bluuebunny/crossref_metadata_2025 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.
A new noninvasive method for the estimation of peak dP/dt.
Authors: Rhodes J , Udelson J E , Marx G R , Schmid C H , Konstam M A , Hijazi Z M , Bova S A , Fulton D R
Published: June 2012

BACKGROUND

Peak dP/dt is a good index of ventricular performance that is not influenced by afterload, wall motion abnormalities, or the variations in ventricular anatomy and morphology commonly encountered among patients with congenital heart disease. Unfortunately, the clinical utility of peak dP/dt has been limited by the fact that its measurement generally requires an intraventricular catheter. However, peak dP/dt occurs during isovolumetric contraction, and the pressure rise during isovolumetric contraction is almost linear. Therefore, the mean dP/dt during isovolumetric contraction (mean dP/dtic), ie, the ratio of the rise in pressure during isovolumetric contraction (aortic diastolic pressure minus the systemic ventricular end-diastolic pressure [VEDP]) over the isovolumetric contraction time, should provide a good estimate of peak dP/dt that could be generated noninvasively.

METHODS AND RESULTS

Echo/phonocardiography was used to measure the isovolumetric contraction time and a blood pressure cuff to estimate aortic diastolic pressure of 27 patients (age, 1 day to 77 years) with congenital or acquired heart disease. VEDP was determined by three methods: (1) intraventricular catheter, (2) assumed VEDP of 10 mm Hg, and (3) assignment of a normal or elevated value on the basis of clinical history. The three estimates of mean dP/dtic thus generated were compared with simultaneous measurements of peak dP/dt obtained during cardiac catheterization. Invasively measured peak dP/dt correlated well with the indirect determinations (r = .95, .89, and .92 for methods 1, 2, and 3, respectively; P < .0001).

CONCLUSIONS

Echo/phonocardiography can be used in conjunction with a blood pressure cuff and indirect estimates of VEDP to generate mean dP/dtic, an index of ventricular function that approximates and closely correlates with peak dP/dt. This noninvasive measurement can be obtained in almost any patient and may be useful in the assessment of ventricular performance in a variety of cardiovascular disorders.
Plasma lipoproteins and progression of coronary artery disease evaluated by angiography and clinical events.
Authors: Phillips N R , Waters D , Havel R J
Published: June 2012

BACKGROUND

There is considerable evidence that remnants of triglyceride-rich lipoproteins may be particularly atherogenic.

METHODS AND RESULTS

Levels of lipoprotein lipids and of apolipoprotein B in low-density lipoproteins were measured in 335 men and women enrolled in a study in which quantitative coronary angiography was carried out at 2-year intervals. Clinical events related to coronary disease occurred in 129 patients during the trial and in the subsequent follow-up period of 4 to 6 years. In multivariate analysis controlled for a number of nonlipid risk factors, high-density lipoprotein cholesterol was inversely related to the mean percentage increase in coronary artery stenosis in both men and women. Neither plasma triglycerides nor low-density lipoprotein cholesterol, triglycerides, or apolipoprotein B was related to change in stenosis, but a measure of remnants of triglyceride-rich lipoproteins, which included cholesterol in intermediate-density lipoproteins, was directly related to lesion progression. The same relations for these measures of plasma lipoprotein concentrations were found to hold for clinical events related to coronary artery atherosclerosis.

CONCLUSIONS

In patients with established coronary heart disease, increased levels of remnants of triglyceride-rich lipoproteins and decreased levels of high-density lipoproteins appear to promote progression of coronary artery atherosclerosis, which in turn may lead to an untoward clinical event. No such relation could be shown for the level of components of low-density lipoproteins. These and other observations call for reevaluation of relations between particular species of lipoproteins containing apolipoprotein B and the pathogenesis of coronary artery atherosclerosis and coronary heart disease.
Mitral valve replacement versus mitral valve repair. A Doppler and quantitative stress echocardiographic study.
Authors: Tischler M D , Cooper K A , Rowen M , LeWinter M M
Published: June 2012

BACKGROUND

Standard mitral valve replacement (MVR) in patients with chronic mitral regurgitation results in consistent reductions in resting postoperative ejection fraction. This has been attributed to removal of the low-impedance ejection pathway into the left atrium or to disruption of the chordal apparatus. Mitral valve repair (MVP) does not reduce ejection fraction at rest. However, whether MVP confers any advantages with regard to dynamic left ventricular performance has not been investigated. The aim of this study was to directly compare standard MVR with MVP and to determine their respective influences on ventricular ejection performance during bicycle exercise.

METHODS AND RESULTS

Ten consecutive patients with pure chronic mitral regurgitation who underwent MVP and 10 patients matched for age, sex, and preoperative ejection fraction who underwent standard MVR for pure chronic mitral regurgitation performed symptom-limited, graded upright bicycle exercise with simultaneous Doppler and quantitative two-dimensional echocardiography. Patients with MVP had significantly greater rest (55 +/- 12%) and exercise (63 +/- 11%) ejection fractions than matched patients with MVR (40 +/- 13% [P < .0001] and 42 +/- 17% [P < .005], respectively). End-systolic circumferential wall stress was significantly lower at rest (190 +/- 36 versus 244 +/- 46; P < .03) and at peak exercise (231 +/- 46 versus 300 +/- 52; P < .02) in patients with MVP. At peak exercise, left ventricular shape was significantly more spherical in patients with MVR than those with MVP (1.84 +/- 0.31 versus 2.45 +/- 0.59; P < .02).

CONCLUSIONS

MVR with chordal transection resulted in significant reductions in rest and exercise ejection fraction. This was caused in part by a significant increase in end-systolic circumferential wall stress. MVP resulted in improved rest and exercise ejection indexes, primarily due to a marked reduction in end-systolic stress and maintenance of a more ellipsoidal chamber geometry.
Gamma-globulin treatment of acute myocarditis in the pediatric population.
Authors: Drucker N A , Colan S D , Lewis A B , Beiser A S , Wessel D L , Takahashi M , Baker A L , Perez-Atayde A R , Newburger J W
Published: June 2012

BACKGROUND

Myocardial damage in myocarditis is mediated, in part, by immunological mechanisms. High-dose intravenous gamma-globulin (IVIG) is an immunomodulatory agent that is beneficial in myocarditis secondary to Kawasaki disease, as well as in murine myocarditis. Since 1990, the routine management of presumed acute myocarditis at Children's Hospital, Boston, and Children's Hospital, Los Angeles, has included administration of high-dose IVIG.

METHODS AND RESULTS

We treated 21 consecutive children presenting with presumed acute myocarditis with IVIG, 2 g/kg, over 24 hours, in addition to anticongestive therapies. A comparison group comprised 25 recent historical control patients meeting identical eligibility criteria but not receiving IVIG therapy. Left ventricular function was assessed during five time intervals: 0 to 7 days, 1 to 3 weeks, 3 weeks to 3 months, 3 to 6 months, and 6 to 12 months. At presentation, the IVIG and non-IVIG groups had comparable left ventricular enlargement and poor fractional shortening. Compared with the non-IVIG group, those treated with IVIG had a smaller mean adjusted left ventricular end-diastolic dimension and higher fractional shortening in the periods from 3 to 6 months (P = .008 and P = .033, respectively) and 6 to 12 months (P = .072 and P = .029, respectively). When adjusting for age, biopsy status, intravenous inotropic agents, and angiotensin-converting enzyme inhibitors, patients treated with IVIG were more likely to achieve normal left ventricular function during the first year after presentation (P = .03). By 1 year after presentation, the probability of survival tended to be higher among IVIG-treated patients (.84 versus .60, P = .069). We observed no adverse effects of IVIG administration.

CONCLUSIONS

These data suggest that use of high-dose IVIG for treatment of acute myocarditis is associated with improved recovery of left ventricular function and with a tendency to better survival during the first year after presentation.
Ventricular proarrhythmic effects of ventricular cycle length and shock strength in a sheep model of transvenous atrial defibrillation.
Authors: Ayers G M , Alferness C A , Ilina M , Wagner D O , Sirokman W A , Adams J M , Griffin J C
Published: June 2012

BACKGROUND

Synchronized cardioversion is generally accepted as safe for the treatment of ventricular tachycardia and atrial fibrillation when shocks are synchronized to the R wave and delivered transthoracically. However, others have shown that during attempted transvenous cardioversion of rapid ventricular tachycardia, ventricular fibrillation (VF) may be induced. It was our objective to evaluate conditions (short and irregular cycle lengths [CL]) under which VF might be induced during synchronized electrical conversion of atrial fibrillation with transvenous electrodes.

METHODS AND RESULTS

In 16 sheep (weight, 62 +/- 7.8 kg), atrial defibrillation thresholds (ADFT) were determined for a 3-ms/3-ms biphasic shock delivered between two catheters each having 6-cm coil electrodes, one in the great cardiac vein under the left atrial appendage and one in the right atrial appendage along the anterolateral atrioventricular groove. A hexapolar mapping catheter was positioned in the right ventricular apex for shock synchronization. In 8 sheep (group A), a shock intensity 20 V less than the ADFT was used for testing, and in the remaining 8 sheep (group B), a shock intensity of twice ADFT was used. With a modified extrastimulus technique, a basic train of eight stimuli alone (part 1) and with single (part 2) and double (part 3) extrastimuli were applied to right ventricular plunge electrodes. Atrial defibrillation shocks were delivered synchronized to the last depolarization. In part 4, shocks were delivered during atrial fibrillation. The preceding CL was evaluated over a range of 150 to 1000 milliseconds. Shocks were also delayed 2, 20, 50, and 100 milliseconds after the last depolarization from the stimulus (parts 1 through 3) or intrinsic depolarization (part 4). The mean ADFT for group A was 127 +/- 48 V, 0.71 +/- 0.60 J and for group B, 136 +/- 37 V, 0.79 +/- 0.42 J (NS, P > .15). Of 1870 shocks delivered, 11 episodes of VF were induced. Group A had no episodes of VF in part 1, two episodes of VF in part 2 (CL, 240 and 230 milliseconds with 2-millisecond delay), and one episode each in parts 3 (CL, 280 milliseconds with 2-millisecond delay) and 4 (CL, 240 milliseconds with 100-millisecond delay). Group B had two episodes in part 1 (CL, 250 and 300 milliseconds with 20-millisecond delay), three episodes in part 2 (CL, 230, 230, and 250 milliseconds with 2-millisecond delay), and one episode each in parts 3 (CL, 260 milliseconds with 2-millisecond delay) and 4 (198 milliseconds with 100-millisecond delay). No episodes of VF were induced for shocks delivered after a CL > 300 milliseconds.

CONCLUSIONS

Synchronized transvenous atrial defibrillation shocks delivered on beats with a short preceding ventricular cycle length (< 300 milliseconds) are associated with a significantly increased risk of initiation of VF. To decrease the risk of ventricular proarrhythmia, short CLs should be avoided.
Abrupt complement activation and transient neutropenia in patients with acute myocardial infarction treated with streptokinase.
Authors: Frangi D , Gardinali M , Conciato L , Cafaro C , Pozzoni L , Agostoni A
Published: June 2012

BACKGROUND

Whether and to what extent complement is activated in acute myocardial infarction (AMI) and how it contributes to inflammation of the ischemic area are not yet clear. Fibrinolytic agents used for thrombolysis are known to activate complement in vitro and may contribute to its activation in vivo. The aim of this study was to measure the extent of complement activation in AMI patients, some treated and some not treated with streptokinase. In addition, because abrupt complement activation in vivo is usually associated with leukocyte margination, plugging of cells in the microcirculation, and hypotension, we correlated complement activation with leukocyte numbers and mean arterial pressure.

METHODS AND RESULTS

Forty AMI patients were studied: 20 were treated with streptokinase (1.5 million IU IV over 60 minutes), and 20 were not given any fibrinolytic agent. The extent and severity of AMI were not significantly different in both groups. Blood samples were drawn on arrival at the hospital, during streptokinase infusion, and then daily for 1 week. Time-matched samples were also drawn from patients not treated with streptokinase. We measured plasma levels of anaphylatoxin C4a, C3a, and C5a by radioimmunoassay and membrane attack complexes SC5b-9 by enzyme immunoassay. Leukocytes and arterial pressure also were measured when samples were obtained. C4a, C3a, and SC5b-9 levels increased about 10-fold (P < .0001) during infusion of streptokinase. There were no significant increases in complement catabolic products in AMI patients not treated with streptokinase. There was a significant transient leukopenia (mean +/- SEM, -29.5 +/- 7.0%; P = .001) and decreases in systolic and diastolic pressures (systolic, -29.3 +/- 3.2%, P < .0001; diastolic, -27.5 +/- 3.4%, P < .0001) after 15 minutes of streptokinase infusion in coincidence with the peak of anaphylatoxins in plasma.

CONCLUSIONS

Streptokinase treatment of AMI causes abrupt activation of the complement system, whereas no significant complement activation can be detected in plasma of AMI patients not treated with fibrinolytic agents. Complement activation causes a transient leukopenia, as reported for such other clinical conditions as dialysis and cardiopulmonary bypass, and possibly contributes to the hypotension observed during streptokinase treatment.
Two-dimensional left ventricular deformation during systole using magnetic resonance imaging with spatial modulation of magnetization.
Authors: Young A A , Imai H , Chang C N , Axel L
Published: June 2012

BACKGROUND

Myocardial tissue tagging with the use of magnetic resonance imaging allows noninvasive regional analysis of heart wall motion and deformation. However, any evaluation of the effect of disease or treatment requires a baseline reference of normal values and variation. We studied the two-dimensional motion of material points imaged within the left ventricular wall using spatial modulation of magnetization (SPAMM) in 12 normal human volunteers.

METHODS AND RESULTS

Five parallel short-axis and five parallel long-axis slices were acquired at five times during systole. SPAMM tags were generated at end diastole using a 7-mm grid. Intersection point data were analyzed for displacement, rotation, and torsion, and triangles of points were analyzed for local rotation and principal strains. Short-axis displacement was the least in the septum for all longitudinal levels (P < .001). Torsion about the long axis was uniform circumferentially because of the motion of the centroids used to reference the rotation. In the long-axis images, the base displaced longitudinally toward the apex, with the posterior wall moving farther than the anterior wall (13.4 +/- 2.2 versus 9.7 +/- 1.8 mm, P < .001) in this direction. The largest principal strain (maximum lengthening) was approximately radially oriented in both views. In the short-axis images, the minimum principal strain (maximum shortening) increased in magnitude toward the apex (P < .001) with little circumferential variation, except at midventricle, where the anterior wall showed greater contraction than the posterior wall (-0.21 +/- 0.03 versus -0.19 +/- 0.02, P < .02).

CONCLUSIONS

Consistent regional variations in deformation are seen in the normal human heart. Displacement and maximum shortening strains are well characterized with two-dimensional magnetic resonance tagging; however, higher-resolution images will be required to study transmural variations.
Visualization of penetrating transmural arteries in situ by monochromatic synchrotron radiation.
Authors: Mori H , Hyodo K , Tobita K , Chujo M , Shinozaki Y , Sugishita Y , Ando M
Published: June 2012

BACKGROUND

Penetrating transmural arteries with a diameter of < 500 microns are considered to be a critical vascular component that causes a transmural variation of myocardial blood flow under various pathophysiological conditions. However, the conventional coronary angiographic system is not oriented to the visualization of such small arteries as these.

METHODS AND RESULTS

We magnified and monochromatized the inherently narrow beam (3 mm along the vertical direction) of synchrotron radiation by using an asymmetrically cut silicon crystal with 311 reflecting planes to obtain a monochromatic x-ray with relatively large beam size (60 x 25 mm) and with an energy of just above (+130 eV) the K-absorption edge of the contrast materials (33.17 and 37.41 ke V for iodine and barium, respectively). We irradiated dogs or excised hearts with the monochromatic x-ray and obtained coronary angiograms using an image intensifier and video system with a spatial resolution of 170 microns. In the anesthetized dog experiments, we visualized the transmural penetrating arteries (5 to 15 mm in length) arising every 4 to 7 mm from the epicardial branch. Visualization of these arteries filled with heavy element-loaded microspheres (15 microns in diameter) in the excised-heart experiments, in which the monochromatic x-ray was irradiated to the hearts through a 10- to 20-cm acrylic plate, indicated that this system could be used for human patients, in whom body absorption of x-ray is substantial.

CONCLUSIONS

Coronary angiogram by means of monochromatic x-ray is useful for a precise evaluation of coronary circulation, both in clinical setting and in physiological animal experiments.
Earlier diagnosis and treatment of acute myocardial infarction necessitates the need for a 'new diagnostic mind-set'.
Authors: Roberts R , Kleiman N S
Published: June 2012

Triaging patients suspected of myocardial infarction is performed primarily in the coronary care unit, with infarction determined within 12 to 24 hours, and only about 20% are subsequently shown to have myocardial infarction. Plasma MB CK is not elevated until 8 to 10 hours after onset, and the ECG is unreliable; thus, the need has arisen for a new "diagnostic mind-set." The need is threefold: (1) more effective triaging in the emergency room to prevent unnecessary use of hospital beds, particularly those in the intensive care units, (2) to administer thrombolytic therapy in the early hours, and (3) earlier detection of coronary reocclusion and reinfarction. Diagnostic imaging techniques such as pyrophosphate, thallium-201 technetium sestamibi, or positron emitting agents lack the necessary early diagnostic specificity, but echocardiography has potential although its specificity is limited. Plasma CK isoforms provide diagnostic sensitivity and specificity of 96% and 94%, respectively, within the initial 4 to 6 hours of onset and can be assayed within minutes. In a prospective study of 1100 patients suspected of infarction, with conventional MB CK, 22% of the patients admitted to the coronary care unit would have had infarction, whereas using the CK isoforms, 75% had infarction and about 50% were discharged home. A scenario for the future might be to initiate thrombolytic therapy outside the hospital (eg, recombinant tissue-type plasminogen activator [r-TPA] 20 mg bolus) and upon arrival, confirm or exclude infarction by the MB CK isoform which can be performed in the emergency room in 20 minutes to determine whether thrombolytic therapy and heparin should be continued.
Guidelines for long-term management of patients with Kawasaki disease. Report from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association.
Authors: Dajani A S , Taubert K A , Takahashi M , Bierman F Z , Freed M D , Ferrieri P , Gerber M , Shulman S T , Karchmer A W , Wilson W
Published: June 2012

Long-term management of patients with Kawasaki disease should be tailored to the degree of coronary arterial involvement. This committee has made recommendations for each risk level about antiplatelet and anticoagulant therapy, physical activity, follow-up assessment by a pediatric cardiologist or primary care physician, and the appropriate diagnostic procedures that may be performed to evaluate cardiac disease. The risk level for a given patient with coronary arterial involvement may change over time because of changes in coronary artery morphology. The recommendations for management presented here are intended as practical interim guidelines until additional prospective or retrospective data are compiled to define more clearly the natural history of Kawasaki disease.
Effects on left ventricular hypertrophy of long-term nonpharmacological treatment with sodium restriction in mild-to-moderate essential hypertension.
Authors: Jula A M , Karanko H M
Published: June 2012

BACKGROUND

Cross-sectional studies on human hypertension have suggested an association between sodium intake and left ventricular hypertrophy (LVH).

METHODS AND RESULTS

The effects on LVH of a nonpharmacological treatment program based mainly on sodium restriction were examined by serial echocardiography in a 12-month controlled, randomized study that included 76 previously untreated subjects with uncomplicated mild-to-moderate hypertension. The mean daily sodium excretion of 38 subjects randomized into the treatment group decreased from 195 +/- 95 to 94 +/- 73 mmol (P < .001) at 6 months and to 109 +/- 74 mmol (P < .001) at 12 months. This was accompanied by a weight decrease from 81.4 +/- 18.0 to 79.2 +/- 17.4 kg (P < .001) at 6 months and to 80.6 +/- 17.5 kg (NS) at 12 months. The net blood pressure decrease (difference in change from baseline between the treatment and control groups) was 8.9 mm Hg (P < .001) in systolic blood pressure and 6.5 mm Hg (P < .001) in diastolic blood pressure during the first 6 months and 6.7 mm Hg (P < .01) in systolic blood pressure and 3.8 mm Hg (P < .01) in diastolic blood pressure during the last 6 months. After 12 months of sodium restriction, left ventricular mass (LVM) had decreased by 5.4% (from 238 +/- 63 to 225 +/- 51 g, P < .01), and LVM index (LVMI) had decreased by 4.7% (from 123 +/- 26 to 117 +/- 22 g/m2, P < .05), whereas no changes occurred in these parameters in the control group. In treated subjects with baseline LVMI of more than the median value of 133 g/m2 in men and 107 g/m2 in women, LVM decreased by 8.6% (from 272 +/- 62 to 249 +/- 51 g, P < .01), and LVMI decreased by 7.1% (from 140 +/- 23 to 130 +/- 22 g/m2, P < .01). LVM and LVMI remained unchanged in treated subjects with LVMI values equal to or less than the median.

CONCLUSIONS

Our data suggest that long-term nonpharmacological treatment with moderate sodium restriction decreases LVH.
Shortening of fast pathway refractoriness after slow pathway ablation. Effects of autonomic blockade.
Authors: Natale A , Klein G , Yee R , Thakur R
Published: June 2012

BACKGROUND

Shortening of the anterograde effective refractory period (ERP) of the fast pathway has been reported after radiofrequency ablation of the slow pathway. We hypothesized that ERP shortening may be related to autonomic changes, possibly catecholamine release, as a result of ablation.

METHODS AND RESULTS

To test this, 10 consecutive patients with atrioventricular node reentry undergoing slow pathway ablation were given autonomic blockade before the ablation procedure. This was achieved by atropine 0.03 mg/kg and propranolol 0.15 mg/kg IV supplemented by half the initial dose after ablation and before the final study. A control group of 10 patients underwent the protocol without autonomic blockade. Before ablation, autonomic blockade did not alter the ERP of either the fast pathway (295 +/- 22 versus 298 +/- 26 milliseconds) or the slow pathway (264 +/- 36 versus 269 +/- 38 milliseconds). Autonomic blockade obscured dual pathway physiology in 2 patients and brought it out in another 2 without dual pathway physiology initially. Slow pathway ablation shortened the ERP of the fast pathway for the group as a whole (331.5 +/- 54 versus 305.5 +/- 60 milliseconds, mean +/- SD, n = 20, P < .04). There was no difference in degree of ERP shortening in control patients (23.5 +/- 58 milliseconds) or autonomic blockade patients (25.5 +/- 52 milliseconds).

CONCLUSIONS

These data suggest that shortening of the ERP of the fast pathway after slow pathway ablation is not mediated by autonomic changes.