bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional atrial distensibility
Authors: Hoit B. D. , Walsh R. A.
Published: December 2017

We studied 12 open-chest dogs to determine whether there are regional differences in left atrial distensibility. Sonomicrometer crystal pairs were used to measure the anteroposterior diameters of the left atrial body and appendage simultaneously over a wide range of intracardiac pressures and volumes obtained by intravenous saline infusion. Left atrial pressure-natural strain data for the body and appendage were fitted to an exponential function. The mean coefficient of the left atrial monoexponential pressure-strain relationship was greater for the body than appendage (3.1 +/- 1.1 vs. 1.9 +/- 0.7 mmHg, P less than 0.01). The Y-intercepts were not significantly different (5.2 +/- 1.7 vs 4.9 +/- 1.8 mmHg). The maximum minus minimum left atrial dimension, an index of the reservoir function of the atrium, increased with volume infusion in both the body and appendage and was significantly greater in the appendage than body at each level of left atrial pressure. Similarly, atrial systolic shortening fraction increased with volume infusion, and regional shortening was greater in the appendage than the body at each level of left atrial pressure. We conclude that regional differences in atrial distensibility exist in vivo and may play an important role in modulating systolic and diastolic function of the left atrium.
Sarcolemmal calcium transport in congestive heart failure due to myocardial infarction in rats
Authors: Dixon I. M. , Hata T. , Dhalla N. S.
Published: December 2017

Because Na(+)-Ca2+ exchange and Ca2+ pump are thought to play a role in sarcolemmal Ca2+ movements, we examined the Na(+)-dependent Ca(2+)-uptake and ATP-dependent Ca(2+)-uptake activities in failing heart after myocardial infarction in rats. The left coronary artery was ligated, and the viable left ventricle was used 4, 8, and 16 wk later; sham-operated animals served as controls. Increased left ventricular diastolic pressure and decreased positive and negative change in pressure over time were observed in experimental animals at 4, 8, and 16 wk; these changes were associated with accumulation of fluid in the abdominal cavity. The sarcolemmal Na(+)-dependent Ca2+ uptake was depressed in 4-, 8-, and 16-wk experimental hearts. The decrease in sarcolemmal Na(+)-dependent Ca2+ uptake in failing hearts was seen when the activity was assayed either as a function of time or Ca2+ concentration; a depression of maximal velocity without any change in activity constant for Ca2+ was observed. No alteration in the Ca2+ pump (ATP-dependent Ca2+ accumulation and Ca(2+)-stimulated adenosinetriphosphatase) activities was evident in the 4-, 8-, and 16-wk experimental groups. These data suggest that changes in the Na(+)-dependent Ca2+ handling by the sarcolemmal membrane may be associated with contractile abnormalities in this model of congestive heart failure.
Phasic and 24-h blood pressure control by endothelium-derived relaxing factor in conscious dogs
Authors: Persson P. B. , Baumann J. E. , Ehmke H. , Nafz B. , Wittmann U. , Kirchheim H. R.
Published: December 2017

The effects of blocking endothelium-derived relaxing factor (EDRF) on 24-h blood pressure and heart rate (HR) were examined in six conscious freely moving foxhounds. The hypothesis tested was that shear stress-dependent EDRF release acts as a physiological blood pressure buffer. Telemetry recordings were obtained before and after the administration of the false substrate for EDRF synthesis NG-nitro-L-arginine (L-NNA, 16.5 +/- 2 mg/kg body wt iv). In response to L-NNA, mean arterial blood pressure (MAP) increased from 116 +/- 5 to 134 +/- 5 mmHg (P less than 0.01) and HR decreased from 97 +/- 6 to 68 +/- 3 beats/min over the entire 24-h period (P less than 0.01). The overall variability of MAP (as indicated by SD of frequency distribution) increased modestly from 9.5 +/- 0.4 to 11.7 +/- 1.1 mmHg (P less than 0.05). A sequential spectral analysis of blood pressure showed a 2.1-fold increase of power in the frequency range of 0.01-0.5 Hz (P less than 0.05) after L-NNA was given. In conclusion, blockade of EDRF led to a sustained hypertension throughout the whole 24-h recordings. Furthermore, EDRF acted as a physiological blood pressure buffer in the frequency range below 0.5 Hz.
Pressure-maximal coronary flow relationship in regionally stunned porcine myocardium
Authors: Duncker D. J. , McFalls E. O. , Krams R. , Verdouw P. D.
Published: December 2017

In view of variable results on maximal coronary blood flow in stunned myocardium, we studied the pressure-maximal coronary flow (PMCF) relationship in stunned myocardium in 12 anesthetized swine by using intracoronary adenosine (20 micrograms/kg). Subendocardial systolic segment shortening (SS) measured with sonomicrometry was 19 +/- 5% (means +/- SD) at baseline and 7 +/- 6% (P less than 0.01) at 30 min of reperfusion after 15 min of low-flow ischemia, at which time postsystolic shortening was present. Myocardial stunning increased the slope of the PMCF regression line (alpha PMCF) from 3.34 +/- 1.03 to 3.89 +/- 1.33 ml.min-1.mmHg-1 (P less than 0.01). Atrial pacing at 40 beats/min above spontaneous heart rate (n = 6) further reduced subendocardial SS to 6 +/- 6% (P less than 0.05). Dobutamine (4 micrograms.kg-1.min-1; n = 6) increased subendocardial SS to 13 +/- 5% (P less than 0.05) and abolished postsystolic shortening. Both interventions left alpha PMCF unchanged. In conclusion, myocardial stunning was associated with an increase in alpha PMCF that most likely resulted from the decreased contractile function. The absence of an effect of dobutamine may be due to its predominant action on diastolic function.
Reduced contractile sensitivity and vasopressin receptor affinity in DOCA-salt hypertension
Authors: Bockman C. S. , Jeffries W. B. , Pettinger W. A. , Abel P. W.
Published: December 2017

The affinity of vascular vasopressin receptors was studied to determine its role in altered vascular contractile sensitivity in deoxycorticosterone acetate (DOCA)-salt hypertension. Ring segments of rat mesenteric arteries were used to study vascular vasopressin receptors. Male Wistar rats were given subcutaneous injections of DOCA and 1% NaCl in the drinking water. Mesenteric arteries from hypertensive rats had a reduced contractile sensitivity to arginine vasopressin (AVP) and lysine vasopressin (LVP). The order of potency of vasopressin receptor agonists (AVP greater than LVP greater than oxytocin) was the same in arteries from hypertensive compared with normotensive animals. The affinity of the vasopressin receptor antagonist [deamino-Pen1,O-Me-Tyr2,Arg8] vasopressin, and the affinities of the vasopressin receptor agonists AVP and LVP were not altered during developing DOCA-salt hypertension. There was no change in contractile sensitivity to norepinephrine and KCl in arteries from hypertensive rats. The reduced vasopressin contractile sensitivity is not due to a change in vasopressin receptor affinity but may be a compensatory response to elevated blood pressure. These data suggest that increased vascular sensitivity does not contribute to elevated blood pressure during the developing stage of DOCA-salt hypertension.
Cardiomyocyte proliferation in mice expressing alpha-cardiac myosin heavy chain-SV40 T-antigen transgenes
Authors: Katz E. B. , Steinhelper M. E. , Delcarpio J. B. , Daud A. I. , Claycomb W. C. , Field L. J.
Published: December 2017

To determine the proliferative potential of adult ventricular cardiomyocytes, we have generated transgenic mice that express the SV40 large T-antigen oncogene in the heart. A fusion gene comprised of the rat alpha-cardiac myosin heavy chain promoter and the SV40 early region was used to target oncogene expression to the myocardium. Expression of SV40 large T-antigen was observed in both atrial and ventricular cardiomyocytes in adult transgenic animals. T-antigen expression was associated with hyperplasia in the targeted cells. Immunohistological analysis indicated that the proliferating cells continued to express sarcomeric myosin. Electron microscopic examination demonstrated that cardiomyocytes in various stages of the cell cycle retained ultrastructural characteristics typical of mitotic cardiac muscle cells in vivo. Cardiomyocytes isolated from transgenic tumors were able to proliferate in culture and retained a differentiated phenotype, as evidenced by spontaneous contractile activity. Preliminary studies indicate that these cells can undergo a limited number of passages while retaining this differentiated phenotype. These studies demonstrate that both ventricular and atrial cardiomyocytes from transgenic mice proliferate in response to targeted T-antigen expression.
Modulation of NO and endothelin by chronic increases in blood flow in canine femoral arteries
Authors: Miller V. M. , Burnett J. C.
Published: December 2017

Experiments were designed to determine whether chronic increases in arterial blood flow alter production of or response to nitric oxide and endothelin. Canine femoral arteries proximal to an arteriovenous fistula- and from the contralateral sham-operated blood vessels were removed, cut into rings, and suspended for measurement of isometric force in organ chambers. The remainder of the artery was homogenized for measurement of endothelin content by radioimmunoassay. NG-monomethyl-L-arginine (10(-4) M) caused concentration-dependent increases in tension only in fistula-operated arteries. Endothelium-dependent relaxations to acetylcholine and BHT-920 were greater in fistula- compared with sham-operated arteries. These differences were reduced by the arginine analogue. Pertussis toxin (100 ng/ml) inhibited relaxations to acetylcholine only in fistula-operated arteries and to BHT-920 only in sham-operated arteries. Contractions to endothelin-1 were greater in fistula- compared with sham-operated arteries. These results suggest that chronic increases in blood flow enhance the tonic and receptor-stimulated production of nitric oxide and its release by receptors coupled to pertussis toxin-sensitive guanine nucleotide regulatory proteins. Furthermore, chronic increases in blood flow may either inhibit the production of endothelin or promote its depletion from endothelial cells while simultaneously increasing the sensitivity of the smooth muscle to its contractile effects.
Dynorphin, naloxone, and overflow of norepinephrine during cardiac nerve stimulation in dogs
Authors: Gu H. , Barron B. A. , Gaugl J. F. , Caffrey J. L.
Published: December 2017

The effects of dynorphin-(1-9) and naloxone on norepinephrine (NE) overflow and myocardial contractility were determined during left cardiac nerve stimulation in the anesthetized dog. Stimulation-induced increases in NE overflow from the left ventricle were monitored during control conditions, during infusion of dynorphin-(1-9), during dynorphin plus naloxone, and after naloxone alone. Four electrical stimulations were applied for 1 min at 20-min intervals. Repeated left cardiac nerve stimulations (control group) reduced stimulated NE overflow 50-60% by 1 h. If stimulations were only conducted at 0 and 1 h, the decline in NE overflow was not observed. Intracoronary dynorphin (2 nmol.min-1.kg-1, 20 min) lowered the stimulation-induced increase in NE overflow further and reduced first time derivative of left ventricular pressure (dP/dt) and myocardial O2 consumption responses. Naloxone (100 micrograms/kg) prevented all of the dynorphin-mediated effects. When given alone, naloxone increased both NE overflow and left ventricular dP/dt during stimulation and prevented or significantly delayed the gradual decline in overflow observed in stimulated controls. A postjunctional effect of dynorphin was evaluated by comparing contractile responses to the intracoronary infusion of NE before and during dynorphin. Dynorphin did not alter contractile function at rest or during NE infusion. In summary, dynorphin-(1-9) depresses nerve stimulation-induced, cardiac NE overflow, and myocardial contractility in a naloxone-reversible fashion. Alone, naloxone appears to regulate stimulated NE overflow through a qualitatively different mechanism. Endogenous opioids may normally moderate myocardial function during cardiac nerve stimulation by regulating junctional NE concentrations through a combination of effects on NE release and/or its subsequent reuptake.
Chemoreceptor responsiveness in fetal sheep
Authors: Boekkooi P. F. , Baan J. , Teitel D. , Rudolph A. M.
Published: December 2017

Fetal peripheral chemoreceptor responses to arterial O2 saturation and changes in PCO2 have not yet been quantitated. In 24 late-term chronically instrumented fetal sheep, we measured the heart rate response to acute hypoxemia induced by uterine arterial occlusion at various resting O2 saturations (25-86%) and at induced reductions and increases in baseline O2 saturation. As an index of fetal chemoreceptor responsiveness we calculated the fall in heart rate divided by the fall in arterial O2 saturation (delta HR/delta sat). delta HR/delta sat was inversely related to resting O2 saturation at levels less than 65%, but greater than 65% this relationship was no longer present. However, an induced increase in baseline O2 saturation from 66 +/- 12 to 76 +/- 10% decreased delta HR/delta sat from 2.6 +/- 1.6 to 1.8 +/- 1.0, indicating that when resting O2 saturation is greater than 65% there may be adaptation of peripheral chemoreceptors. Below 65%, an induced decrease in baseline O2 saturation increased delta HR/delta sat (to 3.8 +/- 1.8), suggesting a lack of adaptation to lower O2 saturations. Concomitant changes in PCO2, or differences in baseline PCO2, did not affect delta HR/delta sat during uterine arterial occlusion, which suggests that there is no interdependence between O2 and CO2 as a stimulus for the fetal peripheral chemoreceptor. However, acute hypercapnia (n = 24 in 8 fetal sheep) induced bradycardia. Furthermore, this bradycardia was related to the increase in fetal arterial PCO2. We conclude that the fetal peripheral chemoreceptor is sensitive to hypoxemia and hypercapnia and that the hypoxemia response is accentuated with decreases in initial O2 saturation.
Comparable sensitivity of flow contraction and relaxation to Na reduction may reflect flow-sensor characteristics
Authors: Bevan J. A. , Joyce E. H.
Published: December 2017

Physiological salt solution infused through the lumen of a resistance branch of the rabbit central ear artery mounted in an isometric myograph causes both contraction and relaxation. The effect of reductions in extracellular Na up to 26 mM (20% of the NaCl content of the physiological saline solution) on these flow-induced changes in wall force and on the contraction to norepinephrine (10(-6) M) and relaxation to acetylcholine (10(-8) to 3 x 10(-6) M) and papaverine (10(-6) to 3 x 10(-5) M) has been studied. Na in the physiological saline solution was reduced by substitution of NaCl with sucrose or N-methyl-D-glucamine. The effect of either of these substitutions was to reduce both responses, contraction and relaxation, to the same extent. This sensitivity is such that physiological changes in blood Na concentration would be expected to influence flow-induced changes in wall tone. Responses to norepinephrine, acetylcholine, and papaverine were not significantly changed by these alterations in Na. It is argued that since reduction of extracellular Na diminished both contraction and relaxation to a similar extent, leading to relaxation and contraction respectively, that this effect probably occurs at a site common to both flow responses. Because both flow effects occur after endothelium removal and the extracellular matrix binds a large proportion of the Na in the blood vessel wall, this may represent the location of a flow-sensitive mechanism.
Quantitation of specific binding of orosomucoid to cultured microvascular endothelium: role in capillary permeability
Authors: Schnitzer J. E. , Pinney E.
Published: December 2017

Orosomucoid (also known as alpha 1-acid glycoprotein) is a highly sialylated, polyanionic serum glycoprotein. Its presence in vascular perfusates alters microvascular permeability, presumably by binding to the endothelial glycocalyx, but the rest of its functions remains unknown. In this study, we assess the binding of bovine serum orosomucoid (BSO) to the surface of bovine pulmonary microvascular endothelial cells (BLMVEC) in culture at 4 degrees C. The binding of radioiodinated BSO (125I-BSO) reached equilibrium after 10 min of incubation, was not calcium dependent, and was reversible by greater than 80% in 30 min. The binding of 125I-BSO was competed with unlabeled BSO but not by transferrin, immunoglobulin, gelatin, ovalbumin, mannan, fucoidan, mucin, or asialomucin. In addition, binding was not affected by the presence of galactose, glucose, fucose, mannose, N-acetyl-D-galactosamine, or N-acetyl-D-glucosamine. This binding behavior is not consistent with carbohydrate recognition by lectin-like molecules such as the asialoglycoprotein receptor. Scatchard analysis of the BSO binding to BLMVEC produced a concave-upward shaped curve, which revealed a higher affinity binding component with an apparent equilibrium affinity constant (Kd) of 8.6 nM and a maximum receptor number of 40,000/cell and revealed a moderate affinity component with a Kd of 9.1 microM with a maximum binding of 10(7) binding sites per cell. Other blood vessel-associated cells clearly bound less BSO with a lower binding affinity than the BLMVEC monolayers. From the binding data, we estimated the total increase in the negative charge of the glycocalyx with orosomucoid binding to be approximately 17 meq/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Cerebral blood flow, blood volume, and brain tissue hematocrit during isovolemic hemodilution with hetastarch in rats
Authors: Todd M. M. , Weeks J. B. , Warner D. S.
Published: December 2017

The influence of isovolemic hemodilution with 6% hetastarch [hematocrits (Hct) ranging from 43 to 20%] on cerebral blood flow (CBF), cerebral red blood cell and plasma volumes, total cerebral blood volume (CBV), and cerebral Hct was examined in normothermic, normocarbic, halothane-anesthetized Sprague-Dawley rats. CBF was measured via the indicator-fractionation method ([3H]nicotine), red blood cell volume was measured using 99mTc-labeled red blood cells, while plasma volume was measured using [14C]dextran. Brain tissue was fixed in situ by microwave irradiation. All data plots (e.g., CBF vs. Hct) were fitted by linear regression methods. Hemodilution was associated with a progressive increase in forebrain CBF (from a fitted value of 78 ml.100 g-1.min-1 at Hct = 43%, to 171 ml.100 g-1.min-1 at 20%). Cerebral plasma volume also rose, while red blood cell volume decreased. Total CBV (i.e., the sum of red blood cell and plasma volumes) increased in parallel with CBF (from 2.51 ml/100 g at Hct = 43 to 4.94 ml/100 g at Hct = 20%). This increase is larger than can be explained by a simple increase in the diameter of arterial/arteriolar resistance vessels and may be due to either capillary recruitment or to an increase in the volume of postarteriolar structures. Calculated cerebral tissue hematocrit decreased. The magnitude of this decrease was larger than the reduction in arterial Hct; the ratio of cerebral to arterial Hct decreased from 0.780 at an arterial Hct equaling 43% to 0.458 at Hct equaling 20%.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of endothelium-derived nitric oxide in myocardial reactive hyperemia
Authors: Yamabe H. , Okumura K. , Ishizaka H. , Tsuchiya T. , Yasue H.
Published: December 2017

In pentobarbital sodium-anesthetized dogs we investigated the role of the endothelium-derived nitric oxide and adenosine in the regulation of the coronary blood flow during myocardial reactive hyperemia. Repayments of flow debt after 10-, 20- and 60-s occlusion of the left circumflex coronary artery (LCX) were measured before and after infusion of NG-monomethyl-L-arginine (L-NMMA; n = 15), 8-phenyltheophylline (8-PT; n = 5), and both L-NMMA and 8-PT (n = 5) into the LCX. Infusion of L-NMMA (2 mumol/min, for 20 min) reduced repayments of flow debt after 10-, 20-, and 60-s LCX occlusion by 30 +/- 4 (P less than 0.01), 34 +/- 3 (P less than 0.01), and 14 +/- 3% (P less than 0.01), respectively. Infusion of 8-PT (0.75 mumol/min for 15 min) also reduced these repayments of flow debt by 31 +/- 7 (P less than 0.01), 30 +/- 7 (P less than 0.01), and 34 +/- 6% (P less than 0.01), respectively. Simultaneous infusion of L-NMMA and 8-PT significantly attenuated the peak reactive flow rate and reduced repayment of flow debt after 20-s LCX occlusion by 57 +/- 1% (P less than 0.001), and this reduction in repayment of flow debt was significantly greater than each of those by the individual administration of L-NMMA and 8-PT (both P less than 0.01). The suppressive effect of L-NMMA on repayment of flow debt after 20-s LCX occlusion was quickly reversed by the infusion of L-arginine (3 mg/min for 10 min; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Free radicals mediate endothelial cell dysfunction caused by elevated glucose
Authors: Tesfamariam B. , Cohen R. A.
Published: December 2017

Impaired endothelium-dependent relaxation occurs in diabetic rabbit aorta and normal aorta exposed to elevated concentrations of glucose and is prevented by cyclooxygenase inhibitors. The role of free radicals in the endothelial cell impairment was examined with free radical scavengers and in aortas from rabbits fed with probucol (1% wt/wt, a lipid-soluble antioxidant). Rings of aorta suspended for measurement of isometric tension were incubated for 6 h in control (5.5 mM) or elevated (44 mM) glucose. Impairment of endothelium-dependent relaxation to acetylcholine caused by exposure to elevated glucose was prevented by superoxide dismutase, catalase, deferoxamine, or allopurinol and did not occur in aortas from probucol-fed rabbits. Similarly, impairment of acetylcholine relaxations in aortas from alloxan-induced diabetic rabbits was restored to normal by superoxide dismutase. Oxygen-derived free radicals generated by xanthine oxidase also caused impaired acetylcholine relaxations. Exposure of aortic segments to elevated glucose or to xanthine oxidase caused a significant increase in release of immunoreactive prostanoids. These data indicate that the endothelial cell dysfunction caused by elevated glucose is mediated by free radicals that are likely generated through the increased cyclooxygenase catalysis occurring in the endothelium. Treatment with antioxidants protects against impaired endothelium-dependent relaxations caused by elevated glucose.
Dynamic response of coronary regulation to heart rate and perfusion changes in dogs
Authors: Dankelman J. , Vergroesen I. , Han Y. , Spaan J. A.
Published: December 2017

The rate of change of coronary adjustment in the anesthetized dog to a step change in heart rate (HR) and in perfusion was analyzed. The left main coronary artery was perfused either at constant pressure (CP) or at constant flow (CF). Coronary arterial pressure and flow were continuously measured and averaged per beat, after which their ratio, being an index of coronary resistance in steady state, was calculated. The rate of change of pressure-to-flow ratio was quantified by t50, the time required to establish half of the completed response. The t50 values for the dilating responses at CP were 5.5 +/- 0.4 (SE) s for an increase in HR and 5.5 +/- 0.1 s for a decrease in perfusion. At CF these values were 9.3 +/- 0.9 and 9.7 +/- 1.6 s, respectively. The t50 values for the constricting responses with CP were 6.6 +/- 0.5 s for a decrease in HR and 6.2 +/- 0.2 s for an increase in perfusion. At CF these values were 12.2 +/- 1.5 and 10.8 +/- 2.2 s. The responses in the dog are faster than in the goat. Furthermore, the directional sensitivity in responses with perfusion changes, observed earlier in goats, is normally absent in dogs.
Difference in effect of atrial natriuretic peptide on cGMP in aortic and coronary smooth muscle cells
Authors: Newman W. H. , Kato J. , Becker B. F. , Currie M. G.
Published: December 2017

Blood vessels show a heterogeneous response to the atrial natriuretic peptide (ANP). In our experiments thoracic aorta from the guinea pig relaxed in response to atriopeptin III (AP; rat ANP-103–126) and to sodium nitroprusside (SNP). In contrast, in perfused guinea pig hearts, AP III produced no change in coronary flow, while SNP increased flow. In smooth muscle cells cultured from the coronary system (CASM) and from the thoracic aorta (TASM), we compared receptor binding and the effects on guanosine 3',5'-cyclic monophosphate (cGMP) production of AP III. AP III bound specifically with equal affinity and with equivalent numbers of binding sites in both cell types. AP III produced a dose-dependent increase in cGMP in TASM (50% effective concentration approximately 3 nM) with a maximum 11-fold increase over basal at 1 microM AP III. In contrast, in CASM, AP III failed to increase cGMP. Nitroprusside increased cGMP in both cell types. Autoradiograms of 125I-labeled AP III linked to cell membranes showed bands at 70 kDa (ANP-C receptor) in both cell types. A second band at 140 kDa (ANP-B receptor) was only seen in TASM. These results suggest that smooth muscle cells of coronary resistance vessels of the guinea pig do not express the particulate guanylyl cyclase that is activated by ANP.
Limited left ventricular inotropic response to exercise in early phase of pressure overload in dogs
Authors: Su J. B. , Hittinger L. , Le Franc P. , Crozatier B.
Published: December 2017

To study the mechanisms of myocardial adaptation to increased stress in the early phase of left ventricular (LV) pressure overload, 12 dogs were instrumented with LV micromanometer, LV dimensional ultrasonic crystals, aortic catheter, and aortic occluder cuff. After recovery, animals performed graded exercise with acute aortic stenosis (AS) or sustained (24 h) aortic stenosis (SS). At baseline, LV functional parameters with SS were not different from those obtained with AS. LV peak pressure increased similarly during exercise with AS or SS, but LV peak dP/dt was lower with SS than with AS (peak values, 6,292 +/- 525 vs. 7,570 +/- 432 mmHg/s; P < 0.05). LV end-diastolic pressure increased from 9.7 +/- 1.7 to 21.4 +/- 3.3 mmHg (P < 0.05) during exercise with SS, but was unchanged with AS. The decrease of the time constant of isovolumic pressure fall during exercise was significantly smaller after SS than during AS (P < 0.05). In addition, the percentage of subendocardial wall thickening did not increase during exercise with SS (30.3 +/- 3.6%), while it increased significantly with AS (from 29.3 +/- 3.3 to 39.4 +/- 4.5%; P < 0.01). Plasma catecholamine levels were similar at baseline and increased to similar levels during exercise with AS and SS. In the early phase of pressure overload, we conclude that exercise capacity is maintained but that the LV inotropic response to exercise is modified with an altered relaxation process and a lesser utilization of subendocardial inotropic reserve.
Correlation of structure and viscoelastic properties in the pericardia of four mammalian species
Authors: Naimark W. A. , Lee J. M. , Limeback H. , Cheung D. T.
Published: December 2017

Although the pericardium is recognized as having important contributions to ventricular function, the relationship between its functional role and structural composition remains poorly understood. Conflicting evidence from low strain rate experiments has shown that differences exist between the mechanical properties of canine, human, and bovine pericardium but with no structural explanation for these differences. This paper examines the pericardia of calves, dogs, pigs, and sheep using a structural/mechanical approach with techniques novel to the pericardial literature. High strain rate mechanical testing for stress-strain response, stress relaxation, and forced vibration response has shown the pericardium to be much more viscoelastic than previously believed under large deformations, but to be quite elastic in small vibrations. The thinner canine and porcine pericardia were found to be significantly stiffer than the thicker bovine and ovine tissues, but equivalently viscoelastic. Biochemical analysis shows these thinner tissues to have significantly higher levels of type III collagen combined with a higher degree of cross-linking. This is the first structural explanation for differences in mechanical properties between the pericardia of different species.
Role of adenosine for reactive hyperemia in normal and stunned porcine myocardium
Authors: Kirkeboen K. A. , Aksnes G. , Lande K. , Ilebekk A.
Published: December 2017

The role of adenosine for reactive hyperemia in normal and stunned myocardium was examined in 16 open-chest barbiturate-anesthetized pigs. Interstitial adenosine concentration was reduced or enhanced by intracoronary infusion of adenosine deaminase or the nucleoside transport inhibitor R 75231, respectively. In normal myocardium, adenosine deaminase reduced volume of hyperemia (Doppler flowmetry) after a 30-s left anterior descending coronary artery (LAD) occlusion by 20% (6-34%; P < 0.05), whereas R 75231 increased volume of hyperemia by 15% (2-24%; P < 0.05). Adenosine deaminase reduced volume of hyperemia after a 2-min LAD occlusion by 27% (13-37%; P < 0.001), whereas R 75231 increased volume of hyperemia by 66% (53-159%; P < 0.001). Adenosine deaminase and R 75231 did not affect maximal hyperemia. Volume of hyperemia after a 2-min LAD occlusion was reduced in stunned myocardium (%systolic segment length shortening reduced by approximately 45%, ultrasonic technique) but not further altered by either adenosine deaminase or R 75231. These findings show that adenosine contributes to reactive hyperemia after 30-120 s of ischemia in normal myocardium and indicate that the reduced reactive hyperemia in stunned myocardium is due to reduced accumulation of adenosine during ischemia.
Stretch-induced increases in intracellular calcium of isolated vascular smooth muscle cells
Authors: Davis M. J. , Meininger G. A. , Zawieja D. C.
Published: December 2017

Vascular smooth muscle responds to stretch with an increase in active force development. To investigate the role of Ca2+ in this response, we used the fluorescent dye fura-2 to quantitate changes in cytosolic Ca2+ in single, vascular smooth muscle cells during rapid stretch. Cells were enzymatically dispersed from pig coronary arteries, loaded with fura-2/AM, and studied using a digital-imaging microscope. Stretch of individual cells was accomplished by attachment with suction to two patch-type micropipettes to apply force to the ends of the cell. Stretch induced the release of Ca2+ from intracellular stores as well Ca2+ influx across the plasma membrane. In physiological saline solution containing 1.5 mM Ca2+, intracellular calcium increased with cell stretch in a sigmoidal fashion. This relationship was shifted upward in 10 mM Ca2+ bath solution and abolished after several minutes in Ca(2+)-free solution. The dihydropyridine Ca2+ channel blocker nifedipine, in doses sufficient to completely block inward Ca2+ current, produced only a partial block of the sustained stretch-induced intracellular Ca2+ response. It is concluded that in isolated pig coronary arterial smooth muscle cells, stretch-induced Ca2+ influx occurs in part via a nifedipine-resistant pathway, which may be a stretch-activated cation channel.
Regulatory effect of thromboxane A2 on proliferation of vascular smooth muscle cells from rats
Authors: Nagata T. , Uehara Y. , Numabe A. , Ishimitsu T. , Hirawa N. , Ikeda T. , Matsuoka H. , Sugimoto T.
Published: December 2017

We investigated the regulatory effects of the vasoconstrictor thromboxane A2 on the proliferation of vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats using 9,11-epithio-11,12-methano-thromboxane A2 (STA2), a stable analogue of thromboxane A2. STA2 dose dependently increased incorporation of [3H]thymidine into DNA in randomly cycling VSMC and significantly shortened the doubling time. Cell cycle analysis revealed that the increased cell cycle progression was primarily due to a rapid transition from the DNA synthetic (S) to the G2/mitotic (M) phase. Moreover, STA2 enhanced protein synthesis in VSMC during the G2/M phase, whereas the protein synthesis was unaffected in the G0/G1 period. In fact, STA2 prompted the cells in G2/M phase to synthesize actin, a major cytoskeleton protein. Conversely, inhibition of protein synthesis by puromycin retarded the transition from S to G2/M. In addition, depolymerization of the actin molecules by cytochalasin D offset the quick progression to the G2/M phase by STA2. These data indicate that thromboxane A2 stimulates the cell cycle progression in VSMC primarily through a rapid transition from S to G2/M. This enhanced progression is attributable partly to a rapid buildup of the cytoskeleton proteins during the G2/M period.
Translation of heart preproenkephalin mRNA and secretion of enkephalin peptides from cultured cardiac myocytes
Authors: Springhorn J. P. , Claycomb W. C.
Published: December 2017

Rat ventricular cardiac muscle has previously been shown to contain exceptionally high levels of preproenkephalin mRNA (ppEnk mRNA). We have recently determined that the level of ppEnk mRNA is developmentally and hormonally regulated in rat ventricular cardiac muscle tissue and in cultured myocytes (J. P. Springhorn and W. C. Claycomb. Biochem. J. 258: 73-77, 1989). We demonstrate in the current study that heart ppEnk mRNA is structurally identical at the 5' end to brain ppEnk mRNA using a ribonuclease protection assay and that heart ppEnk mRNA can be translated in vitro using a rabbit reticulocyte lysate system. In vitro synthesized preproenkephalin peptides were immunoprecipitated with a polyclonal antibody directed to the carboxy-terminal seven amino acids of preproenkephalin. We have also established by radioimmunoassay that enkephalin-containing peptides are secreted from cultured neonatal and adult rat ventricular cardiac muscle cells. This secretion is linear with respect to time and can be stimulated by phorbol 12-myristate 13-acetate (PMA) and adenosine 3',5'-cyclic monophosphate (cAMP). It was determined by column chromatography that cAMP induced neonatal rat ventricular cardiac muscle cells to secrete Met5-enkephalin-Arg6-Phe7, whereas PMA plus 3-isobutyl-1-methylxanthine induced adult rat ventricular cardiac muscle cells to secrete Met5-enkephalin. These studies establish that ventricular heart muscle ppEnk mRNA can be translated and that enkephalin peptides are secreted from ventricular cardiac muscle cells.
Effect of protein kinase C inhibitors on endothelin- and vasopressin-induced constriction of the rat basilar artery
Authors: Murray M. A. , Faraci F. M. , Heistad D. D.
Published: December 2017

The goal of this study was to determine whether inhibitors of protein kinase C (PKC) attenuate constrictor responses of the basilar artery in vivo to endothelin and arginine vasopressin. In anesthetized rats, the diameter of basilar arteries was measured through a cranial window [control diameter 218 +/- 3 (SE) microns]. Vessel diameter was measured during topical application of agonists and antagonists. Sphingosine (10(-6) M), a PKC inhibitor that binds to the regulatory site of PKC, attenuated vasoconstriction in response to endothelin (10(-9), 10(-8), and 10(-7) M) and vasopressin (10(-9) and 10(-8) M). H-7 (10(-9) M), a PKC inhibitor that binds to the catalytic site of PKC, also inhibited vasoconstriction in response to endothelin and vasopressin. Sphingosine and H-7 did not affect baseline diameter and did not attenuate vasoconstriction in response to prostaglandin (PG) F2 alpha. The V1 antagonist [d(CH2)5Tyr(Me)]arginine vasopressin (10(-8) M) significantly inhibited constriction in response to vasopressin (10(-9) and 10(-8) M) but not PGF2 alpha (10(-6) M). These observations suggest that activation of PKC may contribute to endothelin-induced constriction of the basilar artery in vivo and that PKC may also be a mediator of V1-receptor-mediated constriction of the basilar artery in response to vasopressin.
Phospholipid peroxidation deacylation and remodeling in postischemic skeletal muscle
Authors: Rubin B. B. , Chang G. , Liauw S. , Young A. , Romaschin A. , Walker P. M.
Published: December 2017

Reperfusion of ischemic skeletal muscle is associated with white blood cell (WBC) sequestration and hydroperoxy-conjugated diene (HCF) formation, a marker of free radical-mediated phospholipid peroxidation. The purpose of this study was to define the kinetics of phospholipid fatty acyl peroxidation, deacylation, and remodeling in postischemic skeletal muscle during prolonged reperfusion in vivo, and to determine whether reperfusion with WBC and plasma-depleted blood would attenuate postischemic phospholipid peroxidation and myocyte necrosis. The isolated, paired, canine gracilis muscle model was used. After 5 h of ischemia, muscles underwent unaltered reperfusion or initial reperfusion with WBC-deficient blood cells resuspended in hydroxyethyl starch, followed by return to normal circulation (modified reperfusion). The concentration of native fatty acids and HCDs of linoleic acid extracted from muscle phospholipids was quantified by gas chromatography and positively identified by mass spectrometry. Ischemia and reperfusion resulted in phospholipid deacylation and a selective increase in phospholipid stearic acid content, but had no effect on total phospholipid phosphorus. Modified reperfusion decreased 1) early HCD formation (54%) and 2) postischemic skeletal muscle necrosis (49%). These data suggest that reperfusion results in phospholipid deacylation and remodeling, and that the initial oxidant stress during reperfusion may be a significant determinant of ultimate muscle necrosis.
Skeletal muscle arteriolar constriction to ANG II: evaluation of a myogenic component
Authors: Fleming J. T. , Anderson G. L. , Chen J.
Published: December 2017

This study addressed the hypothesis that an increase in blood pressure contributes to the overall constrictive response of skeletal muscle arterioles to angiotensin II (ANG II). Diameters of second-order arterioles (2A) and third-order arterioles (3A) in the rat cremaster muscle were quantitated after intravenous administration of ANG II. Hindquarter blood pressure was either allowed to increase or was maintained at normal levels. Constriction of 3A to bolus injection of ANG II was the same whether hindquarter pressure increased or not. However, the total vascular constrictive response of the cremaster muscle (based on 2A blood flow) and of the entire hindquarter (based on iliac arterial blood flow) to bolus ANG II was greater when hindquarter pressure was held constant. During slow infusion of ANG II, 3A constriction was unaffected by an abrupt decrease or increase in hindquarter pressure. However, an abrupt reduction of hindquarter pressure caused a significant decline in hindquarter vascular resistance. Thus an increase in blood pressure, whether rapid or gradual, does not influence 3A constriction to ANG II. However, in the entire hindquarter, a rapid rise in blood pressure opposes constriction to ANG II, whereas a gradual pressure rise evokes a mechanism that enhances constrictive response to the peptide
Age-related decline in left ventricular filling at rest and exercise
Authors: Schulman S. P. , Lakatta E. G. , Fleg J. L. , Lakatta L. , Becker L. C. , Gerstenblith G.
Published: December 2017

To determine whether the age-associated decline in resting left ventricular diastolic filling persists during aerobic exercise, rest and bicycle exercise filling indexes were measured from gated radionuclide blood pool scans in 88 healthy men aged 22–82 yr. To evaluate the effect of physical conditioning status on these age-related changes, a subset of the subjects consisted of endurance-trained senior athletes with a maximal O2 consumption of 50.5 +/- 5 compared with 32.6 +/- 7 ml.kg-1 x min-1 in age-matched controls. The contribution of beta-adrenergic stimulation to exercise-induced changes in filling was also evaluated by the administration of intravenous propranolol to another subset before testing. Peak filling rate increased progressively at all ages with increasing exercise work loads. The peak filling rates at rest, 50% maximal exercise, and maximum exercise inversely correlated with age (r = -0.64, -0.53, -0.64, respectively). Rest and exercise filling indexes in senior athletes were similar to those of sedentary older subjects. Propranolol decreased exercise peak filling rates in young (37.2 +/- 7.5 yr) but not in older (62.1 +/- 6 yr) subjects. Therefore, filling rates increase with exercise in both young and older healthy men, but age differences persist at comparable relative work loads. This decline is not secondary to a decline in physical conditioning status but appears to be related to a decrease in beta-adrenergic responsiveness in older individuals.
Muscle sympathetic nerve responses to dynamic one-legged exercise: effect of body posture
Authors: Ray C. A. , Rea R. F. , Clary M. P. , Mark A. L.
Published: December 2017

Previous studies examining muscle sympathetic nerve activity (MSNA) during dynamic exercise have focused on upper extremity exercise. The present study was undertaken to investigate 1) MSNA responses to dynamic one-legged knee extensions (DLE) and 2) the role of the cardiopulmonary baroreflexes in the modulation of MSNA responses to DLE. MSNA was measured during 4 min of DLE at 20 (n = 10) and 30 W (n = 9) and during 3 min of DLE at 40 W (n = 9). DLE was performed in the upright (sitting) position and MSNA was recorded in the contralateral leg (peroneal nerve). DLE elicited significant increases in mean arterial pressure (MAP) and heart rate (HR; P < 0.05). In contrast to previous studies using dynamic arm exercise, MSNA (bursts/min) decreased by 25% (P < 0.05) during the first minute of DLE from resting control and remained suppressed during the remaining 3 min of DLE at 20 and 30 W. During the first minute of DLE at 40 W, MSNA (bursts/min) decreased by 18% (P < 0.05), but returned to control levels during the last minute of exercise. Because dynamic leg exercise in the upright position increases venous return, we postulated that upright DLE might increase cardiac filling pressures and stimulate the cardiopulmonary baroreceptors resulting in suppression of MSNA. To investigate this possibility, we measured MSNA and central venous pressure (CVP) during 4 min of both supine and upright DLE at 30 W. MAP, HR, and CVP increased and MSNA decreased from 30 +/- 3 to 22 +/- 3 bursts/min (mean exercise value; P < 0.05) during upright DLE.(ABSTRACT TRUNCATED AT 250 WORDS)
Postural changes in venous pressure gradients in anesthetized monkeys
Authors: Terada N. , Takeuchi T.
Published: December 2017

We examined the hypothesis that head-up and head-down tilt produce a symmetrical hydrostatic load on the veins. Venous pressure was measured in anesthetized monkeys with a transducer-tipped catheter. Changes in venous pressure gradients during head-up tilt corresponded to changes in hydrostatic load. However, changes in venous pressure gradients during head-down tilt were not symmetrical to those during head-up tilt. During head-down tilt, venous pressure in the superior vena cava rose, venous pressure around the right atrium did not change, and venous pressure in the inferior vena cava on the caudal side of the diaphragm rose considerably. The venous pressure of the inferior vena cava caudal to the renal vein then gradually decreased. The inferior vena cava passes through the central tendon of the diaphragm. Thus, during head-down tilt, the gravitational shift of venous blood is impeded by this anatomic structure, and venous pressure around the hepatic vein increases significantly. These data disproved our hypothesis that head-up and head-down tilt induced symmetrical but opposite influences on vena caval pressures.
M&B 22948, a cGMP phosphodiesterase inhibitor, is a pulmonary vasodilator in lambs
Authors: Braner D. A. , Fineman J. R. , Chang R. , Soifer S. J.
Published: December 2017

To investigate the hypothesis that pulmonary vascular tone and endothelium-dependent pulmonary vasodilation are mediated by changes in the vascular smooth muscle cell concentration of cGMP, we studied the hemodynamic effects of M&B 22948, a selective guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor, in eight intact newborn lambs. At rest, M&B 22948 (1.0-2.5 mg/kg) selectively decreased pulmonary arterial pressure (by 8.5 +/- 6.6 to 10.3 +/- 4.5%, P < 0.05). Similarly, M&B 22948 (0.5-5.0 mg/kg) produced selective dose-dependent decreases in pulmonary arterial pressure during pulmonary hypertension induced either by U46619 (by 7.7 +/- 4.2 to 44.2 +/- 4.4%, P < 0.05) or by alveolar hypoxia (by 9.5 +/- 6.2 to 29.0 +/- 11.0%, P < 0.05). In addition, M&B 22948 augmented the pulmonary vasodilating effects of acetylcholine and ATP (both endothelium- and cGMP-dependent vasodilators) but not isoproterenol (an endothelium-independent and cAMP-dependent vasodilator). Because M&B 22948 inhibits the breakdown of cGMP, this study supports the in vitro data that changes in the vascular smooth muscle cell concentration of cGMP, in part, may regulate pulmonary vascular tone and mediate endothelium-dependent vasodilator responses in the pulmonary circulation. In addition, N omega-nitro-L-arginine (an inhibitor of endothelium-derived relaxing factor synthesis) blocked the vasodilating effects of M&B 22948, suggesting that the majority of endogenous cGMP is generated by the release of endothelium-derived relaxing factor.
Alterations of mature arterioles associated with chronically reduced blood flow
Authors: Wang D. H. , Prewitt R. L.
Published: December 2017

Adaptive responses of mature arterioles were examined after a 38% reduction in total blood flow to the cremaster muscle produced by unilateral orchidectomy in 12-wk-old rats. Four weeks later, the muscle was smaller than the contralateral cremaster, which did not increase in size during this period. Measured by closed-circuit television microscopy, the internal diameters of first- through fourth-order arterioles (1A-4A) were smaller, but wall cross-sectional area was reduced only in 3As. The smaller diameter of the 1A in the orchidectomy muscle resulted in unchanged wall shear rate. As determined from the perfusion-fixed, microfilled cremaster muscles, the total length of the arcading arterioles and the number of 3As were not statistically different, but the total number of 4As was significantly reduced on the orchidectomy side. Therefore, chronic load reduction in a mature muscle resulted in reduced blood flow, decreased number of 4As, and smaller arteriolar internal diameters in the absence of net changes in vascular wall cross-sectional area. A local autoregulatory mechanism related to flow-induced shear stress is suggested as the mechanism mediating the changes.