bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous determination of left ventricular end-systolic pressure-volume and pressure-dimension relationships in closed-chest dogs.
Authors: Little W C , Freeman G L , O'Rourke R A
Published: June 2011

The left ventricular end-systolic pressure-volume relationship is a load-insensitive measure of left ventricular performance. The relationship at end-systole between left ventricular pressure and dimension is more easily obtained, but the conflicting results of previous studies make it unclear if it has the same properties as the left ventricular end-systolic pressure-volume relationship. To address this issue, 11 dogs were instrumented to measure left ventricular pressure and three orthogonal left ventricular dimensions. Left ventricular pressure and dimensions were varied by use of caval occlusion. Left ventricular volume was calculated as an ellipsoid. The left ventricular end-systolic pressure-volume relationship and each of the three end-systolic pressure-dimension relations were described by straight lines (r = .97 +/- .02, mean +/- SD). In six animals, dobutamine produced similar significant increases (p less than .01) in the slope of the end-systolic pressure-volume relationship (244 +/- 61% of control), the end-systolic pressure-anterior-posterior dimension relationship (248 +/- 89%), the end-systolic pressure--septal-lateral dimension relationship (211 +/- 95%), and the end-systolic pressure-basal-apical dimension relationship (210 +/- 85%). The intercepts at zero pressure were relatively unchanged by dobutamine. In contrast, occlusion of the distal left anterior descending coronary artery in five animals produced a rightward shift of the left ventricular end-systolic pressure-volume relationship and the pressure--basal-apical dimension relationship, while the pressure--anterior-posterior dimension and pressure--septal-lateral dimension relationships were relatively unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
Results of triple valve replacement in 91 patients: perioperative mortality and long-term follow-up.
Authors: Gersh B J , Schaff H V , Vatterott P J , Danielson G K , Orszulak T A , Piehler J M , Puga F J , Pluth J R , McGoon D C
Published: June 2011

Between 1961 and 1984, 91 patients underwent simultaneous triple valve replacement at the Mayo Clinic. Of the 273 prosthetic valves used, 77% were Starr-Edwards. Perioperative (30 day) mortality was 24% to 27% between 1962 and 1974 and 7% between 1975 and 1983 (p = .17). In patients with NYHA class IV symptoms, perioperative mortality was 44%, and in those with milder symptoms, it was 8% (p less than .0001). The median follow-up was 7.5 years (range, 6 weeks to 20 years). Cumulative survival, which was calculated taking into consideration perioperative mortality, was 64% at 1 year, 55% at 5 years, 40% at 10 years, and 25% at 15 years. Multivariate analysis identified preoperative functional class and age as predictors of late survival. Among causes of late mortality were sudden death in 32.5%, congestive heart failure in 15%, thromboembolism in 12.5%, prosthetic valve dysfunction in 7.5%, and infective endocarditis in 5%. Late complications included systemic emboli in 42% (embolic rate, 12.3 events per 100 patient-years), bleeding in 22%, myocardial infarction in 16%, and infective endocarditis in 6%. Eight patients required reoperation for prosthetic valve dysfunction, and 12 patients had permanent pacemakers. Of the 29 patients still alive, 79% are in NYHA class I or II. In summary, perioperative mortality after triple valve replacement appears to be declining; long-term survival in 30 day survivors is similar to that after single valve replacement and excellent symptomatic improvement can be obtained, although morbidity is high.
The dependence of myocardial ultrasonic integrated backscatter on contractile performance.
Authors: Wickline S A , Thomas L J , Miller J G , Sobel B E , Pérez J E
Published: June 2011

We have recently shown that the cardiac cycle-dependent variation in myocardial ultrasonic integrated backscatter is blunted with regional ischemia in dogs. To determine if global and intramural regional myocardial contractile performance can be quantified by integrated backscatter, we analyzed ultrasonic responses after induction of increased and decreased contractility in five dogs. A recently developed analog data-acquisition system for measuring integrated backscatter in real time was used to sample radiofrequency signals gated from subepicardial or subendocardial regions. Base-line recordings of integrated backscatter, left ventricular pressure, left ventricular dP/dt, and wall thickness were made at 12 left ventricular sites for both intramural regions. Contractility was modified subsequently by either paired pacing or propranolol to produce significantly elevated or depressed values for maximum left ventricular dP/dt compared with baseline (1083 +/- 289 to 3001 +/- 570 mm Hg/sec; p less than .01 for all). The amplitude of the cyclic variation of integrated backscatter was 50% greater (arithmetically) in subendocardial than in subepicardial regions for all treatments (7.6 +/- 0.3 vs 6.0 +/- 0.5 dB, p less than .001). The maximum rate of change in integrated backscatter waveforms during isovolumetric contraction was faster with paired pacing and slower with propranolol than at baseline for all regions (56 +/- 6 to 74 +/- 6 to 82 +/- 5 dB/sec, p less than .005). The maximum rate of change in integrated backscatter also was greater in subendocardial than subepicardial regions (p less than .001). Thus, both regional and global differences in myocardial contractile performance are manifest quantitatively in integrated backscatter waveforms. We propose that the physiologic determinants of these differences may depend on regional and global variations in myofibril elastic characteristics.
Ultrasonic tissue characterization: detection of acute myocardial ischemia in dogs.
Authors: Schnittger I , Vieli A , Heiserman J E , Director B A , Billingham M E , Ellis S G , Kernoff R S , Takamoto T , Popp R L
Published: June 2011

Ultrasonic tissue characterization is a new area of investigation in the field of cardiac ultrasound. The amplitude and frequency of the ultrasound signal are normally altered as the signal penetrates through tissue. It is assumed that the amplitude distribution and frequency shift of diseased or edematous tissue are different than those of normal tissue. A statistical approach to the analysis of the unprocessed radiofrequency signal in the amplitude domain was used to study the effect of acute myocardial ischemia on the parameter mean amplitude/standard deviation of the amplitude (MSR). Ten dogs were anesthetized and underwent left lateral thoracotomy. Baseline mean MSR from the interventricular septum was 1.99 +/- 0.05, but increased by 30 min after coronary artery occlusion and started to plateau at 1 hr (mean 2.24 +/- 0.06). Reproducibility in noninfarcted myocardium (left ventricular inferoposterior wall) was good, with a mean MSR of 2.00 +/- 0.05 at baseline and 1.98 +/- 0.04 3 to 4 hr later. There was no difference in mean MSR when data were obtained through chest wall and when they were obtained directly from the surface of the heart. We conclude that statistical analysis in the amplitude domain of the unprocessed radiofrequency signal can detect acute myocardial ischemia within 30 min after coronary artery occlusion, provides reproducible measurements, and is unaffected by chest wall filtering.
An enzyme histochemical study of human sinus node, coronary sinus, and mitral valve muscle.
Authors: Théry C , Krivosic I , Asseman P , Meijer A E
Published: June 2011

An enzyme histochemical study of the sinoatrial node, the coronary sinus, and the atrial muscle extending into the anterior mitral valve was performed on human hearts. Investigation of the activity and localization of the structurally bound enzymes was performed by conventional histochemical techniques. Determination of the activity of nonstructurally or weakly structurally bound enzymes was performed by histochemical techniques in which leakage of enzymes during the incubation period was reduced by the application of semipermeable membranes. The sinoatrial node is characterized by a high degree of anaerobic enzyme capacity and a relatively low degree of aerobic enzyme capacity. The discriminatory nature of these reactions allows examination of the structure of the sinoatrial node and its approaches. The presence of transitional cells was confirmed; isolated clusters of nodal cells were found in the atrial myocardium around the sinoatrial node, but no evidence of specialized tissue forming the beginning of an internodal pathway was found by this technique. The specific histochemical reactions that characterize the sinoatrial node also occur in the atrial muscle, extending into the anterior mitral valve, the anterior wall of the coronary sinus, and the atrial tissue near the orifice of the coronary sinus. These observations seem to corroborate the hypothesis that arrhythmic ectopic foci can arise in these regions.
Is hypertension more benign when associated with obesity?
Authors: Barrett-Connor E , Khaw K T
Published: June 2011

To determine the effect of obesity on prognosis in hypertensive subjects, a population of 1727 men 50 to 79 years of age was dichotomized by baseline body mass index (less than 27 and greater than or equal to 27 kg/m2) and systolic blood pressure (less than 160 and greater than or equal to 160 mm Hg). After 9 years of follow-up, age-adjusted all-cause, cardiovascular, and ischemic heart disease mortality rates were highest in the nonobese hypertensive subjects. The relative risk for mortality associated with a systolic blood pressure of 160 mm Hg or higher was significantly increased only in the nonobese group, with the largest difference in relative risk between obese and nonobese for ischemic heart disease. Results were consistent after separately excluding those with a history of heart disease, diabetes, current use of antihypertensive medication, and cigarette smoking, and those who died within 2 years of the baseline examination. When the independent effect of risk factors, including age, plasma cholesterol level, cigarette smoking, use of antihypertensive medication, and personal history of heart disease or diabetes was assessed with the Cox model, systolic blood pressure was a significant independent predictor of all-cause, cardiovascular, and ischemic heart disease death only in the nonobese subjects. We do not exclude an adverse effect of raised blood pressure in the obese. However, these data suggest that the prognosis is poorer in leaner hypertensive patients than in those who are overweight.
Factors that modify the flow response to intracoronary injections.
Authors: Emanuelsson H , Holmberg S , Selin K , Wallin J
Published: June 2011

Coronary sinus flow (CSF) was measured in seven patients with normal coronary arteries (group A) during intracoronary injections of 6 ml arterial blood, 6 ml blood from the coronary sinus, 3 and 6 ml isotonic saline, 3 and 6 ml hypertonic glucose, and 6 ml of a contrast agent (sodium metrizoate). In 10 patients with coronary artery disease (group B), CSF was measured after administration of 6 ml isotonic saline, 6 ml sodium metrizoate, and 6 ml of another contrast medium (iohexol). In group A, arterial blood did not affect CSF, while coronary sinus blood induced a 33% increase. After 6 ml isotonic saline, there was a 35% increase in flow and after hypertonic glucose an increase of 70%. Metrizoate induced a rise in flow of 109%. In group B, the increase in CSF after intracoronary injection of saline, metrizoate, and iohexol was 30%, 83%, and 67%, respectively. Blood from the coronary sinus, in contrast to arterial blood, induced a marked rise in peak flow, suggesting a role for reactive hyperemia secondary to myocardial hypoxia in this response. A similar mechanism might have been operative after injection of isotonic saline, as well as after the hyperosmolar contrast agents. However, additional mechanisms mediated by the high osmotic pressure of these substances, such as induction of the Bezold-Jarisch reflex, which will induce coronary vasodilation, may have played a role. Finally, when hyperosmolar agents are used, the possibility of some direct vasodilating properties of the agents cannot be excluded.
Validation of attenuation-corrected equilibrium radionuclide angiographic determinations of right ventricular volume: comparison with cast-validated biplane cineventriculography.
Authors: Dell'Italia L J , Starling M R , Walsh R A , Badke F R , Lasher J C , Blumhardt R
Published: June 2011

To determine the accuracy of attenuation-corrected equilibrium radionuclide angiographic determinations of right ventricular volumes, we initially studied 14 postmortem human right ventricular casts by water displacement and biplane cineventriculography. Biplane cineventriculographic right ventricular cast volumes, calculated by a modification of Simpson's rule algorithm, correlated well with right ventricular cast volumes measured by water displacement (r = .97, y = 8 + 0.88x, SEE = 6 ml). Moreover, the mean volumes obtained by both methods were no different (73 +/- 28 vs 73 +/- 25 ml). Subsequently, we studied 16 patients by both biplane cineventriculography and equilibrium radionuclide angiography. The uncorrected radionuclide right ventricular volumes were calculated by normalizing background corrected end-diastolic and end-systolic counts from hand-drawn regions of interest obtained by phase analysis for cardiac cycles processed, frame rate, and blood sample counts. Attenuation correction was performed by a simple geometric method. The attenuation-corrected radionuclide right ventricular end-diastolic volumes correlated with the cineventriculographic end-diastolic volumes (r = .91, y = 3 + 0.92x, SEE = 27 ml). Similarly, the attenuation-corrected radionuclide right ventricular end-systolic volumes correlated with the cineventriculographic end-systolic volumes (r = .93, y = - 1 + 0.91x, SEE = 16 ml). Also, the mean attenuation-corrected radionuclide end-diastolic and end-systolic volumes were no different than the average cineventriculographic end-diastolic and end-systolic volumes (160 +/- 61 and 83 +/- 44 vs 170 +/- 61 and 86 +/- 43 ml, respectively). Comparison of the uncorrected and attenuation-corrected radionuclide right ventricular volumes demonstrated narrower 95% confidence intervals for the attentuation-corrected right ventricular volume determinations over a wide range of cineventriculographic volumes. Thus we conclude that: (1) attenuation-corrected radionuclide right ventricular end-diastolic and end-systolic volumes compare closely with those obtained by a cast-validated biplane cineventriculographic method and (2) attenuation-corrected radionuclide right ventricular volumes correspond more closely to determinations of biplane cineventriculographic right ventricular volumes and are thus likely to be more accurate than uncorrected radionuclide right ventricular volumes.
The effects of coronary angioplasty and reperfusion on distribution of myocardial flow.
Authors: Wahr D W , Ports T A , Botvinick E H , Dae M , Schechtmann N , Huberty J , Hattner R S , O'Connell J W , Turley K
Published: June 2011

To assess the effects of angioplasty (PTCA) and intracoronary streptokinase (ICSK) on relative myocardial perfusion, we administered 99mTc-macroaggregated albumin (MAA) to the uninvolved coronary artery before successful PTCA in 33 patients and before successful infusion of ICSK in eight patients and of 111In-MAA into the same vessel after the intervention. In 10 patients who underwent PTCA, MAA was injected into the involved, instrumented coronary artery. Computer-processed images were acquired in registry and compared. Similar scintigraphic studies were performed in six control patients and in 11 in whom planned interventions were not performed or were unsuccessful. Distribution of MAA was also compared with angiographic results and with the distribution of 201Tl on images obtained in patients at rest or on redistribution images obtained before and soon after intervention in 22 patients. In control patients and those studied after aborted or unsuccessful intervention, scintigraphic results showed excellent correlation with the angiographic anatomy and were without serial change. When MAA was injected into the uninvolved vessel, the scintigram revealed evidence of collateral perfusion with retraction of the perfusion zone from that of the involved coronary in 19 of 33 patients undergoing PTCA and in three of eight of those receiving ICSK. When MAA was injected into the involved artery, a relative increase in perfusion was seen in eight of 10 patients after PTCA. Although 30 patients demonstrated scintigraphic evidence of collateral vessels, only 10 patients had angiographic evidence of collateral circulation before intervention. The distribution of 201Tl demonstrated little change in its global pattern and regions previously supplied by collaterals were generally well perfused after intervention. Coronary collateral perfusion may be inapparent angiographically and regress rapidly after angioplasty or reperfusion. Native perfusion is generally and quickly restored after successful PTCA or ICSK infusion, which obviates the need for collaterals. After intervention, the distribution of total perfusion may not change, but its regional source may demonstrate beneficial alterations, shifting from collateral to native circulation.
Accuracy of volume measurement by conductance catheter in isolated, ejecting canine hearts.
Authors: Burkhoff D , van der Velde E , Kass D , Baan J , Maughan W L , Sagawa K
Published: June 2011

We evaluated the accuracy of the recently reported technique of estimating intraventricular volume by measurement of intracavitary electrical conductance in six isolated, ejecting, canine left ventricles. Left ventricular volumes were measured directly by a previously validated servosystem that employed an electroconductive balloon placed in the left ventricular cavity. The volume measured continuously by the balloon method (Vbal) was compared with that estimated by the conductance method (Vcath). For this test, the hearts were made to eject and fill physiologically by the use of a previously described computer-simulated arterial loading system. Complex ejection and filling patterns were created by stimulating the atrium mechanically, which resulted in irregular arrhythmatic contractions spanning a wide range of volumes. We found that there was a highly linear relationship (r2 = .982 +/- .014) between Vbal and Vcath: Vcath = 0.82 (+/- .05) Vbal + 26.7 (+/- 11.8) ml. Despite the wide variation in the offset term of this relationship among the different hearts, the offset within a given heart was predicted within 3.5 ml by a previously detailed "dilution" method that is applicable to the heart in situ within a closed thorax. Thus, since the offset term is obtainable in situ, the conductance method provides a signal that is proportional to the actual volume. To determine whether right ventricular volume influenced the accuracy of left ventricular measurement, we compared the relationship between Vcath and Vbal obtained with right ventricular volumes of 0 and 30 ml. Increasing the right ventricular volume shifted the relationship upward by less than 3 ml in the working range.(ABSTRACT TRUNCATED AT 250 WORDS)
Altered left ventricular mechanics in patients with valvular aortic stenosis and coarction of the aorta: effects on systolic performance and late outcome.
Authors: Borow K M , Colan S D , Neumann A
Published: June 2011

Despite similar degrees of left ventricular systolic hypertension shortening characteristics are usually greater in patients with congenital valvular aortic stenosis (VAS) than in patients with coarctation of the aorta (CoA). We hypothesized that these dissimilarities were caused by differences in myocardial mechanics rather than by alterations in contractile state. Eleven patients with VAS (ages 6 to 41 years) and 11 with CoA were matched for age, body surface area, and peak systolic ejection gradient. Results were compared with data from 22 normal subjects matched for age and body surface area. Echocardiographic tracings of the left ventricle were recorded in conjunction with left ventricular pressure measurements (VAS) or calibrated carotid pulse tracings (CoA and normal subjects). Peak and end-systolic wall stresses as well as left ventricular shortening fraction (% delta D) and rate-corrected velocity of fiber shortening (Vcfc) were calculated. No differences for left ventricular dimensions, heart rate or peak wall stress were present. Ventricular peak systolic pressures and wall mass were higher for the patients with VAS or CoA than for the normal subjects (p less than .001). These parameters did not differ between the VAS and CoA groups. The patients with VAS had higher % delta D and Vcfc than either the CoA or normal groups (p less than .01). Afterload, as quantified by end-systolic stress, was 41% lower than normal for the patients with VAS (p less than .001) and 13% higher than normal for those with CoA (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
A new approach to noninvasive evaluation of aortic regurgitant fraction by two-dimensional Doppler echocardiography.
Authors: Kitabatake A , Ito H , Inoue M , Tanouchi J , Ishihara K , Morita T , Fujii K , Yoshida Y , Masuyama T , Yoshima H
Published: June 2011

The aortic regurgitant fraction was estimated noninvasively in 20 patients with aortic regurgitation from systolic aortic and pulmonary volume flow determined by duplex Doppler echocardiography. By assuming that an excess of the aortic volume flow (AF) compared with the pulmonary volume flow (PF) is due to aortic regurgitant flow, the aortic regurgitant fraction (RF) was calculated as follows: RF(%) = (AF - PF)/AF X 100. The aortic and pulmonary volume flows were determined as products of systolic integrals of ejection flow velocities and cross-sectional areas of the left and right ventricular outflow tracts, respectively. The Doppler estimate of the regurgitant fraction was compared by semiquantitative grading (1+ to 4+) by cineaortography and with the measurement of regurgitant fraction by catheter technique. The mean Doppler-determined aortic regurgitant fraction was 2.4% for normal subjects, 28.0% for the patients with 1+, 32.6% for the patients with 2+, 53.3% for the patients with 3+, and 62.4% for the patients with 4+. A fair correlation was found between Doppler estimates of regurgitant fraction and semiquantitative cineaortographic grades (r = .80, p less than .01). In the patients without associated mitral regurgitation, a close correlation was observed between Doppler and catheter estimates of regurgitant fraction (r = .96, p less than .01; y = 1.0x - 0.08). In the patients with associated mild mitral regurgitation, however, Doppler estimates of regurgitant fraction substantially underestimated those determined by the conventional catheter technique, which cannot separately quantitate the aortic regurgitant fraction in the presence of mitral regurgitation. These observations indicate that the proposed Doppler technique provides a useful method to evaluate the aortic regurgitant fraction specifically regardless of the presence of associated mitral lesions.
Improvement in symptoms and exercise tolerance by metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized, placebo-controlled trial.
Authors: Engelmeier R S , O'Connell J B , Walsh R , Rad N , Scanlon P J , Gunnar R M
Published: June 2011

It has been suspected that the increased sympathetic activity seen in patients with chronic congestive heart failure from dilated cardiomyopathy may be harmful. We therefore tested the long-term effect of metoprolol on eight patients in a double-blind, randomized protocol and 12 patients in an unblinded, crossover protocol who were treated for 12 months (range 10 to 24), and compared them with 16 similar subjects who were treated with placebo for 10 months (range 6 to 12) in a double-blind, randomized protocol. Patients were followed by serial clinical assessment, treadmill testing, radionuclide ventriculography, and echocardiography. Metoprolol-treated patients had an improvement in mean exercise capacity by 3 mets (p less than .0001) while experiencing a significant improvement in functional classification (p less than .001) during both the double-blind and open-label crossover studies and had an improved ejection fraction during the double-blind study (p less than .02). These improvements were not seen in matched control subjects receiving placebo. Seven of 20 patients receiving long-term metoprolol therapy had resolution of nearly all symptoms of heart failure, doubled their exercise capacity, and had progressive improvement in resting radionuclide left ventricular ejection fraction (12.6 +/- 3% to 26.9 +/- 6%) and echocardiographic left ventricular end-diastolic dimension (7.7 +/- 0.5 to 6.5 +/- 0.5 cm). Only one of 21 patients treated was intolerant of metoprolol. We conclude that metoprolol can be given safely to a select group of patients with dilated cardiomyopathy in doses that substantially reduce both resting and exercise heart rates. Long-term beta-blockade improved functional class and exercise capacity in 14 of 20 patients while producing an exceptional clinical response in seven that was accompanied by improved resting parameters of left ventricular function.
Metabolic fate of radioiodinated heptadecanoic acid in the normal canine heart.
Authors: Visser F C , van Eenige M J , Westera G , Den Hollander W , Duwel C M , van der Wall E E , Heidendal G A , Roos J P
Published: June 2011

To clarify the metabolic fate of radioiodinated heptadecanoic acid in myocardium, the time course and distribution of the radioactivity over 131I-heptadecanoic acid, free radioiodide, and various lipids (with incorporated iodoheptadecanoic acid) were determined in normal canine myocardium. In 10 dogs seven biopsy specimens were taken over 30 min after injection of 131I-heptadecanoic acid. The radioactivity in the specimens increased until the fifth minute and decreased thereafter, with a half-time of 36 min. In the fifth minute, 61% of the radioactivity was free iodide, and its curve paralleled the curve of the total radioactivity. As early as the first minute 131I-heptadecanoic acid activity was reduced to 14% and decreased further. Activity of radioiodinated phospholipids, (mono, di, tri)-glycerides, and cholesterol-esters remained constant after an initial increase. These results indicate that immediately after uptake, 131I-heptadecanoic acid is either metabolized, liberating the radioiodide, or stored in lipids. Because the activity of radiolabeled lipids remained constant during the study period and because iodide activity paralleled the total activity in biopsy specimens, it is concluded that in normal myocardium, washout of free radioiodide determines the elimination rate as observed during a scintigraphic study. Thus the elimination rate cannot be related to the beta-oxidation rate as previously supposed.
Effect of heart rate on the canine end-systolic pressure-volume relationship.
Authors: Maughan W L , Sunagawa K , Burkhoff D , Graves W L , Hunter W C , Sagawa K
Published: June 2011

Although the rate dependence of isolated muscle contractility is well known, the ventricular end-systolic pressure-volume relationship (ESPVR) has been reported to be insensitive to heart rate. To resolve this contradiction, we used an isolated, ejecting canine heart preparation perfused at a constant coronary arterial pressure. Heart rate was changed from 60 to 200 beats/min in steps of 20 beats/min. At least 10 pressure-volume loops under different filling pressures were obtained at each heart rate in each of six hearts. Over a heart rate range from 60 to 120 beats/min, the slope of the ESPVR (Ees) increased significantly from 3.5 +/- 0.4 (SE) to 5.3 +/- 0.6 mm Hg/ml. In the range between 120 and 180 beats/min there was little change in Ees (5.3 +/- 0.6 to 5.4 +/- 0.6 mm Hg/ml), but at 200 beats/min Ees increased slightly to 5.7 +/- 0.5 mm Hg/ml. The volume axis intercept (V0) of the ESPVR changed little over the range of heart rate from 60 to 160 beats/min (10.2 +/- 2 ml to 9.4 +/- 1.3 ml) but increased to 15.2 +/- 1.2 ml at a rate of 200 beats/min. The change in ESPVR with increase in heart rate from 60 to 120 beats/min (i.e., increase in Ees without change in V0) is the same as those seen with a positive inotropic intervention with calcium or cathecholamines, whereas the V0 changes over the range from 160 to 200 beats/min is similar to those seen with regional ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of platelet function in thrombosis.
Authors: Marcus A J , Safier L B , Ullman H L , Broekman M J , Islam N , Oglesby T D , Gorman R R , Ward J W
Published: June 2011

Accumulating experimental and clinical evidence indicates that a time for reappraisal of therapeutic modalities designed to inhibit the eicosanoid pathway as it may affect vascular disease may be approaching. Pharmacologic agents originally used were chosen because they were capable of suppressing platelet functions such as aggregation, release, and adhesion. The goals of clinical trials were to evaluate medications that would prevent or reduce platelet accumulation in critically located blood vessels of the heart, brain, and extremities and on vascular prostheses. Evaluation of results of therapeutic trials has been difficult and this is superimposed on less-than-complete knowledge of the basic pharmacology of the drugs that have been used. Participation of neutrophils and possibly macrophages in the thrombotic process is now well recognized on morphologic grounds. Because different cell types such as platelets, neutrophils, and endothelial cells have been shown to interact biochemically by sharing precursors and intermediates of the eicosanoid pathway, the pharmacologic approach to inhibition of vascular disease may require reevaluation. Neutrophils appear to lack a cyclooxygenase pathway but serve as a source of the lipoxygenase product leukotriene B4 (LTB4). Actions of LTB4 include neutrophil aggregation, adhesion of neutrophils to endothelial cells, chemotaxis, chemokinesis, and plasma exudation. We have demonstrated in vitro that released free arachidonic acid from aspirin-treated platelets can serve as a source of neutrophil LTB4. Leukotrienes C4, D4, and E4 are agonists for various functions of vascular endothelium and smooth muscle. Most pharmacologic agents used in the treatment of vascular diseases inhibit the cyclooxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of sublingually administered nitroglycerin on forearm vascular resistance in patients with heart failure and in normal subjects.
Authors: Imaizumi T , Takeshita A , Ashihara T , Nakamura M
Published: June 2011

This study examined the effects of sublingually administered nitroglycerin on forearm resistance vessels in normal subjects (n = 9) and in patients with congestive heart failure (n = 8). Forearm blood flow was measured with a strain-gauge plethysmograph and forearm vascular resistance was calculated. To assess the magnitude of reflex forearm vasoconstriction triggered by decreased central venous pressure after sublingual nitroglycerin, lower body negative pressure (LBNP) was applied to produce a comparable decrease in central venous pressure to that after nitroglycerin. The change in forearm vascular resistance during LBNP was compared with that after nitroglycerin. In normal subjects, LBNP increased but nitroglycerin did not change forearm vascular resistance. In patients with congestive heart failure neither nitroglycerin nor LBNP changed forearm vascular resistance. The direct vasodilator effect of nitroglycerin on forearm resistance vessels assessed by the difference between the change in forearm vascular resistance produced by nitroglycerin and that during LBNP tended to be less in patients with congestive heart failure than in normal subjects, which might have resulted from decreased vasodilator capacity of resistance vessels in patients with congestive heart failure. Changes in forearm vascular resistance with a cold pressor test were not different between normal subjects and patients with congestive heart failure. These data suggest that in normal subjects, nitroglycerin does not alter forearm vascular resistance because its dilator effect is offset by reflex vasoconstriction. In patients with congestive heart failure, reflex vasoconstriction is impaired but the direct vasodilator effect of nitroglycerin also tends to be reduced, so that as a net effect forearm vascular resistance is not altered.
Prognostic significance and natural history of left ventricular thrombi in patients with acute anterior myocardial infarction: a two-dimensional echocardiographic study.
Authors: Spirito P , Bellotti P , Chiarella F , Domenicucci S , Sementa A , Vecchio C
Published: June 2011

Fifty-eight patients with transmural anterior myocardial infarction were prospectively studied with serial two-dimensional echocardiography to determine the clinical implications and prognostic significance of detection of left ventricular thrombus during acute myocardial infarction, the incidence of systemic embolization, and the possible occurrence of spontaneous regression of left ventricular thrombi. Patients were not treated with anticoagulants or platelet inhibitors during the acute phase of infarction or during follow-up. Two-dimensional echocardiograms were obtained within 24 hr of myocardial infarction, every 24 hr until day 5, every 48 hr until day 15, and every month for a follow-up of 2 to 11 months (mean 7), in the surviving patients; a total of 774 echocardiograms were obtained. Left ventricular thrombi were identified in 24 (41%) of the 58 study patients, and developed within 48 hr of infarction in 11 of these patients. Ten (91%) of the 11 patients with early thrombus formation died during hospitalization or during follow-up, while only two (15%) of the 13 who developed a thrombus after 48 hr of infarction died (p less than .005). Incidence of Killip class III or IV, total lactic dehydrogenase values, and extent of wall motion abnormalities were significantly higher in patients who developed a thrombus within 48 hr of infarction than in patients without thrombus. On the other hand, in patients who developed a thrombus after 48 hr of infarction, these parameters were not significantly different from those in patients who did not develop a thrombus. Spontaneous regression of thrombi was documented in three (20%) of the 15 patients who survived the acute phase of myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparative long-term effects of coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty on regional coronary flow reserve.
Authors: Bates E R , Aueron F M , Legrand V , LeFree M T , Mancini G B , Hodgson J M , Vogel R A
Published: June 2011

To evaluate the relative long-term improvement in coronary artery hemodynamics after revascularization by coronary artery bypass graft surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA), regional coronary flow reserve (CFR) was measured, by digital computer analysis of 35 mm cine film, in 50 men undergoing cardiac catheterization. CFR (mean +/- SEM) in 12 atherosclerotic arteries before revascularization was 1.02 +/- 0.05. Mean CFR in 29 normal arteries of men with normal coronary arteriograms was significantly higher (2.59 +/- 0.11) than that in 16 atherosclerotic arteries of patients revascularized by CABG (2.02 +/- 0.17, p less than .01) or in 14 atherosclerotic arteries of those revascularized by PTCA (1.97 +/- 0.12, p less than .01). No difference in CFR between the CABG and PTCA groups was found and variables known to influence CFR were similar between groups. Equivalent and significant long-term improvement in coronary artery hemodynamics is provided by CABG or PTCA. We postulate that the difference in CFR in the men with normal arteries and those who underwent revascularization was related to the effects of the general atherosclerotic process, which remain despite successful treatment by these techniques.
Use of an ultra short-acting beta-blocker in patients with acute myocardial ischemia.
Authors: Kirshenbaum J M , Kloner R A , Antman E M , Braunwald E
Published: June 2011

Esmolol is a new ultra short-acting (half-life [t1/2] beta 9 min) beta 1-adrenergic-receptor antagonist reported to have no intrinsic sympathomimetic activity. The safety and efficacy of esmolol in lowering the ventricular rate and rate-pressure product in patients with acute myocardial infarction (n = 5), postmyocardial infarction angina (n = 10), or acute unstable angina (n = 4), and without cardiogenic shock were studied. After a 30 min observation period, esmolol was titrated to a maximum dose of 300 micrograms/kg/min and infused for up to 420 min. The ventricular rate fell from 92 +/- 11 (mean +/- SD) to 77 +/- 13 beats/min (p less than .01) and the systolic arterial pressure decreased from 120 +/- 13 to 97 +/- 11 mm Hg (p less than .01) during the initial 30 min titration period. There was no significant change during the maintenance phase, and both the ventricular rate and arterial pressure returned rapidly toward baseline values within 30 min of termination of the infusion. The cardiac index fell from 2.8 +/- 0.6 to 2.2 +/- 0.6 liters/min/m2 (p less than .01) during the same period, and also returned to the baseline level 30 min after termination of the infusion. There was no significant change in the pulmonary capillary wedge pressure, respiratory rate, or PR interval. Five patients required termination of infusion because of hypotension and all recovered uneventfully within 30 min of stopping the esmolol. One patient required a brief infusion of dopamine to restore hemodynamic stability.(ABSTRACT TRUNCATED AT 250 WORDS)
Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial.
Authors: Mok C K , Boey J , Wang R , Chan T K , Cheung K L , Lee P K , Chow J , Ng R P , Tse T F
Published: June 2011

In a prospective, randomized, parallel study, two regimens of platelet-suppressant therapy (PST)--dipyridamole-aspirin and pentoxifylline-aspirin--were compared with standard oral anticoagulation with warfarin in the prevention of prosthetic heart valve thromboembolism. In the entire group of 254 patients followed for 395.6 patient-years, the thromboembolic rate was significantly less in the warfarin group (warfarin vs dipyridamole-aspirin, p less than .005; warfarin vs pentoxifylline-aspirin, p less than .05). Subgroup analysis disclosed that, in patients with isolated mitral valve replacement, warfarin was superior to both of the PSTs with respect to the prevention of thromboembolism (warfarin vs dipyridamole-aspirin, p = .005; warfarin vs pentoxifylline-aspirin, p less than .05). Furthermore, a significant number of our patients could not tolerate the antiplatelet agents. However, in the rare situation in which repeated significant bleeding occurs despite careful adjustment of the dosage of warfarin, PST may be an acceptable alternate method of thromboembolism prophylaxis.
Amiodarone and its desethyl metabolite: tissue distribution and morphologic changes during long-term therapy.
Authors: Adams P C , Holt D W , Storey G C , Morley A R , Callaghan J , Campbell R W
Published: June 2011

The pharmacokinetic characteristics of amiodarone suggest extensive tissue deposition. We confirmed this by measuring tissue concentrations of the drug and of its major metabolite, desethylamiodarone, in human tissues. These were obtained at autopsy (n = 9), surgery (n = 7), or biopsy (n = 2) from 18 patients who had been treated with amiodarone for varying periods of time. High concentrations of amiodarone were found in fat (316 mg/kg wet weight in autopsy specimens, 344 mg/kg wet weight in biopsy specimens). Amiodarone and desethylamiodarone concentrations (mg/kg wet weight, autopsy samples) were also high in liver (391 and 2354), lung (198 and 952), adrenal gland (137 and 437), testis (89 and 470), and lymph node (83 and 316). We also found high concentrations of amiodarone (306 mg/kg wet weight) and desethylamiodarone (943 mg/kg wet weight) in abnormally pigmented ("blue") skin from patients with amiodarone-induced skin pigmentation. These values were 10-fold higher than those in unpigmented skin from the same patients. These high concentrations were associated with lysosomal inclusion bodies in dermal macrophages in the pigmented skin. The inclusion bodies were intrinsically electron dense and were shown to contain iodine by energy dispersive x-ray microanalysis. Lysosomal inclusion bodies shown by electron microscopy to be multilamellar were seen in other tissues. These tissues included terminal nerve fibers in pigmented skin, pulmonary macrophages, blood neutrophils, and hepatocytes and Kupffer cells. These characteristic ultrastructural findings occur in both genetic lipidoses and lipidoses induced by other drugs, e.g., perhexiline. We conclude that during therapy with amiodarone, widespread deposition of amiodarone and desethylamiodarone occurs. This leads to ultrastructural changes typical of a lipidosis. These changes are seen clearly in tissues associated with the unwanted effects of amiodarone, e.g., skin, liver and lung.
Cesium chloride-induced long QT syndrome: demonstration of afterdepolarizations and triggered activity in vivo.
Authors: Levine J H , Spear J F , Guarnieri T , Weisfeldt M L , de Langen C D , Becker L C , Moore E N
Published: June 2011

The identification of afterdepolarizations and their relationship to arrhythmias in vivo is not available. Experiments were undertaken to determine whether afterdepolarizations could be detected in monophasic action potentials (MAPs) recorded in vivo and whether they were related to arrhythmias in an intact canine preparation of the long QT syndrome. Isolated cardiac tissues from six dogs were studied to validate the technique. In simultaneous MAP and transmembrane recordings, afterdepolarizations induced with barium (early) or acetylstrophanthidin (delayed) were detected in MAPs when present in microelectrode recordings. MAPs were then recorded in situ in eight dogs with cesium chloride-induced long QT syndrome associated with ventricular arrhythmias. Afterdepolarizations were identified in each of the dogs and were similar to early afterdepolarizations identified in vitro; they occurred during phase 3 and were attenuated during overdrive pacing. The afterdepolarizations were closely related to arrhythmias: (1) afterdepolarizations always preceded ventricular arrhythmias, (2) the coupling intervals (CI) of the afterdepolarizations (AD) and the ventricular premature beats (VPB) were nearly identical (VPB CI = 1.06 AD CI -10.24; r2 = .87), (3) the take-off potentials of the ventricular premature beats were nearly identical to the amplitude of the afterdepolarizations (take-off potential = 0.98 afterdepolarization amplitude +0.46, r2 = .87), and (4) afterdepolarizations and ventricular arrhythmias resolved concurrently during overdrive pacing and with time. Thus, a new catheter technique has been validated and has been used to directly identify afterdepolarizations and triggered activity in vivo.
Effects of right ventricular ischemia on left ventricular geometry and the end-diastolic pressure-volume relationship in the dog.
Authors: Goto Y , Yamamoto J , Saito M , Haze K , Sumiyoshi T , Fukami K , Hiramori K
Published: June 2011

We studied the effects of right ventricular ischemia on left ventricular three-dimensional geometry and the end-diastolic pressure-volume relationship in 16 open-chest dogs before and after pericardiectomy. Left ventricular volume was calculated from three internal dimensions measured with ultrasonic crystals. In one group of eight dogs, right coronary artery (RCA) occlusion for 2 min with the pericardium intact reduced aortic flow by 24 +/- 9% (p less than .001) and septal-lateral dimension by 8 +/- 5% (p less than .01), without changing anterior-posterior and apical-basal dimensions. However, parameters of left ventricular systolic function (aortic flow, left ventricular systolic pressure, peak dP/dt, and mean percent systolic shortening) were similar to those observed at a comparable level of left ventricular end-diastolic volume during inferior vena caval occlusion. In the other group of eight dogs, during RCA occlusion before pericardiectomy the left ventricular end-diastolic pressure-volume relationship determined during rapid blood transfusion shifted leftward and upward significantly from the preocclusion relationship. After pericardiectomy, RCA occlusion caused less significant changes in aortic flow and septal-lateral dimension as well as in the left ventricular end-diastolic pressure-volume relationship. We concluded that right ventricular ischemia causes a leftward shift of the interventricular septum in end-diastole and an alteration of the left ventricular end-diastolic pressure-volume relationship without changing left ventricular myocardial performance. These changes are enhanced by the intact pericardium.
The nature of opioid involvement in the hemodynamic respiratory and humoral responses to exercise.
Authors: Staessen J , Fiocchi R , Bouillon R , Fagard R , Lijnen P , Moerman E , De Schaepdryver A , Amery A
Published: June 2011

After 30 min rest in the lying position, 12 healthy male volunteers (average age 22 years) received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg iv followed by a continuous infusion of 10 mg/hr). Thereafter they rested for a further 30 min in the recumbent position and for 15 min sitting on a bicycle ergometer; they then exercised to exhaustion. At rest plasma levels of adrenocorticotropin (ACTH), cortisol, and aldosterone increased during infusion of naloxone, while body temperature decreased. During exercise the difference in plasma ACTH between naloxone and saline periods was abolished, while the differences in plasma cortisol and aldosterone lost statistical significance. Intra-arterial pressure, heart rate, ventilation, O2 uptake, and CO2 output were continuously monitored throughout the experiment and were not affected by naloxone. This was also the case for several hormonal and biochemical measurements, including those of plasma renin, angiotensin II, norepinephrine, 13,14-dihydro-15-keto-prostaglandin F2 alpha, glucose and lactate, and serum insulin and growth hormone. Exercise performance was not changed by naloxone. In conclusion (1) during exhaustive graded exercise of short duration opioidergic inhibition of the pituitary-adrenocortical axis is probably not sustained, (2) apart from the latter mechanism, the present study does not support the hypothesis that endogenous opioids are involved in various hemodynamic, respiratory, and hormonal responses to this type of exercise.
Thromboxane A2 and prostaglandin endoperoxide receptors in platelets and vascular smooth muscle.
Authors: Saussy D L , Mais D E , Knapp D R , Halushka P V
Published: June 2011

9,11-Dimethylmethano-11,12-methano-16-(3-iodo-4-hydroxyphenyl)-13, 14-dihydro-13-aza-15 alpha beta-omega-tetranor-TXA2 (I-PTA-OH), a recently synthesized thromboxane (TX) A2/prostaglandin (PG) H2 receptor antagonist, was shown to be a competitive antagonist of human platelet aggregation induced by the stable endoperoxide analog U46619. This antagonism was due to competitive blockade of the platelet TXA2/PGH2 receptor since I-PTA-OH did not antagonize the first phase of ADP-induced aggregation which is TXA2/PGH2 independent, nor did it inhibit TXA2 synthesis. In addition, analysis of dose-response curves to U46619 (0.1 to 40 microM) in the presence of increasing concentrations of I-PTA-OH (0.5 to 10 microM) showed that I-PTA-OH produced a parallel rightward shift of the dose-response curve. Further analysis of the data in the form of a Schild plot yielded a straight line with a slope (m = 1.03) not significantly different from -1. These results are consistent with the notion that I-PTA-OH acts as a competitive antagonist of the TXA2/PGH2 receptor.