bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of ischemia during percutaneous transluminal coronary angioplasty by transcatheter infusion of oxygenated Fluosol DA 20%.
Authors: Cleman M , Jaffee C C , Wohlgelernter D
Published: June 2011

Catheter balloon inflation performed during percutaneous transluminal coronary angioplasty (PTCA) results in temporary interruption of coronary blood flow and subsequent myocardial ischemia. This produces transient but profound regional left ventricular dysfunction. In an effort to mitigate this inflation-related dysfunction, oxygenated Fluosol DA 20%, a perfluorochemical oxygen transport fluid, was infused distal to the balloon through the central lumen of the dilating catheter during balloon inflation. Regional wall motion during PTCA was assessed by simultaneous continuous two-dimensional echocardiography and was quantified by computer analysis. During control inflations accompanied by no intracoronary infusion or by transcatheter infusion of Ringer's lactate solution or nonoxygenated Fluosol DA 20%, there was profound regional left ventricular dysfunction with a greater than 90% decrease in regional contraction. In contrast, regional contraction during transcatheter infusion of oxygenated Fluosol DA 20% remained at normal levels throughout balloon inflation. Distal infusion of Fluosol DA 20% during balloon inflation is a useful adjunct to PTCA, allowing longer inflation times and perhaps permitting PTCA to be performed safely in patients with significant myocardium at ischemic risk or with limited left ventricular reserve for whom the procedure is currently believed to be too hazardous.
Selective enhancement of function of stunned myocardium by increased flow.
Authors: Stahl L D , Aversano T R , Becker L C
Published: June 2011

Although augmentation of flow does not improve the performance of normal myocardium, the hyperemic response after brief coronary occlusion is associated with transient hyperfunction in the previously ischemic region. In this study we assessed the effect of vasodilator-enhanced coronary blood flow on the systolic function of postischemic stunned myocardium. In 18 open-chest, anesthetized dogs the anterior descending artery was occluded for 5 min, followed by a 10 min period of reflow, repeated 12 times with a final 90 min recovery period. After the recovery period, either 0.06 mg/min dipyridamole (n = 6), 1 mg/min papaverine (n = 6), or 1.5 micrograms/kg/min nitroglycerin (n = 6) was infused intravenously for 15 min. Regional myocardial blood flow, which had returned to normal before administration of vasodilator, was increased 150% above baseline by dipyridamole and 80% by papaverine, but was unchanged by nitroglycerin. Segmental shortening decreased after repeated occlusions: from 17.5% to 0.9% in the group later treated with dipyridamole, from 18.6% to 6.7% in the papaverine group, and from 19.2% to-1.9% in the nitroglycerin group (p less than .005 for all groups). Segmental shortening increased to 8.8% after dipyridamole, 13.6% after papaverine, and 5.1% after nitroglycerin (p less than .05 for all groups), although the load-independent end-systolic pressure-length relationship (ESPLR) showed a significant shift to the left, reflecting enhanced performance, only after dipyridamole and papaverine. For all dogs combined, the percent improvement in ESPLR was correlated with the percent increase in flow (R = -.73, p less than .001). Performance was unchanged in the control region despite similar augmentation of flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Color Doppler detection of multiple ventricular septal defects.
Authors: Ludomirsky A , Huhta J C , Vick G W , Murphy D J , Danford D A , Morrow W R
Published: June 2011

Combined two-dimensional and Doppler echocardiography has a high sensitivity and specificity for detection of isolated perimembranous ventricular septal defects. However, muscular or multiple ventricular septal defects may be difficult to diagnose with noninvasive methods, particularly in older children, necessitating angiography for accurate diagnosis. Detection of single and multiple ventricular septal defects with two-dimensional color flow mapping was compared with detection by standard two-dimensional imaging and Doppler. Both techniques were compared with four-chamber left ventricular angiography. Fifty-one patients (age 3 months to 25 years, mean 5.6 years) were studied. Eighteen had solitary ventricular septal defects, 18 had multiple ventricular septal defects, and 15 patients with intact ventricular septum served as a control group. At least one ventricular septal defect was detected by color Doppler and two-dimensional/Doppler methods in all patients with ventricular septal defect proved by angiography with no false positives. In the detection of multiple ventricular septal defects, the sensitivity of color Doppler was 72% and that of two-dimensional/Doppler was 38% (100% specificity in both). Color Doppler failed to identify multiple ventricular septal defects in five patients (two weighing less than 4 kg and three with reduced pulmonary blood flow). However, no large additional muscular defects were missed by imaging and color Doppler. Color Doppler is useful for the detection of ventricular septal defects and has higher sensitivity than two-dimensional/Doppler for multiple ventricular septal defects. The contribution of color Doppler appears to be in the detection of additional small muscular ventricular septal defects.
Coronary angioplasty for early postinfarction unstable angina.
Authors: de Feyter P J , Serruys P W , Soward A , van den Brand M , Bos E , Hugenholtz P G
Published: June 2011

Coronary angioplasty was performed in 53 patients in whom unstable angina had reoccurred after 48 hr and within 30 days after sustained myocardial infarction. Single-vessel disease was present in 64% of the patients and multivessel disease in 36%. The preceding myocardial infarction had been small to moderate in size in the majority of the patients. The left ventricular ejection fraction was more than 50% in 80% of the patients. Forty-five patients were refractory to pharmacologic treatment; eight were initially stabilized but once again became symptomatic with light exertion. Angioplasty was performed in 35 patients 2 to 14 days and in 18 patients 15 to 30 days after infarction (average 12 +/- 7 days after infarction). The initial success rate was 89% (47/53). The success rate of the patients treated at 2 to 14 days was lower (29/35, 83%) than that of patients treated at 14 to 30 days (18/18, 100%) but did not reach statistical significance (p less than .06). There were no deaths related to the procedure. In four of the six failures, emergency bypass surgery was performed and two patients sustained a myocardial infarction. Furthermore, a myocardial infarction complicated the angioplasty procedure in two other patients; thus the overall procedure-related myocardial infarction rate was 8% (4/53). At 6 months follow-up 26% (14/53) of all the patients who underwent angioplasty had recurrence of angina, which was successfully treated with repeat angioplasty, bypass surgery, or medical therapy. There were no late deaths. Late myocardial infarction occurred in two patients. Thus the total myocardial infarction rate after angioplasty at 6 months was 11% (6/53 patients).(ABSTRACT TRUNCATED AT 250 WORDS)
Magnetic resonance imaging of acute myocardial infarction: gadolinium diethylenetriamine pentaacetic acid as a marker of reperfusion.
Authors: Peshock R M , Malloy C R , Buja L M , Nunnally R L , Parkey R W , Willerson J T
Published: June 2011

We examined the effects of a paramagnetic contrast agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) on magnetic resonance images of acute myocardial infarction with and without reperfusion. Twenty-two dogs underwent occlusion of the left anterior descending coronary artery (LAD). In 10 dogs (group I) the LAD remained occluded for 3 hr and in the other 12 (group II) for 2 hr followed by 1 hr of reperfusion. Gd-DTPA (0.34 mM/kg) was administered to five dogs in group I at 2 hr and 5 min after occlusion and to seven dogs in group II 5 min after reperfusion. At 3 hr after ligation, the hearts were excised and imaged with spin echo and inversion recovery pulse sequences on a 0.35 Tesla magnetic resonance imager. Reperfused hearts given Gd-DTPA demonstrated a significant increase in contrast between normal and reperfused myocardium as compared with nonreperfused hearts and reperfused hearts not given Gd-DTPA. This enhancement was particularly prominent in the inversion recovery images. Studies performed in vivo in two additional dogs demonstrated similar enhancement with reperfusion with Gd-DTPA in gated spin echo images. Contrast-enhanced magnetic resonance imaging allows the detection of reperfusion early in the course of acute infarction.
The association of increased levels of intermediate-density lipoproteins with smoking and with coronary artery disease.
Authors: Steiner G , Schwartz L , Shumak S , Poapst M
Published: June 2011

Studies were undertaken to determine whether there is an association between elevated levels of intermediate-density lipoproteins (IDL) (Sf 12-60 lipoproteins) and coronary artery disease. Forty-five to sixty-five-year-old men with objectively documented coronary artery disease (n = 58) who were free of known risk factors (diabetes, hypertension, obesity, hyperuricemia, and hypercholesterolemia) were compared with similar men who were free of coronary artery disease (n = 52). Smokers could not be excluded. The coronary artery disease group had a higher rate of cigarette smoking (NS, due to large variations); higher concentrations of triglycerides in their plasma (p = .003) and higher levels of very low-density lipoproteins (VLDL) (p = .007), IDL (p = .016), and low-density lipoproteins (LDL) (p = .04); as well as somewhat lower levels of high-density lipoprotein (HDL) cholesterol (p = .04). Chi-squared analysis demonstrated a strong association between coronary artery disease and IDL apolipoprotein (apo) B (p = .006), coronary artery disease and IDL triglyceride (p = .032), and coronary artery disease and IDL apo B times IDL triglyceride (p = .006) when the top quintile of the population was compared with the bottom quintile for each of these variables. Stepwise logistic regression analysis resulted in rejection of an association between coronary artery disease and HDL cholesterol, plasma triglyceride, VLDL triglyceride, or LDL triglyceride. However, it did show that coronary artery disease was most strongly associated with smoking and that the second strongest association was with IDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Circadian variation in the frequency of sudden cardiac death.
Authors: Muller J E , Ludmer P L , Willich S N , Tofler G H , Aylmer G , Klangos I , Stone P H
Published: June 2011

To determine whether sudden cardiac death exhibits a circadian rhythm similar to that recently demonstrated for nonfatal myocardial infarction, we analyzed the time of day of sudden cardiac death as indicated by death certificates of 2203 individuals dying out of the hospital in Massachusetts in 1983. The data reveal a prominent circadian variation of sudden cardiac death, with a low incidence during the night and an increased incidence from 7 to 11 A.M. The pattern is remarkably similar to that reported for nonfatal myocardial infarction and episodes of myocardial ischemia. The finding that the frequency of sudden cardiac death is increased in the morning is compatible with hypotheses that sudden cardiac death results from ischemia or from a primary arrhythmic event. Further study of the physiologic changes occurring in the morning may provide new information supporting or refuting these hypotheses, thereby leading to increased understanding and possible prevention of sudden cardiac death.
Is vasospasm related to platelet deposition? Relationship in a porcine preparation of arterial injury in vivo.
Authors: Lam J Y , Chesebro J H , Steele P M , Badimon L , Fuster V
Published: June 2011

Although aggregating platelets can release potent vasoactive substances in vitro, the importance of platelets in mediating naturally occurring or provoked spasm in vivo is not clear. To investigate the possible role of platelets in arterial spasm following arterial injury induced by angioplasty, quantitative platelet deposition of the dilated arterial segment and the degree of vasoconstriction (average percent diameter narrowing just proximal and distal to the dilated segment) produced during angioplasty of the common carotid arteries were studied in 42 heparinized normal pigs that were killed immediately after the angioplasty procedure. Angiographic films of the carotid arteries were taken before and after the dilatation to assess the vasoconstriction. Vasoconstriction was greater (40% vs 19%, p less than .002) when platelet deposition (X 10(6)/cm2) was in excess of 10, and the severity of vasoconstriction in vivo had a close positive exponential correlation (r = .77, p less than .001) with extent of platelet deposition in 24 untreated pigs. Platelet deposition and vasoconstriction were greater with severe arterial wall injury than with mild injury (58.8 versus 6.9, p less than .0001; 37% vs 21%, p less than .001, respectively). After severe injury in 18 pigs pretreated with 1 mg/kg/day aspirin, platelet deposition decreased (from 58.8 to 19.6, p less than .02) and vasoconstriction decreased (from 37% to 21%, p less than .003) relative to control. After mild injury, platelet deposition and vasoconstriction were mild and unchanged by aspirin. Thus, local vasoconstriction is influenced by the degree of platelet deposition.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparative electrophysiologic effects of intravenous amiodarone and desethylamiodarone in dogs: evidence for clinically relevant activity of the metabolite.
Authors: Talajic M , DeRoode M R , Nattel S
Published: June 2011

It has been suggested that some of the effects of long-term amiodarone therapy may be due to accumulation of a metabolite, desethylamiodarone. To evaluate the pharmacologic actions of the metabolite, we gave single intravenous doses (10 or 25 mg/kg) of amiodarone or desethylamiodarone to anesthetized dogs. The resulting plasma and myocardial concentrations of both agents were similar to levels achieved with long-term oral amiodarone therapy in man. Amiodarone and desethylamiodarone produced frequency-dependent slowing in ventricular and atrioventricular nodal conduction and increased atrial and ventricular refractory periods. The relative effects of these agents on fast- and slow-channel tissues differed, with amiodarone producing significantly greater prolongation of Wenckebach cycle length and desethylamiodarone producing larger increases in QRS duration, atrial refractory period, and ventricular refractory period. We conclude that desethylamiodarone has substantial electrophysiologic effects at clinically relevant concentrations and has relatively greater effect on fast-channel tissue in vivo than does amiodarone. The accumulation of desethylamiodarone probably accounts for some of the delayed electrophysiologic effects in patients receiving long-term treatment with amiodarone.
The effect of acute hypercholesterolemia on myocardial infarct size and the no-reflow phenomenon during coronary occlusion-reperfusion.
Authors: Golino P , Maroko P R , Carew T E
Published: June 2011

The goal of this study was to determine the effects of acute hypercholesterolemia on the evolution of myocardial infarction in a preparation of coronary occlusion-reperfusion. New Zealand white rabbits were fed a 2% cholesterol-enriched diet for 3 days (plasma cholesterol 329 +/- 70 mg/dl), or maintained on the control diet (plasma cholesterol 67 +/- 12 mg/dl). Temporary (30 min) coronary artery occlusion was performed in open-chest rabbits with a suture snare. The snare was released to permit reperfusion. When the animals were killed 5.5 hr later, left ventricles were cut into 3 mm slices. Infarct size was determined by planimetry of tetrazolium-stained slices while the area at risk of infarction (hypoperfused zone) was determined by planimetry of the "cold spots" on autoradiograms of the slices that contained 99m Tc-labeled microspheres that had been injected 1 min after occlusion. Infarct size, expressed as percent of the hypoperfused zone, was 42.8 +/- 1.3% (n = 10) in the control group and was increased by approximately 100% in cholesterol-fed animals to 83.7 +/- 2.0% (n = 10, p less than .001). To test the hypothesis that vascular obstruction (no reflow) might account for the larger infarct size, thioflavin S was injected immediately before the animals were killed to demarcate perfused myocardium in three additional groups of animals: standard chow-fed rabbits (n = 5), cholesterol-fed rabbits (n = 5), and standard chow-fed rabbits that, in addition, received an infusion of isoproterenol (0.1 microgram/kg/min, n = 6), an intervention believed to increase infarct size through a mechanism not dependent on the no-reflow phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
Regression of coronary aneurysms in patients with Kawasaki syndrome.
Authors: Takahashi M , Mason W , Lewis A B
Published: June 2011

Coronary aneurysms were demonstrated echocardiographically in 34 of 186 patients who presented with Kawasaki syndrome between 1979 and 1983. The aneurysms were confirmed by selective coronary angiography in 27 patients and by postmortem examination in one. The 27 surviving patients with proven aneurysms were followed for 2 to 40 months (mean 15), during which they received low dose (5 to 10 mg/kg) aspirin daily. Progressive improvement and resolution of aneurysms were observed by serial echocardiography in 18 patients and confirmed by angiography in 14. Coronary aneurysms persisted, however, in nine other patients for 14 to 40 months (mean 25.7). The incidence of aneurysm resolution was higher in children less than 1 year of age at the onset of the illness than in patients older than 1 year (100% vs 50%; p less than .001). Aneurysms were more likely to resolve in girls than in boys (100% vs 42%; p less than .001). Fusiform aneurysms tended to resolve more frequently than saccular lesions (80% vs 18%; p less than .025). Aneurysms located distally in the coronary arteries appear to regress more rapidly than proximal ones. We conclude that an age of less than 1 year at the onset of Kawasaki syndrome, female sex, and fusiform aneurysm morphology are significant factors that favor resolution of coronary artery aneurysms. However, important questions remain with regard to the long-term fate and functional capabilities of these healed lesions.
Improved sex-specific criteria of left ventricular hypertrophy for clinical and computer interpretation of electrocardiograms: validation with autopsy findings.
Authors: Casale P N , Devereux R B , Alonso D R , Campo E , Kligfield P
Published: June 2011

In a previous study of 543 patients we developed, using echocardiographic left ventricular mass as the reference standard, two new sets of criteria that improve the electrocardiographic diagnosis of left ventricular hypertrophy (LVH). One set of criteria, which is suitable for routine clinical use, detects LVH when the sum of voltage in RaVL + SV3 (Cornell voltage) exceeds 2.8 mV in men and 2.0 mV in women. The second set of criteria, suitable for use in interpretation of the computerized electrocardiogram, uses logistic regression models based on electrocardiographic and demographic variables with independent predictive value for LVH, with separate equations for patients in sinus rhythm and atrial fibrillation. To test these criteria prospectively with use of a different reference standard, antemortem electrocardiograms were compared with left ventricular muscle mass measured at autopsy in 135 patients. Sensitivity of standard Sokolow-Lyon voltage (SLV) criteria (SV1 + RV5 or RV6 greater than 3.5 mV) for LVH was only 22%, but specificity was 100%. The Cornell voltage criteria improved sensitivity to 42%, while maintaining high specificity at 96%. Higher sensitivity (62%) was achieved by use of the new regression criteria, with a specificity of 92%. Overall test accuracy was 60% for SLV criteria, 68% for the Cornell voltage criteria, and 77% for the new regression criteria (p less than .005 vs SLV). We conclude that the Cornell voltage criteria improve the sensitivity of the electrocardiogram for detection of LVH and are easily applicable in clinical practice.(ABSTRACT TRUNCATED AT 250 WORDS)
Nonsurgical closure of patent ductus arteriosus: clinical application of the Rashkind PDA Occluder System.
Authors: Rashkind W J , Mullins C E , Hellenbrand W E , Tait M A
Published: June 2011

The first successful application of a transcatheter closure technique for patent ductus arteriosus (PDA) suitable for use in infants and children was performed by us in 1977. Since that time, there has been continued improvement and simplification of the equipment as well as in the implantation technique. Following a Food and Drug Administration protocol, a multicenter study was conducted to test the safety and effectiveness of this interventional method. The clinical results from three major regional test centers (Philadelphia, Houston, and New Haven) are presented. One hundred forty-six patients from a test population of 156 were treated for PDA with use of the Rashkind PDA Occluder Systems. Successful closure was accomplished in 94 (66%) of the total cases. Ten patients (7%) retained residual ductal murmurs despite correct placement of the occlusion devices; five additional patients (3%) were considered failures due to the presence of abnormal Doppler flow patterns after the procedure. Postrelease embolizations occurred in 19 (15%) instances. One patient required emergency surgical intervention after attempted retrieval of an embolized occluder. With the improvements in the manufacturing of the double-disk occluder systems as well as the perfection of the transvenous delivery technique, the incidences of closure failure and postrelease complications have decreased. Since January 1984, 78% of all transcatheter closure attempts were successful, with 10% embolization.
Quantification of myocardial injury produced by temporary coronary artery occlusion and reflow with technetium-99m-pyrophosphate.
Authors: Jansen D E , Corbett J R , Buja L M , Hansen C , Ugolini V , Parkey R W , Willerson J T
Published: June 2011

Previously, technetium-99m-stannous pyrophosphate (99mTc-PPi) has been used to localize and estimate the size of myocardial infarcts in animals after permanent coronary artery occlusion. This study tested the hypothesis that 99mTc-PPi accurately sizes myocardial infarctions produced by temporary coronary artery occlusion and reflow in dogs. Three groups of dogs were studied: group A underwent 3 hr of occlusion followed by 2 hr of reperfusion, with 99mTc-PPi injected 10 min after reflow (n = 10); group B underwent 3 hr of occlusion followed by 2 hr of reperfusion, with 99mTc-PPi injected 90 min after reflow (n = 11); and group C underwent 3 hr of occlusion followed by reflow with 99mTc-PPi injected at 10 min and again at 48 hr after reflow (n = 5). Myocardial slices from group A and B dogs were imaged in vitro. Group C dogs were imaged with single photon-emission computed tomography (SPECT) in vivo, and myocardial slices were imaged in vitro at the conclusion of the study. The extent of myocardial infarction was defined with triphenyltetrazolium chloride (TTC) staining, and coronary blood flow was estimated with radioactive microspheres. In addition, transmural myocardial tissue samples were taken from the center of the myocardial infarction, the lateral portion of the myocardial infarction, the normal myocardium adjacent to the lateral aspect of the infarcts, and from the normal myocardium and counted for 99mTc-PPi activity. A significant correlation was found between infarct size determined by areas of increased 99mTc-PPi uptake and that estimated from TTC staining for both group A (r = .89) and group B animals (r = .98).(ABSTRACT TRUNCATED AT 250 WORDS)
Protection against atherogenesis with the polymer drag-reducing agent Separan AP-30.
Authors: Faruqui F I , Otten M D , Polimeni P I
Published: June 2011

The inhibitory effect of Separan AP-30, an anionic polyacrylamide, on atherosclerotic plaque formation in aortas of rabbits on a high (2%) cholesterol diet was tested over a period extending from 37 to 170 days. Atherogenesis was quantified morphometrically by application of a computer-assisted image analysis of histologic cross sections of the aorta. The area of vessel wall-atheroma interface, fraction of lumen occluded, and other indexes of atherogenesis were measured in each of 26 segments of aorta excised from the animals, half of which were administered injections (intravenous) of Separan three times a week. Regression analysis of the morphometric data indicates that the polyelectrolyte exerts a powerful antiatherogenic effect in all regions of the aorta, inhibiting the formation of plaque mass to less than half in the aortic arch and about one-fifth in the descending aorta as compared with the aortic plaque masses in untreated rabbits. Results are compatible with the suggestion that a novel hemodynamic principle in vivo, polymer drag reduction, might be effectively applied against atherosclerosis.
Platelet accumulation in experimental angioplasty: time course and relation to vascular injury.
Authors: Wilentz J R , Sanborn T A , Haudenschild C C , Valeri C R , Ryan T J , Faxon D P
Published: June 2011

Since platelet accumulation may be an important determinant of restenosis after angioplasty, the time course of 51Cr-labeled platelet accumulation after experimental angioplasty was evaluated in a deendothelialized, hypercholesterolemic rabbit preparation of atherosclerosis. Marked platelet accumulation (39.5 +/- 8.7 X 10(6) platelets/1 cm vessel length) was observed at 30 min and remained active until 4 hr after angioplasty. Total accumulation over 24 hr was 56.4 +/- 4.7 X 10(6) platelets/1 cm length. Histologic dissection was directly related to the degree of platelet accumulation, with 64 +/- 15 X 10(6) platelets/1 cm in the group with marked dissection and 8.7 +/- 3.7 X 10(6) platelets/1 cm in the group with minimal dissection (p less than .05). Increasing angiographic dissection also resulted in a trend toward increased platelet accumulation, and angiographic change in luminal diameter showed a significant correlation with platelet accumulation. It is concluded that marked platelet accumulation occurs early after transluminal angioplasty and is related to the extent of dissection. Restenosis may result from a complex interaction of platelet accumulation, vascular damage, and blood flow.
Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences.
Authors: Siddoway L A , Thompson K A , McAllister C B , Wang T , Wilkinson G R , Roden D M , Woosley R L
Published: June 2011

The relationship between debrisoquine metabolic phenotype and the pharmacokinetics and pharmacodynamics of propafenone was studied in 28 patients with chronic ventricular arrhythmias (22 extensive metabolizers [EMs] and six poor metabolizers [PMs] of debrisoquine). EMs were characterized by a shorter propafenone elimination half-life (5.5 +/- 2.1 vs 17.2 +/- 8.0, p less than .001), lower average plasma concentration (Cp) (1.1 +/- 0.6 vs 2.5 +/- 0.5 ng/ml/mg daily dosage, p less than .001), and higher oral clearance (1115 +/- 1238 vs 264 +/- 48 ml/min, p less than .001). The active metabolite 5-hydroxypropafenone, assayed in 12 patients, was identified in nine of 10 EMs but in neither of the PMs. A lower incidence of central nervous system side effects was noted in EMs (14% vs 67%, p less than .01). The magnitude of QRS widening at any given propafenone Cp was greater in EMs than PMs. There was no significant difference between EMs and PMs in effective propafenone dose or frequency of antiarrhythmic response. Inhibition of debrisoquine 4-hydroxylation by propafenone was demonstrated both in vivo and in a human liver microsomal system in vitro. We conclude that propafenone is metabolized via the same cytochrome P-450 responsible for debrisoquine's 4-hydroxylation, and that its pharmacokinetics and concentration-response relationships and the incidence of central nervous system side effects are different in patients of different debrisoquine metabolic phenotype.
Long-term nitroglycerin treatment: effect on direct and endothelium-mediated large coronary artery dilation in conscious dogs.
Authors: Stewart D J , Holtz J , Bassenge E
Published: June 2011

We examined the effect of nitroglycerin (GTN) tolerance on an important determinant of nitrate-antianginal action, large coronary artery dilation, in 11 chronically instrumented conscious dogs. In addition, endothelium-mediated coronary artery dilation was studied because this shares a common dilator pathway with the nitrates, i.e., activation of soluble guanylate cyclase. With long-term GTN (1.5 micrograms/kg/min iv for 5 days) the diameters of the left circumflex and anterior descending coronary arteries showed an initial increase of 8.2 +/- 0.3% and 10.8 +/- 0.9%, respectively, returning to control levels by the second to third day of treatment. On days 4 and 5, the dose-response relations for GTN-induced epicardial artery dilation were shifted (p less than .01) to 17- to 20-fold higher doses. However, there was no attenuation of epicardial artery dilation induced by SIN-1 (n = 7), another activator of guanylate cyclase, or of endothelium-mediated dilation assessed both as flow-dependent dilation (n = 7) and as direct intra-arterial acetylcholine-induced dilation (n = 4). In addition, there was no clear tolerance to the peripheral vascular actions of GTN responsible for reflex tachycardia and increased coronary flow. We conclude that a moderate degree of nitrate tolerance to epicardial artery dilation does not affect the responsiveness to other exogenous or endogenous activators of guanylate cyclase. However, this tolerance to epicardial artery dilation, together with the maintenance of peripheral vascular actions that can induce reflex tachycardia, result in a potentially unfavorable balance of GTN effects.
Increased embolic risk in patients with left ventricular thrombi.
Authors: Stratton J R , Resnick A D
Published: June 2011

Although left ventricular thrombi are associated with an increased embolic risk in the first few weeks after acute myocardial infarction, the long-term risk remains undefined. To ascertain the incidence of strictly defined systemic emboli, we followed 85 patients with echocardiographically documented left ventricular thrombi. At the time of the entry echocardiogram, most patients (n = 57) had remote myocardial infarction, while 19 had recent (less than 1 month) infarction, and nine had idiopathic cardiomyopathy. Because of the difficulty in classifying events as embolic in patients with advanced atherosclerosis, a matched control group of 91 patients without thrombi was also studied. The thrombus and control groups were similar with regard to recent myocardial infarction, remote infarction, anterior infarction, ejection fraction, atrial fibrillation, echocardiographic referral for source of emboli, and warfarin therapy. During a mean follow-up of 22 months after echocardiography, embolic events occurred in 13% (11 of 85) of patients with thrombi compared with 2% (two of 91) control patients (p less than .01). The actuarial probability of being embolus free at 2 years after echocardiography was 86% in patients with thrombi compared with 97% in control patients (p less than .01). All embolic events occurred greater than 1 month after myocardial infarction (range 1 to 96 months). The only clinical or echocardiographic features predictive of embolization were protrusion and mobility of thrombus (both p less than .02). We conclude that the incidence of embolic events is definitely increased in patients with left ventricular thrombi compared with control subjects during long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Restrictive cardiomyopathy versus constrictive pericarditis: role of endomyocardial biopsy in avoiding unnecessary thoracotomy.
Authors: Schoenfeld M H , Supple E W , Dec G W , Fallon J T , Palacios I F
Published: June 2011

Despite careful clinical, noninvasive, and hemodynamic assessment of patients with constrictive/restrictive physiology, the differentiation of restrictive cardiomyopathy from constrictive pericarditis remains difficult. We examined the role of right ventricular endomyocardial biopsy in defining the underlying process in 54 patients with evidence of constrictive/restrictive physiology, including 38 patients with profound symptoms of heart failure in whom diagnostic/therapeutic thoracotomy was contemplated (group I) and 16 patients with milder symptoms (group II). All patients in group I had NYHA class III or IV heart failure with depressed cardiac index (mean 2.5 liters/min/m2), right atrial hypertension (mean 15 mm Hg), and normal left ventricular ejection fraction (mean 59%). Endomyocardial biopsy identified a specific source of restrictive cardiomyopathy in 15 of 38 patients (39%) (11 amyloid, four myocarditis). Of the 23 remaining patients with either normal biopsy findings or nonspecific abnormalities on biopsy, 18 had intraoperative or autopsy evaluation of their pericardium, and constriction was found in 14 (77%). A specific form of restrictive cardiomyopathy was also identified in four of the 16 patients with milder symptoms (group II). We conclude that endomyocardial biopsy is useful in patients with severe constrictive/restrictive physiology. It identifies a large subset of patients with specific forms of restrictive cardiomyopathy in whom thoracotomy should be avoided. It supports the need for thoracotomy and the likelihood of finding pericardial constriction in patients without specific pathologic findings.
Cardiovascular effects of verapamil in patients with essential hypertension.
Authors: Schmieder R E , Messerli F H , Garavaglia G E , Nunez B D
Published: June 2011

The cardiovascular effects of intravenous verapamil and 3 months of oral administration of a slow-release form of verapamil (verapamil-SR) were studied in 10 patients with mild-to-moderate essential hypertension. Intravenous verapamil reduced arterial pressure by 15% (p less than .01) through a fall in total peripheral resistance of 29% (p less than .01); provoked a reflexive rise in heart rate (by 19%, p less than .02), cardiac output (by 74%, p less than .01), and plasma catecholamines; and shifted intravascular volume toward the cardiopulmonary circulation indicating peripheral venoconstriction. Quite in contrast to the immediate effects of the intravenous drug, oral therapy with verapamil-SR for 2 to 3 months lowered arterial pressure effectively (by 15%, p less than .01) by inducing vasodilation of 15% (p less than .02), but without causing reflex tachycardia, activation of the sympathetic-adrenergic or renin-angiotensin systems, or volume expansion. Oral therapy with verapamil-SR preserved systemic and renal blood flow and slightly reduced cardiac mass (by 6%, p less than .05) and renal vascular resistance (by 25%, p less than .05). Whereas intravenous verapamil tended to depress myocardial contractility, oral verapamil-SR did not at all affect myocardial contractility or left ventricular function. These cardiovascular effects make verapamil-SR an excellent agent for long-term antihypertensive therapy.
Frequency- and orientation-dependent effects of mexiletine and quinidine on conduction in the intact dog heart.
Authors: Bajaj A K , Kopelman H A , Wikswo J P , Cassidy F , Woosley R L , Roden D M
Published: June 2011

Myocardial conduction depends on the magnitude of the fast inward sodium current as well as on cardiac fiber orientation, with more rapid propagation along myocardial fibers than across them. Although antiarrhythmic drugs depress the sodium current in a frequency-dependent fashion in vitro, their effects on conduction in the intact ventricle have been less well studied. We therefore evaluated the frequency- and orientation-dependent actions of mexiletine, quinidine, and their combination on epicardial conduction in 24 pentobarbital-anesthetized dogs. These interventions were chosen because the time constant of recovery from sodium-channel blockade by mexiletine in vitro is shorter than that from blockade by quinidine, and because we have previously shown that the combination of these drugs is often clinically effective when single-agent therapy fails. An electrode array that permitted measurement of conduction times in multiple orientations over short segments of epicardium without contamination by rapid Purkinje fiber propagation or by latency or virtual cathode effects at the stimulus site was developed for these studies. In all animals, the atrioventricular node was destroyed by injection of formalin to permit measurements over a wide range of cycle lengths (250 to 1500 msec). In the absence of drugs, conduction in any direction was frequency independent. In the presence of mexiletine, however, frequency-dependent increases in conduction times were found at cycle lengths of 600 msec or less; these changes were significantly greater in orientations for which baseline conduction was rapid. Quinidine, on the other hand, increased conduction times at all tested cycle lengths without significant orientation-dependent effects.(ABSTRACT TRUNCATED AT 250 WORDS)
The hemodynamic effects of sympathetic stimulation combined with parasympathetic blockade in man.
Authors: Stratton J R , Pfeifer M A , Halter J B
Published: June 2011

To define the effects of circulating norepinephrine and epinephrine on cardiac function and to determine whether left ventricular function is influenced by parasympathetic mechanisms during catecholamine stimulation, hemodynamic changes were investigated in healthy young human subjects who were supine and awake during infusion of intravenous norepinephrine alone (125 ng/kg/min) (n = 6), norepinephrine (125 ng/kg/min) plus epinephrine (50 ng/kg/min) (n = 6), and norepinephrine plus epinephrine plus parasympathetic blockade induced by atropine (2 mg intravenously) (n = 5). Ejection fraction and changes in cardiac volumes were measured by radionuclide ventriculography. During the infusion of norepinephrine plus epinephrine, plasma norepinephrine increased from 358 +/- 35 to 1782 +/- 123 pg/ml (mean +/- SE) and plasma epinephrine increased from 31 +/- 5 to 355 +/- 90 pg/ml (both p less than .01 vs baseline). These increases in plasma catecholamines were associated with increases in the heart rate (58 +/- 3 to 67 +/- 2 beats/min, p = NS), systolic blood pressure (113 +/- 3 to 140 +/- 6 mm Hg, p less than .01), ejection fraction (0.64 +/- 0.02 to 0.72 +/- 0.02 ejection fraction units, p less than .01), stroke volume (+41 +/- 5%, p less than .01), and cardiac output (+54 +/- 8%, p less than .01), and a decrease in systemic vascular resistance (-31 +/- 3%, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
The importance of the determination of the myocardial area at risk in the evaluation of the outcome of acute myocardial infarction in patients.
Authors: Feiring A J , Johnson M R , Kioschos J M , Kirchner P T , Marcus M L , White C W
Published: June 2011

On the basis of animal studies, we postulated that the size of the perfusion field (risk area) of an occluded coronary artery would be an important determinant of outcome in patients with acute myocardial infarction. To test this hypothesis, we measured size of the risk area in 27 patients with acute myocardial infarction by the intracoronary injection of 99mTc-macroaggregated albumin and gated nuclear imaging. After injection of the albumin spheres (5.3 +/- 1.4 hr after the onset of chest pain) streptokinase was administered and in 16 of 27 patients (59%) effective thrombolysis was achieved. Since none of the patients had evidence of a prior acute myocardial infarction, the 3 day nuclear left ventricular ejection fraction (LVEF) was considered an index of infarct size. Response to thrombolysis was analyzed according to success or failure of reperfusion and the size of the risk area (small risk area less than 25%, large risk area greater than 25% of left ventricular surface area). Standard clinical indexes correlated poorly with size of the risk area: electrocardiographic variables (r = .37), left ventricular end-diastolic pressure (r = .23), cardiac index (r = .55), and the LVEF obtained from a right anterior oblique contrast ventriculogram (r = .31). The coronary vessel responsible for the acute myocardial infarction significantly influenced size of the risk area (left anterior descending, 38 +/- 5% [mean +/- SD] vs circumflex or right coronary artery, 17 +/- 4%). However, knowledge of the site of coronary occlusion within a vessel was not helpful in predicting the size of the area at risk.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiographic and histologic consequences of laser thermal angioplasty: comparison with balloon angioplasty.
Authors: Sanborn T A , Haudenschild C C , Garber G R , Ryan T J , Faxon D P
Published: June 2011

The angiographic and histologic consequences of laser thermal angioplasty were examined and compared with those of conventional balloon angioplasty in an atherosclerotic rabbit iliac artery preparation immediately and 4 weeks after the procedure. Nineteen vessels in 13 rabbits underwent either laser thermal or balloon angioplasty in random order. Laser thermal angioplasty was performed in a total of nine vessels with either a 1.5 or 2.0 mm laser-heated metallic-capped fiber by delivery of 6 or 8 W, respectively, of argon laser energy for 5 sec duration during continuous advancement through the stenosis. Balloon angioplasty was performed in a total of 10 stenotic lesions with a 2.5 mm balloon catheter. The immediate enlargement of the angiographic luminal diameters was similar for both procedures: from 1.0 +/- 0.2 to 1.9 +/- 0.2 mm for laser thermal angioplasty vs 1.0 +/- 0.1 to 2.0 +/- 0.2 mm for balloon angioplasty. However, 4 weeks later the vessels treated with laser thermal angioplasty had less restenosis, defined as a 20% or greater reduction in luminal diameter (two of nine vessels [22%] vs 10 of 10 vessels [100%]; p less than .001), and a significantly larger mean luminal diameter (1.6 +/- 0.5 vs 1.0 +/- 0.4 mm) than those treated with conventional balloon angioplasty (p less than .02). Histologic examination 4 weeks after the procedure revealed less fibrocellular proliferation after laser thermal angioplasty, whereas those vessels treated with balloon angioplasty demonstrated evidence of prior fracture and dissection of the vessel wall with more of a fibrocellular proliferative response.(ABSTRACT TRUNCATED AT 250 WORDS)
Disparity between ejection and end-systolic indexes of left ventricular contractility in mitral regurgitation.
Authors: Berko B , Gaasch W H , Tanigawa N , Smith D , Craige E
Published: June 2011

To examine left ventricular function in mitral regurgitation (MR), we compared the ejection phase indexes of left ventricular contractility with maximal systolic elastance (Emax) in an experimental preparation of MR. In eight anesthetized open-chest dogs, pressure-volume loops were derived during afterload manipulation with methoxamine and nitroprusside from simultaneous left ventricular pressure and dimensional (sonomicrometry techniques) data before and after creation of MR. From these data maximal systolic elastance (Emax), the end-systolic pressure-volume relationship (ESPVR), and the end-systolic stress-volume relationship (ESSVR) were determined by linear regression analysis. After creation of MR, end-diastolic volume increased significantly (40 +/- 13 to 53 +/- 18 ml, p less than .001); likewise end-systolic volume increased (28 +/- 11 to 33 +/- 15 ml, p less than .05). Ejection fraction increased after MR (35 +/- 6% to 44 +/- 8%, p less than .005), as did the mean velocity of fiber shortening (0.62 +/- 0.20 to 1.02 +/- 0.39 sec-1, p less than .02). In contrast, Emax declined significantly (4.63 +/- 2.5 to 3.54 +/- 1.94 mm Hg/ml, p less than .05); ESPVR and ESSVR showed similar directional changes. An inverse relationship was found between systolic elastance and end-diastolic volume in both control and MR states. When Emax, ESPVR, and ESSVR were normalized to end-diastolic volume, they were unchanged after MR. These results suggest that either there was a decline in left ventricular contractile state after MR, or that contractility was unchanged (if elastance is normalized for increased contractility, but occurred as a consequence of increased preload with no significant change in afterload.
Measurement of infarct size and percentage myocardium infarcted in a dog preparation with single photon-emission computed tomography, thallium-201, and indium 111-monoclonal antimyosin Fab.
Authors: Johnson L L , Lerrick K S , Coromilas J , Seldin D W , Esser P D , Zimmerman J M , Keller A M , Alderson P O , Bigger J T , Cannon P J
Published: June 2011

Single photon-emission tomography (SPECT) and indium 111-labeled monoclonal antimyosin Fab fragments were used to measure myocardial infarct size in 12 dogs, six subjected to balloon catheter-induced coronary artery occlusion for 6 hr (late reperfusion) and six subjected to occlusion with reperfusion at 2 hr (early reperfusion). Tomographic imaging was performed 24 hr after the intravenous injection of labeled Fab fragments with the use of a dual-head SPECT camera with medium-energy collimators. Immediately after the first tomographic scan, thallium-201 was injected into nine of 12 dogs and imaging was repeated. Estimated infarct size in grams was calculated from transaxially reconstructed, normalized, and background-corrected indium SPECT images with the use of a threshold technique for edge detection. Estimated noninfarcted myocardium in grams was calculated from obliquely reconstructed thallium SPECT images by a similar method. The animals were killed and infarct size in grams and true infarct size as a percentage of total left ventricular myocardial volume were measured by triphenyl tetrazolium chloride staining. Estimated infarct size from indium SPECT images showed an excellent correlation with true infarct size (r = .95, SEE = 4.1 g). Estimated percentage myocardium infarcted was calculated by dividing estimated infarct size from indium images by the sum of estimated infarct size plus estimated noninfarcted myocardium obtained from thallium images. Correlation between the estimated percentage of myocardium infarcted and true percentage of myocardium infarcted was excellent (r = .93, SEE = 4.4%). We conclude that dual-isotope SPECT with indium 111-monoclonal antimyosin antibodies and thallium-201 can accurately estimate infarct size and percentage myocardium infarcted.