bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventricular response during irregular atrial pacing and atrial fibrillation
Authors: Chorro F. J. , Kirchhof C. J. , Brugada J. , Allessie M. A.
Published: December 2017

In the isolated rabbit heart the ventricular response during irregular atrial pacing and atrial fibrillation was studied. Irregular pacing was performed by an algorithm that generated a population of random stimuli within a chosen range of intervals. During incremental regular pacing atrioventricular (AV) Wenckebach conduction occurred at an atrial cycle length of 164 +/- 24 ms (n = 11). During irregular atrial pacing with a variation of 20, 60, and 100 ms second-degree AV block developed at average cycle lengths of 171, 182, and 198 ms, respectively. In contrast, the pacing interval resulting in stable 2:1 AV block was shortened from 131 ms to 120 and 112 ms during irregular pacing with 20- and 60-ms variation. During pacing with 100-ms variation stable 2:1 AV block no longer occurred. Addition of acetylcholine (0.25-0.75 X 10(-6) M) increased the maximal degree of stable AV block during regular pacing. During irregular pacing, however, stable AV block disappeared. Instead, during second-degree AV block a monophasic inverse relationship (r = -1.5 +/- 1.7) between atrial and ventricular rates appeared as a result of an increased occurrence of concealed conduction in the AV junction. Also during electrically induced atrial fibrillation an inverse relationship was found between the atrial and ventricular rate. We conclude that the ventricular rate during atrial fibrillation is not only determined by the properties of the AV node but also by the rate and irregularity of the fibrillatory process.
Identification of major slow blood pressure oscillations in conscious dogs
Authors: Persson P. B. , Ehmke H. , Kohler W. W. , Kirchheim H. R.
Published: December 2017

All physiological feedback systems (e.g., in arterial pressure control) tend to oscillate in a characteristic manner. Mechanoreceptors can effectively buffer resulting fluctuations in arterial blood pressure. In this study arterial and cardiopulmonary receptors were interrupted in eight conscious foxhounds by sectioning the afferent pathways to the central nervous system. In response, three major peaks were detected in the blood pressure power spectrum: in addition to the well-known rhythms reflecting heart rate and respiration, very slow oscillating waves with a cycle length of 20 +/- 4 min and a 10(5)-fold higher power than the other two waves were detected. The amplitude of these oscillations could exceed 100 mmHg. This peak was also identified under control conditions (at a cycle length of 21 +/- 4 min, n = 6); however, the relative power was greater than 10(3)-fold less with mechanoreceptors intact (P less than 0.001). Thus a major slow oscillating component of arterial pressure control has been identified. Normally, mechanoreceptors buffer the resulting waves of this oscillator. These very strong fluctuations may characterize an important feature of blood pressure regulation.
Hyaluronan in prenodal lymph from skin: changes with lymph flow
Authors: Reed R. K. , Laurent T. C. , Taylor A. E.
Published: December 2017

Hyaluronan, an important structural component of the interstitial matrix in skin, is found in lymph to be subsequently degraded in lymph nodes and liver. Hyaluronan concentration and flux were measured in prenodal lymph from the hindpaw in six pentobarbital-anesthetized mongrel dogs at normal and increased transvascular fluid flux. Lymph flow and hyaluronan concentration in control averaged 16.3 +/- 15.0 (SD) microliters/min (range 6.3-46.5) and 6.16 +/- 3.78 micrograms/ml, respectively. Lymph flow was increased stepwise by raising venous pressure, and measurements were performed at each step after three consecutive and identical measurements of lymph flow and protein concentration taken 15 min apart. Hyaluronan concentration was unchanged until venous pressure was raised above 20 mmHg and then gradually fell to an average of 4.8 +/- 2.67 micrograms/ml at venous pressures around 40 mmHg. The lymphatic hyaluronan flux averaged 0.085 +/- 0.034 micrograms/min in control and 0.28 +/- 0.14 micrograms/min at the highest flows (4.3 times control), draining 2% and 10% of the total interstitial hyaluronan in the tissue in 24 h, respectively. The results suggest that at least part of the hyaluronan in skin is loosely bound and easily removed via lymph.
Cardiac effects induced by chemically activated neurons in canine intrathoracic ganglia
Authors: Butler C. K. , Smith F. M. , Nicholson J. , Armour J. A.
Published: December 2017

Regional or global cardiac responses were elicited when various chemicals were injected into discrete loci within acutely decentralized stellate and middle cervical ganglia. Nicotine (100 micrograms), acetylcholine (100 micrograms), or isoproterenol (1, 2, or 5 micrograms) in 1 microliters of normal saline was administered individually into 30 discrete loci within each stellate ganglion and 25 within each middle cervical ganglion. Cardiac augmentation was elicited when approximately 1 site per ganglion was injected with nicotine or acetylcholine. Similar injections into sites approximately 1-2 mm away from an active site usually failed to elicit cardiac responses. Isoproterenol elicited cardiac augmentations when injected into, on average, 3 different loci per ganglion. The responses elicited by isoproterenol injections were eliminated when the efferent sympathetic nerves arising from an injected ganglion were divided or when timolol maleate (0.1 mg/microliters normal saline) was previously injected into the same locus. These data indicate that the effects elicited by injecting isoproterenol into an intrathoracic ganglion locus were not due to leakage of this agent into the blood in sufficient quantities to directly activate cardiac myocytes. When L-glutamic acid (100 microliters of 1 M solution in normal saline) or L-aspartic acid (100 microliters of 1 M solution in normal saline) was injected into a stellate ganglion or middle cervical ganglion, positive chronotropic and/or inotropic responses were elicited. When DL-homocysteic acid (100 microliters of 1 M solution in normal saline) was administered no augmentation occurred. It is concluded that intrathoracic ganglion cardiac neurons can be activated by nicotinic or beta-adrenergic agonists, as well as by specific amino acids. These neurons are located throughout the stellate and middle cervical ganglia, cardiac neurons in one ganglionic locus being capable of activation by more than one of these chemicals.
Unloaded shortening velocity of skinned rat myocardium: effects of volatile anesthetics
Authors: Herland J. S. , Julian F. J. , Stephenson D. G.
Published: December 2017

The slack test method has been adapted for measurement of unloaded velocity of shortening in rat ventricular trabeculae that were skinned with saponin (50 micrograms/ml for 30 min). The method was sensitive enough to detect a 17% reversible change in the unloaded velocity of shortening produced by a 3 degrees C change in temperature. At pCa 5.30 (80-90% activation), halothane, enflurane, and isoflurane each slowed the shortening velocity by 25-30% at dose levels of 8 mM or greater but not at 4 mM or less. At pCa 5.48 (50-60% activation), halothane slowed the shortening velocity by 20-45% at dose levels of 4 mM or greater but not at 2 mM. The slowing effect of anesthetics on shortening velocity showed saturation at 8 mM for halothane, enflurane, and isoflurane when activation was at pCa 5.30. Saturation occurred at 4 mM for halothane when the pCa was 5.48. This result indicates that the dose-response relationship may be narrow, such that it can be demonstrated between 2 and 4 mM halothane for pCa 5.48 and between 4 and 8 mM halothane for pCa 5.30. The anesthetic dose dependence of isometric force and length axis intercept did not generally follow the same relationship as for the shortening velocity. Thus in several instances force did not significantly decrease when the velocity of shortening did. This may be interpreted as lack of simple inhibition by anesthetics on the number of interacting cross-bridges and as direct influence by anesthetics on the cross-bridge cycle.
Oxygen consumption is less in rat hearts arrested by low calcium than by high potassium at fixed flow
Authors: Burkhoff D. , Kalil-Filho R. , Gerstenblith G.
Published: December 2017

The purpose of the present study was to determine whether myocardial oxygen consumption (MVO2) differs when the heart is arrested by hyperkalemic arresting solution (ASK) or by hypocalcemic arresting solution (ASCa) when coronary flow is maintained constant. MVO2 was measured in 12 isolated, Langendorff-perfused rat hearts alternately perfused with ASK (20 mM K+ and 1.5 mM Ca2+) and ASCa (5 mM K+ and 0.08 mM Ca2+). Six of the hearts were perfused with ASK for 10 min, ASCa for 5 min, ASK for a second 5 min, and finally ASCa for 5 min; ASCa and ASK were opposite in this sequence for the other six hearts. Measurements of MVO2 during ASK and ASCa arrest, taken at the end of each perfusion period, were analyzed to distinguish the independent influences of time and perfusate composition on MVO2 in the arrested hearts (analysis of covariance). Consistent with previous findings, MVO2 decreased with time after the onset of cardiac arrest with both solutions. The average per minute fall was 0.0003 ml O2.min-1.g-1 (P less than 0.01). However, at any given time after arrest, MVO2 averaged 0.004 ml.min-1.g-1 less during ASCa arrest than during ASK arrest (P less than 0.01), which amounted to a 15% reduction in MVO2. To test whether the increased MVO2 during hyperkalemic arrest was dependent on calcium in the perfusion medium, a third series of six hearts was studied in which MVO2 values measured during ASCa and ASK arrest were compared with those measured during arrest by hyperkalemic-hypocalcemic solution (ASK,Ca: 20 mM K+, 0.08 mM Ca2+).(ABSTRACT TRUNCATED AT 250 WORDS)
Activity of canine in situ left atrial ganglion neurons
Authors: Armour J. A. , Hopkins D. A.
Published: December 2017

The responses of 135 spontaneously active neurons were recorded from ganglionated plexi located in the three epicardial fat pads on the ventral surface of the left atrium of ten dogs. Ganglia, some of which were adjacent to the recording sites, containing varying numbers of neurons were identified throughout these fat pads. Spontaneous activity in 50% of the identified neurons was correlated with specific phases of the cardiac cycle when arterial systolic pressure was between approximately 70 and 180 mmHg and in 28% it was correlated with the respiratory cycle. More neurons displaying cardiovascular-related activity were recorded when systolic pressure was increased after administration of positive inotropic agents or aortic occlusion. However, when systolic pressure increased above approximately 150 mmHg the number of active neurons decreased, and when pressure reached approximately 180 mmHg no activity was recorded. The activity of 36% of identified neurons was altered when discrete regions of the heart, great thoracic vessels, lungs, neck, upper limb, chest wall, or abdominal wall were mechanically distorted by gentle touch. After acute decentralization of the intrathoracic nervous system some neurons still displayed spontaneous cardiovascular- or respiratory-related activity. Single stimuli or trains of stimuli delivered to the vagosympathetic complexes, stellate ganglia, or cardiopulmonary nerves activated neurons in intact or acutely decentralized preparations. It is concluded that ventral left atrial ganglionated plexi neurons display activity related to cardiovascular or respiratory dynamics, and that these neurons are influenced by sympathetic and parasympathetic efferent axons, as well as by cardiac and other mechanoreceptors.
Contraction and sarcoplasmic reticulum Ca2+ content in single myocytes of guinea pig heart: effect of ryanodine
Authors: Lewartowski B. , Hansford R. G. , Langer G. A. , Lakatta E. G.
Published: December 2017

The relationship between the ability of sarcoplasmic reticulum (SR) to accumulate and retain Ca2+ and the electrically stimulated contractions (ESCs) of isolated cells from guinea pig ventricular myocardium was investigated. Caffeine contractures or rapid cooling contractures were used as a relative measure of the SR Ca2+ content. Depletion of SR Ca2+ by short exposure to caffeine (15 mM) or by prolonged rest resulted in a reduction of the amplitude of the ESCs by 83 +/- 14 and 65 +/- 11% (means +/- SD), respectively. This result points to SR as a major source of the Ca2+ that activates contraction. However, depriving the SR of the ability to retain Ca2+ by means of prolonged (up to 75 min) exposure to 0.1 microM ryanodine (as shown by the absence of contractile response to caffeine or cooling) did not prevent an ESC of nearly normal amplitude (81 +/- 24% control), albeit with a reduced contraction velocity and a time to peak contraction prolonged by 51 +/- 11%. Additionally, while rest decay of ESCs was present after ryanodine treatment, the time for the ESCs to recover their steady-state amplitude was prolonged at least twofold. Thus, in contrast with the normal guinea pig cells, ESCs of the myocytes exposed to ryanodine are controlled by sarcolemmal processes. This change in the state of excitation-contraction coupling results mainly in modification of the time course of the ESCs and of the time course of the response of the cells to the change in the rate of stimulation.
BBB transport and rapid tissue binding of cyclofoxy: comparison of active and inactive enantiomers
Authors: Kawai R. , Sawada Y. , Channing M. , Newman A. H. , Rice K. C. , Blasberg R. G.
Published: December 2017

The "rapid-phase" brain distribution of 3H-labeled enantiomers of the opiate receptor antagonist cyclofoxy (CF), receptor active (-) and inert (+) forms, was measured during 20- to 180-s intravenous infusion in rats. [14C]iodoantipyrine was coinfused during these experiments to obtain a simultaneous measure of blood flow. The influx clearance (K1) across the blood-brain barrier (BBB) and the rapid binding equilibrium constant (Keq) were estimated in different brain regions for both enantiomers (2-compartmental model); a possible receptor binding process (k3) was also examined for (-)-CF (3-compartment model). K1 (0.46-0.91 ml.min-1.g-1), the capillary permeability-surface area product (PS; 0.75 approximately 1.4 ml.min-1.g-1) and the tissue extraction fraction (E; 0.6-0.7) were found to be identical for both enantiomers in the nonreceptor binding model; Keq was identical in cerebellum but larger for (-)-CF in other brain structures. The difference in Keq between the enantiomers (2-compartment model) correlated with the rank order of opiate receptor density observed in vitro and in vivo. These results suggest that concomitant use of (-)-CF and (+)-CF will be useful for in vivo receptor binding analyses.
Neurotransmission in neonatal rat cardiac ganglion in situ
Authors: Seabrook G. R. , Fieber L. A. , Adams D. J.
Published: December 2017

The intrinsic cardiac ganglia of the neonatal rat heart in situ were studied using electrophysiological and histochemical techniques. The vagal branches innervating the atrial myocardium and cardiac ganglia were identified and individual ganglion cells visualized using Hoffman modulation contrast optics. Histochemical studies revealed the presence of acetylcholinesterase activity associated with neuronal cell bodies and fibers, catecholamine-containing, small intensely fluorescent cells, and cell bodies and nerve fibers immunoreactive for vasoactive intestinal polypeptide. Intracellular recordings from the "principal" cells of the rat cardiac ganglion in situ revealed a fast excitatory postsynaptic potential (EPSP) evoked after electrical stimulation of the vagus nerve, which was inhibited by the nicotinic receptor antagonist, mecamylamine. No spontaneously firing neurons were found, although infrequent (less than 2 min-1) spontaneous miniature EPSPs were observed in most neurons. The quantal content of neurally evoked responses was between 10 and 30 quanta, and the presence of multiple EPSPs in some cells suggested polyneuronal innervation. The neurally evoked EPSP amplitude was dependent on the rate of nerve stimulation, decreasing with increasing frequency of stimulation. Neurons exhibited a sustained depolarization during high frequency stimulation (greater than 1 Hz), and in approximately 15% of the cells a slow depolarization lasting 1-3 min was observed after a train of stimuli. The presence of catecholamine- and neuropeptide-containing neuronal cell body fibers in neonatal rat cardiac ganglia in situ, along with neurally evoked postsynaptic responses resistant to cholinergic ganglionic blockers, suggests a role for noncholinergic transmission in the regulation of the mammalian heart beat.
Role of endothelium in reactive dilation of skeletal muscle arterioles
Authors: Koller A. , Kaley G.
Published: December 2017

In cremaster muscle of pentobarbital-anesthetized rats, the role of endothelium in the reactive dilation of an arteriole (mean control diameter: 18.2 +/- 0.5 microns) during and after short (approximately 20 s) or long (approximately 80 s) occlusion of a parent arteriole was investigated. Distal to the occluder, arteriolar diameter increased during the occlusion (mean peak increase: 6.9 +/- 0.4 and 6.7 +/- 1.1 microns, respectively) and increased even further after the release of the occlusion as blood flow was reestablished (additional mean increase: 6.5 +/- 0.7 and 5.8 +/- 0.8 microns, respectively). The duration of arteriolar dilation after the release of the occlusion was dependent on the duration of occlusion (252.2 +/- 37 vs. 411.3 +/- 57 s; P less than 0.05). After impairment of the arteriolar endothelium by light/dye treatment, a dilation was still present during both the shorter and longer occlusions (mean increase: 4.73 +/- 1.4 and 4.73 +/- 1.3 microns, respectively); however, in both cases the additional dilation after release of the occlusion was greatly diminished. The duration of reactive arteriolar responses following impairment of the endothelium was significantly reduced only on release of the shorter occlusions. The results suggest that reactive dilation (hyperemia) of arterioles is the result of multiple, endothelium-dependent and endothelium-independent vasoactive factors.
Effects of hypoproteinemia on blood volume and arterial pressure of volume-loaded dogs
Authors: Manning R. D.
Published: December 2017

Studies were performed in 14 conscious, anephric dogs to clarify the role of blood volume in the genesis of hypertension. The dogs were splenectomized and had plasma protein concentration (PPC) reduced to 2.7 g/dl by daily plasmapheresis for 9 days. This hypoproteinemia resulted in a 20% decrease in both blood volume and mean arterial pressure. On the 10th day the dogs were nephrectomized. On the 11th day after a 3-h control period with plasmapheresis, lactated Ringer equivalent to 10 or 20% of body weight was intravenously infused. By 25 h postinfusion blood volume had not increased, and the dogs were still hypotensive. At 25 h plasma protein mass was returned to normal by intravenous infusion of autologous plasma, the average blood volume of the three low PPC groups increased approximately 50%, and the arterial pressure increased greater than 60%. The decrease in PPC shifted the regression of blood volume on sodium space down the blood volume axis. In conclusion, the dependence of arterial pressure on blood volume was demonstrated by the decrease in both blood volume and arterial pressure after PPC reduction, the constancy of blood volume and pressure during Ringer infusion, and the increase in both volume and pressure after plasma infusion.
Sarcolemmal Na(+)-K(+)-ATPase: inactivation by neutrophil-derived free radicals and oxidants
Authors: Kukreja R. C. , Weaver A. B. , Hess M. L.
Published: December 2017

One of the targets of free radicals and neutrophil-derived oxidants that is known to be generated during ischemic-reperfusion injury of the myocardium is the sarcolemma. We therefore examined the susceptibility of sarcolemmal Na(+)-K(+)-ATPase and ouabain binding sites to O2-., H2O2,.OH, HOCl, NH2Cl, and stimulated neutrophils. O2-. generated from xanthine oxidase action on xanthine had no significant effect on Na(+)-K(+)-ATPase activity. The inhibition of Na(+)-K(+)-ATPase activity and ouabain binding by H2O2 was dependent on concentration and the time of incubation. H2O2 (10 mM) inhibited 80% of Na(+)-K(+)-ATPase activity at 90 min..OH generated by Fenton's reagent (200 microM Fe2+ + 5 mM H2O2) significantly decreased maximum binding of ouabain (43.06 +/- 1.45 to 31.96 +/- 2.37 pmol/mg) and was significantly protected by 5 mM mannitol (P less than 0.05). The dissociation constant of ouabain binding was unaffected by Fenton's reagent or H2O2. In contrast, lower concentrations of HOCl, NH2Cl, or PMA-stimulated human neutrophils (4 X 10(6) cells/ml) had significant inhibitory effects on Na(+)-K(+)-ATPase activity. We conclude that O-2. per se is not damaging to sarcolemmal Na(+)-K(+)-ATPase activity. The formation of H2O2 and the more destructive .OH or HOCl and NH2Cl disrupt sarcolemmal function by inhibiting Na(+)-K(+)-ATPase activity and destroying ouabain binding sites.
Capillary permeability: an albumin component attenuates active changes in Lp
Authors: Huxley V. H. , Meyer D. J.
Published: December 2017

The mechanisms whereby atrial natriuretic peptide (AP) acutely and reversibly elevates hydraulic conductivity (Lp) are not known. This is the second of two studies of the influence of perfusate albumin composition on AP alterations in capillary Lp. In this study, we investigated the effect of dialysis of the perfusate albumin. A 2.2-fold increase in frog (Rana pipiens) mesenteric microvessel Lp occurred when 100 nM AP was added to the control perfusate containing dialyzed, crystallized bovine serum albumin (DXL-BSA 10 mg/ml; n = 20). By contrast, Lp was unchanged by 100 nM AP in 10 mg/ml untreated, crystallized BSA (XL-BSA; n = 8). The response to AP was unaltered at DXL-BSA contents of 10, 20, or 30 mg/ml (2.4-, 2.2-, and 3.1-fold, respectively; n = 8). Dialysis of the albumin, per se, did not influence control Lp (LpXL-BSA/LpDXL-BSA = 1.0; n = 5). The receptor-independent nitrovasodilator, sodium nitroprusside (SNP; 1 microM) elevated Lp by 1.7-fold in DXL-BSA (n = 30). The response was abolished in XL-BSA (n = 8). We conclude that small hydrophilic albumin-associated substances antagonize AP- and SNP-induced elevations of exchange microvessel hydraulic conductance without interfering with albumin's role in the maintenance of normal exchange vessel permeability.
Parasympathetic postganglionic pathways to the sinoatrial node
Authors: Bluemel K. M. , Wurster R. D. , Randall W. C. , Duff M. J. , O'Toole M. F.
Published: December 2017

Vagal ganglia that innervate the canine sinoatrial node (SAN) have been localized to a fat pad overlying and surrounding the right pulmonary vein complex (PVFP). The ventral epicardial surface of the right atrium was mapped in seven dogs anesthetized with alpha-chloralose after beta-blockade (timolol) and cardiac sympathetic and parasympathetic decentralization. A small, concentric bipolar exploring electrode was used to stimulate (during the atrial refractory period and using trains of five to eight stimuli per beat) systematically in the epicardial regions between the PVFP and the SAN. Changes in SAN rate with stimulation were measured, and the anatomic location was identified on a 150-point grid fitted to conform to size and shape of the atrium. Mapping was performed before and after local (PVFP) and systemic ganglionic blockade (hexamethonium). Data reveal that the primary vagal postganglionic pathways to the sinoatrial nodal region are subepicardial and adjacent to the SAN artery along the sulcus terminalis. Hexamethonium in the PVFP abolishes SAN inhibition during preganglionic vagal excitation, without interrupting vagal suppression of atrioventricular conduction. However, SAN slowing (with varying attenuation) continued to occur after hexamethonium (either PVFP or systemically) when the exploring electrode was applied directly over intramural postganglionic fibers between PVFP and sinus node. Attention is directed to existence of a very few synapses closer to SAN, probably in isolated ganglia immersed in fatty connective tissues along the sulcus terminalis.
Influence of dietary n-3 fatty acids on myocardial ischemia and reperfusion
Authors: Hock C. E. , Beck L. D. , Bodine R. C. , Reibel D. K.
Published: December 2017

We have investigated the effect of elevated n-3 (omega-3) fatty acid content in the diet on arrhythmias, ischemic damage, and inflammatory cell infiltration into the reperfused left ventricular free wall (LVFW). Weanling rats were fed purified diets in which the lipid was replaced with either corn oil (CO) or menhaden oil (MO). After 4 wk, MO feeding resulted in significant elevations in both the ratio of n-3 to n-6 fatty acids and the unsaturation index in myocardial phospholipids. Rats were subjected to 15 min of ischemia followed by reperfusion. After 6 h of reperfusion of the left coronary artery there was significantly less creatine kinase (CK) lost from the LVFW of rats fed MO. Leukocyte infiltration into the LVFW, as measured by myeloperoxidase (MPO) activity, was also significantly reduced with MO feeding at 6 h. Arrhythmias were studied in a separate group of 17 rats; both the incidence and severity of ventricular tachycardia and ventricular fibrillation were significantly reduced during the ischemic and reperfusion periods with MO feeding. After 24 h of reperfusion there was also significantly less CK lost from the LVFW of MO-fed rats; however, there was no significant difference in tissue MPO activity in ventricular homogenates. Survival after 24 h of reperfusion was 76% (16/21) for MO- and 41% (9/22) for CO-fed rats. The data suggest a protective effect for dietary MO in myocardial ischemia-reperfusion, which may involve both an early reduction in leukocyte infiltration and a reduction in the incidence of fatal arrhythmias.
Coronary resistance increase by nondefatted albumin in saline-perfused rabbit hearts
Authors: Van Beek J. H. , Bouma P. , Westerhof N.
Published: December 2017

In isolated hearts perfused with salt solutions, albumin is often added in low concentrations for preservation of endothelial function. Albumin in low concentrations is also sometimes used as an intravascular indicator in such preparations. We perfused isolated rabbit hearts according to Langendorff with a constant flow of Tyrode solution. Despite maximal vasodilation with 10 microM adenosine, coronary vascular resistance increased by 14% after 0.3 g/100 ml nondefatted bovine serum albumin (Sigma A-9647) was added to the perfusate compared with the control resistance with no albumin present. The 50% response time for the vasoconstrictive response to the step change in albumin concentration was 20 +/- 13 s (mean +/- SD). When 0.3 g/100 ml of defatted albumin (Sigma A-6003) was added, the resistance increase was only 1.4% and is explained by increased viscosity. Vasoconstrictive effects of certain nondefatted albumin preparations must be taken into account by investigators who perfuse organs with albumin-containing solutions.
Regulation of heartbeat by G protein-coupled ion channels
Authors: Brown A. M.
Published: December 2017

The coupling of ion channels to receptors by G proteins is the subject of this American Physiological Society Walter B. Cannon Memorial "Physiology in Perspective" Lecture. This subject is particularly appropriate because it includes a molecular explanation of a homeostatic mechanism involving the autonomic nervous system and the latter subject preoccupied Dr. Cannon during most of his career. With the use of reconstitution methods, we and others have shown that heterotrimeric guanine nucleotide-binding (G) proteins couple receptors to ion channels by both membrane-delimited, direct pathways and cytoplasmic second messenger pathways. Furthermore, one set of receptors may be coupled to as many as three different sets of ion channels to form networks. Dual G protein pathways lead to the prediction of biphasic ion current responses in cell signaling, and this prediction was confirmed. In sinoatrial pacemaker cells, the pacemaking hyperpolarization-activated inward current (If) is directly regulated by the G proteins Gs and Go, and the two can act simultaneously. This could explain the classical observation that vagal inhibition of heart rate is greater during sympathetic stimulation. Because deactivation of the muscarinic response occurs much faster than the G protein alpha-subunit hydrolyzes guanosine 5'-triphosphate, we looked for accessory cellular factors. A surprising result was that the small monomeric ras G protein blocked the muscarinic pathway. The significance of this observation is unknown, but it appears that small and large G proteins may interact in ion channel signaling pathways.
Regional blood flow in transected rat spinal cord during hypothermia
Authors: Sakamoto T. , Iwai A. , Monafo W. W.
Published: December 2017

Regional blood flow (RBF) increases in the spinal cord and sciatic nerve of acutely hypothermic rats. To determine whether cord transection affects this response, we measured RBF in rat spinal cord and sciatic nerve 2 h after cord transection at vertebrae T8 (n = 18 rats) and T11 (n = 18 rats) using [14C]butanol distribution. Nine in each group were normothermic controls. In T11 transection-hypothermia (25-27 degrees C rectal temperature), RBF increased in the three rostral cord segments by 28-40% (P less than 0.05); caudally, cord RBF was depressed in two segments (P less than 0.05), unchanged in the other; RBF fell in nerve (P less than 0.05). In T8 transection-hypothermia, RBF was unchanged in the two rostral cord segments; caudally, RBF was depressed in one cord segment (P less than 0.05) and unchanged in the others; RBF was unchanged in nerve. We conclude that RBF does not rise in caudal spinal cord segments or in sciatic nerve during hypothermia in rats with prior spinal cord transection.
Regulation of plasma ANF after increases in afterload in conscious dogs
Authors: Stewart J. M. , Wang J. , Singer A. , Zeballos G. A. , Ochoa M. , Patel M. B. , Gewitz M. H. , Hintze T. H.
Published: December 2017

Although atrial stretch is the primary stimulus for atrial natriuretic factor (ANF) secretion, hormones may directly affect ANF secretion or may indirectly influence ANF by changing left ventricular afterload, thereby altering atrial stretch. To determine whether direct effects are important for the release of ANF in vivo, we measured changes in plasma ANF and in atrial wall function in the conscious dog after the administration of vasopressin, angiotensin II, and phenylephrine and by mechanically increasing left ventricular afterload by partial aortic occlusion. Injections of phenylephrine, angiotensin II, and arginine vasopressin (AVP) that were chosen to cause similar changes in systemic arterial pressure resulted in similar changes in atrial pressure and diameter. Maximum V wave atrial wall stress increased to 283 +/- 12, 311 +/- 41, 327 +/- 24, and 277 +/- 22 g/cm2 for AVP, angiotensin, phenylephrine, and occlusion, respectively, and plasma ANF increased to 242 +/- 81, 248 +/- 62, 299 +/- 95, and 190 +/- 53 pg/ml. There were significant linear correlations between left ventricular afterload and left atrial pressure, and each method for increasing left ventricular afterload shifted the position to the left on an atrial pressure-diameter, compliance curve, by a similar degree. Thus changes in left ventricular afterload result in changes in atrial wall function and similar changes in plasma ANF. No hormonal-specific increase in plasma ANF was found in conscious dogs after increases in afterload.
Direct electrophysiological actions of pentobarbital at concentrations achieved during general anesthesia
Authors: Nattel S. , Wang Z. G. , Matthews C.
Published: December 2017

Pentobarbital and alpha-chloralose are widely used for experimental anesthesia, but their direct electrophysiological actions at anesthetic concentrations are unknown. Trough and peak concentrations measured by high-performance liquid chromatography averaged 27 +/- 3 and 45 +/- 13 mg/l (means +/- SD) for pentobarbital and 41 +/- 15 and 103 +/- 13 mg/l for alpha-chloralose in dogs receiving them for general anesthesia. The direct effects of each agent on papillary muscle action potentials obtained from guinea pigs killed by decapitation were studied in vitro. Pentobarbital increased action potential duration to 95% by 24 +/- 6 and 33 +/- 4% at 25 and 50 mg/l (P less than 0.001 for each), respectively, and caused corresponding increases in effective refractory period. Furthermore, pentobarbital reduced maximum rate of voltage change (Vmax) of phase 0 in a voltage-, rate-, and concentration-dependent fashion, suggesting use-dependent sodium channel blocking actions. The voltage dependence of Vmax was shifted by 3.7 +/- 1.7 (P less than 0.01) and 6.5 +/- 1.8 mV (P less than 0.001) by 25 and 50 mg/l pentobarbital, respectively. In canine ventricular muscle, pentobarbital caused rate- and concentration-dependent decreases in Vmax and increases in action potential duration and refractory period over a concentration range of 5-100 mg/l. alpha-Chloralose was devoid of direct electrophysiological effects in both species. We conclude that pentobarbital has potentially important electrophysiological actions on ventricular tissues at concentrations required for general anesthesia and may confound the results of in vivo studies.
Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth
Authors: Abman S. H. , Chatfield B. A. , Hall S. L. , McMurtry I. F.
Published: December 2017

To examine the potential role of endothelium-derived relaxing factor (EDRF) in regulation of the perinatal pulmonary circulation, we studied the hemodynamic effects of a selective inhibitor of EDRF production, nitro-L-arginine (L-NA), on pulmonary vascular tone and dilator reactivity in the late-gestation ovine fetus and on the pulmonary vasodilation that normally occurs at birth. L-NA infusion decreased pulmonary blood flow from 78 +/- 8 to 65 +/- 6 ml/min (P less than 0.01) and increased pulmonary artery pressure from 48 +/- 2 to 54 +/- 3 mmHg (P less than 0.002, n = 8 animals). To study the selectivity of L-NA on vasodilator responses to endothelium-dependent (acetylcholine) and -independent (atrial natriuretic factor) stimuli, we measured responses to brief infusions of each dilator before and after L-NA treatment. Acetylcholine increased pulmonary blood flow during the control period but not after L-NA treatment. In contrast, L-NA had little effect on the vasodilator response to atrial natriuretic factor. To study the role of EDRF in the transition of the pulmonary circulation from fetal to neonatal conditions, we infused L-NA into the left pulmonary artery immediately before cesarean-section delivery. In comparison with control animals, the rise in pulmonary blood flow at 1 h after delivery was reduced in the L-NA-treated animals (331 +/- 28 in control vs. 185 +/- 16 ml/min in treated, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial blood flow, metabolism, and function with repeated brief coronary occlusions in conscious ponies
Authors: Williams D. O. , Boatwright R. B. , Rugh K. S. , Garner H. E. , Griggs D. M.
Published: December 2017

Studies were performed in the conscious pony instrumented with a Doppler flow probe and hydraulic occluder on the left anterior descending coronary artery (LAD), sonomicrometry crystals and intraventricular micromanometer in the left ventricle, and catheters in the left atrium and anterior interventricular vein. Two-minute LAD occlusions were performed every 30 min continuously or during working hours. Data on release of catabolites (potassium, hydrogen ions, and lactate) and norepinephrine from the initially dysfunctional region were obtained periodically during a regimen of 445 +/- 56 occlusions in six animals. Regional myocardial blood flow was measured (microsphere method) before and after an occlusion regimen in four animals. Marked release of catabolites and norepinephrine from the initially dysfunctional region was noted in association with early occlusions when myocardial segment function was severely reduced. With further occlusions, release of these substances decreased while segment function improved. Blood flow was markedly decreased in the initially dysfunctional region during an early occlusion but was at the control level during a later occlusion. Although the metabolic findings are consistent with protection due to “ischemic preconditioning” and no increase in collateral perfusion, the inverse relationship noted between catabolite release and segment function is best explained by flow-dependent mechanisms. These results, together with the myocardial blood flow data, serve to validate a previous assumption that protection against regional myocardial dysfunction under these conditions is due to increased collateral perfusion.
Impaired myocardial function in spontaneously hypertensive rats with heart failure
Authors: Conrad C. H. , Brooks W. W. , Robinson K. G. , Bing O. H.
Published: December 2017

We have observed that many spontaneously hypertensive rats (SHR) between the ages of 18 and 24 mo develop findings suggestive of heart failure, including pleural and pericardial effusions, left atrial thrombi, and right ventricular hypertrophy. Isolated left ventricular papillary muscle function was studied in these animals (SHR-F), in age-matched SHRs without evidence of heart failure (SHR-NF), and in nonhypertensive controls (WKY). Preparations from SHR-F showed depression of active tension development (3.58 +/- 1.75 g/mm2, means +/- SD) compared with both SHR-NF (7.17 +/- 0.94) and WKY (6.17 +/- 1.00) (P less than 0.01). Shortening velocity was also depressed in SHR-F (0.95 +/- 0.38 lengths/s) compared with SHR-NF (1.60 +/- 0.30; P less than 0.05) and WKY groups (2.15 %/- 0.48; P less than 0.01). Depression of muscle function was not found before 18 mo of age. Thus the aging SHR is a model in which one can observe the transition from chronic stable left ventricular hypertrophy to overt heart failure. Furthermore, left ventricular papillary muscles from SHRs with heart failure show evidence of significant contractile dysfunction, suggesting that impairment of intrinsic myocardial function underlies the development of heart failure.
Mechanical properties of adult feline ventricular myocytes in culture
Authors: Pollack P. S. , Carson N. L. , Nuss H. B. , Marino T. A. , Houser S. R.
Published: December 2017

The contractile and electrophysiological properties of cultured adult feline ventricular myocytes were studied. Cells were field stimulated and contraction was measured using a video-based edge detector. The magnitude of contraction decreased by 36% and the rate of contraction decreased by 52% 2 h after the cells were plated on laminin-coated cover slips. The magnitude and rate of contraction then remained stable for 1 wk. The duration of contraction prolonged and a second component to the twitch frequently, but not invariably, developed after 5 days in culture. This was associated with prolongation of the action potential duration. After 7 days in culture, cells could be divided into two groups based on resting membrane potential. Norepinephrine increased the magnitude of contraction for 5 days after plating. Cultured ventricular myocytes became unresponsive to the effects of norepinephrine after 7 days. Adult cardiac myocytes maintained in primary culture continue to respond to field stimulation and retain many contractile properties for up to 7 days; however, the functional characteristics of these cells do not remain uniform during this time period.
Differential effects of dietary fish oil on myocardial prostaglandin I2 and thromboxane A2 production
Authors: Abeywardena M. Y. , McLennan P. L. , Charnock J. S.
Published: December 2017

Marmoset monkeys (Callithrix jacchus) were maintained for 24 mo on a standard primate diet [reference (Ref) diet] or this diet supplemented (8% wt/wt) with either sheep fat (SF), sunflower seed oil (SSO), or tuna fish oil (TFO). The polyunsaturated fatty acids (PUFA) of myocardial phospholipids demonstrated significant alterations as a result of the dietary (n-3) or (n-6) lipid supplementation. The reduction (P less than 0.05) in prostaglandin (PG) I2 in PUFA diet-fed groups (SSO, 113.8 +/- 7.8; TFO, 87.9 +/- 8.2 compared with Ref, 153.9 +/- 7.4 pg/mg dry wt) seems to be due to the rate limitation of the endogenous substrate, because the addition of exogenous arachidonic acid (AA) has obliterated the dietary difference. However, AA did not increase the basal PGI2 production in the Ref or SF dietary groups, which differed from that for thromboxane (Tx) A2 where 2- to 5-fold stimulation was observed. It is suggested that there exists a preferential channeling mechanism to direct AA derived from phospholipase hydrolysis of membrane phospholipids toward PGI2 synthesis. Conversely, the bulk of the AA for TxA2 biosynthesis appears to be supplied by a cytosolic nonesterified fatty acid pool. The effective replacement of AA of this pool and a specific inhibition of TxA2 synthetase enzyme complex by the (n-3) PUFA of fish oil are offered as likely mechanisms for the greater inhibition of TxA2 compared with PGI2 production observed in the present and previous studies. The present data on myocardial eicosanoids correlate well with the beneficial qualities of (n-3) and (n-6) dietary PUFA on cardiac function that we have reported previously.
Norepinephrine release during autoregulatory escape: effects of alpha 2-receptor blockade
Authors: Chen L. Q. , Riedel G. L. , Shepherd A. P.
Published: December 2017

The partial recovery that intestinal blood flow undergoes during continued sympathetic nerve stimulation is termed autoregulatory escape. This study tested two hypotheses that might explain escape: 1) diminishing norepinephrine (NE) release during sustained stimulation and 2) an alpha 2-receptor-mediated competition between local and neural control mechanisms. The rates of NE release before and during stimulation of the perivascular sympathetic nerves were determined by measuring blood flow in isolated loops of canine small intestine and assaying the concentrations of NE in arterial and venous blood. The presence of functional alpha 2-receptors was demonstrated by clonidine injections, and the effects of alpha 2-receptor blockade were studied during yohimbine infusions. The time course of NE release was inconsistent with a cause-effect relationship; NE release was greatest during the phase when resistance had already escaped. Deliberately altering NE release by changing the stimulus duration did not affect escape. The study demonstrated 1) that diminished NE release during continued sympathetic stimulation does not occur and cannot account for escape, 2) that resistance vessels in the canine intestinal circulation possess functional alpha 2-receptors which are responsible for part of the vasoconstriction caused by sympathetic stimulation, 3) that blockade of presynaptic alpha 2-receptors significantly enhanced NE release during the initial 30-s period but not during the escape phase, and 4) that alpha 2-receptor blockade enhances autoregulatory escape. Altogether these findings indicate that the postsynaptic alpha 2-receptors on intestinal resistance vessels deserve further investigation as the possible site at which local and neural mechanisms compete to influence vascular resistance.
Alpha 1-adrenoceptor-mediated phosphoinositide breakdown and inotropic responses in diabetic hearts
Authors: Xiang H. , McNeill J. H.
Published: December 2017

The mechanism(s) involved in diabetes-induced changes in the heart is still unclear, but one defect appears to occur in the alpha 1-adrenoceptor system. We evaluated the possibility that the changes in the inotropic responsiveness to alpha 1-adrenoceptor stimulation in streptozotocin-diabetic rat hearts may be linked to altered phosphoinositide turnover. Stimulation of alpha 1-adrenoceptor by norepinephrine (in the presence of propranolol) in right ventricles resulted in the formation of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] [measured with an Ins(1,4,5)P3 protein binding assay kit] in a time- and concentration-dependent manner in both control and diabetic rats. The increase in Ins(1,4,5)P3 preceded the increase in the norepinephrine-mediated positive inotropic effect. Diabetic hearts showed a greater maximum inotropic response to norepinephrine stimulation and also had higher Ins(1,4,5)P3 levels. These observations suggest that the changes in Ins(1,4,5)P3 levels may be implicated in the increased inotropic responsiveness to alpha 1-adrenoceptor stimulation in diabetic hearts. Ca2+ overload, induced by Ins(1,4,5)P3, could further be involved in the development of diabetic cardiomyopathy.
Vasopressin stimulates the mobilization and metabolism of triacylglycerol in perfused rabbit hearts
Authors: Palazzo A. J. , Malik K. U. , Weis M. T.
Published: December 2017

Vasopressin stimulates several metabolic processes, including glycogenolysis, gluconeogenesis, and fatty acid oxidation, and promotes lipolysis in rabbit and hamster suprarenal adipose tissue. This study was conducted to determine whether arginine vasopressin (AVP) stimulates the metabolism of triacylglycerols in the isolated perfused rabbit heart. Since the basal output of glycerol in the rabbit heart is very low, the triacylglycerol pool was labeled with [3H]triolein, and triacylglycerol metabolism was followed by analysis of the radioactive products in the perfusate. Administration of AVP (100 ng, 92 pmol) produced a 10-fold increase in the perfusate radioactivity associated with free fatty acids and mono- and diglycerides, as well as an 8-fold increase in the effluent radioactivity associated with triacylglycerol. The V1-receptor antagonist d[(CH2)5Tyr(Me)]AVP blocked the AVP-induced increase in the output of radioactivity in a dose-related manner. The V2-receptor agonist desmopressin (DDAVP) did not increase the outflow of radioactivity. Likewise, AVP-induced release of radioactivity was inhibited when Ca2+ was omitted from the perfusion buffer. Analysis of total lipid extracts of hearts labeled with [3H]triolein showed that the residual radioactivity was associated almost exclusively with authentic triolein both before and after AVP treatment. These data suggest that AVP promotes triacylglycerol mobilization and utilization and that these processes are Ca2+ dependent and mediated by the V1-receptor. Since free fatty acids derived from triacylglycerols are the preferred metabolic substrate for the heart and since plasma AVP levels increase in cardiac stress states such as shock, these findings suggest a metabolic function of AVP in cardiovascular stress states.