bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of arterial reocclusion after thrombolysis with activated protein C. Comparison with heparin in a canine model of coronary artery thrombosis.
Authors: Sakamoto T , Ogawa H , Yasue H , Oda Y , Kitajima S , Tsumoto K , Mizokami H 
Published: June 2012

BACKGROUND
Reocclusion of recanalized coronary arteries often limits the efficacy of coronary thrombolytic therapy in patients with acute myocardial infarction. Activated protein C (APC) is an important regulatory enzyme in hemostasis. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the effect of APC on thrombolysis with recombinant tissue-type plasminogen activator (rTPA) was studied in a canine model of coronary artery thrombosis.

METHODS AND RESULTS
Continuous artery flow monitoring in the left anterior descending coronary artery of 30 anesthetized adult beagles was performed by a magnetic flowmeter. Localized thrombosis was produced in the left anterior descending coronary artery and administration of rTPA (alteplase, 0.45 mg/kg IV) was done for 30 minutes. The dogs were randomly assigned to receive one of the following intravenous adjunctive therapies: (1) control group (n = 10): human albumin at a rate of 0.83 mL/min; (2) APC group (n = 10): human plasma-derived APC (0.6 mg/kg) with human albumin as a vehicle at a rate of 0.83 mL/min; and (3) heparin group (n = 10): heparin (200 U/kg) with saline at a rate of 0.83 mL/min. Each adjunctive therapy was started simultaneously with rTPA and lasted for 60 minutes. Coronary recanalization occurred in all dogs of each adjunctive treatment group in 19.1 +/- 1.9 minutes (mean +/- SEM). In a 120-minute observation after the termination of rTPA, reocclusion developed in all the dogs in the control and heparin groups but in only 3 of the 10 dogs in the APC group (P < .002 versus control and heparin). Time from recanalization to reocclusion (minutes, mean +/- SEM) was prolonged in the APC group (103.2 +/- 14.2) as compared with the control (10.2 +/- 2.3, P < .001) and heparin (30.3 +/- 11.8, P < .002) groups. Activated partial thromboplastin time was prolonged similarly in each group after thrombolytic therapy. On the other hand, bleeding time was prolonged in only the heparin group after the treatment. Serious hemorrhagic side effects were not observed in all three groups.

CONCLUSIONS
APC prevents coronary artery reocclusion after recanalization with rTPA in a canine model of coronary artery thrombosis. This finding suggests that APC may be useful as an adjunctive treatment to enhance the effects of thrombolytic therapy in patients with acute myocardial infarction.
Associations of the HDL2 and HDL3 cholesterol subfractions with the development of ischemic heart disease in British men. The Caerphilly and Speedwell Collaborative Heart Disease Studies.
Authors: Sweetnam P M , Bolton C H , Yarnell J W , Bainton D , Baker I A , Elwood P C , Miller N E 
Published: June 2012

BACKGROUND
The relative importance of HDL2 and HDL3 cholesterol as risk factors for ischemic heart disease (IHD) is still uncertain. Their associations with the incidence of IHD in the Caerphilly and Speedwell prospective studies are described.

METHODS AND RESULTS
The two studies have a common core protocol and are based on a total of 4860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell: 251 major IHD events had occurred. Lipid levels were measured on fasting samples. Different laboratories were used by the two studies. Each laboratory used ultracentrifugation to separate HDL2 and HDL3. Both subfractions were inversely associated with risk of IHD. Standardized relative odds of developing major IHD were 0.95 (95% confidence interval [CI], 0.80 to 1.14) for HDL2 cholesterol and 0.83 (95% CI, 0.68 to 1.00) for HDL3 cholesterol in Caerphilly and 0.76 (95% CI, 0.57 to 1.01) for HDL2 and 0.64 (95% CI, 0.49 to 0.83) for HDL3 in Speedwell. The association with incident IHD appeared to be stronger for HDL3 in both areas. No linear combination of the two subfractions was a better predictor of IHD than total HDL cholesterol alone.

CONCLUSIONS
In British men, both HDL2 and HDL3 cholesterol are inversely associated with the incidence of IHD. However, the prediction of the risk of IHD from total HDL cholesterol alone could not be improved upon by measurement of the two HDL subfractions. The relative value of the two HDL subfractions as predictors of risk is still unresolved. The uncertainty may be due, at least in part, to problems associated with their measurement.
Implantation by electrophysiologists of 100 consecutive cardioverter defibrillators with nonthoracotomy lead systems.
Authors: Strickberger S A , Hummel J D , Daoud E , Niebauer M , Williamson B D , Man K C , Horwood L , Schmittou A , Kalbfleisch S J , Langberg J J 
Published: June 2012

BACKGROUND
Traditional lead systems for implantable cardioverter defibrillators (ICDs) require a thoracotomy for placement. Nonthoracotomy lead systems are available and are usually implanted by an electrophysiologist and a surgeon. The purpose of this study was to prospectively evaluate the safety and efficacy of ICD implantation with a nonthoracotomy lead system by electrophysiologists.

METHODS AND RESULTS
A consecutive series of 100 patients (mean age, 61 +/- 13 years, +/- SD) underwent ICD implantation with a nonthoracotomy lead system while intubated and under general anesthesia. Seventy-seven patients had coronary artery disease, 15 had idiopathic cardiomyopathy, 6 had miscellaneous heart disease, and 2 had structurally normal hearts. The mean ejection fraction was 0.29 +/- 0.13. Sixty-eight patients had suffered a cardiac arrest, and 32 had had ventricular tachycardia or syncope. All patients except 9 underwent electrophysiological testing and had failed 1 +/- 1 drug trials before ICD implantation. Three types of nonthoracotomy lead systems were used. The nonthoracotomy lead with an ICD was successfully implanted in 96 patients (96%). Of the unsuccessful implants, 1 patient did not have venous access, the passive fixation lead in 1 would not remain lodged, 1 had elevated defibrillation thresholds, and 1 developed a hemopneumothorax while venous access was being obtained. The mean defibrillation threshold was 17 +/- 6 J. The mean procedure duration was 161 +/- 57 minutes. When a subcutaneous patch was used (n = 58), the procedure duration was 189 +/- 5 minutes, and when a subcutaneous patch was not required (n = 40), the procedure lasted 123 +/- 37 minutes (P < .0001). Patients remained in the hospital 4.5 +/- 4.1 days after implantation, with no procedure-related deaths. Acute complications occurred in 10 patients; 2 had lead dislodgments, 1 with previous abdominal surgery had his abdominal cavity entered (without other complications) while the ICD pocket was being made, 1 had postoperative heart failure, 1 developed a large hematoma when anticoagulation therapy was initiated, 3 required reintubation because of excessive anesthesia, 1 developed superficial cellulitis, and 1 developed a hemopneumothorax secondary to a lacerated subclavian vein. During 6 +/- 3 months of follow-up, 2 patients developed lead fractures.

CONCLUSIONS
(1) Electrophysiologists can implant an ICD with a nonthoracotomy lead system safely and with a high success rate; (2) use of a subcutaneous patch correlates with longer procedure durations; and (3) special precautions should be taken in patients with previous abdominal surgery.
Mechanism of 'inappropriate' sinus tachycardia. Role of sympathovagal balance.
Authors: Morillo C A , Klein G J , Thakur R K , Li H , Zardini M , Yee R 
Published: June 2012

BACKGROUND
"Inappropriate" sinus tachycardia (IST) is an uncommon and poorly defined atrial tachycardia characterized by inappropriate tachycardia and exaggerated acceleration of heart rate with "normal" P wave. The mechanism of this tachycardia is unknown. The purpose of the present study was to determine the role of autonomic balance in the genesis of IST.

METHODS AND RESULTS
Six female patients aged 23 to 38 years with IST and 10 age- and sex-matched control subjects were assessed with the following autonomic function tests: (1) sympathovagal balance to the sinus node assessed by calculating the LF/HF (low frequency/high frequency) ratio using power spectral analysis both in the supine position and after 10 minutes of head-up tilt to 60 degrees, (2) cardiovagal reflex assessed by cold face test (CFT), (3) beta-adrenergic sensitivity as determined by calculating isoproterenol dose-response curves and isoproterenol chronotropic dose 25 (CD25), and (4) intrinsic heart rate (IHR) assessed after autonomic blockade with atropine 0.04 mg/kg and propranolol 0.2 mg/kg administered as an intravenous bolus. No significant differences in the LF/HF ratio both in the supine position (2.8 +/- 0.3 versus 2.6 +/- 0.4) and during upright tilt (8.7 +/- 1.3 versus 8.5 +/- 0.5) were observed between control subjects and IST patients. Cardiovagal response to CFT was markedly depressed in all patients (6.3% IST patients versus 24.2% control subjects, P < .001). beta-Adrenergic hypersensitivity to isoproterenol was noted in all patients (mean CD25, 0.29 +/- 0.10 microgram IST patients versus 1.27 +/- 0.4 microgram control subjects; P < .001), and high IHR was noted in all cases. The patients were treated with high doses of beta-blockers with adequate short-term control. Radiofrequency catheter ablation of the sinus node area was performed in one drug-refractory patient.

CONCLUSIONS
These findings suggest that the mechanism leading to IST is related to a primary sinus node abnormality characterized by a high IHR, depressed efferent cardiovagal reflex, and beta-adrenergic hypersensitivity.
Mononuclear cells from dogs with acute lung allograft rejection cause contraction of pulmonary arteries.
Authors: Cale A R , Ricagna F , Wiklund L , McGregor C G , Miller V M 
Published: June 2012

PURPOSE
Experiments were designed to determine whether or not leukocytes activated by acute pulmonary rejection cause contractions of isolated pulmonary arteries.

METHODS AND RESULTS
Separate suspensions of (a) polymorphonuclear cells (> 95%) and (b) mononuclear cells (85% lymphocytes/10% monocytes/5% polymorphonuclear cells), respectively, were obtained from the arterial blood of four groups of adult male mongrel dogs: unoperated dogs (controls), dogs with single-lung autotransplants, dogs with rejecting single-lung allotransplants, and unoperated dogs treated with the same immunosuppressants as allotransplanted dogs. These suspensions were added to rings of control intralobar pulmonary arteries suspended in organ chambers for measurement of isometric force. The endothelium was removed mechanically from selected rings. No significant change in basal tension of pulmonary arterial rings occurred by adding suspensions of polymorphonuclear cells from any of the four groups of dogs. Significant cell-number-dependent increases in tension occurred with suspensions of mononuclear cells from unoperated dogs, autotransplanted dogs, and unoperated, medicated dogs. These increases in tension were less in rings with compared to those without endothelium. Addition of a synthetic analogue of L-arginine abolished this difference. Suspensions of mononuclear cells from rejecting allotransplanted dogs caused significantly greater contractions in rings with endothelium than those observed with suspended cells from either unoperated, autotransplanted dogs or unoperated, medicated dogs. Addition of superoxide dismutase plus catalase or an antagonist of endothelin-A receptors (BQ-123) reduced contractions in rings with endothelium but not in those without endothelium to suspensions of mononuclear cells from rejecting allotransplanted dogs.

CONCLUSIONS
The results of this study suggest that mononuclear cells cause contraction of pulmonary arteries, which can be partially inhibited by endothelium-derived nitric oxide. However, if the mononuclear cells are activated by acute pulmonary rejection, contractions are no longer inhibited by the endothelium. Under conditions of rejection, contractions are mediated in part by oxygen radicals and endothelin(s).
Neutrophil implications in platelet deposition and vasoconstriction after deep arterial injury by angioplasty in pigs.
Authors: Merhi Y , Lacoste L L , Lam J Y 
Published: June 2012

BACKGROUND
Experimental studies in vitro suggest that neutrophils can modulate platelet function and vasomotor responses. In the present study, the interactions among neutrophils, platelets, and arterial responses to injury in vivo were assessed.

METHODS AND RESULTS
The acute thrombotic and vasomotor responses of porcine carotid arteries to balloon injury in vivo were evaluated in three groups of animals: neutropenic pigs treated (n = 11) or not treated (n = 12) with aspirin and healthy untreated control pigs (n = 15). Neutropenia was achieved by treatment with cyclophosphamide (50 mg/kg, 4 days before the experiment), which decreased circulating leukocyte count by 92% and almost abolished neutrophil aggregation to N-formyl-methionyl-leucyl-phenylalanine without affecting blood platelet count, hematocrit, hemoglobin concentration, or whole blood platelet aggregation to ADP. 51Cr platelet deposition on deeply injured and uninjured arterial segments was not statistically influenced by neutrophil depletion, whereas the angiographic vasoconstrictive response at the site of endothelial injury distally was significantly reduced by 41% from 46.3 +/- 2.9% in the control group to 27.2 +/- 4.1% in the neutropenic group (P < .05). Aspirin treatment in combination with neutropenia produced a 50% reduction in whole blood platelet aggregation, resulted in a significant inhibition of platelet deposition to deeply injured arteries, and decreased vasoconstriction by 66% to 15.6 +/- 3.0% (P < .05 versus control and neutropenic).

CONCLUSIONS
Neutrophils can influence the vasoconstrictive response at the site of endothelial injury in vivo. In addition to platelets, neutrophil interaction with the injured vessel wall may be implicated in the pathophysiological response to arterial injury in vivo.
Variable participation of 5-HT1-like receptors and 5-HT2 receptors in serotonin-induced contraction of human isolated coronary arteries. 5-HT1-like receptors resemble cloned 5-HT1D beta receptors.
Authors: Kaumann A J , Frenken M , Posival H , Brown A M 
Published: June 2012

BACKGROUND
Serotonin may contract human large coronary arteries through two 5-hydroxytryptamine (5-HT) receptors, 5-HT1-like and 5-HT2. These 5-HT1-like receptors resemble both cloned 5-HT1D receptor subtypes, 5-HT1D alpha and 5-HT 1D beta. Although these subtypes have similar pharmacology, 5-HT1D beta receptors appear to have lower affinity for ketanserin than 5-HT1D alpha receptors. We assessed the relative participation of 5-HT1-like and 5-HT2 receptors and attempted to identify whether vasoconstrictor 5-HT1-like receptors are 5-HT1D alpha or 5-HT1D beta.

METHODS AND RESULTS
Epicardial coronary arteries were dissected from the hearts of 29 patients (including 1 healthy (donor) undergoing heart transplant operation. Endothelium-denuded strips were set up to contract at 37 degrees C. To assess the relative contributions of 5-HT1-like and 5-HT2 receptors, we blocked the latter with ketanserin (0.1 to 1.0 mumol/L) and ketanserin-resistant receptors with methiothepin (0.1 mumol/L). Concentration-effect curves for 5-HT, in the absence and presence of ketanserin, were analyzed by using a model for two receptor subtypes. The fractional contributions of 5-HT1-like and 5-HT2 receptors to the maximum effect of 5-HT, f1 and f2, were estimated in arteries from 28 patients: f1 (0.71 +/- 0.20, mean +/- SD) was significantly larger than f2 (0.29 +/- 0.20) (P < .0001). Using [3H]-serotonin to label transfected and expressed receptors, we verified that ketanserin has lower affinity for 5-HT1D beta (pKi [-log Ki, mol/L] less than 5.0) than for 5-HT1D alpha (pKi = 7.1 +/- 0.1) receptors. A concentration of ketanserin (1 mumol/L) that would occupy more than 90% of 5-HT1D alpha receptors failed to block 5-HT-induced contractions (4 patients). The 5-HT1-like receptor stimulant sumatriptan evoked maximal contractions that matched f1 and was equipotent with 5-HT through 5-HT1-like receptors (8 patients). No systematic influence of disease, atheroma, or therapy on f1 and f2 was detected.

CONCLUSIONS
Coronary artery contractile 5-HT1-like receptors resemble cloned 5-HT1D beta receptors and predominate over 5-HT2 receptors in mediating serotonin-evoked contractions. Sumatriptan contracts coronary arteries as a full agonist through 5-HT1-like receptors.
Serum lipoproteins in African Americans and whites with non-insulin-dependent diabetes in the US population.
Authors: Cowie C C , Howard B V , Harris M I 
Published: June 2012

BACKGROUND
Despite the significant role that dyslipidemia is believed to play in the development of cardiovascular disease in diabetes, most studies examining diabetic dyslipidemia in the United States have not been population based, and very little data are available for African Americans with diabetes. We used data from a national survey to compare the effect of diabetes on lipid concentrations in African-American and white men and women. In addition, we examined other factors related to lipid concentrations and controlled for these factors in our analyses.

METHODS AND RESULTS
The Second National Health and Nutrition Examination Survey included a representative sample of 4177 African Americans and whites in the US civilian noninstitutionalized population 20 to 74 years old. These persons were classified as having non-insulin-dependent diabetes mellitus (NIDDM) (n = 720) or as being nondiabetic (n = 3457) based on an oral glucose tolerance test and a medical history of diabetes. Subjects were given an interview and physical examination that included measurement of serum lipoproteins, body mass index, body fat distribution, dietary fat intake, alcohol consumption, frequency of smoking, and use of medications. By univariate analysis, a worse profile of mean cholesterol, triglycerides, and high-density lipoprotein cholesterol levels was generally apparent in NIDDM than in nondiabetic subjects, regardless of race or sex; a similar pattern was found for the prevalence of abnormal concentrations of these lipids. Lipid profiles appeared to be worse in whites with NIDDM than in African Americans. For mean total and low-density lipoprotein cholesterol, concentrations tended to be worse in women with NIDDM than in men. When other factors significantly affecting lipid levels were adjusted by multivariate analysis, we found that in all race/sex groups, total cholesterol was higher in NIDDM than in nondiabetic subjects but differences were not significant (P = 54), triglyceride concentrations were significantly higher in NIDDM subjects (P < .0001), and high-density lipoprotein cholesterol concentrations were lower in NIDDM subjects (P = .003). An interaction of diabetes with race was found for low-density lipoprotein cholesterol (P = .0001), where concentrations were substantially lower in NIDDM than in nondiabetic subjects among African Americans (P < .01) but slightly higher in NIDDM subjects among whites (P = .33). For other lipids, no differential effect of NIDDM was found by race or sex.

CONCLUSIONS
In African-American and white men and women in the United States, NIDDM is associated with a pattern of dyslipidemia that may potentiate the atherosclerotic process. Diabetic treatment should include aggressive treatment of dyslipidemia to reduce this increased risk.
Chelation therapy for intermittent claudication. A double-blind, randomized, controlled trial.
Authors: van Rij A M , Solomon C , Packer S G , Hopkins W G 
Published: June 2012

BACKGROUND
The use of repeated intravenous infusions of EDTA, which has become known as "chelation therapy," has been promoted for treating intermittent claudication as well as a wide range of other disorders. Multiple reports of excellent results in large numbers of patients have encouraged the use of this regimen. The lack of well-controlled studies substantiating the benefits of this treatment has limited its use mainly to private clinics. The aim of the study was to assess the benefits of chelation therapy in patients with intermittent claudication.

METHODS AND RESULTS
A double-blind, randomized, controlled trial included 32 patients with intermittent claudication who were randomized to a treatment group (15) and a control group (17). Main outcome measures were subjective and measured walking distances and ankle/brachial pulse indices. Other outcome measures included lifestyle and subjective parameters of improvement, cardiac function, ECG, renal function, hematology, blood glucose, and lipid biochemistry. No clinically significant differences in main outcome measures between chelation therapy and placebo groups were detected up to 3 months after treatment. Measures of mood state, activities of daily living, and quality of life factors were not consistently affected by chelation therapy. An equal proportion (13%) of each group thought that they had received the active agent. The proportion of patients showing an improvement in walking distance was not significantly different between the chelation group (60%) and the control group (59%).

CONCLUSIONS
Chelation therapy has no significant beneficial effects over placebo in patients with intermittent claudication.
Age-related changes in beta-adrenergic neuroeffector systems in the human heart.
Authors: White M , Roden R , Minobe W , Khan M F , Larrabee P , Wollmering M , Port J D , Anderson F , Campbell D , Feldman A M 
Published: June 2012

BACKGROUND
Aging decreases cardiac beta-adrenergic responsiveness in model systems and in humans in vivo. The purpose of this study was to comprehensively evaluate the age-related changes in the beta-receptor-G protein-adenylyl cyclase complex in nonfailing human hearts.

METHODS AND RESULTS
Twenty-six nonfailing explanted human hearts aged 1 to 71 years were obtained from organ donors and subjected to pharmacological investigation of beta-adrenergic neuroeffector systems. When the population was subdivided into the 13 youngest and 13 oldest subjects, total beta-receptor density assessed by maximum [125I]ICYP binding (beta max) was reduced in older hearts by 37% in left ventricles and 31% in right ventricles (both P < .05), and the downregulation was confined to the beta 1 subtype (r = .78 left ventricle beta 1 density versus donor age). Older donor hearts exhibited a 3- to 4-fold rightward shift of ICYP-isoproterenol (ISO) competition curves and demonstrated 43% fewer receptors in a high-affinity agonist binding state (P < .05). Older hearts exhibited decreased adenylyl cyclase stimulation by ISO, by zinterol (beta 2-agonist), and by the G protein-sensitive probes forskolin, Gpp(NH)p, and NaF. In contrast, there was no change in response to manganese, a specific activator of the adenylyl cyclase catalytic subunit. Toxin-catalyzed ADP ribosylation in membranes prepared from older versus younger hearts revealed a 29% to 30% reduction (P < .05) with cholera toxin (Gs) but no difference with pertussis toxin (Gi). The systolic contractile response of isolated right ventricular trabeculae to ISO was decreased by 46%, with a 10-fold increase in ISO EC50 in older relative to younger donor hearts.

CONCLUSIONS
There is a profound decrease in cardiac beta-adrenergic responsiveness with aging. This occurs by multiple mechanisms including downregulation and decreased agonist binding of beta 1-receptors, uncoupling of beta 2-receptors, and abnormal G protein-mediated signal transduction.