bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracoronary thrombus and complex morphology in unstable angina. Relation to timing of angiography and in-hospital cardiac events.
Authors: Freeman M R , Williams A E , Chisholm R J , Armstrong P W
Published: June 2011

In 78 consecutive patients with unstable angina, we performed coronary angiography randomized to either the first day of presentation or later during the hospital admission to assess the frequency of intracoronary thrombus and complex coronary morphology relative to the time of symptomatic presentation and the impact of these angiographic features on outcome. Early angiography (17 +/- 6 hours) was performed in 42 patients and late angiography in 36 patients (5.7 +/- 2.1 days). Twelve patients randomized to late angiography required urgent cardiac catheterization 3.9 +/- 2.2 days after admission. Coronary thrombi were present in 43% (18 of 42) of early angiography patients and in 38% (14 of 36) of late angiography patients (p = NS). Only 21% (five of 24) late elective angiography patients had coronary thrombi, but 75% (nine of 12) of late urgent angiography patients had thrombi (p less than 0.05 vs. both early and late elective angiography patients). There was no difference in the frequency of complex coronary morphology among patients randomized to early angiography (42%, or 15 of 36), late urgent angiography (42%, or five of 12), and late elective angiography (38%, or nine of 24). Cardiac events (death, myocardial infarction, and urgent revascularization) were more frequent in the patients with coronary thrombus (73%, or 23 of 32), complex coronary morphology (55%, or 16 of 29), and multiple-vessel disease (58%, or 29 of 50) than in the patients without these angiographic features (17%, or eight of 46; 31%, or 15 of 49; and 7%, or two of 28, respectively; all p less than 0.05). Multiple regression analysis demonstrated that coronary thrombus was the best angiographic predictor of cardiac events. Thus, angiographic detection of intracoronary thrombi varies according to the temporal relation between angiography and chest pain at rest.
An overview of randomized trials of rehabilitation with exercise after myocardial infarction.
Authors: O'Connor G T , Buring J E , Yusuf S , Goldhaber S Z , Olmstead E M , Paffenbarger R S , Hennekens C H
Published: June 2011

Of 22 randomized trials of rehabilitation with exercise after myocardial infarction (MI), one trial had results that achieved conventional statistical significance. To determine whether or not these studies, in the aggregate, show a significant benefit of rehabilitation after myocardial infarction, we performed an overview of all randomized trials, involving 4,554 patients; we evaluated total and cardiovascular mortality, sudden death, and fatal and nonfatal reinfarction. For each endpoint, we calculated an odds ratio (OR) and 95% confidence interval (95% CI) for the trials combined. After an average of 3 years of follow-up, the ORs were significantly lower in the rehabilitation than in the comparison group: specifically, total mortality (OR = 0.80 [0.66, 0.96]), cardiovascular mortality (OR = 0.78 [0.63, 0.96]), and fatal reinfarction (OR = 0.75 [0.59, 0.95]). The OR for sudden death was significantly lower in the rehabilitation than in the comparison group at 1 year (OR = 0.63 [0.41, 0.97]). The data were compatible with a benefit at 2 (OR = 0.76 [0.54, 1.06]) and 3 years (OR = 0.92 [0.69, 1.23]), but these findings were not statistically significant. For nonfatal reinfarction, there were no significant differences between the two groups after 1 (OR = 1.09 [0.76, 1.57]), 2 (OR = 1.10 [0.82, 1.47]), or 3 years (OR = 1.09 [0.88, 1.34]) of follow-up. The observed 20% reduction in overall mortality reflects a decreased risk of cardiovascular mortality and fatal reinfarction throughout at least 3 years and a reduction in sudden death during the 1st year after infarction and possibly for 2-3 years. With respect to the independent effects of the physical exercise component of cardiac rehabilitation, the relatively small number of "exercise only" trials, combined with the possibility that they may have had a formal or informal nonexercise component precludes the possibility of reaching any definitive conclusion. To do so would require a randomized trial of sufficient size to distinguish between no effect and the most plausible effect based on the results of this overview.
Relative impact of targeted versus populationwide cholesterol interventions on the incidence of coronary heart disease. Projections of the Coronary Heart Disease Policy Model.
Authors: Goldman L , Weinstein M C , Williams L W
Published: June 2011

We used the Coronary Heart Disease Policy Model, a state-transition computer simulation, to assess the absolute and relative effects of two different national cholesterol interventions: a targeted program to identify and treat all individuals with elevated serum cholesterol levels (greater than or equal to 250 mg/dl) versus a populationwide program to reduce everyone's serum cholesterol level. Based on the assumptions inherent in our model, which uses the Framingham Heart Study coefficients, we estimate the targeted program would reduce projected coronary heart disease absolute incidence by 8-10% in men ages 35-54 years and by 1-4% in men ages 55-74 years. Our model suggests that similar reductions in coronary heart disease incidence could be achieved by a 10 mg/dl populationwide reduction in serum cholesterol levels. In women, the targeted program would yield greater relative and absolute benefits and would be equivalent to a approximately 23 mg/dl populationwide reduction in serum cholesterol. We conclude that it would be inadvisable to rely solely on targeted cholesterol reduction programs to reduce national coronary heart disease.
Dynamic mitral regurgitation. An important determinant of the hemodynamic response to load alterations and inotropic therapy in severe heart failure.
Authors: Keren G , Katz S , Strom J , Sonnenblick E H , LeJemtel T H
Published: June 2011

Cardiac performance and mitral regurgitation were measured by Doppler echocardiography and right heart catheterization in 12 patients with severe congestive heart failure who performed isometric exercise during control and intravenous administration of dobutamine and nitroglycerin. During control isometric exercise, mitral regurgitant volume increased from 18 +/- 13 to 31 +/- 17 ml (p less than 0.01), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially decreased. At rest, dobutamine decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 10 ml (p less than 0.05), while forward stroke volume increased from 46 +/- 13 to 55 +/- 15 ml (p less than 0.05). During isometric exercise, dobutamine tended to decrease mitral regurgitant volume (24 +/- 12 vs. 31 +/- 17 ml; NS) when compared with control exercise. At rest, nitroglycerin decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 11 ml (p less than 0.05), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially increased. Similarly, during isometric exercise, nitroglycerin decreased mitral regurgitant volume from 31 +/- 17 to 20 +/- 14 ml (p less than 0.05), while significantly increasing forward stroke volume. At control rest, the median mitral regurgitant fraction was 24% for the 12 patients. Neither dobutamine nor nitroglycerin changed significantly forward stroke and mitral regurgitant volumes at rest and during isometric exercise in the six patients with resting mitral regurgitant fraction below the median. In contrast, dobutamine and nitroglycerin significantly decreased mitral regurgitant volume and increased forward stroke volume both at rest and during isometric exercise in the six patients with mitral regurgitant fraction greater than the median.(ABSTRACT TRUNCATED AT 250 WORDS)
HLA-DR/DQ antigens and reactivity to B cell alloantigen D8/17 in Indian patients with rheumatic heart disease.
Authors: Taneja V , Mehra N K , Reddy K S , Narula J , Tandon R , Vaidya M C , Bhatia M L
Published: June 2011

D8/17, a B cell alloantigen, and its occurrence with DR/DQ antigens was examined in 54 patients with rheumatic heart disease and matched North Indian controls. Thirty-four patients (62.9%) carried D8/17 as compared with a frequency of 12.5% in controls (chi 2 by Yates', 18.75; p less than 0.0001). A marginally increased frequency of human leukocyte antigen (HLA)-DR3 (44.2% vs. 28.8%) and a significantly reduced frequency of HLA-DR2 (21.1% vs. 46.6%; p less than 0.005) was observed in patients as compared with controls. However, the most significant positive association was observed with HLA-DQw2 (63.4% in patients and 31.5% in controls; chi 2 by Yates', 9.85; p less than 0.005). The DQw2 association was significant only in the D8/17-positive patients. These observations suggest that the disease susceptibility gene in rheumatic heart disease may be nearer to the HLA-DQ locus than to the HLA-DR.
Natural history of aortoarteritis (Takayasu's disease).
Authors: Subramanyan R , Joy J , Balakrishnan K G
Published: June 2011

The natural history of aortoarteritis was studied in 88 patients (54 women and 34 men). The average age was 24.0 +/- 8.8 years at onset of symptoms and 28.3 +/- 9.9 years at diagnosis. The follow-up period was 83.6 +/- 74.4 months from onset and 33.2 +/- 37.0 months from diagnosis. Ten patients (11.4%) died during follow-up (0.016 deaths/patient year), and 22 patients (25%) suffered major nonfatal events (0.042 events/patient year). The cumulative survival at 5 and 10 years after the onset was 91.0 +/- 3.3% and 84.0 +/- 5.6% (mean +/- SEM), respectively. The event-free survival rates at the same intervals after onset were 74.9 +/- 5.0% and 64.0 +/- 7.4%, respectively. The overall survival and event-free survival at 10 years after diagnosis was 80.3 +/- 6.5% and 61.6 +/- 7.5%, respectively. Patients with no complications or a mild single complication at diagnosis had a higher event-free survival rate than those with severe single complication or multiple complications at 5 years--97.0 +/- 2.9% and 59.7 +/- 7.3%, respectively (p less than 0.001). Severe hypertension (p less than 0.01), severe functional disability (p less than 0.01), and evidence of cardiac involvement (p less than 0.05) were good predictors of either death or major event on follow-up. These data are useful in making an objective assessment of the prognosis and in planning elective interventions.
The N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of the atrial natriuretic factor prohormone each circulate in humans and increase in congestive heart failure.
Authors: Winters C J , Sallman A L , Baker B J , Meadows J , Rico D M , Vesely D L
Published: June 2011

Two peptides consisting of amino acids 1-30 and 31-67 of the N-terminus of the prohormone of atrial natriuretic factor (pro-ANF) that have vasodilatory and natriuretic properties were investigated to determine if they circulate in humans. Specific and sensitive radioimmunoassays were developed to amino acids 1-30, 31-67, and 99-126 of pro-ANF. Evaluation of human plasma that had been subjected to reverse-phase high-pressure liquid chromatography suggested that pro-ANFs 1-30 and 31-67 as well as ANF were distinct peaks in human plasma corresponding exactly to pure synthetic peaks of these peptides on high-pressure liquid chromatography. Molecular weight determination of the endogenous immunoreactive peptides measured in plasma by G-50 Sephadex gel permeation chromatography revealed that the pro-ANF 1-30 radioimmunoassay recognized a peptide of 10,000 MW, which is consistent with it measuring the whole N-terminus of pro-ANF (amino acids 1-98) but without ANF (C-terminus) attached to it. The pro-ANF 31-67 radioimmunoassay recognized mainly (more than 95%) a peptide of 3,900-4,000 MW, which corresponds closely with its actual molecular weight of 3,878. Our ANF radioimmunoassay recognizes a peptide in plasma of 3,000 MW with the known molecular weight of ANF being 3,081. The mean circulating concentrations of immunoreactive pro-ANF 1-98, pro-ANF 31-67, and ANF in 54 control subjects were 531 +/- 25, 371 +/- 18, and 22 +/- 1 fmol/ml (+/- SEM), respectively. Thirty patients with varying severity of congestive heart failure were also studied. The N-terminus, C-terminus, and pro-ANF 31-67 increased: twofold for New York Heart Association functional Class II, threefold to ninefold for Class III, and 10- to 20-fold for Class IV patients with congestive heart failure. Thus, the N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of pro-ANF as well as ANF circulate normally and increased proportionately to the increasing severity of congestive heart failure. However, because the pro-ANF 31-67 radioimmunoassay was the only assay that discriminated between patients with Class I congestive heart failure and control subjects, this assay may be the most useful to accurately classify the severity of congestive heart failure.
Assessment of severity of coronary stenoses using a Doppler catheter. Validation of a method based on the continuity equation.
Authors: Johnson E L , Yock P G , Hargrave V K , Srebro J P , Manubens S M , Seitz W , Ports T A
Published: June 2011

The coronary Doppler catheter has been used primarily in the measurement of coronary vasodilator reserve, most often as the ratio of peak to resting velocity in response to an intracoronary dose of papaverine. We have developed a new method based on the continuity equation using a Doppler catheter for the assessment of stenosis severity in the coronary circulation by means of quantitative velocity measurements obtained by complex spectral analysis of the Doppler signal. With this system we have been able to detect a high-velocity stenosis jet in a canine model of coronary stenosis of known cross-sectional area. Using the peak velocity obtained by complex spectral analysis, we found a strong correlation between cross-sectional areas determined by the continuity equation and known cross-sectional areas (r = 0.93, SEE = 0.23 mm2). We also found a strong correlation between the ratio of peak stenosis velocity to proximal vessel velocity and percent diameter and percent area stenosis (r = 0.91 and 0.92, respectively). When the velocity was determined with conventional zero-crossing methods for these parameters, there was no correlation between calculated and known values for cross-sectional area and percent diameter or area stenosis. Measurements of the vasodilator reserve in response to intracoronary papaverine before and after implantation of the stenosis did not correlate with any of the anatomic parameters of stenosis severity regardless of the method of signal analysis (zero-crossing or complex spectral analysis). The measurement of quantitative peak coronary velocity with a Doppler catheter using complex spectral analysis may provide an accurate method for determining the severity of a coronary stenosis.
Details of coronary stenosis morphology influence its hemodynamic severity and distal flow reserve.
Authors: Fedele F A , Sharaf B , Most A S , Gewirtz H
Published: June 2011

Differences in coronary flow reserve with anatomically similar coronary artery stenoses have been attributed to 1) nonstandard physiologic conditions, 2) inadequacies of measurements of coronary artery stenosis dimension and/or coronary blood flow, and 3) inadequate hyperemic stimulus. Our study tested the hypothesis that details of coronary artery stenosis geometry, which may or may not be apparent on coronary angiograms, also may contribute importantly to such differences. A simple and complex coronary artery stenosis, each of which reduced vessel cross-sectional area by 84%, was introduced in random order into the left anterior descending coronary artery of nine closed-chest, sedated swine. The simple stenosis had a single lumen while the complex stenosis had five small lumena whose combined area equaled that of the single lumen stenosis. Measurements of hemodynamics and regional myocardial blood flow (microspheres) were made at control and after 10 minutes of adenosine infused at 400 micrograms/min and then at 800 micrograms/min distal to each stenosis. Both heart rate and aortic mean pressure were controlled and thus did not change versus initial baseline (129 +/- 4 minutes and 120 +/- 10 mm Hg, mean +/- SD, respectively) during the study. Baseline total flow (ml/sec) distal to the stenosis was similar at each control (1.05 +/- 0.35 vs. 0.92 +/- 0.34, simple versus complex, respectively; p = NS). At maximal adenosine, total flow with the simple stenosis was 3.44 +/- 0.92 versus 2.77 +/- 0.51 for complex (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of cardiac beta-adrenergic receptors by captopril. Implications for congestive heart failure.
Authors: Maisel A S , Phillips C , Michel M C , Ziegler M G , Carter S M
Published: June 2011

The interaction of the renin-angiotensin system and the sympathetic nervous system in patients with congestive heart failure is not well understood. We tested the hypothesis that angiotensin-converting enzyme inhibitors can resensitize the beta-adrenergic receptor system. Guinea pigs were given captopril, isoproterenol, or both for 2 weeks. At death, cardiac sarcolemmal and light vesicle fractions and intact mononuclear leukocytes were prepared. Captopril treatment led to an up-regulation of cardiac beta 1- but not mononuclear leukocyte beta 2-adrenergic receptors and an increase in isoproterenol-stimulated adenylate cyclase activity in the heart. Animals treated with isoproterenol developed cardiac hypertrophy, had increased plasma norepinephrine levels, and had a decreased number and responsiveness of both cardiac and mononuclear leukocyte beta-adrenergic receptors. Concomitant treatment with captopril attenuated alterations of heart weight, plasma norepinephrine levels, and cardiac beta-receptor density and function. In contrast to its cardiac effects, captopril treatment did not diminish the down-regulation of mononuclear leukocyte beta 2-adrenergic receptors by isoproterenol. Our data suggest that captopril may resensitize the cardiac but not the mononuclear leukocyte beta-adrenergic receptor-adenylate cyclase system after long-term catecholamine exposure.
Assessment of prosthetic heart valve function by Doppler echocardiography. A decade of experience.
Authors: Labovitz A J
Published: June 2011

Since the first report of the application of Doppler echocardiography in the evaluation of prosthetic heart valves 10 years ago, dozens of studies have reaffirmed the usefulness of this technique in the noninvasive assessment of transvalvular hemodynamics. Most of these studies have established "normal values" for Doppler-determined pressure gradients and valve areas of prosthetic mitral and aortic valves. Although these studies have established the "normal range," they have all emphasized the individual variability in clinically normal functioning valves. Most of these studies have confirmed the extraordinary sensitivity and specificity of Doppler in detecting prosthetic valve dysfunction. The study by Burstow et al further emphasizes the excellent correlation obtained with simultaneous Doppler and catheter transvalvular pressure gradient measurements. The addition of both color flow Doppler techniques and transesophageal echocardiography can only serve to enhance the clinical diagnostic accuracy of this technique. At the present time, Doppler echocardiography is clearly the procedure of choice for the evaluation of the patient with suspected prosthetic heart valve dysfunction.
Mechanisms and risk factors for proarrhythmia with type Ia compared with Ic antiarrhythmic drug therapy.
Authors: Levine J H , Morganroth J , Kadish A H
Published: June 2011

Proarrhythmia defined as the exacerbation of existing arrhythmias or the genesis of new arrhythmias de novo may result from any antiarrhythmic agent. The two general clinical syndromes of sustained arrhythmias that result appear to have distinct clinical properties that are consistent with the proposed basic mechanisms of arrhythmogenesis. Torsades de points occurs most commonly in association with administration of type Ia antiarrhythmic agents and has characteristics most consistent with triggered activity mediated by early after depolarization. Conversely, incessant, sustained, monomorphic, wide complex ventricular tachycardia occurs most commonly in association with type Ic antiarrhythmic agents and has characteristics most consistent with incessant reentry. These general subdivisions are probably oversimplified, and in fact, much overlap likely exists. In addition, these proposed mechanisms may not apply to other forms of proarrhythmia such as an increased frequency of isolated ventricular premature couplets or repetitive forms. Furthermore, proarrhythmia may also occur during treatment of supraventricular arrhythmias; although some of these described syndromes are consistent with incessant reentry, the clinical syndromes are not sufficiently defined to better characterize potential mechanisms. Further investigation, therefore, is needed to better define the mechanisms in question, but the mechanisms proposed in this article help to provide a rational approach toward understanding and dealing with clinical proarrhythmia.
Intravascular ultrasound cross-sectional arterial imaging before and after balloon angioplasty in vitro.
Authors: Tobis J M , Mallery J A , Gessert J , Griffith J , Mahon D , Bessen M , Moriuchi M , McLeay L , McRae M , Henry W L
Published: June 2011

A prototype ultrasound imaging catheter was evaluated in vitro using 17 human atherosclerotic artery segments before and after balloon dilatation angioplasty. The catheter was 1.2 mm in diameter and incorporated a single 20-MHz ultrasound transducer to obtain cross-sectional images of the arterial lumen. In 15 of the 17 (88%) arteries, high quality images were obtained, which demonstrated clear demarcation between the lumen and the endothelium, the atheroma plaque, the muscular media, and the adventitia. Qualitative characteristics of plaque disruption, dissection, and residual flaps were readily visible. In addition, quantitative information about cross-sectional lumen area was obtained before and after balloon dilatation. The mean cross-sectional lumen area increased from 8.7 to 15.1 mm2 (p less than 0.01) following balloon dilatation. The lumen area measured from the ultrasound images following dilatation correlated closely with the area measured from histologic sections (r = 0.88). The results from this study indicate that a small-diameter ultrasound imaging catheter can be developed that will provide high-resolution qualitative and quantitative information during peripheral and coronary angioplasty.
Ultrasonic tissue characterization of human hypertrophied hearts in vivo with cardiac cycle-dependent variation in integrated backscatter.
Authors: Masuyama T , St Goar F G , Tye T L , Oppenheim G , Schnittger I , Popp R L
Published: June 2011

Integrated ultrasonic backscatter (IB) is a noninvasive measure of the acoustic properties of myocardium. Previous experimental studies have indicated that altered acoustic properties of the myocardium are reflected by the magnitude of variation of IB during the cardiac cycle. In our study, cardiac cycle-dependent variation of IB was noninvasively measured using a quantitative IB imaging system in 12 patients with uncomplicated pressure-overload hypertrophy and 13 patients with hypertrophic cardiomyopathy. Sixteen normal subjects served as a control. The magnitude of cardiac cycle-dependent variation of IB for the posterior wall was 6.0 +/- 0.9 dB in normal subjects, 5.7 +/- 0.8 dB in the patients with uncomplicated pressure-overload hypertrophy, and 6.7 +/- 2.1 dB in the patients with hypertrophic cardiomyopathy. There were no significant differences among any of these groups. In contrast, the magnitude of cardiac cycle-dependent variation of IB for the septum was significantly smaller in the patients with uncomplicated pressure-overload hypertrophy (2.8 +/- 1.3 dB) and in the patients with hypertrophic cardiomyopathy (3.1 +/- 2.3 dB) than in normal subjects (4.9 +/- 1.0 dB). The magnitude of cardiac cycle-dependent variation of IB was smaller as the wall-thickness index increased (r = -0.53, p less than 0.01, n = 82 for all data). This IB measure also correlated with percent-systolic thickening of the myocardium (r = 0.67, p less than 0.01, n = 82). Thus, alteration in the magnitude of cardiac cycle-dependent variation of IB was observed in hypertrophic hearts and showed apparent regional myocardial differences.
The diastolic hyperemic flow versus pressure relation. A new index of coronary stenosis severity and flow reserve.
Authors: Mancini G B , McGillem M J , DeBoe S F , Gallagher K P
Published: June 2011

The measurement of coronary flow reserve, traditionally calculated as the ratio of maximal hyperemic blood flow divided by basal flow, is difficult to interpret in serial studies because fluctuating hemodynamic parameters may affect either basal or hyperemic flow measurements. To determine the magnitude of this problem and to develop alternative approaches for measuring vascular reserve, 10 anesthetized dogs were instrumented with aortic and inferior vena cava occluders, electromagnetic coronary flow probes, and high-fidelity micromanometers in the left ventricle and aortic root. Coronary flow was measured in the basal state and during maximal hyperemia induced by a steady-state adenosine infusion. Observations were made in the absence of a stenosis and in the presence of two incremental degrees of subcritical stenosis produced by a rigid, external screw occluder. Several parameters of vascular reserve were determined: 1) coronary flow reserve (defined above), 2) mean hyperemic flow divided by mean aortic pressure, 3) mean hyperemic flow divided by the difference between mean aortic pressure and left ventricular end-diastolic pressure, and 4) the slope of the instantaneous relation between diastolic hyperemic flow versus pressure. Each parameter was measured during five steady-state pressure levels achieved by partial occlusion of either the inferior vena cava or the aorta and the levels ranged from 82 +/- 8 mm Hg (mean +/- SD) to 127 +/- 9 mm Hg during hyperemia. All measures of vascular reserve were found to be dependent on hemodynamic parameters such as heart rate and mean aortic pressure. The slope of the instantaneous relation between diastolic hyperemic flow and pressure, however, showed only minimal dependence on heart rate and, in contrast to coronary flow reserve measurements, distinguished between the normal and the two stenotic states. Further, this optimal performance of the hyperemic flow versus pressure slope index was shown in a model in which coronary flow and myocardial work were not independently controlled. This index provides a sensitive and reliable indication of subcritical stenosis severity that may have clinical applications.
Current approaches to drug therapy for the hypercholesterolemic patient.
Authors: Witztum J L
Published: June 2011

CAD is a complex disease with multiple etiologies and aggravating events. Yet, elevated plasma cholesterol levels, chiefly in the form of LDL, are essential for the progression of the atherosclerotic lesion. Any total plasma cholesterol level above an ideal of 180 mg/dl (and an LDL cholesterol level of 100 mg/dl) must be considered atherogenic in the presence of other risk factors. In patients at high risk for death from CAD, combined diet and drug therapy should have as a goal the attainment of ideal lipoprotein values. Drug therapies are now available that make it possible to substantially lower elevated LDL levels in almost all patients and even to achieve ideal levels in those at highest risk.
Primary pulmonary hypertension. Vascular structure, morphometry, and responsiveness to vasodilator agents.
Authors: Palevsky H I , Schloo B L , Pietra G G , Weber K T , Janicki J S , Rubin E , Fishman A P
Published: June 2011

The use of pharmacologic agents in the treatment of pulmonary hypertension has not proved to be uniformly successful or predictable. One possible reason for the vagaries in response is that the pulmonary vascular lesions are not consistent. We examined the relation between the structure of the pulmonary resistance vessels in unexplained (primary) pulmonary hypertension and the response to pulmonary vasodilators. Our study involved 19 patients with clinically unexplained pulmonary hypertension (mean pressure, 59 +/- 14 mm Hg). After characterizing them clinically and performing control hemodynamic measurements, we determined the acute effects of a series of vasodilator agents that have different mechanisms of action. In 16 patients, lung biopsy material was related to the hemodynamic studies; in nine patients, including six who had undergone open lung biopsy, the hemodynamic studies were related to the pathologic changes found at autopsy. Histologic specimens from all 19 patients were evaluated qualitatively and sorted into three subsets of hypertensive pulmonary arteriopathy: medial hypertrophy (with minimal intimal proliferation), arteriopathy with plexiform lesions (associated predominantly with concentric laminar intimal proliferation and fibrosis), and arteriopathy with microthrombotic lesions (associated predominantly with eccentric intimal proliferation and fibrosis). The 16 lung biopsies were also quantitated by morphometric techniques. Using a decrease in calculated pulmonary vascular resistance of more than 30% accompanied by a decrease in mean pulmonary arterial pressure of at least 10% to define vasodilation, only four patients were responders. The patients varied considerably in their responses to different vasodilator agents. Patients with similar clinical and hemodynamic profiles differed considerably with respect to the nature of their pulmonary vascular obstructive lesions and their responses to vasodilator agents. Qualitative histologic examination of lung tissue did not provide a basis for predicting how individual patients would respond to vasodilator agents. However, quantitative morphologic analysis of the initial open lung biopsy specimens did prove helpful in predicting acute responsiveness to vasodilator agents and the subsequent clinical course of these patients with unexplained (primary) pulmonary hypertension. An intimal area of more than 18% of the vascular cross-sectional area had an 85% predictive value for identifying the patients who did poorly during the first 36 months of follow-up.
Intracoronary adenosine administered after reperfusion limits vascular injury after prolonged ischemia in the canine model.
Authors: Babbitt D G , Virmani R , Forman M B
Published: June 2011

Myocardial salvage after reperfusion may be limited by deleterious vascular changes in the previously ischemic microcirculatory bed. This could result in a progressive decrease in blood flow in the capillary bed to potentially viable myocytes (no-reflow phenomenon). The effect of intracoronary adenosine on these changes was assessed in 15 closed-chest dogs subjected to 2 hours of proximal left anterior descending artery (LAD) occlusion followed by 3 hours of reperfusion. Animals randomly received adenosine (n = 8) 3.75 mg/min into the proximal LAD or an equivalent volume of saline (control) (n = 7) for 1 hour after reperfusion. Endothelial-dependent and independent coronary vasodilator reserve was determined using a chronically implanted volume-flowmeter on the mid-LAD at baseline and 1 and 3 hours after reperfusion with acetylcholine and papaverine infusions, respectively, into the proximal vessel. Regional myocardial blood flow was measured serially with radioactive microspheres and regional contractile function with contrast ventriculography. Both agonists produced a significant increase in LAD flow before occlusion. Endothelial-dependent and independent vasodilatory reserve was significantly reduced (p less than 0.05) at 1 and 3 hours after reperfusion in control animals compared with adenosine treatment. A progressive decrease in mid-LAD flow and increase in coronary vascular resistance after reperfusion was observed in control animals (p less than 0.05). The treated group manifested improved regional myocardial blood flow in endocardial regions from the central (0.73 +/- 0.15 versus 0.24 +/- 0.11 ml/g/min; p less than 0.02) and lateral ischemic zones (0.80 +/- 0.15 versus 0.34 +/- 0.12 ml/g/min; p less than 0.05) 3 hours after reperfusion. A significant reduction (p less than 0.05) in endocardial and midmyocardial flow compared with baseline was seen in control animals at 3 hours. Intravascular and interstitial neutrophil infiltration was reduced in adenosine animals and this was associated with relative ultrastructural preservation of endothelial cells. Regional ventricular function in the ischemic zone was improved in the adenosine group 3 hours after reperfusion (13.4 +/- 3.9% versus -5.3 +/- 1.6%; p less than 0.001). This study demonstrates that selective administration of adenosine after reperfusion significantly attenuates functional and structural abnormalities in the microvasculature after prolonged (2 hours) regional ischemia in the canine model. Prevention of microvascular injury and the non-reflow phenomenon by adenosine may preserve reversibly injured myocytes following restoration of blood flow to previously ischemic myocardium.
Increased adenosine concentration in blood from ischemic myocardium by AICA riboside. Effects on flow, granulocytes, and injury.
Authors: Gruber H E , Hoffer M E , McAllister D R , Laikind P K , Lane T A , Schmid-Schoenbein G W , Engler R L
Published: June 2011

Morbidity and mortality from acute coronary artery occlusion may be reduced if local myocardial adenosine concentration is augmented because 1) coronary collateral blood flow during ischemia increases with adenosine infusion, and 2) granulocytes that accumulate in the microcirculation during ischemia are, to a large extent, inhibited by adenosine from generating superoxide anion free radicals, from adhering to vascular endothelium, and from damaging endothelial cells in culture. Using a cultured lymphoblast model system, we found that 5-amino-4-imidazole carboxamide (AICA) riboside enhanced adenosine accumulation during ATP catabolism. Therefore, AICA riboside pretreatment was used in canine myocardium to selectively increase adenosine concentration in the ischemic area during 1 hour of ischemia. At 5 minutes of ischemia, endocardial flow to ischemic myocardium in saline-treated and AICA riboside-treated dogs was 0.06 +/- 0.03 and 0.34 +/- 0.11 ml/min/g, respectively (p less than 0.01); flow to nonischemic myocardium was not affected. Ventricular tachycardia and premature ventricular depolarizations were significantly attenuated in the AICA riboside-treated dogs. Blood pressure and heart rate were not affected by AICA riboside. In venous blood from ischemic tissue, adenosine increased from undetectable levels (less than 0.01 microM) to 0.22 +/- 0.08 microM in saline and 1.79 +/- 0.06 microM in AICA riboside-treated dogs, respectively (p less than 0.001). Coronary vein inosine concentrations were greater in saline than in AICA riboside-treated dogs. In separate in vitro studies, AICA riboside did not alter the removal rate of adenosine from canine blood. Indium-labeled granulocyte accumulation was significantly less in ischemic myocardium in AICA riboside-treated compared with saline-treated dogs. In addition, adenosine, but not AICA riboside, inhibited in vitro canine granulocyte superoxide production. We conclude that AICA riboside given before myocardial ischemia augments adenosine concentration, decreases arrhythmias, decreases granulocyte accumulation, and improves collateral flow to ischemic myocardium. One of the beneficial mechanisms could be an increased production of adenosine rather than inosine from ATP catabolism that causes vasodilation and inhibition of granulocytes. We propose a new hypothesis regarding regulation of the inflammatory reaction to ischemia in the microcirculation. Adenosine, in addition to its vasodilator action, is an anti-injury autacoid that links ATP catabolism to inhibition of granulocyte adherence, microvascular obstruction, and superoxide anion formation.
Slow and long-lasting modulation of myocardial repolarization produced by ectopic activation in isolated rabbit hearts. Evidence for cardiac "memory".
Authors: Costard-Jäckle A , Goetsch B , Antz M , Franz M R
Published: June 2011

Prolonged ventricular pacing induces T wave polarity changes that persist long after cessation of pacing. To examine how ventricular repolarization is modulated by prolonged changes in activation sequence, we studied the effect of ectopic pacing on the distribution of action potential durations (APDs) in nine isolated Langendorff-perfused rabbit hearts. A contact electrode probe was used to map right and left ventricular-epicardial monophasic action potentials during three consecutive changes in stimulus site, that is, 1) during 45 minutes of right atrial pacing, 2) during 120 minutes of right ventricular pacing, and 3) again, during 60 minutes of right atrial pacing. During each of these phases, the effect of activation sequence on repolarization was examined by linear-regression analysis of APD on activation time (AT). Results averaged for all nine hearts showed that during the initial atrial-pacing phase, APD was inversely related to AT (slope [S] = -1.63; r = 0.76), indicating that sites with earlier activation repolarized later. With the onset of ventricular pacing, the inverse correlation between AT and APD disappeared (S = -0.19; r = 0.31). Continuing ventricular pacing, however, produced slow changes in APD that restored the inverse relation (S = -0.71; r = 0.68 at 120 minutes; p less than 0.0002 versus 5 minutes). Switching from ventricular to atrial pacing again perturbed the inverse correlation (S = 0.28; r = 0.35) but at 60 minutes of atrial pacing, a significant inverse correlation was reestablished (S = -1.25; r = 0.53; p less than 0.01 versus 5 minutes). An inverse correlation between AT and APD tends to synchronize repolarization time (RT, the sum of AT and APD).(ABSTRACT TRUNCATED AT 250 WORDS)
Singlet oxygen-induced arrhythmias. Dose- and light-response studies for photoactivation of rose bengal in the rat heart.
Authors: Kusama Y , Bernier M , Hearse D J
Published: June 2011

In a study of aerobically perfused rat hearts, the in situ photoactivation (530-590 nm) of rose bengal (a process that leads to the production of singlet oxygen and superoxide) has been shown to lead to the rapid development of electrocardiographic abnormalities and arrhythmias. With rose bengal concentrations of 1,000, 500, 250, 100, and 50 nmol/l (n = 6/group), photoactivation (3,600 lx) led to electrocardiographic changes (inversion of the T wave, Q-T prolongation, or both) after 3.8 +/- 0.9, 4.5 +/- 0.7, 11.8 +/- 2.1, 24.8 +/- 3.9, and 65.3 +/- 6.0 seconds), respectively; ventricular premature beats occurred in 100% of hearts after 0.5 +/- 0.2, 1.1 +/- 0.3, 2.2 +/- 0.7, 4.4 +/- 0.8, and 6.6 +/- 1.2 minutes, respectively. Ventricular tachycardia occurred in 83%, 83%, 83%, 67%, and 50% of hearts after 2.1 +/- 0.2, 2.1 +/- 0.4, 2.8 +/- 0.7, 5.7 +/- 2.0, and 11.2 +/- 1.9 minutes, respectively, and complete atrioventricular block in 100%, 100%, 100%, 100%, and 67% of hearts after 3.8 +/- 0.7, 6.5 +/- 1.0, 5.5 +/- 0.9, 13.8 +/- 1.0, and 14.1 +/- 0.9 minutes, respectively. With a fixed concentration (250 nmol/l) of rose bengal, similar light-response relations were observed. Photoactivation of rose bengal had no effect on heart rate but caused a transient (0-4 minutes) vasodilation followed by a progressive vasoconstriction. In further studies in which rose bengal was washed out for 10 minutes before photoactivation, several arrhythmias still developed, indicating that rose bengal binds strongly to tissue and acts as a cellular level rather than in the vascular compartment. To assess the reversibility of rose bengal-induced effects, hearts (n = 6/group) were perfused with rose bengal (250 nmol/l) for 1, 2, 4, 6, and 20 minutes followed by perfusion in the dark for 19, 18, 16, 14, and 0 minutes, respectively. During dark perfusion, the incidence of arrhythmias declined and any decrease in coronary flow was reversed. However, analysis of contents of adenosine triphosphate, creatine phosphate, lactate, and creatine kinase leakage indicated the occurrence of severe injury that did not abate on termination of photoactivation. Finally, although many arrhythmias developed before the onset of vasoconstriction, the reduction in flow with consequent ischemia was shown to exacerbate vulnerability to arrhythmias. In conclusion, short-lived reactive oxygen intermediates such as singlet oxygen and superoxide, which are produced during the photoactivation of rose bengal, can cause rapid and major damage to the heart and its function.
Impact of compensatory enlargement of atherosclerotic coronary arteries on angiographic assessment of coronary artery disease.
Authors: Stiel G M , Stiel L S , Schofer J , Donath K , Mathey D G
Published: June 2011

To determine whether compensatory enlargement of atherosclerotic coronary arteries occurs and to what degree it affects the angiographic assessment of coronary artery disease, we performed postmortem coronary angiography of 30 human hearts with suspected coronary artery disease and studied 70 histologic cross sections of the proximal left anterior descending artery and proximal right coronary artery. Angiographic and morphometric analyses of 50 stenoses in proximal and middle sections of the left anterior descending artery, right coronary artery, and left circumflex artery were performed. The control group of 10 human hearts without suspected coronary artery disease was evaluated in the same way. For this purpose, coronary arteries were filled with a methylmethacrylic radiopaque resin at a pressure of 100 mm Hg and closely embedded in a methylmethacrylic resin by use of which shrinkage and mechanical artifacts could be avoided. The area circumscribed by the internal elastic lamina was taken as a measure of the area of the arterial lumen if no plaque had been present. The angiographic and corresponding morphometric degree of stenosis was assessed. A significant correlation (r = 0.85, p less than or equal to 0.0001) was found between the internal elastic lamina area and the area of the plaque (lesion area), suggesting that coronary arteries may enlarge as lesion area increases. With the morphometric degree of stenosis, the expected anatomic diminution of the coronary artery was abolished (r = 0.79, p less than or equal to 0.0001), indicating compensatory enlargement in atherosclerotic segments. Accordingly, the degree of stenosis assessed from in vitro angiograms was underestimated. Compensatory coronary enlargement of the stenotic segment was the main reason for angiographic underestimation. The underestimation factor of up to 3.50 for very mild stenoses decreased to 1.37 at an angiographic degree of 50% area stenosis and 30% diameter stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Two-dimensional echocardiographic and color flow Doppler evaluation of ductal occlusion with the Rashkind prosthesis.
Authors: Musewe N N , Benson L N , Smallhorn J F , Freedom R M
Published: June 2011

To evaluate the results of ductal occlusion with the Rashkind prosthesis, 78 children (group 1, 19 boys and 59 girls; mean age at occlusion, 4.5 +/- 4.0 years) with isolated patent ductus arteriosus (n = 73) or in association with other lesions (n = 5) were evaluated by pulsed and color flow Doppler 9 +/- 7 months (range, 2-26 months) after occlusion. Thirty children who had undergone patent ductus arteriosus ligation (group 2, 9 boys and 21 girls; mean age at study, 5.7 +/- 4.9 years; mean follow-up after ligation, 44 +/- 58 months) were evaluated in the same way. The prevalence of residual ductal shunting and the main pulmonary arterial flow patterns were recorded. Residual ductal shunting in group 1 was 38% on day 1, decreasing slowly to 31% at 3 months, 27% at 6 months, and 19.7% at 1 year or more due to further spontaneous shunt resolution. The residual shunting rate in group 2 (6%) was significantly lower than that at 1 year or more in group 1 (p less than 0.001). Successful reocclusion in 5 of 6 in a subset of patients in group 1 followed for 1 year or less reduced further the prevalence of residual shunting. Residual shunting after patent ductus arteriosus occlusion is more common than after ligation, but continues to decrease during follow-up.
Intimal fibromuscular hyperplasia at the venous anastomosis of PTFE grafts in hemodialysis patients. Clinical, immunocytochemical, light and electron microscopic assessment.
Authors: Swedberg S H , Brown B G , Sigley R , Wight T N , Gordon D , Nicholls S C
Published: June 2011

Failure of arteriovenous communications used for chronic hemodialysis was studied during sequential 5-year periods after placement of either endogenous Brescia-Cimino (B-C) fistulas (50 patients) or polytetrafluoroethylene (PTFE, Gore-Tex) grafts (66 patients). Venous stenosis near the anastomosis was the reason for failure in 45% of PTFE grafts compared with 16% of B-C fistulas (p less than 0.001). Failure occurred, on average, 16 months after PTFE graft placement compared with 22 for B-C fistulas (p = NS). Proximal vein segments removed from five failed and two functioning PTFE graft communications were studied using light and electron microscopy and immunocytochemical techniques. All venous segments removed during surgical shunt repair exhibited a marked intimal hyperplasia. The intimal cellular component was almost exclusively smooth muscle. Accumulation of intracellular lipid droplets was not seen. Foam cells as well as extracellular lipid deposits were absent; macrophages and lymphocytes were absent from the zone of proliferation. Ultrastructural examination revealed a large proportion of extracellular matrix surrounding smooth muscle cells in the neointima. Collagen and elastin were present in the extracellular matrix, in greatest concentration deeper in the intima. Closer to the lumen, most of the extracellular volume consisted of proteoglycan. Hemosiderin was absent from the lesions as were consistent signs of luminal and intimal fibrin. Uniform intimal gradients of actin, collagen, and proteoglycan suggest that this is a steadily progressive, rather than episodic, proliferative response. These clinical and histologic observations and an analysis of hemodynamic stresses support the postulate that upstream release of platelet-derived growth factor, and possibly, shear-induced intimal injury stimulate this response. This myointimal proliferative process provides a readily accessible model of fibromuscular hyperplasia in humans; its understanding may lead to effective methods for its prevention and may provide clues to the pathogenesis of arteriosclerosis.