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Biomedical subjects

M A Quinones

Publications and source records attributed to M A Quinones.

At least 37 records · Page 2Linked to original sources

Mid-cavity obstruction in apical hypertrophy: Doppler evidence of diastolic intraventricular gradient with higher apical pressure.

Three cases of apical left ventricular hypertrophy demonstrating a sequestered small left ventricular apical cavity with complete systolic and partial diastolic intraventricular obstruction are described. Doppler studies revealed that flow from the apical chamber is aborted during early systole with further emptying during diastole through a narrow intraventricular channel, where a diastolic high-velocity jet (greater than or equal to 2.5 m/sec) directed from apex to base was localized. This indicated a significantly higher pressure in early diastole in the sequestered apical cavity. Filling of the apical chamber occurred late in diastole and during isovolumic ventricular contraction. The observations by Doppler of complete intraventricular systolic and partial diastolic obstruction in apical hypertrophy are new and may have significant clinical implications.

Aged↗

Assessment of myocardial perfusion in humans by contrast echocardiography. I. Evaluation of regional coronary reserve by peak contrast intensity.

Myocardial contrast echocardiography was performed during coronary angiography with 2 ml of sonicated meglumine diatrizoate sodium 76% (meglumine) in 40 patients (ranging in age from 25 to 79 years) before and 10 to 15 s after intracoronary injection of papaverine, 8 mg into the right coronary artery (n = 43) and 10 mg into the left (n = 46). The same protocol was repeated in 17 patients 5 to 10 min after completion of coronary angioplasty. In 13 patients with normal coronary angiograms, peak contrast intensity corrected for background myocardial intensity was measured in 36 regions and was found to increase after papaverine from 36 +/- 16 to 55 +/- 22 U (p less than 0.001). In contrast, in the 27 patients with angiographic evidence of coronary artery disease, peak intensity in 64 regions remained unchanged after papaverine (35 +/- 22 versus 36 +/- 23 U). An increase in peak intensity greater than or equal to 10 U was 80% sensitive and 92% specific for coronary artery disease. After successful coronary angioplasty, peak intensity in the involved regions improved significantly (p less than 0.001) during baseline contrast injections (from 32 +/- 16 to 50 +/- 25 U) as well as in the postpapaverine contrast injections (from 30 +/- 12 to 60 +/- 26 U). In conclusion, measurement of peak contrast intensity after intracoronary injections of sonicated meglumine provides a relative index of myocardial perfusion that allows assessment of regional coronary reserve in patients with coronary artery disease. This may be of particular value in evaluating the immediate effects of coronary angioplasty on myocardial perfusion.

Adult↗

Quantitative assessment of left ventricular wall motion by two-dimensional echocardiography: validation during reversible ischemia in the conscious dog.

This study was designed to test the accuracy of echocardiographic radial shortening measurements during variable degrees of regional dysfunction produced by 14 transient (less than or equal to 10 min) coronary occlusions (8 left anterior descending coronary artery, 6 left circumflex coronary artery) followed by up to 24 h of reperfusion in chronically instrumented conscious dogs. Independent measurement of regional myocardial thickening was obtained using epicardial pulsed Doppler probes and served as a standard for comparison. Radial shortening fraction was derived from two-dimensional short-axis views along 12 equidistant radii. Six reference systems from the epicardial and endocardial centers of geometry (centroids) in a fixed or a floating position were explored. In the ischemic zone, percent thickening fraction averaged 22 +/- 5% at baseline, decreased to -4 +/- 4% during occlusion and gradually returned to baseline values after reperfusion. Percent change in radial shortening correlated significantly with percent change in thickening fraction in the ischemic zone. The worst correlation was seen with the floating endocardial centroid (r = 0.68), and the best was observed with the epicardial floating reference (r = 0.91). Moreover, the epicardial floating reference provided narrower 95% confidence limits of radial shortening and less heterogeneity among radii than did fixed reference systems. Thus, compared with an independent standard, echocardiographic measurement of radial shortening from the short axis provided recognition of discrete grades of regional dysfunction induced by transient reversible ischemia. This technique may be amenable for serial assessment of regional function after interventions on the ischemic myocardium.

Animals↗

Design of rat renin inhibitory peptides.

Because several well-studied strains of rats manifest spontaneous hypertension, we set out to design a renin inhibitor suitable for use in this species. On the basis of the sequence of the renin substrate, a series of substrate analogue inhibitory peptides were synthesized by systematically modifying the P5, P3, P2, P1P1', P2', P3', and P4' positions. In assays against rat plasma renin, we found that modifications at the C-terminal segment have a marked influence on potency, and that a secondary butyl side chain at the P2' position is important for obtaining optimal activity. The structure at the P3' position, however, could vary considerably without significant effect. The steric effect of the P2 position was important; there an isopropyl side chain provided optimal binding between the inhibitor and the enzyme. At the P3 and P5 positions, potency appeared to depend on aromatic side chains. The effects at the P1P1' position of the transition-state residue (3S,4S)-4-amino-3-hydroxy -6-methylheptanoic acid (statine) and its congeners (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA) and (3S,4S)-4-amino-3-hydroxy-5-cyclohexylpentanoic acid (ACHPA) were found to depend on the sequence of the C-terminal segment. For peptides with an unfavorable C-terminal segment (-Ile-Phe-NH2), AHPPA and ACHPA resulted in a surprising retention of potency. For peptides with a favorable C-terminal segment (-Leu-Phe-NH2), the effect of AHPPA was mild, even though ACHPA still significantly enhanced potency. The hypotensive and plasma renin inhibitory effects of three of the analogues were then studied in anesthetized sodium-depleted rats. One of the compounds, acetyl-His-Pro-Phe-Val-Statine-Leu-Phe-NH2 (IC50 against rat plasma renin of 30 nM at pH 7.4), proved to be a potent hypotensive agent and a potentially useful probe for the study of the renin-angiotensin system in rats.

Amino Acid Sequence↗

Guidelines for optimal physician training in echocardiography. Recommendations of the American Society of Echocardiography Committee for Physician Training in Echocardiography.

Over the past few years, the clinical use of echocardiography has continued to expand. Echocardiographic techniques are used widely to define normal and abnormal cardiac anatomy, evaluate cardiac chamber sizes and dynamics, assess valvular and pericardial diseases, detect intracavitary masses, measure pressure gradients across discrete stenoses, determine flow volumes, detect and assess the severity of valvular regurgitation, demonstrate and quantitate intracardiac shunts, and measure the timing of cardiac events. These and related applications have led to the increasing use of echocardiography in the diagnostic evaluation of many cardiac disorders. Echocardiography requires considerable theoretical knowledge, technical skill and practical experience to be used in an optimal manner. Previous publications have suggested guidelines for physician training in the techniques of M-mode and 2-dimensional echocardiography. The clinical applications of echocardiography continue to grow, however, and Doppler techniques for evaluating blood flow have become an established component of the echocardiographic evaluation of many disorders. This article presents the current recommendations of the American Society of Echocardiography as to the background knowledge, the nature and amount of practical experience, and the type of training site that are optimal for the training of physicians who take responsibility for the conduct and interpretation of echocardiographic studies.

Cardiology↗

Quantification of atrial contribution to left ventricular filling by pulsed Doppler echocardiography and the effect of age in normal and diseased hearts.

Atrial filling fraction, or the fraction of stroke volume resulting from atrial contraction, was measured by Doppler echocardiography from the time-velocity integral of mitral anulus inflow with a method that allows separation of conduit or passive flow from flow resulting from the atrial contraction. The method was validated in 17 patients with externally programmable ventricular demand pacemakers by showing that the time-velocity integral of passive flow (excluding the A wave) during sinus or sequential atrioventricular pacing was almost identical to the time-velocity integral during ventricular pacing. Atrial filling fractions were then measured in 41 normal subjects, aged 20 to 80 years; 28 patients with echocardiographic evidence of concentric left ventricular hypertrophy; 24 with dilated cardiomyopathy (13 of whom had an ischemic origin); and 19 with acute myocardial infarction. Atrial filling fraction increased significantly with age in normal subjects (r = 0.77; p less than 0.001) and ranged from 12% in a 20-year-old man to 46% in a normal 80-year-old woman. In the hypertrophy group, atrial filling fraction had a weak relation with age (r = 0.47; p = 0.006), and the values were significantly higher than in normal subjects. In patients with cardiomyopathy or infarction, atrial filling fraction varied over a wide range and showed no relation to age. Thus, atrial filling fraction as determined by Doppler echocardiography is significantly altered by both age and left ventricular disease. Age-corrected nomograms are essential when assessing atrial filling fraction in individual patients.

Adult↗

Relation of Doppler-derived left ventricular filling parameters to age and radius/thickness ratio in normal and pathologic states.

Transmitral diastolic inflow velocities determined by Doppler echocardiography have been shown to reflect left ventricular (LV) filling rates, and are therefore dependent on ventricular compliance. Radius to wall thickness ratio is an index of cavity to wall volume ratio, an important determinant of LV compliance. Accordingly, Doppler measurements of mitral anulus peak early diastolic velocity, peak atrial velocity and atrial filling fraction were made in 25 normal control subjects, mean age 46 years (range 28 to 75), and 29 patients with dilated cardiomyopathy or concentric LV hypertrophy, mean age 54 years (range 12 to 78). In addition, radius/thickness ratio was determined by 2-dimensionally guided M-mode recordings of the left ventricle. In the normal group, peak early velocity, the ratio of early to atrial velocity and atrial filling fraction correlated with age (r = -0.905, -0.823 and 0.810, respectively), but not with radius/thickness ratio. In the group with LV hypertrophy or dilatation, peak early velocity, ratio of early to atrial velocity and atrial filling fraction correlated with radius/thickness ratio (r = 0.625, 0.752 and -0.631, respectively), but not with age. Thus, with normal aging, early LV filling is reduced and atrial systole is augmented, probably reflecting intrinsic alterations in myocardial stiffness with age. In chronic LV disease, changes in radius/thickness ratio and, consequently, in chamber stiffness, influence early filling directly and atrial filling inversely, overriding the effects of age. Age-related standards are needed, however, to evaluate individual effects of a disease process on LV filling dynamics by Doppler.

Adult↗

Assessment of left ventricular diastolic filling by two-dimensional echocardiography.

Although two-dimensional echocardiography has provided accurate measurements of left ventricular ejection fraction, the technique has been limited in the evaluation of diastolic function. First half-filling fraction, representing the difference between mid-diastolic and end-systolic volumes divided by stroke volume, is a recently introduced index of diastolic function. We developed a method for determining half-filling fraction by two-dimensional echocardiography with the use of the average of left ventricular internal diameters measured at the base, middle, and apical third of the ventricular cavity in multiple longitudinal planes. In 27 patients with a wide range of ventricular function, we compared angiographic measurements of half-filling fraction to results obtained by two-dimensional echocardiography. Half-filling fraction measured angiographically averaged (mean +/- SD) 0.58 +/- 0.15 (range 0.26 to 0.77) and measured by two-dimensional echocardiography averaged 0.58 +/- 0.15 (range 0.35 to 0.90). A significant correlation was found between angiographic and echocardiographic half-filling fractions (r = 0.84, SEE = 0.08). Results were similar in the presence or absence of segmental wall motion abnormalities. All seven patients with half-filling fractions below 0.50 by echocardiography had depressed half-filling fractions by angiography; three of these patients had ejection fractions of greater than or equal to 0.55. Thus half-filling fraction can be derived with two-dimensional echocardiography providing a noninvasive assessment of diastolic function.

Adult↗

End-systolic radius to thickness ratio: an echocardiographic index of regional performance during reversible myocardial ischemia in the conscious dog.

Regional myocardial dysfunction induced by ischemia is associated with less thickening and a larger ventricular radius at end-systole. Thus, end-systolic radius to thickness ratio measured by echocardiography may provide an accurate index of regional left ventricular function that is totally independent of cardiac motion. To test this hypothesis, a total of 14 transient (less than or equal to 10 minutes) coronary artery occlusions (8 left anterior descending, 6 left circumflex) followed by up to 24 hours of reperfusion were performed in six chronically instrumented conscious dogs providing multiple grades of regional ventricular dysfunction. Regional myocardial thickening fraction was determined with epicardial pulsed Doppler probes and served as an independent standard for comparison with simultaneous echocardiographic measurements. End-systolic radius to thickness ratio and radial shortening fraction were derived from the two-dimensional echocardiographic short-axis view along 12 equidistant radii. In the ischemic zone, percent thickening fraction averaged 22 +/- 5% during baseline, decreased to -4 +/- 4% during occlusion with gradual return to baseline after reperfusion. End-systolic radius to thickness ratio averaged 1.39 +/- 0.25 before coronary occlusion and increased to 2.97 +/- 0.48 during occlusion with a gradual return to baseline values. A significant correlation was found between Doppler-determined thickening fraction measurements and echocardiographic end-systolic radius to thickness ratio as well as radial shortening fraction for absolute values (r = -0.83 and 0.75, respectively; n = 65) and percent change from baseline (r = -0.86 and 0.78, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hemodynamic effects of moricizine at rest and during supine bicycle exercise: results in patients with ventricular tachycardia and left ventricular dysfunction.

To evaluate the hemodynamic effects of moricizine, 20 patients with frequent nonsustained ventricular tachycardia (VT) with a mean left ventricular ejection fraction (EF) of 39 +/- 14% were enrolled in a prospective single-blind, placebo-controlled study. Hemodynamic measurements were performed at rest and during supine bicycle exercise on placebo and moricizine therapy (10 mg/kg/day). Although 16 of 19 patients experienced no rest or exercise deterioration in hemodynamic parameters during drug dosing, three patients had acute deterioration of pulmonary capillary wedge pressure and cardiac index (CI) on moricizine. During follow-up of 6 +/- 3 months, two subgroups were identified: 10 of 19 patients had effective long-term reduction in VT, whereas 9 of 19 patients had poor control of ventricular arrhythmia or congestive heart failure and were discontinued from the trial. Baseline EF and hemodynamic parameters at rest were similar in both patient subgroups. However, protocol dropouts had a hemodynamic response to exercise on moricizine that was significantly depressed as compared to patients with a favorable antiarrhythmic outcome (p less than 0.02). The following hemodynamic profile characterizes patients unlikely to have an antiarrhythmic response to moricizine: an increase in CI of less than 1.0 L/min/m2 and no increase in left ventricular stroke work index during supine exercise.

Exercise Test↗

Complex ventricular arrhythmias associated with the mitral valve prolapse syndrome. Effectiveness of moricizine (Ethmozine) in patients resistant to conventional antiarrhythmics.

On the basis of epidemiologic studies, more than 10 million Americans have echocardiographic evidence of mitral valve prolapse. Although ventricular arrhythmias occur frequently (over 50 percent of patients with mitral valve prolapse), they rarely result in sustained ventricular tachycardia or sudden cardiac death. However, a common problem in clinical practice is a patient with mitral valve prolapse and symptomatic complex ventricular arrhythmias refractory or intolerant to both beta blockers and conventional type I antiarrhythmics. These drugs are known to have frequent side effects, toxicity, and proarrhythmic effects. In 17 patients with mitral valve prolapse who presented with symptomatic complex ventricular arrhythmias and who were unresponsive to an average of the three conventional agents, moricizine (Ethmozine) was effective in suppressing 90 percent of ventricular premature depolarizations, 99 percent of nonsustained runs of ventricular tachycardia, as well as all sustained runs of ventricular tachycardia, resulting in abolition of palpitations, dizziness, and syncopal episodes. Its efficacy as well as its low frequency of minor side effects makes it ideal for future consideration in the population with mitral valve prolapse, who are frequently young and may therefore require therapy for many years.

Adult↗

Determination of regurgitant fraction in isolated mitral or aortic regurgitation by pulsed Doppler two-dimensional echocardiography.

Measurements of mitral and aortic valve flows were obtained with two-dimensional Doppler echocardiography in 25 patients with isolated mitral (n = 19) or aortic (n = 6) regurgitation and regurgitant fraction was calculated as the difference between the two flows divided by the flow through the regurgitant valve. Results were compared with measurements of regurgitant fraction determined by combined left ventricular angiography and thermodilution. Regurgitant fraction averaged 56 +/- 18% (range 19 to 79) by Doppler echocardiography and 48 +/- 17% (range 13 to 72) by angiography. A significant correlation was observed between the two methods (r = 0.91; SEE = 7%). In contrast, no significant correlation was found between regurgitant fraction measured by either method and the angiographic 1+ to 4+ qualitative classification of regurgitation. Doppler echocardiography appears to be an accurate method for the non-invasive quantification of severity of regurgitation in isolated left-sided valve lesions.

Adolescent↗

Accurate noninvasive quantification of stenotic aortic valve area by Doppler echocardiography.

Laminar flow through a conduit is equal to the mean velocity times the cross-sectional area of the orifice. Therefore, volume is equal to the time-velocity integral multiplied by the cross-sectional area. In aortic stenosis, flow in the stenotic jet is laminar and the aortic valve area should be equal to the volume of blood ejected through the valve divided by the time-velocity integral of the aortic jet velocity recorded by continuous-wave Doppler echocardiography. To test whether this concept can be used to accurately determine aortic valve area noninvasively by the Doppler method, 39 patients (age 35 to 82 years, mean 63) underwent pulsed Doppler combined with two-dimensional echocardiography for measurement of stroke volume at the aortic, pulmonic, and mitral anulus as well as continuous-wave Doppler recording of the aortic jet. Aortic valve area determined at cardiac catheterization by the Gorlin equation ranged between 0.4 and 2.07 cm2 (mean 0.89 +/- 0.45). Doppler-derived valve area, determined with the stroke volume value from either the aortic, pulmonic, or mitral anulus, correlated well with the area determined at cardiac catheterization (r = .95, .97, and .96, respectively). A simplified method for measuring aortic valve area derived as the cross-sectional area of the aortic anulus times peak velocity just proximal to the aortic valve divided by peak aortic jet velocity correlated well with measurements obtained at cardiac catheterization (r = .94). An excellent separation between critical and noncritical aortic stenosis was seen using either one of the Doppler methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Efficacy and safety of moricizine in patients with ventricular tachycardia: results of a placebo-controlled prospective long-term clinical trial.

This was a prospective, placebo-controlled, single-blind trial of moricizine (ethmozine) in a dose averaging 10 mg/kg/day in 50 patients, the single entrance criterion being the presence of 10 or more runs of nonsustained ventricular tachycardia (VT) on a screening 24 hr ambulatory electrocardiographic (ECG) recording. Electrophysiologic study was not included as part of this trial design. The placebo frequency of VT (average 3 days of recording) was 1036 +/- 479 runs of VT per day. Most patients (31/50) had coronary artery disease. The study population had a mean left ventricular ejection fraction (LVEF) of 36 +/- 16%; 20 patients also had a history of sustained VT. Protocol failure was defined as failure to achieve a 75% or greater reduction in runs of VT (as judged by ambulatory ECG recording) and/or recurrence of sustained VT while on moricizine. Among the 48 patients treated with moricizine, the drug was initially efficacious in 35 (73%), with two-thirds having total abolition of nonsustained VT. Although it was effective in reducing runs of nonsustained VT, moricizine was ineffective in preventing the recurrence of sustained VT (63% failure rate). Side effects were uncommon and the drug was well tolerated in most patients with LVEFs of 30% or less.

Aged↗

Determination of cardiac output by Doppler echocardiography: a critical appraisal.

Doppler echocardiography enables noninvasive determination of blood velocity and flow area through which quantitation of blood flow in vessels and across valvular orifices can be achieved. The stroke volume is rendered as the product of the flow area and the area beneath the velocity curve; on taking the heart rate into consideration, the cardiac output can be calculated. Essentially, this method can be used in the region of all four cardiac valves, the ascending aorta and the pulmonary artery. For calculation of the mitral and tricuspid velocity, the sample volume is positioned in the region of the tips of the leaflets or in the valve anulus. The flow area is most frequently calculated from the diameter of the valve anulus under the assumption of a circular cross-section. Additionally, in some studies, with respect to correction for area changes during diastole, separation of the leaflets in the M-mode echocardiogram has been employed. Determination of the right ventricular output is accomplished through the combination of the blood flow velocity in the pulmonary artery and the cross-sectional area of this vessel, the right ventricular outflow tract or the pulmonic anulus. To calculate flow in the ascending aorta, both pulsed and continuous-wave Doppler techniques have been employed and the diameter of the ascending aorta or the aortic root is derived echocardiographically. Comparative studies of the various methods show that measurement of flow in the region of the aortic anulus yields results somewhat superior to that of the other methods. Possible sources of error in these methods result from simplifying assumptions with respect to calculation of the area of flow, that is, equating the anatomical area with the area of flow, circular or elliptical cross-sectional models, temporal constancy of the areas as well as the velocities, that is, constant position of the sample volume, flat velocity profile and neglect of angle deviations.

Aorta↗

The changing base line of complex ventricular arrhythmias. A new consideration in assessing long-term antiarrhythmic drug therapy.

Initial base-line electrocardiograms are used to assess the efficacy of treatment for ventricular arrhythmias. This approach assumes that in the absence of treatment the frequency of arrhythmia would remain constant. To test the validity of this assumption, we studied 26 clinically stable patients with symptomatic but not life-threatening ventricular arrhythmias, during two periods of placebo treatment separated by a mean of 17 months. As compared with the initial placebo period, there were significant reductions in ventricular premature depolarizations (50 per cent), pairs (65 per cent), and ventricular tachycardia (83 per cent) during the second period of placebo administration (P less than or equal to 0.05 for all comparisons). Over one third of the patients gave the appearance of receiving successful therapy during the second placebo period, even when the reported spontaneous variability of ventricular arrhythmia was taken into consideration. If unrecognized, these long-term spontaneous changes in the frequency of arrhythmia could result in continuation of unnecessary and potentially toxic therapy and lead to incorrect conclusions regarding the efficacy of antiarrhythmic drugs in clinical trials. We therefore recommend that the frequency of arrhythmia be reassessed annually in the absence of treatment in patients similar to those in our study. These recommendations should not be applied to patients with life-threatening ventricular arrhythmias.

Adult↗