were demonstrated as splitting of His bundle potentials. Gaps between the AV node or the His bundle and the ventricular specialized conduction system were more easily demonstrated at long cycle lengths, but gaps between the atrium and the AV node were more easily demonstrated at short cycle lengths. Therefore, the previous subdivision of gaps into two types is an oversimplification, because gaps can occur between multiple sites in the conduction system. The gap phenomenon may be potentiated by both long and short cycle lengths; long cycle lengths increase the effective refractory period of a distal site, e.g., the His bundle and the ventricular specialized conduction system, and the short cycle lengths decrease the functional refractory period of a proximal site, e.g., the atrium and the AV node.
Ontogenesis of the Renin-Angiotensin System in Spontaneously Hypertensive and Normal Wistar Rats
Authors: SINAIKO ALAN , MIRKIN BERNARD L.
Published: June 2012

Kidney renin activity was investigated in spontaneously hypertensive and normotensive control Wistar rats. Kidneys were obtained from fetal rats after 18 and 21 days of gestation and from neonatal rats 1, 7, 14, and 21 days old. Kidney renin activity was determined by a modification of the radioimmunoassay for angiotensin I developed in this laboratory, and tissue from each age group was stained for juxtaglomerular granules. Kidney renin activity progressively increased in both strains from day 18 of fetal life until day 1 of neonatal life when a plateau level developed. In 1-day-old neonatal rats, significant differences in the kidney renin activity of the spontaneously hypertensive and the normotensive strains were initially noted. Kidney renin activity was maintained at significantly higher levels in the spontaneously hypertensive strain under 21 days of age when, because of a rise in the kidney renin activity of the normotensive control strain and a fall in the kidney renin activity of the spontaneously hypertensive strain, the difference between the two strains became statistically insignificant. In both strains, juxtaglomerular granules were first noted in 1-day-old neonatal rats and in each age group thereafter.
Effect of A Renal Prostaglandin on Distribution of Blood Flow in the Isolated Canine Kidney
Authors: ITSKOVITZ HAROLD D. , TERRAGNO NORBERTO A. , MCGIFF JOHN C.
Published: June 2012

In isolated blood-perfused canine kidneys, progressive increases in renal blood flow and its fractional distribution to the inner cortex were correlated with increases in perfusate concentrations of a prostaglandin E-like (PGE-like) substance. The ratio of blood flow to the outer and inner halves of the renal cortex measured by the radioactive-microsphere method changed from 77:23 to 68:32 (
P
< 0.001) after 90 minutes of perfusion; simultaneously, the concentration of the PGE-like substance increased from 0.04 ng/ml to 0.59 ng/ml (
P
< 0.02). Thus, the greatest rate of increase in the concentration of the PGE-like substance occurred coincidently with the largest increase in inner cortical blood flow, i.e., from 30 ml/min to 69 ml/min (
P
< 0.001). During the two subsequent 90-minute perfusion periods, the ratio of outer cortical blood flow to inner cortical blood flow fell to 61:39, and the concentration of the PGE-like substance increased further. When indomethacin was added to the perfusate, the concentration of the PGE-like substance decreased from 1.00 ng/ml to 0.24 ng/ml (
P
< 0.05), and renal blood flow decreased, especially in the inner cortex where the decline was from 34% to 19% of total renal blood flow (
P
< 0.05). Thus, renal blood flow was redistributed after indomethacin was administered. PGE
2
was infused to determine whether substitution for the loss of circulating PGE-like substance could prevent the effects of indomethacin on the distribution of renal blood flow. Despite administration of exogenous PGE
2
, renal blood flow redistributed after administration of indomethacin, and the ratio of outer cortical blood flow to inner cortical blood flow increased from 68:32 to 80:20 (
P
< 0.05). These results suggest that the intrarenal site of synthesis and release of PGE
2
determines its action as a local hormone affecting deep cortical blood flow.
Chemical Composition of the Rabbit Aorta during Development
Authors: MCCLOSKEY D. IAN , CLEARY EDWARD G.
Published: June 2012

Changes in both the relative and the absolute amounts of collagen and elastin in segments of the aortic wall of New Zealand white rabbits (1-130 weeks old) were determined by chemical analysis. As in other mammals, elastin was the major component of the wall of the thoracic aorta although the proportion of collagen increased along the abdominal aorta and into the more distant arteries. Data on the absolute amounts of collagen and elastin per aorta showed that collagen and elastin deposition was most rapid during the early postnatal weeks. Although this deposition slowed in later weeks, it continued in both segments of the aorta throughout the period of this study. The proportion of the wall mass attributable to collagen and to elastin increased very rapidly during the first postnatal weeks and then, after 20 weeks, declined. The results of the present study indicate that there is a significant increase in some unidentified nonscleroprotein component within the aortic wall of older rabbits.
Effect of Prolonged Alcohol Administration on Calcium Transport in Heart Muscle of the Dog
Authors: BING RICHARD J. , TILLMANNS HARALD , FAUVEL JEAN-MARIE , SEELER KEITH , MAO JAMES C.
Published: June 2012

The effect of prolonged administration of alcohol on calcium binding and uptake by sarcoplasmic reticulum and mitochondria and on respiratory function of mitochondria was investigated in heart muscle of dogs. Dogs were paired and maintained with and without alcohol for 6 months; alcohol was administered by adding it to drinking water and food with vitamin supplements. Measurements were made after alcohol had been temporarily withheld for 2 days. Prolonged alcohol ingestion resulted in a decline in calcium binding and uptake by sarcoplasmic reticulum and mitochondria, suggesting a diminished affinity of the reticular and mitochondrial membranes for calcium ions. The endogenous calcium content of mitochondria and sarcoplasmic reticulum decreased. Prolonged alcohol administration failed to alter cardiac contractility, although contraction and relaxation tended to diminish following the administration of angiotensin. The results illustrate that one link in the regulation of the state of contraction or relaxation involving myofibrillar calcium transport is weakened in dogs maintained on alcohol for prolonged periods of time.
Influence of Muscle Afferents on Cutaneous and Muscle Vessels in the Dog
Authors: CLEMENT DENIS L. , SHEPHERD JOHN T.
Published: June 2012

In 13 anesthetized dogs with their vagi cut and their carotid sinuses kept at constant pressure, the gracilis artery, cranial tibial artery, and lateral saphenous vein of the left hind limb were isolated and perfused at constant flow. In the right hind limb, muscle afferents were stimulated by electrodes in the thigh muscles. At 5 Hz, aortic blood pressure decreased 45 ± 8 mm Hg; perfusion pressure decreased in the gracilis muscle and the paw (26 ± 6 mm Hg and 26 ± 5 mm Hg, respectively) and increased in the saphenous vein (13 ± 3 mm Hg). These effects were not prevented by paralysis of the stimulated muscles, beta-receptor blockade, or administration of atropine or antihistaminic drugs. At 40 Hz, aortic blood pressure increased 29 ± 8 mm Hg; perfusion pressure increased in the gracilis muscle and the paw (33 ± 5 mm Hg and 33 ± 3 mm Hg, respectively) and decreased in the saphenous vein (20 ± 2 mm Hg). These effects were prevented or reversed by paralysis of the stimulated muscles. Similar effects were obtained by central stimulation of the femoral nerve. Left sympathectomy or alpha-receptor blockade abolished the responses in the isolated vascular beds. Thus, muscle contraction is necessary only to activate the muscle afferents which cause constriction of resistance vessels in muscle and paw and dilation of cutaneous veins.
Right Lymphatic Duct Distribution Volume in Dogs
Authors: MEYER EDWARD C. , OTTAVIANO ROSEMARIE
Published: June 2012

Steady-state ratios of the concentration in lymph to that in plasma were measured for
125
I-serum albumin after 4 days of equilibration in unanesthetized dogs. Subsequently, acute experiments 3-8 hours in duration were carried out in the same dogs under anesthesia to measure the exchange kinetics of
131
I-serum albumin in right duct lymph and thoracic duct lymph. The albumin distribution volume in the field of right lymphatic duct drainage was calculated and compared with the pulmonary interstitial fluid volume measured using
14
C-sucrose. For the right lymphatic duct, a single rate constant (

K
R

) was sufficient to account for equilibration up to 3-8 hours. The mean value of

K
R

was 2.35 x 10
-3
± 0.99 x 10
-3
min
-1
(half-time 5.6 ± 1.96 hours). In contrast, equilibration of thoracic duct lymph was multiexponential over this period. The concentration of
125
I-albumin in lung interstitial water was 74% of that in corresponding right duct lymph. At 3-8 hours (termination of the acute experiment), fractional equilibration of interstitial albumin calculated from
131
I-albumin wash-in kinetics was 0.33 ± 0.1 and that of right duct lymph was 0.34 ± 0.11, indicating that the

K
R

measured for the latter reflects the equilibration process in lung interstitial fluid. The mean distribution volume drained by the right lymphatic duct was 0.92 ± 0.42 ml/kg. Subtracting the reported cardiac lymph distribution volume and correcting the remainder for albumin concentration relative to lymph suggests that about 28% of the lung lymph drains into the right lymphatic duct.
Cyclic Adenosine Monophosphate Modulation of Slow Calcium Influx Channels in Guinea Pig Hearts
Authors: WATANABE AUGUST M. , BESCH HENRY R.
Published: June 2012

The relationship between cellular levels of cyclic adenosine monophosphate (AMP) and slow inward calcium ion (Ca
2+
) current was studied in isolated perfused guinea pig hearts in which fast sodium ion (Na
+
) channels had been inactivated by depolarization with potassium ions (K
+
) or blockade with tetrodotoxin. Perfusion with 22 mM K
+
depolarized cardiac tissue to approximately -40 mv and rendered hearts inexcitable. Tetrodotoxin (3 x 10
-5
M) blocked excitability without altering resting membrane potential. Excitability and contractions could be restored to these hearts with a variety of inotropic agents that also raised the measured tissue levels of cyclic AMP or with high concentrations of Ca
2+
. The magnitude of steady-state tension developed by restored hearts was directly related to the external Ca
2+
concentration as well as to the concentration of the restoring agent used. The tension of restored hearts was markedly reduced by Ca
2+
-channel antagonists. Elevation of cyclic AMP levels preceded restoration of excitability to inactivated hearts. A highly significant positive correlation was found between the magnitude of Ca
2+
-dependent tension developed by restored hearts and the level of cyclic AMP in those hearts. Glucagon and ouabain, inotropic drugs that do not elevate myocardial levels of cyclic AMP, failed to restore depolarized or tetrodotoxin-blocked hearts. Therefore, cyclic AMP appears to modulate slow Ca
2+
influx channels in myocardial cells.
Comparison of Angiotensin II Antagonist and Antiserum Infusion with Nephrectomy in the Rat with Two-Kidney Goldblatt Hypertension
Authors: THURSTON HERBERT , SWALES JOHN D.
Published: June 2012

Factors responsible for maintaining blood pressure were studied in rats with one renal artery constricted and the contralateral kidney intact. Rats with short-term (< 3 weeks) and chronic (> 4 months) hypertension were infused with angiotensin II antiserum until the pressor effect of exogenous angiotensin II was blocked. The blood pressure response to an infusion of an angiotensin antagonist (1-Sar-8-Ala-angiotensin II) was then recorded. Blood pressure was also measured following subsequent unilateral nephrectomy (ischemic kidney). Antiserum produced a small, sustained, nonsignificant fall in mean blood pressure, whereas the antagonist produced a major reduction. In rats with short-term hypertension, the antagonist reduced blood pressure to normal or near-normal levels. In rats with chronic hypertension, mean blood pressure fell but still remained above the upper limit of the normal range. Removal of the ischemic kidney produced a fall in blood pressure to a mean level close to that obtained after antagonist infusion. Mean cumulative sodium balance in the rats with short-term hypertension was slightly negative. On the basis of this and previously reported work, it is suggested that angiotensin II is generated at a vascular site which is inaccessible to antibody but readily accessible to antagonist. Moreover, since the effects of angiotensin II antagonist and nephrectomy do not differ significantly, it seems that the ischemic kidney sustains hypertension in this two-kidney model through activity of the renin-angiotensin system, although extrarenal factors assume greater importance when blood pressure remains elevated for longer periods.
Transmural Gradient of Retrograde Collateral Blood Flow in Acutely Ischemic Canine Myocardium
Authors: DOWNEY H. FRED , BASHOUR FOUAD A. , STEPHENS A. Jude , KECHEJIAN SARKIS J. , UNDERWOOD RONALD H.
Published: June 2012

The contribution of retrograde coronary flow to total collateral flow was examined transmurally in anesthetized, open-chest dogs subjected to acute obstruction of the left anterior descending coronary artery. Regional coronary flow in normal and ischemic tissue was reflected by the tissue content of radioisotopes of potassium and rubidium and by radioactive microspheres. To measure total collateral flow, one isotope was administered when the retrograde cannula was clamped. The other isotope was administered when the cannula was opened to divert retrograde coronary flow away from acutely ischemic myocardium. Significant quantities of this isotope reached the ischemic region despite diversion of retrograde flow at an average rate of 3.5 ml/min. These results confirm earlier, but disputed, reports that total coronary collateral flow exceeds retrograde flow and are indicative of collateral pathways associated more closely with the microcirculation than with the larger epicardial arteries. Furthermore, the transmural distribution of myocardial blood flow in the ischemic tissue was altered nonuniformly by diversion of retrograde flow:
42
K or
86
Rb uptake was reduced to 25% of control in subepicardial tissue but only to 70% of control in subendocardial tissue. The transmural distribution of radioactive microspheres was similarly affected by diversion of retrograde flow. The results suggest that collateral pathways differ transmurally and may include significant luminal connections. Retrograde coronary flow is not a sensitive index of collateral flow to acutely ischemic subendocardial tissue.
Relationship of Ventricular Excitability Characteristics to Ventricular Arrhythmias in Dogs
Authors: HARUMI KENICHI , OWENS JOHN , BURGESS MARY JO , ABILDSKOV J. A.
Published: June 2012

The relationship of the form of ventricular anodal strength-interval curves to the types of arrhythmias induced by trains of low-intensity stimuli was studied in 16 dogs. Strength-interval curves were determined after basic atrial driven beats and after induced premature ventricular depolarizations. The test stimuli for these determinations were 2-msec anodal square waves delivered in 1-msec decrements during the first half of the cardiac cycle and in 10-msec decrements during the last half of the cycle. At each time step, the stimulus intensity was increased in 5-µamp steps until a ventricular response occurred or a level of 1.2 mamp was reached. Three types of strength-interval curves were observed. Each form of the strength-interval curve was associated with a specific type of arrhythmia induced by a train of 50-Hz, 2-msec anodal stimuli of minimum threshold intensity which was applied for periods of up to several minutes. When the minimum threshold in the strength-interval curve following the basic driven beat was lower than the minimum threshold following the induced premature ventricular depolarization, the train of stimuli induced stable ventricular bigeminy. Accelerating ventricular tachycardia followed by ventricular fibrillation resulted if there were deep dips in the strength-interval curves following both the basic driven beats and the premature ventricular depolarizations. When the strength-interval curves following both the basic driven beats and the premature ventricular depolarizations smoothly approached diastolic levels without deep dips or supernormal periods, the train of stimuli caused either occasional premature ventricular depolarizations with long coupling intervals or slow ventricular tachycardia. These relationships may participate in the initiation and the maintenance of arrhythmias.
Deleterious Effects of Hypertension on the Development of Aortic and Coronary Atherosclerosis in Stumptail Macaques (
Macaca Speciosa
) on an Atherogenic Diet
Authors: PICK RUTH , JOHNSON PHILIP J. , GLICK GERALD
Published: June 2012

Utilizing the stumptail macaque, we studied the atherosclerotic lesions produced in the aorta and coronary arteries by an atherogenic diet alone and by the diet coupled with hypertension produced by a modified Goldblatt technique. One group of monkeys was subjected concomitantly to the diet and hypertension for 10-12 months; a second group was on the diet for 29-32 months, but hypertension was induced for only the last 7-9 months of this period. In both of these groups, hypertension led to more severe lesions in the aorta. When an index of coronary involvement was plotted as a function of either arterial systolic or diastolic blood pressure, a significant correlation was found in both groups of monkeys. Additionally, in the monkeys with hypertension, morphologic criteria indicated that increased amounts of elastic fibers were present in the plaques in a disorganized, fragmented manner; in the monkeys on the diet alone, the elastic fibers were disposed in well-formed, reduplicated lamellas. Fat deposition was also different between these two groups: fat was located in the depths and at the periphery of the lesions in the hypertensive monkeys, whereas it was evenly dispersed throughout the plaques in the monkeys on the atherogenic diet alone. Thus, hypertension coupled with an atherogenic diet increases the extent of aortic and coronary lesions in proportion to the elevation in arterial blood pressure and, furthermore, may modify the morphologic characteristics of the lesions.
Limitation of the Coronary Vascular Response to Ischemia in the Awake Dog
Authors: BACHE ROBERT J. , COBB FREDERICK R. , GREENFIELD JOSEPH C.
Published: June 2012

During reactive hyperemia following a brief coronary artery occlusion, excess arterial inflow exceeds the blood flow debt incurred during occlusion by 300-600%. The present study was performed to determine whether this marked reactive hyperemia is essential for restoration of coronary vascular tone. Coronary blood flow was measured in unanesthetized dogs with electromagnetic flowmeters and hydraulic occluders chronically implanted on their left circumflex coronary arteries. When 10-second coronary artery occlusions were performed in pairs separated by a brief interval during which excess arterial inflow equaled the blood flow debt incurred during the first occlusion, reactive hyperemia following the second occlusion was no greater than that following an isolated control occlusion. Thus, approximately 100% repayment of the blood flow debt resulted in restoration of normal reactivity to a second occlusion. To further ascertain whether coronary vascular tone could be regained without the usual excess inflow, the reactive hyperemia following a 10-second occlusion was mechanically limited by partial inflation of the occluder. When reactive hyperemia equal to 115 ± 10% repayment of the blood flow debt was allowed, final complete release of the occluder was followed by no additional hyperemia. These studies demonstrated that the markedly excess arterial inflow which occurs during coronary reactive hyperemia is not essential for restoration of coronary vascular tone.
Differential Effects of an Angiotensin II Analogue on Pressor and Adrenal Receptors in the Rabbit
Authors: STEELE JOHN M. , LOWENSTEIN JEROME
Published: June 2012

The 1-sarcosine-8-alanine analogue of angiotensin II (1-Sar-8-Ala-angiotensin II) was infused at 1 and 5 µg/kg min
-1
into conscious rabbits on normal or sodium-deficient diets. Blood pressures during the control period were comparable in both groups; plasma renin activity, angiotensin II concentration, and aldosterone concentration were higher in the rabbits on the sodium-deficient diet than they were in the rabbits on the normal diet. The analogue caused a 6-mm Hg fall in mean arterial blood pressure in sodium-depleted rabbits. Plasma renin activity increased in both groups to eight to ten times the control values with the higher rate of infusion. Angiotensin II concentration paralleled plasma renin activity. Plasma aldosterone concentration increased after infusion of the analogue at 1 µg/kg min
-1
to three to four times the control values but decreased from these high levels after an additional 90-minute infusion at 5 µg/kg min
-1
to only one to two times the control values in both groups. Infusion of angiotensin II during the administration of the analogue caused a clear-cut increase in aldosterone concentration without a change in blood pressure. The persistence of elevated aldosterone levels during inhibitor blockade in the sodium-depleted rabbits does not prove that factors other than angiotensin participate in the aldosterone response to sodium deprivation. However, the data do indicate that 1-Sar-8-Ala-angiotensin II is a less effective antagonist of angiotensin II at the adrenal receptors than it is at the vascular smooth muscle receptors and suggest that the pressor and adrenal receptors differ.
Stimulation of Vascular Smooth Muscle Sodium, Potassium--Adenosinetriphosphatase by Vasodilators
Authors: LIMAS CONSTANTINOS J. , COHN JAY N.
Published: June 2012

A ouabain-sensitive, Mg
2+
-dependent, Na
+
, K
+
-stimulated adenosinetriphosphatase (ATPase) isolated from canine mesenteric arteries was activated by the following vasodilators: hydralazine, diazoxide, PGE
1
, PGE
2
, PGA
2
, and minoxidil. Epinephrine, norepinephrine, and isoproterenol also stimulated the ATPase, but PGF
2α
was ineffective. Since these vasodilators activate the adenylate cyclase of vascular smooth muscle, the effects of cyclic adenosine monophosphate (AMP) and theophylline on the Na
+
, K
+
-ATPase were studied; both substances caused a concentration-dependent increase in enzymatic activity. Propranolol blocked the catecholamine-induced stimulation of Na
+
, K
+
-ATPase, and polyphloretin phosphate antagonized the effects of the prostaglandins. It is concluded that vasodilatation in response to these substances is associated with the stimulation of the Na
+
, K
+
-ATPase of vascular smooth muscle probably mediated through cyclic AMP.
Pharmacological Characterization of Adrenergic Alpha and Beta Receptors Mediating the Vasomotor Responses of Cerebral Arteries Ir Vitro
Authors: EDVINSSON LARS , OWMAN CHRISTER
Published: June 2012

The adrenergic receptors in the isolated feline middle cerebral artery were characterized pharmacologically using a sensitive system for recording circular contractions in vitro. Epinephrine. norepinephrine, isoproterenol. and phenylephrine contracted the vessel in the mentioned order of potency. Together with the inhibitory patterns obtained with graded doses of piperoxan (reversible competitive inhibition) and dibenamine or phenoxybenzamine (irreversible competitive inhibition), these results showed that the contraction was mediated by alpha receptors. With piperoxan and norepinephrine, the mean value for pA
2
was 7.06 and for K
H
1.24 x 10
-7
M. The mean value for K
A
calculated for norepinephrine before and after partial irreversible blockade of the alpha receptors with phenoxybenzamine was 1.73 x 10
-6
M. The norepinephrine response was not directly proportional to the amount of receptors occupied; ED
50
was reached when only about 11% of the receptors were occupied and the E
Am
response was obtained when 75% of the receptors were occupied. Dilation was achieved only after an active tonic contraction had been induced (with 5-hydroxytryptamine) in the vessels, and the order of potency was isoproterenol > norepinephrine - epinephrine > terbutaline. Inhibition with INPEA and propranolol was competitive, as confirmed by Arunlakshana-Schild plots, showing that the dilatory response was a beta-receptor effect. The values for pA
2
(8.78 and 9.17) and K
H
(2.31 x 10
-9
M and 1.77 x 10
-9
M) for propranolol were indistinguishable in tests with terbutaline and isoproterenol, respectively. Comparison of the relative potencies of norepinephrine and epinephrine as well as isoproterenol and terbutaline suggested that the receptors were of the beta
1
type.
Inhibition of the Vasodilator Effect of Hypercapnic Acidosis by Hypercalcemia in Dogs and Rats
Authors: WEI ENOCH P. , THAMES MARC D. , KONTOS HERMES A. , PATTERSON. JOHN L.
Published: June 2012

The vasodilator effect of local hypercapnic acidosis, produced by intra-arterial infusion of an acid buffer solution consisting of a mixture of glycine and hydrochloric acid, in the perfused hind limb and in the perfused gastrocnemius muscle of anesthetized dogs was examined at normal plasma calcium concentration and during elevation of the plasma calcium concentration produced by intra-arterial infusion of calcium chloride. Hypercalcemia inhibited the vasodilator action of hypercapnic acidosis so that the effect was not apparent until venous blood pH decreased below 7. The dilator effect of local application of acidified Ringer's solution on arterioles of the cremaster muscle of the rat was also inhibited by elevation of the plasma calcium concentration induced by intravenous administration of calcium chloride. The available evidence suggests that this inhibition of the dilator effect of hypercapnic acidosis by calcium ions is related to competition between calcium and hydrogen ions for binding at one or more cellular sites such as the sarcolemma, the sarcoplasmic reticulum, or the contractile proteins of vascular smooth muscle.
On the Mechanism of Idioventricular Pacemaker Suppression by Fast Drive
Authors: KRELLENSTEIN DANIEL J. , PLIAM MICHAEL B. , BROOKS CHANDLER McC. , VASSALLE MARIO
Published: June 2012

The role of vagal activity, potassium concentration, and temperature in overdrive suppression of ventricular pacemakers, was studied in anesthetized dogs with and without surgical atrioventricular block. The results were as follows. (1) Overdrive of an idioventricular pacemaker during vagal stimulation was followed by a second pause. (2) Hypothermia increased the duration of the vagal and overdrive pauses. (3) Coronary sinus plasma potassium concentration ([K]
cs
) decreased with the onset of vagal stimulation and increased with overdrive during vagal stimulation. (4) The increase in [K]
cs
during ventricular overdrive was greater in hypothermia than it was in normothermia when the same absolute rate of overdrive was used and was unchanged when the same relative rate of overdrive was used. (5) Hypothermia increased overdrive suppression more than can be accounted for by the decrease in spontaneous rate, (6) By predriving the ventricles and then overdriving them, the increase in [K]
cs
was dissociated from the pause duration. It is concluded that during vagal stimulation ventricular arrest is due to the inhibition of idioventricular pacemakers by the sinus node by virtue of its faster rate and that changes in [K]
cs
are due to rate changes and not to acetylcholine release. Overdrive suppression can be dissociated from an increase in extracellular potassium concentration. Its prolongation in hypothermia provides evidence for a metabolism-dependent mechanism.
Vascular Effects of Procaine Amide in the Dog
Authors: SCHMID PHILLIP G. , NELSON LOREN D. , HEISTAD DONALD D. , MARK ALLYN L. , ABBOUD FRANCOIS M.
Published: June 2012

The mechanism of the vasodilator effect of procaine amide in dogs was investigated in isolated gracilis muscle and hindpaw perfused at constant flows with arterial blood. Inhibition of sympathetic ganglionic transmission contributed predominantly to the vasodilatation in muscle that accompanied intravenous administration of procaine amide (20 mg/kg). In contrast, comparable amounts of procaine amide administered locally had no detectable effects on resistance vessels; in both muscle and paw, no decreases in base-line perfusion pressures and no inhibition of constrictor responses to phenylephrine, angiotensin, and 5-hydroxytryptamine occurred. Also, procaine amide had no detectable effects on constrictor responses to stimulation of sympathetic postganglionic nerves. Procaine amide reduced the reflex vasoconstrictor response to carotid hypotension, but this reduction was comparable to the inhibition of sympathetic ganglionic transmission. The absence of direct inhibitory effects on baroreceptors and central reflex pathways was supported by the failure of intracarotid administration of procaine amide to alter detectably in gracilis muscle base-line perfusion pressures and reflex constrictor responses to carotid hypotension. Procaine amide reduced reflex responses to carotid chemoreceptor stimulation with nicotine but not those to stimulation with cyanide, suggesting a direct selective inhibitory action on the carotid body but not on the central pathways of the reflex. We conclude that the vasodilator effect of procaine amide results from inhibition of ganglionic transmission. A similar hexamethoniumlike effect may account for the inhibition of carotid chemoreceptor stimulation by nicotine.
Localization of heart vectors produced by epicardial burns and ectopic stimuli; validation of a dipole ranging method.
Authors: Ideker R E , Bandura J P , Larsen R A , Cox J W , Keller F W , Brody D A
Published: June 2012

Location of the equivalent cardiac dipole has been estimated but not fully verified in several laboratories. To test the accuracy of such a procedure, injury vectors were produced in 14 isolated, perfused rabbit hearts by epicardial searing. Strongly dipolar excitation fronts were produced in 6 additional hearts by left ventricular pacing. Twenty computer-processed signals, derived from surface electrodes on a spherical electrolyte-filled tank containing the test preparation, were optimally fitted with a locatable cardiac dipole that accounted for over 99% of the root-mean-square surface potential. For the 14 burns (mean radius 5.0 mm), the S-T injury dipole was located 3.4 plus or minus 0.7 (SD) mm from the burn center. For the 6 paced hearts, the dipole early in the ectopic beat was located 3.7 mm (range 2.6 to 4.6 mm) from the stimulating electrode. Phase inhomogeneities within the chamber appeared to have a small but predictable effect on dipole site determination. The study demonstrates that equivalent dipole location can be determined with acceptable accuracy from potential measurements of the external cardiac field.
Increased plasma catecholamine concentrations and vas deferens norepinephrine biosynthesis in men with elevated blood pressure.
Authors: DeQuattro V , Miura Y , Lurvey A , Cosgrove M , Mendez R
Published: June 2012

Systemic biochemical indexes of sympathetic nerve functionplasma catecholamine concentrations and serum dopamine-beta-hydroxylase activitywere correlated with regional indexesnorepinephrine concentration activities of norepinephrine biosynthetic enzymes in the vas deferensānd with blood pressures and pulse rates of 57 men at the time of vasectomy. Mean plasma catecholamine content was increased 66% and 60% in men with elevated systolic and elevated systolic and diastolic blood pressures, respectively. The norepinephrine concentration, tyrosine hydroxylase activity, and dopa decarboxylase activity in the vas deferens were increased in 12%, 26%, and 17% of the men with elevated blood pressure, respectively. Tyrosine hydroxylase and dopa decarboxylase in the men with elevated systolic blood pressure were increased 41% and 68%, respectively, compared with values in the men with normal blood pressure (P less than 0.05 and P less than 0.02). Individual plasma catecholamine content was related directly to both systolic and mean blood pressure (P less than 0.01) and to activities of vas deferens tyrosine hydroxylases (P less than 0.05) and dopa decarboxylase (P less than 0.01). There was a weak, but not significant, correlation of plasma catecholamine concentration with serum dopamine-beta-hydroxylase activity. Raised plasma catecholamine concentration in men with elevated blood pressure prior to vasectomy was associated with increased neurotransmitter biosynthesis in their vas deferens, which may indicate increased sympathetic nerve tonicity and perhaps be a factor contributing to the blood pressure elevation.
Hemodynamic effects of acute experimental aortic coarctation in the dog.
Authors: Newman D L , Walesby R K , Bowden N L
Published: June 2012

Pressure and flow pulses were recorded immediately proximal and distal to a temporary stenosis of the thoracic aorta of the dog. The severity of the stenosis was varied, and the magnitude of the pulse changes was correlated with the degree of stenosis expressed as the area ratio, As/All, where As is the cross-sectional area of the stenotic section and A-s that of the normal vessel. The harmonic amplitudes of the pressure and flow waves during the stenotic period were obtained by Fourier analysis and normalized to their values when the stenosis was released. It was found that as A-s/All yields 0 the proximal pressure amplitude increased and the distal pressure and the proximal and distal flow amplitudes decreased. These changes were such that the proximal fluid impedance calculated from the corresponding pressure and flow amplitude ratios increased as A-s/A-ll yields 0; the distal impedance remained relatively unaffected. These findings can be interpreted in terms of reflection of the pulse waves at the stenosis. The normalized proximal pressure amplitudes approximate to 1 + R and the distal pressure and both the proximal and the distal flow vary according to 1 minus R, where R is the reflection coefficient. The variation of R with A-s/A-ll can be determined from the proximal fluid impedance changes; we found that R increased relatively slowly for moderate stenoses, varying from 0 at A-s/A-ll 1.0 (no stenosis) to similar to 0.2 at A-s/A-ll equals 0.2. At more severe stenoses, it increased more rapidly approaching 1.0 at A-s/A-ll equals 0. The generation of turbulence was most marked at A-s/A-ll yields 0.2.
Motion of the tricuspid valve annulus in anesthetized intact dogs.
Authors: Tsakiris A G , Mair D D , Seki S , Titus J L , Wood E H
Published: June 2012

Phasic variations in the size, position, and geometry of the tricuspid valve annulus during the cardiac cycle were studied in five normal anethetized dogs 2-6 weeks after 8-11 lead beads had been sutured on the endocardial surface of the valve ring during cardiopulmonary bypass. Field-by-field measurements from biplane videoangiograms were used to assess changes in valve ring size and shape during control hemodynamic conditions and during increased heart rates. In addition, the percutaneous production of a complete atrioventricular block in two dogs enabled us to observe the effect of isolated atrial contractions on the valve annulus. During normal sinus rhythm, progressive narrowing of the annulus during atrial and ventricular contractions reduced its area by 20-39% of the maximal valve circumference during diastole; approximately two-thirds of the total ring narrowing was associated with atrial systole. These findings suggest that one of the functions of atrial contraction is the reduction in size of the atrioventricular valve orifices prior to the onset of ventricular systole.
Static and dynamic components in the vascular myogenic response to passive changes in length as revealed by electrical and mechanical recordings from the rat portal vein.
Authors: Johansson B , Mellander S
Published: June 2012

The effects of static and dynamic passive stretch and shortening on electrical activity and active force were analyzed in the isolated rat portal vein. Static stretch by 40% of muscle length evoked moderate excitatory effects with enhanced mechanical activity and an average increase in spike discharge of 12% above the control value of 55 plus or minus 2.6 spikes/min. The dynamic responses studied at various rates of length change (dL/dt) over the range between minus 12 and plus 12 mm/min, i.e., minus 3 and plus 3% muscle length/sec, were much more pronounced. Active force and spike activity showed graded increases with increasing rates of stretch. The electrical activity reached a value of 180 spikes/min (approximately equal to 325% of control) at 5 mm/min; this frequency was then maintained for stretch rates up to 12 mm/min. Mechanical activity during stretch was further reinforced by the shift along the length-tension diagram. Passive shortening at rates from minus 1 to minus 12 mm/min caused graded decreases in mechanical and electrical activity below the control levels, complete inhibition being observed at the latter dL/dt. Blockade of alpha and beta receptors indicated that the responses were myogenic in nature. The findings seem to provide direct support for the myogenic hypothesis of vascular tone and responses to stretch of the vascular wall, but they indicate that emphasis should be placed on the dynamic characteristics of the stimulus rather than its static nature. This emphasis constitutes a new concept in the myogenic control of the peripheral circulation.
Red cell permeability effect on the mean transit of an indicator transported through an organ by red cells and plasma.
Authors: Perl W
Published: June 2012

When an indicator that permeates red blood cells with an equilibration time of the order of the mean transit time of the indicator through an organ is bolus injected solely into the plasma inflow to that organ, the mean transit time of the indicator is greater than it is when the indicator is injected preequilibrated between the plasma inflow and the red cell inflow. The mean transit time for equilibrated entry is in turn greater than that for indicator injected solely into the red cell inflow. A simplified method of calculation of this effect is given in the present paper; it requires only a model solution for the indicator steady state as distinguished from a more complicated time-dependent solution. The dependence of the effect on red cell membrane permeability allows this permeability to suitable indicators to be deduced. The method was applied to existing data on urea and thiourea passage through the dog kidney.