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Biomedical subjects

S E Lewis

Publications and source records attributed to S E Lewis.

At least 127 records · Page 7Linked to original sources

Radionuclide ventriculography to evaluate myocardial function.

Developments over the past decade have allowed one to visualize the right and left ventricles using radionuclide techniques and to study the influence of a wide range of physiologic, pharmacologic and surgical interventions on global and regional ventricular function thereby providing important diagnostic insight and improved therapeutic capabilities. These tests are relatively non-invasive, they can be performed serially, they may be performed in patients that are seriously ill, and they have no recognized risk other than low level radiation exposure. With continued improvement in noninvasive imaging and processing and in the sophistication of associated computer systems, one may expect significant and wide ranging additional contributions in the assessment of myocardial function using radionuclide ventriculographic techniques.

Cardiac Output↗

Alterations in left ventricular volumes and ejection fraction during atrial pacing in patients with coronary artery disease: assessment with radionuclide ventriculography.

The present study was performed to determine the utility of radionuclide ventriculography (RNV) in conjunction with atrial pacing in the identification of individuals with coronary artery disease. Accordingly, left ventricular end-diastolic volume index, end-systolic volume index, ejection fraction, and regional wall motion were measured with radionuclide ventriculography before and during atrial pacing in 37 patients: 27 with and 10 without (control subjects) coronary artery disease. In the control subjects, pacing caused a decrease in end-diastolic volume index (77 +/- 19 [mean +/- SD] ml/M2 at rest, 50 +/- 18 ml/M2 at peak pacing; p less than 0.001), a decrease in end-systolic volume index (34 +/- 14 ml/M2 at rest, 19 +/- 9 ml/M2 at peak pacing; p less than 0.001), an increase in ejection fraction (0.61 +/- 0.11 at rest, 0.66 +/- 0.11 at peak pacing; p = 0.006); and no deterioration in wall motion. In 16 patients with coronary artery disease who developed ECG and/or metabolic evidence of ischemia during pacing, end-diastolic volume index decreased (87 +/- 26 ml/M2 at rest, 69 +/- 24 ml/M2 at peak pacing; p less than 0.001), end-systolic volume index was unchanged (43 +/- 20 ml/M2 at rest, 44 +/- 21 ml/M2 at peak pacing; p = NS), ejection fraction decreased (0.55 +/- 0.12 at rest, 0.40 +/- 0.14 at peak pacing; p less than 0.001), and new wall motion abnormalities developed in 14. In 11 patients with coronary artery disease but no ECG or metabolic evidence of ischemia, pacing caused a decrease in end-diastolic volume index (80 +/- 26 ml/M2 to 61 +/- 31 ml/M2; p less than 0.001), a decrease in end-systolic volume index (36 +/- 17 ml/M2 to 28 +/- 20 ml/M2; p = 0.002), no change in ejection fraction (0.60 +/- 0.11 to 0.60 +/- 0.13; p = NS), and new wall motion abnormalities in four. Although the specificity of these scintigraphic measurements for the identification of patients with coronary artery disease was excellent (1.0), the combined sensitivity of all scintigraphic measurements was high only if ECG or metabolic evidence of ischemia was present: 0.94 in patients with evidence of ischemia but only 0.36 in those without ischemia. Thus radionuclide ventriculography during incremental atrial pacing is useful in the identification of patients with coronary artery disease only if ischemia is induced.

Cardiac Output↗

Prognostic value of resting and submaximal exercise radionuclide ventriculography after acute myocardial infarction in high-risk patients with single and multivessel disease.

In patients who survive the acute phase of myocardial infarction, those with multivessel coronary artery disease generally have a worse prognosis than those with single-vessel disease. However, some patients with significant multivessel stenoses have a good prognosis, whereas some with a significant single-vessel stenosis have a poor prognosis. Thus, although definition of coronary anatomy may be helpful, it is a not a fail-safe prognosticator. In this retrospective analysis, the association of abnormalities at rest and during submaximal exercise testing with radionuclide ventriculography after acute myocardial infarction with major cardiac complications (death, recurrent infarction, severe angina or congestive heart failure) in the ensuing 6 months was assessed in patients with single and multivessel disease. Coronary angiography and submaximal exercise testing with radionuclide ventriculography were performed within 3 months of each other in 42 patients. Eleven of the 16 patients with single-vessel coronary stenosis had major cardiac complications. The subsequent course of these 16 patients was correctly predicted by left ventricular ejection fraction (LVEF) less than or equal to 0.40 in 8 patients, by LVEF less than 0.55 in 7 patients, by failure of LVEF to increase by 0.05 units in 13 patients, and by an increase in left ventricular end-systolic volume index (LVESVI) during exercise greater than 5% above baseline in 11 patients. Of the 26 patients with multivessel coronary artery disease, 24 had major cardiac complications. The subsequent course of these 26 patients was correctly predicted in 13 by LVEF less than or equal to 0.40, in 20 by LVEF less than 0.55, in 25 by a failure of LVEF to increase by 0.05 units during exercise, and in 20 by an increase in LVESVI by greater than 5% during exercise. Thus, submaximal exercise testing with radionuclide ventriculography may provide valuable prognostic information concerning the occurrence of major cardiac events after myocardial infarction not only in patients with multivessel disease, but also in those with single-vessel disease. Exercise-induced abnormalities of left ventricular function may have greater prognostic importance than the delineation of coronary arterial anatomy or the assessment of residual left ventricular function at rest.

Adult↗

Symptomatic, electrocardiographic, metabolic, and hemodynamic alterations during pacing-induced myocardial ischemia.

Atrial pacing has been used to assess the physiologic impact of coronary artery disease (CAD). Several variables have served as markers of pacing-induced myocardial ischemia, but their specificities and sensitivities are unknown. Accordingly, in 28 patients, incremental atrial pacing was performed. Of the 28, 10 had no CAD. The left ventricular ejection fraction (LVEF) (by gated equilibrium blood pool scintigraphy) increased in this group (0.60 +/- 0.11 [mean +/- standard deviation] before pacing to 0.67 +/- 0.13 at peak-pacing, p = 0.002). In no patient did left ventricular end-diastolic pressure increase by greater than 5 mm Hg. No patient had lactate production, and 2 (20%) had electrocardiographic S-T segment depression greater than or equal to 0.1 mV. Four (40%) had chest pain with atrial pacing. In the remaining 18 patients with CAD, atrial pacing caused a decrease in LVEF greater than or equal to 0.05 (0.46 +/- 0.10 to 0.33 +/- 0.09, p less than 0.001) and new segmental wall motion abnormalities in all, indicating pacing-induced myocardial ischemia. Only 8 (44%) had an increase in left ventricular end-diastolic pressure of greater than 5 mm Hg, and only 9 (50%) had lactate production. Ten (56%) had ischemic electrocardiographic changes, and 12 (67%) had chest pain. Thus, the electrocardiographic, metabolic, and hemodynamic alterations that may accompany pacing-induced ischemia are specific but relatively insensitive markers of ischemia. In contrast, chest pain during atrial pacing is a nonspecific occurrence, appearing with similar frequency in normal subjects and patients with CAD and pacing-induced ischemia.

Adult↗

Left ventricular functional alterations at rest and during submaximal exercise in patients with recent myocardial infarction.

Submaximal exercise testing with radionuclide ventriculography was performed in 117 patients prior to hospital discharge 16.7 +/- 6.7 days (SD) following acute myocardial infarction. The hypothesis tested in this study was that patients with different locations and types of infarction have different functional responses to submaximal exercise prior to discharge. The distribution of the myocardial infarctions were anterior transmural in 33, inferior transmural in 39, anterior nontransmural in 23, inferior nontransmural in 19, and indeterminant in three. Patients with transmural infarction generally had significantly larger resting left ventricular volumes at end-diastole and end-systole and lower ejection fractions and systolic blood pressure/end-systolic volume indexes than patients with nontransmural infarctions (p less than 0.05). During submaximal exercise, the change in end-systolic volume was significantly different in these two groups. When patients were separated further into anterior and inferior transmural subgroups, the patients with anterior transmural infarction had significantly lower left ventricular ejection fractions and higher right ventricular ejection fractions than the group with inferior transmural infarction (p less than 0.05). In response to exercise, the group with anterior transmural infarction had a significant decrease in left ventricular ejection fraction and a blunted systolic blood pressure/left ventricular end-systolic volume index, in comparison to patients with inferior myocardial infarction (p less than 0.05); this was the only group to have a significant increase in end-systolic volume. The group variance for the parameters studied was large, particularly during exercise when the individual responses were frequently directionally opposite from the group means. The group with anterior transmural infarction was the most homogeneous, with 26 of 33 having a directionally abnormal response to submaximal exercise. It was concluded that the group with anterior transmural infarction generally displayed the most abnormal left ventricular function. However, despite significant group differences in resting ventricular function with different infarcts, the intragroup variability at rest and in response to exercise was too great to permit an accurate prediction of the subject's resting ventricular performance or to permit a prediction of exercise response based solely on location of the infarct.

Aged↗

A mouse model for beta-thalassemia.

A mutation that produces an absolute deficiency of normal beta-major globin polypeptides has been recovered from a DBA/2J male mouse. Most mice homozygous for the deficiency survived to adulthood and reproduced but were smaller at birth than their littermates and demonstrated a hypochromic, microcytic anemia with severe anisocytosis, poikilocytosis, and reticulocytosis and the presence of inclusion bodies in a high proportion of circulating erythrocytes. Mice heterozygous for the deficiency demonstrated a mild reticulocytosis but were not clinically anemic. Analysis of globin chain synthesis in vitro by 3H-leucine incorporation revealed that beta-globin synthesis was nearly normal (95%) in heterozygotes and about 75% of normal in deficiency homozygotes. Molecular characterization of the mutation by restriction analysis revealed a deletion of about 3.3 kb of DNA, including regulatory sequences and all coding blocks for beta-major globin. Based on genetic and hematological criteria, mice homozygous for the mutant allele, designated Hbbth-1, represent the first animal model of beta-thalassemia (Cooley's anemia), a severe genetic disease of humans.

Animals↗

Role of cardiovascular nuclear medicine in evaluating trauma and the postoperative patient.

In the patient with cardiac trauma, radionuclide imaging may provide important information about cardiac mechanical function, vascular anatomy and integrity, myocardial perfusion, and myocardial metabolism. Studies require only minimal patient cooperation, can be performed relatively rapidly and often at the bedside, and may be repeated at frequent intervals for serial evaluations. These studies provide valuable adjunctive knowledge when selected and interpreted with knowledge of the mechanism of injury, timing of the examination relative to the time of injury, and most likely differential diagnoses.

Aged↗

Analysis of a mouse alpha-globin gene mutation induced by ethylnitrosourea.

A DBA/2 mouse treated with ethylnitrosourea sired an offspring whose hemoglobin showed an extra band following starch gel electrophoresis. The variant hemoglobin migrated to a more cathodal position in starch gel. Isoelectric focusing indicated that chain 5 of the mutant hemoglobin migrated to a more cathodal position than the normal chain 5 from DBA/2 mice and that the other alpha-globin, chain 1, was not affected. On focusing gels the phenotype of the mutant allele, Hbay9, was expressed without dominance to normal chain 5, and Hbay9/Hbay9 homozygotes were fully viable in the laboratory. The molecular basis for the germinal mutation was investigated by analyzing the amino acid sequence of chain 5y9, the mutant form of alpha-chain 5. A single amino acid substitution (His leads to Leu) at position 89 was found in chain 5y9. We propose that ethylnitrosourea induced an A leads to T transversion in the histidine codon at position 89 (CAC leads to CTC). This mutation has apparently not been observed previously in humans, mice or other mammals, and its novel occurrence may be indicative of other unusual mutational events that do not ordinarily occur in the absence of specific mutagen exposure.

Amino Acid Sequence↗

A comparison of infarct identification with technetium-99m pyrophosphate and staining with triphenyl tetrazolium chloride.

The topographic relationship between the uptake of technetium-99m pyrophosphate (PPi) and myocardial infarction delineated by 2,3,5-triphenyl tetrazolium chloride (TTC) was studied in a canine model of permanent coronary occlusion (24-48 hr). Photographs of TTC staining and scintigraphic images of PPi uptake were planimetered for infarct area. In addition, narrow tissue samples (3 X 10 mm) were taken on both sides of the TTC border and counted for PPi uptake. A significant correlation (p less than 0.001) was found between area of PPi uptake and area of myocardium unstained by TTC (r = 0.84 in epicardium and r = 0.91 in endocardium). The slope relating PPi to TTC for all infarcts was 1.01 +/- 0.11, indicating that variations in infarct size were followed equally by the two techniques. Tissue counting showed the ratio of PPi activity just inside the infarct to activity just outside the infarct to be 9.2 +/- 0.6 (mean +/- s.e.m.). Thus, PPi is distributed topographically in a manner identical to the distribution of irreversibly injured myocardium as delineated by TTC.

Animals↗

The effects of calcium on protein turnover in skeletal muscles of the rat.

Several experimental procedures were used to increase the intracellular concentration of Ca2+ and determine its effects on protein turnover in isolated extensor digitorum longus and soleus muscle. These methods included the use of ionophore A23187, caffeine, dibucaine, thymol and procaine, all agents known to induce the release of calcium by acting either on the sarcolemma and/or on the sarcoplasmic reticulum. Another approach involved varying the external concentration of Ca2+ in the media in which the muscles were incubated. The changes in muscle Ca2+ concentrations after exposure to the various calcium-releasing agents were in keeping with accepted modes of action of these agents on muscle membranes. The findings suggest that increasing the sarcoplasmic concentration of Ca2+ inhibits protein synthesis and enhances protein breakdown. These catabolic effects of Ca2+ are compared with the changes induced in muscle protein turnover after exposure to insulin or cyclic nucleotides, and in myopathic muscle and situations of work overload. Attention is also drawn to some of the difficulties involved in definitively implicating Ca2+ as a factor involved in the normal regulation of protein turnover.

Animals↗

Increased incidence and clinical correlation of persistently abnormal technetium pyrophosphate myocardial scintigrams following acute myocardial infarction in patients with diabetes mellitus.

"Persistently abnormal" technetium-99m stannous pyrophosphate myocardial scintigrams (PPi+) appear to be associated with a relatively poor prognosis after acute myocardial infarction (AMI). To assess the incidence and implications of PPi+, we performed a retrospective analysis in 29 patients with and 25 patients without diabetes mellitus who had abnormal myocardial scintigrams within 4 days of AMI and who had follow-up scintigrams at least 3 months after hospital discharge. There were no significant differences between patients with and without diabetes as regards age, incidence of transmural or nontransmural AMI, or degree of left ventricular dysfunction after AMI. Persistently abnormal PPi+ occurred more commonly in patients with diabetes than in nondiabetic patients (18 of 29, 62%, compared to 3 of 25, 12%; p less than 0.001). Patients with chronic PPi+ had more frequent cardiac complications following hospital discharge (p less than 0.005) including death, recurrent AMI, unstable angina, and intractable congestive heart failure. Postmortem analysis in two patients with diabetes and chronic PPi+ revealed marked myocytolysis. Thus, patients with diabetes mellitus have an increased incidence of post-AMI "persistently abnormal" technetium (PPi+) scintigrams and relatively poor prognosis following myocardial infarction.

Aged↗

Detection of acute right ventricular infarction by right precordial electrocardiography.

The value of 0.1 mV or greater of S-T segment elevation in at least one right precordial lead (V4R to V6R) in defining right ventricular myocardial infarction was assessed prospectively in 43 subjects (33 consecutive patients with enzymatically confirmed infarction of varying type and location, 4 patients with unstable angina and 6 healthy volunteers). Patients with acute myocardial infarction were studied with radionuclide ventriculography and technetium-99m stannous pyrophosphate myocardial scintigraphy 18.2 +/- 14.3 (mean +/- standard deviation) and 85.1 +/- 18.0 hours after the onset of symptoms, respectively. Eleven patients (Group A: 9 patients with transmural inferior infarction, 1 with transmural inferolateral infarction and 1 with transmural anteroseptal infarction) demonstrated right precordial S-T segment elevation and 22 patients (Group B: 6 patients with transmural inferior infarction, 2 with transmural posterior infarction, 3 with transmural inferolateral infarction, 3 with transmural anteroseptal infarction, 3 with transmural extensive anterior infarction, 4 with subendocardial anterior infarction and 1 with unclassified infarction) did not. Right ventricular ejection fraction was significantly lower in Group A (0.47 +/- 0.11) than in Group B (0.60 +/- 0.12) (p less than 0.01). Right ventricular total wall motion score was 63.8 +/- 15.6 percent of normal in Group A versus 94.3 +/- 8.5 percent in Group B (p less than 0.001). Technetium-99m pyrophosphate uptake (2+ or greater) over the right ventricle occurred in nine patients (81.8 percent) in Group A and in one patient (4.5 percent) in Group B (p less than 0.001). No patient with unstable angina and no healthy volunteer had S-T segment elevation in a right precordial lead. S-T segment elevation of 0.1 mV or greater in one or more of leads V4R to V6R is both highly sensitive (90 percent) and specific (91 percent) in identifying acute right ventricular infarction.

Aged↗

Clinical implications of anterior S-T segment depression in patients with acute inferior myocardial infarction.

To assess various factors associated with anterior S-T segment depression during acute inferior myocardial infarction, 47 consecutive patients with electrocardiographic evidence of a first transmural inferior infarction were studied prospectively with radionuclide ventriculography an average of 7.3 hours (range 2.9 to 15.3) after the onset of symptoms. Thirty-nine patients (Group I) had anterior S-T depression in the initial electrocardiogram and 8 (Group II) did not have such "reciprocal" changes. There was no difference between the two groups in left ventricular end-diastolic or end-diastolic volume index or left ventricular ejection fraction. Stroke volume index was greater in Group I than in Group II. There were no group differences in left ventricular total or regional wall motion scores. A weak correlation existed between the quantities (mV) or inferior S-T segment elevation and reciprocal S-T depression. No relation between anterior S-T segment depression and the left ventricular end-diastolic volume index could be demonstrated; the extent of left ventricular apical and right ventricular wall motion abnormalities, both frequently associated with inferior infarction, did not correlate with the quantity of anterior S-T depression. These data show that anterior S-T segment depression occurs commonly during the early evolution of transmural inferior infarction, is not generally a marker of functionally significant anterior ischemia and cannot be used to predict left ventricular function in individual patients. Anterior S-T segment depression may be determined by reciprocal mechanisms.

Cardiac Catheterization↗

Myocardial rupture after myocardial infarction. Detection by multi-gated image-acquisition scintigraphy.

Myocardial rupture following infarction usually is an acute and dramatic event. Rarely, it may take a subacute course, allowing surgical treatment. We report herein a case of subacute rupture of the heart in a 54 year old patient with acute myocardial infarction. The rupture was diagnosed by the appearance of a radiopaque halo around the heart during radionuclide ventriculography. The patient subsequently underwent surgical resection of a large anterolateral aneurysm and a 2 inch long rupture of the myocardium and survived. Clinical suspicion, prompt diagnosis, and surgical intervention are important in the management of this relatively unusual complication of infarction.

Heart Aneurysm↗

"Doughnut" technetium pyrophosphate myocardial scintigrams. A marker of severe left ventricular dysfunction.

The "doughnut" pattern on Tc-99m pyrophosphate (PPi) myocardial scintigraphy is characterized by a border of tracer uptake surrounding a central zone of relatively decreased activity. This pattern is generally associated with large transmural anterior myocardial infarcts (MI) caused by occlusion or critical stenosis of the left anterior descending coronary artery. Such infarcts typically involve a significant portion of the anterior wall and are associated with a complicated clinical course and poor prognosis. In order to evaluate the relationship between the presence of the doughnut pattern and left ventricular (LV) function, radionuclide ventriculography was performed within 15 days after infarction in 58 patients with transmural anterior MI. In patients without previous MI, 15/38 (39.5%) had doughnut scintigrams. These patients demonstrated significant reductions in LV ejection fraction (EF) (28 +/- 10% versus 45 +/- 12%, P less than 0.001) and normalized LV wall motion scores (29 +/- 11% versus 61 +/- 10%, P less than 0.001) when compared with patients with "nondoughnut" scintigrams. Patients with doughnut scintigrams had a significantly greater incidence of severe septal hypokinesis (P less than 0.001) and apical dyskinesis (P less than 0.03). LV end-systolic volumes were also larger in the patients with doughnut scintigrams (73 +/- 32 ml versus 40 +/- 17 mI/M2, P less than 0.005). In contrast, there was no significant difference in LVEF, normalized LV wall motion score, or LV volumes between doughnut and nondoughnut groups in patients with previous MI.

Diphosphates↗