bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ductus arteriosus. Advanced differentiation of smooth muscle cells demonstrated by myosin heavy chain isoform expression in rabbits.
Authors: Kim H S , Aikawa M , Kimura K , Kuro-o M , Nakahara K , Suzuki T , Katoh H , Okamoto E , Yazaki Y , Nagai R 
Published: June 2012

BACKGROUND
The closure of the ductus arteriosus (DA) is one of the most striking cardiovascular events that occur at birth. It has been attributed to oxygenation and intrinsic prostaglandins. However, selective constriction of DA suggests the presence of highly specialized contractile mechanisms in DA. We previously reported that smooth muscle myosin heavy chain isoforms, SM1 and SM2, are molecular markers for smooth muscle differentiation because of their unique expression pattern during vascular development. SM1 and SM2 are generated from a single gene through developmentally regulated alternative RNA splicing; SM1 is expressed in almost all stages of differentiation of the vascular smooth muscles, but SM2 is found only after birth.

METHODS AND RESULTS
Immunohistochemistry was performed to study the expression of the different types of myosin heavy chain isoforms in DA of fetal and neonatal rabbits. Electron microscopic examinations were also carried out to demonstrate ultrastructural characteristics of ductus muscles. We found that SM2 is expressed before birth in the medial layer of DA, indicating advanced differentiation of smooth muscle cells in DA. The exact location of immunoreactivity for SM2 was in the smooth muscle cell of the medial layer of DA. Immunoreactivity for SM1, however, was not different for DA and adjacent great arteries. Transmission electron microscopy demonstrated greater amounts of myofilaments in medial smooth muscles of DA than those of aorta.

CONCLUSIONS
These results indicate that smooth muscles in DA are more differentiated than those in other arteries, which may be one of the cellular mechanisms responsible for the unique closure of DA at birth.
Role of ATP-sensitive K+ channel on ECG ST segment elevation during a bout of myocardial ischemia. A study on epicardial mapping in dogs.
Authors: Kubota I , Yamaki M , Shibata T , Ikeno E , Hosoya Y , Tomoike H 
Published: June 2012

BACKGROUND
ATP-sensitive K+ channels are activated when the myocardium becomes ischemic. However, the role of the ATP-sensitive K+ current in the emergence of ECG ST changes during ischemia remained unclarified.

METHODS AND RESULTS
The left anterior descending coronary artery (LAD) was cannulated and perfused with arterial blood from the carotid artery through a bypass tube in 8 anesthetized, open-chest dogs. An array of 60 unipolar electrodes mounted on a sock was used to record epicardial electrograms of the whole heart. Pinacidil (10 micrograms.kg-1 x min-1), an ATP-sensitive K+ channel opener, was infused into the bypass tube for 2 minutes, and the electrograms were recorded before and after the infusion. The elevation of the ST segment and the increase of QRST area were observed spatially over the LAD-perfused region. At the electrode showing the largest ST segment elevation, the activation recovery interval, an index of action potential duration, was shortened from 202 +/- 9 to 111 +/- 18 milliseconds (P < .001). These electrographic changes were similar to those noted in 2-minute coronary occlusion (n = 8). The extent of ST segment elevation during coronary occlusion was attenuated after the intravenous pretreatment with glibenclamide (0.3 mg/kg), a blocker of the KATP channel (n = 5).

CONCLUSIONS
The findings of this study suggest that the activation of ATP-sensitive K+ channels during a bout of acute myocardial ischemia plays an important role in the emergence of ECG ST elevation.
Entrainment of reentrant ventricular tachycardia in anisotropic rings of rabbit myocardium. Mechanisms of termination, changes in morphology, and acceleration.
Authors: Boersma L , Brugada J , Kirchhof C , Allessie M 
Published: June 2012

BACKGROUND
Entrainment of ventricular tachycardia can either terminate or change the rate and/or morphology of ventricular tachycardia. The purpose of this study was to elucidate the underlying mechanisms by mapping of entrainment of ventricular tachycardia.

METHODS AND RESULTS
In 10 Langendorff-perfused rings of anisotropic rabbit left ventricular epicardium created by a cryoprocedure, ventricular tachycardia with a cycle length of 167 +/- 17 milliseconds was induced by incremental pacing. During transient entrainment (10 stimuli), the circulating wave was extinguished by collision with the paced antidromic wave, whereas ventricular tachycardia was reset by the paced orthodromic wave. At shorter pacing intervals, the site of collision shifted deeper into the circuit. Entrainment at high rates (104 +/- 11 milliseconds) resulted in either termination (n = 54), a change in morphology (n = 8), or acceleration (n = 6) of ventricular tachycardia. Termination of ventricular tachycardia was due to complete (84%) or partial (16%) block of the paced orthodromic wave. Partial block induced microreentry within the circuit, resulting in a reflected echo wave that terminated ventricular tachycardia. A change in morphology of ventricular tachycardia was due to reversion of the direction of propagation of the circulating wave around the obstacle. Acceleration of ventricular tachycardia was caused by double-wave reentry induced by block of the paced antidromic wave. In 28 cases, the sequence of activation during entrainment was not stable but changed from beat to beat due to varying arcs of conduction block. Block occurred predominantly (86%) during slow transverse propagation. Before termination, local oscillations in interval occurred, resulting in a shortening of the last local interval at the site of block by 10 +/- 6 milliseconds.

CONCLUSIONS
Termination of ventricular tachycardia by entrainment was due either to complete orthodromic block or to a reflected echo wave. A change in morphology occurred when the direction of the circulating wave reversed. Acceleration of ventricular tachycardia was due to initiation of double-wave reentry. All changes were preceded by conduction block during one or more stimuli at one or multiple sites in the circuit. Block occurred predominantly during slow transverse propagation and was preceded by local oscillations in interval at the site of block.
Mechanism of spontaneous termination of stable atrial flutter in the canine sterile pericarditis model.
Authors: Ortiz J , Igarashi M , Gonzalez H X , Laurita K , Rudy Y , Waldo A L 
Published: June 2012

BACKGROUND
We tested the hypotheses that spontaneous termination of stable atrial flutter is directly related to spontaneous beat-to-beat cycle length oscillations and that block of the circulating reentrant wave front occurs in an area of slow conduction.

METHODS AND RESULTS
We studied 30 episodes of spontaneous termination of stable atrial flutter induced by atrial stimulation in 11 conscious, nonsedated dogs with sterile pericarditis. Additionally, in 5 dogs, 14 episodes of spontaneous termination of stable atrial flutter were studied with a multisite mapping system to record simultaneously from 190 right atrial electrodes. In the conscious-state studies, atrial flutter cycle length oscillations began 6 +/- 1 (mean +/- SEM) beats before termination in 26 episodes, stable atrial flutter evolved into atrial fibrillation in 3 episodes, and no cycle length change occurred before termination in 1 episode. In the open-chest studies, in all instances, spontaneous oscillations began 7 +/- 1 beats before termination. The only consistent oscillation pattern occurred for the last two beats: a long cycle length (149 +/- 9 milliseconds) followed by a much shorter cycle length (110 +/- 6 milliseconds) (P < .01). Activation maps demonstrated that all cycle length oscillations were explained by changes of conduction in an area(s) of slow conduction in the reentrant circuit. In two instances, the last (short) cycle length was associated with disappearance of an area of slow conduction. In all episodes, the last circulating reentrant wave front blocked in an area of slow conduction in the reentrant circuit. Although not tested, during the last beat, the very early arrival of the circulating reentrant wave front at an area of slow conduction suggests an important role for refractoriness, with head and tail interactions, resulting in block.

CONCLUSIONS
Spontaneous termination of stable atrial flutter in the sterile pericarditis model (1) is preceded by beat-to-beat cycle length oscillations that result from changes in conduction in areas of slow conduction in the reentrant circuit and (2) results from block of the circulating reentrant wave front in an area of slow conduction.
Recombinant hirudin in patients with chronic, stable coronary artery disease. Safety, half-life, and effect on coagulation parameters.
Authors: Zoldhelyi P , Webster M W , Fuster V , Grill D E , Gaspar D , Edwards S J , Cabot C F , Chesebro J H 
Published: June 2012

BACKGROUND
Because the specific antithrombin hirudin prevents platelet-rich arterial thrombus and accelerates thrombolysis in a variety of animal models, it has promise as antithrombotic therapy. We therefore studied the half-life, effect on anticoagulant parameters, and safety of hirudin in patients with coronary artery disease.

METHODS AND RESULTS
Thirty-eight men and 1 woman (age [mean +/- SD], 60.4 +/- 6.9 years) with angiographic coronary disease were allocated in a single-blind ascending dosage study to a 6-hour i.v. infusion of recombinant hirudin (CGP 39,393) or matching placebo. The median terminal half-life for hirudin, measured by ELISA, was 2.7, 2.3, 2.9, 3.1, and 2.0 hours for the 0.02, 0.05, 0.1, 0.2, and 0.3 mg.kg-1 x h-1 groups, respectively. Activated partial thromboplastin times (aPTT) at 3, 4, and 6 hours were averaged into a plateau value. The aPTT plateau-to-baseline ratios were 1.5 +/- 0.1, 2.0 +/- 0.1, 2.3 +/- 0.1, 2.7 +/- 0.1, and 2.9 +/- 0.1, respectively, with hirudin infused at 0.02, 0.05, 0.1, 0.2, and 0.3 mg.kg-1 x h-1. From 62% to 77% of the aPTT plateau value was seen within 30 minutes of starting the infusions and was directly related to dose. The aPTT-to-baseline ratios correlated well with plasma hirudin levels (r = .88), whereas poor correlation and sensitivity were observed between plasma hirudin levels and activated coagulation time (ACT)-to-baseline ratios (r = .44). Plasma levels of hirudin and ACT in seconds correlated overall well (r = .80), but considerable overlap occurred between baseline ACT and ACT at plasma hirudin concentrations < 1000 ng/mL. Prothrombin times were significantly prolonged only at a dosage of > or = 0.05 mg.kg-1 x h-1 and were 11.8 +/- 0.5 (INR = 1.0), 12.3 +/- 0.7 (INR = 1.1), 13.3 +/- 1.2 (INR = 1.4), 14.2 +/- 0.4 (INR = 1.7), and 15.8 +/- 0.9 (INR = 2.3) seconds for each respective hirudin dosage. Thrombin times were beyond range (> 600 seconds) at 6 hours in all except 2 patients who received the lowest dosage. All parameters returned to baseline between 8 and 18 hours after the infusion. Bleeding times were not significantly prolonged. No side effects occurred. No antibodies to hirudin were detected 2 weeks after the infusion.

CONCLUSIONS
Recombinant hirudin has a terminal half-life of 2 to 3 hours. The aPTT correlates well with plasma levels of hirudin and allows close titration over a wide range of anticoagulation, while ACT and prothrombin time are relatively insensitive for monitoring hirudin administration. At anticoagulant levels effective in experimental thrombosis, a 6-hour infusion of hirudin is well tolerated and safe in a predominantly male group of patients with stable coronary atherosclerosis.
Profound platelet degranulation is an important side effect of some types of contrast media used in interventional cardiology.
Authors: Chronos N A , Goodall A H , Wilson D J , Sigwart U , Buller N P 
Published: June 2012

BACKGROUND
Thrombotic complications occurring during coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) are relatively frequent and can be influenced by the type of radiographic contrast media used. Low osmolar contrast media (LOCM), both ionic and nonionic, have been considered to be safer than the older high osmolar contrast media (HOCM), causing less haemodynamic and symptomatic side effects. Recently, however, nonionic LOCM have been associated with an increased incidence of thrombotic events, including coronary occlusion and stroke.

METHODS AND RESULTS
The effects of commonly used contrast media on platelets in native blood were investigated using immunolabeling and flow cytometry to detect platelet activation in vitro. A nonionic LOCM (Omnipaque) caused profound platelet degranulation in nearly 80% of platelets compared with 2 to 3% of platelets in the control. Conversely, an ionic HOCM (Urografin) caused only 25% degranulation, whereas an ionic LOCM (Hexabrix) caused no platelet activation and, furthermore, it inhibited the effects of thrombin on platelets. Platelet degranulation, quantified by immunolabeling, was paralleled by release of beta-thromboglobulin and platelet factor 4 from platelet alpha-granules. Blood from patients anticoagulated with heparin and pretreated with standard-dose aspirin in preparation for PTCA showed the same pattern of contrast media-induced platelet activation as normal subjects.

CONCLUSIONS
These results suggest that the type of contrast media used during invasive imaging of the vasculature could have a significant effect on platelets. Platelet degranulation within a PTCA-damaged vessel would be increased by a nonionic contrast medium, releasing procoagulant molecules and platelet-derived growth factors into the damaged vessel lumen, which might contribute to acute thrombosis and the initiation of the restenosis process.
After correcting for worse baseline characteristics, women treated with thrombolytic therapy for acute myocardial infarction have the same mortality and morbidity as men except for a higher incidence of hemorrhagic stroke. The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Study.
Authors: White H D , Barbash G I , Modan M , Simes J , Diaz R , Hampton J R , Heikkilä J , Kristinsson A , Moulopoulos S , Paolasso E A 
Published: June 2012

BACKGROUND
In the prethrombolytic era, women with myocardial infarction were reported to have a worse outcome than men. This analysis evaluates the association of sex with morbidity and mortality after thrombolytic therapy.

METHODS AND RESULTS
Data were analyzed from 8261 of the 8387 randomized patients with acute myocardial infarction who received thrombolytic therapy in the International Tissue Plasminogen Activator/Streptokinase Mortality Study (baseline data were missing for 126 patients) and were followed for 6 months. Women made up 23% (n = 1944) of the study population. Baseline characteristics were worse in women: they were 6 years older, were more likely to have a history of previous infarction (P < .01), antecedent angina (P < .01), hypertension (P < .0001), or diabetes (P < .0001); were in a higher Killip class on admission (P < .0002); and received thrombolytic therapy 18 minutes later than men (P < .0001). Fewer women were smokers (P < .0001). Women had a higher hospital (12.1% versus 7.2%, P < .0001) and 6-month mortality (16.6% versus 10.4%, P < .0001) and were more likely to develop cardiogenic shock (9.1% versus 6.3%, P < .0001), bleeding (7.2% versus 5.3%, P < .01), and hemorrhagic (1% versus 0.3%, P < .001) or total stroke (2.2% versus 1.1%, P < .0001) during hospitalization. Reinfarction rates and requirement for angioplasty or surgery did not differ. After correction for worse baseline characteristics, women had similar morbidity and mortality apart from a significantly higher incidence of hemorrhagic stroke, which remained significant even after accounting for weight and treatment allocation (odds ratio, 2.90; P < .01).

CONCLUSIONS
After thrombolytic therapy for acute myocardial infarction, women have similar morbidity and mortality to men but suffer from a higher incidence of hemorrhagic stroke.
Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.
Authors: Johnstone M T , Creager S J , Scales K M , Cusco J A , Lee B K , Creager M A 
Published: June 2012

BACKGROUND
Endothelium-dependent vasodilation is abnormal in experimental models of diabetes mellitus. We postulated that abnormalities of endothelial function are also present in patients with insulin-dependent diabetes mellitus and may contribute to the pathogenesis of vascular disease in these individuals.

METHODS AND RESULTS
Vascular reactivity was measured in the forearm resistance vessels of 15 patients with insulin-dependent diabetes mellitus and 16 age-matched normal subjects. No patient had hypertension or dyslipidemia. Each subject was pretreated with aspirin to inhibit endogenous production of prostanoids. Methacholine chloride (0.3 to 10 micrograms/min) was administered via the brachial artery to assess endothelium-dependent vasodilation. Sodium nitroprusside (0.3 to 10 micrograms/min) and verapamil (10 to 300 micrograms/min) were infused intra-arterially to assess endothelium-independent vasodilation; phenylephrine (0.3 to 3 micrograms/min) was administered to examine vasoconstrictor responsiveness. Forearm blood flow was determined by venous occlusion plethysmography, and dose-response curves were generated for each drug. Basal forearm blood flow in diabetic and normal subjects was comparable (2.6 +/- 0.2 versus 2.1 +/- 0.3 mL x 100 mL-1 x min-1, respectively; P = NS). The forearm vasodilative response to methacholine was less in diabetic than in normal subjects. At the highest dose of methacholine, the forearm blood flow increased 9.5 +/- 1.1 mL x 100 mL-1 x min-1 in diabetic subjects and 15.3 +/- 1.4 mL.100 mL-1 x min-1 in normal subjects (P < .01). The forearm blood flow responses to nitroprusside and verapamil and the forearm vasoconstrictor responses to phenylephrine were similar in diabetic and healthy subjects. In diabetic subjects, endothelium-dependent vasodilation correlated inversely with serum insulin concentration but not with glucose concentration, glycosylated hemoglobin, or duration of diabetes.

CONCLUSIONS
Endothelium-dependent vasodilation is abnormal in forearm resistance vessels of patients with insulin-dependent diabetes mellitus. This abnormality may be relevant to the high prevalence of vascular disease that occurs in these individuals.
Coronary heart disease case fatality in four countries. A community study. The Acute Myocardial Infarction Register Teams of Auckland, Augsburg, Bremen, FINMONICA, Newcastle, and Perth.
Authors: Löwel H , Dobson A , Keil U , Herman B , Hobbs M S , Stewart A , Arstila M , Miettinen H , Mustaniemi H , Tuomilehto J 
Published: June 2012

BACKGROUND
Community-based registers participating in the MONICA Project of the World Health Organization show markedly different attack and death rates of coronary heart disease. This variation is a function of both the incidence and case fatality occurring within countries. The contribution of case fatality to the international variation in coronary heart disease mortality rates is not well understood.

METHODS AND RESULTS
The register data from eight study populations--Augsburg and Bremen in Germany, Auckland in New Zealand, Perth and Newcastle in Australia, and North Karelia, Kuopio, and Turku/Loimaa in Finland--were compared. All patients with definite myocardial infarction or coronary death aged 35 to 64 years occurring in the study populations in 1985 through 1989 are the basis for the case fatality calculations by different definitions: 28-day case fatality for all cases, for hospitalized cases, and for hospitalized 24-hour survivors; out-of-hospital case fatality; and 24-hour case fatality for hospitalized cases. Differences in case fatality were much smaller than differences in attack and mortality rates in these populations. About two thirds of deaths occurred before the patients reached a hospital. The 28-day case fatality ranged from 37% for men in Perth to 58% for women in Augsburg. Among those who reached the hospital alive, 28-day case fatality was 13% to 27% for men and 20% to 35% for women. In those who survived 24 hours from the onset of symptoms, 28-day case fatality was 8% to 17% for men and 12% to 26% for women.

CONCLUSIONS
Differences in case fatality were not associated with differences in coronary mortality rates between these populations. As most deaths occurred before reaching a hospital, opportunities for reducing case fatality through improved hospital care are limited. This emphasizes the primary role of prevention in reducing coronary death rates.
Optimization of biphasic waveforms for human nonthoracotomy defibrillation.
Authors: Swartz J F , Fletcher R D , Karasik P E 
Published: June 2012

BACKGROUND
Biphasic waveforms reduce defibrillation threshold (DFT) in a wide variety of models. Although there are several human studies of long-duration, high-tilt biphasic waveform defibrillation, the specific biphasic waveform shape required to achieve optimal DFT reduction is unknown.

METHODS AND RESULTS
This study tested the effect of single capacitor biphasic waveform tilt modification on DFT using a paired study design in 18 patients undergoing nonthoracotomy defibrillator implantation. Baseline DFT was obtained using a 65% tilt, simultaneous pulse, bidirectional monophasic shock from a right ventricular cathode to a coronary sinus or superior vena cava lead and a subscapular patch. The single-capacitor biphasic waveform shocks, delivered over the same pathways, consisted of either both phases at 65% tilt (65/65 biphasic waveform) to produce an overall tilt of 88% and a delivered energy 11% greater than monophasic shock or both phases at 42% tilt (42/42 biphasic waveform) to produce an overall tilt of 66% and delivered energy equal to monophasic shock. The 65/65 biphasic waveform reduced stored energy DFT 25%, from 16.2 +/- 4.4 J with monophasic shock to 12.1 +/- 5.3 J (P < .02); however, it did not significantly reduce the delivered energy DFT. In contrast, the 42/42 biphasic waveform required 49% less stored energy (16.2 +/- 4.4 J, monophasic shock, vs 8.3 +/- 3.3 J, biphasic waveform; P < .001) and 49% less delivered energy (14.2 +/- 3.8 J, monophasic shock, vs 7.3 +/- 2.9 J, biphasic waveform; P < .001) than monophasic shock for successful defibrillation. The 42/42 biphasic waveform delivered energy DFT was 4.6 +/- 5.2 J (39%) less than 65/65 biphasic waveform DFT (P < .002).

CONCLUSIONS
DFT reduction is an inherent electrophysiological property of biphasic waveforms that is independent of delivered energy. Overall biphasic waveform tilt and the relative amplitudes of the waveform phases are important factors in defibrillation efficacy. Defibrillation with a 42/42 biphasic waveform is more efficacious than 65/65 biphasic waveform defibrillation; however, the optimal biphasic waveform remains unknown.