Joseph Askenazi

Use of changes in the epicardial QRS complex to assess interventions which modify the extent of myocardial necrosis following coronary artery occlusion.

SUMMARY The goal of this study was to determine if changes in the epicardial QRS complex after coronary artery occlusion (CAO) can be used to evaluate the efficacy of interventions designed to limit infarct size. Forty-one open-chest dogs with CAO were studied: 15 were controls, 18 received hyaluronidase and eight received propranolol starting 20 minutes after CAO. Epicardial ECGs were recorded at specific time intervals to analyze ST-segment elevation and changes in Q and R waves. Transmural specimens were obtained 24 hours after CAO from the same sites at which ECGs were recorded. Q wave development (ΔQ), R wave fall (ΔR), and their combination (ΔR + ΔQ) at 24 hours correlated with the extent of necrosis, as de- termined by myocardial creatine phosphokinase activity depression and histologic appearance. In the control group ST-segment elevation 15 minutes after CAO (ST18m) predicted changes in Q and R waves 24 hours later; in the treated groups, the same STism prior to drug administration resulted in significantly less QRS changes. Thus, I) Q wave development and R wave fall 24 hours after CAO accurately reflect myocardial necrosis. 2) ST18m predicts subsequent changes in Q and R waves. 3) The efficacy of hyaluronidase and propranolol, agents previously shown to reduce myocardial necrosis, can be detected by less Q wave development and a smaller fall in R wave voltage.

Quantitative radionuclide angiocardiography: Detection and quantitation of left to right shunts

In 105 patients defection and quantitation of left to right shunts was performed using quantitative radionuclide angiocardiography. The radionuclide angiocardiograms were acquired and analyzed by a gamma camera interfaced to a digital computer system. Pulmonary to systemic flow (Qp/As) ratios were calculated by analysis of pulmonary time-activity histograms using a gamma variate model. All patients were studied with cardiac catheterization, left ventricular angiocardiography and radionuclide angiocardiography. The radionuclide method allowed precise detection and quantitation of left to right shunts with a Qp/Qs ratio of 1.2 to 3.0. There was good agreement between the Ap/As ratio calculated by oximetry at cardiac catheterization and radionuclide angiocardiography (r = 0.94). The information gathered with this nontraumatic method appears sufficiently reliable to be used in the management of patients.

Echocardiographic evaluation of the Valsalva Maneuver in healthy subjects and patients with and without heart failure.

SUMMARY The Valsalva maneuver was evaluated by echocardiography in three groups: A) 10 normal volunteers, B) 10 patients with no history of heart failure and normal ejection fractions, and C) 10 patients with heart failure and depressed ejection fractions. Groups A and B had a significant fall in left ventricular internal dimensions and calculated stroke volume by end strain which returned rapidly to baseline in recovery without significant overshoot. Arterial pressure showed a sigmoidal strain pattern with a normal overshoot in early recovery in all group B patients. In group C ventricular dimen- sions did not diminish during strain; arterial pressures showed a “square wave” pressure elevation during strain without an overshoot in recovery. Echocardiography allows a new approach to evaluate further the left ventricular response to the Valsalva maneuver. Patients with severely depressed ejection fractions, unlike those with normal ventricular function, are unable to alter stroke output in response to acutely increased intrathoracic pressure. A square wave pressure response is a likely consequence of a fixed stroke output during the strain maneuver.

Value of the QRS complex in assessing left ventricular ejection fraction

The relation between electrocardiographic findings and the angiographic left ventricular ejection fraction and the augmented ejection fraction after a premature ventricular contraction was investigated in 73 patients with documented chronic coronary artery disease. The patients were separated into four groups according to the presence or absence of abnormal Q waves. Twenty-four patients had diaphragmatic myocardial infarction, 21 had anterior myocardial infarction, 15 had both and 13 had no myocardial infarction. There was no statistically significant differences in cardiac index, left ventricular end-diastolic pressure or number of coronary vessels showing critical narrowing in the four groups. The sum of R waves (in mv) in leads aVL, aVF and V1 to V6 (sigmaR) was correlated with the ejection fraction (EF) and the augmented ejection fraction (EFa). EF in percent = 6.6 sigmaR mv + 9.4 (no. =73, r = 0.61); and EFa in percent = 8.6 sigmaR mv + 11.0 (no. = 73, r = 0.77). Among patients with sigmaR of less than 4.0 mv, augmented ejection fraction was less than 0.45 in 73 percent; among patients with sigmaR of 4.0 mv or more the augmented ejection fraction was greater than 0.45 in 93 percent (P less than 0.001). Thus, the sigmaR, calculated from six precordial and two augmented leads in patients with chronic coronary artery disease, correlated with both ejection fraction and augmented ejection fraction. The electrocardiogram in patients with coronary artery disease may prove useful as a simple, readily available and noninvasive guide in the assessment of left ventricular function in patients with coronary artery disease.

The effects of hyaluronidase on coronary blood flow following coronary artery occlusion in the dog.

In an attempt to determine the mechanism by which hyaluronidase reduces myocardial injury following coronary artery occlusion, myocardial blood flow was studied in 20 open-chest dogs with occlusion of the left anterior descending coronary artery. Ten dogs served as controls, and 10 received hyaluronidase (500 NF units/kg) intravenously 20 minutes after occlusion. At 15 minutes and at 6 hours after occlusion, regional myocardial blood flow in the epicardial and endocardial halves of both ischemic and nonischemic zones were determined with radiolabeled microspheres. Mean arterial pressure, heart rate, and cardiac output were similar in the untreated and treated dogs through the 6 hours of the experiment. Moreover, regional blood flow to nonischemic myocardium (areas without epicardial S-T segment elevation 15 minutes after occlusion) was similar in the two groups 15 minutes and 6 hours after occlusion. Fifteen minutes after occlusion, the flow to the ischemic myocardium subjacent to sites with S-T segment elevation exceeding 2 mV) in the untreated group was: transmural, 28.1 ± 2.2 (mean ± SE) ml/min per 100 g; endocardial, 20.7 ± 1.8; and epicardial, 38.5 ± 3.1. The endocardial-epicardial flow ratio was 0.56 ± 0.04. Six hours after occlusion, the untreated group demonstrated a further decrease in blood flow to the ischemic myocardium: transmural, 15.2 ± 1.4 ml/min per 100 g; endocardial, 6.8 ± 1.1; and epicardial, 24.3 ± 1.9. The endocardial-epicardial flow ratio fell to 0.28 ± 0.04. In contrast, the hyaluronidase-treated dogs showed no further reduction in blood flow to ischemic myocardium 6 hours after occlusion: transmural, 30.3 ± 3.1 ml/min per 100 g; endocardial, 21.3 ± 2.5; and epicardial, 38.8 ± 3.8. These regional myocardial flows were significantly higher than those of the untreated dogs 6 hours after occlusion. Thus, salvage of damaged myocardium by hyaluronidase might be explained by its beneficial effect on collateral blood flow to the ischemic tissue, though this effect on collateral flow could be the consequence rather than the cause of this salvage.

Effect of the kallikrein inhibitor aprotinin on myocardial ischemic injury after coronary occlusion in the dog.

The effect of administration of aprotinin (a kallikrein inhibitor) on the extent and severity of acute myocardial ischemic injury, subsequent necrosis and collateral blood flow was studied in 55 dogs after acute coronary occlusion. Two 20 minute occlusions of the left anterior coronary artery were performed in eight dogs and epicardial electrograms were recorded from 10 to 14 sites. The sum of S-T segment elevations (σST) 15 minutes after the occlusion without drug administration was 38.7 ± 7.0 mv (mean ± standard error of the mean). Before the second occlusion aprotinin was administered and σST decreased to 22.6 ± 5.6 mv (P < 0.01). Similarly, the number of sites exhibiting S-T segment elevations of more than 2 mv (NST) decreased from 6.4 ± 0.8 after the first occlusion to 4.2 ± 1.2 (P < 0.01) after the occlusion following aprotinin administration. The effect of aprotinin on myocardial necrosis administered 30 minutes after coronary occlusion was established by means of the relation between epicardial S-T segment elevation 15 minutes after coronary occlusion and myocardial creatine kinase (CK) activity and histologic appearance at the same sites 24 hours later. In the control group the relation was: log CK = −0.059S-T + 1.53 (no. = 92 specimens, r = 0.74); in the treated group it was: log CK = —0.036S-T + 1.54 (no. = 60 specimens, r = 0.79). These slopes differed (P < 0.001), indicating that aprotinin prevented myocardial CK depletion. In the control group all sites exhibiting S-T elevations of more than 2 mv 15 minutes after occlusion showed early signs of myocardial infarction 24 hours later when examined by light microscopy. In contrast, in dogs that received aprotinin, only 66 percent of sites with abnormally elevated S-T segments showed abnormal histologic features, indicating that administration of the drug led to preservation of structural integrity in many sites. Similarly, significantly deeper Q waves evolved in the control than in the treated group: ΔQ (6 hours) = 0.82 S-T (15 min) + 0.86 (no. = 9 dogs, r = 0.76) and in the treated group: ΔQ (6 hours) = 0.46S-T (15 min) + 0.72 (no. = 10 dogs, r = 0.64) (P < 0.02). Regional myocardial blood flow decreased from 15 minutes to 6 hours after occlusion in both the control and treated groups. However, the decrease was less in the treated than in the control group (37 versus 16 percent and the distribution of flow endocardialepicardial ratio was significantly better with aprotinin. Thus, it is concluded that aprotinin diminishes myocardial damage after acute coronary occlusion.

Computerized orthogonal electrocardiogram: relation of QRS forces to left ventricular ejection fraction.

Several studies have suggested a relation between Q wave or R wave amplitude in the standard 12 lead electrocardiogram and the left ventricular ejection fraction. Accordingly, we analyzed the relation between Q wave and R wave amplitudes obtained with computerized orthogonal (Frank) electrocardiography and the angiographically determined left ventricular ejection fraction. A computerized orthogonal electrocardiogram was obtained before cardiac catheterization in 52 consecutive patients being evaluated for chest pain. The electrocardiographic diagnosis indicated 14 normal tracings, 20 inferior, 12 anterior and 6 lateral myocardial infarctions. Linear correlations were made between X, Y and Z axis lead voltages and ejection fraction. A significant correlation was obtained between the voltages of the R waves in the X, Y and Z leads (Rx, Ry, Rz) and of the Q waves in lead Z (Qz) as well as total amplitude Qx + Rx, Qy + Ry and ejection fraction (P <0.01). Arithmetic summation of Rx + Ry + Qz (∑R) significantly augmented the correlation with ejection fraction (r = 0.78, P <0.001); this was only slightly improved by multivariate analysis of Rx, Ry, Qz (r = 0.80, P <0.001) or Rx, Ry, Rz, Qx, Qy, Qz (r = 0.82, P <0.001). ∑R, utilized as a means of predicting whether an ejection fraction was more or less than 50 percent, had an accuracy rate of 92 percent. Thus, ∑R contains important information that can be used practically in the precatheterization evaluation of patients with chest pain and follow-up evaluation of patients with myocardial infarction.

Mitral valve area in combined mitral stenosis and regurgitation.

SUMMARY Eight patients with mixed mitral stenosis and regurgitation underwent hemodynamic and angiographic study prior to mitral valve replacement. The stenotic orifice of the mitral valve was calculated employing the total left ventricular stroke volume by cineangiography as the numerator of the Gorlin Formula. Excellent agreement with the measured orifice of the mitral valve was obtained using a value of 37.9 (0.85 × 44.5) for the constant in the Gorlin formula as recommended by Cohen and Gorlin. Recalculation of this constant independently by our data yielded a value that was almost identical. Regurgitant flows and orifice sizes were calculated for each patient using the same constant as for calculation of the stenotic orifices.