bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing pericardial effusion in cardiac transplant recipients.
Authors: Valantine H A , Hunt S A , Gibbons R , Billingham M E , Stinson E B , Popp R L
Published: June 2011

Although pericardial effusion after cardiac surgery is frequent and usually benign, its etiology and prognosis after cardiac transplantation are unknown. During 1 year (1985-1986), 12 of our current transplant population (total, 189) developed moderate or large pericardial effusions confirmed by two-dimensional echocardiography. These effusions occurred within 1 month of transplantation in 10 patients and at 3 months and 4.5 years in the other two. Pericardiocentesis was performed because of clinical evidence of increasing effusions in eight patients, with demonstrable hemodynamic compromise secondary to tamponade in five. Pericardial fluid was sterile in all but one. Endomyocardial biopsy at the time of increasing effusion revealed moderate acute rejection in five patients, mild rejection in three, and no rejection in four. All three patients with mild rejection had moderate acute rejection on subsequent biopsy performed within 7 days. In two of the four with no rejection, repeat biopsy within 5 days showed moderate acute rejection; in a third, moderate rejection was present on biopsy performed 14 days later. Legionella dumoffii was isolated from the pericardial fluid of the fourth patient, whose subsequent biopsies never showed rejection. Three of the 12 patients developed progressive ventricular dysfunction sufficiently severe to require retransplantation. One patient died suddenly 12 months after transplantation, and autopsy examination revealed severe coronary artery disease. Two died of sepsis within 3 months of transplantation. Intense inflammatory infiltrates and thickening of the pericardium and epicardium were characteristically present in explanted and autopsy hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of thrombin inhibition on the development of acute platelet-thrombus deposition during angioplasty in pigs. Heparin versus recombinant hirudin, a specific thrombin inhibitor.
Authors: Heras M , Chesebro J H , Penny W J , Bailey K R , Badimon L , Fuster V
Published: June 2011

The effect of recombinant hirudin and the dosage of heparin on acute platelet-thrombus deposition during carotid angioplasty in anesthetized pigs was prospectively assessed. Fifty-five animals (mean weight, 33.9 kg) were randomized to one of six heparin dosages: heparin boluses of 35, 50, 100, 150, 200, or 250 units/kg followed by a continuous infusion of 35, 50, 100, 150, 200, or 250 units/kg/hr, respectively. Another five pigs received a bolus of 1 mg/kg hirudin (recombinant desulphatohirudin), a specific thrombin inhibitor, followed by an infusion of 1 mg/kg/hr. Bilateral carotid angioplasty was performed in all pigs 20 minutes after starting the infusion; they were sacrificed 57 +/- 12 minutes after the procedure. Deep medial arterial injury was present in approximately 75% of the dilated segments, and subendothelial injury in the remaining 25%. Mean log of number of platelets and molecules of fibrinogen per centimeter squared of deep injury in segments from all the animals treated with heparin were 4.74 +/- 1.03 and 5.02 +/- 0.64, respectively. A regression analysis showed an inverse correlation of the log of platelet deposition with the heparin group (r = -0.56, p = 0.0001) with administered total units of heparin (r = -0.55, p = 0.0003) and with mean plasma heparin concentration (r = -0.55, p = 0.0004) in deeply injured arteries. Similar inverse relations were obtained for fibrinogen. In contrast, the deposition of platelets and fibrinogen in subendothelial injury was very low and independent of the heparin administered.(ABSTRACT TRUNCATED AT 250 WORDS)
Quinidine-induced action potential prolongation, early afterdepolarizations, and triggered activity in canine Purkinje fibers. Effects of stimulation rate, potassium, and magnesium.
Authors: Davidenko J M , Cohen L , Goodrow R , Antzelevitch C
Published: June 2011

Early afterdepolarization (EAD)-induced triggered activity is thought to contribute to the cardiac arrhythmogenic effects of several class I antiarrhythmic agents. The combination of quinidine therapy, bradycardia, and hypokalemia is known to predispose to torsade de pointes, which is a form of atypical polymorphous ventricular tachycardia commonly associated with long QT intervals. Recent clinical reports have shown suppression of quinidine-induced torsade de pointes with intravenous administration of magnesium sulfate. To provide further understanding of these relations, we used standard microelectrode techniques to examine the time course of quinidine-induced action potential prolongation, EAD, and triggered activity development and the dependence of these changes on [K+]0, [Mg2+]0, and stimulation frequency in isolated Purkinje fiber preparations exposed to low concentrations of the drug. At slow stimulation rates, the quinidine-induced increase of action potential duration was slow to develop and failed to reach a steady state after 3 hours of exposure to the drug. EAD and EAD-induced triggered activity generally became apparent 70-90 minutes after adding the drug. Quinidine produced triggered activity in 10 of 22 preparations superfused with Tyrode's solution containing normal [K+]0 (3.5-4.0 mM) and in six other preparations when [K+]0 was reduced. In the presence of normal [K+]0, two types of EAD and triggered activity were distinguished. In four of 10 preparations, this activity arose from phase 2 of the action potential; in eight of 10, it was associated with phase 3; and in two experiments, both types were present in the same preparation. The incidence of both forms of triggered responses depended greatly on the rate of stimulation. Triggered activity arising from phase 3 was always manifest at rates considerably slower than those giving rise to phase 2 activity. Both forms of triggered activity were sensitive to changes in the extracellular concentration of potassium and magnesium. Lower-than-normal levels of these electrolytes facilitated the manifestation of triggered activity, whereas elevated levels suppressed or caused a shift in the frequency-dependence of the activity. Phase 2, but not phase 3, EADs were abolished in response to increased [Mg2+]0. The data show a clear congruity between the conditions that predispose to torsade de pointes in the clinic and the conditions under which quinidine may induce triggered activity and marked action potential prolongation in isolated Purkinje fibers.(ABSTRACT TRUNCATED AT 400 WORDS)
Circadian variation and triggers of onset of acute cardiovascular disease.
Authors: Muller J E , Tofler G H , Stone P H
Published: June 2011

Information obtained during the past decade suggests the need to reexamine the possibility that the onset of myocardial infarction and sudden cardiac death is frequently triggered by daily activities. The importance of physical or mental stress in triggering onset of coronary thrombosis is supported by the findings that 1) the frequencies of onset of myocardial infarction, sudden cardiac death, and stroke show marked circadian variations with parallel increases in the period from 6:00 AM to noon, 2) transient myocardial ischemia shows a similar morning increase, and episodes are often preceded by mental or physical triggers, 3) a ruptured atherosclerotic plaque, often nonobstructive by itself, lies at the base of most coronary thrombi, 4) a number of physiologic processes that could lead to plaque rupture, a hypercoagulable state or coronary vasoconstriction, are accentuated in the morning, and 5) aspirin and beta-adrenergic blocking agents, which block certain of these processes, have been shown to prevent disease onset. The hypothesis is presented that occlusive coronary thrombosis occurs when 1) an atherosclerotic plaque becomes vulnerable to rupture, 2) mental or physical stress causes the plaque to rupture, and 3) increases in coagulability or vasoconstriction, triggered by daily activities, contribute to complete occlusion of the coronary artery lumen. Recognition of the circadian variation--and the possibility of frequent triggering--of onset of acute disease suggests the need for pharmacologic protection of patients during vulnerable periods, and provides clues to mechanism, the investigations of which may lead to improved methods of prevention.
Tissue acidosis: role in sustained arteriolar dilatation distal to a coronary stenosis.
Authors: Gewirtz H , Weeks G , Nathanson M , Sharaf B , Fedele F , Most A S
Published: June 2011

This study tested the hypothesis that myocardial tissue acidosis is responsible for maintenance of reduced arteriolar tone distal to a severe coronary arterial stenosis. Domestic swine (n = 10) were instrumented with a coronary arterial stenosis that reduced vessel diameter 80%. Measurements of hemodynamic indexes were made 1) before stenosis, 2) at 5, 20, and 60 minutes after stenosis placement, and 3) after each of three, 20-minute NaOH infusions (0.05 M, 0.1 M, and 0.5 M) distal to the stenosis (group 1). Intracellular pH at the end of 30 minutes of 0.5 M NaOH infusion distal to the stenosis was measured in a second group (n = 6) of swine (group 2). After stenosis placement in group 1, endocardial blood flow declined significantly, and evidence of regional acidosis (increased coronary venous Pco2 and decreased coronary venous pH) and ischemia (lactate production) developed. One hour later, evidence of acidosis persisted, though to a lesser extent. Myocardial oxygen and lactate metabolism exhibited similar patterns. Infusion of 0.5 M NaOH (0.38 ml/min) reduced (p less than 0.01) distal zone epicardial blood flow but did not change endocardial flow. Regional myocardial oxygen extraction (75 +/- 8%, mean +/- SD) and consumption (8.2 +/- 2.3 ml/min/100 g) also declined significantly (p less than 0.01) in response to 0.5 M NaOH infusion compared with 60 minutes after stenosis (86 +/- 4 and 12.4 +/- 2.8 ml/min/100 g respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of verapamil and propranolol on changes in extracellular K+, pH, and local activation during graded coronary flow in the pig.
Authors: Watanabe I , Johnson T A , Engle C L , Graebner C , Jenkins M G , Gettes L S
Published: June 2011

The beta-adrenergic and calcium channel blocking agents are known to reduce heart rate and alter myocardial contractility. More recent evidence suggests that both agents affect the metabolic consequences of ischemia, independent of their effects on heart rate and contractility. We used a low-flow model of ischemia in swine with heart rate held constant by atrial pacing. Blood was shunted from the carotid artery to the left anterior descending coronary artery through a controlled-flow roller pump to assess the threshold flow for the rise in extracellular potassium ([K+]e) and fall in extracellular pH (pHe) associated with ischemia during control situations and after the administration of either propranolol or verapamil. We also measured the changes in activation delay and contractility associated with graded flow reductions in the presence and absence of these drugs. We found that when heart rate is held constant, 1) verapamil shifts the threshold flow for [K+]e and pHe to lower levels, but propranolol does not; 2) verapamil lessens activation delay, while propranolol aggravates the delay; and 3) verapamil reduces afterload and selectively depresses contractility in the reperfused ischemic zone. We conclude that the calcium channel blockers and the beta-adrenergic-blocking agents have different effects and possibly different modes of action and should not be considered interchangeable when evaluating therapeutic options for patients with ischemic heart disease.
Amplification of flecainide-induced ventricular conduction slowing by exercise. A potentially significant clinical consequence of use-dependent sodium channel blockade.
Authors: Ranger S , Talajic M , Lemery R , Roy D , Nattel S
Published: June 2011

Proarrhythmic effects of flecainide acetate have been reported during exercise, but the mechanism for the arrhythmogenic interaction between flecainide and exercise is unknown. We hypothesized that the sinus tachycardia of exercise may enhance flecainide-induced conduction slowing by increasing use-dependent sodium channel blockade, thereby facilitating the occurrence of ventricular reentry. To evaluate the modulation of flecainide's effects by exercise, we studied 19 patients who were receiving therapeutic doses of flecainide for the treatment of cardiac arrhythmias. Sixteen patients underwent treadmill exercise testing by a modified Bruce protocol. During exercise, QRS duration increased progressively from 94 +/- 22 msec (mean +/- SD) at rest to 116 +/- 25 msec (p less than 0.001) at a mean heart rate increase of 84 +/- 32 beats/min. The patient with the greatest QRS increase developed a monomorphic ventricular tachycardia at peak exercise. At rest, the QRS duration after treatment with flecainide increased 12.1 +/- 10.0% compared with the pretreatment value, and with exercise, the QRS duration increased by a further 28.1 +/- 17.0% compared with the predrug value. We found that the best predictor of further exercise-induced QRS slowing was the change in QRS duration produced by flecainide at rest (r = 0.76, p = 0.001). In an age- and disease-matched control group, the QRS duration did not change during exercise that caused a similar heart rate increase.(ABSTRACT TRUNCATED AT 250 WORDS)
Verapamil prevents silent myocardial perfusion abnormalities during exercise in asymptomatic patients with hypertrophic cardiomyopathy.
Authors: Udelson J E , Bonow R O , O'Gara P T , Maron B J , Van Lingen A , Bacharach S L , Epstein S E
Published: June 2011

Recent studies indicate that reversible 201Tl perfusion defects, compatible with silent myocardial ischemia, commonly develop during exercise in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy (HCM). To determine whether this represents a dynamic process that may be modified favorably by medical therapy, we studied 29 asymptomatic or minimally symptomatic patients with HCM, aged 12-55 years (mean, 28), with exercise 201Tl emission computed tomography under control conditions and again after 1 week of oral verapamil (mean dosage, 453 mg/day). Treadmill time increased slightly during verapamil (21.0 +/- 3.6 to 21.9 +/- 2.7 minutes, p less than 0.005), but peak heart rate-blood pressure product was unchanged (26.3 +/- 6.0 X 10(3) compared with 25.0 +/- 6.4 X 10(3). Two midventricular short-axis images per study were divided into five regions each, and each of these 10 regions was then analyzed on a 0-2 scale by three observers blinded with regard to the patients' therapy. Average regional scores of 1.5 or less were considered to represent perfusion defects, and a change in regional score of 0.5 or more was considered to constitute a significant change. During control studies, 15 patients (52%) developed perfusion defects with exercise (average, 3.7 regions per patient). In 14 of these patients, all perfusion defects completely reversed after 3 hours of rest; one patient had fixed defects. After administration of verapamil, exercise perfusion scores improved in 10 of the 14 patients (71%) with reversible defects; there was overall improvement in 34 of 50 (68%) regions with initially reversible perfusion defects.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical merit of endomyocardial biopsy.
Authors: Mason J W , O'Connell J B
Published: June 2011

At this time, endomyocardial biopsy has proven validity as a diagnostic method in few circumstances. However, it is overused. In the near term, the extent of its use should be modified by knowledge of its therapeutic relevance in patients with myocarditis. In the long term, numerous new techniques for studying pathophysiology at the subcellular and molecular levels will demand a central role for endomyocardial biopsy in the diagnosis, treatment and fundamental understanding of myocardial diseases. We believe that endomyocardial biopsy will serve as an indispensible link between basic scientists and clinicians in the effort to describe disease mechanisms.
Asymptomatic left main coronary artery disease in the Coronary Artery Surgery Study (CASS) registry.
Authors: Taylor H A , Deumite N J , Chaitman B R , Davis K B , Killip T , Rogers W J
Published: June 2011

Left main coronary artery disease (i.e., greater than or equal to 50% stenosis) was found in 1,477 of 20,137 patients in the Coronary Artery Surgery Study (CAS) registry. Of these patients, 53 (3.6%) were asymptomatic. Asymptomatic and symptomatic patients were similar in regard to 1) severity of left main coronary artery stenosis (67% vs. 70%), 2) extent of proximal coronary artery disease (no differences in number of or severity of proximal stenoses), 3) left ventricular end-diastolic pressure (13 mm Hg vs. 14 mm Hg), 4) left ventricular wall motion score 9.1 vs. 8.7), and 5) number of coronary artery segments with greater than 70% stenosis (4.4 vs. 4.8). Among the asymptomatic patients, 47% received medical and 49% received surgical treatment. In the symptomatic group, 20% received medical and 78% received surgical therapy. The survival rate 5 years after surgery for treatment of left main coronary artery stenosis was 84% for the symptomatic patients and 88% for the asymptomatic patients (p = NS). Medical management of left main coronary artery disease produced a 5-year survival rate of 57% for asymptomatic patients and 58% for symptomatic patients. Within the asymptomatic subgroup, 88% of those surgically treated survived 5 years, whereas only 57% of those medically treated survived 5 years (p = 0.02). Thus, for CASS patients with left main coronary artery disease, the percentage of those that were asymptomatic is low (3.6%); asymptomatic and symptomatic patients with left main coronary artery disease had no significant difference in severity of left main coronary artery stenosis, extent of overall coronary artery disease, or left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)
Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease.
Authors: Malinow M R , Kang S S , Taylor L M , Wong P W , Coull B , Inahara T , Mukerjee D , Sexton G , Upson B
Published: June 2011

A micromethod adapted for automated determinations was used to measure basal plasma levels of homocyst(e)ine [H(e)]. These levels included the sum of free and bound forms of homocysteine, its disulfide oxidation product, homocystine, and the homocysteine-cysteine-mixed disulfide. Two groups of subjects were studied: apparently healthy individuals (n = 103) and patients with peripheral arterial occlusive disease (PAOD) (n = 47). Because age in PAOD patients was higher than in control subjects, the control subjects were subdivided into younger and older groups (aged 60 years or less and more than 60 years, respectively). The H(e) levels in the younger groups were 11.18 +/- 3.58 (mean +/- SD, expressed as homocysteine) and 8.58 +/- 2.82 nmol/ml in men and women, respectively; in the older groups, the levels were 10.74 +/- 2.16 and 9.04 +/- 2.16 nmol/ml in men and women, respectively. There was a positive correlation of H(e) levels with age in the younger control women (r = 0.373; p less than 0.02); no significant correlations were present in the other three control groups. Levels of H(e) in PAOD patients (15.44 +/- 5.76 and 17.04 +/- 8.26 nmol/ml in men and women, respectively) were significantly higher than those indicated above in the older controls. Next, the PAOD patients were assigned to two subgroups: 1) those with normal levels of H(e) (within two standard deviations of the mean of the control values) and 2) those with elevated levels of H(e). Age, cholesterolemia, and the prevalence of smoking and diabetes were similar in both subgroups. These results suggest that elevated plasma H(e) is an independent risk factor for arterial occlusive disease.
Percutaneous balloon valvuloplasty in patients with severe aortic stenosis and low ejection fraction. Immediate results and 1-year follow-up.
Authors: Berland J , Cribier A , Savin T , Lefebvre E , Koning R , Letac B
Published: June 2011

The efficacy, morbidity, and 1-year follow-up of balloon aortic valvuloplasty in patients with low ejection fraction (less than 40%) were studied on a consecutive series of 55 patients (mean age, 77 years) treated from September 1985 to February 1987. Because of their age (20 patients greater than 80 years old), poor left ventricular function, and associated diseases, 45 patients were definitely not surgical candidates. Balloon dilatation with 15-23-mm diameter balloon catheters decreased the transvalvular gradient from 66 +/- 24 to 28 +/- 14 mm Hg (p less than 0.001) and increased the valve area from 0.47 +/- 0.15 to 0.83 +/- 0.27 cm2 (p less than 0.001). Immediately after dilatation, ejection fraction mildly increased from 29 +/- 7% to 34 +/- 9% (p less than 0.001) in 38 patients who had undergone a second left ventricular angiogram after dilatation. No significant change in the degree of aortic regurgitation was found after the procedure. Three patients died in hospital (femoral arterial complications in two, septicemia in one). Immediate clinical improvement was noted in 80% of the patients. During the follow-up (mean, 11 months), 22 patients died (heart failure in 15 patients, sudden death in five patients, myocardial infarction in one patient, cancer in one patient). Thirty patients survived, 21 with persistent clinical improvement. Repeat cardiac catheterization was performed at 6 months in 20 patients, of whom eight had recurrence of symptoms. Nine patients had restenosis: their hemodynamic indexes had returned to prevalvuloplasty values.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of alteration in preload on the pattern of left ventricular diastolic filling as assessed by Doppler echocardiography in humans.
Authors: Stoddard M F , Pearson A C , Kern M J , Ratcliff J , Mrosek D G , Labovitz A J
Published: June 2011

We examined the influence of alterations in preload on pulsed Doppler indexes of left ventricular diastolic function in 50 patients including 12 without cardiovascular disease, 29 with coronary artery disease, and nine with critical aortic stenosis. Micromanometer left ventricular pressure was recorded simultaneously with pulsed Doppler echocardiography of left ventricular inflow and M-mode echocardiography of left ventricular diameter. Chamber stiffness constants, kd and kv, were obtained from the diastolic pressure-diameter and pressure-volume relations, respectively. Relaxation was measured by the isovolumic relaxation time constants, TL and TD, derived from the exponential left ventricular pressure decay and maximum negative dP/dt. In 41 patients after nitroglycerin treatment, left ventricular end-diastolic pressure decreased from 18 +/- 5 to 13 +/- 4 mm Hg (p less than 0.001). The ratio of peak early to peak atrial filling velocities and time-velocity integral ratios decreased from 1.08 +/- 0.57 to 0.90 +/- 0.42 (p less than 0.001) and from 1.77 +/- 0.95 to 1.41 +/- 0.71 (p less than 0.001), respectively. The peak early filling velocity and time-velocity integral decreased from 56.1 +/- 15.7 to 49.9 +/- 14.5 cm/sec (p less than 0.001) and from 7.9 +/- 2.7 to 6.8 +/- 2.8 cm (p less than 0.001), respectively. Relaxation (TL, TD, and maximum negative dP/dt) and chamber stiffness (kd and kv) were not impaired after nitroglycerin administration. In 48 patients after ventriculography, left ventricular end-diastolic pressure increased from 18 +/- 6 to 22 +/- 8 mm Hg (p less than 0.001). The peak early and peak atrial filling velocities increased from 57.4 +/- 15.2 to 68.3 +/- 19.7 cm/sec (p less than 0.001) and from 61.0 +/- 22.7 to 69.4 +/- 23.2 cm/sec (p less than 0.01), respectively. As a result, the ratio of peak early to peak atrial filling velocity was unchanged. However, in the aortic stenosis group, the ratio of peak early to peak atrial filling velocity increased from 0.95 +/- 0.64 to 1.10 +/- 0.72 (p less than 0.02). Relaxation and chamber stiffness were unchanged. Thus, a reduction or increase in preload may induce a diastolic filling pattern that mimics or masks diastolic dysfunction, respectively. Preload conditions need to be accounted for when the status of diastolic function is extrapolated from the pulsed Doppler mitral inflow velocity profile.
Effects of aspirin and prostaglandin E1 on in vitro thrombolysis with urokinase. Evidence for a possible role of inhibiting platelet activity in thrombolysis.
Authors: Terres W , Beythien C , Kupper W , Bleifeld W
Published: June 2011

The formation of thrombi in vivo includes the activation of both platelets and the coagulation cascade. Conventional thrombolytic therapy is primarily directed toward the dissolution of fibrin. To evaluate the possibility that platelet activity impairs the lysis of thrombi, we studied the effects of aspirin and platelet-deaggregating prostaglandin E1 on thrombolysis with urokinase. Combined platelet and fibrin thrombi were produced in vitro by adding CaCl2 and collagen (1 microgram/ml) to citrated platelet-rich plasma (250,000 platelets per microliters). Urokinase (500-10,000 units/ml) caused a dose-dependent weight loss of the thrombi that was maximal at 2,000 units/ml. The addition of aspirin (10-200 micrograms/ml) to platelet-rich plasma before thrombus formation markedly enhanced thrombolysis with urokinase. This effect was most pronounced at 20 micrograms/ml aspirin. However, when aspirin was added after completion of thrombus formation, no significant effect on thrombolysis was noted. Prostaglandin E1 (1-100 mumol/l) improved the lysis with urokinase of the combined platelet and fibrin thrombi. This effect was maximal at 20 mumol/l prostaglandin E1. When pure fibrin thrombi were produced in platelet-free plasma, prostaglandin E1 was without effect on lysis. Thus, in vitro lysis with urokinase of combined platelet and fibrin thrombi was enhanced by the addition of platelet-deaggregating prostaglandin E1 and by pretreatment with aspirin.
A new method for noninvasive quantification of valvular regurgitation based on conservation of momentum. In vitro validation.
Authors: Cape E G , Skoufis E G , Weyman A E , Yoganathan A P , Levine R A
Published: June 2011

The noninvasive Doppler assessment of regurgitant volume from jet size is limited by the fundamental inequality of jet volume and regurgitant volume and by the dependence of jet dimensions on driving pressure and instrument settings for a given flow volume. Therefore, this study addresses the hypothesis that an equation could be derived from basic physical principles to quantify regurgitant volume with velocities that can be directly measured by Doppler echocardiography. The principle of conservation of momentum for free turbulent jets resembling many cardiac lesions yields an equation for regurgitant volume as a function of maximum jet velocity, a distal centerline velocity, and the intervening distance. This theory was tested throughout a range of physiologic flow rates and pressures (orifice velocities) in steady flow for 0.08-0.40 cm2 circular orifices and a noncircular orifice and in physiologic pulsatile flow for 0.08 and 0.20 cm2 circular orifices. Plots of centerline velocities versus axial distance coincided with those expected for such jets. Calculated and actual volumetric flows agreed well by linear regression in the turbulent jet: for steady flow rates, y = 0.98x + 0.09 (r = 0.99, SEE = 0.14 l/min), with similar correlations for circular and noncircular orifices; for pulsatile flow, y = 1.02x + 0.03 for peak flow rate (r = 0.98, SEE = 0.18 l/min) and y = 1.02x + 0.58 for total regurgitant volume (r = 0.95, SEE = 0.81 ml). There was no significant effect of orifice size or location of velocity measurement within the turbulent jet. Therefore, for free jets resembling many clinical lesions, regurgitant flow rate and volume can be calculated noninvasively from Doppler velocities without planimetry of jet area. Because the required information is intrinsic to the jet, this method should apply regardless of associated valvular lesions. It should also apply to orifices of variable shape because turbulent eddies obliterate the details of flow at the orifice. The special case of jets impinging on walls must be considered separately for both this technique and flow mapping.
Exercise response before and after termination of atrial tachycardia after congenital heart disease surgery.
Authors: Wessel H U , Benson D W , Braunlin E A , Dunnigan A , Paul M H
Published: June 2011

We studied exercise performance before and after conversion of atrial tachycardia to sinus rhythm, atrial bradycardia, or junctional rhythm in 10 patients 9-25 years of age 8-20 years after congenital heart disease surgery (complete transposition of the great arteries, seven of 10 patients). The same maximal cycle (five of 10 patients) or treadmill (five of 10 patients) exercise protocol was performed in atrial tachycardia and sinus rhythm 1-232 days after atrial tachycardia (mean, 34 days). Electrocardiogram, heart rate, and pulmonary gas exchange were recorded. Sinus rhythm exercise increased peak VO2 (mean, 28.7 [sinus rhythm] vs. 24.7 [atrial tachycardia], p less than 0.01), exercise time (p less than 0.01), and O2 pulse at rest (p less than 0.01) and at peak exercise (NS). Mean resting heart rate decreased from 109 to 70 beats/min (p less than 0.01). In atrial tachycardia, peak exercise heart rate was low (80-163 beats/min) because of fixed conduction (six of 10 patients) or high as conduction approached 1:1 (176-252 beats/min) (four of 10 patients). In sinus rhythm, rest to peak exercise heart rate increased in six of 10 patients (p less than 0.05). The data show improved exercise performance in sinus rhythm primarily because of improved heart rate adaptation to exercise, by either permitting increased heart rate response or eliminating excessively high heart rate with inadequate diastolic filling.
Time-series analysis of heart rate variability during submaximal exercise. Evidence for reduced cardiac vagal tone in animals susceptible to ventricular fibrillation.
Authors: Billman G E , Hoskins R S
Published: June 2011

Periodic fluctuations in the R-R interval have been used as noninvasive measures of cardiac autonomic tone. For example, a reduced heart rate variability has been shown to correlate with an increased mortality in patients recovering from myocardial infarction. The effects that physiologic perturbations such as exercise have on this heart rate variability have not been investigated. Therefore, heart rate variability was measured throughout a submaximal exercise test in 36 mongrel dogs with healed anterior myocardial infarctions. The amplitude of the respiratory component (0.24-1.04 Hz) was determined by time-series analysis techniques and was used as an index of cardiac vagal tone. On a subsequent day, a 2-minute coronary occlusion was initiated during the last minute of exercise. Twenty-two animals developed ventricular fibrillation (susceptible), whereas 14 animals did not (resistant). Exercise elicited a significantly greater increase in heart rate (resistant, 205.4 +/- 7.1; susceptible, 227.0 +/- 5.4 beats/min) in susceptible animals, which was accompanied by a greater reduction in the cardiac vagal tone index (resistant, 2.7 +/- 0.3; susceptible, 1.1 +/- 0.2 ln msec2) as compared with resistant animals. Conversely, atropine sulfate (50 micrograms/kg) given during exercise elicited a greater heart rate increase in the resistant dogs (heart rate change: resistant, 54.2 +/- 7.0; susceptible, 18.7 +/- 4.4 beats/min). Taken together, these data suggest that exercise elicited a greater reduction in cardiac vagal tone in animals known to be susceptible to ventricular fibrillation.
Prevention of postischemic cardiac injury by the orally active iron chelator 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and the antioxidant (+)-cyanidanol-3.
Authors: van der Kraaij A M , van Eijk H G , Koster J F
Published: June 2011

In this study, we investigated the role of oxygen-derived free radicals and iron in mediating myocardial injury during ischemia and reperfusion. Iron is of special interest because it may enhance tissue injury during ischemia and reperfusion by catalyzing the formation of highly reactive hydroxyl radicals (by modified Haber-Weiss or Fenton reactions). Rat hearts, perfused by the Langendorff method, were subjected to global ischemia (15 minutes at 37 degrees C) and reperfusion. The effects of two iron chelators, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and 5-hydroxy-2-hydroxymethyl-4-pyrone (kojic acid), and one antioxidant, (+)-cyanidanol-3, on contractile function, coronary flow, lactate dehydrogenase release, and lactate production were studied. The combination of these iron chelators is of special importance because L1 is known to prevent lipid peroxidation, induced by ADP/Fe3+ and NADPH in microsomes, in contrast to kojic acid. We found significant protection of contractile function (apex displacement) during reperfusion with 50 microM L1 and 20 microM (+)-cyanidanol-3 (p less than 0.01, n = 6), whereas no protection was found with 50 microM kojic acid (n = 6). Measurements of lactate dehydrogenase release during reperfusion showed a protective pattern similar to that found for heart contractile function, although 50 microM kojic acid also showed a significantly lower lactate dehydrogenase release during the first 10 minutes of reperfusion. No differences in coronary resistance or lactate release were found between the various groups. Our findings indicate that iron and oxygen-derived free radicals are important in the pathogenesis of postischemic reperfusion injury probably because of the formation of hydroxyl radicals.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial energetics in patients with dilated cardiomyopathy. Influence of nitroprusside and enoximone.
Authors: Hasenfuss G , Holubarsch C , Heiss H W , Meinertz T , Bonzel T , Wais U , Lehmann M , Just H
Published: June 2011

Cardiotonic agents influence myocardial energy consumption by vasodilation, which may reduce energy demand, and by inotropism, which may increase it. To distinguish between the two effects, myocardial oxygen consumption must be analyzed in relation to its hemodynamic determinants. The coupling of myocardial oxygen consumption with its determinants was investigated in 22 patients with idiopathic dilated cardiomyopathy (NYHA Class II and III). Predicted myocardial oxygen consumption by the pressure-work index, the Bretschneider index, and the pressure-volume area correlated moderately with measured myocardial oxygen consumption (r = 0.57, p less than 0.001; r = 0.52, p less than 0.005; and r = 0.63, p less than 0.001). Multiple regression analysis, including left ventricular peak systolic wall stress, systolic stress-time integral, pressure-volume work, maximum rate of left ventricular pressure rise, and mean velocity of circumferential fiber shortening indicated that systolic stress-time integral is the major determinant of myocardial oxygen consumption (r = 0.75, p less than 0.001) in these patients. Enoximone, a phosphodiesterase inhibitor, has an inotropic and a vasodilating effect. To investigate the inotropic portion of the energy cost of this phosphodiesterase inhibitor, the influence of enoximone on myocardial oxygen consumption and systolic stress-time integral was compared with the effects of nitroprusside, which is a vasodilator only. Nitroprusside (10 patients) and enoximone (12 patients) reduced left ventricular systolic stress-time integral from 109 +/- 22 to 71 +/- 21 (p less than 0.005) and from 104 +/- 23 to 42 +/- 10 (p less than 0.001) 10(3) dynes.sec/cm2, respectively. Myocardial oxygen consumption decreased from 159 +/- 44 to 112 +/- 23 (p less than 0.005) and from 134 +/- 28 to 109 +/- 21 (p less than 0.001) microliters/beat/100 g, respectively. In both groups, there was a significant correlation between the decrease in myocardial oxygen consumption and the decrease in systolic stress-time integral. The slopes of the respective linear regression lines were significantly different (1.27 for nitroprusside and 0.51 nl.cm2/100 g.dynes.sec for enoximone, p less than 0.05), indicating a smaller decrease of myocardial oxygen consumption for a given decrease of stress-time integral with enoximone. Applying the pressure-work index or the pressure-volume area instead of systolic stress-time integral yielded comparable results. Thus, vasodilation reduces myocardial oxygen consumption in proportion to the reduction of stress-time integral. With enoximone, the energy-saving effect of vasodilation is counteracted in part by the increased energy d
Nifedipine potentiates cardiopulmonary baroreflex control of sympathetic nerve activity in healthy humans. Direct evidence from microneurographic studies.
Authors: Ferguson D W , Hayes D W
Published: June 2011

Nifedipine augments baroreflex mechanisms in in vivo animal models. Previous studies in our laboratory demonstrate that nifedipine potentiates baroreflex control of heart rate and vascular resistance in normal human subjects. To further define the neuroeffector mechanism of the autonomic effects of nifedipine, we directly measured postganglionic sympathetic nerve activity to muscle (MSNA, microneurography), before and after drug administration, during selective unloading of cardiopulmonary baroreceptors with lower body negative pressure (-10 mm Hg, LBNP-10), and during the cold pressor test. Twenty-three normal subjects (age, 23 +/- 1 years; mean +/- SEM) were studied in the control state and 20 minutes after administration of either nifedipine (10 mg s.l., 10 subjects), during nitroprusside infusion (0.37 +/- 0.03 microgram/kg/min i.v., eight subjects), or 20 minutes after sublingual administration of placebo (five subjects). We measured systemic arterial pressure, central venous pressure, heart rate, and MSNA. Nifedipine and nitroprusside produced similar increases in resting heart rate and MSNA and similar decreases in central venous pressure, whereas placebo had no effect on resting hemodynamics. During LBNP-10, hemodynamic changes were not significantly different among the three treatment groups. However, the percentage increase in MSNA during LBNP-10 was significantly augmented from a 24 +/- 9% increase before nifedipine to a 56 +/- 7% increase after nifedipine (p less than 0.05). Decreases in central venous pressure with LBNP-10 were nearly identical before compared with after nifedipine. Thus, nifedipine increased the cardiopulmonary baroreflex sympathetic sensitivity (change in total MSNA per mm Hg decrease in central venous pressure during LBNP-10) from 26.5 +/- 10.7 units/mm Hg to 74.9 +/- 19.0 units/mm Hg (p less than 0.01). In contrast, administration of hemodynamically similar doses of nitroprusside resulted in an attenuation of MSNA responses to LBNP-10. During LBNP-10, MSNA increased 57 +/- 12% before nitroprusside but only 14 +/- 4% during nitroprusside (p less than 0.01). The cardiopulmonary baroreflex sympathetic sensitivity was not significantly altered by nitroprusside (45.1 +/- 12.4 units/mm Hg before compared with 33.1 +/- 20.8 units/mm Hg during nitroprusside, p = NS). Placebo had no effect on the responses to LBNP-10. Nifedipine did not augment MSNA responses to the cold pressor test. To evaluate the linearity of sympathetic responses to cardiopulmonary baroreceptor unloading, graded LBNP (0, -5, -10, and -15 mm Hg) was applied in three additional subjects before and after nifedipine (10 mg s.l.).(ABSTRACT TRUNCATED AT 400 WORDS)
Prognostic importance of dipyridamole-echocardiography test in coronary artery disease.
Authors: Picano E , Severi S , Michelassi C , Lattanzi F , Masini M , Orsini E , Distante A , L'Abbate A
Published: June 2011

We studied the value of dipyridamole-echocardiography test in comparison with clinical, resting electrocardiogram and echocardiogram variables in predicting cardiac events occurring in 539 consecutive patients referred for dipyridamole-echocardiography test from 1984 to 1987. There were 118 cardiac events: 11 cardiac deaths, 12 nonfatal myocardial infarctions, and 95 coronary revascularization (bypass or angioplasty) procedures. A Cox survival analysis identified echocardiographic positivity after dipyridamole administration as the best predictor of cardiac events (relative risk ratio, 2.7). The next most powerful predictor was angina after dipyridamole administration (relative risk ratio, 1.9). Cardiac events occurred in 14 (6%) of 253 patients with normal high-dose dipyridamole echocardiographic test results, in 21 (26%) of 82 patients with high-dose dipyridamole echocardiographic positivity (0.84 mg/kg during 10 minutes), and in 83 (41%) of 204 patients with low-dose dipyridamole echocardiographic positivity (0.56 mg/kg during 4 minutes) (p less than 0.0001). In a subset of 341 patients, exercise electrocardiography stress test and coronary angiography were also available. A Cox survival analysis again identified echocardiographic positivity after dipyridamole as the best predictor of cardiac events (relative risk ratio, 1.9) followed by a pathologic coronary arteriography (relative risk ratio, 1.2). We conclude that the presence and timing of a transient dyssynergy during dipyridamole stress are useful predictors of subsequent cardiac events.
Persistence of sympathetic-mediated forearm vasoconstriction after alpha-blockade in hypertensive patients.
Authors: Taddei S , Salvetti A , Pedrinelli R
Published: June 2011

Sympathetic vasoconstriction not mediated by alpha-adrenoceptors has been identified in vitro and in animals but not in humans. We evaluated the effect of alpha-adrenoceptor blockade on either endogenous vascular sympathetic activation (obtained through the application of a nonhypotensive lower-body negative pressure, -10 mm Hg for 5 minutes) or selective postsynaptic alpha-adrenoceptor stimulation by exogenous norepinephrine (0.005 micrograms/100 ml forearm tissue/min for 3 minutes) in the presence of beta-blockade by propranolol (10 micrograms/100 ml forearm tissue/min for 15 minutes). Drugs were infused into the brachial artery at systemically ineffective rates while continuously monitoring forearm blood flow (by venous plethysmography), intra-arterial mean arterial pressure, and heart rate in patients with essential hypertension. The irreversible antagonist phenoxybenzamine was used at a rate of 20 micrograms/100 ml forearm tissue/min for 1 hour, which antagonized the local responses to norepinephrine in a range of 0.005-0.05 micrograms/100 ml forearm tissue/min. During saline administration, either lower-body negative pressure or exogenous norepinephrine decreased forearm blood flow comparably. However, after phenoxybenzamine administration, forearm vasoconstriction to norepinephrine was abolished while a residual response to lower-body negative pressure remained in each patient. To exclude insufficient alpha-adrenoceptor blockade, the same experimental protocol was repeated by doubling phenoxybenzamine concentrations. No difference from the data obtained with the lower level of antagonist was found. Further studies were performed to confirm the sympathetic origin of the residual vasoconstriction. Bretylium tosylate, a neurotransmitter blocker, infused into the brachial artery (50 micrograms/100 ml forearm tissue/min for 90 minutes) abolished the effect of endogenous sympathetic activation but did not alter the effect of exogenous norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy. A population-based study in Olmsted County, Minnesota, 1975-1984.
Authors: Codd M B , Sugrue D D , Gersh B J , Melton L J
Published: June 2011

Using the records linkage system of the Mayo Clinic and of the Rochester Epidemiology Project, which accesses diagnostic data on the entire population of Olmsted County, Minnesota, we identified 45 new cases of idiopathic dilated cardiomyopathy (DCM) and 19 new cases of hypertrophic cardiomyopathy (HCM) among county residents for the years 1975-1984. Overall age- and sex-adjusted incidence rates were 6.0/100,000 and 2.5/100,000 person-years, respectively. The incidence of DCM doubled from 3.9/100,000 in the first 5 years to 7.9/100,000 person-years in the last 5 years of study. The corresponding change for HCM was from 1.4 to 3.6/100,000 person-years. Age- and sex-adjusted prevalence rates as of January 1, 1985, for DCM and HCM were 36.5/100,000 and 19.7/100,000 population, respectively. The prevalence of DCM in persons less than 55 years old was 17.9/100,000, over a third of whom were New York Heart Association functional Class III or IV at diagnosis. These estimates may be of value in determining the potential use of health care resources, particularly cardiac transplantation.
Time-dependent risk of and predictors for cardiac arrest recurrence in survivors of out-of-hospital cardiac arrest with chronic coronary artery disease.
Authors: Furukawa T , Rozanski J J , Nogami A , Moroe K , Gosselin A J , Lister J W
Published: June 2011

One hundred one consecutive patients with chronic coronary artery disease who had survived out-of-hospital cardiac arrest in the absence of acute myocardial infarction underwent electrophysiologic evaluation and were followed prospectively. Ventricular tachyarrhythmias were inducible in 76 patients (75%) in the control state and were suppressed by antiarrhythmic drugs or surgery in 32 of the 76 patients (42%). During a mean follow-up of 27 months, cardiac arrest recurred in 21 patients: in two of the 25 patients in whom ventricular tachyarrhythmias were not inducible in the control state, three of the 32 in whom inducible ventricular tachyarrhythmias were suppressed after treatment, and 16 of the 44 in whom inducible ventricular tachyarrhythmias could not be suppressed after treatment. Actuarial rate of cardiac arrest recurrence was 11.2% during the first 6 months of follow-up ("high-risk early phase") and then decreased to less than 4% in each subsequent 6-month period. Multivariate Cox proportional hazards analysis identified an ejection fraction less than 35% (p = 0.0013) and persistent inducibility of ventricular tachyarrhythmias (p = 0.0025) as independent predictors of cardiac arrest recurrence for the entire follow-up period. Separate analysis of variables within and after the first 6 months showed that an ejection fraction less than 35% was the strongest predictor for early phase recurrence (p = 0.0078) but had only marginally significant predictive value for late phase recurrence (p = 0.0516). Persistent inducibility of ventricular tachyarrhythmias had no significant predictive value for early phase recurrence (p = 0.1382) but was the strongest predictor for late phase recurrence (p = 0.0061). These data suggest that, in patients with chronic coronary artery disease who survive out-of-hospital cardiac arrest, poor ejection fraction and persistent inducibility of ventricular tachyarrhythmias have a different predictive influence on early and late phase recurrence. Time-dependent risk factor analysis may have great clinical relevance in assessing an individual's changing risk over time.