bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced phosphorylation of myocardial sarcoplasmic reticulum in experimental hyperthyroidism
Authors: Limas C. J.
Published: December 2017

Calcium transport by cardiac sarcoplasmic reticulum (SR) was compared in hyperthyroid (HT) and euthyroid (ET) rats. Both Ca2+ uptake (97 +/- 3.1 nmol/mg per min in HT vs. 63 +/- 2.9 nmol/mg per min in ET, P less than 0.01) and CA2+ -stimulated ATPase activity (61 +/- 4.1 vs. 37 +/- 1.6 nmol Pi/mg per min, P less than 0.01) were higher in the thyroxine-treated animals. These changes were accompanied by enhanced cyclic AMP-dependent phosphorylation of cardiac SR in hyperthyroid rats (180 +/- 4.3 pmol Pi/mg per min vs. 117 +/- 4.2 pmol Pi/mg per min, P less than 0.01). SDS-polyacrylamide gel electrophoresis of cardiac SR showed that phosphorylation of a 22,000-dalton protein (phospholamban) primarily accounted for the differences between the two groups. There was no difference in the rate of SR dephosphorylation by endogenous phosphoprotein phosphatase between HT and ET rats. Differences in cyclic AMP-dependent phosphorylation between the two groups were blunted in the presence of excess exogenous cyclic AMP-dependent protein kinase. These results suggest that increased levels or activity of endogenous cyclic AMP-dependent protein kinases may partially explain enhanced calcium transport by the cardiac SR of hyperthyroid animals.
Hypotensive effect of [Sar1,Thr8]angiotensin II in spontaneously hypertensive sodium-depleted rats
Authors: Munoz-Ramirez H. , Khosla M. C. , Bumpus F. M. , Khairallah P. A.
Published: December 2017

Under inactin anesthesia, intravenous infusion of [Sar1,Thr8]angiotensin II produced a hypotensive effect in young spontaneously hypertensive rats (SHR) treated with furosemide and in mature SH rats fed a low-sodium diet. The angiotensin antagonist also lowered blood pressure of young and mature SH rats receiving a normal diet. Deoxycorticosterone acetate (DOCA) plus saline reversed the hypotensive effect of [Saru,Thr8]angiotensin II in young SH rats, but did not do so in mature SH rats. Plasma renin activity (PRA) was not significantly changed by anesthesia. Furosemide or the low-sodium diet significantly increased PRA in young and mature SH rats. In contrast, DOCA plus saline significantly reduced PRA in both young and mature SH rats. However, there was no correlation between PRA and the action of the angiotensin II antagonist. These data suggest that the renin-angiotensin system is involved in genetic hypertension.
Role of sodium in strophanthidin toxicity of Purkinje fibers
Authors: Lin C. I. , Vassalle M.
Published: December 2017

The action of strophanthidin on the membrane potentials and contractile force of canine Purkinje fibers was studied in vitro. Purkinje fibers were exposed to strophanthidin (10(-6) M) until spontaneous fast discharge occurred. In Tyrode solution, strophanthidin increased and subsequently decreased ("mechanical toxicity") contractile force. The onset of spontaneous rhythms ("electrical toxicity") usually occurred when force was declining. In low-Na Tyrode (-71 mM NaCl), force increased: on exposure to strophanthidin, mechanical toxicity occurred sooner and electrical toxicity later. In low-Na low-Ca Tyrode, electrical toxicity developed sooner than in low-Na Tyrode. In high-Na Tyrode (+27 mM NaCl), force increased, and the time to electrical and mechanical toxicities was decreased. Increasing osmolarity (+54 mosM) with either sucrose or choline chloride increased force and shortened the time to the onset of strophanthidin toxicities. In the presence of arrhythmias, lowering [Na]o decreased transient oscillations and led to disappearance of arrhythmias. It is concluded that Na plays a role in strophanthidin-induced electrical toxicity, whereas Ca appears more important for mechanical toxicity.
Role of cyclic AMP in rat aortic microsomal phosphorylation and calcium uptake
Authors: Bhalla R. C. , Webb R. C. , Singh D. , Brock T.
Published: December 2017

The role of adenosine 3',5'-monophosphate (cyclic AMP)-dependent membrane phosphorylation in the regulation of microsomal calcium transport in rat aortic smooth muscle was studied. Cyclic AMP-dependent protein kinase augmented the phosphorylation of serine residues in a microsomal protein component with a molecular weight of about 44,000 (determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and the majority of 32P incorporation was in serine residue(s). The phosphorylated protein had stability characteristics of a phosphoester. The phosphorylated substrate was not extracted from the trichloroacetic acid (TCA) precipitate with organic solvents or by suspension in hot TCA; and the demonstrated hydroxylamine insensitivity suggested that the substrate was not lipid or nucleic acid. Intrinsic phosphoprotein phosphatase cleaved the labeled phosphate from the cyclic AMP-stimulated microsomes in the first 5 min of incubation. Microsomes phosphorylated in the presence of 1 micron cyclic AMP or 1 micron cyclic AMP plus 0.1 mg/ml protein kinase exhibited enhanced calcium uptake. We suggest that reversible phosphorylation of microsomal membranes may play an important role in the regulation of aortic microsomal calcium transport by cyclic AMP.
Myocardial ATP synthesis and mechanical function following oxygen deficiency
Authors: Reibel D. K. , Rovetto M. J.
Published: December 2017

The relationship between oxygen deficiency-reduced high energy phosphate levels and their resynthesis upon return to aerobic conditions was investigated in the isolated perfused rat heart. Any net adenosine triphosphate (ATP) hydrolysis during anoxia tended to impair ATP resynthesis with subsequent aerobic perfusion. Thirty minutes of ischemia reduced myocardial ATP 50%, and with restoration of aerobic conditions ATP increased to only 60% of control levels. The major source of postischemic and postanoxic ATP was adenosine 5'-monophosphate and adenosine 5'-disphosphate. Loss of purine base from oxygen-deficient cells limited restoration of ATP. The inclusion of adenosine, ATP, or creatine phosphate (CP) in the perfusate did not enhance postischemic tissue adenine-nucleotide concentrations. Postischemic and postanoxic CP concentrations returned to control values and were independent of ischemic and anoxic ATP and CP concentrations. Complete resynthesis of CP suggests that cellular energy-producing pathways were functional. Ventricular performance was directly related to tissue ATP concentration in aerobic control, postischemic, and postanoxic hearts. Thus, loss of adenine nucleotides during oxygen deficiency may impair subsequent aerobic synthesis of ATP and mechanical function.
Effects of coronary flow reduction on capillary-myocardial exchange in dogs
Authors: Harris T. R. , Gervin C. A. , Burks D. , Custer P.
Published: December 2017

The effects of coronary flow reduction on tracer capillary permeability surface area (PS) and distribution volumes were studied in open-chest dog preparations. A mixture of 51Cr-labeled red blood cells, 125I-labeled albumin, [14C]sucrose, and tritiated water (3H2O) was introduced into a shunt connecting the carotid and left anterior descending coronary arteries. Sampling from the coronary sinus produced a multiple indicator curve from which [14C]sucrose PS and 3H2O volumes were computed. Curves were observed in control situations and after the cannula was partially clamped. In six dogs, cardiac lymph was collected and analyzed for total protein. Paired comparison of control and flow-restricted indicator curves showed that flow reduction decreased the absolute values of PS and tracer volumes. The ratio of sucrose volume to weight of perfused tissue increased with flow reduction. The ratio of sucrose PS to weight of perfused tissue increased with moderate flow reduction and decreased with severe flow reduction. The results suggest that flow reduction has two effects which competively affect exchange: 1) flow restriction reduces surface area by capillary derecruitment, and 2) the remaining functional capillaries appear to undergo an increase in permeability to small molecules.
Increased in blood flow to ischemic myocardium caused by a new dopamine analog
Authors: Diana J. N. , Brenton B. C. , Long J. P. , Cannon J. G. , Laughlin M. H. , Dittrich H. C. , Montag M. J.
Published: December 2017

In the anesthetized, open-chest dog, intravenous infusion 8– 13 microgram . kg-1. min-1) of a new dopamine analog 5,6-dihydroxy-2-methylaminotetralin hydrobromide (M-8) demonstrated potent coronary vasodilator properties. Blood flow to normal myocardium was increased an average of 53% above control flow values and this was associated with a decrease in coronary vascular resistance of 50%. The increase in blood flow was distributed uniformly to all portions of the myocardium (left ventricular free wall, right ventricular free wall, and septum). Subendocardial/subepicardial (endo/epi) flow ratios of the left ventricle, right ventricle, and septum were not significantly changed from control. In dog hearts subjected to acute, sudden occlusion of portions of the left anterior branch of the left coronary artery, M-8 produced a 93% increase in flow to the whole heart over postocclusion flow values. Flow to tissues of the heart made ischemic by the occlusive procedure in creased by an average of 94% during M-8 administration despite the fact that the occlusive ligatures remained in place. The vasodilation produced by M-8 was accompanied by a 22–24% increase in myocardial capillary surface area available for exchange of lipid-insoluble substances, fructose and sucrose. Hemodynamic changes associated with M-8 include a transient decrease in aortic pressure, but no change in heart rate, left ventricular (dP/dt)/P, or central venous pressure. Propranolol blocked the vasodilator activity of M-8. It was concluded that M-8 is a beta2-adrenergic receptor agonist having potent coronary vasodilator properties which also has the ability to open preexisting collateral blood flow channels and provide nutritive flow to ischemic, marginally ischemic, and normal myocardium. The cardiovascular actions of M-8 increase blood flow and oxygen delivery to the myocardium while decreasing the work and oxygen utilization by the heart, suggesting that it may have important antianginal characteristics.
Transplacental gradients in the guinea pig
Authors: Woods L. L. , Thornburg K. L. , Faber J. J.
Published: December 2017

We measured plasma concentrations of Na+, K+, Mg2+, Cl-, Ca2+, HCO3-, phosphate, lactate, glucose, total amino acids, and total protein, and also the total (freezing point depression) osmolality and the colloid osmotic pressures. Conversion of chemically measured concentrations to osmolalities showed that unrecognized solute (s) were present in maternal (7 mM) and fetal (12 mM) plasma. Statistically reliable transplacental gradients existed only for calcium ion, phosphate, and amino acids, Ionic Na, K Mg, Cl, Ca, HCO3 and lactate were in electrochemical equilibrium at potential differences of -4.2 to +1.3 mV. Total plasma osmolalities were not significantly different in maternal and fetal plasmas in preparations in good condition, but fetal plasma osmolalities rose due to lactate secretion in asphyxiated fetuses. Colloid osmotic pressures were about 5 cmH2O higher in maternal plasmas before 45 days gestation and about 6 cmH2O higher in fetal plasmas after 60 days gestation. In the guinea pig, colloid osmotic pressures are at least as important as intravascular pressures in the regulation of transplacental water flow.
Effects of prostaglandin E2, analogs, fatty acids, and indomethacin on fibrinogen level
Authors: Carlson T. H. , Wentland S. H. , Leonard B. D. , Ruder M. A. , Reeve E. B.
Published: December 2017

Dose-response relations in rabbits for 3-h intravenous infusion of prostaglandin E2 (PGE2) and (15S)-15-methyl-1-prostaglandin E2 methyl ester (MePGE2) on plasma fibrinogen and systolic blood pressure were determined and described by regression equations. MePGE2 was 20 times more active than PGE2. Fibrinogen synthetic rate responses to PGE2 and MePGE2 were estimated. Infusion of the PGE2 precursor, arachidonic acid, elevated plasma fibrinogen, but fibrinogen response to 0.5-9 mg/kg arachidonic acid was unrelated to dose and half that given by 3 mg/kg PGE2. Slow infusion of several other fatty acids raised plasma fibrinogen as effectively as arachidonic acid, but prostaglandins D2 and F2alpha had only a slight effect. Infusion of 30 times the indomethacin dose that blocks platelet prostaglandin synthetase did not alter the plasma fibrinogen response to arachidonic acid. Indomethacin did not inhibit plasma fibrinogen elevations following ACTH or endotoxin infusion, or subcutaneous turpentine injection. Intravenous infusion of two cyclic ether prostaglandin endoperoxide analogs, (15S)-hydroxy-9alpha, 11alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid, and (15S)-hydroxy-11alpha, 9alpha(epoxymethano) prosta-5Z, 13E-dienoic acid, failed to increase plasma fibrinogen.
Regional variations in calculated diastolic wall stress in rat left ventricle
Authors: Role L. , Bogen D. , McMahon T. A. , Abelmann W. H.
Published: December 2017

Principal radii of curvature and wall thickness were measured at the apex and three other loci on the free wall of the left ventricle in 16 rat hearts that had been fixed at end-diastolic pressure. The law of Laplace was applied to calculate the mean tensile stress at each locus. No significant variation was found among the nonapical loci, but apical stress was approximately twice the stress calculated for any nonapical locus. The higher stresses that must be borne by the apex may be a predisposing factor for apical aneurysm in certain cardiomyopathies such as Chagas' disease. These higher stresses may also help to promote apical aneurysms in patients with ischemic heart disease.
Effect of velocity distribution on red cell distribution in capillary blood vessels
Authors: Yen R. T. , Fung Y. C.
Published: December 2017

Through the use of simulated model experiments, data on blood cell distribution into a bifurcating capillary blood vessel are obtained. The results show that the movement of red blood cells at a bifurcation point is influenced by the difference in velocities of flow in the daughter branches. If the velocity of flow in one branch is slower than that in the other, the hematocrit decreases in the slower branch and increases in the faster branch. For velocity ratios sufficiently smaller than a certain critical value, the hematocrit ratio can be expressed by a linear relationship, (H1/H2) − 1 = a[(v1/v2) −1], in which v1, v2 and H1, H2 denote the particle velocities and tube hematocrits in the branches 1 and 2, respectively, and a is a dimensionless constant dependent upon a number of factors, the most important of which are the ratio of cell diameter to tube diameter, the shape and rigidity of the pellets, and the hematocrit in the feeding tube. For velocity ratios beyond a critical value, nearly all the cells flow into the faster branch. The smaller the feeding-tube hematocrit is, the smaller is the critical velocity ratio at which this phenomenon occurs.

model experiment; critical velocity ratio; hematocrit: tube, feed-tube, discharge; velocity: particle, mean flow

Submitted on August 15, 1977

Accepted on March 2, 1978
Transient force responses in blood-perfused papillary muscle after step changes in load
Authors: Suga H. , Sagawa K.
Published: December 2017

In in situ canine papillary muscles, we studied transient responses in peak isometric force at control length, after contraction was suddenly switched from isotonic contractions at various forces and isometric contractions at different lengths. Peak isometric force rapidly decreased after isotonic contractions at relatively low forces and isometric contractions at shorter lengths. In contrast, peak isometric force rapidly increased after isotonic contractions at relatively high forces and isometric contractions at longer lengths. There was no transient response when the preceding isotonic force was about half of the present peak isometric force. Magnitude and direction of the transient force response depended on magnitude and direction of the change in the mean muscle force level produced by the sudden switch of loading conditions. Transient force responses were accompanied by simultaneous changes in time to peak isometric force in the same direction. We proposed that, in the blood-perfused papillary muscle, a sudden change in the mean muscle force causes an abrupt change in coronary flow supply-demand relation which in turn causes a transient change in contractile force.
Norepinephrine uptake as an indicator of cardiac reinnervation in dogs
Authors: Kaye M. P. , Tyce G. M.
Published: December 2017

To study the possible role of uptake of [3H]norepinephrine ([3H]NE) as an indicator of sympathetic reinnervation of the surgically denervated canine heart, uptake was determined from multiple areas of hearts at various stages of reinnervation (1--6 mo), and these data were correlated with myocardial catecholamine content and functional response of the heart to electrical stimulation of the sympathetic nerves. Our experiments confirm that NE content correlates poorly with the degree of reinnervation of the previously denervated canine heart. There is, however, a progressive increase of [3H]NE uptake from 1 mo to 6 mo, at which time uptake has returned to approximately 57% of control values in the left atrium. The development of the storage mechanism lags far behind the specific-membrane mechanism for uptake in the reinnervating surgically denervated canine heart.
Platelet removal from the circulation by the liver and spleen
Authors: Kaplan J. E. , Saba T. M.
Published: December 2017

Previous studies on the clearance of intravenously administered platelets have focused primarily on the long-term survival of platelets rather than the mechanisms responsible for the rapid removal of altered platelets from the blood. In the present study the short-term blood clearance and organ localization of circulating labeled platelets were evaluated in rats during particle induced reticuloendothelial (RE) blockage and after intravenous injection of increasing platelet loads in normal rats. Platelet disappearance conformed to a two-compartment exponential clearance with quantifiable rapid (K1) and slow (K2) rate constants. As platelet load increased, the rapid rate constant decreased. This clearance alteration was associated with a decrease in the percent of the injected platelet load localized in the liver and an increase in lung localization. During RE blockade, a decrease was observed in the clearance rates of both the rapid and slow compartments. Such clearance alterations were associated with decreased hepatic platelet localization and increased pulmonary and splenic platelet localization. Thus, the hepatic reticuloendothelial system may represent a rapid cellular clearance system for altered platelets. When this cellular system is impaired or overloaded, the consequences are decreased hepatic and increased extrahepatic platelet localization.
Myocardial nuclear protein kinases during postnatal development
Authors: Limas C. J.
Published: December 2017

Chromatin template activity of isolated rat myocardial cells declines progressively during the first few weeks of postnatal life, a time period also characterized by restriction in myocardial proliferative capacity. Multiple protein kinases have been isolated from the nuclei of myocardial cells. Protein kinase activity decreased progressively during the first 3 wk of postnatal development, mostly in two fractions (III and V). Cyclic AMP dependency, substrate specificity, and phosphorylation patterns of endogenous substrates did not change appreciably with age. Higher phosphorylating activity of protein kinases from younger rats correlated with increased capacity to enhance myocardial RNA synthesis in vitro. This suggests the possibility that the decrease in chromatin template activity with age may be, in part, related to the decline in nuclear phosphokinase activities.
Mechanism of rhythm determination among pacemaker cells of the mammalian sinus node
Authors: Sano T. , Sawanobori T. , Adaniya H.
Published: December 2017

The isolated rabbit sinus node was partly divided into two parts by a cut in the middle portion. Microelectrode recording near the bridge connecting the two parts revealed an interference between action potentials from the two parts. Comparison of microelectrode recordings from the two parts taken near the bridge suggested that an induced peculiar rhythm change in one part was probably induced by the electrotonic effects of the action potentials of the other part. To prove this, a subthreshold depolarizing square-wave pulse was applied extracellularly to the isolated uncut sinus node. When the pulse was applied in the early portion of slow diastolic depolarization, diastole was prolonged, and when it was applied in the later portion, diastole was shortened. These findings can explain the observed peculiar thythm and suggest that in the mammalian sinus node, pacemaker cells accelerate or decelerate mutually by the electrotonic effects of their action potentials, depending on the phase of application of the effects. In particular, for some time the faster pacemaker cells could be influenced by dragging effects from the neighboring slower pacemaker cells and the slower pacemaker cells by pulling effects from the neighboring faster pacemaker cells.
Pulmonary artery catheterization in the rat
Authors: Hayes B. E. , Will J. A.
Published: December 2017

A method of pulmonary artery (PA) catheterization in the closed-chest rat is described. This catheterization is best accomplished with teflon catheters having a (shepherd's crook) tip. Catheter preparation is detailed. The functional advantages of such a PA catheter are: 1) the tip can remain free within the right ventricle (RV) without becoming occluded by contact with the ventricular wall, and 2) entry into the PA is simple and reproducible. Dual catheterization of the RVand PA produced only a small systolic gradient (3 mmHg) across the pulmonic valve. We concluded that the PA catheter does not unduly obstruct blood flow through this valve.
Evaluation of methods of measuring glomerular and nutrient blood flow in rat kidneys
Authors: Yarger W. E. , Boyd M. A. , Schrader N. W.
Published: December 2017

In normal rats, glomerular plasma flow rates (GPF) were estimated from the uptake of microspheres, and single-nephron filtration rates were estimated by Hanssen's technique in order to calculate single-nephron filtration fractions (SNFF) for outer (C1), middle, (C2), and deep (C3) nephrons. With large microspheres (15 micron), SNFF averaged 0.19, 0.41, and 0.63, and with small microspheres (9 micron), SNFF averaged 0.25, 0.48, and 0.42 for areas C1, C2, and C3, respectively. Kidney filtration fractions (FF) averaged 0.36. Because microsphere experiments in normal rats have generally suggested that SNFF-C1 and FF are similar, we conclude that both types of microspheres overestimated outer cortical plasma flow rates, and probably underestimated inner cortical plasma flow rates. In addition, not all of the smaller microspheres were trapped in the glomeruli. Nutrient blood flow rates were estimated from the uptake of 86Rb. Values ranged from 7.3 ml/g per min in the outer cortex to 4.7 ml/g per min in the inner cortex. Because these values are very similar to measurements made by several other techniques, we conclude that 86Rb uptake adequately estimates cortical blood flow. Medullary blood flow estimates, however, increased with time and were probably too high.
Acute cardiac ischemia and reperfusion: contractility, relaxation, and glycolysis
Authors: Apstein C. S. , Deckelbaum L. , Hagopian L. , Hood W. B.
Published: December 2017

The mechanical and metabolic effects of 3 min of complete global ischemia and 25 min of reperfusion were studied in the isolated rat heart. The decrease in contracile function was biphasic; a rapid 50% decline occurred in the first 10 s of ischemia, after which contractile function transiently stabilized and then fell at a slower rate. During reperfusion, recovery of relaxation was impaired relative to recovery of contractile function. A second period of ischemia and reflow produced changes in contractility, relaxation, and lactate production virtually identical to the initial one. In the absence of glycolytic blockade, tissue lactate accumulation developed, no contracture occurred, the pacing threshold did not increase, and reperfusion after 3 min of ischemia resulted in complete recovery of contractile function. Glycolytic blockade with 0.1 mM iodoacetate (IAA) prevented ischemic lactate production, accelerated the fall in contractility, caused irreversible contracture after 30 s of ischemia, an irreversible increase in pacing threshold within 3 min of ischemia, and poor recovery of contractile function with reperfusion. Thus during the first 3 min of severe ischemia, glycolysis exerted a net beneficial effect on myocardial function despite significant tissue lactate accumulation.
Volume overload heart failure: length-tension curves, and response to beta-agonists, Ca2+, and glucagon
Authors: Newman W. H.
Published: December 2017

Left ventricular force-generating capacity was determined in 19 anesthetized dogs with heart failure (HF) from aortocaval fistula. At the time of study all dogs had ascites, edema, and elevated pulmonary wedge pressure. Length-contractile force (CF) curves recorded from the left ventricle (LV) with a modified Walton-Brodie arch indicated that the LV was operating on the ascending limb of the length-CF curve at 62.4 +/- 0.1% Lmax in the normal group and in the HF group at 83.4 +/- 2.7% Lmax. In HF the length-CF curve was depressed when compared to normal and was further depressed when CF in grams was normalized for changes in LV wall thickness and expressed as g/cm2. Additionally, dose-response curves of CF in response to injected norepinephrine, isoproterenol, glucagon, and calcium were depressed when compared to the normal group while the response of heart rate and blood pressure was not different. These findings indicate that volume overload HF is associated with depressed ventricular muscle function and a depressed response to inotropic drugs.
Effects of adenosine on intestinal hemodynamics, oxygen delivery, and capillary fluid exchange
Authors: Granger D. N. , Valleau J. D. , Parker R. E. , Lane R. S. , Taylor A. E.
Published: December 2017

Systemic arterial pressure, superior mesenteric arterial and venous pressures, blood flow, arteriovenous oxygen difference, lymph flow, and intestinal volume were monitored continuously from an autoperfused loop of cat ileum to determine the effects of locally infused adenosine on intestinal hemodynamics, oxygen consumption, and capillary fluid exchange. The results indicate that adenosine, inosine, and hypoxanthine are vasodilators in the intestinal circulation. Local infusion of adenosine significantly reduces vascular resistance, but lymph flow, lymph oncotic pressure, and lymphatic protein flux remained unchanged from control, and the intestinal volume rapidly became constant after an initial blood volume shift. Intestinal oxygen consumption decreased significantly in both autoperfused and constant flow preparations. Pretreatment with aminophylline prevented the reduction in oxygen consumption and greatly attenuated the vasodilatory effect of adenosine. The reactive hyperemic response to 60-s arterial occlusions was virtually unchanged following aminophylline treatment. Adenosine depressed oxygen utilization of mucosal and muscularis strips in vitro and caused a significant redistribution of blood flow from the mucosal-submucosal layer to the muscularis in autoperfused preparations. The results of this study indicate that adenosine significantly reduces vascular resistance and oxygen consumption, yet does not alter fluid exchange in the small intestine.
Effects of acute global ischemia on diastolic relaxation in canine hearts
Authors: Palacios I. , Newell J. B. , Powell W. J.
Published: December 2017

It is not known whether ventricular relaxation can be altered by ischemia independent of associated hemodynamic changes. The effect of acute myocardial ischemia on diastolic relaxation was studied under controlled hemodynamic conditions in 16 anesthetized dogs on right-heart bypass. In nine dogs, left ventricular end-diastolic pressure was maintained constant throughout the experiments. Ischemia produced a significant prolongation of the isovolumetric relaxation period (IVRP) from 29 +/- 3 (SE) to 88 +/- 7 ms (P less than 0.01). Ischemia, per se, the associated decrease in contractility, or the fall in peak left ventricular pressure (LVP) may have contributed to the increase in IVRP. The latter was not the only mechanism involved, because in seven dogs studied with constant peak LVP, IVRP again was prolonged from 64 +/- 8 to 95 +/- 8 ms (P less than 0.01). Moreover, in five nonischemic hearts in which peak LVP was maintained constant, contractility was decreased by sodium pentobarbital to the same extent as with ischemia; IVRP did not change. Thus, the additional prolongation of the IVRP in the ischemia experiments is secondary to a direct effect of ischemia on the relaxation process of the myocardium.
Survival and microvascular responses to hemorrhage with three anesthetic combinations
Authors: Wiegman D. L. , Harris P. D. , Miller F. N. , Morff R. J. , Wilmoth F. R.
Published: December 2017

The effects of different anesthetic combinations on the responses to hemorrhage were investigated while using a single fixed protocol. Small artery (x +/- SE = 112 +/- 3 micron)) and vein (172 +/- 5 micron) responses to hemorrhage were quantitated in the cremaster muscle of 38 Sprague-Dawley rats via closed-circuit television microscopy. Rats were anesthetized intraperitoneally with pentobarbital (50 mg/kg), urethan (800 mg/kg), and alpha-chloralose (60 mg/kg), or urethan (600 mg/kg) and alpha-chloralose (120 mg/kg). After a 15-min control period, arterial blood pressure was lowered to 30 mmHg and maintained at that level for 60 min via hemorrhage from the femoral artery. The hemorrhaged blood was then reinfused, and recovery was monitored for 30 min. Survival was monitored for 7 days. Rats with heavier body weights (greater than or equal to 160 g) had a significantly greater survival rate, 81%, than did the lighter weight rats (less than 160 g), with a 32% survival rate. There were, however, no statistical differences in survival or microvascular responses among rats anesthetized with the three combinations of anesthetics. The combined data for all rats were: survival, 53%; small artery constriction, 45 +/- 2%; and small vein constriction, 21 +/- 3%.
Reflex circulatory changes due to the afferent stimulation of cat pericoronary nerve
Authors: Shimizu T. , Peterson D. F. , Bishop V. S.
Published: December 2017

Two different types of circulatory reflexes evoked by electrical stimulation of afferent fibers in the left pericoronary nerves were studied in anesthetized cats. A depressor response (-32.5 mmHg) with bradycardia (-48.7 beats/min) in 21 of 31 cats was mediated by the C fibers in the right vagal cardiac nerve trunk. The efferent pathway for the bradycardia was in caudal cardiac branches of the right vagus. Neither sympathetic denervation to the heart nor atropine attenuated the hypotensive response significantly, suggesting that the depressor response results from reflex inhibition of peripheral sympathetic activity. A pressor reflex without heart rate change was observed either when the vagi were blocked or when the distribution of vagal afferents in the pericoronary nerve was considered to be small. The pressor reflex was mainly mediated by the afferent C fibers within the left cardiac sympathetic nerves. The depressor response was enhanced by sympathectomy, suggesting the sympathetic counteraction on the inhibitory vagal afferents, Similarly, an enhancement of the pressor reflex by vagal blockade was observed, indicating tonic vagal restraint on excitatory sympathetic reflexes.
Catecholamines and cardiac rhythms in the unanesthetized dog with chronic AV block
Authors: Boucher M. , Duchene-Marullaz P. , Lavarenne J.
Published: December 2017

The effects of epinephrine, norepinephrine, and isoproterenol were studied in the nonanesthetized dog with chronic atrioventricular block before and after blockade of cholinergic receptors. Epinephrine and norepinephrine reduced the atrial rate in a reflex manner, whereas isoproterenol increased it. In contrast, all three substances increased idioventricular rate. After atropine, atrial and ventricular rate increases were observed after administration of the three catecholamines. Moreover, blockade of cholinergic receptors led to an increase in ventricular acceleration induced by epinephrine and norepinephrine, but did not significantly modify the acceleration induced by isoproterenol. These results appear to indicate the possibility of the involvement (intensified by a reflex mechanism) of ventricular cholinergic innervation.
Myocardial performance in the newborn lamb
Authors: Berman W. , Musselman J.
Published: December 2017

We compared myocardial performance in newborn lambs over the first 3 wk of life with that of ewes. Heart rate was higher in newborn lambs than in ewes. The ratio of left ventricular preejection period to left ventricular ejection time was similar for newborns (0.31 +/- 0.02) and ewes (0.31 +/- 0.01). Cardiac output in ml/min per kg body weight in the newborn was 397 +/- 55 at 1 wk, 314 +/- 30 at 2 wk, and 274 +/- 10 at 3 wk, compared to 125 +/- 8 in ewes. Stroke work was comparable in both age groups. Left ventricular dP/dtmax averaged 3,723 mmHg/s in lambs compared to a mean value of 2,257 in ewes. These studies establish that the myocardium of newborn sheep contracts vigorously in vivo and equals or exceeds the level of performance of the myocardium of adult sheep, as estimated by a variety of indices of myocardial function.
Hemodynamics of central infusion of angiotensin II in normal and sodium-depleted dogs
Authors: Brosnihan K. B. , Berti G. A. , Ferrario C. M.
Published: December 2017

The intraventricular (IVT) administration of angiotensin II (AII) (100 ng.kg-1.min-1) produced significant elevations of arterial blood pressure in pentobarbital-anesthetized dogs on either normal or sodium-deficient diets. In both groups of dogs the intraventricular administration of AII caused comparable and significant elevations in blood pressure averaging 15 +/- 2 and 17 +/- 4 mmHg, respectively, within 10 min after onset of the infusion. The rises in blood pressure were due to increased peripheral resistance (2.87 +/- 1.20 vs. 1.67 +/- 0.43 units). At the peak of the pressor response bradycardia was a constant feature in sodium-depleted animals, but was not present in the normal ones. In both groups of dogs regional cerebral blood flow (rCBF), determined by the xenon-133 washout method, remained unchanged during the development of the pressor response, and peripheral plasma renin activity failed to increase in response to the central infusion of AII. In conclusion, sodium deprivation appears not to influence the sensitivity of the central AII receptor because comparable pressor responses and hemodynamic changes were obtained following the intraventricular administration of AII in both normal and sodium-depleted dogs.
Vagal and sinoaortic reflexes in postural control of circulation and renin release
Authors: Dampney R. A. , Stella A. , Golin R. , Zanchetti A.
Published: December 2017

Anesthetized cats were subjected to two 10-min trials of head-up tilting spaced 60 min apart. Bilateral cervical vagotomy, performed after the first tilting episode, did not affect the hemodynamic response to the change in posture, but significantyly and markedly reduced the increase in renin release from the innervated kidney. After sinoaortic denervation a marked and sustained arterial hypotension occurred during tilting, and the postural increase in renin release, though still limited to the innervated kidney, was even greater. When pressure homeostasis to tilting was disturbed, the renin release response was seen to be independent of the vagi, as it occurred after combined vagotomy and sinoaortic denervation. Maintenance of arterial pressure during tilting is mainly due to sinoaortic reflexes, whereas vagal reflexes are mostly responsible for the postural increase in renin release. The vagally independent release of renin observed when the cardiovascular response to tilting is impaired, is probably due to a direct action of arterial hypotension on intrarenal receptors, an action occurring only in innervated kidneys.
In vitro effects of desoxycorticosterone on vascular smooth muscle
Authors: Koehler M. F. , Webb R. C. , Jones A. W. , Bohr D. F.
Published: December 2017

We present evidence in accord with the observations of S. Kalsner (Br. J. Pharmacol. 36: 582-593, 1969) that in the rabbit aorta, desoxycorticosterone (DOC) potentiates the contractile response to certain catecholamines by inhibiting their degradation by catechol-O-methyltransferase. In contrast, DOC depresses the contractile responses in rat aorta and tail arteries. To elucidate the mechanism of this depression the effect of DOC was evaluated under various conditions. DOC depressed the contractile response to epinephrine, phenylephrine, KCl, and angiotensin II. The depression was unaltered by ouabain or by a potassium-free solution, indicating that DOC did not produce its depression by altering Na-K-ATPase activity. The depression is unaltered in a chloride-free solution, demonstrating that the DOC effect is not caused by a change in membrane permeability to chloride. Radioisotope studies demonstrate that DOC does not alter membrane permeability to potassium. Removal of extracellular calcium with EGTA (ethylene glycol-bis (beta-aminoethyl ether) N, N'-tetraacetic acid) significantly reduced the magnitude of the DOC depression. Indirect evidence is presented suggesting that DOC might increase calcium binding to the plasma membrane, resulting in its stabilization and hence in a depression of the contractile response.
Formation of angiotensin III from [des-Asp1]angiotensin I in the mesentric vasculature
Authors: Sexton J. M. , Britton S. L. , Beierwaltes W. H. , Fiksen-Olsen M. J. , Romero J. C.
Published: December 2017

The effects of [des-Asp1]angiotensin I and angiotensin III on mesenteric blood flow were compared in 15 pentobarbital-anesthetized dogs. These agonists were administered as bolus injections directly into the vasculature supplied by the superior mesenteric artery. Both [des-Asp1]angiotensin I and angiotensin III produced dose-dependent decreases in mesenteric blood flow, with angiotensin III being more potent than [des-Asp1]angiotensin I at all doses tested. The constrictor responses to [des-Asp1]angiotensin I were markedly attenuated in the presence of an angiotensin-converting enzyme inhibitor (SQ20881); SQ20881 did not alter responses to angiotensin III or norepinephrine. The administration of [Ile7]angiotensin III (an angiotensin III antagonist) attenuated the responses to both [des-Asp1]angiotensin I and angiotensin III, without altering the responses to norepinephrine. These results suggest that the decrease in mesenteric blood flow produced by [des-Asp1]angiotensin I is largely caused by its local enzymatic conversion to angiotensin III. This conversion in one transit through the mesenteric vasculature is approximately 24%.
Myocardial adenosine salvage rates and restoration of ATP content following ischemia
Authors: Reibel D. K. , Rovetto M. J.
Published: December 2017

The isolated perfused rat heart was utilized to determine the maximum rate of adenosine incorporation into adenine nucleotides and the effect of ischemia on this rate. In aerobic hearts, the rates of [8-14C]adenosine incorporation into nucleotides in nanomoles/minute per gram dry tissue were ATP 34 +/- 2, ADP 6 +/- 0.4, AMP 3 +/- 0.3, and IMP, 1 +/- 0.2. Following ischemia these values were not significantly different except for the rate of incorporation into IMP, which doubled. The extent of adenosine deamination with one pass through the coronary vasculature was the same in aerobic and postischemic hearts: 2% and 7% of the perfusate adenosine was converted to hypoxanthine and inosine, respectively. These percentages were similar at 50, 100, and 200 micron adenosine. Perfusion of aerobic hearts for 5 h with adenosine did not change ATP concentrations. Therefore, [8-14C]adenosine incorporation into ATP in these hearts appeared to represent ATP turnover. In contrast, 5 h perfusion of postischemic hearts with adenosine restored ATP concentrations to control values. The synthesis rate calculated from the increase in ATP concentration was comparable to the synthesis rate calculated from [8-14C]adenosine incorporation. Thus, incorporation of [8-14C]adenosine into ATP in postischemic hearts represented net ATP synthesis.
Intramural PCO2: a reliable index of the severity of myocardial ischemic injury
Authors: Khuri S. F. , Kloner R. A. , Hillis L. D. , Tow D. E. , Barsamian E. M. , Maroko P. R. , Braunwald E.
Published: December 2017

The present study was performed to evaluate the usefulness of changes in intramural oxygen (PmO2) and carbon dioxide (PmCO2) tensions shortly after coronary artery occlusion as indices of the severity of myocardial ischemic injury. In 14 open-chest, anesthetized dogs, a 60-min coronary artery occlusion was performed, during which PmO2 and PMCO2 were measured continuously with a mass spectrometer. Regional myocardial blood flow (RMBF) adjacent to the mass spectrometer probes was measured by the xenon-127 washout technique both before and 30 min after coronary artery occlusion. At the end of 60 min of occlusion, the dogs were killed, and biopsies for histological examination of 1-micron-thick sections were obtained from the tissue surrounding each mass spectometer probe. The decline in PmO2 during the 60-min occlusion bore no relationship either to the severity of ischemic injury as assessed by histological examination, or to the reduction of RMBF. In contrast, the magnitude of rise in PmCO2 during the 60 min of occlusion corresponded closely to both the severity of injury assessed histologically and the reduction of RMBF.
Application of an isolated heart model to investigate blood-oxygen delivery
Authors: Rand P. W. , Nelson C. V. , Lacombe E. H. , Barker N. D. , Pirone L. A.
Published: December 2017

To avoid the compensatory hemodynamic responses, which have limited interpretation of hemoglobin-oxygen affinity modifications in animal experimentation, an isolated blood-perfused rabbit heart model providing metabolic, functional, and vectorcardiographic measurements has been developed. Fixed-flow perfusions of unchanged or affinity-modified red blood cell suspensions were carried out to assess the benefits of high affinity during hypoxic hypoxia and of low affinity during posthypoxic recovery. Using fully saturated suspensions, the influence of affinity level during restricted flow and reperfusion was also studied. Higher myocardial oxygen consumption (MVO2) was associated with high-affinity blood during mild hypoxia and low-affinity blood during posthypoxic recovery. At low flows, heart rate and MVO2 tended to be lower in high-affinity perfusions, and to recover more completely during low-affinity reperfusions. Ventricular function, vectorcardiographic patterns, and lactate levels were affected by hypoxia and ischemia, but not by level of affinity. The relevance of these observations to the therapeutic potential of hemoglobin-oxygen affinity modification is discussed.
Intracellular recording from beating heart in situ using a special micropipette holder
Authors: Akiyama T. , Serrino P.
Published: December 2017

Use of a motion-compensated micropipette holder, which senses cardiac motion and lifts and lowers the micropipette and supporting apparatus in synchrony with the heart beat, allows for stable recording of transmembrane action potentials from subepicardial cells of an in vivo beating heart in an open-chest dog without significantly impairing cardiac hemodynamics. This technique may be used to study the effects of ischemia, hypertrophy, or pharmacologic agents on the cellular electrophysiological parameters of subepicardial ventricular cells of an in vivo beating heart.
Blockade of the pressor response to muscle ischemia by sensory nerve block in man
Authors: Freund P. R. , Rowell L. B. , Murphy T. M. , Hobbs S. F. , Butler S. H.
Published: December 2017

Differential nerve block from peridural anesthesia was used to determine a) if the pressor response to muscle ischemia in man is caused by stimulation of small sensory nerve fibers and b) if these fibers contribute to cardiovascular-respiratory responses during dynamic exercise. Four men exercised at 50-100 W for 5 min. Muscle ischemia and a sustained pressor response were produced by total circulatory occlusion of both legs beginning 30 s before the end of exercise and continuing for 3 min postexercise. During regression of full motor and sensory block, motor strength recovered while sensory block continued; the pressor response was blocked as long as sensory anesthesia persisted (two subjects). During blockade of the pressor response, cardiovascular-respiratory responses to exercise gradually returned from augmented to normal (preblock) levels. Sensory blockade was incomplete in two subjects and the pressor response was not fully blocked. We conclude that stimulation of small sensory fibers during ischemia elicits the pressor response, but that these fibers appear not to contribute to cardiovascular-respiratory responses during mild dynamic exercise with adequate blood flow.
Role of cardiac sympathetics in the tonic circulatory restraint by vagal afferents
Authors: Shimizu T. , Peterson D. F. , Bishop V. S.
Published: December 2017

In anesthetized cats with aortic nerves sectioned and carotid arteries occluded, we determined the role of cardiac sympathetic nerves on the tonic inhibitory restraint by cardiac vagal afferents on the cardiovascular system. The effect of afferent vagal blockade on mean arterial pressure and cardiac contractility was determined when sympathetic tone to the heart was altered. Bilateral cardiac sympathectomy produced a significant decrease in left ventricular dP/dt and attenuated the arterial pressure response to afferent vagal cold block to less than 40% of the control. The increase in dP/dt normally observed with vagal blockade was also reduced significantly. Increasing dP/dt by efferent stimulation of cardiac sympathetic nerves restored the arterial pressure response to vagal blockade to near control levels. While the vagal inhibitory activity appeared to be dependent on the resting dP/dt, left ventricular peak pressure did not seem to be contributing to the reflex. Thus, the inhibitory effects of vagally mediated reflexes from the heart which contribute to arterial pressure regulation appear to be influenced by changes in cardiac contractility induced by cardiac sympathetic nerve stimulation.
Interaction between carotid sinus baroreceptor and aortic nerve pressor reflexes in the dog
Authors: Kendrick J. E. , Matson G. L.
Published: December 2017

In dogs anesthetized with morphine-chloralose, strong, low-frequency (2 Hz) electrical stimulation of the aortic nerve (AN) causes pressure in the perfused hindlimbs to rise. This pressor response is followed by a large depressor phase upon cessation of stimulation. Simultaneous stimulation of the ipsilateral carotid sinus nerve (CSN) with intermittent trains of stimuli enhanced the AN pressor response by 113%. Similar stimulation of the contralateral CSN had little effect on the AN pressor response. Constant-frequency stimulation of the ipsilateral CSN also failed to enhance this response. Possible mechanisms of the interaction between these antagonistic reflexes were investigated. The results suggest that the augmentation of the AN pressor response results from a central neuronal interaction between these antagonistic reflexes.