bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated Induction of Two-Kidney Hypertension in Rats and Renin-Angiotensin Sensitivity
Authors: SKULAN THOMAS W. , Brousseau Armand C. , Leonard Kathleen A.
Published: June 2012

Studies were performed to substantiate the hypothesis that a physiological change, apart from the rise in blood pressure, occurs in two-kidney hypertensive rats. Both the slow development of hypertension following renal arterial constriction versus its rapid reversal following removal of the constriction and the early increase in plasma renin activity which subsides in the chronic hypertensive phase suggest such a progressive change. We studied the development of hypertension following initial renal arterial constriction (clipping) and after reclipping in rats that had been relieved of two-kidney hypertension by unclipping for 2 or 21 days. Full hypertensive blood pressure levels were established within 1-2 hours after reclipping in 2-day unclipped rats, but similar levels were not reached in either of the other two groups for at least 1 week. These changes in response to renal arterial constriction were paralleled by differences in responsiveness to hog renin and angiotensin infusions. Plasma renin activity 1 hour after clipping or reclipping was adequate to account for the observed blood pressure increases in all groups. These data suggest that (1) a physiological change resulting in increased vasoresponsiveness to renin and angiotensin occurs concomitantly with the development of two-kidney hypertension and (2) this type of hypertension is dependent on both renin and increased sensitivity to angiotensin. Moreover, we suggest that study of recently unelipped, normotensive rats may help to uncover the causes for the angiotensin sensitivity change.
Measurement of Sinoatrial Conduction Time by Premature Atrial Stimulation in the Rabbit
Authors: MILLER HUGH C. , STRAUSS HAROLD C.
Published: June 2012

The premature atrial stimulation technique was investigated as a method of measuring sinoatrial conduction time in the rabbit. Fifteen studies were performed in which intracellular recordings were obtained from a sinus node cell and atrial electrical activity was recorded from the crista terminalis by a surface electrogram. An additional ten studies were performed without microelectrode recordings. Atrial premature depolarizations late in the cardiac cycle produced compensatory atrial return cycles, but earlier premature depolarizations produced less than compensatory return cycles. Compensatory return cycles only occurred with atrial premature depolarizations that failed to capture the sinus node cell. The transition from compensatory to less than compensatory return cycles occurred with late atrial premature depolarizations that failed to capture the sinus node. Therefore, the transition from compensatory to less than compensatory atrial return cycles failed to indicate sinus node capture by an atrial premature depolarization. Although these premature depolarizations were too late to capture the sinus node cell, they still shortened the sinus node and atrial return cycles to make the atrial return cycle less than compensatory. This shortening of the sinus node return cycle was due to a shortening of the sinus node action potential by electrotonic interaction between sinus node and adjacent cells during repolarization. The electrotonic effect resulted in shortening of the sinus node action potential and accounted for the poor correlation (
r
= 0.64) between estimated and measured values of sinoatrial conduction time. These data indicate that there are significant limitations to the use of the premature atrial stimulation technique for estimating sinoatrial conduction time.
Prior receptor occupancy as a determinant of the pressor activity of infused angiotensin II in the rat.
Authors: Thurston H , Laragh J H
Published: June 2012

The pressor responsiveness to angiotensin II and norepinephrine was examined in rats before and during blockade of coverting enzyme activity with the nonapeptide SQ 20881. Responses to angiotensin II were impaired by sodium deprivation but enhanced by sodium loading or bilateral nephrectomy. During the period of converting enzyme blockade, a twofold increase in the angiotensin II pressor response was observed in the salt-restricted rats, whereas only a small change occurred in the salt-loaded rats. Infusion of the inhibitor produced a profound fall in the blood pressure of the salt-depleted rats with a relatively minor fall in the sodium-loaded rats. Norepinephrine pressor responses were slightly potentiated in the salt-restricted rats after administration of SQ 20881, but no change occurred in the salt-loaded or the nephrectomized rats. These observations support the view that the decreased angiotensin II pressor activity during salt deprivation is the result of a prior occupancy of receptor sites by endogenous hormone. Therefore, a change in the number or the affinity of receptors consequent to changes in sodium balance need not be postulated to explain the phenomenon.
Enhanced renal prostaglandin production in the dog. II. Effects on intrarenal hemodynamics.
Authors: Chang L C , Splawinski J A , Oates J A , Nies A S
Published: June 2012

The effects of enhanced endogenous production of prostaglandins by the kidney on the distribution of blood flow in the renal cortex were assessed by infusing sodium arachidonate, the precursor of the renal prostaglandins, into one renal artery of the dog. The changes produced with arachidonate (3 times 10--6 g/kg min-1 and 10--5 g/kg min--1) were compared with those produced by infusions of prostaglandin (PG) E2 (10--7 g/kg min--1) and PGF2alpha (3 times 10--7 g/kg min--1) into one renal artery. Distribution of renal blood flow was measured by the radioactive microsphere technique. Sodium arachidonate caused an increase in blood flow to the inner cortical zones with no change in flow to the nephrons in the outermost quarter of the cortex. PGE2 increased flow to all cortical zones, and PGF2alpha produced no change in flow. Since arterial blood pressure did not change, changes in vascular resistance were reciprocal to changes in flow. Thus, vascular resistance fell in the inner cortical regions but not in the outer regions, with arachidonate infusions and in all regions of the cortex with PGE2 infusions; no changes were seen with PGF2alpha infusions. These data indicate that prostaglandin formed endogenously in the kidney affects the vascular resistance of only the inner cortical nephrons; the data thus support the hypothesis that renal prostaglandins are one mediator of renal autoregulation of blood flow.
Permeability of connective tissue linings isolated from implanted capsules; implications for interstitial pressure measurements.
Authors: Granger H J , Taylor A E
Published: June 2012

Quantification of the permeability of connective tissue linings isolated from implanted capsules was achieved by two types of experiments. The objective of the first type was to determine the restriction offered by the lining to diffusion of 125I-labeled human serum albumin. The restricted diffusion coefficient of albumin with respect to the connective tissue lining the luminal capsule surface (internal lining) averaged 3.0 times 10-7 plus or minus 0.4 times 10-7 cm2/sec in ten experiments indicating that the rate if migration of albumin across the structure was 35% of its free diffusion rate in water. In contrast, the albumin diffusion coefficient obtained for the abluminal (external) lining suggested that diffusion of albumin through this structure was 73% of the free diffusion rate in water. The objective of the second type of experiment was to determine solute reflection coefficients for inulin, serum albumin, and gamma-globulin with respect to the internal and external linings. For the internal lining, the reflection coefficients were: inulin 0.07, albumin0.23, and gamma-globulin 0.53. The external lining showed greater leakiness as evidenced by its lower reflection coefficient for a given molecule and its higher hydraulic conductivity. An equivalent pore calculation resulted in a calculated pore radius of 250-350 angstrom for the internal lining and a calculated pore radius of 500-600 angstrom for the external lining. The ineffectiveness of the leaky capsule lining in transmitting oncotic pressure suggests that under normal conditions the capsule measures interstitial hydrostatic pressure rather than oncotic pressure.
Intimal injury and regrowth in the rabbit aorta; medial smooth muscle cells as a source of neointima.
Authors: Spaet T H , Stemerman M B , Veith F J , Lejnieks I
Published: June 2012

The present study was undertaken to determine the mechanism of neointima formation in rabbit arteries subjected to extensive endothelial desquamation. Endothelial cells were selectively removed from the abdominal aorta by passing an inflated balloon catheter through the vessel. The healing response was then studied serially for up to a week, when neointima formation had provided a virtually complete cover. In en face preparations, the early neointimal cells appeared in random locations; they did not develop in apposition to residual, healthy endothelium. The possibility of blood cell colonization was explored by inserting killed aortic homografts. Since these homografts showed neointima formation only close to the site of junction with the normal aorta and as a direct extension of healthy endothelium, the likelihood of significant blood cell colonization was deemed small. Histologic and electron microscopic sections provided evidence that the early neointimal cells in the healing aorta were derived from medial smooth muscle cells. Healing of the injured arterial intima was accompanied by thickening instead of prompt restoration to normal, and the thickened intima resembled an arteriosclerotic plaque. The present study thus supports the concept that arteriosclerosis is a disease involving proliferation of medial smooth muscle cells.
A mechanism for the electrocardiogram response to left ventricular hypertrophy and acute ischemia.
Authors: Thiry P S , Rosenberg R M , Abbott J A
Published: June 2012

A proposed mechanism for explaining the electrocardiographic response in left ventricular hypertrophy and in subendocardial and epicardial acute ischemia was incorporated in a mathematical model of electrical heart activity. The model of hypertrophy was simply an increase in cell size, and the principal effect on the computer-generated 12-lead electrocardiograms (ECGs) was an increase in R-wave amplitude and ventricular activation time and a flattening or polarity reversal of the T wave. The model of acute ischemia was a reduction between plateau and resting potential of the transmembrane action potential. The principal effect on the computer-generated 12-lead ECGs was an S-T segment displacement up or down depending on the location of the lesion. This shift was linearly proportional to the severity of the ischemia, i.e., the reduction in electrical activity of the ischemic cell, and for a lesion of given severity the S-T segment shift was a measure of the area, not the volume, of ischemic tissue. Therefore, this model suggests that a direct correlation does not necessarily exist between volume-measuring tests such as serum enzyme values in the case of necrosis and S-T segment shifts.
Hemodynamic and humoral characteristics of hypertension induced by prolonged stellate ganglion stimulation in conscious dogs.
Authors: Liard J F , Tarazi R C , Ferrario C M , Manger W M
Published: June 2012

Recent evidence has suggested that cardiac factors may play a role in the evolution of arterial hypertension. To test the possibility that an increase in cardiac-performance can lead to a sustained increase in systemic blood pressure, we electrically stimulated the left stellate ganglion of six conscious dogs continuously for a 7-day period and monitored cardiac output and arterial blood pressure. In all six dogs, stimulation elicited an abrupt rise in systemic blood pre-sure that was entirely due to rise in cardiac output that lasted at least 6 hours. After 1 day of continuous stimulation, cardiac output retured to control values, but blood pressure remained elevated. After 7 days of stimulation, blood pressure was increased by an average of 25 mm Hg and peripheral resistance by 35 plus and minus 4%. Measurements of blood volume, plasma renin activity, circulating catecholamines (three of the six dogs), and sodium balance showed that none of these factors could explain the development pf this sustained hypertension. Pharmacologic blockade with phenoxybenzamine prevented in large part the rise in blood pressure in short-term stellate ganglion stimulations, whereas propranolol had very little effect on the pressor response, although it nearly abolished the increase in cardiac output. The data indicate that continuous stimulation of the stellate ganglion in conscious dogs leads to substained rises in both blood pressure and peripheral resistance; these changes are apparently mediated by increased activity of the sympathetic nervous system.
The heart as a target organ in systemic allergic reactions: comparison of cardiac analphylaxis in vivo and in vitro.
Authors: Capurro N , Levi R
Published: June 2012

The purpose of this investigation was to define and quantitatively evaluate cardiac anaphylaxis in vivo. Guinea pigs, passively sensitized with graded amounts of rabbit antipenicilloyl antibody, were anesthetized, ventilated, and challenged intravenously with a constant amount of antigen (anaphylaxis in vivo). In other experiments, guinea pig hearts were excised, perfused in a Langendorff apparatus, and challenged (analphylaxis in vitro). During in vivo anaphylaxis, sinus rate increased 10-30 beats/min, conduction arrhythmias occurred in 15 of 22 experiments, and ventricular fibrillation was seen in 8 of 22 experiments. Tachycardia and arrhythmias began approximately 20 seconds after antigen administration and were accompanied, but not preceded, by respiratory and pressor changes. During in vitro anaphylaxis, sinus rate increased 70-110 beats/min, coronary flow rate decreased 2-22%, conduction arrhythmias occurred in 21 of 31 experiments, and ventricular ectopic activity was seen in 13 of 31 experiments. Tachycardia and arrhythmias began approximately 15 seconds after antigen administration. Sinus tachycardia, atrioventricular conduction block, increased ventricular automaticity, and histamine release were characteristic features of cardiac anaphylaxis in vivo and in vitro. Both in vivo and in vitro, the intensity of the cardiac reaction depended on the amount of antibody used in passive sensitization. Our results clearly indicate that the heart reacts as a target organ in systemic anaphylaxis of the guinea pig.
Correlation between the response of the heart to sympathetic stimulation and the release of endogenous catecholamines into the coronary sinus of the dog.
Authors: Yamaguchi N , de Champlain J , Nadeau R
Published: June 2012

The relationship between the increase in catecholamine levels of the coronary sinus blood and the amplitude of various cardiac responses to adrenergic nerve stimulation was studied in anesthetized dogs. Plasma catecholamine levels in both coronary sinus and aortic blood were measured by a modification of the radiometric enzymatic assay for tissue catecholamines and were found to be 0.622 plus or minus 0.104 (SE) ng/ml and 0.933 plus or minus 0.116 ng/ml, respectively, under basal conditions. The catecholamine levels in coronary sinus blood increased linearly during right cardioaccelerator nerve stimulation up to a frequency of 10 Hz. At this frequency, maximum values were observed in both coronary sinus blood catecholamine levels and cardiac responses. The correlation between the response in heart rate, mean coronary blood flow, and dP/dt of left ventricular pressure and the increase in endogenous catecholamine levels of coronary sinus blood was significant, but the relationship was nonlinear. The present experimental design may prove to be a reliable means of studying the role of the sympathetic nervous system in the regulation of cardiovascular function in vivo.
Evidence for the existence of an acetone soluble renin inhibiting factor in normal human plasma.
Authors: Kotchen T A , Talwalkar R T , Kotchen J M , Miller M C , Welch W J
Published: June 2012

After addition of exogenous human renin, the in vitro rate of angiotensin I generation is faster in plasma of patients with chronic renal insufficiency and, to a lesser extent, in plasma of patients with essential hypertension than in plasma from normotensive control subjects. The increased reactivity of renin in hypertensive and uremic plasma is not related to differences of endogenous renin activity, angiotensinase activity, renin substrate concentration, or substrate reactivity. Addition of normal, hypertensive, and uremic plasma to a human renin-sheep renin substrate system inhibited the rate of angiotensin generation, although significantly less inhibition was observed with uremic plasma. The reactivity of renin increased in normal plasma but not in uremic plasma after treatment with 95% acetone. After acetone extraction renin reactivity in normal and plasma inhibited the rate of angiotensin generation in a renin-renin substrate system. Less inhibition occurred with the acetone extract from a pool of uremic plasma. These results provide evidence for the existence of a naturally occurring acetone soluble renin inhibiting factor in normal and uremic plasma. The increased reactivity of renin in uremic plasma may be related to a deficiency of this factor.
Mechanism of vascular hyperresponsiveness in the spontaneously hypertensive rat.
Authors: Lais L T , Brody M J
Published: June 2012

Hyperresponsiveness of resistance vessels has been described in various vascular beds of spontaneously hypertensive rats perfused with artificial medium. This change has been attributed to altered vascular dimensions secondary to the development of hypertension. To test the possibility that true changes in sensitivity might contribute independently to vasoconstrictor hyperresponsiveness in spontaneously hypertensive rats, threshold vasoconstrictor doses of norepinephrine and barium chloride were determined in denervated hindquarters of rats perfused at constant flow with autologous blood. Threshold constrictor responses to norepinephrine were elicited in the hypertensive rats at concentrations averaging less than one-third that required in controls. Threshold vasoconstrictor concentrations of barium were not significantly different between the two groups. The ratio of norepinephrine/barium sensitivity was also significantly elevated in the hypertensive group. These data suggest that in the presence of a full humoral complement, excitability (barium sensitivity) in resistance vessels of spontaneously hypertensive rats is not altered, whereas the smooth muscle is hypersensitive to norepinephrine. Thus, it appears that changes in sensitivity as well as altered vascular geometry are important in the production of vascular hyperresponsiveness in the spontaneously hypertensive rat.
Pharmacological effects of alpha-methyldopa, alpha-methylnorepinephrine, and octopamine on rat arteriolar, arterial, and terminal vascular smooth.
Authors: Altura B M
Published: June 2012

Experiments on rat mesenteric arterioles, metarterioles, and aortae demonstrate that although alpha-methylnorepinephrine is much less potent in inducing contraction than epinephrine on all three blood vessel types, it is either equivalent or only one and a half to two times less potent than the natural postganglionic neurotransmitter, norepinephrine, on these blood vessels. Furthermore, alpha-methylnorepinephrine is equivalent to norepinephrine in its ability to induce maximal contractile responses on rat arterioles, metarterioles, and aortae. Systemic administration of alpha-methyldopa to rats for 15 days shifted the log dose-response curves for all three catecholamines, but not vasopressin or potassium chloride, to the right of all three blood vessel types; the maximal contractile responses to these amines were, however, not affected by chronic treatment with alpha-methyldopa. In addition, acute, intra-arterial administration of 500 mg/kg of alpha-methyldopa was found not only to induce mesenteric arteriolar vasodilatation gradually but also to depress arteriolar reponsiveness to catecholamines. In view of these direct findings, it is difficult to accept the hypothesis that alpha-methyldopa induces hypotension via formation of a "false" postganglionic neurotransmitter substance, namely, alpha-methylnorepinephrine. The present findings suggest that alpha-methyldopa may exert some of its anti-hypertensive action, at least in the rat, by (1) depressing arteriolar responsiveness to circulating and released catecholamines and (2) some unknown direct action on peripheral vascular muscle. In addition, the present study indicates that octopamine is (1) between 60 and 15,000 times less potent than norepinephrine on rat arterioles and metarterioles and (2) incapable of eliciting more than a 40% occlusion of these terminal vessels. It is suggested that such data support the concept that octopamine, in contrast to alpha-methylnorepinephrine, could serve as a false adrenergic neurotransmitter agent and thus account for part or all of the hypotensive action of monoamine oxidase inhibitors like pargyline. The use of complete dose-response curves, several different adrenergic compounds (i.e., epinephrine, norepinephrine, alpha-methylnorepinephrine, octopamine, phenylephrine, and dopamine), and different rat blood vessels supports the concept that adrenergic molecules containing a catecholamine nucleus and a beta-hydroxyl group elicit the most potent constrictor responses from peripheral blood vessels. In addition, the data suggest that the structure-activity relationships for catecholamines and their analogs on terminal vascular smooth muscle are probably different from those for arterial smooth muscle.
A circulating renin activator in essential hypertension.
Authors: Sambhi M P , Eggena P , Barrett J C , Tuck M , Wiedeman C E , Thananopavarn C
Published: June 2012

The rate of angiotensin generation with added renin in plasma from patients with benign essential hypertension has been shown to be higher than in plasma from norm ensive controls. An index of the angiotensin generation rate in relation to to al plasma renin substrate (PRS-r index) has been defined which allows for screening for "activated" plasma. In hypertensive subjects, this index was shown to be higher than that of the normotensive subjects (61 plus or minus 2.4 SE, and 45 plus or minus 5 SE). The index did not correlate with the absolute levels of blood pressure, 24-hour sodium excretion, or plasma renin activity in hypertensive subjects either during the control period or during acute alterations of blood pressure, but was shown to respond in a parallel fashion with chronically induced changes in blood pressure and circulating levels of angiotensin I. By the use of an isolated system of human renin and homologous renin substrate, we have demonstrated that plasma from hypertensive subjects contains a modifier of the renin reaction which increases both V-max and Km of the system, behaving as an uncompetitive activator. No significant change was noted with the addition of normal plasma to the same isolated system.
Response of type B atrial vagal receptors to changes in wall tension during atrial filling.
Authors: Recordati G , Lombardi F , Bishop V S , Malliani A
Published: June 2012

In anesthetized curarized cats with their chests open, we recorded the activity of type B right atrial vagal stretch receptors, right atrial pressure, and instantaneous dimensional changes of the right atrium. The nervous activity was analyzed during alterations in atrial dynamics produced by acute volume loading of the right atrium under control conditions and during sympathetic and vagal stimulations. Our results demonstrated that the mean frequency of discharge in the burst was dependent on the absolute tension and the rate of change in tension developed in atrial muscles during filling. The responses of different receptors to changes in atrial dynamics were qualitatively similar but characteristic for each receptor studied. In some experiments nervous activity was recorded after the cats had been killed: static and dynamic changes in atrial tension were then produced by injecting blood into the right atrium. Under these conditions dynamic stimuli always activated the receptors at tensions below the threshold for static stimuli. During dynamic stimuli the instantaneous firing rate was always higher than it was during static stimuli applied at the same level of tension. This study indicates that the nervous activity of type B atrial vagal receptors is closely dependent on static and dynamic changes in atrial wall tension.
Correlation of the glycoside response, the force staircase, and the action potential configuration in the neonatal rat heart.
Authors: Langer G A , Brady A J , Tan S T , Serena D
Published: June 2012

The rat heart demonstrates marked alterations in its responses to ouabain and increased frequencies of stimulation and in the duration of its action potential during the initial 21 days of life. At an age of 6.2 days 5 times 10- minus 5M ouabain produced a 158.2% increase in dP/dt compared with a 17.2% increase at 21.1 days (P less than 0.001). At 6.2 days dP/dt increased by 53.4% when the heart rate was accelerated from 30 to 90 beats/min compared with an increase of 12.2% at 21.1 days (P less than 0.005). The positive glycoside and staircase responses at the younger age were virtually eliminated when the hearts were perfused with a solution containing 50% [Na+]o and 25% [Ca-2+]o ([Ca-2+]o/[Na+]o-2 maintained constant). The duration of the ventricular action potential progressively decreased from 350-400 msec at birth to 100-150 msec at 21 days of life. This decrease was due to a shortening and a decrease in the potential level of the plateau phase. The prominent plateau typical of the early neonatal period was significantly diminished by perfusion with 50% [Na+]o. The results suggest that Na+ flux through a slow membrane channel plays a significant role in the positive staircase and glycoside responses of the early neonatal rat heart. As the heart matures and becomes functionally anomalous relative to other mammalian species, the slow channel progressively closes.
Mechanism of the serotonin effect on lung transvascular fluid and protein movement in awake sheep.
Authors: Brigham K L , Owen P J
Published: June 2012

To see how serotonin affects filtration from lung vessels, we measured vascular pressures, lung lymph flow, lung lymph and blood plasma protein concentrations, arterial blood gases, cardiac output, and lung water content in unanesthetized sheep before and during intravenous serotonin infusions and compared serotonin effects with the effects of inflating a balloon in the left atrium in the same sheep. Serotonin caused a dose-related increase in lung lymph flow and a dose-related decrease in lymph-plasma protein concentration ratios. Steady-state 4-hour serotonin infusions at 4 mu-g/kg min-1 caused lymph flow to increase from 5.4 plus or minus 0.7 (SE) ml/hour to 8.3 plus or minus 1.3 ml/hour, lymph-plasma albumin ratios to fall from 0.78 plus or minus 0.05 to 0.72 plus or minus 0.04, lymph-plasma globulin ratios to fall from 0.64 plus or minus to 0.56 plus or minus 0.02, and pulmonary arterial and left atrial pressures to increase by 3 cm H-20 each. Lymph clearance and permeability-surface area products for eight protein fractions ranging from 36 A to 96 A in molecular radius during steady-state serotonin infusion studies were not significantly different from those during steady-state increased pressure studies. Four-hour infusions of serotonin at 4 mu-g/kg/kg min-1 caused a moderate fall in arterial Po-2 and a slight increase in arterial pH but did not affect cardiac output or cause pulmonary edema. We conclude that serotonin increases lung transvascular filtration primarily by increasing the transmural pressure gradient in exchanging vessels rather than by increasing vascular permeability.
Determinants of fast- and slow-pathway conduction in patients with dual atrioventricular nodal pathways.
Authors: Wu D , Denes P , Dhingra R , Wyndham C , Rosen K M
Published: June 2012

Electrophysiological studies were performed in two patients with documented paroxysmal supraventricular tachycardia and dual atrioventricular (AV) nodal pathways as defined by the atrial extra-stimulus technique. Both patients manifested two ranges of A-H intervals (AV nodal conduction times) at critical cycle lengths, reflecting fast- and slow-pathway conduction. The occurrence of fast- and slow-pathway conduction at the same cycle length depended on a long fast-pathway effective refractory period relative to the spontaneous or driven cycle length. At critical cycle lengths with fast-pathway conduction, a shift to slow-pathway conduction could be induced by a premature atrial impulse falling within the effective refractory period of the fast pathway. Repetitive retrograde concealed conduction to the fast pathway then maintained antegrade slow-pathway conduction. Resumption of fast-pathway conduction was induced with premature atrial impulses falling within the effective refractory periods of both the fast and the slow pathways, allowing recovery of the fast pathway for antegrade conduction. Atrial echoes and AV nodal reentrant paroxysmal supraventricular tachycardia occurred when sufficient slow-pathway delay was achieved to allow recovery of the fast pathway for retrograde conduction.
Radioiodinated soluble canine fibrin. Preparation and evaluation as a thrombus localizing agent in the dog.
Authors: Coleman R E , Harwig S S , Harwig J F , Sherman L A , Welch M J
Published: June 2012

To develop a thrombus localizing tracer which has characteristics superior to labeled fibrinogen for external detection, we evaluated radioiodinated soluble fibrin. Labeled soluble fibrin was prepared by clotting and dissolving radioiodinated (131I) canine fibrinogen under specified conditions. Biological clearance studies revealed rapid clearance of the labeled soluble fibrin from the blood with a half-life of 5 hours. The accumulation of labeled soluble fibrin and fibrinogen in induced venous thrombi, coronary artery thrombi, and the myocardium was compared in dogs. In venous thrombi, soluble fibrin and fibrinogen exhibited maximum thrombus-blood ratios when they were injected 4 hours after thrombus induction; the thrombus-blood ratio was greater for soluble fibrin than it was for fibrinogen when these agents were injected 4, 8, or 24 hours after thrombosis induction. In induced coronary artery thrombi, soluble fibrin and fibrinogen accumulated to the same extent. Since the blood clearance of soluble fibrin is faster than that of fibrinogen, a higher thrombus-blood ratio was obtained with soluble fibrin in coronary artery thrombi. The thrombus-infarcted myocardium, thrombus-normal myocardium, and infarcted myocardium-normal myocardium ratios obtained with soluble fibrin were slightly higher than those obtained with fibrinogen. Thus, soluble fibrin offers some advantages when it is compared with fibrinogen as a thrombus detecting agent.
The differences in atrioventricular conduction of premature beats in young and adult goats.
Authors: Gough W B , Moore E N
Published: June 2012

Atrioventricular (AV) conduction was studied in anesthetized, open-chest, 1-35-day-old goats. Atrial, bundle of His, and ventricular bipolar electrograms were recorded, and the functional refractory periods of the AV conduction system and the ventricles were determined. Supraventricular premature excitation invaded the ventricles during their vulnerable period. This AV conduction property is different from that of the adult goat heart; thus, the existence of a lateral accessory bypass tract was investigated. Electrocardiographic leads I, aVF, and V10 revealed no delta waves indicative of ventricular preexcitation. Bundle of His electrograms showed that: (1) bundle of His excitation always preceded the onset of ventricular depolarization, (2) no shortening occurred in the bundle of His to ventricular activation time following early atrial premature beats, and (3) the functional refractory period of the AV node was less than that of the ventricle. The ventricular epicardial excitation sequence indicated no involvement of a lateral bypass tract in the AV conduction of basic or premature beats. Interruption of the bundle of His caused complete AV block. Therefore, no functional lateral accessory bypass tracts are present in the young goat heart, and the AV node and the ventricular specialized conduction system of the young goat are capable of conducting premature atrial excitation to the ventricles within plus or minus 10 msec of the expiration of the ventricular functional refractory period.
Localization patterns of plasma apolipoproteins in human atherosclerotic lesions.
Authors: Hoff H F , Heideman C L , Jackson R L , Bayardo R J , Kim H S , Gotto A M
Published: June 2012

The localization patterns of human plasma lipoproteins and their respective apoproteins and of neutral lipid were determined in normal and atherosclerotic arteries. Specific antisera were prepared against plasma low-density lipoproteins(LDL) and their apoproteins (apoB), high-density lipoproteins(HDL) and one of their major apoproteins (apoA-I1, and apoC-III, which is a major apoprotein of very low-density lipoproteins (VLDL). Using immunofluorescence techniques, the various antigens were localized in arterial samples obtained at surgery or autopsy. The three apoproteins and neutral lipid were localized to the same tissue areas, namely, lipid core regions and certain connective tissue of atherosclerotic lesions, in 61% of the fibrous plaques and 48% of the fatty streaks examined. In marked contrast, none of the uninvolved arterial regions showed the presence of all four factors together. As controls, the localization of other serum proteins was also determined in these arteries using immunofluorescence techniques. Fibrinogen was associated with regions of maximum complementary localization of factors in 37% of the fibrous plaques and 64% of the fatty streaks. However, albumin was found in only 4-5% of these same regions. The present results suggest that not only LDL but also HDL and VLDL or their respective apoproteins as well as fibrinogen are specifically retained by certain tissue components of the atherosclerotic lesion.
Effects of neurotransmitters injected into the posterior and the anterior septal artery on the automaticity of the atrioventricular junctional area of the dog heart.
Authors: Motomura S , Iijima T , Taira N , Hashimoto K
Published: June 2012

The effects of neurotransmitters injected into the posterior and the anterior septal artery on the automaticity of the atrioventricular (AV) junctional area were examined in the excised, blood-perfused canine AV node preparation. An AV rhythm of 57.4 +/- 2.8 beats/min (N = 28) developed after the destruction of the sinoatrial node. l-Norepinephrine injected into the anterior septal artery increased the frequency of AV rhythm, but l-norepinephrine injected into the posterior septal artery caused a pacemaker shift from the anterior septal artery area to the posterior septal artery area. Acetylcholine injected into the posterior septal artery blocked retrograde conduction but did not decrease the frequency of AV rhythm; however, acetylcholine injected into the anterior septal artery decreased AV rhythm but did not affect retrograde conduction. Destruction of the posterior septal artery area failed to change AV rhythm. The surgically separated anterior septal artery preparation had the same rate as did the AV node preparation. The posterior septal artery preparation had a definitely lower rate and responded to smaller doses of l-norepinephrine than did the AV node preparation. The results of the present study indicate that AV rhythm in the AV node originates in the area supplied by the anterior septal artery and that the area supplied by the posterior septal artery, which has extremely low automaticity, is highly responsive to l-norepinephrine, resulting in nodal tachycardia.
The sequence of retrograde atrial activation in the canine heart. Correlation with positive and negative retrograde P waves.
Authors: Waldo A L , Vitikainen K J , Hoffman B F
Published: June 2012

The relationship of P-wave polarity and morphology in leads II, III, and aVF to the sequence of atrial activation was studied in the canine heart when the atria were paced from the region of the sinus node or the posterior-inferior left atrium and when retrograde activation of the atria occurred with right ventricular epicardial pacing. Deeply negative P waves in leads II, III, and aVF which occurred when the posterior-inferior left atrium was paced were associated with true retrograde activation of the atria. Positive P waves recorded in leads II, III, and aVF during retrograde atrial capture with right ventricular pacing were associated with rapid retrograde spread of the impulse in the interatrial septum to the region of Bachmann's bundle from which site the impulse spread to depolarize significant portions of both atria in a manner similar to that demonstrated during pacing from the region of the sinus node. When the atria were paced from a site just anterior to the coronary sinus ostium, positive P waves recorded in leads II, III, and aVF were associated with early activation in the vicinity of Bachmann's bundle and later activation of the posterior-inferior left atrium. When the atria were paced from a site just posterior to the coronary sinus ostium, negative P waves in leads II, III, and aVF were associated with early activation of the posterior-inferior left atrium and later activation in the vicinity of Bachmann's bundle. It was concluded that the time of arrival of the impulse at Bachmann's bundle relative to that at the posterior left atrium and the direction of spread of the impulse from and within Bachmann's bundle are critical in determining P-wave polarity and morphology.
Ventricular intramural and epicardial potential distributions during ventricular activation and repolarization in the intact dog.
Authors: Spach M S , Barr R C
Published: June 2012

Ventricular intramural and epicardial potential distributions were measured during normal excitation and repolarization in intact dogs. Potential distributions were chosen because they can be unambiguously measured, are useful in understanding the shapes of wave forms at many specific sites, and provide a direct measure of repolarization. Unipolar wave forms were recorded from intramural and epicardial electrodes and converted into potential distributions. Well-known shapes of wave forms recorded at the inner and outer layers of the ventricles as well as peak-to-peak voltages were shown by the potential distributions to be determined primarily by superposition effects of distant excitation waves. These effects were most prominent before epicardial breakthrough and then receded during the last half of the QRS complex. However, the potential distributions became more complex as excitation waves merged, collided, and terminated. During terminal depolarization, there were scattered positive repolarization potentials intramurally. Normal repolarization was characterized by positive potentials over the ventricular epicardium while there were changes intramurally and on the atrium. Throughout the T wave, there was a predominant transmural unidirectional gradient with the inner wall being more negative than the outer wall. This finding confirms that the sequence of repolarization is from the epicardium to the endocardium with the middle layers having an intermediate time.
Sinoatrial transmission and atrial invasion during normal rhythm in the rabbit heart.
Authors: Masuda M O , Paes de Carvalho A
Published: June 2012

Intracellular microelectrodes and small unipolar leads applied to endocardial surface of the right atrium in vitro were used to study the complex extracellular wave patterns recorded from the neighborhood of the cardiac pacemaker during spontaneous activity. Sinus activity propagated slowly toward the site of atrial invasion on the venous border of the crista terminalis. Atrial activation was marked by a primary negative wave that appeared 20-40 msec after pacemaker firing. Two sources of complex multiphasic waves were found. First, potentials from transitional sinus tissue propagated toward the atrium and caused low-voltage waves that preceded and slurred the onset of the atrial initial negativity. Second, bundles and layers of the crista terminalis muscle were excited asynchronously around the invasion region, as if cross-connections were infrequent. Waves originating from this source occurred after the firing of the invasion site. No extracellular wave could be associated with the firing of the true pacemaker cells. The sinoatrial ring bundle (SARB) yielded a discrete biphasic deflection along most of its way toward the coronary sinus. This potential appeared most frequently after that of the adjoining cristal muscle, raising questions about the functional role of the SARB as an internodal preferential pathway.
Influence of cardiopulmonary vagal afferent activity on carotid chemoreceptor and baroreceptor reflexes in the dog.
Authors: Koike H , Mark A L , Heistad D D , Schmid P G
Published: June 2012

The goal of this study was to determine if physiological levels of cardiopulmonary vagal afferent activity modulate carotid chemoreceptor and baroreceptor reflexes. In anesthetized, ventilated dogs, the aortic nerves and the cervical sympathetic trunks were cut, and atropine was administered so that vagotomy would interrupt only cardiopulmonary afferent impulses. Reflex vascular responses were observed in perfused gracilis muscle and hindpaw. Carotid chemoreceptors were activated with nicotine or hypoxic, hypercapnic blood; carotid baroreceptors were stimulated by changes in carotid pressure. Interruption of vaga afferents augmented reflex vascular responses during changes incarotid pressure from 75 to 125 mm Hg. Interruption of cardiopulmonary vagal afferents potentiated reflex vasoconstrictor (muscle), vasodilator (paw), and vasopressor responses to activation of the carotid chemoreceptors. The potentiation of the chemoreceptor reflex frequently occurred in the absence of increases in base-line vascular resistance. Vagotomy also potentiated ventilatory responses to stimulation of the carotid chemoreceptors in spontaneously breathing dogs. The results indicate that interruption of cardiopulmonary afferents potentiates the vascular and ventilatory responses to activation of the carotid chemoreceptors and augments the gain of the carotid baroreceptor reflex at low carotid pressures. These findings suggest that physiological levels of cardiopulmonary vagal afferent impulses suppress carotid baroreceptor and chemoreceptor reflexes through an interaction in the central nervous system. The suppressive effect on the chemoreceptor reflex may be distinct from tonic restraint of the vasomotor center by vagal afferents, since it involves sympathetic vasodilator as well as vasoconstrictor responses and may occur without suppression of base-line adrenergic constrictor tone.
Effect of spatial variations in shear on diffusion at the wall of an arterial branch.
Authors: Friedman M H , Ehrlich L W
Published: June 2012

The effect of spatially varying shear on transport to the wall of a two-dimensional branch was examined, using oxygen as the test solute and the results of earlier fluid mechanical calculations to provide the shear profiles in a region characterizing the aortic bifurcation. The numerical technique employed allowed both blood-phase and mural resistances to solute uptake to be treated simultaneously and self-consistently. The calculated profiles of wall concentration and mural flux were significantly different from those which would have obtained if the shear had been uniform. The calculations suggest that, even when solute is rapidly taken up from the blood, the occasional high-shear and flow-development sites encountered along the arterial tree prevent the diffusion boundary layer adjacent to the wall from thickening to the point at which nutrition is compromised. The indirect effect of arterial geometry on transport, consequent to its direct effect on the magnitude and the distribution of the relevant hemodynamic variables, was illustrated using the branch area ratio as the geometric parameter. The shapes of the flux and interfacial concentration profiles along the branch wall were markedly dependent on the extent to which wall shear affected intimal permeability.
Abnormalities of renal perfusion and the renal pressor system in dogs with chronic aortic coarctation.
Authors: Bagby S P , McDonald W J , Strong D W , Porter G A , Bennett W M , Bonchek L I
Published: June 2012

To clarify the role of the renin-angiotensin system in coarctation hypertension, 2-year-old inbred dogs with chronic neonatally induced thoracic aortic coarctation were subjected to 6 days of rigorous salt restriction. The following parameters were then measured: glomerular filtration rate, renal plasma flow, plasma renin activity, plasma renin concentration, renin reactivity, and renin substrate concentration. Glomerular filtration rate and renal plasma flow were significantly lower in salt-restricted coarcted dogs: 3.0 +/- 0.2 and 9.0 +/- 1.5 ml/min kg-1, respectively, compared with values of 4.0 +/- 0.2 (P less than 0.005) and 13.2 +/- 0.6 (P less than 0.025) ml/min kg-1 in salt-restricted controls. Plasma renin activity was abnormally high in experimental dogs: 13.5 +/- 2.5 vs. 4.5 +/- 1.5 ng angiotensin I/ml hour-1 in controls (P less than 0.005). In addition, a significant elevation of renin reactivity (indicating a relative increase in circulating accelerators or a relative decrease in inhibitors of the renin reaction) was apparent in the plasma of coarcted dogs. Plasma renin concentration was elevated but to an insignificant degree in coarcted dogs, and renin substrate concentration was comparable with that of controls. The impaired renal perfusion and abnormal elevation of plasma renin activity during salt restriction is analogous to clinical and experimental observations in hypertensive states associated with total renal underperfusion and supports a major role for the renal pressor system in the pathogenesis of coarctation hypertension. The insignificant elevation of plasma renin concentration is not incompatible with this view. The demonstration of increased renin reactivity in coarctation hypertension provides additional evidence that acceleration of the renin reaction is common to all hypertensive states.
Membrane currents and tension in cat ventricular muscle treated with cardiac glycosides.
Authors: McDonald T F , Nawrath H , Trautwein W
Published: June 2012

The effect of cardiac glycosides on membrane currents and tension in cat ventricular muscle was studied using the single sucrose gap voltage clamp method. Complete tension-voltage and current-voltage relations were obtained in five preparations before and during treatment with dihydro-ouabain (DHO, 1.7 X 10(-5)M). After 1-2 minutes of DHO, the developed tension was 15% greater than control, but there was no change in either the slow inward (calcium) current (Ica) or the level of the outward current flowing at the end of a 300-msec depolarization (Iout). After 6-8 minutes of DHO, there was a 60% increase in developed tension, a noticeable increase in resting tension, a 20% decrease in Ica, and a smaller increase in Iout. It seems possible that the reduction of Ica was due to a reduced driving force. In preparations treated with ouabain (5 X 10(-7)M, 3-5 minutes), developed tension was 45-150% greater than control with no change in Ica or Iout between -45 and + 15 mv. We conclude that the inotropic action of these cardiac glycosides is not mediated by an increase in Ica.