Hiram W. Marshall

A Randomized Trial of Intracoronary Streptokinase in the Treatment of Acute Myocardial Infarction

Fifty patients with acute myocardial infarction were randomly assigned to receive either intracoronary streptokinase or standard (control) therapy within about three hours after the onset of pain. Coronary perfusion was reestablished in 19 of 24 patients receiving streptokinase. Streptokinase alleviated pain (as indicated by differences in subsequent morphine use). The Killip class was significantly improved after therapy with streptokinase, as were changes in radionuclide ejection fraction between Days 1 and 10 in surviving patients (+3.9 vs. -3.0 per cent, P less than 0.01). The echocardiographic wall-motion index also showed greater improvement after streptokinase treatment (P less than 0.01). Streptokinase therapy was associated with rapid evolution of electrocardiographic changes, which were essentially complete within three hours after therapy, but loss of R waves, ST elevation, and development of Q waves in the convalescent period were greater in the control group (P less than 0.01). The time required to reach peak plasma enzyme concentrations was significantly shorter after streptokinase. The incidence of early and late ventricular arrhythmias was not affected by treatment. We conclude that intracoronary streptokinase appears to have a beneficial effect on the early course of acute myocardial infarction.

Coronary Spasm Producing Coronary Thrombosis and Myocardial Infarction

THE pathophysiology of acute myocardial infarction has been a subject of considerable discussion, as indicated in two recent reviews.1 , 2 The respective roles of coronary thrombosis and coronary s...

Three-dimensional reconstruction of moving arterial beds from digital subtraction angiography

A system for three-dimensional reconstruction of dynamic (moving) vascular bed structures has been developed and is described. Input images are obtained from two-view (bi-plane or ECG correlated) X-ray angiograms. A target structure consisting of vessel branch points (nodes) and lines between the branch points is entered on the first of a sequence of images in one view. The movement of the nodes is indicated on subsequent images and on the images of the second view. The target is linearly warped according to the motion of the node points. Automatic edge detection (with subsequent operator correction) is used to detect centerlines and edges of vessels. Three-dimensional reconstruction is accomplished using a distance minimizing point matching technique. Finally, angle-corrected densitometric methods are used to refine the vessel cross section. Standard shaded surface display techniques are then used to display the moving arterial bed. Flow measurements are obtained by tracking the leading edge of the bolus down the three-dimensional arterial tree.

A randomized trial of intravenous and intracoronary streptokinase in patients with acute myocardial infarction.

The clinical effects of intravenous streptokinase in patients with acute myocardial infarction were compared with those of intracoronary streptokinase in a randomized, prospective study. Comparisons were also made with a historical control group. Fifty patients were entered into the study at 2.4 +/- 1.2 hr after onset of pain, and 27 were assigned to intravenous and 23 to intracoronary therapy. The doses of streptokinase averaged 212,000 U ic and 845,000 U iv (0.75 X 10(6) U/5 hr, n = 14 or 10(6) U/1 hr, n = 13). Results of studies of the two intravenous dosage schedules were similar and so were combined. Streptokinase was administered at 2.8 +/- 1.0 hr after onset of pain in the intravenous and at 4.3 +/- 1.4 hr in the intracoronary drug group (p less than .001). Convalescent (day 10) radionuclide ejection fractions were 54 +/- 14% for the intravenous and 50 +/- 16% for the intracoronary drug group. Change in ejection fraction from day 1 to 10 tended to be greater after intravenous drug: 5.1% (p less than .08) vs 1.2% (NS). Semiquantitative regional wall motion indexes in the infarct zone showed significant and similar modest improvement from admission to day 10 in both groups (p less than .02). Accelerated enzyme-release kinetics were noted after both therapies. Times of peak enzyme levels for patients on intravenous and intracoronary drug were, respectively, 12.5 +/- 5.0 and 11.5 +/- 4.3 hr for creatine kinase MB isoenzyme and 31.7 +/- 11.8 and 28.1 +/- 12.7 hr for lactic dehydrogenase (LDH). Peak LDH-1 level was lower in patients receiving intravenous drug than in the historical control group (p less than .05). Electrocardiographically summed ST segments diminished rapidly after therapy in both groups; Q wave development was similar and overall R wave loss was equivalent and less extensive compared with in historical control subjects. Infarct pain requiring morphine was diminished similarly in both treatment groups. Incidence of early arrhythmias and heart failure also did not differ. Posttherapy ischemic events and early surgery tended to be more common in the intracoronary group and bleeding was more common in the intravenous group. Intravenous drug did not decrease early hospital mortality (intravenous drug = 5, historical control = 4, intracoronary drug = 1); the differences in this parameter among groups were not significant. At convalescent angiographic evaluation, anterograde perfusion was present in 73% of those receiving intravenous and 76% of those receiving intracoronary drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Apolipoprotein polymorphisms fail to define risk of coronary artery disease. Results of a prospective, angiographically controlled study.

BackgroundBecause genetic factors are believed to contribute to the etiology of coronary artery disease (CAD), it has been suggested that DNA polymorphisms at candidate loci might identify individuals at high risk for developing disease. In this regard, apolipoprotein genes represent extremely promising loci because levels of apolipoproteins and their associated lipoproteins represent a major risk factor for CAD, and rare dysfunctional mutations in these genes result in a significant risk for CAD. To date, although some reports indicate that DNA polymorphisms at these loci are associated with increased risk of CAD, other reports have failed to find such associations. Methods and ResultsTo resolve the question of whether genetic polymorphisms at apolipoprotein loci can be used to identify individuals at increased risk for CAD, we evaluated the distribution of apolipoprotein genetic polymorphisms in a large series of subjects (n=848) undergoing coronary angiography. Blinded assessment of angiograms was used to discriminate between patients with CAD (≥60% stenosis of any major branch, n=444) and control subjects without disease (<10% stenosis, n=404). A total of 12 polymorphisms were evaluated at the following loci: apolipoprotein (apo) A-I/C-III/A-IV (five restriction site polymorphisms–Msp I, Pst I, Sst I, Pvu Ila, Pvu Ib), apo B (three restriction site polymorphisms–Xba I, EcoRI, Msp I, plus an insertion/deletion polymorphism), apo A-II (Msp I polymorphism), apo C-II (Taq I polymorphism), and apo E (protein isoforms revealed by DNA analysis). All subjects were of Northern European (primarily Angloscandinavian) descent, and, within each sex, patients and control subjects were of comparable age. All 12 loci were in Hardy- Weinberg equilibrium, with no indication of population heterogeneity. As expected, patients were distinguished from control subjects by their lipid profiles and a higher frequency of known risk factors for CAD. However, analysis by log-linear models indicated that there were no significant associations between apolipoprotein polymorphisms and the risk of CAD (P = .10 to .90). The lack of association was maintained irrespective of whether the analysis was carried out for the entire sample or the contrast was made more stringent by comparing patients most likely to have a genetic component to their disease (ie, young patients with early-onset CAD) with the control subjects least likely to have genetic susceptibility (ie, older control subjects who had ample time to develop CAD). ConclsionsDespite the fundamental role of apolipoprotein genes in lipid metabolism, we find no evidence that common genetic polymorphisms of the major apolipoprotein loci have a significant influence on the risk of developing angiographically defined CAD in this representative population. Therefore, at this time we find no support for the hypothesis that mass screening for genetic polymorphisms at candidate loci can reduce the burden of CAD by identifying a substantial proportion of high-risk individuals. Instead, it appears more appropriate to direct attention toward modifying high-risk behaviors to alleviate the consequences of traditional environmental risk factors.

The characteristic sequence for the onset of contraction in the normal human left ventricle.

The sequence for the onset of segmental contraction of the left ventricle was studied in 25 normal patients by analyzing sequential frames obtained at 16.7-msec intervals of right anterior oblique (RAO) ventriculograms by two independent methods. In the first method, we compared the times of onset of contraction of the hemidiameters associated with each of 54 segments with the time of onset of contraction of the average of all the hemidiameters for the ventricular contour. In the second method we used a radial coordinate system and determined relative phase relationships by plotting the motion of each of 54 segments against the average motion of all segments.The resulting pattern showed that, on the average, the midregion of the inferior wall began to contract 25 msec before the apex and the midregion of the anterior wall began contraction 18 msec before the apex. In 12 of 25 patients the interior and anterior walls both began to contract before the apex. In only one of 25 patients did the apex begin to contract first. This sequence of contraction corresponds to the reported sequence of electrical activation for normal human left ventricles.

The femoral venous approach to endomyocardial biopsy: comparison with internal jugular and transarterial approaches.

Endomyocardial biopsy is often used in the clinical evaluation of cardiac disease. Among 134 consecutive procedures (280 myocardial samples), 3 approaches were compared: right internal jugular (n = 69), femoral arterial (n = 30) and femoral venous (n = 35). The femoral venous approach is a new method with which a preformed guiding sheath is used to allow sampling of the apical right ventricular portion of the ventricular septum. Vascular access and myocardial sampling were successful in all femoral venous and left ventricular (LV) procedures; however, the internal jugular vein could not be located to allow biopsy in 12% of neck approaches (p less than 0.025). One case of pneumothorax occurred after an internal jugular approach. Chest pain occurred after 10% (3 patients) of the LV, 4% (3 patients) of internal jugular and 3% (1 patient) of femoral venous procedures. Hypotension associated with biopsy was noted after 3 internal jugular and 2 LV procedures. Pericardial effusion was observed in 3 patients after an LV procedure (p less than 0.01). In 1 of these patients tamponade developed. The femoral venous approach had the highest overall efficiency (successful biopsy, lack of adverse events, p less than 0.05). This approach may become the procedure of choice for routine endomyocardial biopsy because it allows reliable vascular access and myocardial sampling with a low incidence of adverse reactions.

A technique for the detection of asynergistic motion in the left ventricle.

Abstract A method is described whereby 60/second, monoplane, video images of the opacified left ventricle are digitized and the location of the endocardial surface is determined by a computer-based algorithm. For each contour, representing the location of the endocardial surface in a single plane at a given point in time, a reference point is defined as the midpoint of a straight line connecting the center of the aortic valve to the apex. The radial distances from the reference point to the contour are determined at five-degree increments around the contour for each of the contours during systole. The correlation coefficients and linear regression slopes for each radius sequence versus the mean radius sequence are calculated and plotted. The correlation coefficient and linear regression slope means and ranges are determined for normal hearts and then compared with the values from a heart demonstrating an abnormal pattern. By a computer method, the location and characteristics of the motion abnormality are described.

A steady-state transfer function analysis of portions of the circulatory system using indicator dilution techniques☆

A digital computer program has been developed whereby the distribution of dye-particle transit times across circulatory pathways can be found from recordings of upstream and downstream indicator-dilution curves. This distribution or transfer function is computed from Fourier-series representations of the upstream and downstream indicator curves and makes possible, for the first time, the calculation of transit-time distributions independent of the effects of recirculating dye. Since a discontinuity is introduced into the tails of the upstream and downstream curves at the end of sampling, the method requires an iterative approach in the termination of the upstream and downstream curves. The accuracy of the calculated distribution pattern is determined by comparison of the recorded downstream curve with the results of the convolution of the recorded upstream curve and computed transfer function. Effects of noise, bandwidth and sampling rate have been investigated through the use of analog computer models of the circulatory pathways. These studies show that the transfer-function description is limited by the bandwidth of the upstream (input) curve. Noise, or variations in magnitude and phase angle of input- and output-curve frequencies, tends to introduce oscillations into the time-domain representation of the transfer function as does the use of too few frequencies. This means that in biological systems the upstream sampling site must be relatively close to the dye injection site if the input and output sampling sites are close together. Circulatory transfer functions have been obtained from dogs across their lower extremity, renal and systemic circulations before, during and following moderate exercise (walking on treadmill at two miles per hour for four minutes).

Three Dimensional Reconstruction of Vascular Beds

This chapter discusses the mathematics and computer processing required to generate three dimensional representations of vascular beds from multiple digital angiographic projections. In order to compensate for the deficiencies of conventional reconstruction techniques, a method is presented which directly reconstructs a vascular tree structure. This method appears to take good advantage of vessel characteristics such as connectivity and uniform internal density. Direct reconstruction takes full advantage of the information contained in multiple images, using a dynamic programming technique to determine the vessel centerline, edges, and densitometric profiles in each of the views. With the knowledge of the artery locations from each projection, reconstruction of the arterial tree centerline is overdetermined and averaging or least squares techniques can be used. The vessel lumen geometry may be estimated using the edge information and attenuation profile. The lumen geometry can then be refined by densitometric reprojection of the vascular tree and comparison with original profiles. Examples of direct reconstruction and perspective display of a pig heart coronary artery cast are given.