bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between angiotensin II and the baroreceptor reflex in the control of adrenocorticotropic hormone secretion and heart rate in conscious dogs.
Authors: Brooks V L , Reid I A
Published: June 2012

The present studies were designed to examine the effect of angiotensin II on baroreflex control of adrenocorticotropic hormone secretion and heart rate in conscious dogs. Baroreflex function was assessed by examining the relationship between blood pressure and plasma corticosteroid concentration (used as an index of adrenocorticotropic hormone secretion) and between blood pressure and pulse interval (the inverse of heart rate). Blood pressure was varied by intravenous infusion of four doses (0.3, 0.6, 1.5, and 3.0 micrograms/kg per min) of the vasodilator nitroprusside. Nitroprusside infusion produced an increase in plasma corticosteroid concentration and a decrease in pulse interval, both of which were linearly related to the fall in arterial blood pressure. During infusion of angiotensin II (10 ng/kg per min), however, the lines relating blood pressure to plasma corticosteroid concentration or blood pressure to pulse interval were shifted to a higher pressure level, suggesting that angiotensin II resets the baroreceptor reflex. Angiotensin II blockade with saralasin, an angiotensin II antagonist, or with captopril, a converting enzyme inhibitor, in sodium-depleted dogs with elevated plasma angiotensin II levels produced a shift in the opposite direction in these relationships. Because baroreflex function in sodium-depleted dogs before angiotensin II blockade was similar to that in sodium-replete dogs, despite the increased plasma angiotensin II levels, and because treatment of sodium-replete dogs with saralasin did not affect baroreflex function, these results suggest that endogenous angiotensin II is necessary for the maintenance of normal baroreflex control of adrenocorticotropic hormone secretion and heart rate during sodium depletion. Previous studies designed to evaluate the physiological significance of angiotensin II in the control of adrenocorticotropic hormone secretion showed that high, perhaps supraphysiological, levels of exogenous angiotensin II are required to increase adrenocorticotropic hormone secretion. An additional finding of the present study was that exogenous angiotensin II produces a larger increase in adrenocorticotropic hormone secretion when the pressor effect of angiotensin II was eliminated with simultaneous infusion of the vasodilators nitroprusside or hydralazine. This result suggests that experiments that evaluate the physiological role of angiotensin II in the control of adrenocorticotropic hormone secretion with infusions of exogenous AII may underestimate the importance of endogenously produced angiotensin II, which is normally released without an increase in pressure.
Kinetic identification of an intracellular calcium compartment sensitive to phosphate and dinitrophenol in intact isolated rabbit aorta.
Authors: Hai C M , Phair R D
Published: June 2012

Previous work from this laboratory revealed the presence of at least three distinct intracellular calcium compartments in intact segments of rabbit aorta. In this study one of these intracellular compartments is shown to be sensitive to dinitrophenol and to increased extracellular phosphate. Intact aortic segments were loaded with 45Ca in bicarbonate-buffered physiologic salt solution for 1 hour, and then transferred to a flow-through chamber perfused with physiologic salt solution. Effluent from the chamber was collected for 8 hours, and 45Ca efflux curves were analyzed using compartmental analysis. When aortic segments were loaded and washed out in dinitrophenol, the slowest component of the efflux curve was less prominent; in high phosphate it was more prominent. The rate constant changes required to account for these data were primarily in the exchange between the cytosolic and slowest intracellular calcium compartment, suggesting that the slowest calcium compartment resolved during the 8-hour washout was mitochondrial. This compartment contained 5.4 +/- 3.2 nmol calcium/g wet wt. tissue. The calcium flux across its membranes was 0.32 +/- 0.04 nmol min-1g-1. Because this flux is much smaller than the plasma-membrane calcium flux, we suggest that, in normal physiological circumstances, plasma-membrane extrusion is more important for the removal of Ca from the smooth muscle cytosol than is uptake into this slow intracellular compartment.
Atrial natriuretic peptide decreases circulatory capacitance in areflexic rats.
Authors: Trippodo N C , Cole F E , Frohlich E D , MacPhee A A
Published: June 2012

The short-term hemodynamic response to atrial natriuretic peptide appears to be partly mediated by decreased venous return, which could result from increased circulatory capacitance or decreased blood volume. To determine if rat atrial natriuretic peptide 99-126 (0.5 microgram/kg/min IV for 30-70 minutes) dilated capacitance vessels or decreased blood volume, mean circulatory filling pressure (measured during brief circulatory arrest by inflating an intraatrial balloon) and blood volume (51Cr-erythrocytes) were measured in anesthetized rats. Mean circulatory filling pressure, central venous pressure, and blood volume decreased by 0.4 mm Hg, 0.5 mm Hg, and 3.4 ml/kg, respectively. To determine the total circulatory pressure-volume relationship without influence from autonomic reflexes, mean circulatory filling pressure and blood volume were measured in spinal-cord-transected rats before and immediately after infusing or withdrawing 5 ml blood. Atrial natriuretic peptide decreased mean circulatory filling pressure, central venous pressure, and blood volume by 0.9 mm Hg, 1.7 mm Hg, and 8.0 ml/kg, respectively, and displaced the pressure-volume relationship toward the pressure axis by decreasing extrapolated unstressed volume. Similar results were obtained in spinal-cord-transected rats that had initial vascular tone restored to a greater level by norepinephrine infusion. In anephric rats, atrial natriuretic peptide decreased central venous pressure by 0.3 mm Hg and blood volume by 1.6 ml/kg. The results indicate that short-term infusion of atrial natriuretic peptide reduced circulatory capacitance in rats and suggest that this reduction resulted from diminished blood volume due to urinary fluid loss followed by passive vascular recoil and active venoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Porcine heart valves produce a protein that induces cell-mediated connective tissue degradation: II. Biochemical properties of the partially purified protein.
Authors: Decker R S , Henney A M , Dingle J T
Published: June 2012

A cardiac catabolic factor (CCF) has been partially purified from serum-free medium conditioned by minced porcine heart valves. CCF was prepared by a series of chromatographic techniques and compared directly with porcine synovial catabolin purified by the same protocol. CCF displayed a somewhat higher molecular weight (Mr 21,000) and isoelectric point (pI 5.2) than did synovial catabolin (Mr 18,000 and pI 4.8), but the two factors clearly resemble one another closely. CCF stimulated the release of glycosaminoglycans from cultured cartilage and mitral valve and provoked porcine valves to degrade their own collagen extracellular matrix. The release of hydroxyproline was inhibited by corticosteroids, whereas proteoglycan breakdown was not. Partially pure preparations of CCF and synovial catabolin stimulated murine thymocyte proliferation; moreover, that activity was almost totally abolished by an antibody raised against pure porcine interleukin-1. These observations suggest that CCF may represent a catabolic factor that belongs to the interleukin-1 family and that it could potentially regulate the composition of valvular connective tissue.
Diphenylhydantoin blocks cardiac calcium channels and binds to the dihydropyridine receptor.
Authors: Yatani A , Hamilton S L , Brown A M
Published: June 2012

Diphenylhydantoin was studied for its effects on Ca currents in single isolated guinea pig ventricular cells. The whole-cell patch-clamp technique was used, and Ca currents were studied after suppressing Na and K currents. At low frequencies (0.1 Hz) and negative holding potentials (-50 mV), diphenylhydantoin produced a concentration-dependent decrease in Ca currents without any significant change in the current-voltage relations. Half blocking effect occurred at 2 X 10(-4) M. The effects of diphenylhydantoin on Ca currents were dependent upon the holding potential. Inactivation curves for Ca currents were shifted to more negative potentials by the drug. The recovery of Ca currents from inactivation was prolonged by diphenylhydantoin, and the repriming of the current displayed an additional component, attributed to slow release of the drug from the channels. The voltage-dependent block was attributed to preferred binding by the inactivated channel state. Diphenylhydantoin also blocked specific [3H]-nitrendipine binding to guinea pig ventricular membrane preparations. The inhibition of [3H]-nitrendipine binding by diphenylhydantoin was competitive. Diphenylhydantoin also blocks cardiac Na channels in a voltage-dependent manner. We suggest that diphenylhydantoin binding sites exist on both Ca and Na channels.
Hydrolysis of diadenosine 5',5''-P',P''-triphosphate (Ap3A) by porcine aortic endothelial cells.
Authors: Goldman S J , Gordon E L , Slakey L L
Published: June 2012

Diadenosine triphosphate is present in platelet-dense granules and released quantitatively on platelet aggregation. We have found that intact porcine aortic endothelial cells can efficiently hydrolyze extracellular diadenosine triphosphate. The products of diadenosine triphosphate hydrolysis are adenosine monophosphate and adenosine diphosphate. Adenosine diphosphate is a potent stimulus of platelet aggregation. Since platelet-dense granules contain high concentrations of adenosine triphosphate and adenosine diphosphate, we examined endothelial cell hydrolysis of a mixture of diadenosine triphosphate and adenosine triphosphate. We find that the presence of adenosine triphosphate severely inhibits the hydrolysis of diadenosine triphosphate. Thus, although endothelial cells can rapidly clear extracellular diadenosine triphosphate, during platelet aggregation the hydrolysis of diadenosine triphosphate may be slow due to the presence of high concentrations of other adenine nucleotides. This phenomenon may be important physiologically if, as current evidence implies, diadenosine triphosphate is involved in the maintenance of hemostasis.
Effect of norepinephrine and cyclic AMP on intracellular sodium ion activity and contractile force in canine cardiac Purkinje fibers.
Authors: Pecker M S , Im W B , Sonn J K , Lee C O
Published: June 2012

The effect of norepinephrine on the Na+-K+ pump was investigated by simultaneously measuring intracellular sodium ion activity (aiNa) and contractile force of canine cardiac Purkinje fibers driven at 1.0 Hz in K+-free solution, high K+ solution, and in the presence of tetrodotoxin. In Tyrode solution containing 5.4mM [K+]o, 10(-6) M norepinephrine decreased aiNa, whereas in K+-free solution 10(-6) M norepinephrine did not lower aiNa. 16.2 mM [K+]o decreased aiNa from 8.8 +/- 0.9 mM to 6.5 +/- 0.5 mM (mean +/- SD, n = 5). Exposure to 10(-6) M norepinephrine in the presence of high [K+]o further decreased aiNa by 0.7 +/- 0.4 mM. This further decrease was prevented by exposure to 2.5 X 10(-6) M strophanthidin (n = 4). Blockade of the fast sodium channel with 5 X 10(-6) M tetrodotoxin lowered aiNa from 8.5 +/- 1.3 mM to 7.4 +/- 1.1 mM (n = 4). Exposure to 10(-6) M norepinephrine in the presence of tetrodotoxin further lowered aiNa by 0.9 +/- 0.2 mM. We also studied the effects of the analogues of adenosine 3':5'-cyclic monophosphate, N6, 2'-0-dibutyryladenosine 3':5'-cyclic monophosphate, and 8-(4-chlorophenylthiol)-adenosine 3':5'-cyclic monophosphate on aiNa and twitch tension. Both analogues lowered to aiNa and increased twitch tension mimicking the effects of norepinephrine. Our results support the hypothesis that norepinephrine lowers aiNa by stimulating the Na+-K+ pump in this tissue. This stimulation appears to be mediated by adenosine 3':5'-cyclic monophosphate and does not appear to be due to intercellular K+ accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Sympathetic innervation alters growth and intrinsic heart rate of fetal rat atria maturing in oculo.
Authors: Tucker D C , Gist R
Published: June 2012

The influence of sympathetic innervation on the growth and intrinsic rate of beating established by fetal rat heart was studied by culturing fetal atrial tissue in sympathetically innervated and denervated anterior eye chambers of adult Sprague-Dawley rats. One anterior eye chamber in each host rat was sympathetically denervated by removing the ipsilateral superior cervical ganglion. In oculo, atrial grafts were vascularized by blood vessels sprouting from the iris and innervated by sympathetic and parasympathetic fibers from the ground plexus of the iris. Innervation was assessed by light-activated efferent nerve stimulation to the grafts that changed their rates of beating. The norepinephrine contents of 16 atria cultured for 2.5 months in sympathetically innervated and denervated eye chambers were 5.7 +/- 1.1 ng/implant vs. 0.2 +/- 0.07 ng/implant (mean +/- SEM), indicating permanent sympathetic denervation of the anterior eye chamber and the implanted atria. By 8 weeks in oculo, atria maturing in sympathetically innervated anterior eye chambers were 86% larger than those in denervated eye chambers (2.22 +/- 0.29 vs. 1.19 +/- 0.13 mm2); the weight of innervated transplants was over 3 times that of noninnervated grafts (2.35 +/- 0.75 vs. 0.76 +/- 0.21 mg). After implanted atria had ceased growing rapidly (2.5 months in oculo), bipolar electrodes were implanted adjacent to the cornea to record impulses from atrial grafts while host rats were unanesthetized. The dark-adapted baseline heart rates of sympathetically innervated and noninnervated atria were virtually identical (289 vs. 290 bpm). Graft intrinsic heart rate was estimated by combined beta-adrenergic and muscarinic receptor blockade with atenolol (1.0 mg/kg) and methylatropine (10 micrograms/kg). Sympathetically innervated transplants had lower intrinsic heart rates than noninnervated atria (134 +/- 25 vs. 213 +/- 12 bpm). These data suggest that sympathetic innervation of the developing heart influences both growth and intrinsic rate of beating.
Modulation of the natriuretic response to atrial natriuretic peptide by alterations in peritubular Starling forces in the rat.
Authors: Mendez R E , Dunn B R , Troy J L , Brenner B M
Published: June 2012

The mechanisms underlying the natriuretic response to infusions of atrial natriuretic peptide (ANP) remain incompletely defined. By acting as renal vasodilators, atrial peptides may serve to alter peritubular capillary physical forces and favor a decrease in tubule solute reabsorption. Therefore, we studied the effects of known modifiers of intrarenal Starling forces on the natriuresis induced by infusion of intravenous hANP [4-28] (0.5 microgram/kg/min) in anesthetized, euvolemic Munich-Wistar rats. In the first series of studies, infusion of ANP resulted in a significant natriuresis, diuresis, and increase in inulin clearance and in a slight fall in systemic arterial pressure, as compared to vehicle infusion. Subsequent elevation of renal perfusion pressure by superimposition of angiotensin II infusion (0.1-0.2 microgram/kg/min i.v.) on continued ANP infusion resulted in marked further enhancement of natriuresis, independent of changes in glomerular filtration rate (GFR). In the second set of experiments, in which oncotic pressure in the postglomerular capillaries was elevated by hyperoncotic exchange transfusion, administration of ANP did not result in natriuresis, even though GFR increased by the same magnitude as that seen in isooncotic animals given ANP. These observations are consistent with the view that peritubular capillary hydraulic and oncotic pressures modulate the natriuretic and diuretic effects of ANP.
Human cardiac myosin heavy chain genes. Isolation of a genomic DNA clone and its characterization and of a second unique clone also present in the human genome.
Authors: Catanzaro D F , Morris B J
Published: June 2012

A gene sequence coding for myosin heavy chain (MHC) of human cardiac muscle was isolated by screening a human genomic library with a 32P-labelled 1.1kb SacI restriction fragment from a previously characterized cDNA clone specifying the light meromyosin and 3' untranslated region of mRNA encoding rabbit cardiac alpha-MHC. The DNA of this human genomic clone (lambda HCMHC8) hybridized much more strongly than did other clones isolated under similar, low stringency conditions both to the rabbit cDNA probe and to mRNA isolated from rat cardiac, but not skeletal, muscle tissue. Probe made from a DNA restriction fragment of lambda HCMHC8 hybridized a single 31S band of human ventricular mRNA. This size is identical to that of cardiac MHC mRNA of other species. Heteroduplex analysis showed hybridization of lambda HCMHC8 with exon segments in a rabbit cardiac MHC genomic clone (lambda MHC alpha 12/1). It also showed that lambda HCMHC8 spanned 14 kb of DNA and contained exon segments estimated to code for two-thirds of a MHC including the carboxylic acid terminus. By rescreening the library under more stringent conditions, where only DNA sequences having strong homology to cardiac MHC genes would be expected to hybridize, clones having restriction maps overlapping lambda HCMHC8 were isolated together with a unique clone (lambda HCMHC9). DNA gel blot hybridization of human genomic DNA with lambda HCMHC8 probe at medium stringency gave a pattern of restriction fragments similar to the restriction map of lambda HCMHC8. A weaker set of bands also appeared which corresponded in pattern to the map of lambda HCMHC9.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of histamine on contraction frequency, sodium influx, and cyclic AMP in cultured rat heart cells.
Authors: McCall D , Lui C Y
Published: June 2012

Histamine has been shown to have both positive inotropic and chronotropic effects. To evaluate the chronotropic effects, spontaneously contracting monolayers of cultured rat myocardial cells were treated with histamine, 10(-7) M-10(-4) M. This resulted in a dose-dependent increase in contraction frequency reaching a maximum in 10(-5) M histamine. Contraction frequency (mean +/- SEM) increased from a control of 121 +/- 5 contractions per minute to 153 +/- 4.5, 181 +/- 9, 212 +/- 4, and 216 +/- 1 in 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M histamine, respectively (for each n = 10, p less than 0.001). The effect was time-dependent, taking 30 minutes to develop fully. Changes in contraction frequency were accompanied by parallel dose- and time-dependent increases in the verapamil-sensitive sodium influx. Verapamil-sensitive sodium influx (pmol/cm2/sec) increased from a control of 10.45 +/- 1.44 (mean +/- SEM) to 24.34 +/- 2.41 and 32.57 +/- 2.35 at 10- and 30-minute treatment with 10(-6) M histamine (n = 5, p less than 0.001). These data fit the previously described relation between verapamil-sensitive sodium influx and contraction frequency in these cells. Cimetidine (10(-4) M) but not diphenhydramine (10(-4) M) abolished both the contraction frequency and sodium influx response to histamine. Subsequent studies showed a dose- and time-dependent elevation of cyclic adenosine monophosphate (cAMP) with histamine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Determinations of DPN (TPN) Thiamine, Amino Acids and Amino Sugars in Blood of Animals with Experimental Myocardial Infarction
Authors: CABRERA G. , BEUREN A. , BING R. J.
Published: June 2012

An investigation was made of the possible release from heart muscle of substances of small molecular weight following experimental myocardial infarction. These resulting chemical changes in coronary vein blood may be due to metabolic alterations of the cell which would either precede cell death or take place in cells with reversible metabolic changes. The coronary arteriovenous differences of pyridine nucleotides, thiamine and its phosphorylated derivatives, amino acids and amino sugars were investigated. No changes from the control were found. The negative results may have been caused by the rapid turnover of these substances in blood.
Approximation of "Total Vascular Space" and its Distribution in Three Sizes of Blood Vessels in Rats by Plastic Casts
Authors: KNISELY WILLIAM H. , MAHALEY M. S. , JETT HARRIMAN H.
Published: June 2012

To know where given amounts of blood might be, we need to know the potential vascular space and what the distribution among various sized vessels is. Methyl methacrylate was injected via the cannulated aorta into 4 rats, and vascular casts made. Polymerization caused 15 per cent shrinkage. The casts were separated into 3 compartments: 150 µ. and smaller, 150 to 600 µ., and 600 µ. and larger. Using the shrinkage, specific density, and weights of plastic, the "total vascular spaces" in cc./100 Gm. were found to be 8.9, 10.6, 11.1 and 11.1, respectively. The mean percentages for the 3 compartments were 10.4 in vessels 706 µ and larger, 6.7 in 188 to 706 µ., and 82.9 in vessels 188 µ. and smaller. Because the only observed distortions of the casts on the basis of comparisons with the in vivo vasculature of a number of organs were some noninjected capillaries and nonmaximally injected veins, the approximations of "total vascular space" are considered too low. The utility of methyl methacrylate casts for gravimetric determinations of volumes was demonstrated. The finding of over 80 per cent of the vascular space in vessels 188 µ. and smaller is relevant to the potential location of blood within the body.
Cardiac Responses to Transthoracic Capacitor Discharges in the Dog
Authors: MILNOR WILLIAM R. , KNICKERBOCKER G. GUY , KOUWENHOVEN WILLIAM B.
Published: June 2012

Many previous investigators have presented data suggesting that the processes involved in excitation and recovery in heart muscle limit the "vulnerable period" to a relatively small part of the heart cycle in late systole. Evidence presented in this report indicates that there are exceptions to this rule, at least in the intact animal, since under some conditions multiple extrasystoles and ventricular fibrillation can be elicited by single stimuli of short duration and high voltage applied at almost any time in systole or diastole.
The Renal Rheoplethysmogram of the Dog
Authors: BURCH G. E. , PHILLIPS J. H.
Published: June 2012

The renal circulation of the dog was studied by a rheoplethysmographic method capable of simultaneously recording the time courses of volume, rate, and acceleration of inflow, outflow and difference between inflow and outflow of blood. The studies were done first under control conditions and then under conditions of relatively acute circulatory change induced by intravenous injection of norepinephrine and hexamethonium.
Effects of Different Oxygen and Carbon Dioxide Concentrations on the Activity of the Embryonic Chick Heart
Authors: PAFF GEORGE H. , BOUCEK ROBERT J.
Published: June 2012

The 72 hour chick embryo heart reacts to progressive hypoxia by the appearance of arrhythmias and asystole. In the presence of 4 per cent CO
2
, complete anoxia is tolerated for a period of 30 min. with carbon dioxide apparently augmenting the buffering capacity of the plasma clot which supports the heart. A gaseous environment of 4 per cent O
2
/4 per cent CO
2
/92 per cent N
2
induced a steady and entirely reversible state of cardiac stress.
Cardiac Output in Rats During the Development of Cardiac Hypertrophy
Authors: BEZNAK MARGARET
Published: June 2012

Cardiac output, reserve force of the heart, total peripheral resistance and weights of the heart and other organs were determined in normal rats, and in rats at different times after their aortas were narrowed just below the diaphragm. Although the output of the hypertrophied heart was normal, its reserve force was greater.
Effect of Unilateral Anoxia on Pulmonary Circulation
Authors: LANARI-ZUBIAUR FELIPE J. , HAMILTON W. F.
Published: June 2012

Measurements were made of venous drainage from the right and left lower lobes of dogs' lungs. Blood supply was normal and breathing spontaneous. One lung was ventilated with air or oxygen and the other with nitrogen. Control and experimental flows were highly variable and though the anoxic lung received a smaller flow that was significantly different, the physiologic consequence of this fact is doubtful.
Effect of Acute Mitral Insufficiency of Various Degrees on Mean Arterial Blood Pressure, Coronary Blood Flow Cardiac Output and Oxygen Consumption
Authors: WÉGRIA RENÉ , MUELHEIMS GERHARD , JREISSATY ROBERT , NAKANO JIRO
Published: June 2012

In anesthetized dog, acute mitral insufficiency of variable severity results in an increase in coronary blood flow and myocardial oxygen consumption. The increase in oxygen consumption is interpreted as meaning either that the left ventricle expends a significant amount of energy in regurgitating blood into the left atrium during mitral insufficiency, or that mitral insufficiency induces a decrease of the efficiency of the left ventricle or both.
Respiratory Responses to Experimental Unilobar Pulmonary Edema
Authors: GRAY FRANK D. , SHEDD DONALD P. , KATO EIICHI
Published: June 2012

The effect of unilobar engorgement and edema in a dog's lung on the effort of breathing was studied by expressing the latter as the velocity of air-flow attained per unit of pressure change across the lung, and as static compliance. Edema of the left lower lobe, produced by shunting blood from the femoral into the pulmonary artery, affected the effort of breathing only at high infusion rates and volumes, otherwise changes in resting (mid) position and respiratory rate kept the effort of breathing constant. Static compliance decreased with infusion, possibly because the infused blood encroached on the air space.
Standing-Wave Components in Arterial Pulses of Hypothermic Dogs
Authors: ALEXANDER ROBERT S. , pindar J.
Published: June 2012

Anesthetized dogs were artificially cooled to temperatures at which a marked prolongation of systole was observed. Under these conditions, it was possible to identify undulations in pressure during the prolonged systole without confusion with incisural pressure changes. These pressure undulations in the aortic arch were observed to occur simultaneously with but in opposite phase relations to the primary peak and dicrotic oscillations recorded from the femoral artery. This evidence offers additional support to the standing-wave theory.
Oxygen Uptake of the Nonworking Left Ventricle
Authors: MCKEEVER W. P. , GREGG D. E. , CANNEY P. C.
Published: June 2012

Comparisons have been made in the open chest dog of the oxygen usage of the left ventricle whose external work has been reduced to zero by 4 different procedures. The average oxygen usage of the left myocardium/100 Gm./min. is about 2.0 cc. in complete arrest with vagal stimulation or with intracoronary potassium injection; 3.8 cc. in fibrillation; and 3.4 cc. in the empty but beating heart. The oxygen value in the arrested heart approximates 27 per cent of that in the control state and the uptake during vagal stoppage varies directly with the control metabolic level. In the fibrillating ventricle the higher values are related to the intensity of fibrillatory movements, and in the empty beating heart to the control metabolic rate and to the frequency of the heart beat. The experiments with vagal arrest also permit estimation of the oxygen debt of the myocardium.
Effect of Glucose on Appearance of Plasma-Clotting Accelerator Activity, Lactescence, and Plasma Lipids in Fat-Fed Dogs
Authors: TILDEN JOHN H. , SHIPLEY R. E.
Published: June 2012

The influence of glucose, given orally and intravenously, on the acceleration of plasma clotting and appearance of lipemia following the feeding of peanut oil was determined in dogs. Oral glucose blocked or masked the appearance of plasma lactescence and clotting accelerator activity, whereas intravenous administration tended to delay their appearance. In other experiments heparin abolished or reduced plasma lactescence without modifying clotting accelerator activity induced by fat feeding.
Further Observations on the Effects of Thyroid Hormone Preparations on Cholesterolemia and Atherogenesis in Cholesterol-Fed Cockerels
Authors: STAMLER J. , PICK R. , KATZ L. N.
Published: June 2012

Administration of large doses of thyroid hormone preparations (desiccated thyroid powder, thyroxine, triiodothyronine, diiodotyrosine) to cholesterol-fed chicks was associated with decreased rate of weight gain and partial inhibition of hypercholesterolemia. Consistent, definitive inhibition of aorta and coronary atherogenesis was not observed, despite partial suppression of hypercholesterolemia. Potassium iodide and thyroid-stimulating hormone of the anterior pituitary were essentially without effect.
Intestinal vasodilation by epoxyeicosatrienoic acids: arachidonic acid metabolites produced by a cytochrome P450 monooxygenase.
Authors: Proctor K G , Falck J R , Capdevila J
Published: June 2012

Purified synthetic products from the cytochrome P450 pathway of arachidonate metabolism were applied to the intestinal serosa. Arteriolar blood flow was calculated using video microscopy. After a steady-state baseline, a bolus containing 10-60 micrograms 14,15-epoxyeicosatrienoic acid/ml (14,15-EET) had no detectable effect on blood flow. However, 25 +/- 3 micrograms 11,12-EET/ml and 36 +/- 2 micrograms 8,9-EET/ml caused increases (134 +/- 8% and 127 +/- 6%) that were similar to those elicited by 8 +/- 2 micrograms adenosine/ml (138 +/- 12%). Furthermore, the increases (275 +/- 38%) produced by 32 +/- 6 micrograms 5,6-EET/ml exceeded those elicited (160 +/- 10%) by a similar concentration (27 +/- 3 micrograms/ml) of adenosine. Thus, a structure-activity relationship is suggested. Nevertheless, these values probably underestimate the potency of the EETs because the vasoactivity was reduced by contact with water. The activity of the cyclooxygenase pathway seemed to limit the formation of vasoactive quantities of EETs, or other nonprostanoids, from exogenous arachidonate in the serosa but not the mucosa. A bolus (1.3 +/- 0.2 mg/ml) or continuous application (122 +/- 45 micrograms/ml) of arachidonate caused blood flow increases (236 +/- 14% or 229 +/- 27%) that were almost eliminated (129 +/- 5% or 121 +/- 9%) by a cyclooxygenase inhibitor; the residual response was abolished by a cytochrome P450 inhibitor. However, cytochrome P450 inhibitors alone did not attenuate the arachidonate response. In contrast, a continuous application of 194 micrograms arachidonate/ml to the mucosa caused a markedly smaller blood flow increase (119 +/- 8%) and cyclooxygenase inhibitors potentiated (132 +/- 8%), rather than reduced, this response. We conclude that EETs are a labile class of vasodilators with a potency comparable to adenosine in the intestinal microcirculation. Indirect evidence suggests regional differences in the formation of vasoactive quantities of arachidonate metabolites within the intestinal wall.
Myocardial contractile function during ischemia and hypoxia.
Authors: Allen D G , Orchard C H
Published: June 2012

There is good evidence that elevated [Ca2+]i, produced by an influx of Ca2+ in exchange for Na+, is the underlying pathology in reperfusion or reoxygenation damage. Further measurements of [Na+]i and [Ca2+]i during ischemia and reperfusion, coupled with information about metabolic levels, are needed to confirm or refute this hypothesis. Contributions to cell damage by other mechanisms, e.g., oxygen free radicals, certainly cannot yet be excluded.
Antihypertensive drug therapy prevents cerebral microvascular abnormalities in hypertensive rats.
Authors: Harper S L
Published: June 2012

Studies were performed on anesthetized 16-18 week old normotensive Wistar-Kyoto rats, spontaneously hypertensive rats, and Goldblatt two-kidney one clip renal hypertensive rats, treated from age 4-5 weeks with an oral antihypertensive regimen consisting of hydralazine, reserpine, and chlorothiazide. Measurements of flow and intravascular pressure in the cerebral microvasculature were made via a constantly suffused open cranial window using video microscopy. A significant upward shift was seen in the pressure range for cerebral blood flow autoregulation in both groups of untreated hypertensive animals. Following treatment, the autoregulatory range in both hypertensive models was restored to a level nearly identical to control. The prevention of this shift in treated animals was due primarily to the prevention of structural microvascular adaptations that occur in untreated hypertensive animals. By preventing elevations in microvascular pressure, treatment may have eliminated the major stimulus for development of hypertrophy in resistance vessels. However, a persistent increment of arteriolar wall mass in treated spontaneously hypertensive rats may represent a hyperplastic response not influenced by treatment. Likewise, a persistent constriction of the smallest arterioles in treated renal hypertensive rats may represent a differential sensitivity of microvessels to circulating vasoactive agents. It appears that treatment initiated in the prehypertensive state, or before significant sustained hypertension has occurred, can markedly reduce the cerebrovascular morbidity associated with two different forms of hypertension.
Electron probe x-ray microanalysis of sarcolemma and junctional sarcoplasmic reticulum in rabbit papillary muscles: low sodium-induced calcium alterations.
Authors: Wheeler-Clark E S , Tormey J M
Published: June 2012

This project was undertaken to determine whether electron probe x-ray microanalysis (microprobe analysis) could be utilized to determine the subcellular sites responsible for low sodium-induced calcium accumulation in myocardium. Ultrathin cryosections of rabbit papillary muscles were analyzed using microprobe analysis, and the concentrations (mmol/kg dry wt) of Na, Mg, I, S, Cl, K, and Ca were compared against low sodium (36 mM) and control (139 mM NaCl) muscle groups. Visual resolution of junctional sarcoplasmic reticulum in freeze-dried myocardial sections was achieved, and systematic analysis of junctional sarcoplasmic reticulum and sarcolemma was performed. Myofibrils and mitochondria were also analyzed. Reductions in Na and Cl concentration were measured in virtually all compartments of muscles bathed in low sodium. In addition, low sodium produced a doubling of junctional sarcoplasmic reticulum and sarcolemmal calcium concentrations (p less than 0.01). No significant changes in calcium were observed at other analyzed sites. The increased calcium at the junctional sarcoplasmic reticulum and sarcolemma correlates with (but may not completely account for) the threefold increase in contractility measured after 40 minutes in low sodium concentrations. This work demonstrates that elemental changes associated with the myocardial junctional sarcoplasmic reticulum and sarcolemma are amenable to direct, in situ microprobe analysis and further defines these structures as primary sites of calcium accumulation in low sodium concentrations.
Disruption of myofibrillar energy use: dual mechanisms that may contribute to postischemic dysfunction in stunned myocardium.
Authors: Greenfield R A , Swain J L
Published: June 2012

The abnormalities in regional function produced by myocardial ischemia persist after the ischemic episode resolves. Since a close functional coupling exists between myofibrillar creatine kinase and myosin ATPase, a disruption of this coupling could adversely influence myocardial function and might provide a mechanism for the myocardial dysfunction observed. The purpose of the present study was to determine if an alteration in the activity of creatine kinase associated with the myofibril occurs in the postischemic period. Anesthetized open-chest dogs (n = 6) underwent coronary occlusion for 15 minutes, followed by reperfusion for 15 minutes. In reperfused myocardium, adenine nucleotide content was decreased (72 +/- 10% of nonischemic myocardium, p less than 0.05), documenting the presence of previous ischemia. The creatine phosphate content of reperfused myocardium returned to normal, indicating resumption of myocardial energy production. The creatine kinase activity of purified myofibrils isolated from reperfused myocardium was decreased by 17 +/- 7% compared to that of nonischemic myofibrils (p less than 0.03). In addition, the free adenosine diphosphate concentration in reperfused myocardium was calculated to be 96 microM and was less than the Km of adenosine diphosphate determined for myofibrillar creatine kinase (105 microM). The results suggest two putative mechanisms for disruption of energy use in postischemic myocardium: decreased creatine kinase activity associated with the myofibril, and limitation of substrate necessary for maximal creatine kinase activity.
In vivo characterization of synthetic thromboxane A2 in canine myocardium.
Authors: Holzgrefe H H , Buchanan L V , Bunting S
Published: June 2012

Recently, total chemical synthesis of thromboxane was achieved. The in vitro activity of synthetic thromboxane A2 is indistinguishable from biologically generated material. The present study describes the in vivo characterization of synthetic thromboxane A2 on the regional blood flow distribution of the canine heart. Local injections of synthetic thromboxane A2 into the coronary vasculature caused marked reductions in coronary blood flow, measured by both radiolabeled microsphere injection and an electromagnetic flow device. The threshold concentration required to bring about this effect varied greatly between dogs and ranged from 0.125 microgram/kg to 2.0 micrograms/kg. Similarly, the dose of thromboxane A2 required to aggregate dog platelets in vitro varied from 30 ng/ml to 1,000 ng/ml. Bolus injections of 2 micrograms/ml thromboxane A2 into the circumflex or left anterior coronary artery resulted in a simultaneous reduction in platelet count in coronary sinus blood of 83 +/- 5.2% (mean +/- SEM, n = 4, p = .0005). Both flow reduction and platelet effects were transient and localized. The time taken from onset to recovery of the response to control levels was 77 +/- 6.0 seconds (mean +/- SEM) for flow and 70-80 seconds for platelet count. Injections of thromboxane A2 caused a small but significant increase in heart rate with no change in systemic blood pressure. In conclusion, the in vivo actions of synthetic thromboxane A2 are consistent with the vasoconstrictor and platelet aggregatory effects seen in vitro, but dogs vary considerably in their sensitivity.
Isozyme specific modification of myosin ATPase by cAMP in rat heart.
Authors: Winegrad S , Weisberg A
Published: June 2012

The total ATPase activity of myosin and the values for the isozyme V1 have been measured in hearts from rats of different ages and with different levels of thyroid function. The contribution of V3 was calculated from the difference between total and V1 ATPase, neglecting the small contribution of V2. Hearts were quickly frozen after rapid removal from the animals in order to preserve the state of ATPase activity that existed in the intact animal, and ATPase activity was measured in thin sections of tissue by a microphotometric technique. In euthyroid hearts, although cAMP increases total myosin ATPase activity and the activity of V1, the cyclic nucleotide inhibits the ATPase activity of V3. In hearts from rats with developing hypothyroidism following thyroidectomy, the same occurs. After a sufficient period has elapsed after thyroidectomy for V1 to have practically disappeared, cAMP has no effect on ATPase activity, but the injection of thyroid hormone restores the effect. Total myosin ATPase activity is maintained relatively constant as the animal ages from 80 to 165 days and during the first 10-11 days following thyroidectomy even though the concentration of V1 is dropping. The explanation proposed for these observations is that myosin can exist in two different forms, only one of which can participate in the active generation of force. The transition between the two forms is regulated by a soluble factor that is itself controlled by the adrenergic system. The factor(s) involved in this regulatory mechanism is soluble and can be transferred between different thin sections cut from a frozen heart.
Cytoskeletal damage during myocardial ischemia: changes in vinculin immunofluorescence staining during total in vitro ischemia in canine heart.
Authors: Steenbergen C , Hill M L , Jennings R B
Published: June 2012

The role of cytoskeletal damage in the disruption of the plasma membrane observed during myocardial ischemia has been studied using antibodies to vinculin to identify changes in the distribution of this membrane associated cytoskeletal protein. Vinculin is a component of the cytoskeletal attachment complex between the plasma membrane and the Z-line of the underlying myofibrils. The effects of varying periods of total ischemia on the localization of vinculin were assessed by immunofluorescence and evidence of membrane disruption was evaluated by electron microscopy. Thin tissue slices prepared from the ischemic tissue were incubated in oxygenated Krebs-Ringer phosphate buffer at 37 degrees C to assess inulin permeability, ultrastructure, and any changes in the distribution of vinculin associated with incubation. The previously reported costameric pattern of vinculin staining was observed in longitudinal sections of control myocardium, myocardium subjected to 60 minutes of total ischemia, and myocardium subjected to 60 minutes of ischemia followed by 60 minutes of incubation in oxygenated media. Electron microscopy and inulin permeability measurements confirmed that plasma membrane integrity was preserved under these conditions. However, when the duration of total ischemia was extended to 120 minutes or longer, there was a progressive loss of vinculin staining along the lateral margin of myocytes. This change correlates with the appearance of subsarcolemmal blebs and breaks in the plasma membranes observed by electron microscopy and confirmed by the increase in inulin permeability observed in tissue slices.(ABSTRACT TRUNCATED AT 250 WORDS)
Release of endothelium-derived relaxing factor from human umbilical vessels.
Authors: Van de Voorde J , Vanderstichele H , Leusen I
Published: June 2012

The ability of human umbilical endothelial cells to release relaxing substance(s) in response to different agonists was investigated. Endothelium-denuded aortic rings of rats were used for the bioassay and tension recording. After precontraction, this preparation showed no response to histamine, acetylcholine, A 23187, or adenosine triphosphate while serotonin elicited further contraction. Superfusion of the precontracted preparations with the perfusate from umbilical veins and arteries stimulated with histamine (10(-7)-10(-5) M), A23187 (10(-7)-10(-6) M), or adenosine triphosphate (10(-5)-10(-4) M) elicited a relaxation. No relaxation was obtained with acetylcholine (10(-8)-10(-6) M) or serotonin (10(-8)-10(-6) M). The relaxation of bioassay aortic rings under the influence of the perfusate from histamine-stimulated umbilical vessels was inhibited by mepyramine (10(-5) M) but not by cimetidine (10(-4) M) suggesting the involvement of H1-receptors. The relaxation was also inhibited by increasing the transit time between the donor and the detector preparation, by methylene blue (5 X 10(-5) M), and by nordihydroguaiaretic acid (5 X 10(-5) M) but not by indomethacin (5 X 10(-5) M), and which have been reported for endothelium-derived relaxing factor. The involvement of umbilical endothelial cells in the relaxation response was further confirmed by studying precontracted, rubbed rat aortic rings seeded with cultured endothelial cells from human umbilical veins. Such preparations relaxed in response to histamine (10(-7)-10(-4) M) in contrast with the control preparations. No relaxations of these preparations were observed in response to acetylcholine (10(-9)-10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Whole-cell and single-channel calcium currents of isolated smooth muscle cells from saphenous vein.
Authors: Yatani A , Seidel C L , Allen J , Brown A M
Published: June 2012

Whole-cell and single-channel calcium currents in enzymatically isolated dog saphenous vein cells were recorded by the patch-clamp method. Test pulses to negative potentials from holding potentials of -90 to -40 mV elicited currents that inactivated quickly and in a voltage-dependent manner (called I low for low threshold). A second calcium current persisted even at relatively positive holding potentials of -30 to -10 mV, required stronger depolarizations for maximum current, and inactivated slowly (I high for high threshold). I high transported barium more than calcium, whereas I low transported the two ions equally. Single-channel current records (90 mM barium) showed a larger conductance that activated at relatively positive potentials and a smaller (about one-third) conductance that activated at weak depolarizations. Nitrendipine suppressed I high, and the effect was voltage dependent as observed in cardiac cells, although block of resting channels was much greater in vein cells (KR approximately 10(-8) M). Exposure to the stereoisomer (-)Bay K 8644 increased I high but not I low. The (-)Bay K 8644 also increased the channel activity and prolonged the open time of the larger conductance current. Thus, two types of calcium channels, differing in potential-dependence of activation and inactivation, calcium/barium selectivity, single-channel conductance, and sensitivities to dihydropyridines were identified in smooth muscle cells isolated from a large cutaneous vein.
Cardiac calmodulin-stimulated protein phosphatase: purification and identification of specific sarcolemmal substrates.
Authors: Manalan A S , Werth D K
Published: June 2012

A calmodulin-stimulated protein phosphatase has been purified from bovine myocardium. The purification procedure involves sequential DEAE-Sephacel ion exchange chromatography, calmodulin-Sepharose affinity chromatography, and high performance liquid chromatography using a Spherogel TSK DEAE 5PW column. By SDS polyacrylamide gel electrophoresis, the purified cardiac phosphatase consists of two subunits of Mr 61,000 and 19,000, similar to the brain enzyme, calcineurin. Protein phosphatase activity of the cardiac enzyme is stimulated by Ca2+-calmodulin and inhibited by the calmodulin antagonist drug, calmidazolium. Effects of a series of divalent cations on catalytic activity of the cardiac calmodulin-stimulated protein phosphatase are similar to those observed with calcineurin, when the two enzymes are assayed under identical conditions. Highly enriched preparations of bovine cardiac sarcolemma contain substrates of cAMP-dependent protein kinase of Mr 166 K, 133 K, 108 K, 79 K, 39 K, and 14 K, which are specifically dephosphorylated by the calmodulin-stimulated phosphatase with pseudofirst-order rate constants of 0.23, 0.46, 0.69, 0.35, 0.69, and 0.115 min-1, respectively. These substrates are not present in purified preparations of cardiac sarcoplasmic reticulum. These results support a role of the calmodulin-stimulated phosphatase in the Ca2+-regulation of specific sarcolemmal processes by protein dephosphorylation.
Hypothyroidism delays ischemia-induced contracture and adenine nucleotide depletion in rat myocardium.
Authors: Carter L S , Mueller R A , Norfleet E A , Payne F B , Saltzman L S
Published: June 2012

Isolated perfused paced hearts from rats rendered hypothyroid by chronic administration of propylthiouracil have a delayed onset of ischemia-induced myocardial contracture in contrast to hearts from control rats. In addition, the time to reach maximum contracture is delayed, and the magnitude of the contracture pressure is reduced. Preischemia myocardial adenosine triphosphate (ATP) values in the hypothyroid rat hearts are similar to those of control, but the rate of decrease in ATP is slower in the hearts of hypothyroid rats. Thus, it appears that in the hypothyroid state the development of ischemic contracture is associated with a slower fall of ATP.