bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Left Ventricular Preload and Afterload by Quantitative Echocardiography in Man
Authors: RATSHIN ROBERT A. , RACKLEY CHARLES E. , RUSSELL RICHARD O.
Published: June 2012

Left ventricular circumferential wall stress at end-diastole (preload) and at the end of isovolumic left ventricular contraction (afterload) was calculated in 48 subjects with chronic myocardial and valvular heart disease by using left ventricular internal dimensions and wall thickness measured by quantitative echocardiography, left ventricular end-diastolic pressure, and aortic end-diastolic pressure. These calculations were then compared with similar determinations made using quantitative angiocardiography. Left ventricular preload and afterload determined by quantitative echocardiography and quantitative angiocardiography correlated significantly (
r
= 0.978 and 0.864, respectively). Left ventricular preloads of 30 x 10
3
dynes/cm
2
in subjects with mitral stenosis and 39 x 10
3
dynes/cm
2
in subjects with coronary artery disease unassociated with left ventricular dysfunction or mitral regurgitation were close to or within the normal range (32 x 10
3
± 4 x 10
3
dynes/cm
2
). Left ventricular preload in subjects with compensated volume overload was comparable with the angiocardio-graphically calculated values of 63 x 10
3
, 57 x 10
3
, and 53 x 10
3
dynes/cm
2
in subjects with coronary artery disease plus mitral regurgitation, mitral regurgitation, and aortic regurgitation, respectively. Left ventricular preload was most elevated in subjects with coronary artery disease associated with segmental left ventricular dyskinesis or akinesis. No significant differences in left ventricular afterload were noted between subject groups, although those with hypertrophic cardiac disease had the lowest calculated values. Quantitative echocardiography is an accurate technique for measuring left ventricular circumferential wall stress (preload and afterload) when left ventricular end-diastolic pressure and aortic end-diastolic pressure can be obtained.
Experimental Production of Rate-Dependent Bundle Branch Block in the Canine Heart
Authors: ELIZARI MARCELO V. , NAU GERARDO J. , LEVI RAÚL J. , LÁZZARI JULIO O. , HALPERN M. SUSANA , ROSENBAUM MAURICIO B.
Published: June 2012

The main ventricular conducting fascicles were slightly injured in anesthetized dogs by gently scratching them with a blunt needle introduced through the ventricular wall. Initially the bundle branch block that resulted was rate independent (stage 1). When conduction returned to normal, both premature atrial and vagal stimulation reproduced the bundle branch block (stage 2). During stage 2 (5-15 minutes), three conduction ranges were documented: an early (phase 3) block range, a late (phase 4) block range, and an intermediate normal conduction range. The normal conduction range was narrow at the beginning but widened progressively, mostly at the expense of the phase 4 block range. Another period during which only phase 4 bundle branch block occurred (stage 3) preceded total normalization (stage 4). The escape beats that arose from the injured fascicle were most abundant and had the shortest coupling during stage 1, they were less common and their coupling became longer during stages 2 and 3, and they disappeared in stage 4. The tachycardia-dependent or phase 3 bundle branch block was related to a prolongation of refractoriness; the bradycardia-dependent or phase 4 bundle branch block was attributed to slight hypopolarization, enhanced spontaneous diastolic depolarization, and a shift in the threshold potential toward zero. These abnormalities were assumed to be secondary to the hypopolarization, which was probably the basic derangement. This hypothesis satisfactorily accounts for the observation that phase 3 and phase 4 bundle branch block commonly coexist in the same injured fascicle.
Copper Content and Exchange in Mammalian Hearts
Authors: PAGE ERNEST , EARLEY JUDY , McCALLISTER LAWRENCE P. , BOYD CHANTAL
Published: June 2012

Determination of the copper (Cu) content of rat, rabbit, and mouse hearts proved to be a sensitive microassay for mitochondrial content and membrane area of mitochondrial cristae per unit myocardial cell volume. The direction of variations in Cu content correlated well with variations in membrane area of mitochondrial cristae determined by morphometry of electron micrographs during normal postnatal growth, ventricular hypertrophy after aortic constriction, and thyroxin-stimulated myocardial cell growth. Right and left ventricular and interventricular septal Cu contents per unit dry weight were the same, did not vary during postnatal growth, and significantly exceeded atrial Cu content. Among different mammalian species, ventricular Cu content per unit dry weight tended to vary inversely with adult animal size and thus with adult resting heart rate. The existence of mechanisms for transport of
67
Cu across the myocardial cell plasma membrane and for incorporation of
67
Cu into mitochondrial cristae from an intracellular precursor pool was demonstrated by injecting
67
Cu-labeled blood serum into rats.
Altered Myocardial Function and Metabolism in Chronic Diabetes Mellitus without Ischemia in Dogs
Authors: REGAN TIMOTHY J. , ETTINGER PHILIP O. , KHAN MOHAMMAD I. , JESRANI MOHAN U. , LYONS MICHAEL M. , OLDEWURTEL HENRY A. , WEBER MARILYN
Published: June 2012

Myocardial disease in diabetes mellitus is usually attributed to coronary atherosclerosis. To examine the influence of uncomplicated diabetes on the left ventricle, a mild noninsulin-requiring diabetes was produced in male mongrel dogs after three intravenous doses of alloxan were administered at monthly intervals. There was a persistent decline in glucose tolerance and a reduced insulin content in the pancreas of each alloxan-diabetic dog at the termination of the experiment. The dogs were anesthetized for hemodynamic and metabolic studies after approximately 11 months. Left ventricular end-diastolic volume and cardiac output were measured by the indicator-dilution method. An increase in afterload with moderate aortic pressure elevations elicited a significant rise in end-diastolic volume and stroke volume in normal control dogs. In diabetes, despite a similar end-diastolic pressure response, the end-diastolic volume and the stroke volume responses were significantly less than those in control dogs. During acute volume expansion of the ventricle with saline, the end-diastolic pressure increment in diabetic dogs was twice that in control dogs. These responses were attributed to an increased stiffness of the left ventricle that was apparently due to accumulation of glycoprotein (measured by periodic acid-Schiff staining) in the interstitium. Since similar abnormalities were observed in dogs with diabetes occurring spontaneously and were absent when the pancreatic effects of alloxan were inhibited in a separate group of dogs, the pathogenetic role of alloxan via a direct action on myocardium was excluded. Analysis of lipids in the left ventricle revealed elevated triglyceride and cholesterol concentrations despite normal plasma levels. During infusion of
14
C-1-oleic acid, cardiac oxidation appeared to be normal, but fatty acid incorporation, which was predominantly into phospholipid in the control dogs, was diverted to triglyceride in the diabetic dogs. Since an aberration of de novo synthesis was not found during studies with
14
C-acetate, triglyceride accumulation was attributed to altered intracellular metabolism, perhaps related to glycerol phosphate acyl transferase activity. The basis for cholesterol accumulation was less clear, since neither
14
C-acetate nor
14
C-oleate incorporation into sterol was enhanced. Myocardial ischemia was excluded on the basis of patency of coronary arteries and normal coronary blood flow, myocardial cation content, and mitochondrial morphology. Thus, it was concluded that chronic diabetes mellitus can alter myocardial composition and function independent of vascular effects.
Autonomic Nervous System and Benign Essential Hypertension in Man
Authors: CUCHE JEAN-LOUIS , KUCHEL OTTO , BARBEAU ANDRÉ , LANGLOIS YVES , BOUCHER ROGER , GENEST JACQUES
Published: June 2012

The clinical entity of benign essential hypertension is often subdivided into labile essential hypertension and stable essential hypertension. To establish less arbitrary limits between normotension and labile and stable benign essential hypertension, 70 subjects (56 with benign essential hypertension) were classified according to (a) the usual blood pressure index for each subject and (b) the upper limit of variation of the usual blood pressure indexes of a normotensive population. Catecholamines, plasma renin activity, and urinary creatinine, sodium, and potassium were measured in recumbent subjects who had received a controlled-sodium diet. Our findings suggest that (1) benign essential hypertension represents a heterogeneous entity and a continuous spectrum of clinical and biochemical changes when it is related to the level of blood pressure, (2) adrenergic involvement is more evident in labile hypertension, (3) regardless of the urinary excretion of catecholamines in subjects with benign essential hypertension the urinary ratio of dopamine to norepinephrine always remains lower, and (4) a negative correlation exists between urinary sodium excretion and usual blood pressure indexes.
Evidence of the Limitations of Water as a Freely Diffusible Tracer in Brain of the Rhesus Monkey
Authors: EICHLING JOHN O. , RAICHLE MARCUS E. , GRUBB ROBERT L. , TER-POGOSSIAN MICHEL M.
Published: June 2012

The extraction of
15
O-labeled water by the brain during a single capillary transit was studied in vivo in 20 adult rhesus monkeys by external detection of the time course of the tracer subsequent to the internal carotid injection of 0.2 ml of whole blood labeled with H
2
15
O. The data showed that labeled water does not freely equilibrate with the exchangeable water in the brain when the mean cerebral blood flow exceeds 30 ml/100 g min
-1
. At the normal cerebral blood flow in the rhesus monkey (∼50 ml/100 g min
-1
), only 90% of the H
2
15
O is extracted during a single capillary transit. In addition, cerebral blood flow was determined with H
2
15
O and
133
Xe in these monkeys using residue detection and employing the central volume principle. The data supported the hypothesis that a diffusible tracer, H
2
15
O, need not be in complete equilibrium between the phases of a system for the application of the central volume principle to be valid. Finally, the brain capillary permeability-surface area product was computed from these data; it was approximately 0.023 cm
3
/sec g
-1
.
Effect of Verapamil on the Sinoatrial and Atrioventricular Nodes of the Rabbit and the Mechanism by Which it Arrests Reentrant Atrioventricular Nodal Tachycardia
Authors: WIT ANDREW L. , CRANEFIELD PAUL F.
Published: June 2012

The effects of verapamil, an antiarrhythmic drug that apparently blocks slow inward currents, were studied on the isolated, superfused sinoatrial (SA) and atrioventricular (AV) nodes of the rabbit heart with intracellular microelectrodes. Verapamil decreased the rate of spontaneous impulse initiation by the SA node. This effect could be overcome with epinephrine. Concomitantly, verapamil decreased the amplitude of SA node action potentials without reducing maximum diastolic potential. The peak of the action potential fell well short of reversal after exposure to the drug. Verapamil had similar effects on the action potentials of the upper and middle AV nodal regions, reducing action potential amplitude so that the overshoot vanished without significantly reducing maximum diastolic potential. Action potentials of fibers in the lower region of the AV node were not affected as greatly. Verapamil slowed conduction of atrial impulses through the AV node; such slowing increased when the atrial rate increased. Verapamil also prolonged the effective refractory period of the AV node, thus slowing or blocking conduction of premature impulses. Verapamil prevented AV nodal reentry and initiation of atrial tachycardia by causing premature impulses to block rather than to conduct with the delay needed to initiate reentry. Verapamil had no effect on the rate of depolarization, action potential amplitude, or maximum diastolic potential of atrial or His bundle fibers. The results are consistent with the hypotheses that fibers in the SA and AV nodes show slow response activity, that the slow response plays a crucial role in causing certain cardiac arrhythmias, and that drugs that block the slow response are therefore antiarrhythmic.
Measured Turbulence and Its Effect on Thrombus Formation
Authors: STEIN PAUL D. , SABBAH HANI N.
Published: June 2012

Turbulence is one of the hydraulic disturbances implicated in thrombus formation, even though absolute proof of its contributory effect is lacking. Because of the importance of a possible effect of turbulence on thrombus formation, the relation was studied in eight dogs. In each dog, two arteriovenous shunts were established, one from each femoral artery to the contralateral femoral vein. Only one shunt contained a turbulence-producing device; otherwise, the shunts were identical in shape, size, and material. The intensity of turbulence distal to the turbulence generator was quantified in vitro by measuring the relative magnitude of the randomly fluctuating velocities. In each of the eight dogs, more thrombi, by weight, accumulated in the turbulent shunt than in the laminar shunt (
P
< 0.001). Thrombi from the turbulent shunt weighed 180 ± 30 (
SE
) mg, whereas those from the laminar shunt weighed 0.9 ± 0.6 mg. The weight of thrombi that accumulated within the turbulent system appeared to be related to the intensity of turbulence. A linear relation was observed between the Reynolds number in the region of the turbulence-producing orifice and the weight of the thrombi within the turbulent shunt (
r
= 0.90). The relative intensity and the absolute intensity of turbulence distal to the turbulence generator were also linearly related to the Reynolds number (
r
= 0.97 and 0.90, respectively). The results of this study therefore indicate that turbulence is a characteristic of blood flow that can contribute to the formation of thrombi.
Neurogenic and Humoral Factors Controlling Vascular Resistance in the Spontaneously Hypertensive Rat
Authors: Lais Lyman T. , Shaffer Richard A. , Brody Michael J.
Published: June 2012

The mechanism of sustained hypertension in spontaneously hypertensive rats has not been elucidated. In the present investigation, vasoconstrictor responses to a variety of neurogenic and humoral interventions were studied in the perfused hindquarters of Okamoto spontaneously hypertensive rats and normotensive Wistar rats. In addition, central sympathetic electrical discharge was measured. Vasoconstrictor responses in the hindquarters to lumbar sympathetic nerve stimulation were unchanged or reduced in the spontaneously hypertensive rats, but the responses to intra-arterially administered norepinephrine and epinephrine were enhanced. Vascular responses to intra-arterially administered tyramine, angiotensin, and barium chloride were also greater in the spontaneously hypertensive rats. Vascular resistance was significantly higher in the spontaneously hypertensive rats, and this difference remained following bilateral lumbar sympathectomy. Despite elevated systemic blood pressure, integrated nerve activity at rest was not different in the spontaneously hypertensive rats. The inverse relationship between arterial blood pressure and sympathetic nerve discharge was not different between spontaneously hypertensive and control rats when pressure was either raised or lowered. Changes in efferent sympathetic discharge produced by activation of chemoreceptors (asphyxia) were somewhat less in the spontaneously hypertensive rats. The contribution of low-pressure baroreceptors (45° tilt) to activation of sympathetic vasomotor tone was not different in the spontaneously hypertensive rats despite a greater decline in systemic blood pressure during the procedure. These data demonstrate that established hypertension in the spontaneously hypertensive rat does not derive from either enhanced central adrenergic discharge or altered central integration of afferent information from peripheral sensory receptors but may result from humoral (e.g., increased reactivity to vasoconstrictors) or structural factors.
Supernormal Excitability and Conduction in the His-Purkinje System of the Dog
Authors: Spear Joseph F. , Moore E. Neil
Published: June 2012

The electrophysiological characteristics of the period of supernormal excitability and supernormal conduction were investigated in the isolated canine His-Purkinje system. Strength-interval curves were determined as the minimum transmembrane current required to bring the impaled fiber to threshold potential following a conducted action potential. During the period of supernormal excitability, 17.0 ± 4.6% (SD) less current than that required during diastole was needed to reexcite fibers throughout the left and right bundle branch-Purkinje system. A period of supernormal excitability was not found in the His bundle proximal to its pseudobifurcation or in ventricular muscle. The period of supernormal excitability was voltage dependent in the bundle branch-Purkinje system; it began during phase 3 at full repolarization (88.8 ± 5.6 [SD] mv) and reached minimum current requirements at about 74.3 ± 5.8 mv. Action potentials evoked during this period were conducted faster than they were during diastole. The maximum rates of depolarization of these supernormally conducted action potentials were not greatly depressed compared with control rates. A period of supernormal conduction was not observed in the His bundle. When the external potassium concentration was increased from 2.7 mM to 5.0 um or 7.5 mM, both the supernormal period of excitability and the period of supernormal conduction were eliminated in Purkinje fibers.
Dimensions and Geometric Relationships of the Human Aortic Value as a Function of Pressure
Authors: SWANSON W. MILTON , CLARK RICHARD E.
Published: June 2012

In a continuing effort to develop improved prosthetic heart valves, a redefinition of the anatomy of the human aortic valve as a function of stress was undertaken. Dimensions and geometric relationships of the human aortic valve as a function of intraaortic pressure between 0 and 120 mm Hg were obtained from a series of silicone rubber valve casts. The axial length of the valve region was found to vary negligibly with pressure, but significant variations in geometry and angular dimensions were seen. The leaflet attachment annulus forms an ellipse at the plane of intersection with the cylindrical surface passing from the left ventricular tract through the aorta. Deductions from stress considerations for the measured geometry indicate that the loaded leaflet is a section of a cylindrical surface. The equation for this developed surface was obtained, and a prosthetic design was determined using average values at 100 mm Hg. The leaflet is developable onto a plane with a cut required along part of the junction line between the initially cylindrical part and the plane coapting surfaces. Optimum valve shape mandates a base angle between the cylindrical leaflet and the center axis of 70° (α =20-22°, where α is the leaflet angle).
Regional Myocardial Function during Acute Coronary Artery Occlusion and Its Modification by Pharmacologic Agents in the Dog
Authors: THEROUX PIERRE , FRANKLIN DEAN , ROSS JOHN , KEMPER WILLIAM S.
Published: June 2012

Myocardial regional function during acute coronary artery occlusion was studied using ultrasonic dimension gauges in open-chest dogs. Three pairs of 2-mm ultrasonic crystals were implanted 1 cm apart near the endocardium in an ischemic segment, a control segment, and a segment at the margin of the ischemic zone. In the ischemic segment, coronary artery occlusion resulted in prompt dyskinesis which progressed to holosystolic expansion; length at enddiastole (diastolic length) increased by 11%, segment stroke work decreased by 91%, and the diastolic pressure-length relationship was displaced and steepened. In the marginal segment, active shortening and stroke work decreased by 37% and diastolic length increased by 4%. In the control segment, an initial increase in active shortening was observed, followed by compensatory operation of the Frank-Starling mechanism. Nitroglycerin administered during coronary artery occlusion decreased diastolic length and increased shortening in all three segments. An early beneficial effect of isoproterenol on all segments was later replaced by deterioration in marginal and ischemic segments. After propranolol administration, the decrease in shortening of the marginal segment was reduced to half of that observed during a control coronary artery occlusion, suggesting a protective effect of this drug. These results indicate the power of this approach, which provides continuous quantification of regional wall function in myocardial ischemia and during therapeutic interventions.
A model of psychosocial hypertension showing reversibility and progression of cardiovascular complications.
Authors: Henry J P , Stephens P M , Santisteban G A
Published: June 2012

The sequence of pathophysiological changes that can result from the stimulating effects of a sustained disturbance of the social environment was studied in ten colonies of socially deprived mice. Sixteen formerly isolated males were placed with 16 normal females in population cages consisting of seven intercommunicating boxes. Six of these socially disturbed 32-member colonies were terminated after periods of interaction ranging from 2 days to 9 months. The remaining four were terminated a month or more after the males had been returned to individual isolation. Indirect blood pressure measurements, body and heart weights, and sections of hearts and aortas were studied in the males. Following the shorter exposures, blood pressure reverted to normal in a few days. Exposure of 6 months or more were associated with unchanged body weights and sustained increases in heart weight and blood pressure readings. In addition, there was a significant development of aortic arteriosclerosis and myocardial fibrosis. These changes persisted despite prolonged return to isolation.
In vivo electrophysiological effects of lidocaine in canine acute myocardial infarction.
Authors: Kupersmith J , Antman E M , Hoffman B F
Published: June 2012

Lidocaine was administered as a rapid intravenous bolus injection followed by a constant-rate intravenous infusion to nine dogs with 2-hour-old myocardial infarctions. Bipolar electrograms were recorded from and effective refractory periods were determined in the infarcted and normal zones of the heart. Intervals (Q-EG) were measured from the onset of the QRS complex in a standard electrocardiogram limb lead to the major deflection of the recorded electrograms from the normal and infarcted zones. QRS duration and serum lidocaine concentration were also determined. At serum concentrations considered to be therapeutic, lidocaine prolonged the Q-EG intervals in the infarcted zones of the heart 17-26% at peak effect (P less than 0.01), but it had no effect on the Q-EG intervals in the normal zone except for a slight (1.5%) prolongation shortly after the initial intravenous bolus injection. Lidocaine also had no effect on QRS duration. Similarly, lidocaine prolonged the effective refractory period of the infarcted zone 23% (P less than 0.01) at peak effect but had no effect on the effective refractory period of the normal zone. Prior to lidocaine administration, the mean effective refractory period of the normal zone was 26 msec longer than that of the infarcted zone, but at peak drug effect the disparity in refractoriness was reduced to 1 msec. The present study thus shows that lidocaine has different effects in infarcted and normal zones of the heart. In delaying activation and prolonging the effective refractory period of the infarcted zone of the heart, lidocaine has local anesthetic actions which might explain its effectiveness in curtailing ventricular arrhythmias after acute myocardial infarction.
Diminished inotropic response of aged myocardium to catecholamines.
Authors: Lakatta E G , Gerstenblith G , Angell C S , Shock N W , Weisfeldt M L
Published: June 2012

The effect of advanced age on the response of active tension, maximal rate of tension development (dT/dt), and contraction duration to catecholamines and to calcium was evaluated in isometric trabeculae carneae from young adult (6-month-old), middle-aged (12-month-old), and aged (25-month-old) rats. Control values were not age dependent except for that for contraction duration which was prolonged in the aged group. At a norepinephrine concentration of 8 times 10-5M, dT/dt increased to 163.8 plus or minus 5.3% of control in the young adult group and to 125.9 plus or minus 6.3% of control in the aged group (P smaller than 0.001). Active tension increased to 121.3 plus or minus 4.0% of control in the young adult muscles but did not increase in the aged muscles (P smaller than 0.01). Contraction duration shortened proportionately in both age groups. Similar results were obtained with isoproterenol. In contrast to the response to catecholamines, there was no age difference in the response of active tension and dT/dt to increasing concentrations of calcium. It is concluded that the intrinsic inotropic response to catecholamines is diminished in the aged myocardium. This finding does not appear to result from differences in tachyphylaxis, tissue uptake of catecholamines, or the ability of the contractile proteins to respond to increasing concentrations of calcium but instead may result from a decreased ability of catecholamines to increase the intracellular calcium available for contraction.
Functional and hemodynamic adaptation to progressive renal ablation.
Authors: Kaufman J M , Siegel N J , Hayslett J P
Published: June 2012

Removal of renal tissue stimulates functional and anatomical adaptation in the remaining renal parenchyma. Since recent studies have demonstrated no apparent limitation in compensatory growth following progressive surgical ablation, experiments were performed to determine the changes in glomerular filtration rate and renal blood flow. After removal of 50% of the renal mass mean nephron glomerular filtration rate increased 60%, and after ablation of 75% of the renal tissue it increased 150%. These changes paralleled the increases in renal growth under the same conditions. In comparison, mean glomerular blood flow rose 90% and 240% after 50% and 75% nephrectomy, respectively; these changes in relation to the changes in glomerular filtration rate resulted in a progressive fall in the filtration fraction. Intrarenal blood flow distribution was examined with labeled microspheres. The marked increase in renal blood flow after surgical ablation was characterized by a disproportionate rise in blood flow to the inner cortex. The present investigation, therefore, described the remarkable functional changes that occur as overall glomerular filtration rate declines and provides further insight into the mechanism responsible for maintaining water and electrolyte homeostasis after loss of functioning renal mass.
Sphingomyelin and other phospholipid metabolism in the rabbit atheromatous and normal aorta.
Authors: Seth S K , Newman A I
Published: June 2012

Hypercholesterolemia induces atheroma formation, and the concentration of sphingomyelin is increased compared with that in the normal aortic intima-media. The aortic intima-media sphingomyelin concentration appears to increase exponentially with time on the cholesterol diet. Moreover, the entry rate of serum sphingomyelin into the aortic wall also appears to increase exponentially with time on the cholesterol diet and with the extent of aortic exposure to hypercholesterolemia. 32P-Phosphate incorporation into sphingomyelin and other phospholipids in the perfused rabbit aorta does not increase with atheromatosis, but the rate of sphingomyelin entry increases 27-fold during approximately the same period of atheroma formation and can account for all of the increase in sphingomyelin concentration in the intima-media.
Effect of insulin on the proliferation of cultured primate arterial smooth muscle cells.
Authors: Stout R W , Bierman E L , Ross R
Published: June 2012

Smooth muscle cells were grown from thoracic aortas of 1-year-old monkeys (Macaca nemistrina). The effect of insulin on the proliferation of these cells was studied by comparing the growth of cells in culture medium to which insulin had been added with that of cells in basal (1% monkey serum) medium and in growth-promoting 5% monkey serum. Insulin in concentrations of 10, 100, 1,000, and 10,000 muunits/ml resulted in successively greater stimulation of growth which was highly significant (P smaller than 0.001) by analysis of variance. There was a significant linear relationship between the logarithm of the insulin dose and cell growth. However, the highest concentration of insulin produced only 50% of the effect of 5% monkey serum. Serum from which insulin had been removed stimulated growth less well (P smaller than 0.05) than did untreated serum at the same concentration (5%) but had significant (P smaller than 0.05) stimulating properties compared with whole serum at a lower concentration. Cells that were older in culture life (eight or nine passages) did not show a growth response to insulin and had an attenuated response to 5% serum. The effect of insulin (100 muunits/ml) was inhibited by dibutyryl cyclic adenosine monophosphate (db-cAMP) (5 times 10-5 M), although there was a latent period of 3 days before inhibition occurred; db-cAMP had no effect on cell counts in the absence of insulin. The electron microscopic appearance of the cells was unaltered by insulin.
Hypothermic arrest and potassium arrest: metabolic and myocardial protection during elective cardiac arrest.
Authors: Hearse D J , Stewart D A , Braimbridge M V
Published: June 2012

Hypothermic arrest, potassium arrest, and ischemic arrest, either singly or in combination, with or without coronary perfusion were studied in an isolated perfused rat heart preparation. Procedures that permitted the maintenance of high cellular levels of adenosine triphosphate (ATP) and creatine phosphate during arrest, e.g., coronary perfusion with hypothermic solutions or solutions containing 16.0 mM potassium, produced a fully reversible arrest with complete cardiac recovery. Cardiac arrest and coronary flow were related to the degree of hypothermia and the concentration of potassium in the coronary perfusate, and the minimum conditions required to induce complete cardiac arrest were ascertained. The effects of hypothermia and potassium were additive; total cardiac arrest could be obtained by combining small evaluations of potassium with moderate hypothermia. Under these conditions, cellular high-energy phosphates were maintained, and complete recovery was possible. Under conditions in which arrest was obtained without maintaing coronary perfusion, e.g., ischemic arrest, cellular high-energy phosphates declined rapidly, and the hearts exhibited poor recoveries. Some protection could be afforded to the ischemic myocardium by topical hypothermia or by combining the ischemia with potassium arrest. In both instances, ATP and creatine phosphate were maintained at higher levels, and improved recoveries were observed.
Continuous inhibition of renin release in dogs by vagally innervated receptors in the cardiopulmonary region.
Authors: Mancia G , Romero J C , Shepherd J T
Published: June 2012

Inhibition of the release of renin by vagal afferents from the heart and lungs was studied in 14 dogs with their aortic nerves cut and their carotid sinuses vascularly isolated. The release of renin from one kidney was calculated from the venous-arterial difference in plasma renin activity (radioimmunoassay) and the renal blood flow (electromagnetic flowmeter). Renin release was determined before and during temporary interruption of afferent vagal nerve traffic (bilateral cooling of the cervical vagi). With carotid sinus pressure maintained at 40 mm Hg, vagal cooling increased mean aortic blood pressure (24%), decreased renal blood flow (19%), and increased renin release (241%). With sinus pressure maintained at the mean aortic blood pressure existing during the control period, vagal cooling caused a lesser increase in mean aortic blood pressure (12%), little decrease in renal blood flow (7%), and a marked increase in renin release (522%). The changes in renal blood flow and renin release with vagal cooling were prevented by renal denervation. Thus, vagal afferents from the cardiopulmonary region exert a tonic restraint on the release of renin; this restraint occurs in circumstances in which these afferents cause little change in total renal blood flow.
Local cerebral blood volume determined by three-dimensional reconstruction of radionuclide scan data.
Authors: Kuhl D E , Reivich M , Alavi A , Nyary I , Staum M M
Published: June 2012

We developed a method to determine in man absolute values of local cerebral blood volume (LCBV) localized throughout the brain in three dimensions and presented in a cross-sectional picture format. Previously, absolute values of LCBV have been determined in vivo by stimulated X-ray fluorescence, but these determinations have been limited to one point in the brain at a time. All other previous estimates of LCBV by external emission counting have been contaminated by the significant contribution of blood in the overlying scalp and cranium. In our method, a transverse section scan is made after the injection of -99m-Tc-labeled red blood cells into a peripheral vein. Data processing then gives a point-to-point estimate of absolute radionuclide concentration analogous to an autoradiograph. After the concentration of blood activity is determined, counting data are converted to a two-dimensional map of LCBV representing a cross section at a known level of the brain. In a series of five baboons, the following equation was obtained for the regression plane that relates LCBV in the center of the brain to arterial carbon dioxide tension (P-ALPHA-CO2) and mean arterial blood pressure (MABP): LCBV equals 2.88 + 0.049P-ALPHA-CO2 MINUS 0.013MABP. In patients, LCBE values ranged from 2 to 4 ml/100 g depending on location; higher values corresponded to regions of cerebral cortex. Differences in blood volumes of focal brain lesions were also quantified.
Effect of sympathetic nerve stimulation on cerebral and cephalic blood flow in dogs.
Authors: Traystman R J , Rapela C E
Published: June 2012

The effect of sympathetic stimulation (stellate ganglion) on dog cerebral and cephalic blood flows was studied via a cervical or a thoracic approach to the stellate ganglion under sodium pentobarbital or chloralose anesthesia. Two different stimulation voltages (3v and 5v) of monophasic pulses were applied for 1 minute. Venous outflow was measured at the confluence of the sagittal, straight and lateral sinuses with the lateral sinuses occluded and with them patent. When the lateral sinuses were occluded, stellate ganglion stimulation resulted in a marked decrease in common carotid blood flow to 38 plus or minus 2.5% (SE) of control and dilation of the ipsilateral pupil, but cerebral blood flow did not change. Similar effects were observed with each of the anatomic approaches, anesthetics, and voltages used and in dogs with low cerebral vascular tone induced by hypercapnia. When the lateral sinuses were kept patent, sympathetic nerve stimulation decreased the venous outflow to 89 plus or minus 2.9% of control and clamping both of the external jugular veins increased venous outflow to 120 plus or minus 2.7% of control. When the lateral sinuses were kept patent and the extracranial venous pressure was increased by clamping both of the external jugular veins, the decrease in venous outflow in response to sympathetic stimulation was even larger: venous outflow was only 65 plus or minus 4.9% of control. We conclude that stimulation of the stellate ganglion has no effect on the cerebral vasculature. Sympathetic stimulation significantly decreases venous blood flow measured at the confluence of the sinuses only when communications between the intracranial and extracranial venous vasculatures are present.
Histamine potentiation of nerve- and drug-induced responses of a rabbit cerebral artery.
Authors: Bevan J A , Duckles S P , Lee T J
Published: June 2012

Rabbit basilar artery rings are normally relatively unresponsive to transmural stimulation of their sympathetic nerve supply. However, in the presence of histamine (0.55 muM), contractile responses to nerve stimulation were markedly increased. Norepinephrine and serotonin concentrations that produce 50% of a maximum contractile response (ED50) were considerably decreased in the presence of histamine; maximum responses to both norepinephrine and serotonin were increased. Although a prejunctional effecto of histamine has not been eliminated, potentiation of responses to transmural nerve stimulation is probably due to an increase in smooth muscle responsiveness to norepinephrine. In rabbit saphenous artery rings, histamine produced a qualitatively similar potentiation of responses to nerve stimulation, norepinephrine, and serotonin except that maximum responses were not increased. Serotonin (0.084 muM) did nog potentiate contractile responses of the basilar artery to transmural nerve stimulation or norepinephrine. Since histamine and serotonin are released from rabbit platelets in response to tissue injury the synergistic effect of these agents on vascular smooth muscle contraction might be advantageous in minimizing hemorrhage. But such a response could also be deleterious if the effects of these vasoconstrictors were prolonged.
Altered cardiac responsiveness and regulation in the normal cardiac output type of borderlind hlpertension.
Authors: Julius S , Randall O S , Esler M D , Kashima T , Ellis C , Bennett J
Published: June 2012

Of 145 patients with borderline hypertension, 30% had increased resting cardiac index (QI), whereas the remainder had normal values. The specific aim of this study was to investigate cardiac regulation in patients who had normal resting QI. Eighty-five control subjects were used for comparison. At rest, patients with normal QI showed evidence of decreased parasympathetic inhibition; the QI after injection of atropine increased less than in control subjects. After complete cardiac autonomic blockade with propranolol and atropine, QI and stroke volume were significantly lower in patients than in control subjects. The mechanism of this low QI was further analyzed. Central blood volume, which strongly correlates with stroke volume, was used as an estimate of the cardiac venous filling. After blockade, stroke volume was decreased in patients, but central blood volume was normal. Patients also showed a decreased heart rate and QI response to infusion of isoproterenol. It is therefore postulated that two components may be responsible for the low QI in the "denervated" heart: patients exhibit a decreased responsiveness to sympathetic stimulation, and they may also be less responsive to venous filling. Behind the facade of cardiac normality in these borderline hypertensive patients with normal cardiac output, there is evidence of altered autonomic control of the heart (decreased vagal inhibition) and of changed cardiac response to sympathetic stimulation and possibly to venous filling.
Primary role of renal homografts in setting chronic blood pressure levels in rats.
Authors: Dahl L K , Heine M
Published: June 2012

The genotype of homograft kidneys plays the primary role in determining chronic blood pressure levels in two strains of rats with opposite genetically controlled propensities for hyptertension. In hypertensive rats from the hypertension-prone (S) strain, a renal homograft from the same strain resulted in a slight rise in blood pressure to a level that was equivalent to that in appropriate uninephrectomized S controls. In contrast, a renal homograft from the hypertension-resistant (R) strain led to a sharp fall in blood pressure in hypertensive S recipients. Opposite results were found when the host came from the R strain: R homografts maintained the same low pressure as that seen in controls, whereas S homografts resulted in hypertension. We concluded that genetically controlled factors operating through the kidney can chronically modify the blood pressure up or down. The central role of the kidney in hypertension is thus further documented.
Differentiation of neurogenic and myocardial angiotensin II receptors in isolated rabbit atria.
Authors: Blumberg A L , Ackerly J A , Peach M J
Published: June 2012

The effect of angiotensin on the action of tyramine was studied in isolated rabbit left atria paced by point and field stimulation to more clearly define the interaction of angiotensin with the sympathetic nervous system. Administration of angiotensin resulted in similar increases in contractility in both point- and field-stimulated atria. In point-stimulated preparations only the muscle is stimulated to contract, whereas in field-stimulated preparations both nerve and muscle are stimulated. 1-Sar-8-Ala-angiotensin II completely blocked the direct inotropic effect of angiotensin in a molar dose ratio of 3:1 in both point- and field-stimulated preparations. However, angiotensin (0.05-10 ng/ml) potentiated the inotropic effect of tyramine in field-stimulated atria only. This facilitatory effect was not inhibited by 1-Sar-8-Ala-angiotensin II at a molar dose ratio of 3:1; indeed, a ratio of 500:1 was necessary for complete blockade of this angiotensin-induced potentiation. This antagonist in odses of 0.1-1000 ng/ml was without contractile effect in any preparation, regardless of whether tyramine was present. The data suggest the presence of (1) a presynaptic angiotensin receptor that, in the presence of sympathetic nerve stimulation, modulates the release of norepinephrine and (2) a second angiotensin receptor in cardiac tissue that directly influences myocardial contractility.
Des-1-Asp-angiotensin II. Possible intrarenal role in homeostasis in the dog.
Authors: Freeman R H , Davis J O , Lohmeier T E
Published: June 2012

The relative effects of des-a-Asp-angiotensin 3I and angiotensin II on renal function, including renin secretion, were investigated in normal and sodium-depleted dogs. Intrarenal arterial infusion of the heptapeptide fragment into normal dogs at a rate which was calculated to increase blood levels by only 7 ng/100 ml decreased renal blood flow from 254 +/- 9 ml/min to 220 +/- 12 and 219 +/- 12 ml/min (P less than 0.01 for both values) after 10 and 30 minutes of infusion, respectively; renin secretion decreased from 502 +/- 214 ng/min to 253 +/- 109 and 180 +/- 53 ng/min (P less than 0.05 for both values). Infusion of angiotensin II at the same rate decreased renal blood flow from 251 +/- 26 ml/min to 224 +/- 22 and 220 +/- 16 ml/min (P less than 0.01 and 0.025, respectively) and decreased renin secretion from 374 +/- 25 ng/min to 166 +/- 76 and 131 +/- 37 ng/min (P less than 0.025 for both values). Neither peptide significantly changed mean arterial blood pressure, creatinine clearance, or excreted sodium in these dogs. Infusion of des-1-Asp-angiotensin II into sodium-depleted dogs decreased renin secretion from 1094 +/- 211 ng/min to 768 +/- 132 and 499 +/- 31 ng/min (P less than 0.025 for both values) after 10 and 30 minutes of infusion. Angiotensin II infusion decreased renin secretion from 1102 +/- 134 to 495 +/- 235 and 502 +/- 129 ng/min in these dogs (P less than 0.05 and 0.025, respectively). Neither peptide significantly altered renal blood flow, arterial blood pressure, creatinine clearance, or excreted sodium in the sodium-depleted dogs. The data demonstrated that these two peptides have similar effects on the renin secretory mechanism and the vascular receptor at the level of the renal arterioles.
Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon.
Authors: Strandgaard S , Jones J V , MacKenzie E T , Harper A M
Published: June 2012

The effect of arterial hypertension on cerebral blood flow was studied by the intracarotid 133Xe clearance method in baboons. The arterial blood pressure was raised in gradual steps with angiotensin. Baboons with renal hypertension of 8-12 weeks duration were studied along with normotensive baboons. In initially normotensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had risen to the range of 140 to 154 mm Hg; thereafter cerebral blood flow increased with each rise in mean arterial blood pressure. In the chronically hypertensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had been elevated to the range of 155 to 169 mm Hg. Thus, in chronic hypertension it appears that there are adaptive changes in the cerebral circulation which may help to protect the brain from further increases in arterial blood pressure.
Alpha-receptor stimulation by endogenous and exogenous norepinephrine and blockade by phentolamine in pial arteries of cats.
Authors: Kuschinsky W , Wahl M
Published: June 2012

The question regarding the existence of an alpha-adrenergic component of pial arterial tone was investigated using a microapplication technique combined with the measurement of vascular diameter. Concentration-response curves for the alpha-receptor blocker, phentolamine, revealed no vascular reaction for a concentration range from 2.5 x 10(-11) to 2.5 x 10(-7) M. At higher concentrations (up to 1.3 x 10(-3) M) concentration-dependent dilations were observed. Constrictions of pial arteries induced by perivascular injection of 2.5 x 10(-6) M norepinephrine could be reduced by 38% and 73% when phentolamine was applied simultaneously in concentrations of 2.5 x 10(-7) and 2.5 x 10(-6) M, respectively, whereas constrictions due to 2.5 x 10(-4) M norepinephrine were not reduced by 2.5 x 10(-6) M phentolamine, indicating a competitive antagonism between norepinephrine and phentolamine for pial arteries. Stimulation of the cervical sympathetic chain (90 seconds, 10 v, 1.4 msec, 20 Hz) induced constrictions of pial arteries (mean 12%) which could be reduced by two-thirds during the simultaneous application of 2.5 x 10(-7) M phentolamine. Since the constriction induced by norepinephrine applied exogenously or released endogenously could be reduced by a concentration of phentolamine which had no vascular effect per se, we conclude that the resting tone of the pial arteries is not influenced by an alpha-adrenergic component under our experimental conditions. The dilations induced by high concentrations of phentolamine are believed to be nonspecific.