bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of dietary fish oil on mitochondrial function and response to ischemia
Authors: McMillin J. B. , Bick R. J. , Benedict C. R.
Published: December 2017

Dietary supplementation with marine oils may reduce the incidence of thromboembolism and decrease cardiac arrhythmias during myocardial ischemia. However, function of subcellular organelles isolated from hearts of these animals is impaired. In contrast to studies where marine oil was the sole source of dietary lipid in rats, menhaden oil was used to supplement standard canine laboratory chow. In mitochondria isolated from hearts of dogs fed this diet for 60 wk, the phospholipid content of arachidonic acid was replaced by the n-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Mitochondrial levels of linoleic and linolenic acids were not altered. The mitochondrial membrane phospholipid from the menhaden oil-fed dogs demonstrated increased cardiolipin. The respiratory function of heart mitochondria from the menhaden oil-supplemented dogs was not decreased from that of dogs on standard chow only. Increased succinate-supported respiration paralleled increased cytochrome oxidase in mitochondria from menhaden oil-fed dogs. The activity of the cardiolipin-dependent carnitine acylcarnitine translocase was unaffected. Myocardial ischemia decreased mitochondrial respiration in menhaden-fed dogs. Decreased palmitoylcarnitine-carnitine exchange following ischemia resulted from decreased matrix carnitine rather than decreased translocase activity. Normal levels of the essential fatty acids in the n-3-enriched mitochondrial membrane phospholipids appear to eliminate the mitochondrial dysfunction observed in essential fatty acid-deficient membranes.
Downregulation of blood and bone marrow neutrophils decreases expression of acute lung injury in sheep
Authors: McKenna P. J. , Rosolia D. L. , Ishihara Y. , Albertine K. H. , Staub N. C. , Gee M. H.
Published: December 2017

We have shown that infusion of zymosan-activated plasma (ZAP) in sheep causes acute lung injury and downregulates peripheral blood neutrophils in that elicited superoxide release is reduced for at least 24 h after the infusion. The present study was designed to test the following hypotheses: 1) peripheral blood neutrophils are representative of neutrophils marginated in the pulmonary circulation, 2) blood neutrophils are downregulated because neutrophils developing in bone marrow are similarly affected, and 3) downregulated neutrophils have a reduced capacity to produce tissue injury. In a series of experiments in 21 sheep, we showed that elicited superoxide release was similar in peripheral blood neutrophils and in marginated neutrophils washed out of the pulmonary vascular bed. Measurements of superoxide release from blood and bone marrow neutrophils collected 2-24 h after ZAP infusion revealed progressive downregulation with time and greater downregulation of superoxide release in bone marrow neutrophils compared with peripheral blood neutrophils. Finally, after downregulating peripheral blood neutrophils, subsequent infusion of ZAP in conscious sheep produced sequestration of neutrophils in the pulmonary circulation but failed to produce a sustained increase in lung lymph protein clearance. The results suggest that neutrophil downregulation, as measured in vitro, is expressed in vivo as reduced ability of neutrophils to produce tissue injury when challenged by an activating agent.
Left ventricular dimensions during hemorrhagic shock measured by biplane cinefluorography
Authors: Horton J. W. , Mitchell J. H.
Published: December 2017

The effects of hemorrhagic shock on left ventricular dimensions and volume were studied in 15 splenectomized dogs. A 42 +/- 1% decrease in total blood volume caused arterial blood pressure to fall 60% (from 120 +/- 5 to 48 +/- 3 mmHg); the first derivative of left ventricular pressure at a developed pressure of 40 mmHg fell 54% (from 1,930 +/- 94 to 905 +/- 93 mmHg/s, P < 0.05). Cardiac output fell 76% due to a 73% decrease in stroke volume; heart rate was unchanged at the end of hemorrhage but increased 50% during 3 h of sustained shock (from 110 +/- 6 to 166 +/- 8 beats/min, P < 0.05). During hemorrhage the septal-lateral and the anterior-posterior end-diastolic dimensions fell to a greater extent (7.8 mm, -21% and 7.0 mm, -18%, respectively) than the apex-base dimension (2.3 mm, -3.3%, P < 0.05). As a result of these dimensional changes, left ventricular end-diastolic volume fell 39% (from 48 +/- 2 to 28 +/- 1 cm3, P < 0.01). End-systolic dimensions fell in the same proportion during hemorrhage, resulting in a 30% decrease in end-systolic volume (from 30 +/- 2 to 21 +/- 1 cm3, P < 0.05). After 120 min of sustained shock, all end-diastolic dimensions remained unchanged, but end-systolic dimensions and volume increased significantly from values measured at end hemorrhage (P < 0.05), causing ejection fraction and stroke volume to fall to a greater extent. This study confirms a pronounced reduction in the minor axes of the left ventricle during hemorrhagic shock with subsequent reduction in ventricular function.
Intracavitary ultrasound impairs left ventricular performance: presumed role of endocardial endothelium
Authors: Gillebert T. C. , De Hert S. G. , Andries L. J. , Jageneau A. H. , Brutsaert D.
Published: December 2017

Pages H857–H865: T. C. Gillebert, S. G. De Hert, L. J. Andries, A. H. Jageneau, and D. Brutsaert. “Intracavitary ultrasound impairs left ventricular performance: presumed role of endocardial endothelium.” Because of typographical errors in the numbering of the references, some of the text citations were inconsistent. Therefore this entire article is reprinted at the end of this December issue.
Force-frequency relations and response to ryanodine in failing rabbit hearts
Authors: Ezzaher A. , el Houda Bouanani N. , Crozatier B.
Published: December 2017

Force-frequency relations were studied in an isolated-perfused rabbit heart model. Heart failure was induced by a double volume plus pressure overload. Studies were performed at the early stage of heart failure when basal ventricular function was not decreased. The normal positive staircase induced by pacing in control hearts (CH) was replaced by a negative staircase in failing hearts (FH) with an increase in end-diastolic pressure for increased heart rates in FH. Postpacing potentiation and postextrasystolic potentiation (PESP) were significantly reduced in FH as compared with CH. Ventricular function decreased by 60% in both CH and FH under ryanodine with similar dose-response curves. Postpacing and PESP disappeared under ryanodine in CH and in FH with a reversal of the negative staircase in FH. The abnormal force-frequency relations observed in heart failure are thus attributed to sarcoplasmic reticulum dysfunction. Basal ventricular function during spontaneous heart rate may be normal in the early stage of heart failure, but sarcoplasmic reticulum dysfunction produces abnormalities in ventricular function when heart rate is abruptly modified, particularly during tachycardia.
Desensitization to acetylcholine in single sinoatrial node cells isolated from rabbit hearts
Authors: Honjo H. , Kodama I. , Zang W. J. , Boyett M. R.
Published: December 2017

The negative chronotropic effect of acetylcholine (ACh) on the sinoatrial node fades in the continuous presence of ACh as a result of desensitization. We have investigated the mechanism underlying desensitization in single rabbit sinoatrial node cells using the whole cell patch clamp technique. The negative chronotropic effect resulting from the injection of a constant hyperpolarizing current faded. ACh activated an inwardly rectifying potassium current (iK,ACh), which faded in the continuous presence of ACh. ACh had no effect on “basal” L-type calcium current (iCa), but ACh decreased iCa, which had been potentiated by isoprenaline. This effect did not fade during a 2-min exposure to ACh. ACh decreased the hyperpolarization-activated current (i(f)). This effect again did not fade. These results suggest that desensitization of the negative chronotropic response to ACh is, in part, the result of the membrane hyperpolarization and, in part, the result of the fade of iK,ACh. These results also suggest that, whereas the activation of potassium current by ACh rapidly fades, the effects resulting from the inhibition of adenylate cyclase do not.
Divergent regulation of atrial natriuretic factor receptors in high-output heart failure
Authors: Garcia R. , Bonhomme M. C. , Schiffrin E. L.
Published: December 2017

We have investigated whether binding parameters and subtypes of glomerular, papillary, and vascular atrial natriuretic factor (ANF) receptors differ in rats with moderate high-output heart failure [aortocaval (AC) shunt] from their sham-operated controls. Body weight was lower and relative heart weight was higher in the AC shunt group than in the control group. Plasma renin activity (PRA) was also greater in AC shunt rats. Plasma COOH- and NH2-terminal ANF levels were higher in AC shunt animals than in their control counterparts. Total atrial ANF content was elevated in both the right and left atria of the AC shunt group. Glomerular and papillary ANF receptor density (Bmax) and ANF receptor affinity (Kd) were similar in both AC shunt and control rats. Vascular ANF receptor density and affinity were lower in AC shunt (Bmax = 65 +/- 13 fmol.mg protein; Kd = 467 +/- 52 pM) than in control rats (Bmax = 188 +/- 34 fmol.mg protein; Kd = 278 +/- 11 pM). Irreversible cross-linking of 125I-labeled ANF followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions and radioautography demonstrated that both high- and low-molecular weight receptors were unchanged in glomerular membranes and downregulated in vascular membranes from AC shunt animals. However, guanosine 3',5'-cyclic monophosphate (cGMP) production by the isolated glomeruli of AC shunt rats was lower than that of controls. We conclude that in the presence of elevated plasma ANF levels, glomerular, papillary, and vascular ANF receptors may be regulated differently.
Antiadrenergic effect of M-cholinoceptor stimulation on human ventricular contractility in vivo
Authors: Von Scheidt W. , Bohm M. , Stablein A. , Autenrieth G. , Erdmann E.
Published: December 2017

The relevance of an indirect negative inotropic effect of pharmacological or vagally mediated M-cholinoceptor stimulation in the human ventricle in vivo is unknown. The inotropic response induced by isoproterenol (isoprenaline, 20 ng.kg-1 x min-1), measured by m-mode echocardiography as the increase of fractional shortening in seven healthy subjects, was reduced from 17.1 +/- 4.3 to 9.1 +/- 3.9% (P < 0.01) by M-cholinoceptor stimulation using intravenous injection of 3.6 micrograms/kg carbachol. However, the inotropic response of increasing doses of isoprenaline (5-20 ng.kg-1 x min-1) did not differ in 13 healthy subjects without and after M-cholinoceptor blockade (atropine, 0.015 mg/kg i.v.); the increase of fractional shortening amounted to 17.4 +/- 4.0 vs. 19.5 +/- 4.8% (NS) in response to 20 ng.kg-1 x min-1 isoprenaline. It is concluded that pharmacological M-cholinoceptor stimulation of the human ventricle significantly reduces the inotropic response of beta-adrenoceptor stimulation. This may offer a new therapeutic approach to attenuate an increased cardiac sympathetic tone. However, M-cholinoceptor blockade, i.e., interruption of parasympathetic influences, does not augment the inotropic response to beta-adrenoceptor stimulation. Therefore, in healthy resting humans a physiological role of the parasympathetic nervous system in mediating an indirect negative inotropic effect on ventricular contractility seems to be absent.
Functional distribution of coronary vascular volume in beating goat hearts
Authors: Van der Ploeg C. P. B. , Dankelman J. , Spaan J. A. E.
Published: December 2017

Pages H770–H776: C. P. B. Van der Ploeg, J. Dankelman, and J. A. E. Spaan. “Functional distribution of coronary vascular volume in beating goat hearts.” Page H776: The acknowledgments should include the following: this study was supported by Grant 88.095 from the Netherlands Heart Foundation.
Changes in regional myocardial function and external work in exercising dogs with ischemia
Authors: Miyazaki S. , Goto Y. , Guth B. D. , Miura T. , Indolfi C. , Ross J.
Published: December 2017

Changes in regional myocardial work of the nonischemic wall and left ventricular (LV) asynchrony of the nonischemic wall during exercise-induced ischemia were examined in seven conscious dogs instrumented with a micromanometer for LV pressure measurement and sonomicrometers for control and ischemic wall thickness and LV external short and long axes. Ischemia was produced during steady-state exercise by a pneumatic constrictor on the left circumflex coronary artery. Time difference between peak thickening of control (anterior) and ischemic (posterior) walls was measured as an index of LV asynchrony. LV pressure-wall thickness loop area of both the control wall (LVP-CW loop) and ischemic wall was calculated as an index of regional myocardial external work. With ischemia during exercise, peak LV pressure decreased by 11%, and time difference of peak thickening in the two walls increased, accompanied by marked deformation of the LVP-CW loop during early relaxation, which was related to protodiastolic thickening of the ischemic wall. Thus, despite a significant increase in percent systolic thickening during exercise, loop area of control wall was not enhanced. These changes of the LVP-CW loop were confirmed by calculation of stress-strain loop areas as an additional index of regional myocardial external work but having true dimensions of work. Stress-strain loop area in the control wall during ischemic exercise showed a similar value to that during control exercise, thereby confirming lack of compensatory increase. Thus, during exercise-induced ischemia, regional myocardial external work in the normal region does not increase despite an increase in systolic wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)
Rapid stimulation of Ins (1,4,5)P3 production in rat aorta by NE: correlation with contractile state
Authors: Pijuan V. , Sukholutskaya I. , Kerrick W. G. , Lam M. , van Breemen C. , Litosch I.
Published: December 2017

Rapid stimulation of Ins(1,4,5)P3 production in rat aorta by NE: correlation with contractile state. Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H126-H132, 1993.--The isomeric composition of inositol phosphates generated in response to norepinephrine (NE) stimulation and the relationship of inositol phosphate production to release of intracellular Ca2+ as measured by contraction were characterized in rat aorta prelabeled with [3H]inositol. NE stimulated a rapid and transient increase in labeled D-myo-inositol 1,4,5-trisphosphate [Ins-(1,4,5)P3] levels. A maximal increase in labeled Ins(1,4,5)P3 occurred within 15 s of stimulation followed by a decline to control levels at 5 min. D-Myo-inositol 1,3,4-trisphosphate [Ins-(1,3,4)P3] and D-myo-inositol 1-monophosphate [Ins(1)P] levels also increased rapidly in response to NE. In contrast to the transient production of Ins(1,4,5)P3, Ins(1,3,4)P3 and Ins(1)P production was maintained in the presence of NE. Half-maximal stimulation of Ins(1,4,5)P3 production and Ca2+ release occurred at 0.3 microM NE, and maximal effects were obtained with 10 microM NE. The concentration-response curve and time course for production of Ins(1,4,5)P3 correlated with the neurotransmitter-induced Ca2+ release from intracellular stores, indicating that the level of Ins(1,4,5)P3 regulated the Ca(2+)-release mechanism. In the continued presence of NE, the intracellular pools did not completely refill with Ca2+ despite the return of Ins-(1,4,5)P3 levels to basal at 5 min. These results demonstrate that NE stimulates a rapid increase in Ins(1,4,5)P3 that correlates with contraction in Ca(2+)-free buffer. The reuptake of Ca2+ into intracellular stores is regulated by a mechanism that may not involve Ins(1,4,5)P3.
Effects of thyroid hormones on cardiac development in oculo
Authors: Torres A. , Tucker D. C.
Published: December 2017

Embryonic rat myocardium was grafted into the anterior eye chamber (in oculo) of adult host rats in a series of two experiments that studied the effects of thyroid hormones [triiodothyronine (T3) and thyroxine (T4)] on heart tissue developing without hemodynamic load. In each experiment, surgical sympathectomy of one eye chamber was used to define possible interactions between thyroid hormones and sympathetic innervation to the graft. In the first experiment, propylthiouracil (PTU, 20 mg/kg sc) greatly suppressed growth and beating rate of whole heart grafts, while excess T4 (0.1 mg/kg sc) transiently increased beating rate but not growth. In the second experiment, T3 (5 mg/21 days, slow-release pellet) failed to promote growth in ventricular grafts. However, the size of atrial grafts in surgically sympathectomized eye chambers was larger in T3-treated compared with control rats. T3 administration increased beating rate in ventricular grafts. In both experiments, thyroid hormone treatments were effective in increasing heart weight-to-body weight ratios in the host rats. The data suggest that exposure to normal levels of thyroid hormones may be necessary for optimal cardiac growth. The data also support the hypothesis that a hemodynamic load is required for thyroid hormone-induced cardiac growth.
Differential effects of nitric oxide synthesis inhibitors on vascular resistance and responses to acetylcholine in cats
Authors: Bellan J. A. , McNamara D. B. , Kadowitz P. J.
Published: December 2017

The effects of dose and the duration of treatment with N omega-nitro-L-arginine (L-NNA) and N omega-nitro-L-arginine methyl ester (L-NAME) on vascular resistance and the vasodilator response to acetylcholine (ACh) were investigated in the hindquarters vascular bed of the cat under constant flow conditions. L-NNA and L-NAME increase perfusion pressure and reduce vasodilator responses to ACh in the hindquarters vascular bed; however, the dose and time of exposure required to produce these effects are different. When L-NNA (2.5-5 mg/min) was infused into the hindquarters vascular bed, the increase in perfusion pressure was observed 10 min after onset of the infusion, at which time responses to ACh were not changed. The time of exposure for 50% of the maximal change in hindquarters perfusion pressure was significantly less than the time of exposure for 50% of the maximal decrease in the vasodilator response to ACh during infusion of L-NNA. A similar pattern was observed after the intravenous administration of 3-300 mg/kg L-NAME, while 1 mg/kg L-NAME produced a large but submaximal pressor response and lesser decreases in responses to ACh. The arginine analogues did not completely inhibit the vasodilator response to ACh in the hindquarters vascular bed, with a 30-fold increase in dose producing no additional blockade; however, L-NNA completely inhibited the relaxant response to ACh in the isolated aorta of the cat.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial responses to isoproterenol are altered by chronic alcoholism and infection
Authors: McDonough K. H. , Causey K. M.
Published: December 2017

Alcohol, consumed as 36% of the caloric intake for 8-10 wk, causes a potentiation of cardiac dysfunction induced by a second insult, sepsis. Because chronic alcoholism may attenuate the responsiveness of the myocardium to catecholamine stimulation, and because catecholamine support seems to be essential for the myocardium to generate an adequate cardiac output in sepsis, we hypothesized that the heart from the alcoholic septic rat would show a compromised inotropic responsiveness to catecholamines compared with the heart from the nonalcoholic septic rat. To test this hypothesis, rats were fed an ethanol-containing or control liquid diet for 8-10 wk and were then made septic with live Escherichia coli (10(10) E. coli) through a dorsal subcutaneous catheter. The next day, hearts were removed and perfused at a constant hydrostatic pressure, and a compliant balloon was placed in the left ventricule for measurement of pressure (LVP). Hearts were paced at 350-360 beats/min. Hearts were allowed to stabilize for 15 min, and then the response to a submaximal dose of isoproterenol (Iso) was measured. Hearts recovered for 30 min, at which time the response to a maximum dose of Iso was recorded. Basal (pre-Iso) LVP was lower in the control septic and alcoholic septic groups than in the control and alcohol groups. However, the maximum increase in LVP in response to Iso was greater in the two septic groups than in the two nonseptic groups. The peak LVP in response to Iso was similar in the control, septic, and alcoholic septic groups, and was significantly greater than in the alcohol group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine 3',5'-cyclic monophosphate attenuates neutrophil-mediated increase in endothelial permeability
Authors: Siflinger-Birnboim A. , Bode D. C. , Malik A. B.
Published: December 2017

We studied the effects of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) and cholera toxin (CT) on 125I-labeled albumin flux across confluent monolayers of bovine pulmonary microvessel endothelial cells (BMVEC) grown on polycarbonate filters (10(5) BMVEC/filter). 8-BrcAMP and CT increased endothelial adenosine 3',5'-cyclic monophosphate (cAMP) concentrations about twofold. Polymorphonuclear leukocytes (PMN) were layered on BMVEC monolayers (ratio of 10:1) and activated with phorbol 12-myristate 13 acetate (PMA; 5 x 10(-9) M). Transendothelial 125I-labeled albumin clearance rate was measured to determine the endothelial permeability alterations. Activation of PMN in control monolayers resulted in an increase in transendothelial 125I-labeled albumin clearance rate from 0.090 +/- 0.011 to 0.37 +/- 0.06 microliters/min (P < 0.01). Treatment of endothelial monolayers with 8-BrcAMP (10(-3) M) significantly attenuated the increase in endothelial permeability after PMN activation (transendothelial 125I-labeled albumin clearance rate increased to 0.19 +/- 0.03 microliters/min; P < 0.01). Pretreatment of BMVEC monolayers with CT (10(-8) M) for 3 h before PMN activation prevented the PMN-mediated increase in endothelial permeability (125I-labeled albumin clearance rate only increased to 0.13 +/- 0.018 microliters/min). To simulate the effect of PMN activation, hydrogen peroxide (H2O2) was added directly onto BMVEC; both 8-BrcAMP and CT were shown to reduce the H2O2-mediated increase in endothelial permeability. 8-BrcAMP and CT pretreatment did not prevent PMN adhesion to BMVEC monolayer and superoxide anion and H2O2 production after PMA activation of PMN. We conclude that increased endothelial cAMP concentration prevents PMN-mediated endothelial injury by an action of the cyclic nucleotide on endothelial cells.
Properties of veratridine-modified single Na+ channels in guinea pig ventricular myocytes
Authors: Sunami A. , Sasano T. , Matsunaga A. , Fan Z. , Swanobori T. , Hiraoka M.
Published: December 2017

Modification of single Na+ channels by the alkaloid neurotoxin veratridine was investigated in guinea pig ventricular myocytes using the cell-attached configuration of the patch-clamp technique. Pipette application of veratridine (50 microM) induced long-lasting openings with two different single-channel conductances of 7.6 and 3.0 pS, in addition to normal type of short openings with a single-channel conductance of 16 pS. The veratridine-modified high- and low-conductance channels appeared commonly, and they could coexist with the normal one in the same patch. The open-time distributions for the high- and low-conductance channels could be fitted by a single exponential. The mean open time for the high- and low-conductance events ranged between 19.1 ms at -120 mV and 86.0 ms at -10 mV and between 4.5 ms at -120 mV and 16.2 ms at -10 mV, respectively. The closed-time distributions for the two conductance channels consisted of at least two components, and their values and voltage dependence were similar. External Ca2+ block resulted in an apparent reduction of unitary current amplitudes with a similar voltage dependence and affinity for Ca2+ in the high- and low-conductance channels. However, the low-conductance channel was more resistant to tetrodotoxin than the high one. The probability of simultaneous occurrence of the high and low events was equal to the product of the probabilities of occurrence of the high event times that of the low event. Furthermore, we observed modified channel openings after a normal opening for the two conductance channels and a modified one turning into a normal one for the high-conductance channel. It is concluded that veratridine induces the two different types of modified Na+ channels in cardiac myocytes and these are correlated with normal openings.
Cultured adult cardiac myocytes maintain protein synthetic capacity of intact adult hearts
Authors: Clark W. A. , Rudnick S. J. , Simpson D. G. , LaPres J. J. , Decker R. S.
Published: December 2017

Previous studies have shown that the rates of protein synthesis observed in embryonic and neonatal heart cells in culture are as much as nine times greater than the rates of synthesis observed in the intact adult heart either in situ or in isolated perfusion studies. This study addressed whether adult cardiomyocytes in long-term culture maintain the protein synthetic capacity of the adult myocardium or, rather, whether the protein synthetic capacity expands or falls as adult cardiac myocytes progress in culture. Protein synthesis was evaluated in isolated adult feline cardiomyocytes maintained in serum and insulin-supplemented medium for up to 53 days in vitro. With the use of both pulse- and saturation-labeling techniques it was determined that the rate of protein synthesis in adult cardiomyocytes was maintained at a level very close to that observed in the intact heart for over 1 mo in culture. Saturation-labeling studies indicate a fractional rate of protein synthesis at 6.1%/day and an absolute synthesis rate of 1,300 nmol leucine incorporated.g protein-1.h-1. Pulse-labeling studies revealed an initial increase in protein synthesis rates during adaptation to culture and a further increase after activation of beating and cellular hypertrophy.
Mesenteric lymph flow responses to splanchnic nerve stimulation in sheep
Authors: Thornbury K. D. , Harty H. R. , McGeown J. G. , McHale N. G.
Published: December 2017

The main mesenteric lymph duct was cannulated in halothane-anesthetized sheep, and continuous recordings were made of lymph flow, lymphatic pressure fluctuations, and arterial pressure. Stimulation of the left greater splanchnic nerve at frequencies of 1, 4, and 10 Hz caused lymph flow to increase by 30 +/- 9, 74 +/- 19, and 80 +/- 21%, respectively. Lymphatic contraction frequency and mean arterial pressure showed graded increases in response to increasing stimulus frequencies. These responses were reduced after intravenous infusion of phentolamine, suggesting that they were mediated by alpha-adrenoceptors. Lymph protein concentration remained unchanged during stimulation, suggesting that lymph formation in the nodes was not responsible for the increased lymph flow. The lymph flow response during 20 min of stimulation was biphasic, showing an initial transient increase followed by a depression to 45% of control. It is concluded that the initial increase in flow may be explained by stimulation of the lymphatic pump by nerves and/or circulating catecholamines, while the subsequent decrease reflected a reduction in lymph formation.
Thrombin inhibits induction of nitric oxide synthase in vascular smooth muscle cells
Authors: Schini V. B. , Catovsky S. , Durante W. , Scott-Burden T. , Schafer A. I. , Vanhoutte P. M.
Published: December 2017

Experiments were designed to examine whether thrombin affects the production of nitric oxide-like factor(s) evoked by interleukin-1 beta (IL-1 beta) in cultured smooth muscle cells from the rat aorta. IL-1 beta stimulated the release of nitrite (a stable oxidation product of nitric oxide) from cultured smooth muscle cells. Thrombin inhibited in a concentration-dependent manner the release of nitrite caused by IL-1 beta. The inhibition was prevented by hirudin (a thrombin inhibitor) and required the presence of thrombin before or during the induction period. Under bioassay conditions, the perfusates from columns containing IL-1 beta-treated smooth muscle cells relaxed detector rat aortic rings without endothelium. The addition of IL-1 beta-treated smooth muscle cells to suspensions of indomethacin-treated platelets inhibited their aggregation. Control untreated smooth muscle cells or cells treated with thrombin alone did not have such effects. The treatment of smooth muscle cells with IL-1 beta in combination with thrombin blunted both the relaxing activities of the perfusates under bioassay conditions and the inhibition of platelet aggregation. These observations indicate that thrombin inhibits the production of nitric oxide-like factor(s) evoked by the inducible nitric oxide synthase in cultured smooth muscle cells from rat aorta.
Phenylephrine and endothelin differentially stimulate cardiac PI hydrolysis and ANF expression
Authors: McDonough P. M. , Brown J. H. , Glembotski C. C.
Published: December 2017

In ventricular myocytes, phenylephrine (PE) and endothelin (ET) stimulate phosphoinositide (PI) hydrolysis, cell growth, and expression of several genes [e.g., atrial natriuretic factor (ANF)] often associated with cardiac hypertrophy. In this study the production of inositol monophosphate (InsP) and diglyceride (DG), both products of PI hydrolysis, and ANF were monitored during long-term exposure (up to 72 h) to PE or ET. For PE, InsP production increased and continued unabated throughout the time course; DG levels also increased and remained elevated, and similar rates of ANF production were observed from 24 to 72 h. For ET, the initial InsP and DG responses equaled those to PE, but diminished by 24 h. ET-stimulated ANF production equaled the PE response at 24 h but subsided by 72 h. Adding PE to cells previously desensitized to ET elicited maximal InsP formation, indicating the desensitization was ET specific. These data emphasize that while phenylephrine and endothelin have similar initial effects on cardiac second messenger production and ANF expression, hormonally specific patterns develop over extended periods of exposure.
A reappraisal of ventricular fibrillation threshold testing
Authors: Cha Y. M. , Peters B. B. , Birgersdotter-Green U. , Chen P. S.
Published: December 2017

To test the hypothesis that ventricular fibrillation (VF) threshold testing is a probability function, 12 open-chest dogs were studied. The VF thresholds were tested by scanning the T wave with either the single premature stimulus method or with the train stimulus method. The dose-response curve method was used to determine the probability of inducing VF with different strengths of premature stimulation. Conventional methods and up-down methods were also used to test the VF threshold. The results showed that the VF threshold is a probability function. The conventional method VF threshold for the single premature stimulus and for the train stimulus methods corresponded to the current strength associated with a 23.4 +/- 13.2 and a 33.2 +/- 19.5% probability of VF (P < 0.05), respectively. In comparison, the triplicate VF threshold determined by the up-down algorithm method resulted in values that were not significantly different from a 50% probability of inducing VF, with a good correlation (r = 0.90, P < 0.001 for single and r = 0.89, P = 0.003 for the train stimulus method). We conclude that: 1) The VF threshold is a probability function, and 2) the triplicate VF threshold determined by the up-down algorithm method is the best alternative to the dose-response curve method in estimating 50% probability of inducing VF.
Coronary arterial inflow impediment during systole is little affected by capacitive effects
Authors: Bouma P. , Sipkema P. , Westerhof N.
Published: December 2017

During cardiac contraction coronary arterial inflow is impeded, whereas venous flow is augmented. These effects are assumed to be caused by diameter reductions of intramyocardial blood vessels. The reduction in vascular diameter (and thus vascular volume) during contraction increases coronary resistance and/or decreases back pressure so that flow decreases and the rate of change of volume results in a capacitive flow. The aim of this study was to estimate the contribution of capacitive flow to total coronary inflow impediment. Isolated blood-perfused (100 mmHg and constant), maximally vasodilated, ryanodine-pretreated rat hearts (n = 8) with intraventricular balloons were used. The coronary inflow impediment during isovolumic beats at a heart rate of 2–3 Hz (dynamic contractions) and during prolonged systoles obtained by fast pacing (static contractions, no capacitive flow impediment) were compared. Changing left ventricular balloon volume enabled us to vary left ventricular pressure and to relate systolic flow to systolic left ventricular pressure. We found that for the same contractility (expressed in terms of systolic pressure-volume relationship and maximal elastance) and same left ventricular pressure, the ratio of coronary inflow impediment in dynamic and static contractions is not significantly different from unity (P < 0.005). This implies that under our experimental conditions coronary inflow impediment in dynamic contractions is little affected by capacitive effects.
Initiation of cardiac hypertrophy in response to thyroxine is not limited by age
Authors: Tomanek R. J. , Butters C. A. , Zimmerman M. B.
Published: December 2017

We examined the role of age in the initiation of thyroxine-induced (T4) cardiac hypertrophy. T4 (0.4 mg/kg sc) was administered to prepubescent (2 mo), young adult (6 mo), and senescent (24 mo) Fischer 344 rats for 4 days. While significant increases in left ventricular (LV) mass and RNA/LV were evident at 4 days in all T4-treated groups, the elevation in RNA/LV occurred earlier (2 days) in the senescent group. A 0.2-mg/kg dose of T4 elevated RNA values within 24 h in senescent, but not in prepubescent, rats. LV norepinephrine levels were measured to determine whether it plays a role in this model of cardiac hypertrophy. When synthesis of this catecholamine was blocked with alpha-methyl-p-tyrosine, tissue levels fell significantly in all groups, and the decrement was similar in T4-treated and control rats in the two younger groups. We conclude that: 1) the initiation of T4-induced cardiac hypertrophy is not compromised in senescent rats, 2) hearts of senescent rats respond earlier and to a lower dose of T4 than young rats, and 3) the cardiac hypertrophy that occurs in hyperthyroidism is not due to enhanced levels of available cardiac norepinephrine.
Constrained optimization of ventricular efficiency in normal and failing hearts
Authors: Nevo E.
Published: December 2017

Optimal ventriculoarterial coupling, in terms of maximal energetic efficiency, was recently analyzed by analytic and experimental studies. Whereas for normal hearts the analytic predictions agreed well with measured data, failing hearts were found to operate remote from the predicted optimal conditions. An analysis of optimal coupling is developed in the present study, based on constrained optimization. The constraints are based on the concept that the system must comply with physiological requirements (restrictions) under all conditions. Optimization using the mean pressure as a constraint yielded results similar to the unconstrained case in the normal heart but different with the failing heart: in the failing heart the optimal arterial elastance was found to be larger than the ventricular elastance, whereas the opposite was predicted by the unconstrained optimization. If an additional constraint on the end-systolic pressure is used, a unique solution of the coupling state is obtained. The predicted coupling ratio was found to match published data from normal subjects and heart failure patients, where in the latter group it was found to be remote from the optimal efficiency state. An increase in ventricular contractility and reduction in afterload were shown to shift the nonoptimal coupling state toward the optimal one. This prediction complies with the use of inotropic agents and vasodilators as the mainstay of heart failure treatment. This study may provide a convenient framework of analysis for the assessment of the ventriculoarterial coupling and for the evaluation of the cardiovascular effects of specific drug treatments.
Progressive feline pressure-overload: noninvasive assessment correlates with abnormalities in single cells
Authors: Pollack P. S. , Bailey B. A. , Budjak R. , Fernandez E. , Houser S. R.
Published: December 2017

Serial echocardiography and Doppler were used to monitor the progression of pressure-overload produced by banding the ascending aortas of young cats. The peak Doppler gradient across the band increased (as the animals grew in size) from 42 +/- 4.2 mmHg at 1 wk to 78 +/- 4.5 mmHg at 2-3 mos. Echocardiographic measurements of septal wall thickness increased significantly at 1 wk. Global ventricular function was unaltered in banded cats versus shams at each time point. However, in the subgroup of animals with an aortic-constricted area of < 0.025 cm2 at 1 wk, fractional shortening decreased by 40% at 2-3 mos. Contractile abnormalities were present in isolated myocytes from hypertrophied hearts. Mechanical function was more profoundly depressed in cells from hearts with echocardiographic evidence of ventricular decompensation. Echocardiographic and Doppler studies assessed cardiac size and function and identified indexes predictive of global and cellular myocardial dysfunction. The use of noninvasive techniques as a predictor of failure makes the feline model of progressive left ventricular pressure-overload useful for studies of cellular and molecular factors regulating not only the development of cardiac hypertrophy but also the transition from compensated hypertrophy to myocardial failure.
Albumin modulation of paracellular permeability of pig vena caval endothelium shows specificity for pig albumin
Authors: Ramirez-Vick J. , Vargas F. F.
Published: December 2017

We measured endothelial hydraulic conductivity (Lp,e) and endothelial electrical resistance (Re) of pig vena cava in pig serum albumin (PSA) and bovine serum albumin (BSA) to determine whether specificity for the autologous albumin found in dog vena cava is a general property of mammalian endothelium. Pigs were anesthetized with pentobarbital sodium for surgical removal of the thoracic inferior vena cava. A vessel segment was placed as a membrane separating two compartments in a chamber. Vessels kept in 30 mg/ml BSA had Lp,e values of 1.30 +/- 0.81 x 10(-7) cm.s-1.cmH2O-1 (n = 9) and Re values of 13.8 +/- 2.6 omega.cm2 (n = 3). Vessels kept in PSA had Lp,e values of 0.257 +/- 0.125 x 10(-7) cm.s-1.cmH2O-1 (n = 5) and Re values of 21 +/- 6.3 omega.cm2 (n = 4). The differences between Lp,e and Re in BSA and PSA were statistically significant (P < 0.05). In vessels kept in PSA, switching to BSA caused a doubling of Lp,e. Lower Lp,e and higher Re in PSA as compared with those in BSA suggest that specificity for the autologous albumin is a general phenomenon in mammalian endothelium and that albumin binding to specific sites is associated with its permeability effect.
Molecular determinants of shear rate-dependent leukocyte adhesion in postcapillary venules
Authors: Bienvenu K. , Granger D. N.
Published: December 2017

Recent studies have demonstrated that reductions in shear rate are associated with the recruitment of rolling and adherent leukocytes in postcapillary venules. The objective of this study was to define the molecular determinants of the leukocyte-endothelial cell adhesive interactions elicited by low venular shear rates. Three different monoclonal antibodies (MAb) were used to assess the relative contributions of CD18 (MAb R15.7), intercellular adhesion molecule 1 (ICAM-1; MAb RR1/1), and P-selectin (MAb PB1.3) to shear rate-dependent leukocyte rolling and adherence. Erythrocyte velocity, vessel diameter, leukocyte adherence, and leukocyte rolling velocity were monitored in cat mesenteric venules (25-40 microns diam). Venular shear rate was varied in a stepwise fashion by graded occlusion of an arterial circuit between the femoral and superior mesenteric arteries. Shear rates were maintained at each level for a period of 2 min. The MAbs directed against either CD18 or ICAM-1, but not P-selectin, significantly attenuated the recruitment of adherent leukocytes normally observed at low shear rates. However, the MAb against P-selectin, but not CD18 or ICAM-1, was effective in reducing the recruitment of rolling leukocytes elicited by low shear rates. These observations indicate that shear rate-dependent recruitment of adherent leukocytes involves an interaction between CD11/CD18 on leukocytes and ICAM-1 on vascular endothelium, while P-selectin on endothelial cells mediates, at least part of, the recruitment of rolling leukocytes.
Albumin fraction and measurement of total protein concentration
Authors: Peterson B. T. , Tate R. W.
Published: December 2017

The standard curve of a typical colorimetric assay for total protein is often nonlinear and dependent on the albumin fraction of the protein standard. We developed a simple mathematical transformation to make the standard curve linear and a computational method to correct for differences in albumin concentrations among the samples. This method uses data from total protein assays on two sets of standards (albumin and gamma globulin) and provides accurate measures of total protein over the full range of albumin fractions. Comparison of this two-standard method with the a method that uses only albumin as a standard shows that this method prevents physiologically significant overestimations in total protein concentration and calculated protein osmotic pressure differences in the lungs.
Extracellular potassium activity and cerebral blood flow during moderate hypoglycemia in anesthetized dogs
Authors: Sieber F. E. , Wilson D. A. , Hanley D. F. , Traystman R. J.
Published: December 2017

Moderate hypoglycemia (MH) may be associated with blunting of cerebral hypocapnic vasoconstriction. Coincident with this change, electroencephalogram (EEG) flattening occurs. Previous reports show that brain extracellular potassium activity ([K+]o) increases in association with the onset of isoelectricity during severe hypoglycemia and that K+ increases cause pial vessel vasodilation. Using a model of MH, we tested the hypothesis that increases in [K+]o (approximately 15 mM) correlate with blunting of cerebral hypocapnic vasoconstriction. Cerebral blood flow (CBF), [K+]o, and EEG were measured during normocapnia [arterial Pco2 (Paco2) = 35 Torr)] and hypocapnia (PaCO2 = 15 Torr) in MH (< 2 mM) and normoglycemic dogs. During MH, increases in [K+]o occurred in association with EEG flattening (from 4.2 +/- 0.5 to 13.8 +/- 3.8 mM). During normoglycemia and MH without [K+]o elevations, hypocapnic vasoconstriction occurred. [K+]o elevations with MH were associated with increased CBF and decreased vascular resistance (146 +/- 5 and 42 +/- 2% of control, respectively) during normocapnia, and blunting of cerebral hypocapnic vasoconstriction (93 +/- 16% normocapnic control) when [K+]o increased during hypocapnia. This study shows that increases in [K+]o during MH are necessary for both normocapnic increases in CBF and blunting of cerebral hypocapnic vasoconstriction. Increases in [K+]o may represent a mechanism for decreases in cerebral vascular resistance during MH.
Measurement of hydraulic conductivity in isolated arterioles of rat brain cortex
Authors: Kimura M. , Dietrich H. H. , Huxley V. H. , Reichner D. R. , Dacey R. G.
Published: December 2017

We have developed a new method for quantification of arteriolar hydraulic conductivity (Lp) from isolated rat brain vessels. The volume flux of water per unit surface area across the arteriole wall (Jv/S) was assessed from measurements of silicon oil drop movement within an occluded vessel at two to three pressures (between 20 and 70 mmHg); the Lp was derived from the slope of the relationship between Jv/S and applied pressure. Lp was measured in isolated cerebral arterioles 1) at room temperature (22 degrees C) without spontaneous vessel tone (control Lp; n = 11), 2) at room temperature with 10(-4) M adenosine (n = 5), and 3) at 37 degrees C with vessels dilated submaximally with 10(-4) M adenosine (n = 6). Lp at 22 degrees C without adenosine was 13.2 +/- 4.2 x 10(-9) (+/- SE) cm.s-1.cmH2O-1 for all vessels studied. Lp values ranged from 1.2 to 44.1 x 10(-9) cm.s-1.cmH2O-1 with a median value that was 5.9 x 10(-9) cm.s-1.cmH2O-1. Lp increased significantly (on average, 2.6-fold) with adenosine at 37 degrees C but not with adenosine at 22 degrees C. Control Lp bore no relationship to either the development of spontaneous tone or the diameter response to pH change, two recognized indicators of vessel viability.
Heterogeneous effects of nitroglycerin on the conductance and resistance coronary arterial vasculature
Authors: Zhang J. , Somers M. , Cobb F. R.
Published: December 2017

This study assessed the effects of nitroglycerin (NTG) on epicardial conductance and blood flow regulatory vessels over a wide dose range (10(-10) to 10(-6) mol NTG) in chronically instrumented awake mongrel dogs. NTG bolus injection caused dose-dependent dilation of both conductance and blood flow regulatory vessels. The dose-response curves for blood flow were shifted markedly to the right of the response of conductance vessels so that the proximal vessels had reached 50% of their maximum vasodilation before significant increases in blood flow. The calculated doses for half-maximal vasodilation were 2.8 x 10(-8) and 7.8 x 10(-7) mol for conductance and blood flow, respectively, indicating an approximately 39 times greater sensitivity of the proximal vessels to NTG. NTG had a striking dose-dependent effect on the duration of vasodilation of conductance vessels but did not have a dose-dependent duration effect on coronary blood flow. Although acetylcholine demonstrated a dose-dependent response effect on the conductance vessels similar to NTG, the conductance and resistance vessels demonstrated the same sensitivity to acetylcholine, supporting the view that differences in the mechanics of vasodilation of the two vessel segments did not account for the differential sensitivities to NTG.
Transient depression of responses to sympathetic nerve stimulation overlying a subendocardial infarct
Authors: Martins J. B. , Cable D. G. , Rath T. E. , Hingtgen L. , Horn M. , Lund D. D.
Published: December 2017

In previous work, the normal epicardial rim overlying a subendocardial infarct was demonstrated to be parasympathetically denervated. In the present study, we determined responses of effective refractory period (ERP) in this rim during sympathetic nerve stimulation (SNS). Eighteen dogs were studied 1-3 days after a 1-h or permanent coronary artery occlusion (group I). SNS shortened ERP in sites basal, septal, and lateral in the rim by 8 +/- 2, 7 +/- 2, and 7 +/- 2% (SE), respectively, which were similar to sites remote from the infarct (10 +/- 1%). These results were not altered by site of infarction or by atropine administration. To eliminate dissection of the coronary vessel and spontaneous ventricular tachycardia, 19 dogs were studied 6 h after a permanent bead embolization of a coronary artery (group II). In contrast to group I, ERP shortening in the rim sites of group II was depressed (3 +/- 3, 0 +/- 2, and 1 +/- 2%, respectively) compared with remote sites (10 +/- 1%, P < 0.05). In this group, collateral blood flow in the rim was no different than remote epicardium before and during SNS, and norepinephrine shortened ERP in the rim equivalent to remote sites. In an additional 31 animals (group III), the alteration in ATP-dependent K+ channel function was evaluated. Pretreatment with glyburide (an ATP-dependent K+ channel blocker) preserved ERP response to SNS (9 +/- 1% shortening of ERP vs. 12 +/- 2% at baseline) compared with only 3 +/- 0% shortening of ERP with vehicle (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)