H De Geest

Coronary thrombolysis with intravenously administered human tissue-type plasminogen activator produced by recombinant DNA technology.

Coronary thrombolysis was induced by intravenous infusion of human tissue-type plasminogen activator (recombinant human t-PA or rt-PA) obtained by expression of the cloned gene in a mammalian cell system. Thrombolysis was detected by the appearance of reperfusion arrhythmia and confirmed by repeat angiography in anesthetized dogs with 1-hr-old thrombi of the left anterior descending coronary artery that were induced with a copper coil. Infusion of 1000 IU (10 micrograms)/kg/min intravenous rt-PA (n = 9) elicited reperfusion within 13.7 +/- 1.9 min (mean +/- SE) without producing systemic fibrinolysis or distal coronary embolization. Infusion of urokinase at the same rate elicited thrombolysis in seven of 10 dogs within an average of 19.3 +/- 2.2 min. However, distal coronary embolization occurred in two dogs and systemic fibrinolysis was observed in all. In three dogs treated with urokinase thrombolysis was obtained only with subsequent intracoronary infusion. Restoration of myocardial perfusion and metabolism assessed with positron-emission tomography was consistently noted in dogs treated with rt-PA. Thus, rt-PA, a clot-selective thrombolytic agent that does not activate the fibrinolytic system systemically and that is potentially available in large quantities, in view of its synthesis by recombinant DNA technology, offers a promising practical approach for coronary thrombolysis in patients with acute myocardial infarction.

Intravascular ultrasound versus angiography for measurement of luminal diameters in normal and diseased coronary arteries

Quantitation of coronary luminal diameter with a 20 MHz mechanically rotating intravascular ultrasound (IVUS) catheter was compared with orthogonal-view cineangiography by use of a semiautomated edge-detection algorithm in 48 patients undergoing coronary angioplasty. Quantitative comparison of 196 matched segments was attempted, but in only 174 (88.8%) was a direct comparison of the two techniques possible. In angiographically normal coronary arteries (46 segments) the correlation between the values obtained by quantitative coronary angiography (QCA) and those achieved by IVUS was excellent (r = 0.92, p < 0.0001). For mild stenoses (80 segments) the correlation coefficient was only fair (r = 0.467, p < 0.001). After percutaneous transluminal coronary angioplasty the correlation coefficient between IVUS and QCA data (48 segments) was very weak (r = 0.282, p < 0.05). In conclusion, coronary IVUS is feasible and safe and even for a limited range of coronary arterial narrowing, significant correlations between IVUS and QCA measurements of minimal lumen diameter were found. They were excellent in normal coronary arteries, moderate in mildly diseased arteries, and weak after balloon angioplasty.

Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction.

Seventeen patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (scu-PA), obtained by expression of the cDNA encoding mature human scu-PA in Escherichia coli. In eight patients, recombinant scu-PA (rscu-PA) was given as a 10 mg bolus followed by 30 mg over 1 hr. Recanalization was obtained in six patients, but with persistent delayed opacification of the vessel in four of these patients. During infusion, a plateau level of rscu-PA antigen in plasma of 3.4 micrograms/ml (median value, range 1.4 to 5.5) was reached. At the end of the infusion the alpha 2-antiplasmin level had decreased to 54% (median, range 22% to 82%) of the preinfusion level, the fibrinogen level to 89% (median, range 26% to 101%), and fibrinogen degradation products (FDPs) to 20 micrograms/ml (median, range 8 to 387). In nine patients, rscu-PA was administered as a 10 mg bolus followed by 60 mg over 1 hr. This resulted in recanalization with normal distal filling of the vessel in seven patients, within 46 +/- 17 min (mean +/- SD). During infusion the concentration of rscu-PA in plasma increased to a median value of 7.4 micrograms/ml (range 4.0 to 13.3). At the end of the infusion the alpha 2-antiplasmin level was 22% of baseline (range 5% to 47%), the fibrinogen level 45% (range 4% to 94%), and the concentration of FDPs 87 micrograms/ml (range 6 to 1034). No significant bleeding or short-term side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PROSPECTIVE STUDY ON PREVALENCE OF ESOPHAGEAL CHEST PAIN IN PATIENTS REFERRED ON AN ELECTIVE BASIS TO A CARDIAC UNIT FOR SUSPECTED MYOCARDIAL ISCHEMIA

The prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. A group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography. The clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them. In 37 of these 48 patients full esophageal testing was performed including 24-hr intraesophageal pH and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and ergonovine stimulation, all performed under continuous esophageal manometric and electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest pain could be reproduced by esophageal provocative testing without ischemic ST-T segment alterations; six of these 19 patients had also a positive 24-hr pH and pressure recording. These data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram.

Diastolic properties of the left ventricle in normal adults and in patients with third heart sounds.

To explore the pathogenesis of the third heart sound (S3), left ventricular hemodynamics in early diastole were studied during catheterization in normal adults without S3S (group I, n = 12) and in cardiac patients with S3S as the result of severe mitral regurgitation (group II, n = 11), dilated cardiomyopathy (group III, n = 24) or restricted left ventricular filling (group IV, n = 4). The height and steepness of the rise in left ventricular pressure after minimum diastolic pressure (the so-called rapid filling wave), maximum dV/dt, and the time constant of fall in isovolumetric pressure were measured. The completeness of relaxation was evaluated from the number of time constants elapsed at the time of minimum diastolic pressure. Pressure-volume data were fitted to simple elastic and viscoelastic models incorporating inflow rate into the equation. In all patients with S3S a significantly higher and steeper rapid filling wave was found than in normal adults. Maximum dV/dt was significantly greater in group II (1084.9 +/- 416 ml/sec; mean +/- SD) than in the other groups (463.9 +/- 177.1 ml/sec in group I, 448.8 +/- 134.0 ml/sec in group III, and 709.9 +/- 226.8 ml/sec in group IV). No significant differences in left ventricular chamber elastic properties in the different groups were found. However, intrapatient comparisons of the results of the use of elastic and viscoelastic equations revealed a significantly better curve fit (r = .930 vs .968, p less than .005) and a much higher viscous constant for group III. Similar results were found in group IV.(ABSTRACT TRUNCATED AT 250 WORDS)

The genesis of the third and fourth heart sounds. A pressure-flow study in dogs.

To examine the mechanism of mitral flow deceleration in diastole and its potential influence on the genesis of third (S3) and fourth (S4) heart sounds, we simultaneously recorded left atrial and left ventricular pressures (micromanometers), mitral flow velocity (electromagnetic catheter-tip flow velocity meter), and internal and external phonocardiograms in 25 open-chest dogs. Diastolic time intervals, transmitral pressure gradients (planimetry), maximum mitral flow velocity, and acceleration and deceleration of flow were measured under different loading conditions. It was found that deceleration of mitral flow in early and late diastole is always caused by a negative transmitral pressure gradient. After volume loading, diastolic pressures, positive (forward) and negative (backward) transmitral pressure gradients, and acceleration and deceleration of flow increased, and an S3 or S4 appeared (20:25 dogs). These sounds occurred during the phase of flow deceleration and could be recorded from the chest wall, inside the left ventricle, and directly from the epicardial surface of the freely exposed left ventricular wall. After balloon occlusion of the inferior vena cava (17:25 dogs), the opposite changes were observed and gallop sounds disappeared. The results indicate that the left ventricular pressure rise in response to filling reverses the transmitral pressure gradient and decelerates flow. Deceleration of inflow by the left ventricular wall in early and late diastole may represent a key mechanism in the genesis of S3 and S4.

Bradycardia, ventricular pauses, syncope, and sports

16 athletic patients were examined because of syncope, Stokes-Adams attacks, or both. The life-threatening condition required pacemaker implantation in 7 patients. 8 of the 9 other subjects became symptom-free after stopping heavy physical training. 37 top-ranking athletes underwent 24 h Holter monitoring. Pauses longer than 2 s occurred in 19% and resulted from sinus arrest. The longest pause lasted 2.5 s. Second-degree atrioventricular block was noted in 13%.

The mechanism of disappearance of the physiologic third heart sound with age.

To study the mechanism of disappearance of the physiologic third heart sound (S3) with advancing age, combined phonoechocardiographic and phonomechanocardiographic recordings from 165 normal subjects between 6 and 62 years old were quantitatively analyzed. Nearly all individuals under 40 years old had a recordable S3. Although recordable in 38.6% of the 44 subjects over 40 years old, the physiologic S3 found in adults was less intense and occurred later in diastole when compared with that in children and adolescents. Marked changes in left ventricular filling hemodynamics were observed with aging, including an increase in left ventricular wall thickness and mass, a prolongation of the left ventricular isovolumetric relaxation period, a decrease in left ventricular early diastolic filling and wall thinning rates, and a reduction in the height and steepness of the rapid filling wave measured on the calibrated left apexcardiogram (linear correlation with age significant at p less than .001 for all parameters). Although less pronounced, these changes were very similar to the diastolic abnormalities found in patients with pressure overload left ventricular hypertrophy. Therefore, the higher pressure load imposed on the left ventricular wall due to the well-known gradual increase in blood pressure that occurs during normal growth and adulthood appears to be the most likely explanation for the observed changes in diastolic filling. It is concluded that the later occurrence, the diminishing amplitude, and the eventual complete disappearance of the physiologic S3 with age results from a decrease in early diastolic left ventricular filling and subsequent deceleration of inflow caused by the development of relative left ventricular hypertrophy in adulthood as compared with childhood.

Reduction in infarct size and enhanced recovery of systolic function after coronary thrombolysis with tissue-type plasminogen activator combined with beta-adrenergic blockade with metoprolol.

The effect of beta-adrenergic blockade on the salvage and functional recovery of reperfused myocardium was investigated in anesthetized dogs. Immediately after thrombotic occlusion of the left anterior descending coronary artery, the cardioselective beta-blocking agent metoprolol was given intravenously at a dose of 0.5 mg/kg infused over 10 min. One hour after the onset of occlusion, recanalization was initiated by intravenous infusion of recombinant human tissue-type plasminogen activator (rt-PA, 10 micrograms/kg/min for 30 min). Anatomic infarct size expressed as percent of the left ventricular mass (I/LV), global ejection fraction, and mean systolic shortening of the segmental radii (SS) of the infarcted area were measured either after 24 hr or 1 week in six groups of six dogs each: group I (rt-PA + metoprolol, evaluated at 24 hr), group II (rt-PA + metoprolol, evaluated at 1 week, group III (rt-PA alone, evaluated at 24 hr), group IV (rt-PA alone, evaluated at 1 week), group V (persistent occlusion, evaluated at 24 hr), and group VI (persistent occlusion, evaluated at 1 week). The smallest infarcts were found in reperfused dogs given metoprolol, but the differences from dogs receiving rt-PA alone were not statistically significant (I/LV, expressed as mean +/- SEM: 5.5 +/- 0.9% in group I, 6.7 +/- 1.9% in group II, 15.4 +/- 5.0% in group III, 11.4 +/- 3.5% in group IV, 23.6 +/- 2.5% in group V, and 26.9 +/- 2.3% in group VI).(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal Shock Wave Lithotripsy and Cardiac Arrhythmias

ECTOR, H., et al.: Extracorporeal Shock Wave Lithotripsy and Cardiac Arrhythmias Holter monitoring was performed in 400 patients undergoing extracorporeal shock wave lithotripsy (ESWL). The highest heart rate occurred before and after ESWL. During respiratory‐triggered ESWL, 30% of the patients had one or more ventricular premature beats (VES), and 7% had couplets of VES. The number of ventricular and supraventricular premature contractions was significantly lower during ECG‐triggered ESWL. Ventricular tachycardia occurred in seven patients during respiratory‐triggered ESWL, and in one patient during nontriggered ESWL. All ventricular tachycardias were nonsustained, asymptomatic, and slow. Supraventricular tachycardia was seen in nine patients. The preference of the urologist for respiratory‐triggered ESWL, conflicts with its higher incidence of ventricular arrhythmias.