bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of atrium and ventricle to sustained sympathetic nerve stimulation
Authors: Furuyama M. , Haneda T. , Ikeda J. , Hiramoto T. , Sakuma T. , Kanda H. , Shirato K. , Takishima T.
Published: December 2017

To determine whether chronotropic and atrial inotropic responses to sympathetic nerve stimulation are maintained longer than ventricular inotropic response, the present study was performed with control and acute reserpinized dogs. We stimulated the right stellate ganglion of both groups supramaximally for 60 min and compared right atrial responses (chronotropism and inotropism) with left ventricular (LV) dP/dtmax. In the control group, heart rate (HR) immediately increased and was only slightly attenuated with 60 min of stimulation, and right atrial (RA) inotropic response was less attenuated than was LV response (7% in HR, 33% in RA dP/dtmax, 50% in LV dP/dtmax, P less than 0.01, from the peak value of each response). RA and LV norepinephrine (NE) content was decreased by the stimulation but remained higher than the LV control value. In the reserpinized group, NE content in the RA was low before the stimulation and was further decreased by the stimulation. In this group, HR response was attenuated (27% in HR, P less than 0.01) as was LV dP/dtmax, and the difference in contractile responsiveness between atrium and ventricle disappeared (58% in RA dP/dtmax vs. 61% in LV dP/dtmax, NS). The results indicate that the chronotropic response was only slightly attenuated and that the atrial contractile response was attenuated less than the ventricular response, with sustained sympathetic nerve stimulation in the normal heart. This can be ascribed to the much higher NE content in the RA than that in the LV.
Cigarette smoke extract attenuates endothelium-dependent arteriolar dilatation in vivo
Authors: Rubenstein I. , Yong T. , Rennard S. I. , Mayhan W. G.
Published: December 2017

The purpose of this study was to examine the effects of cigarette smoke extract on endothelium-dependent and endothelium-independent dilatation of arterioles in vivo. Using intravital microscopy, we measured diameter of arterioles contained within the microcirculation of the hamster cheek pouch during suffusion with acetylcholine and nitroglycerin, before and after treatment with cigarette smoke extract. Under control conditions, acetylcholine and nitroglycerin produced dose-related dilatation of cheek pouch arterioles. Superfusion of cigarette smoke extract (1.0%) did not alter baseline diameter of arterioles or vasodilatation in response to nitroglycerin but impaired dilatation of arterioles in response to acetylcholine. Next, we examined the possibility that impaired dilatation of cheek pouch arterioles in response to acetylcholine after exposure to cigarette smoke extract may be related to the release of substances produced via the cyclooxygenase pathway. In indomethacin-pretreated hamsters, acetylcholine produced similar vasodilatation before and after exposure to cigarette smoke extract. Thus these findings suggest that cigarette smoke extract impairs endothelium-dependent responses of cheek pouch arterioles. The mechanism of impaired responses of cheek pouch arterioles after exposure to cigarette smoke extract appears to be related to the release of substances produced via the cyclooxygenase pathway.
Rhythmicity of urinary sodium excretion, mean arterial blood pressure, and heart rate in conscious dogs
Authors: Palm U. , Boemke W. , Reinhardt H. W.
Published: December 2017

The existence of urinary excretion rhythms in dogs, which is a matter of controversy, was investigated under strictly controlled intake and environmental conditions. In seven conscious dogs, 14.5 mmol Na, 3.55 mmol K, and 91 ml H2O.kg body wt-1.24 h-1 were either administered with food at 8:30 A.M. or were continuously infused at 2 consecutive days. During these 3 days, automatized 20-min urine collections, mean arterial blood pressure (MABP), and heart rate (HR) recordings were performed without disturbing the dogs. Fundamental and partial periodicities, the noise component of urinary sodium excretion (UNaV), MABP, and HR were analyzed using a method derived from Fourier and Cosinor analysis. Oral intake (OI) leads to powerful 24-h periodicities in all dogs and seems to synchronize UNaV. UNaV on OI peaked between 1 and 3 P.M. Under the infusion regimen, signs of nonstationary rhythms and desynchronization predominated. UNaV under the infusion regimen could be separated into two components: a rather constant component continuously excreted and superimposed to this an oscillating component. No direct coupling between UNaV and MABP periodicities could be demonstrated. On OI, an increase in HR seems to advance the peak UNaV in the postprandial period. HR and MABP signals were both superimposed with noise. We conclude that UNaV rhythms are present in dogs. They are considerably more pronounced on OI.
Effect of naloxone on hypertension in Dahl salt-sensitive rats
Authors: Johnson M. D. , Richmond B. K.
Published: December 2017

Experiments were conducted to test the hypothesis that chronic administration of an opioid receptor antagonist, naloxone, would affect the outcome of the developmental phase of hypertension in Dahl salt-sensitive (S/JR strain) rats. Accordingly, S/JR rats were maintained on either a low-salt (0.45% NaCl) or a high-salt (7% NaCl) diet for 4 wk. Half of the animals of each dietary group were treated with naloxone (100-130 micrograms/h) by osmotic minipump. Food and water intakes of the high-salt animals were measured for the first 25 days, and blood pressure was measured at the end of the 4 wk via an indwelling femoral arterial catheter. Naloxone treatment slightly but significantly reduced the level of hypertension attained in the high-salt animals (158 +/- 2 mmHg in naloxone-treated animals vs. 168 +/- 3 mmHg in control animals; P less than 0.05) and also attenuated food (and hence salt) and water intakes. Naloxone did not affect the blood pressure of the low-salt animals. To determine whether the slight attenuation of hypertension might be secondary to a reduction of salt intake, a group of control S/JR animals were fed a moderately high-salt diet (2% NaCl), and naloxone-treated S/JR animals were salt-intake matched to this group by daily adjustment of the dietary salt content. Blood pressures after 4 wk of treatment were not different between these two groups. Finally, acute administration of 1 and 30 mg/kg of naloxone failed to lower blood pressure of animals with established hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Contractile response of individual cardiac myocytes to norepinephrine declines with senescence
Authors: Sakai M. , Danziger R. S. , Xiao R. P. , Spurgeon H. A. , Lakatta E. G.
Published: December 2017

The present study utilized individual isolated left ventricular cardiac myocytes from hearts of animals of a broad age range to evaluate the response to norepinephrine and to other stimuli that augment myocardial cell contractile performance. During electrical stimulation before drugs neither the amplitude nor the velocity of shortening normalized for resting cell length differed among cells isolated from 2-, 6- to 8-, or 24-mo-old animals. Norepinephrine augmented twitch amplitude and velocity about fourfold in cells from 2-mo-old hearts but only by 2.5-fold in cells from 24-mo-old hearts (age effect, P less than 0.001). In contrast, the contractile response to increases in bathing [Ca2+] or to the addition of the calcium channel agonist BAY K 8644 or of 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT cAMP) did not vary with age. These results indicate that the age-associated contractile deficit during beta-adrenergic stimulation is specific to the beta-adrenergic pathway and an age-associated deficit in the net production of cAMP. This can be attributed to a diminished cardiac myocyte response to beta-adrenergic agonists, in contrast to modulation of the beta-adrenergic response by other receptor agonists, which are present in intact tissue but absent under the conditions of the present study.
Contribution of extravascular compression to reduction of maximal coronary blood flow
Authors: Abel F. L. , Zhao R. R. , Bond R. F.
Published: December 2017

Effects of ventricular compression on maximally dilated left circumflex coronary blood flow were investigated in seven mongrel dogs under pentobarbital anesthesia. The left circumflex artery was perfused with the animals' own blood at a constant pressure (63 mmHg) while left ventricular pressure was experimentally altered. Adenosine was infused to produce maximal vasodilation, verified by the hyperemic response to coronary occlusion. Alterations of peak left ventricular pressure from 50 to 250 mmHg resulted in a linear decrease in total circumflex flow of 1.10 ml.min-1 x 100 g heart wt-1 for each 10 mmHg of peak ventricular to coronary perfusion pressure gradient; a 2.6% decrease from control levels. Similar slopes were obtained for systolic and diastolic flows as for total mean flow, implying equal compressive forces in systole as in diastole. Increases in left ventricular end-diastolic pressure accounted for 29% of the flow changes associated with an increase in peak ventricular pressure. Doubling circumferential wall tension had a minimal effect on total circumflex flow. When the slopes were extrapolated to zero, assuming linearity, a peak left ventricular pressure of 385 mmHg greater than coronary perfusion pressure would be required to reduce coronary flow to zero. The experiments were repeated in five additional animals but at different perfusion pressures from 40 to 160 mmHg. Higher perfusion pressures gave similar results but with even less effect of ventricular pressure on coronary flow or coronary conductance. These results argue for an active storage site for systolic arterial flow in the dilated coronary system.
Thrombin inhibition enhances tissue-type plasminogen activator-induced thrombolysis and delays reocclusion
Authors: Yao S. K. , McNatt J. , Anderson H. V. , Eidt J. , Cui K. X. , Golino P. , Glas-Greenwalt P. , Maraganore J. , Buja L. M. , Willerson J. T.
Published: December 2017

The objectives of this study were to test the hypotheses that thrombin inhibitors 1) enhance tissue-type plasminogen activator (t-PA)-induced coronary thrombolysis and 2) prevent or delay coronary artery reocclusion. Seventy-one dogs developed occlusive coronary thrombi after introducing a copper coil into the left anterior descending coronary artery (LAD). Coronary blood flows were monitored by an externally positioned pulsed Doppler flow probe. t-PA was given with or without heparin at different times after LAD occlusions. In some experiments, hirugen, a synthetic hirudin-based peptide and specific thrombin inhibitor, was given as 4 mg/kg i.v. bolus and 3 mg.kg-1.h-1 i.v. infusion at 30 min after LAD occlusion with t-PA and a bolus of heparin. Thrombolysis times were significantly shorter in t-PA- and heparin-treated dogs than in dogs treated with t-PA alone. Reocclusion times were significantly longer in t-PA- and heparin-treated dogs than in dogs treated with t-PA alone. Continuous heparin infusions prolonged reocclusion times to greater than 180 min in all treated dogs. The addition of hirugen to t-PA plus one bolus heparin prolonged reocclusion times to 90 +/- 6 min in dogs with 30-min thrombi. Thus heparin enhances t-PA-induced thrombolysis and delays reocclusion. Addition of a specific thrombin inhibitor, such as hirugen, to heparin enhances its effect on delaying reocclusion.
Mechanical effects of coronary perfusion in the passive canine left ventricle
Authors: McCulloch A. D. , Hunter P. J. , Smaill B. H.
Published: December 2017

Mechanical effects of coronary perfusion on passive left ventricular filling were studied in seven isolated potassium-arrested dog hearts subjected to static pressure loading. With the use of a biplane video method, midanterior epicardial deformations were measured before, during, and after perfusion of the coronary circulation with a cardioplegic solution. During perfusion, there was a highly significant reduction (P less than 0.001) in ventricular compliance; the mean cavity volume change decreased by 50% at a filling pressure of 12 mmHg. The loss of compliance was reversible and increased with coronary artery pressure. The magnitudes of the principal epicardial extensions, determined by homogeneous strain analysis, also decreased significantly (P less than 0.001) by an average of 30-40% at ventricular pressures of 4-12 mmHg. But there was no change in the pattern of epicardial deformations. These findings, and similar significant falls in epicardial in-plane rotation (P less than 0.05) and angular translation (P less than 0.001), suggest that the main mechanical effect of the coronary circulation is homogeneous and uniform and is, therefore, probably associated with the microcirculation. We propose that this effect may be modeled by treating the myocardium as a porous elastic medium swollen with an incompressible fluid rather than by an increase in ventricular wall thickness due to filling of the coronary vessels.
Modulation of autoregulatory escape by capsaicin-sensitive afferent nerves in rat stomach
Authors: Leung F. W.
Published: December 2017

Visceral C fibers are stimulated by ischemia and hypoxia, which can be produced by intense vasoconstriction. Epinephrine applied to the gastric submucosa produces a marked vasoconstriction followed by autoregulatory escape. We hypothesize that the autoregulatory escape from epinephrine-induced vasoconstriction in the rat stomach is mediated partly by capsaicin-sensitive C fibers. Functional ablation of these afferent fibers by high-dose systemic capsaicin pretreatment will significantly reduce the magnitude of the autoregulatory escape. Rats received capsaicin (125 mg/kg sc) 10 days before blood flow studies to produce functional impairment of the capsaicin-sensitive afferent nerves. Control rats received vehicle. Under urethan anesthesia, a small area (2 mm diam) of the serosa from the anterior gastric wall was removed to expose the submucosa. The tip of a side-viewing laser-Doppler flow probe was placed inside the stomach directly beneath the exposed submucosa. At 20-min intervals, 20 microliters of buffer, 5 x 10(-4) M epinephrine, 1.6 x 10(-4) M capsaicin, or 3.3 x 10(-2) M histamine was applied topically to the exposed submucosa, with saline washes between applications at 10 min after each application. Blood pressure and laser-Doppler flow signals were monitored continuously. The escape index during the period of epinephrine application was significantly lower in the capsaicin-pretreated rats (0.239 +/- 0.046) than in the vehicle-pretreated rats (0.474 +/- 0.079). Functional ablation of the capsaicin-sensitive afferent fibers was confirmed by a significant blockade of the vasodilatation induced by topical capsaicin. Histamine-induced vasodilatation was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of subendocardial ischemia on transmural myocardial function
Authors: Edwards N. C. , Sinusas A. J. , Bergin J. D. , Watson D. D. , Ruiz M. , Beller G. A.
Published: December 2017

The relationship between regional myocardial perfusion and function under ischemic conditions was examined by using a nontraumatic single-crystal pulsed Doppler system that permits complete transmural assessment of myocardial thickening. Sixteen open-chest dogs underwent either 50 (n = 4) or 180 (n = 12) min of partial coronary artery occlusion. Simultaneous measurements of myocardial thickening fraction (TF) and microsphere-determined blood flow (BF) were taken in the subepicardial, midwall, and subendocardial thirds of the left ventricular wall. During ischemia, there was an excellent correlation between BF and TF in the subendocardium. Mean subendocardial BF was reduced to 0.45 +/- 0.3 ml.min-1.g-1, resulting in a subendocardial TF of 0.8 +/- 19%. Although subepicardial BF was relatively preserved at 1.03 +/- 0.4 ml.min-1.g-1, subepicardial TF was diminished markedly and not significantly different from subendocardial TF. Subepicardial and midwall TF were highly dependent on subendocardial flow rather than on the actual flow in these areas. Hence these studies show a marked dependence of transmural myocardial function on subendocardial blood flow. Outer wall function is more dependent on subendocardial than subepicardial blood flow.
Vasoactive intestinal peptide in canine hearts: effect of total cardiac denervation
Authors: Anderson F. L. , Wynn J. R. , Kimball J. , Hanson G. R. , Hammond E. , Hershberger R. , Kralios A. C.
Published: December 2017

The effect of total cardiac denervation on the distribution of cardiac immunoreactive vasoactive intestinal peptide (IR-VIP) was determined in four groups of dogs. Denervated dogs killed at either 7 days (group 1) or 30 days (group 3) were compared with sham-operated dogs killed at either 7 days (group 2) or 30 days (group 4). The highest concentrations of IR-VIP were found in the left atrium and proximal left anterior descending and circumflex coronary arteries and were not affected by denervation. Concentrations of IR-VIP in the left ventricle were barely detectable. Only right ventricular IR-VIP concentrations were significantly lower in denervated compared with sham-operated dogs in both groups. Thus these data provide evidence of intrinsic VIP innervation of the atria and epicardial coronary arteries and localized extrinsic VIP innervation of the right ventricle of the canine heart.
Effects of amrinone and isoproterenol on mechanoenergetics of blood-perfused rabbit heart
Authors: Goto Y. , Slinker B. K. , LeWinter M. M.
Published: December 2017

To compare the effects of amrinone (AMR) and isoproterenol (Iso) on left ventricular contractility and energetics, we assessed Emax (ventricular contractility index) and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA, a measure of left ventricular total mechanical energy) in isolated cross-circulated (blood-perfused) rabbit hearts during infusion of AMR or Iso in either a constant-flow (CF) or constant-pressure (CP) perfusion mode. Both Emax and the VO2 intercept of the linear VO2-PVA relation increased significantly during AMRCP (increase in Emax 15% and increase in VO2 intercept 11%), ISOCF (49 and 43%), and ISOCP (55 and 54%) but not during AMRCF. However, neither drug changed the slope of the VO2-PVA relation (reciprocal of contractile efficiency) in either perfusion mode. Furthermore, with both drugs the relation between increases in Emax and the VO2 intercept fell on a single regression line (r = 0.92). We conclude that 1) although the mechanism of action and inotropic potency of the two drugs differ, their effects on cardiac energetic cost are essentially the same, i.e., both drugs increase the nonmechanical oxygen cost in proportion to the increase in contractility without changing contractile efficiency, and 2) a significant portion of the inotropic effect of AMR in the whole ventricle is likely due to increased coronary blood flow, i.e., Gregg's phenomenon.
Contraction of single vascular smooth muscle cells by phenylephrine at constant [Ca2+]i
Authors: Collins E. M. , Walsh M. P. , Morgan K. G.
Published: December 2017

The mechanism of alpha-adrenergic agonist-mediated force generation was investigated in single hyperpermeable vascular smooth muscle cells. By use of a previously described method, force was recorded from individual ferret aortic cells made hyperpermeable by exposure to saponin. When the cells were clamped at pCa 7, addition of protein kinase M (PKM), the constitutively active form of protein kinase C (PKC), caused a sustained increase in force, which was reversible upon addition of the PKC pseudosubstrate inhibitor peptide (PSSI) corresponding to residues 19-31 of PKC. Phenylephrine at pCa 7 caused a dose-dependent increase in contractile force of the hyperpermeable cells, which was reversible on addition of phentolamine. The phenylephrine contraction could also be inhibited by the same concentration of PSSI that was effective toward the PKM-induced contraction. The response of the cells to a constant [phenylephrine] in different Ca buffers showed a lack of Ca dependence between pCa 8.6 and 7.0. The addition of PSSI to unstimulated cells caused a small but significant drop in basal tone. Taken together, these results suggest that a fraction of the basal tone, as well as the phenylephrine contraction that occurs in the skinned cells at constant intracellular free Ca2+ concentration, is the result of activation of a Ca-independent isozyme of PKC.
Converting-enzyme inhibitors potentiate bradykinin-induced relaxation in vitro
Authors: Feletou M. , Germain M. , Teisseire B.
Published: December 2017

Experiments were designed to study the effects of converting-enzyme inhibitors (captopril and S 10211) on the endothelium-dependent relaxation to bradykinin in isolated porcine arteries. Rings of femoral arteries with and without endothelium were suspended in organ chambers to record isometric tension. Rings of coronary arteries without endothelium were used as bioassay tissue to record release of endothelium-derived relaxing factor (EDRF) from perfused femoral arteries. In organ chambers, bradykinin induced endothelium-dependent relaxation and, inconsistently, endothelium-independent contraction of the femoral artery rings. The relaxation is mediated by endothelial B2 bradykinin receptors, the contraction through B1 bradykinin receptors. Converting-enzyme inhibitors induced a weak potentiation of the contractile response and weak or no potentiation of the endothelium-dependent relaxation. In the presence of indomethacin, the response to bradykinin was not modified and no potentiation from the inhibitor could be observed. Blockade of the contractile response with a B1 bradykinin antagonist did not unmask a potentiation of the bradykinin endothelium-dependent relaxation by the converting-enzyme inhibitors. However, in the presence of B2 bradykinin antagonist, when high concentrations of bradykinin are required to induce relaxation, converting-enzyme inhibitors potentiated the effects of bradykinin. In contrast, in bioassay conditions with a perfused vascular segment, converting-enzyme inhibitors selectively enhanced the release of EDRF by bradykinin. This effect is observed in the bioassay tissue and in the donor segment. These results suggest that converting enzyme is indeed a powerful modulator of bradykinin action and that other enzymatic pathways of bradykinin metabolism present in the vascular wall could mask its action.
Influence of opioids on CSF vasopressin concentration in newborn pigs
Authors: Armstead W. M. , Crofton J. T. , Share L. , Mirro R. , Zuckerman S. L. , Leffler C. W.
Published: December 2017

This study was designed to determine the influence of opioids on periarachnoid cortical cerebrospinal fluid (CSF) vasopressin concentration in newborn pigs equipped with closed cranial windows. Topical dynorphin-(1-13) produced tone-dependent pial arterial responses (dilation during normotension, constriction when cerebrovascular tone was decreased by hypotension). Dynorphin-(1-13) increased periarachnoid cortical CSF vasopressin concentrations in both normotensive and hypotensive piglets (5 +/- 1, 11 +/- 1, and 233 +/- 27 microU/ml for control, 10(-10), and 10(-6) M dynorphin-(1-13) during normotension, respectively). Dynorphin-(1-8) and U 50488H, a purported selective kappa-opioid receptor agonist, produced similar tone-dependent responses associated with smaller increases in CSF vasopressin concentration. beta-Endorphin caused only cerebral vasoconstriction associated with modest increases in CSF vasopressin (3 +/- 1, 5 +/- 1, 9 +/- 2 microU/ml for control, 10(-10), and 10(-6) M beta-endorphin, respectively). In contrast, methionine enkephalin- and leucine enkephalin-induced dilations were not associated with changes in CSF vasopressin concentration. Naloxone (1 mg/kg i.v.) blocked both the opioid-induced vascular effects and associated changes in CSF vasopressin concentration. Naloxone also attenuated the increase in CSF vasopressin concentration in response to hemorrhagic hypotension. These data show that dynorphin- and beta-endorphin-induced cerebrovascular effects are associated with increased CSF vasopressin concentration. Furthermore, these data indicate that opioids could contribute to the increase in CSF vasopressin concentration observed in response to hemorrhagic hypotension.
Effects of adenosine analogues on ADP ribosylation of GS protein in coronary artery
Authors: Hussain T. , Mustafa S. J.
Published: December 2017

The coupling of adenosine receptor(s) to G proteins was investigated in bovine coronary artery smooth muscle membranes. Western blotting of membrane proteins with specific antisera confirmed the presence of 45- and 52-kDa proteins as alpha-subunits of stimulatory (Gs) protein. Cholera toxin (CT) also ADP ribosylated 45- and 52-kDa proteins. Guanosine 5'-O-(3-thiotriphosphate) (10 nM to 10 microM) stimulated the CT-induced ribosylation, suggesting that the ribosylation can be modulated by the activation of G proteins. 2-Chloroadenosine and (R)-phenylisopropyladenosine produced a concentration (10(-7) to 10(-4) M)-dependent increase in CT-induced ribosylation. These responses were completely blocked by adenosine receptor antagonist 8-sulfophenyltheophylline (10 microM). 5'-(N-ethylcarboxamido)adenosine (NECA) alone or in the presence of 8-cyclopentyl-1,3-dipropylxanthine (50 nM) did not affect the ribosylation. Furthermore, NECA did not counter the effects of 2-chloroadenosine and isoproterenol on CT-induced ribosylation. The data provide evidence for the adenosine receptor(s) coupling to Gs proteins and further suggest a different site or mechanism for the action of NECA in bovine coronary artery.
ATP-sensitive K+ channels regulate resting potential of pulmonary arterial smooth muscle cells
Authors: Clapp L. H. , Gurney A. M.
Published: December 2017

ATP-sensitive K+ (KATP) channels have been proposed to be the target for hyperpolarizing vasodilators. However, the existence of a whole cell KATP current that can regulate membrane potential has not been demonstrated in vascular muscle. Using the patch-clamp technique, we have examined the effects of varying intracellular ATP on membrane potential and currents in isolated rabbit pulmonary arterial smooth muscle cells. With 1 mM ATP in the pipette, cells had a mean resting potential of -55 mV. When ATP was omitted, the resting potential became significantly more hyperpolarized (-70 mV) and the depolarizing response to the KATP-channel blocker, glibenclamide, was potentiated. In contrast, the hyperpolarizing effect of lemakalim was reduced. These hyperpolarized resting potentials were associated with increased activity of a basal, glibenclamide-sensitive time-independent K+ current. Furthermore, flash photolysis of ATP, 3-O-[1(4,5-dimethoxy-2-nitrophenyl)ethyl] ester, disodium salt ("caged ATP") in ATP-depleted cells caused rapid depolarization (less than 1 s) and block of the background K+ current. Our results are consistent with the idea that intracellular ATP can directly modulate the resting potential by inhibition of K+ channels. We propose that this ATP-sensitive K+ current plays an important role in the maintenance of the resting potential in arterial muscle.
Heart rate control in awake dog after selective SA-nodal parasympathectomy
Authors: Randall D. C. , Randall W. C. , Brown D. R. , Yingling J. D. , Raisch R. M.
Published: December 2017

Selective surgical sinoatrial (SA)-nodal parasympathectomy (PSX) was used to distinguish the role of the cardiac autonomic nerves in heart rate (HR) control in awake dogs (n = 8) during rest and behavioral arousal. Resting HR increased from 85 +/- 9 beats (mean +/- SE) before surgery to 114 +/- 6 beats after denervation (P less than 0.05). Atrioventricular (AV)-nodal block occurred during the first 1-3 wk post-PSX, but subsequently resolved. Dogs were behaviorally conditioned by following a 30-s tone (CS+) by a 0.5-s shock. Before denervation the CS+ evoked an initial, rapidly developing tachycardia (phase 1), which was followed by a more slowly developing, but larger, phase 2 tachycardia. The selective SA-nodal parasympathectomy essentially abolished the phase 1 conditional HR response (magnitude: 23 +/- 5 vs. 5 +/- 2 beats, pre- vs. postdenervation, respectively). The phase 2 HR increase was similar before and after the denervation (magnitude: 44 +/- 6 vs. 33 +/- 6 beats; rate of increase: 5 +/- 1 vs. 6 +/- 1 beats/s, pre- vs. post-PSX). Beta-Blockade (propranolol, 1 mg/kg) after PSX decreased phase 2 (magnitude: 7 +/- 3 beats; rate of increase: 1 +/- 0.3 beats/s). These data reveal a sterotypic pattern of change in cardiac autonomic nervous drive during a sudden arousal from rest. Phases 1 and 2 appear to be selective and specific indexes of changes in SA-nodal parasympathetic and sympathetic tone, respectively. The selective denervation unmasks during stress a component of HR control that occurs in the absence of adrenergic or cholinergic mechanisms. These data suggest that multiple interactions occur within the intrinsic ganglion plexuses of the heart with respect to HR control.
Interaction of sepsis and sepsis plus sympathomimetics on myocardial oxygen availability
Authors: Bersten A. D. , Sibbald W. J. , Hersch M. , Cheung H. , Rutledge F. S.
Published: December 2017

The ability to regulate myocardial blood flows (Q) in accord with changing myocardial O2 needs may be depressed in sepsis. This could be an important concern when sympathomimetics are used to augment systemic oxygen delivery (QO2) in this syndrome as increased myocardial O2 needs may accompany an infusion of this class of drugs. Therefore after measuring the effect of sepsis on myocardial O2 metabolism, we then infused various sympathomimetics to evaluate the sepsis+sympathomimetic interaction on myocardial QO2. We measured Q to the left (LV) and right (RV) ventricles by the radioactive microsphere technique in 36 unanesthetized mature sheep, before and during the infusion of dopamine, dobutamine, dopexamine, norepinephrine, salbutamol, or placebo. Randomly selected for infusion, these drugs were titrated to augment the thermodilution-derived cardiac index (CI) by greater than 20%. This study was repeated 24-48 h after cecal ligation and perforation had resulted in a hyperdynamic septic state [change (delta) in CI = sepsis - baseline = +54%; P less than 0.01]. During the septic study, both Q-LV (delta = +80%; P less than 0.01) and Q-RV (delta = +84%; P less than 0.01) were increased above baseline values; the augmented Q to both LV and RV was directly correlated with the arterial perfusion pressure (PA) x CI product and the mean pulmonary artery pressure (PPA) x CI product, respectively. Only 23% of study animals demonstrated net transmyocardial lactate production during the septic study. When the infusion of sympathomimetics was accompanied by an increase in the PPA x CI and PA x CI products, a further increase in both Q-RV and Q-LV, respectively, occurred. Also, neither the ventricular endocardial-to-epicardial flow ratios nor transmyocardial lactate extraction were modified by the sympathomimetics infusion. We conclude that the septic response to infection in this animal model was not accompanied by significant abnormalities in the metabolic regulation of myocardial QO2 (R. E. Cunnion, G. L. Scher, and M. M. Parker, Circulation 73: 637-644, 1986).
Calcium currents in hearts with persistent truncus arteriosus
Authors: Aiba S. , Creazzo T. L.
Published: December 2017

We have used the neural crest model of defective heart development to characterize both L- and T-type Ca2+ currents (ICa,L and ICa,T) in ventricular myocytes from embryonic chick hearts with a severe outflow tract anomaly known as persistent truncus arteriosus (PTA). Because of smaller whole embryo weights but no significant change in the weights of ventricles with PTA, the ventricle to whole embryo weight ratios from hearts with PTA were 61% larger than normal at day 11 of incubation. There was a 51% reduction in the peak magnitude of ICa,L at a test potential of +10 mV (-1.4 vs. -0.7 microA/cm2), whereas ICa,T, a proportionately large fraction of the total Ca2+ current in the embryonic chick ventricle, was unaffected. In comparison to sham-operated controls, ICa,L was otherwise not different. Half-activation occurred at about -1 and -41 mV, whereas half-inactivation occurred at -19 and -61 mV for ICa,L and ICa,T, respectively. The time for half-recovery from inactivation were not different and were 200 and 230 ms for ICa,L and ICa,T, respectively. The time for half-decay of the currents and their responses to BAY K 8644 were also similar in both sham-operated and experimental hearts. Although the dihydropyridine receptor binding experiments suggest that the total number of L-type Ca2+ channels was not different, the results from the physiological experiments indicate that the number of functional L-type channels available for opening and/or the single-channel conductance may be reduced in hearts with PTA. Finally, our results with the neural crest model indicate that it is unlikely that the development of Ca2+ currents is influenced by the onset of cholinergic innervation in the heart.
Oxygen uptake during early cardiogenesis of the chick
Authors: Raddatz E. , Servin M. , Kucera P.
Published: December 2017

Oxidative metabolism of the isolated embryonic heart of the chick has been determined using a spectrophotometric technique allowing global as well as localized micromeasurements of the O2 uptake. Entire hearts, excised from embryos of 10 somites (primordia fused, stage 10 HH) and 40 somites (S shaped, stage 20 HH) were placed in a special chamber under controlled metabolic conditions where they continued to beat spontaneously and regularly. During the 32 h of development, the O2 consumption of the whole heart increased from 0.9 +/- 0.1 to 5.3 +/- 0.8 nmol O2/h. These values corrected for protein content were, however, comparable (0.45 nmol O2.h-1.micrograms-1). At stage 10-12, the O2 uptake varied along the cardiac tube (from 0.74 to 1.0 nmol O2.h-1.mm-2). From stage 10 to 20, the O2 uptake per unit area of ventricle wall increased from 0.7 +/- 0.2 to 1.8 +/- 0.2 nmol O2.h-1.mm-2, and the O2 uptake per myocardial volume during one cardiac cycle varied from 7 to 2.5 nmol O2/cm3. These results indicate that, despite an intense morphogenesis, the cardiac tissue has a rather low and stable oxidative metabolism, although the O2 requirement of the whole heart increases significantly. Moreover, the normalized suprabasal aerobic energy expenditure decreases throughout early cardiogenesis. The functional integrity of the isolated embryonic heart combined with the experimental possibilities of the microtechnique make the preparation appropriate for studying the changes in cardiac metabolism during development.
Effect of fasting and refeeding on mesenteric autoregulation in conscious rabbits
Authors: Kiel J. W. , Bishop V. S.
Published: December 2017

To determine whether feeding improves the efficacy of mesenteric autoregulation in conscious animals, rabbits were instrumented with pulsed-Doppler flow probes on the superior mesenteric artery and distal abdominal aorta to record mesenteric and hindquarters blood flow velocity. Hydraulic occluders were placed on the abdominal aorta (just below the celiac artery) and the thoracic vena cava to vary mesenteric and hindquarters arterial pressure (MAP), which was monitored via a catheter positioned in the distal abdominal aorta. Heart rate (HR) and lumbar sympathetic nerve activity (LSNA) were monitored as indexes of sympathetic nervous system activity. Pressure-velocity curves were obtained by aortic and caval occlusions on two consecutive days; first after a 24-h fast and after approximately 24 h of ad libitum refeeding. In the fed state, mesenteric velocity was significantly increased and MAP was decreased slightly; the slight decrease in MAP was counteracted by significant increases in HR and LSNA, whereas hindquarters perfusion was unchanged. The mesenteric and hindquarters pressure-velocity curves were all highly linear (r greater than or equal to 0.9) and showed no evidence of autoregulation in the fasted or fed state when pressure was changed by either the aortic or the caval occlusions. We conclude that autoregulation plays a minor role in the short-term regulation of mesenteric blood flow in the conscious rabbit.
Development and characterization of a model of eosinophil-mediated cardiomyopathy in rats infected with Toxocara canis
Authors: Schaffer S. W. , Dimayuga E. R. , Kayes S. G.
Published: December 2017

This study begins testing the hypothesis that a causal relationship exists between hypereosinophilia and cardiac dysfunction. Rats infected with the nematode Toxocara canis develop marked hypereosinophilia, with peak blood eosinophil levels of approximately 3,500 eosinophils/mm3 whole blood observed approximately 14 days postinfection. Corresponding to the increase in blood eosinophils of infected animals was a decrease in cardiac performance. By 14 days postinfection, cardiac work had declined approximately 25% while negative first derivative of pressure (-dP/dt) fell approximately 10%. As the extent of hypereosinophilia declined from a peak of approximately 3,500 eosinophils/mm3 whole blood to a new steady state of approximately 1,000 eosinophils/mm3, the degree of cardiac dysfunction also was reduced. Cardiac work was 10-15% less in rats 28-42 days postinfection while -dP/dt was 5% depressed in these animals. Myocardial dysfunction was also observed following exposure of perfused hearts obtained from uninfected rats to buffer containing activated eosinophils. The hearts exposed to activated eosinophils exhibited marked histological alterations, characterized by distention of the intermyocyte space, increased pericapillary space, and focal losses of striated staining pattern. These changes were associated with the accumulation of eosinophils within the myocardium, as evidenced by the cytochemical demonstration of eosinophil peroxidase activity within the heart. The data support the hypothesis that hypereosinophilia can lead to cardiac dysfunction.
Similarities between effects of superoxide-mediated endothelium-derived relaxing factor and cromakalim
Authors: Kim C. D. , Lee W. S. , Rhim B. Y. , Hong K. W.
Published: December 2017

A stable endothelium-derived relaxing factor has been reported to be generated on exposure of endothelial cells to the superoxide anion. In this study, we first evaluated the effects of the relaxing factor and cromakalim on mechanical tone and, second, assessed their consequences on the 86Rb efflux rate. On application of hypoxanthine-xanthine oxidase to a bath for generating superoxide anion, the precontracted rabbit mesenteric artery exhibited another transient increase in contraction, followed by sustained relaxation. This relaxation was lost in the K(+)-physiological salt solution (PSS) (greater than 35 mM) and was inhibited by glibenclamide (10 microM) but not by N-methyl-L-arginine or methylene blue. Hypoxanthine-xanthine oxidase application did not increase either basal or stimulated synthesis of guanosine 3',5'-cyclic monophosphate. In the presence of 2 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and 10 mM MgCl2, the relaxing factor caused a significant increase in 86Rb efflux from the aortic and mesenteric arterial segments, as did the cromakalim. The increased 86Rb efflux, either by the relaxing factor or by cromakalim, was wholly inhibited by glibenclamide. These results suggest that superoxide-mediated endogenous relaxing factor may have a similar mechanism of action to cromakalim in vasodilatation.
Increased concentration of leukotriene B4 but not thromboxane B2 in intestinal lymph of cats during brief ischemia
Authors: Longhurst J. C. , Benham R. A. , Rendig S. V.
Published: December 2017

Mesenteric ischemia stimulates both A delta- and C-fiber afferents to reflexly activate the cardiovascular system. Leukotriene B4 (LTB4) concentration is increased in intestinal mucosa following prolonged ischemia (3 h) followed by reperfusion. Because LTB4 sensitizes afferent nerve endings in the skin, we determined whether LTB4 is produced during brief mesenteric ischemia and thus would be present to sensitize afferent nerve endings in the abdominal visceral region. Cannulas were placed in the portal vein and in a mesenteric lymphatic vessel distal to the lymph node. Mesenteric lymph and portal venous immunoreactive LTB4 (iLTB4) and immunoreactive thromboxane B2 (iTxB2) concentrations were measured before, during, and after 5-7 min of ischemia induced by occlusion of the descending thoracic aorta in cats. Simultaneously, lymph and plasma lactate concentrations were measured. During arterial occlusion, femoral arterial pressure dropped to less than 30 mmHg, and portal venous and mesenteric lymph lactate concentrations were increased significantly (3.3 +/- 0.6 to 6.3 +/- 1.0 mM and 5.2 +/- 0.9 to 7.2 +/- 1.1 mM, respectively, P less than 0.05). During ischemia, iLTB4 concentration increased in lymph from 261 +/- 70 to 424 +/- 102 pg/0.1 ml (P less than 0.05) but did not increase in portal venous blood (135 +/- 26 vs. 168 +/- 44 pg/0.1 ml, control vs. ischemia). iTxB2 concentration was not increased during ischemia in either portal venous blood or lymph (12 +/- 4 to 24 +/- 9 pg/0.1 ml and 19 +/- 7 to 24 +/- 11 pg/0.1 ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine modification of energy substrate use in isolated hearts perfused with fatty acids
Authors: Finegan B. A. , Clanachan A. S. , Coulson C. S. , Lopaschuk G. D.
Published: December 2017

The objective of this study was to determine the effect of adenosine on overall myocardial substrate utilization and mechanical function in isolated working rat hearts. Hearts were perfused with Krebs-Henseleit buffer containing 11 mM glucose (no fat) or with 11 mM glucose and 0.4 mM palmitate (normal fat). Steady-state rates of glycolysis, glucose oxidation, and fatty acid oxidation were measured by determination of quantitative 3H2O and 14CO2 production from radiolabeled substrates. The ratio of glycolysis (6.07 +/- 0.57 mumol.min-1.g dry wt-1) to glucose oxidation (3.12 +/- 0.28 mumol.min-1.g dry wt-1) under no fat conditions was 2:1. The addition of palmitate per se decreased glucose oxidation (to 0.81 +/- 0.09 mumol.min-1.g dry wt-1) and increased the glycolysis-to-glucose oxidation ratio to 6:1. Adenosine (100 microM) reduced this ratio to 3:1 by decreasing glycolysis (to 3.75 +/- 0.32 mumol.min-1.g dry wt-1) and increasing glucose oxidation (to 1.28 +/- 0.18 mumol.min-1.g dry wt-1) in the presence of palmitate. Steady-state palmitate oxidation rates were not altered by adenosine. Adenosine increased efficiency (work performed per unit O2 consumed) of spontaneously beating hearts but had no effect in paced hearts. These effects of adenosine on glucose metabolism may explain the beneficial actions of adenosine during reperfusion post ischemia.
Single perturbed beat vs. steady-state beats for assessing systolic function in the isolated heart
Authors: Campbell K. B. , Taheri H. , Kirkpatrick R. D. , Slinker B. K.
Published: December 2017

Single-beat and steady-state techniques for evaluating end-systolic pressure-volume relationship (ESPVR) and Frank-Starling mechanism (FSM) in the crystalloid-perfused isolated rabbit heart were compared. In the single-beat technique, a train of stable isovolumic beats was interrupted with a single perturbed beat that either ejected against various levels of imposed isobaric load (ESPVR protocol) or beat isovolumically against various levels of end-diastolic volume (V(ED); FSM protocol). In steady-state technique, sustained beating was established, isobarically, at each of various loads (ESPVR protocol) or, isovolumically, at each of various V(ED) values (FSM protocol). ESPVR from steady-state technique lay above and to the left of that from single-beat technique. Contractile state was not uniform within steady-state technique, whereas it was uniform within single-beat technique. In the FSM protocol, single-beat technique exhibited the following features relative to steady-state technique: 1) greater range of developed pressures, 2) steeper ascending limb and more sharply defined maxima, 3) higher maximal developed pressure (Pdmax), and 4) greater volume at Pdmax(Vmax). Again. a common contractile state existed within single-beat technique but not within steady-state technique. It was concluded that single-beat technique was preferable to steady-state technique for evaluating ESPVR and FSM because 1) single-beat technique required less time for obtaining data, 2) single-beat technique allowed identification of uncomplicated values of Pdmax and Vmax, and 3) single-beat technique provided a common contractile-state reference for all data, whereas steady-state technique did not.
Endothelial dysfunction of hindquarter resistance vessels in experimental heart failure
Authors: Drexler H. , Lu W.
Published: December 2017

Local vascular alterations may contribute to increased peripheral vasoconstriction in chronic heart failure. To test whether endothelial dysfunction might be involved, the effect of acetylcholine, nitroglycerin, and NG-monomethyl-L-arginine (L-NMMA) was investigated in a constant-flow perfused hindquarter of rats with and without chronic heart failure (CHF) due to myocardial infarction. Changes in perfusion pressure were measured as an index of changes in hindlimb vascular resistance. The endothelium-dependent vasodilator effect of acetylcholine was significantly reduced in rats with large infarcts (greater than 40% of the left ventricle). However, the endothelium-independent vasodilator effect of nitroglycerin and the vasoconstrictor effect of L-NMMA were similar for infarct and normal animals. The vasodilator response to acetylcholine was partially inhibited by pretreatment with L-NMMA. Thus the basal release of nitric oxide from hindquarter resistance vessels is preserved in CHF. However, the endothelium-mediated dilation in response to acetylcholine is attenuated, in part, due to a depressed stimulated release of nitric oxide. The latter mechanism might be involved in the impaired vasodilatory capacity in the peripheral circulation in CHF, e.g., during exercise.
Substance P modulates autonomic nerve activity in canine hearts
Authors: Smith D. C. , Priola D. V. , Blomquist T. M.
Published: December 2017

We examined the hypothesis that substance P (SP) acts as an “afferent neuromodulator” in the heart regulating the response of the cardiac autonomic nerves to reflexes originating in the heart. We employed the acute, isovolumic canine heart preparation in which the amplitude of the chamber pressure accurately reflects changes in contractility. The heart was decentralized except for one-half of the right vagus, which was left intact to permit afferent communication with the central nervous system, while the remaining one-half was tightly ligated so that the distal part could be used for efferent stimulation. SP was injected in doses of 2–10 micrograms ic. There were no significant inotropic responses to 2 and 5 micrograms SP, whereas 10 micrograms produced positive inotropy of 5–15%. When vagal tone was elevated with sustained vagal stimulation, the same doses of SP increased contractility by 12–28%. Similarly, during right stellate ganglion stimulation (SS), SP decreased contractility 8–22%. After the intact half of the right vagus was sectioned, SP modulation of vagal responses was unaffected, while modulation of atrial, but not ventricular, responses to SS was significantly attenuated. When tested on a series of cardiac-denervated dogs, SP had no effect on cardiac inotropy at any dose. However, when contractility was increased with isoproterenol infusion, SP caused a small decrease in ventricular contractility. These results suggest that SP acts as a modulator of cardiac autonomic neural tone. It is possible that the neuropeptide is released from intramyocardial afferent collateral fibers and inhibits the elevation in vagal or sympathetic nerve activity initiated by activation of cardiac primary afferent nerves.