bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Distribution of Diffusible Tracers and Carbonized Microspheres in the Left Ventricle of Isolated Dog Hearts
Authors: YIPINTSOI TADA , DOBBS WILLIAM A. , SCANLON PAUL D. , KNOPP THOMAS J. , BASSINGTHWAIGHTE JAMES B.
Published: June 2012

Microspheres of different sizes,
125
I-labeled antipyrine (I-Ap), and
42
KCl or
86
RbCl were injected into the aortic inflow of isolated, Langendorff, perfused, nonworking dogs hearts at blood flows of 1.3-4.8 ml/min g
-1
. After 15 seconds to 5 minutes, the left ventricle was sectioned into about 300 ordered pieces, and the amount of each tracer was determined. For all tracers, the relative density of deposition was generally higher in the endocardial region, except in one heart in which the aortic pressure and the total coronary flow were low. The deposition of
42
K and that of I-Ap were essentially similar in three hearts over a large range of regional variation. This finding suggests either that both tracers were distributed in proportion to flow or that a small diminution in relative density of deposition of
42
K in high-flow regions due to lower transcapillary extraction was quantitatively similar to a decrease in the residual fraction of I-Ap in these same regions due to faster washout in the first 15-30 seconds after injection. Large microspheres were deposited preferentially in regions of high flow, exaggerating the apparent heterogeneity of regional flows. The distribution of the smaller microspheres was closer to that for I-Ap or
42
K.
Hemodynamic and Biochemical Effects of a New Positive Inotropic Agent
Authors: SCHWARTZ ARNOLD , LEWIS ROBERT M. , HANLEY HENRY G. , MUNSON RONALD G. , DIAL FREDERICK D. , RAY MARTHA V.
Published: June 2012

The antibiotic ionophores RO 2-2985 (Hoffman-LaRoche; X537A) and A23187 (Lilly) produced an abrupt release of previously bound calcium from isolated sarcoplasmic reticulum. Only RO 2-2985 produced a significant inhibition of sodium, potassium-adenosinetriphosphatase activity. In anesthetized, open-chest dogs, RO 2-2985 caused a marked increase in right and left ventricular contractile force, aortic and coronary flow, and mean central aortic blood pressure with modest changes in heart rate and no change in calculated mean peripheral resistance. A single injection of 1 mg/kg produced a sustained augmentation of mean blood pressure from a control of 45 mm Hg in dogs that were in induced shock to approximately 125 mm Hg for a period up to 7-9 hours. At that time, tyramine produced a release of catecholamines, and norepinephrine and isoproterenol produced a marked increase in force of contraction. Dogs that were treated with reserpine did not respond to the drug. RO 2-2985, but not A23187, produced positive inotropism in isolated rabbit atrial and perfused ventricular preparations. RO 2-2985 still produced an augmentation in blood pressure after β-receptor blockade. It is suggested that RO 2-2985 acts by a mechanism involving a very slow release of humoral substances, by a direct effect on a specific calcium-proton exchange, or by both. It is thought that this agent has potential therapeutic applications.
Sensitization of the Adrenal Cortex to Angiotensin II in Sodium-Deplete Man
Authors: OELKERS WOLFGANG , BROWN JEHOIDA J. , FRASER ROBERT , LEVER ANTHONY F. , MORTON JAMES J. , ROBERTSON J. IAN S.
Published: June 2012

The effect of sodium depletion on the dose-response relationships of angiotensin II to aldosterone and blood pressure was studied. Arterial plasma angiotensin II and aldosterone and arterial blood pressure were measured before and during the incremental infusion of angiotensin II into sodium-replete and sodium-deplete subjects. Sodium depletion caused a distinct steepening of the angiotensin Il-aldosterone dose-response curves in four of five subjects and a concurrent diminution in the pressor effect of angiotensin II. Administration of angiotensin II did not demonstrably alter the half-life of aldosterone. Sodium depletion did not change the plasma concentrations of sodium or potassium, but it was accompanied by a significant increase in plasma levels of 11-hydroxycorticosteroids and magnesium. The contrasting effects of sodium depletion on the aldosterone and the pressor dose-response curves favored sodium retention. These results are consistent with an important role for the renin-angiotensin system in the control of aldosterone secretion in man.
Effects of Halothane on Left Ventricular Function and Distribution of Regional Blood Flow in Dogs and Primates
Authors: VATNER STEPHEN F. , SMITH N. TY
Published: June 2012

Left ventricular and regional vascular effects of halothane were assessed in dogs and primates in which coronary, mesenteric, renal, and iliac blood flows, arterial blood pressure, left ventricular diameter and pressure, dD/dt (i.e., the velocity of myocardial fiber shortening), and dP/dt were continuously measured in the control resting state, while the conscious animals were breathing O
2
, and during halothane-O
2
anesthesia maintained at 1% or at 2% for 90 minutes (separate experimental days). Halothane caused a concentration-dependent depression of myocardial contractility: (dP/dt)/P fell 68 ± 5% during 2% halothane anesthesia and left ventricular end-diastolic diameter rose. Halothane also caused a redistribution of regional blood flows. At a concentration of 1% halothane, the most intense vasodilatation occurred in the renal bed (renal resistance fell 46 ± 5%), but mesenteric resistance rose (42 ± 15%). With 1% halothane regional vascular resistances tended to rise with time, but with 2% halothane regional blood flows rose with time. A direct vasodilating action of halothane was observed following direct intra-arterial injection of the drug. Probably this action was responsible for the renal and iliac vasodilatations and for the opposition to the metabolically induced vasoconstriction in the coronary bed. Thus, the administration of the most commonly employed potent inhalation anesthetic, halothane, substantially alters myocardial contractility and regional blood flows and resistances. These effects are, in many instances, a function of the concentration of the anesthetic and the duration of its administration.
Hot-Film Anemometer Velocity Measurements of Arterial Blood Flow in Horses
Authors: NEREM ROBERT M. , RUMBERGER JOHN A. , GROSS DAVID R. , HAMLIN ROBERT L. , GEIGER GARY L.
Published: June 2012

Blood velocity measurements were carried out using a constant-temperature hot-film anemometer system in both anesthetized and conscious horses. Catheter probes were used to measure velocity wave forms in conscious horses and L-shaped needle probes inserted by direct vessel puncture were used to measure the profiles in regions of the thoracic and abdominal aorta of anesthetized, open-chest horses. Both catheter and L-shaped probes were used for coronary velocity wave-form measurements. The flow conditions were characterized by peak Reynolds numbers of 200-10,000 and unsteadiness parameter of 2-30. These measurements indicate that in the thoracic aorta the flow at peak systole is largely inviscid with a thin-wall boundary layer; in the abdominal aorta the flow is more fully developed but skewed due to branching effects. Highly disturbed flows were observed in the thoracic aorta of both anesthetized and conscious horses, but not in the abdominal aortic region or in the coronary arteries. The results of this study indicate that the flow in the arterial system, although in many cases laminar and disturbance free, is extremely varied in character. It may be asymmetric and certainly is not representative of fully developed, Poiseuille flow.
Effects of Carbon Monoxide on Myocardium
Authors: KJELDSEN KNUD , THOMSEN HENRIK KLEM , ASTRUP POUL
Published: June 2012

Sixteen rabbits were placed in exposure chambers: eight were continuously exposed to 180 ppm of carbon monoxide and eight were exposed to atmospheric air for 2 weeks. The myocardial ultrastructure of all the rabbits was examined. In rabbits exposed to carbon monoxide, local areas of partial or total necrosis of the myofibrils and degenerative changes of the mitochondria were found. Extra- and intracellular edema, increases in the number of ribosomes and lipofuscin granules, and reparative fibrotic changes also occurred. Varying degrees of injury were noted in the blood vessels. Capillary edema, but never total stenosis, was seen in some areas. Stasis and occasional small perivascular hemorrhages were typical on the venous side; on the arterial side the characteristic picture was one of endothelial swelling, formation of subendothelial edema, and degenerative changes of the myocytes. The present study supports the hypothesis that chronic exposure to low levels of carboxyhemoglobin can produce myocardial damage and account for the increased risk of myocardial infarction and sudden death seen in heavy cigarette smokers.
Direct Measurement of Coronary Collateral Blood Flow in Conscious Dogs by an Electromagnetic Flowmeter
Authors: ELLIOT ERIC C. , KHOURI EDWARD M. , SNOW JERRY A. , GREGG DONALD E.
Published: June 2012

The development of collateral circulation has been indirectly monitored by determining peripheral coronary pressure and
133
Xe clearance. In the present experiments, the development of collateral blood flow following gradual (three dogs) and rapid (three dogs) complete occlusion of the central circumflex branch, during partial central occlusion, and in parallel with a rise in peripheral coronary pressure was directly demonstrated by finding phasic coronary flow patterns in distal branches of the circumflex coronary artery. Collateral blood flow patterns were not consistently observed until a flow of 4-6 ml/ min developed. In five dogs branch flow before central occlusion averaged 20 ml/min, but peak collateral blood flow after occlusion averaged 11.6 ml/min (range 7 to 17 ml/min). To circumvent central occlusion collateral blood flow must enter the circumflex bed retrograde; we proved this fact by finding collateral blood flow patterns that were mirror images of normal antegrade patterns and flow values that were negative with respect to mechanical reference zeros. Unexpectedly, collateral blood flow was antegrade in some branches indicating a redistribution of retrograde collateral blood flow within the circumflex bed. In a terminal open-chest experiment, there was indirect evidence of alternate collateral blood flow opposing measured collateral blood flow; this finding could explain some of the small reactive hyperemias observed after the release of a temporary occlusion of a distal branch. In summary, phasic collateral blood flow patterns in distal epicardial branches that developed rapidly in response to occlusion of the central circumflex branch and in conjunction with a rise in peripheral coronary pressure were demonstrated, and reversal from antegrade to retrograde collateral blood flow was documented.
Influence of Right Ventricular Filling Pressure on Left Ventricular Pressure and Dimension
Authors: BEMIS CHARLES E. , SERUR JUAN R. , BORKENHAGEN DAVID , SONNENBLICK EDMUND H. , URSCHEL CHARLES W.
Published: June 2012

The effects of alterations in the diastolic filling pressure of the right ventricle on left ventricular (LV) geometry and filling pressure were studied in six isolated, supported canine hearts. This experimental preparation permitted graded increments in right ventricular (RV) end-diastolic pressure while LV cardiac output, heart rate, and mean aortic pressure were held constant. Endocardial radiopaque markers were placed in the ventricular septum, the anterior wall, the posterior wall, and the free wall in a plane perpendicular to the aortoapical axis. LV end-diastolic dimensions were recorded by x-ray cinematography at 60 frames/sec. The effects of varied RV end-diastolic pressure (0-16 mm Hg) on LV end-diastolic pressure and dimensions were studied at several LV cardiac outputs (780-2880 ml/min) and at several initial LV end-diastolic pressures (1-18 mm Hg). Increments of 5 mm Hg in RV end-diastolic pressure increased LV end-diastolic pressure 2.3 mm Hg. The septum-to-free wall distance decreased by 4.5% from the control distance, but the anterior-to-posterior dimension increased by 4.4%.Thus, LV end-diastolic pressure and LV end-diastolic dimensions were significantly related to RV end-diastolic pressure; LV end-diastolic geometry was increasingly distorted at elevated RV end-diastolic pressure. These data suggest that the high RV filling pressures that characterize certain diseases can secondarily alter LV filling pressures and geometry.
Inability of Potassium Canrenoate to Convert Experimentally Induced Ouabain Arrhythmias in the Canine Heart
Authors: NIELSEN CARL J. , LUCCHESI BENEDICT R.
Published: June 2012

The antiarrhythmic effects of potassium canrenoate were examined in 20 closed-chest, pentobarbital-anesthetized dogs with ouabain-induced ventricular tachycardia. In a group of 8 dogs, a mean dose of ouabain of 64.4 ± 3.7 µg/kg induced sustained ventricular tachycardia. Subsequent administration of potassium canrenoate (30 mg/kg, iv) caused ventricular fibrillation in 1 dog and sinus tachycardia in 3 dogs. Stimulation of the distal end of the cut right vagus in the latter 3 dogs slowed the sinus rhythm enough to permit the ventricular focus to become the dominant pacemaker. In the other 4 dogs, potassium canrenoate did not alter the ouabain-induced ventricular tachycardia. In a second group of 12 dogs, ventricular tachycardia was also induced by administering a toxic dose of ouabain (65.5 ± 2.9 µg/kg, iv). After ouabain intoxication, atrial overdrive suppression of the ventricular rhythm was initiated by electrically pacing the right atrium at a mean frequency of 184.5 ± 7.9 beats/min. Subsequent administration of potassium canrenoate (30 mg/kg, iv) to these dogs restored sinus rhythm in 4 of the dogs; however, stimulation of the distal end of the cut right vagus caused a reappearance of the ventricular ectopic focus. After potassium canrenoate administration, the minimum atrial pacing rate required to capture the ventricular rhythm was 160.9 ± 9.4 beats/min. This rate represents a significant reduction (
P
< 0.005) in the rate of the ouabain-induced ventricular ectopic focus, but in no instance was the focus directly suppressed by potassium canrenoate. Propranolol, in contrast to potassium canrenoate, restored normal sinus rhythm in all 20 ouabain-intoxicated dogs and suppressed the ouabain-induced ectopic pacemaker during the period of vagally induced sinoatrial arrest. The results of this study show that potassium canrenoate fails to exert an antiarrhythmic effect against digitalis-induced arrhythmias and that any apparent restoration of sinus rhythm in response to potassium canrenoate is due to overdrive suppression of the ouabain-induced ventricular ectopic pacemaker.
Pulmonary Arterial Blood Volume and Tissue Volume in Man and Dog
Authors: SACKNER MARVIN A. , ATKINS NEAL , GOLDBERG JOSEPH , SEGEL NATHAN , ZARZECKI STEPHEN , WANNER ADAM
Published: June 2012

After the injection of an ethyl ether-alcohol solution above the pulmonic valve, the pulmonary arterial circulation time was determined in conscious man by an established body plethysmographic technique and in anesthetized man by a newly developed pneumotachographic method. In the anesthetized dog, estimates of pulmonary arterial circulation time determined by this new method were compared with those simultaneously determined by the plethysmographic method; agreement was good. The usefulness of applying corrective factors for the right-to-left intrapulmonary shunt and the uptake of ether gas from the alveoli into the blood while the ether gas is being evolved from the initial injection was evaluated from the dog experiments. In five humans with normal pulmonary arterial pressures, pulmonary arterial blood volume estimated by these methods was 172 ± 22 (sd) ml. Estimates of pulmonary tissue volume in both dogs and man were much larger than previously reported values determined from the tritiated water space of the lungs but more in keeping with previously published estimates of the total water content of the lungs determined at postmortem examination.
Interaction of Epinephrine and Ouabain on Automaticity of Canine Purkinje Fibers
Authors: TSE WARREN W. , HAN JAOK
Published: June 2012

The interaction of ouabain and epinephrine on diastolic depolarization of canine Purkinje fibers was studied using conventional microelectrode techniques. When the Purkinje fibers were treated with ouabain alone, they developed slow diastolic depolarization accompanied by a proportionate decrease in the maximum diastolic potential. When these digitalized Purkinje fibers were further treated with epinephrine, the rate of these changes was greatly accelerated, resulting in rapid spontaneous activity in some Purkinje fibers. The rate of development of increased automaticity observed in the preparations treated with both ouabain and epinephrine was two to three times faster than that observed in the preparations exposed to ouabain alone. Epinephrine alone at the same concentration caused minimal changes in diastolic depolarization of these preparations. Propranolol in a beta-receptor blocking dose prevented the potentiating effect of epinephrine but did not interfere with the effect of ouabain on diastolic depolarization of Purkinje fibers. It is concluded that epinephrine potentiates the ouabain-induced increase in automaticity of Purkinje fibers by stimulating beta receptors.
Cardiac Myosin Adenosinetriphosphatase of Rat and Mouse
Authors: YAZAKI YOSHIO , RABEN MAURICE S.
Published: June 2012

Cardiac myosin obtained from rats and mice (smaller animals) had a higher adenosinetriphosphatase (ATPase) activity in the presence of calcium ions (Ca
2+
) than did cardiac myosin from rabbits and dogs (larger animals). Structural differences between the two types of cardiac myosin were suggested by the lower apparent activation energy of the Ca
2+
activated ATPase reaction catalyzed by cardiac myosin from the smaller animals and by the lower rate of inactivation of ATPase at pH 9.0. No evidence for activators of myosin ATPase was found in heart muscle or cardiac myosin from rats and mice. The cardiac myosin from these animals was also distinctive with respect to the pattern of activation and inhibition of ATPase by salts and sulfhydryl reagents. ATPase activity of cardiac myosin from the smaller animals was less sensitive to the inhibitory effect of KCl in the presence of Ca
2+
and was not activated by
N
-ethylmaleimide, suggesting a difference in the myosin molecule at or near the active site. When sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed, no difference was observed in the molecular weight or the proportion of the light chains between the two types of cardiac myosin. ATPase activity of skeletal myosin was approximately the same in all animals and showed a pattern similar to that of the cardiac myosins from rabbits and dogs. The structural difference in the cardiac myosin from rats and mice suggested by these experiments appears to account for the enhanced myocardial contractility found in these animals.
Relationship of the Functional Refractory Period to Conduction in the Atrioventricular Node
Authors: FERRIER GREGORY R. , DRESEL PETER E.
Published: June 2012

The functional refractory period of atrioventricular (AV) transmission has been accepted as a measure of AV nodal refractoriness and has been assumed to be determined solely by conduction of interpolated extrasystoles through the AV node when it is partially refractory. In the present study, we found an important effect of the conduction time of the regular beats by measuring AV nodal conduction times of atrial extrasystoles from the His bundle of isolated, blood-perfused dog hearts. We separated three independent components that determine AV nodal conductivity: (1) a "basal conduction time" measured with a "postmature" extrasystole at low heart rates (<120 /min), (2) a rate-dependent increment in conduction time (previously called "fatigue") that affects both normal and premature cycles equally and (3) an exponential change in conduction time that depends entirely on the immediately preceding interval and, therefore, is not further affected by heart rate. The functional refractory period is one point defining this continuous exponential function. We showed that an important cause of the decrease in the functional refractory period that occurs when heart rate is increased is the change in the conduction time of the regular beats.
A Protein-Bound Form of Porcine Renal Renin
Authors: BOYD GRAHAM W.
Published: June 2012

Two interconvertible renins were isolated from extracts of the pig renal cortex at neutral pH and shown to be protein-bound (renin B, molecular weight 60,000) and free (renin A, molecular weight 40,000) forms of renin. The protein-bound form (renin B) gave a much more prolonged pressor response than did the free form (renin A) on direct bioassay in the rat; it could be converted to renin A by the action of various salts or by acidification below pH 3. The renin-binding protein associated with renin B was isolated by DEAE-cellulose column chromatography under special conditions of elution and appeared to be specific for renin. When pig kidneys were perfused in situ with Krebs-Ringer's solution, isoproterenol stimulation (1-8 µg/min) resulted in release of renin in the protein-bound form. It is suggested that renin-binding protein may act as a carrier for the transport of renin to local tissue sites of uptake under some circumstances and thus alter the mode of expression of the renin-angiotensin system in vivo to one of local angiotensin generation and effect.
A Dissociation of Positive Staircase (Bowditch) from Ouabain-Induced Positive Inotropism
Authors: McCANS JOHN L. , LINDENMAYER GEORGE E. , MUNSON RONALD G. , EVANS RANDOLPH W. , SCHWARTZ ARNOLD
Published: June 2012

The effects of verapamil on myocardial contractility were examined in perfused rabbit ventricular preparations. Verapamil (0.2 µ
M
) decreased the time derivative of developed force (dF/dt) of the preparations paced at 90 beats/min to 39 ± 3% (
SE
) of the control value. Partial reversal to 76 ± 5% of the control value was achieved by subsequent perfusion with drug-free Krebs solution. Verapamil hastened the decline and delayed the return of contractility in response to a cycle of calcium washout and reperfusion. It converted the response to increased heart rate from positive (Bowditch effect) to negative inotropism. Moreover, the sensitivity to the drug was frequency related; the drug concentration required to induce a 50% decrease in dF/dt was an inverse function of heart rate, suggesting that the drug altered contractility by interfering with a phenomenon associated with systole. Verapamil did not decrease the magnitude of the positive inotropic response to 0.5 µ
M
ouabain, although a significant delay in the development of the response was observed. After 8 minutes of ouabain perfusion dF/dt had increased 35 ± 2% in the absence of verapamil but only 13 ± 1% in the presence of 1.0, µ
M
verapamil. The maximum response to ouabain was a 39 ± 4% increase at 9 minutes in the absence of verapamil and a 34 ± 2% increase at 23 minutes in the presence of verapamil. These results suggest that the responses to increased frequency and to cardiac glycosides are not explained by a common mechanism such as sodium-calcium exchange occurring during diastole or any other diastole-related mechanism for calcium influx. However, the possibility that both events are mediated by some common mechanism occurring during systole has not been eliminated.
Acute Effects of Alpha-Methyldopa on Mean Blood Pressure and Plasma Renin Activity
Authors: HALUSHKA PERRY V. , KEISER HARRY R.
Published: June 2012

α-Methyldopa significantly lowered mean blood pressure and plasma renin activity in dogs anesthetized with sodium pentobarbital. After unilateral ligation of the right renal vessels and contralateral denervation of the kidney, α-methyldopa significantly lowered mean blood pressure but did not change plasma renin activity. It was concluded that α-methyldopa acutely lowers plasma renin activity via an action mediated through the adrenergic nervous system. However, this decrease in plasma renin activity is not responsible for the decrease in mean blood pressure produced by the drug.
Dispersion of Indicator Measured from Microvessels of Cat Mesentery
Authors: NELLIS STEPHEN H. , LEE JEN-SHIH
Published: June 2012

The indicator-dilution method was used to investigate blood flow in the microvascular network of the mesenteric membrane of the cat by replacing the normal blood flow into the mesenteric artery with a dextran-saline solution for a finite period of time. The dilution of the dextran-saline bolus as it flowed downstream was measured in a selected arteriole and its adjacent venule with a microphotometric system. Based on an in vitro calibration study done on glass capillary tubes, the measured optical density was converted to the hematocrit. The dilution curve for a finite injection and for a step injection, the mean transit time (MTT), and the appearance time for the arteriole and the venule were computed. The dispersion found in the arterial system, a network of diverging branches, was reasonably well simulated by the dispersion in a parabolic flow system. However, the dispersion found in the venules, where the irregular capillary blood flow converges, was considerably skewed from that in a parabolic system. A wide distribution of MTT was found for the arterioles and the venules, and there was considerable overlap in the MTT distribution for these two groups. This finding cannot be simulated by a network with a parallel arrangement. The difference in MTT for pairs of arterioles and venules was distributed over a narrow range, probably indicating shunt flow in the mesenteric microvascular network.
The Renin-Angiotensin System and Aldosterone Secretion during Sodium Depletion in the Rat
Authors: SPIELMAN WILLIAM S. , DAVIS JAMES O.
Published: June 2012

The role of the renin-angiotensin system in the control of aldosterone secretion was studied in the sodium-depleted rat. Administration of angiotensin II produced a significant increase in aldosterone secretion and arterial blood pressure in normal rats; simultaneous infusion of the angiotensin analogue. 1-sarcosine-8-alanine-angiotensin II, blocked both the pressor and the steroidogenic actions of angiotensin. Since the angiotensin II analogue was effective in blocking exogenous angiotensin II, an attempt was made to block endogenously formed angiotensin II in the sodium-depleted rat; infusions of large doses of the analogue produced a significant fall in arterial blood pressure, but aldosterone secretion failed to change. Bilateral nephrectomy also failed to decrease aldosterone secretion in the sodium-depleted rat even though arterial blood pressure fell. Since the secretion of corticosterone in these rats was high, it seemed likely that the failure of aldosterone secretion to fall resulted from an overriding influence of adrenocorticotropic hormone (ACTH). To test this hypothesis, the renin-angiotensin system was again blocked in sodium-depleted rats with three levels of anterior pituitary function. With high or intermediate rates of corticosterone secretion, a nonapeptide converting enzyme inhibitor (CEI) failed to influence aldosterone secretion. However, when the influence of ACTH was completely eliminated by hypophysectomy in sodium-depleted rats, the nonapeptide CEI produced a striking fall in aldosterone secretion. In contrast, arterial blood pressure was significantly reduced by CEI in rats with all three levels of anterior pituitary function. The data suggest a role for angiotensin II in the regulation of aldosterone secretion and the maintenance of arterial blood pressure in the sodium-depleted rat.
Central and Reflex Regulation of Sympathetic Vasoconstrictor Activity to Limb Muscles during Desynchronized Sleep in the Cat
Authors: BACCELLI GIORGIO , ALBERTINI RENATO , MANCIA GIUSEPPE , ZANCHETTI ALBERTO
Published: June 2012

Desynchronized sleep (DS) in the cat is accompanied by a long-lasting (tonic) constriction of muscle blood vessels (conductance decrease 5-30%), on which are superimposed short-lasting (phasic) vasoconstrictor waves that occur simultaneously with bursts of rapid eye movements and body twitches. Both the tonic and the phasic vasoconstrictions are abolished after regional sympathectomy (conductance increase 5-10%). Tonic vasoconstriction can also be prevented by hind-limb deafferentation (bilateral section of the dorsal roots from L5 down) or by transection of the spinal cord at L4 in such a way as to separate sympathetic innervation from afferent input from the hind limbs. These procedures do not affect the phasic vasoconstrictions. After lumbar sympathectomy or hind-limb deafferentation, iliac blood flow decreases during the tonic fall in blood pressure associated with DS by exactly the amount (1-2 ml/min) predicted by pressure flow relationships observed during artificial lowering of iliac blood pressure. We conclude that tonic and phasic vasoconstrictions are both due to sympathetic discharges. However, phasic sympathetic discharges are driven by central descending influences, and tonic sympathetic vasoconstriction depends on reflex influences originating from the limbs themselves. When tonic sympathetic vasoconstriction is prevented, muscle blood vessels exhibit autoregulatory behavior during DS.
Contribution of Recirculation and Fat Diffusion to Myocardial Washout Curves Obtained by External Counting in Man
Authors: MASERI ATTILIO , PESOLA ANTONIO , L'ABBATE ANTONIO , CONTINI CARLO , MICHELASSI CLAUDIO , D'ANGELO TOMMASO
Published: June 2012

133
Xenon and
125
I-iodoantipyrine (IAP) solutions were simultaneously injected into the left coronary artery in four normal patients and four patients with coronary artery obstructions. Recirculation was computed by convolution of the fractional decrease of the curve following inlet injection over a second curve obtained following right atrial injection. Uncorrected xenon and IAP curves were not statistically different in spite of the lower myocardium-blood partition coefficient and the recirculation of xenon. Corrected IAP curves could be followed down to 1.7%, whereas xenon curves could be followed only to 7.5%, indicating significant xenon diffusion holdup in fat. Corrected IAP curves deviated from a monoexponential course below 5% of peak in normal patients and at about 10% in patients with coronary artery obstructions. Stochastic analysis gave flow values 22% lower and 45% higher, respectively, than those computed from monoexponential extrapolation of corrected IAP and uncorrected xenon curves. With the double-injection technique, IAP washout can be calculated down to about 1% of peak, accounting for the distribution of 99% of the flow through the tissue to which the indicator is delivered. Monoexponential analysis of corrected IAP curves overestimates flow, because it cannot fit the initial delay component and the final reduction of slope. Xenon washout does not allow quantification of myocardial flow in man.
Relationship between Serum Dopamine-β-Hydroxylase Activity, Catecholamine Metabolism, and Hemodynamic Changes during Paroxysmal Hypertension in Quadriplegia
Authors: NAFTCHI N. ERIC , WOOTEN G. FREDERICK , LOWMAN EDWARD W. , AXELROD JULIUS
Published: June 2012

During the chronic phase of spinal cord injury, serum dopamine-β-hydroxylase activity, arterial blood pressure, and blood flow in the fourth finger, the hallux, and the calf were measured in nine quadriplegic subjects before, during, and after expansion of the urinary bladder. In addition, in five chronic quadriplegic subjects, serum dopamine-β-hydroxylase activity, urinary catecholamine metabolites, and arterial blood pressure were measured before and during spontaneous hypertensive episodes. There was a significant correlation between the different stages of hypertension, the serum dopamine-β-hydroxylase activity, and the concentration of urinary catecholamine metabolites. The highest levels were found at the height of intracystic pressure when the arterial blood pressure was at its maximum but the pulse rate had dropped to its lowest level. At the same time the blood flow in the upper and lower extremities and the calf musculature was below detection limits, and peripheral vascular resistance was markedly enhanced. Serum dopamine-β-hydroxylase and arterial blood pressure levels correlated directly with urinary concentrations of normetanephrine but not with those of metanephrine. The data provide evidence for an in vivo simultaneous, proportional release of dopamine-β-hydroxylase and norepinephrine, suggesting release by exocytosis. The data further show that dopamine can also be released together with norepinephrine and dopamine-β-hydroxylase as evidenced by increased urinary concentrations of its major catabolite, homovanillic acid, during hypertensive stress. The hypertensive response in quadriplegic subjects during routine test of bladder function renders these subjects ideal models for self-controlled studies of neurogenic hypertension and its biochemical parameters. The results indicate that hypertension in quadriplegia, whether spontaneous or induced, is caused by increased release of norepinephrine and that the half-life of dopamine-β-hydroxylase released during stress is shorter than that previously reported.
Dobutamine: development of a new catecholamine to selectively increase cardiac contractility.
Authors: Tuttle R R , Mills J
Published: June 2012

We systematically modified isoproterenol's chemical structure to reduce chronotropic, arrhythmogenic, and vascular side effects. Experiments on dogs showed that the resulting drug, dobutamine, had an inotropic efficacy as great as that of epinephrine due to a direct action on beta1 cardiac receptors. However, unlike epinephrine, dobutamine's effect on alpha and beta2 vascular receptors was slight. At equivalent inotropic doses, dobutamine had less than a fourth of the chronotropic effect of isoproterenol. Desmethylimipramine (DMI), which blocks the sympathetic nerve fiber uptake mechanism, had no effect on dobutamine's actions. In contrast, DMI antagonized dopamine's inotropic effect, and marked chronotropic and pressor responses occurred when we used doses of dopamine large enough to elicit a direct inotropic effect. Dobutamine increased the contractility of isolated cat papillary muscles more but the automaticity less than did isoproterenol. In ischemic dog hearts, dobutamine lacked significant arrhythmic activity, whereas dopamine, norepinephrine, and isoproterenol caused severe ectopic activity. In dogs with experimentally induced low cardiac contractility, low cardiac output, and hypotension, dobutamine produced dose-related increases in cardiac contractility and output, restored arterial blood pressure, and reduced total peripheral resistance slightly. In contrast, isoproterenol failed to restore blood pressure, had only a meager effect on cardiac contractility and output, cuased extreme tachycardia, and lowered peripheral resistance more than did dobutamine. Norepinephrine, which did not increase cardiac contractility or output as much as dobutamine, excessively elevated peripheral resistance and arterial blood pressure.
Renal intracortical blood flow distribution, function, and sodium excretion in unanesthetized dogs following vena caval ligation.
Authors: Gutman R A , McRae R L
Published: June 2012

We studied the renal function and the intrarenal blood flow of nine dogs whose thoracic inferior vena cava had been previously ligated (caval dogs) and nine other dogs. Following preparative surgery which included placement of a left atrial catheter, a femoral artery catheter, and bilateral ureteral catheters, the caval dogs gained an average of 2.1 kg of fluid weight, whereas the normal dogs gained no weight. Although neither the caval dogs' blood pressure (114 plus or minus 7 vs 120 plus or minus 4 mm Hg) nor their inulin clearance (0.64 plus or minus 0.06 vs. 0.79 plus or minus 0.06 ml/min g-1 kidney weight) was significantly reduced, their estimated renal blood flow (Cpah/[1-hematocrit]) was considerably lower (2.30 plus or minus 0.24 vs. 3.25 plus or minus 0.15 ml/min g-1). During the clearance study, the caval dogs' excretion of sodium (79 plus or minus 18 vs. 158 plus or minus 17 muEq/min) and their fractional clearance of sodium (2.0 plus or minus 0.4 vs. 3.4 plus or minus 0.5%) were reduced. Studies with microspheres failed to demonstrate a selective decrease in blood flow. However, comparison studies of nine other dogs (five caval and four normal) demonstrated that microsphere results were less reproducible in caval dogs than they were in normal dogs. We have concluded taht reduced blood flow is the only consistent alteration of renal function in this edematous animal model and that previous suggestions of altered distribution are not supported by these studies.
Control of cardiac sarcolemmal adenylate cyclase and sodium, potassium-activated adenosinetriphosphatase activities.
Authors: Tada M , Kirchberger M A , Iorio J M , Katz A M
Published: June 2012

A plasma membrane preparation purified from guinea pig ventricles without the use of high concentrations of detergents or structure-disrupting salts was used to compare the mechanisms of controlling sodium, potassium-activated adenosinetriphosphatase (Na, K-ATPase) and adenylate cyclase activities. The basal ATPase activity of 4-6 mu moles P1/hour mg-1 protein, measured in 120 mM NaC1 or KC1, was approximately doubled in 100 mM NaC1 plus 20 mM KC1. This increment, the Na, K-ATPase, was abolished by 10-5M ouabain, the K1 for ouabain being approximately 3 X 10-7M. 1-Epinephrine had no effect on Na, K-ATPase, but NaF was inhibitory. Adenylate cyclase, which had a basal activity of approximately 50% by NaC1 or KC1 alone at concentrations up to 0.2M. There was no additional stimulation of adenylate cyclase activity when na+ K+ included together. Both 1-epinephrine and NaF cause significant stimulation of adenylate cyclase, but neither basal nor activated cyclic AMP PRODUCTION WAS INFLUENCED BY OUABAIN. Half-maximal stimulation was seen at approximately 5 X 10-6M 1-epinephrine. Both the catecholamine and NaF increased the V-max ofcardiac plasma membrane adenylate cyclase without significantly influencing Km. Increasing Ca2+ in the range between 10-7 and 10-3M inhibited basal, 1-epinephrine-stimulated, and NaF-stimulated activities. Basal rates of cyclic AMP production were more sensitive to Ca2+ than was 1-epinephrine stimulation was increased from approximately 60% in 0.5 mM EGTA to approximately 150% in 10-7M Ca2+ and 400% in 10-5M Ca2+. The inhibitory effect of Ca2+ on adenylate cyclase activity may represent a negative feed back mechanism by which elevation of intracellular Ca2+ concentration lowers cellular levels of cyclic AMP and thus reduces Ca2+ influx into the myocardium.
Dissociations between changes in myocardial cyclic adenosine monophosphate and contractility.
Authors: Henry P D , Dobson J G , Sobel B E
Published: June 2012

The relationship between changes in the myocardial concentration of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and cardiac contractility was studied in guinea pig and rat myocardium. When isolated perfused guinea pig heart were perfused with 10-5-M papaverine, a potent inhibitor of cyclic AMP phosphodiesterase activity, myocardial cyclic AMP concentration increased significantly from 1.7 plus and minus 0.2 (SE) pmoles/mg protein (N equal 12) to 3.3 plus and minus 0.2 pmoles/mg protein (N equal 12), and the percent of phosphorylase aual 6) (P less than 0.01). However, perfusion with papaverine had no effect on contractility in the absence or the presence of exogenous epinephrine. In perfused rat hearts, 10-5 M glucagon increased myocardial cyclic AMP concentration from 1.5 plus and minus 0.1 pmoles/mg protein (N equal 12) to 2.6 plus and minus 0.1 pmoles/mg protein (N equal 12) (P less than 0.001). In contrast, cyclic AMP levels did not increase detectably in guinea pig heart perfused with glucagon. Glucagon increased adenylate cyclase activity more than twofold in rat myocardial broken cell preparations but failed to stimulate the enzyme in preparations from guinea pigs. Despite these differences, the positive inotropic effects of glucagon on rat and guinea pig hearts were very similar over a wide dose range. Thus, with both papaverine and glucagon, changes in cardiac contractility were dissociated from stimulation of adenylate cyclase activity, increases in myocardial cyclic AMP levels, and conversion of phosphorylase b to phosphorylase a in perfused hearts.
A one-dimensional viscoelastic model of cat heart muscle studied by small length perturbations during isometric contraction.
Authors: Loeffler L , Sagawa K
Published: June 2012

To develop a model of heart muscle, we studied cat papillary muscle contracting in a quasi-isometric condition under a fixed inotropic state. The properties of resting muscle were determined by using a step stretch of less than 1.2% of Lmax for initial lengths from 85 to 100% Lmax. The passive force response suggested the model of the passive branch (Fig. 1). All five parameters were small at muscle lengths below 95% of Lmax but increased markedly at longer lengths. The properties of contracting muscle were studied with a sinusoidal length change (amplitude less than 0.15% of Lmax, frequency 0.1-35.0 Hz). The frequency response of active (total minus passive) stiffness suggested the model of the active branch (Fig. 1). We determined the dependency of the elastic elements (K, Ks) and the viscous element (C) on length and time by recording the frequency response at various combinations of length and time Ks varied linearly with active force (FA). K and C exhibited time courses that paralleled FA up to 0.6tmax, and they maintained their values until 1.4tmax. K then fell toward zero, whereas C exhibited a secondary rise before it fell toward zero. K was dependent of length up to 95% of Lmax and then began to decline, but C varied in proportion to muscle length.
In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts.
Authors: Roskoski R , Schmid P G , Mayer H E , Abboud F M
Published: June 2012

Choline acetyltransferase activity, which is rate limiting in acetylcholine biosynthesis, was measured in the four heart chambers of guinea pigs subjected to (1) sham surgery, (2) constriction of the ascending aorta, (3) constriction of the descending thoracic aorta, and (4) constriction of the pulmonary artery. After 30 days when hypertrophy and heart failure were fully established, choline acetyltransferase was quantified in vitro by a radiochemical assay. In the sham-operated group, enzyme activity expressed in terms of unit weight of cardiac tissue was greatest in the right atrium and the right ventricle and lower in th left atrium and the left ventricle (3.62 plus or minus 0.30, 2.96 plus or minus 0.52, 1.64 plus or minus 0.15, and 1.67 plus or minus 0.22 nmoles/min g-1, respectively). Enzyme activity was reduced (P less than 0.05) in the right atria and the right ventricles of guinea pigs with constriction of the pulmonary artery (1.68 plus or minus 0.37 and 1.31 plus or minus 0.29 nmoles/min g-1, respectively). Enzyme activity also tended to be reduced in the left atria and the left ventricles of guinea pigs with constriction of the aorta. These changes represented a relative dilution of enzyme activity per unit weight but not an absolute depletion, since choline acetyltransferase activity per ventricle was not reduced. The absence of significant changes in the total amount of the neuronal enzyme, choline acetyltransferase, per ventricle contrasted with the observed increases in the myocardial enzyme, carnitine acetyltransferase. These results confirm the presence of significant parasympathetic innervation of the ventricles as well as the atria but do not demonstrate alterations in parasympathetic neurotransmitter biosynthesis in hypertrphied and failing myocardium. The absence of absolute reductions in choline acetyltransferase activity in hypertrophied and failing ventricle contrasts strikingly with the previously reported reductions in tyrosine hydroxylase, which is rate limiting in sympathetic neurotransmitter biosynthesis.
Role of the collecting duct in the regulation of sodium balance.
Authors: Stein J H , Kirschenbaum M A , Bay W H , Osgood R W , Ferris T F
Published: June 2012

A large body of evidence has accumulated which demonstrates that sodium transport in some distal nephron segment is altered in response to changes in extracellular fluid volume. Sodium reabsorption in the loop of Henle and distal tubule is directly related to delivery rate and is not inhibited by volume expansion. In contrast, recent studies have shown that Ringer loading causes a greater natriuretic response than hyperoncotic albumin because of diminished collecting duct sodium transport in the former model. Additional studies in animals with different basal extracellular fluid volumes and in DOCA-escape rats indicate further that the collecting duct is an important regulator of sodium balance. Although the factors that modulate sodium transport in the collecting duct are not clear, it is postulated that the local release of prostaglandins may be of major importance.
Malignant hypertension due to musculo-mucoid intimal hyperplasia of intrarenal arteries. Absence of renal fibrinoid necrosis.
Authors: Pitcock J A , Johnson J G , Share L , Hatch F E , Acchiardo S R , Black W D , Muirhead E E
Published: June 2012

Severe essential hypertension in a subset of American black subjects is associated with marked stenosis of interlobular arteries and arterioles of the kidneys, observed by renal biopsy and binephrectomy specimens. The interlobular arterial stenosis is caused by marked thickening of the intima due mainly to the presence of smooth muscle cells, basement membrane material, and acid mucopolysaccharide. Because of this makeup, we propose the term "musculo-mucoid intimal hyperplasia" for this lesion. The media of these arteries appears maximally dilated, and by electron microscope displays degenerative changes of the smooth muscle cells. The arterioles are thickened, due mainly to hyalinization, but also due to the musculo-mucoid change (onionskin effect). The smooth muscle cells are degenerated and atrophic. These patients do not exhibit fibrinoid necrosis of the arteries, arterioles, and glomeruli, presumably because of the rapidity of the development of the arterial stenotic lesion. Accordingly, the glomeruli are destroyed by ischemia, and there is no evidence of glomerulitis (no "Kombinations" form of Fahr). A unifying hypothesis concerning renal hypertensive arterial disease is suggested by these studies. This hypothesis places the main emphasis for all the morphological expressions of the intrinsic visceral vasculature on changes involving the main functional unit of the vessel wall, the medical smooth muscle.