bluuebunny/crossref_metadata_2025 huggingface dataset:
The relation of localized myocardial warming to changes in cardiac surface electrograms in dogs.
Authors: Burgess M J , Lux R L , Wyatt R F , Abildskov J A
Published: June 2012

We studied the relationship of the size and severity of alteration of recovery properties in localized areas to changes in cardiac surface electrograms in experiments on six open-chest dogs. Alterations in recovery properties were induced thermally because size and severity of the affected area could be controlled on the basis of physical principles which were modeled. We recorded unipolar electrograms from 75 cardiac surface sites simultaneously during stimulation of atria and pulmonary conus in control periods and in the presence of warmed areas of varying sizes and intensities. Size of the areas was controlled by the diameter of an aperture through which a light source was directed. Intensity was controlled by the light source excitation voltage. Myocardial temperature was monitored with a thermistor. The QRS, STT, and QRST deflection areas were determined by computer processing and displayed as isoarea maps. Difference maps also were determined by subtracting control QRST isoarea maps from those obtained in the presence of warmed areas. QRST area difference maps were related closely to the size and severity of the thermally induced changes in recovery properties. With areas of the same size and increasing myocardial temperatures, the magnitude of the change in QRST area increased, and the gradient of contour lines between the affected and unaffected areas increased. When myocardial temperature at the center of the warmed area was kept constant and the size of the warmed area was increased, the affected cardiac surface area increased, but the number of isoarea contours remained approximately the same. These findings suggest that the change in QRST isoarea maps may be a useful indicator of lesion size when combined with an index of lesion severity such as the QRST area change in the electrogram with the maximum change. QRST areas during both activation orders were similar, suggesting that the QRST area is independent of changes in activation sequence.
Effects of inotropic and arrhythmogenic digoxin doses and of digoxin-specific antibody on myocardial monovalent cation transport in the dog.
Authors: Hougen T J , Lloyd B L , Smith T W
Published: June 2012

The effects of digoxin on monovalent cation active transport were determined in cardiac tissue obtained from dogs given inotropic, toxic, or lethal doses of digoxin. In hemodynamically monitored dogs, active uptake of the K+ analogue Rb+ was determined in vitro in a control myocardial biopsy, and then in serial biopsies from the same dog after the infusion of [3H]digoxin in doses sufficient to cause a sustained positive inotropic effect in the absence of toxicity, and finally after additional doses to induce overt toxicity. Nontoxic digoxin doses producing a mean increase of 20% in left ventricular (LV) dP/dt significantly reduced Rb+ active transport by 25% below control values. At the onset of digoxin-induced arrhythmias, maximal LV dP/dt was 53% above control whereas active Rb+ transport was reduced by 60% below baseline values (P less than 0.001). Control dogs given vehicle alone showed no significant change in contractility or in monovalent cation active transport. In another group of dogs given a lethal dose of digoxin, Rb+ active transport was reduced 59% below control levels at the onset of overt toxicity and was further reduced 80% below control at the time of onset of a fatal rhythm disturbance. When dogs were given high affinity digoxin-specific IgG or Fab fragments at the onset of overt toxicity, toxicity was rapidly reversed, and monovalent cation active transport increased to 51% of control at the time of restoration of sinus rhythm. Twenty-four hours after antibody reversal of arrhythmias, monovalent cation transport values approximated normal control levels. These data provide quantitative estimates of the extent of inhibition of monovalent cation transport by digoxin at inotropic, toxic, and lethal endpoints. Similar degrees of transport inhibition were present at the time of onset of digoxin-induced arrhythmias and at the time or arrhythmia reversal by digoxin-specific antibodies.
Biochemical and morphological correlates of acute experimental myocardial ischemia in the dog. IV. Energy mechanisms during very early ischemia.
Authors: Wood J M , Hanley H G , Entman M L , Hartley C J , Swain J A , Busch U , Chang C H , Lewis R M , Morgan W J , Schwartz A
Published: June 2012

Tissue energy metabolism was examined in posterior (ischemic) and anterior ("control") regions of canine ventricles after 5 and 10 minutes of left circumflex coronary artery occlusion. When compared to identical regions of normal hearts, the following changes were found: (1) decreases in glycogen and phosphorylase activity in the anterior and posterior regions, (2) depressed state 3 rates of oxygen consumption of isolated mitochondria in both anterior and posterior regions, (3) shifts in optimum substrate concentrations for palmityl-CoA (+ carnitine) oxidation by mitochondria in the anterior and posterior regions, and (4) decreases in the apparent zero order and first order rates of mitochondrial palmitylcarnitine production. These changes correlated with a marked decrease in developed tension in the posterior regions. Depression in tension development in the posterior regions of the heart still was present after 30--60 minutes of reperfusion following a 10-minute period of occlusion. Glycogen content in the reperfused areas was significantly decreased after 60 minutes of reperfusion when compared to normal areas and to control hearts perfused for 70 minutes. After reperfusion, mitochondrial function appeared to return toward "normal." However, the slow restoration of contraction of the ischemic area suggests that cellular mechanisms operative in vivo to restore pump function still might be abnormal.
High energy phosphate stores and lactate levels in different layers of the canine left ventricle during reactive hyperemia.
Authors: Dunn R B , McDonough K M , Griggs D M
Published: June 2012

To study postischemic recovery of myocardial energy metabolism in relation to the reactive hyperemic response, the tissue levels of creatine phosphate (CP), adenosine triphosphate (ATP), and lactate were estimated in the outer, middle, and inner layers of the left ventricle before, during, and at several times after a 20-second bilateral coronary arterial occlusion in the open-chest dog. The reactive hyperemic response was characterized by monitoring blood flow in the cannulated coronary sinus in a separate group of dogs. Substantial changes in myocardial CP and lactate, but not ATP, were produced by the occlusion and reciprocal transmural gradients in CP and lactate occurred such that CP was lowest and lactate was highest in the inner layer. Recovery of high energy phosphate stores (CP + ATP) occurred long before blood flow returned to the preocclusion level, this being achieved in two of the three layers after completion of only 29% of the reactive hyperemic response when the blood flow debt repayment was 151%. Lactate returned to control levels during the response, but recovery times in the different layers were delayed compared to those for the high energy phosphate stores. A transmural lactate gradient was maintained as the regional levels declined, and recovery times were different for each of the three layers, being longest in the inner layer. The results suggest that during the reactive hyperemic response (1) kinetically different processes are involved in the repletion of energy stores and the removal of anaerobically produced metabolites, and (2) metabolic vasodilation of coronary vessels probably is more pronounced and sustained longer in the inner than in the outer ventricular layer.
Effects of K+ and K+-induced polarization on (dV/dt)max, threshold potential, and membrane input resistance in guinea pig and cat ventricular myocardium.
Authors: Kishida H , Surawicz B , Fu L T
Published: June 2012

We studied the non-membrane potential-dependent effect of K+ on (dV/dt)max and threshold potential in guinea pig and cat ventricular myocardium. Membrane potential (MP) was changed uniformly in segments (length less than or equal to 1.0 mm) of papillary muscles by applying extracellular polarizing current pulses across a single sucrose gap. Control [K+]o was 5.4 mM and test [K+]o values were 2.0, 10.0, 11.5, 13.0, 16.2, 20, 22, and 24.0 mM. Each muscle was studied under four conditions: (1) control [K+]o and unaltered (control level) resting MP (Em); (2) one of the test [K+]o values and the unaltered (test level) Em; (3) the same test [K+]o and Em held at the control level; (4) control [K+]o and Em held at the test level. At all [K+]o greater than or equal to 11.5 mM, (dV/dt)max showed a decrease significantly (P less than 0.01) greater than the corresponding MP-dependent decrease in both guinea pig and cat myocardium. This non-MP-dependent decrease averaged 7.5% at 11.5 mM, 26.5% at 13.0 mM, 37.2% at 16.2 mM, and 22.7% at 20.0 mM. At [K+]o greater than or equal to 20.0 mM, (dV/dt)max was predominantly slow-channel-dependent; it was increased by hyperpolarization to -110 mV at [K+]o = 20 and 22 mM but not at [K+]o = 24mM. Threshold potential became progressively less negative with increasing [K+]o, but this effect was dependent only on MP. The membrane input resistance (rm) was determined by two opposing factors: at a given [K+]o, rm increased with depolarization; and at a given MP, rm decreased with increasing [K+]o. Our study shows that non-MP-dependent depression of (dV/dt)max in the ventricular myocardium occurs at [K+]o concentrations that may be encountered in vivo.
Stimulation of renin by acute selective chloride depletion in the rat.
Authors: Abboud H E , Luke R G , Galla J H , Kotchen T A
Published: June 2012

To determine whether acute chloride depletion per se stimulates renin, we produced selective chloride depletion without sodium depletion in rats by peritoneal dialysis (PD) against 0.15 M NaHCO3 or 0.15 M NaNO3. Control rats were dialyzed against 0.15 M NaCl. Plasma renin activity (PRA) was measured before (PRA1) and 105 minutes after (PRA2) PD. Plasma volume was expanded after PD by infusion of salt-free albumin and was measured immediately after PRA2 by [131I]albumin. In experiment 1, rats were prepared on a normal diet. PRA2 (7.0 +/- 1.0 ng/ml per hr, mean +/- SEM) was increased (P less than 0.05) over PRA1 (4.7 +/- 0.7 ng/ml per hr) in Cl-depleted but not in control rats (PRA1 = 5.3 +/- 0.7, PRA2 = 6.1 +/- 0.7, P = NS). In experiment 2, to produce greater chloride depletion, all rats were prepared for 2 weeks on a low salt diet. PRA2 (47 +/- 5 ng/ml per hr) was increased as compared to PRA1 (24 +/- 2 ng/ml per hr, P less than 0.005) in the Cl-depleted group but not in the control group (PRA1 = 24 +/- 3, PRA2 = 27 +/- 6 ng/ml per hr, P = NS). Serum potassium and final plasma volume were slightly but not significantly lower than controls in these Cl-depleted rats. To exclude an additive effect of these two stimuli for renin, in experiment 2a we infused chloride-depleted rats with three times as much albumin as controls and with KHCO3, 100 mEq/liter. Despite volume expansion and potassium loading, PRA2 (41 +/- 6 ng/ml per hr) was significantly elevated as compared to PRA1 (25 +/- 4 ng/ml per hr, P less than 0.01). Since acute metabolic alkalosis also was present in all Cl-depleted renin-stimulated rats, an additional group (2b) was dialyzed against 0.15 M NaNO3; final plasma arterial pH (7.43) was not different from controls (7.42). Nevertheless, PRA2 levels again were higher (36 +/- 6 ng/ml per hr, P less than 0.05) as compared to PRA1 (23 +/- 4 ng/ml per hr). In all experiments, arterial blood pressure, glomerular filtration rate, and filtered sodium load were not different. Free water reabsorption was lower in Cl-depleted than in control rats. We conclude that acute selective chloride depletion per se is a potent stimulus for renin release.
Potential arrhythmogenic electrophysiological derangements in canine Purkinje fibers induced by lysophosphoglycerides.
Authors: Corr P B , Cain M E , Witkowski F X , Price D A , Sobel B E
Published: June 2012

We have recently detected accumulation of lysophosphoglycerides, catabolites of phospholipids, in ischemic myocardium early after coronary occlusion. In the present study we delineated effects of selected concentrations of albumin-bound lysophosphatidyl choline (LPC) comparable to those accompanying ischemia in vivo on action potentials of isolated canine Purkinje fibers. Lysophosphoglycerides induced concentration-dependent (0.75-3.0 mM) decreases in resting membrane potential, overshoot of phase 0, maximal velocity of upstroke (Vmax) of phase 0, and action potential duration. The highest concentrations (2.0-3.0 mM) induced fractionation of the action potential into several components, unresponsiveness to external stimulation, and enhanced automaticity at normal and reduced membrane potentials. LPC induced a rightward shift in the membrane response curve, a 40-fold prolongation of conduction time, and an increase in the ratio of effective refractory period to action potential duration such that the effective refractory period persisted beyond action potential duration, resulting in postrepolarization refractoriness. These electrophysiological alterations were entirely reversible after 70 minutes of perfusion without LPC, with the exception of a persistent depression in the Vmax of phase 0. Lysophosphatidyl ethanolamine (LPE) elicited alterations in action potentials indentical to those elicited by LPC. Furthermore, LPC (3.0 mM) induced comparable alterations in action potentials recorded from isolated rabbit papillary muscles. Since lysophospholipids accumulate early after myocardial ischemia, and since concentrations equivalent to those occurring in vivo induce electrophysiological alterations resembling those seen in ischemic myocardium in vivo, lysophosphoglycerides may be of major importance as biochemical mediators of malignant dysrhythmia induced by ischemia.
Correlative electrophysiological and anatomical studies concerning the site of origin of escape rhythm during complete atrioventricular block in the dog.
Authors: James T N , Isobe J H , Urthaler F
Published: June 2012

Complete heart block was produced in eight dogs by the selective perfusion of physostigmine or neostigm into the atrioventricular (AV) node artery. A characteristic escape AV junctional rhythm emerged in each dog. After reversal of the cholinesterase paralysis with atropine, in each dog partial heart block was produced by an incision into the AV nodal region. In three of these eight dogs, a second incision placed slightly more anteriorly produced complete AV block which was followed by the emergence of an escape AV junctional rhythm similar to the one produced pharmacologically. Hearts of these three dogs were examined histologically with serial sections to determine the exact location of the incisions and their relationship to the AV node and His bundle. In each dog the incision that produced complete heart block passed directly through the junction of AV node with His bundle. In this region previous studies had demonstrated numerous P cells, which are thought to be the site of origin of normal cardiac automaticity. In each of the three hearts there were abundant P cells in continuity with the His bundle distal to the cut producing heart block. Significance of these findings is discussed relative to the locus of action of acetylcholine within the AV junction, the site of origin of AV junctional rhythm, and sme aspects of the experimental and therapeutic production of heart block.
Neither dorsal root nor baroreceptor afferents are necessary for eliciting the renal responses to acute intravascular volume expansion in the primate Macaca fascicularis.
Authors: Gilmore J P , Peterson T V , Zucker I H
Published: June 2012

We determined the contribution of the dorsal roots, vagi, and sino-aortic nerves to the renal responses to acute isotonic, isooncotic intravascular volume expansion in the nonhuman primate, Macaca fascicularis. Expansion of the estimated blood volume by 15% produced a significant natriuresis and diuresis. There was no significant difference between the time to peak response for either. Neither dorsal rhizotomy (C6-T7) nor vagotomy and sino-aortic denervation had a significant effect on these responses. We conclude that these pathways are not necessary for eliciting the renal responses to hypervolemia in the nonhuman primate.
Dissociation between the electrophysiological properties and total tissue cyclic guanosine monophosphate content of guinea pig atria.
Authors: Mirro M J , Bailey J C , Watanabe A M
Published: June 2012

The purpose of this study was to investigate the role of cyclic guanosine monophosphate (cyclic GMP) in mediating the direct electrophysiological effects of acetylcholine in guinea pig atria. Acetylcholine significantly diminished spontaneous rate of right atria without increasing cyclic GMP content. Reductions in rate following acetylcholine were augmented by pretreatment with physostigmine, but cyclic GMP levels remained unchanged. In left atria, acetylcholine significantly shortened action potential duration within 5 seconds (both with and without physostigmine pretreatment), but cyclic GMP content was not significantly elevated. Cyclic GMP levels in right atria were significantly increased in response to acetylcholine when the Ca2+ content of the buffer was elevated from 1.25 mM TO 2.5 MM; however, reductions in automaticity in the right atria were not augmented in the high Ca2+ buffer. Marked increases in cyclic GMP content were produced by Na nitroprusside superfusion without changing automaticity of right atria or action potential duration of left atria. Finally, both right and left atria were superfused with cyclic GMP analogs (8-bromo cyclic GMP and dibutyryl cyclic GMP) at high concentrations (10(-4)) for 15 minutes without producing significant effects on spontaneous rate or action potential duration. These results failed to show a correlation between total tissue cyclic GMP content and the electrophysiological effects of acetylcholine on guinea pig atria. The reasons for this are either that cyclic GMP does not mediate directly the electrophysiological effects of acetylcholine, or that small changes in cyclic GMP concentrations, undetectable when total tissue nucleotide levels are measured, occur in discrete effector pools of the cardiac cell to mediate the intracellular effects of the choline ester.
Rate of rise of myocardial PCO2 during early myocardial ischemia in the dog.
Authors: Case R B , Felix A , Castellana F S
Published: June 2012

We have investigated the rate of rise of myocardial PCO2 (PmCO2) after coronary artery occlusion using a new method for this measurement. Previous studies of PmCO2 have been limited by the slow response of the only available method, and no increase in MmCO2 prior to 3 minutes after occlusion has been found. We have implanted a miniature PCO2 electrode, with a 63% response time of 14 seconds, into the left ventricle of 14 open-chest dogs. After abrupt coronary occlusion, PmCO2 began to rise in 13.6 +/- 1.1 seconds in heparinized dogs and in 7.5 +/- 0.7 seconds in unheparinized dogs. The subsequent magnitude of the increase in PmCO2 was 24, 88, 171, and 222 mm Hg at 2, 5, 10, and 15 minutes after occlusion. The rate of rise of PmCO2 was essentially linear from 1 minute to 10 minutes at a rate of 18.3 mm Hg/min. The rate of rise was slower during the first 30 seconds after occlusion (6.1 mm Hg/min) and also from 30 seconds to 1 minute (9.7 mm Hg/min). This rate of rise is much greater than that previously observed and reflects the severe myocardial acidosis developing during ischemia. A rise in PmCO2 is one of the earliest metabolic changes that has been observed during myocardial ischemia.
Normal levels of fibrinopeptide A in patients with primary hyperlipidemia.
Authors: Nossel H L , Smith F R , Seplowitz A H , Dell R B , Sciacca R R , Merskey C , Goodman D S
Published: June 2012

Fibrinopeptide A (FPA) levels were measured in a group of 130 controls and patients with various types of primary hyperlipidemia to investigate whether an increased steady state level of thrombin activity is present in hyperlipidemic patients. In a subset of 56 subjects, levels of clotting factors II, VII, and X were measured as well. FPA levels in hyperlipidemic patients were not significantly different from those of control subjects. Furthermore, on multiple regression analysis, no significant relationships were found between FPA levels and the concentrations of serum cholesterol or triglyceride, or log triglyceride levels. Statistically significant relationships were found between all three clotting factor levels and triglyceride concentration. The correlation coefficients for these relationships, however, were low, so that the correlations are of questionable pathophysiological significance. A weak relationship also was found between the plasma levels of cholesterol and of factor II. Thus, although small increases in various clotting factors may be found in patients with hyperlipidemia, plasma FPA levels are normal. These data indicate that hyperlipidemia is not associated with a steady state of increased thrombin activity in vivo in humans.
Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.
Authors: Hyman A L , Kadowitz P J
Published: June 2012

We studied the pulmonary vascular effects of prostacylin, PGI2, in the cat with intact chest under conditions of controlled blood flow. Intralobar injections of PGI2, 0.03--1 microgram, decreased arterial pressure in the perfused lobe in a dose-dependent manner. Inasmuch as lobar blood flow was held constant and left artrial pressure was unchanged, the fall in lobar arterial pressure reflects a decrease in lobar vascular resistance. Prostaglandin E1 (PGE1) and nitroglycerin also decreased lobar arterial pressure; however, PGI2 had greater vasodilator activity than did these substances. Vasodilator responses to PGI2, PGE1, and nitroglycerin in absolute terms were dependent on the baseline level of tone in the pulmonary vascular bed. Prostacyclin reversed the hypertensive and platelet aggregating effects of ADP in the lobar vascular bed. These data indicate that PGI2 has significant vasodilator activity in the feline pulmonary lobar vascular bed.
The effect of fluid volume loading on exclusion of interstitial albumin and lymph flow in the dog lung.
Authors: Parker J C , Falgout H J , Parker R E , Granger D N , Taylor A E
Published: June 2012

The excluded volume fraction for interstitial albumin (FE) was estimated in the lungs of seven mongrel dogs during steady state conditions following intravenous infusions of Ringer's solution, amounting to 0, 5, 10, and 15% of body weight (BW). We estimated the tissue blood volume with 51Cr red cells, extracellular space with 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA), and the albumin pool with 125I human serum albumin. A prenodal tracheobronchial lymphatic was cannulated for recording lymph flow (QL), total protein (CL), and albumin [CL(A)] concentrations. From these measurements, we calculated the extravascular albumin content (QA) and 99mTc-DTPA space (VI) of lung tissue samples collected at the successive volume expansions. The apparent tissue concentration of albumin (CApp = QA/VI) decreased from a control value (mean +/- SE) of 0.89 +/- 0.06 to 0.46 +/- 0.04 g/dl following the 15% BW infusion, whereas CL(A) decreased from 1.43 +/- 0.16 to 0.50 +/- 0.07 g/dl for the same volume expansion. By assuming that pulmonary lymph represented tissue fluid, we calculated a control FE of 0.38 +/- 0.02 using the equation, FE = 1 - [CApp/CL(A)]. FE decreased following successive infusions to 0.28 +/- 0.03, 0.16 +/- 0.02, and 0.10 +/- 0.02. These data indicate a significant contribution by the decrease in FE to the total decrease in tissue albumin concentration as interstitial fluid volume increased. Somewhat unexpectedly, the mean steady state QL increased by only 2.1-fold following the 5% BW expansion, but did not further increase following subsequent volume expansions. This has been attributed to a nonlinear interstitial compliance, sequestration of interstitial fluid, or possible deterioration of the experimental preparation.
Coronary vasoactivity of adenosine in the conscious dog.
Authors: Olsson R A , Khouri E M , Bedynek J L , McLean J
Published: June 2012

Intracoronary adenosine infusions in conscious dogs produced half-maximal coronary vasodilation at 0.57 +/- 0.18 (SD) microns and at 1.01 +/- 0.25 microns in open-chest dogs. In both preparations, adenosine at concentrations in the range found in cardiac muscle by direct analysis produced coronary vasodilation equal to that attained during a maximum reactive hyperemic response. The quantitative structure-activity relationship technique was applied to data on the coronary vasoactivity of 68 adenosine analogs to identify the chemical features of this molecule that determine its vasoactivity. These are: (1) the size of the purine base; (2) the inductive effect of C-2 substituent; (3) the electron-withdrawing effect of the C-6 substituent; (4) the glycosylic torsion angle; (5) the ability of the C-2' and C-3' hydroxyls to participate in hydrogen bonding; (7) the absence of sterically hindering groups in the vicinity of C-2' and, more importantly, C-3'; and (8) the inductive effect of the C-5' substituent. The hydrophobicity of these analogs did not correlate with vasoactivity, suggesting that the hydrophilicity of the ribose moiety overshadows any hydrophobic influence of the very weakly aromatic purine base.
Participation of adrenergic and noradrenergic neurones in central connections of arterial baroreceptor reflexes in the rat.
Authors: Chalmers J P , Petty M A , Reid J L
Published: June 2012

We examined activities of tyrosine hydroxylase (TH) and phenylethanolamine-N-methyl transferase (PNMT) and concentrations of norepinephrine (NE) in seven brain regions and the spinal cord of Wistar rats with elevated blood pressures 1 week and 4 weeks after denervation of carotid and aortic baroreceptors, and compared them to values in sham-operated control rats. TH activity was increased in the solitary tract nucleus (to 188% of control), parahypoglossal nucleus (to 254%), locus ceruleus (to 191%), and posterior hypothalamus (to 225%) at 1 week but not at 4 weeks after denervation. Similarly, NE concentrations were significantly altered in a number of brain regions at 1 week but not at 4 weeks after denervation. The only change in NE concentration at 4 weeks was in spinal cord where the level was reduced to 80% of control in the denervated rats. In contrast, the only change in PNMT activity 1 week after denervation was in posterior hypothalamus (to 59% of control), whereas at 4 weeks there was in increase in the spinal cord (to 159%) and a decrease in both the anterior and posterior hypothalamus (to 59% and 64% of control, respectively). The experiments suggest that increased activity of noradrenergic neurones in the brain may play a significant role in initiating the increase in pressure produced by baroreceptor denervation, whereas decreased activity of hypothalamic adrenergic neurones may be more important in maintaining the raised pressure. An increase in the activity of both adrenergic and noradrenergic nerves in the spinal cord, however, could contribute to maintaining the increase in blood pressure 4 weeks after denervation.
Cardiac atrial myosin adenosine triphosphatase of animals and humans: distinctive enzymatic properties compared with cardiac ventricular myosin.
Authors: Yazaki Y , Ueda S , Nagai R , Shimada K
Published: June 2012

Cardiac myosin obtained from atria had a higher Ca2+-activated ATPase activity than did cardiac myosin from ventricles in various species of animals and in humans. The increased specific activity of Ca2+-activated adenosine triphosphatase (ATPase) of atrial myosin appeared to correlate with the level of the activity of ventricular myosin ATPase in the animal, since the same order in ATPase activity, as observed in ventricular myosins from various animals, was noted in atrial myosins. The enzymatic properties of atrial myosin also were characterized by no activation by N-ethylmaleimide, low activating energy, and a lower rate of inactivation at alkaline pH compared with the same properties of ventricular myosin. These findings suggest a difference in the myosin molecule at or near the active site, involving some sulfhydryl groups, between the two types of cardiac myosin. The Mg2+-activated ATPase activity, both in the presence and absence of actin (which is thought to be closely related to the basic contraction mechanism), also was enhanced in atrial myosin. Thus, the ATPase activities of atrial and ventricular myosins were different with special reference to the reaction pathway involving calcium and magnesium ions and appear to account for the difference in the velocity of contraction between the atria and the ventricles.
Decreased cardiac beta-adrenergic receptors in deoxycorticosterone-salt and renal hypertensive rats.
Authors: Woodcock E A , Funder J W , Johnston C I
Published: June 2012

The development of experimental deoxycorticosterone-salt (DOCA-salt) and renal artery clip hypertension in rats is associated with alterations in the sensitivity of the myocardium to adrenergic stimulation. We studied beta-adrenergic receptors and isoproterenol-stimulated adenylate cyclase in myocardial membranes from hypertensive rats to determine whether this altered sensitivity is associated with any change in beta-adrenergic receptors. The specific binding of the beta-adrenergic antagonist, 125I-iodohydroxybenzylpindolol, was used to measure numbers and affinities of receptors in myocardial membrane preparations. Cardiac membranes from both DOCA-salt and renal hypertensive rats showed significantly fewer beta-receptors than did membranes from control, normotensive rats. Receptor affinity remained unchanged. This decrease was from 110 +/- 19 to 49 +/- 5 fmol/mg protein for DOCA-salt hypertension and from 110 +/- 18 to 75 +/- 16 fmol/mg protein for renal artery clip hypertension. Isoproterenol-stimulated adenylate cyclase activity also was lower in membranes from hypertensive rats, whereas basal and fluoride-stimulated activities were unchanged.
Relationship between changes in left ventricular bipolar electrograms and regional myocardial blood flow during acute coronary artery occlusion in the dog.
Authors: Ruffy R , Lovelace D E , Mueller T M , Knoebel S B , Zipes D P
Published: June 2012

The purpose of this study was to determine whether a quantitative relationship existed between a reduction in regional myocardial blood flow, measured by radiolabeled microspheres, and the degree and type of changes in myocardial activation recorded in bipolar left ventricular subepicardial and subendocardial electrograms, in open-chest dogs following acute coronary artery occlusion. We found that the degree of regional myocardial ischemia was related quantitatively to the reduction in amplitude recorded with bipolar electrograms in the subepicardium and subendocardium, and to the increase in duration of subepicardial electrograms. Other characteristics measured in electrograms did not relate to the degree of ischemia. Despite a comparable reduction in regional myocardial blood flow, subepicardial conduction delay exceeded that recorded in the subendocardium, which often exhibited accelerated conduction.
Effect of acute hypoxia on the pulmonary conversion of angiotensin I to angiotensin II in dogs.
Authors: Szidon P , Bairey N , Oparil S
Published: June 2012

We studied the effect of acute hypoxia on pulmonary conversion of angiotensin I to II in anesthetized dogs. When arterial PO2 was decreased from 86 +/- 14 (SD) to 33 +/- 8 mm Hg without changing pH or PCO2, the single passage conversion of intravenous boluses of radiolabeled angiotensin I in tracer doses fell significantly (P less than 0.005) from 72 +/- 4 to 67 +/- 6%. The effect of comparable levels of hypoxemia on the conversion of continuous intravenous infusions of pharmacological doses (1000 times physiological) of angiotensin I was greater: from 55 +/- 14 to 33 +/- 13% (P less than 0.025). There was prompt return of percent conversion ratios to control levels when hypoxemia was reversed. We conclude that acute hypoxia is associated with a reversible decrease in pulmonary angiotensin converting enzyme availability.
Identification of an angiotensin receptor in rabbit renomedullary interstitial cells in tissue culture. Correlation with prostaglandin biosynthesis.
Authors: Brown C A , Zusman R M , Haber E
Published: June 2012

High affinity binding sites of angiotensin II (A II) have been characterized in rabbit renomedullary interstitial cells in tissue culture. Binding was rapid, specific, and saturable. Scatchard analysis of steady state saturation binding data at 22 degrees C indicated a single binding site with an equilibrium dissociation constant of 3.1 mM. The binding inhibition activities of analogues of angiotensin II correlated with their biological potencies: [Sar1, Ala8]A II greater than [des-Asp1]A II greater than greater than 3--8 hexapeptide. The biologically inactive 1--7 heptapeptide failed to displace the labeled angiotensin II from its binding sites. Angiotensin II directly stimulated prostaglandin E2 biosynthesis by the rabbit renomedullary interstitial cells in tissue culture. The concentration of angiotensin II that resulted in half maximal stimulation of prostaglandin E2 biosynthesis (6.5 nM) correlated with the concentration of angiotensin II that resulted in half maximal occupancy of binding sites (3.1 nM). The relative potency of [des-Asp1] A II as a stimulus for prostaglandin E2 biosynthesis was proportional to its relative binding inhibition activity. These findings demonstrate the biological significance of the angiotensin II binding sites in the rabbit renomedullary interstitial cells in tissue culture and suggest that the cells may provide a homogeneous model tissue for the study of the angiotensin receptor.
Mechanisms by which angiotensin II affects the heart rate of the conscious sheep.
Authors: Lee W B , Ismay M J , Lumbers E R
Published: June 2012

Intravenous infusions of angiotensin II were given to conscious sheep. During these infusions, the pressor action of angiotensin was antagonized by concomitant infusion of sodium nitroprusside. Under these conditions, angiotensin produced a dose-dependent tachycardia. This dose-dependent tachycardia was not affected by propranolol and therefore it was not due to an action of angiotensin on sympathoadrenal mechanisms. The dose-dependent tachycardia was reduced by atropine, and abolished by increases in systolic pressure. We conclude that iv infusions of angiotensin cause a central, dose-dependent reduction in vagal tone. This action is normally antagonized by the baroreceptor reflex response to the hypertensive action of angiotensin. Therefore, in those conditions in which endogenous angiotensin production is increased and blood pressure is not elevated (e.g., sodium deficiency and pregnancy), angiotensin may influence heart rate.
The mass uptake of cholesterol ester from low density lipoproteins by cultured smooth muscle and adventitial cells of human aortas.
Authors: Alam S S , Solen K A , Layman D L , Riddle M C , Connor W E
Published: June 2012

Cultured human smooth muscle and adventitial cells were incubated with human serum and low density lipoprotein (LDL) to study the uptake and accumulation of cholesterol ester from exogenous LDL. The cellular total cholesterol varied with the amount of LDL cholesterol in the medium. The cholesterol ester content increased 4-fold after 2 hours of incubation. A 6-fold rise occurred by 24 hours and continued to 72 hours. The cholesterol ester of the adventitial cells was markedly depleted by incubation with abetalipoproteinemic serum or with a lipid-depleted plasma fraction. By the use of 14C-labeled LDL free cholesterol in the incubation medium, we calculated that some 70-80% of the total accumulated cholesterol ester after 24 hours of incubation was derived from LDL cholesterol ester, and only 20-30% was synthesized by the cells. These studies demonstrated conclusively that human cells greatly increase their cholesterol ester mass after incubation with LDL.
Effect of phospholipid methylation on beta-adrenergic receptors in the normal and hypertrophied rat myocardium.
Authors: Limas C J
Published: June 2012

Abdominal aortic constriction in rats results in mild cardiac hypertrophy (20% increase in left ventricular weight compared to sham-operated controls) which is associated with increased numbers of beta-adrenergic receptors (123 +/- 7.3 fmol/mg protein (mean +/- SE) vs. 87 +/- 4.3 fmol/mg in controls, P < 0.01) without changes in their affinities for dihydroalprenolol. In vitro synthesis of phosphatidylcholine through successive methylation of phosphatidylethanolamine by S-adenosyl-L-methionine is enhanced in the hypertrophied myocardium) 0.38 +/- 0.03 nmol/mg per 30 minutes vs. 0.23 +/- 0.03 nmol/mg per 30 minutes in controls, P < 0.01). In both experimental groups, methyltransferase activity has a high affinity for S-adenosyl-L-methionine (Km = 6.8 microM), depends on Mg2+, is optimal around pH 9.0, and is inhibited by S-adenosyl-L-homocysteine (ki = 8.3 microM). The possible relationship between phospholipid methylation and changes in myocardial beta-adrenergic receptors was studied in both normal and hypertrophied hearts. Preincubation of cardiac membranes with S-adenosyl-L-methionine increased the numbers of b eta-adrenergic receptors in proportion to the duration of incubation and the concentration of S-adenosyl-L-methionine. In both groups, S-adenosyl-homocysteine, but not 5'-AMP or L-methionine, attenuated the increase in beta-adrenoreceptors. These results indicate that phospholipid methylation may be an important mechanism for regulation of beta-adrenergic mechanisms in both normal and hypertrophied myocardium.
Local anesthetics and the role of sodium in the force development by canine ventricular muscle and purkinje fibers.
Authors: Vassalle M , Bhattacharyya M
Published: June 2012

We studied the effects of the local anesthetics, procaine and benzocaine, on the action potential and force of canine ventricular muscle and Purkinje fibers. In ventricular muscle, procaine often shifted the plateau to a more positive value and increased the force of contraction, whereas benzocaine shortened the action potential and decreased contractile force. In Purkinje fibers, both local anesthetics reduced contractile force and decreased the duration of the action potential markedly. In ventricular muscle fibers norepinephrine potentiated the positive inotropic effect of procaine and changed the effects of benzocaine from a negative to a positive inotropic effect. The potentiating effect of procaine on contraction was eliminated by propranolol. In the presence of norepinephrine (and the absence of propranolol), in Purkinje fibers both anesthetics decreased force but less than in the absence of norepinephrine. In the presence of tetrodotoxin (TTX) and norepinephrine, procaine and benzocaine increased contractile force of muscle fibers. Under the same conditions in Purkinje fibers, procaine increased contractile force and benzocaine decreased it (but less than in the absence of TTX). Administration of veratridine increased contractile force in both ventricular muscle and Purkinje fibers: under these conditions, both local anesthetics decreased contractile force in both tissues. We conclude that: (1) the positive inotropic effects of procaine and benzocaine are mediated through an adrenergic mechanism; (2) the negative inotropic effect is at least in part mediated through a reduction of sodium influx; and (3) the negative inotropic effect is more pronounced in Purkinje fibers because of a larger steady state sodium influx during the plateau.
Electrical activity from the sinus node region in conscious dogs.
Authors: Hariman R J , Hoffman B F , Naylor R E
Published: June 2012

In an attempt to understand the way automatic cells in the sinus node (SN) control the cardiac rhythm, we studied extracellular electrograms recorded from the SN region in conscious dogs. A SN electrode, containing 48 silver terminals arranged 1.5 mm apart, was implanted over the node, and an indifferent electrode was implanted on the superior vena cava. Through terminals of the SN electrode paired with the vena caval electrode, "unipolar" electrograms were recorded at 100 microV/cm and with a time constant of 0.1 second. Low amplitude and low frequency deflections (dV/dt less than or equal to 20 mV/sec) which resulted from electrical activity of the node could be differentiated from the more rapid deflections due to atrial electrical activity. Electrical activity due to the inherent automaticity of what appeared to be groups of automatic cells was recognized as a slow negative-going diastolic slope followed by a slow negative-going, or negative and then positive-going, SN potential. Impulse propagation toward the SN electrode terminal in groups of automatic cells appeared as a slow positive-going deflection interrupting the diastolic slope. Adjacent groups of automatic cells located near the sites of earliest atrial activation discharged asynchronously before the earliest atrial activity; this suggests that multiple groups of automatic cells might initiate atrial activation. In addition to changes in rate and in location of the pacemaking groups of automatic cells, significant beat-to-beat variation in the sinoatrial interval contributed to the changes in atrial rate in "sinus arrhythmia." These studies provide a better understanding of SN function in conscious animals.
The effect of diabetes on performance and metabolism of rat hearts.
Authors: Penpargkul S , Schaible T , Yipintsoi T , Scheuer J
Published: June 2012

To explore the effects of diabetes on myocardial function and metabolism we injected male rats with streptozotocin and studied their hearts 8 weeks later. Blood sugar levels in the treated rats were about 600 mg/100 ml. Body and heart growth rates were diminished. When studied in an isolated working rat heart apparatus using 5.5 mM glucose, hearts of diabetic animals showed diminished cardiac output and stroke work at high filling pressures. There also were significant depressions in peak left ventricular systolic pressure, peak aortic flow rate, maximum negative dP/dt, myocardial oxygen extraction, myocardial lactate production, and effluent lactate:pyruvate ratios. Myocardial glycogen stores, calculated glycogen utilization, and pyruvate production were increased in hearts of diabetics, and myocardial oxygen consumption was the same as in control hearts. The end-diastolic pressure-volume relationship was shifted to the right in hearts of diabetics. Most of the abnormalities observed in hearts of diabetic rats persisted when insulin and 15 mM glucose were included in the perfusion medium. Hearts from young rats or from age-matched food-restricted rats with heart weights similar to those of diabetics did not show depressed function or a pressure-volume shift. Our findings indicate that streptozotocin diabetes in rats results in abnormal myocardial performance. This is not due to restrictions in coronary flow or myocardial oxygenation and is not correctable by the provision of high glucose plus insulin in the perfusion medium.
Developmental aspects of the renal response to hypoxemia in the lamb fetus.
Authors: Robillard J E , Weitzman R E , Burmeister L , Smith F G
Published: June 2012

The effects of fetal hypoxemia on renal hemodynamics and renal function were studied in two groups of chronically catheterized young (< 120 days of gestation) and near-term lamb fetuses (> 130 days). Fetal hypoxemia produced, in both groups, a significantly decrease in renal blood flow (RBF) and a significant increase in the filtration fraction. However, the glomerular filtration rate (GFR) did not change significantly suggesting that the renal vasoconstriction associated with fetal hypoxemia was more important at the efferent than at the afferent arteriolar level. In the group of near-term fetuses, the decrease in RBF correlated closely with changes in plasma renin activity (PRA) (r = 0.77). No changes in PRA were observed during hypoxemia in the group of young fetuses. After hypoxemia, reactive hyperemia associated with a significant increase in urinary prostaglandin excretion (PGE and PGF2 alpha) was observed in near-term fetuses but not in young fetuses. It also was demonstrated that fetal hypoxemia produced a significant increase in fetal plasma concentrations of vasopressin associated with an antidiuresis in all but one near-term fetus and in 50% of the young fetuses, suggesting that the ability of the fetal kidney to reabsorb free water is more developed in near-term fetuses. Finally, fetal hypoxemia had no effect on mean arterial pressure and heart rate in young fetuses; however, in near-term fetuses, a significant increase in blood pressure and a decrease in heart rate were observed. In summary, it appears that the response of the fetal kidney to hypoxemia depends on the degree of fetal maturation.
Role of changes in microsomal calcium uptake in the effects of reperfusion of Ca2+-deprived rat hearts.
Authors: Alto L E , Dhalla N S
Published: June 2012

This study was designed to investigate changes in contractile force, resting tension, and microsomal Ca2+ uptake in isolated rat hearts perfused under conditions associated with reversible and irreversible stages of the calcium paradox phenomenon. Five minutes of reperfusion with normal medium containing 1.25 mM calcium after 5 minutes of Ca2+-free perfusion produced a marked rise in resting tension, no recovery of contractile force, and a 63% depression in microsomal Ca2+ uptake. When reperfusion was carried out after 5 minutes of perfusion with 0.025 mM or greater concentrations of Ca2+, after less than 5 minutes of Ca2+-free exposure or after 5 minutes of varying degrees of hypothermic Ca2+-free perfusion, the increase in resting tension and decrease in contractile force development as well as microsomal Ca2+ accumulation were either absent or reduced. Furthermore, reperfusion-induced increases in resting tension and decreases in microsomal Ca2+ uptake also were found to be dependent on the duration of reperfusion as well as on the calcium concentration of the reperfusion medium. Microsomes isolated from control, Ca2+-free perfused or reperfused hearts were found to have similar phospholipid composition, protein profiles (SDS-polyacrylamide gel electrophoresis), and electron microscopic appearance. Whereas Ca2+-free perfusion alone had no effect on any of the parameters studied, reperfusion also depressed microsomal Ca2+-binding, Mg2+-ATPase, and Ca2+-stimulated ATPase activities. Changes in microsomal Ca2+ uptake exhibited sigmoidal relationships with the ability of Ca2+-depleted hearts to recover their contractile force or increase their resting tension upon reperfusion. Our findings suggest that reperfusion-induced contracture and intracellular calcium overload may be associated in part with a defect in the ability of sarcoplasmic reticulum to regulate calcium.