bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectral analysis of 87-lead body surface signal-averaged ECGs in patients with previous anterior myocardial infarction as a marker of ventricular tachycardia.
Authors: Hosoya Y , Kubota I , Shibata T , Yamaki M , Ikeda K , Tomoike H
Published: June 2012

BACKGROUND

There were few studies on the relation between the body surface distribution of high- and low-frequency components within the QRS complex and ventricular tachycardia (VT).

METHODS AND RESULTS

Eighty-seven signal-averaged ECGs were obtained from 30 normal subjects (N group) and 30 patients with previous anterior myocardial infarction (MI) with VT (MI-VT[+] group, n = 10) or without VT (MI-VT[-] group, n = 20). The onset and offset of the QRS complex were determined from 87-lead root mean square values computed from the averaged (but not filtered) ECG waveforms. Fast Fourier transform analysis was performed on signal-averaged ECG. The resulting Fourier coefficients were attenuated by use of the transfer function, and then inverse transform was done with five frequency ranges (0-25, 25-40, 40-80, 80-150, and 150-250 Hz). From the QRS onset to the QRS offset, the time integration of the absolute value of reconstructed waveforms was calculated for each of the five frequency ranges. The body surface distributions of these areas were expressed as QRS area maps. The maximal values of QRS area maps were compared among the three groups. In the frequency ranges of 0-25 and 150-250 Hz, there were no significant differences in the maximal values among these three groups. Both MI groups had significantly smaller maximal values of QRS area maps in the frequency ranges of 25-40 and 40-80 Hz compared with the N group. The MI-VT(+) group had significantly smaller maximal values in the frequency ranges of 40-80 and 80-150 Hz than the MI-VT(-) group. These three groups were clearly differentiated by the maximal values of the 40-80-Hz QRS area map.

CONCLUSIONS

It was suggested that the maximal value of the 40-80-Hz QRS area map was a new marker for VT after anterior MI.
Functional significance of collateral blood flow in patients with recent acute myocardial infarction. A study using myocardial contrast echocardiography.
Authors: Sabia P J , Powers E R , Jayaweera A R , Ragosta M , Kaul S
Published: June 2012

BACKGROUND

We hypothesized that myocardial contrast echocardiography (MCE) can be used to both measure collateral blood flow as well as assess the functional significance of collaterals in patients with acute myocardial infarction (AMI).

METHODS AND RESULTS

MCE was performed in 33 patients with recent AMI (12 +/- 7 days) and an occluded infarct-related artery (IRA), both before and after attempted percutaneous transluminal coronary angioplasty (PTCA). The size of the occluded bed was defined in patients with successful PTCA by injecting contrast directly into the opened IRA and expressed as a percent of the myocardium in the short-axis view. The percent of the perfusion bed supplied by collaterals before PTCA was determined. Transit rates of the microbubbles within the collateralized regions were also measured and were expressed as a percent of the transit rates in the normal adjacent beds. Regional function within the occluded bed was assessed using echocardiography and was graded as 1 (normal) to 5 (dyskinetic). Collaterals were graded on coronary angiography as 0 (none) to 3 (abundant). The perfusion bed size was larger for the left anterior descending (LAD) than for the right (RCA) and left circumflex (LCx) coronary arteries (37 +/- 6% versus 27 +/- 12% of the myocardium, p = 0.02). The percent of the occluded bed supplied by collateral flow was greater for RCA and LCx compared with the LAD (87 +/- 30% versus 72 +/- 22%, p less than 0.01). There was poor correlation between MCE-defined percent of occluded bed supplied by collaterals and angiographic collateral grade (r = 0.13). Regions supplied by collaterals were less likely to show confluent hypoperfused zones after reperfusion compared with those not supplied by collaterals. Similarly, the percent of myocardium not perfused by either anterograde or collateral flow correlated well (r = 0.67, p less than 0.01) with peak creatine kinase levels and was more likely to be associated with Q waves. Finally, although there was poor correlation between angiographic collaterals and regional function (r = 0.20), there was a significant negative correlation between MCE-defined spatial extent of collateral flow and regional function (r = -0.57, p less than 0.01).

CONCLUSION

MCE can be used to measure collateral flow in patients with recent AMI and to assess the functional significance of collaterals in these patients. This technique may be ideally suited for the assessment of collateral perfusion in patients undergoing cardiac catheterization.
Multivariate prediction of in-hospital mortality associated with coronary artery bypass graft surgery. Northern New England Cardiovascular Disease Study Group.
Authors: O'Connor G T , Plume S K , Olmstead E M , Coffin L H , Morton J R , Maloney C T , Nowicki E R , Levy D G , Tryzelaar J F , Hernandez F
Published: June 2012

BACKGROUND

A prospective regional study was conducted to identify factors associated with in-hospital mortality among patients undergoing isolated coronary artery bypass graft surgery (CABG). A prediction rule was developed and validated based on the data collected.

METHODS AND RESULTS

Data from 3,055 patients were collected from five clinical centers between July 1, 1987, and April 15, 1989. Logistic regression analysis was used to predict the risk of in-hospital mortality. A prediction rule was developed on a training set of data and validated on an independent test set. The metric used to assess the performance of the prediction rule was the area under the relative operating characteristic (ROC) curve. Variables used to construct the regression model of in-hospital mortality included age, sex, body surface area, presence of comorbid disease, history of CABG, left ventricular end-diastolic pressure, ejection fraction score, and priority of surgery. The model significantly predicted the occurrence of in-hospital mortality. The area under the ROC curve obtained from the training set of data was 0.74 (perfect, 1.0). The prediction rule performed well when used on a test set of data (area, 0.76). The correlation between observed and expected numbers of deaths was 0.99.

CONCLUSIONS

The prediction rule described in this report was developed using regional data, uses only eight variables, has good performance characteristics, and is easily available to clinicians with access to a microcomputer or programmable calculator. This validated multivariate prediction rule would be useful both to calculate the risk of mortality for an individual patient and to contrast observed and expected mortality rates for an institution or a particular clinician.
Quantitative histological analysis of the human sinoatrial node during growth and aging.
Authors: Shiraishi I , Takamatsu T , Minamikawa T , Onouchi Z , Fujita S
Published: June 2012

BACKGROUND

Fibrosis or fatty infiltration of the human sinoatrial (SA) node is generally believed to represent replacement of the SA nodal cells by connective tissue. Quantitative analysis, however, has not been performed precisely to validate the interpretation of such histological changes.

METHODS AND RESULTS

The actual volume of the SA node and its components were calculated according to the sum of the pixel number representing the colors of SA nodal cells and connective tissue in serial sections using a digital color image analyzer. Average volume occupied by the total SA nodal cells in adolescents and adults (n = 7) was 3.55 +/- 0.45 mm3, which was 2.4 times greater than that in infants (n = 3). The rate of increase was smaller than that of the total SA node (4.2 times, 16.68 +/- 2.56 mm3 in adolescents and adults). The considerable discrepancy in the growth ratio between the SA nodal cells and the total SA node resulted from an increase in the volume of connective tissue (7.4 times). In the elderly (n = 9), the volume of total SA node and SA nodal cells actually decreased (13.10 +/- 1.85 mm3 and 2.18 +/- 0.44 mm3), whereas that of fibrous connective tissue remained unchanged. Constant DNA ploidy patterns of SA nodal cells determined by cytofluorometry indicated that SA nodal cells never synthesize DNA during growth.

CONCLUSIONS

Until adulthood, the actual volume of SA nodal cells does not decrease, although the increase in volume ratio of the interstitial tissue to the total SA node has merely given a false impression of involution of SA nodal cells. Atrophy of SA nodal cells, however, occurs during aging together with reduction of the SA node and/or infiltration of fatty tissue.
Association between rheology and components of lipoproteins in human blood. Results from the MONICA project.
Authors: Koenig W , Sund M , Ernst E , Mraz W , Hombach V , Keil U
Published: June 2012

BACKGROUND

Recent studies have suggested that several hemostatic factors, leukocyte count, and plasma viscosity are predictive of coronary heart disease. Detailed analyses on lifestyle correlates, in particular plasma lipids and lipoproteins, of determinants of blood rheology have not been reported from epidemiological studies.

METHODS AND RESULTS

We studied the relation between determinants of blood rheology and components of lipoproteins in a large sample of a population aged 25-64 years. The rheological parameters investigated were plasma viscosity, hemoglobin, and total serum protein; the lipoprotein variables included total cholesterol, high density lipoprotein (HDL) cholesterol, and the apoproteins A-I, A-II, and B. Covariables considered for possible confounding effects were age, body mass index, smoking behavior, alcohol consumption, and hypertension. Plasma viscosity was found to have a positive linear association with total cholesterol and apoprotein B (partial correlations after adjustment for all covariables including total serum protein for men and women were r = 0.23/0.19 and 0.24/0.25, respectively) and a small negative linear association with HDL cholesterol (r = -0.14/-0.10) and with apoprotein A-I (r = -0.08/-0.06). Polynomial regression showed a strong quadratic relation with HDL cholesterol in men, whereas no other variable revealed an appreciable deviation from linearity. The covariables had only a small, if any, confounding effect. Total serum protein, after control for the covariables, appeared to be associated only with total cholesterol. No association was found with hemoglobin.

CONCLUSIONS

We conclude that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. However, the finding that in particular men with very low HDL cholesterol exhibit increased plasma viscosity cannot be explained in pure rheological terms but may be, at least in part, the result of concomitant hypertriglyceridemia. This was not assessed in this study.
Noninvasive measurement of the time constant of left ventricular relaxation using the continuous-wave Doppler velocity profile of mitral regurgitation.
Authors: Chen C , Rodriguez L , Levine R A , Weyman A E , Thomas J D
Published: June 2012

BACKGROUND

The time constant of isovolumic relaxation (tau) is an important parameter of ventricular diastolic function, but the need for invasive measurement with high-fidelity catheters has limited its use in general clinical cardiology. The Doppler mitral regurgitant velocity spectrum can be used to estimate left ventricular (LV) pressure throughout systole and may provide a new noninvasive method for estimating tau.

METHODS AND RESULTS

Mitral regurgitation was produced in nine dogs, and ventricular relaxation was adjusted pharmacologically and with hypothermia. High-fidelity ventricular pressures were recorded, and tau was calculated from these hemodynamic data (tau H) assuming a zero-pressure asymptote. Continuous-wave mitral regurgitant velocity profiles were obtained, and the ventriculo-atrial (VA) pressure gradient was calculated by the simplified Bernoulli equation; tau was calculated from the Doppler data from the time of maximal negative dP/dt until LV-LA pressure crossover. Three methods were used to correct the Doppler VA gradient to better approximate the LV pressure before calculating tau: 1) adding actual LA V wave pressure (to yield tau LA); 2) adding 10 mm Hg (tau 10); and 3) no adjustment at all (actual VA gradient used to calculate tau 0). The agreement between tau H and the three Doppler estimates of tau was assessed by linear regression and by the mean and standard deviation of the error between the measurements (delta tau). the measurements (delta tau). tau H ranged from 29 to 135 msec. Without correction for LA pressure, the Doppler estimate of tau seriously underestimated tau H: tau 0 = 0.30 tau H + 9.4, r = 0.79, delta tau = -35 +/- 18 msec. This error was almost completely eliminated by adding actual LA pressure to the VA pressure gradient: tau LA = 0.92 tau H + 7.6, r = 0.95, delta tau = 2 +/- 7 msec. Addition of a fixed LA pressure estimate of 10 mm Hg to the VA gradient yielded an estimate that was almost as good: tau 10 = 0.89 tau H + 4.9, r = 0.88, delta tau = -2 +/- 12 msec. In general, tau was overestimated when actual LA pressure was below this assumed value, and vice versa. Numerical analysis demonstrated that assuming LA pressure to be 10 mm Hg should yield estimates of tau accurate to +/- 15% between true LA pressures of 5 and 20 mm Hg.

CONCLUSIONS

This study demonstrates that the Doppler mitral regurgitant velocity profile can be used to provide a direct and noninvasive measurement of tau. Because mitral regurgitation is very common in cardiac patients, this method may allow more routine assessment of tau in clinical and research settings, leading to a better understanding of the role of impaired ventricular relaxation in diastolic dysfunction and the effect of therapeutic interventions.
Protamine releases endothelium-derived relaxing factor from systemic arteries. A possible mechanism of hypotension during heparin neutralization.
Authors: Pearson P J , Evora P R , Ayrancioglu K , Schaff H V
Published: June 2012

BACKGROUND

When used to reverse the anticoagulant effect of heparin, protamine sulfate often causes vasodilation that can lead to systemic hypotension. Protamine is rich in the basic amino acid arginine, which is the precursor of endothelial cell synthesis of nitric oxide, and nitric oxide is the active component of endothelium-derived relaxing factor (EDRF).

METHODS AND RESULTS

To determine whether the hypotensive effect of protamine could be due to stimulated release of EDRF, we studied rings (4-5 mm) of canine coronary, femoral, and renal artery suspended in organ chambers containing physiological salt solution (37 degrees C and 95% O2-5% CO2). Arterial rings with and without endothelium were contracted with prostaglandin F2 alpha (2 x 10(-6) M) and exposed to increasing concentrations of protamine (final organ bath concentration, 40-400 micrograms/ml). In arterial segments without endothelium, protamine caused only a modest decrease in tension. However, protamine induced concentration-dependent relaxation in all arterial segments with endothelium, which was significantly greater than in segments without endothelium (p less than 0.05). The endothelium-dependent relaxation induced by protamine was inhibited by NG-monomethyl-L-arginine (L-NMMA) (10(-5) M), but L-NMMA had no effect on rings without endothelium. The action of L-NMMA could be reversed by L-arginine (10(-4) M) but not D-arginine (10(-4) M).

CONCLUSIONS

This study demonstrates that protamine stimulates the release of EDRF from arterial endothelium, and that endothelium-dependent vasodilation may be an important cause of systemic hypotension during protamine infusion.
Evidence for transient linking of atrial excitation during atrial fibrillation in humans.
Authors: Gerstenfeld E P , Sahakian A V , Swiryn S
Published: June 2012

BACKGROUND

Atrial fibrillation is usually thought of as a "random" pattern of circulating wavelets. However, local atrial activation should be influenced by the constant anatomy and receding tail of refractoriness from the previous activation. The general tendency for wave fronts to follow paths of previous excitation has been termed "linking." We examined intra-atrial electrograms recorded during atrial fibrillation for evidence of linking.

METHODS AND RESULTS

Two minutes of atrial fibrillation were recorded in 15 patients with an orthogonal catheter. We have previously demonstrated that this catheter can be used to detect changes in the direction of local atrial activation. A mean vector was calculated for each electrogram. The similarity of the direction of the vectors from two consecutive electrograms can be quantified on a scale of 1 to -1 by calculating the cosine (cos) of the smallest angle (theta) between them. Two vectors pointing in the same or opposite directions then have cos(theta) = 1 or -1, respectively. For the entire group of patients, mean cos(theta) was significantly greater than 0 (mean, 0.36; p less than 0.001). In nine of 15 patients, there were groups of six or more consecutive beats (total, 44 groups; range, six to 14 beats per group) in which the direction of activation of each beat was within 30 degrees of the previous beat. The likelihood of one group of six or 14 consecutive similar beats occurring by chance in any one patient in 1 minute is less than 0.05 and less than 0.0000001, respectively. There was a significant correlation (r = 0.90) between the amount of linking during the first and second minutes of atrial fibrillation in each patient.

CONCLUSIONS

Transient similarities in the direction of wavelet propagation in the majority of patients with atrial fibrillation is consistent with the presence of transient linking. To our knowledge, this is the first direct evidence that atrial activation during atrial fibrillation in humans is not entirely random.
Electrocardiographic body surface mapping in patients with ventricular tachycardia. Assessment of utility in the identification of effective pharmacological therapy.
Authors: Mitchell L B , Hubley-Kozey C L , Smith E R , Wyse D G , Duff H J , Gillis A M , Horacek B M
Published: June 2012

BACKGROUND

Body surface maps of net QRST deflection areas (isointegrals) reflect regional ventricular repolarization properties. Vulnerability to ventricular tachyarrhythmias is associated with maps that feature multiple islands (extrema) of positive and negative values; such maps reflect regional disparity of ventricular recovery properties. The value of body surface mapping in prediction of the efficacy of antiarrhythmic therapy for ventricular tachyarrhythmias has not been determined.

METHODS AND RESULTS

Isointegral ECG body surface mapping was performed in 51 patients with inducible ventricular tachycardia having programmed stimulation studies at baseline and after oral quinidine therapy. The degree of nondipolarity of QRST isointegral distribution was expressed by the number of extrema and by the percentage contribution of nondipolar eigenvectors after Karhunen-Loeve transformation. QRST isointegral nondipolarity was greater in ventricular tachycardia patients than in 51 age- and sex-matched normal subjects expressed as mean number of extrema (4.1 +/- 2.8 versus 2.0 +/- 0.2, respectively), mean eigenvector-determined nondipolar content percentages (12.4 +/- 10.1% versus 4.5 +/- 4.9%), prevalence of abnormal numbers of extrema (63% versus 4%), or prevalence of abnormal nondipolar content percentages (33% versus 4%) (each p less than 0.01). Quinidine prevented ventricular tachycardia induction in 14 patients. Patients for whom quinidine was or was not effective had similar nondipolarity indexes at baseline. However, maps on quinidine differed as a function of antiarrhythmic efficacy. Although effective therapy produced no significant mean changes in nondipolarity, ineffective therapy increased the number of extrema compared with baseline (5.4 +/- 3.4 versus 3.8 +/- 2.5, respectively) (p = 0.002). Individually, 43% of patients on effective therapy had drug-induced decreases in numbers of extrema compared with 14% of those on ineffective therapy (p = 0.02). Furthermore, 29% of patients on effective therapy showed drug-induced increases in numbers of extrema compared with 62% of those on ineffective therapy (p = 0.03).

CONCLUSIONS

QRST isointegral body surface mapping shows promise as a noninvasive measure of drug efficacy in patients with ventricular tachycardia.
A recombinant, chimeric enzyme with a novel mechanism of action leading to greater potency and selectivity than tissue-type plasminogen activator.
Authors: Robinson J H , Browne M J , Carey J E , Chamberlain P D , Chapman C G , Cronk D W , Dodd I , Entwisle C , Esmail A F , Kalindjian S B
Published: June 2012

BACKGROUND

Early intervention with thrombolytic agents has been shown unequivocally to reduce mortality after acute myocardial infarction. Presently used agents have disadvantages such as short half-life, immunogenicity, hypotension, and bleeding complications. Therefore, there is a need to develop improved thrombolytic drugs with novel mechanisms of action leading to improved properties.

METHODS AND RESULTS

Hybrid plasminogen/tissue-type plasminogen activator (t-PA) complementary DNA was constructed and expressed in Chinese hamster ovary cells. The chimeric protein, comprising the fibrin-binding domains of plasminogen covalently linked to the catalytic domain of t-PA, was purified and evaluated in vitro and in vivo. The hybrid was inhibited rapidly in human and animal plasmas. The mediator of this rapid inhibition was shown to be alpha 2-antiplasmin. The active center of the hybrid could be protected by reversible active center acylation with a novel inverse acylating agent, 4'-amidinophenyl-4-chloroanthranilic acid (AP-CLAN). An acylated (CLAN-) hybrid was cleared from the bloodstream of guinea pigs at 0.35 +/- 0.02 ml/min.kg-1 compared with a clearance rate of 36 +/- 4 ml/min.kg-1 for t-PA. The CLAN-plasminogen/t-PA hybrid was evaluated in a quantitative, "humanized" guinea pig pulmonary embolism model and shown to be approximately threefold more potent when given by bolus than an infusion of t-PA. Furthermore, the acylated hybrid was more fibrin selective than t-PA as determined by the relation between clot lysis and fibrinogen degradation.

CONCLUSIONS

An acylated, recombinant plasminogen/t-PA hybrid has sufficiently slow clearance to be administered by bolus and is more potent and fibrin selective than t-PA in vivo.
Severe right ventricular pressure loading in fetal sheep augments global myocardial blood flow to submaximal levels.
Authors: Reller M D , Morton M J , Giraud G D , Wu D E , Thornburg K L
Published: June 2012

BACKGROUND

It has previously been shown that the fetal right ventricle (RV) is sensitive to changes in arterial pressure and that its stroke volume is significantly reduced with acute increases in pulmonary arterial pressure. However, the myocardial blood flow (MBF) response to increases in pulmonary arterial pressure have not been investigated in the fetus.

METHODS AND RESULTS

To assess whether the RV afterload sensitivity to arterial pressure is associated with limitation in MBF, seven fetal lambs were instrumented at 130 days of gestation with a pulmonary arterial occluder and intravascular catheters. RV stroke volume was measured by an electromagnetic flow probe and MBF by 15-microns labeled microspheres. MBF was determined at baseline and during incremental increases in pulmonary arterial pressure. Maximal MBF was determined in seven additional fetuses during adenosine infusion. The highest tolerated pressure was associated with a 50% reduction in RV stroke volume. The highest pulmonary arterial occlusion pressure resulted in a doubling of MBF to all regions of the heart (266 +/- 99 to 504 +/- 158, 193 +/- 69 to 387 +/- 100, and 171 +/- 66 to 338 +/- 134 ml/min/100 g for the RV, septum, and left ventricle, respectively). The best correlation for increases in both RV and global MBF was the RV heart rate-systolic pulmonary pressure product. Adenosine infusion was associated with a threefold increase in global MBF that was significantly greater than the MBF achieved during pulmonary arterial occlusion.

CONCLUSIONS

The fetal RV sensitivity to acute pressure loading is not associated with limitation of MBF. The fetal myocardium has a remarkable flow reserve that allows for preservation of function during acute increases in arterial pressure.
Abnormal laterality and congenital cardiac anomalies. Relations of visceral and cardiac morphologies in the iv/iv mouse.
Authors: Seo J W , Brown N A , Ho S Y , Anderson R H
Published: June 2012

BACKGROUND

In the management of hearts with deranged laterality, it is essential that the left and right atrial chambers are correctly identified. There are two major approaches, which are based on venous connections or on the morphology of the atrial appendages, and there is no consensus as to which is the most useful. We used the iv/iv mouse mutant, which is known to be pertinent to this problem, to evaluate the relations of cardiac defects with atrial, venous, and other visceral morphologies.

METHODS AND RESULTS

The morphology of the heart and other organs was examined in 275 iv/iv mice using criteria based on abnormal laterality in humans. The arrangement of the atrial appendages was determined by morphological examination of the junction between the appendage and the venous component of the atrium. On this basis, 45.1% of cases were shown to have usual atrial arrangement, 50.2% had mirror imagery, 1.5% had right isomerism, and 3.3% had left isomerism. Every case of atrial isomerism had a cardiac lesion; the morphological types were similar to those seen in human cases. Of cases with either usual or mirror-image arrangement of the appendages, 33.2% had abnormal spleens, but only 3.1% had cardiac defects. Similarly, venous abnormalities were much more common (30.1%) than cardiac defects.

CONCLUSIONS

Study results endorse the importance of the morphology of atrial appendages in predicting cardiac abnormalities and point to the marked inconsistency of the arrangement of other organs, including the spleen and the connections of the systemic veins.
Assessment of postreperfusion myocardial hemorrhage using proton NMR imaging at 1.5 T.
Authors: Lotan C S , Bouchard A , Cranney G B , Bishop S P , Pohost G M
Published: June 2012

BACKGROUND

Intramyocardial hemorrhage occurs frequently after reperfusion of acute myocardial infarction. However, its significance has not yet been established, mainly because of the lack of methods for detecting such hemorrhage. The following ex vivo study was carried out to assess the potential of nuclear magnetic resonance (NMR) imaging to detect and quantitate postreperfusion intramyocardial hemorrhage.

METHODS AND RESULTS

Sixteen adult mongrel dogs underwent 3 hours of coronary occlusion followed by 1 hour of reperfusion, and three dogs underwent 4 hours of occlusion without reperfusion. Radiolabeled microspheres and 51Cr-labeled red blood cells were used to assess flow and evaluate the extent of hemorrhage. These results were later compared with both NMR and histology. Spin-echo NMR imaging was performed on the excised hearts using a 1.5-T system. Macroscopic assessment of the sliced myocardium revealed the existence of hemorrhage in 14 of the 16 dogs that underwent reperfusion but in none of those with occlusion only. In all 16 dogs with reperfusion, zones of increased signal intensity (SI) ratio (1.68 +/- 0.41 compared with control, p less than 0.05) were seen in regions relating to the distribution of the occluded coronary artery, whereas in 13 of the 16 dogs, areas of decreased SI within the zone of increased SI ratio (0.81 +/- 0.16 compared with control, p less than 0.05) were also seen, corresponding to regions with macroscopic hemorrhage. In contrast, in the three dogs without reperfusion, no macroscopic hemorrhage was observed, and likewise, no NMR zones of reduced SI were detected. Hemorrhage size by NMR (decreased SI zones), correlated well with hemorrhage size calculated from tissue slices (r = 0.96, SEE = 0.92%, p less than 0.01), or by 51Cr labeling (r = 0.78, SEE = 1.5, p = 0.1). In the reperfusion group, T2 relaxation times in the infarcted hemorrhagic zone (58 +/- 9 msec) were significantly lower than the infarcted zones without hemorrhage (98 +/- 13 msec, p less than 0.001). In contrast, when compared with control (964 +/- 72 msec), T1 relaxation times were significantly increased in both infarct zones, either with (1,284 +/- 176 msec) or without (1,266 +/- 103 msec) hemorrhage. The selective shortening of T2 relaxation times in the hemorrhagic regions is consistent with the paramagnetic effects of deoxyhemoglobin.

CONCLUSIONS

NMR imaging may provide a noninvasive approach for the detection and quantitation of intramyocardial hemorrhage. This observation may provide a means to further characterize pathological processes associated with acute myocardial infarction and assess the role of myocardial hemorrhage after reperfusion therapy.
Cross-sectional early mitral flow-velocity profiles from color Doppler in patients with mitral valve disease.
Authors: Samstad S O , Rossvoll O , Torp H G , Skjaerpe T , Hatle L
Published: June 2012

BACKGROUND

Cross-sectional flow-velocity profiles from early mitral flow in 20 patients (10 with mitral regurgitation and 10 with mitral stenosis) were constructed from the velocity data from each point in sequentially delayed two-dimensional digital Doppler ultrasound maps.

METHODS AND RESULTS

The data suggested that the early mitral flow studied in an apical four-chamber view was variably skewed in both patient groups. The maximum flow velocity overestimated the cross-sectional mean velocity at the same time by a factor of 1.12-1.86. The maximum time-velocity integral was 1.13-1.77-fold greater than the cross-sectional mean time-velocity integral. In patients with mitral regurgitation, the cross-sectional flow-velocity profile appeared to be most skewed at the level of the mitral leaflet tips. The level of the mitral annulus appeared to give the most homogenous flow-velocity distribution in both patient groups.

CONCLUSIONS

When calculations of volume flow are based on pulsed Doppler ultrasound recordings with a single sample volume, the possibility of a skewed flow-velocity profile must be taken into account.
Morphological predictors of acute complications after percutaneous excimer laser coronary angioplasty. Results of a comprehensive angiographic analysis: importance of the eccentricity index.
Authors: Ghazzal Z M , Hearn J A , Litvack F , Goldenberg T , Kent K M , Eigler N , Douglas J S , King S B
Published: June 2012

BACKGROUND

Percutaneous excimer laser coronary angioplasty (ELCA) is a new technique for recanalization of arteries obstructed by coronary atherosclerosis. This study was conducted to assess the complication rate and determine the influence of clinical and angiographic characteristics on complications after ELCA.

METHODS AND RESULTS

A detailed, quantitative, angiographic core laboratory analysis of patients undergoing ELCA was performed by two experienced angiographers who were not the primary laser angioplasty operators. Two hundred patients underwent 203 separate procedures on 220 lesions at three medical centers. Laser success was achieved in 180 lesions (81.8%) and procedural success in 199 (90.5%). Emergency coronary artery bypass graft (CABG) was required in five patients (2.5%). One patient suffered a Q wave myocardial infarction; there were no deaths. Also, acute closure and perforation occurred in 10 (4.5%) and three (1.4%) vessels, respectively. Coronary dissections after laser treatment were seen in 36 vessels (16.4%). Multivariate analysis found two independent preprocedural factors related to complications: eccentricity index, which is the percent deviation of the lesion lumen from the center of the artery (p = 0.0007), and proximal vessel diameter (p = 0.033). In addition, an abrupt proximal face of the lesion was associated with angiographic complications by univariate analysis (p = 0.051). Multivariate analysis showed the eccentricity index (p = 0.032) to be the only independent predictor for the occurrence of any one or more of the important complications (emergency CABG, perforation, acute closure, or Q wave myocardial infarction), whereas lesion angle greater than 45 degrees was a significant univariate predictor (p = 0.029). Other predictors of complications with balloon percutaneous transluminal coronary angioplasty, such as increased lesion length, rough edges, calcification, ulceration, and branch point, were not predictive of complications with the excimer laser.

CONCLUSIONS

The degree of lesion eccentricity is the most powerful predictor of complications after ELCA. This and other morphological predictors may be of benefit in the selection of patients for ELCA as well as directing future development of this new technology.
Anatomical progression of coronary artery disease in humans as seen by prospective, repeated, quantitated coronary angiography. Relation to clinical events and risk factors. The INTACT Study Group.
Authors: Lichtlen P R , Nikutta P , Jost S , Deckers J , Wiese B , Rafflenbeul W
Published: June 2012

BACKGROUND

At present, there is extensive knowledge on the clinical course of coronary artery disease (CAD), whereas data on the underlying anatomical changes and their relation to clinical events are still limited.

METHODS AND RESULTS

We investigated progression and regression of CAD prospectively over 3 years in 230 patients (average age, 53.2 years) with mild to moderate disease by applying quantitated, repeated coronary angiography. Minimal stenotic diameters, segment diameters, and percent stenosis were analyzed by the computer-assisted Coronary Angiography Analysis System (CAAS). Progression was defined either as an increase in percent stenosis of preexisting stenoses by greater than or equal to 20% including occlusions or as formation of new stenoses greater than or equal to 20% and new occlusions in previously angiographically "normal" segments. At first angiography, we found 838 stenoses greater than or equal to 20% (average degree, 39.3%) and 135 occlusions in the four major coronary branches (4.23 lesions per patient). At second angiography, 82 (9.8%) of the preexisting stenoses had progressed, 15 of them up to occlusion (1.8%; preocclusion degree averaging 46.6%; 29.7-65.6%). In addition, there were 144 newly formed stenoses (average degree, 39.2%) and 10 new occlusions. Hence, 25 (2.6%) of all stenoses had become occluded. Altogether, 129 patients (56.1%) showed progression: 68 (29.6%) with new lesions only, 27 (11.7%) with preexisting lesions, and 34 (14.8%) with both types. Regression (decrease in degree of stenoses greater than or equal to 20%) was present in 29 stenoses (3.6%) and 28 patients (12%). The incidence of new myocardial infarctions was low, with three originating from occluding preexisting stenoses and one from new stenoses; hence, only four (16%) of the 25 new occlusions led to myocardial infarctions. Risk factor analysis showed that cigarette smoking correlated significantly with the formation of new lesions (p = 0.001), whereas total cholesterol correlated with the further progression of preexisting stenoses (p = 0.017) but not with the incidence of new lesions.

CONCLUSIONS

In patients with mild to moderate CAD, the angiographic progression is slow (in this study 18.7% of patients and 7% of stenoses per year) but exceeds regression (4.1% of patients and 1.2% of stenoses per year). Progression is predominantly seen in the formation of new coronary stenoses and less in growth of preexisting ones. Most of the stenoses were of a low degree (less than 50%), clinically not manifest including those going into occlusion and leading to myocardial infarction. Progression was influenced by risk factors, especially cigarette smoking (formation of new lesions) and high cholesterol levels (progression of preexisting stenoses).
Effects of oxygen inhalation on skin microcirculation in patients with peripheral arterial occlusive disease.
Authors: Bongard O , Bounameaux H , Fagrell B
Published: June 2012

BACKGROUND

Oxygen administration is currently used in clinical medicine to improve peripheral oxygen delivery to tissues threatened by ischemia. However, conflicting results have been reported on the effects of oxygen in ischemic areas. This study was aimed at investigating the effects of 40% oxygen inhalation on the skin microcirculation in the feet of patients with peripheral arterial occlusive disease (PAOD).

METHODS AND RESULTS

Transcutaneous oxygen tension (tc PO2) was measured on the dorsal skin of the foot, and the nailfold microcirculation was investigated by a combination of laser Doppler flowmetry (LDF) and dynamic capillaroscopy (CBV) in the great toes of 17 legs of 11 patients, with 13 legs of eight normal subjects as a control group. Inhalation of oxygen induced a significant decrease of both the total (delta LDF, -307%, p less than 0.02) and nutritional (delta CBV, -17%, p less 0.002) skin microcirculation in normal legs compared with baseline values. A similar response was observed in 10 legs of patients who showed a significant increase of the tc PO2 (greater than or equal to 10 mm Hg) (delta LDF, -14%, NS; delta CBV, -13%, p less than 0.005). By contrast, both the total (+21%, p less than 0.03) and nutritional (+52%, p less than 0.05) circulation significantly increased in the seven legs without significant tc PO2 increase. In addition, the flow motion, which was impaired in the patients, was significantly (p less than 0.05) improved by oxygen inhalation.

CONCLUSIONS

Inhalation of 40% oxygen induces a vasoconstriction in the skin microcirculation of toes of the normal subjects and patients with moderate PAOD but induces an increase of the skin microcirculation in patients with severe PAOD.
Neurophysiological assessment of skeletal muscle fatigue in patients with congestive heart failure.
Authors: Minotti J R , Pillay P , Chang L , Wells L , Massie B M
Published: June 2012

BACKGROUND

Recent research has demonstrated that patients with congestive heart failure (CHF) exhibit significant functional impairment of skeletal muscle and that these changes may be important determinants of exercise capacity. Although muscle strength may be mildly reduced, the most significant abnormality is markedly enhanced muscle fatigue. The goal of the present study is to determine whether accelerated fatigue is caused by impaired muscle activation, as a result of inadequate central motor drive or neuromuscular transmission, or by a change in the muscle itself.

METHODS AND RESULTS

The study population consisted of nine patients with New York Heart Association class I-III CHF and eight sedentary, age- and sex-matched control subjects. Maximal voluntary contraction force of the foot dorsiflexors (primarily the tibialis anterior) was quantified as a measure of muscle strength, isometric endurance was quantified by the time required for force to decline to 60% of maximal during a sustained maximal contraction, and dynamic endurance was defined as the number of maximal contractions required for force to decline to 60% of maximal under a protocol of six repetitions per minute with an incremental duty cycle. The degree of central motor drive failure was quantified by the degree of force augmentation produced by a superimposed tetanic stimulus delivered to the peroneal nerve during the initial maximal voluntary contraction and at the time when force during the sustained isometric contraction declined to 60% of maximal. Neuromuscular junction transmission was examined by quantifying the amplitude of the compound muscle action potential (M wave) in response to a single nerve stimulus during fatiguing exercise. Muscle strength was relatively preserved in the CHF patients versus the control subjects (93 +/- 41 versus 105 +/- 34 lb; p = NS), but isometric endurance (time to decline to 60%, 34 +/- 15 versus 54 +/- 19 seconds; p less than 0.02) and dynamic endurance (number of repetitions before decline to 60%, 30 +/- 6 versus 43 +/- 7 contractions; p less than 0.001) were both impaired. Tetanic nerve stimulation increased force by similar degrees in the two groups, and the amplitude of the M wave did not decline in either group during exercise.

CONCLUSIONS

These findings indicate that enhanced muscle fatigue in patients with CHF is not caused by impaired central motor drive or an abnormality of neuromuscular junction transmission but rather by an abnormality in the muscle itself.
Coronary endothelial and cardiac protective effects of a monoclonal antibody to intercellular adhesion molecule-1 in myocardial ischemia and reperfusion.
Authors: Ma X L , Lefer D J , Lefer A M , Rothlein R
Published: June 2012

BACKGROUND

Intercellular adhesion molecule-1 (ICAM-1) is a major ligand on endothelial cells for adherence of activated polymorphonuclear leukocytes (PMNs). The major purpose of this study was to study the effects of RR1/1, a monoclonal antibody against ICAM-1 (i.e., MAb RR1/1), on myocardial injury and endothelial dysfunction associated with myocardial ischemia and reperfusion.

METHODS AND RESULTS

Either MAb RR1/1 (2 mg/kg, n = 7), an antibody that was found to bind selectively to endothelial cells in the cat, or MAb R3.1 (2 mg/kg, n = 7), a nonbinding control antibody, was given as an intravenous bolus 10 minutes before reperfusion. Two hundred eighty minutes later, hearts were excised. The left ventricle area-at-risk (AAR) was similar in MAb RR1/1 (29 +/- 2%) and MAb R3.1 (30 +/- 3%) groups. In MAb R3.1-treated cats, 90 minutes of myocardial ischemia plus 4.5 hours of reperfusion induced a significant myocardial injury (necrotic tissue/AAR, 28 +/- 2%), high myeloperoxidase activity (0.65 +/- 0.16 units/100 mg ischemic tissue), and a marked decrease in endothelium-dependent vasorelaxation in isolated left anterior descending coronary arteries (vasorelaxation to acetylcholine, 29 +/- 3%) with no change in endothelium-independent vasorelaxation (relaxation to NaNO2, 91 +/- 3%). However, cats treated with MAb RR1/1 developed significantly less myocardial necrosis (10 +/- 2% of the AAR, p less than 0.01), lower myeloperoxidase activity in ischemic myocardial tissue (0.2 +/- 0.03 units/100 mg ischemic tissue, p less than 0.01), and enhanced vasorelaxant responses to endothelial-dependent relaxation to acetylcholine (53 +/- 5%) compared with ischemic/reperfused cats treated with Mab R3.1. Furthermore, addition of MAb RR1/1 in vitro significantly inhibited unstimulated PMN adherence to ischemic-reperfused coronary artery endothelium.

CONCLUSIONS

These results suggest that ICAM-1-dependent PMN adherence plays an important role in reperfusion injury, and that PMN adherence and infiltration contribute significantly to coronary endothelial dysfunction.
Cellular mechanisms of differential action potential duration restitution in canine ventricular muscle cells during single versus double premature stimuli.
Authors: Kobayashi Y , Peters W , Khan S S , Mandel W J , Karagueuzian H S
Published: June 2012

BACKGROUND

We tested the hypothesis that action potential duration (APD) restitution of normal ventricular muscle cells is different during double premature stimuli (S3) compared with a single premature stimulus (S2). We propose a possible ionic mechanism for such a difference.

METHODS AND RESULTS

Action potentials and isometric tension were recorded simultaneously from isolated canine right ventricular trabeculae (2 x 2 x 10 mm) (n = 35). APD and tension restitution curves (APD) and peak tension versus diastolic interval [DI] of S2 and S3 were constructed by the extrastimulus method during pacing at 1,500 msec. The following results were obtained. 1) The APD restitution curve of S2 was different from that of S3. During the restitution of S2, an early biphasic upward hump was present at short DIs. In contrast, a smooth exponential rise was consistently seen during S3 restitution. 2) Peak tension remained significantly (p less than 0.001) lower during the restitution of S2 than during S3 restitution at all DIs tested. 3) The variation of APD during the initial 100 msec of DI was significantly longer during S3 than S2 (22 +/- 5 msec versus 41 +/- 5 msec, p less than 0.001). 4) Caffeine (2 mM, n = 5) and ryanodine (10 microM, n = 5) blocked cyclic variations of tension, presumably by blocking cyclic variations of intracellular calcium ion concentrations ([Ca2+]i), and eliminated the differences in APD restitution between S2 and S3. 5) Nisoldipine at high (5 microM) but not at lower (2 microM, n = 5) concentration eliminated the differences in restitution of both APD and tension between S2 and S3. 6) BAY K 8644 (100 nM, n = 5) had no effect on this difference.

CONCLUSIONS

Greater variations of APD occur during the restitution of S3 than during S2 at short DIs. These differences appear to be caused by cyclic variations in tension and thus in [Ca2+]i. Calcium-sensitive outward currents could explain these differences in APD restitution.
Clinical characteristics and outcome of patients with high defibrillation thresholds. A multicenter study.
Authors: Epstein A E , Ellenbogen K A , Kirk K A , Kay G N , Dailey S M , Plumb V J
Published: June 2012

BACKGROUND

Successful defibrillation by an implantable cardioverter-defibrillator (ICD) depends on its ability to deliver shocks that exceed the defibrillation threshold. This study was designed to identify clinical characteristics that may predict the finding of an elevated defibrillation threshold and to describe the outcome of patients with high defibrillation thresholds.

METHODS AND RESULTS

The records of 1,946 patients from 12 centers were screened to identify 90 patients (4.6%) with a defibrillation threshold greater than or equal to 25 J. Excluding three patients who received ICDs that delivered greater than 30 J, there were 81 men and six women with a mean age of 59.5 +/- 10.1 years, a mean left ventricular ejection fraction of 0.32 +/- 0.14, and a 76% prevalence of coronary artery disease. Sixty-one patients (70%) were receiving antiarrhythmic drugs, and 45 (52%) were receiving amiodarone. Seventy-one patients (82%) received an ICD. Death occurred in 27 patients--19 of the 71 (27%) with an ICD (eight arrhythmic), and eight of the 16 (50%) without an ICD (four arrhythmic). Actuarial survival for all patients at 5 years was 67%. Actuarial survival rates at 2 years for patients with and without an ICD were 81% and 36%, respectively (p = 0.0024). Actuarial survival at 5 years for the ICD patients was 73%; no patient without an ICD has lived longer than 32 months. Actuarial survival free of arrhythmic death in the ICD patients at 5 years was 84%. Although the only variable to predict survival was ICD implantation (p = 0.003), it is entirely possible that in this retrospective analysis, clinical selection decisions to implant or to not implant an ICD differentiated patients destined to have better or worse outcomes, respectively.

CONCLUSIONS

Antiarrhythmic drug use may be causally related to the finding of an elevated defibrillation threshold. When patients with high defibrillation thresholds receive an ICD, arrhythmic death remains an important risk (42% of deaths in these patients were arrhythmia related, with 16% actuarial incidence at 5 years). Vigorous testing to optimize patch location can potentially benefit patients by enhancing the margin of safety for effective defibrillation.