bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelin-1 myocardial clearance, production, and effect on capillary permeability in vivo
Authors: Dupuis J. , Goresky C. A. , Rose C. P. , Stewart D. J. , Cernacek P. , Schwab A. J. , Simard A.
Published: December 2017

Myocardial metabolism of endothelin-1 (ET-1) and its effect on coronary microcirculatory exchanges were obtained in anesthetized dogs by combining the indicator-dilution technique with immunoreactive ET-1 measurements. The myocardium extracted 17.7 +/- 4.6% of tracer ET-1 (n = 12). Simultaneously measured ET-1 levels in the aorta (0.97 +/- 0.46 pg/ml) and coronary sinus (0.96 +/- 0.53 pg/ml) were not different, supporting a production of ET-1 by the heart that balances the amount extracted. Intracoronary infusion of ET-1 (5 ng.kg-1.min-1) increased coronary sinus ET-1 levels approximately 50-fold, decreased coronary blood flow per unit of interstitial space by approximately 30% (P = 0.006), and increased myocardial microcirculatory transit times (n = 6). Permeability to albumin was unaffected by ET-1, whereas the permeability-surface area product for sucrose decreased following derecruitment of myocardial capillaries. We conclude that there is a normal myocardial metabolic balance of ET-1 and that the heart marginally contributes to circulating ET-1. Pharmacological doses of ET-1 may adversely affect myocardial metabolism by reducing blood flow and the permeability-surface area product for small circulating substances.
Myocardial bioenergetics during acute hibernation
Authors: Zhang J. , Ishibashi Y. , Zhang Y. , Eijgelshoven M. H. , Duncker D. J. , Merkle H. , Bache R. J. , Ugurbil K. , From A. H.
Published: December 2017

During moderate reductions of blood flow, the myocardium downregulates contractile function and ATP utilization to result in reduced but stable ATP levels, recovery or stability of (reduced) creatine phosphate (CP), and preservation of myocyte viability. The intent of this study was to determine the influence of the level of ischemic blood flow and the major determinants of myocardial O2 consumption (MVO2) (heart rate and systolic blood pressure) on recovery of CP during prolonged moderate myocardial hypoperfusion. 31P-nuclear magnetic resonance spectroscopy was used to measure CP, ATP, and Pi in the subepicardium (Epi) and subendocardium (Endo) of 13 open-chest dogs. Wall thickening was measured with sonomicrometry. A coronary stenosis reduced mean myocardial blood flow (microspheres) from 1.10 +/- 0.07 to 0.71 +/- 0.06 ml.g-1.min-1 (P < 0.01) and the Endo-to-Epi blood flow ratio from 1.12 +/- 0.07 to 0.59 +/- 0.06 (P < 0.01), and dyskinesis developed. Coronary blood flow and systolic wall thickening did not change significantly during 4 h of hypoperfusion. Epi CP and ATP fell to 80 +/- 4% (P < 0.05) and 93 +/- 3% of control, respectively, at 30 min. Epi CP then recovered to 87 +/- 5% while ATP decreased further to 83 +/- 5% of baseline by the end of the 240-min ischemic period. Endo CP and ATP fell to 53 +/- 4 and 77 +/- 5% of control, respectively, at 30 min; then Endo CP recovered to 85 +/- 6% while ATP decreased further to 68 +/- 6% of baseline at 240 min of hypoperfusion. ADP levels were significantly increased at 30 min but recovered to baseline by 240 min of hypoperfusion. delta Pi/CP increased significantly (Endo > Epi) at the onset of ischemia and then progressively decreased. At 30 min, mild myocardial acidosis was observed in some hearts with variable pH recovery during continuing hypoperfusion. The data demonstrate that variations in blood flow cannot account for the magnitude of the initial fall in CP or for the final extent of recovery. However, the rate at which CP recovered was significantly correlated with the level of blood flow. Variations in the determinants of MVO2 did not account for differences in CP recovery.
Enhanced constrictor responses of skeletal muscle arterioles during chronic myocardial infarction
Authors: Didion S. P. , Carmines P. K. , Ikenaga H. , Mayhan W. G.
Published: December 2017

The goal of this study was to test the hypothesis that chronic myocardial infarction potentiates agonist-induced constrictor responses of rat skeletal muscle arterioles in vivo. Eight weeks after we performed coronary artery ligation or sham (control) surgery, the spinotrapezius muscle was prepared for direct visualization of the microcirculation. Diameter of third-order arterioles (40.7 +/- 0.5 microns) to topical suffusion of angiotensin II (ANG II; 0.1-10 nM), arginine vasopressin (AVP; 0.1-10 nM), endothelin-1 (ET-1; 1.0-100 pM), and the thromboxane analog U-46619 (1.0-100 nM) was measured in both groups. Myocardial-infarcted rats exhibited enhanced arteriolar constrictor responses to ANG II and AVP compared with the responses in controls. In contrast, ET-1- and U-46619-induced constrictor responses were similar in control and myocardial-infarcted rats. Additional experiments explored the impact of NG-monomethyl-L-arginine (L-NMMA; 0.1 mM) on arteriolar reactivity. In control animals, L-NMMA potentiated ANG II- and AVP-induced vasoconstriction, achieving values similar to those observed in myocardial-infarcted rats. L-NMMA did not alter vasoconstrictor responses in rats with chronic myocardial infarction. These observations suggest that enhanced agonist-induced vasoconstriction during heart failure may reflect a loss of nitric oxide-mediated modulation of arteriolar tone.
Adenosine inhibition of neutrophil damage during reperfusion does not involve KATP-channel activation
Authors: Zhao Zhi-Qing , Todd James C. , Sato Hiroki , Ma Xin-Liang , Vinten-Johansen J.
Published: December 2017

This study tests the hypothesis that cardioprotection exerted by adenosine A2-receptor activation and neutrophil-related events involves stimulation of ATP-sensitive potassium (KATP) channels on neutrophils during reperfusion. The adenosine A2agonist CGS-21680 (CGS) inhibited superoxide radical generation from isolated rabbit polymorphonuclear neutrophils (PMNs) in a dose-dependent manner from 17.7 ± 2.1 to 7.4 ± 1.3 nmol/5 × 106PMNs ( P < 0.05). Pinacidil, a KATP-channel opener, partially inhibited superoxide radical production, which was completely reversed by glibenclamide (Glib). Incremental doses of Glib in combination with CGS (1 μM) did not alter CGS-induced inhibition of superoxide radical generation. CGS significantly reduced PMN adherence to the endothelial surface of aortic segments in a dose-dependent manner from 189 ± 8 to 50 ± 6 PMNs/mm2( P < 0.05), which was also not altered by incremental doses of Glib. Infusion of CGS (0.025 mg/kg) before reperfusion reduced infarct size from 29 ± 2% in the Vehicle group to 15 ± 1% in rabbits undergoing 30 min of ischemia and 120 min of reperfusion ( P< 0.05). Glib (0.3 mg/kg) did not change the infarct size (28 ± 2%) vs. the Vehicle group and did not attenuate infarct size reduction by CGS (16 ± 1%). Glib did not change blood glucose levels. Cardiac myeloperoxidase activity was decreased in the ischemic tissue of the CGS group (0.15 ± 0.03 U/100 mg tissue) compared with the Vehicle group (0.37 ± 0.05 U/100 mg tissue; P < 0.05). We conclude that adenosine A2activation before reperfusion partially reduces infarct size by inhibiting neutrophil activity and that this effect does not involve KATP-channel stimulation.
MCI-154, a Ca2+ sensitizer, decreases the oxygen cost of contractility in isolated canine hearts
Authors: Onishi Katsuya , Sekioka Kiyotsugu , Ishisu Ryoichi , Abe Yuji , Tanaka Hideyuki , Nakamura Mashio , Ueda Yuji , Nakano Takeshi
Published: December 2017

An increase in the responsiveness of the contractile machinery to Ca2+could theoretically enhance the mechanoenergetics of the heart. To clarify this unresolved issue, we studied the effects of MCI-154, a Ca2+ sensitizer, on the mechanoenergetics in terms of the left ventricular contractility index [slope of end-systolic pressure-volume relationship ( E max)] and the relationship between myocardial oxygen consumption (Vo 2) and left ventricular pressure-volume area in excised cross-circulated canine hearts. MCI-154 increased E max by 42 ± 31% (SD), although the slope of the Vo 2-PVA relationship (an indicator of contractile efficiency) was unchanged by MCI-154. Despite equal increases in E max, the relative increase in unloaded Vo 2(ΔVo 2/Δ E max) during infusion of MCI-154 was, however, significantly less than that during CaCl2 infusion (0.0016 ± 0.0018 vs. 0.0059 ± 0.0054; P < 0.05). By contrast, ΔVo 2/Δ E maxfor milrinone was the same as that for CaCl2 (0.0043 ± 0.0041 vs. 0.0039 ± 0.0045; P > 0.05). Basal metabolism in KCl-arrested hearts was unchanged by MCI-154, indicating that MCI-154 consumes less energy than CaCl2 for excitation-contraction coupling. These findings suggest that MCI-154 acts energetically as a Ca2+ sensitizer in beating canine whole hearts.
Estimating a cardiac age by means of heart rate variability
Authors: Colosimo A. , Giuliani A. , Mancini A. M. , Piccirillo G. , Marigliano V.
Published: December 2017

A data set of R-R intervals recorded for at least 15 min in 141 healthy individuals of different ages and under two different conditions (“resting” and “tilted” states) has been considered. The data have been subjected to spectral analysis by fast Fourier transform methods and considered in view of the possibility to work out a model in which the chronological and cardiac age could be compared. Understanding the results was greatly facilitated by 1) working out a number of derived variables from the original ones to highlight the presence of small but conceptually important variability factors; 2) extraction of the principal components from the original as well as from the derived variables to exclude redundancies and correlation effects; and 3) automatic clustering of the subjects in age classes, which allowed removal of individual variability within each class. The main conclusion is that, within the examined individuals, cardiac and chronological ages do not match for ages higher than ∼50 years; this could reflect the presence of subtle (and difficult-to-envisage) biases in the data analysis or a real discrepancy. The latter hypothesis should be confirmed by similar observations in different systemic contexts. The use of a simple equation relating chronological and cardiac age, derived from a careful regression analysis on our data set and of general use for screening purposes, is demonstrated.
Pontine neurons are elements of the network responsible for the 10-Hz rhythm in sympathetic nerve discharge
Authors: Barman Susan M. , Kitchens Heather L. , Leckow Aaron B. , Gebber Gerard L.
Published: December 2017

The current study was designed to test the hypothesis that pontine neurons are elements of the network responsible for the 10-Hz rhythm in sympathetic nerve discharge (SND). The first series of experiments tested whether chemical inactivation of neurons in the rostral dorsolateral pons (RDLP) or caudal ventrolateral pons (CVLP) affected inferior cardiac postganglionic SND of urethan-anesthetized cats. Muscimol microinjections into either region eliminated the 10-Hz rhythm in SND, supporting the view that pontine neurons are involved in the expression of this rhythm. Additional experiments were designed to determine if pontine neurons have activity correlated to the 10-Hz rhythm in SND or whether they merely provide a tonic (nonrhythmic) driving input to the rhythm generator. Coherence analysis revealed that local field potentials recorded from the RDLP or CVLP had a 10-Hz component that was significantly correlated to SND. Also, spike-triggered averaging and coherence analysis showed that the naturally occurring discharges of individual RDLP or CVLP neurons were correlated to the 10-Hz rhythm in SND. Taken together, these data support the hypothesis that RDLP and CVLP neurons are essential for the expression of the 10-Hz rhythm in SND and that they are elements of or receive input from the rhythm generator.
Contribution of angiotensin-converting enzyme to the cardiac metabolism of bradykinin: an interspecies study
Authors: Blais Charles , Drapeau Guy , Raymond Philippe , Lamontagne Daniel , Gervais Nicole , Venneman Ingrid , Adam Albert
Published: December 2017

The role of angiotensin-converting enzyme (ACE) in the metabolism of bradykinin (BK) has been studied in several tissues. However, and contrary to angiotensin I, the metabolism of BK at the cardiac level has not been investigated. In this study, we define the participation of ACE in the carboxy-terminal degradation of BK in heart membranes of the dog, human, rabbit, and rat. The calculation of the kinetic parameters characterizing the metabolism of BK and the generated des-Arg9-BK can be summarized as follows: the half-life ( t 1/2) of BK [dog (218 ± 32 s) > human (143 ± 9 s) = rat (150 ± 4 s) > rabbit (22 ± 2 s)] and of des-Arg9-BK [dog (1,042 ± 40 s) > human (891 ± 87 s) > rat (621 ± 65 s) > rabbit (89 ± 8 s)] both showed significant differences according to species. Enalaprilat, an ACE inhibitor, significantly prevented the rapid degradation of BK and des-Arg9-BK in all species studied, whereas retrothiorphan, a neutral endopeptidase inhibitor, and losartan, an angiotensin II type I receptor antagonist, did not affect this metabolism. The relative importance of ACE in the cardiac metabolism of BK was species related: dog (68.4 ± 3.2%) = human (72.2 ± 2.0%) > rabbit (47.7 ± 5.0%) = rat (45.3 ± 3.9%). ACE participation in the metabolism of des-Arg9-BK was as follows: rabbit (57.0 ± 4.0%) > dog (39.9 ± 8.8%) = human (25.4 ± 5.5%) = rat (36.0 ± 7.0%). The participation of cardiac kininase I (carboxypeptidase M) in the transformation of BK into des-Arg9-BK was minor: human (2.6 ± 0.1%) > dog (0.9 ± 0.1%) = rabbit (1.0 ± 0.1%) = rat (1.0 ± 0.1%). These results demonstrate that ACE is the major BK-degrading enzyme in cardiac membranes. However, the metabolism of exogenous BK by heart membranes is species dependent. Our observations could explain some discrepancies regarding the contribution of kinins in the cardioprotective effects of ACE inhibitors.
Muscle cooling delays activation of the muscle metaboreflex in humans
Authors: Ray Chester A. , Hume Keith M. , Gracey Kathryn H. , Mahoney Edward T.
Published: December 2017

Elevation of muscle temperature has been shown to increase muscle sympathetic nerve activity (MSNA) during isometric exercise in humans. The purpose of the present study was to evaluate the effect of muscle cooling on MSNA responses during exercise. Eight subjects performed ischemic isometric handgrip at 30% of maximal voluntary contraction to fatigue followed by 2 min of postexercise muscle ischemia (PEMI), with and without local cooling of the forearm. Local cooling of the forearm decreased forearm muscle temperature from 31.8 ± 0.4 to 23.1 ± 0.8°C ( P = 0.001). Time to fatigue was not different during the control and cold trials (156 ± 11 and 154 ± 5 s, respectively). Arterial pressures and heart rate were not significantly affected by muscle cooling during exercise, although heart rate tended to be higher during the second minute of exercise ( P = 0.053) during muscle cooling. Exercise-induced increases in MSNA were delayed during handgrip with local cooling compared with control. However, MSNA responses at fatigue and PEMI were not different between the two conditions. These findings suggest that muscle cooling delayed the activation of the muscle metaboreflex during ischemic isometric exercise but did not prevent its full expression during fatiguing contraction. These results support the concept that muscle temperature can play a role in the regulation of MSNA during exercise.
Increased vascular responsiveness to α2-adrenergic stimulation during NOS inhibition-induced hypertension
Authors: Kanagy Nancy L.
Published: December 2017

Increased vascular resistance during systemic nitric oxide synthase (NOS) inhibition is dependent on adrenergic vasoconstriction. This study tested the hypothesis that increased vascular sensitivity to adrenergic agonists contributes to this vasoconstriction. Superior mesenteric arteries and thoracic aortae from male Sprague-Dawley rats drinking water containing N ω-nitro-l-arginine (l-NNA; 14 days, 60 mg ⋅ kg−1 ⋅ day−1) and control rats were cut into helical strips, and endothelium was removed for contractile experiments.l-NNA arteries were more sensitive to UK-14304 (α2-adrenergic agonist) and norepinephrine (NE), whereas responses to phenylephrine (PE) were not different [concentration causing 50% maximal response (EC50),l-NNA vs. control: UK-14304, 0.071 vs. 0.71 μmol/l; NE, 1.15 vs. 9.95 nmol/l]. Yohimbine, an α2-selective antagonist, caused a concentration-dependent inhibition of contraction to NE only inl-NNA arteries (EC50 = 6.3 vs. 1.6 nmol/l at 1 nmol/l yohimbine), whereas prazosin shifted NE curves similarly in arteries from both groups. Yohimbine (10 nmol/l) inhibited contractions to UK-14304 (EC50 = 59 μmol/l vs. 17 μmol/l) but not contractions to PE, whereas prazosin inhibited both. These data indicate thatl-NNA-induced hypertension leads to increased sensitivity of prazosin-sensitive α2-adrenoceptors, an upregulation that could cause the increased vasoconstrictor response to NE in this model of hypertension.
Effect of barodenervation on c-Fos expression in the medulla induced by static muscle contraction in cats
Authors: Li Jianhua , Potts Jeffrey T. , Mitchell Jere H.
Published: December 2017

A previous study has shown increased Fos-like immunoreactivity (FLI), a marker of neural activation, in the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM) after static muscle contraction elicited by electrical stimulation of L7 and S1 ventral roots of the spinal cord in anesthetized, baroreceptor-intact cats. Because the electrically induced static muscle contraction reflexly increased arterial blood pressure, the concomitant activation of the arterial baroreceptor reflex during static muscle contraction may have resulted in some of the FLI labeling that was observed in the medulla. The purpose of this study was to determine regions in the medulla that are activated by muscle contraction in the absence of arterial baroreceptor input. Electrical stimulation of L7 and S1 ventral roots of the spinal cord was used to elicit static muscle contraction, and FLI in the medulla was determined in barointact and barodenervated cats. In barointact contraction cats, FLI was observed in the lateral reticular nucleus (LRN), NTS, lateral tegmental field (FTL), subretrofacial nucleus (SRF), and A1 region of the medulla. In barodenervated contraction cats, FLI increased in the same regions; however, the number of FLI-labeled cells in the NTS, FTL, and A1 region was significantly less than in barointact contraction animals. No significant difference in the number of FLI-labeled cells was found in the LRN and SRF between the two groups. These results clearly demonstrate that cardiovascular regions in the medulla are activated by input from afferent activity originating in skeletal muscle independently of concomitant arterial baroreceptor reflex activation.
Venous and arterial behavior during normal pregnancy
Authors: Edouard D. A. , Pannier B. M. , London G. M. , Cuche J. L. , Safar M. E.
Published: December 2017

To assess the contribution of the arterial and venous systems in the hemodynamic changes of normal pregnancy, we studied blood flow, vascular resistance, venous tone, and the viscoelastic properties (“creep”) of the upper and lower limbs (using plethysmography), aortic distensibility (using pulse wave velocity measurements), and cardiac dimensions (using echocardiography) in nine healthy women. Studies were longitudinally performed at the first (10–13 wk) and third (33–38 wk) trimesters of pregnancy in comparison with the period between the third and sixth month after delivery. From the first trimester, heart rate significantly increased while systemic blood pressure and limb vascular resistances did not change significantly and aortic distensibility increased ( P < 0.05). Lower limb viscoelastic properties decreased at the third trimester ( P < 0.05) and venous tone increased from the first trimester ( P < 0.01), whereas little changes were observed at the site of upper limbs. The decrease in calf venous tone was significantly correlated with the increase in left ventricular diastolic diameter at the first ( P < 0.001) and the third trimester ( P < 0.05). The study provides evidence that during normal pregnancy, changes in the arterial and venous sides of the circulation occur independently of pressure alterations. The increase in venous tone, contributing to preload augmentation, and the decrease in aortic stiffness, reducing afterload, both optimize cardiac function until delivery.
d-[Ala2]endomorphin 2 and endomorphin 2 have nitric oxide-dependent vasodilator activity in rats
Authors: Champion Hunter C. , Kadowitz Philip J.
Published: December 2017

Endomorphin 1 and 2, newly discovered endogenous ligands for the μ-opioid receptor, have vasodepressor activity in the rat. In the present study, the mechanism mediating hemodynamic responses to endomorphin 2 and the endomorphin analog [D-Ala2]endomorphin 2 (TAPP) was investigated in the rat. Intravenous injections of TAPP and endomorphin 2 produced similar dose-dependent decreases in systemic arterial pressure and were ∼10-fold more potent than Met-enkephalin. TAPP and endomorphin 2 decreased heart rate, cardiac output, and total peripheral resistance. Under constant-flow conditions, injections of TAPP and endomorphin 2 into the perfusion circuit produced decreases in hindquarter perfusion pressure, and vasodilator responses were attenuated by the opioid receptor antagonist naloxone. Hindquarter vasodilator responses to TAPP and endomorphin 2 were attenuated by the nitric oxide synthase inhibitor N ω-nitro-l-arginine methyl ester (L-NAME; 50 mg/kg iv), whereas responses to the endothelium-independent vasodilators calcitonin gene-related peptide, diethylamine/nitric oxide, and isoproterenol were not changed. Hindquarter vasodilator responses to TAPP and endomorphin 2 were not altered by the cyclooxygenase inhibitor sodium meclofenamate, the ATP-dependent K+ channel antagonist U-37883A, or the presence of a time-delay coil in the perfusion circuit. These results indicate that vasodilator responses to TAPP and endomorphin 2 are mediated by the activation of a naloxone-sensitive opioid receptor and the release of nitric oxide from the endothelium within the hindquarter vascular bed of the rat.
Effective diffusion distance of nitric oxide in the microcirculation
Authors: Vaughn Mark W. , Kuo Lih , Liao James C.
Published: December 2017

Despite its well-documented importance, the mechanism for nitric oxide (NO) transport in vivo is still unclear. In particular, the effect of hemoglobin-NO interaction and the range of NO action have not been characterized in the microcirculation, where blood flow is optimally regulated. Using a mathematical model and experimental data on NO production and degradation rates, we investigated factors that determine the effective diffusion distance of NO in the microcirculation. This distance is defined as the distance within which NO concentration is greater than the equilibrium dissociation constant (0.25 μM) of soluble guanylyl cyclase, the target enzyme for NO action. We found that the size of the vessel is an important factor in determining the effective diffusion distance of NO. In ∼30- to 100-μm-ID microvessels the luminal NO concentrations and the abluminal effective diffusion distance are maximal. Furthermore, the model suggests that if the NO-erythrocyte reaction rate is as fast as the rate reported for the in vitro NO-hemoglobin reaction, the NO concentration in the vascular smooth muscle will be insufficient to stimulate smooth muscle guanylyl cyclase effectively. In addition, the existence of an erythrocyte-free layer near the vascular wall is important in determining the effective NO diffusion distance. These results suggest that 1) the range of NO action may exhibit significant spatial heterogeneity in vivo, depending on the size of the vessel and the local chemistry of NO degradation, 2) the NO binding/reaction constant with hemoglobin in the red blood cell may be much smaller than that with free hemoglobin, and 3) the microcirculation is the optimal site for NO to exert its regulatory function. Because NO exhibits vasodilatory function and antiatherogenic activity, the high NO concentration and its long effective range in the microcirculation may serve as intrinsic factors to prevent the development of systemic hypertension and atherosclerotic pathology in microvessels.
Regional expansion during myocardial ischemia predicts ventricular fibrillation and coronary reocclusion
Authors: Barrabés José A. , Garcia-Dorado David , González Miguel A. , Ruiz-Meana Marisol , Solares Julia , Puigfel Yolanda , Soler-Soler Jordi
Published: December 2017

Primary ventricular fibrillation (VF) complicating acute myocardial infarction is associated with occluded infarction-related arteries. The relationship between VF during ischemia and spontaneous coronary reocclusion was analyzed in 48 anesthetized pigs submitted to 48 min of coronary ligation and 6 h of reflow. Reocclusion was associated with ischemic VF (6 of 11 animals with VF but only 6 of 37 without it had reocclusion) but not with reperfusion arrhythmias, the size of the ischemic area, the magnitude of electrocardiogram changes or contractile dysfunction during ischemia, or the severity of intimal injury at the occlusion site. The increase in end-diastolic length in the ischemic region during coronary occlusion was associated with ischemic VF (15 min after occlusion, end-diastolic length was 116 ± 2 and 111 ± 1% of baseline in animals with or without presenting subsequent VF, respectively) and was retained by multiple logistic regression analysis as the only independent predictor of ischemic VF and reocclusion. Thus ischemic VF is strongly associated with an increased rate of spontaneous coronary reocclusion during subsequent reperfusion. Acute expansion of ischemic myocardium appears as a prominent determinant of both ischemic VF and reocclusion.
Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficiency
Authors: Suto Naoyuki , Mikuniya Atsushi , Okubo Tomoyuki , Hanada Hiroyuki , Shinozaki Nobuyo , Okumura Ken
Published: December 2017

Nitric oxide (NO) affects myocardial contractility and myocardial oxygen consumption (MV˙o 2) in vitro. In α-chloralose-anesthetized dogs instrumented for the measurements of left ventricular (LV) pressure, LV volume using a conductance catheter, coronary blood flow, and coronary venous oxygen saturation (S[Formula: see text]) using a fiber-optic catheter, LV end-systolic pressure-volume relationships (ESPVR) and the relationship between MV˙o 2 and LV pressure-volume area (PVA) were analyzed before and after intravenous infusions of the NO synthase inhibitor N G-monomethyl-l-arginine acetate (l-NMMA; 5 mg/kg, 8 dogs) and the NO substrate l-arginine (600 mg/kg, 7 dogs). l-NMMA increased the slope of the ESPVR ( E max) ( P < 0.05) without changing contractile efficiency indicated by the inverse of the slope of the MV˙o 2-PVA line.l-NMMA also increased unloaded MV˙o 2, indicated by the y-axis intercept of the MV˙o 2-PVA line ( P < 0.05). In contrast,l-arginine decreased E max( P < 0.05) while decreasing MV˙o 2( P < 0.05), and without changing contractile efficiency. The basal oxygen metabolism was not affected byl-NMMA andl-arginine. These data imply that endogenous NO spares MV˙o 2 by reducing oxygen use in excitation-contraction coupling and attenuates cardiac contractility without changing contractile efficiency.
Quantitative assessment of independent contributions of pericardium and septum to direct ventricular interaction
Authors: Baker A. E. , Dani R. , Smith E. R. , Tyberg J. V. , Belenkie I.
Published: December 2017

In the intact animal, it is difficult to discriminate between the independent effects of series and direct ventricular interaction (DI) or the individual contributions of the pericardium and septum to DI. Left ventricular (LV) venous return (LVVR) and right ventricular (RV) end-diastolic pressure (RVEDP) were varied independently in a right-heart bypass model. LV minor-axis diameters were measured, and the product of the two diameters was used as an index of LV volume (LVVI). At each RVEDP (0, 5, 10, and 15 mmHg), increased LVVR caused an increased LVVI. When RVEDP was increased, increased pump output was required to maintain a given LVVI. RV-to-LV pressure gain (ΔLVEDP/ΔRVEDP) reflects coupling and DI. With the pericardium closed, the gain was dependent on RVEDP; when RVEDP was increased from 0 to 5 mmHg, the gain was not statistically different from zero, indicating little or no DI. When RVEDP was increased from 10 to 15 mmHg, the gain was not statistically different from 1.0, indicating ∼1:1 coupling of the ventricles. Opening the pericardium reduced the gain, but significant interaction remained. When the septal contribution was accounted for, the remaining interaction was eliminated. In conclusion, DI substantially affects LVEDP-volume relations. Considerable increases in RV output may be required to counterbalance increased constraint to LV filling. With the pericardium closed, RV-to-LV coupling is minimal when RVEDP is low and increases to 1:1 coupling when RVEDP is high. Opening the pericardium reduces DI, but significant septum-mediated interaction remains.
Receptors in lateral hypothalamic area involved in insular cortex sympathetic responses
Authors: Butcher Kenneth S. , Cechetto David F.
Published: December 2017

Previous evidence has shown that sympathetic nerve responses to insular cortical (IC) stimulation are mediated by synapses within the lateral hypothalamic area (LHA) and ventrolateral medulla. The present study determined the receptor(s) involved at the synapse in the LHA associated with stimulation-evoked IC sympathetic responses. Twenty-seven male Wistar rats were instrumented for renal nerve activity, arterial pressure, and heart rate recording. The right IC was stimulated with a bipolar electrode (200–1,000 μA, 2 ms, 0.8 Hz) resulting in sympathetic nerve responses. Antagonists were then pressure injected into the ipsilateral LHA (300–500 nl). Kynurenate (250 mM) injections resulted in 51 ± 8% (range 0–100%) block of IC-stimulated sympathetic nerve responses. Similarly, the N-methyl-d-aspartic acid (NMDA)-receptor antagonistdl-2-amino-5-phosphonopentanoic acid (200 μM) resulted in an inhibition (82 ± 8%; range 51–100%) of IC-stimulated sympathetic responses. Injection of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (200 μM) had no effect on IC sympathetic responses. Injection of antagonists to GABA, acetylcholine, and adrenergic receptors was also without effect. No antagonist injections had any effects on baseline sympathetic nerve discharge, arterial pressure, or heart rate. These results suggest that the IC autonomic efferents projecting to the LHA utilize NMDA glutamatergic receptors.
Effects of abdominal CO2insufflation and changes of position on hepatic blood flow in anesthetized pigs
Authors: Klopfenstein Claude-Eric , Morel Denis R. , Clergue François , Pastor Catherine M.
Published: December 2017

During surgical laparoscopy, total hepatic blood flow (THBF) may be modified by CO2insufflation, changes of tilt, ventilation with high tidal volume, hypercapnia, and anesthesia, but little information is available on the THBF during the procedure. To investigate the changes of hepatic blood flow following the combination of abdominal CO2 insufflation and changes of tilt, we measured mean arterial pressure (MAP), cardiac output, portal vein blood flow (PVBF), and hepatic artery blood flow (HABF) in anesthetized and ventilated pigs. CO2 was insufflated in the abdomen [intra-abdominal pressure (IAP) ∼15 mmHg], and the hepatic blood flow was measured in various positions (horizontal, 10° and 20° head down, and 10° and 20° head up) before and during CO2 insufflation. CO2 insufflation in the horizontal position did not modify MAP, cardiac output, or PVBF but increased HABF. The head-up tilt decreased MAP, cardiac output, and both hepatic flows in the absence of pneumoperitoneum, but in the presence of abdominal CO2 only cardiac output and PVBF were decreased. The head-down tilt increased MAP and THBF in the absence of pneumoperitoneum, whereas no change was observed in the presence of abdominal CO2. The combination of CO2 insufflation and changes of tilt was not deleterious to hepatic perfusion. These results suggest that hepatic blood flow may be preserved during surgical laparoscopy if the tilt does not exceed 20° and if IAP after CO2 insufflation remains <15 mmHg.
Minimal Exposures Needed to Acclimatize Rats to Cold
Authors: Fregly Melvin J.
Published: December 2017

Page 394: Melvin J. Fregley, "Minimal Exposures Needed to Acclimatize Rats to Cold." In column 2, line 5, 10°C should read 18°C.
Biphasic Effects of Graded Doses of Pitressin
Authors: Friedman Sydney M. , Nakashima Miyoshi , Friedman Constance L.
Published: December 2017

Pitressin was administered subcutaneously at three dose levels (20 mu, 100 mu and 1000 mu) to rats made hypertensive with DCA. The excretion of Na, K and water was followed in each case during two consecutive collection periods of 4 hours each. These two periods were selected as corresponding to the pressor and depressor phases of Pitressin action, respectively. The selection of control and hypertensive animals was based on a preliminary blood pressure determination obtained by direct electromanometry from the femoral artery. At the low dose level of 20 mu a simple antidiuretic effect predominates and is apparent during the first collection period. At the intermediate dose level of 100 mu the simple antidiuresis is still evident during the first collection period. The second collection period is, however, marked by well defined Na retention with a lesser degree of water retention. The Na retention is not preceded by any antecedent Na loss. At the high dose level of 1000 mu the first period is distinguished as a phase of marked Na loss. In this phase the excretions of water and K are also increased but these appear to be only secondarily affected. The second period is again marked by well defined Na retention. These effects also occur in the normal animal given this dose of Pitressin. These experiments are taken to demonstrate that the biphasic effect of Pitressin on salt and water handling may be elicited in both the salt loaded and nonloaded rat. Attention is also drawn to the fact that there is a rough correlation between the effects of Pitressin on blood pressure and on salt and water metabolism.
Cholinesterase of Leucocytes
Authors: Philippu A. J.
Published: December 2017

By using the Michel's method specific cholinesterase was found in the leucocytes of man, dog and rabbit. The largest quantities were found in the leucocytes of rabbit, followed by that of man and lastly by that found in the dog. The pus cells do not contain cholinesterase.
Estimates of Extracellular Fluid Volume of Myocardium
Authors: Robertson William Van B. , Peyser Pincus
Published: December 2017

The extracellular fluid volume of the myocardium was determined in nephrectomized cats using sucrose as a reference material. This was allowed to equilibrate for one day before analysis. The chloride space, sodium space and an extracellular fluid volume based on the Conway-Boyle hypothesis were also determined. The sucrose space was smaller than, but bore no consistent relation to any of the other volumes. The sucrose space increased following an injection of epinephrine.
Action of Physostigmine (Eserine) Sulfate on Peripheral Nerve
Authors: Wright Ernest B.
Published: December 2017

The effect of eserine (physostigmine) sulfate on frog and rabbit nerve has been studied. Concentrations ranging from 0.005–0.08 m caused: a) a reversible block of conduction in from 50–120 minutes in frog nerve, 20–40 minutes in rabbit nerve; b) the threshold (rheobase) to rise to three times normal value in frog nerve and up to five times normal value in rabbit nerve; c) No change in the value of the excitability constant k; d) The refractory periods to be greatly lengthened. Absolute periods of 10 msec., relative periods of 50 msec were obtained; e) a 60% reduction in the conduction velocity; f) a slight depolarization of less than 2 mv.

A constant anodal voltage applied along 3 cm length of nerve partially relieves the eserine blocking action, cathodal voltage enhances the drug action.

Nerve conduction is blocked much quicker with continuous stimulation, due to the lengthening of the refractory period.

Following a brief interruption of continuous stimulation, a second or less, an action potential can be elicited again. This spike is almost identical with the action potential of a nonstimulated nerve subjected to eserine for the same period of time.

The blocking action cannot be due to acetylcholine accumulation by the anticholinesterase activity of eserine, but rather is due to the inactivation of the sodium mechanism by the drug. Eserinized nerve loses some sodium quickly, large amounts of potassium more slowly.
Cholesterolemic Rabbit Lipoproteins: Serum Lipoproteins of the Cholesterolemic Rabbit
Authors: Schumaker Verne Norman
Published: December 2017

The chemical composition of the low density lipoproteins (Sf 0 to 25. Sf 15 to 100, and Sf 20 to 400) has been investigated by isolating the molecules centrifugally and separating the various lipid constituents on silicic acid columns and analyzing the fractions so obtained by infrared spectrophotometry. Quantitative protein determinations were also made upon each group of lipoproteins. The molecules are shown to contain 40–60% cholesterol esters, 10–20% unesterified cholesterol, 10–20% phospholipid, and 3–30% protein, depending upon the sedimentation characteristics. The quantity of glyceride was usually less than 10% for all of the above mentioned groups of lipoproteins. The quantity of unesterified fatty acids was always less than 6%. Two of the four animals from which samples were withdrawn and analyzed had previously received daily heparin injections for a period of 10 weeks. The effects of heparin injections upon the ultracentrifugal patterns of a larger group of rabbits was also studied. No significant changes in the concentrations of the Sf 5 to 15, Sf 15 to 40, and Sf 40 to 100 species of lipoproteins were found which could be attributed to the heparin injections. The major peak, usually to be found in the Sf 5 to 15 region, did show a small but significant decrease in sedimentation coefficient in response to heparin injection. Serum from all of the animals receiving heparin did show a definite lipolytic activity in vitro.
Effect of Desoxycorticosterone on Distribution of Water and on Electrolyte Excretion During Enforced Hydration in the Dog and Rat
Authors: Cheek Donald B. , West Clark D.
Published: December 2017

Enforced hydration was produced in dogs and rats by simultaneous administration of Pitressin and of water loads totaling 15% or more of body weight in the dogs and 19% in the rats. The effect of desoxycorticosterone on the distribution of the added water was determined in the dogs by means of bromide and antipyrine spaces and chloride balance. In both species the modifying effect of DCA on the natriuresis and chloruresis of enforced hydration was studied. In the normal dog, the retained water load was distributed evenly throughout total body water. Addition of DCA to the water loading and Pitressin regimen resulted in a disproportionate expansion of the chloride space and in the production of edema. In the dog, DCA appears to exert a direct effect on the distribution of a water load which can be demonstrated in the absence of electrolyte retention. Edema was not noted with DCA administration to rats subjected to the water loading-Pitressin regimen, suggesting a species difference with respect to this action of the hormone. In both the dog and rat, the natriuresis and chloruresis associated with overexpansion of body fluid volume produced by water loading was neither inhibited nor enhanced by the administration of DCA. In certain of the dogs receiving DCA, the timing of the natriuretic and chloruretic response differed from that seen in normal animals but the deviations were neither consistent nor reproducible.
Arterial Blood Epinephrine Levels During Hemorrhagic Hypotension in Dogs
Authors: Watts D. T.
Published: December 2017

Eight dogs were hemorrhaged by 5-ml/kg increments at 6–10-minute intervals until the animals died after an average time of 73.5 minutes. Arterial blood epinephrine levels were quantitatively estimated using a rat uterus as a test object driven by an automatic stimulating device. Significant quantities of epinephrine were found in the blood after a hemorrhage of 15 ml/kg and reached a maximum of 37.2 ug/l., as the bitartrate, after a total hemorrhage of 40 ml/kg. The maximum eplnephrine levels observed during hemorrhagic hypotension were in the range of those found 2 minutes after the intravenous injection of 0.05–0.10 ml/kg epinephrine and could be expected to produce marked physiological effects.
Pressor Factor in Normal Human Urine
Authors: Handler Philip
Published: December 2017

In consequence of previous studies ( Am. J. Physiol. 166: 528, 1951), a hitherto unrecognized ‘pressor’ factor has been sought and found in the urine of normal human beings, rats and dogs. The activity of this factor was demonstrated in partially nephrectomized rats maintained in the normotensive state by feeding a low protein, normal salt diet and in normotensive, bilaterally nephrectomized rats. Excretion of this material is dependent upon adequate protein nutrition, adrenocortical and renal function. Data are presented which are consistent with the hypothesis that renal hypertension may, at least in part, be a consequence of failure to excrete this new factor. Some chemical properties of the active agent in urine and procedure for its concentration and partial purification are described.
Glucose Tolerance in Relation to Obesity and Food Intake
Authors: Bloom Roy A. , Fenton Paul F.
Published: December 2017

Glucose tolerance tests were carried out on two strains of mice, one highly susceptible, the other only moderately susceptible to nutritional obesity. With glucose administered on the basis of body weight or fat-free weight, the highly susceptible strain disposed more rapidly of the administered glucose than did the moderately susceptible strain. Fasting blood sugar levels in both strains were found to increase with the logarithm of body weight. These observations are not readily explained in terms of the ‘glucostatic’ theory of the control of food intake.
Limitations of the Use of Indicators for Determination of Acidity in the Gastric Lumina
Authors: White Thomas D. , Swigart Richard H. , Rehm Warren S.
Published: December 2017

Hydrogen ion indicators were injected intravenously in dogs with an actively secreting exteriorized gastric flap. The flap was frozen, sectioned and observed microscopically at –18°C. Only neutral red and Prussian blue were seen microscopically in the lumina and then only when the secretory rate was depressed to essentially zero. Control experiments revealed that the indicators, when in true solution and in concentrations equal to the maximum obtained in gastric juice, cannot be seen microscopically when examined through depths comparable to the diameters of the lumina. They can be seen when precipitated or adsorbed to particulate matter. The implications of these findings with respect to the problem of the pH of the lumina are discussed.
Combined Action of Potassium and Histamine on Mice and Guinea Pigs
Authors: Zwemer R. L. , Martorano J. J. , Truscoe R.
Published: December 2017

When body cells are damaged by force, burns, lack of oxygen or decreased blood supply, they release substances which in large enough quantities induce shock often resulting in death. Two of these substances have been identified as histamine and potassium. Either of these when injected into normal intact animals can induce shock and death. The lethal dose curves for each of the two agents when given in solution intraperitoneally to mice and to guinea pigs were determined. Potassium toxicity was quite comparable in both species, but histamine resistance in mice was more than 100 times that of guinea pigs. When both histamine and potassium are combined in a single injection the mortality rate goes up. The addition of a small amount of one will increase the toxicity of a known amount of the other to a point much greater than the sum of each given separately. A variety of combinations of both were tested in about 1600 mice and about 500 guinea pigs. The results suggest that in future studies of traumatic and anaphylactic shock, the simultaneous blood levels of both substances should be determined. Further experiments gave evidence that enhancement of toxicity diminished when the two agents were injected separately and that a plasma potassium rise did not follow histamine injection in all species. Glutathione which has been shown to protect against potassium, also had a protective action in mice against the histamine-potassium combination. An antihistaminic (Chlor-Trimeton) which protected guinea pigs against histamine alone did not protect them or mice against the combination.
Solar and Lunar Rhythmicity in the Rat in ‘Constant Conditions’ and the Mechanism of Physiological Time Measurement
Authors: Brown F. A. , Shriner J. , Ralph C. L.
Published: December 2017

The spontaneous activity of one male rat under constant conditions was recorded for 120 consecutive days. During the first 70 days in constant illumination of 1 fc the 12-hour daily period of activity occurred regularly about 1 1/4 hours later each day, with the period scanning the solar day about four times during the 70-day period. During the succeeding 25-day period in darkness the daily cycles averaged exactly 24 hours with the time of day of activity, that of the last day in constant light. This was followed by 8 days in constant light followed by 18 days in constant darkness with completely comparable results. The daily running cycle randomized relative to the hours of the solar day, exhibited a daily cycle of amount of activity at each hour of the solar day, and randomizing both the daily activity period and the solar-day basic cycle revealed a cycle of lunar-day length, with minimum of lunar zenith and a maximum at nadir. There were also strong suggestions in the mean daily activities of 27-day and synodic monthly cycles.
Excretion of Na22 and K42 by the Perfused Bullfrog Kidney and the Effect of Some Poisons
Authors: Hoshiko T. , Swanson Robert E. , Visscher M. B.
Published: December 2017

Perfusion of the bullfrog (Rana catesbiana) kidney with Na22 and K42 via the renal portal system results in a urine with a high content of both isotopes. These isotopes must enter the urine by passing though the wall of the renal tubule or the collecting ducts since glomerular filtration of the portal fluid was negligible. The descending order of equilibration of these radioisotopes and of D2O is in general from D2O to K42 to Na22. Calculation of the unidirectional-reabsorptive and excretory movements across the tubules suggest that the depression in net reabsorption of sodium and potassium by azide, cyanide, and dinitrophenol is due more to a decrease in the unidirectional reabsorptive movement than to an increase in the excretory movement. The unidirectional excretory movements of sodium and of potassium show no consistent trend during the control periods and continue in the same fashion during the perfusion of the poisons. It is inferred that the excretory movements of sodium and potassium are of a passive nature, or that they depend upon a type of energetic process different from that involved in the reabsorptive movement.