bluuebunny/crossref_metadata_2025 huggingface dataset:
A Specific Competitive Antagonist of the Vascular Action of Angiotensin II
Authors: Pals Donald T. , Masucci Frederick D. , Sipos Frank , Denning George S.
Published: June 2012

The effect of 1-Asn-8-Ala-angiotensin II (Asn-Arg-Val-Tyr-Val-His-Pro-Ala) on the vascular action of angiotensin II was studied with rabbit aortic strips, pithed rats, and conscious rats. Dose-response (contraction) curves for angiotensin II on rabbit aortic strips shifted progressively to the right with increasing bath concentrations of 1-Asn-8-Ala-angiotensin II. The pA
2
value (an indication of the relative affinity of a competitive antagonist for an agonist's receptor site) was 6.84 ± 0.03. Dose-response curves for norepinephtine, serotonin, and histamine were relatively unaffected. No pA
3
values could be obtained with these agonists in the concentration range tested. Partial dose-response (pressor) curves for angiotensin II in pithed rats shifted to the right during infusions of 1-Asn-8-Ala-angiotensin II at 20 and 60 µg/kg min
-1
Partial dose-response curves for vasopressin, phenylephririe, and tyramine were unaffected. Infusions of 1-Asn-8-Ala-angiotensin II counteracted the pressor effect of angiotensin II infusions in pithed and conscious rats. Infusions of 1-Asn-8-Ala-angiotensin II (200 µ/ kg min
-1
) effective in reducing the blood pressure of conscious angiotensin II-infused rats caused only small pressor effects in conscious normotensive rats but reduced the blood pressure in 75% of the conscious rats with acute unilateral renal hypertension. The data presented are consistent with the conclusion that 1-Asn-8-Ala-angiotensin II is a specific competitive antagonist of the vascular action of angiotensin II both in vitro and in vivo.
Mechanism of Pulmonary Conversion of Anglotensin II to Angiotensin II in the Dog
Authors: Oparil Suzanne , Tregear Geoffery W. , Koerner Terry , Barnes Benjamin A. , Haber Edgar
Published: June 2012

The mechanism of conversion of angiotensin I to angiotensin II was studied in vivo in the pulmonary circulation of the intact anesthetized dog and in vitro in plasma by using L-Leu-anglotensin I, D-Leu-angiotensin I, and des-Leu-angiotensin I which had been synthesized by the solid-phase technique. None of the peptides were active in the rabbit aortic strip preparation; D-Leu-angiotensin I and des-Leu-angiotensin I gave less than 5% of the pressor response of L-Leu-angiotensin I in the pentolinium-treated rat. D-Leu-angiotensin I and des-Leu-angiotensin I were not converted to angiotensin II when incubated with diluted human or dog plasma or partially purified converting enzyme from dog plasma. In a single pulmonary circulation time, following injection of a 20-nmole bolus of L-Leu-angiotensin I into the dog right ventricle, 56% of the material recovered had been converted to angiotensin II, as measured by radioimmunoassay. Conversion was accompanied by a rise in mean blood pressure of 30 mm Hg. After injection of equimolar amounts of D-Leu-angiotensin I and des-Leu-angiotensin I, no generation of angiotensin II and no pressor response occurred. These observations indicate that pulmonary conversion in vivo and plasma conversion in vitro occur via a dipepridylcarboxypeptidase and that a D-amino acid at the C-terminus prevents conversion.
Venomotor Tone in Hemorrhage and Shock
Authors: ALEXANDER ROBERT S.
Published: June 2012

Employing the injection technic for venous distensibility determinations in intestinal loops of anesthetized dogs, an index to venomotor tone has been developed by measuring the volumes of blood required to produce specified changes in venous pressure. Application of this index in hemorrhage and shock experiments demonstrates a marked venomotor compensation to hemorrhage, and oscillations in venomotor tone correlating with the vasomotor waves in arterial blood pressure encountered in hemorrhagic hypotension. In the hypotension of shock, a serious deficiency in venomotor compensation develops, which should result in pooling of blood in the venous system and contribute significantly to the circulatory failure.
Pulmonary Blood Flow and Venous Return During Spontaneous Respiration
Authors: BRECHER GERHARD A. , HUBAY CHARLES A.
Published: June 2012

During normal spontaneous inspiration pulmonary blood flow increases in spite of an increase in resistance to flow in the pulmonary bed. The enhancement of pulmonary flow is caused by an augmentation of venous return due to thoracic aspiration. The right heart acts as a moderator for the pulmonary flow by temporarily storing part of the large influx of venous blood during inspiration and ejecting the stored part during expiration and the expiratory pause.
Cellular Hyperplasia and Hypertrophy in Cardiomegalies Induced by Anemia in Young and Adult Rats
Authors: NEFFGEN JOACHIM F. , KORECKY BORIVOJ
Published: June 2012

In our previous studies a twofold cardiomegaly associated with a proportional increase in cardiac DNA was found in rats subjected to a low-iron diet after weaning. To localize the newly synthesized DNA, control and anemic rats 24-34 days of age were given three intraperitoneal injections of
3
H-thymidine (1 µc/g body weight; 22c/mM) at 2-hour intervals. The radioautographs were prepared from sections of the left ventricle stained with PAS-hematoxylin. Between 26 and 34 days of age, significantly larger numbers of labeled nuclei were found in both muscle (31-160/1000) and nonmuscle cells, (29-139/1000) in the hearts of anemic rats as compared to controls (11-49/1000 and 6-35/1000, respectively). When 80-day-old rats were given a low-iron diet, a cardiomegaly of approximately 50% developed. A nonsignificant increase in total cardiac DNA and a small significant increase in labeled cardiac nonmuscle nuclei (16-35/1000) was observed in the anemic groups. We conclude that hyperplasia of cardiac muscle and nonmuscle cells is responsible for the increased cardiac mass if cardiomegaly is induced during early postweaning life, while cardiomegaly induced in adult life gives rise to hypertrophy of cardiac muscle cells and hyperplasia of cardiac nonmuscle cells.
Experimental Subendocardial Ischemia in Dogs with Normal Coronary Arteries
Authors: BUCKBERG GERALD D. , FIXLER DAVID E. , ARCHIE JOSEPH P. , HOFFMAN JULIEN I.E.
Published: June 2012

Subendocardial ischemia without anatomic coronary artery obstruction may result from a discrepancy between metabolic needs and available blood supply. We studied this in open-chest anesthetized dogs and measured pressures in aorta and left ventricle (LV), phasic left coronary arterial blood flow (CBF) by electromagnetic flowmeter, total CBF and LV subendocardial (endo) and subepicardial (epi) flow with radioactive microspheres 8-10µ, in diameter. Since LV Subendocardial flow is mainly or entirely diastolic, it should depend on coronary driving pressure and duration of diastole (i.e., the area between aortic and left ventricular diastolic pressures). This diastolic pressure time index (DPTI) was varied by opening arteriovenous fistulas to lower aortic diastolic pressure, constricting the ascending aorta to raise LV diastolic pressure and pacing to shorten diastole. Myocardial oxygen needs were estimated from the tension time index (TTI). Normal endo-epi flow ratios per gram (1:1) fell to 0.1:1 with these procedures and paralleled a fall in diastolic flow fraction (often nearly zero) and postischemic coronary reactive hyperemic responses. These changes occurred despite normal or raised mean CBF and 300-500% increase in systolic CBF. The altered flow ratios were best predicted by relating them to the ratio of DPTI (supply) to TTI (demand).
Direct Measurement of Superficial and Deep Venous Flow in the Cat Kidney
Authors: NISSEN OLE I. , GALSKOV Åge
Published: June 2012

In an excised cat kidney, the subcapsular veins were clipped near their connections with the renal vein and cut open distal to the clamps. The kidney was then placed in an oil-filled lucite chamber and perfused from a donor cat via tubes entering the chamber through its close-fitting lid. The blood leaking from the cut subcapsular veins was led to one flowmeter; that leaving via the cannulated renal vein (supplied now only by the arcuate vein system) was led to another flowmeter. Catecholamines and stimulation of the renal nerves reduced the arcuate blood flow more than the subcapsular blood flow, the two average reductions being 28% and 20% with epinephrine and 22% and 14% with stimulation of the renal nerves. Angiotensin reduced both flows equally. Microspheres reduced the subcapsular flow more than the arcuate flow, the two average reductions being 42% and 25% of the control flows. This effect was probably caused by trapping of the microspheres in the distal ends of the interlobular arteries beyond the inlets to the afferent arterioles, since these vessels are too narrow to allow free entrance of the microspheres. The preferential effect of epinephrine and nerve stimulation on the deep circulation is thought to be the result of the special structure of the juxtamedullary glomerular units.
Increase in Skeletal Muscle Performance during Emotional Stress in Man
Authors: BERDINA N. A. , KOLENKO O. L. , KOTZ I. M. , KUZNETZOV A. P. , RODIONOV I. M. , SAVTCHENKO A. P. , THOREVSKY V. I.
Published: June 2012

An emotional stress arising as a result of intense mental arithmetic causes (in most subjects) an increase in blood flow through resting forearm muscle by an average of 85%. Combination of voluntary sustained handgrip contraction with mental arithmetic has shown that the duration of contraction increases by an average of 46%. This effect appears only in subjects who display an increase in blood flow as a result of mental arithmetic. A rise in muscle performance is also observed during mental arithmetic when contraction of forearm muscle is caused by direct stimulation of the motor nerve in the upper arm. Intra-arterial injection of atropine sharply reduces both the increase in blood flow through the resting muscle and the increase in muscle performance associated with mental arithmetic. Control performance (without mental arithmetic) is not altered by administration of atropine. Analysis of blood flow during muscle contraction leads to the conclusion that an increase in muscle performance during emotional stress is not dependent on an increase in muscle blood flow. The data suggest that during emotional stress the sympathetic nervous system causes metabolic changes in skeletal muscles that lead to an increase in muscle performance when oxygen deficiency exists.
Myosin Synthesis and Degradation during Development of Cardiac Hypertrophy in the Rabbit
Authors: MORKIN E. , KIMATA S. , SKILLMAN J. J.
Published: June 2012

Metabolism of left ventricular myosin was studied in rabbits (2.7-3.2 kg) following banding of the ascending aorta (65% occlusion). In 26 rabbits the incorporation of amino acid into myosin was determined 2, 3, 4, 9, and 15 days after either stenosis or sham operation by injecting
3
H-lysine (0.5 mc/kg) 4 hours before the animals were killed. In 32 rabbits the same dose of
3
H-lysine was injected 24 hours before surgery, and disappearance of isotope from myosin was measured by killing the rabbits after 3, 5, 7, 10, or 16 days. Specific radioactivity of free lysine, myosin, and total proteins was determined in left ventricular samples from each animal. The experimental results indicate that: (1) left ventricular peak systolic pressure increased from 97 to 163 mm Hg; (2) the ratio of left ventricular weight to body weight increased about 16% (3) disappearance of free
3
H-lysine was similar in rabbits with aortic stenosis and those with sham operations; (4) after the second day myosin synthesis was greater in rabbits with aortic coarctations, reaching a maximum increase of 117% on the tenth day; (5) synthesis of left ventricular total proteins also reached a maximum of about 56% on the tenth day; (6) the decrease in specific radioactivity of myosin in rabbits with aortic coarctation was slower than it was in sham-operated animals. The experimental results were analyzed by a computerized simulation of myosin metabolism which allowed the rate constant for myosin degradation to be calculated on successive days after coarctation. The best fit to the observed changes in myosin content was obtained when degradation was increased with the increase in synthesis; when degradation was assumed to be unchanged from sham-operated animals or was decreased, myosin content was overestimated. Moreover, these calculations showed that decay in specific radioactivity of labeled myosin was affected very little even by a large (hundredfold) decrease in degradation. It is concluded that the increased myosin content during development of cardiac hypertrophy is primarily a consequence of increased synthesis.
Focal Transient Cerebral Ischemia in the Squirrel Monkey
Authors: SUNDT THORALF M. , MICHENFELDER JOHN D.
Published: June 2012

Cerebral adenosine triphosphate and lactate concentrations were measured in the squirrel monkey (
Saimiri sciureus
) before, during, and at selected times after various periods of middle cerebral artery occlusion. The gradual decrease in ATP to 55, 35, and 20%, of normal and the increase in lactate to 7, 8, and 10 times normal after 2, 3, and 4 hours of occlusion, respectively, were reversible with restoration of flow. Electrocorticograms recorded in acute preparations indicated potential for recovery. The correlation of lactate levels with previous determinations of blood flow in this preparation supports the theory that loss of autoregulation and "luxury perfusion" in cerebral ischemia results from localized metabolic acidosis due to accumulation of lactic acid. In a separate group of monkeys, the ischemic lesions were found to be largely reversible after 2 or 3 hours and irreversible after 4 hours of middle cerebral artery occlusion; the cause of death in the monkeys subjected to 4 hours of occlusion was edema, which progressed even after restoration of flow.
Release of a Prostaglandin E-Like Substance from Canine Kidney by Bradykinin
Authors: McGiff John C. , Terragno Norberto A. , Malik K. U. , Lonigro Andrew J.
Published: June 2012

Renal vasodilation produced by two dissimilar vasodepressor polypeptides, bradykinin and eledoisin, was correlated with changes in renal venous concentrations of substances having the properties of prostaglandins of the E and F series in anesthetized dogs. Samples of renal venous blood were extracted for acidic lipids, and the prostaglandin E and prostaglandin F zones of the chromatographed extracts were eluted and assayed in vitro for prostaglandins of the E and F series by a parallel bioassay system (sensitivity 0.015 ng/ml blood). During the first 2 minutes of infusion, bradykinin increased the concentration of a prostaglandin E-like substance in renal venous blood from a mean control level of 0.16 ng/ml to 1.05 ng/ml (
P
<0.01); this increase occurred simultaneously with the greatest increase in renal blood flow to 432 ml/min from a control value of 282 ml/min. After 12 minutes of bradykinin infusion, the concentration of the prostaglandin E-like substance had decreased to 0.30 ng/ml, and renal blood flow had fallen to 398 ml/min. In contrast, eledoisin infused in equidilator doses did not increase the concentration of the prostaglandin E-like substance. The concentration of prostaglandin F-like substances was not affected by either polypeptide. A transient increase in urine flow occurred during the first 2 minutes of bradykinin infusion only. These results suggest that a prostaglandin E-like substance participates in the renal vasodilator and the diuretic responses to bradykinin.
Effects of Experimentally Produced Heart Failure on the Peripheral Vascular Response to Severe Exercise in Conscious Dogs
Authors: Higgins Charles B. , Vatner Stephen F. , Franklin Dean , Braunwald Eugene
Published: June 2012

The peripheral vascular response to severe exercise in eight dogs with heart failure produced by tricuspid avulsion and progressive pulmonary stenosis was compared to the response determined in eight control dogs. After full recovery from implantation of Doppler flow probes and miniature pressure gauges, measurements of arterial blood pressure and blood flow were telemetered from untethered dogs running behind a mobile recording vehicle at speeds of 10-25 mph over distances averaging 1 mile. Severe exercise in control dogs increased heart rate from 78 to 281 beats/min and mean arterial blood pressure from 93 to 134 mm Hg. Iliac blood flow rose from 151 to 897 ml/min, but mesenteric and renal blood flows did not change significantly. Iliac vascular resistance decreased from 0.64 to 0.15 mm Hg/ml min
-1
, but mesenteric vascular resistance increased from 0.31 to 0.47 mm Hg/ml min
-1
and renal vascular resistance increased from 0.49 to 0.75 mm Hg/ml min
-1
. Severe exercise in dogs with heart failure increased heart rate from 102 to 274 beats/min, but mean arterial blood pressure only increased from 100 to 107 mm Hg. Iliac blood flow rose from 96 to 360 ml/min, whereas mesenteric blood flow decreased from 237 to 89 ml/min and renal blood flow decreased from 226 to 79 ml/min. Iliac vascular resistance decreased from 1.09 to 0.34 mm Hg/ml min
-1
, but mesenteric vascular resistance increased from 0.49 to 1.31 mm Hg/ml min
-1
and renal vascular resistance increased from 0.47 to 1.81 mm Hg/ml min
-1
. Thus, in heart failure a distinctly abnormal peripheral vascular response to severe exercise occurs, characterized by a very small elevation in mean arterial blood pressure and intense visceral vasoconstriction resulting in diversion of visceral blood flows.
Determinants of Pulmonary Vascular Volume
Authors: Maseri Attilio , Caldini Paolo , Harward Peter , Joshi Ramesh C. , Permutt Solbert , Zierler Kenneth L.
Published: June 2012

This study attempted to evaluate the relative roles of vessel distensibility and vessel recruitment in the changes in pulmonary blood volume induced by changes in pulmonary intravascular pressure. Pulmonary blood volume was determined by a double-injection indicator-dilution technique in eight anesthetized open-chest dogs with a right and left ventricular bypass which allowed independent control of pulmonary artery and left atrial pressures. In three dogs, measurements were also taken during reverse perfusion (from the left atrium to the pulmonary artery). During forward perfusion, when left atrial pressure was increased from 7 to 26 cm H
2
O, and, by reducing flow from 3.4 to 1.2 liters'/min, pulmonary artery pressure was maintained at 30 cm H
2
O so that recruitment could be considered constant, pulmonary blood volume did not change but remained at about 260 ml. Pulmonary blood volume also did not change during reverse perfusion when pulmonary artery pressure was increased from 8 to 27 cm H
2
O at a constant left atrial pressure (inflow pressure). By contrast, when pulmonary artery pressure was raised by increasing flow, so that vessel recruitment could occur, pulmonary blood volume increased 12 ml for each 1-cm H
2
O increase in pulmonary artery pressure at a constant left atrial pressure of 5 cm H
2
O, and pulmonary blood volume increased 7 ml for each 1-cm H
2
O increase in pulmonary artery pressure at a constant left atrial pressure of 33 cm H
2
O. Therefore, in the range of pressures that we explored, the role of large-vessel distensibility in the changes in pulmonary blood volume observed when intravascular pressures were raised was small.
Venous Endothelium of Experimental Arteriovenous Fistulas in Rabbits
Authors: Fallon J. T. , Stehbens W. E.
Published: June 2012

Since hemodynamic factors have been implicated in the localization and pathogenesis of atherosclerosis, the effect of hemodynamic stress on endothelium was investigated. The endothelium of the inferior vena cava of 24 rabbits with aortocaval fistulas was stained in situ and examined by the Hautchen technique at postoperative intervals ranging from 1 to 50 weeks. Cell counts revealed that, in the anastomosed vein of the fistula, an initially high frequency of abnormal cells decreased 3-12 weeks postoperatively but rose again within 20-50 weeks to levels significantly higher than those in either normal venous endothelium or sham-operated veins. An originally high mitotic index at 1-2 weeks decreased with time but still remained significantly larger than that observed in sham-operated rabbits. In most rabbits with arteriovenous shunts, a small area of the inferior vena cava near the fistula was devoid of endothelium, covered with a thin deposit of mural thrombi, and considered to be a jet lesion. The findings demonstrate that hemodynamic factors can cause endothelial injury, increased turnover of endothelial cells, and formation of multinucleated endothelial cells characteristic of regenerating endothelium.
Cardiac Muscle Models
Authors: Pollack Gerald H. , Huntsman Lee L. , Verdugo Pedro
Published: June 2012

Quick-stretch and quick-release experiments were performed on right ventricular cat papillary muscles to test the applicability of the Hill model to cardiac mechanics. Series elastic component (SEC) force-length curves were calculated from stretches and releases carried out at various times during the contractile cycle. At any SEC force, the SEC elastic modulus depended on the time during the contractile cycle at which it was measured. When measured at the same time and at the same SEC force, elastic moduli obtained by releases of less than 1% of muscle length differed from those obtained by corresponding stretches. Larger stretches, in fact, appeared to yield negative elastic moduli. Thus, a unique SEC modulus could not be identified at any level of SEC force. It is concluded that the concept of the SEC as a passive elasticity appears unsatisfactory and, as a consequence, that the quantitative validity of the Hill model for cardiac muscle is questionable. Moreover, since an anatomical counterpart of the SEC has not been identified, the Hill model also appears unsatisfactory from a structural point of view.
Regulation of Blood Pressure by Sympathetic Nerve Fibers and Adrenal Medulla in Normotensive and Hypertensive Rats
Authors: de Champlain Jacques , van Ameringen Marie Reine
Published: June 2012

The respective roles of the sympathetic nerve fibers and adrenal medulla in the regulation of blood pressure and heart rate were studied in normotensive and hypertensive rats. Chemical sympathectomy alone, by treatment with 6-OH-DA, or bilateral adrenalectomy reduced blood pressure only slightly in normotensive animals. In animals made hypertensive with deoxycorticosterone (DOCA) and saline, each of these procedures reduced blood pressure to a greater extent than in normotensive animals, but the blood pressure remained at hypertensive levels. The combination of both procedures resulted in a greater fall in blood pressure than could have been predicted from individual effects, suggesting that the removal of one component of the sympathetic system can be compensated for by a hyperactivity of the remaining component. After chemical sympathectomy, adrenalectomy produced a rapid and marked fall in blood pressure in both normotensive and hypertensive animals and the blood pressure stabilized around 50 mm Hg within 1 hour after adrenalectomy. Since the basal blood pressure was identical in normotensive and hypertensive animals after removal of both components of the sympathetic system, this suggests that the most likely factor which would account for an elevated blood pressure in rats treated with DOCA and sodium is a synergic hyperactivity of the sympathetic fibers and adrenal medulla.
Renal Vascular Responses to Angiotensin and Norepinephrine in Normal Man: EFFECT OF SODIUM INTAKE
Authors: HOLLENBERG NORMAN K. , SOLOMON HAROLD S. , ADAMS DOUGLASS F. , ABRAMS Herbert L. , MERRILL John P.
Published: June 2012

The effect of sodium intake on renal vascular responses to angiotensin and norepinephrine infused intra-arterially was assessed in normal man by xenon washout. In subjects on an unrestricted diet, the dose of angiotensin inducing a 50% reduction in mean blood flow (ED
50
) was 38.2 ± 12.6 ng/min, a hundredfold lower dose than that for norepinephrine. Sodium restriction reduced the sensitivity to angiotensin tenfold: the ED
50
rose to 378 ± 12 ng/min. This diet, conversely, potentiated responses to norepinephrine: the threshold dose fell from 37 ± 10 to 3.6 ± 1.9 ng/min. Thus, the reduction in sensitivity to angiotensin induced by sodium restriction was not a nonspecific effect on the vascular smooth muscle. Sodium restriction also reduced the variability in the vascular response to angiotensin, and a close correlation was found between urine sodium content and angiotensin responsiveness. The blood vessels of the normal human kidney are remarkably sensitive to angiotensin: the threshold dose is approximately 1 ng/min for intra-arterial infusion. Circulating angiotensin may be a mediator of renal vascular tone, but circulating catecholamines probably play a minimal role.
Dependency of Pial Arterial and Arteriolar Diameter on Perivascular Osmolarity in the Cat
Authors: WAHL M. , KUSCHINSKY W. , BOSSE O. , THURAU K.
Published: June 2012

The effect of perivascular osmolarity on the diameter of pial arteries was studied in cats by the microapplication technique. Between 251 and 360 mosmoles/liter, concentration-response curves were obtained for single vessels. Constriction occurred when perivascular osmolarity was decreased below 317 mosmoles/liter, and dilation occurred at osmolarities above this value. The effect was the same whether the osmolarity was changed by addition of mannitol or NaCl. Reduction of sodium concentration from 156 to 133 mEq/liter at constant osmolarity did not affect arteriolar diameter, but greater reductions in sodium concentration induced vasoconstriction. The results indicate that the resistance of pial arteries can be influenced by local changes in perivascular osmolarity.
Load Independence of the Instantaneous Pressure-Volume Ratio of the Canine Left Ventricle and Effects of Epinephrine and Heart Rate on the Ratio
Authors: SUGA HIROYUKI , SAGAWA KIICHI , SHOUKAS ARTIN A.
Published: June 2012

As a means of assessing ventricular performance, we analyzed the time-varying ratio of instantaneous pressure, P(t), to instantaneous volume, V(t), in the canine left ventricle. Intraventricular volume was measured by plethysmography, while the right heart was totally bypassed. The cardiac nerves were sectioned, and an epinephrine infusion was used to alter the contractile state. The instantaneous pressure-volume ratio was defined as E(t) = P(t)/[V(t) - V
d
], where V
d
is an experimentally determined correction factor. We found that (1) all the E(t) curves thus defined were similar in their basic shape and attained their peak near the end of the ejection phase regardless of the mechanical load, the contractile state, or the heart rate, (2) under a constant heart rate and contractile state extensive changes in preload, afterload, or both did not alter the peak value of E(t), Emax, or the time to Emax from the onset of systole, Tmax, and (3) these parameters of E(t) markedly changed with epinephrine infusion or increases in heart rate. At an epinephrine infusion rate of 2 µg/kg min
-1
, Emax increased to 12.2 ± 4.5 (
SD
) mm Hg/ml (N = 9) from its control value of 6.6 ± 1.2 mm Hg/ml before the infusion. Simultaneously, Tmax shortened from 191 ± 29 msec to 157 ± 26 msec. Increases in the paced heart rate proportionally shortened Tmax (45% per 100-beats/min change in heart rate) without any effect on Emax. We concluded that E(t), represented by Emax and Tmax, explicitly reflects the ventricular contractility.
Selective In Situ Parasympathetic Control of the Canine Sinoatrial and Atrioventricular Nodes
Authors: LAZZARA RALPH , SCHERLAG BENJAMIN J. , ROBINSON MORTON J. , SAMET PHILIP
Published: June 2012

Methods were devised for the selective alteration of parasympathetic control over the sinoatrial (SA) or the atrioventricular (AV) node in anesthetized, thoracotomized mongrel dogs. Two epicardial sites were located at which parasympathetic nerve fibers enroute to the SA or the AV node could be stimulated or blocked. Selective nerve stimulation was accomplished with brief pulses (0.05 msec), and blockade was accomplished with topically applied lidocaine. At the intercaval site, only the SA node was affected. At the site near the coronary sinus ostium, only the AV node was affected in terms of parasympathetic control, but sometimes there were modest sympathetic effects on the SA node. The effects of stimulation at these sites, except for the SA speeding produced by stimulation at the site near the coronary sinus, were blocked by atropine. The effects were also blocked by ganglionic blockade. Probably, preganglionic parasympathetic fibers to the nodes are concentrated at these sites.
Action of Manganese Ions and Tetrodotoxin on Atrioventricular Nodal Transmembrane Potentials in Isolated Rabbit Hearts
Authors: ZIPES DOUGLAS P. , MENDEX CARLOS
Published: June 2012

In the isolated rabbit heart, it was shown that (1) manganese ions (Mn
2+
) (2-4 m
M
) suppressed the activity of atrioventricular (AV) nodal cells located in the AN, N, and NH regions without preventing regenerative responses in atrial or His bundle fibers when these fibers were directly stimulated, (2) tetrodotoxin (TTX) in concentrations of 5 x 10
-6
g/ml Tyrode's solution rendered atrial and His bundle fibers inexcitable without preventing AV nodal potentials of automatic origin and without affecting the rate of rise of cells located in the N region, and (3) in the presence of TTX (5 x l0
-6
g/ml of Tyrode's solution) the addition of epinephrine (2 µg/ml solution) restored atrial activity. It was concluded that the different effects of Mn
2+
and TTX on AV nodal action potentials is consistent with the postulate, made by Rougier et al. (8) and Vassort et al. (9) for frog atrial fibers treated with TTX, that AV nodal action potentials probably result from the operation of a slow ionic channel.
Functional Transverse Interconnections within the His Bundle and the Bundle Branches
Authors: LAZZARA RALPH , YEH BILLY K. , SAMET PHILIP
Published: June 2012

The existence of transverse interconnections within the His bundle and the bundle branches was investigated in excised preparations from dogs and rabbits. The preparations included the His bundle or one of the bundle branches along with portions of the peripheral conduction system. They were superfused with Tyrode's solution, and conventional electrophysiological techniques for extra- and intracellular recordings were employed. The effects of incisions and of intracellular stimulation within the proximal conduction system on distal activation were observed. Transection of 90% of a right bundle branch or intracellular stimulation within that bundle branch did not alter the distal activation pattern observed during surface stimulation of fully recovered fibers. Transection of 90% of the left bundle branch or intracellular stimulation produced a temporal shift of no more than 4 msec in the activation of widely scattered distal sites. Intracellular stimulation in the left bundle branch never produced dispersion of more than 3 msec in distal activation compared with the effects of surface stimulation. Intracellular stimulation at various points within the His bundle always activated the right bundle branch in a manner identical with activation during physiological atrioventricular conduction. Transverse velocity in the conduction system was less than longitudinal velocity. It is concluded that functional transverse interconnections are relatively numerous in the His bundle and the bundle branches.
Influence of Flow and Pressure on Wave Propagation in the Canine Aorta
Authors: HISLAND MICHAEL B. , ANLIKER MAX
Published: June 2012

Data on wave speed acquired from 20 anesthetized dogs showed that the thoracic aorta was essentially nondispersive for small artificially generated pressure waves traveling in the downstream or the upstream direction and having frequencies between 40 and 120 Hz. The amplitude of these waves decayed exponentially with the distance traveled. The attenuation was independent of frequency and pressure if the distance was measured in wavelengths. The logarithmic decrement of the downstream waves ranged between 0.7 and 1.0, whereas that of the retrograde waves was between 1.3 and 1.5. The discrepancy in the attenuation for the two directions appeared to be due to the taper of the thoracic aorta. Simultaneous measurements of the transmission times of waves traveling downstream and upstream indicated that small pressure perturbations were convected with a speed that was approximately equal to the mean flow velocity. The speed of such perturbations depended strongly on the aortic pressure level at which they were generated. For normal pressure pulses generated by the heart, the speed of small perturbations at systole might be 30% higher than that at diastole. Theoretical studies have shown that such changes in wave speed due to variations in pressure and flow produce marked nonlinear effects in hemodynamics.
Depressed Transmembrane Potentials during Experimentally Induced Ventricular Failure in Cats
Authors: GELBAND HENRY , BASSETT ARTHUR L.
Published: June 2012

Transmembrane potentials and isometric force were recorded in right ventricular muscles from cats with right ventricular failure 3-127 days after chronic partial pulmonary artery obstruction. For the majority of failed muscles (at 36°C, 30 stimuli/min), resting potential, action potential overshoot, action potential maximum rate of rise, isometric active force at optimal length (P
o
), and dP/dt were decreased compared with the same parameters in normal muscles. Time to peak force and duration of contraction were unaltered. Action potential configuration was changed and action potential duration was lengthened in failed muscles. Epinephrine (10
-6
M) markedly increased P
o
and resting potential in severely depolarized failed muscles. These data suggest that electrical depression might exacerbate the contractile deficit in experimental chronic right ventricular failure.
Comparison of the Effects of Anoxia and Whole Heart Ischemia on Carbohydrate Utilization in Isolated Working Rat Hearts
Authors: ROVETTO MICHAEL J. , WHITMER JEFFREY T. , NEELY JAMES R.
Published: June 2012

The rates of utilization of glycogen and exogenous glucose by hearts perfused at low coronary flows and high perfusate oxygen tension (ischemia) and by hearts perfused at high coronary flows and low perfusate oxygen tension (anoxia) were studied in the isolated, working rat heart. Ischemic tissue had a glycolytic rate that was 25% of the anoxic rate and 50% of the control rate. Inhibition of carbohydrate utilization during ischemia was due to a lower flux through the glycolytic pathway and not to a lower rate of glucose transport or substrate availability. Insulin and elevated perfusate glucose increased glucose transport and caused accumulation of free intracellular glucose, but ischemia still inhibited glucose utilization. Insulin failed to maintain tissue levels of high-energy phosphates or to prevent mechanical failure in ischemic hearts. In the absence of insulin, tissue lactate increased tenfold during 20 minutes of ischemia, although it increased only threefold in anoxic tissue. The increased tissue lactate in ischemic hearts corresponded to the inhibition of glycolysis and to the failure of mechanical performance. Insulin caused a further increase in tissue lactate during ischemia. These findings illustrate several important differences between anoxia and ischemia and suggest that insulin may be more harmful than it is beneficial in severely ischemic tissue.
Time Course of Vascular Resistance and Venous Oxygen Changes following Brief Tetanus of Dog Skeletal Muscle
Authors: MOHRMAN DAVID E. , CANT JAMES R. , SPARKS HARVEY V.
Published: June 2012

The time courses of vascular resistance and venous blood oxygen (O
2
) saturation following a brief tetanus of isolated dog calf muscle were studied during free-flow (constant-pressure), high constant-flow (>30 ml/100 g min
-1
), and low constant-flow (<24 ml/100 g min
-1
) perfusion. A monophasic decrease in resistance followed a 1-second tetanus during either free-flow or high constant-flow perfusion. The transient decrease in vascular resistance during high constant-flow perfusion returned to control before the return of the decrease in end-capillary oxygen tension. Thus, it seems unlikely that the vascular response to a brief tetanus during free-flow or high constant-flow perfusion was controlled by a factor related to oxidative metabolism. A biphasic resistance response followed a brief tetanus during low constant-flow perfusion. This vascular response had a longer duration than the response during free-flow or high constant-flow perfusion. It returned to control with approximately the same time course as that for tissue O
2
consumption and could therefore be controlled by factors related to oxidative metabolism. These findings support the hypothesis that exercise hyperemia is due to multiple factors. Moreover, they indicate that, under the conditions of free-flow perfusion or high constant-flow perfusion, the vascular response to a brief tetanus is not solely controlled by factors directly associated with tissue oxidative metabolism.
Contribution of Intrarenal Generation of Prostaglandin to Autoregulation of Renal Blood Flow in the Dog
Authors: HERBOCZYNSKA-CEDRO KRYSTYNA , VANE JOHN R.
Published: June 2012

The mechanism of autoregulation of renal blood flow was investigated in anesthetized dogs, using either constant-flow or constant-pressure perfusion of the kidney. Prostaglandinlike material in the renal venous blood was assayed by the blood-bathed organ technique. Compensatory renal vasodilation, induced either by lowering the blood flow or the perfusion pressure, was accompanied by increased output of prostaglandinlike material into the renal venous blood. The prostaglandin synthetase inhibitor, indomethacin, abolished this output, and, at the same time, autoregulation of renal blood flow was abolished. A converting enzyme inhibitor, however, had no effect on renal autoregulation. The results support the hypothesis that autoregulation in the kidney is mediated by release of a vasodilator, prostaglandin, rather than by formation of a vasoconstrictor substance such as angiotensin II.
Effect of Verapamil on the Normal Action Potential and on a Calcium Dependent Slow Response of Canine Cardiac Purkinje Fibers
Authors: CRANEFIELD PAUL F. , ARONSON RONALD S. , WIT ANDREW L.
Published: June 2012

The effect of verapamil on normal sodium (Na)-dependent and slow calcium (Ca)-dependent action potentials recorded from canine cardiac Purkinje fibers was studied. The Ca-dependent slow response was obtained in fibers exposed to solutions in which all NaCl was replaced by tetraethylammonium chloride and in which Ca ranged from 4 m
M
to 16.2 m
M
. Verapamil (0.25-2 mg/liter) had little or no effect on the upstroke of the normal action potential, but such concentrations of verapamil suppressed rhythmic activity and depressed excitability in fibers that showed Ca-dependent slow responses. Spontaneous activity and rhythmic activity evoked by long depolarizing pulses were depressed. Verapamil decreased the amplitude and the upstroke velocity and shifted the threshold potential toward zero in fibers that showed Ca-dependent slow responses. The effectiveness of verapamil varied with the level of Ca; 0.25 mg/liter of verapamil was as effective in suppressing activity in fibers exposed to 4 m
M
Ca as was 2 mg/liter of verapamil in fibers exposed to 16.2 m
M
Ca. Although verapamil did not alter the upstroke of the normal Na-dependent action potential, it did depress the plateau and prolong the action potential of fibers exposed to normal Tyrode's solution.
Mechanisms of Renal Release of Renin by Electrical Stimulation of the Brainstem in the Cat
Authors: RICHARDSON DAVID , STELLA ANDREA , LEONETTI GASTONE , BARTORELLI ALBERTO , ZANCHETTI ALBERTO
Published: June 2012

Electrical stimulation of the dorsolateral pons for 5-minute periods in anesthetized cats produced a rise in blood pressure of 40%, a reduction in renal blood flow of 28%, and an increase in the rate of renin release (the product of renal plasma flow and the venoarterial difference of plasma renin activity) of more than 100% in intact kidneys. Comparison of an intact kidney with the contralateral denervated one showed that denervation abolished the decrease in renal blood flow and the increase in renin release induced by pontine stimulation. Infusion of phenoxybenzamine into an otherwise intact kidney prevented the decrease in renal blood flow on that side, but brain-induced renin release was at least equal to that from the contralateral kidney in which the vasomotor response remained unchanged. Treatment of the animal with intravenously administered propranolol (1.3-3.0 mg/kg) abolished any rise in renin release, although propranolol accentuated the reduction in renal blood flow during stimulation of the brainstem. We concluded that the increased renal release of renin induced by electrical stimulation of a pressor area of the brainstem was dependent on intact renal nerves and on mechanisms blocked by propranolol but was not dependent on changes in renal blood flow or on renal alpha receptors.
Upper Limit of Autoregulation of Cerebral Blood Flow in the Baboon
Authors: STRANDGAARD SVEND , MACKENZIE ERIC T. , SENGUPTA DIPANKAR , ROWAN JACK O. , LASSEN NIELS A. , HARPER A. MURRAY
Published: June 2012

The upper limit of autoregulation of cerebral blood flow was studied in ten young baboons. Blood pressure was increased by infusing angiotensin, and cerebral blood flow was measured by the intracarotid
133
xenon injection method. Autoregulation was maintained until blood pressure was 30-40% above resting values. At this blood pressure level, cerebrovascular resistance reached a maximum. Any additional increase in blood pressure resulted in an increase in cerebral blood flow and a decrease in cerebrovascular resistance; this situation is designated the "breakthrough of autoregulation." In four baboons subjected to unilateral sympathetic denervation, autoregulation of cerebral blood flow was studied bilaterally; no difference in the upper limit of autoregulation was found between the intact and the sympathectomized hemisphere. The breakthrough of autoregulation supposedly plays an important role in the pathogenesis of acute hypertensive encephalopathy. The old concept of hypertensive cerebral vasospasm has been revised in recent years, and it is now generally recognized that acute hypertensive encephalopathy is caused by focal overdistention of brain arterioles with lesions of the blood-brain barrier. However, whether this condition is associated with a high cerebral blood flow in the clinical syndrome has not been investigated.
Influence of Experimental Edema on Metabolically Determined Blood Flow
Authors: ZELIS ROBERT , LEE GARRETT , MASON DEAN T.
Published: June 2012

To evaluate the effects of edema and elevated tissue pressure on metabolically determined blood flow, forelimb vascular resistance was determined by two techniques. Peak reactive hyperemic blood flow after release of a 5-minute arterial occlusion was bilaterally measured in the brachial arteries of 11 dogs before and after venous congestion of one limb for 4 hours at 70 mm Hg and after infusion of 1,000 ml of 6% Dextran 70. Before determining peak reactive hyperemic blood flow, congestion was released; venous pressure was then similar in both limbs. Congestion reduced peak reactive hyperemic blood flow from 23.9 ± 5.7 (SE) to 16.0 ± 3.6 ml/min 100 g
-1
(
P
< 0.05). Peak reactive hyperemic blood flow was unchanged in the uncongested control limb (21.2 ± 5.2 to 20.4 ± 4.5 ml/min 100 g
-1
,
P
> 0.5) at the time when it was reduced in the congested limb. Total tissue pressure measured with a needle was greater in the congested limb (9.1 ± 1.7 mm Hg) than it was in the uncongested limb (2.5 ± 1.5 mm Hg,
P
< 0.01). Likewise, pressure in a chronically implanted perforated capsule was -2.1 ± 2.0 mm Hg in the control limb but was +7.2 ± 1.5 mm Hg (
P
< 0.01) in the contralateral limb following congestion. Dextran 70 was infused after venous congestion; this procedure produced peak reactive hyperemic blood flows and tissue pressures which were similar in both limbs. Similarly, minimum vascular resistance following an ischemic stimulus in an isolated, denervated constant-perfused forelimb was increased from 17.7 ± 2.2 to 23.9 ± 1.8 mm Hg/ml min
-1
100 g
-1
(
P
< 0.01) following congestion in five dogs. Brachial arterial sodium content was unchanged in four dogs following 4 hours of congestion. These data suggest that, in the presence of edema, metabolic arteriolar dilation may be impaired.
Human Splanchnic and Forearm Vasoconstrictor Responses to Reductions of Right Atrial and Aortic Pressures
Authors: JOHNSON JOHN M. , ROWELL LORING B. , NIEDERBERGER MANFRED , EISMAN MARTIN M.
Published: June 2012

Regional vascular responses to gradual reductions in right atrial pressure and aortic pressure were investigated in nine men. In each study, lower body negative pressure was applied in a ramp of -1 mm Hg/min for 40-50 minutes. During the range from control to -20 mm Hg, right atrial pressure (4 studies) fell from 4.2 mm Hg to -0.6 mm Hg; heart rate was slightly reduced (2 beats/min), and aortic mean pressure and pulse pressure (6 studies) were unchanged. The maximal rate of rise of aortic pressure showed no consistent trends. Forearm blood flow (30 studies) fell with the onset of lower body negative pressure and reached 67% of the control value by -20 mm Hg. Splanchnic blood flow (14 studies) was significantly reduced by -7 mm Hg and fell to 89% of control by -20 mm Hg. During the range from -20 to -50 mm Hg, right atrial pressure continued to fall. Aortic mean pressure fell slightly or was unchanged in four subjects and fell dramatically at -35 mm Hg in two subjects. Aortic pulse pressure began to fall at about -20 mm Hg and fell linearly thereafter. Heart rate paralleled aortic pulse pressure (
r
= -0.86 to -0.93). Forearm blood flow fell to 55% and splanchnic blood flow fell to 65% of control at -50 mm Hg. Thus, significant vasoconstriction occurred without measurable change in arterial blood pressure. We concluded that low-pressure baroreceptors, presumably in the cardiopulmonary region, initiate splanchnic and forearm vasoconstriction with more pronounced vasoconstriction occurring in the forearm.