bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosine production in the ischemic kidney.
Authors: Miller W L , Thomas R A , Berne R M , Rubio R
Published: June 2012

We conducted experiments to determine (1) tissue, blood, and urine levels of adenosine produced by the ischemic kidney under conditions of renal artery occlusion, and (2) the site(s) of production and release of adenosine by the kidney. Concentrations of adenosine, inosine, and hypoxanthine in the dog urine were found to increase after 2 minutes of renal artery occlusion as were concentrations of these metabolites in renal tissue after 10 minutes of renal artery occlusion. Renal venous plasma levels of inosine and hypoxanthine also were elevated after 3 minutes of arterial occlusion. In modified stop-flow experiments, adenosine appeared in the urine in a peak that corresponded most closely with proximal tubule fluid. 5'-Nucleotidase, the enzyme which catalyzes the dephosphorylation of 5'-AMP or 5'-IMP to adenosine or inosine, respectively, was found to be located primarily on the external membranes and mitochondria of proximal tubule cells, but not in distal tubule or collecting duct cells. Since adenosine has been demonstrated to elicit renal vasoconstriction and is produced by the ischemic kidney, it is suggested that adenosine may be involved in the mediation of postocclusion renal ischemia.
Subpressor angiotensin infusion, renal sodium handling, and salt-induced hypertension in the dog.
Authors: DeClue J W , Guyton A C , Cowley A W , Coleman T G , Norman R A , McCaa R E
Published: June 2012

We studied the combined effect of subpressor amounts of angiotensin and long-term sodium chloride infusion on arterial pressure in 16 dogs for periods of 2--8 weeks. In dogs receiving 3.5 liters of isotonic NaCl daily, but no angiotensin, the arterial pressure increased an average of only 3 mm Hg. When angiotensin was infused continuously at a rate of 5 ng/kg per min (a rate too small to cause an observable immediate increase in pressure, subsequent infusion of 3.5 liters of saline daily then increased the pressure by 39 mm Hg. The urinary output of sodium increased to the same extent in both instances, that is, there was no extra sodium loss because of the elevated pressure. This suggests that the angiotensin significantly blocked the normal "pressure natriuresis" usually seen with such large increases in pressure. However, the plasma aldosterone levels during angiotensin infusion were not found to be different from those in the absence of angiotensin. Therefore, we have suggested that the tendency of the kidneys to retain sodium under the influence of angiotensin was probably caused mainly by a direct effect of angiotensin on the kidney itself. Such a direct renal sodium-retaining effect also could be a contributing factor in the marked hypertension that results from salt administration in the presence of small amounts of angiotensin.
Role of the peripheral vasculature in changes in venous return caused by isoproterenol, norepinephrine, and methoxamine in anesthetized dogs.
Authors: Imai Y , Satoh K , Taira N
Published: June 2012

We studied effects on venous return of alpha- and beta-adrenergic agonists in anesthetized dogs. Blood from the superior and inferior venae cavae (venous return) was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant rate. Isoproterenol infused into the ascending aorta or the right atrium increased the venous return and heart rate and decreased systemic blood pressure. The increase in venous return produced by isoproterenol given into the right atrium was not significantly different from that produced by isoproterenol administered into the ascending aorta, although the increase in heart rate was more marked with the latter route of administration. Norepinephrine infused into the ascending aorta increased the systemic blood pressure, venous return, and heart rate. Methoxamine infused into the ascending aorta increased the systemic blood pressure and decreased the venous return but produced no change in heart rate. Isoproterenol increased the venous return even when the sinoaortic baroreceptor reflex was eliminated. Propranolol abolished the increase in venous return caused by isoproterenol and reversed the increase in venous return caused by norepinephrine. The results suggest that a decrease in venous resistance mediated through a beta-adrenergic mechanism is important in increasing venous return, whereas an increase in venous resistance mediated through an alpha-adrenergic mechanism is responsible for a decrease in venous return.
The distribution of blood rheological parameters in the microvasculature of cat mesentery.
Authors: Lipowsky H H , Kovalcheck S , Zweifach B W
Published: June 2012

In vivo studies of the rheological behavior of blood in the microcirculation were conducted by direct in situ measurements in cat mesentery. Upstream to downstream pressure drops were measured in unbranched arterioles, capillaries, and venules, with diameters from 7 to 58 micrometer. Simultaneous measurements of red cell velocity and vessel geometry facilitated computation of bulk velocity, pressure gradient, apparent viscosity, wall shear stress, and resistance. Arteriovenous distributions of these parameters revealed the following. Maximum pressure gradient (0.015 cm H20/micrometer) occurs in the true capillaries (7 micrometer in diameter); intravascular wall shear stress averaged 47.1 dynes/cm2 in arterioles and 29.0 dynes/cm2 in venules. Extreme values as great as 200 dynes/cm2 were observed in a few shunting arterioles. Apparent viscosity averaged 3.59 cP in arterioles, 5.15 cP in venules, and 4.22 cP overall. Intravascular resistance per unit length of microvessel varied with luminal diameter as a power law function with exponents of -4.04 for arterioles, -3.94 for venules, and -3.99 for all vessels combined. This apparent maintenance of Poiseuille's law is attributed to the opposing processes of hematocrit reduction and decreasing shear rate as blood is dispersed in successive arteriolar segments, and the converse action of these processes in the venous confluences which lessen the extent of network variations in apparent viscosity. Reductions in bulk velocity from the normal flow state to below 0.5 mm/sec resulted in increases in apparent viscosity by a factor of 2 to 10, which are attributed primarily to obstruction of the lumen by leukocyte-endothelium adhesion.
The effects of nifedipine on acute experimental myocardial ischemia and infarction in dogs.
Authors: Selwyn A P , Welman E , Fox K , Horlock P , Pratt T , Klein M
Published: June 2012

We studied 25 anesthetized and thoracotamized dogs before and during 5 hours of acute regional myocardial ischemia. Krypton-81m (81mKr) was infused constantly into the aortic sinuses. The myocardial equilibrium of this tracer was used to image and assess the distribution of regional myocardial perfusion using a gamma camera and digital computer. The epicardial ECG was recorded, S-T segment elevation and the loss of R and appearance of Q waves were measured, and the plasma activity of creatine kinase (CK) was determined in aortic and coronary venous blood throughout these experiments. Ten dogs underwent left anterior descending coronary artery (LAD) narrowing for 5 hours and received no drugs. Five dogs received nifedipine 13 microgram/kg, and another five received 1.0 microgram/kg intravenously 30 minutes after LAD narrowing. Those dogs receiving nifedipine, 13 microgram/kg, showed a 30% fall in aortic pressure, a 12% rise in heart rate, and an extension of regional ischemia. The ECG showed an extension of infarct size, and CK release into the coronary vein appeared earlier than in the controls. Dogs receiving nifedipine, 1 microgram/kg, showed a 12% fall in blood pressure, no rise in heart rate, an improvement in regional perfusion, and ECG signs that suggested limitation of infarct size. There also was delayed release of coronary venous CK. The effects of nifedipine on the natural history of regional myocardial perfusion, the electrocardiogram, and enzyme release from the heart were dose related and cannot be generalized. These observations warrant further clinical investigation to improve the use of this agent in man.
The dilating effect of histamine on pial arteries of cats and its mediation by H2 receptors.
Authors: Wahl M , Kuschinsky W
Published: June 2012

We studied the effect of histamine and H1 or H2 blockers on the diameter of pial arteries (39-227 micron) using microapplication into the perivascular space. Concentration-response curves for histamine showed dilations which started at 10(-7) M and were maximal at 10(-5) and 10(-4) M. The H2 blocker, cimetidine, induced no vascular reaction over the whole concentration range tested (10(-7) to 10(-3) M). The H1 blocker, mepyramine, was not vasoactive in the concentration range from 10(-7) to 5 X 10(-5) M and evoked dilations at higher concentrations. The concentration-response curve for histamine was only slightly displaced by 10(-5) M mepyramine but was significantly shifted to the right by 10(-5) M cimetidine. The dilating effect of histamine could be reduced in a stepwise manner by increasing concentrations of cimetidine. These findings are in accordance with a selective antagonism between histamine and cimetidine at the H2 receptors of smooth muscle cells of pial arteries. The insignificant role of H1 receptors in histamine-induced dilations is supported by the finding that a combination of H1 and H2 blockers resulted in the same reduction of histamine-induced dilation as did the application of the H2 blocker.
Acetylcholine antagonism of the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers.
Authors: Bailey J C , Watanabe A M , Besch H R , Lathrop D A
Published: June 2012

The purpose of these experiments was to determine whether or not acetylcholine modulated the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers. Conventional microelectrode techniques were used. Predictably, isoproterenol produced shortening of action potential duration; acetylcholine significantly blunted this effect of isoproterenol. Isoproterenol restored excitability to fibers exposed to 22 mM potassium solutions, and acetylcholine abolished this isoproterenol-restored excitability. Both of these antagonistic effects of acetylcholine were blocked by atropine. Acetylcholine alone did not affect action potential duration in polarized fibers or excitability in potassium-depolarized fibers. Furthermore, acetylcholine had no effect on the decrease in action potential duration induced by premature electrical stimulation or by acetylstrophanthidin administration, or on excitability of fibers exposed to a zero sodium, high calcium superfusant. These data demonstrate a direct cellular basis for cholinergic antagonism of the electrophysiological effects of beta-adrenergic stimulation of canine cardiac specialized intraventricular conducting tissue.
Central serotonergic agents raise the repetitive extrasystole threshold of the vulnerable period of the canine ventricular myocardium.
Authors: Blatt C M , Rabinowitz S H , Lown B
Published: June 2012

Systemic administration of three central serotonergic agents, melatonin, 5-methoxytryptophol, and 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), produced significant increases in the threshold of the vulnerable period for repetitive electrical activity in the canine cardiac ventricle. MK-212 was effective despite bilateral vagotomy. The specific serotonin antagonist, metergoline, blocked the effect of MK-212 on the threshold. An increase in central serotonergic activity may inhibit the flow of arrhythmogenic sympathetic nerve traffic from the brain to the heart.
Effect of hypoxia on the sinoatrial node, atrium, and atrioventricular node in the rabbit heart.
Authors: Senges J , Mizutani T , Pelzer D , Brachmann J , Sonnhof U , Kübler W
Published: June 2012

We used intracellular microelectrodes to study the effects of hypoxia on the isolated, superfused sinoatrial (SA) node, atrium, and atrioventricular (AV) node of the rabbit heart. Hypoxia decreased the rate of spontaneous impulse initiation in SA nodal fibers by decreasing the slope of diastolic depolarization. With gradually decreasing Po2, the sinus rate was reduced; concomitantly, the corrected sinus node recovery time after rapid atrial stimulation was much less affected demonstrating marked prolongation only under severe anoxic conditions. Hypoxia decreased the amplitude of action potentials of the SA node and of the AV node but not of the atrium. SA and AV nodal conduction were slowed by hypoxia; intraatrial conduction was not significantly affected. AV nodal conduction block occurred at lower atrial rates, and the effective refractory period of the AV node was prolonged. Inhomogeneity of SA and AV nodal impulse propagation often was observed in the presence of hypoxia. This was associated with concealed reentry within both nodal areas. The extracellular K+ concentration of the atrial tissue was measured with ion-sensitive microelectrodes. [K+]o remained unchanged even after prolonged periods of severe hypoxia. These results are consistent with the hypothesis that acute hypoxia predominantly inhibits slow response activity but has only little effect on the fast inward sodium current.
Brain adenosine production in the rat during 60 seconds of ischemia.
Authors: Winn H R , Rubio R , Berne R M
Published: June 2012

In rats, cerebral perfusion pressure were altered abruptly by aortic transection to determine the production by ischemic brain of adenosine and its metabolites, inosine and hypoxanthine. Brain samples were obtained after 0, 5, 10, 15, 30, and 60 seconds of ischemia. Also measured were ATP, ADP, AMP, phosphocreatine (PCr), lactate, and pyruvate. Blood pressure was monitored continuously, and arterial PO2, PCO2, and pH were measured just prior to induction of ischemia. Adenosine was elevated t 2.30 +/- 0.31 (SE) nmol/g at 5 seconds from a control value of 0.96 +/- 0.07. A significant elevation of adenosine continued to 60 seconds (5.50 +/- 1.24). Furthermore, inosine showed a progressive upward trend during the entire 60 seconds of ischemia, whereas no change in hypoxanthine occurred between the moment of transection (31.81 +/- 2.01 nmol/g) and 60 seconds of ischemia (34.72 +/- 2.93). PCr decreased by 1.24 mumol/g within the first 5 seconds. After the onset of hypotension, significant changes did not occur in AMP and ADP until 30 seconds, and in ATP and pyruvate until 60 seconds after aortic transection; lactate was elevated by 10 seconds. The rapid rise of cerebral adenosine within 5 seconds after the onset of ischemia supports a role for adenosine in the regulation of cerebral blood flow.
Sarcomere length-resting tension relation in single frog atrial cardiac cells.
Authors: Tarr M , Trank J W , Leiffer P , Shepherd N
Published: June 2012

It generally has been thought that the relatively high resting tension characteristic of cardiac tissue resides in structures (collagen, elastin) external to the individual cardiac cells, but the evidence to support this conclusion has been indirect, since the resting tension of intact single cardiac cells has not been determined previously. The purpose of the present investigation was to determine the resting tension (stress)-sarcomere length relationships of single intact frog atrial cells. For tension determinations, a single cell was attached between two poly-L-lysine coated glass beams; one beam served as a compliant calibrated cantilevered force beam, and length changes were imposed on the cell by movement of the other beam. Coventional bright-field light microscope techniques were used to view the cell, the sarcomere pattern within the cell, and the position of the force beam. The resting tension of the intact cell increased from a value of about 10 nN at a sarcomere length of 2.35 microns to a value of about 130 nN at a sarcomere length of 3.45 microns. Lagrangian and Eulerian resting stress-sarcomere length relationships were computed from the resting tension-sarcomere length relationships. The Lagrangian stress increased from a value of about 0.6 mN/mm2 at a sarcomere length of 2.35 microns to a value of about 7 mN/mm2 at a sarcomere length of 3.45 microns. These values of stress are about 8- to 30-fold less than those previously reported for intact frog atrial tissue and indicate that the resting tension of intact frog atrial preparations resides primarily in structures external to the individual cardiac cell.
Effects of neural stimuli on blood flow through vasa vasorum in dogs.
Authors: Heistad D D , Marcus M L , Martins J B
Published: June 2012

The purpose of this study was to determine whether neural stimuli alter blood flow through vasa vasorum in the thoracic aorta. We measured flow with microspheres in anesthetized dogs and observed responses to sympathetic stimulation and baroreceptor stimulation. During these interventions, changes in arterial pressure were prevented with propranolol or an arterial reservoir, to minimize indirect effects on vasa vasorum mediated through changes in aortic wall tension. Electrical stimulation of the stellate ganglion at 10 Hz reduced blood flow to vasa vasorum in the thoracic aorta from 11 +/- 1.6 (mean +/- SE to 6.8 +/- 1.1 ml/min per 100 g (p less than 0.05). Aortic diameter, measured with a sonomicrometer technique, did not change during sympathetic stimulation. Thus, the reduction in blood flow through vasa vasorum during sympathetic stimulation appears to be a direct effect, and not the result of constriction of the aorta and compression of vasa. To determine effects of physiological alterations in neurogenic vasoconstrictor activity, we examined responses to stimulation of carotid baroreceptors. When pressure in isolated, perfused carotid sinus baroreceptors was raised from 81 +/- 3 to 198 +/- 2 mm Hg, blood flow to vasa vasorum of the thoracic aorta increased from 3.7 +/- 0.6 to 10 +/- 2.2 ml/min per 100 g (P less than 0.05). We conclude that vasa vasorum are responsive to neural stimuli, since they constrict during sympathetic stimulation and dilate in response to baroreceptor stimulation.
Cardiotonic activity of amrinone--Win 40680 [5-amino-3,4'-bipyridine-6(1H)-one].
Authors: Alousi A A , Farah A E , Lesher G Y , Opalka C J
Published: June 2012

The cardiotonic activity of a new, noncatechol, nonglycoside agent, amrinone, was investigated in vitro and in anesthestized and unanesthetized dogs. Amrinone (3-100 microgram/ml) caused a dose-dependent increase in papillary muscle developed tension and df/dt without significant changes in duration of the contractile cycle or time-to-peak tension. Amrinone induced slight increases in right atrial rate with no changes in electrophysiological properties of the cat papillary muscle or dog Purkinje fibers. In anesthetized dogs, intravenous bolus injections of amrinone at doses ranging from 1 to 10 mg/kg caused increases in cardiac contractile force and left ventricular dp/dt max with relatively small changes in heart rate and blood pressure. No significant changes in lead II ECG were observed. In unanesthetized dogs, intravenous infusion of amrinone (10-100 microgram/kg per min) caused increases in left ventricular dp/dt max and only small changes in heart rate and blood pressure. Amrinone, tested orally in this model at doses of 2-10 mg/kg, produced a positive inotropic effect with a rapid onset and long duration of action. The inotropic response to amrinone was not blocked by propranolol, dibenzyline, chlorisondamine, atropine, metiamide, or reserpine. Amrinone's inotropic response was not associated with significant alterations in cardiac norepinephrine, phosphodiesterase, cyclic AMP, or Na+, K+-activated ATPase.
Pulmonary leukostasis and its relationship to pulmonary dysfunction in sheep and rabbits.
Authors: Fountain S W , Martin B A , Musclow C E , Cooper J D
Published: June 2012

Pulmonary leukostasis, as a result of complement activation, has been invoked as a cause of pulmonary dysfunction. To investigate this phenomenon, we studied the pulmonary response to infusion of autologous complement-activated plasma in sheep and rabbits. Complement activation was produced by plasma incubation with zymosan. Leukopenia, with selective loss of polymorphonuclear leukocytes into the lungs, occurred in all animals immediately after the onset of plasma infusion. Complement-activated plasma infusion in sheep produced a significant fall in the arterial PO2 and a marked rise in pulmonary vascular resistance, whereas no such effects were observed in rabbits. Pretreatment of the sheep with sulfinpyrazone eliminated the pulmonary response to complement-activated plasma without altering the leukopenic response. Pulmonary histology in rabbits and sheep confirmed the presence of intracapillary leukostasis after the plasma infusions, whether or not sulfinpyrazone had been administered previously. The pulmonary response to complement activation is associated with pulmonary capillary leukostasis, but leukostasis alone is not an adequate explanation of the phenomenon.
The mechanism of alpha-adrenergic activation of the dog coronary artery.
Authors: van Breemen C , Siegel B
Published: June 2012

Norepinephrine (NE) activates isolated coronary conduit arteries by stimulating Ca2+ uptake into the smooth muscle cells. Blockade of Ca2+ influx by removal of Ca2+ from the bathing medium or addition of 10 mM LaCl3 prevents the NE-induced contraction in the dog coronary artery but still allows NE to induce a rapid transient contraction in the rabbit aorta. Under these conditions, NE stimulates 45Ca2+ efflux from rabbit aorta but fails to do so in the coronary artery. The difference in behaviour between the two arteries is attributed by the presence of an intracellular NE-sensitive Ca2+ fraction in the rabbit aorta and its absence from the dog coronary artery. This difference also explains the much greater sensitivity of the NE-induced contractions in the dog coronary to the relaxant effects of the Ca2+ antagonists, D600 and SKF525A, than that seen in the rabbit aorta. High K+-induced contractions of both the coronary artery and the aorta are equally sensitive to the Ca2+ antagonists.
Prostaglandins and potassium relaxation in vascular smooth muscle of the rat. The role of Na-K ATPase.
Authors: Lockette W E , Webb R C , Bohr D F
Published: June 2012

We explored the hypothesis that postaglandin-induced vasodilation is caused by activation of the electrogenic sodium-potassium pump which results in membrane hyperpolarization and relaxation of vascular smooth muscle. Helical strips of rat tail artery relax in response to potassium after norepinephrine-induced contractions in physiological salt solution containing a low-potassium concentration. The amplitude of this potassium relaxation is used as an index of sodium-potassium ATPase activity. It was observed that PGA1, PGE2, and PGF2alpha (10(-6) g/ml) significantly enhanced the magnitut. PGE2 caused relaxation of contractions induced by either 25 mM KCl or norepinephrine (10(-9) g/ml), and these relaxations were inhibited by 10(-4) M ouabain. Indomethacin (5.3 x 10(-6) g/ml) and meclofenamate (10(-6) g/ml) reduced the magnitude of potassium-induced relaxation by more than 30% of control. PGF2alpha (10(-5) g/ml) reversed the inhibition of potassium relaxation by meclofenamate. These observations suggest that prostaglandins induce vascular smooth muscle relaxation by stimulation of the sodium pump and that endogenous prostaglandins normally potassium relaxation.
The elastic modulus of canine aortic valve leaflets in vivo and in vitro.
Authors: Thubrikar M , Piepgrass W C , Bosher L P , Nolan S P
Published: June 2012

Aortic valve leaflets undergo extraordinary flexion due to the complete reversal of their curvature during billions of cardiac cycles. The flexion stresses in the leaflet depend on its elastic modulus which we investigated in vivo and in vitro. In six dogs, we placed radiopaque markers on an aortic leaflet. Leaflet length was calculated from the marker positions recorded fluoroscopically. Aortic and ventricular pressures were recorded. Dogs were killed and leaflet stress-strain curves determined in vitro. Leaflet length in vivo decreased 10.4 +/- 4.7% from diastole to systole in each cardiac cycle. Using the law of LaPlace, pressure gradients across the leaflets were converted into the stresses in the leaflets. The leaflets had an initial "elastic phase" of low modulus in systole followed by an "inelastic phase" of high modulus in diastole. The elastic modulus was 2.4 +/- 0.7 x 10(6) dynes/cm2 in systole and 5.2 +/- 1.7 x 10(7) dynes/cm2 in diastole. These results were similar to those obtained in vitro. Since flexion rigidity is proportional to (elastic modulus) x (thickness)3, the lower modulus in systole greatly reduces flexion stresses in the leaflet and increases leaflet longevity. The higher elastic modulus in diastole prevents excessive bulging or prolapse of the leaflet while it is subjected to the diastolic pressure gradient. We conclude that a natural or prosthetic leaflet which is thickened or has a high elastic modulus throughout the cardiac cycle will have a greater flexion stress that could cause early failure.
Altered myocardial mechanics in diabetic rats.
Authors: Fein F S , Kornstein L B , Strobeck J E , Capasso J M , Sonnenblick E H
Published: June 2012

Diabetes mellitus is associated frequently with congestive heart failure in humans, even in the absence of associated coronary disease or hypertension. Nevertheless, the effects of the diabetic state on myocardial mechanics have not been studied. Accordingly, diabetes was induced in female Wistar rats by injection of streptozotocin (60 mg/kg). Left ventricular papillary muscles were studied 5, 10, and 30 weeks later and compared with controls. Relaxation was delayed significantly and velocity of shortening was depressed at all loads. However, the passive and active force-length curves, as well as the series elastic properties, were not altered. The changes in cardiac performance were found over a range of muscle lengths, stimulus frequencies, and bath concentrations of calcium, glucose, and norepinephrine. The duration of diabetes had no major effect on the mechanical changes observed. The possible influences of drug-induced cardiac toxicity, malnutrition, and altered thyroid hormone levels have been considered; the latter two factors could not be excluded completely from having some influence on the mechanical properties of diabetic cardiac muscle. Evidence is cited showing abnormalities in calcium uptake by sarcoplasmic reticulum and depressed actomyosin ATPase activity. Thus a cardiomyopathic state has been produced in the rat consequent to the induction of experimental diabetes mellitus. Various mechanisms for this entity have been suggested.
Effects of cholinergic nerves on cerebral blood flow in cats.
Authors: Busija D W , Heistad D D
Published: June 2012

We studied the effects of parasympathetic nerves on cerebral blood flow (CBF). The greater superficial petrosal nerve, which apparently supplies cholinergic fibers to cerebral vessels and the lacrimal gland, was sectioned on one side at the internal auditory meatus in anesthetized cats. CBF was measured with 15-microns microspheres. Section of the petrosal nerve did not alter resting CBF. In addition, electrical stimulation of the distal cut end of the petrosal nerve had no effect on total CBF. In one area of the brain, the caudate nucleus, stimulation increased blood flow from 29 +/- 2 to 36 +/- 2 (mean +/- SE) ml/min per 100 g. Lacrimal gland blood flow increased from 42 +/- 7 to 198 +/- 32 ml/min per 100 g during petrosal stimulation, which indicates that the stimulus was potent. In the same experiments, CBF increased 3- to 4-fold during hypercapnia; thus, cerebral vessels were responsive to another dilator stimulus. In other experiments, petrosal nerve section did not alter the response of cerebral vessels to hypercapnia (PCO2 > 50 mm Hg) or hypoxia (PO2 < 34 mm Hg). We conclude: (1) there is little or no resting vasodilator tone provided to cerebral vessels by the petrosal nerve; (2) petrosal nerve stimulation has a major effect on blood flow to the lacrimal gland but does not increase CBF; and (3) petrosal nerve section has little effect on the response of cerebral vessels to hypercapnia or hypoxia.
Inhibition by free radical scavengers and by cyclooxygenase inhibitors of pial arteriolar abnormalities from concussive brain injury in cats.
Authors: Wei E P , Kontos H A , Dietrich W D , Povlishock J T , Ellis E F
Published: June 2012

We studied the role of prostaglandins and free radicals in the induction of the functional and morphological pial arteriolar abnormalities produced by concussive brain injury. Anesthetized cats equipped with a cranial window for the observation of the pial microcirculation were subjected to concussive brain injury using a fluid-percussion device following administration of cyclooxygenase inhibitors (indomethacin or AHR-5850) or the vehicle for the solution of these agents (NaCl or Na2CO3 solution). Pial arterioles from vehicle-treated animals displayed sustained dilation, reduced responsiveness to the vasoconstrictor effect of arterial hypocapnia, and a high density of endothelial lesions. Animals pretreated with cyclooxygenase inhibitors showed less pronounced vasodilation, normal responsiveness to hypocapnia, and a significantly reduced number of lesions. The vasodilation and reduced responsiveness to the vasoconstrictor effects of hypocapnia after brain injury also were inhibited by topical application of free radical scavengers (nitroblue tetrazolium, superoxide dismutase, or mannitol). The vessels from cats pretreated with free radical scavengers also had a lower density of endothelial lesions than controls. The results support the view that the immediate cause of cerebral arteriolar damage in concussive brain injury is the generation of free oxygen radicals associated with increased prostaglandin synthesis.
Mechanisms mediating the coronary vascular response to behavioral stress in the dog.
Authors: Billman G E , Randall D C
Published: June 2012

Left circumflex coronary blood flow (CBF) was measured in eight mongrel dogs with 8 MHz continuous wave Doppler flow transducers during classical aversive conditioning. The cardiovascular condition response consisted of significant (P less than 0.01) increases in: (1) mean aortic pressure (16.1%), (2) d(left ventricular pressure)/dt (64.2%), and (3) heart rate (63.2%). The coronary vascular response to behavioral stress consisted of an initial late diastolic decrease in CBF (12.5%) between 5 and 10 seconds after conditional stimulus onset, followed by a significant increase in CBF (96.8%). Concurrently, late diastolic coronary vascular resistance (CVR) first significantly increased (21.9%), then significantly decreased (39.8%). The increase in CVR was attenuated by cardiac pacing and converted into a significant decrease after alpha-receptor blockade. The decrease in CVR was reduced either by cardiac pacing or cardioselective beta-receptor blockage and eliminated by the combination of alpha- and beta-receptor blockade. Thus, these data indicate that the coronary vascular response to stress consisted of two components: an initial alpha-adrenergic coronary vasoconstriction, followed by a more complex vasodilation which was probably mediated by metabolites released secondarily to increases in heart rate and inotropic state.
Effects of exercise on aortic input impedance and pressure wave forms in normal humans.
Authors: Murgo J P , Westerhof N , Giolma J P , Altobelli S A
Published: June 2012

The effects of supine bicycle exercise on the input impedance of the ascending aorta were studied in thirteen male subjects undergoing cardiac catheterization, but in whom no cardiovascular disease was found. Ascending aortic flow velocity and pressure were recorded simultaneously from a multisensor catheter with an electromagnetic flow velocity probe and a pressure sensor mounted at the same location. A second pressure sensor at the catheter tip provided left ventricular pressure. Fick cardiac outputs were used to scale the velocity signal to instantaneous volumetric flow. Input impedance was calculated from 10 harmonics of aortic pressure and flow. For each subject, impedance moduli and phases from a minimum of 15 beats during rest and exercise were averaged. Peripheral resistance decreased from a resting value of 1142 +/- 51 (+/- SE) dynes sec/cm5 to 712 +/- 39 dynes sec/cm5 during exercise. Characteristic impedance remained unchanged with a resting value of 47 +/- 4 dynes sec/cm5 and an exercise value of 45 +/- 4 dynes sec/cm5. These results were associated with an increase in aortic pressure (96 +/- 2 to 111 +/- 2 mm Hg) and pulse wave velocity implying a decrease in aortic compliance. An increase in aortic cross-sectional area apparently offsets the effects of these changes in compliance and pulse wave velocity to result in an unchanged characteristic impedance. The increase in pulse wave velocity caused wave reflections to occur earlier during exercise, but the general characteristics of the pressure wave shapes remained unchanged.
Leukocytes are required for increased lung microvascular permeability after microembolization in sheep.
Authors: Flick M R , Perel A , Staub N C
Published: June 2012

We studied the effects of uneven pulmonary artery obstruction by microemboli on steady state transvascular fluid and protein exchange in normal and leukopenic sheep. We measured pulmonary artery and left atrial pressures, cardiac output, lung lymph flow, and lymph plasma protein concentrations. Sheep were made profoundly leukopenic by administration of intra-arterial mechlorethamine hydrochloride (0.4 mg/kg, two doses) and colchicine (0.1-0.2 mg/kg, anesthetized sheep only). In anesthetized sheep, we injected glass beads 200 micrometers in diameter via the right atrium to raise pulmonary vascular resistance to 2-3 times baseline values. With normal levels of circulating leukocytes, sheep developed an increased protein-rich lymph flow from the lung characteristic of increased permeability edema. Leukopenic sheep had a significantly attenuated response after embolization for equivalent degrees of vascular obstruction. In unanesthetized sheep, we continuously infused air bubbles 1 mm in diameter via the right atrium to raise pulmonary vascular resistance to about 2 times baseline values. Each sheep served as its own control. With normal circulating leukocyte levels, there was an increase in protein-rich lymph flow from the lung during embolization. When the air infusion ended, the sheep recovered to the baseline condition in 24 hours. We induced emboli with the same amount of air when the sheep were profoundly leukopenic; lymph and protein flow from the lung were significantly less for equivalent degrees of obstruction. We conclude that circulating leukocytes are essential for the microvascular injury that results in increased permeability in the lungs of sheep after microembolization.
Effects of anesthesia on the canine carotid chemoreceptor reflex.
Authors: Zimpfer M , Sit S P , Vatner S F
Published: June 2012

We studied the effects of alpha-chloralose (100 mg/kg, iv), Na pentobarbital (25 mg/kg, iv) and halothane (1 vol% and 2 vol%) on the response to carotid chemoreceptor stimulation (CCRS) in eight chronically instrumented dogs. CCRS was accomplished by means of intracarotid injections of nicotine while ventilation was held constant in the unanesthetized state and following administration of one of three different anesthetics. In the conscious state, CCRS elicited intense bradycardia and peripheral vasoconstriction as reflected by a 173 +/- 14% increase in initial cardiac cycle length and a 216 /+- 22% increase in mean iliac vascular resistance. Each anaesthetic, studied on separate days, attenuated these responses to CCRS strikingly (P less than 0.01). For instance, after alpha-chloralose, CCRS increased iliac resistance by only 55 +/- 14% and cardiac cycle length by only 27 +/- 13%. After Na pentobarbital, CCRS increased iliac resistance by 12 +/- 4% and cardiac cycle length by 8 +/- 5%. After inhalation of halothane (1 vol%), CCRS increased iliac resistance by 28 +/- 7% and cardiac cycle length by 11 +/- 5%, whereas halothane (2 vol%) abolished these responses to CCRS. Thus, general anesthesia interferes severely with carotid chemoreceptor control of the circulation. Whereas halothane and Na pentobarbital altered responses to CCRS the most, we found that even alpha-chloralose, which has been thought to maintain or augment reflex responses, was able to depress the response to CCRS strikingly.
The selective inhibition of serotonin-induced contractions of rabbit cerebral vascular smooth muscle by calcium-antagonistic dihydropyridines. An investigation of the mechanism of action of nimodipine.
Authors: Towart R
Published: June 2012

I studied the role of calcium in the activation of isolated rings of saphenous and basilar arteries of the rabbit by comparing the effect of calcium withdrawal with the effect of the calcium antagonist nimodipine [isopropyl(2-methoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate]. Serotonin-induced contractions of both vessels were inhibited quickly by incubation in calcium-free solution, showing the contractions of both vessels to be dependent on extracellular calcium. Potassium-induced contractions of both vessels were inhibited markedly by nimodipine (basilar: ID50 = 1.7 X 10(-10) mol/liter; saphenous: ID50 = 2.6 X 10(-10) mol/liter), showing depolarization-induced calcium influx (probably through "potential sensitive channels", PSCs) to be sensitive to nimodipine. In the basilar artery the sustained, tonic phase of serotonin-induced contractions (probably through "receptor operated channels," ROCs) was potently inhibited (ID50 = 7.3 X 10(-10) mol/liter) by nimodipine. However, the initial short-lived phase of this contraction of the basilar artery was relatively unaffected (ID50 = 2 X 10(-6) mol/liter), indicating that the inhibitory action of nimodipine on tonic contractions of the basilar artery was not due to antagonism at the serotonin receptor level. In contrast, in the saphenous artery the serotonin-induced contractions were unaffected by nimodipine in doses up to 2.4 X 10(-5) mol/liter. It is postulated that the selective inhibition of the sustained tonic contraction of the basilar artery is due to a selective inhibition by nimodipine of calcium movement through ROCs in this vessel. Agonist-induced activation of ROCs in peripheral blood vessels does not seem to be affected by calcium antagonists.
Negative diastolic pressure in the intact canine right ventricle. Evidence of diastolic suction.
Authors: Sabbah H N , Stein P D
Published: June 2012

To determine whether the canine right ventricle (RV) can develop a negative diastolic pressure indicative of suction, RV pressure was measured in 15 dogs, with catheter-tip micromanometers. Six dogs were studied only with the chest closed. In these dogs, intrapleural pressure was measured medially (near the heart) in four and laterally in two. In nine dogs, RV pressure was evaluated with the chest closed and after the chest had been opened. In all dogs, with the chest closed, minimal RV diastolic pressure during expiration was negative, -4.8 +/- 0.3 mm Hg. The lowest diastolic pressures occurred during early diastole. Intrapleural pressure during expiration was never this low. Intrapleural pressure measured medially in four dogs was positive during expiration (1.0 +/- 0.6 mm Hg). In the two dogs which it was measured in the lateral pleural space, it was somewhat negative during expiration (-2.5 and -1.3 mm Hg, respectively). After the chest had been opened (nine dogs) minimal RV pressure during early diastole was negative in six dogs and positive in three (range: -1.8 to 0.8 mm Hg). These results indicate that the negative RV diastolic pressure during expiration did not result from a negative intrathoracic pressure. It appears that the RV during early diastole can create a sucking effect which may contribute to the filling process.
Time course of changes in porcine myocardial phospholipid levels during ischemia. A reassessment of the lysolipid hypothesis.
Authors: Shaikh N A , Downar E
Published: June 2012

This study was performed to determine the early and delayed metabolic effects of myocardial ischemia on the major membrane phospholipids and to reassess the potential role of lysophospholipids in the genesis of malignant dysrhythmias induced by ischemia. Samples taken from in situ hearts before ant at various intervals up to 40 minutes after abrupt ligation of LAD were extracted by the classical Folch technique with modifications to avoid artifactual lysophospholipid production and losses. Following thin layer chromatography of lipid extracts, phospholipid fractions were quantified by phosphorus estimation and lysophospholipids by a more sensitive method employing gas liquid chromatography. The total phospholipid content with the exception of lysophospholipids remained essentially constant throughout the early phases of acute ischemia, but fell by 6 and 14% after 8 and 24 ours, respectively. At 8 minutes, lysophospholipid levels n ischemic myocardium were significantly increased by 60% compared to pre-occlusion controls in the ischemic zone and by 25% in post-occlusion controls. They changed little thereafter. The molecular species of lysophospholipids remained unchanged throughout the period of ischemia studied. The mole fraction of other phospholipids as well as their fatty acyl and aldehyde profiles also were unchanged. Despite significant elevations in lysophospholipids levels, their absolute quantities were very small (0.6% of total phospholipid P) and 15-fold smaller than that reported in vitro to simulate electrophysiological manifestation of ischemia. However, such small amounts in vivo, if produced in the microenvironment of certain membrane-bound enzymes along with acidosis, hypoxia, and fatty acids, could be potentially deleterious to cell functions.
Improvement in the relationship between flow to ischemic myocardium and the extent of necrosis with glycolytic intermediates that decrease blood oxygen affinity in dogs.
Authors: Pantely G A , Oyama A A , Metcalfe J , Lawson M S , Welch J E
Published: June 2012

Reducing blood oxygen affinity may enhance myocardial oxygen delivery during ischemia. We evaluated this hypothesis in awake, previously instrumented dogs that received a 20 ml/kg infusion of a solution of dihydroxyacetone, phosphate, and pyruvate after acute occlusion of either the left anterior descending or circumflex coronary artery. This infusion reduced blood oxygen affinity (BOA) after 2 hours; the P50 increased from 29.9 +/- 0.7 torr (mean +/- SD) to 32.1 +/- 0.6 torr; P less than 0.01 (BOA group). Four dogs received 20 ml/kg of phosphate and pyruvate solution to assess volume effects (V group), and five dogs were controls (C group). The 2-hour P50 values in V and C were unchanged. Regional flow (15-mum spheres) reduction 2 hours postocclusion was compared to the percent tissue infarcted determined by histology 7-9 days after occlusion for multiple samples from the endocardial layer of the left ventricle. When flow was less than 40% of normal, V and C had 55% infarction while BOA had 37% (P less than 0.05); at flow less than 20% of normal, V and C had 79% infarction while BOA had 38% (P less than 0.001); and at less than 10% of normal, V and C 87% and 94% infarction, respectively, while BOA had 56% (P less than 0.001). Reducing blood oxygen affinity after coronary artery occlusion significantly decreased the extent of myocardial necrosis for the same degree of ischemia. Reducing BOA may increase oxygen delivery to ischemic myocardium when flow is restricted.
Pulse wave propagation.
Authors: Li J K , Melbin J , Riffle R A , Noordergraaf A
Published: June 2012

This report evaluates pulse wave propagation with respect to contributions by vascular wall elastic and geometric properties, vessel wall and blood viscosity, and nonlinearities in system parameters and in the equations of motion. Discrepancies in results obtained with different experimental methods and theory are discussed and resolved. A three-point pressure technique was used to obtain measurements from the abdominal aorta, carotid, iliac, and femoral arteries of dogs. Computations involved linear, as well as nonlinear methods. Results are presented along a continuous path of transmission (abdominal aorta, iliac, femoral), and it is shown that variations in phase velocity can be explained entirely by the geometric variation of these vessels. Phase velocities are shown to be frequency independent at approximately greater than 4 Hz whereas attenuation increases progressively for higher frequencies. Determination of propagation coefficients using maximal, compounded values of reported viscoelastic and geometric properties just manages to span the range of phase velocities, determined in different laboratories, but does not do so for attenuation. Also, differences in experimental techniques cannot explain these discrepancies. Consideration of geometric taper, nonlinear compliance, all the terms in the equation of motion, and the effect of wall and blood viscosity resolves discrepancies between theoretical and experimentally derived phenomena.
The arrhythmogenic actions of histamine on human atrial fibers.
Authors: Levi R , Malm J R , Bowman F O , Rosen M R
Published: June 2012

We used standard microelectrode techniques to study the effects of histamine on right atrial tissues from patients undergoing corrective cardiac surgery. In the 10(-6) to 10(-4) M range, histamine increased maximum diastolic potential, action potential amplitude, and automaticity. In some preparations, histamine also induced delayed afterdepolarizations and triggered activity. The potency of histamine in increasing automaticity was about 10 times less than that of epinephrine. Propranolol (2 x 10(-7)M), which abolished the chronotropic effect of epinephrine, did not alter the effect of histamine. Conversely, the effect of histamine but not that of epinephrine was antagonized by cimetidine (3 x 10(-6) to 1 x 10(-5) M). This suggests that H2 receptors mediate the chronotropic effects of histamine on the human heart. The slow channel blocker verapamil (2 x 10(-8) to 2 x 10(-6) M) counteracted the effects of histamine on automaticity, delayed afterdepolarizations, and triggered activity, suggesting that in human atrium histamine may act by increasing slow inward (presumably Ca2+) current. If one considers these arrhythmogenic effects of histamine and the fact that human cardiac tissue contains large amounts of histamine, our experiments lend further support to the concept that histamine release can induce arrhythmias.
Hormone receptors of the baboon cardiovascular system. Biochemical characterization of myocardial cytoplasmic androgen receptors.
Authors: Lin A L , McGill H C , Shain S A
Published: June 2012

Using the synthetic androgen R1881 (17 beta-hydroxy-17alpha-methyl-estra-4, 9, 11-trien-3-one) as probe, we identified cytoplasmic androgen receptors in baboon myocardium. The relative binding affinity of selected steroids for the androgen receptor was R1881, 100%; 5alpha-dihydrotestosterone, 32.6%; testosterone, 29.6%, progesterone, 7.2%; R5020, 1.0%; and estradiol-17beta, 5.8%. The androgen receptor migrated on low ionic strength linear sucrose density gradients as a macromolecule with a sedimentation coefficient of 8.5S. Saturation analysis performed at 2 degrees C (available sites) showed that the androgen receptor content of baboon myocardial cytoplasmic extracts was 5.9 +/- 1.4 fmol/mg protein and that the dissociation constant for R1881 was 1.16 +/- 0.30 nM. These cytoplasmic androgen receptors are indicated to be physiologically functional by previous autoradiographic studies (McGill et al., 1980; McGill and Sheridan, 1981) that showed localization of radioisotope in nuclei of myocardial fibers following injection of baboons with 5 alpha-dihydrotestosterone.