摘要:

Background Myocardium undergoes complex cellular and histochemical alterations after acute myocardial infarction.These structural changes directly affect the mechanical stiffness of infarcted and remote myocardia. Previous investigations of infarct stiffness have been limited to uniaxial testing, which does not provide a unique description of the tissue's three-dimensional material properties. This study describes the first serial measurements of biaxial mechanical properties of sheep myocardium after anterioapical infarction.Methods and Results Anterioapical infarctions of 23.7+-2.5% of the left ventricular mass were produced by coronary arterial ligation in sheep. Biaxial force-extension measurements were made on freshly excised squares (6.45 cm2) of remote, noninfarcted, and infarcted myocardia before and 4 hours, 1 week, 2 weeks, and 6 weeks after ligation. Adjacent myocardial samples were assayed for hydroxyproline content. Force-extension data and a derived constitutive Equation wereused to describe stresses and strains and material properties of each sample. In sheep, anterioapical infarctions evolve into thin left ventricular aneurysms that consist of predominantly fibrous tissue with disrupted groups of muscle cells encased in scar. In the infarct, Cauchy stresses at 15% extensions (control stresses: circumferential, sigmaC, 19.4+-3.3 g/cm2; longitudinal, sigmaL, 54.8+-34.8 g/cm2) increase within 4 hours, peak at 1 to 2 weeks (sigmaC, 338.5+-143.6 g/cm2; sigmaL, 310.7+-45.9 g/cm2), and then decrease 6 weeks after infarction (sigmaC, 115+-47.2 g/cm2; sigmaL, 53.2+-28.9 g/cm2). Stresses in the remote myocardium follow a similar time course but to a lesser extent than the infarcted region. Hydroxyproline content, a measure of collagen content, does not correlate with infarct stiffness but progressively increases to 69.7+-7.6 micrograms/mg after 6 weeks. Stress-extension curves demonstrate directional anisotropy of both infarcted and remote myocardia.Conclusions The findings indicate that infarcted myocardium becomes more stiff during the first 1 to 2 weeks after anterioapical infarction and then more compliant.The infarct also exhibits directional anisotropy. These observations underscore the importance of ventricular material properties during the remodeling process after acute myocardial infarction and may partially explain the progressive left ventricular dilatation and functional deterioration that occur in some patients after anterioapical infarction. (Circulation. 1994;89:2315-2326.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Angiopeptin, a synthetic cyclic octapeptide analogue of somatostatin, reduces neointimal hyperplasia after balloon denudation of rabbit aorta if administered before injury.The aim of this study was to analyze the effect of angiopeptin pretreatment on the level of expression of the c-fos and c-jun protooncogenes, early markers of smooth muscle cell proliferation, after balloon denudation of rabbit aorta.Methods and Results For histological analysis of the effect of angiopeptin on neointimal thickening after aortic balloon denudation, rabbits were randomized into three groups:group 1 (controls), twice-daily injections of saline begun 24 hours before balloon denudation (n=9); group 2, twice-daily injections of angiopeptin 10 micrograms/kg begun 24 hours before balloon denudation (n=9); and group 3, twice-daily injections of angiopeptin 10 micrograms/kg begun 1 hour after balloon denudation (n=7). The degree of neointimal thickening 28 days after balloon denudation was significantly less in group 2 than in group 1 (neointimal area: group 1, 0.59+-0.11 mm2; group 2, 0.22+-0.05 mm2; P<.05. Neointima/media: group 1, 0.85+-0.17; group 2, 0.23+-0.05; P<.05). When angiopeptin was started 1 hour after denudation (group 3), however, the neointimal area (0.52+-0.09 mm2) and the neointima/media ratio (0.76+-0.10) were not statistically different from the control group. For analysis of protooncogene induction, rabbits received twice-daily subcutaneous injections of saline (n=7), angiopeptin 10 micrograms/kg (n=8), or angiopeptin 100 micrograms/kg (n=4) begun 24 hours before balloon denudation. The animals were killed 30 minutes after balloon denudation, and total aortic RNA was hybridized with fos and jun probes. Expression of c-fos and c-jun was detected 30 minutes after injury; angiopeptin pretreatment at 20 micrograms x kg-1x d-1induced a 41% reduction in c-fos expression and a 42% reduction in c-jun expression compared with control animals. The inhibitory effect at the higher dose of angiopeptin was similar.Conclusions Our results show that the inhibitory effect of angiopeptin on neointimal thickening is related to events that occur very early after injury and suggest that the inhibition of smooth muscle cell activation may be responsible, at least in part, for this effect.(Circulation. 1994;89:2327-2331.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Technetium-99m-labeled methoxyisobutyl isonitrile (Technetium-99m-sestamibi) is a myocardial perfusion agent that clears slowly from the myocardium. This study evaluates the early and late myocardial distributions of Technetium-99m-sestamibi and Thallium-201 in the presence of low-flow ischemia to determine whether Technetium-99m-sestamibi demonstrates rest "redistribution."Methods and Results Low-flow ischemia was produced in 18 anesthetized, open-chest dogs by partial occlusion of the left anterior descending coronary artery. Dogs were injected intravenously with Technetium-99m-sestamibi, Thallium-201, and radiolabeled microspheres during sustained low-flow ischemia. The hearts were excised either 20 minutes (group 1, 10 dogs) or 2.5 hours (group 2, 8 dogs) after injection for gamma well counting to evaluate the early and late myocardial distributions of these radiotracers, relative to microsphere flow. The early myocardial distributions of Technetium-99m-sestamibi and Thallium-201 were comparable and correlated with the flow deficit (group 1). We observed a significant difference in myocardial Thallium-201 (P=.005) and Technetium-99m-sestamibi (P<.0001) activities between groups 1 and 2 dogs relative to flow, suggesting some redistribution of both tracers. Myocardial slices were imaged postmortem with a gamma camera, and Technetium-99m-sestamibi defect intensity was quantified. There was excellent correlation (r=.97) between the early relative Technetium-99m-sestamibi defect intensity on postmortem images and the flow deficit (group 1). Among group 2 dogs, the correlation was good (r=.87), but the Technetium-99m-sestamibi defect was less severe than the flow deficit, again suggesting redistribution.Conclusions The myocardial distributions of Technetium-99m-sestamibi and Thallium-201 early after injection are comparable and proportional to flow. Under conditions of sustained low flow, there was detectable rest "redistribution" of Technetium-99m-sestamibi verified by both gamma well counting and high-resolution postmortem imaging of myocardial slices. Whether this degree of Technetium-99m-sestamibi rest redistribution will be detectable by serial clinical imaging remains uncertain. Nevertheless, these data suggest that imaging should be delayed after the resting injection of Technetium-99m-sestamibi when assessing myocardial viability in the presence of a critical stenosis. (Circulation. 1994;89:2332-2341.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Current two-dimensional echocardiographic measures of right ventricular volume are limited by the asymmetrical and crescentic shape of the ventricle and by difficulty in obtaining standardized views. Three-dimensional echocardiographic reconstruction, which does not require geometric assumptions or standardized views, may therefore have potential advantages for determining right ventricular volume. Three-dimensional techniques, however, have not been applied to the right ventricle in vivo, where cardiac motion and contraction could affect accuracy. The purpose of this study was to determine the feasibility and accuracy of three-dimensional echocardiographic reconstruction for quantifying right ventricular volume and function in vivo. In particular, it was designed to test the accuracy of a newly developed system that provides rapid, efficient, and automated three-dimensional data collection (minimizing motion effects) and takes advantage of the full three-dimensional data set to obtain volume.Methods and Results The three-dimensional system was applied to reconstruct the right ventricle and measure its volume and function during 20 hemodynamic stages created in five dogs. Actual instantaneous volumes were measured continuously by an intracavitary balloon connected to an external column. Hemodynamics were varied by volume loading and induction of ischemia. Three-dimensional reconstruction successfully reproduced right ventricular volume compared with actual values at end diastole (y=1.0x-3.4, r=.99, SEE=1.8 mL) and end systole (y=1.0x+2.0, r=.98, SEE=2.5 mL). The mean difference between calculated and actual volumes throughout the cycle was 2.1 mL, or 4.9% of the mean. Ejection fraction also correlated well with actual values (y=0.96x-0.3, r=.98, SEE=3.3%).Conclusions Despite the irregular crescentic shape of the right ventricle, this newly developed three-dimensional system and surfacing algorithm can accurately reconstruct its shape and quantitate its volume and function in vivo without geometric assumptions. The increased efficiency of the system should increase applicability to issues of clinical and research interest. (Circulation. 1994;89:2342-2350.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Atrioventricular junctional (AV nodal) reentrant tachycardia can be cured by catheter ablation of the slow pathway, which is part of the reentrant circuit.Previous work has suggested that extracellular double potentials may help identify the site of the slow pathway, but the origin and significance of these potentials are controversial. The aim of this study was to identify the source of these potentials.Methods and Results Studies were performed in isolated, blood-perfused porcine (n=8) and canine (n=4) hearts. Several methods were used to identify the origin of potentials: microelectrode recording, extracellular mapping, pacing from multiple sites, and light microscopy. Two types of double potentials, similar to those found in humans, were found in all hearts. LH potentials consisted of a low-frequency deflection followed by a high-frequency deflection during sinus rhythm or anterior septal pacing. HL potentials consisted of a high-frequency deflection followed by a low-frequency deflection. LH potentials were found close to the coronary sinus orifice. They were caused by asynchronous activation of the sinus septum and the region between the coronary sinus orifice and tricuspid annulus. HL double potentials were found along the tricuspid annulus. They were caused by asynchronous activation of two cell layers. The high-frequency component was caused by depolarization of atrial-type cells in the deep subendocardial layer. The low-frequency component was caused by depolarization of cells with nodal characteristics close to the endocardium. These cells were present around the entire tricuspid annulus, were not part of the compact AV node, and could be dissociated from the bulk of the atria by rapid atrial pacing.Conclusions LH potentials are caused by asynchronous activation of muscle bundles above and below the coronary sinus orifice.Their proximity to the site of the slow pathway is probably serendipity. HL double potentials are caused by asynchronous activation of atrial cells and a band of nodal-type cells close to the tricuspid annulus. The band of nodal-type cells is not part of the compact AV node and may represent the substrate of the slow AV nodal pathway. (Circulation. 1994;89:2351-2360.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Previous studies from our laboratory have shown pronounced augmentation of the force-frequency relation on myocardial contraction during exercise, but the influence of this effect on diastole has not been investigated.Methods and Results Accordingly, the effect of changing heart rate on left ventricular (LV) relaxation, filling dynamics, and pressure-volume relations during exercise was studied in eight conscious dogs. The exercise heart rate was slowed from 208+-21 (SD) to 163+-11 beats per minute by injection of a specific sinus node inhibitor (UL-FS 49, or zatebradine, 0.6 mg/kg) during continuous exercise. Heart rate was then abruptly restored to the predrug level by atrial pacing during continued exercise. LV volume was calculated by use of implanted ultrasonic crystals, and LV pressure was determined with an implanted micromanometer. Comparing conditions after pacing back to a heart rate of 210 beats per minute with those obtained when the heart rate was slowed by atrial pacing, LV dP/dtmaxwas increased by 27% at the higher rate (P<.01), despite a marked decrease in LV end-diastolic pressure (24+-4 versus 10+-5 mm Hg, P<.01), and the time constant of isovolumic LV pressure decay (tau) was significantly shortened (19+-5 versus 14+-4 milliseconds, P<.01). The peak rapid filling rate in early diastole (PFR) was not significantly changed by increasing the heart rate, since it was maintained at the slower rate. During exercise, at the slowed heart rate the early portion of the diastolic pressure-volume curve was significantly shifted upward and to the right compared with that at the physiological heart rate, but the late portion of the curve was unchanged.Conclusions These data indicate that the negative inotropic effect of the force-frequency relation when heart rate was slowed during exercise caused pronounced impairment of LV relaxation and early filling dynamics. Conversely, an important component of the pronounced improvement of diastolic ventricular function during normal exercise was shown to result from exercise-induced enhancement of the positive inotropic effects of the force-frequency relation on myocardial contraction and relaxation. (Circulation. 1994;89:2361-2368.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background A directionally changing shock electrical vector could facilitate defibrillation by depolarizing myocytes with different orientations vis-a-vis the shock field. Such a changing vector can be achieved by a new waveform for transthoracic defibrillation: overlapping sequential pulses. Our purpose was to evaluate this waveform.Methods and Results Ventricular fibrillation was induced in closed-chest dogs. Single and overlapping truncated exponential waveform pulse shocks were then administered from self-adhesive chest electrodes. Single pulse (control) shocks were 7.5-millisecond duration, while the sequential overlapping pulse shocks, using two different pathways, consisted of two pulses, each 5.0-millisecond duration; the second pulse began 2.5 milliseconds after the start of the first pulse and ended 2.5 milliseconds after the end of the first pulse. Thus, the total duration of the sequential overlapping shock was 7.5 milliseconds. During the overlap phase (2.5 milliseconds), the electrical vector orientation is the summation of the individual vectors. Two different electrode placements and corresponding electrical vector orientations were studied: group 1 (n=14), left lower chest to right upper chest (pulse 1), overlapped by right lower chest to left upper chest (pulse 2), with the sequence then reversed; and group 2 (n=11), left chest to right chest (pulse 1) overlapped by dorsal (vertebral column) to ventral (sternum) (pulse 2) with the sequence then reversed. At voltages equivalent to energies of 50, 100, and 150 J, the sequential overlapping pulse shocks achieved higher success rates than the single pulse shocks: At the low energy, 50 J, single pulse shock success rates were 0% (group 2) and 14% (group 1), while the overlapping pulse shocks achieved success rates of 39% (group 2) and 55% (group 1) (P<.05). Similarly, at the highest energy tested, 150 J, single pulse shock success rates were 45% (group 2) and 61% (group 1), while the overlapping pulse shock success was 91% (group 2) and 95% (group 1) (P<.05). In a third group of dogs (n=3), intracardiac plunge electrodes placed orthogonally in the septum showed that the orthogonal components of intracardiac voltage gradient change varied markedly during the three phases of the sequential overlapping shocks, demonstrating the changing direction of the net electrical vector as the shock proceeded. In a fourth group of dogs (n=5), short-duration (2.5-millisecond) single pulse shocks were compared with longer 7.5-millisecond single pulse shocks and with the sequential overlapping pulse shocks, all at equivalent energies. Despite substantially higher current flow, the 2.5-millisecond-duration single pulse shocks were not more effective than 7.5-millisecond single pulse shocks, and both 2.5- and 7.5-millisecond duration single pulse shocks had markedly inferior success rates compared with the sequential overlapping pulse shocks.Conclusions Sequential overlapping pulse shock waveforms facilitate defibrillation compared with single pulse shocks of the same total energy.This is due at least in part to the changing orientation of the electrical vector during the multiple pulse shock. (Circulation. 1994;89:2369-2379.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background In 1952, Prinzmetal induced preexcitation in the normal dog heart using subthreshold stimulation (SS) delivered to the right ventricle.Methods and Results In 12 dogs we recorded ECG leads II, aVR, His (Hb) and proximal right bundle potentials with electrode catheters at the aortic root and a special electrode that was inserted through the right ventricular (RV) free wall.In 12 others, SS was delivered to the Hb area by a catheter placed under the septal leaflet of the tricuspid valve. During SS, the HV interval shortened from 35+-4 milliseconds (mean+-SD) to 19+-7 milliseconds (P=.0001), but AH intervals were unchanged. The ECG showed delta waves with aberrant QRS complexes. Endocardial electrograms showed that the origin of activation in the preexcitation beats was localized to the muscle adjacent to the Hb or proximal right bundle. When vagal stimulation induced sudden AV block, no ventricular excitation was seen, confirming the subthreshold nature of the applied stimulation. By adjusting the levels of SS, latent forms of preexcitation could be induced, eg, early local septal muscle activation but no change in the ECG leads. Premature ventricular stimuli delivered to the RV apex or outflow tract could cause manifest preexcitation in the ECG leads or inhibit expression of latent preexcitation in endocardial recordings.Conclusions SS delivered to the RV apex or Hb area causes ventricular preexcitation, as shown previously by Prinzmetal et al.SS delivered at the insertion sites of an accessory pathway may facilitate localization of such abnormal connections, particularly when preexcitation is concealed. (Circulation. 1994;89:2380-2389.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Radiofrequency (RF) catheter ablation lesion size has been limited by the small volume of tissue directly heated by the RF electrode.Microwave (MW) energy has been proposed as an alternative energy source to generate larger lesions because of its increased volume of direct tissue heating. To further characterize MW ablation of myocardium, we studied the temperature-versus-distance profiles during MW ablation in an in vitro model of perfused and superfused porcine right ventricular free wall.Methods and Results Radial tissue temperatures in 19 isolated porcine right ventricles were measured and recorded with four fluoroptic thermometry probes placed within the myocardium at 2.5-mm radial increments from the catheter. The MW antenna catheters used were monopolar and helical-coil antennas resonating at 915 and 2450 MHz. Durations of energy delivery for a 915-MHz MW monopolar antenna (60 to 600 seconds) and a 4-mm-tip RF electrode (60 and 300 seconds) were varied to compare time courses of lesion formation. For each lesion, the temperature at the lesion border zone (the isotherm of irreversible tissue injury) was determined. Similar lesion size and temperature profiles were observed for 915-versus 2450-MHz MW antennas and monopolar versus helical-coil MW antennas. Lesion depth for the 915-MHz monopolar antenna increased monoexponentially with a half-time of 170 seconds. The isotherms for all MW antenna designs were not significantly different. The mean isotherm of irreversible tissue injury for MW lesions was not significantly different from the mean isotherm for RF lesions (54.4 degrees C versus 53.6 degrees C, respectively).Conclusions Microwave ablation has the potential to directly heat a greater volume of tissue than RF ablation but only with efficient MW antennas.The primary mechanism of tissue injury for both MW and RF ablation appears to be thermal. (Circulation. 1994;89:2390-2395.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Therapy with racemic compounds produces effects that can be attributed to both (S)-and (R)-enantiomers. Here we have tested the hypothesis that an enantiomer-enantiomer interaction would modulate the effects of treatment with a racemate, the antiarrhythmic propafenone. Previous studies have shown that while the enantiomers of propafenone exert similar sodium channel-blocking (QRS widening) effects, it is the (S)-enantiomer that produces beta -blockade; moreover, we have demonstrated recently that (R)-propafenone inhibits the metabolism of (S)-propafenone in vitro.Methods and Results This single-blind, randomized study compared the effects of (R/S)-, (S)-, and (R)-propafenone (150 mg q 6 hours for 4 days) and placebo on QRS duration (Delta QRS) and on maximum exercise heart rate (Delta HRmax), an index of beta -blockade. The clearance of (S)-propafenone was significantly lower (-55+-24%, P<.001) during treatment with (R/S)-propafenone than with the (S)-enantiomer alone, and Delta HRmaxwas significantly altered during (R/S)-propafenone (-8.8+-6.6 beats per minute; P<.01) and during (S)-propafenone (-4.3+-4.8 beats per minute; P<.01) but not during (R)-propafenone (-1.8+-6.4 beats per minute) or placebo (0.3+-7.1 beats per minute). In contrast, (R/S)-, (S)-, and (R)-propafenone all prolonged QRS compared with placebo.Conclusions These data indicate that (R)-propafenone impairs the disposition of (S)-propafenone in humans. As a result, the beta -blocking effects of 150 mg of racemic propafenone (75 mg of the (S)-enantiomer) were more pronounced than those of 150 mg of (S)-propafenone alone. Thus, the effects of racemic drug therapy are not necessarily those predicted by summation of the effects of the individual enantiomers. (Circulation. 1994;89:2396-2400.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID