bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic and genetic adaptation of soleus muscle mitochondria to physical training in rats
Authors: Murakami T. , Shimomura Y. , Fujitsuka N. , Nakai N. , Sugiyama S. , Ozawa T. , Sokabe M. , Horai S. , Tokuyama K. , Suzuki M.
Published: December 2017

To evaluate the effects of physical training on mitochondrial gene expression and mitochondrial biogenesis in slow-twitch muscle, adult female Sprague-Dawley rats were trained for 3, 6, and 12 wk by running on a motor-driven treadmill (speed of 25 m/min and duration of 90 min/day, 5 days/wk), and the activities of citrate synthase, ubiquinol-cytochrome-c oxidoreductase, cytochrome oxidase, mitochondrial cytochrome b mRNA (by Northern blot analysis), and mitochondrial DNA (by slot-blot and Southern blot analyses) were measured in rat soleus muscle. A DNA probe for detection of mitochondrial mRNA and DNA was prepared from a 1,500-bp fragment of human mitochondrial DNA that included the coding region of the cytochrome b gene. Training for 3, 6, and 12 wk significantly increased the activities of citrate synthase (31, 28, and 47%, respectively), ubiquinol-cytochrome-c oxidoreductase (61, 63, and 77%, respectively), and cytochrome oxidase (25, 26, and 32%, respectively) in muscle. The concentration of cytochrome b mRNA in the muscle was proportionally elevated with the enzyme activities. On the other hand, the mitochondrial DNA concentration in the muscle was not altered by training for 3 or 6 wk but increased significantly after training for 12 wk (35% in the slot-blot analysis and 31% in the Southern blot analysis). These results suggest that an increase in the oxidative capacity of slow-twitch muscle by the relatively short-term training is regulated at the pretranslational step in mitochondrial protein synthesis but that the increase by the long-term training involves mitochondrial replication.
Release of gastric inhibitory polypeptide from cultured canine endocrine cells
Authors: Kieffer T. J. , Buchan A. M. , Barker H. , Brown J. C. , Pederson R. A.
Published: December 2017

Canine intestinal duodenal and jejunal epithelial cell preparations enriched for endocrine cells were obtained by sequential collagenase digestion and centrifugal elutriation and maintained in culture for a 40-h period. Adherent cells contained a total cell content (TCC) of 11.5 +/- 2.5 ng (mean +/- SE) immunoreactive gastric inhibitory peptide (IRGIP)/well and 1.4 +/- 0.2 ng immunoreactive somatostatin (IRS)/well. Release experiments were performed by incubation of the cells with various stimuli over a 2-h period. Basal release of IRGIP in 5 mM glucose-5 mM K+ was 2.7 +/- 0.4% TCC. Incubation with concentrations of K+ > 20 mM or glucose > 15 mM significantly increased IRGIP release, as did the addition of a somatostatin immunoneutralizing antibody to the basal media. The addition of the Ca2+ ionophore, A-23187 (10 microM), or the adenylate cyclase activator, forskolin (100 microM), resulted in an IRGIP output greater than four times basal. Porcine gastrin-releasing peptide (GRP), at 1-100 nM, significantly stimulated IRGIP release in a concentration-dependent fashion. IRS release was increased significantly by 55 mM K+, 20 mM glucose, 10 microM A-23187, 100 nM GRP, or 100 microM forskolin.
Sympathetically and nonsympathetically mediated onset of excess fat deposition in Zucker rats
Authors: Kortner G. , Petrova O. , Vogt S. , Schmidt I.
Published: December 2017

To evaluate whether a low sympathetic activity is essential for the onset of Zucker rat obesity, we artificially reared fa/fa and Fa/fa littermates from 4 days of age with identical amounts of milk containing norepinephrine (NE). The NE concentration was adjusted to keep the mass-specific metabolic rate (MR) roughly either 100 or 50% above its thermoneutral level. At both doses, no genotype difference in total MR occurred before day 16, but between 16 and 21 days of age, total MR of fa/fa pups was 10% less than that of their Fa/fa littermates. The 21-day-old fa/fa pups had approximately 1 g more body fat than their lean littermates, and this was energetically accounted for to 50–80% by their lower MR and to 10–25% by the reduced growth of their fat-free dry mass. We conclude that factors not dependent on decreased sympathetic outflow trigger the onset of excess fat deposition in the 3rd postnatal wk, even if sympathetic activity was high throughout the previous weeks during which excessive fat deposition is mainly dependent on decreased thermoregulatory thermogenesis.
Post-GLUT-2 defects in beta-cells of non-insulin-dependent diabetic obese rats
Authors: Ohneda M. , Johnson J. H. , Lee Y. H. , Nagasawa Y. , Unger R. H.
Published: December 2017

Zucker diabetic fatty (ZDF) rats develop non-insulin-dependent diabetes mellitus concomitantly with loss of glucose responsiveness and GLUT-2, the high-Michaelis constant glucose transporter of beta-cells. To determine the integrity of beta-cell glucose metabolism distal to the level of glucose transport and phosphorylation, we examined the insulin responses of isolated pancreata to 5, 10, and 20 mM D-glyceraldehyde and monomethylsuccinate, as well as to glucose. The insulin response of diabetic pancreata to glucose was 90% below the response prior to the onset of diabetes, whereas the responses to glyceraldehyde and succinate had declined to 65 and 44%, respectively, below the prediabetic responses. D-[14C]glyceraldehyde oxidation by diabetic islets was 74% below that of islets from lean nondiabetic controls. We conclude that 1) the insulin responses to glyceraldehyde and monomethylsuccinate, as well as to glucose, are impaired in the diabetes of ZDF rats and 2) the impairment of the glucose response was greater than that of the glyceraldehyde response, which was, in turn, greater than that of the monomethylsuccinate response; this decrescendo pattern of impairment is consistent with defects at multiple sites in glucose metabolism; if the defect were entirely due to a postmetabolic signaling defect, the impairment to glucose and its metabolites should be comparable.
Comparison of ANG II in fetal and pregnant sheep: metabolic clearance and vascular sensitivity
Authors: Rosenfeld C. R. , Gresores A. , Roy T. A. , Magness R. R.
Published: December 2017

Fetal sheep appear less responsive to infused angiotensin II (ANG II) than pregnant ewes. This may reflect a greater fetal metabolic clearance rate (MCRANGII) and thus lower plasma ANG II levels. We therefore determined fetal MCRANGII, half-life (T1/2), and placental removal of ANG II. Fetal sheep (n = 13; 113-139 days of gestation) received 0.573-5.73 micrograms ANG II/min iv for 30 min while arterial pressure and heart rate were monitored. Serial blood samples were obtained before and during a 30-min infusion to measure ANG II and calculate MCRANGII and after stopping the infusion to determine T1/2. MCRANGII was similar across gestation and at doses < or = 2.29 micrograms/min (683 +/- 49 vs. 74 +/- 5 ml.min-1.kg-1 for adults) but was 30-40% lower with 5.73 micrograms ANG II/min (494 +/- 57 ml.min-1.kg-1, P < 0.05). T1/2 was 15-21 s. Fetal placental ANG II removal averaged 87 +/- 3 vs. 20 +/- 6% for uteroplacental removal; this was unaffected by dose and was linear with plasma ANG II levels, and saturation was not evident. Plasma ANG II levels rose proportionally with infusion rate and did not change significantly over time; thus fetal plasma ANG II concentrations can be predicted from MCRANGII. Measured and predicted ANG II levels at each infusion rate and time point were similar: r = 0.87, slope = 0.87 (P < 0.001). At equivalent predicted plasma ANG II levels fetal and maternal pressor responses were similar (P > 0.1); however, increases in umbilical vascular resistance exceeded those in uteroplacental vascular resistance (P < 0.03). Fetal MCRANGII is approximately 10-fold greater than maternal, partially reflecting the extensive capacity of ANG II removal by the placental circulation. Contrary to previous conclusions, fetal-maternal pressor sensitivity to ANG II does not differ, whereas the placental vasculature is more sensitive to ANG II than the uteroplacental circulation.
Long-term adaptive responses to dietary protein restriction in chronic renal failure
Authors: Tom K. , Young V. R. , Chapman T. , Masud T. , Akpele L. , Maroni B. J.
Published: December 2017

Six patients with chronic renal failure (glomerular filtration rate 18 +/- 2 ml/min) underwent two 10-day admissions separated by at least 1 yr of outpatient therapy with a very low-protein diet (VLPD) providing 0.28 g protein.kg-1.day-1 plus an amino acid-ketoacid supplement. During each Clinical Research Center admission, subjects completed a 5-day nitrogen balance (BN), and whole body protein turnover was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Outpatient dietary protein compliance was very good (25 vs. 20 g protein/day or 125% goal), whereas energy intake was only 69% of goal (24 vs. 35 kcal.kg-1.day-1). During the 16 +/- 2 mo of dietary therapy, there were no changes in serum proteins or anthropometrics. BN after > or = 1 yr of dietary therapy was neutral and did not differ from initial values (+0.46 +/- 0.20 vs. +0.55 +/- 0.19 g N/day). Similarly, rates of whole body protein synthesis, degradation, and leucine oxidation after long-term therapy with the VLPD regimen did not differ from baseline values, and neutral BN was maintained by a marked suppression of amino acid oxidation and postprandial inhibition of protein degradation. This is the first evidence that the compensatory changes in whole body protein turnover activated in response to dietary protein restriction are sustained during long-term therapy.
Hyperresponsiveness of arterial rings induced by renal prehypertensive rabbit plasma
Authors: Dostal D. E. , Johnson J. A. , Langevin P. B. , Abas N.
Published: December 2017

Vascular rings from normal rabbit renal arteries, when bathed in processed plasma from 3-day renal artery stenosis (RAS) rabbits, had greater contractile responses to norepinephrine than did matched rings bathed in processed plasma from sham-operated rabbits. This vascular hyperresponsiveness of the rings produced by 3-day RAS plasma was abolished by the angiotensin II (ANG II) antagonist [Sar1, Ile8] ANG II but not by [Sar1, Ala8] ANG II at a dose that completely blocked the contractile responses of the rings to ANG II. The addition of [Sar1, Ala8]-ANG II to rings bathed in normal rabbit plasma did not alter the contractile responses to norepinephrine, indicating a lack of agonistic action by this ANG II analogue. These studies demonstrated that the ANG II receptors involved in the hormonally mediated vascular hyperresponsiveness in 3-day RAS rabbits are contained in the tissues that comprise these renal arterial rings.
Augmentation of contraction in remote nonischemic zone during acute ischemia
Authors: Noma S. , Askenase A. D. , Weintraub W. S. , Klein L. W. , Agarwal J. B. , Helfant R. H.
Published: December 2017

We studied how left ventricular loading conditions and the size of the ischemic zone affect regional segmental shortening (% delta L) in ischemic (IZ) and remote nonischemic zones (NZ) after acute coronary occlusion. Distal and proximal portions of the left anterior descending artery (group I, 10 dogs) or the left circumflex artery (group II, 10 dogs) were occluded in two stages. Segment length sonomicrometers were placed in the distal and proximal IZ and in the distal and proximal NZ. % delta L was divided into isovolumic and ejection phases. Left ventricular end-diastolic pressure (LVEDP) was decreased 3 +/- 1 mmHg by blood withdrawal and then increased 6 +/- 2 mmHg by blood transfusion before and after distal and proximal coronary occlusions. LVEDP was brought back to its initial value before distal and proximal coronary occlusions. Regional blood flow and total blood flow deficit were measured with microspheres. Similar results were obtained in group I and II experiments. After coronary occlusion, the IZ showed systolic bulging occurring primarily in isovolumic systole. In the NZ, total and isovolumic % delta L increased from control, whereas ejection % delta L did not change. As LVEDP was raised, IZ isovolumic bulging decreased and ejection % delta L was unchanged, whereas NZ isovolumic % delta L decreased and ejection % delta L increased. Thus IZ bulging and NZ isovolumic % delta L changed in opposite directions when load was varied. The larger IZ after proximal coronary occlusion tended to increase the amount of NZ isovolumic % delta L. In conclusion, at low LVEDP NZ augmentation is predominantly caused by an increase in isovolumic % delta L, whereas if LVEDP is increased it is because of an increase in ejection % delta L. In addition, in open-chest animals augmented contraction in the NZ may be related to the size of the IZ.
Cardioprotective actions of thromboxane receptor antagonism in ischemic atherosclerotic rabbits
Authors: Osborne J. A. , Lefer A. M.
Published: December 2017

Atherosclerosis was induced in New Zealand White rabbits by feeding them a 0.5% cholesterol-enriched rabbit chow for 10–12 wk. Half of the cholesterol-fed rabbits were given BM 13505, a specific thromboxane A2/endoperoxide (TxA2/PGH2) receptor antagonist, and the other half were given its vehicle (i.e., 2% Na2CO3). At the end of 10–12 wk, the rabbits underwent experimental myocardial ischemia or an identical sham operation, except that the coronary artery was not occluded. BM 13505 was shown to protect the ischemic rabbit myocardium by three different methods: 1) maintenance of myocardial tissue creatine kinase (CK) activity in the ischemic myocardium; 2) reduced loss of free amino nitrogen-containing compounds from the myocardium; and 3) blunting the rise of plasma CK activity. Part of the mechanism for these effects may be due to inhibition of platelet aggregation and blockade of the vasoconstrictor effect of TxA2. However, these protective effects were not due to differences in myocardial oxygen demand among the groups. Finally, BM 13505 exhibited an antiatherogenic effect by reducing the deposition of cholesterol in the aortic wall and by retarding plaque formation in coronary arteries. However, it does not achieve this antiatherogenic effect by lowering plasma cholesterol concentrations or by scavenging superoxide free radicals. Thus blockade of TxA2 receptors exerts a variety of beneficial effects that reduce the severity of ischemic damage resulting from myocardial ischemia.
Similar normalized Emax and O2 consumption-pressure-volume area relation in rabbit and dog
Authors: Goto Y. , Slinker B. K. , LeWinter M. M.
Published: December 2017

The end-systolic pressure-volume relation (ESPVR), a measure of ventricular contractile state, and systolic pressure-volume area (PVA), a primary determinant of cardiac oxygen consumption per beat (VO2), have been derived from the pressure-volume diagram of the cross-circulated dog left ventricle. The slope of the PVA-VO2 relation represents the efficiency of chemomechanical energy transduction of the contractile machinery. To see whether these relationships were similar in other animals, we studied the isovolumic ESPVR and the VO2-PVA relation in nine excised, cross-circulated rabbit left ventricles. The base-line ESPVR was linear (r = 0.94-0.99) with the slope (Emax) and volume-axis intercept (V0) equal to 83.4 +/- 18.3 mmHg/ml and 0.43 +/- 0.17 ml, respectively. When normalized for left ventricular weight, Emax (4.1 +/- 1.1 mmHg.ml-1.100 g) and V0 (8.9 +/- 3.7 ml/100 g) were similar to values reported for the dog left ventricle. The correlation between PVA and VO2 was linear (r = 0.93-1.00), and the slope (1.90 X 10(-5) +/- 0.44 X 10(-5) ml O2.mmHg-1.ml-1) and VO2-axis intercept (0.040 +/- 0.009 ml O2.beat-1.100 g-1) were similar to values found in the dog left ventricle. Hence, despite the greatly different heart size, the base-line contractile state and chemomechanical energy conversion efficiency of the excised, cross-circulated rabbit left ventricle are similar to those of the dog left ventricle.
Evaluation of baroreceptor reflex by blood pressure monitoring in unanesthetized cats
Authors: Bertinieri G. , DiRienzo M. , Cavallazzi A. , Ferrari A. U. , Pedotti A. , Mancia G.
Published: December 2017

Page H377–H383: G. Bertinieri, M. DiRienzo, A. Cavallazzi, A. U. Ferrari, A. Pedotti, and G. Mancia. “Evaluation of baroreceptor reflex by blood pressure monitoring in unanesthetized cats.” Page H380: Table 3 should appear as the following:

(See PDF)
Coupling of albumin flux to volume flow in skin and muscles of anesthetized rats
Authors: Renkin E. M. , Gustafson-Sgro M. , Sibley L.
Published: December 2017

Bovine serum albumin (BSA) labeled with 131I or 125I was injected intravenously in pentobarbital sodium-anesthetized rats, and tracer clearances into leg skin and muscles were measured over 30, 60, and 120 min. BSA labeled with the alternate tracer was used as vascular volume reference. Two minutes before injection of the tracer, a ligature was tied around one femoral vein to occlude outflow partially and raise capillary pressure in that leg. The unoccluded leg served as control. Skin and muscles of the occluded leg had variably and substantially higher water contents (delta W) than paired control tissues and slightly but consistently increased albumin clearances (CA). The delta CA/delta W, equivalent to the albumin concentration of capillary filtrate relative to plasma determined by linear regression, were as follows: leg skin 0.004 (95% confidence limits -0.001 to +0.009), muscle biceps femoris 0.005 (0.001-0.010), muscle gastrocnemius 0.011 (0.004-0.019), muscle tibialis anterior 0.016 (0.012-0.021). All these values are significantly less than 0.10, which corresponds to a reflection coefficient for serum albumin (sigma A) of 0.90. Convective coupling of albumin flux to volume flux in skin and muscles of intact, anesthetized rats is low, with sigma AS in the range 0.98 to greater than 0.99.
Supersensitivity to acetylcholine of canine sinus and AV nodes after parasympathetic denervation
Authors: Kaseda S. , Zipes D. P.
Published: December 2017

Supersensitivity of the sinus (SAN) and atrioventricular (AVN) nodes to acetylcholine (ACh) after parasympathetic denervation has not been demonstrated conclusively. In this study, we denervated the SAN and AVN by surgically removing parasympathetic ganglia and painting the area with phenol. Sham dogs underwent thoracotomy without denervation. Four to 9 days later, vagal denervation was proved by supramaximal bilateral vagal stimulation, which prolonged the sinus cycle length (SCL) only 32 +/- 7% (mean +/- SE) and the AVN conduction time (AH interval) 15 +/- 7% in denervated dogs. We tested for supersensitivity by obtaining dose-response curves to ACh (1 ml, 10(-8.0) to 10(-4.0) M in 10(0.5) steps) infused over 15 s into the sinus nodal and posterior septal arteries in open chest-denervated (Den) dogs and in sham-operated (Sham) dogs that were anesthetized with alpha-chloralose. ACh concentration (Log[ACh], M) required to prolong SCL 50, 100, and 300% was -5.7 +/- 0.1, -5.6 +/- 0.1, and -5.4 +/- 0.1 in 10 Sham dogs vs. -6.4 +/- 0.1 (P less than 0.001), -6.3 +/- 0.1 (P less than 0.001) and -6.1 +/- 0.1 (P less than 0.001) in 11 Den dogs. ACh concentration necessary to produce second degree and complete AV block was -5.7 +/- 0.1 and -5.3 +/- 0.1 in 11 Sham dogs vs. -6.3 +/- 0.1 (P less than 0.001) and -5.8 +/- 0.1 (P less than 0.01) in 10 Den dogs. Because significantly lower doses of ACh prolonged SCL or produced AV block in Den compared with Sham dogs, we conclude that dogs with vagally denervated SAN and AVN develop a supersensitive response to ACh.
Perfused microvascular morphometry during middle cerebral artery occlusion
Authors: Buchweitz-Milton E. , Weiss H. R.
Published: December 2017

This study compared the arteriolar and capillary bed perfusion in the ischemic vs. contralateral cortex 1 h after middle cerebral artery (MCA) ligation in anesthetized rat. Fluorescein isothiocyanate (FITC)-dextran identified the perfused vascular beds. Regional cerebral blood flow (CBF) was monitored with [14C]iodoantipyrine. Morphometric parameters were determined through comparisons of the perfused FITC-labeled vessels with alkaline phosphatase-stained preparations of the total microvascular network. Regional CBF was significantly different when the contralateral cortex (54 +/- 7 ml.min-1.100 g-1) (means +/- SE) and the MCA-occluded cortex (31 +/- 8 ml.min-1.100 g-1) were compared. There were no significant regional differences in any morphometric index of structure in the total microvascular bed. The percentage of the total capillary and arteriolar volume that was perfused in the MCA-ligated cortex was significantly lower than the value obtained from the contralateral cortex. The change in the perfusion pattern of the cerebral microvasculature in the ischemic cortex was not due to vessel blockade. The altered temporal perfusion pattern of capillary and arteriolar vessels in the occluded cortex may be due to an altered microvascular perfusion cycle, longer perfusion pathways, vasoconstriction, or partial vessel obstruction.
Dexamethasone attenuates reversal of hypertension in one-kidney, one-clip rats
Authors: McGowan H. M. , Vandongen R. , Smith B.
Published: December 2017

This study examines the effect of dexamethasone (Dex), a phospholipase A2 inhibitor, on the reversal of 1-kidney, 1-clip (1K,1C) hypertension and the synthesis of phospholipase A2-dependent products. Male Sprague-Dawley 1K,1C hypertensive rats [blood pressure (BP) greater than 190 mmHg] were allocated to three groups: two groups were given daily oral doses of Dex (0.142 mg/kg in water) for 72 h, whereas the third group was given water only (controls). One of the Dex-treated groups was then sham unclipped (n = 9), while the other Dex-treated group (n = 8) and the control group (n = 8) were unclipped. Dex attenuated the BP fall in the unclipped (223 +/- 8-148 +/- 9 mmHg) compared with the control unclipped (226 +/- 9-114 +/- 5 mmHg) animals (P less than 0.005). Aortic 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) was reduced in unclipped Dex-treated rats (13.4 +/- 1.2 ng/mg) compared with unclipped control rats (16.3 +/- 1.4 ng/mg; P less than 0.05) but was higher than in the sham-unclipped Dex group (11.5 +/- 1.2 ng/mg; P less than 0.05). Serum thromboxane B2 (TxB2) in the unclipped Dex-treated group was lower than in the unclipped control rats (P less than 0.05) but higher than in sham-unclipped rats (P less than 0.05). Dex significantly increased urinary prostaglandin E2 (PGE2) excretion, whereas urinary 6-keto-PGF1 alpha was unaltered. After unclipping, both urinary PGE2 and 6-keto-PGF1 alpha increased significantly, although there was no obvious difference between Dex-treated and control animals. These findings demonstrate opposite effects of Dex on renal compared with extrarenal prostanoid synthesis and support the hypothesis that attenuation of aortic 6-keto-PGF1 alpha synthesis may be responsible for the smaller fall in BP after unclipping in Dex-treated rats.
Properties of single gap junctional channels between isolated neonatal rat heart cells
Authors: Rook M. B. , Jongsma H. J. , van Ginneken A. C.
Published: December 2017

The electrophysiological properties of single cardiac gap junctional channels that evolve one after another during the process of coupling between pairs of isolated neonatal rat heart myocytes obtained by enzymatic dispersion were investigated. Adjacent cells were brought in contact with each other by pushing them together by means of suction microelectrodes, which allow simultaneous voltage- or current-clamp recordings from each cell. Under these circumstances, the junctional channels had quite different properties from those reported in the literature. As long as only a few channels were present, they exhibited marked voltage-dependent gating as measured under voltage-clamp conditions and tended to close when transjunctional voltages greater than 50 mV were applied. Their single-channel conductance, depending on the composition of the solution in the recording pipettes, was approximately 45 or 60 pS, but also a lower conductance of 20 or 30 pS was encountered. As the junctional conductance increased concomitantly with an increase in the number of channels, this voltage dependence gradually diminished and eventually seemed to have disappeared completely. At that stage, the electrical properties of these newly formed junctions were identical with those of gap junctions between well-coupled cell pairs isolated as such.
Influence of shock strength and timing on induction of ventricular arrhythmias in dogs
Authors: Shibata N. , Chen P. S. , Dixon E. G. , Wolf P. D. , Danieley N. D. , Smith W. M. , Ideker R. E.
Published: December 2017

We delivered strong shocks via electrodes on the left ventricular apex and the right atrium in seven dogs during the T wave of atrial pacing while recordings were made from 56 epicardial electrodes. After shocks that induced arrhythmias were given, the earliest activation occurred in the middle of the ventricles for lower-energy shocks and in the base for higher-energy shocks. For shocks late in the vulnerable period, activation was recorded soon after the shock, whereas for shocks early in the vulnerable period activation was not recorded for a mean of 70 ms (+/- 17 ms SD) after the shock. We also gave 1-J shocks during right and left ventricular pacing. For shocks early in the vulnerable period, activation initiating fibrillation arose in a focal pattern from the paced region. For shocks during the midportion of the vulnerable period, fibrillation arose by two leading circle reentrant loops rotating in opposite directions, one on the left and the other on the right ventricle. For shocks at the end of the vulnerable period, the two reentrant loops fused on the side of the heart opposite the pacing site to again form a single focal activation pattern. Thus the initial activation patterns of arrhythmias initiated by shocks, the time from the shock until earliest postshock activation, and the site of earliest postshock activation are strongly influenced by the coupling interval and strength of the shock.
Relation of blood flow to VO2, PO2, and PCO2 in dog gastrocnemius muscle
Authors: Mohrman D. E. , Regal R. R.
Published: December 2017

We pump-perfused gastrocnemius-plantaris muscle preparations at constant pressure to study the relationship of muscle blood flow (Q) to muscle oxygen consumption (VO2), venous oxygen tension (PVO2), and venous carbon dioxide tension (PVCO2) during steady-state exercise at different rates. Tests were performed under four experimental conditions produced by altering the perfusate blood-gas status with a membrane lung. The consistency of the relationship of Q to other variables was evaluated by statistical analysis of fitted curves. Not one of the above listed variables had the same relationship with Q in all four of the experimental conditions we tested. However, we did find that a consistent relationship existed among Q, PVO2, and PVCO2 in our data. That relationship is well described by the equation (Q-23).[PVO2 - (0.5.PVCO2) - 3] = 105 (when Q is expressed in ml.100 g-1.min-1 and PVO2 and PVCO2 in mmHg). One interpretation of this result is that both PO2 and PCO2 are important variables in the control of blood flow in skeletal muscle the combined influence of which could account for nearly all of the hyperemia response to steady-state muscle exercise.
Pulmonary and systemic blood flow contributions to upper airways in canine lung
Authors: Barman S. A. , Ardell J. L. , Parker J. C. , Perry M. L. , Taylor A. E.
Published: December 2017

The blood flow contributions and drainage patterns of the pulmonary and systemic circulations in the upper airways (trachea and main bronchi) were assessed in anesthetized dogs by injecting 15-micron radiolabeled microspheres into the right and left heart, respectively. After the animals were killed, the tracheal cartilage, tracheal muscle-mucosa, and main bronchi were excised. The tracheal cartilage and tracheal muscle-mucosa were divided into lower, middle, and upper segments for blood flow determinations. The pulmonary contribution to tracheal blood flow was very small, averaging only 0.6 +/- 0.3 ml.min-1.100 g-1 (means +/- SE), being higher in the lower segments. The systemic contribution to these same tracheal regions was significantly (P less than 0.05) higher, averaging 20.9 +/- 5.5 ml.min-1.100 g-1 (means +/- SE) and higher in the upper segments. The pulmonary and systemic circulations each contributed approximately 50% to the main bronchi blood flow, which averaged 11.2 +/- 4.2 ml.min-1.100 g-1 (means +/- SE). The pulmonary blood flow contribution alone to the trachea and main bronchi was also determined in subsequent experiments that utilized the isolated lung, and these blood flows were not significantly different from the pulmonary contribution measured in the intact lungs. The present results indicate that the systemic (bronchial) circulation is the primary source of tracheal blood flow and that both the pulmonary and systemic circulations may contribute approximately 50% of the blood flow to the main bronchi in dog lungs.
Effects of arterial hypoxia and isoproterenol on in vitro postnatal intestinal circulation
Authors: Nowicki P. T. , Miller C. E. , Haun S. E.
Published: December 2017

We have previously speculated that intestinal vasodilation and hyperemia that occur in response to moderate arterial hypoxia in newborn swine in vivo are mediated by factors intrinsic to the intestinal circulation. To test this speculation, we vascularly perfused in vitro loops of jejunum from postnatal swine with control (PO2 98 +/- 4 mmHg) and hypoxic (PO2 38 +/- 2 mmHg) blood obtained from donor swine. In response to hypoxic perfusion, jejunal vascular resistance decreased 12 +/- 2, 13 +/- 3, 33 +/- 5, and 42 +/- 3% in in vitro loops from 1-, 7-, 14-, and 30-day-old swine, respectively, whereas jejunal oxygen uptake decreased 53 +/- 6, 29 +/- 6, 31 +/- 4, and 13 +/- 6% in these age groups. To clarify whether this age-dependent vasodilation was unique to the stimulus of arterial hypoxia or a response characteristic of the postnatal swine intestine to other vasodilator stimuli, we also determined the effect of intra-arterial isoproterenol infusion at rates of 0.01, 0.1, and 1.0 micrograms/min on jejunal hemodynamics and oxygenation in vitro. In jejunal loops taken from 7- and 30-day-old swine, isoproterenol caused a similar degree of vasodilation at each drug-infusion rate. We conclude that vasodilation of the postnatal swine intestine in response to moderate arterial hypoxia is mediated, at least in part, by intrinsic vascular regulation. We speculate that the age dependency of hypoxic vasodilation may reflect a relative inability of the intestine from very young swine to respond to the stimulus of arterial hypoxia.
Myocardial neutrophil accumulation during reperfusion after reversible or irreversible ischemic injury
Authors: Go L. O. , Murry C. E. , Richard V. J. , Weischedel G. R. , Jennings R. B. , Reimer K. A.
Published: December 2017

Recent studies suggest that polymorphonuclear leukocytes (PMNs) may cause additional myocyte injury during reperfusion of ischemic myocardium. The present study was done to investigate whether PMNs accumulate in myocardium during early reperfusion after reversible or irreversible ischemic injury. Open-chest anesthetized dogs underwent circumflex coronary occlusions for 12 min (n = 5), 40 min (n = 8), or 90 min (n = 8), followed by 1 h of reperfusion. Autologous PMNs were radiolabeled with 111In and reinjected to quantitate myocardial PMN influx during reflow. 125I-labeled albumin was injected simultaneously to correct for 111In associated with plasma proteins in myocardial tissue. The number of PMNs was determined in the inner, middle, and outer one-third of nonischemic and ischemic-reperfused myocardium. In the 12-min group, 40% fewer PMNs were present in the reperfused than in the nonischemic control tissue. In contrast, in both the 40- and 90-min groups, PMN accumulation was two- to sixfold greater in the ischemic-reperfused than nonischemic myocardium, with a transmural gradient of PMN influx increasing from the outer to inner layers. Collateral blood flow, measured with radioactive microspheres, was not significantly different among the three groups. The failure of PMNs to accumulate during reperfusion after 12 min of ischemia does not support the hypothesis that PMNs contribute to postischemic dysfunction of reversibly injured myocytes. Whether PMNs caused cell death during early reperfusion after longer ischemic episodes remains unknown; however, the rapidity of PMN accumulation in the zones of predicted infarction is consistent with this possibility.
Carotid sinus pressure and plasma vasopressin in anesthetized rabbits
Authors: Courneya C. A. , Rankin A. J. , Wilson N. , Ledsome J. R.
Published: December 2017

The arterial baroreceptors are known to influence the release of vasopressin, but the quantitative relationship between baroreceptor stimulation and plasma vasopressin concentration has not been defined. These experiments examine the effect of stepwise changes in carotid sinus pressure (40-160 mmHg) on the plasma concentration of vasopressin in chloralose-urethan anesthetized rabbits. Plasma vasopressin concentration (9.2 +/- 1.2 pg/ml, n = 27) did not change in response to changes in carotid sinus pressure when the aortic depressor nerves were intact. These results were unaltered by bilateral cervical vagotomy. However, after aortic depressor nerve section, decreases in carotid sinus pressure were associated with increases in plasma vasopressin concentration. There appeared to be a greater redundancy in the baroreceptor control of plasma vasopressin than in the baroreceptor control of arterial pressure or heart rate. The results provided no evidence that receptors with vagal afferents have a tonic influence on the baroreceptor control of vasopressin release in the anesthetized rabbit.
Synergism of intraventricular NaCl infusion and subpressor angiotensins in rats
Authors: Katahira K. , Mikami H. , Ogihara T. , Kohara K. , Otsuka A. , Kumahara Y. , Khosla M. C.
Published: December 2017

The effect of selective salt infusion to the central nervous system on the blood pressure (BP) regulation was examined in male Wistar rats. Hypertonic NaCl (0.8 M, 1 microliter/h) was infused into the lateral ventricle concomitantly with intravenous infusion of a subpressor dose (5.4 pmol.kg-1.min-1) of angiotensin II (ANG II) or its analogues for 7 days using osmotic minipumps. The BP was not increased by intracerebroventricular infusion of NaCl alone at this dose but was significantly and consistently increased by concomitant intravenous infusion of ANG II or its analogues. The increases in the BP over the base-line values on day 7 in groups on infusions of ANG II, ANG III, and pentasarcosyl-ANG II [(Sar)5ANG II] were 29 +/- 5 mmHg (n = 9, P less than 0.05), 8 +/- 2 mmHg (n = 8, P less than 0.05), and 19 +/- 3 mmHg (n = 6, P less than 0.05), respectively. The responses to hexamethonium, prazosin, and antagonists of arginine vasopressin and ANG II were examined in separate sets of conscious and unrestrained animals that had received intracerebroventricular infusion of NaCl and intravenous infusion of ANG II for the preceding 6 days. These animals showed significantly greater depressor responses only to hexamethonium and prazosin than control. These results indicate that the pressor effect of continuous and concomitant administration of intracerebroventricular NaCl and intravenous ANG II is mainly due to activation of the sympathetic nerve function. Synergism of the effects of selective central sodium administration and a subpressor dose of ANG II in the central nervous system is suggested.
Transfer function analysis of autonomic regulation. II. Respiratory sinus arrhythmia
Authors: Saul J. P. , Berger R. D. , Chen M. H. , Cohen R. J.
Published: December 2017

An efficient new technique was developed to investigate heart rate control at all physiologically relevant frequencies by using respiratory activity as a frequency probe of the autonomic nervous response. The transfer function from respiratory activity to heart rate was determined during 6-min periods in which the respiratory rate was voluntarily controlled in a predetermined but erratic fashion. Changes in posture were used to manipulate autonomic balance. Respiratory sinus arrhythmia was determined to be a frequency-dependent phenomenon with the magnitude and phase characteristics of a low-pass filter. In agreement with previous work, at typical respiratory frequencies (greater than 0.15 Hz) increases in heart rate occurred simultaneously with the onset of inspiratory activity; however, at frequencies less than 0.15 Hz the phase relationship was quite different, such that increases in heart rate preceded inspiration. Between 0.15 and 0.45 Hz, the transfer magnitude was consistently lower while the subjects were in the upright posture than when in the supine posture, but below 0.15 Hz, it was equal in both postures. A model for respiratory modulation of heart rate, based on the atrial rate response characteristics determined in the companion paper [Am. J. Physiol. 256 (Heart Circ. Physiol. 25): H142-H152, 1989], suggests that the magnitude and phase characteristics of the subjects in the supine and upright postures differ because of relatively increased sympathetic outflow in the upright posture. A precise and efficient characterization of respiratory sinus arrhythmia can yield considerable insight into the autonomic regulation of the heart.
Oxygen exchange in the microcirculation of hamster retractor muscle
Authors: Swain D. P. , Pittman R. N.
Published: December 2017

We determined percent hemoglobin oxygen saturation (SO2) in arterioles and venules of the hamster retractor muscle at rest. We found that SO2 decreased from 69.9 +/- 1.4% (SE) in large input arterioles (first order, 1A, ID = 60 +/- 3 micron) to flow-weighted values of 56.7% in small arterioles (4A, ID = 20 +/- 1 micron), 51.3% in small venules (4V, ID = 28 +/- 1 micron), and to 50.6 +/- 1.0% in large venules (1V, ID = 147 +/- 13 micron). Thus approximately two-thirds of the net decline in SO2 for this tissue occurred by diffusion of oxygen from arterioles, whereas only about one-third occurred by diffusion from capillaries. Furthermore, no net shunting of oxygen from the arterioles to the venules was detected as evidenced by the absence of any significant change in venular SO2. By determining the SO2 at upstream and downstream ends of arterioles in four consecutive branching orders (1A-4A), we found that the decrease in SO2 per unit length (delta SO2/L) increased approximately 20-fold from 1A to 4A. This increase in delta SO2/L was directly proportional to estimated luminal minus tissue oxygen tension and inversely proportional to red blood cell flow.
Beta-adrenergic receptor regulation during hypoxia in intact cultured heart cells
Authors: Marsh J. D. , Sweeney K. A.
Published: December 2017

Regulation of cardiac beta-adrenergic receptors during hypoxia and ischemia is an area of active investigation, with some investigators reporting an increase in sarcolemmal beta-receptor number after ischemia. Previous studies have been limited by the necessity of examining beta-adrenergic receptor properties in membrane preparations from hypoxic or ischemic cardiac tissue and drawing conclusions about receptor localization in intact tissue from the behavior of a fraction of total receptors in membrane populations. As an approach to examining beta-receptor properties under well-defined pathophysiological conditions in intact heart cells, we studied cell-surface beta-receptors and adenylate cyclase activity in intact cultured chick embryo ventricular cells under conditions of controlled hypoxia and reoxygenation. During 2 h of hypoxia (PO2 less than 1.5 Torr) there was a progressive decline in cell surface beta-receptors from 26 +/- 2 to 10 +/- 6 fmol/mg (P less than 0.003) with no change in antagonist or agonist affinity. Receptor number recovered fully during 2 h of reoxygenation. Basal adenosine 3',5'-cyclic monophosphate (cAMP) production was unchanged, but response to isoproterenol in the absence or presence of a phosphodiesterase inhibitor decreased to about half of the response for normoxic cells but fully recovered during reoxygenation in a pattern similar to that for receptor number. Although [ATP] declined significantly during hypoxia (from 35 to 25 nmol/mg), the decline in [GTP] was marginal (4.3 to 3.9 nmol/mg), making it unlikely that substrate for guanine nucleotide regulatory protein was limiting for beta-adrenergic signal transduction.(ABSTRACT TRUNCATED AT 250 WORDS)
Distribution of perfusate flow during vasodilation in isolated guinea pig heart
Authors: Gorman M. W. , Wangler R. D. , Sparks H. V.
Published: December 2017

The purpose of this study was to determine the effect of vasodilation on the distribution of perfusate flow in the isolated guinea pig heart. Hearts were perfused retrogradely through the aorta with oxygenated Krebs-Henseleit buffer solution at 37 degrees C. Regional myocardial flows were measured with 15-micron radioactive microspheres. Each heart was subdivided into 45 pieces (average size 44 mg), and heterogeneity of flow was quantified as the relative dispersion (standard deviation/mean). Under control conditions at a perfusion pressure of 46 mmHg (60 cm water), the relative dispersion of left ventricular (LV) flow was 30 +/- 2% (n = 8). Vasodilation was induced via infusion of dipyridamole (10(-5) M). When flow was held constant at the resting value, relative flow dispersion increased to 43 +/- 6% (n = 8). When perfusion pressure was held constant and flow allowed to increase, relative dispersion fell to 20 +/- 5% (n = 5). Heterogeneity for the heart as a whole was higher than for the left ventricle but followed the same pattern with vasodilation. In a separate series of hearts (n = 5) equipped with LV balloons but without microsphere flow measurements, vasodilation at constant flow decreased LV pressure development, dP/dt, and O2 consumption. Vasodilation at constant pressure increased O2 consumption, but did not increase LV pressure or dP/dt. We conclude that vasodilation in this preparation will increase flow heterogeneity during constant-flow perfusion but decrease heterogeneity during constant-pressure perfusion. Furthermore, increased flow heterogeneity can compromise ventricular function.
Role of acetylcholine in induction of repetitive activity in human atrial fibers
Authors: Hou Z. Y. , Lin C. I. , Vassalle M. , Chiang B. N. , Cheng K. K.
Published: December 2017

The actions of acetylcholine and its interactions with epinephrine were studied in human atrial tissues by recording transmembrane potentials and contractile force. Acetylcholine (0.55-5.5 microM) reduced force, shortened the duration and shifted to more negative values the plateau of action potentials, abolished phase 4 depolarization, and suppressed the activity of spontaneous fibers. During the recovery, often there was a rebound increase in some parameters of the action potential and in force. Epinephrine (0.3-2.8 microM) induced oscillatory potentials and aftercontractions and acetylcholine abolished them. However, during the washout of acetylcholine in the presence of epinephrine, the oscillatory potentials and aftercontractions were larger than before acetylcholine, and repetitive activity was often induced. The inhibitory and excitatory effects of acetylcholine were mimicked by methacholine (5.1 microM) and abolished by atropine (1.5 microM). The postacetylcholine rebound was also potentiated by theophylline (0.6-2 mM) but was not blocked by propranolol (1-3.4 microM), prazosin (1 microM), and diltiazem (0.1 microM). It is concluded that in human atrial fibers acetylcholine has inhibitory as well as excitatory effects that are exaggerated in the presence of epinephrine and are mediated by the activation of the muscarinic receptor. The interaction between acetylcholine and epinephrine involves an antagonism at an intracellular level.
Single cardiac sarcoplasmic reticulum Ca2+-release channel: activation by caffeine
Authors: Rousseau E. , Meissner G.
Published: December 2017

Caffeine is thought to affect excitation-contraction coupling in cardiac muscle by activating the sarcoplasmic reticulum (SR) Ca2+-release channel. The effect of caffeine at the single channel level was studied by incorporating canine cardiac SR vesicles into planar lipid bilayers. Cardiac Ca2+-release channels were activated in a steady-state manner by millimolar cis-caffeine and displayed a unitary conductance (77 pS in 50 mM Ca2+ trans) similar to that previously observed for the Ca2+-activated cardiac channel. The caffeine-activated channel was moderately sensitive to the voltage applied across the bilayer, was sensitive to further activation by ATP, and was inhibited by Mg2+ and ruthenium red. Kinetic analysis showed that at low Ca2+ concentration, caffeine activated the channel by increasing the frequency and the duration of open events.
Contractile function of heterogeneously perfused myocardium in conscious dogs
Authors: Nagata M. , Lavallee M.
Published: December 2017

The contractile function of heterogeneously perfused segments (HET) after circumflex coronary artery occlusion (CAO) was examined in conscious dogs. At 1 h after CAO, regional shortening (SH) in nonischemic segments did not change from pre-CAO base line, and regional endocardial blood flow (REBF) increased (P less than 0.05) to 1.52 +/- 0.20 from 1.06 +/- 0.08 ml.min-1.g of tissue-1. In ischemic segments, SH was replaced by paradoxical bulging, and REBF averaged 0.07 +/- 0.02 ml.min-1.g of tissue-1. In HET with one crystal of each pair in nonischemic myocardium and the other in severely ischemic myocardium, SH at 1 h after CAO was reduced (P less than 0.01) by 53.2 +/- 3.4%. REBF maps constructed with serial sections of ventricular rings containing the crystals revealed that in HET 50 +/- 5% of the myocardium was ischemic. Therefore, in the acute phase of ischemia, the reductions in SH in HET were proportional to the amount of ischemic myocardium between recording sites. In HET, SH significantly recovered (P less than 0.01) over 4 wk after CAO but remained depressed by 26.8 +/- 5.1%. In contrast, SH in ischemic segments did not improve after CAO. In HET, the effects of inotropic stimulation and changes in left ventricular afterload on SH (as percent of base line) were similar before and at 1-4 wk after CAO. Thus, in HET, the level of dysfunction is acutely determined by the amount of ischemic myocardium between recording sites. Over 4 wk after CAO, SH improved substantially in these segments, and contractile function was not adversely influenced by an inotropic stimulation or an increase in ventricular afterload.