A multicenter randomized trial of ionic (ioxaglate) and nonionic (iopamidol) low-osmolality contrast agents in cardiac angiography

A multicentered double-blind randomized study was performed comparing the electrocardiographic and hemodynamic changes induced by two new low osmolar contrast agents used for cardiac angiography. The low osmolar ionic (ioxaglate) contrast agent was compared with a low osmolar nonionic (iopamidol) contrast agent in 150 patients with angina pectoris undergoing angiography. Systolic blood pressure, left ventricular end-diastolic pressure, heart rate, and QT interval were measured just before and for 90 s following the left ventricular angiography and selective coronary angiography. Each group was also evaluated for adverse events and quality of radiographic images. Following left ventricular angiography, the systolic blood pressure dropped slightly in both groups with a greater decrease seen in the iopamidol group at 5 s (p less than 0.05). After selective right and left coronary angiography, systolic blood pressure decreased transiently and equally in both treatment groups. The left ventricular end-diastolic pressure increased after the ventriculogram in both groups (15.9 +/- 6.3 to 18.9 +/- 8.6 mmHg in the ioxaglate group and 16.1 +/- 6.7 to 20.1 +/- 7.8 mmHg in the iopamidol group), the change being significant only in the iopamidol group (p less than 0.05). Heart rate increased slightly but significantly in the ioxaglate-treated patients following left ventricular angiography (71.4 +/- 15.2 to 74.4 +/- 13.7 beats/min) (p less than 0.01). QT interval transiently increased following left ventriculography with ioxaglate (407 +/- 59.5 to 420 +/- 58.3 ms) (p less than 0.05) compared with iopamidol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic changes induced by cardiac angiography with ioxaglate: comparison with diatrizoate

The hemodynamic and electrocardiographic changes induced by left ventriculography and coronary arteriography with ioxaglate (a new low osmolality angiographic contrast agent) were characterized and compared with the changes induced by a commercial formulation of the commonly used angiographic contrast agent, diatrizoate (Renografin-76). Left ventriculography and coronary arteriography were performed in 25 patients utilizing ioxaglate and in another 25 patients utilizing diatrizoate. Both agents increased left ventricular end-diastolic pressure and decreased arteriovenous oxygen difference after left ventriculography, but the magnitude of the increase caused by ioxaglate was significantly less than that caused by diatrizoate (changes in left ventricular end-diastolic pressure was 5.3 +/- 1.3 mm Hg with ioxaglate and 9.5 +/- 1.5 mm Hg with diatrizoate [p less than 0.02] ). Change in arteriovenous oxygen difference was -0.33 +/- 0.19 ml/100 ml with ioxaglate and -0.85 +/- 0.13 ml/100 ml with diatrizoate (p less than 0.05). Both agents were well tolerated when used for coronary arteriography with no adverse events occurring in either group. Ioxaglate is a well tolerated cardiac angiographic contrast agent that produces less hemodynamic disturbance than diatrizoate. Accordingly, it may be particularly well suited to use in patients with impaired left ventricular function.     

Comparative studies of diatrizoate, ioxaglate and iohexol as angiocardiographic contrast media

We did 2 consecutive randomized studies to compare the effects of diatrizoate, ioxaglate, and iohexol. Sixty patients were studied: 15 with diatrizoate (group I) versus 15 with ioxaglate (IIA), and 15 with ioxaglate (IIB) versus 15 with iohexol (III). Group I had hypotension and severe increase in end-diastolic pressure. Severe bradycardia was seen in 27% of the cases. Group IIA and IIB had identical changes, with a moderate increase in systolic and end-diastolic pressure. Group III only presented a mild increase in end-diastolic pressure. None of the low-osmolar contrast media produced severe bradycardia, but ioxaglate induced frequent (20%) nausea. Our results suggest the best contrast media for angiocardiography is, in decreasing order: iohexol, ioxaglate, and diatrizoate.     

Radiographic contrast agents and platelet function: a quenched-flow study

Radiographic contrast media (RCM) may alter platelet behavior at concentrations achieved during cardiac angiography. We used quenched-flow aggregometry coupled to single-particle counting to study the influence of RCM on the kinetics of platelet aggregation (less than 5.0 sec) induced by adenosine diphosphate (ADP, 2.86 microM). At a concentration in platelet-rich plasma (PRP) of 5 per cent RCM by volume, platelet aggregation was inhibited by diatrizoate, iopamidol and ioxaglate either directly or following incubation of each contrast agent with PRP for 20 minutes. Diatrizoate inhibited more than did iopamidol or ioxaglate (56 +/- 6, versus 39 +/- 3 and 40 +/- 9 per cent respectively; P less than 0.003, p less than 0.009, n = 20 normal subjects). A small reduction (about 16 per cent) in aggregation velocity occurred within 5 seconds of exposure of PRP to all 3 RCM and the onset time (t) or lag period before aggregation begins was significantly prolonged by diatrizoate (p less than 0.03). The RCM vehicles alone (iodinated moiety removed, osmolality readjusted) had no effect on the ADP-induced aggregation. Platelet counts fell significantly after incubation with diatrizoate (12%; p = 0.04). Our data therefore show that early platelet aggregation was inhibited by 3 commonly-used ionic and nonionic contrast agents. Inhibition was apparently caused by the iodinated contrast molecule, began within seconds of platelet-RCM contact and was independent of vehicle composition. Since diatrizoate inhibited aggregation more than iopamidol or ioxaglate, its use may be of additional value during angiographic procedures in clinical situations involving enhanced platelet activation.     

The effects of ionic and nonionic radiographic contrast media on coronary hyperemia in patients during coronary angiography.

The purpose of this study was to compare the differential effects of ionic, high-osmolar meglumine diatrizoate; ionic, low-osmolar ioxaglate meglumine; and nonionic, low-osmolar iohexol (all radiographic contrast agents) on coronary blood flow velocity and hyperemic responses during diagnostic coronary angiography. Coronary flow velocity and arterial pressure were measured at baseline and during maximal hyperemia after contrast media were randomly injected (4 to 6 ml into left coronary artery) in 22 patients with the use of a Judkins-style 20 MHz Doppler-tipped angiographic catheter. Contrast media-induced hyperemic responses were compared to those induced with intracoronary nitroglycerin (200 micrograms) and papaverine (10 mg). There were no significant differences in systolic, diastolic, or mean arterial pressure measurements among the three contrast agents. The increase in mean coronary flow velocity during hyperemia was 118 +/- 93%, 133 +/- 73%, and 136 +/- 86% for iohexol, ioxaglate meglumine, and diatrizoate, respectively (p = NS among agents vs 264 +/- 109% for papaverine; p less than 0.05 for all). Coronary vasodilatory reserve (calculated as the ratio of hyperemic to basal mean flow velocity) was also similar among agents. It was comparable to the coronary vasodilatory reserve with nitroglycerin (2.1 +/- 1.0 to 2.2 +/- 1.1) and significantly less than that with papaverine (3.3 +/- 2.2, p less than 0.05). These data indicate that the clinical advantages of nonionic or low-osmolar contrast media are not mechanistically related to significant attenuation of the coronary hyperemic response.     

Differential hemodynamic effects of Hypaque-76 and Renografin-76 during coronary angiography: the role of calcium-binding additives

Hypaque-76 (H76) and Renografin-76 (R76) are nearly identical ionic contrast media, except that R76 binds more calcium than H76 because of the presence of sodium citrate and EDTA in R76. To determine whether the calcium-binding additives in ionic contrast media contribute to the hemodynamic effects of contrast media during coronary angiography, left coronary angiography was performed in anesthetized dogs. In nine closed-chest dogs, 10 cc of H76 and R76 were injected in each dog in a blinded, randomized fashion. The effect of H76 and R76 on left ventricular systolic pressure (LVSP) and left ventricular diastolic pressure (LVDP), on mean aortic pressure (MAP), and on left ventricular (LV) dp/dt was recorded. Compared with H76, R76 produced a greater decrease in the LVSP (77 +/- 25 mmHg vs 48 +/- 17 mmHg P less than .05), MAP (72 +/- 24 mmHg vs 38 +/- 18 mmHg P less than .01), and LV dp/dt (747 +/- 87 mmHg/sec vs 460 +/- 81 mmHg/sec P less than .01). In nine additional open-chest dogs, left coronary angiography was performed 1 hour after occlusion of the proximal LAD coronary artery. Seven cc R76 produced a 35 +/- 15 mmHg decrease in LVSP, compared with 20 +/- 9 mmHg with H76 (P less than .01). The LV dp/dt decreased 720 +/- 387 mmHg/sec with R76, compared with 462 +/- 222 mmHg/sec with H76 (P less than 0.05). Thus, R76 produces significantly greater hemodynamic abnormalities than H76. Contrast media lacking calcium-binding agents may be preferable for coronary angiography.     

Comparison of the electrocardiographic and hemodynamic responses to ionic and nonionic radiocontrast media during left ventriculography: a randomized double-blind study

The ECG and hemodynamic responses to a standard ionic radiographic contrast agent (diatrizoate) were measured and compared to those induced by iopamidol, a newly developed nonionic agent, during left ventriculography. Studies were performed using randomized double-blind techniques in 46 patients with suspected coronary artery disease who were scheduled for cardiac catheterization. A nuclear probe was used to measure left ventricular ejection fraction and relative ventricular volume before and immediately after left ventriculography. Bolus injections of diatrizoate and iopamidol induced similar significant decreases in left ventricular end-diastolic and end-systolic volume and similar significant increases in both left ventricular end-diastolic pressure (p less than 0.05) and systolic ejection fraction (p less than 0.01 vs baseline). Both agents induced modest increases in heart rate, but only the increase induced by diatrizoate was significant (p less than 0.01). The maximal rate of left ventricular pressure rise was not significantly altered by either agent. Iopamidol induced a slight increase in QRS duration (p less than 0.05); neither agent effected a significant change in QT duration. We conclude that the hemodynamic effects during left ventriculography using diatrizoate and iopamidol are similar. These findings do not justify the large-scale substitution of more expensive nonionic radiographic contrast agents for standard ionic agents such as diatrizoate in left ventriculography.     

Hemodynamic effects of contrast media during coronary angiography: a comparison of three nonionic agents to Hypaque-76

Coronary angiography with standard ionic contrast media is associated with marked alterations in cardiac hemodynamics because of the depressant effects of the contrast media on cardiac contractility. Nonionic contrast media have been reported to produce less hemodynamic alteration than standard ionic contrast media. However, there is no information on how one nonionic media compares to another. Thus we compared the hemodynamic effects of three nonionic contrast media, Iopamidol (IOP), Iohexol (IOH), and Ioversol (IOV) to each other as well as to the standard ionic contrast media Hypaque-76 (H76). In 20 closed-chest anesthetized dogs, we recorded the maximal change in left ventricular systolic pressure (LVSP), mean aortic pressure, left ventricular diastolic pressure (LVDP), and left ventricular dp/dt during 10-cc left main coronary artery injections of H76, IOP, IOH, and IOV. The mean aortic pressure and LVSP decreased 36 +/- 17 mm Hg and 46 +/- 21 mm Hg with H76 but only 5 +/- 5 mm Hg and 6 +/- 5 mm Hg with IOP, 5 +/- 4 mm Hg and 6 +/- 6 mm Hg with IOH, and 5 +/- 4 mm Hg and 7 +/- 6 mm Hg with IOV (P less than 0.001). The LVDP increased 6 +/- 5.0 mm Hg with H76 but only 0.2 +/- 0.5 mm Hg with IOP, 0.2 +/- 0.3 mm Hg with IOH, and 0.5 +/- 1.0 mm Hg with IOV (P less than 0.001). The LV dp/dt decreased 545 +/- 261 mm Hg/sec with H76 but increased 886 +/- 477 mm Hg/sec with IOP, 910 +/- 96 mm Hg/sec with IOH, and 473 +/- 335 mm Hg/sec with IOV (P less than 0.001). Whereas each nonionic agent produced significantly less hemodynamic abnormalities than H76, there was no significant difference between any of the nonionic agents on any hemodynamic parameter. Thus, as compared to H76, these nonionic contrast media produced only trivial alterations in hemodynamics and LV dp/dt. These agents may be preferable in patients with LV dysfunction.     

The haemodynamic effects of left ventriculography in coronary artery disease and mitral valve disease: a comparison of high and low osmolality contrast media

We compared the haemodynamic effects of a low osmolality contrastmedium Hexabrix 320 (meglumine/sodium ioxaglate) with a highosmolality medium Urografin 370 (meglumine/sodium diatrizoate)in 32 patients. Each underwent left ventriculography with bothmedia, which caused similar small and transient increases inheart rate and systolic pressure. In 15 patients with coronaryartery disease, the mean left ventricular end-diastolic pressureincreased by 4 mmHg after hexabrix compared with 10 mmHg afterurografin (P<0.01); it returned to normal more quickly afterhexabrix. Changes after both media did not correlate with baselineend-diastolic pressure, ejection fraction, or extent of coronaryartery disease, and thus left ventriculography was unhelpfulas a stress test. In 14 patients with mitral stenosis, hexabrixproduced a smaller increase in left ventricular end-diastolicpressure (P<0.001), left atrial pressure (P<0.01) andmitral valve gradient (P<0.05) than urografin. Patients preferredthe low osmolality medium (P<0.01). There was no differencein angiographic quality We advocate low osmolality contrastmedia for patients with poor left ventricular function or severemitral stenosis.     

Comparison of low osmolality ionic (ioxaglate) versus nonionic (iopamidol) contrast media in cardiac angiography

A double-blind randomized study was performed in 60 patients to compare the electrocardiographic and hemodynamic changes induced during cardiac angiography by 2 contrast media with relatively low osmolality. Ioxaglate meglumine sodium, an ionic dimer contrast medium, was compared with iopamidol, a nonionic compound. Of the 30 patients who received ioxaglate, 13 (43%) experienced a mild to moderate adverse reaction to the contrast media, while only 2 of the 30 patients (7%) in the iopamidol group had similar side effects (p less than 0.005). Significant prolongations of the QT intervals occurred with the ioxaglate injections. The QT intervals increased from 402 +/- 46 to 442 +/- 59 ms (p less than 0.001) with the right coronary artery injection and similar changes were observed after the left coronary artery injection and left ventriculography. Significant ST-segment and T-wave amplitude changes also occurred in the ioxaglate group. With iopamidol injections, there were no significant changes in any of these parameters. After the left ventriculogram, there were similar decreases in the systolic arterial pressures in both groups (-14 +/- 10 mm Hg with ioxaglate and -21 +/- 9 mm Hg with iopamidol). The left ventricular end-diastolic pressures increased after the ventriculogram in both groups (5 +/- 5 vs 2 +/- 3 mm Hg with ioxaglate and iopamidol, respectively, 60 seconds after the injection). This report demonstrates that mild to moderate adverse reactions, QT-interval prolongations, ST and T-wave changes were significantly greater during coronary angiography with ioxaglate when compared with iopamidol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventricular fibrillation during coronary angiography: reduced incidence with nonionic contrast media

Ventricular fibrillation during coronary angiography with Renografin-76 has been attributed to the high osmolar ionic and calcium binding additive properties. Isovue-370 is a new low osmolar nonionic contrast medium lacking calcium binding additives. The present investigation compared the incidence of contrast media-induced ventricular fibrillation in patients undergoing coronary angiography with Renografin-76 to that with Isovue-370. Group I consisted of 2,000 consecutive patients undergoing coronary angiography with Renografin-76, and group II consisted of 2,000 subsequent consecutive patients in whom Isovue-370 was employed as the contrast medium. There was no significant difference between groups I and II with respect to volume of contrast media used per patient (125 +/- 35 vs. 140 +/- 45 ml), age (63.5 +/- 15 vs. 60 +/- 17 years), sex (74% male vs. 76% male), ejection fraction (55% vs. 55%), valvular heart disease (8% vs. 9%), prior coronary artery bypass graft surgery (5.8% vs. 5%), or extent of coronary artery disease. Contrast media-induced ventricular fibrillation occurred in 20 patients in group I (incidence 1%), whereas eight episodes occurred in group II (incidence 0.4%) (P less than 0.03). Thus the present investigation suggests that the incidence of ventricular fibrillation during coronary angiography can be significantly decreased by using low osmolar nonionic contrast media lacking calcium binding additives.     

Accuracy of Doppler ultrasound in evaluating changes of left ventricular diastolic properties

In order to evaluate the effect of an increase in preload caused by contrast medium (Renografin-75) on Doppler echocardiographic indices of left ventricular diastolic properties, left ventricular pressure using a catheter tip micromanometer and pulsed-Doppler measurement of transmitral flow signals were measured simultaneously in 15 patients with coronary artery disease pre- and post-left ventricular angiography. After left ventricular angiography, changes in indices determined from left ventricular pressure were significant: left ventricular end-diastolic pressure increased from 17 +/- 2 mmHg to 24 +/- 2 mmHg (mean +/- SE) (P less than 0.001), maximum -dP/dt increased from 1,129 +/- 63 to 1,307 +/- 90 mmHg/sec (P less than 0.005), and time constant decreased from 73 +/- 2 to 67 +/- 1 msec (P less than 0.01). Changes in Doppler-derived indices were also significant: A/E ratio decreased from 0.99 +/- 0.08 to 0.81 +/- 0.07 (P less than 0.01), peak velocity of early diastolic filling increased from 0.61 +/- 0.03 to 0.79 +/- 0.03 M/sec (P less than 0.01), and deceleration rate increased from 3.1 +/- 0.2 to 4.6 +/- 0.2 M/sec 2 (P less than 0.01). Changes in Doppler echocardiographic indices (DR, acceleration half time, deceleration half time, and A/E ratio) were accompanied by changes in time constant and maximum -dP/dt after left ventricular angiography. However, the correlations between changes in hemodynamic indices and changes in Doppler echocardiographic indices were poor (r = 0.06 to 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic abnormalities during coronary angiography: comparison of Hypaque-76, Hexabrix, and Omnipaque-350

The hemodynamic effects induced by coronary angiography in dogs with low osmolar ionic dimer Hexabrix (HB) and nonionic Omnipaque-350 (OM) were compared to the standard ionic contrast medium, Hypaque-76 (H76), both in the normal heart and in one with simulated severe cardiac disease. Left coronary angiography was performed in 12 "normal" closed-chest dogs with 10-cc injections of H76, HB, and OM in a randomized, blinded fashion. The maximal change in the left ventricular (LV) systolic pressure (SP), mean aortic pressure (MAP), left ventricular end diastolic pressure (LVEDP), and LV dp/dt were recorded. The LVSP and MAP fell 30 +/- 3 mm Hg and 26 +/- 4 mm Hg with H76, 22 +/- 2 mm Hg and 19 +/- 2 mm Hg with HB, and 7 +/- 1.5 mm Hg and 5 +/- 1 mm Hg with OM (P less than .001). The LVEDP increased 4.8 +/- 0.5 mm Hg with H76, 3 +/- 0.5 mm Hg with HB, but only 0.2 mm Hg with OM (P less than .001). The LV dp/dt decreased 392 +/- 63 mm Hg/sec with H76 and 235 +/- 21 mm Hg/sec with HB, but increased 411 +/- 50 mm Hg with OM (P less than .001). In eight additional open-chest dogs, left coronary angiography was performed 1 hr after occlusion of the proximal LAD coronary artery and in the presence of a critical circumflex coronary artery (CX) stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of pirmenol, a new antiarrhythmic agent, assessed noninvasively

The cardiovascular effects of a new antiarrhythmic Class I agent, pirmenol, were assessed noninvasively in 10 patients without heart failure. Infusion of 100 mg pirmenol was given over 30 min following baseline M-mode echocardiography, cuff blood pressure and systolic time interval measurements. The measurements were repeated after the infusion, and 15 and 60 min later. Heart rate increased by 14.7% (P less than 0.01). Significant increases were also noted in afterload parameters, mean arterial pressure (+10.1%; P less than 0.001) and mid-systolic left ventricular wall stress (+8.0%; P less than 0.05). Concomitantly a slight increase was observed in preload, reflected in lengthening of left ventricular end-diastolic diameter (+4.8%; P less than 0.05). A decrease in fractional shortening (-6.5%; P less than 0.05) and an increase in pre-ejection period/left ventricular ejection time ratio (+16.2%; P less than 0.01) suggested a negative inotropic effect. The increased afterload and heart rate may have contributed to changes in these indices, and therefore myocardial depression may appear more pronounced than it actually was. The main effects of intravenous administration of pirmenol are elevations in heart rate and blood pressure. The induced decrease in myocardial contractility is slight.     

Behavior of left ventricular mechanoreceptors with myelinated and nonmyelinated afferent vagal fibers in cats

The purpose of this study was to determine the behavior of left ventricular mechanoreceptors with myelinated vagal afferents and to compare them with endings with nonmyelinated vagal afferents. Single unit activity was recorded from 13 endings with nonmyelinated vagal afferents (conduction velocity 2.1 +/- 0.3 m/sec) and from 16 endings with myelinated vagal afferents (conduction velocity 7.3 +/- 1.3 m/sec). Resting discharge frequencies of nonmyelinated afferents and of myelinated vagal afferents were 1.7 +/- 0.3 and 2.7 +/- 0.5 imp/sec (P less than 0.1), respectively (at left ventricular end diastolic pressure of 6 mm Hg for both groups). Ten of 16 myelinated vagal afferents had pulse synchronous discharge under basal condition, whereas only 3 of 13 nonmyelinated vagal afferents had such activity. During aortic occlusion, the discharge of myelinated vagal afferents increased 1.7 +/- 0.3 imp/sec per mm Hg, whereas nonmyelinated vagal afferents increased significantly (P less than 0.05) less (0.5 +/- 0.1 imp/sec per mm Hg). Discharge for both groups was linearly related to left ventricular end-diastolic pressure but not to left ventricular systolic pressure. Increases in left ventricular systolic pressure alone did not increase firing for either group. During aortic occlusion, the maximum discharge rates of myelinated vagal afferents (43 +/- 7 imp/sec) were significantly higher than those of nonmyelinated vagal afferents (14 +/- 3 imp/sec) at left ventricular end-diastolic pressure of 30 +/- 2 and 24 +/- 2 mm Hg, respectively. Both groups increased their discharge during volume expansion with myelinated vagal afferents showing greater sensitivity than nonmyelinated vagal afferents. All endings studied were in the inferoposterior wall of the left ventricle. All nonmyelinated vagal afferents were in or near the epicardium. In contrast, myelinated vagal afferents were equally distributed between the endocardium and the epicardium. Myelinated vagal afferents had discrete receptive fields (1-2 mm2) whereas those of nonmyelinated vagal afferents were much larger (1 cm2). In conclusion, the discharge of left ventricular endings with nonmyelinated vagal afferents and myelinated vagal afferents both appear to be determined mainly by changes in left ventricular end-diastolic pressure. They may be located at different depths in the left ventricular wall. Myelinated vagal afferents have greater sensitivity and maximum firing frequencies than nonmyelinated vagal afferents.     

Risk of thrombosis during coronary angioplasty with low osmolality contrast media

Studies in vitro have suggested that nonionic low osmolar contrast agents produce an increase in thrombogenicity. To determine the incidence of thrombi related to the use of nonionic low osmolar contrast media during coronary angioplasty, a double-blind randomized study was performed in 100 patients. Medication before angioplasty included oral aspirin (250 mg/day) in all cases. At the beginning of the procedure, aspirin (250 mg) and heparin (10,000 U) were intravenously administered. During the procedure patients were randomly assigned to receive either an ionic low osmolar contrast agent ioxaglate (n = 50), or a nonionic low osmolar contrast media iohexol (n = 50). The presence of thrombus was evaluated on the angiogram and on the guidewire immediately after its retrieval from the patients. Clinical, angiographic and procedural variables were similar in the 2 randomized groups. Angiographic evidence of thrombus was observed in 1 patient (2%) assigned to ioxaglate and in 11 patients (22%) assigned to iohexol (p less than 0.005). One patient (2%) from the ioxaglate group and 6 patients (12%) from the iohexol group showed thrombotic residues on the guidewire (p = not significant). Three patients had acute myocardial infarction, 1 patient (2%) receiving ioxaglate and 2 patients (4%) iohexol (p = not significant). There were no deaths. Thus, compared with an ionic low osmolar contrast media ioxaglate, the nonionic low osmolar contrast agent iohexol increases the incidence of thrombus during coronary angioplasty.     

Regression of left ventricular mass is accompanied by improvement in rapid left ventricular filling following antihypertensive therapy with metoprolol

Left ventricular hypertrophy is associated with abnormal left ventricular diastolic filling in patients with hypertension. To assess the effects of antihypertensive therapy on the heart in nine previously untreated patients with echocardiographically-detected left ventricular hypertrophy, left ventricular mass and rapid left ventricular filling rate were compared before and after 6 months of treatment with metoprolol monotherapy. Metoprolol was given in doses of 100 to 400 mg/day (average dose, 167 mg/day in two divided doses) and significantly reduced both casual, office blood pressure (150/101 to 130/86 mm Hg, p less than 0.01) and 24-hour ambulatory blood pressure (139/91 to 126/79 mm Hg, p less than 0.05 for systolic, p less than 0.01 for diastolic). Following treatment with metoprolol, left ventricular mass index decreased from 135 +/- 20 to 120 +/- 13 gm/m2 (p less than 0.05), while rapid left ventricular filling rate increased from 1.89 +/- 0.24 to 2.09 +/- 0.27 end-diastolic volumes/sec (p less than 0.01). The reduction in left ventricular mass index was secondary to decreased posterior and septal wall thicknesses (13% and 11%, respectively, p less than 0.05 for both), as there were no changes in the left ventricular internal dimensions. Neither resting nor exercise left ventricular ejection fraction changed on metoprolol therapy compared to the baseline values. These data demonstrate that regression of left ventricular hypertrophy in never-previously-treated hypertensive patients is accompanied by improved diastolic performance following beta-adrenergic blocker monotherapy.     

Comparative effects of ionic and nonionic contrast materials on indexes of isovolumic contraction and relaxation in humans

The effects of contrast media on left ventricular (LV) relaxation as assessed by the time constant of isovolumic relaxation have not previously been studied. A new nonionic contrast agent (iohexol) has been shown to have fewer deleterious effects than standard ionic agents. Nineteen patients received iohexol and sodium meglumine diatrizoate (Renografin-76) in a double-blind, crossover study during left and right coronary arteriography and with simultaneous high-fidelity micromanometer measurements of LV pressure. Neither agent induced significant changes in LV end-diastolic pressure after right or left coronary arteriography. After right coronary arteriography, neither agent produced significant deterioration of peak positive dP/dt or (dP/dt)/DP40 (dP/dt at a developed pressure of 40 mm Hg). However, after right coronary arteriography both agents caused a transient deterioration in peak negative dP/dt and the time constant of isovolumic relaxation (p less than 0.05 at 20 seconds after arteriography). After left coronary arteriography, sodium meglumine diatrizoate induced deterioration of systemic blood pressure (p less than 0.05), peak positive dP/dt (p less than 0.01), (dP/dt)/DP40 (p less than 0.05), peak negative dP/dt (p less than 0.01) and the relaxation time constant (p less than 0.01). These effects were not induced by iohexol. Thus, nonionic contrast media exert negligible alterations on LV function when used for coronary arteriography. The findings are of potential clinical importance in view of the large number of patients with depressed LV function who undergo coronary arteriography.     

Effects of contrast media on endothelial cell monolayers under controlled flow conditions

To compare the biocompatibility of nonionic and ionic intravascular contrast media in a more physiologic in vitro system, key aspects of blood flow through a microvessel were simulated. Toward this end, monolayers of endothelial cells placed in a specially designed flow chamber, real-time imaging of the monolayers by brightfield and phase videomicroscopy, and real-time imaging and computer-aided quantitation at normal hematocrit levels of platelet adhesion/aggregation to sites of monolayer injury by means of epifluorescence videomicroscopy were used. At a concentration in culture medium of 20% by volume, it was found that monolayer morphology was least altered by iohexol when compared with diatrizoate and ioxaglate; monolayer production of prostacyclin was enhanced (p less than 0.001) by ioxaglate compared with saline controls; and at a concentration in citrated blood of 20% by non-red-cell volume, platelet adhesion/aggregation was reduced by all 3 contrast agents in the order diatrizoate greater than ioxaglate greater than iohexol.     

Abnormalities of left ventricular function and geometry in adults with an atrial septal defect. Ventriculographic, hemodynamic and echocardiographic studies.

Left ventricular function and motion in 12 adults with an ostium secundum atrial septal defect were analyzed utilizing biplane cineangiography. Values for left ventricular end-diastolic volume index, stroke volume index, ejection fraction, left ventricular end-diastolic pressure and mean rate of circumferential fiber shortening were compared with values in an age-matched group of 11 normal subjects. Comparisons of ventriculographic and echocardiographic data were also made in 5 patients and 10 control subjects. Cardiac index was smaller in patients than in the normal subjects (3.6 vs. 4.5 liters/min per m2, P less than 0.01). Although left ventricular end-diastolic pressure was similar (8 mm Hg in both groups), the end-diastolic volume index was significantly smaller in patients than in normal subjects (56 vs. 76 ml/m2, P less than 0.05). Stroke volume index was also significantly smaller in patients (40 vs. 52 ml/m2, P less than 0.01). The two groups had similar values for ejection fraction (65 +/- 2 percent [standard error of the mean] in patients vs. 68 +/- 2 percent in normal subjects), circumferential fiber shortening velocity (1.67 +/- 0.13 vs. 1.81 +/- 0.15 circumferences/sec.), heart rate (91 +/- 7 vs. 90 +/- 5 beats/min) and mean systemic arterial pressure (92 +/- 5 vs. 87 +/- 3 mm Hg). Early systolic bulging of the upper ventricular septum toward the right ventricle was seen in 10 of 12 patients with an atrial septal defect but in no normal subject. Echocardiographic data supported these findings. No other abnormalities of motion were consistently noted. It is concluded that the left ventricle of patients with an atrial septal defect is subnormal in volume and abnormal in sequence of contraction of the septum and is characterized by apparent decreased distensibility.