bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium paradox of the heart: a role for intracellular sodium ions
Authors: Chapman R. A. , Rodrigo G. C. , Tunstall J. , Yates R. J. , Busselen P.
Published: December 2017

Hearts that have been perfused in low calcium fluids suffer, on return to normal calcium solutions, an impairment of function which can be irreversible-- the "calcium paradox." In hypothermic mammalian, amphibian, and fish heart the strong contracture, which is a typical first stage in the development of the calcium paradox, is reversible and appears to depend on a large rise in intracellular Na concentration ([Na]i), which occurs during the period of Ca deprivation. This rise is mainly due to a maintained inward Na flux through the Ca channels and causes a depolarization of the membrane potential, which stabilizes at about -20 mV. In frog atrial muscle if the membrane potential is clamped to values more negative than -50 mV during the period of Ca deprivation, no contracture develops on the restoration of the extracellular Ca concentration ([Ca]o). In all tissues the depolarization, the rise in [Na]i, and the Ca addition contracture are blocked by Ca channel blockers, antiarrhythmic drugs, and Mg ions if present in the Ca-free fluid. These agents are ineffective, however, if applied after a period of Ca deprivation when [Na]i has already risen. The influx of Ca ions, on Ca repletion, is therefore unlikely to be via the Ca channels and would seem to be through the Na-Ca exchange.
Phospholipase D increases cell surface Ca2+ binding and positive inotropy in rat heart
Authors: Burt J. M. , Rich T. L. , Langer G. A.
Published: December 2017

An increase in the content of anionic phospholipid (AP) in the sarcolemma may lead to increased Ca2+ binding and a concomitant inotropic response. To test this hypothesis we treated cultured neonatal rat myocardial cells with phospholipase D (PLD), an enzyme that converts membrane phospholipids to phosphatidic acid. PLD treatment resulted in an increase in total exchangeable Ca2+ of 36%, or 1.56 +/- 0.27 mmol Ca2+/kg dry wt, 79 +/- 3% of which remained displaceable by La3+. The quantity of Ca2+ displaced by polymyxin B, a drug that displaces Ca2+ preferentially from anionic phospholipid sites, increased by 85% from a predicted 0.74 +/- 0.07 to 1.37 +/- 0.19 mmol Ca2+/kg dry wt. Simultaneously the contractility of neonatal rat ventricular tissue increased by 1.7- to 2.5-fold. Spontaneous electrical activity of treated cells was not significantly altered. Thus PLD treatment, which increases the quantity of AP in the membrane, resulted in an 85% increase in Ca2+ bound to AP and concomitantly resulted in a significant increase in contractility. Present results, in association with published results on the effect of PLD on Na+-Ca2+ exchange (J. Biol. Chem. 259: 16-19, 1984), indicate that Ca2+ bound to anionic sarcolemmal phospholipids plays a major role in the control of transsarcolemmal Ca2+ flux and force development.
A new method for preparation of isolated single adult myocytes
Authors: Bkaily G. , Sperelakis N. , Doane J.
Published: December 2017

A new technique for isolation of single cardiac cells from adult rat ventricles is described. The mechanical method is modified from the method of Jacobson (Cell Struct. Funct. 2: 1-9, 1977) by employing an enzyme-free dispersion medium containing Sr2+ or Ba2+ to replace Ca2+. This method produces a high yield of isolated rod-shaped adult mammalian cardiomyocytes that do not contract spontaneously, have a normal resting potential, and are Ca2+ tolerant. This method represents a promising technique for isolation of single, viable, intact, adult myocytes.
Comparison of renin-specific IgG and antibody fragments in studies of blood pressure regulation
Authors: Dzau Victor J. , Kopelman Richard I. , Barger A. Clifford , Haber Edgar
Published: December 2017

Page H404: Dzau, Victor J., Richard I. Kopelman, A. Clifford Barger, and Edgar Haber. Page H404: Dzau, Victor J., Richard I. Kopelman, A. Clifford Barger, and Edgar Haber. “Comparison of renin-specific IgG and antibody fragments in studies of blood pressure regulation.” The author line should read Dzau, Victor J., Richard I. Kopelman, A. Clifford Barger, Jürg Nussberger, and Edgar Haber. Dr. Nussberger was inadvertently listed in the acknowledgments instead of as an author.Comparison of renin-specific IgG and antibody fragments in studies of blood pressure regulation.” The author line should read Dzau, Victor J., Richard I. Kopelman, A. Clifford Barger, Jürg Nussberger, and Edgar Haber. Dr. Nussberger was inadvertently listed in the acknowledgments instead of as an author.
Skin blood flow reduction induced by cigarette smoking: role of vasopressin
Authors: Waeber B. , Schaller M. D. , Nussberger J. , Bussien J. P. , Hofbauer K. G. , Brunner H. R.
Published: December 2017

The effect of vasopressin released by cigarette smoking on blood pressure (BP), heart rate (HR), and skin blood flow (SBF) was investigated in 12 normotensive habitual smokers. At a 1-wk interval, each subject smoked within 10 min two cigarettes before and after intravenous injection of either the specific vascular vasopressin antagonist d(CH2)5Tyr(Me)AVP (5 micrograms/kg) or its vehicle administered in double-blind fashion. SBF was assessed with a laser Doppler flowmeter. Smoking increased plasma vasopressin (P less than 0.01). In six subjects subsequently treated with the antagonist, plasma vasopressin rose to greater than 10 pg/ml and SBF fell by 18.2 +/- 4.8%. This SBF reduction was prevented by the vasopressin antagonist. In contrast, the vehicle had no effect. In the 24 studies taken together, there was a significant correlation (r = -0.60, P less than 0.01) between the SBF decrease during the first smoking period and the plasma vasopressin levels measured afterwards. The BP and HR rise caused by smoking was not modified by the antagonist. Thus it appears that the decrease in SBF induced by smoking is due to enhanced vasopressin secretion.
Na transport and blood pressure in the adrenalectomized rat
Authors: Friedman S. M. , McIndoe R. A. , Tanaka M.
Published: December 2017

The transmembrane distribution of Na, K, and water in freshly excised rat tail artery was measured 7 days after adrenalectomy, 3 days after withdrawal of support with 1% NaCl as drinking water. Cell Na decreased from 35.8 +/- 0.9 to 31.6 +/- 0.7 mmol/kg dry wt, tissue water increased from 2.93 +/- 0.03 to 3.08 +/- 0.04 l/kg dry wt, and tissue K remained unchanged. As concentration, [Na]i decreased from 22.5 +/- 0.9 to 18.3 +/- 1.0 mM in parallel with [Na]o which fell from 140.6 +/- 0.3 to 133.6 +/- 1.0. Conversely, while [K]i fell from 140 +/- 2 to 128 +/- 3, [K]o rose from 2.15 +/- 0.12 to 5.40 +/- 0.33 so that EK dropped from -109 to -83 mV. Aldosterone (120 micrograms X 100 g-1 X 24 h-1 sc; 3 X 10(-7) M if immediately distributed in the extracellular fluid) partially restored blood pressure, plasma [Na] and [K], and tissue water within 24-26 h but did not increase cell Na. Similar effects were produced with corticosterone at 400 microgram X 100 g-1 X 24 h-1 (3 X 10(-6) M if immediately distributed in the extracellular fluid). We conclude that the restoration of blood pressure in the adrenalectomized rat is independent of [Na]i or [Na]o/[Na]i but is associated with enhanced Na transport activity.
Coordination of cardiac myofibrillar and sarcotubular activities in rats exercised by swimming
Authors: Pagani E. D. , Solaro R. J.
Published: December 2017

We measured the functional activity of both myofibrils and fragmented sarcoplasmic reticulum (FSR) in microsomal fractions and homogenates of hearts of sedentary rats and rats exercised by swimming 75 min twice daily for 8 wk. Ca2+ transport was measured under conditions that restricted uptake of Ca2+ to the SR vesicles in the homogenates or microsomal fractions. There was a significant increase in myosin Ca2+-ATPase activity of myofibrils prepared from hearts of swimmers, indicating that a “training effect” had occurred. The mean rate of Ca2+ transport and mean storage capacity were the same for SR vesicles in the homogenates and microsomal fractions from hearts of controls and swimmers. At the same free Ca2+ concentration, the velocity of Ca2+ transport by FSR in homogenate preparations was inversely related to the myofibrillar ATPase activity in a series of preparations from hearts of swimmers, but there was little correlation between the same activities measured in preparations from a series of sedentary rats. Our results suggest that the increase in the rate of relaxation of hearts from exercised rats is not due to an increase in the rate of Ca2+ transport by the SR but may be due to other factors, which include an increase in the rate of cross-bridge cycling or an alteration in the relation and coordination between cross-bridge cycling and SR Ca2+ transport activity.
Renal effects of volume expansion in the renal-denervated nonhuman primate
Authors: Peterson T. V. , Chase N. L. , Gray D. K.
Published: December 2017

Experiments were performed to determine the role of renal nerves in mediating the renal excretory effects of volume expansion in the nonhuman primate. Male Macaca fascicularis monkeys underwent chronic bilateral renal denervation or sham surgery. After a 1- to 2-wk recovery period, each animal was anesthetized with pentobarbital sodium and volume expanded 20% of estimated blood volume. Two types of volume expansion were used, a hemodilutional expansion using 6% dextran in isotonic saline and an isohemic expansion using each monkey's own blood that had previously been withdrawn in exchange for dextran. Renal denervation did not attenuate the excretory responses to volume expansion in that similar increases in urine flow, sodium excretion, filtered load of sodium excreted, osmolar and free water clearances occurred in both the renal-denervated and sham-operated groups. The onset of the responses was not delayed by renal denervation. Furthermore, the results were the same with both volume expansions. These results suggest that, in the monkey, decreases in renal nerve activity that occur with volume expansion are not necessary for eliciting the excretory responses to this hypervolemic stimulus or that other factors compensate if the kidneys are chronically denervated. In addition, the failure of renal denervation to attenuate the excretory effects of a cell-free volume expansion is not related to any dilutional characteristics of the expansion.
Perinatal nutritional modification of weanling rat heart contractile protein
Authors: Dowell R. T. , Martin A. F.
Published: December 2017

The present study ascertained the influence of litter-size-induced perinatal nutritional modification on cardiac contractile protein enzymatic activity and isomyosin composition. Myofibrillar enzyme activities for Mg2+ -ATPase, Ca2+ -ATPase, and creatine kinase (CK) in the weanling heart were unaltered by nutritional modification. However, these enzyme activities were all significantly augmented in the adult heart. Hill plot analyses of Mg2+ -ATPase activities indicated that myofibrillar calcium regulation was not influenced by either nutritional modification or the weanling-to-adult developmental progression. Isomyosin V1 composition (90 +/- 1%) correlated with plasma thyroid hormone level in normal-growth (8/litter) weanlings. Undernutrition retarded conversion of V3 isomyosin to the V1 species while overnutrition enhanced isomyosin conversion. Isomyosin composition in weanling rats subjected to perinatal nutritional modification was independent of thyroid status. In the adult rat, plasma thyroxine levels were increased, whereas V1 isomyosin remained unchanged (88 +/- 2%) compared with that of the weanling groups. Discrepancies in the relationship between contractile protein enzymatic activities, myosin composition, and heart function are apparent between both the litter-size-adjusted weanling rats and between weanling and adult animals. These discrepancies indicate the complex relationship between heart function and contractile protein properties.
Differential effect of vasopressin on angiotensin and norepinephrine pressor action in rats
Authors: Elijovich F. , Barry C. R. , Krakoff L. R. , Kirchberger M.
Published: December 2017

The effect of vasopressin infusion on the pressor dose responses to angiotensin II and norepinephrine was studied in pentobarbital-anesthetized and unanesthetized nephrectomized rats. Pressor vasopressin (2–15 ng X kg-1 X min-1) given to anesthetized rats decreased sensitivity to angiotensin II in a dose-dependent manner (r = 0.88), an effect completely reversible by dPMeTyrAVP, a vasopressin vascular antagonist. Subpressor vasopressin (0.5-1 ng X kg-1 X min-1) given to unanesthetized rats diminished sensitivity to angiotensin II in the presence or absence of pentolinium (10 mg/kg). Shifts in dose-response curves to angiotensin II were always parallel. In contrast, dose responses to norepinephrine were not modified by vasopressin in pentolinium-treated rats and showed a small nonparallel rightward shift in animals without pentolinium. In animals without pentolinium, the baroreflex-mediated reduction in heart rate elicited by angiotensin II was not altered by vasopressin infusion. Our data suggest that vasopressin reduces angiotensin II pressor action by diminishing pressor sensitivity to the peptide. They indicate that the effect may be specific, mediated through the vascular receptor for vasopressin and independent of actions of this hormone on the autonomic nervous system.
Effects of arterial input impedance on mean ventricular pressure-flow relation
Authors: Maughan W. L. , Sunagawa K. , Sagawa K.
Published: December 2017

The mean left ventricular pressure-flow relationship (Pv-Fv), determined under a constant preload and variable peripheral resistance, has been proposed as a quantitative representation of ventricular pump function (9). We determined the Pv-Fv relation in seven isolated cross-perfused canine hearts by varying resistance of a simulated arterial load in five steps from 6.0 to 0.375 mmHg X s X ml-1 while keeping end-diastolic volume, inotropic state, compliance, and characteristic impedance at various constant values. All of the 27 Pv-Fv relations thus determined were moderately nonlinear. Varying end-diastolic volume at three levels shifted the relation curve in an approximately parallel fashion (P less than 0.0001). At three levels of inotropic state (mean LVP of isovolumic contractions 34.3 +/- 8.2, 48.0 +/- 6.3, and 59.2 +/- 9.6 mmHg), the Pv-Fv relation shifted with predominantly a slope change (P less than 0.0001). Changing compliance at three levels (0.2, 0.4, and 0.8 ml/mmHg) caused a statistically significant but quantitatively small crossover of the Pv-Fv curves (P less than 0.0001). Changing characteristic impedance to 0.1, 0.2, and 0.4 mmHg X s X ml-1 caused a highly significant (P less than 0.0001) divergence of Pv-Fv relation over the high Fv range. We conclude that this sensitivity of the Pv-Fv relation to characteristic impedance limits its use as a contractility index.
Coronary venous outflow persists after cessation of coronary arterial inflow
Authors: Chilian W. M. , Marcus M. L.
Published: December 2017

During single long diastoles we simultaneously measured coronary arterial blood flow and coronary venous outflow. When vasomotor tone was intact, approximately 20% of the total volume of diastolic coronary venous outflow appeared after cessation of inflow. During maximal coronary dilation, approximately 40% of the total volume of diastolic coronary venous outflow appeared after cessation of inflow. Theoretically, coronary capacitance could enable persistence of diastolic coronary venous outflow during zero coronary artery inflow. Intramyocardial coronary capacitance calculated from these data was 0.10 ml X mmHg-1 X 100 g-1 with vasomotor tone intact and 0.21 during maximal coronary dilation. These results indicate that the diastolic coronary arterial stop-flow pressure cannot be equated with cessation of flow throughout the coronary vasculature due to the significant contribution of intramyocardial capacitance. We also found that the arterial pressure at which coronary outflow stopped (10–14 mmHg) was substantially less than that at which coronary artery inflow ceased (19–31 mmHg), yet slightly above right atrial pressure (5–9 mmHg). These studies indicate that coronary venous outflow stops at a lower pressure than arterial inflow. Furthermore, the cessation of venous blood flow in the coronary system during long diastoles occurs at pressures only a few mmHg above right atrial pressure.
Hemodynamic and neural mechanisms of acute neurogenic hypertension in the rat
Authors: Werber A. H. , Bryan W. J. , Fink G. D.
Published: December 2017

Experiments were performed to test the hypothesis that acute hypertension caused by aortic baroreceptor deafferentation (ABD) is the result of sympathetic vasoconstriction. Cardiac output (CO), mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured before and after ABD in anesthetized and conscious rats. The role of the sympathetic nervous system in acute ABD-induced hypertension was evaluated by examining the ability of adrenalectomy, adrenal demedullation, guanethidine or combined adrenal demedullation, and guanethidine pretreatment to prevent, and total autonomic blockade to reverse, ABD-induced hypertension. CO did not change significantly after ABD at any time, whereas MAP and TPR increased significantly (P less than 0.05). Only combined adrenal demedullation and guanethidine pretreatment prevented ABD-induced hypertension, and autonomic blockade normalized MAP in ABD rats. Normalization of blood pressure was the result of a decreased TPR. It is concluded that acute ABD-induced hypertension results from vasoconstriction caused by neurally released and/or circulating catecholamines.
Regional blood flow and O2 transport during hypoxic and CO hypoxia in neonatal and adult sheep
Authors: Koehler R. C. , Traystman R. J. , Jones M. D.
Published: December 2017

We compared regional blood flow in unanesthetized newborn lambs with that in adult sheep during acute, isocapnic hypoxic hypoxia [HH, 40-50% reduction of arterial O2 content (CaO2)]. The HH response in lambs and adults was qualitatively similar in heart, brain, and skeletal muscle, where flow increased; and in spleen, where it decreased. The response differed in skin and kidney, where flow decreased in lambs and was unchanged in adults, and in small intestine, where it was unchanged in lambs and increased in adults. Thus vasoconstriction during HH was less prominent in skin, kidney, and small intestine in adults. However, the trend toward lesser vasoconstriction in the adult cannot be attributed to a diminishing carotid chemoreflex and/or a more prominent vasodilatory lung inflation reflex because the same trend occurred during carbon monoxide hypoxia (COH). COH reduces CaO2 but stimulates neither the carotid chemoreflex nor, since hyperpnea is absent, the lung inflation reflex. Within each age group the responses to COH and HH were qualitatively the same. These data therefore provide no evidence for an active carotid chemoreflex in unanesthetized postnatal sheep. This is either because the peripheral circulatory effect of the chemoreflex is suppressed by the lung inflation reflex or, less likely, because the chemoreflex does not operate in the sheep at this level of HH.
Enhanced adrenergic sensitivity of the diabetic neonatal heart
Authors: Downing S. E. , Lee J. C.
Published: December 2017

We have previously shown that insulin reduces inotropic responses to norepinephrine (NE) in isolated cardiac muscle and intact hearts. This inhibition also occurs in vascular smooth muscle. The present study was designed to examine inotropic sensitivity of insulin-deficient diabetic (D) hearts to mixed (NE) and pure beta 1 (isoproterenol, Iso) adrenergic agonists. Lambs were given alloxan (150 mg/kg) and studied 2 days later (glucose, 392 mg/dl). Results from eight controls (C) were compared. All animals were prepared for measurements of ventricular performance and coronary flow (CF) under conditions of constant arterial pressure, aortic flow, and heart rate (paced). Dose-response dP/dtmax curves were obtained by stepped increases of agonist infusion (iv). Iso (40 ng X min-1 X kg-1) caused a 30% increase of CF in both C and D, but no change occurred with NE (0.4 micrograms X min-1 X kg-1). Myocardial O2 consumption did not differ among groups and was unaltered by either agonist. Initial values for heart rate and dP/dt did not differ between C and D. NE dose-response curves were consistently higher in D and the slopes significantly steeper than C. However, Iso curves did not differ. Insulin (10 U/kg) was given to both groups, and the studies were repeated. Dose-response curves in C did not differ significantly with either NE or Iso after insulin. In contrast, curves with both agonists were lower following insulin replacement in the diabetic animals. It is concluded that coronary resistance is reduced by beta-activation but unchanged by NE, which is also an alpha-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
A new preparation for microcirculatory studies of the hamster cheek pouch
Authors: Davis M. J. , Gore R. W.
Published: December 2017

Existing methods of preparing the hamster cheek pouch for observation under an intravital microscope have several disadvantages. The everted method, described by Duling (Microvasc. Res. 5: 423-429, 1973), appears to restrict blood flow by placing unnatural tension on the retractor muscle and by requiring an incision in the tip of the pouch. The method of Yamaki et al. (Microvasc. Res. 21: 299-301, 1981) requires an incision in the tip of the pouch and complete disconnection of the retractor muscle. The chamber method of Greenblatt et al. (Microvasc. Res. 1: 420-432, 1969) has a limited optical resolution because the tissue cannot easily be transilluminated with properly condensed light. We have devised a less traumatic method of preparing the pouch, which eliminates these disadvantages. The hamster is anesthetized, and a thin, glass support plate is inserted into the left cheek pouch. The plate is constructed and positioned so that it does not restrict flow to any part of the pouch. The free end of the plate is secured to the animal stage. An incision is made in the skin to expose the cheek pouch, and the loose, avascular connective tissue investing the pouch and the retractor muscle is removed. The pouch is positioned at an angle of 20 degrees from the hamster's body in a temperature-controlled chamber over a standard microscope condensor system. Throughout both surgical and experimental procedures, the pouch is superfused with Ringer-bicarbonate solution at 37.5 degrees C. This preparation minimizes surgical trauma and allows the entire vascular supply to the cheek pouch to be studied.
Charged amphiphiles regulate heart contractility and sarcolemma-Ca2+ interactions
Authors: Philipson K. D. , Langer G. A. , Rich T. L.
Published: December 2017

We have used charged amphiphiles as phospholipid analogues to modulate the interaction of Ca2+ with myocardial sarcolemma. The amphiphiles were dodecyl sulfate, dodecyltrimethylamine, and lauryl acetate; these are anionic, cationic, and neutral molecules, respectively. The hydrophobic alkyl chain is identical in each case; only the hydrophilic head group is varied. The anionic dodecyl sulfate (50-100 microM) augmented the Ca2+ binding and Na+-Ca2+ exchange activity of sarcolemmal vesicles by approximately 80% and increases the contractility of rabbit papillary muscle. Both developed force and its derivative were increased by approximately 100% with no increase in rest tension. Cationic dodecyltrimethylamine (20-100 microM) produced nearly opposite effects. Neutral lauryl acetate (100 microM) had little apparent effect on any measurement. The charged amphiphiles should be useful tools for further elucidation of excitation-contraction coupling processes in a variety of contractile tissues.
Inhibition of sarcolemmal Na+-K+-ATPase by palmitoyl carnitine: potentiation by propranolol
Authors: Kramer J. H. , Weglicki W. B.
Published: December 2017

Native sarcolemma (SL) from adult canine cardiac myocytes (Na+-K+-ATPase activity 74.2 +/- 3.0 mumol X mg-1 X h-1) was preincubated (10 min, 37 degrees C, pH 7.2) with 1) 20-600 microM palmitoyl carnitine, 2) 250 nM-2.5 mM propranolol, or 3) 20-600 microM palmitoyl carnitine plus propranolol at various concentrations (0.0, 0.025, 0.25, 0.5, 1.0, and 2.5 mM); after preincubation, Na+-K+-ATPase activity was assayed. Palmitoyl carnitine alone (series 1) had no effect on ATPase activity over the range of 20-400 microM but was inhibitory (30%) at 600 microM. Propranolol alone (series 2) did not alter ATPase activity at any concentration. When SL membranes were exposed to both palmitoyl carnitine and propranolol (series 3), a dose-dependent inhibition of ATPase activity was observed. The inhibitory effect was not reversed by 3.0% bovine serum albumin. Propranolol concentrations greater than 0.025 mM significantly inhibited the activity of SL exposed to palmitoyl carnitine (above 150 microM). Palmitoyl carnitine and propranolol do not have to be added simultaneously to produce combined inhibition. Activity was inhibited 50% when SL were pretreated with 100 microM palmitoyl carnitine followed by addition of 2.5 mM propranolol no inhibition occurred if preincubation conditions were reversed. Thus exposure of SL to propranolol and reported physiological levels of palmitoyl carnitine leads to irreversible inhibition of the Na+-K+-ATPase, which may be due to the combined membrane-perturbant actions of these amphipathic agents.
Exercise training modifies myocardial mitochondria and myofibril growth in spontaneously hypertensive rats
Authors: Crisman R. P. , Tomanek R. J.
Published: December 2017

We tested the hypothesis that exercise training provides a stimulus that could modify the decrement in mitochondria-to-myofibril volume ratio characteristic of myocardial cells hypertrophied in response to a pressure overload. Spontaneously hypertensive rats (SHR) were trained 5 days/wk on a treadmill at 70-90% maximal VO2 between the ages of 6 and 16 wk corresponding to the development of hypertension and cardiac hypertrophy. The training program increased maximal VO2 and effected a resting bradycardia but did not alter blood pressure, left ventricular hypertrophy, or peak cardiac output. Our stereological data from electron micrographs shows that the decrement in mitochondrial volume density and the increase in myofibril volume density characteristic of SHR compared with their normotensive controls (WKY, Wistar-Kyoto rats) were reversed. Thus the relative volumes of mitochondria and myofibrils and their ratio in trained SHR were similar to those of the WKY group. The similarity was noted in myocytes from both the subepicardium and subendocardium. These data suggest that exercise training facilitates a proportional growth of energy-producing and energy-consuming organelles in SHR and that this effect is not secondary to modification of blood pressure or left ventricular mass.
Efferent vagal innervation of canine ventricle
Authors: Takahashi N. , Barber M. J. , Zipes D. P.
Published: December 2017

The route efferent vagal fibers travel to reach the left ventricle is not clear and was the subject of this investigation. We measured left ventricular and septal effective refractory period (ERP) changes during vagal stimulation and a constant infusion of norepinephrine, before and after phenol was applied at selected sites of the heart to interrupt efferent vagal fibers that may be traveling in that area. Phenol applied to the atrioventricular (AV) groove between the origin of the right coronary artery anteriorly to the posterior descending branch of the circumflex coronary artery completely eliminated vagal-induced prolongation of ERP in the anterior and posterior left ventricular free wall and reduced, but did not eliminate, ERP prolongation in the septum. A large (3-cm radius) epicardial circle of phenol prevented vagal-induced ERP prolongation within the circle in all dogs, while a small (1-cm radius) epicardial circle of phenol failed to prevent vagal-induced ERP changes within the circle in any dog. An intermediate (2-cm radius) circle eliminated vagal effects on ERP in 13 of 18 dogs. Arcs of phenol, to duplicate the upper portion of the circle, applied sequentially from apex to base eliminated efferent vagal effects only when painted near or at the AV groove. We conclude that the majority of efferent vagal fibers enroute to innervate the anterior and posterior left ventricular epicardium cross the AV groove within 0.25-0.5 mm (depth of phenol destruction) of the epicardial surface.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of reduced resistive afterload on left ventricular pressure-volume relationship
Authors: Ducas J. , Schick U. , Girling L. , Prewitt R. M.
Published: December 2017

In seven anesthetized, beta-blocked dogs, we investigated the effects of a reduction in systemic vascular resistance (SVR) on left ventricular (LV) systolic mechanics. LV pressure and volumes (scintigraphic techniques) were measured in base-line condition, after opening one and then two arteriovenous fistulas (AVF). Volume was infused to maintain LV end-systolic pressure (LVESP). Despite a constant ESP, the mean end-systolic volume (LVESV) fell from 42 to 31 ml (P less than 0.025) when the SVR fell from 81 to 48 units (P less than 0.0025), and the LVESV fell further to 24 ml (P less than 0.0025) when the SVR was decreased to 30 units (P less than 0.025). In six similarly prepared dogs, aortic flow was measured, and when resistive afterload decreased, instantaneous flow increased. Since end-diastolic volume was not significantly changed when resistive afterload decreased, instantaneous LV volume decreased despite constant systolic LV pressure. In two of these dogs, LV pressure-volume (PV) trajectories were drawn for the ejection period. When SVR decreased there was a marked leftward shift of the PV trajectory as the end of ejection was approached. It is concluded that at a given contractile state and ventricular pressure, alterations in resistive load directly affect rate and extent of ventricular shortening.
Effects of coronary and extravascular pressure on intramyocardial and epicardial blood velocity
Authors: Chilian W. M. , Marcus M. L.
Published: December 2017

In open-chest anesthetized dogs we measured phasic coronary blood velocity in an epicardial artery (left anterior descending), a small epicardial artery (within 0.5 cm before penetration into the myocardium), and an intramyocardial artery (septal) during changes in perfusion pressure and extravascular pressure. Circumflex artery diameter was also measured during pressure changes to directly assess vascular compliance. At low and normal arterial pressures (less than 125/86 mmHg) and during aortic insufficiency, the phasic character of blood flow velocity in the large epicardial arteries was markedly different from that in the small epicardial and septal arteries: there was retrograde systolic blood flow velocity in the septal artery and small epicardial artery, whereas antegrade blood flow velocity persisted in the left anterior descending artery. At pressures greater than 150/106 mmHg, the differences in the phasic character of blood flow velocity in the left anterior descending artery from that in the septal artery and small epicardial artery were small and decreased as aortic pressure increased. At pressures greater than 125 mmHg, the cross-sectional area change per millimeter of mercury was approximately three times less than at pressures between 30 and 75 mmHg, indicating decreased coronary compliance at the higher pressures. Increasing extravascular pressure in the septum (right ventricular hypertension) greatly increased retrograde systolic blood flow velocity in the septal artery (P less than 0.05). However, right ventricular bypass (0 right ventricular pressure) did not alter the phasic nature of blood flow velocity in the septal artery. From these results we confirmed that epicardial capacitance is inversely related to distending pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
Measurements on the internal structure of freeze-fractured cardiac plasma membrane
Authors: Kordylewski L. , Karrison T. , Page E.
Published: December 2017

We describe a quantitative analysis of the internal structure of cardiac plasma membranes freeze fractured in situ, including the P-face particle density (lambda), the P-face particle diameter (d), the percent of fracture face area occupied by particles (Ap), and the spatial distribution of particles (random, clustered, or ordered). This analysis has been applied to seven sheep hearts to compare the plasmalemmal internal structures in ventricular and atrial myocytes and Purkinje strands of the same hearts and also to myocytes of frog, chicken, rabbit, and rat ventricles (to compare internal plasmalemmal structure of different vertebrate classes). Measurements were made on tissues conventionally prepared for freeze fracture by glutaraldehyde fixation and cryoprotection. We found that, in the same sheep hearts, lambda and Ap for ventricular plasmalemma significantly exceeded those for atrial plasmalemma and that the distribution of atrial P-face particles was more clustered than that for ventricle. d and Ap for frog ventricular plasmalemmal P-face significantly exceeded values for some of the other vertebrates.
An antihypertensive substance associated with erythrocytes
Authors: McCumbee W. D. , Rankin G. O. , Wright G. L.
Published: December 2017

An extract was prepared from hemolyzed erythrocytes of spontaneously hypertensive rats (SHR) which inhibits lanthanum-resistant calcium uptake by aortic segments and lowers blood pressure in several models of hypertension. Erythrocyte hemolysates were extracted with Triton X-100 and partially purified by boiling and Sephadex G-150 column chromatography. The effects of the extract on calcium uptake by aortic segments in vitro were reversible and dose dependent. The extract was administered by intraperitoneal injection to male and female SHR, deoxycorticosterone-NaCl hypertensive rats (DOCA-NaCl), one-kidney one-clip (1K,1C) and two-kidney, one-clip (2K,1C) renovascular hypertensive rats, and their appropriate control groups. At 24 h postinjection, the antihypertensive factor (AHF) lowered the systolic blood pressure (SBP) in the conscious SHR male (200 +/- 7 to 132 +/- 11 Torr), SHR female (172 +/- 4 to 117 +/- 11), DOCA-NaCl (187 +/- 6 to 121 +/- 8), 2K,1C (165 +/- 8 to 127 +/- 7), and 1K,1C (167 +/- 8 to 146 +/- 13) models of hypertension. The duration of the effect on the SBP was model dependent. The SBP was significantly decreased for 4-8 days in SHR, 4 days in 1K,1C and 2K,1C, and 2 days in DOCA-NaCl. In contrast to the results obtained in hypertensive rats, AHF had little effect on the SBP of normotensive animals. Both the blood pressure and calcium effects were abolished by digestion with phospholipase D, tentatively suggesting that the compound(s) inducing these effects may be a phospholipid or have a phospholipid moiety.
Stroke volume effect of changing arterial input impedance over selected frequency ranges
Authors: Sunagawa K. , Maughan W. L. , Sagawa K.
Published: December 2017

We investigated the effect of changing arterial input impedance over three selected frequency ranges on stroke volume (SV) in nine isolated canine left ventricles. The input impedance was simulated with a three-element Windkessel model (i.e., resistance, characteristic impedance, and compliance) and was imposed on the ventricles with a servo-controlled loading system. Under a constant end-diastolic volume [33.1 +/- 1.5 (SE) ml], we changed the modulus of the afterloaded impedance over a low frequency range (below 0.13 Hz) by changing the resistance, over a transitional frequency range (in which the impedance modulus decreases from total resistance to characteristic impedance) by changing the compliance, and over a high frequency range (above 2.0 Hz) by changing the characteristic impedance. Each of the impedance components was changed from control to 50 and 200% of control. SV sensitively decreased from 16.1 +/- 0.7 to 7.4 +/- 0.5 ml in response to the increase in the low-frequency impedance modulus. SV was relatively insensitive, however, to the same percent increase in the impedance modulus over the transitional frequency range (from 11.2 +/- 0.6 to 12.3 +/- 0.7 ml) and over the high frequency range (from 11.9 +/- 0.6 to 11.6 +/- 0.7 ml). The average relative sensitivities of SV to the increase and decrease in impedance moduli in these frequency ranges were 1.2:0.12:0.04. We conclude that the modulus of impedance in the low frequency range is, by far, a more important determinant of SV than those in the transitional and high frequency ranges.
Chronic norepinephrine infusion and adrenergic function of hypertrophied hearts
Authors: Siri F. M.
Published: December 2017

The ability of chronic subpressor norepinephrine infusion to prevent depletion of myocardial norepinephrine stores and deterioration of myocardial adrenergic nerve function in congestive heart failure was examined. Four groups of adult male Wistar rats were subjected to aortic constriction or sham aortic constriction, along with either norepinephrine infusion or infusion of vehicle alone. After 7 days of treatment, these animals were evaluated for myocardial norepinephrine content, ventricular mass, and resting hemodynamics. Chronotropic and inotropic responses to electrical stimulation of the left and right cervical sympathetic trunks and to intravenous injections of tyramine and norepinephrine were measured. Chronic norepinephrine infusion normalized myocardial norepinephrine content in aortic-constricted rats but did not significantly affect heart size or mortality. Norepinephrine infusion diminished responses to sympathetic nerve stimulation, despite apparently normal myocardial norepinephrine sensitivity. The results suggest that chronic norepinephrine infusion suppresses neurotransmission in the heart by some means unrelated to its norepinephrine store. This suppression may be compensatory and reversible.
Effect of erythrocyte storage and oxyhemoglobin affinity changes on cardiac function
Authors: Apstein C. S. , Dennis R. C. , Briggs L. , Vogel W. M. , Frazer J. , Valeri C. R.
Published: December 2017

Storage of blood can depress erythrocyte 2,3-diphosphoglycerate (DPG) levels and thereby increase oxyhemoglobin affinity and potentially decrease capillary-to-tissue oxygen transport. We measured myocardial function and metabolism in isolated rabbit hearts with fixed coronary flow under basal conditions and during isoproterenol stress at 37 and 30 degrees C, comparing high and low oxyhemoglobin affinity (OHA) erythrocytes. The high OHA state resulted from standard storage conditions, which caused depressed values of DPG and P50 (the oxygen tension at which hemoglobin is 50% saturated). The low OHA erythrocytes were initially stored and then underwent biochemical treatment to restore the DPG and P50 values to normal. The low OHA cells released more oxygen, and myocardial oxygen consumption and contractile function were increased relative to the high OHA cells during both the basal and stress states at both 37 and 30 degrees C. These observations may be relevant for patients with limited coronary flow when such patients receive large transfusions of stored blood.
Erythrocyte adenosine transport: effects of Ca2+ channel antagonists and ions
Authors: Ford D. A. , Sharp J. A. , Rovetto M. J.
Published: December 2017

On the basis of observations of adenosine-Ca2+ competition, we assessed the effects on erythrocyte adenosine transport of Ca2+ channel antagonists, mono- and divalent cations, and Cl- and Cl- transport inhibitors. The Ca2+ channel antagonists, diltiazem and verapamil, competitively inhibited adenosine influx (Ki = 158 +/- 17.4 and 13.5 +/- 1.3 microM at 10 microM adenosine, respectively), despite no apparent effect on transport by Ca2+, Mg2+, Na+, or K+. Verapamil also inhibited uridine efflux (Ki = 1.7 +/- 0.3 microM at 84-100 microM intracellular uridine). The absence of Cl- decreased adenosine influx rates from 0.615 +/- 0.013 to 0.386 +/- 0.008 nmol X s-1 X ml intracellular H2O-1. The Cl- transport inhibitors, diisothiocyanostilbene disulfonate (10 microM), furosemide (1 mM), and NO-3 (145 mM), decreased adenosine influx rates to 0.301 +/- 0.008, 0.325 +/- 0.013, and 0.430 +/- 0.009 nmol X s-1 X ml intracellular H2O-1, respectively. These studies indicate that the Ca2+ channel antagonists inhibit adenosine release and uptake and therefore may modulate adenosine-mediated events. Additionally, they suggest that adenosine and anion transport systems are linked or share common features.
Effects of infarction, procainamide, coupling interval, and cycle length on refractoriness of extrastimuli
Authors: Marchlinski F. E. , Cain M. E. , Falcone R. A. , Corky R. F. , Spear J. F. , Josephson M. E.
Published: December 2017

The effects of prematurity, cycle length, site of stimulation, and procainamide on ventricular refractoriness following an extrastimulus (S2) were assessed in 10 dogs with and 10 dogs without infarction. Extrastimuli were introduced at preselected coupling intervals (S1-S2) from normal right and left ventricular sites and from left ventricular sites of infarction during drive cycle lengths (S1-S1) of 350 and 250 ms. At each S1-S2 interval, the effective refractory period of S2 was determined by introducing a second extrastimulus (S3). At all stimulation sites, cycle lengths, and before and during infusion of procainamide (mean concn 18.6 +/- 3.5 micrograms/ml), shortening (greater than 10 ms change) in refractoriness was most marked over a narrow range of closely coupled S1-S2 intervals. Regardless of stimulation site, the effective refractory period of S2 was less during a cycle length of 250 ms compared with a cycle length of 350 ms. In dogs without infarction, the effective refractory periods of S2 from left ventricular sites tended to be longer than from right ventricular sites, particularly during procainamide administration. The refractory period of S2 at sites of infarction did not differ consistently from those at normal sites. Finally, at all stimulation sites and cycle lengths, procainamide prolonged refractoriness of S2 at each S1-S2 interval and blunted the total shortening in refractoriness in response to S2.
Transmembrane potassium fluxes in isolated feline ventricular myocytes
Authors: Silver L. H. , Houser S. R.
Published: December 2017

Radioactive tracer (42K) flux techniques were used to determine transmembrane K+ influx and efflux in isolated cardiac myocytes. Ca2+-tolerant adult feline ventricular myocytes were isolated by retrograde perfusion of the coronary arteries with a collagenase-containing solution. The isolated cells had intracellular Na+ (17.2 +/- 0.2 mM) and K+ (135.0 +/- 3.9 mM) concentrations that were stable over time. 42K influx and efflux were both described by a single exponential function. The rate constant describing 42K influx was 5.86 +/- 0.40 X 10(-2) min-1, and the calculated total K+ influx was 18.4 +/- 1.6 pmol X cm-2 X s-1. Ouabain produced a dose-dependent decrease in K+ influx with maximal inhibition at 10(-4) M. In the presence of 10(-4) M ouabain, total K+ influx was resolved into both active (ouabain-sensitive 12.2 pmol X cm-2 X s-1) and passive (ouabain-insensitive 6.2) components. The rate constant describing 42K efflux was 6.46 +/- 0.50 X 10(-2) min-1, and the calculated total K+ efflux was 22.0 +/- 1.5 pmol X cm-2 X s-1. K+ efflux was not significantly altered (P greater than 0.5) in the presence of 10(-4) M ouabain. The absolute magnitudes of total K+ influx and efflux were not significantly different (P greater than 0.1), thus suggesting that the cells were in a steady state with respect to K+. These studies demonstrate that transmembrane tracer kinetics and K+ fluxes were readily described using isolated adult cardiac myocytes and that both the active and passive components of these unidirectional fluxes were identified in the presence of ouabain.
Interaction of left atrial receptors and carotid sinus baroreceptors on heart rate in the dog
Authors: Teo K. K. , Man G. C. , Kappagoda C. T.
Published: December 2017

This study was undertaken to determine the influence of 1) the left atrial receptors (LA) on the ability of the carotid sinus baroreceptors (CS) to regulate heart rate and 2) the CS on the reflex increase in heart rate mediated by the LA. The LA were stimulated by stretching the pulmonary vein-atrial junctions in dogs anesthetized with alpha-chloralose. Aortic pressure was controlled, and the pressure in the CS was regulated. Stimulus-response curves were obtained relating heart rate to pressures in the CS, in the control state, and during stimulation of LA (6 dogs). Factorial analysis revealed that LA exerted a significant influence on heart rate (P less than 0.01). Next the CS pressure was set at mid, low, and high levels and the LA stimulated. It was found that the effect on heart rate was greatest at the mid setting (+19.3 +/- 2.9 beats/min) and least at the low setting of the pressure in the CS (+0.9 +/- 0.5, 11 dogs). Sympathetic blockade attenuated significantly the response in the mid setting of the CS pressure and left intact the response at the high setting of the pressure in the CS. It is concluded that there is a significant interaction between these two reflexes.
Myocardial adenine pool depletion and recovery of mechanical function following ischemia
Authors: Humphrey S. M. , Holliss D. G. , Seelye R. N.
Published: December 2017

The loss of nucleotide pool precursors from the heart during ischemia and reperfusion may affect resynthesis of ATP and consequently mechanical recovery. Isolated working rat hearts were made globally ischemic for from 15 to 25 min, and the tissue content of adenine pool metabolites, creatine, creatine phosphate (CP), and inorganic phosphate (Pi), were measured after 20 min of reperfusion. In addition, the coronary effluent was assayed for nucleotides, nucleosides, and oxypurines. Hearts that recovered 75% or more of their preischemic hemodynamic function had significantly lower ATP and NAD but greater CP and Pi than controls. Complete failure of hearts was associated with severely depleted ATP but not CP. All hearts released 25% or more of their preischemic adenine pool during the 20-min reperfusion. This loss correlated more closely with a reduction in recovery from 100 to 75% than with complete failure. Thus extensive loss of adenine pool precursors is not critically related to the failure of heart muscle to recover function but may be an important limiting factor in determining the extent and time course of mechanical recovery.
Pregnancy-induced changes in sheep uterine and carotid arteries
Authors: Griendling K. K. , Fuller E. O. , Cox R. H.
Published: December 2017

To characterize the effects of pregnancy on vascular tissue, intact segments of the uterine and carotid arteries were removed from nonpregnant and near-term pregnant sheep. Pressure-diameter relations were measured on isolated segments under activated (122 mM K+, 10(-4) M phenylephrine) and passive (0.1 mM Ca2+, 10(-5) M iodoacetic acid) conditions. DNA and RNA were determined spectrophotometrically. Collagen, elastin, and water contents were also measured. Pregnancy had no effect on either the mechanics or the biochemical properties of the carotid artery. However, there was a marked increase in internal radius in the uterine artery with pregnancy (0.060 +/- 0.016 vs. 0.198 +/- 0.019 cm). Active tangential stress increased, as did passive stiffness of the uterine artery. The collagen fraction decreased during pregnancy (57.2 +/- 2.4 vs. 45.7 +/- 2.2%), while elastin and RNA remained unchanged. A small decrease in DNA produced a significant increase in the RNA-to-DNA ratio. These data suggest that, in pregnancy, the uterine artery selectively undergoes a characteristic hypertrophy of its vascular smooth muscle.