bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of hypercapnic acidemia on anisotropic propagation in the canine ventricle.
Authors: Vorperian V R , Wisialowski T A , Deegan R , Roden D M 
Published: June 2012

BACKGROUND
Impulse propagation in the ventricle depends on both sodium channel availability and cell-to-cell coupling through gap junctions. Sodium channel block has been shown to depress conduction velocity (theta) more longitudinal (LONG) to than transverse (TRANS) to fiber orientation. Because exposure to CO2 produces intracellular acidosis and decreased gap junction conductance in vitro, we tested the hypothesis that increased PCO2 would result in preferential depression of transverse conduction in vivo.

METHODS AND RESULTS
In anesthetized dogs, when atrial pH was reduced to 6.70 +/- 0.04 by increasing the fraction of inhaled CO2 to 40%, theta TRANS fell from 0.23 +/- 0.04 to 0.19 +/- 0.02 m/s (-16 +/- 8%, P < .03), while theta LONG was unchanged (-3 +/- 7%, P = NS). In contrast, with the same degree of acidemia produced by HCl infusion, only theta LONG fell (-8 +/- 7%), coincident with a rise in serum K+.

CONCLUSIONS
The observed effect of CO2 on propagation in the intact heart is consistent with its previously described in vitro actions to uncouple cell-to-cell communication and may provide a model to study the role of cell-to-cell coupling in normal and abnormal propagation.
Effects of enalapril versus losartan on regression of volume overload-induced cardiac hypertrophy in rats.
Authors: Ruzicka M , Yuan B , Leenen F H 
Published: June 2012

BACKGROUND
The role of nonhemodynamic cardiac trophic mechanisms differs not only between different models of cardiac hypertrophy but also within the same model for development versus maintenance of cardiac hypertrophy. Our previous studies pointed to a major role for the renin-angiotensin system (RAS) as a cardiac trophic stimulus in the remodeling of the heart in response to volume overload by aortocaval shunt or minoxidil treatment.

METHODS AND RESULTS
In the present study, we evaluated the effects of blockade of the RAS by the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor blocker losartan on left ventricular (LV) and right ventricular mass and LV dilation in relation to changes in central hemodynamics during the maintenance of minoxidil and aortocaval shunt-induced cardiac hypertrophy. Both blockers similarly decreased LV end-diastolic pressure (LVEDP) and LV peak systolic pressure, whereas cardiac output remained unchanged in both models of volume overload. This suggests a major contribution of improved LV performance and decreased afterload to the decrease in cardiac preload by the two blockers rather than decreased venous return. Both blockers reversed LV hypertrophy in parallel to their effects on LVEDP in both models of volume overload. In minoxidil-treated rats, the extent of reversal in LV mass and dilation by the two blockers was similar to "spontaneous regression" after discontinuation of minoxidil treatment.

CONCLUSIONS
These results indicate that in contrast to the development phase of cardiac hypertrophy, the RAS does not contribute to the maintenance of volume overload-induced cardiac hypertrophy in these two models via direct cardiac trophic effects. The RAS, however, maintains cardiac hypertrophy indirectly by contributing to the persistence of high filling pressures.
Fluid restitution and blood volume redistribution in anesthetized rabbits in response to vasoactive drugs.
Authors: Anderson S M , Rich G F , Roos C , Lee L P , Lee J S 
Published: June 2012

BACKGROUND
Vasoactive drugs could alter the fluid restitution from the tissue and redistribute blood volume between the macrocirculation and microcirculation.

METHODS AND RESULTS
With bolus injections of vasoactive drugs in anesthetized rabbits, we measured the changes in blood and plasma density for the determination of the volume of restitution and redistribution. Epinephrine 3.5 micrograms/kg caused a fluid loss to the tissue, leading to a transient decrease in total blood volume by 2.30 mL/kg. Because of blood volume redistribution, the peak volume reduction was accompanied by a volume reduction of 0.81 mL/kg from the macrocirculation and 1.49 mL/kg from the microcirculation. Phenylephrine 70 micrograms/kg caused a peak reduction in total blood volume of 1.40 mL/kg (with 0.41 mL/kg from macrocirculation and 0.99 mL/kg from microcirculation). Nitroprusside 7 micrograms/kg increased the blood volume by 1.44 mL/kg (0.83 mL/kg macro and 0.61 mL/kg micro), nitroglycerin 7 micrograms/kg by 1.48 mL/kg (0.97 mL/kg macro and 0.51 mL/kg micro), and isoproterenol 7 micrograms/kg by 2.07 mL/kg (0.68 mL/kg macro and 1.39 mL/kg micro). All plasma (or blood) density changes measured for the five drugs (with epinephrine, phenylephrine, and nitroprusside done over a wide dosage range) correlated linearly with the drug-induced changes in arterial pressures.

CONCLUSIONS
These results indicate that vasoactive drugs alter total blood volume and the volume of microcirculation and macrocirculation.
Preferential vasoconstriction to cysteinyl leukotrienes in the human saphenous vein compared with the internal mammary artery. Implications for graft performance.
Authors: Allen S P , Chester A H , Dashwood M R , Tadjkarimi S , Piper P J , Yacoub M H 
Published: June 2012

BACKGROUND
Platelet aggregation with the release of their vasoactive mediators is an important factor contributing to the patency of coronary bypass grafts. However, the role of leukocyte-derived mediators on graft performance is unclear. Leukotrienes (LTs) are proinflammatory mediators released from a variety of leukocytes that possess both vasoactive and mitogenic properties. We have therefore compared the effects of the cysteinyl LTs (C4, D4, and E4) on the human saphenous vein (SV) and human internal mammary artery (IMA).

METHODS AND RESULTS
Human SVs from 43 patients (mean age, 58 years) and IMAs from 33 patients (mean age, 57 years) were obtained from individuals undergoing coronary artery bypass surgery for coronary artery disease. The samples were set up in organ baths to record changes in vessel wall tension. In undistended SVs the cysteinyl LTs elicited concentration-dependent contractions. The Emax for LTE4 (4.23 +/- 1.0 mN; n = 6) was significantly less than that observed with either LTC4 (25.7 +/- 4.01 mN; n = 7; P < .001) or LTD4 (26.19 +/- 3.16 mN; n = 7; P < .001). In addition, the LTD4 receptor antagonist ICI 198615 (30 nmol/L) significantly inhibited the LTD4 concentration-response curve but not the LTC4 responses. Furthermore, treatment of the SV with acivicin (0.05 mmol/L), a gamma-glutamyl transpeptidase inhibitor, caused a significant rightward displacement of the LTC4 concentration-response curve. In contrast, LTC4 and LTD4 produced a response in IMAs from only 3 of 29 patients. LTC4 and LTD4 produced small contractions, of which the maximum responses were 3.28 +/- 1.92 mN (n = 5) and 3.12 +/- 1.38 mN (n = 5). LTE4 produced no responses in the IMA. Experiments in which the SV was pretreated with L-NG-monomethyl-L-arginine (L-NMMA; 10(-4) mol/L) or indomethacin (10(-5) mol/L) or was denuded of endothelium had no significant effect on the Emax values for LTE4. Also, the IMA remained unresponsive to cysteinyl leukotrienes after treatment with L-NMMA or indomethacin or endothelium removal. In vitro autoradiography localized specific [3H]-LTC4 and [3H]-LTD4 binding sites (putative receptors) to the smooth muscle cells of both SV and IMA, with greater binding to the SV.

CONCLUSIONS
Our data show that there is a preferential contraction to LTs in SV compared with IMA. This difference in smooth muscle cell reactivity to the cysteinyl LTs suggests that endogenous LT production from circulating or infiltrating leukocytes may be an important factor contributing to graft function.
Induction of acidic fibroblast growth factor and full-length platelet-derived growth factor expression in human cardiac allografts. Analysis by PCR, in situ hybridization, and immunohistochemistry.
Authors: Zhao X M , Yeoh T K , Frist W H , Porterfield D L , Miller G G 
Published: June 2012

BACKGROUND
Further understanding of cardiac allograft vasculopathy (CAV) is needed to improve long-term survival after cardiac transplantation. The diffuse hyperplasia of coronary intima characteristic of CAV suggests that growth factors may play a role in the development of CAV. Fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) are potent mitogens for smooth muscle cells (SMCs), and PDGF is an important cofactor in the pathogenesis of native coronary atherosclerosis.

METHODS AND RESULTS
Reverse transcriptase/polymerase chain reaction (RT/PCR), in situ hybridization, and immunohistochemistry were used to determine whether transplantation results in increased cardiac expression of acidic (a) FGF, basic (b) FGF, and PDGF-A and -B chains. Sixty-eight myocardial biopsies from 36 heart transplant recipients and 7 normal hearts were analyzed by PCR. aFGF mRNA was present in 54 of 61 allograft biopsies and was not found in any normal heart. In situ hybridization and immunohistochemistry demonstrated diffuse, intense expression of a FGF mRNA and protein in allograft biopsies, predominantly in myocytes and vascular walls. Only scattered aFGF expression was observed in normal hearts. mRNA for the full-length isoform of PDGF-A chain was found in 43 of 61 allograft biopsies and was not detected in any normal heart. In situ hybridization and immunohistochemistry confirmed that full-length PDGF-A chain mRNA and PDGF protein were present in myocytes and vascular walls.

CONCLUSIONS
Expression of aFGF and PDGF-A chain is significantly increased in cardiac allografts. Cardiac myocytes and vascular walls are the predominant sources of aFGF and PDGF. Diffuse expression of these growth factors in cardiac allografts may be important in the pathogenesis of CAV.
Determinants of coronary artery reactivity in premenopausal female cynomolgus monkeys with diet-induced atherosclerosis.
Authors: Williams J K , Shively C A , Clarkson T B 
Published: June 2012

BACKGROUND
The purpose of this study was to identify determinants of coronary artery reactivity among premenopausal female monkeys. Estrogen replacement therapy in postmenopausal females modulates reactivity of atherosclerotic coronary arteries. However, no studies have evaluated the factors that modulate coronary artery reactivity among premenopausal females.

METHODS AND RESULTS
Twenty-five adult premenopausal female monkeys were fed an atherogenic diet for 32 months. During this time, monkeys were housed in small social groups and determined to be socially dominant (associated with normal ovarian function) or subordinate (associated with impaired ovarian function). After 32 months, coronary artery vasomotor responses to intracoronary acetylcholine, nitroglycerin, and serotonin were assessed by computer-assisted quantitative coronary angiography. Coronary arteries of dominant monkeys dilated (+9 +/- 2%), whereas those of subordinate monkeys constricted (-6 +/- 2%) in response to acetylcholine (P < .05). There was no effect of social status on vascular response to nitroglycerin or serotonin (P > .10). Vascular responses to acetylcholine were independent of social status effects on plasma lipids, blood pressure, and atherosclerosis extent. The correlation between acetylcholine responses and plasma estradiol concentration measured on the day of angiography was r = .7 (P = < .01). Furthermore, dilation occurred only if plasma estradiol concentrations were greater than 60 pg/mL.

CONCLUSIONS
Psychosocial factors and endogenous estrogen production are important modulators of acetylcholine-mediated dilation of atherosclerotic coronary arteries among premenopausal female monkeys.
Adenovirus-mediated transfer of a gene encoding human apolipoprotein A-I into normal mice increases circulating high-density lipoprotein cholesterol.
Authors: Kopfler W P , Willard M , Betz T , Willard J E , Gerard R D , Meidell R S 
Published: June 2012

BACKGROUND
In animal models of atherosclerosis, augmentation of circulating high-density lipoprotein (HDL) cholesterol exerts a protective effect against development of fatty streaks and promotes plaque regression.

METHODS AND RESULTS
To investigate the potential of gene transfer to increase HDL cholesterol, a fusion gene encoding human apolipoprotein A-I (apo A-I) under the control of the human cytomegalovirus (CMV) immediate-early promoter was packaged into a recombinant adenovirus (AdCMV apo A-I). BALB/c mice infected with AdCMV apo A-I by intravenous injection accumulate immunoreactive apo A-I in serum; levels 5 days after infection averaged 168 mg/dL. A 35% increase in HDL cholesterol and a 47% increase in total cholesterol were observed in mice infected with AdCMV apo A-I compared with control viruses. Analysis of size-fractionated lipoproteins revealed that human apo A-I is incorporated into murine HDL particles. Expression of human apo A-I declined to < 10% of maximum after 12 days and mRNA encoding apo A-I, prevalent 5 days after infection, was undetectable in the livers of infected mice after 12 days.

CONCLUSIONS
We conclude that adenovirus-mediated transfer of a gene encoding apo A-I produces transient elevations of circulating HDL cholesterol of a magnitude correlated with important physiological effects. These observations suggest the potential for gene-based therapeutic strategies to reduce cardiovascular risk.
Left ventricular end-systolic elastance is incorrectly estimated by the use of stepwise afterload variations in conscious, unsedated, autonomically intact dogs.
Authors: Crottogini A J , Willshaw P , Barra J G , Pichel R H 
Published: June 2012

BACKGROUND
End-systolic elastance (Ees), the slope parameter of the end-systolic pressure (ESP)-volume (ESV) relation (ESPVR), is usually estimated in patients by producing stepwise, steady-state pharmacological afterload variations and collecting one ESP-ESV point from each step. The ESPVR is then constructed by fitting a linear equation to these points. In sedated, autonomically blocked dogs, it has been shown that when one point from control, one point from a state of increased afterload, and one point from a state of decreased afterload are used, the resulting Ees incorrectly estimates true Ees, defined as the slope of the ESPVR obtained by transient vena caval occlusion. We investigated if this was also the case in unsedated, autonomically intact dogs when the points used belonged to steady states of progressively decreasing or progressively increasing afterload pressure.

METHODS AND RESULTS
In 10 conscious dogs instrumented with left ventricular (LV) endocardial sonomicrometers to measure LV volume, a LV pressure transducer, and an inferior vena caval (IVC) occluder, two protocols were carried out on separate days. In each protocol, an ESPVR was generated by IVC occlusion in the control state and in two steady-state levels of afterload change produced by stepwise infusion of nitroprusside (protocol 1, afterload decrease) and angiotensin II (protocol 2, afterload increase). In each protocol, steady-state ESP-ESV data points were averaged from the control state and from each level of afterload variation. Linear equations were fitted to the three steady-state points from each protocol, and the estimated Ees values obtained (EesEST) were compared with the Ees values of the control ESPVRs obtained by IVC occlusion (EesTRUE). In protocol 1, EesEST underestimated EesTRUE by about 16% (EesEST, 6.49 +/- 1.55 mm Hg/mL; EesTRUE, 7.48 +/- 1.29 mm Hg/mL; P < .02). In protocol 2, EesEST overestimated EesTRUE by about 37% (EesEST, 9.99 +/- 3.97 mm Hg/mL; EesTRUE, 6.43 +/- 3.88 mm Hg/mL; P < .007).

CONCLUSIONS
In conscious, autonomically intact dogs, the use of stepwise, steady-state afterload variations to obtain ESP-ESV data points to construct the ESPVR incorrectly estimates Ees. In the case of afterload reduction, EesTRUE is underestimated an average of 16.3%, and in the case of afterload increase, EesTRUE is overestimated an average of 37.1%. These errors should be taken into account when interpreting clinical studies using this methodology.
Cytomegalovirus infection-enhanced allograft arteriosclerosis is prevented by DHPG prophylaxis in the rat.
Authors: Lemström K B , Bruning J H , Bruggeman C A , Koskinen P K , Aho P T , Yilmaz S , Lautenschlager I T , Häyry P J 
Published: June 2012

BACKGROUND
Major risk factors for accelerated allograft arteriosclerosis include humoral and cellular immune response, hyperlipidemia, and viral infections. We demonstrated earlier that rat cytomegalovirus (RCMV) infection doubles smooth muscle cell proliferation and intimal thickening of rat aortic allografts. In this study, the effects of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) on RCMV-enhanced rat allograft arteriosclerosis are investigated.

METHODS AND RESULTS
Aortic allografts from the DA to the WF rat strain were used. The recipients were inoculated with 10(5) plaque-forming units of RCMV 1 day after transplantation. Two groups of RCMV-infected rats were treated with DHPG with an initial dose of 20 mg/kg IP and a maintenance dose of 10 mg/kg IP twice a day for a period of 14 days. In the DHPG prophylaxis group (n = 22), the drug administration started 1 day before infection, and in the DHPG treatment group (n = 17), 7 days after infection. One group of infected rats was left untreated (n = 21). The grafts were removed 7 and 14 days and 1, 3, and 6 months after transplantation. In the DHPG prophylaxis group, no virus could be recovered by plaque assays. In the treatment group, 50% of rats were virus-positive at 1 month and 40% at 3 months. DHPG prophylaxis prevented the infiltration of inflammatory cells and their proliferation in the adventitia of RCMV-infected recipients (P < .01), with a 60% reduction in the interleukin-2 receptor expression (P < .05) and a 30% decrease in major histocompatibility complex class II expression (P = NS). DHPG prophylaxis did not significantly alter the levels of insulin-like growth factor-1, epidermal growth factor, platelet-derived growth factor-BB, transforming growth factor-beta 1, acidic fibroblast growth factor, and basic fibroblast growth factor messages in the allograft vascular wall. Early media necrosis was reduced. Arteriosclerotic alterations and proliferation of smooth muscle cells were both reduced 50% to 70% by DHPG prophylaxis (P < .05 at 3 months). The responses in the DHPG treatment group were quite similar but less impressive and statistically nonsignificant.

CONCLUSIONS
We consider it likely that DHPG inhibits arteriosclerotic alterations primarily by reducing the infectious virus and thereby the inflammatory response in the allograft vascular wall; another possibility is a direct antiproliferative effect on smooth muscle cell replication. A dose-dependent inhibitory effect of DHPG on smooth muscle cell replication was recorded in an in vitro study.
Vagal cardiopulmonary reflexes after left ventricular deafferentation.
Authors: Minisi A J , Cersley T L 
Published: June 2012

BACKGROUND
Cardiac transplantation and chronic myocardial infarction interrupt vagal afferent nerve fibers, which originate mainly from the ventricles. Marked abnormalities of reflexes mediated by cardiopulmonary receptors with vagal afferent fibers have been demonstrated after both cardiac transplantation and chronic myocardial infarction. The relation between these reflex abnormalities and ventricular deafferentation is not known.

METHODS AND RESULTS
To further assess this relation, we investigated the effects of left ventricular (LV) deafferentation on the control of renal sympathetic nerve activity (RSNA) by the vagal cardiopulmonary reflex in chloralose-anesthetized, mechanically ventilated dogs with sinoaortic denervation. Responses of left atrial pressure (LAP) and RSNA to hemorrhage and volume expansion were measured before and after application of 88% phenol to either the inferoposterior LV (n = 12) or the entire LV (n = 14). In control experiments, measurements were made before and after application of saline to the LV (n = 12). Reflex sensitivity (percent change in RSNA per mm Hg change in LAP) measured during volume expansion was mildly attenuated after both total (prephenol, -9.1 +/- 0.7; postphenol, -6.6 +/- 0.7; P < .05) and inferoposterior (pre, -12.5 +/- 1.8; post, -8.1 +/- 0.6; P = .055) LV deafferentation. Reflex sensitivity measured during hemorrhage was not significantly altered by inferoposterior or total LV deafferentation. Epicardial saline had no significant effect on reflex sensitivity values measured during either volume expansion or hemorrhage. Reflex inhibition of RSNA in response to intracoronary nicotine was abolished after phenol application, indicating adequate ventricular deafferentation. Phenol application had no significant effect on LAP-myocardial segment length relations measured by sonomicrometry (n = 6).

CONCLUSIONS
Interruption of vagal afferent input from the LV has only modest effects on the control of RSNA by the vagal cardiopulmonary reflex. These data indicate that there is considerable redundancy in the vagal cardiopulmonary reflex such that receptors from the lungs and other cardiac chambers can largely compensate for the loss of afferent input from the LV.
Do fish oils prevent restenosis after coronary angioplasty?
Authors: Leaf A , Jorgensen M B , Jacobs A K , Cote G , Schoenfeld D A , Scheer J , Weiner B H , Slack J D , Kellett M A , Raizner A E 
Published: June 2012

BACKGROUND
The omega-3 polyunsaturated fatty acids derived from fish oils have been shown to modulate many factors believed to affect the pathogenesis of atherosclerosis. Because certain features of restenosis following angioplasty mimic some of the early changes of atherogenesis, some researchers have suggested that fish oil might prevent restenosis following angioplasty. We report the effects of omega-3 fatty acids on the rate of restenosis following percutaneous intraluminal coronary angioplasty (PTCA).

METHODS AND RESULTS
From August 1989 through September 1992, 551 patients were randomized to start receiving a daily dietary supplement of ten 1.0-g capsules containing 80.6% ethyl esters of omega-3 fatty acids providing 4.1 g eicosapentaenoic acid (EPA) and 2.8 g docosahexaenoic acid (DHA) for 6 months or an equal amount of an ethyl ester of corn oil. Four hundred seventy subjects who were well matched for risk factors completed successful angioplasty of one or multiple lesions in native coronary vessels and constituted the study cohort, of whom 447 were evaluable at 6 months after PTCA. The criteria for restenosis were that the quantitative coronary angiography at 6 months show a > 30% increase in narrowing at the stenosis site or loss of at least half of the gain achieved at the time of PTCA and final restenosis with < 50% luminal diameter remaining. In 93% of the patients, the end point was determined by angiography and in all except 1% of these by quantitative coronary angiography. Compliance with the fish oil supplement was good as judged by incorporation of EPA and DHA in plasma and red blood cell phospholipids. The restenosis rate among analyzable patients was 46% for corn oil and 52% for fish oil (P = .37). The addition of 200 mg alpha-tocopherol for all subjects during the study had no effect on restenosis rates.

CONCLUSIONS
This was the largest of such trials to date, and a supplement of 8 g/d of omega-3 fatty acids failed to prevent the usual high rate of restenosis after PTCA. No adverse effects were attributable to this large daily supplement of omega-3 fatty acids.