bluuebunny/crossref_metadata_2025 huggingface dataset:
Action potential changes under varied [Na+]0 and [Ca2+]0 indicating the existence of two inward currents in cells of the rabbit atrioventricular node.
Authors: Ruiz-Ceretti E , Zumino A P
Published: June 2012

In the perfused rabbit heart,the upstroke of the transmembrane action potential of fibers of the atrioventricular (AV) node presents two distinct components. The first depends strongly on extracellular sdoium concentration, but the degree to which it is activated is influenced by extracellular calcium, as indicated by the correlation between its Vmax and [Ca2+]0. The second component depends on calcium and sodium concentrations and is blocked by Mn ions. An analysis comparing action potentials from atrial (A), atrionodal (AN), and nodal (N) fibers shows that the second component of the upstroke of the action potential contributes 12%, 27%, and 34% to the total depolarization. The results suggest that the upstroke of the nodal action potential results from the activation of two inward currents, as in ordinary cardiac fibers. We postulate that (1) the degree of steady state inactivation of gNa is larger in N than in A fibers because of the low resting potential of the former, and (2) the contribution of the second channel to the upstroke depends on the time course of the previous depolarization and the potential level at which this component is activated.
Effects of treatment with pyruvate and tromethamine in experimental myocardial ischemia.
Authors: Liedtke A J , Nellis S H , Neely J R , Hughes H C
Published: June 2012

Failure of glycolysis to increase sufficiently to supply optimal levels of energy production in ischemic heart muscle is due in part to the cummulative restrainst of acidosis on rate-limiting enzymes, particularly glyceraldehyde-3-phosphate dehydrogenase. In an effort to modify this inhibition and salvage jeopardized myocardium, treatment with excess levels of pyruvate and tromethamine (Tris), designed to buffer intracellular hydrogen ion accumulations and improve the oxidation-reduction ratio, NAD+/NADH, was tested in 59 swine hearts in two separate preparations of global and regional ischemia. Global ischemia, per se, caused hemodynamic deterioration and shortened survival time (44.3 +/- 3.1 minutes). Myocardial oxygen consumption, fatty acid oxidation, and glucose uptake were all significantly (P less than 0.001) reduced as were estimates of glycolysis and tissue stores of creatine phosphate and ATP (P less than 0.01). Although treatment with Tris alone was inconclusive, administrations of pyruvate (40-50 mM) buffered with Tris (added directly into the coronary perfusate) effected an improvement in mechanical function and a significant prolongation in survival time (56.9 +/- 2.6 minutes. P less than 0.01). Glycogenolysis was enhanced and levels of key glycolytic intermediates were reduced, suggesting an acceleration of glycolytic flux. Excess levels of pyruvate (1.52 +/- 0.48 mumol/ml of coronary perfusate) provided added substrate for oxidation and led to a greater than 5-fold incrase in rates of pyruvate decarboxylation as compared to untreated ischemic hearts...
Suppression of plasma renin activity by indomethacin in man.
Authors: Frölich J C , Hollifield J W , Dormois J C , Frölich B L , Seyberth H , Michelakis A M , Oates J A
Published: June 2012

The effect of indomethacin or placebo on aldosterone, plasma renin activity (PRA), sodium excretion, and urinary prostaglandin (PG) levels was investigated in five hypertensive subjects in 100 mEq sodium balance who had experienced malignant hypertension with a disturbance of their renin-aldosterone relationship in the past. Indomethacin significantly lowered aldosterone levels by 43%, PRA by 58%, 24-hour sodium excretion by 49%, and urinary PG excretion, an indicator of renal PG synthesis, by 67%. Angiotensin infusion increased aldosterone to the same level before and after treatment with indomethacin. Similarly, in normal subjects in 150 mEq sodium balance, indomethacin lowered PRA by 47%; sodium excretion fell by 33%, and urinary prostaglandin E (PGE) excretion, by 55%. The acute elevation in PRA 10 minutes after intravenous furosemide was completely abolished by indomethacin. Five subjects with essential hypertension were classified as normal renin hypertensives according to their response to orally administered furosemide. Indomethacin pretreatment resulted in 60% reduction of PRA following furosemide, and three of these subjects now fell into the low renin category. Studies in vitro demonstrated that indomethacin has no effect on the renin-renin substrate interaction. Thus, indomethacin lowers PRA concomitantly with a reduction in renal PG synthetase activity. Whether indomethacin inhibits renin release by an intrarenal, PG-related mechanism or secondarily via sodium retention is discussed.
Lower limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon.
Authors: Jones J V , Fitch W , MacKenzie E T , Strandgaard S , Harper A M
Published: June 2012

The effect of chronic renovascular hypertension on the autoregulation of cerebral blood flow was studied in anesthetized baboons. Cerebral blood flow was measured by the intracarotid 133Xe clearance method. Six baboons with renal hypertension of 8-12 weeks' duration were compared with six normotensive controls. The lower limit of autoregulation was determined following controlled hemorrhage. In the initially normotensive baboons, cerebral blood flow remained constant until mean arterial pressure had decreased to the range of 45-59 mm Hg. Thereafter, cerebral blood flow decreased with each further decrease in mean arterial pressure. In the chronically hypertensive baboons cerebral blood flow autoregulated until the mean arterial pressure had decreased to the range of 75-89 mm Hg. Therefore, the lower limit of autoregulation of cerebral blood flow was shifted to higher absolute levels of mean arterial pressure in baboons with chronic renovascular hypertension presumably due to adaptive changes in the cerebral circulation.
Morphology and relationship to extensibility curves of human mitral valve chordae tendineae.
Authors: Lim K O , Boughner D R
Published: June 2012

Human mitral valve chordae tendineae in which elastic response curves are nonlinear have also been found to exhibit extensibility that increases with chordal size and decreases with chordal age. We used selective enzymatic digestion and scanning transmission electron microscopy to explain these observations. Removal of the outer elastin sheath by enzymatic digestion did not significantly affect the elastic response of this tissue. Scanning electron microscopy revealed that the collagen fibers in the central core of young chordae exhibited a very wavy pattern but the pattern in adult specimens was relatively straight. The increased waviness accounted for the greater extensibility of the young specimens. The collagen fibers from young and old chordae consisted of a network of collagen fibrils that became more collapsed when the tissue was fixed under tension. This network arrangement of the fibrils explains the nonlinearity in the elastic response of the tissue. Transmission electron micrographs showed that the density of collagen fibrils decreased as chordal size increased. The number of fibrils per 10(-8) cm2 of the central core decreased from 182.4 (SE = 1.3) to 131.3 (SE = 1.6) as average chordal cross-sectional area increased from 0.0016 cm2 to 0.0268 cm2. This difference in fibril density provides an explanation for the greater extensibility shown by the thicker chordae. The collagen fibril diameters ranged from 516 A to 552 A.
The effects of iron deficiency on the respiratory function and cytochrome content of rat heart mitochondria.
Authors: Blayney L , Bailey-Wood R , Jacobs A , Henderson A , Muir J
Published: June 2012

We have examined the effects of total body iron deficiency on the function of mitochondria isolated from rat hearts. Male Wistar rats were weaned at 21 days and divided into an experimental iron-deficient group and a control group. Both groups received identical diet but an iron supplement (180 mg of ferrous sulfate per kg of diet) was added for the control group. Rats were studied at 7 and 14 weeks. Iron-deficient rats weighed less than controls but showed significantly increased ventricle to body weight ratio at both 7 and 14 weeks, indicating relative cardiac hypertrophy. Isolated mitochondrial fractions from iron-deficient and control rats contained similar proportions of whole homogenate protein and succinic cytochrome c reductase activity, indicating that the fractions isolated from the experimental and control rats were comparable. In iron-deficient rats NADH cytochrome c reductase, succinic cytochrome c reductase, succinic dehydrogenase, and NADH ferricyanide oxidoreductase activities were all significantly reduced at 7 and 14 weeks. Cytochrome c oxidase activity was significantly reduced only at 14 weeks as were the concentrations of cytochromes a3, c1, and b. The rate of oxygen uptake by mitochondria was significantly lower at both 7 and 14 weeks but the P/O ratio was unaltered. We conclude that iron deficiency is associated with impairment of myocardial mitochondrial electron transport.
Intrarenal site of action of calcium on renin secretion in dogs.
Authors: Watkins B E , Davis J O , Lohmeier T E , Freeman R H
Published: June 2012

We studied the effects of intrarenal calcium infusion on renin secretion in sodium-depleted dogs in an attempt to elucidate the major site of calcium-induced inhibition of renin release. Both calcium chloride and calcium gluconate reduced renal blood flow and renin secretion while renal perfusion pressure was unchanged. These data indicate that calcium inhibition of renin secretion did not occur primarily at the renal vascular receptor; decreased renal blood flow is usually associated with increased renin secretion. Calcium chloride infusion increased urinary chloride excretion without affecting sodium excretion, and calcium gluconate failed to increase either sodium or chloride excretion. Also, the filtered loads of sodium and chloride were unchanged during the calcium infusions. These results give no indication that calcium inhibited renin secretion by increasing the sodium or chloride load at the macula densa. The effects of intrarenal calcium infusion on renin release were also assessed in dogs with a nonfiltering kidney in which renal tubular mechanisms could not influence renin secretion. The observation that calcium still suppressed renin release in these dogs provides additional evidence that the the major effect of calcium involved nontubular mechanisms. Thus, it appears likely that calcium acted directly on the juxtaglomerular cells to inhibit renin secretion.
Stimulation of renin release from rabbit renal cortex by arachidonic acid and prostaglandin endoperoxides.
Authors: Webber P C , Larsson C , Anggard E , Hamberg M , Corey E J , Nicolaou K C , Samuelsson B
Published: June 2012

The mechanism by which renal prostaglandins stimulate renin secretion in vivo is unknown. In this in vitro study we measured the effects of activation of the prostaglandin (PG) system on renin release from slices of rabbit renal cortex. The PG precursor arachidonic acid (C20:4), a natural PG endoperoxide (PGG2), two stable synthetic PG endoperoxide analogues (EPA I and II), PGE2, PGF2alpha, and two different PG synthesis inhibitors [indomethacin and 5,8,11,14-eicosatetraynoic acid (ETA)] were used to evaluate the possibility of a direct action of the cortical PG system on renin secretion. Renin release increased significantly with time after addition of C20:4, PGG2, EPA I, and EPA II to the incubation medium. Stimulation of renin release was se-related for C20:4 in concentrations of 0.6 to 4.5 X 10(-6) M, for EPA I in concentrations of 0.7 to 2.8 X 10(-6) M, and for EPA II in concentrations of 1.4 to 14.0 X 10(-6) M. Indomethacin (10(-4) M) and ETA (10(-4) M) significantly decreased basal renin release as well as the renin release stimulated by C20:4 and EPA I. PGE2(10(-12) to 10(-6) M) had no effect on renin release, whereas PGF2alpha (10(-12) to 10(-6) M) decreased renin release in a dose-dependent manner. These data raise the possibility of a direct action of the renal cortical PG system on renin secretion. The results further indicate that stimulation of renin release by C20:4 may depend more specifically on the action of PG endoperoxides than on the primary prostaglandins.
Investigation of the theory and mechanism of the origin of the second heart sound.
Authors: Sabbah H N , Stein P D
Published: June 2012

To investigate further the origin of the second heart sound we studied human subjects, dogs, and a model in vitro of the cardiovascular system. Intra-arterial sound, pressure, and, where possible, flow and high speed cine (2,000 frames/sec) were utilized. The closure sound of the semilunar valves was of higher amplitude in be ventricles than in their respective arterial cavities. The direction of inscription of the main components of intra-arterial sound were opposite in direction to the components of intraventricular sound. Notches, representative of pressure increments, were noted on the ventricular pressure tracings and were coincident with the components of sound. The amplitude of the closure sound varied with diastolic pressure, but remained unchanged with augmentation of forward and retrograde aortic flow. Cines showed second sound to begin after complete valvular closure, and average leaflet closure rate was constant regardless of pressure. Hence, the semilunar valves, when closed, act as an elastic membrane and, when set into motion, generate compression and expansion of the blood, producing transient pressure changes indicative of sound. The magnitude of the initial stretch is related to the differential pressure between the arterial and ventricular chambers. Sound transients which follow the major components of the second sound appear to be caused by the continuing stretch and recoil of the leaflets. Clinically unexplained findings such as the reduced or absent second sound in calcific aortic stenosis and its paradoxical presence in congenital aortic stenosis may be explained by those observations.
Time Relationship of Dynamic Events in the Cardiac Chambers, Pulmonary Artery and Aorta in Man
Authors: BRAUNWALD EUGENE , FISHMAN ALFRED P. , COURNAND ANDRÉ
Published: June 2012

Exposure of the heart in the course of chest surgery affords a means of faithfully recording pressure pulses in the four chambers of the heart and in the large vessels of human subjects. This study in 13 individuals without any clinical evidence of cardiovascular disease, is concerned with the time relationship between electric and mechanical events and with the temporal sequence and respective characteristics of similar phases of the cardiac cycle in both sides of the heart. The results obtained by permutation of simultaneous pressure recordings confirm the classical observations made in dogs.
Some Effects of Partial Pulmonary Valvectomy
Authors: FOWLER NOBLE O. , MANNIX EDGAR P. , NOBLE WILLIAM
Published: June 2012

Partial pulmonary valvectomy was performed in 19 dogs. No change in pulmonary arterial pulse pressure was seen when less than one valvular cusp was removed; frequently no change was observed when an entire cusp was removed. Widening of the pulmonary arterial pulse pressure could be produced by
removal
of more than one cusp or by inducing pulmonary hypertension after removal of only one cusp. Observation as long as six months postoperatively revealed no evidence of right ventricular failure resulting from the operation.
Distribution of Blood (Fe
59
) and Plasma (I
131
) Volumes of Rats Determined by Liquid Nitrogen Freezing
Authors: EVERETT NEWTON B. , SIMMONS BARBARA , LASHER EARL P.
Published: June 2012

A standard method is described which gives reproducible blood volume values for rats and their various organs and tissues.
Quantitative Method for the In Vivo Testing of Fibrinolytic Agents: Effect of Intravenous Trypsin on Radioactive Thrombi and Emboli
Authors: AMBRUS J. L. , BACK N. , MIHALYI E. , AMBRUS CLARA M.
Published: June 2012

Quantitative methods for testing fibrinolytic agents in vivo are described. Methods based on the incorporation into the clot of P
32
labeled blood cells or Cr
51
labeled erythrocytes were found to be unsatisfactory. Clots were produced with I
131
labeled fibrinogen. Dissolution of a clot resulted in decrease of radioactivity. This was recorded by placing segments of blood vessels in a special lead shield containing a scintillation detector head, connected to a radiation rate meter and an Esterline recorder. Pulmonary, peripheral and coronary emboli were produced by injecting radioactive clots produced and ground, in vitro. Using these methods it was found that maximal tolerated doses of trypsin showed no significant fibrinolytic effect.
In Vitro Study of Cholesterol Metabolism in the Calf Aorta
Authors: WERTHESSEN NICHOLAS T. , NYMAN MELVIN A. , HOLMAN RUSSELL L. , STRONG JACK P.
Published: June 2012

The calf's aorta, has been maintained in vitro for prolonged periods under aseptic conditions. Studying the aorta's function as regards cholesterol biosynthesis, accumulation and release, under the experimental conditions of hyper and normal blood pressure, estrone administration, and dilutions of serum have led to the conclusion that cholesterol metabolism can be markedly altered by these conditions and that there may be factors or systems normally present in blood which regulate lipid metabolism in the organ.
Lidocaine in Cardiac Resuscitation from Ventricular Fibrillation
Authors: CARDEN NORMAN L. , STEINHAUS JOHN E.
Published: June 2012

The interruption of ventricular fibrillation following coronary occlusion in dogs was effected with the use of lidocaine. This technic caused no obvious sequelae and the recurrence of fibrillation was rare. It was used successfully in both normothermic and hypothermic animals although the proportion of successful resuscitations was less in the latter group.
A Theoretical Analysis of Intracavitary Blood Mass Influence on the Heart-Lead Relationship
Authors: BRODY DANIEL A.
Published: June 2012

As a result of theoretic advances made during the past 10 years, it is now feasible to record scalar and vector electrocardiograms in a manner which is independent of body shape and cardiac location. A similar independence of the body's electric inhomogeneities has not yet been achieved. On the contrary, the evidence presented here shows that inhomogeneity phases in the body, especially the intracavitary blood mass, exert a powerful influence on the heart-lead relationship. The particular effect of the intracavitary phase is to augment the manifest strength of normal components of myocardial doublets, and to reduce the manifest strength of tangential components. This augmentation-reduction effect is quantitatively predictable under conditions of simple idealization, and has been confirmed by experiments on electrocardiograpic models. The net effect of the intracavitary phase is probably to produce quasi-vectorial registration of the electromotive forces of the heart, at least during the normal depolarization phase.
Regional myocardial function and dimensions early and late after myocardial infarction in the unanesthetized dog.
Authors: Theroux P , Ross J , Franklin D , Covell J W , Bloor C M , Sasayama S
Published: June 2012

Pairs of ultrasonic dimension gauges and a micromanometer implanted in the subendocardium of the left ventricles of unanesthetized dogs were used to analyze serial changes in hemodynamic status and segmental function for up to 4 weeks after permanent circumflex coronary artery occlusion. Regional function was studied in control segments and in segments identified as marginal (hypokinetic) and ischemic. In three dogs, after transient regional dysfunction, no myocardial infarction developed, whereas in five dogs regional dysfunction at 3 hours after occlusion was followed by the development of persistent dysfunction and infarction. Left ventricular end-diastolic segment length (EDL) changes over time; EDL of the control segments increased progressively, but in marginal segments EDL was 12% below control and in the ischemic segments 30% below control by 4 weeks. Progressive increases in percent active shortening occurred in control segments; but holosystolic bulging was replaced by akinesia in ischemic segments, and persistent reduction in shortening was present in marginal segments at 4 weeks. Correlations were found between percent scar and reductions in percent shortening, EDL, and the ratio of change in diastolic length to change in diastolic pressure. These methods have detected hyperfunction in normal regions and variable segmental loss of contractile function, together with reduction of subendocardial dimensions and changes that may reflect decreased diastolic compliance in ischemic regions. We conclude that this model for the conscious animals may be useful for studying the influence of therapy on the extent of myocardial damage after experimental coronary occlusion.
Effect of intrarenal angiotensin II blockade on renal function in conscious dogs.
Authors: Kimbrough H M , Vaughan E D , Carey R M , Ayers C R
Published: June 2012

The effects of intrarenal infusion of 1-sar-8-ala angiotension II (P 113) and a converting enzyme inhibitor, SQ 20881, at doses that did not affect systemic blood pressure (2.0 mug/kg per min) were studied in conscious, uninephrectomized dogs. In dogs receiving approximately equal to 5 mEq/day of sodium, intrarenal infusion of P 113 increased renal blood flow (RBF) from 219.8 +/- 32.3 to 282.7 +/- 20.0 ml/min (P less than 0.004), and with intrarenal SQ 20881 infusion from 215.3 +/- 14.2 to 278.0 +/- 22.2 ml/min (p less than 0.005). In sodium-restricted dogs (approximately equal to 5 mEq/day), glomerular filtration rate (GFR) also increased with intrarenal P 113 infusion from 57.9 +/- 5.7 to 66.3 +/- 6.6 ml/min (P less than 0.05), and with SQ 20881 infusion from 43.1 +/- 2.1 to 55.7 +/- 4.5 ml/min (P less than 0.01). Dogs on approximately equal to 5 mEq/day of sodium showed significant increases in plasma renin activity (PRA) with intrarenal infusion of the peptides, unmasking a negative feedback inhibition of renin release by angiotensin II. No increases in RBF, GFR, or PRA were seen with infusion without inhibitors, or in dogs give P 113 or SQ 20881 while on approximately equal to 80 mEq/day of sodium. In addition, angiotensin II inhibition increased sodium excretion during sodium restriction. These findings suggest that intrarenal angiotensin II is intimately involved in renal responses to sodium restriction which result in conservation of sodium and water.
Prostaglandins and the control of blood flow in the canine myocardium.
Authors: Hintze T H , Kaley G
Published: June 2012

A comprehensive study was undertaken to evaluate the effects of inhibition of prostaglandin (PG) synthesis on a variety of reactions in the coronary vascular bed of anesthetized, open-chest dogs. In 23 dogs an electromagnetic flow probe (EMFP) and hydraulic occluder were placed around either the left anterior descending or circumflex branches of the coronary artery and a needle was inserted distral to the EMFP. Injections into the coronary artery of arachidonic acid (AA), bradykinin, adenosine, angiotensin, and PGE2 were given before and after inhibition of PG synthesis by indomethacin (IND) or meclofenamate (MF). The effects of the inhibitors on reactive hyperemia resulting from 5-, 10-, 15-, and 20-second occlusions and the dilation resulting from 90-second exposure to 8% O2 were also examined. In each experiment, inhibition of PG synthesis was ascertained by the elimination of vasodilation to AA. After administration of IND or MF, while baseline coronary blood flow was slightly reduced, the total increment of blood flow to vasodilator agents was not significantly altered. Whereas the peak dilation and volume of reactive hyperemia were decreased, the percent flow debt repaid was unchanged and total increment of coronary flow due to hypoxia-induced vasodilation was not significantly modified. Vasoconstrictor responses to angiotensin were also unchanged. These results indicate that while inhibitors of PG synthesis increase coronary resistance, they do not adversely affect vascular responsiveness. We conclude that prostaglandins play little, if any, role in modulating coronary blood flow.
Autonomic control of cardiovascular functions during neonatal development and in adult sheep.
Authors: Woods J R , Dandavino A , Murayama K , Brinkman C R , Assali N S
Published: June 2012

We studied the autonomic control of resting heart rate of systemic and pulmonary vascular blood pressures (BP) in chronically instrumented neonatal lambs 1-8 weeks of age. The maximum response to ganglionic blockade and sympathetic and parasympathetic antagonists was taken as an index of the magnitude of the total neural, adrenergic, and cholinergic tones. The reactivity of the circulatory parameters to adrenergic and cholinergic agonists also was investigated. All findings were compared with those in adult nonpregnant sheep studied concomitantly and with data previously obtained from term fetal lambs. The results of our studies show: (1) resting heart rate declines spontaneously throughout the 8 weeks of neonatal life approaching that of adult sheep; (2) the progressive bradycardia is not related to changes in the parasympathetic or sympathetic tone; (3) resting systemic BP is under strong neurohumoral control during the first two to three weeks of neonatal life; the control decreases progressively, becoming similar to that of adult sheep; (4) resting pulmonary artery pressure of neonatal and adult sheep has no neurohumoral control; (5) the systemic BP response of the neonate to autonomic agonists is greater than that of the term fetus and is similar to that of the adult; (6) in neonatal and adult sheep, compared to the term fetus, the pressor response to norepinephrine is accompanied by a baroreceptor-mediated bradycardia, and acetylcholine-induced systemci hypotension is accompanied by a "paradoxical" tachycardia mediated through beta-adrenergic stimulation; (7) in contrast to our finding for the fetus, the pulmonary vascular pressure of neonatal and adult sheep is unresponsive to autonomic agonists.
Input impedance of the systemic circulation in man.
Authors: Nichols W W , Conti C R , Walker W E , Milnor W R
Published: June 2012

To determine the systemic input impedance, pulsatile pressure and flow were measured in the ascending aorta in 16 human subjects who were undergoing diagnostic cardiac catheterization. Blood flow was measured with a catheter-tip electromagnetic velocity meter, and pressure with an external transducer connected with the fluid-filled lumen of the catheter. Five subjects were found to have no evidence of cardiovascular disease (group A, mean age 32 +/- 2 years, mean aortic pressure 97 +/- 4 mm Hg). Seven had clinical and angiographic signs of coronary arterial disease, and mean pressures less than 100 mm Hg (group B, mean age 48 +/- 2 years). Four subjects had signs of coronary disease and mean pressures greater than 100 mm Hg (group C, mean age 48 +/- 3 years). The frequency spectra of impedance were qualitatively similar in all three groups and resembled those previously observed in the canine aorta. Characteristic impedance was lower in the normal subjects (group A, average 53 dyn sec cm-5) than in the subjects with coronary artery disease (groups B and C, average 129 dyn sec cm-5). Among the subjects with coronary disease, characteristic impedance was higher in the hypertensive subjects (group C, average 202 dyn sec cm-5) than in those with lower mean pressures (group B, average 95 dyn sec cm-5). External left ventricular work per unit time (hydraulic power) averaged 1715 milliwatts (mW) in group A, 1120 mW in group B, and 2372 mW in group C. Cardiac outputs were within normal limits in all subjects, but tended to be lower in group B than in group C. These results suggest that the subjects of group C were better able to meet the increased energy demands imposed by an abnormally high aortic input impedance. Further investigation is needed to learn whether the high impedances in subjects with coronary disease represent an increase with age and transmural pressure alone, or whether some additional factor is involved. The data on relatively normal subjects permit a tentative definition of the normal limits for aortic input impedance in man: 26-80 dyn sec cm-5.
Effect of stellectomy and vagotomy on ventricular refractoriness in dogs.
Authors: Schwartz P J , Verrier R L , Lown B
Published: June 2012

The influence of tonic sympathetic and parasympathetic nervous system activity on ventricular refractory period duration was studied in 13 mongrel dogs. Strength-interval curves were obtained from the apex of the right ventricular endocardium with a transvenous bipolar catheter. The effects of sympathetic activity were assessed by unilateral and bilateral stellectomies and tonic vagal effects were studied by inducing cholinergic blockade with atropine (0.2 mg/kg) and by sectioning the cervical vagi bilaterally. Right stellectomy shifted the strength-interval curve 3-5 msec earlier (P less than 0.005). In contrast, left stellectomy shifted the strength-interval curve 4-7 msec later (P less than 0.001). Thus, right and left unilateral stellectomy produced opposite effects. However, when the contralateral ganglion was removed, right and left stellectomy produced qualitatively similar effects, increasing refractoriness. The net effect of bilateral stellectomy was to shift the strength-interval curve 8-10 msec later (P less than 0.001) and this was primarily dependent on left stellectomy. Blockade of vagal efferent activity with atropine shifted the strength-interval curve 3-6 msec earlier (P = .001). Removal of vagal afferent activity by vagotomy during atropine blockade shifted the strength-interval curve 2-3 msec earlier (P = 0.03). It is concluded that both stellate ganglia exert qualitatively similar effects on cardiac refractoriness; however, the left ganglion dominates and unilateral right stellectomy produces a paradoxical decrease in refractoriness. The sympathetic effects are tonically antagonized by vagal activity.
The effects of hyaluronidase on coronary blood flow following coronary artery occlusion in the dog.
Authors: Askenazi J , Hillis L D , Diaz P E , Davis M A , Braunwald E , Maroko P R
Published: June 2012

In an attempt to determine the mechanism by which hyaluronidase reduces myocardial injury following coronary artery occlusion, myocardial blood flow was studied in 20 open-chest dogs with occlusion of the left anterior descending coronary artery. Ten dogs served as controls, and 10 received hyaluronidase (500 NF units/kg) intravenously 20 minutes after occlusion. At 15 minutes and at 6 hours after occlusion, regional myocardial blood flow in the epicardial and endocardial halves of both ischemic and nonischemic zones were determined with radiolabeled microspheres. Mean arterial pressure, heart rate, and cardiac output were similar in the untreated and treated dogs through the 6 hours of the experiment. Moreover, regional blood flow to nonischemic myocardium (areas without epicardial S-T segment elevation 15 minutes after occlusion) was similar in the two groups 15 minutes and 6 hours after occlusion. Fifteen minutes after occlusion, the flow to the ischemic myocardium subjacent to sites with S-T segment elevation exceeding 2 mV) in the untreated group was: transmural, 28.1 +/- 2.2 (mean +/- SE) ml/min per 100 g; endocardial, 20.7 +/- 1.8; and epicardial, 38.5 +/- 3.1. The endocardial-epicardial flow ratio was 0.56 +/- 0.04. Six hours after occlusion, the untreated group demonstrated a further decrease in blood flow to the ischemic myocardium: transmural, 15.2 +/- 1.4 ml/min per 100 g; endocardial, 6.8 +/- 1.1; and epicardial, 24.3 +/- 1.9. The endocardial-epicardial flow ratio fell to 0.28 +/- 0.04. In contrast, the hyaluronidase-treated dogs showed no further reduction in blood flow to ischemic myocardium 6 hours after occlusion: transmural, 30.3 +/- 3.1 ml/min per 100 g; endocardial, 21.3 +/- 2.5; and epicardial, 38.8 +/- 3.8. These regional myocardial flows were significantly higher than those of the untreated dogs 6 hours after occlusion. Thus, salvage of damaged myocardium by hyaluronidase might be explained by its beneficial effect on collateral blood flow to the ischemic tissue, though this effect on collateral flow could be the consequence rather than the cause of this salvage.
Hemodynamics of arterial stenoses at elevated flow rates.
Authors: Young D F , Cholvin N R , Kirkeeide R L , Roth A C
Published: June 2012

This study is concerned with the pressure drop that develops across an arterial stenosis, with particular emphasis on the effect of the stenosis at high blood flow rates induced by a locally administered vasodilator drug. Stenoses, ranging in severity from 55.7% to 91.0% reduction in lumen area were artificially induced in the femoral and carotid arteries of large mongrel dogs. Instantaneous flow rates and pressure drops were measured over a wide range of flow conditions. Mean velocities varied from 3.9 to 88.8 cm/sec. Experimental data support the applicability of a relatively simple equation for predicting the pressure drop over this wide range of velocities and stenosis geometries. Results show that blood flow through a particular artery can increase by a large factor, in the range of 4-5, under conditions of vasodilation with a corresponding large decrease in pressure distal to the stenosis. The pressure drop increases in a nonlinear manner with velocity and thereby accentuates the importance of the stenosis at elevated flow rates. We suggest that a critical stenosis be defined in terms of its effect on maximal flow rather than resting flow.
Detection of myocardial infarction in vitro based on altered attenuation of ultrasound.
Authors: Mimbs J W , Yuhas D E , Miller J G , Weiss A N , Sobel B E
Published: June 2012

This study was designed to determine whether attenuation of ultrasound by myocardium is potentially useful in detecting and quantifying infarction. Accordingly, we analyzed 44 regions of myocardium from 11 dogs 4-10 weeks after coronary occlusion. Attenuation of ultrasound in each region was assessed by transmitting a broadband pulse through the tissue in vitro and carefully gating the appropriate pulse into a spectrum analyzer for Fourier analysis (frequency range, 2-9.5 MHZ). An ultrasonic index of attenuation was derived from the slope of the best-fit line relating attenuation and frequency obtained from the Fourier transform. Acquistion of ultrasonic data was improved with the use of a specially designed small diameter receiving transducer. Myocardial creatine kinase content was assayed in each region to provide an independent index of regional injury. Results obtained from ultrasonic and biochemical analyses correlated with a correlation coefficient between the two of 0.80 in 24 regions of myocardium from the six dogs studied 4-5 weeks after infarction, and 0.72 in 20 regions from the five dogs studied 9-11 weeks after infarction. These findings indicate that regional infarction is associated with quantitative changes in ultrasonic attenuation.
Elastin and collagen accumulation in rabbit ascending aorta and pulmonary trunk during postnatal growth. Correlation of cellular synthetic response with medial tension.
Authors: Leung D Y , Glagov S , Mathews M B
Published: June 2012

Absolute and relative quantities of elastin, collagen, and DNA in anatomically defined segments of rabbit ascending aorta (AA) and pulmonary trunk (PT) were compared at intervals from birth to 2 months of age. Identical in size, weight, and composition at birth, the vessels maintained similar lengths and diameters at each age but diverged markedly in weight and scleroprotein content after 1 week. By 2 months, 3 times as much elastin and 1.7 times as much collagen had accumulated in the AA as compared to the PT. By contrast, the increase in total DNA content was the same for both segments. Differences in total fibrous protein accumulation, total elastin accumulation, and elastin content relative to DNA paralleled differences in estimated total medial tangential tension. Proportions of elastin and collagen relative to dry weight increased markedly only between 4 and 2 weeks of age and not thereafter despite continuing rapid growth, steadily increasing medial tension, and increasing total scleroprotein content. Thus, medial cells were capable of adapting their quantitative scleroprotein synthetic response to differences in medial tension throughout growth but established a fixed qualitative response within 2 weeks.
Quantitative studies of microcirculatory structure and function. III. Microvascular hemodynamics of cat mesentery and rabbit omentum.
Authors: Zweifach B W , Lipowsky H H
Published: June 2012

We made simultaneous measurements of intravascular pressure and red blood cell velocity for vessels which make up the modular configuration of microvascular networks in mesentery and omentum. An analysis of these variables and the computed volumetric flow rates is presented for arterioles which had a maximum diameter of 56 micrometer through the "true capillaries" (typically 7 micrometer for mesentery and 8 micrometer for omentum) to 56-micrometer venules. The spatial variance of pressure and flow is related to topographical features of each network. Vascularization statistics for each network are presented and demonstrate a unique ratio of potential microvascular exchange area to module planar area, with values of 0.71 +/- 0.22 (SD) for omentum and 0.19 "/- 0.03 (SD) for mesentery. Analysis of the volumetric flow rate for each module demonstrates a linear relationship to the planar area of tissue serviced by each modular network. In situ perfusion rates of 1180 ml/min per 100 g and 105 ml/min per 100 g were determined for omentum and mesentery, respectively. The hemodynamic resistance of the omental and mesenteric circuitry was evaluated, and in the case of the omentum, found to be inversely proportional to the planar area of the module. The arterial to venous distribution of pressure and flow for the mosaic of contiguous modules in omentum and mesentery is described and related to the deployment of parallel and serial microvessels of each network.
Absence of a lateral border zone of intermediate creatine phosphokinase depletion surrounding a central infarct 24 hours after acute coronary occlusion in the dog.
Authors: Hirzel H O , Sonnenblick E H , Kirk E S
Published: June 2012

Myocardial creatine phosphokinase (CPK) activity was measured as an indicator of cell viability 24 hours after ligation of the left anterior sescending coronary artery (LAD) in normal myocardium, the entire region supplied by the LAD, and individual samples from the border and center of the infarct. Tissue supplied by the LAD and delineated by dye was carefully dissected from normal tissue along the stained border, CPK activity in the ischemic myocardium was calculated by assuming normal CPK activity in the ischemic myocardium was calculated by assuming normal CPK activity in normal myocardium interdigitating with ischemic tissue at the border. Normal tissue was marked prior to occlusion with microspheres injected into the left atrium, whereas the distal portion of the LAD was perfused separately with unlabeled blood from a reservoir. With this correction, the CPK activity in the ischemic tissue from the lateral border of the infarct was essentially the same as in samples from the center, whereas that in the normal tissue immediately adjacent to the stained border was equal to values in remote normal myocardium. Thus, CPK depletion throughout the entire ischemic myocardium was nearly equal to CPK depletion in the center of the infarct. The uncorrected intermediate CPK levels in the individual samples from the border of the stained region correlated with the amount of normal tissue contaminating these samples. However, differences in CPK depletion across the heart wall resulted in the most depletion in the subendocardium and the least in the epicardium. Further more, coronary collateral blood flow measured 10 minutes after occlusion correlated well with the subsequent extent of CPK depletion.
The mechanism of K+-induced vasodilation of the coronary vascular bed of the dog.
Authors: Murray P A , Sparks H V
Published: June 2012

We tested a number of hypotheses concerning the mechanism of K+-induced vasodilation of the coronary vascular bed. Blood flow in the circumflex artery was measured in pentobarbital-anesthetized, open-chest dogs. Intracircumflex artery bolus injections of 40 mumol of isomotic KCl produced decreases in coronary vascular resistance ranging from 34% to 48%, depending on the initial resistance of the vascular bed. K+ administration had no effect on heart rate and produced a 4 mm Hg decrease in mean arterial pressure. K+ injection caused a 0.2 vol% increase in coronary sinus O2 content in a preparation in which left common coronary flow was held constant. The magnitude of K+-induced vasodilation was not significantly affected by the administration of propranolol, atropine, phentolamine, or lidocaine. K+-induced vasodilation was attenuated (50%) by ouabain plus lidocaine. Acetylcholine-induced vasodilation was not significantly diminished by ouabain plus lidocaine. We conclude that the mechanism of K+-induced vasodilation does not involve an increase in the metabolic activity of the heart or an interaction between K+ and tissue neural elements. Our data do support the hypothesis that K+-induced vasodilation is at least partly the result of an activation of the electrogenic Na+-K+ transport system of coronary smooth muscle.
Regional distribution of blood flow during arterial hypertension produced by lesions of the nucleus tractus solitarii in rats.
Authors: Snyder D W , Doba N , Reis D J
Published: June 2012

Changes in the fractional distribution of cardiac output (FF), organ blood flow, and regional vascular resistance were measured by the isotope dilution technique of Sapirstein using 86Rb as indicator in unanesthetized rats during acute arterial hypertension produced by bilateral lesions of the nucleus tractus solitarii (NTS). After NTS lesions, the FF was significantly reduced in skin, muscle, and colon, increased in ventricular myocardium, spleen, and adrenal glands, and was unchanged elsewhere. Because of a marked reduction in cardiac output (CO) during hypertension, the absolute organ blood flow (FF X CO) was reduced in lesioned rats to 30-40% of control in skin, muscle, and colon and between 60% and 75% of control in most of the remainder of the gastrointestinal tract and renal cortex; it was unchanged in myocardium and endocrine glands. Resistance was substantially increased (4- to 6-fold) in skin, muscle and colon but was only moderately increased (1.5- to 2.5-fold) in the remaining organs. The results indicate that, while NTS lesions will increase resistance in most vascular beds, the response is unequally distributed, influencing skin, muscle, and colon disproportionately to other tissues. Because of an interaction between a reduction in CO and little autoregulation, blood flow is reduced primarily in skin, muscle, and colon. The pattern of redistribution of CO was consistent with the interpretation that NTS hypertension results from interrupting baroreceptor reflexes centrally. The pattern of redistribution of blood flow in rats with NTS lesions differs from that produced by deoxycorticosterone acetate-salt and renal ischemia.
Effects of bilateral and unilateral stellate stimulation on canine ventricular refractory periods at sites overlapping innervation.
Authors: Haws C W , Burgess M J
Published: June 2012

The efffects of unilateral right, unilateral left, and bilateral stellate stimulation on ventricular refractory periods at sites of overlapping cardiac sympathetic innervation were studied in 11 pentobarbital anesthetized dogs. The stellates were stimulated with 10 Hz pulses 4 msec in duration with intensities strong enough to produce T wave changes in a vertical ECG lead and just below the intensity at which control of drive of the ventricle at a 400-msec cycle length was lost. Refractory periods shortened more with left stellate stimulation, 17.8 +/- 5.9 msec (mean +/- SD) than with right stellate stimulation, 10.3 +/- 5.1 msec, P less than 0.001. During bilateral stimulation, shortening of refractory periods was no greater whether stimulation was applied first to the left and then right stimulation was added, 19.7 +/- 6.9 msec, or the stimulation was applied first to the left and then right stimulation was added, 18.3 +/- 6.5 msec. The shortening of refractory periods with bilateral stellate stimulation was not significantly different from that with left stellate stimulation alone. The results of this study suggest that ventricular recovery properties in areas of overlapping cardiac sympathetic innervation are less influenced by increases in tone of the right sympathetics than by increases in left sympathetic tone. In addition, the findings indicate that a bilateral increase in cardiac sympathetic tone has no greater effect on recovery properties than the effects of the left cardiac sympathetics alone.
Morphometry of the small pulmonary arteries in man.
Authors: Horsfield K
Published: June 2012

From a resin cast of a normal pulmonary arterial tree, the diameter, length, and number of branches in each order were determined for arteries from 25 to 300 micrometer in diameter. Histological sections 120-micrometer thick were cut from a normal human lung in which the pulmonary artery had been injected with a mixture of ink and gelatin. Similar measurements were made on arteries from 10 to 70 micrometer in diameter, and the mode of origin of the capillaries was studied. The data thus obtained were found to correspond reasonably well to values previously estimated by extrapolation from data for arteries of 100 micrometer or more in diameter. The branching rules apply down to arteries of about 10-15 micrometer in diameter, the estimated number of which is 73 million. Distal to these vessels, capillaries arise either directly from small arteries or indirectly via precapillaries which are given off in great numbers and diverse patterns from the small arteries
Pressure-flow characteristics of coronary stenoses in unsedated dogs at rest and during coronary vasodilation.
Authors: Gould K L
Published: June 2012

The pressure-flow characteristics of 100 left circumflex stenoses in 10 chronically instrumented unsedated dogs were studied under resting conditions and during pharmacological coronary vasodilation. At rest, the pressure loss (deltaP) due to a stenosis and arterial flow velocity (V) were related by the equation, deltaP = FV + SV2, where F is the coefficient of pressure loss due to viscous friction in the stenotic segment and S is the coefficient of pressure loss due to flow separation at the diverging end of the stenosis. The linear term due to viscous friction accounted for 65% and the nonlinear term due to flow separation accounted for 35% of the total pressure loss at resting coronary flow. At peak coronary flow after coronary vasodilation, the pressure loss due to viscous friction accounted for 33% and pressure loss due to flow separation accounted for 67% of the total pressure loss. The pressure gradient-velocity relationship at high flows was characterized by the same general equation but with proportionately larger values of the coefficient S and therefore greater pressure loss associated with flow separation than predicted by the resting gradient-velocity relationship. The pressure loss predicted for high coronary flow velocities on the basis of the gradient-velocity equation at rest was only 64% of the actual experimentally observed pressure gradient at peak coronary flow. The augmented separation loss following coronary vasodilation probably was due to dilation of the epicardial artery adjacent to the fixed stenotic segment which caused more severe relative percent narrowing and a larger divergence angle at the distal end of the stenosis, the primary geometric determinants of separation losses.