bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonischemic ventricular tachycardia. Clinical course and long-term follow-up in patients without clinically overt heart disease.
Authors: Lemery R , Brugada P , Bella P D , Dugernier T , van den Dool A , Wellens H J
Published: June 2011

This report describes the clinical, laboratory, and electrophysiologic features of 52 patients with ventricular tachycardia (VT) who had no clinical evidence of heart disease. The mean age of patients was 36 years, cardiovascular collapse occurred in 18 patients (35%), and exercise-related symptoms were present in 24 of 49 patients (49%). There were 20 patients with sustained monomorphic VT, 11 with incessant VT, and 21 with nonsustained VT. Abnormalities were present in 14 of 38 patients (37%) during echocardiography and in 21 of 47 patients (45%) who underwent cardiac catheterization. During baseline evaluation while patients were not receiving antiarrhythmic drugs, ambulatory monitoring and exercise testing showed an 88% and 57% incidence, respectively, of nonsustained or sustained monomorphic VT, whereas 31 of 50 patients (62%) had inducible VT (requiring an infusion of isoproterenol in 11 patients) during programmed electrical stimulation. The clinical VT (when a 12-lead electrocardiogram was available for analysis) had a left bundle branch block (LBBB) configuration in 20 of 33 patients (61%) and a right axis deviation in 17 of 33 patients (51%). The VT occurring during exercise testing and programmed electrical stimulation had the same configuration as the clinical VT in 22 of 22 patients. Three patients have received an antitachycardia pacemaker, and one patient underwent endocardial resection. Forty-eight patients (92%) were treated medically. One patient died of cancer; the remaining 47 patients were alive at a mean follow-up of 96 months after initial symptoms and 46 months after programmed electrical stimulation. We conclude that in patients without clinical evidence of heart disease, VT may be incessant, sustained, or nonsustained and that VT originates from the right ventricular outflow tract in more than 50% of patients. Although cardiac abnormalities may be found in more than 30% of patients, the exact significance of these abnormalities is unclear because of the absence of progressive changes and the excellent prognosis of this group of patients.
Amiloride. Antiarrhythmic and electrophysiologic actions in patients with inducible sustained ventricular tachycardia.
Authors: Duff H J , Mitchell L B , Kavanagh K M , Manyari D E , Gillis A M , Wyse D G
Published: June 2011

This study assessed the antiarrhythmic activity of amiloride in 35 patients with inducible sustained ventricular tachycardia. Patients had failed to respond to 3.6 +/- 1.0 antiarrhythmic drugs. Ventricular tachycardia was reproducibly induced by programmed electrical stimulation in all patients at the baseline study. Amiloride was given at 10 and 20 mg/day p.o. on a twice-daily schedule that achieved serum concentrations of 21 +/- 17 and 36 +/- 18 ng/ml, respectively. The mean left ventricular ejection fraction was unchanged from 36 +/- 14% at baseline to 37 +/- 17% during amiloride treatment. Amiloride significantly increased serum potassium from 4.6 +/- 0.4 to 5.1 +/- 0.4 mM. Four patients failed amiloride therapy with spontaneous nonsustained ventricular tachycardia. The remaining 31 patients were assessed by repeat programmed stimulation. Six patients had complete antiarrhythmic response, and an additional six patients had less than 15 beats of ventricular tachycardia induced. Therefore, amiloride was an efficacious antiarrhythmic treatment in 12 of 35 (34%) patients. Amiloride concentrations were significantly higher (52 +/- 20 ng/ml) in patients that responded than in patients that did not respond (30 +/- 15 ng/ml). The only electrophysiologic measurement that changed significantly was the ventricular functional refractory period (from 269 +/- 24 to 283 +/- 25 msec, p less than 0.05). Amiloride also suppressed frequent, spontaneous ventricular premature beats in eight of 15 patients (53%). No somatic side effects occurred. Two of the five patients discharged on amiloride therapy developed asymptomatic nonsustained ventricular tachycardia, and this prompted a change in antiarrhythmic therapy. Both died suddenly of arrhythmia during substitute empiric antiarrhythmic drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantification of mitral regurgitation with amplitude-weighted mean velocity from continuous wave Doppler spectra.
Authors: Jenni R , Ritter M , Eberli F , Grimm J , Krayenbuehl H P
Published: June 2011

Amplitude-weighted mean velocity from continuous wave (CW) Doppler spectra was used to measure aortic flow (QAo) and left ventricular mitral inflow (QLVin). These flows were used to quantify mitral regurgitation fraction: RFm = (QLVin-QAo).QLVin-1.100(%).QLVin was calculated from the diastolic time integral of amplitude-weighted mean velocity that was derived from CW spectra with the transducer placed in the apical window and the CW beam directed toward the left ventricular inflow tract. QAo was obtained from the systolic time integral of amplitude-weighted mean velocity by using the same apical window and directing the CW beam toward the left ventricular outflow tract. In 20 normal subjects, RFm ranged between -6.2% and +8% (mean, -0.8%). In 25 patients with pure mitral regurgitation, RFm obtained by Doppler (y) was compared with RFm calculated from biplane left ventriculography and the Fick method (x). The correlation was r = 0.96, SEE = 6.1% of the mean or 12% of the angio-Fick mean; the regression line was y = 0.96x + 0.18; mean y = 49%, mean x = 51%. It is concluded that RFm can be determined accurately by using amplitude-weight mean velocities from CW Doppler spectra. The advantages of this method are its independence from the measurement of the left ventricular inflow or outflow tract area.
Monoclonal antibody therapy for prevention of acute coxsackievirus B3 myocarditis in mice.
Authors: Kishimoto C , Abelmann W H
Published: June 2011

The efficacy of monoclonal antibodies against T cell subsets in the therapy of experimental myocarditis caused by coxsackievirus B3 (CB3) was investigated. Two-week-old male C3H/He mice were inoculated with CB3 virus. Treatment was begun in the viremic stage (starting on the day of inoculation) in experiment 1 and in the later aviremic stage (starting on day 10) in experiment 2. Rat anti-mouse monoclonal antibodies, Lyt 1 (helper/inducer T) at 1 microgram/mouse (group 2 in experiment 1; group 6 in experiment 2), Lyt 2 (suppressor/cytotoxic T) at 1 microgram/mouse (group 3 in experiment 1; group 7 in experiment 2), and Lyt 1 at 1 microgram plus Lyt 2 at 1 microgram/mouse (group 4 in experiment 1; group 8 in experiment 2), were administered subcutaneously daily for 2 weeks. The treatment groups were compared with infected controls (group 1 in experiment 1; group 5 in experiment 2). In experiment 1, the survival rate in group 4 was higher (p less than 0.01) than in group 1. In experiment 2, mice treated with Lyt 1 plus Lyt 2 (group 8) survived significantly longer (p less than 0.05) than did controls (group 5). In experiment 1, myocardial virus titers on days 5 and 6 did not show any significant differences among the four groups. Serum-neutralizing antibody titers between group 1 and group 4 in experiment 1 or between group 5 and group 8 in experiment 2 did not differ significantly. Histologic examination showed extensive myocardial necrosis and cellular infiltration in untreated groups: there was less infiltration in group 4 and in group 8 and less severe necrosis in group 8.(ABSTRACT TRUNCATED AT 250 WORDS)
Ambulatory follow-up of aortic dissection by transesophageal two-dimensional and color-coded Doppler echocardiography.
Authors: Mohr-Kahaly S , Erbel R , Rennollet H , Wittlich N , Drexler M , Oelert H , Meyer J
Published: June 2011

Follow-up of 18 patients with aortic dissection (five with type I, one with type II, 11 with type III dissection according to DeBakey) by transesophageal, two-dimensional and color-coded Doppler echocardiography showed a persistence of the false lumen in five of seven patients (71%) after surgery and in nine of 11 patients (82%) after medical therapy. In two patients treated with surgery, the dissected part of the aorta had been resected, whereas in two patients treated medically, a progressive and complete obliteration of the false lumen was observed. In the false lumen, thrombus formation was absent in four, localized in four, and progressive in six patients. Flow within the false lumen could be registered in 14 patients, and two distinct flow patterns were differentiated (laminar biphasic flow or slowly circulating flow). Persisting intimal tears were visualized by two-dimensional echocardiography in four patients, whereas color-coded Doppler showed an additional one to three intimal tears in the descending aorta in 10 patients. Flow across these intimal tears was biphasic in 75% of patients; that is, systolic flow was directed from the true to the false lumen with diastolic flow reversal. Unidirectional flow was detected in 25% of the communications, directed in 20% from the true to the false lumen, serving as an entry only and in one (5%) as reentry only. Additional information concerning complications like extension of the dissection (one of 18 patients), localized dilatation of the regurgitation (three of 18 patients) were detected by this method. Concerning the morphologic findings and the detection of flow characteristics, the transesophageal approach was superior to conventional echocardiography especially in the descending thoracic aorta. Thus, transesophageal two-dimensional and color-coded Doppler echocardiography seems to be an ideal method not only for the easy detection of aortic dissection but also for follow-up.
Marked decline of coronary heart disease mortality in 35-44-year-old white men in Allegheny County, Pennsylvania.
Authors: Kuller L H , Traven N D , Rutan G H , Perper J A , Ives D G
Published: June 2011

Trends in coronary heart disease (CHD) mortality were examined among 35-44-year-old white men during 1970-1986. Death certificates were obtained for 1,216 cases. All were coroner-certified natural deaths and noncoroner-certified deaths due to vascular diseases and diabetes mellitus. Autopsy data, coroner's reports, hospital records, physician's reports, and informants were used to validate diagnoses. The reviewers rejected 73 of 805 CHD certifications, but they validated 54 cases not certified as CHD on the death certificate as CHD. The CHD mortality rate fell from 90.6/100,000/year in 1970-1972 to 40.3/100,000/year in 1985-1986. Approximately two thirds of the decline was related to a decline in sudden deaths including 41.6% due to incident sudden CHD death. The proportion of diabetics among validated CHD deaths rose dramatically from 6.5% in 1970-1972 to 23.0% in 1985-1986. The CHD mortality rate among diabetics apparently did not decline during the 17 years of the study. We conclude that primary prevention has contributed substantially to the CHD decline in the 35-44-year age group. Better diagnoses and treatment, especially of angina pectoris and of patients after a myocardial infarction, may also have been important. Control of CHD in diabetics must take high priority in further prevention strategies.
One-year follow-up results of the 1985-1986 National Heart, Lung, and Blood Institute's Percutaneous Transluminal Coronary Angioplasty Registry.
Authors: Detre K , Holubkov R , Kelsey S , Bourassa M , Williams D , Holmes D , Dorros G , Faxon D , Myler R , Kent K
Published: June 2011

In 1,801 patients in the 1985-1986 Percutaneous Transluminal Coronary Angioplasty Registry, overall 1-year mortality was 3.2%, the 1-year myocardial infarction rate was 7.2%, and the 1-year coronary artery bypass surgery rate was 13.2%. In the 78% of the cohort with all lesions successfully dilated and without major procedural complications (successful patients), the corresponding rates were 1.9%, 2.6%, and 6.4%. Nearly 20% of all deaths, 40% of all infarctions, and 25% of all bypass operations occurred in the small subset of patients (6.8%) who sustained periprocedural occlusion. Event rates were higher in patients with multivessel disease than in those with one-vessel disease. At 1 year, angina-free status was reported by approximately three fourths of all surviving patients, regardless of initial success. However, compared with successful patients, unsuccessful patients underwent intervening bypass surgery (42% vs. 6%) to achieve asymptomatic status more frequently. Comparison of the 1-year event rates in the 1985-1986 registry with those in the 1977-1981 registry indicated reductions in all major untoward events. These reductions became apparent after controlling for the more extensive disease of the 1985-1986 registry patients. In contrast, use of repeat angioplasty has increased by 50%. We conclude that the improved initial results reported in the 1985-1986 registry cohort were maintained at 1-year follow-up.
Influence of mitral valve morphology on double-balloon catheter balloon valvuloplasty in patients with mitral stenosis. Analysis of factors predicting immediate and 3-month results.
Authors: Reid C L , Chandraratna P A , Kawanishi D T , Kotlewski A , Rahimtoola S H
Published: June 2011

To determine if mitral valve morphology influences the results of double-balloon catheter balloon valvuloplasty (CBV) for mitral stenosis, two-dimensional echocardiography was performed in 33 patients before CBV. The two-dimensional echocardiographic features of leaflet motion, leaflet thickness, subvalvular disease, and commissural calcium and 14 pre-CBV clinical and hemodynamic variables were then correlated to the immediately post-CBV mitral valve area (MVA). At 3 months after CBV, the two-dimensional echocardiographic features of patients with a 25% or greater decrease in MVA were analyzed to determine whether mitral valve morphology had influenced early results. Leaflet motion had a significant relation with the immediately post-CBV MVA (r = 0.67, y = 4.5x + 0.29, and SEE = 0.45). Leaflet thickness had a weak and negative relation (r = -0.48, y = -0.17x + 2.6, and SEE = 0.53) with the immediately post-CBV MVA. Subvalvular disease and commissural calcium had no significant relation to the immediately post-CBV MVA. When leaflet motion and leaflet thickness were considered as grades of mild, moderate, and severe and assigned a score of 0-2, patients with more severe disease (total score, 3 or 4) had a significant lower MVA immediately after CBV (1.4 +/- 0.4 cm2) than patients with moderate disease (score, 1-2; MVA, 2.0 +/- 0.5 cm2; p less than 0.05) or mild disease (score, 0; MVA, 2.6 +/- 0.6 cm2; p less than 0.05). In 96% of patients with a total score of 0-2, the immediately post-CBV MVA was more than 1.4 cm2, whereas only 29% of patients with a total score of 3-4 had an immediately post-CBV MVA of more than 1.4 cm2. Analysis of all two-dimensional echocardiographic features showed that leaflet motion score had the strongest influence on the post-CBV MVA (p less than 0.001). When all two-dimensional echocardiographic, clinical, and hemodynamic variables were included, leaflet motion, effective balloon dilating area, and cardiac output were the strongest predictors of the immediate post-CB MVA.(ABSTRACT TRUNCATED AT 400 WORDS)
Diagnostic value of QRST isointegral maps in detecting myocardial infarction complicated by bundle branch block.
Authors: Hayashi H , Watabe S , Yabe S , Takami K , Ohsugi S , Hirai M , Mizutani M , Saito H
Published: June 2011

The clinical usefulness of QRST isointegral maps (IQRST map) for detecting myocardial infarction that was complicated by intraventricular conduction disturbances was evaluated in patients with right bundle branch block (group RBBB, 64 patients) and left bundle branch block (group LBBB, 40 patients) by comparison with the normal mean IQRST map derived from 50 normal subjects. Myocardial infarction complicated the conduction disturbances in 24 of the 64 RBBB and in 18 of the 40 LBBB patients. A correlation coefficient was used for assessing the similarity of each map pattern with the normal mean IQRST map. The difference map was made by subtracting the average normal IQRST map from each abnormal IQRST map, and those differences that were less than 2 SD from the mean were retained as a significant area. The number of leads and their sum of differences were used to represent the size of the difference map. Correlation coefficients were significantly (p less than 0.001) smaller in patients with bundle branch block complicated by myocardial infarction than in patients with conduction disturbances not complicated by myocardial infarction. A significant area emerged in the difference map in all patients with myocardial infarction complicated by conduction disturbances. The emergence of a significant area revealed high diagnostic accuracy for detecting myocardial infarction in group RBBB (89.1%). The size of a significant area in a difference map was significantly larger in cases with complicated myocardial infarction than in cases with uncomplicated myocardial infarction in either group RBBB or group LBBB (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Long-term beta-blockade in dilated cardiomyopathy. Effects of short- and long-term metoprolol treatment followed by withdrawal and readministration of metoprolol.
Authors: Waagstein F , Caidahl K , Wallentin I , Bergh C H , Hjalmarson A
Published: June 2011

To evaluate the short- and long-term effects of beta-adrenergic blockade (metoprolol) as well as the reaction to withdrawal and readministration of metoprolol in severe heart failure, 33 patients (25 men and eight women; mean age, 47.6 +/- 14.0 years) with dilated cardiomyopathy were studied by right and left heart catheterization, right ventricular biopsy, two-dimensional and Doppler echocardiography, and external pulse recordings. Twenty-six of 33 patients survived more than 6 months, and 24 of the 26 patients improved their functional class (from mean 3.3 to 1.8, p less than 0.0001). These 24 patients were subjected to withdrawal of metoprolol until the number of symptoms increased and deterioration occurred as observed noninvasively (group 1, n = 16), whereas the eight patients did not deteriorate during a 12-month period (group 2). During long-term treatment with metoprolol, there was an increase in ejection fraction from 0.24 to 0.42 (p less than 0.0001), whereas there was a decrease in the left ventricular (LV) end-diastolic dimension (from 7.3 to 6.4 cm, p less than 0.0001), in the grade of mitral regurgitation (from 1.7 to 0.4, p less than 0.0001), and in the grade of tricuspid regurgitation (from 0.6 to 0.05, p less than 0.007). There was a decrease in pulmonary wedge pressure (from 23.8 to 10.7 mm Hg, p less than 0.0001), LV end-diastolic pressure (from 24.1 to 13.4 mm Hg, p less than 0.002), and systolic vascular resistance (from 1,782 to 1,499 dynes/sec/cm, p less than 0.04). There was an increase in systolic blood pressure (from 116 to 132 mm Hg, p less than 0.003), cardiac index (from 2.17 to 2.58 l/min/m2, p less than 0.005), and LV stroke work index (from 31 to 65 g.m/m2, p less than 0.0001). During withdrawal of metoprolol, the heart rate and left atrial dimension increased (p less than 0.0001), whereas ejection fraction decreased (p less than 0.0001). The 12 (of 16) patients in group 1 who survived the withdrawal period had metoprolol readministered, and subsequently, ejection fraction increased (from 0.23 to 0.33, p less than 0.002). Patients had a low number of ventricular beta-adrenergic receptors compared with healthy control subjects (30.3 +/- 2.9 vs. 97.4 +/- 8.7 fmol/mg protein, p less than 0.001), but long-term treatment with metoprolol caused a moderate up-regulation (from 30.3 +/- 2.9 to 49.0 +/- 7.1 fmol/mg protein, p less than 0.05), which may facilitate a more normal response to sympathetic stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Endothelium-dependent inhibition of ergonovine-induced contraction is impaired in porcine coronary arteries with regenerated endothelium.
Authors: Shimokawa H , Flavahan N A , Shepherd J T , Vanhoutte P M
Published: June 2011

The inhibitory effects of the endothelium against ergonovine-induced contraction were examined in isolated porcine coronary arteries under normal conditions and after endothelial regeneration. Endothelium-dependent responses were examined in vitro in normal Yorkshire pigs (n = 16) and in pigs that had undergone balloon endothelium removal of the left anterior descending coronary artery (LAD) 4 weeks before the study (n = 10). The presence of a complete endothelial lining was confirmed histologically. In rings from normal arteries contracted with prostaglandin F2 alpha in the presence of indomethacin and ketanserin (a 5-HT2-serotonergic blocker), ergonovine caused endothelium-dependent relaxations. They were attenuated by rauwolscine (an alpha 2-adrenergic blocker), inhibited by methiothepin (a combined 5-HT1- and 5-HT2-serotonergic blocker) or by pertussis toxin (an inhibitor of several G proteins) and abolished by oxyhemoglobin (a selective inactivator of endothelium-derived relaxing factor). In quiescent rings from normal arteries, ergonovine caused contractions that were inhibited by the presence of the endothelium; this endothelium-dependent inhibition was abolished by oxyhemoglobin. The direct contractions were not affected by prazosin (an alpha 1-adrenergic blocker), rauwolscine, 6-hydroxydopamine (an agent causing chemical sympathetectomy), or diphenhydramine (an H1-histaminergic blocker) but were inhibited by ketanserin. In rings with regenerated endothelium contracted with prostaglandin F2 alpha, the endothelium-dependent relaxations to ergonovine were reduced significantly and were not inhibited by pertussis toxin. In quiescent rings with regenerated endothelium, the endothelium-dependent inhibition of ergonovine-induced contraction was less.(ABSTRACT TRUNCATED AT 250 WORDS)
Functional significance of hypertrophy of the noninfarcted myocardium after myocardial infarction in humans.
Authors: Ginzton L E , Conant R , Rodrigues D M , Laks M M
Published: June 2011

Hypertrophy of the noninfarcted left ventricle as a chronic response to myocardial infarction has been demonstrated in animals and at autopsy in humans. However, the functional significance of postmyocardial infarction hypertrophy is a subject of dispute. The purpose of this study was to determine the time course of development of postmyocardial infarction hypertrophy of the noninfarcted myocardium in humans and to assess its functional significance. Subcostal view, two-dimensional echocardiograms were recorded at rest and during peak exercise, 6 and 40 weeks postmyocardial infarction in 45 patients (16 anterior, 20 inferior, nine non-Q wave infarcts), for measurement of left ventricular mass and ejection fraction. The left ventricular mass index increased from 94 +/- 30 to 118 +/- 27 g/m2 (p less than 0.01) during the time of the two studies. There was a significant correlation between the change in left ventricular mass index and improved resting ejection fraction (r = 0.48, p less than 0.001) and exercise ejection fraction (r = 0.48, p less than 0.001) at the follow-up study. Of the 32 patients who increased their left ventricular mass index greater than 7%, 18 improved their rest ejection fraction greater than 0.05 units and 17 improved their exercise ejection fraction greater than 0.05 units. Conversely, of the 13 patients who failed to increase their left ventricular mass index, only three improved their rest ejection fraction and one improved the exercise ejection fraction (Fisher's exact test, p less than 0.05). We reached three conclusions. First, in humans, significant hypertrophy of the noninfarcted myocardium can be detected by two-dimensional echocardiography, 9 months postmyocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
The safety of maximal exercise testing.
Authors: Gibbons L , Blair S N , Kohl H W , Cooper K
Published: June 2011

Previous reports on the safety of exercise testing have been based on surveys from different testing facilities with a variety of testing protocols and patient types. From 1971 through 1987, 71,914 maximal exercise tests conducted in a population with a low prevalence of known coronary heart disease under uniform conditions at a single medical facility resulted in six major cardiac complications including one death. No complications have occurred in the past 10 years in 45,000 maximal tests. The overall cardiac complication rate in men and women is 0.8 complications per 10,000 tests with 95% confidence intervals of 0.3-1.9 complications per 10,000 tests. Maximal exercise testing appears safer than some previously published reports have suggested and seems to be getting safer with time.
Regional myocardial oxygen consumption determined noninvasively in humans with [1-11C]acetate and dynamic positron tomography.
Authors: Armbrecht J J , Buxton D B , Brunken R C , Phelps M E , Schelbert H R
Published: June 2011

Experimental studies of animals have previously demonstrated the validity of [1-11C]acetate as a tracer of oxidative metabolism for use with positron emission tomography. The present study was undertaken to define in normal human volunteers the relation between myocardial clearance kinetics of [1-11C]acetate, and the rate-pressure product as an index of myocardial oxygen consumption. Twenty-two studies were performed of 12 volunteers. The rate-pressure product was increased with continuous supine bicycle exercise in six studies. Of the 16 resting studies, seven were performed in the fasted state and nine following an oral glucose load, to define possible effects of substrate availability on the tracer-tissue kinetics. Myocardial tissue time-activity curves were biexponential. Clearance of activity was homogeneous throughout the myocardium. The rate constants k1, obtained from biexponential fitting, and kmono, obtained by monoexponential fitting of the initial linear portion of the time-activity curves, correlated well with the rate-pressure product. Although the correlation coefficient was higher for k1 than for kmono (0.95 vs. 0.91), analysis on a sectorial basis showed less regional variability in kmono. This suggests that kmono, which is more practical than k1 because it requires shorter acquisition times, may be more clinically and experimentally useful for detection of myocardial segments with abnormal oxygen consumption. Overall, changes in myocardial substrate supply were without significant effect on the relation between the rate constants (k1 and kmono) and the rate-pressure product, although a small decrease in kmono/rate-pressure product was observed following oral glucose by paired analysis in four subjects. It is concluded that [1-11C]acetate can be used for the noninvasive measurement of myocardial oxygen consumption in humans with positron emission tomography, and, thus, has clinical and experimental potential as a tool for the understanding and diagnosis of myocardial disease.
Blunted sympathetic response to cardiopulmonary receptor unloading in hypertensive patients with left ventricular hypertrophy. A possible compensatory role of atrial natriuretic factor.
Authors: Trimarco B , Lembo G , De Luca N , Volpe M , Ricciardelli B , Condorelli G , Rosiello G , Condorelli M
Published: June 2011

To investigate whether or not hypertension with left ventricular hypertrophy (LVH) modifies the mechanisms underlying the vascular adjustments to orthostatic stress, we evaluated the hemodynamic and hormonal effects of graded lower-body negative pressure (LBNP) (-10 and -40 mm Hg) before and after sympathetic blockade in 10 hypertensive patients with LVH and in five age- and sex-matched normotensive subjects. In control conditions, LBNP elicited comparable vasoconstrictor responses in the forearm in the two groups. In normotensive subjects, graded increases in plasma norepinephrine and plasma renin activity (PRA) and reductions in plasma immunoreactive atrial natriuretic factor (irANF) were recorded. In hypertensive patients, a significant increase in plasma norepinephrine and plasma renin activity was obtained only with the higher level of LBNP, whereas irANF plasma levels decreased progressively. In both groups, sympathetic blockade abolished the increase in plasma renin activity and did not modify the changes in plasma irANF induced by both levels of LBNP in control conditions. The vascular response to -10 mm Hg LBNP remained unchanged after sympathetic blockade in both groups. However, after sympathetic blockade, the vasoconstrictor response to -40 mm Hg LBNP in normal subjects was no longer different from that elicited by -10 mm Hg LBNP, whereas in hypertensive patients the vasoconstrictor response was still significantly higher than that induced by -10 mm Hg LBNP. Direct correlations between the percent changes in forearm vascular resistance and those in plasma norepinephrine and plasma renin activity were found only in normal subjects in control conditions but were not observed after sympathetic blockade. On the contrary, the inverse correlation between changes in irANF plasma levels and in forearm vascular resistance found in control conditions in both groups was still observed after sympathetic blockade. In a separate group of hypertensive patients with left ventricular hypertrophy, exogenous infusion of ANF induced an increase in venous irANF plasma levels of the same magnitude of the decrease evoked by LBNP and significantly reduced forearm vascular resistance. These data show that in hypertensive patients with left ventricular hypertrophy, sympathetic activation does not contribute to the vascular response to cardiopulmonary receptor unloading (-10 mm Hg LBNP). They also suggest that in these patients inhibition of ANF secretion may play a role in the response to a low level of LBNP so that the peripheral vasoconstriction induced by cardiopulmonary receptor unloading is comparable to that observed in normal subjects despite the lack of appropriate sympathetic reflex vasoconstriction.
Chronic incomplete atrioventricular block induced by radiofrequency catheter ablation.
Authors: Huang S K , Bharati S , Graham A R , Gorman G , Lev M
Published: June 2011

To determine if catheter ablation of the atrioventricular (AV) junction with radiofrequency energy can induce chronic incomplete (first- and second-degree) AV block to avoid the need for a permanent pacemaker, 20 closed-chest dogs were studied. Group 1 (10 dogs) received radiofrequency energy (750 kHz) with a fixed power setting (5 or 10 W) while increasing the pulse duration from 10 to 50 seconds for each application. Group 2 (10 dogs) received energy with a fixed pulse duration (20 or 30 seconds) while increasing the power setting from 5 to 10 W or from 10 to 20 W during each energy delivery. Radiofrequency energy was delivered between a chest-patch electrode and the distal electrode of a regular 7F tripolar His bundle catheter. For each application, the energy delivery was interrupted when 1) the PR interval prolonged (greater than 50%) or 2) second-degree or complete AV block occurred and persisted up to 5 seconds. The ablation procedure ended when there was 1) persistent PR prolongation (greater than 50%) or persistent second-degree AV block (lasting greater than 30 minutes) after ablation, 2) occurrence of two consecutive transient (less than 1 minute) complete AV blocks after each energy delivery, or 3) complete AV block (lasting greater than 2 minutes) after ablation. Of seven dogs in group 1 and five dogs in group 2 in which incomplete AV block was achieved 1 hour after the procedure, six in group 1 and five in group 2 remained in incomplete AV block 2-3 months after ablation. One dog in group 1 progressed into complete AV block. Of the remaining three dogs in group 1 and five dogs in group 2 in which complete AV block was initially achieved 1 hour after ablation, two in group 1 and four in group 2 continued to have complete AV block, whereas one in each group had AV conduction returned to incomplete at 1-2 months of follow-up. Thus, a total of 13 dogs had chronic incomplete AV block induced by radiofrequency catheter ablation. Pathologic examination of the conduction system in two dogs with first-degree AV block, two dogs with second-degree AV block, and one dog with complete AV block showed discrete scars involving the approaches to the AV node and the AV node itself. It is concluded that, in most dogs studied, chronic incomplete AV block could be achieved by careful titration of the dosage of radiofrequency energy and by regulation of the ablation end points.
Ventricular expression of atrial natriuretic polypeptide and its relations with hemodynamics and histology in dilated human hearts. Immunohistochemical study of the endomyocardial biopsy specimens.
Authors: Takemura G , Fujiwara H , Horike K , Mukoyama M , Saito Y , Nakao K , Matsuda M , Kawamura A , Ishida M , Kida M
Published: June 2011

To investigate the mechanism of expression of atrial natriuretic polypeptide (ANP) in human ventricles, we conducted an immunohistochemical study of ANP in biventricular endomyocardial biopsy specimens obtained from a total of 49 patients with cardiac dilatation due to dilated cardiomyopathy (21 patients), postmyocarditis (18 patients), or volume overload (five patients) and subjects with no dilatation as controls (five patients). Four-micron thick sections were stained by an indirect immunoperoxidase method using monoclonal antibody to alpha-human ANP as the primary antibody. The frequency of ANP-present myocytes was calculated in each specimen and compared with clinical, echocardiographic, hemodynamic, angiographic, and histologic parameters. ANP-present myocytes were noted in all of the 21 patients with dilated cardiomyopathy, in 11 of the 18 patients with postmyocarditis, in four of the five patients with volume overload, and in zero of the five controls. The mean percentage of ANP-present myocytes was significantly greater in the left-side specimens (35 +/- 37%) than in the right-side ones (2 +/- 4%). The percentage of ANP-present myocytes in the left-side specimens significantly correlated with peak systolic or end-diastolic wall stress (r = 0.67 and 0.58), left ventricular end-systolic or end-diastolic volume index (r = 0.75 and 0.69), or left ventricular end-diastolic pressure (r = 0.42) and inversely correlated with ejection fraction (r = -0.73), systolic left ventricular wall thickness (r = -0.58), or cardiac index (r = -0.30). Expression of ANP was rarely seen in the cases with normal wall stresses, normal ejection fraction, normal volume, or normal myocyte size. However, it was seen frequently even in hearts with normal levels of left ventricular end-diastolic pressure and cardiac index (compensated hearts). The percent of ANP-present myocytes in both sides significantly correlated with size of myocytes (r = 0.48 at right and r = 0.57 at left side) or degree of fibrosis (r = 0.45 at right and r = 0.48 at left side). These results suggest that ANP expression is augmented in the dilated ventricles regardless of the causes of dilatation and that the augmentation is a compensatory mechanism as prevention against decompensation responding to reduced contractility, excess of wall stresses, or both, concomitantly occurring with cardiac dilatation and myocardial hypertrophy.
Dispatcher-assisted cardiopulmonary resuscitation. Validation of efficacy.
Authors: Kellermann A L , Hackman B B , Somes G
Published: June 2011

Dispatcher-delivered telephone instruction in cardiopulmonary resuscitation (CPR) has been proposed to increase rates of bystander CPR in cases of out-of-hospital cardiac arrest. We tested the efficacy of a previously developed CPR message using a recording mannikin in a high stress, simulated cardiac arrest scenario. Community volunteers were unaware they would perform CPR until immediately before each trial. Performance of volunteers without prior CPR training (group A, n = 65) who received telephone instruction was compared with that of previously trained volunteers (group B, n = 43) who received the same message. Performances of both groups were also compared with a third group (group C, n = 43) composed of previously trained volunteers who did not receive the message. Quality of CPR was graded by three CPR instructors using explicit criteria. Printout strips from the recording mannikins were also analyzed. Evaluators were unaware of the training status of volunteers. The three groups were of comparable sex, race, and educational level, but group C was significantly younger than groups A and B (31.7 vs. 37.7 years, p less than 0.001). Because of the time required for telephone instruction, groups A and B started chest compressions a mean of 4.0 minutes after collapse compared with 1.2 minutes for group C (p less than 0.0001). We found that the previously untrained volunteers of group A performed CPR of an overall quality comparable to that performed by previously trained members of group C. Group A performed chest compressions significantly better than group C (p less than 0.02) but had greater problems performing effective ventilations.(ABSTRACT TRUNCATED AT 250 WORDS)
Antiarrhythmic efficacy, clinical electrophysiology, and pharmacokinetics of 3-methoxy-O-desmethyl encainide (MODE) in patients with inducible ventricular tachycardia or fibrillation.
Authors: Roden D M , Lee J T , Woosley R L , Echt D S
Published: June 2011

In most patients, the clinical effects of therapy with encainide are mediated by the generation of the active metabolites O-desmethyl encainide and 3-methoxy-O-desmethyl encainide (MODE). Data from in vitro and animal studies have indicated that MODE has electrophysiologic and pharmacokinetic features that make its further evaluation desirable; in earlier studies, we found that MODE suppressed chronic high-frequency nonsustained ventricular arrhythmias at plasma concentrations of 50-160 ng/ml. We now report the clinical electrophysiology, antiarrhythmic activity, and pharmacokinetics of MODE in 17 patients with inducible ventricular tachyarrhythmias (VTs) in whom programmed electrical stimulation was performed before drug administration and after one or two sequences of loading and maintenance infusions of MODE. Because the relation between plasma concentration and effect had been incompletely defined, a dose-titration approach was adopted: available pharmacokinetic data were used to construct loading and maintenance infusion regimens that were predicted to attain low plasma concentrations in initial patients while higher infusion rates were evaluated in subsequent patients. MODE prevented VT induction in three of 17 patients and VT cycle length was increased by greater than or equal to 100 msec in a further seven of 17; most responses to MODE occurred at plasma concentrations greater than 556 ng/ml (greater than 1 SD above mean plasma MODE during encainide therapy). Response to MODE did not predict subsequent response to oral therapy with encainide. MODE increased intracardiac conduction times, QT intervals during atrial and ventricular pacing, and right ventricular effective refractory periods (RVERP); changes in RVERP were most prominent at rapid pacing rates, while changes in intracardiac conduction were rate-independent at cycle lengths between 400 and 600 msec. Plasma MODE concentrations measured during electrophysiology study correlated well with those predicted by the pharmacokinetic simulations (r = 0.91, p less than 0.001). Serial plasma sampling after programmed electrical stimulation indicated a minimum MODE elimination half-life of 8.2 +/- 5.4 hours. Side effects were confined to three instances of asymptomatic conduction system depression in subjects with latent conduction system disturbances. We conclude that MODE slows intracardiac conduction, delays repolarization, and can suppress or substantially modify inducible VT. Moreover, it was only with the adoption of the dose-titration strategy that we were able to safely demonstrate that plasma MODE concentrations higher than those routinely observed during encainide therapy were required to substantially alter cardiac electrophysiology.
Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure.
Authors: Mancini D M , Coyle E , Coggan A , Beltz J , Ferraro N , Montain S , Wilson J R
Published: June 2011

Patients with heart failure frequently exhibit abnormal skeletal muscle metabolic responses to exercise, as assessed with 31P NMR. To investigate whether these metabolic abnormalities are due to intrinsic skeletal muscle changes, we performed gastrocnemius muscle biopsies on 22 patients with heart failure (peak VO2, 15.4 +/- 4.7 ml/kg/min; ejection fraction, 20 +/- 7%) and on eight normal subjects. Biopsies were analyzed for fiber type and area, capillarity, citrate synthase, phosphofructokinase, lactate dehydrogenase, and beta-hydroxyacyl CoA dehydrogenase activity. All patients with heart failure also underwent 31P NMR studies of their calf muscle during plantarflexion at three workloads. Muscle pH responses and the relation of the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) to systemic VO2 were then evaluated. Compared with normal subjects, patients with heart failure exhibited a shift in fiber distribution with increased percentage of the fast twitch, glycolytic, easily fatigable type IIb fibers (normal subjects, 22.7 +/- 10.1; heart failure, 33.1 +/- 11.1%; p less than 0.05), atrophy of type IIa (normal subjects, 5,477 +/- 1,109; heart failure, 4,239 +/- 1,247 microns 2; p less than 0.05) and type IIb fibers (normal subjects, 5,957 +/- 1,388; heart failure, 4,144 +/- 945 microns 2; p less than 0.01), and decreased activity of beta-hydroxyacyl CoA dehydrogenase (normal subjects, 5.17 +/- 1.44; heart failure, 3.67 +/- 1.68 mol/kg protein/hr; p less than 0.05). No significant linear correlation could be identified between the slope of the Pi/PCr to VO2 relation and muscle histochemistry or enzyme activities. Similarly, no linear relation was found between intracellular pH at peak exercise and any muscle variable.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular volume measurement by conductance catheter in intact dogs. Parallel conductance volume depends on left ventricular size.
Authors: Boltwood C M , Appleyard R F , Glantz S A
Published: June 2011

The conductance catheter is a promising new instrument for continuously measuring left ventricular (LV) volume. Absolute LV volume (V[t]) is related to uncorrected conductance volume, B(t), according to the equation: V(t) = (1/alpha)(B(t) - alpha Vc). The alpha Vc factor represents parallel-conductance volume due to conducting material outside the LV blood pool, and may be estimated by transiently changing blood conductivity using a bolus injection of hypertonic saline. alpha is the slope in the relation between B(t) and true LV volume. We tested the assumption that alpha Vc and alpha are constant over a range of hemodynamic conditions. We performed multiple hypertonic saline alpha Vc determinations in seven intact dogs during control conditions and subsequent temporary balloon occlusions of inferior vena cava (IVCO), aorta (AO), and pulmonary artery (PAO). We also compared B(t) with simultaneous biplane angiographic LV volume during similar control and intervention conditions. The saline-derived alpha Vc was 76 +/- 2 ml during control and fell significantly by -7 +/- 2 ml during IVCO (p less than 0.001) but not during AO or PAO. According to multiple linear regression analyses, the strongest predictor of saline-derived alpha Vc was uncorrected end-systolic Bes, with a sensitivity coefficient of 0.60 +/- 0.06 ml/ml (p less than 0.001). Angiographically derived alpha Vc showed a similar dependence on Bes, with a coefficient of 0.77 +/- 0.14 ml/ml (p less than 0.001). Angiographically determined alpha also showed significant variation with hemodynamic interventions, largely reflecting an underlying dependence on alpha Vc. The variation in alpha Vc and alpha with LV size may stem from nonlinearity in the B(t)-V(t) relation. Although the conductance catheter provides a useful measure of relative LV volume, measurement of absolute LV volume over a wide hemodynamic range using constant alpha Vc and alpha factors is unrealistic. This result calls into question the current use of this technique for the measurement of the absolute end-systolic--pressure-volume relation.
Four-year follow-up study in patients with angina pectoris and normal coronary arteriograms ("syndrome X")
Authors: Opherk D , Schuler G , Wetterauer K , Manthey J , Schwarz F , Kübler W
Published: June 2011

In patients with typical stress-induced anginal pain, normal coronary arteries, and unimpaired left ventricular performance at rest ("syndrome X"), a reduced coronary dilatory capacity, abnormal lactate metabolism during stress, and reduction of left ventricular functional reserve have been described. A group of 40 patients with syndrome X was followed for several years to determine their long-term prognosis. In 27 patients pulmonary artery pressure and in 19 patients left ventricular ejection fraction were reassessed during rest and exercise approximately 4 years after the initial examination. In patients with stress-induced ST-segment depression, these variables did not change during the observation period. In patients with constant or rate-dependent left bundle branch block, however, there was significant deterioration of left ventricular performance during rest (pulmonary artery mean pressure, 16 +/- 3 vs. 17 +/- 4 mm Hg, p = NS; left ventricular ejection fraction, 62 +/- 5% vs. 55 +/- 5%, p less than 0.05) and exercise (pulmonary artery, 30 +/- 6 vs. 39 +/- 10 mm Hg, p less than 0.005; left ventricular ejection fraction, 59 +/- 6% vs. 49 +/- 5%, p less than 0.01). These findings suggest that in syndrome X two subgroups with distinctly different prognoses may be defined: In patients with stress-induced ST-segment depression during exercise, left ventricular performance remains well preserved; however, in patients with either constant or rate-dependent left bundle branch block, there is significant deterioration of left ventricular function within several years.
Effects of atrial natriuretic peptide on the coronary arterial vasculature in humans.
Authors: Chu A , Morris K G , Kuehl W D , Cusma J , Navetta F , Cobb F R
Published: June 2011

The effects of the synthetic 28-amino-acid alpha-human atrial natriuretic peptide (ANP) on the proximal coronary arteries and coronary blood flow were evaluated in 17 patients. Proximal coronary dimension was quantitated by digital angiography, and coronary flow was quantitated with 3F Doppler flow catheters. ANP, when given as a 2.5-micrograms/kg bolus in the left ventricle, caused sustained significant proximal coronary dilations from 3.49 +/- 0.57 to 4.09 +/- 0.76 mm, lasting more than 30 minutes. The proximal coronary diameter did not increase further after intracoronary injection of 0.3 mg nitroglycerin (4.08 +/- 0.79 mm). Coronary flow (resistance coronary dilation) was not significantly increased at 5 minutes after ANP (87 +/- 55 to 102 +/- 54 vol flow units), indicating that the proximal coronary dilations were not flow dependent. The persistent proximal coronary dilations were associated with minor and transient decreases in aortic pressure and left ventricular end-diastolic pressure and with minor and transient increases in heart rate, cardiac output, and left ventricular contractility. Plasma ANP level increased significantly by more than sixfold from 39.8 +/- 8.8 to 245.8 +/- 168.5 pg/ml. The time course of proximal coronary dilations was related more closely to the time course of increase in plasma cyclic guanosine monophosphate than that of plasma ANP. This study demonstrates that bolus injection of ANP (2.5 micrograms/kg), an endogenous vasodilator, caused marked sustained preferential proximal coronary dilations and brief minor changes in cardiac and systemic hemodynamics. Although additional studies are needed to assess its clinical efficacy as a coronary dilator in the treatment of coronary artery disease, these data suggest a potential of ANP in the therapy of ischemia.