bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of individual and combined effects of procainamide and amiodarone in patients with sustained ventricular tachyarrhythmias.
Authors: Marchlinski F E , Buxton A E , Kindwall K E , Miller J M , Rosenthal M E , Gottlieb C D , Bloom R B , Josephson M E
Published: June 2011

To compare the individual and combined electrophysiological effects of amiodarone and procainamide, 35 patients with sustained ventricular arrhythmias underwent programmed stimulation in the control state, after procainamide (mean concentration, 8.7 +/- 2.8 micrograms/ml), after 13 +/- 2 days of amiodarone (1,400 mg/day x 7 days, then 400 mg/day), and after amiodarone with procainamide (mean procainamide concentration, 7.8 +/- 2.2 micrograms/ml). Sustained ventricular tachycardia (VT) was inducible in all 35 patients during treatment with procainamide alone and with amiodarone alone. Procainamide and amiodarone similarly increased the VT cycle length (+68 vs. +61 msec), the corrected QT interval (+63 vs. +49 msec), and the ventricular effective refractory period measured at paced cycle lengths of 600-550 msec (+23 vs. +21 msec) and 400 msec (+25 vs. +23 msec). Procainamide had a more pronounced effect on QRS duration than amiodarone during sinus rhythm (+18 vs. +8 msec, p less than 0.01) and during paced cycle lengths of 600-550 msec (+32 vs. +23 msec, p less than 0.01) and 400 msec (+37 vs. +28 msec, p less than 0.1) but a similar effect on the QRS duration during VT (+32 vs. +29 msec). During combination therapy, VT initiation was prevented in only two (6%) patients. The combination therapy produced a greater increase (p less than 0.001) than individual therapy in all the electrophysiological intervals assessed, with the exception of the sinus cycle length. On each drug regimen, a cycle length-dependent increase (p less than 0.05) in paced QRS duration was noted (400 more than 600-550 msec).(ABSTRACT TRUNCATED AT 250 WORDS)
Characterization in vivo of the fibrin specificity of activators of the fibrinolytic system.
Authors: Eisenberg P R , Sobel B E , Jaffe A S
Published: June 2011

Development of appropriate clinical dose regimens of individual plasminogen activators such as tissue-type plasminogen activator (t-PA) has generally relied primarily on nonpharmacological endpoints such as angiographically documented clot lysis. The recent availability of monoclonal antibodies that differentiate products of plasmin lysis of fibrin from those of lysis of fibrinogen should permit delineation of the relative fibrin specificity of different plasminogen activators or of different doses of the same activator in vivo. Thus, their use should accelerate and facilitate development of implementation of optimal dose regimens for diverse activators and combinations of activators. The present study was designed to determine whether assay of such markers effectively differentiates effects of two doses of t-PA, each of which are comparably effective in opening infarct-related arteries, in patients studied at the Washington University Clinical Unit of the National Institutes of Health-sponsored Thrombolysis in Myocardial Infarction Trial. The extent of lysis of fibrin and of lysis of fibrinogen by plasmin resulting from administration of t-PA was evaluated in 19 patients given 150 mg t-PA over 6 hours and 17 given 100 mg over the same interval by assay of serially obtained plasma samples for crosslinked fibrin degradation products (XL-FDP) and B beta 1-42, a peptide released when fibrinogen is degraded to fragment X by plasmin. XL-FDP were markedly elevated after 6-hour infusions of both doses of t-PA. However, elevations were not more with the higher dose [peak value, 4,321 +/- 986 ng/ml (+/- SEM)] compared with the lower dose (3,397 +/- 1,096 ng/ml) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Excimer laser-induced simultaneous ablation and spectral identification of normal and atherosclerotic arterial tissue layers.
Authors: Laufer G , Wollenek G , Hohla K , Horvat R , Henke K H , Buchelt M , Wutzl G , Wolner E
Published: June 2011

A krypton-fluorine excimer laser at a 248-nm wavelength was used to irradiate normal and severely atherosclerotic segments of human postmortem femoral arteries. Single pulses and multiple pulses required for penetration or perforation of the arterial wall were applied with 16 nsec pulse width and 5 J/cm2/pulse energy fluence. The total fluorescence of irradiated and ablated tissue was analyzed in real-time mode by means of spectroscopy. Each laser pulse produced one spectrum that was characteristic of the composition of the tissue layer, which was ablated. Fluorescence spectroscopy indicated a broad-continuum emission between 300 and 700 nm with peak fluorescence of equal intensity at wavelengths of 370 and 460 nm (ratio, 1.004 +/- 0.087) for normal media layers. Atheromas without calcification (lipid, fibrous, and mixed) were found with spectral maxima at the same wavelengths but with significantly reduced intensity at 460 nm (ratio, 1.765 +/- 0.263; p less than 0.001). In contrast to this broad-continuum fluorescence, calcified plaques displayed multiple-line emission with the most prominent peaks at wavelengths of 397, 442, 450, 461, 528, and 558 nm. These fluorescence criteria identified the histologically classified target tissue precisely. Histological examination of the corresponding arterial layers indicated sharply delineated and circumscribed tissue ablation. These results indicate that simultaneous tissue identification (diagnosis) and ablation (treatment) by excimer laser irradiation is feasible under strict laboratory conditions. We conclude that this principle demonstrates the potential for laser beam control by means of target-specific ablation.
Effect of ischemia on calcium-dependent fluorescence transients in rabbit hearts containing indo 1. Correlation with monophasic action potentials and contraction.
Authors: Lee H C , Mohabir R , Smith N , Franz M R , Clusin W T
Published: June 2011

The effects of acute global ischemia on cytosolic calcium transients were studied in perfused rabbit hearts loaded with the fluorescent calcium indicator indo 1. Indo 1-loaded hearts were illuminated at 360 nm, and fluorescence was recorded simultaneously at 400 and 550 nm from the epicardial surface of the left ventricle. The F400/F550 ratio was calculated by an analog circuit, which allowed cancellation of optical motion artifact. Resulting calcium transients demonstrated a rapid upstroke and slow decay similar to those recorded in isolated ventricular myocytes. Global ischemia rapidly suppressed contraction, but it produced a concurrent increase in the systolic and diastolic levels of the calcium transients, together with an increase in the duration of the peak. The effects of ischemia were reversed by reperfusion, inhibited by verapamil, and mimicked by perfusion of nonischemic hearts with acidified (CO2-rich) solution. In addition to elevation of the calcium transients, ischemia caused a pattern of intracellular calcium alternans that was discernible after 2-3 minutes. The pattern of alternans was stable at a given epicardial site, but it could be out of phase at different sites. Similar nonuniformities were observed in contraction strength and in the duration of monophasic action potentials recorded immediately adjacent to the fiber-optic probe. Abnormalities in intracellular calcium may be a causal factor in the loss of electrical and mechanical synchrony in the acutely ischemic heart.
Doppler evaluation of results of percutaneous aortic balloon valvuloplasty in calcific aortic stenosis.
Authors: Nishimura R A , Holmes D R , Reeder G S , Orszulak T A , Bresnahan J F , Ilstrup D M , Tajik A J
Published: June 2011

To evaluate the short-term results of percutaneous aortic balloon valvuloplasty, 55 consecutive elderly patients with symptomatic, severe aortic stenosis who were at high risk for surgical intervention underwent the procedure, with follow-up by clinical evaluation and Doppler echocardiography. Over a mean follow-up of 6.2 months, there were three early deaths (less than 30 days) and eight late deaths. Nine patients underwent subsequent aortic valve surgery, and four had repeat balloon valvuloplasty. Doppler echocardiography revealed a reduction in aortic valve mean gradient from 48 +/- 18 to 33 +/- 12 mm Hg after the procedure (p less than 0.0001) but a return to 46 +/- 16 mm Hg at follow-up (p less than 0.05). The aortic valve area increased from 0.54 +/- 0.15 to 0.85 +/- 0.23 cm2 after the procedure (p less than 0.0001), but there was a significant decrease to 0.67 +/- 0.19 cm2 at follow-up (p less than 0.05). Of patients free of aortic valve operation or death after 30 days after the procedure, 76% were severely symptomatic before the procedure as compared with 38% at follow-up. In patients undergoing percutaneous aortic balloon valvuloplasty, there is a continued high short-term mortality and a significant incidence of restenosis over short-term follow-up. Nonetheless, a subset of patients do experience sustained clinical improvement from this procedure.
Quantification of infarct size by 201Tl single-photon emission computed tomography during acute myocardial infarction in humans. Comparison with enzymatic estimates.
Authors: Mahmarian J J , Pratt C M , Borges-Neto S , Cashion W R , Roberts R , Verani M S
Published: June 2011

We prospectively investigated whether 201Tl single-photon emission computed tomography (SPECT) could accurately diagnose the presence and quantify the extent of acute myocardial infarction when compared with infarct size assessed by plasma MB-creatine kinase activity. Thirty patients with enzymatic evidence of infarction were imaged within 12-36 hours of chest pain (mean, 23.4 hours). No patient had a previous infarction, and none underwent intervention seeking to restore coronary patency. Infarct size was quantified with computer-generated polar maps of the myocardial radioactivity and expressed as a percentage of the total left ventricular volume. To assess left and right ventricular performance, blood-pool gated radionuclide angiography was performed immediately after SPECT. All 30 patients had perfusion defects consistent with myocardial infarction. Scintigraphic and enzymatic estimates of infarct size correlated well for the group as a whole (r = 0.78, p less than 0.001, SEE = 9.1) but especially for those patients with anterior infarction (r = 0.91, p less than 0.001, SEE = 7.9). The poor correlation observed in patients with inferior infarction (r = 0.50, p less than 0.05, SEE = 10.0) was believed to be related to the frequent occurrence of right ventricular involvement because SPECT assessed only left ventricular damage, whereas the enzymatic method estimated the myocardial injury in both ventricles. A quantitative index of right ventricular infarct size, derived from the relation between the scintigraphic and enzymatic estimates, had a strong inverse correlation with right ventricular ejection fraction (r = -0.89, p less than 0.001, SEE = 3.6).(ABSTRACT TRUNCATED AT 250 WORDS)
Subsidiary pacemaker function in complete heart block after His-bundle ablation.
Authors: Schmidinger H , Probst P , Schneider B , Weber H , Kaliman J
Published: June 2011

To investigate the electrophysiological properties of ventricular impulse formation after His-bundle ablation in 11 patients, incremental ventricular overdrive stimulation studies were performed. The studies, which were spread over a follow-up period of up to 601 days, were carried out invasively with temporary leads as well as noninvasively with the implanted pacemakers and chest wall inhibition. The overdrive pacing rate was increased in steps of 10 beats/min, and the pacing duration was 2 minutes at each level. Ten out of 11 patients had a reliable ventricular escape rhythm; in the remaining patient, consistently no subsidiary pacemaker function was observed up to 10 seconds. In 83% of the studies, incremental ventricular overdrive stimulation caused progressive suppression of ventricular impulse formation with exponential increase in ventricular recovery time and progressive postrecovery subsidiary pacemaker depression. In the remaining 17%, ventricular recovery time showed a heterogeneous response to overdrive stimulation--as possible cause alterations in the sympathetic tone and limitations attributable to the method used are discussed. The results of this study demonstrate a rate-dependent overdrive suppression of subsidiary ventricular pacemaker tissue. This can be of clinical importance in patients with complete heart block and rate-adaptive pacemakers because sudden pacemaker failure or temporary pacemaker inhibition at high stimulation rates may cause Stokes-Adams attacks not reproducible at lower pacing rates.
Atrial natriuretic peptide distribution in fetal and failed adult human hearts.
Authors: Tsuchimochi H , Kurimoto F , Ieki K , Koyama H , Takaku F , Kawana M , Kimata S , Yazaki Y
Published: June 2011

The distributions of atrial natriuretic peptide (ANP) in human hearts during the developmental stage and in adult pathological states was examined with an antibody specific to human alpha-ANP. With immunoblotting and immunofluorescence methods, we found that a 17-kDa protein, which is a pro ANP, was expressed in human fetal ventricles, in which the numbers of myofibers containing ANP granules were more abundant in the subendocardial region than the subepicardial region. As determined by radioimmunoassay, the content of immunoreactive ANP (per milligram protein) in the developing heart was greatest in the left atrium and occurred decreasingly in the right atrium, right ventricle, and left ventricle, respectively. Because ANP content in the left ventricle declined during the progress of gestation in developing hearts and because it was very low, if ever detectable, in normal adult hearts, ventricular ANP expression appears to be developmentally regulated from the early gestational stage. However, it was reexpressed in the ventricles of patients who had suffered from severe congestive heart failure. In this situation, we found that the ventricular ANP expression was more marked in patients with dilated cardiomyopathy than in patients with severe valvular disease. Interestingly, in the ventricles of patients with dilated cardiomyopathy, ANP contents were higher in the left ventricular free wall than in the right ventricular free wall, although the left ventricular subendocardium contained more ANP than the subepicardium, showing a transmural gradient similar to that expressed in fetal ventricles. Thus, the expression of ANP in human ventricles is developmentally regulated from the early gestational stage, and even adult ventricular myofibers can synthesize ANP during severe congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Current therapy of the failing heart.
Authors: Cohn J N
Published: June 2011

Myocardial dysfunction eventuating in systolic and diastolic pump function abnormalities is a consequence of a wide variety of cardiac diseases. The symptoms that develop in this syndrome appear to be related as much to peripheral and neurohormonal mechanisms as to the underlying pathological and cardiac functional abnormality. Relief of symptoms, slowing of the progression of the cardiac functional abnormality, and prolongation of life provide the major agenda for the physician faced with the management of these patients. Judicious use of vasodilators, diuretics, digoxin, dietary therapy, and exercise therapy can relieve symptoms and improve the quality of life in most patients suffering from this syndrome. Recent evidence that vasodilator drugs can prolong life now provides the physician with further justification for routine use of this class of compounds. The eventual solution to the high mortality in this common disease process may be prevention of the development of overt heart failure by more prompt recognition and early treatment of the signs of ventricular dysfunction. This possibility must await the completion of current and proposed clinical trials.
Emergency stenting for acute occlusion after coronary balloon angioplasty.
Authors: Sigwart U , Urban P , Golf S , Kaufmann U , Imbert C , Fischer A , Kappenberger L
Published: June 2011

Acute coronary artery occlusion complicates 2-12% of the balloon angioplasty procedures, and despite repeat angioplasty, emergency surgical revascularization is often necessary. We report our initial experience with the emergency implantation of endoluminal stents for acute vessel closure after coronary balloon angioplasty. Nine patients received one stent, and two patients received two stents during the study period. Implantation was technically successful in all patients; there were no deaths, no myocardial infarctions as evidenced by Q wave on the electrocardiogram, and no need for emergency surgery. One additional patient, not satisfying the study inclusion criteria, died 16 hours after stent implantation from left ventricular failure and intractable arrythmias. Two patients in the study group had a moderate creatinine phosphokinase rise during the first 48 hours after implantation. During a median follow-up period of 3 months (range, 1-20 months), there have been no deaths and no need for elective coronary bypass surgery. One patient required emergency recanalization 3 months after implantation because of acute occlusion of the stented segment with limited myocardial infarction. Six patients have undergone control angiography, and none has developed chronic restenosis within the stented segment. For selected patients, coronary artery stenting appears to be a promising alternative to emergency bypass surgery after acute vessel occlusion during balloon angioplasty.
Prediction of defibrillation success from a single defibrillation threshold measurement with sequential pulses and two current pathways in humans.
Authors: Jones D L , Klein G J , Guiraudon G M , Sharma A D , Yee R , Kallok M J
Published: June 2011

The ultimate aim of defibrillation testing is to predict consistent defibrillation. This study tested the hypothesis that defibrillation success could be predicted from a single measurement of defibrillation threshold. We measured defibrillation threshold by using three patch electrodes and a standard protocol intraoperatively in 49 patients undergoing arrhythmia surgery. Each patient was then assigned to one of five energy subgroups (0.5, 1.0, 1.5, 2.0, or 2.5 times defibrillation threshold) for a single shock (followed by a rescue shock if necessary) for a subsequent ventricular fibrillation episode. A curve relating percent success to energy was then constructed for the group. Defibrillation threshold averaged 4.7 +/- 2.98 J for the group (mean +/- SD). There was a curvilinear relation between the energy of the defibrillation threshold ratio test shock and percent success: 33.3%, 58.3%, 81.8%, 91.7%, and 100% at mean defibrillation threshold ratios of 0.56 +/- 0.14, 1.02 +/- 0.07, 1.53 +/- 0.14, 1.88 +/- 0.09, and 2.60 +/- 0.14, respectively. We conclude that consistent defibrillation is predictable from a single measurement of defibrillation threshold. Furthermore, for an individual patient, a safety margin of 2.6 times defibrillation threshold should approximate 100% successful defibrillation for a single test shock.
Comparison of blood-flow velocity waveforms in different coronary artery bypass grafts. Sequential saphenous vein grafts and internal mammary artery grafts.
Authors: Fujiwara T , Kajiya F , Kanazawa S , Matsuoka S , Wada Y , Hiramatsu O , Kagiyama M , Ogasawara Y , Tsujioka K , Katsumura T
Published: June 2011

Characteristics of blood-flow velocities were investigated at different sites in two types of coronary artery bypass grafts, sequential saphenous vein grafts (SSVG) and internal mammary artery grafts (IMAG). The latter appear to have the longest life span. The patency rate of the side-to-side anastomosis of the SSVG is better than that of the end-to-side anastomosis. The SSVG was anastomosed to the major diagonal branch by side-to-side anastomosis and to the left anterior descending coronary artery (LAD) by end-to-side anastomosis in 13 patients who had 75-100% and 75-90% stenoses in the LAD and major diagonal branch, respectively. IMAG anastomoses were performed to the LAD in 10 patients with 75-100% stenoses of the artery. The blood-flow velocities were measured by the 20-MHz, eighty-channel ultrasound pulsed Doppler method during surgery. In six patients in the SSVG group, we investigated the configuration of velocity profiles at the region just proximal to the side-to-side anastomosis and at the bridge portion between the side-to-side and end-to-side anastomosis. In the other seven patients, we measured the blood-flow velocity at several centimeters proximal to the side-to-side anastomosis and compared it with that in the IMAG. At the region just proximal to the side-to-side anastomosis, the velocity profile skewed toward the anastomosis side wall in all patients, and the flow velocity near the wall opposite to the side-to-side anastomosis was reversed in five of six patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1).
Authors: Angleton P , Chandler W L , Schmer G
Published: June 2011

Previous studies have shown that overall fibrinolytic activity in blood follows a diurnal rhythm with a peak in the morning and a trough in the evening. The purpose of this study was to determine which fibrinolytic factor(s) was responsible for this diurnal rhythm. Resting and postvenous occlusion tissue-type plasminogen activator (t-PA) activity, resting t-PA antigen, and resting plasminogen activator inhibitor 1 (PAI-1) activity were measured in the morning and evening in 33 healthy men (mean age, 31 years) and in 15 patients (mean age, 57 years) with previous myocardial infarction or unstable angina. PAI-1 activity and t-PA antigen were significantly higher (p less than 0.01) in the morning compared with the evening in controls and patients. In contrast, resting t-PA activity was significantly lower in the morning (p less than 0.01) in both groups and was inversely correlated with PAI-1 activity (r = -0.57, p less than 0.0001). Postvenous occlusion t-PA activity and t-PA capacity were not significantly different between morning and evening in either group. Because t-PA antigen levels and PAI-1 activity were highest in the morning, the variation in t-PA activity was probably not due to decreased secretion of t-PA but instead to changes in the secretion of PAI-1. Our findings indicate that diurnal variations in PAI-1 activity may reduce fibrinolytic activity in the morning in healthy individuals and in patients with coronary artery disease.
In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin.
Authors: Gerrard J M , Taback S , Singhroy S , Docherty J C , Kostolansky I , McNicol A , Kobrinsky N L , McKenzie J K , Rowe R
Published: June 2011

The effects of smoking, aspirin ingestion, and sex differences on bleeding times and bleeding time thromboxane B2 and 6-keto-prostaglandin (PG)F1 alpha production were examined. Nonsmoking men produced more thromboxane B2 (3.99 +/- 0.76 ng/ml) than nonsmoking women (2.13 +/- 0.24 ng/ml). Female smokers produced more thromboxane B2 (5.01 +/- 0.97 ng/ml) than nonsmoking women. Twenty-four hours after a single dose of 600 mg aspirin, in vitro production of thromboxane B2 in response to collagen fell by 95%, whereas in vivo production of thromboxane B2 and 6-keto-PGF1 alpha in bleeding time blood fell by 87% and 66%, respectively. Subjects with the lowest absolute levels of thromboxane B2 24 hours after aspirin were also those with the longest postaspirin bleeding times. Recovery of 6-keto-PGF1 alpha production was faster than recovery of thromboxane B2 production, but 6-keto-PGF1 alpha production for most subjects was still below basal 72 hours after aspirin. The influence of two different doses of long-term aspirin (80 mg every other day and 325 mg daily) on the in vivo production of thromboxane B2 and 6-keto-PGF1 alpha was studied in normals and diabetics. After 14 days of 80 mg aspirin every other day, thromboxane B2 and 6-keto-PGF1 alpha production were both substantially inhibited (93% and 78%, respectively). After 14 days of 325 mg aspirin daily, thromboxane B2 production was similarly substantially inhibited (93%), whereas 6-keto-PGF1 alpha was significantly less affected (only 45% inhibition). Study of a second group of five normal subjects confirmed that 6-keto-PGF1 alpha production was significantly inhibited 24 hours after the first dose of 325 mg aspirin but was not significantly less than basal after 14 days of 325 mg aspirin. The results suggest that 325 mg aspirin daily is more antithrombotic compared with 80 mg every other day due to the superior preservation of prostacyclin production.
Visualization of subendocardial myocardial ischemia with myocardial contrast echocardiography in humans.
Authors: Lim Y J , Nanto S , Masuyama T , Kodama K , Ikeda T , Kitabatake A , Kamada T
Published: June 2011

Previous studies indicate the degree of myocardial echo contrast enhancement may be related to regional myocardial perfusion. In this study, myocardial contrast echocardiography was used to characterize changes in the transmural myocardial blood flow distribution that were provoked by rapid atrial pacing in 11 patients with one-vessel coronary artery disease. Ten patients without coronary artery disease served as controls. Myocardial contrast echocardiography was performed by intracoronary injection of 2 ml hand-agitated amidotrizoate sodium meglumine (Urografin-76) and by imaging a short-axis view of the left ventricle with two-dimensional echocardiography before and during injection of the contrast agent. The two-dimensional echocardiographic images at end diastole, before and after injection of the contrast agent, were digitized off-line into a 512 x 512 pixel matrix with 256 gray levels/pixel to quantify the degree of the enhancement of the peak gray level after injection. Transmural myocardial blood flow distribution was evaluated by measuring the ratio of the enhanced gray level in the endocardial half (endo) to that in the epicardial half (epi) (endo:epi gray level ratio) in the anteroseptal, posterolateral, and inferior segments before and just after rapid atrial pacing in each patient. In patients without coronary artery disease, there were no differences in the endo:epi gray level ratio between any of the three segments both before and after pacing. Mean values of the three segments were 0.95 +/- 0.08 before pacing and 0.90 +/- 0.13 after pacing, respectively. In contrast, in patients with coronary artery disease, the endo:epi gray level ratio for the segment supplied with stenotic coronary artery decreased after pacing (0.40 +/- 0.21 vs. 0.93 +/- 0.18, p less than 0.01), probably reflecting subendocardial myocardial ischemia, whereas that for the segment supplied with nonstenotic coronary artery remained unchanged (0.88 +/- 0.20 vs. 0.99 +/- 0.23, NS). Thus, changes in transmural myocardial blood flow distribution with rapid pacing, which may be due to transient subendocardial ischemia, are visualized with myocardial contrast echocardiography.
Beta-adrenergic supersensitivity of the transplanted human heart is presynaptic in origin.
Authors: Gilbert E M , Eiswirth C C , Mealey P C , Larrabee P , Herrick C M , Bristow M R
Published: June 2011

An increase in cardiac beta-adrenergic sensitivity or beta-receptor density or both has been described in several animal species after denervating the heart. The transplanted human heart is also denervated and, therefore, may exhibit supersensitivity to beta-adrenergic agonists and an increase in beta-adrenergic receptor density. In 16 patients examined 1-3 months after orthotopic cardiac transplantation, beta-adrenergic receptor density measured by [125I]iodocyanopindolol binding in endomyocardial biopsy specimens was not significantly different in transplant recipients compared with normal controls (transplant = 1,429 +/- 199, control = 1,728 +/- 263 fmol/g wet wt; p = NS). However, when normalized to Lowry protein, the [125I]iodocyanopindolol in beta-adrenergic receptor density in biopsy tissue from transplant recipients was significantly lower than in tissue from controls (transplant = 58.1 +/- 6.2, control = 93.5 +/- 13.4 fmol/g Lowry protein; p = 0.011). Atrial sinus node activity of the denervated donor heart and the innervated atrial cuff of the native recipient heart could be detected on the surface electrocardiogram in six patients. In these six patients, the heart rate response to graded infusions of epinephrine (taken up by the adrenergic nerve terminals) and isoproterenol (not taken up by the adrenergic nerve terminals) was measured. The epinephrine dose-response curve in transplanted donor atria was significantly to the left of the native recipient atrial dose-response curve (p less than 0.0001). The isoproterenol dose-response curves for native and transplanted atria were not different. We conclude that myocardial beta-adrenergic receptors are not increased in human orthotopic cardiac allografts and that there is no evidence for beta-receptor-mediated supersensitivity of postsynaptic origin.(ABSTRACT TRUNCATED AT 250 WORDS)
Synergistic combinations of recombinant human tissue-type plasminogen activator and human single-chain urokinase-type plasminogen activator. Effect on thrombolysis and reocclusion in a canine coronary artery thrombosis model with high-grade stenosis.
Authors: Ziskind A A , Gold H K , Yasuda T , Kanke M , Guerrero J L , Fallon J T , Saito T , Collen D
Published: June 2011

The synergistic effects of recombinant human tissue-type plasminogen activator (rt-PA) and single-chain urokinase-type plasminogen activator (scu-PA) on coronary arterial thrombolysis were investigated in open-chest dogs with thrombosis of the left anterior descending coronary artery and a superimposed high-grade stenosis. A 90% stenosis was generated by external constriction, reducing blood flow to 40 +/- 10% of baseline. Localized thrombosis was produced by endothelial cell injury and instillation of thrombin and fresh blood. Intravenous infusion for 60 minutes of either 30 micrograms/kg/min rt-PA alone or 10 micrograms/kg/min scu-PA alone consistently produced coronary artery recanalization (six of eight dogs and five of five dogs, respectively) but was almost always associated with reocclusion during or shortly after the end of the infusion (four of six dogs and five of five dogs, respectively). Infusion of either 15 micrograms/kg/min rt-PA or 5 micrograms/kg/min scu-PA for 60 minutes did not cause coronary artery recanalization (none of four dogs in each group). Combined infusion of 7.5 micrograms/kg/min rt-PA and 2.5 micrograms/kg/min scu-PA for 60 minutes (one fourth of the minimum thrombolytic dose of each agent) induced coronary artery recanalization (six of six dogs) but was also associated with early reocclusion (six of six dogs). Combined infusion of 3.75 micrograms/kg/min rt-PA and 1.25 micrograms/kg/min scu-PA for 60 minutes did not consistently cause recanalization (one of four dogs). Combined infusion of 15 micrograms/kg/min rt-PA and 5 micrograms/kg/min scu-PA for 60 minutes caused recanalization in all of six dogs but was associated with reocclusion in all six.(ABSTRACT TRUNCATED AT 250 WORDS)
Activation mapping of reentry around an anatomic barrier in the canine atrium. Observations during entrainment and termination.
Authors: Boyden P A , Frame L H , Hoffman B F
Published: June 2011

We determined total right atrial activation sequences during entrainment and termination of flutter induced in dogs with a surgically induced atrial lesion. This type of atrial flutter is due to circus movement of an impulse around the tricuspid valve orifice. We recorded simultaneously from 96 bipolar intracavity electrodes in the right atrium of the isolated, perfused heart. By constructing isochronal maps, we demonstrated the pattern of atrial activation during atrial pacing protocols that either entrained or entrained and then terminated the reentrant rhythm. We show that during pacing the antidromic wavefront from the paced impulse (An) collides with the orthodromic wavefront from the previous paced impulse (On-1). During entrainment, the site of collision of the orthodromic and antidromic wavefronts was constant during pacing at a fixed rate but shifted in the antidromic direction as the pacing rate increased. Furthermore, the last paced beat was entrained only up to the site of collision of the previous paced beat. During one period of entrainment, termination of the reentrant arrhythmia occurred because On-1 blocked in the reentrant pathway due to refractory tissue left by On-2. However, subsequent An did not collide directly with On as was expected, but rather On blocked by an interaction with tissue left refractory by An. Because On was blocked, no reentry occurred when pacing ended.
ST segment shifts are poor predictors of subsequent Q wave evolution in acute myocardial infarction. A natural history study of early non-Q wave infarction.
Authors: Boden W E , Gibson R S , Schechtman K B , Kleiger R E , Schwartz D J , Capone R J , Roberts R
Published: June 2011

Acute ST segment elevation is regarded generally as the sine qua non of evolving Q wave myocardial infarction (MI) because such electrocardiographic (ECG) injury is believed to be a marker of transmural ischemia and a forerunner of transmural necrosis. Alternatively, ST segment depression with or without T wave inversion is viewed as the dominant ECG feature of non-Q wave MI. However, this hypothesis has not been assessed prospectively in an acute MI population. We analyzed 2,304 serial ECGs at study entry (admission), day 2, day 3, and predischarge (mean, 10.2 +/- 2 days) from 576 patients with creatine kinase MB confirmed acute non-Q wave MI to determine what percentage of patients with early ST segment elevation culminated in subsequent Q wave development. Of this group, 187 patients (32%) exhibited 1 mm or greater ST segment elevation in two or more contiguous entry ECG leads. Of those patients whose non-Q wave MI could be localized on the basis of diagnostic admission ST segment shifts, the prevalence of early ST segment elevation was 43% (187 of 439). The sum total mean (+/- SD) peak ST segment elevation by lead group (anterior, inferior, lateral) was 4.0 +/- 2.4, 4.5 +/- 2.4, and 2.5 +/- 0.6 mm, respectively. Despite this, only 20% of patients with ST segment elevation (37 of 187) developed Q waves. Of 252 patients who exhibited early ST segment depression or T wave inversion or both, 39 (15%) evolved subsequent Q waves. Thus, while the prevalence of early ST segment elevation in acute evolving non-Q wave MI was higher than previously reported, 80% of patients with and 85% of patients without ST segment elevation and absent Q waves on the admission ECG did not develop subsequent Q waves during a 2-week period of observation (p = NS). In addition, when patients with ST segment elevation were compared with patients with ST segment depression or T wave inversions or both, there were no between-group differences in log peak creatine kinase (404 vs. 383 IU), reinfarction (6% vs. 8%), postinfarction angina (50% vs. 42%), or early recurrent ischemia (49% vs. 45%), defined as postinfarction angina with transient ECG changes. Thus, in patients who present with initial acute non-Q wave MI, ST segment shifts on admission are unreliable predictors of subsequent Q wave evolution and do not discriminate significant differences in postinfarction outcome. In particular, ST segment elevation during the early hours of evolving infarction is not an invariable harbinger of subsequent Q wave development.
Scintigraphic assessment of regional cardiac adrenergic innervation.
Authors: Dae M W , O'Connell J W , Botvinick E H , Ahearn T , Yee E , Huberty J P , Mori H , Chin M C , Hattner R S , Herre J M
Published: June 2011

To assess the feasibility of noninvasively imaging the regional distribution of myocardial sympathetic innervation, we evaluated the distribution of sympathetic nerve endings, using 123I metaiodobenzylguanidine (MIBG), and compared this with the distribution of myocardial perfusion, using 201Tl. Twenty dogs were studied: 11 after regional denervation, and nine as controls. Regional denervation was done by left stellate ganglion removal, right stellate ganglion removal, and application of phenol to the epicardial surface. Computer-processed functional maps displayed the relative distribution of MIBG and thallium in multiple projections in vivo and excised heart slices in all animals. In six animals, dual isotope emission computed tomograms were acquired in vivo. Tissue samples taken from innervated and denervated regions of the MIBG images were analyzed for norepinephrine content to validate image findings. Normal controls showed homogeneous and parallel distributions of MIBG and thallium in the major left ventricular mass. In the left stellectomized hearts, MIBG was reduced relative to thallium in the posterior left ventricle; whereas in right stellectomized hearts, reduced MIBG was in the anterior left ventricle. Phenol-painted hearts showed a broad area of decreased MIBG extending beyond the area of phenol application. In both stellectomized and phenol-painted hearts, thallium distribution remained homogeneous and normal. Norepinephrine content was greater in regions showing normal MIBG (550 +/- 223 ng/g) compared with regions showing reduced MIBG (39 +/- 44 ng/g) (p less than 0.001), confirming regional denervation. Combined MIBG-thallium functional maps display the regional distribution of sympathetic innervation. This new ability to noninvasively map the distribution of sympathetic nerves with simultaneous comparison to regional perfusion may provide important new insights into mechanisms, whereby an imbalance in sympathetic activity may relate to clinical disorders.
Increased immunoreactivity of plasma after fibrinolytic activation in an anti-DD ELISA system. Role of soluble crosslinked fibrin polymers.
Authors: Francis C W , Doughney K , Brenner B , Klingbiel K , Marder V J
Published: June 2011

After addition of a low concentration of thrombin to normal plasma, a progressive and significant increase in crosslinked fibrin polymers was found by sodium dodecyl sulfate agarose gel electrophoresis, reaching 27% of total fibrinogen and fibrin before gel formation. As measured by enzyme-linked immunosorbent assay with a monoclonal antibody specific for an epitope near the gamma gamma crosslink site, increased immunoreactivity of plasma did not occur after adding thrombin despite formation of crosslinked fibrin polymers, which indicates that the antibody does not recognize the epitope in the polymers. Addition of tissue-type plasminogen activator (t-PA) to plasma resulted in a more rapid degradation of fibrin polymers than of fibrinogen, indicating that the fibrin specificity of t-PA is retained with soluble fibrin. Coincident with degradation of plasma crosslinked fibrin polymers, plasma DD immunoreactivity increased 70-fold from 50.3 +/- 4.5 (mean +/- SD) to 3,560 +/- 1,235 ng/ml. The presence of increased crosslinked fibrin polymers produced by adding thrombin to plasma significantly increased maximum immunoreactivity after t-PA-induced degradation to 18,500 +/- 11,780 ng/ml. The increase in DD immunoreactivity was dependent on t-PA concentration; no elevation occurred below 0.01 micrograms/ml, and maximal increases occurred above 100 micrograms/ml. Analysis of gel electrophoretic patterns of thrombin and t-PA-treated plasma samples suggests that the DD reactivity of t-PA-treated plasma is mainly due to degradation of soluble crosslinked fibrin polymers. Our findings indicate that plasmic degradation of soluble fibrin polymers in plasma may be an important source of fragment DD during thrombolytic therapy.
Physical exercise conditioning in the absence of weight loss reduces fasting and postprandial triglyceride-rich lipoprotein levels.
Authors: Weintraub M S , Rosen Y , Otto R , Eisenberg S , Breslow J L
Published: June 2011

The effect of physical exercise conditioning on fasting and postprandial lipoprotein levels was studied in six normolipidemic subjects. The study consisted of two phases: a baseline stabilization phase in which subjects maintained their regular physical activity and an exercise conditioning phase in which subjects had 29 exercise sessions during a 7-week period. Each of these sessions consisted of jogging on a treadmill for 30 minutes. The subjects averaged 15.2 miles/wk. To control for possible confounding factors, such as changes in diet composition and weight loss, we placed the subjects on a metabolic diet and increased their daily caloric intake during the exercise phase. At the end of each phase of the study, a vitamin A-fat loading test was done to specifically label and follow postprandial lipoprotein levels, and a maximum oxygen consumption test was done to evaluate the subjects' physical fitness. The exercise conditioning phase significantly increased the subjects' aerobic capacity and postheparin lipoprotein lipase activity, and the phase decreased fasting triglyceride levels. Physical exercise also significantly decreased chylomicron (Sf greater than 1,000) levels by 37%. In summary, this study suggests that physical exercise conditioning reduces fasting and postprandial lipoprotein levels by increasing the catabolism of triglyceride-rich particles. Because these particles may have a role in atherogenesis, this could be a major mechanism by which exercise prevents coronary heart disease.
Sympathetic vasoconstriction during exercise in ambulatory patients with left ventricular failure.
Authors: Wilson J R , Frey M J , Mancini D M , Ferraro N , Jones R
Published: June 2011

In patients with heart failure, exercise is thought to increase sympathetic vasoconstrictor tone. To investigate the extent of this sympathetic activation, we studied the effect of maximal exercise on nonexercising vascular beds in 35 patients with left ventricular failure (ejection fraction, 21 +/- 8%; peak exercise oxygen uptake (VO2), 12.3 +/- 3.5 ml/min/kg). In 28 patients, cardiac output and leg blood flow were measured during maximal upright bicycle exercise. Total flow to nonexercising tissue was then calculated as cardiac output--(2 x leg flow). In seven patients and six normal subjects, forearm blood flow was measured during supine bicycle exercise before and after alpha-adrenergic blockade with intravenous phentolamine. Maximal upright exercise increased the vascular resistance of nonexercising tissue from 34 +/- 16 units at upright rest to 45 +/- 25 units (p less than 0.02) but did not affect total flow to nonexercising tissue (rest, 2.9 +/- 1.0; maximal exercise, 2.8 +/- 1.4 l/min; p = NS). Supine exercise had no significant effect on forearm blood flow or vascular resistance in the normal subjects. In the patients with heart failure, supine exercise increased forearm vascular resistance from 45 +/- 17 to 58 +/- 25 mm Hg/ml/min/100 ml (p less than 0.02), again with no change in tissue flow (rest, 2.4 +/- 0.1; maximal exercise, 2.4 +/- 0.9 ml/min/100 ml; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Direct vasoconstriction and endothelium-dependent vasodilation. Mechanisms of acetylcholine effects on coronary flow and arterial diameter in patients with nonstenotic coronary arteries.
Authors: Hodgson J M , Marshall J J
Published: June 2011

An endothelium-dependent vasodilator response to acetylcholine has been described recently in patients with coronary artery disease. Those studies determined responses only of large epicardial arteries. Our study was designed to determine the integrated effects of acetylcholine on epicardial diameter, coronary flow, and vascular resistance. Patients (n = 64) with nonstenotic epicardial coronaries underwent coronary angiography with simultaneous recording of coronary flow velocity using a 3F subselective Doppler catheter. Measurements of epicardial arterial cross-sectional area (ECA), velocity, estimated flow (velocity times area), and vascular resistance were made before and after bolus administration of acetylcholine (100 micrograms i.c.). Similar measurements were made after papaverine (12-15 mg i.c.), a nonendothelium-dependent vasodilator. Acetylcholine resulted in a reduction of ECA of 19 +/- 3%, whereas papaverine increased ECA by 9 +/- 2%. Estimated flow increased 69 +/- 12% after acetylcholine and 147 +/- 12% after papaverine. Resistance fell after both agents (acetylcholine, -17 +/- 13%; papaverine, -61 +/- 2%). Transvascular resistance fell after acetylcholine in all but five patients. These patients had dramatic epicardial artery constriction (40 +/- 8% decrease in ECA). The effect of acetylcholine on both ECA and resistance was blocked by atropine (1 mg i.c.). Nitroglycerin (300 micrograms i.c.) resulted in epicardial dilatation (7.5 +/- 2.8%) in the same patients in whom acetylcholine caused constriction (-11.2 +/- 3.1%).(ABSTRACT TRUNCATED AT 250 WORDS)
Sources of variability in normal body surface potential maps.
Authors: Kozmann G , Lux R L , Green L S
Published: June 2011

Within-group variability of body surface potential maps was assessed on data from 685 carefully validated normal subjects (348 men and 337 women). Sources of within-group variability were evaluated by subgrouping maps by patient sex, age, height, and weight. Contribution of reproducibility error to total variance was assessed in a separate group of 52 normal subjects in whom multiple maps were recorded. Total variance was significantly lower in women than in men. Total variance tended to decrease with age, and the greatest decrease occurred in men during the 3rd decade. The ratio of total variance to mean signal energy showed a slow decrease with age for each group. Results suggest that the dominant source of within-group variability arises from variability of cardiac electric sources while the influence of volume conductor variability is significantly less. Variability due to measurement reproducibility was approximately half of the total variance.
Induction of mRNA for low-density lipoprotein receptors in heterozygous Watanabe heritable hyperlipidemic rabbits treated with CS-514 (Pravastatin) and cholestyramine.
Authors: Kume N , Kita T , Mikami A , Yokode M , Ishii K , Nagano Y , Kawai C
Published: June 2011

We administered CS-514, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, alone and in combination with cholestyramine to heterozygous Watanabe heritable hyperlipidemic rabbits. This rabbit model for heterozygous familial hypercholesterolemia has hepatic low-density lipoprotein receptors that are assumed to be half as many as in normal rabbits. CS-514 alone lowered plasma low-density lipoprotein cholesterol levels by 50%, and in combination with cholestyramine, it lowered levels by 80%. The membrane-binding assay showed these drugs caused 1.5- and 1.8-fold increases in the number of hepatic low-density lipoprotein receptors, respectively. We also measured the amount of mRNA for low-density lipoprotein receptor by S1 nuclease protection assay in the same livers as above. These drugs induced mutant mRNA for the low-density lipoprotein receptor, which has an in-flame deletion of 12 nucleotides, as well as normal receptor mRNA. CS-514 alone produced a 1.8-fold increase in the amount of mRNA for the normal receptor and a 2.3-fold increase for the mutant mRNA, whereas CS-514 in combination with cholestyramine produced 1.9- and 3.1-fold increases, respectively. We conclude that CS-514 induces mRNA for the low-density lipoprotein receptor, subsequently increasing the receptor protein in the liver, and then reduces the levels of plasma cholesterol, and that the induction is augmented when the drug is administered in combination with cholestyramine.