bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting ventricular tachycardia cycle length after procainamide by assessing cycle length-dependent changes in paced QRS duration.
Authors: Marchlinski F E , Buxton A E , Josephson M E , Schmitt C
Published: June 2011

To determine if paced cycle length-dependent changes in the QRS duration correlate with the change in ventricular tachycardia (VT) cycle length after procainamide, we measured the QRS duration during sinus rhythm and during right ventricular pacing before and after procainamide (mean concentration, 9.9 micrograms/ml) in 18 patients with morphologically identical VT induced at both study periods. Pacing was performed at 600 msec or the longest cycle length that allowed for uninterrupted capture and at a cycle length that was within 50 msec of the VT cycle length observed during the control study (mean, 313 +/- 51 msec). After procainamide, the VT cycle length increased from 285 +/- 62 to 368 +/- 70 msec (percent change, 30 +/- 13%). The QRS duration during sinus rhythm increased from 125 +/- 25 to 145 +/- 29 msec (percent change, 16%). The QRS duration at both paced cycle lengths was the same in the baseline state (191 +/- 26 msec). However, the change in QRS duration after procainamide at the shorter paced cycle length compared to a 39 +/- 13 msec (18%) increase at the longer paced cycle, p less than 0.001. There was a significant correlation between the percent change in QRS duration at the shorter paced cycle length and the percent change in VT cycle length (r = 0.84, p less than 0.001) with the relation expressed by the regression equation: percent change in VT cycle length = -2.8 + 1.16 x percent change in QRS duration.(ABSTRACT TRUNCATED AT 250 WORDS)
Arterial baroreflex abnormalities in heart failure. Reversal after orthotopic cardiac transplantation.
Authors: Ellenbogen K A , Mohanty P K , Szentpetery S , Thames M D
Published: June 2011

Arterial baroreflex control of the heart and peripheral circulation is markedly impaired in humans and animals with congestive heart failure. After reversal of heart failure in animal models, arterial baroreflex control of heart rate remains impaired for up to 8 months. Cardiac transplantation restores normal ventricular function and completely reverses heart failure, but does it normalize arterial baroreflex control of heart rate in humans? We studied baroreflex sensitivity in 11 patients with severe heart failure, six normal control patients, and 23 patients at 2 weeks to 4 years after orthotopic cardiac transplantation. Baroreflex sensitivity was assessed with intravenous bolus injections of phenylephrine and is expressed as change in RR or PP interval (msec) per millimeters of mercury rise in systolic arterial pressure. Atrial rate of both donor (denervated) and recipient (innervated) atria were measured in the transplant group. Baroreflex sensitivity in patients with severe heart failure was 2.0 +/- 0.3 msec/mm Hg, but in patients after cardiac transplantation, it was 13.0 +/- 0.9 msec/mm Hg (p less than 0.001). The responses in the transplant group were similar to those observed in normal controls (10 +/- 1.2 msec/mm Hg, p = NS). Our data indicate that patients with severe congestive heart failure have marked abnormalities of baroreflex control, which are reversed as early as 2 weeks after cardiac transplantation. In view of this rapid reversal, we consider it unlikely that abnormal baroreflex sensitivity seen in heart failure is due to structural alterations in the baroreceptors. We speculate that neurohumoral rather than structural abnormalities account for depressed baroreflex sensitivity in heart failure.
Improved diagnostic performance on the severity of left ventricular hypertrophy with body surface mapping.
Authors: Yamaki M , Ikeda K , Kubota I , Nakamura K , Hanashima K , Tsuiki K , Yasui S
Published: June 2011

To improve the diagnostic usefulness of electrocardiography (ECG) in determining the severity of left ventricular hypertrophy (LVH) with body surface mapping, 87 unipolar ECGs were recorded from 57 patients with left ventricular (LV) concentric hypertrophy and 30 with LV dilatation. Body surface ECG features due to LVH were evaluated by increase of QRS voltage and delayed local activation. We measured for each lead R voltage, net area of QRS (AQRS), ventricular activation time (VAT), and departure index (DI) of AQRS and VAT (DI = mean/SD). From these measurements, seven parameters were calculated for each patient: Rmax, the maximal R wave voltage; AQRSmax, the maximal AQRS; AQRS-Dmax, the maximal AQRS DI; AQRS-Darea, the area size where DIs of AQRS are more than 2; VATmax, the maximal VAT; VAT-Dmax, the maximal VAT DI; and VAT-Darea, the area size where DIs of VAT are more than 2. Among these parameters, the most effective for diagnosis of LVH were selected by stepwise multiple regression analysis. In the concentric hypertrophy group, the combination of VAT-Darea and Rmax was determined to be the best for estimating wall thickness. The regression equation determined from them correlated well to wall thickness (r = 0.73). In the LV dilatation hypertrophy group, only AQRSmax was selected for estimating LV dilatation. A good correlation between AQRSmax and LV internal dimension was observed (r = 0.73). With the body surface distribution of VAT prolongation, septal hypertrophy was separated from the other LVH. These were superior to the conventional method of 12-lead ECGs. ECG diagnosis of LVH severity improved by incorporating a mapping study. Also, prolongation of VAT and increase in QRS voltage were shown to be important when determining the severity of LVH.
Transcoronary chemical ablation of ventricular tachycardia.
Authors: Brugada P , de Swart H , Smeets J L , Wellens H J
Published: June 2011

After identification of the artery supplying blood to the arrhythmogenic area, transcoronary chemical ablation of ventricular tachycardia was undertaken in three patients with incessant tachycardia in whom the other therapeutic options had failed. Sterile ethanol (96%) was given at a dose of 1.5 ml in two patients and a total of 6 ml in the third. The arrhythmia was cured in two patients and suppressed during a 1-month period in the third until new collateral blood supply to the arrhythmogenic area developed and ventricular tachycardia recurred. The procedure was then repeated successfully. After administration of ethanol in the high interventricular septum, one patient developed temporary complete atrioventricular block and a pacemaker was implanted. No other complications occurred. We observed that in patients with ventricular tachycardia after myocardial infarction, it is possible to identify and catheterize small coronary arteries responsible for blood supply to the site of origin or pathway of ventricular tachycardia. After careful transcoronary mapping with saline, chemical ablation can prevent further episodes of the arrhythmia in selected patients.
Contrasting peripheral short-term and long-term effects of converting enzyme inhibition in patients with congestive heart failure. A double-blind, placebo-controlled trial.
Authors: Drexler H , Banhardt U , Meinertz T , Wollschläger H , Lehmann M , Just H
Published: June 2011

To discover the underlying mechanisms involved in the beneficial long-term effects of angiotensin converting enzyme (ACE) inhibitors, we investigated the systemic and peripheral effects of short- and long-term ACE inhibition in patients with chronic heart failure. After assessing the short-term effects and dose titration with cilazapril, a new long-acting ACE inhibitor, 21 patients were randomized to receive either placebo or the ACE inhibitor. Seventeen patients completed the 3-month treatment. Central hemodynamic output, femoral blood flow (measured by thermodilution), oxygen saturation, and lactate and norepinephrine levels were determined simultaneously in the femoral vein and radial artery during treatment and after a 3-month rest and during symptom-limited bicycle exercise. Short-term ACE inhibition improved rest and exercise hemodynamic output, but it did not alter peak femoral blood flow, calculated leg oxygen consumption, or systemic oxygen uptake during exercise, despite significant reduction in femoral norepinephrine extraction and arterial angiotensin levels during exercise. In contrast, long-term ACE inhibition further improved exercise cardiac output and increased leg blood flow (from 2.3 to 2.9 l/min, p less than 0.05), leg oxygen consumption (from 277 to 403 ml/min, p less than 0.05), and systemic oxygen uptake (from 1,133 to 1,453 ml/min, p less than 0.05), whereas these variables remained unchanged with placebo treatment (p less than 0.02 between groups). Moreover, a moderate but significant increase in femoral oxygen extraction occurred after long-term therapy (ACE inhibitor: from 76% to 83%, p less than 0.05; placebo: from 75% to 74%, NS; p less than 0.01 between groups). We conclude that long-term ACE inhibition is clinically beneficial in that it improves blood flow to skeletal muscle during exercise over time. The long-term effects of ACE inhibition are, in part, probably related to peripheral (vascular) mechanisms, for example, by reversing the inability of peripheral vessels to dilate and by improving oxygen utilization.
Trends for coronary heart disease and stroke and their risk factors in Japan.
Authors: Shimamoto T , Komachi Y , Inada H , Doi M , Iso H , Sato S , Kitamura A , Iida M , Konishi M , Nakanishi N
Published: June 2011

Disease surveillance and population surveys of risk characteristics in a northeast rural community of Japan (1965 census population, 7,030) are combined in an attempt to relate morbidity and risk factor trends for coronary heart disease and stroke during the last 2 decades. Between 1964 and 1983, the incidence of coronary heart disease (i.e., combined myocardial infarction, angina pectoris, and sudden death) did not change significantly among men and women ages 40-69, and was lower than that for stroke. The incidence of all stroke declined about 60% for both men and women, ages 40-69, with a significant decrease in cerebral hemorrhage for both sexes and in cerebral infarction for men. Between 1963-1966 and 1980-1983, significant upward shifts occurred in the means and distributions of serum total cholesterol and serum total protein in every age and sex group, primarily during the 1st decade. Age-adjusted mean cholesterol levels rose 22 mg/dl to the 1980-1983 mean of 179 mg/dl in men ages 40-69. In women ages 40-69, the mean rose 29 mg/dl to 192 mg/dl. Among nutrients, animal fat intake doubled in men ages 40-59 from 4.5% of daily calories in 1969 to 9.6% in 1980-1983. Animal protein intake also increased, from 5.8% to 7.1%. Most of this increase occurred between 1969 and 1972-1975 and may be attributable to an increased intake of meat, eggs and dairy products. From 1963-1966 to 1980-1983, mean relative weight index rose significantly for all age-sex groups except men ages 50-69. Mean systolic and diastolic blood pressure levels declined for every age-sex group, with a 15-mm Hg age-adjusted decrease in systolic, 4-mm Hg decrease in diastolic pressure among men ages 40-69, and a 11-mm Hg systolic and 4-mm Hg diastolic decrease for women. Two cohorts of men and women ages 40-69 at baseline were followed for disease incidence: an early cohort (2,257 persons) followed from 1963-1966 to 1973 and a later cohort (2,711 persons) followed from 1972-1975 to 1983. In these cohorts, significant risk prediction for cerebral hemorrhage and infarction was obtained with blood pressure level and end organ effects in the electrocardiogram and fundus photographs. Serum cholesterol was inversely associated with cerebral hemorrhage in the early cohort but not in the later.(ABSTRACT TRUNCATED AT 400 WORDS)
Relation of baseline characteristics to suppression of ventricular arrhythmias during placebo and active antiarrhythmic therapy in patients after myocardial infarction.
Authors: Anderson J L , Hallstrom A P , Griffith L S , Ledingham R B , Reiffel J A , Yusuf S , Barker A H , Fowles R E , Young J B
Published: June 2011

In the Cardiac Arrhythmia Pilot Study (CAPS), patients early (6-60 days) after acute myocardial infarction (MI) with ventricular premature complexes (VPCs) of over 10 per hour were randomized to receive, unaware, therapy with one of four antiarrhythmic drugs (n = 402) or placebo (n = 100). Treatment success was defined as 70% or more decrease in VPC rate and 90% or more decrease in VPC runs. If the first active drug was ineffective, a second drug was given. If placebo was ineffective, a second placebo was given. To determine whether or not baseline clinical characteristics predict the response to antiarrhythmic therapy, 10 baseline variables were selected for investigation: age, prior MI, time from CAPS MI to randomization, ejection fraction, baseline VPC frequency, presence of runs (greater than or equal to 3 consecutive VPCs, greater than or equal to 100 beats/min), beta-blocker therapy, digitalis therapy, MI transmurality, and MI location. At the end of the first drug treatment, apparent treatment success in patients receiving placebo was associated on univariate analysis with absence of prior MI, with trends for younger age and Q wave MI, whereas in patients receiving active therapies, higher ejection fraction and younger age were associated with better suppression. In the encainide and flecainide treatments, where the greatest response was observed, absence of prior MI, higher ejection fraction, and younger age were associated with more successful treatment. In a multivariate analysis with these variables, ejection fraction and age remained significant for all active therapies, absence of prior MI and ejection fraction remained significant in the encainide and flecainide treatments, and absence of prior MI in the placebo treatment. Few variables except ejection fraction were associated with VPC suppression during the 1-year follow-up, and only lower ejection fraction and older age related to loss of long-term suppression. Thus, there are only a few independent baseline clinical variables (notably, ejection fraction) that substantially affect antiarrhythmic drug efficacy in suppressing VPCs in patients early after MI. Some variables, however, may be associated with spontaneous arrhythmia variability, leading to an apparent (placebo) response. These findings will be helpful in designing and interpreting treatment studies in patients after MI.
Effect of acute volume load on refractoriness and arrhythmia development in isolated, chronically infarcted canine hearts.
Authors: Calkins H , Maughan W L , Weisman H F , Sugiura S , Sagawa K , Levine J H
Published: June 2011

In normal isolated, perfused canine ventricles, increased ventricular volume leads to shortening of refractoriness. To test the hypothesis that myocardium within an infarction zone is more susceptible to volume-induced changes in refractoriness than is normal myocardium, we measured strength-interval curves at low and high end-diastolic volumes at control and infarcted sites in 14 isolated, blood perfused, canine hearts with chronic (greater than 25 days) infarctions. In addition, the effect of volume load on inducing ventricular arrhythmias was studied at one to six sites in 11 hearts. Differences in refractoriness and inducibility at low (22 +/- 5 ml) and high (48 +/- 6 ml) end-diastolic volumes were compared. At control sites, volume load reduced the absolute refractory period from 178 +/- 16.5 to 175 +/- 16.7 msec (p less than 0.05), but no significant change in the relative refractory period occurred. At infarcted sites, the change in refractoriness with volume load was greater, and the absolute refractory period decreased from 171.5 +/- 21 to 160.6 +/- 26.3 msec (p less than 0.01), and the relative refractory period decreased from 180.1 +/- 22.1 to 169.9 +/- 26 msec (p = 0.05). This differential effect of volume load on refractoriness led to an increased dispersion of overall refractoriness at high volume. Infarcted sites showing the largest changes in refractoriness were characterized by patchy scars extending at least to the midmyocardium, whereas sites located within areas of transmural scar, endocardial scar, or rare microfoci of fibrosis showed no increased sensitivity to volume load. Of eight hearts in which no tachyarrhythmias were inducible during programmed electrical stimulation at low volume, four had tachyarrhythmias induced at high volume. Sites of stimulation associated with a conversion from noninducible to inducible tachyarrhythmias showed a larger degree of shortening of refractoriness (change in absolute refractory period: 24.7 +/- 16.5 vs. 3.9 +/- 6.5 msec, p less than 0.05). These data indicate that volume loading may have electrophysiologic significance and that it may be of greater functional importance under pathologic conditions.
Effect of early and advanced atherosclerosis on vascular responses to serotonin, thromboxane A2, and ADP.
Authors: Lopez J A , Armstrong M L , Piegors D J , Heistad D D
Published: June 2011

In monkeys with early and advanced atherosclerosis, we examined responses to the three major vasoactive agonists that are released when platelets aggregate. Measurements were obtained in normal cynomolgus monkeys and in monkeys fed an atherogenic diet for 4 +/- 1, 9 +/- 1, and 19 +/- 1 months (mean +/- SEM). Morphometry of femoral and iliac arteries indicated that 4 months of atherogenic diet produced only slight intimal thickening, 9 months produced early lesions, and 19 months produced approximately 5-10 fold greater intimal proliferation than did 9 months of atherogenic diet. Serotonin and adenosine 5'-diphosphate (ADP), which are endothelium-dependent agonists, and adenosine and phenylephrine, which are endothelium-independent agonists, were injected intra-arterially into the perfused hind limb. Thromboxane A2 analogue U46619 also was studied. Vasoconstrictor responses to serotonin were potentiated, and vasodilator responses to ADP were impaired by early and advanced atherosclerosis. In contrast, vasoconstrictor responses to phenylephrine and vasodilator responses to adenosine were similar in all groups. Vasoconstrictor responses to U46619 were potentiated by advanced atherosclerosis. Thus, vascular responses to serotonin, ADP, and thromboxane A2 are altered by atherosclerosis in a direction that would favor vasoconstriction when platelets aggregate. Furthermore, because responses to endothelium-dependent agonists are altered, these data suggest that endothelium is dysfunctional in early atherosclerosis. These findings may explain, in part, the propensity for exaggerated vasoconstriction even in arteries with minimal atherosclerotic lesions.
Epinephrine-induced reversal of verapamil's electrophysiologic and therapeutic effects in patients with paroxysmal supraventricular tachycardia.
Authors: Morady F , Kou W H , Kadish A H , Toivonen L K , Kushner J A , Schmaltz S
Published: June 2011

The purpose of our study was to determine whether an infusion of epinephrine reverses the electrophysiologic effects of verapamil and whether reversal of verapamil's effects on the induction of paroxysmal supraventricular tachycardia (PSVT) by epinephrine during electropharmacologic testing is predictive of stress-related recurrences of PSVT during long-term treatment with verapamil. The infusion rates of epinephrine used in this study were 25 and 50 ng/kg/min, which previously have been demonstrated to result in plasma epinephrine concentrations in the range that occurs during a variety of stresses in humans. The subjects of this study were 17 patients with recurrent PSVT who underwent an electrophysiologic study in the control state and after at least 2 days of treatment with 240-480 mg/day verapamil. After assessing the response to verapamil, epinephrine was infused and testing was repeated. Verapamil significantly slowed atrioventricular conduction and prolonged refractoriness in the atrium and atrioventricular node. The effects of the two infusion rates of epinephrine were generally similar in magnitude and, therefore, the results were pooled. Epinephrine partially or completely reversed all of verapamil's electrophysiologic effects. Verapamil suppressed the induction of sustained PSVT in 15 patients. Epinephrine facilitated the induction of PSVT in seven of these 15 patients. All 15 patients were treated on a long-term basis with verapamil. The eight patients in whom epinephrine did not facilitate the induction of PSVT had no recurrences of PSVT during 9-18 months of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Evidence for cholinergically mediated vasodilation at the beginning of isometric exercise in humans.
Authors: Sanders J S , Mark A L , Ferguson D W
Published: June 2011

Vasodilation occurs in the nonexercising forearm at the beginning of isometric handgrip despite activation of sympathetic vasoconstrictor reflexes. The mechanism of this response remains unclear. In 33 normal humans, age 24 +/- 1 years (mean +/- SEM), we measured mean arterial pressure, heart rate, and forearm blood flow (plethysmography) in the nonexercising arm during sustained contralateral isometric handgrip at 30% maximal voluntary contraction. Sympathetic nerve activity to calf muscles (microneurography) was also measured in 15 subjects. Handgrip resulted in increases in arterial pressure from 86 +/- 2 to 97 +/- 3 mm Hg (p less than 0.05). Despite increases in nerve activity to calf muscles from 229 +/- 43 to 337 +/- 66 units (p less than 0.005), which would be expected to produce forearm vasoconstriction, forearm vascular resistance in the contralateral resting arm decreased from 20 +/- 3 to 18 +/- 2 units (p less than 0.05). To determine the mechanism of this vasodilatory influence, additional studies were performed with regional autonomic blockade with intra-arterial administration of atropine (0.8 mg, 10 subjects) or propranolol (2.0 mg, eight subjects) into the nonexercising forearm before contraction. Propranolol and vehicle had no effect on forearm vascular responses in the resting arm during SHG in the other arm. In contrast, atropine blocked the vasodilatory response in the resting arm during contraction (delta forearm vascular resistance during contraction, control = -2.1 +/- 0.6 units; postatropine = +0.2 +/- 0.9 units, p less than 0.05). Atropine did not attenuate the vasodilator response to isoproterenol or the vasoconstrictor response to norepinephrine. We conclude 1) a dissociation exists between sympathetic neural and forearm vascular responses to isometric exercise; 2) the vasodilatory response in the nonexercising forearm is not due to sympathetic withdrawal or beta 2-adrenergic-mediated vasodilation; and 3) this response is mediated primarily by cholinergic mechanisms. These studies provide the first direct evidence for active, cholinergically mediated vasodilation during exercise in humans.
Functional abnormalities in isolated left bundle branch block. The effect of interventricular asynchrony.
Authors: Grines C L , Bashore T M , Boudoulas H , Olson S , Shafer P , Wooley C F
Published: June 2011

Eighteen patients with isolated left bundle branch block (LBBB) were compared with 10 normal control subjects. Apexcardiograms, phonocardiograms, electrocardiograms, two-dimensional and dual M-mode echocardiograms, and radionuclide ventriculograms (RNV) were performed. There were no differences in the timing of right ventricular events between LBBB and normal subjects; however, striking delays in left ventricular systolic and diastolic events were apparent in the LBBB group. The delay was associated with shortening of left ventricular diastole and resultant increase in the ratio of right to left ventricular diastolic time in LBBB (1.2 +/- 0.08) compared with normal (1.0 +/- 0.06), p less than 0.0001. First heart sound (S1) amplitude, expressed as the ratio S1/S2, was decreased in LBBB compared with normal (0.67 +/- 0.2 compared with 1.34 +/- 0.25, p less than 0.01), in part due to wide separation of the valvular contributors to S1. The abnormal interventricular septal motion in LBBB corresponded to periods of asynchrony in contraction, ejection, end systole, and end diastole between right and left ventricles. Radionuclide ventriculograms revealed decreased regional ejection fraction of the septum in LBBB (40 +/- 16%) compared with 67 +/- 7% in normal subjects (p less than 0.001), while the apical and lateral regional ejection fractions were similar in the two groups. This loss of septal contribution resulted in a reduction in global ejection fraction in LBBB compared to normals (54 +/- 7% compared with 62 +/- 5%, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
Arterial hemodynamic indexes in Marfan's syndrome.
Authors: Yin F C , Brin K P , Ting C T , Pyeritz R E
Published: June 2011

Aortic impedance, wave reflection magnitude, and compliance were measured in patients with Marfan's syndrome during diagnostic cardiac catheterization. Impedance and wave reflections were calculated from standard Fourier series analysis of ascending aorta micromanometer pressure and electromagnetic flow records. Compliance was estimated by a method recently proposed that uses the area under the pressure-time curve assuming a two-element Windkessel model of the circulation. Measurements were made in the baseline state, during vasodilatation with nitroprusside, after beta-adrenergic receptor blockade with intravenous propranolol, and during vasodilatation after beta-blockade. Marfan's syndrome produces alterations from normal in some hemodynamic variables: during baseline conditions, the magnitude of wave reflection was higher than in normal patients. This was normalized by vasodilatation and further increased by beta-blockade. Despite the greatly dilated aortic root, the aortic characteristic impedance was in the normal range, suggesting increased aortic wall stiffness. The baseline total arterial compliance was greatly increased with nitroprusside and was reduced by beta-blockade. beta-Blockade did not decrease the maximum acceleration of blood into the ascending aorta. These are the first detailed measurements of hemodynamic indexes in this disease. The results suggest that acute beta-blockade is not necessarily beneficial in reducing hemodynamic loading on an already dilated aortic root.
Stress-shortening relations and myocardial blood flow in compensated and failing canine hearts with pressure-overload hypertrophy.
Authors: Gaasch W H , Zile M R , Hoshino P K , Apstein C S , Blaustein A S
Published: June 2011

Serial changes in left ventricular (LV) size and function during the adaptation to chronic pressure overload and the transition to pump failure were studied in 16 conscious dogs (aortic bands placed at 8 weeks of age). Echocardiographic data at baseline and at 3, 6, 9, and 12 months after banding revealed a progressive increase in LV mass in all dogs. In six dogs with LV pump failure, there was a progressive decline in circumferential fiber shortening (29 +/- 4% at 12 months); this was significantly less than that seen in five littermate controls (38 +/- 3%, p less than 0.05). The average LV to body weight ratio in this group was 9.8 +/- 2.7 g/kg. In 10 dogs without pump failure (compensated LVH group), shortening exceeded that seen in the controls (43 +/- 4%, p less than 0.05); the LV to body weight ratio was 7.7 +/- 1.0 g/kg. At 12 months (cardiac catheterization), the LV end-diastolic pressure was higher in the failure (25 +/- 15 mm Hg) than in the compensated group (8 +/- 5 mm Hg, p less than 0.05); mean systolic stress was also higher in the failure group (313 +/- 67 g/cm2) than in the compensated group (202 +/- 53 g/cm2, p less than 0.05). The transmural distribution of myocardial blood flow was measured (at 12 months) with the radioactive microsphere technique; flow data were then related to an index of demand (a stress-time index). There was preferential blood flow to the subendocardial layers in the control (endo/epi = 1.28) and compensated hearts (endo/epi = 1.10), but in the failure group there was a relative decrease in subendocardial flow (endo/epi = 0.92). However, the absolute values for subendocardial flow in the normal, compensated, and failure groups were 77 +/- 54, 125 +/- 48, and 113 +/- 64 ml/min/100 g; the stress-time indexes in the subendocardial shell were 38 +/- 11, 74 +/- 19, and 93 +/- 34 g sec.10(2)/cm2/min. Despite what appears to be a marginal balance between blood flow and the stress time index in the failure group, the myocardial high energy phosphates were not depleted and the inoptropic state was not depressed. In this model of LV hypertrophy, the observed differences in fiber shortening can be explained on the basis of the inverse afterload-shortening relation; pump failure was due to an inadequate LV hypertrophy with afterload excess.(ABSTRACT TRUNCATED AT 400 WORDS)
Tear or dissection after coronary angioplasty. Morphologic correlates of an ischemic complication.
Authors: Black A J , Namay D L , Niederman A L , Lembo N J , Roubin G S , Douglas J S , King S B
Published: June 2011

Intimal tear or dissection is an important descriptor of ischemic complications after coronary angioplasty, but only the minority of patients will develop an acute ischemic event. To identify additional factors that may predict the development of an ischemic event when arterial disruption occurs during otherwise uncomplicated angioplasty, the records of 1,346 patients prospectively identified as having tear or dissection without immediate vessel closure were examined. Ischemic complications, defined as ischemic chest pain, myocardial infarction, the need for coronary bypass surgery, or death, occurred in 120 patients (9%). Significant multivariate correlates of an ischemic complication were the presence of unstable angina or a totally occluded vessel before angioplasty and diameter stenosis of greater than 30% after angioplasty. Detailed geometric and videodensitometric analysis of the postdilatation angiograms of a subset of 96 consecutive patients was carried out. Ischemic complications occurred in 11 patients (11%). Multivariate analysis revealed that the independent correlates of complications, in decreasing order of importance, were the length of the tear or dissection (p = 0.001), diameter stenosis after angioplasty (p = 0.001), cross-sectional area after dilatation measured by videodensitometric methods (p = 0.013), and the presence of extraluminal contrast (p = 0.044). When tear or dissection occurs during otherwise uncomplicated coronary angioplasty, patients at risk of developing delayed ischemic complications can be identified and may benefit from measures designed to minimize this risk. By controlling for the geometric or mechanical factors that result in tear or dissection, it has been possible to identify factors not previously thought associated with ischemic complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Stereoselective disposition and pharmacologic activity of propafenone enantiomers.
Authors: Kroemer H K , Funck-Brentano C , Silberstein D J , Wood A J , Eichelbaum M , Woosley R L , Roden D M
Published: June 2011

Propafenone is an antiarrhythmic drug that produces a variable degree of beta-blockade in humans and is administered as a racemate. To examine the relative contribution of the individual enantiomers to pharmacologic effects seen during treatment with propafenone, we assessed the steady-state plasma concentrations of (+)-S-propafenone and (-)-R-propafenone in seven patients who were on long-term oral therapy, and we evaluated the electrophysiologic and beta-blocking properties of both enantiomers in vitro. The metabolism of propafenone is known to be polymorphic and to cosegregate with that of debrisoquine-4-hydroxylation. Among five patients with the extensive metabolizer phenotype (EM), the ratio of the area under the plasma concentration-time curve of (+)-S-propafenone to (-)-R-propafenone was 1.73 +/- 0.15 (mean +/- SD). In the other two patients, who had the poor metabolizer phenotype (PM), the concentrations of both enantiomers were elevated but the S/R ratios were similar to those seen in patients with EM. In canine cardiac Purkinje fibers, both enantiomers produced similar frequency-dependent depression of maximum upstroke of phase 0. In contrast, the affinity of the human lymphocyte beta 2-adrenoceptor was approximately 100-fold greater for (+)-S-propafenone (Ki, 7.2 +/- 2.9 nM) than for the (-)-R-enantiomer (Ki, 571 +/- 141 nM). We conclude that during long-term oral therapy, propafenone undergoes stereoselective disposition in patients with either EM or PM. beta-Blockade during propafenone therapy is likely related to accumulation of (+)-S-propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)
Transcatheter closure of atrial septal defects. Experimental studies.
Authors: Lock J E , Rome J J , Davis R , Van Praagh S , Perry S B , Van Praagh R , Keane J F
Published: June 2011

Recent experience with the spring-loaded patent ductus arteriosus (PDA) occluder has demonstrated several advantages of this device in the closure of intracardiac defects compared with previously described techniques. Pathologic and animal model studies were performed to identify which atrial septal defects (ASDs) might be suitable for device closure and to test a new septal closure double umbrella. Fifty specimens from the Cardiac Registry with unrepaired ASD secunda (2 degrees) were analyzed. Mean ASD size was 8 x 10 mm (range, 3 x 4 to 30 x 30 mm); 80% (n = 40) of ASDs were judged closable with the new device. ASD closure was attempted in four lambs with the Rashkind (hooked single umbrella) ASD occluder. One of four umbrellas was correctly positioned; no ASDs were closed. A new double-hinged ("clamshell") umbrella device was designed: eight ASD closures were attempted with this device (defects ranged from 8 to 20 mm in diameter). Six of eight umbrellas were correctly positioned; four of four animals observed more than 1 day appeared to have complete closure on postmortem examination with endothelialization of the device. We conclude that 1) most ASD 2 degrees are far enough from vital structures to permit closure, 2) initial placement of hooked umbrellas is often incorrect and cannot be altered, 3) clamshell double umbrellas were successfully placed in six of eight attempts, and 4) endothelialization of closed ASDs appears complete within weeks of implantation. These preliminary studies appear promising and support testing the clamshell ASD device in clinical trials.
Effects of magnesium on the tone of isolated human coronary arteries. Comparison with diltiazem and nitroglycerin.
Authors: Kimura T , Yasue H , Sakaino N , Rokutanda M , Jougasaki M , Araki H
Published: June 2011

To study the effects of magnesium (Mg2+) on human coronary arteries and to compare those effects with those of diltiazem and nitroglycerin, we measured the tension of ring segments from isolated human coronary arteries obtained at autopsy within 5 hours after death. Precontracted segments with 3 x 10(-6) M prostaglandin F2 alpha were studied after adding cumulative concentrations of these agents (1.0-8.0 mM, 10(-9)-10(-5) M, and 10(-10)-10(-6) M, respectively). Mg2+ significantly inhibited the tonic contraction compared with the time-matched controls at 1.0 and 2.0 mM (48.7 +/- 5.6% vs. 88.6 +/- 2.2%, p less than 0.01, 36.2 +/- 6.1% vs. 78.9 +/- 3.0%, p less than 0.01, respectively). 1.0 and 2.0 mM Mg2+ did not suppress, but actually increased, the amplitude of periodic contraction, but 8.0 mM Mg2+ reduced the amplitude compared with the controls (6.6 +/- 5.2% vs. 73.3 +/- 10.7%, p less than 0.01). Diltiazem at a concentration of 10(-5) M moderately inhibited the tonic contraction, and reduced the amplitude of periodic contraction almost completely. Nitroglycerin reduced the tonic contraction almost completely at a concentration of 10(-6) M but did not reduce the amplitude of periodic contraction at any concentration. We conclude that 1.0 and 2.0 mM Mg2+ inhibits the tonic contraction and that 8.0 mM Mg2+ inhibits the periodic as well as the tonic contraction of isolated human coronary arteries. Diltiazem inhibits the periodic contraction, whereas nitroglycerin suppresses tonic contraction without affecting the periodic contraction.
Distribution of beta-adrenergic receptors in failing human myocardium. Implications for mechanisms of down-regulation.
Authors: Murphree S S , Saffitz J E
Published: June 2011

The density of beta-adrenergic receptors is reduced in crude membranes prepared from failing human myocardium. We used quantitative autoradiography of radioligand binding sites in intact tissue slices to determine whether the total tissue content of receptors is reduced and to characterize the transmural distribution of receptors in cardiac myocytes and the coronary vasculature in hearts obtained from nine cardiac transplant patients with severe congestive failure. Binding of [125Iodo]cyanopindolol to transmural slices of human myocardium was rapid, saturable, stereoselective, and displaceable by agonists and antagonists with an appropriate rank order of potency. Binding isotherms in four normal and nine failing ventricles showed a significant reduction in the total tissue content of beta-receptors in failing myocardium (38.3 +/- 2.0 fmol/mg protein) compared with normal tissue (52.4 +/- 1.7 fmol/mg protein, p = 0.038). In the normal ventricles, the greatest receptor density was observed autoradiographically in myocytic regions of the subendocardium. Receptor density of the coronary arterioles was approximately 70% of that in adjacent myocytic regions. The density of binding sites in both myocytic regions and arterioles was diminished in all regions of the failing ventricles, but down-regulation was due primarily to a selective reduction of beta-receptors of subendocardial myocytes (63 +/- 5% of subepicardial receptor density vs. 115 +/- 6% in controls, p less than 0.0001). These observations indicate that down-regulation occurs nonuniformly in the transmural distribution and thus is likely not related simply to elevated circulating catecholamine levels.
Left ventricular contractility and function in Kawasaki syndrome. Effect of intravenous gamma-globulin.
Authors: Newburger J W , Sanders S P , Burns J C , Parness I A , Beiser A S , Colan S D
Published: June 2011

To investigate the effect of Kawasaki syndrome on myocardial function, as well as the influence of high-dose intravenous gamma-globulin therapy on resolution of functional abnormalities, we studied 98 patients with Kawasaki syndrome during five time intervals from onset of illness: 1) 10 days or less, 2) 11-31 days, 3) 1-3 months, 4) 3-12 months, and 5) 1-3 years. Normal controls included 48 children under age 8 years, without known cardiovascular disease. Using two-dimensional directed M-mode echocardiograms, we obtained chamber dimensions, fractional shortening, rate-corrected velocity of shortening (Vcfc) adjusted for end-systolic wall stress, and early diastolic function parameters that included adjusted peak rates of left ventricular dimension change, wall thinning, and their respective timing. Left ventricular systolic and diastolic dimensions were larger (both p less than 0.01) in patients than in normal subjects in period 1. Stress-adjusted Vcfc was much lower in patients in the 3 months after disease onset; by period 5, contractility was comparable in patients and normal subjects. Adjusted indexes of early diastolic function did not differ significantly between patients and normal subjects. To investigate the effect of gamma-globulin, we analyzed data on 47 patients prospectively randomized to therapy with aspirin alone (n = 19, 40%) or to aspirin plus gamma-globulin, 400 mg/kg/day for 4 consecutive days (n = 28, 60%). In period 1, before treatment, the two groups had mean fractional shortening and stress-adjusted Vcfc comparable to each other but much lower than those of normal subjects (p less than or equal to 0.001). Patients treated with aspirin alone continued to have diminished fractional shortening and Vcfc compared with normal subjects in periods 2, 3, and 4 (all p less than or equal to 0.05). In contrast, fractional shortening and Vcfc in gamma-globulin-treated patients in these periods were comparable to those of normal subjects. By period 5, no difference was detected in systolic function or contractility between either treatment group and normal subjects. We conclude that early abnormalities of left ventricular contractility and myocardial function, as assessed by echocardiography, generally resolve by 1-3 years after disease onset and that recovery is accelerated by administration of IVGG in the acute phase.
Myocardial inotropic responses to aggregating platelets and modulation by the endocardium.
Authors: Shah A M , Meulemans A L , Brutsaert D L
Published: June 2011

Ventricular mural thrombi complicate many cardiac diseases. The endocardial endothelium can modulate the mechanical performance of subjacent myocardium and mediate responses to certain physiopharmacologic agents. We studied the effects of aggregating platelets on the contractile performance of isolated cardiac muscle. The role of the endocardium was investigated by selectively damaging it by very brief (1 second) exposure to 1% Triton X-100 in some muscle preparations before experiments. Cat papillary muscles (n = 54) were attached to an electromagnetic length-tension transducer in organ baths containing Krebs-Ringer solution (1.25 mM Ca2+, 35 degrees C), and stimulated electrically at 0.2 Hz. Homologous washed platelets (final concentration 3 x 10(11)/l) aggregated spontaneously on addition to baths. Mechanical performance increased significantly more in muscles with damaged endocardium than in intact muscles (p less than 0.05); total peak isometric twitch tension increased by 31.8 +/- 7.8% (with damaged endocardium) and 11.8 +/- 2.6% (with intact endocardium), and peak isotonic twitch shortening increased by 36.7 +/- 7.8% (with damaged endocardium) and 9.6 +/- 2.0% (with intact endocardium). Increases in maximum velocity of unloaded shortening were similar in both muscle groups. Time to half isometric twitch tension decline decreased in intact muscles (3.6 +/- 1.0%) but increased in Triton-treated muscles (2.5 +/- 1.3%, p = 0.003 for difference between groups). The inotropic response to platelets in muscles with intact endocardium was unaltered by pretreatment of muscles with indomethacin (10 microM) or by stimulation of platelet aggregation with thrombin (0.1 unit/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Vasopressin and the mature coronary collateral circulation.
Authors: Peters K G , Marcus M L , Harrison D G
Published: June 2011

In isolated vascular rings, we have shown that mature coronary collateral vessels are highly responsive to the vasoconstrictor effects of vasopressin. The purpose of the present study was to determine the effect of concentrations of vasopressin encountered in pathophysiologic states on the collateral circulation in vivo. We studied eight open-chest anesthetized dogs with mature coronary collateral vessels 3-6 months after placement of an ameroid constrictor on the left circumflex coronary artery. The left anterior descending coronary artery was perfused at constant pressure, and peripheral coronary pressure was monitored continuously throughout each experiment. At baseline and during intracoronary infusion of vasopressin, which resulted in concentrations ranging from 8 +/- 3 to 1,340 +/- 327 microM/ml, we measured regional myocardial perfusion with radiolabeled microspheres. At baseline, regional myocardial perfusion to the collateral-dependent myocardium and to the normally perfused myocardium was similar; however, during vasopressin infusion, collateral-dependent zone flow decreased by 49 +/- 14% whereas normal zone flow decreased by only 9 +/- 9% (p less than 0.0005, normal zone perfusion vs. collateral perfusion). Vasopressin increased transcollateral resistance by 242 +/- 95% above baseline but produced a more modest increase in normal zone resistance (15 +/- 10%). The subendocardial to subepicardial perfusion ratio increased by 28 +/- 12% in the normal zone in response to vasopressin but decreased by 18 +/- 11% in the collateral-dependent zone. These data show that mature coronary collateral vessels are responsive to the vasoconstrictor effects of vasopressin at concentrations encountered in various pathophysiologic states.(ABSTRACT TRUNCATED AT 250 WORDS)
Organ blood flow and somatosensory-evoked potentials during and after cardiopulmonary resuscitation with epinephrine or phenylephrine.
Authors: Schleien C L , Koehler R C , Gervais H , Berkowitz I D , Dean J M , Michael J R , Rogers M C , Traystman R J
Published: June 2011

Pure alpha-adrenergic agonists, such as phenylephrine, and mixed alpha- and beta-adrenergic agonists, such as epinephrine, raise perfusion pressure for heart and brain during cardiopulmonary resuscitation (CPR). However, with the high doses used during CPR, these drugs may directly affect vascular smooth muscle and metabolism in brain and heart. We determined whether at equivalent perfusion pressure, continuous infusion of phenylephrine (20 micrograms/kg/min) or epinephrine (4 micrograms/kg/min) leads to equal organ blood flow, cerebral O2 uptake, and cerebral electrophysiologic function. During 20 minutes of CPR initiated immediately upon ventricular fibrillation in anesthetized dogs, left ventricular blood flow was similar with epinephrine (45 +/- 9 ml/min/100 g) or phenylephrine (47 +/- 8 ml/min/100 g) infusion. The ratio of subendocardial to subepicardial blood flow fell equivalently during CPR with either epinephrine (1.23 +/- 0.06 to 0.70 +/- 0.05) or phenylephrine (1.32 +/- 0.07 to 0.77 +/- 0.05) administration. At similar levels of cerebral perfusion pressure (44 +/- 3 mm Hg), similar levels of cerebral blood flow were measured in both groups (27 +/- 3 ml/min/100 g). Cerebral O2 uptake was maintained at prearrest levels in both groups. Somatosensory-evoked potential amplitude was modestly reduced during CPR, but it promptly recovered after defibrillation. During CPR and at 2 hours after resuscitation, there were no differences between drug groups in the level of regional cerebral or coronary blood flow, cerebral O2 uptake, or evoked potentials. Therefore, with minimal delay in the onset of CPR and with equipotent pressor doses of phenylephrine and epinephrine, we found no evidence that one agent provides superior coronary or cerebral blood flow or that epinephrine by virtue of its beta-adrenergic properties adversely stimulates cerebral metabolism at a critical time that would impair brain electrophysiologic function. Moreover, epinephrine did not preferentially impair subendocardial blood flow as might be expected if it enhanced the strength of fibrillatory contractions.
Exercise training after experimental myocardial infarction increases the ventricular fibrillation threshold before and after the onset of reinfarction in the isolated rat heart.
Authors: Posel D , Noakes T , Kantor P , Lambert M , Opie L H
Published: June 2011

Previous work has shown that exercise training increases the ventricular fibrillation threshold of the isolated perfused rat heart. The aim of our study was to determine whether exercise training that begins after myocardial infarction can similarly increase the ventricular fibrillation threshold. Rats that had suffered an experimental myocardial infarction were subject to a running training program. Thereafter, the ventricular fibrillation threshold was measured before and after the onset of acute reinfarction induced by a second coronary artery ligation. Ventricular fibrillation thresholds were significantly elevated in trained rats during normoxia (13.7 +/- 2.2 vs. 4.7 +/- 0.8 mA, p less than 0.01) and during acute ischemia (6.8 +/- 1.6 vs. 3.0 +/- 0.7 mA, p less than 0.02). The myocardial cyclic AMP level was lower in the nonischemic zone of the trained hearts (0.21 +/- 0.01 vs. 0.28 +/- 0.01 nmol/g, p less than 0.05), which also had lower cyclic AMP levels after epinephrine challenge (0.50 +/- 0.05 vs. 0.73 +/- 0.09 nmol/g, p less than 0.01; 1.41 +/- 0.11 vs. 1.85 +/- 0.09 nmol/g, p less than 0.02 after epinephrine 10(-7) M and 5 x 10(-6) M injection, trained vs. untrained). Both propranolol 10(-6) M and epinephrine 5 x 10(-7) M attenuated the difference in ventricular fibrillation thresholds before and after second coronary artery ligation and eliminated any difference in cyclic AMP content of both the nonischemic and ischemic myocardial tissue.(ABSTRACT TRUNCATED AT 250 WORDS)