bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of supine and lateral positions on cardiac output and intracardiac pressures: an experimental study.
Authors: Nakao S , Come P C , Miller M J , Momomura S , Sahagian P , Ransil B J , Grossman W
Published: June 2011

Hemodynamic measurements in human subjects and in experimental animals are generally made in the supine position; not much attention is paid to potential beneficial or harmful effects of right or left lateral positions on cardiac output or other hemodynamic variables. To evaluate the potential influence of such positional changes on cardiac performance, we measured cardiac output and left and right ventricular pressures (with micromanometer catheters) in anesthetized experimental animals (eight dogs and nine pigs) in the supine, right lateral, and left lateral positions. Cardiac output increased from supine to left lateral (mean +/- SD, 2.6 +/- 0.9 to 3.1 +/- 1.0 liters/min; p less than .001) and from supine to right lateral positions (2.6 +/- 0.9 to 3.1 +/- 1.1 liters/min; p less than .001). There was an associated decrease in arteriovenous oxygen saturation difference from supine to left lateral position (31 +/- 8% to 24 +/- 4%; p less than .001) and from supine to right lateral position (32 +/- 9% to 25 +/- 6%; p less than .001). Left ventricular systolic and end-diastolic pressures increased from supine to left lateral (128 +/- 17/9 +/- 2 to 147 +/- 19/16 +/- 4 mm Hg; both p less than .001) and from supine to right lateral positions (128 +/- 19/9 +/- 2 to 141 +/- 16/16 +/- 7 mm Hg; p less than .01 and p less than .001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Smoking-induced coronary vasoconstriction in patients with atherosclerotic coronary artery disease: evidence for adrenergically mediated alterations in coronary artery tone.
Authors: Winniford M D , Wheelan K R , Kremers M S , Ugolini V , van den Berg E , Niggemann E H , Jansen D E , Hillis L D
Published: June 2011

In patients with atherosclerotic coronary artery disease, cigarette smoking increases myocardial oxygen demand but may cause an inappropriate decrease in coronary blood flow and myocardial oxygen supply. This study was performed to explore the mechanism of smoking-induced coronary vasoconstriction and, specifically, to determine if smoking causes an alpha-adrenergically mediated increase in coronary artery tone. In 36 chronic smokers with coronary artery disease (27 men and nine women, 50 +/- 9 [mean +/- SD] years old), heart rate-systolic arterial pressure double product and coronary sinus blood flow (by thermodilution) were measured before and during smoking both before and after (1) normal saline (n = 5, control subjects), (2) an alpha-adrenergic-blocking agent, phentolamine, 5 mg (n = 15), (3) a beta-adrenergic-blocking agent, propranolol, 0.1 mg/kg (n = 12), or (4) sodium nitroprusside, 0.4 to 0.8 micrograms/kg/min, given in a dose sufficient to diminish systolic arterial pressure by 15% (n = 4). During the initial smoking period, rate-pressure product increased and coronary sinus blood flow was unchanged by smoking in all groups. After 30 to 75 min, saline, phentolamine, propranolol, or sodium nitroprusside was given, and measurements were repeated. In the control subjects, rate-pressure product and coronary sinus blood flow responded in a similar manner to that observed previously. In those receiving phentolamine, rate-pressure product was unchanged, but coronary sinus blood flow rose substantially with smoking (percent change +2 +/- 15% during the first smoking period [before phentolamine] and +32 +/- 17% during the second smoking period [after phentolamine]; p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Efficacy and safety of moricizine in patients with ventricular tachycardia: results of a placebo-controlled prospective long-term clinical trial.
Authors: Pratt C M , Wierman A , Seals A A , English L , Leon C , Young J B , Quinones M A , Roberts R
Published: June 2011

This was a prospective, placebo-controlled, single-blind trial of moricizine (ethmozine) in a dose averaging 10 mg/kg/day in 50 patients, the single entrance criterion being the presence of 10 or more runs of nonsustained ventricular tachycardia (VT) on a screening 24 hr ambulatory electrocardiographic (ECG) recording. Electrophysiologic study was not included as part of this trial design. The placebo frequency of VT (average 3 days of recording) was 1036 +/- 479 runs of VT per day. Most patients (31/50) had coronary artery disease. The study population had a mean left ventricular ejection fraction (LVEF) of 36 +/- 16%; 20 patients also had a history of sustained VT. Protocol failure was defined as failure to achieve a 75% or greater reduction in runs of VT (as judged by ambulatory ECG recording) and/or recurrence of sustained VT while on moricizine. Among the 48 patients treated with moricizine, the drug was initially efficacious in 35 (73%), with two-thirds having total abolition of nonsustained VT. Although it was effective in reducing runs of nonsustained VT, moricizine was ineffective in preventing the recurrence of sustained VT (63% failure rate). Side effects were uncommon and the drug was well tolerated in most patients with LVEFs of 30% or less.
Electrophysiologic effects of papillary muscle traction in the intact heart.
Authors: Gornick C C , Tobler H G , Pritzker M C , Tuna I C , Almquist A , Benditt D G
Published: June 2011

In this study we used transmural multipolar electrodes, sonomicrometers implanted within the left ventricular wall, and cardiac electrical stimulation techniques to examine the effect of transient mechanical posterior papillary muscle traction on local myocardial electrophysiologic characteristics. Nine open-chest dogs were atrially paced (cycle length 400 msec) followed by insertion of timed premature extrastimuli at left ventricular epicardial pacing sites either in the vicinity of (traction zone) or remote from (nontraction zone) the site of papillary muscle traction. Electrophysiologic recordings were made before and during periods of intermittent papillary muscle traction of predetermined timing, application rate (25 cm/sec), and duration (170 msec). Papillary muscle traction was applied in late diastole just before the last beat of each atrial drive train. In seven of nine dogs application of transient papillary muscle traction resulted in significantly earlier local ventricular activation (mean activation advancement 30 +/- 13 msec), altered QRS morphology of the last conducted atrial drive-train beat, and relative prolongation of ventricular functional refractory period in the traction zone. Conversely, in nontraction zones in these seven dogs, early activation did not occur and refractoriness remained unchanged as tested by a locally placed extrastimulus. In two of nine dogs traction failed to induce early activation and changes in refractoriness did not occur. Alterations in regional myocardial blood flow (assessed by radioactive microsphere technique) did not appear responsible for the observed changes, since there was no demonstrable traction-induced difference in regional blood flow between the traction and nontraction zones.(ABSTRACT TRUNCATED AT 250 WORDS)
Calculation of aortic valve area by Doppler echocardiography: a direct application of the continuity equation.
Authors: Richards K L , Cannon S R , Miller J F , Crawford M H
Published: June 2011

The continuity equation suggests that a ratio of velocities at two different cardiac valves is inversely proportional to the ratio of cross-sectional areas of the valves. To determine whether a ratio of mitral/aortic valve orifice velocities is useful in determining aortic valve area in patients with aortic stenosis, 10 control subjects and 22 patients with predominant aortic stenosis were examined by Doppler echocardiography. The ratio of (mean diastolic mitral velocity)/(mean systolic aortic velocity), (Vm)/(Va), and the ratio of (mitral diastolic velocity-time integral)/(aortic systolic velocity-time integral), (VTm)/(VTa), were determined from Doppler spectral recordings. Aortic valve area determined at catheterization by the Gorlin equation was the standard of reference. High-quality Doppler recordings were obtained in 30 of 32 subjects (94%). Catheterization documented valve areas of 0.5 to 2.6 (mean 1.1) cm2. There was good correlation between Doppler-determined (Vm)/(Va) and Gorlin valve area (r = .90, SEE = 0.23 cm2); a better correlation was noted between (VTm)/(VTa) and Gorlin valve area (r = .93, SEE = 0.18 cm2). The data demonstrate the usefulness of Doppler alone in the determination of aortic valve area in adults with absent or mild aortic or mitral regurgitation and no mitral stenosis. Although the use of mean velocity and velocity-time integral ratios requires accurate measurement of mitral and aortic velocities, it does not require squaring of these velocities or measurement of the cross-sectional area of flow.
Plasma apoproteins and the severity of coronary artery disease.
Authors: Sedlis S P , Schechtman K B , Ludbrook P A , Sobel B E , Schonfeld G
Published: June 2011

Plasma levels of lipids, lipoproteins, and apoproteins in 281 patients undergoing cardiac catheterization were correlated with the incidence and severity of coronary artery disease (CAD) to determine if measurements of apoprotein levels are more predictive of the presence and severity of CAD than the corresponding levels of lipoprotein lipids. In 156 men with CAD among 194 men in the study the only variable other than age that correlated with the severity of CAD, defined by the number of lesions and percent stenosis, was the ratio of apoprotein AI to apoprotein B (r = .1908, p less than .03). The ratio of apoprotein AI to apoprotein B was a more accurate predictor of the severity of CAD than was the ratio of the corresponding high-density to low-density lipoprotein levels (coefficients of partial determination of .07 and .035; p less than .001 and p less than .07, respectively). Multivariate analysis confirmed the independent effect of the ratio of apoprotein AI to apoprotein B on the severity of CAD even after adjustments were made for lipid levels, age, presence of hypertension or diabetes, and therapy with beta-blockers or diuretics. Among men with total occlusion of a coronary artery apoprotein E and apoprotein B levels were significantly higher than in control subjects with a similar extent of CAD (p less than .03). The lipid profiles of the 37 women with CAD were very different from those of the men.(ABSTRACT TRUNCATED AT 250 WORDS)
Diastolic 'locking' of the mitral valve: possible importance of diastolic myocardial properties.
Authors: David D , Michelson E L , Naito M , Chen C C , Schaffenburg M , Dreifus L S
Published: June 2011

The effects of pharmacologically induced changes in myocardial properties on diastolic mitral valve mechanics were studied in five open-chest dogs. After the induction of complete atrioventricular block, the dogs were subjected to a protocol of programmed pacing. During prolonged diastolic pauses, programmed atrial contractions were induced at progressively increasing coupling intervals. Echocardiographically determined mitral valve reopening time was established for each coupling interval in the control state as well as under the influence of calcium or verapamil. Compared with control, calcium caused an increase in myocardial tension from 23.8 +/- 3.0 to 30.0 +/- 4.6 g/cm2 (mean +/- SD, p less than .005) as well as an increase in mean septal contraction and relaxation velocities from 142 +/- 25.9 and 144 +/- 15.2 mm/sec to 188 +/- 21.7 and 174 +/- 19.5 mm/sec, respectively (each p less than .001). Conversely, verapamil caused a decrease in mean myocardial tension from 23.8 +/- 3.0 to 19.4 +/- 5.3 g/cm2 (p less than .001) and in mean septal contraction and relaxation velocities from 142 +/- 25.9 and 144 +/- 15.2 mm/sec to 112 +/- 32.7 and 112 +/- 21.6 mm/sec, respectively (each p less than .001). At every coupling interval, calcium significantly (p less than .01 to .001) prolonged, whereas verapamil significantly shortened (p less than .01 to .001), mitral reopening time compared with the control state. These pharmacologically induced changes in mitral valve mechanics occurred despite variations in left ventricular volume, as well as left ventricular and left atrial pressures that under normal conditions exert opposite effects on mitral valve mechanics.(ABSTRACT TRUNCATED AT 250 WORDS)
Geographic origin of the family as a determinant of serum levels of lipids in Finnish children.
Authors: Pesonen E , Viikari J , Akerblom H K , Räsänen L , Louhivuori K , Sarna S
Published: June 2011

Children in the eastern part of Finland have higher serum total and low-density lipoprotein (LDL) cholesterol levels than children in the western part of the country. This is consonant with the high mortality rate for coronary heart disease in eastern Finland. Eastern and western Finns are assumed to have different geographic origins; because of this we divided into groups 630 newborns and 3554 children and adolescents according to their grandparents' birthplace, which, in Finland, reflect the origins of the children. No differences in serum lipid levels were found in the newborns but in the 3- to 18-year-old children the differences in mean serum total and LDL cholesterol levels were accentuated by this division. Boys with grandparents from the extreme eastern part and those with grandparents from the western part of the country showed the greatest differences. Prepubescent boys 3 to 12 years old living in the west but with grandparents from the east had total and LDL cholesterol levels similar to those of boys living in and descended of grandparents from the east, despite their diet being of the western type. Thus, although diet is known to be a major determinant of serum cholesterol level, genetic factors also seem to play a role.
Effects of vasopressin on the circulation and its baroreflex control in healthy men.
Authors: Aylward P E , Floras J S , Leimbach W N , Abboud F M
Published: June 2011

Information on the hemodynamic effects of vasopressin (AVP) in healthy humans is very limited despite its known importance in body fluid homeostasis and release in pathologic states such as hemorrhage and trauma. Although it is a potent vasoconstrictor in vitro, it does not cause the expected rise in arterial pressure when given systemically to animals with intact baroreflexes. It has been proposed that this is because AVP facilitates baroreflex control of the circulation. In this study, we assessed the effect of infusion of AVP on resting circulatory variables and on the baroreflex control of forearm vascular resistance and heart rate in healthy men. AVP in a dose of 0.4 ng/kg/min, which raised plasma level of AVP to 24 +/- 4 pg/ml, a value known to have a significant antidiuretic effect, had little hemodynamic effect, producing only mild bradycardia and a slight increase in central venous pressure. Reflex changes in heart rate during neck suction (-15 and -30 mm Hg) and neck pressure (+15 and +30 mm Hg) were not altered. Reflex responses to lower body negative pressure and to its release were also unchanged by this dose of AVP. In contrast, a higher dose of AVP (4 ng/kg/min), which raised plasma levels to 290 +/- 41 pg/ml, a concentration known to occur as a result of hemorrhagic hypotension and circulatory stresses, did cause hemodynamic changes. There was tachycardia (from 63 +/- 2 to 68 +/- 2 beats/min), a decrease in pulse pressure (from 62 +/- 2 to 53 +/- 2 mm Hg), an increase in central venous pressure (from 2.6 +/- 0.5 to 4.1 +/- 0.4 mm Hg), and surprisingly in view of the known vasoconstrictor effect of AVP, an increase in forearm flow (from 4.4 +/- 0.7 to 5.9 +/- 1.2 ml/min/100 ml tissue) and a decrease in forearm vascular resistance (from 24 +/- 4 to 18 +/- 3 U); there was no significant change in mean arterial pressure (from 83 +/- 2 to 83 +/- 3 mm Hg). Reflex changes in heart rate were unaltered. The maximal vasoconstrictor response in the forearm attained during lower body negative pressure was not influenced by AVP, but the reflex vasodilator response to the sudden release of lower body negative pressure was significantly augmented, vascular resistance falling to 23 +/- 4 U before and 13 +/- 2 U during AVP. The unanticipated findings in this study include the biphasic changes in heart rate with increasing doses of AVP, the absence of a pressor response, and the vasodilatation in forearm vessels.(ABSTRACT TRUNCATED AT 400 WORDS)
The prevalence and clinical significance of residual myocardial ischemia 2 weeks after uncomplicated non-Q wave infarction: a prospective natural history study.
Authors: Gibson R S , Beller G A , Gheorghiade M , Nygaard T W , Watson D D , Huey B L , Sayre S L , Kaiser D L
Published: June 2011

Despite having smaller infarct size and better left ventricular function, patients with non-Q wave myocardial infarction (NQMI) appear to have an unexpectedly high long-term mortality that is ultimately comparable to that of patients with Q-wave myocardial infarction (QMI). Patients with NQMI may lose their initial prognostic advantage because there is more viable tissue in the perfusion zone of the infarct-related vessel, rendering myocardium more prone to reinfarction. We tested this hypothesis in a prospective study of 241 consecutive patients 65 years of age or younger with acute uncomplicated myocardial infarction confirmed by creatine kinase levels (MB fraction). All patients received customary care and none underwent thrombolytic therapy or emergency angioplasty. Predischarge coronary angiography, radionuclide ventriculography, 24 hr Holter monitoring, and quantitative thallium-201 (201T1) scintigraphy during treadmill exercise were performed 10 +/- 3 days after infarction. Infarcts were designated as QMI (n = 154) or NQMI (n = 87) by accepted criteria applied to serial electrocardiograms obtained on days 1, 2, 3, and 10. The baseline Norris coronary prognostic index, angiographic jeopardy scores, and prevalence of Lown grade ventricular arrhythmias were similar between groups despite evidence for less necrosis with NQMI vs QMI, reflected by lower peak creatine kinase levels (520 vs 1334 IU/liter; p = .0001, 4 hr sampling), higher resting left ventricular ejection fraction (53% vs 46%; p = .0001), fewer akinetic or dyskinetic segments (1.2 vs 2.4; p = .0001), and fewer persistent 201Tl defects in the infarct zone (0.9 vs 1.9; p = .0001). Patients with NQMI also had more patent infarct-related vessels (54% vs 25%; p less than .0001) and a shorter time from onset of infarction to peak creatine kinase level (16.9 vs 22.5 hr; p = .0001). Importantly, the prevalence and extent of quantitatively determined 201Tl redistribution within the infarct zone on exercise scintigraphy was greater in patients with NQMI vs those with QMI (60% vs 36%, p = .007; and 0.98 vs 0.53 myocardial segments, p = .0003); when the two groups were stratified on the basis of the infarct-related vessel, subset analysis revealed the same findings. During 30 months median follow-up, cardiac mortality was low, 8.4% in the QMI group and 9.2% in the NQMI group (p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)
Intraoperative evaluation of coronary artery bypass graft anastomoses with high-frequency epicardial echocardiography: experimental validation and initial patient studies.
Authors: Hiratzka L F , McPherson D D , Lamberth W C , Brandt B , Armstrong M L , Schröder E , Hunt M , Kieso R , Megan M D , Tompkins P K
Published: June 2011

There is currently no accepted approach for intraoperative evaluation of the technical adequacy of coronary artery bypass graft anastomoses. High-frequency epicardial echocardiography performed intraoperatively could assess coronary artery bypass graft anastomoses by providing on-line short-axis (cross-sectional) and longitudinal two-dimensional images of the vessels. To validate measurements of anastomoses with high-frequency epicardial echocardiography, luminal diameter determined by high-frequency epicardial echocardiography was compared with that determined histologically after perfusion fixation in 12 dogs studied after coronary artery bypass grafting. Technical errors were deliberately created in some grafts. The results of these animal validation studies showed that maximum luminal diameter of the anastomosis by high-frequency epicardial echocardiography correlated well with histologic measurements (r = .92; high-frequency epicardial echocardiography = 0.8 histology + 0.3). All deliberately created technical errors were detected by an independent observer using high-frequency epicardial echocardiography. After completion of the animal studies, we demonstrated the clinical applicability of this approach in 12 patients. Fifteen coronary artery bypass graft anastomoses were examined intraoperatively with high-frequency epicardial echocardiography. The measured maximum luminal diameter of the anastomosis was greater than the maximum luminal diameter of the native artery, as expected, in all end-to-side anastomoses. However, the maximum luminal diameter of the side-to-side anastomoses was equal to or slightly less than that of the native artery. In this initial patient group, minor technical errors were noted in two of 15 graft anastomoses. In conclusion, high-frequency epicardial echocardiography can accurately measure coronary arterial bypass graft anastomoses and has potential for intraoperative detection of technical errors and inadequacies.
Surgical ablation of ventricular tachycardia: improved results with a map-directed regional approach.
Authors: Krafchek J , Lawrie G M , Roberts R , Magro S A , Wyndham C R
Published: June 2011

To determine whether a regional approach to surgery for ventricular tachycardia would improve on the results of previously reported methods of endocardial resection, an analysis was performed of our surgical experience over a 5 year period. Of 46 consecutive patients operated on for recurrent sustained ventricular tachycardia or ventricular fibrillation, 39 patients with ischemic heart disease underwent subendocardial resection and/or cryoablation. The mean age of the patients was 61 +/- 8 (SD) years, the mean left ventricular ejection fraction was 32 +/- 11%, and the mean number of ineffective antiarrhythmic drugs was 3.8 +/- 1.2 per patient. In 35 of 39 patients in whom mapping data were obtainable, 56 (86%) tachycardias had earliest sites of activation in the left ventricle and nine (14%) had earliest sites in the right ventricle. Ten patients had 14 tachycardias (21%) mapped to areas outside visible dense scar. Of these 35 patients, 10 underwent localized subendocardial resection and 25 underwent a regional procedure in which all areas activated before the surface QRS during ventricular tachycardia were excised and/or cryoablated. In the operative survivors of electrophysiologically guided surgery, three of eight (38%) patients with the localized and one of 24 (4%) patients who underwent the regional procedure had recurrence of ventricular tachycardia during a follow-up period of 1 to 59 (mean 22 +/- 17) months (p = .04). The favorable outcome of regional surgery was not influenced by the presence of multiple morphologies in 54%, disparate sites of origin in 29%, or inferior wall foci in 46% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of diltiazem on regional coronary hemodynamics during atrial pacing in patients with stable exertional angina: implications for mechanism of action.
Authors: De Servi S , Ferrario M , Ghio S , Bartoli A , Mussini A , Poma E , Angoli L , Bramucci E , Aimè E , Rondanelli R
Published: June 2011

To investigate the mechanism of the antianginal action of diltiazem in stress-induced myocardial ischemia, we studied 12 patients with stable exertional angina and disease of the proximal left anterior descending artery by measuring great cardiac vein flow (GVCF) and calculating anterior regional coronary resistance (ARCR) during myocardial ischemia induced by atrial pacing before and after intravenous administration of diltiazem (0.25 mg/kg in a bolus dose followed by continuous infusion of 0.005 mg/kg/min). Diltiazem increased the pacing time to angina from 6.9 +/- 3.5 to 10.7 +/- 4 min (p less than .001). At peak pacing heart rate was increased after diltiazem (from 128 +/- 17 to 145 +/- 17 beats/min, p less than .005), while mean arterial pressure was decreased (from 131 +/- 19 to 113 +/- 17 mm Hg, p less than .025), leaving the double product unaltered. At peak pacing no changes were observed in GCVF (from 115 +/- 46 to 119 +/- 46 ml/min, p = NS), ARCR (from 1.3 +/- 0.4 to 1.1 +/- 0.4 mm Hg/ml/min), or myocardial oxygen consumption of the anterior region (from 14.5 +/- 4.2 to 13.4 +/- 4.7 ml/min). Reduction of myocardial oxygen demand plays a major role in the antianginal action of diltiazem in patients with stress-induced myocardial ischemia.
The effect of medical and surgical treatment on subsequent sudden cardiac death in patients with coronary artery disease: a report from the Coronary Artery Surgery Study.
Authors: Holmes D R , Davis K B , Mock M B , Fisher L D , Gersh B J , Killip T , Pettinger M
Published: June 2011

The effect of medical and surgical treatment on subsequent sudden cardiac death was assessed in 13,476 patients in the Coronary Artery Surgery Study registry who had significant coronary artery disease, operable vessels, and no significant valvular disease. (Patients were assigned to medical or surgical therapy on the basis of clinical judgment and not according to a randomization scheme; therefore, biases associated with unknown variables could not be evaluated.) Sudden cardiac death occurred in 452 patients (3.4%) during a mean follow-up of 4.6 years. Five year survival free of sudden death for medically treated patients was 94 +/- 0.3%, and that for surgically treated patients was 98 +/- 0.2% (p less than .0001). Twelve baseline clinical, electrocardiographic, and angiographic variables were significantly different between patients alive at the last follow-up and those suffering sudden death. Data on these variables were available for 11,508 patients. Sudden death occurred in 257 (4.9%) of 5258 medically treated and 101 (1.6%) of 6250 surgically treated patients. In a high-risk patient subset with three-vessel disease and history of congestive heart failure, 91% of surgically treated patients had not suffered sudden death compared with 69% of medically treated patients. After Cox survival analysis was used to correct for baseline variables, surgical treatment had an independent effect on sudden death (p less than .0001). This reduction was most pronounced in high-risk patients.
Pharmacodynamics of tissue-type plasminogen activator characterized by computer-assisted simulation.
Authors: Tiefenbrunn A J , Graor R A , Robison A K , Lucas F V , Hotchkiss A , Sobel B E
Published: June 2011

Prospective characterization of pharmacodynamics of tissue-type plasminogen activator (t-PA) is needed for diverse clinical applications. Accordingly, we used physiologically based, computer simulation of participating biochemical reactions in response to concentrations of circulating t-PA seen with infusions of 1 to 7 hr duration in 45 patients. Predicted values were compared with those from a "training set" obtained in six patients given t-PA for coronary thrombosis and six receiving therapy for peripheral arterial occlusion. Subsequently, results of simulation were compared prospectively with observations from a "test set" of 33 consecutive patients given low doses of t-PA for as long as 7 hr or higher doses for 1 to 2 hr and with data from 101 patients given t-PA in the European Cooperative Trial. Fits between observed and predicted values were close. Based on observations in the training set, the alpha 2-macroglobulin reaction with circulating plasmin and ongoing synthesis of plasminogen were incorporated in the simulations. Fibrinogenolysis in vitro was documented despite supplementation of samples with aprotinin, particularly when concentrations of t-PA were high. This phenomenon can lead to overestimation of fibrinogen depletion and was found to be obviated by the use of PPACK, a novel serine protease inhibitor. Results indicate that the simulation approach developed permits economic, prospective evaluation of regimens of t-PA suitable for diverse conditions and delineation of the impact of individual constituents and reactions on pharmacodynamics of t-PA and on the risk of induction of a systemic lytic state.
Effects of varying electrode configuration with catheter-mediated defibrillator pulses at the coronary sinus orifice in dogs.
Authors: Coltorti F , Bardy G H , Reichenbach D , Greene H L , Thomas R , Breazeale D G , Ivey T D
Published: June 2011

We compared two methods of delivering single damped sine-wave defibrillator pulses to the coronary sinus orifice in 20 dogs. Ten dogs had "unipolar" (coronary sinus to precordial disc) and 10 had "bipolar" (coronary sinus proximal to coronary sinus distal electrode) discharges. Delivered voltage, current, and energy were recorded during each pulse. Electrophysiologic testing was done before and 4 weeks after the procedure. Histologic examination of the atrioventricular groove was done at 1 mm serial sections. For the unipolar configuration a 200 J defibrillator pulse resulted in a peak voltage of 3370 +/- 125 V, a peak current of 21 +/- 4 A, and a delivered energy of 253 +/- 29 J as compared with 3010 +/- 99 V, 70 +/- 4 A, and 144 +/- 18 J, respectively, for the bipolar configuration (p less than .001). Three dogs (two with bipolar, one with unipolar pulses) had gross coronary sinus rupture and died from acute pericardial tamponade. In addition, irrespective of electrode configuration, all dogs showed microscopic rupture of the coronary sinus internal elastic membrane. Transmural atrial scarring occurred in all 10 dogs that received a unipolar pulse but in only two dogs that received a bipolar pulse (p = .0004). Unlike the atrium, injury to the left ventricle was limited in both groups. Similarly, injury to the periannular myocardium was inconsistent and not transmural in either group. No significant electrophysiologic changes were observed. With the present technique, unipolar rather than bipolar catheter-mediated defibrillator pulses result in transmural atrial injury that might prevent accessory pathway conduction. Regardless of electrode configuration, high-energy defibrillator pulses consistently cause some degree of coronary sinus rupture, most likely related to a barotraumatic mechanism.
Effects of encainide and its metabolites on energy requirements for defibrillation.
Authors: Fain E S , Dorian P , Davy J M , Kates R E , Winkle R A
Published: June 2011

Encainide, a class IC antiarrhythmic agent, has been associated with proarrhythmic responses of ventricular tachycardia and fibrillation requiring defibrillation in patients. We examined the short-term effects of intravenous encainide and its two major metabolites, O-demethyl-encainide (ODE) and 3-methoxy-ODE (MODE), on the energy requirements for successful defibrillation in 25 pentobarbital-anesthetized, open-chest dogs. Truncated exponential (60% tilt) defibrillation shocks were administered through right atrial spring and left ventricular epicardial patch electrodes identical to those used in man with the automatic implantable defibrillator. At baseline multiple shocks of varying energy were applied to construct curves of percent successful defibrillation as a function of energy (DF curves) for each animal. Encainide, ODE, or MODE was then infused in loading and maintenance doses to achieve QRS widening of 20% to 50%. Saline was administered to animals serving as controls. Determination of the DF curve was repeated, after which the infusion was discontinued. After 1 hr washout period, an additional DF curve was constructed. The data were analyzed by logistic regression, and the energies required for 50% successful defibrillation (E50) were compared. No significant differences existed between the four groups in body or heart weight, extent of QRS widening, or baseline E50 values. After administration of encainide and ODE, the E50 increased by 129 +/- 43% (p less than .001) and 76 +/- 34% (p less than .005), respectively. Return of E50 toward baseline was observed after the washout periods in both groups (p less than .025), demonstrating the reversibility of the drugs' effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of nifedipine on intrinsic myocardial stiffness in man.
Authors: Kurnik P B , Courtois M R , Ludbrook P A
Published: June 2011

To determine whether alteration of intrinsic myocardial stiffness is responsible for the reduction of left ventricular filling pressure and volume by nifedipine in patients with impaired baseline ventricular function, we evaluated the hemodynamic responses in 32 patients undergoing diagnostic cardiac catheterization. Micromanometric pressure and ventriculographic dimensional data were acquired before and 30 min after randomly assigned administration of nifedipine (20 mg sublingual) or placebo. A mathematical model requiring no assumptions about the stress-radius relationship or direct measurement of strain was used. No hemodynamic variables were changed after placebo. Left ventricular end-diastolic volume and pressure declined and cardiac output increased after nifedipine, particularly in subjects with impaired ventricular performance. Despite these salutary effects, intrinsic myocardial stiffness, elastic stiffness at a common level of stress, chamber stiffness, and rate of isovolumic relaxation were unchanged after nifedipine, even in patients with abnormal baseline ventricular function. The potent peripheral arteriodilator effect of nifedipine, rather than any direct myocardial or ventricular effects, appears to be responsible for the improved systolic and diastolic performance.
Regional myocardial volume perfused by the coronary artery branch: estimation in vivo.
Authors: Koiwa Y , Bahn R C , Ritman E L
Published: June 2011

Seven closed-chest dogs were anesthetized with intramuscular Innovar and a N2O/O2 gas mixture. Maximal coronary vasodilation was induced by intra-aortic injection of nitroglycerin (200 micrograms/kg) and continuous infusion of adenosine (1 mg/kg/min) into the main pulmonary artery. Superselective coronary arteriograms were obtained at varying distances along the left circumflex and left anterior descending coronary arteries during scans using the dynamic spatial reconstructor rapid tomographic x-ray scanner. At end-diastole the images of the coronary arteries and opacified myocardium were analyzed for cross-sectional area (CSA) of the coronary artery lumen and regional myocardial volume (Vdsr) perfused by that coronary artery. Postmortem regional myocardial volume (Vpath) was related to the volume perfused by the same artery measured in vivo by the dynamic spatial reconstructor as follows: Vdsr = 4.56 + 0.93 Vpath (r = .98, p less than .001). In addition, the cross-sectional area of the coronary artery supplying a volume of myocardium was related to that volume as follows: Vdsr = - 1.95 + 6.34 CSAmax (r = .88, p less than .001). This suggests that a maximally dilated coronary artery luminal cross-sectional area is linearly related to the volume of muscle it perfuses. We speculate that this relationship may be useful in expressing the physiologic significance of coronary arterial narrowing.
Pharmacologic conversion and suppression of experimental canine atrial flutter: differing effects of d-sotalol, quinidine, and lidocaine and significance of changes in refractoriness and conduction.
Authors: Feld G K , Venkatesh N , Singh B N
Published: June 2011

The electrophysiologic determinants of conversion and the prevention of atrial flutter are poorly defined. This issue was therefore investigated by evaluating the effects of the new class III antiarrhythmic drug d-sotalol and the class I antiarrhythmic drugs quinidine and lidocaine. Atrial flutter was reproducibly induced in the open-chest anesthetized dog with intercaval crush and rapid atrial pacing. In this preparation, intravenous d-sotalol restored sinus rhythm in 14 of 15 (93%) dogs, whereas quinidine converted nine of 15 (60%) and lidocaine two of 10 (20%). d-Sotalol prevented reinduction in eight (53%), whereas quinidine was effective in four (27%) and lidocaine in none (0%). In the atria, d-sotalol induced significant increases in effective refractory period (+32%; p less than .01), functional refractory period (+30%; p less than .01), conduction time at an atrial paced cycle length of 150 msec (+9%; p less than .05), and atrial flutter cycle length (+8%; p less than .01). Quinidine increased effective refractory period (+40%; p less than .01), functional refractory period (+27%; p less than .01), conduction time at sinus cycle length (+13%; p less than .01), conduction time at an atrial paced cycle length of 150 msec (+18%; p less than .01), and atrial flutter cycle length (+31%; p less than .01). Lidocaine decreased functional refractory period (-6%; p less than .05) while lengthening the atrial flutter cycle length (+13%; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Use-dependent effects of lidocaine on conduction in canine myocardium: application of the modulated receptor hypothesis in vivo.
Authors: Davis J , Matsubara T , Scheinman M M , Katzung B , Hondeghem L H
Published: June 2011

Lidocaine is a commonly used antiarrhythmic drug that causes use-dependent blockade of sodium channels in vitro and reduces conduction velocity in vitro and in vivo. According to the modulated receptor hypothesis of antiarrhythmic drug action, lidocaine has a low affinity for rested sodium channels but a high affinity for open and inactivated channels. In the present experiments, we characterized use-dependent conduction slowing and recovery from slowing by lidocaine in anesthetized dogs. The His-to-ventricular conduction interval was used as the indicator of conduction velocity. We found that prolongation of conduction time was greater as the stimulation frequency was increased. Moreover, on abruptly changing the stimulation frequency, a new steady-state conduction time was approached in two to three depolarizations. On discontinuation of stimulation, the conduction time of progressively less premature extrastimuli shortened exponentially with a terminal phase time constant of 152 +/- 115 msec. These effects by lidocaine were enhanced during acidosis and enhancement was reversed by correction of the acidosis. It is concluded that the effects in vivo of lidocaine on conduction under several conditions of rate, rhythm, and pH are similar to its effects on the maximum upstroke velocity of the action potential in vitro. Although these experiments were not designed to validate the modulated receptor hypothesis, it appears that the modulated receptor hypothesis can predict the effects of lidocaine on conduction in vivo.
Evolution of a hereditary cardiac conduction and muscle disorder: a study involving a family with six generations affected.
Authors: Graber H L , Unverferth D V , Baker P B , Ryan J M , Baba N , Wooley C F
Published: June 2011

This study describes six generations of a family with autosomal dominant cardiac conduction system and myocardial disease with recognizable clinical stages. A 20 year follow-up of nine family members, a medical questionnaire of 196, electrocardiographic screening of 91, noninvasive testing of 20, and catheterization with endomyocardial biopsy of six are the basis of this report. The clinical stages are as follows: Stage I occurs in the second and third decades of life and is characterized by an absence of symptoms, normal heart size, sinus bradycardia, and premature atrial contractions. Stage II is marked by first-degree atrioventricular block in the third and fourth decades. Stage III occurs in the fourth and fifth decades and is accompanied by chest pain, fatigue, lightheadedness, and advanced atrioventricular block followed by the development of atrial fibrillation or flutter. Stage IV, in the fifth and sixth decades of life, is characterized by congestive heart failure and recurrent ventricular arrhythmias. Light microscopy of right ventricular endomyocardial biopsy specimens from patients in stage II revealed very mild fibrosis; electron microscopy of the specimens demonstrated mild dilatation of tubules, mitochondrial swelling, and minimal myofibrillar loss. Biopsy specimens from patients with stage III disease were similar to those from patients with stage II disease except for an increase of myofibrillar loss. The stage IV specimens had diffuse fibrosis and more severe tubular dilatation, mitochondrial cristolysis, and myofibrillar loss. At autopsy in the proband, the atrial changes were more severe than the ventricular and were especially marked in the sinoatrial and atrial myocardium. Early recognition of the disease and use of pacemakers and antiarrhythmic agents have proved beneficial for affected family members. Thorough family studies of patients with conduction system disease and/or dilated cardiomyopathy are necessary to better understand the hereditary basis and natural course of this category of disease.
Blacks in the Coronary Artery Surgery Study: risk factors and coronary artery disease.
Authors: Maynard C , Fisher L D , Passamani E R , Pullum T
Published: June 2011

In this paper we examine the relationship between risk factors and angiographically determined coronary artery disease for blacks and whites enrolled in the Coronary Artery Surgery Study (CASS). Analysis of data from the CASS registry indicated that blacks had a higher incidence of hypertension and current cigarette smoking than did whites in CASS and that chest pain was the major reason that both blacks and whites underwent coronary angiography for suspected or proven coronary disease. The CASS data also showed that, despite high levels of risk factors and chest pain, blacks had minimal or absent coronary disease. The results of this study raise several questions. First, to what extent are blacks in CASS representative of blacks in the general population and blacks undergoing coronary angiography? Additionally, are risk factors for coronary artery disease different for blacks than for whites? And finally, how does the physician effectively treat the black patient with high levels of risk factors and minimal coronary disease?
Assessment of the end-systolic pressure-volume relationship in human beings with the use of a time-varying elastance model.
Authors: McKay R G , Aroesty J M , Heller G V , Royal H D , Warren S E , Grossman W
Published: June 2011

The analysis of left ventricular end-systolic pressure-volume relationships in human beings has been hindered by the lack of a practical method of serial volume assessment and by an imprecise definition of end-systole. Modifications of the end-systolic relationship that have been used to circumvent these problems have included the use of single-point end-systolic pressure-volume ratios, the use of peak systolic pressure/minimum ventricular volume points for end-systolic points, and the use of end-ejection as a marker for end-systole. To assess the correlation between the parameters generated by these modifications with the slope (Emax) and volume intercept (VO) of the end-systolic line as defined by Sagawa's model of time-varying elastance, simultaneous measurement of left ventricular pressure and gated radionuclide volume was made in 26 patients under various loading conditions and pressure-volume diagrams were constructed for each loading condition from 32 simultaneous pressure-volume coordinates. Two pressure-volume diagrams were recorded in 14 patients and three pressure-volume diagrams were recorded in 12 patients. Emax and VO were determined in all patients from the slope and volume intercept of the isochronic pressure-volume line with the maximum time-varying elastance as described by Sagawa's model and were designated true Emax and true VO, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Polymorphous ventricular tachycardia: clinical characterization, therapy, and the QT interval.
Authors: Nguyen P T , Scheinman M M , Seger J
Published: June 2011

Forty-five consecutive patients with polymorphous ventricular tachycardia (PVT) were studied. The arrhythmia proved to be of a drug-related cause in 27 and due to an electrolyte disorder in four patients. Coexistent cardiac diseases without metabolic or drug-related abnormalities included ischemic heart disease in three, cardiomyopathy in three, and mitral valve prolapse in two. PVT was exercise-induced in four and associated with bradyarrhythmias in two. A prolonged QT or corrected QT interval was inconsistently related to the occurrence of PVT. In patients in whom PVT was induced by certain type I drugs, other type I antiarrhythmic drugs were usually either ineffective or resulted in aggravation of arrhythmia. For the group as a whole, treatment with lidocaine resulted in inconsistent beneficial effects, while cardiac pacing was almost universally effective for those with drug-induced PVT, regardless of the length of the QT interval. Long-term amiodarone therapy proved safe and effective for 12 of the 24 patients with drug-induced PVT who required long-term therapy for their original arrhythmia. We conclude that identification of PVT is the key clinical issue and that the QT interval is not necessarily the prime abnormality nor the variable to be considered in predicting success of therapy. Temporary cardiac pacing appears to be very effective in the short-term management of these patients. Use of type I antiarrhythmic agents in patients with drug-induced PVT generally resulted in aggravation of arrhythmia. In contrast, long-term amiodarone therapy for control of the original arrhythmia appears to be a promising approach for those with PVT associated with type I agents.
Preliminary experience with synchronized coronary sinus retroperfusion in humans.
Authors: Gore J M , Weiner B H , Benotti J R , Sloan K M , Okike O N , Cuénoud H F , Gaca J M , Alpert J S , Dalen J E
Published: June 2011

Synchronized coronary sinus retroperfusion (SCSR) with arterial blood has been extensively tested in animals. This intervention offers temporary support to areas of ischemic myocardium while a method of definitive revascularization is being sought. The feasibility and safety of this procedure for patients with unstable angina was therefore tested. A No. 7F autoinflatable retroperfusion balloon catheter (USCI) was inserted percutaneously into the coronary sinus of the study patients. Arterial blood was obtained through a No. 8F catheter placed in the femoral artery. Arterial blood was infused in a retrograde fashion into the coronary venous system during cardiac diastole by means of a piston-driven pump that was electrocardiographically synchronized with the drainage of the venous system during systole. This procedure was performed in five patients with unstable angina refractory to maximum medical therapy. SCSR significantly decreased the frequency of anginal episodes and the requirement for antianginal medications. SCSR also provided time for patient stabilization before diagnostic cardiac catheterization or therapeutic intervention. This preliminary experience suggests that synchronized coronary sinus retroperfusion is a feasible and safe procedure. It can be performed at the bedside with no apparent adverse effects to the patient. Retroperfusion also appears to be effective in relieving ischemic symptoms as assessed by clinical parameters. Based on our preliminary experience, further delineation of its clinical applications is warranted.