bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged abnormalities of myocardium salvaged by reperfusion
Authors: Kloner R. A. , DeBoer L. W. , Darsee J. R. , Ingwall J. S. , Hale S. , Tumas J. , Braunwald E.
Published: December 2017

The purpose of this study was to determine if biochemical, functional, and ultrastructural abnormalities persist in nonnecrotic postischemic myocardium salvaged by coronary reperfusion. Anesthetized dogs were subjected to 15 min of occlusion of the left anterior descending (LAD) coronary artery followed by 3 days of reperfusion. Biopsies were obtained for measurement of adenosine 5'-triphosphate (ATP) and creatine phosphate (CP) nmol/mg protein), and regional function was evaluated using sonomicrometry. Myocardial ATP concentration after 15 min of occlusion was 37 +/- 1 nmol/mg cardiac protein in nonischemic subendocardium and 19 +/- 2 nmol/mg in ischemic subendocardium. After the hearts underwent 90 min and 72 h of reperfusion, ATP remained significantly depressed in reperfused subendocardium with values of 25 +/- 5 and 29 +/- 2 nmol/mg, respectively (P less than 0.05 and P less than 0.01 compared with the nonischemic zone in which ATP remained normal). CP levels fell during ischemia but returned to normal by 90 min of reperfusion. Percent systolic shortening of myocardial segments fell from +18 +/- 1% (active shortening) to -13 +/- 2% (passive lengthening) during ischemia and was still significantly depressed at +11 +/- 1% (P less than 0.05 vs. preocclusion) at 72 h of reperfusion. Histological examination showed no necrosis, but ultrastructural abnormalities were present. Therefore brief periods of myocardial ischemia are not associated with necrosis but result in functional, biochemical, and ultrastructural abnormalities, which are present for at lest 3 days after coronary reperfusion.
Rabbit carotid baroreflexes after carotid sympathectomy, vagotomy, and beta blockade
Authors: Stinnett H. O. , Sepe F. J. , Mangusson M. R.
Published: December 2017

Factors that modify carotid vascular baroreflexes were studied in anesthetized rabbits after section of the cervical aortic nerves. We recorded steady-state reflex responses of heart rate (HR) and mean arterial pressure (MAP) to changes in isolated nonpulsatile carotid intrasinus pressures (ISP) over a wide range. These measurements and the procedures were repeated 1) after sympathetic denervation of the carotid sinuses by section of the cervical sympathetic nerve below the superior cervical ganglia; 2) after cervical vagotomy; and 3) after beta-receptor blockade by propranolol administration. The linearity of the MAP-ISP relation curve slope was determined between ISP levels of 63 and 100 mmHg. Comparison of results before and after sympathetic denervation of the sinuses indicated that the denervation significantly lowered the position of the MAP-ISP relation curve over a mid-ISP range. Subsequent vagotomy significantly elevated both HR-ISP relation curve and MAP-ISP relation curve. AFter beta-receptor blockade HR remained constant, whereas the slope of the MAP-ISP relation curve decreased to -1.34 from the slope of -2.26 before blockade. Comparison of results before and after beta blockade in the vagotomized animals suggested a substantial cardiac influence on carotid reflex control of MAP.
Ca2+ mobilization in blood platelets as visualized by chlortetracycline fluorescence
Authors: Owen N. E. , Le Breton G. C.
Published: December 2017

Binding of intracellular Ca2+ was measured in intact human blood platelets using the fluorescent Ca2+ probe, chlortetracycline, and a photon-counting microspectrofluorometer. Low doses of epinephrine, A23187, or prostaglandin endoperoxide analog U46619 induced a release of intraplatelet membrane-bound Ca2+. When platelet transmembrane Ca2+ flux was blocked by verapamil or ethylenediaminetetraacetic acid (EDTA), Ca2+ mobilization in response to epinephrine was inhibited, whereas A23187- or U46619-induced Ca2+ release was unchanged. When indomethacin was used to inhibit cyclo-oxygenase activity, Ca2+ mobilization in response to epinephrine or U46619 was partially blocked, whereas Ca2+ release in response to A23187 was unaltered. The relationship between platelet cyclic adenosine 3',5'-monophosphate (cAMP) and intraplatelet Ca2+ binding was also investigated. Prostaglandin E1 or prostacyclin was found to markedly elevate cAMP as well as enhance platelet Ca2+ binding. These effects were augmented by inhibition of phosphodiesterase activity using RO201724. The relationship between cAMP and Ca2+ binding was linear in the range of 10-60 pmoles cAmP/ml platelet-rich plasma. In addition the increase in cAMP stimulated by prostaglandin E1 or prostacyclin reduced the ability of epinephrine, A23187, or U46619 to induce intraplatelet Ca2+ mobilization.
Effect of acetylstrophanthidin on myocardial function and K+ and Ca2+ exchange in newborn rabbit
Authors: Naklanishi T. , Jarmakani J. M.
Published: December 2017

The effects of acetylstrophanthidin (AS) on the mechanical function, tissue potassium content, and tissue calcium content were studied in the isolated, arterially perfused newborn and adult rabbit septum. Newborn and adult muscles were perfused with Krebs-Henseleit solutions containing 0.25, 0.5, 1.0, 1.5, 2.5, or 5.0 X 10(-6) M AS. 42K and 47Ca were used in the measurement of tissue uptakes of these ions. The inotropic effect of AS in the newborn was equal to that in the adult for AS concentrations less than 1.0 X 10(-6) M but was greater (P less than 0.01) than that in the adult at higher concentrations. In muscles perfused with solutions containing AS concentrations higher than 0.5 X 10(-6) M in the adult and 1 X 10(-6) M in the newborn, contractility increased initially and then decreased (mechanical toxicity). Mechanical toxicity in the adult occurred sooner than in the newborn. A decrease in tissue potassium and an increase in tissue calcium were observed immediately after AS infusion in the two age groups. The rates of tissue potassium loss and calcium gain in the newborn were not significantly different from those in the adult. Mechanical toxicity in the newborn was less than that in the adult for an equal amount of tissue potassium loss and/or tissue calcium gain. These data indicate that, in the isolated arterially perfused septal preparation, the newborn myocardium tolerates larger concentrations of AS, resulting in a greater inotropic effect which is observed before the onset of toxicity.
Intramitochondrial adenine nucleotides and energy-linked functions of heart mitochondria
Authors: Asimakis G. K. , Sordahl L. A.
Published: December 2017

Isolated rabbit heart mitochondria were incubated with varying amounts of inorganic pyrophosphate in 250 mM sucrose to specifically decrease the pool size of endogenous adenine nucleotides. The endogenous adenine nucleotide content decreased by as much as 80% as a result of this treatment. Phosphorylating respiration (state 3) declined from about 340 to 180 nAtoms O . min-1 . mg protein-1 over the full range of intramitochondrial adenine nucleotides measured (approx 7.5-1.5 nmol/mg protein). Uncoupled and nonphosphorylating (state 4) rates of respiration were not greatly affected by adenine nucleotide depletion. Respiratory activity of the adenine nucleotide-depleted mitochondria was enhanced by addition of exogenous adenosine 5'-triphosphate (ATP). Partial depletion (approx 40%) of the intramitochondrial adenine nucleotides resulted in an impaired ability of heart mitochondria to retain Ca2+. Premature Ca2+ efflux was associated with organelle swelling and altered energy coupling. Exogenous ATP or adenosine 5'-diphosphate (ADP) added prior to Ca2+ efflux restored Ca2+ retention in these mitochondria. Atractyloside inhibited the restoration of Ca2+ retention. This study indicates a significant role for endogenous adenine nucleotides in maintaining oxidative phosphorylation and Ca2+ transport in heart mitochondria. The results are discussed with regard to significance in ischemic heart damage.
Estimates of isogravimetric capillary pressures during alveolar hypoxia
Authors: Parker R. E. , Granger D. N. , Taylor A. E.
Published: December 2017

Isogravimetric capillary pressures (Pci) and pre-(Ra) and postcapillary (Rv) pulmonary vascular resistances were estimated in isolated dog lungs when ventilated with 95% O2-5% CO2 and during alveolar hypoxia, which was simulated by ventilation with a 95% N2-5% CO2 gas mixture. In addition, the filtration coefficient (KF,C) was measured during alveolar hypoxia and compared with prehypoxic measurements. When both arterial and venous pressures were maintained constant during the alveolar hypoxia, Pci decreased from 8 to 6.9 mmHg, and total pulmonary vascular resistance increased from 0.040 to 0.083 (cmH2O . ml-1 . min . 100 g lung). Ra increased significantly from 0.027 to 0.067, and Rv remained unchanged, averaging 0.013 and 0.015 for control and hypoxic conditions, respectively. The changes in vascular resistance observed in alveolar hypoxia appear to be confined to blood vessels that are probably located in larger preseptal blood vessels. KF,C increased significantly from 0.092 to 0.179 ml . min-1 . cmH2O-1 . 100 g lung-1 during hypoxia. Either the surface area available for fluid exchange or the vascular permeability increases with alveolar hypoxia in the isolated dog lung. Inasmuch as vascular pressures were maintained constant in the present study, then the increase in KF,C with alveolar hypoxia is probably associated with changes in vascular permeability rather than an increased surface area of the fluid exchange vessels.
Reflex effects of left atrial pressure elevation on total intravascular volume
Authors: Rutlen D. L.
Published: December 2017

The reflex autonomic influence of left atrial baroreceptor stimulation on the total capacitance vasculature has not been examined. To this end, left atrial pressure was increased in 25 anesthetized dogs, in which blood from the vena cavae was drained into an extracorporeal reservoir and returned to the right atrium at a constant rate, so that changes in intravascular volume could be recorded as reciprocal changes in reservoir volume. Left atrial pressure was elevated from 5 +/- 1 (mean +/- SE) to 11 +/- 1 mmHg by inflating a balloon at the mitral orifice for 12-20 min. With left atrial pressure elevation, total intravascular volume decreased 25 +/- 10 ml (P less than 0.025). In six of the dogs, intravascular volume decreased 37 +/- 12 ml with left atrial pressure elevation before bilateral cervical vagectomies and increased 66 +/- 8 ml with atrial pressure elevation after vagectomies (P less than 0.001). In eight of the dogs, volume decreased 42 +/- 19 ml with atrial pressure elevation before propranolol administration and increased 44 +/- 29 ml after propranolol (P less than 0.03). Phenoxybenzamine in five of the animals and atropine in three did not attenuate the change in intravascular volume with left atrial pressure elevation. Thus left atrial baroreceptor stimulation is associated with an autonomic reflex, which acts to decrease intravascular volume. The afferent limb is mediated by the vagi, and the efferent limb, by beta-adrenergic receptor stimulation.
A method for continuously assessing coronary blood flow velocity in the rat
Authors: Wangler R. D. , Peters K. G. , Laughlin D. E. , Tomanek R. J. , Marcus M. L.
Published: December 2017

We have developed a directional pulsed-Doppler system to make blood flow velocity measurements in the coronary arteries of the rat. The probe consists of a 1-mm2 crystal mounted in a 6-mm suction cup, which can be attached by vacuum to the vessel without requiring dissection. Recordings of phasic coronary blood flow velocity (CBV) in the rat indicate that 82 +/- 2% (mean +/- SE) of the area under the CBV recording occurs in diastole. CBV increased during an infusion of dipyridamole and changed in parallel with alterations in left-ventricular pressure. To validate the technique we correlated changes in CBV wih changes in microsphere-measured left-ventricular perfusion (range, 20—;780 ml/min x 100 g). These two methods of estimating coronary flow correlated closely (r = 0.93). Measurements of phasic CBV in the rat with this Doppler system should permit a detailed characterization of the coronary circulation in many models of disease that have been developed in the rat.
Diameter, wall tension, and flow in mesenteric arterioles during autoregulation
Authors: Burrows M. E. , Johnson P. C.
Published: December 2017

The effect of arterial pressure on vessel diameter, blood velocity, and intravascular pressure was examined in cat mesenteric arterioles in the arterial pressure range of 120—40 mmHg. Circumferential wall tension and volume flow in individual vessels were calculated. Twenty-nine arterioles with an average diameter of 25.1 micrometers were studied. Twenty-six reactive vessels dilated by an average of 6.5 micrometers with arterial pressure reduction, whereas three nonreactive arterioles narrowed by an average of 5.9 micrometers. When pressure was reduced, circumferential wall tension in reactive arterioles tended to be maintained, whereas in nonreactive vessels tension decreased more than pressure. Data from 25 of 26 reactive arterioles were consistent with the hypothesis that regulation of wall tension accounts for the autoregulatory response; however, in 18 of these vessels a flow-dependent mechanism could also account for the response. Thus the hypothesis that wall tension is a controlled variable responsible for autoregulation is supported, but an important role for flow regulation in local control is also supported.
Maintained ability of carotid baroreflex to regulate arterial pressure during exercise
Authors: Melcher A. , Donald D. E.
Published: December 2017

In conscious dogs bilateral carotid occlusion increased arterial pressure by similar amounts at rest (+ 27 mmHg) and during graded exercise (+ 29 mmHg). During exercise stimulus-response curves for arterial pressure and heart rate derived from isolated carotid sinuses were displaced upward proportionately to the work load, but the curve characteristics were unchanged. After acute bilateral vagotomy similar responses to carotid occlusion were obtained at rest (+ 85 mmHg) and at 21% grade (+ 84 mmHg); the range and maximal slope of the arterial pressure stimulus-response curve during exercise was similar to that at rest, but the exercise curve was displaced downward and to the left. It was concluded that the carotid baroreflex was able to modulate arterial pressure as well during running as at rest. Dogs with neither carotid, aortic, or cardiopulmonary receptors able to respond to the exercise stress became and remained hypotensive during mild exercise; during severe exercise hypotension was present initially, but after 90 s arterial pressure recovered toward the preexercise level. The data indicated that arterial and cardiopulmonary baroreceptors have a major role in the support of arterial pressure in the first moments of exercise.
Sequential hemodynamic and oxygen transport responses in hypovolemia, anemia, and hypoxia
Authors: Schwartz S. , Frantz R. A. , Shoemaker W. C.
Published: December 2017

Sequential cardiorespiratory measurements were made in 30 mongrel dogs during controlled hypovolemia, normovolemic anemia, and hypoxia. The responses to each of these three types of O2 deprivation were studied both as a function of time and of the rate of O2 delivery (normalized cardiac output x arterial O2 content). With progressively decreasing O2 delivery, compensations appeared, reached a maximum, and fell before the final circulatory deterioration. O2 extraction increased in each experiment, but there was differences in the hemodynamic responses to the three types of O2 deprivation; e.g., cardiac output increased in the anemic dogs, and there were greater increases in systemic and pulmonary resistances after hemorrhage. The striking finding was that O2 consumption (VO2) remained relatively constant until the preterminal stage. At this time O2 delivery had fallen from about 27 to less than 10 ml . min-1 . kg-1, blood volume was less than 50%, hematocrit was less than 8%, and arterial O2 tension was less than 30 Torr at an average fractional inspired O2 concentration of 8%, for the hypovolemic, anemic, and hypoxic groups, respectively. Then VO2 dropped precipitously and death rapidly occurred. These results suggest that VO2 represents a physiological marker of impending death in the face of progressively diminishing O2 delivery.
Sense and nonsense about the Fenn effect
Authors: Rall J. A.
Published: December 2017

One of the most influential papers in muscle physiology was published by W. O. Fenn (J. Physiol. London 58: 175-203) in 1923. Fenn determined the quantitative relationship between muscle energy liberation and work performance. Despite the importance of this work, the implications of Fenn's observations are sometimes misunderstood. In this review article, Fenn's experiments are reexamined and the Fenn effect delineated in light of the viscoelastic model of muscle contraction prevalent in the 1920's. The generality of Fenn's results and conclusions are considered in view of more recent results from skeletal and cardiac muscle. Factors responsible for the considerable deviation from Fenn's original results are discussed. Much of the confusion surrounding the generality of Fenn's observations seems to be attributable to the problem of determining an energetic base line for comparing isotonic and isometric contractions. Mommaerts (Physiol. Rev. 49: 427-508, 1969) has suggested the use of an equivalent force base line, which appears to be useful and unifying concept.
Construction and characterization of branched, elastic, transparent vessel models
Authors: Melbin J. , Gopalakrishnan R. , Riffle R. , Noordergraaf A.
Published: December 2017

A technique is presented for the construction of compliant branched vessel models. Properties include wall transparency and geometric reproduction to any scale. A method for characterization of vessel compliance is discussed, as is the requirement for hydrodynamic similarity.
Relationships between adenosine and coronary resistance in conscious exercising dogs
Authors: McKenzie J. E. , Steffen R. P. , Haddy F. J.
Published: December 2017

The relation between myocardial adenosine content, coronary sinus plasma concentration, and coronary vascular resistance was studied in conscious dogs during rest or treadmill exercise. Exercise at 5 mi/h for 7 min on a 20% slope had a significant threefold increase in cardiac work over that of dogs at rest. Exercise increased myocardial adenosine content from 1.35 +/- 0.54 to 8.18 +/- 0.60 nmol/g and decreased coronary vascular resistance from 1.07 +/- 0.13 to 0.69 +/- 0.08 mmHg.ml-1.min.100 g; the former correlated negatively with the latter (r = -0.74, P less than 0.01). The adenosine concentration in coronary sinus plasma increased from 108 +/- 16 to 184 +/- 18 nmol/l plasma and correlated negatively with coronary vascular resistance (r = -0.83, P less than 0.01). Myocardial adenosine content correlated positively with coronary sinus plasma adenosine concentration (r = 0.77, P less than 0.05). Low myocardial lactate content, continued lactate uptake, lack of change in the lactate-pyruvate ratio, and stable coronary sinus oxygen tension values indicated no myocardial hypoxia. These findings demonstrate the release of adenosine into coronary sinus blood and show significant correlations between myocardial adenosine content, coronary sinus adenosine concentration, and coronary vascular resistance during physiological exercise in the dog. The results support the hypothesis that adenosine regulates coronary blood flow during increased metabolic activity.
Pressor response to vasopressin and impaired baroreflex function in DOC-salt hypertension
Authors: Matsuguchi H. , Schmid P. G.
Published: December 2017

Baroreflexes and pressor responses to intravenous arginine vasopressin (AVP) and phenylephrine (PE) were evaluated in conscious, less severely hypertensive desoxycorticosterone (DOC)-salt-treated rats, hypertensive DOC-salt-treated rats, and control rats (n = 6, each group). Pressor responses were retested after ganglionic blockade. In control rats pressor responses to AVP were augmented more than those to PE after ganglion blockade; thus AVP appeared uniquely to augment baroreflex buffering. In hypertensive DOC-salt-treated rats baroreflexes were impaired (P less than 0.05); pressor responsiveness to AVP was augmented compared with control rats (P less than 0.05). After ganglion blockade augumentation of pressor responses was similar for AVP and PE. In less severely hypertensive rats baroreflexes were normal; pressor responses to AVP and PE were like those in control rats before and after ganglion blockade. These results suggest that AVP augments baroreflex buffering, which imposes a restraint on pressor effects of AVP that is not evident with PE. In hypertensive DOC-salt-treated rats a defect in baroreflex buffering during infusion of AVP may contribute to augmented pressor effects of AVP.
Effects of glucagon on cardiac chronotropic response to vagal stimulation in the dog
Authors: Stuesse S. L. , Levy M. N. , Zieske H.
Published: December 2017

Glucagon accelerates the heart independent of sympathetic nervous system stimulation. The effect of glucagon on the chronotropic responses to repetitive bursts of vagal stimulation was determined in open-chest anesthesized dogs. When the cervical vagi were stimulated at constant frequencies, the change in heart rate was not affected by glucagon administration, i.e., no vagolytic effect caused by glucagon was apparent. Thus glucagon did not alter the reaction of acetylcholine with cardiac postsynaptic receptors. When the vagi were stimulated intermittently with one short burst of vagal stimuli delivered each cardiac cycle, the resultant heart period was dependent on the time of vagal stimulus delivery. Both maximum and minimum cardiac cycle lengths obtained during phasic vagal stimulation were decreased by glucagon. As it has been previously demonstrated that vagal impulses to the heart tend to be clustered during certain times of the cardiac cycle, by accelerating the heart glucagon may shift the cardiac response to vagal stimulation.
Effect of increased magnesium on recovery from ischemia in rat and rabbit hearts
Authors: Bersohn M. M. , Shine K. I. , Sterman W. D.
Published: December 2017

Perfusates containing high magnesium concentrations have been suggested to have a protective effect for ischemic myocardium, but the mechanism for such an effect is unclear. We investigated the recovery of isolated perfused rabbit and rat hearts from ischemia under varied conditions of increased Mg. Hearts were made ischemic in the presence of normal 1.2 mM Mg or elevated 15 mM Mg. Rabbit hearts, which show minimal alteration in contractility in the presence of 15 mM Mg, were not protected from ischemia by high Mg perfusate. Rat hearts, which have a large negative inotropic response to 15 mM Mg, exhibited significantly better recovery of mechanical function following ischemia in the presence of high Mg than following ischemia with normal Mg. This protective effect was abolished by increasing both Ca and Mg in the perfusate to prevent the decline in contractility that normally occurred with Mg. Reperfusion with 15 mM Mg after ischemia also had no protective effect if the rat heart had been made ischemic in the presence of normal Mg. We conclude that elevated Mg protects ischemic myocardium only under circumstances in which it has a negative inotropic effect before the onset of ischemia, i.e., in the rat heart perfused with normal Ca. These results suggest that the mechanism of protection by high Mg involves sparing of ATP. However, the different responses to Mg of the species studied in these experiments should be a caution against extrapolating such results from rat hearts to other species.
Capillary density in rat myocardium during timed plasma staining
Authors: Vetterlein F. , dal Ri H. , Schmidt G.
Published: December 2017

In urethan-anesthetized thoracotomized rats the density of myocardial capillaries that had been stained during timed infusions of a plasma label was determined. gamma-Globulin-coupled fluorochromes [lissamine-rhodamine B 200 (RB 200) and fluoresceinisothiocyanate (FITC)] were applied to the vascular system for different intervals of time. The circulation in the heart was freeze stopped, and the dye-containing capillaries were counted in histological cross sections of the organ. When the dyes had been infused into the left atrium for 1, 2, 5, or 10 s the number of stained vessels continuously increased (1,960 +/- 170, 2,780 +- 160, 3,310 +/- 130, and 3,340 +/- 140 cap/mm2 in the subepicardium and 1,990 +/- 210, 2,490 +/- 190, 3,090 +/- 160, and 3,210 +/- 160 cap/mm2 in the subendocardium, respectively). However, further prolongation of dye exposure (2, 10, or 30 min) did not increase significantly the number of marked capillaries. The induction of a general hypoxia (30-s stop of ventilation) after dye application also did not induce higher capillary counts than were found in the normoxic animals during long-time plasma labeling. Changes in red blood cell-containing capillaries were not covered by these observations. The distribution of stained capillaries in the evaluated areas was more inhomogeneous after incomplete filling with RB 200 for 1 s than after complete staining with FITC for 4 min. The results favor the view that in the rat heart at rest the blood plasma passes the microcirculation in an inhomogeneous manner; in all capillaries the slowest transit times do not exceed 5 s, however.
beta-Adrenergic relaxation and cAMP kinase activation in coronary arterial smooth muscle
Authors: Silver P. J. , Schmidt-Silver C. , DiSalvo J.
Published: December 2017

If beta-adrenergic relaxation of smooth muscle is partly mediated by the adenosine 3',5'-cyclic monophosphate (cAMP) system, then beta-stimulation should be correlated to activation of cAMP-dependent protein kinase (cPK). Studies were performed with bovine coronary arterial strips to identify isozymic forms of cPK and to determine if beta-relaxation is correlated to activation of cPK (reflected by elevated ratios of cPK activity without cAMP to cPK activity with cAMP). Both ion exchange chromatography and a new electrophoretic technique revealed two cPK isozymes (types I and II). No change in cPK activity occurred in strips contracted with 30 mM KCl. In contrast, dose- and time-dependent relaxation during beta-stimulation with isoproterenol was highly correlated to parallel increases in cPK activity. Increased cPK activity was inhibited in assays performed with a specific inhibitor of cPK. Both relaxation and activation of cPK were abolished during beta-adrenergic blockade with propranolol. Relaxation by KCl removal or the ionophore R02-2985, unlike beta-mediated relaxation, did not increase cPK activity. These findings show that beta-mediated relaxation of isolated coronary arterial strips specifically activates cPK, and they support the hypothesis that beta-induced relaxation of vascular smooth muscle involves the cAMP system.
Sympathetic transients caused by abrupt alterations of carotid baroreceptor activity in humans
Authors: Wallin B. G. , Eckberg D. L.
Published: December 2017

We examined the role of carotid baroreceptors in the short-term modulation of sympathetic outflow to the muscle vascular bed and parasympathetic outflow to the heart in 10 healthy adults. Afferent carotid baroreceptor activity was modified with 30-mmHg neck suction or pressure applied during held expiration, and efferent sympathetic activity was measured with microelectrodes inserted percutaneously into peroneal nerve muscle fascicles. Sympathetic responses were conditioned importantly by directional changes of carotid transmural pressure: increased pressure (onset of neck suction or offset of neck pressure) inhibited (totally) sympathetic activity, and reduced pressure (offset of neck suction or onset of neck pressure) augmented sympathetic activity. Responses occurred after a latency of about 2 s and did not persist as long as changes of neck-chamber pressure. Cardiac intervals were prolonged by increased carotid transmural pressures and shortened by decreased carotid transmural pressures, but, in contrast to sympathetic responses, cardiac responses adapted only slightly during neck-chamber pressure changes. Our results suggest that in the human a common baroreceptor input is processed differently in central vagal and sympathetic networks. Muscle sympathetic responses to changing levels of afferent baroreceptor traffic are profound but transitory. They appear to be conditioned more by changes of arterial pressure than by its absolute levels.
Dissociation of Ca2+ accumulation from protein release in calcium paradox: effect of barium
Authors: Nayler W. G. , Grinwald P. M.
Published: December 2017

Experiments were undertaken to establish whether Ba2+ can substitute for Ca2+ in maintaining the structural and functional integrity of the glycocalyx. Adult rat hearts were perfused with Ca2+-free buffer at 37 degrees C, with and without added Ba2+. Ten minutes later Ba2+-free, Ca-containing medium was reintroduced. Hearts that had been perfused with Ca2+-free medium exhibited a distorted glycocalyx. On reperfusion with Ca2+-containing medium these hearts released protein (P less than 0.001), gained Ca2+ (P less than 0.001), and depleted their tissue stores of ATP (P less than 0.001) and CP (P less than 0.001). Hearts that had been perfused with Ca2+-free, Ba2+-containing medium retained an apparently intact glycocalyx. On reperfusion with Ca2+-containing. Ba2+-free medium they gained Ca2+ but did not lose protein. These results suggest that Ba2+ only partially replaces Ca2+ in maintaining the integrity of the cell surface. It is also concluded that the absence of protein release does not necessarily exclude the occurrence of severe changes in ionic permeability after cell injury.
Effect of acute regional ischemia on pressure in the subepicardium and subendocardium
Authors: Sabbah H. N. , Stein P. D.
Published: December 2017

The effects of acute ischemia on regional intramyocardial pressure were studied in eight open-chest dogs. Aortic, left ventricular, subepicardial, and subendocardial pressures were measured with catheter-tip micromanometers. During the control period subendocardial pressure during systole (180 +/- 13 mmHg; mean +/- SE) was higher than left ventricular intracavitary pressure (137 +/- 9 mmHg; P less than 0.001). Subepicardial pressure during systole was lower (95 +/- 6 mmHg; P less than 0.001). Acute ischemia caused a reduction of subendocardial pressure during systole to levels below left ventricular systolic pressure (92 +/- 7 mmHg vs. 116 +/- 6 mmHg; P less than 0.01). Ischemia also caused a reduction of systolic subepicardial pressure to 67 +/- 2 mmHg (P less than 0.001). After reperfusion all pressures returned nearly to control values. During diastole subendocardial pressure during the control period (13 +/- 1 mmHg) was high than left ventricular end-diastolic pressure (6 +/- 1 mmHg; P less than 0.001). Subepicardial pressure during diastole (29 +/- 2 mmHg) was higher than subendocardial pressure and left ventricular end-diastolic pressure (P less than 0.001). Acute ischemia had little or no effect on subendocardial pressure during diastole, whereas it caused a reduction of subepicardial diastolic pressure to 16 +/- 1 mmHg (P less than 0.001). Reperfusion of the ischemic region caused a return of all diastolic pressures nearly to control values. These observations indicate that coronary extravascular resistance is affected by ischemia and that the most prominent effects are in the subendocardium during systole and in the subepicardium during diastole.
A dual-channel signal averager for spontaneous signals
Authors: Fabiato A. , Wist A. O.
Published: December 2017

This signal averager has been developed for spontaneous transients of tension and of aequorin bioluminescence in skinned cardiac cells. The signal with the largest signal-to-noise ratio (generally the tension transient) is entered in Channel 1 and triggers the system. Then the averager will unmask the signal entered in Channel 2 if it was buried in the noise during the direct recording. This signal averager uses an inexpensive microcomputer and a program written in Assembly Language. To facilitate its use, the averager is remotely controlled by a potentiometer for the adjustment of the threshold voltage above which the signal in Channel 1 will be collected and by three push buttons for starting the data collection, for averaging and displaying the results, and for resetting the system. The display is purely analog on the recorder, including averaged signals and interval for the signals in both channels together with a graphical representation of the standard deviations and of the number of observations. This signal averager could be used for any preparations developing spontaneous signals with variable intervals, provided that at least one of the synchronous signals has a large enough signal-to-noise ratio to trigger the system.
Effects of diltiazem on smooth muscles and neuromuscular junction in the mesenteric artery
Authors: Suzuki H. , Itoh T. , Kuriyama H.
Published: December 2017

Effects of diltiazem on membrane properties, neuromuscular transmissions, and mechanical responses were investigated in intact and skinned muscles of the guinea pig mesenteric artery. Diltiazem (greater than 10(-6) M) depolarized the membrane, increased the membrane resistance, and suppressed the spike evoked by either electrical depolarization or summation of excitatory junction potentials (EJPs). This drug also suppressed the facilitation process of amplitudes of EJPs produced by repetitive perivascular nerve stimulations. These suppressions of EJPs were not caused by a reduced number of active nerves contributing to the generation of EJP but but rather to a reduction in the release of chemical transmitters. Norepinephrine (NE)-induced and K-induced contractions were suppressed by diltiazem noncompetitively, but the contraction evoked in Na-deficient solution was not suppressed, i.e., diltiazem is not a nonselective inhibitor of the Ca influx. In the saponin-treated skinned muscles diltiazem did not suppress the release from or the accumulation into the Ca store site, nor did it suppress activation of the Ca receptor in contractile proteins. These results indicate that diltiazem acts on the surface membrane and nerve terminal as a Ca antagonist or Ca-channel blocker.
Quantitation of regional chondro-osseous circulation in canine tibia and femur
Authors: Schnitzer J. E. , McKinstry P. , Light T. R. , Ogden J. A.
Published: December 2017

Regional osseous blood flow (OBF) to various regions of the femur and tibia was measured using radioactively labeled 15-micrometers microspheres injected into the right atrium of neonatal, skeletally immature, and skeletally mature canines. Each bone was divided into as many as 41 anatomically distinct sections to assess developmental and regional comparisons in OBF. A quantitative decrease in OBF with increasing chondro-osseous maturity was observed for both the whole bones as well as many regions within a given bone. This was particularly significant in the tibia in which OBF to the mature tibia was much lower than in the immature tibia or even the mature femur. In the immature and neonatal bones, the epiphyseal and metaphyseal regions nearest the physes had the highest flow. The physis had a statistically significant high flow rate. Furthermore, regional differences in OBF correlated well with known regional functions in both endochondral and membranous (periosteal) bone formation. OBF tended to be greater in regions of greater metabolic activity associated with hematopoiesis and endochondral osteogenesis. OBF values correlated well with regional predilections of various diseases such as acute hematogenous osteomyelitis prior to skeletal maturity and osseous metastases, and, by extrapolation, strongly support a physiological reason for delayed healing and nonunion in tibial fractures in the skeletally mature human.
Relation of canine atrial activation sequence to anatomic landmarks
Authors: Hayashi H. , Lux R. L. , Wyatt R. F. , Burgess M. J. , Abildskov J. A.
Published: December 2017

Activation sequence in the atria was investigated in 35 dogs. The atria were studied as four regions, and activation sequence in one region was determined in each experiment. In each region 60 electrograms were recorded simultaneously from bipolar electrodes. The maximal first derivative of the electrograms was taken as activation time. Dried atrial specimens, which permitted identification of pectinate muscles, crista terminalis, and the axis of fiber direction, were prepared. Nonuniform activation was demonstrated with more rapid conduction over the long axis of fiber direction and in Bachmann's bundle, crista terminalis, and pectinate muscles. These regions of rapid conduction were the same during sinus rhythm and ectopic and retrograde activation. Findings confirm the presence of paths with relatively rapid conduction in the atria and demonstrate that these are related to gross anatomic features. Findings also demonstrate that the paths are accessible to activation from multiple sites rather than insulated conduction paths with limited sites for entry and exit of activation.
Mechanism of tissue Ca2+ gain during reoxygenation after hypoxia in rabbit myocardium
Authors: Nakanishi T. , Nishioka K. , Jarmakani J. M.
Published: December 2017

The mechanism of increased tissue Ca2+ uptake during reoxygenation after hypoxia was studied in isolated, arterially perfused rabbit septum maintained at 27 degrees C or 37 degrees C. Tissue 47Ca2+, 85Sr2+, or 133Ba2+ uptake was measured by a juxtaposed gamma-probe and a counter. At 27 degrees C, Ba2+ flux across the sarcolemma is similar to that of Ca2+ and Sr2+, but Ba2+ is not taken up by sarcoplasmic reticulum or mitochondria. Therefore 133Ba2+ flux studies were used to delineate the effects of hypoxia and reoxygenation on sarcolemmal permeability to divalent cations. In muscles maintained at 27 degrees C, reoxygenation after 40 min of hypoxia caused significant increases in both 47Ca2+ and 85Sr2+ uptakes. In contrast, there was no change in tissue 133Ba2+ uptake, 133Ba2+ efflux, determined from 133Ba2+ washout studies, was also unchanged. When the sarcolemma was disrupted by perfusing the muscle with a solution containing phospholipase C, tissue 133Ba2+ uptake as well as 47Ca2+ and 85Sr2+ uptakes increased. Moreover an increase in 133Ba2+ efflux was observed after phospholipase infusion. Addition of an inhibitor or an uncoupler of mitochondrial respiration [sodium cyanide (5 X 10(-3) M) or dinitrophenol (5 X 10(-4) M), respectively] in the perfusate caused significant decreases in reoxygenation-induced tissue Ca2+ gain. In muscles perfused with a solution that did not contain permeant anions capable of proton donation (Tris buffer without HCO3(-) and H2PO4(-)), tissue CA2+ gain during reoxygenation was significantly reduced. Perfusion with Tris buffer also caused greater recovery of mechanical function and myocardial ATP concentration during reoxygenation. In muscles maintained at 37 degrees C, both tissue 47Ca2+ and 133Ba2+ uptakes increased during reoxygenation after 40 min of hypoxia. Isolated mitochondria accumulated both Ca2+ and Ba2+ at 37 degrees C. These data suggest that the reoxygenation-induced tissue Ca2+ uptake is primarily caused by an active uptake by mitochondria and that the increase in mitochondrial Ca2+ uptake can occur without any changes in sarcolemmal permeability to divalent cations (Ca2+, Sr2+, or Ba2+). The data also suggest that the increased mitochondrial Ca2+ uptake is responsible, at least in part, for the impaired recovery of myocardial mechanical and cellular function after hypoxia.
Effects of fatty acid intermediates on Na+-K+-ATPase activity of cardiac sarcolemma
Authors: Owens K. , Kennett F. F. , Weglicki W. B.
Published: December 2017

The effect of amphiphilic lipid intermediates on the Na+-stimulatable activity of the Na+-K+-ATPase of sarcolemma from adult canine cardiac myocytes was studied. Sarcolemma (mean Na+-stimulatable ATPase activity of 73 mumol.mg sarcolemmal protein-1.h-1) was preincubated (37 degrees C for 10 min at pH 7.2) or rapidly mixed at 0 degrees C with amphiphilic lipid intermediates prior to dilution and assay of enzyme activity. Their effects were dependent on temperature, initial concentration, and the ratio of bound amphiphile to sarcolemmal protein. In particular, pretreatment of freshly prepared sarcolemma at 0 degrees C with arachidonyl CoA (up to 0.25 mM) caused 110% stimulation above control activity; palmitoyl CoA or palmitoyl carnitine under the same conditions caused no significant effect. Despite strong binding to the sarcolemmal vesicles, palmitoyl carnitine (up to 0.4 mM or 5 mumol/mg protein) and palmitoyl CoA (0.1 mM or 1.0 mumol of membrane-bound palmitoyl CoA/mg protein) were ineffective even with preincubation. Palmitoyl CoA was inhibitory above this level. Preincubation (22 degrees C for 10 min) with lysophosphatidylcholine only produced inhibition (40% at 0.75 mM). Thus fatty acyl thioesters of CoA and lysophosphatidyl choline but not palmitoyl carnitine perturb sarcolemmal Na+-K+-ATPase activity.
Effect of lung thromboxane generation on regional blood flow during sheep bypass
Authors: Schuette A. H. , Huttemeier P. C. , Watkins W. D. , Zapol W. M.
Published: December 2017

Acute pulmonary artery hypertension and an increased plasma concentration of thromboxane B2 (TXB2), the stable metabolite of the potent vasoconstrictor thromboxane A2, occur within minutes of the onset of venovenous (VV) partial bypass in the awake sheep. To search for systemic vasoconstriction, we assessed systemic blood flow distribution by radioactive microspheres and correlated the changes to alterations in plasma TXB2 and 6-keto-F1 alpha concentration. In 10 control sheep mean plasma TXB2 concentration increased from 0.39 ng/ml prebypass to about 1.1 ng/ml at 8 and 16 min of bypass. Despite marked pulmonary vasoconstriction with a threefold elevated resistance, the blood flow to the heart, brain, and kidney were unchanged at 8 and 16 min of bypass. However, hepatic vascular resistance increased twofold at 8 min of bypass. Indomethacin treatment (10 mg/kg) of six sheep blocked the increase of both pulmonary and hepatic vascular resistance as well as reduced TXB2 levels below 0.1 ng/ml. Thus VV bypass induces transient and selective vasoconstriction of the lung and liver mediated by vasoconstrictor eicosanoids.
Insulin reversal of diabetes-induced inhibition of vascular contractility in the rat
Authors: Pfaffman M. A. , Ball C. R. , Darby A. , Hilman R.
Published: December 2017

Contractures induced by 10(-9)-10(-4) M phenylephrine (PE) or 10-70 mM KCl were observed in aortas isolated from untreated and insulin-treated streptozotocin-diabetic rats. The experiments were conducted at 2-wk intervals for a 12-wk period after the induction of diabetes. Diabetes caused an average decrease of 58 and 60% in the K and PE contractures, respectively. Although the PE contractures in aortas from the insulin-treated diabetic animals (81%) were significantly greater than those in aortas from the untreated diabetic animals (60%), they were significantly less than those in control tissues (100%). Insulin treatment completely reversed the diabetes-induced decrease in the K contracture (102%). It appears that the diabetes-induced decreases in tension may result from an altered sensitivity of the tissues to KCl but not PE. Histological examination of the tissues revealed that the diminished contractions were not due to any detectable change in mural structure. The data indicate that diabetes-induced inhibition of the mechanisms involved in mediating the K contracture are completely reversible by insulin treatment, whereas those mediating the PE contracture are only partially reversible.
Differential effects of histamine on protein permeability in dog lung and forelimb
Authors: Maron M. B.
Published: December 2017

In this study, the effects of histamine on the microvascular permeability of a canine, isolated perfused left lower lung lobe (LLL) and a forelimb preparation were evaluated by comparing the apparent filtered volumes (VF) calculated from the increases in hematocrit (Hct) and plasma protein concentration (Pr) observed during filtration. In the LLL and forelimb, the elevation of venous pressure (Pv) to 15.5 Torr resulted in a ratio of filtered volumes (VF,Pr/VF,Hct) of 0.97 and 0.99, respectively. In the LLL, histamine administration did not significantly change this ratio, whereas the addition of methylene blue decreased it to 0.62. In the forelimb, histamine transiently decreased VF,Pr/VF,Hct to 0.23. After recovery, the elevation of Pv to cause further filtration resulted in a ratio of 0.94. These data suggest that intrinsic differences in the regulation of microvascular permeability exist between blood vessels of the lung and forelimb, in that a histamine dose that significantly increased the protein permeability of the forelimb had no measurable effect on the LLL.
Pneumotoxicity and thrombocytopenia after single injection of monocrotaline
Authors: Hilliker K. S. , Bell T. G. , Roth R. A.
Published: December 2017

Adult Sprague-Dawley rats were treated once with 105 mg/kg monocrotaline (MCT) subcutaneously or an equivalent volume of isotonic saline and examined 2, 5, 10, and 14 days later. The earliest changes observed were in the platelet count, which was decreased in the MCT animals at 2, 5, and 10 days postinjection. Clearance of perfused 5-hydroxytryptamine, a function of pulmonary vascular endothelium, was unaltered in isolated lungs of treated rats until 5 days after dosing but decreased progressively thereafter in the MCT animals and was 24% less than controls by 14 days. The magnitude of this effect was dose related. Inflow perfusion pressure was elevated in perfused lungs of MCT-treated animals at day 14. Right heart hypertrophy, measured as an increase in the ratio of right ventricle to left ventricle plus septum weights, was not evident until 14 days after treatment. A larger dose of MCT (130 mg/kg) resulted in significant mortality, whereas a lower dose (60 mg/kg) did not result in right ventricular hypertrophy 2 wk after treatment. The treatment regimen described has advantages over administration of MCT by ingestion and may prove suitable for investigations of the mechanism by which MCT results in pulmonary hypertension.
Extracellular K+ accumulation during myocardial ischemia in isolated rabbit heart
Authors: Weiss J. , Shine K. I.
Published: December 2017

Double-barreled valinomycin K+-sensitive electrodes were used to record extracellular K+ activity ([K+]o) in the isolated arterially perfused rabbit interventricular septum under conditions of global ischemia. During ischemia a triphasic pattern of [K+]o accumulation was observed consisting of an initial rise, a plateau phase, and a second rise. The initial rise (0.5-1 mM/min) was homogeneous throughout the preparation, reversible, and reproducible. It was augmented by increases in heart rate, contractility, and temperature. The level of the plateau phase (onset 12.3 +/- 3.1 min) was dependent on temperature and heart rate. Hyperkalemia, acidosis, or catecholamine release did not appear to be responsible for the plateau. The second rise in [K+]o (onset 24.2 +/- 4.6 min) was inhomogeneous and always associated with the development of rest tension and irreversible damage to the preparation. Cellular K+ influx mechanisms appeared to be at least partially intact throughout the plateau phase. K+ loss during ischemia could not be attributed to acidosis or catecholamine release, but substrate depletion may play a contributory role.