bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence that bradykinin stimulates renal prostaglandin synthesis by a mechanism distinct from that of other vasoactive substances.
Authors: Cooper C L , Malik K U
Published: June 2012

Arginine-vasopressin (AVP), angiotensin II (AII), and norepinephrine (NE) are known to stimulate prostaglandin (PG) synthesis in the intact rat kidney perfused with Tyrode's solution by a mechanism that requires intracellular Ca2+, while PG synthesis elicited by bradykinin (BK) is independent of Ca2+. To elucidate further the differences in the mechanism of action of BK and other vasoactive agents, in this preparation we have investigated the effect of caffeine, an agent known to interfere with the uptake and storage of Ca2+ in intracellular sites, on renal output of PGE2 and 6-keto-PGF1 alpha elicited by AVP, AII, NE, and BK; various combinations of the maximal doses of BK, AII, AVP, and NE on renal PG synthesis; and RHC 80267, an inhibitor of diglyceride and monoglyceride lipase, on the output of PGs produced by these vasoactive agents. Infusion of 1 mM caffeine inhibited PG output elicited by AVP, AII, and NE but not that caused by BK in the absence of extracellular Ca2+. Combined administration of maximal doses of BK (2.8 nmol) with that of AII (0.28 nmol), AVP (0.27 nmol), or NE (3.2 nmol) but not AVP and AII, NE and AVP, or NE and AII produced an additive effect on renal PG output in the presence or absence of Ca2+. The renal vasoconstrictor effect of AVP, AII, and NE produced in the presence of Ca2+ was not additive and remained unaltered when given together with BK.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung water and vascular permeability-surface area in premature newborn lambs with hyaline membrane disease.
Authors: Sundell H W , Harris T R , Cannon J R , Lindstrom D P , Green R , Rojas J , Brigham K L
Published: June 2012

Extravascular lung water and vascular permeability-surface area products were measured with a multiple indicator dilution method in 6 premature lambs with hyaline membrane disease 1-5 hours following delivery by cesarean section. The indicators used were 51Cr-labelled erythrocytes, 125I-albumin, 3H-water, and 14C-urea. Results were compared with previously obtained data in newborn lambs without hyaline membrane disease also delivered by cesarean section. Extravascular lung water was significantly higher in lambs with hyaline membrane disease [23.2 +/- 1.0 (SEM) vs. 10.7 +/- 1.4 ml/kg body wt]. Vascular permeability-surface area products for 14C-urea were significantly lower in lambs with hyaline membrane disease (0.30 +/- 0.10 vs 0.78 +/- 0.11 ml/s per kg). It is concluded that extravascular lung water is high in lambs with hyaline membrane disease. Permeability-surface area products for 14C-urea is low in lambs with hyaline membrane disease, which probably indicates a decrease in detectable surface area for exchange due to derecruitment or hypoperfusion of pulmonary exchange vessels in edematous and hypoxic areas of the lungs.
Changes in contractility fail to alter the size of the functional border zone in anesthetized dogs.
Authors: Drake D H , McClanahan T B , Ning X H , Gerren R A , Dunham W R , Gallagher K P
Published: June 2012

The functional border zone is nonischemic myocardium that exhibits reduced function adjacent to an ischemic area. To determine if the functional border zone can be modified by pharmacologic interventions that alter contractility, we infused isoproterenol (0.04-0.10 micrograms/kg/min) or administered propranolol (2 mg/kg) during circumflex coronary occlusion in nine anesthetized, open-chest dogs. We measured systolic wall thickening on both sides of the perfusion boundary, which was delineated with myocardial blood flow (microsphere) maps constructed from small tissue samples. By fitting sigmoid curves to the composite systolic wall thickening data after coronary occlusion, we modeled the distribution of functional impairment across the perfusion boundary. Defined as the distance from the perfusion boundary to 97.5% of the nonischemic asymptote of the sigmoid fits, the functional border zone was 31 degrees of circumference after coronary occlusion alone. Isoproterenol increased +dP/dt by 58% and augmented nonischemic systolic wall thickening without changing the lateral extent of the functional border zone (32 degrees). Propranolol reduced +dP/dt by 24% and depressed nonischemic systolic wall thickening, but the size of the functional border zone remained limited to 28 degrees. Within the functional border zone, wall thickening was significantly but only moderately reduced (-28%) compared with thickening in nonischemic myocardium more than 10 mm away from the perfusion boundary. The ratio of nonischemic border zone to central nonischemic area wall thickening remained the same with each intervention. We conclude that the dimensions of the functional border zone are fixed early after coronary occlusion and that inotropic interventions do not modify the extent or relative severity of nonischemic regional dysfunction.
Effect of edema on segmental vascular resistance in isolated lamb lungs determined by micropuncture.
Authors: Raj J U , Chen P
Published: June 2012

We have studied the mechanical effects of fluid accumulation on the pulmonary vasculature in 28 isolated blood perfused lungs of newborn lambs. Vascular resistance in the pulmonary arteries, microvessels, and veins was determined by micropuncture measurement of microvascular pressures, and regional distribution of blood flow in the lungs was determined using radiolabelled microspheres both before and after the development of varying degrees of hydrostatic edema. Edema was induced by raising venous pressure. During measurements, alveolar and venous pressures were kept constant at 7 and 8 cm H2O, respectively, as well as lung blood flow (540 +/- 107 ml/min). All vascular pressures were referenced to the superior surface of the lung, site of all micropunctures. Active vasomotor changes were eliminated by addition of papaverine to the perfusate. Under baseline nonedematous conditions in the absence of vasomotor tone, 17% of the total pressure drop was in arteries, 41% was in microvessels, and 42% was in veins. With the development of alveolar edema (80 +/- 13% weight gain), there was no change in total or segmental vascular resistance, but after 148 +/- 97% weight gain, total pulmonary vascular resistance increased by 74%. Segmental pressure drop increased in arteries by 172% and in microvessels by 132% but decreased by 22% in the venous segment. Regional distribution of blood flow remained unchanged. Possible mechanisms for increased resistance to blood flow may be compression of small arterioles and venules (less than 20 micron diameter) by liquid cuffs and/or occlusion of microvessels by the weight of alveolar liquid.
Transitions in cardiac isomyosin expression during differentiation of the embryonic chick heart.
Authors: Sweeney L J , Zak R , Manasek F J
Published: June 2012

The expression of different isoforms of the contractile protein myosin plays a major role in determining contractile characteristics in both cardiac and skeletal muscle in the adult. There is little evidence pertaining to putative changes in myosin phenotype during cardiac embryogenesis or if such changes could play a role in modulating the contractile characteristics of the developing heart. We examined isomyosin expression during cardiogenesis in the chick by indirect immunofluorescence microscopy with monoclonal antibodies to adult ventricular and atrial myosin heavy chains. Antibody specificity was characterized in the adult on the basis of immunofluorescence localization, ELISA, and protein blot immunoassay. Results show that the early embryonic chick heart has a different myosin phenotype than the later embryonic or adult heart. Both the embryonic ventricular and atrial myocardia initially expressed a myosin heavy chain that was recognized by antibody specific (in the adult) for ventricular myosin heavy chain. The ventricles remained reactive throughout life with the ventricular antibody, but reactivity of the atrial myocardium was confined to the initial 6 days of embryonic development. On the other hand, reactivity of the embryonic heart with multiple antibodies specific (in the adult) for atrial myosin was confined to the atrial myocardium throughout development. Thus, the distribution of myosin isoforms became similar to that of the adult myocardium by the time the embryonic heart achieved a 4-chambered configuration at 6 days in ovo.
Contracture and the calcium paradox in the rat heart.
Authors: Daly M J , Elz J S , Nayler W G
Published: June 2012

The role of contracture in the manifestation of calcium paradox-induced damage was examined using 2,3-butanedione monoxime (BDM) to inhibit myofibrillar activity. Calcium and sodium gain, loss of intracellular components, and changes in structure were monitored. If 30 mM BDM was added at the time of calcium repletion after 10 minutes of calcium-free perfusion, some protection was afforded, particularly at the early stages of calcium repletion. However, much greater protection was obtained if BDM was present during the final 2 minutes of calcium-free perfusion and throughout repletion. Sodium gain and loss of intracellular components were markedly attenuated, as was the incidence of severely contracted cells. Calcium gain, although significantly reduced during the period of repletion, was not abolished. After 10 minutes of repletion, a calcium content of 11.44 +/- 1.57 mumol/g dry wt was observed. This suggests that other noncontracture related routes of calcium entry are involved. If BDM is removed after 5 minutes of calcium repletion and perfusion is continued with BDM-free perfusate, there is a rapid gain of sodium, further gain of calcium, loss of intracellular components and the cells contract severely, tearing away from neighboring cells. It is evident, therefore, that returning calcium to hearts after a period of calcium-free perfusion under conditions that significantly reduce the typical calcium paradox-associated damage does not necessarily repair the underlying defect. These results support the hypothesis that contracture-induced sarcolemmal disruption may be responsible for the terminal manifestation of the calcium paradox.
Quantification of intestinal microvascular growth during maturation: techniques and observations.
Authors: Unthank J L , Bohlen H G
Published: June 2012

This study was undertaken to determine what changes occur in the intestinal microvasculature during the rapid growth associated with juvenile maturation. A technique was developed that permitted the comparison of the same microvessels in exactly the same intestinal region at two time periods of an animal's life. A region of the terminal ileum of 5-week-old rats was exposed and marked, and photographs and video recordings were made of the microvessels. Four weeks later, the marked intestinal region was located, and photography and videography of the microvessels were repeated. Comparison of indexes for body, intestinal, and microvascular growth for the treated rats and age- and colony-matched controls revealed no significant differences. The number and branching pattern of arterioles observed in the marked region remained remarkably constant during the 4 weeks between observation periods, even though body and bowel mass of the treated animals increased approximately 2.5 times. The lengths of the arterioles were increased (18%) by almost the same proportion as the axis of bowel (22%) in which they were oriented. The average distance between capillaries in the radial intestinal muscle layer was also increased by about the same percentage (24%) as that of tissue elongation (22%). The overall data are consistent with the hypothesis that during the growth spurt of juvenile life, the arterioles present at the weanling stage are elongated and new branches do not develop. The net effect of tissue growth with a minimal change in numbers of arterioles is a decreased ratio of number of arterioles to tissue mass as a normal consequence of maturation.
Enhanced responsiveness to carotid baroreceptor unloading in conscious dogs during development of perinephritic hypertension.
Authors: Kirby D A , Vatner S F
Published: June 2012

The effects of unloading the carotid sinus baroreceptors before and during the development of perinephritic hypertension were studied in conscious dogs instrumented with aortic catheters to measure arterial pressure and heart rate, and electromagnetic flow probes to measure cardiac output and calculate total peripheral resistance. Prior to hypertension, bilateral carotid occlusion (BCO) increased mean arterial pressure by 38 +/- 2 from 101 +/- 2 mm Hg and total peripheral resistance by 19 +/- 2 from 46 +/- 3 mm Hg/l/min, while cardiac output and heart rate did not change from 2,299 +/- 128 ml/min and 84 +/- 4 beats/min, respectively. At 2 weeks after renal wrapping, there were significant increases in baseline mean arterial pressure, cardiac output, and total peripheral resistance and decreases in heart rate; BCO increased mean arterial pressure by 59 +/- 5 from 130 +/- 4 mm Hg, heart rate by 36 +/- 5 beats/min from 69 +/- 3 beats/min, and cardiac output by 458 +/- 103 from 2,711 +/- 239 ml/min. By 4 weeks after renal wrapping, heart rate and mean arterial pressure responses to BCO were approaching baseline levels. After beta-adrenergic receptor blockade, responses to BCO of mean arterial pressure, cardiac output, and heart rate were no longer significantly enhanced during the development of hypertension. Thus, in conscious dogs, reflex pressor responses to baroreceptor unloading via BCO were enhanced during the development of hypertension but no longer present 3 weeks later. The augmented mean arterial pressor responses to BCO were mediated by increases in cardiac output and heart rate, which in turn, appeared to be controlled by beta-adrenergic receptor mechanisms.
Immunologic identification of lymphocyte subsets in experimental murine myocarditis with encephalomyocarditis virus. Different kinetics of lymphocyte subsets between the heart and the peripheral blood, and significance of Thy 1.2+ (pan T) and Lyt 1+, 23+ (immature T) subsets in the development of myocarditis.
Authors: Kishimoto C , Kuribayashi K , Fukuma K , Masuda T , Tomioka N , Abelmann W H , Kawai C
Published: June 2012

To clarify the immune mechanism in myocarditis, immunofluorescence techniques with laser flow cytometry were used to examine serial changes in lymphocyte subsets in the heart, spleen, and peripheral blood of DBA/2 and BALB/c mice inoculated with encephalomyocarditis virus (Experiment I). B cells were identified by staining with fluorescein isothiocyanate-labelled rabbit anti-mouse immunoglobulin. T-cell subsets were identified with rat anti-Thy 1.2, and nonpolymorphic Lyt 1 and Lyt 2 monoclonal antibodies plus fluorescein isothiocyanate-labelled anti-mouse immunoglobulin. On days 7 and 14 postinfection, the percentage of Thy 1.2+ (pan T) cells in both strains had decreased in the peripheral blood; B cells showed no significant changes throughout the entire period. On the other hand, Thy 1.2+ (pan T) and Lyt 1+, 23+ (precursor and immature) T cells appeared to occupy the major portion of the myocardium on days 7 and 14 when congestive heart failure developed. To confirm this, serial immunohistologic studies (immunoperoxidase staining) of the hearts of DBA/2 and BALB/c mice with encephalomyocarditis virus-induced myocarditis were performed (Experiment II). In Experiment II, most of the stained cells in the hearts of both strains were Thy 1.2 positive and Lyt 1 and Lyt 2 positive on days 7 and 14. Thus, Experiments I and II demonstrated that lymphocytes at the site of inflammation in acute viral myocarditis carried antigenic markers that differed from those of peripheral lymphocytes and suggested that Thy 1.2+ (pan T) cells, especially the Lyt 1+, 23+ subset (immature T cells and T-cell subset precursors) were involved in the development of myocarditis in these animals.
Cardiovascular and respiratory effects of adenosine in conscious man. Evidence for chemoreceptor activation.
Authors: Biaggioni I , Olafsson B , Robertson R M , Hollister A S , Robertson D
Published: June 2012

The cardiovascular and respiratory effects of intravenous adenosine were studied in conscious normal volunteers. Bolus injections of adenosine increased systolic and diastolic pressures initially (+15 and +13 mm Hg after 100 micrograms/kg) followed by a subsequent reduction in systolic and diastolic pressures (-12 and -16 mm Hg). Heart rate increased during trough blood pressure (R-R interval shortening of 298 msec after 100 micrograms/kg). Adenosine steady-state infusions increased heart rate (+30 beats/min during 140 micrograms/kg/min), systolic pressure (+16 mm Hg), and pulse pressure (+21 mm Hg) but decreased diastolic pressure slightly (-5 mm Hg), resulting in no significant change in mean arterial pressure. Adenosine stimulated respiration, resulting in decreased PaCO2 (41 to 31 mm Hg), increased PaCO2 (101 to 113 mm Hg), and increased pH (7.42 to 7.50). The increased ventilation was not explained by bronchoconstriction, hypotension, or hypoxia. The observed pressor and tachycardic effects are mediated through reflex autonomic mechanisms since they are completely abolished in patients with severe autonomic failure. These autonomic mechanisms probably involve chemoreceptor activation since adenosine is pressor when infused in the aortic arch proximal to the origin of the carotid arteries but depressor when infused in the descending aorta. It is concluded that the hemodynamic and respiratory effects of adenosine observed in normal volunteers are in part due to chemoreceptor stimulation. These findings raise the possibility that adenosine is an endogenous modulator of respiration in man.
Decreased atrial natriuretic peptide binding in renal medulla in rats with chronic heart failure.
Authors: Tsunoda K , Mendelsohn F A , Sexton P M , Chai S Y , Hodsman G P , Johnston C I
Published: June 2012

The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantitation of receptors was performed by computerized in vitro autoradiography with 125I-labeled alpha-rat ANP (1-28) as the radioligand. When compared with controls, rats with myocardial infarction had markedly elevated plasma immunoreactive ANP concentrations (462 +/- 82 versus 124 +/- pg/ml, p less than 0.01) and reduced densities of ANP binding in the inner renal medulla (2.93 +/- 0.19 versus 3.53 +/- 0.22 fmol/mg protein, p less than 0.01). Extensive myocardial infarction was associated with a significant decrease in receptor numbers in the inner medulla (33.6 +/- 5.7 versus 95.6 +/- 9.6 fmol/mg protein, p less than 0.01) without significantly altering the affinity constant (1.76 +/- 0.51 versus 1.03 +/- 0.15 x 10(9) M-1, p greater than 0.05). Right ventricular weight increased in proportion to infarct size (r = 0.71, p less than 0.01), and both were correlated with plasma immunoreactive ANP levels (r = 0.74, p less than 0.01 and r = 0.75, p less than 0.01, respectively). Binding densities in the inner medulla of rats with infarcts were negatively correlated with right ventricular weight, plasma immunoreactive ANP concentrations, and also with infarct size (r = -0.92, p less than 0.001; r = -0.78, p less than 0.001; r = -0.77, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic modulation of the transient outward current in isolated canine Purkinje cells.
Authors: Nakayama T , Fozzard H A
Published: June 2012

Single canine Purkinje cells were voltage clamped under Ca2+-free conditions using the patch pipette. Depolarizing pulses from a holding potential of -42 mV induced a time-dependent rapidly activating-slowly inactivating outward current, which was identified as the transient outward current. The current showed two exponential time constants of inactivation (48,352 msec at +58 mV and 53,325 msec at +78 mV). Norepinephrine in concentrations exceeding 10(-9) M modified the inactivation kinetics of this current without affecting the activation kinetics. The half-maximum dose for norepinephrine effect was 1.9 X 10(-8) M, and the effect was saturated at 10(-6) M. Norepinephrine reduced the amplitude of the fast time constant component of inactivation, while increasing the amplitude of the slow component, without changing their time constants. Norepinephrine also increased the amplitude of a time-independent current component. The beta-antagonist sotalol blocked the norepinephrine effect on the transient outward current. On the other hand, both activation of adenyl cyclase by forskolin and increase of intracellular cAMP concentration produced the same effect as exposure to norepinephrine. These results suggest a role for neurotransmitter regulation of the transient outward current in cardiac cells, perhaps by channel phosphorylation.
Methionine-induced positive inotropic effect in rat heart: possible role of phospholipid N-methylation.
Authors: Panagia V , Gupta M P , Ganguly P K , Dhalla N S
Published: June 2012

Perfusion of isolated rat heart with L-methionine produced a positive inotropic effect that was temporally preceded, as well as accompanied, by an increase of methyl group incorporation into N-methylated phospholipids of the myocardium. Maximal increase in contractile force development was associated with maximal methyl group incorporation. Both parameters showed a dose-related dependence on methionine and correlated positively (r = 0.965) upon regression analysis of the data. The presence of adenosine, L-homocysteine thiolactone and erythro-9-(2-hydroxy-3-nonyl) adenine in the perfusion medium inhibited the positive inotropic effect as well as the incorporation of methyl groups into phospholipids. Cycloleucine, an inhibitor of S-adenosylmethionine synthetase, also reduced the increase in contractility by methionine. Methionine-induced positive inotropic effect could be modulated by varying Ca2+ concentration in the perfusate and was inhibited by ryanodine, a blocker of sarcoplasmic reticular Ca2+ release. These observations indicate that L-methionine may serve as a powerful positive inotropic agent and suggest that phospholipid N-methylation plays an important role in functional activity of rat heart.
Mechanics of cerebral arterioles in hypertensive rats.
Authors: Baumbach G L , Dobrin P B , Hart M N , Heistad D D
Published: June 2012

Chronic hypertension is associated with hypertrophy of cerebral blood vessels. Previous studies of the mechanical properties of cerebral vessels in chronic hypertension have examined large cerebral arteries. The goals of this study were first to develop a method to examine vascular mechanics of cerebral arterioles in vivo and second to determine whether the stiffness of cerebral arterioles is altered in the presence of chronic hypertension. We calculated circumferential stress and strain of pial arterioles in age-matched, anesthetized stroke-prone spontaneously hypertensive rats (SHRSP) and in Wistar Kyoto rats (WKY) from measurements of pial arteriolar pressure, inner diameter, and wall thickness. Pial arteriolar pressure was measured with a servonull system. Smooth muscle of pial arterioles was deactivated with ethylenediaminetetraacetic acid (EDTA), and pressure-diameter relations were examined during step-wise reductions in pressure. Prior to deactivation of smooth muscle in 3-4-month-old rats, pial arteriolar pressure was greater in SHRSP than in WKY (110 +/- 4 versus 75 +/- 2 mm Hg [mean +/- SE]; p less than 0.05). Pial arteriolar diameter, which was measured at prevailing levels of pial arteriolar pressure, was less in SHRSP than in WKY (52 +/- 5 versus 63 +/- 3 microns; p less than 0.05). Following deactivation of smooth muscle, diameter of pial arterioles at 70 mm Hg of pial arteriolar pressure was similar in the two groups: 104 +/- 6 microns in SHRSP and 109 +/- 3 microns in WKY (p greater than 0.05). Wall thickness was 4.5 +/- 0.2 microns in SHRSP and 4.1 +/- 0.1 microns in WKY (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Maximal twitch tension in intact length-clamped ferret papillary muscles evoked by modified postextrasystolic potentiation.
Authors: Urthaler F , Walker A A , Reeves D N , Hefner L L
Published: June 2012

A modified test of postextrasystolic potentiation achieved with a brief episode of rapid pacing followed by a 6-second pause (RPP maneuver) was used to evoke maximal force in isolated intact ferret right ventricular papillary muscles. Maximal RPP tensions were examined under length-clamped conditions and compared with the steady-state forces obtained when further increases in [Ca2+]o, did not further increase force and to the tensions recorded at the point of saturation of force when similarly length-clamped muscles were subjected to caffeine-induced tetanization. The results show that the calculated maximal twitch tension achieved with RPP is comparable to the 25-35 g/mm2 observed in intact single skeletal muscle fibers. The study also shows that the beat-to-beat decay of the potentiated contraction is exponential. While the amount of the constant fractional beat-to-beat decay is a function of [Ca2+]o, it is not influenced by length. During the decay of potentiation, the ratio of the potentiation of any beat divided by that of the previous beat is a constant, called (X). With certain assumptions, it is shown that (X) is a measure of the fraction of activator calcium taken up by the sarcoplasmic reticulum in each beat and, in the steady state, the fraction of activator calcium that comes from the sarcoplasmic reticulum. The (X) amounted to 33%, 50%, and 65% when [Ca2+]o was 1.25, 2.50, and 5.0 mM, respectively. Thus, at 1.25 mM [Ca2+]o, some two thirds of the total calcium required to activate the myofilaments comes from the extracellular compartment during excitation and only one third is contributed via release from the sarcoplasmic reticulum. In the region of optimal myofilament overlap, RPP force-length curves are remarkably shallow and almost indistinguishable from the sarcomere length-tension relation observed in skinned single cardiac cells. Tetanus plateau tensions are significantly smaller than RPP forces at any length, and the slope of the tetanus force-length curves is greater than that obtained with RPP. Thus, and by exclusion, we also suggest that caffeine may exert significant downstream inhibitory effects.
Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor.
Authors: Edwards B S , Zimmerman R S , Schwab T R , Heublein D M , Burnett J C
Published: June 2012

The current studies were designed to investigate the mechanisms in the intact anesthetized dog that control the release of atrial natriuretic factor (ANF). In vitro, mechanical stretch of atrial tissue produces an increased release of ANF. In vivo, changes in atrial pressure correlate positively with circulating ANF levels. The present investigations used 6 open-chest anesthetized dogs to evaluate the role of atrial pressure versus atrial stretch, the latter determined by atrial transmural pressure, in the release of ANF. In a paired design, animals underwent cardiac tamponade followed by constriction of the aorta and pulmonary artery. Tamponade produces a balanced increase in intra-atrial and pericardial pressures. Thus, despite an elevated atrial pressure, there is no increase in transmural pressure producing atrial stretch. Great artery constriction increases intra-atrial but not pericardial pressure, resulting in an increase in atrial transmural pressure and atrial stretch. Cardiac tamponade increased right atrial pressure (0.8 +/- 0.3 to G.6 +/- 0.6 mm Hg, p less than 0.001) and pulmonary capillary wedge pressure (3.7 +/- 0.6 to 8.8 +/- 0.6 mm Hg, P less than 0.001). Constriction of the aorta and pulmonary artery also increased right atrial pressure (1.5 +/- 0.8 to 6.3 +/- 0.8 mm Hg, p less than 0.05) and pulmonary capillary wedge pressure (4.6 +/- 0.3 to 7.8 +/- 1.0 mm Hg, p less than 0.05). Atrial transmural pressure increased only during great artery constriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma atrial natriuretic factor during chronic thoracic inferior vena caval constriction.
Authors: Paganelli W C , Cant J R , Pintal R R , Kifor I , Barger A C , Dzau V J
Published: June 2012

The effects of chronic constriction of the thoracic inferior vena cava (TIVCC) on plasma atrial natriuretic factor (pANF) were studied in conscious dogs (n = 5). TIVCC decreased left and right atrial pressure and led to a decrease in pANF concentration from 199 +/- 12 to 104 +/- 14 pg/ml while plasma renin and vasopressin concentrations increased. These hormonal changes were associated with a significant fall in sodium excretion to less than 5 meg/day. pANF remained suppressed during chronic TIVCC as the dogs expanded their extracellular fluid volume and developed ascites. Acute release of TIVCC resulted in abrupt increases in left and right atrial pressure but only a modest rise in pANF from 96 +/- 16 to 185 +/- 45 pg/ml. The magnitude of the rise in pANF (twofold) contrasted sharply with the eightfold increase in sodium excretion that occurred over the first 24 hours. Our data suggest that decrease in atrial pressure below normal results in a decline in pANF, which, acting in concert with the activated renin-angiotensin system and vasopressin, may contribute to sodium retention. On the other hand, during acute release of TIVCC, which markedly increased atrial pressure and sodium excretion, pANF only returned to control levels. These data suggest that ANF release may be attenuated during chronic reduction in atrial pressure and also raise a question concerning the magnitude of the primary role of ANF in this natriuretic response.
Adrenergic coronary vasoconstriction helps maintain uniform transmural blood flow distribution during exercise.
Authors: Huang A H , Feigl E O
Published: June 2012

The hypothesis that alpha-adrenergic coronary vasoconstriction helps maintain a uniform transmural distribution of myocardial blood flow during exercise was tested in dogs. Carotid artery loops were surgically constructed and a splenectomy performed three weeks prior to study. On the day of study, the dog was anesthetized briefly (fentanyl and nitrous oxide) for percutaneous catheterization, and alpha-receptors in one myocardial region were blocked with phenoxybenzamine (0.25 mg/kg) infused selectively into the left circumflex coronary artery. Recirculation of phenoxybenzamine was minimized by drainage of coronary sinus outflow during the infusion. After the dog recovered from the anesthesia, regional blood flow was measured at rest and during graded treadmill exercise with the microsphere technique calibrated by reference blood samples. Average transmural flow was limited by alpha-vasoconstriction and was less in the region where alpha-receptors were intact than in the region where they were blocked, as has been described by others. The ratio of inner layer myocardial blood flow to outer layer flow was better maintained in the region with alpha-receptors intact than in the region with alpha-receptors blocked when myocardial oxygen consumption was 150 microliter/min/g or greater (p less than 0.001). Even though average transmural flow was limited by alpha-receptor activation, inner layer myocardial blood flow was greater in the region with alpha-receptors intact than in the region with alpha-receptors blocked when myocardial oxygen consumption was 500 microliter/min/g or more (p less than 0.05). In conclusion, adrenergic coronary vasoconstriction mediated by alpha-receptors helps to maintain a uniform transmural distribution of myocardial blood flow during exercise in spite of limiting average transmural flow.
Role of a pertussis toxin-sensitive protein in the modulation of canine Purkinje fiber automaticity.
Authors: Rosen M R , Steinberg S F , Chow Y K , Bilezikian J P , Danilo P
Published: June 2012

We previously have shown that alpha-adrenergic stimulation of canine Purkinje fibers and rat ventricle decreases automaticity. Experiments on rat ventricular myocytes in tissue culture have suggested that the decrease in automaticity induced by alpha-adrenergic stimulation depends on the development of sympathetic innervation and the presence of a pertussis toxin-sensitive, 41-kDa guanosine triphosphate (GTP)-regulatory protein. In the present study, microelectrode and biochemical techniques were used to test the role of the pertussis toxin-sensitive protein and sympathetic innervation in modulating automaticity of adult canine Purkinje fibers. Fibers were incubated in Tyrode's solution alone or in Tyrode's solution plus pertussis toxin (0.1-0.5 microgram/ml) for 24 hours and were then superfused with phenylephrine. Phenylephrine in the 5 x 10(-9)-5 x 10(-8) M range induced a decrease in automaticity in 63% of the 16 fibers not treated with pertussis toxin and an increase in automaticity in 37%. The former group had a higher level of pertussis toxin-sensitive substrate by the [32P]nicotinamide adenine dinucleotide adenosine diphosphate (ADP)-ribosylation assay than the latter. In contrast, all fibers treated with pertussis toxin (0.5 microgram/ml) showed increased automaticity in response to phenylephrine and had no detectable pertussis toxin-sensitive substrate. Over the range of pertussis toxin concentrations studied, there was a smooth concentration-response relation between the substrate levels measured and the automatic response to phenylephrine. As ADP-ribosylatable substrate levels decreased, the percent of fibers showing an increase in automaticity increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunoreactive atrial natriuretic peptide in ventricles, atria, hypothalamus, and plasma of genetically hypertensive rats.
Authors: Ruskoaho H , Leppäluoto J
Published: June 2012

To evaluate the role of extra-atrial atrial natriuretic peptide (ANP) in volume and blood pressure regulation, the plasma, atrial, ventricular, and hypothalamic levels of immunoreactive atrial natriuretic peptide (IR-ANP) were measured simultaneously in the spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at the ages of 2, 6, and 12 months. Plasma IR-ANP in the 12-month-old, conscious SHR was significantly higher than that of the WKY (300 +/- 18 versus 200 +/- 20 pg/ml, p less than 0.05, n = 9), while no differences in plasma IR-ANP levels were found between the strains in younger rats. Acute volume expansion with saline (1.1 ml/100 g body wt) in hypertensive as well as in normotensive rats resulted in marked increases in right atrial pressure and plasma IR-ANP concentration. The older SHR had attenuated ANP release to volume loading as shown by the shift of the ANP versus right atrial pressure curve to the right. Right auricular IR-ANP concentration decreased, while that of left auricle increased with increasing age in both strains. No substantial differences were noted in auricular ANP concentration between SHR and WKY. However, the total atrial IR-ANP content (micrograms/atria) was consistently lower in SHR compared with WKY. In both ventricles, IR-ANP concentrations and contents increased with increasing age in WKY and SHR, but the ventricular levels of ANP were reduced in ventricles of the SHR heart compared with normotensive controls. The depletion of total ventricular IR-ANP was greatest in SHR with greatest ventricular hypertrophy and coincided with the attenuated ANP release to acute volume load. The increase of left but not right ventricular weight occurring secondary to 6 weeks minoxidil treatment was accompanied by higher ANP concentration in both strains. In contrast to the ventricles, the hypothalamic IR-ANP concentration was significantly increased in SHR compared with that of WKY and decreased in both strains after 6 weeks' treatment with antihypertensive drugs. Thus, ventricular and hypothalamic, as well as atrial, ANP respond to increased pressure overload in genetically hypertensive rats. Our results suggest that chronic stimulation of ANP release from ventricles is associated with depleted stores of ANP from both ventricles and reduced response to acute volume load. Our findings that ventricular ANP increased with increasing weight and in response to a hypertrophic stimulus in WKY and was decreased in SHR with severe ventricular hypertrophy suggest that ANP may locally have an inhibitory effect on the development of cardiac hypertrophy.
Vasa vasorum in atherosclerotic coronary arteries: responses to vasoactive stimuli and regression of atherosclerosis.
Authors: Williams J K , Armstrong M L , Heistad D D
Published: June 2012

The goals of this study were to determine whether vasa vasorum in atherosclerotic coronary arteries respond to vasoactive stimuli and to examine effects of regression of atherosclerosis on blood flow through vasa vasorum in coronary arteries. We studied three groups of monkeys: normal, atherosclerotic, and regression. Blood flow to vasa vasorum was measured with microspheres. Blood flow to intima-media (ml/min x 100 g) was 5 +/- 1 (mean +/- SEM) in normal and 47 +/- 7 in atherosclerotic monkeys (p less than 0.05). Infusion of phenylephrine or serotonin did not alter flow through vasa in normal monkeys. In atherosclerotic monkeys, phenylephrine decreased flow through vasa vasorum in intima-media of coronary arteries to 24 +/- 4 (p less than 0.05), and serotonin decreased flow to 27 +/- 5 (p less than 0.05). In regression monkeys, blood flow to intima-media was sixfold less (7 +/- 2 ml/min x 100 g) than in atherosclerotic monkeys (p less than 0.05). During infusion of adenosine, blood flow to vasa was fourfold greater in atherosclerotic monkeys than after regression of atherosclerosis. This finding suggests that loss of vessels, not constriction of existing vessels, accounts for the decrease in flow through vasa in intima-media after regression of atherosclerosis. We conclude that vasa vasorum in atherosclerotic coronary arteries respond to vasoconstrictor stimuli and that there is loss of vasa vasorum and a large decrease in blood flow through vasa to intima-media of coronary arteries after regression of atherosclerosis.
Angiotensin II increases spontaneous contractile frequency and stimulates calcium current in cultured neonatal rat heart myocytes: insights into the underlying biochemical mechanisms.
Authors: Allen I S , Cohen N M , Dhallan R S , Gaa S T , Lederer W J , Rogers T B
Published: June 2012

The effect of angiotensin II on cultured neonatal rat heart myocytes was studied by measuring changes in cell length, the magnitude and kinetics of the calcium current, and changes in cyclic adenosine 3',5'-monophosphate (cAMP) and phosphoinositide metabolism. Spontaneous beating frequency of multicellular networks was increased by angiotensin II with a maximal increase of 100% above control values at concentrations of 5 nM or greater. The half-maximal response occurred at 0.6 nM angiotensin II. Shortening amplitude, shortening velocity, and relaxation velocity decreased concomitantly with the increasing contractile rate. In voltage-clamped single myocytes, both steady-state and transient components of the calcium current were increased by the addition of angiotensin II. Angiotensin II had no effect on either control or isoproterenol-stimulated adenylate cyclase activity in myocyte membranes. Neither the basal levels nor the isoproterenol-stimulated cAMP accumulation in intact cells was affected by addition of hormone. In myocytes labeled with [3H]inositol, angiotensin II stimulated the formation of [3H]inositol phosphates. One minute after addition of 5 nM angiotensin II, inositol monophosphate and inositol bisphosphate levels were increased to 73% and 99%, respectively, above control values and remained elevated at 10 minutes. Inositol trisphosphate levels were not significantly different from control values at either time point. Nifedipine (10 microM) had no effect on angiotensin II-induced increases in [3H]inositol phosphates. We conclude that the increases in both spontaneous beating rate and calcium current in angiotensin II-stimulated cultured neonatal heart cells are not dependent on cAMP or inositol trisphosphate levels but may involve sustained phosphoinositide hydrolysis.
Electrophysiological effects of acute ventricular dilatation in the isolated rabbit heart.
Authors: Reiter M J , Synhorst D P , Mann D E
Published: June 2012

We examined the effects of left ventricular dilatation on epicardial pacing threshold, conduction velocity, and effective refractory period (ERP) in the isolated, retrograde perfused rabbit heart. Left ventricular size was modified by acutely changing the volume of a fluid-filled balloon anchored within the vented left ventricle. Increases in left ventricular volume, associated with increases in left ventricular end-diastolic pressure from 0 +/- 1 to 35 +/- 2 mm Hg, were not associated with significant changes in pacing threshold or conduction velocity. The left ventricular ERP decreased significantly with an added volume of 1.5 ml (91.4 +/- 5.5 msec) compared with starting volume (117.7 +/- 3.8 msec, p less than 0.01). Right ventricular ERP did not change significantly with increases in left ventricular volume. The left and right ventricular ERPs were comparable at starting volume (117.7 +/- 3.8 and 117.6 +/- 3.5 msec, respectively; p = NS) but were significantly different with an added volume of 1.5 ml (91.4 +/- 5.5 and 112 +/- 5.6 msec, p less than 0.05). These changes were independent of coronary perfusion pressure and paced cycle length, suggesting that ischemia is an unlikely explanation for the observed effects. Changes in left ventricular volume decreased left ventricular ERP in a regionally heterogeneous manner, increasing the temporal dispersion of recovery over the left ventricle nearly twofold. Induced ventricular arrhythmias (ventricular tachycardia or fibrillation) were significantly more frequent at high (35%) than at low (3%) volumes during left ventricular pacing. We conclude that ventricular dilatation is associated with increased dispersion of refractoriness in this model, a finding that correlates with propensity for reentrant arrhythmias.
Activation sequence during atrial flutter in dogs with surgically induced right atrial enlargement: I. Observations during sustained rhythms.
Authors: Boyden P A
Published: June 2012

The atrial activation sequences during 15 episodes of sustained atrial flutters were determined in the isolated hearts of four dogs with surgically induced right atrial enlargement (TI/PS dogs). These sequences were compared with the activation sequences of six episodes of nonsustained atrial tachyarrhythmias induced in three control hearts. Total endocardial activation of both atria during normal sinus rhythm and during the arrhythmias was determined first by recording simultaneously from 192 pairs of recording electrodes positioned into egg-shaped electrode arrays, and then by determining the moment of activation from each of the recorded electrograms. Isochronal maps of total activation were constructed by computer. Nonsustained atrial rhythms inducible in control hearts were due to circus movement excitation either in the left atrium (two episodes) or in the right atrium (four episodes). On the other hand, all 15 episodes of sustained atrial flutter induced and mapped in the TI/PS dog hearts were due to reentrant excitation in the enlarged right atrium. The reentrant pattern could be in a clockwise or counterclockwise pattern. In these episodes of stable flutter an area of functional block was an essential component to the reentrant excitation.
Effect of platelet-activating factor on microvascular permselectivity: dose-response relations and pathways of action in the hamster cheek pouch microcirculation.
Authors: Dillon P K , Durán W N
Published: June 2012

Platelet-activating factor (PAF) has recently been described as a mediator of inflammatory processes. In this study, we quantitated the dose-response effects of topically applied PAF on microvascular permselectivity and investigated the biochemical pathways of this compound. Permselectivity alterations were assessed by measuring the clearance of macromolecules with fluorescein isothiocyanate dextran 150 (FITC-dx 150) as a tracer. The microvascular bed of the hamster cheek pouch served as a model. PAF was found to induce leakage of macromolecules from postcapillary venules. Control FITC-dx 150 plasma clearance (+/- SEM) was 72 +/- 10 nl/90 min. Clearances of 61 +/- 10 474 +/- 145, 622 +/- 57, 301 +/- 86, and 142 +/- 3 nl/90 min were obtained at PAF concentrations of 10(-9), 10(-8), 10(-7), 10(-6), and 10(-5) M, respectively. A one-way analysis of variance showed that the population means were not equal. Multiple comparison by the Student-Newman-Keuls test demonstrated that the clearances obtained with 10(-8), 10(-7), and 10(-6) M were significantly greater than controls. Significant differences existed between 10(-7) M PAF and 10(-9), 10(-6), and 10(-5) M PAF. In an effort to elucidate the biochemical pathways of PAF activity, several inhibitors of the arachidonic acid cascade and receptor blockers were used. Dexamethasone and kadsurenone attenuated the clearance response to PAF in a statistically significant manner, while indomethacin, OKY-046, and chlorpheniramine were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Transmural variation in autoregulation of right ventricular blood flow.
Authors: Yonekura S , Watanabe N , Downey H F
Published: June 2012

We examined transmurally the right coronary autoregulatory flow response to varied perfusion pressures in 11 anesthetized, open-chest dogs. Right coronary artery flow was measured electromagnetically, and its transmural distribution was defined with 15-micron radioactive microspheres. Heart rate, mean aortic blood pressure, right ventricular systolic pressure, end-diastolic pressure, and dP/dtmax were constant. At 100 mm Hg, subepicardial flow averaged 0.48 +/- 0.04 ml/min/g, and subendocardial flow averaged 0.56 +/- 0.05 ml/min/g. In contrast to the left coronary circulation, right coronary hypotension did not cause preferential subendocardial ischemia. As right coronary perfusion pressure was decreased from 100 to 40 mm Hg in five dogs, subepicardial and subendocardial flows were reduced similarly by 35-36%. As right coronary perfusion pressure was elevated from 100 to 150 mm Hg in six dogs, right ventricular subepicardial blood flow increased by 31%, whereas subendocardial blood flow increased by 70%. Right ventricular subendocardial-to-subepicardial flow ratios averaged 1.15-1.20 for perfusion pressures of 40 to 120 mm Hg, and they increased to 1.36 +/- 0.05 at 150 mm Hg. Right coronary artery autoregulatory closed-loop gain averaged 0.47 +/- 0.06 between 70 and 100 mm Hg and was greater than zero from 40 to 120 mm Hg. Between 120 and 150 mm Hg, gain fell to -0.15 +/- 0.10. Regional gain varied from 0.59 +/- 0.10 to 0.44 +/- 0.08 in subepicardium as pressure was decreased from 100 to 40 mm Hg. Subendocardial gains were similar to subepicardial gains over this pressure range.(ABSTRACT TRUNCATED AT 250 WORDS)