Experimental myocardial infarction. IV. Reduction of left ventricular compliance in the healing phase.

Compliance of the infarcted left ventricle was studied in dogs 3-5 days after occlusion of the left anterior descending coronary artery. Compliance was assessed from postmortem pressure-volume curves and from pressure-length measurements (mercury-in-silastic segment length gauges) made both in vivo and postmortem. Postmortem pressure-volume curves showed reduced compliance compared to sham-operated animals. Postmortem pressure-length curves of infarcted and adjacent normal myocardium indicated that the diminished total compliance could be attributed to an increase in stiffness of the infarcted area. This was confirmed by in vivo end-diastolic pressure-length changes produced by transient aortic occlusion. The infarcted area was akinetic, showing neither contraction nor aneurysmal bulging. In addition, anesthetized dogs with infarcts, when compared with sham-operated animals, had similar left ventricular end-diastolic volumes (indicator dilution method), but higher left ventricular end-diastolic pressures. Taken with previous observations, which show that systolic aneurysmal bulging is uniformly present at the onset of ischemia, these results indicate that stiffening of the ischemic myocardium occurs during the first 5 days after infarction, and show that elevation of left ventricular filling pressure does not necessarily signify ventricular dilatation. The results also suggest a mechanism whereby ventricular performance may improve during recovery from acute myocardial infarction.

Phase Ib trial of pentoxifylline and ciprofloxacin in patients treated with interleukin-2 and lymphokine-activated killer cell therapy for metastatic renal cell carcinoma.

The dose of interleukin 2 (IL-2) which can be administered to cancer patients is limited largely by a capillary leak syndrome. Pentoxifylline (PTX) is a methylxanthine which reduces IL-2 toxicity in animals. Ciprofloxacin (Cipro) modifies the metabolism of methylxanthines and, when coadministered with PTX, increases levels of PTX and certain of its metabolites. We conducted a phase Ib trial in patients receiving IL-2 and lymphokine-activated killer cell (LAK) cell therapy for metastatic renal cell carcinoma to identify the maximum tolerated dose of PTX which could be coadministered with Cipro in this setting. Eighteen patients received IL-2 (Roche) by continuous infusion at 6 x 10(6) units/m2/day on days 1-5 and underwent leukapheresis on days 7-9. LAK cells were infused on days 12-14. IL-2 was administered at 2 x 10(6) units/m2/day on days 10-20. Cohorts of patients received PTX at 2.5 (n = 3), 3.1 (n = 6), 3.9 (n = 6), and 4.9 (n = 3) mg/kg by 30 min i.v. infusion every 4 h on days 0-5 and 10-20 and Cipro (500 mg p.o. every 12 h) on days 1-5 and 10-20. Toxicity was compared with that observed in 33 historical control patients who received 37 cycles of an identical regimen of IL-2/LAK without PTX/Cipro. PTX at 2.5-3.9 mg/kg and Cipro were well tolerated. The maximum tolerated dose of PTX was 3.9 mg/kg. Dose-limiting emesis (n = 1) and atrial fibrillation (n = 2) occurred at 4.9 mg/kg and were reversible. Two complete, one partial and one minor, responses were observed. Patients treated with 3.9 mg/kg PTX received 95.0% of the planned dose of IL-2 as compared to 72.8% in the control patients (P < 0.025), primarily due to a lower incidence of azotemia and metabolic acidosis in PTX/Cipro recipients than had been seen in the historical control patients. The results of this study demonstrate that PTX/Cipro can be administered to patients receiving IL-2/LAK without apparent loss of therapeutic efficacy. Moreover, PTX/Cipro recipients exhibited less toxicity than historical controls. Therefore, treatment with PTX/Cipro may allow delivery of higher doses of IL-2, which might induce more responses in IL-2-responsive tumors and regression of tumors unresponsive to conventional doses of IL-2.

Lisofylline inhibits transforming growth factor beta release and enhances trilineage hematopoietic recovery after 5-fluorouracil treatment in mice.

The effectiveness of endogenous or exogenously administered colony-stimulating factors may be modulated by the presence of hematopoietic inhibitory molecules. Cytotoxic therapy may result in the induction of hematopoietic inhibitors contributing to prolonged myelosuppression, whereas preventing the induction of such inhibitors may accelerate multilineage recovery. Lisofylline [LSF; (R)-1-(5-hydroxyhexyl)-3,7, dimethyl-xanthine], inhibits the signaling and/or release of certain hematopoietic inhibitory molecules such as tumor necrosis factor alpha, macrophage inflammatory protein 1 alpha, transforming growth factor beta, and IFN-gamma. Treatment of murine bone marrow cells with the cytotoxic agent 5-fluorouracil (5-FU) results in the release of a nondialyzable inhibitor of progenitor (colony-forming unit-granulocyte macrophage; CFU-GM) proliferation. When murine bone marrow cells were treated with 5-FU plus LSF, release of this inhibitor of CFU-GM proliferation was blocked. Neutralizing antibody and Western blot analysis indicated that the inhibitor was TGF-beta. We tested the effect of LSF (100 mg/kg i.p., b.i.d.) on multilineage regeneration after high-dose 5-FU or thiotepa treatment in BALB/c mice. In 4 of 5 experiments, LSF significantly accelerated neutrophil recovery (P < or = 0.05, Wilcoxon paired-signed test). In addition, platelet, reticulocyte, and CFU-GM regeneration were significantly accelerated in mice treated with LSF compared to control mice (P < or = 0.05). LSF had no significant effects on the ability of 5-FU to kill hematopoietic progenitor cells, nor did LSF stimulate or inhibit proliferation of CFU-GM. LSF had no effect on chemotherapy-induced killing of tumor cells in vitro, nor on the antitumor activity of 5-FU or thiotepa in BALB/c mice implanted with P388 leukemia cells. Inhibition of hematopoietic inhibitor release may accelerate multilineage recovery after cytotoxic therapy and, as such, may represent an alternative or additional therapy to the use of positively acting lineage specific colony-stimulating factors.

Phase I study of busulfan and cyclophosphamide in preparation for allogeneic marrow transplant for patients with multiple myeloma.

PURPOSE: To study the toxicity and potential efficacy of busulfan (BU) and cyclophosphamide (CY) as a conditioning regimen before allogeneic bone marrow transplantation (ABMT) in patients with multiple myeloma (MM). PATIENTS AND METHODS: Twenty patients with MM underwent conditioning, which was followed by ABMT from 16 HLA-identical donors, three one-antigen-mismatched donors, and one HLA A, B, D-identical unrelated donor. Four levels of BU plus CY were evaluated. RESULTS: Severe regimen-related toxicity occurred in two of five patients who received BU 16 mg/kg and CY 120 mg/kg, in none of the four patients who received BU 14 mg/kg and CY 120 mg/kg, in one of eight patients who received BU 14 mg/kg and CY 147 mg/kg, and in two of three patients who received BU 14 mg/kg and CY 174 mg/kg. Twelve of 15 (80%) assessable patients achieved a complete remission with the disappearance of M-protein and the return of normal marrow morphology. Ten patients died of complications related to the ABMT, and two patients died of progressive or relapsed MM. Overall, eight of 20 patients were alive; seven (35%) were in complete remission 190 to 1,271 days after ABMT. CONCLUSIONS: The maximum-tolerable dose given in this setting was BU 14 mg/kg and CY 147 kg/mg. These results suggest that this regimen may have significant antimyeloma activity. Further phase II studies are warranted.

Accumulation of radioiodinated 15-(p-iodophenyl)-6-tellurapentadecanoic acid in ischemic myocardium during acute coronary occlusion and reperfusion.

The myocardial uptake of 15-(p-iodophenyl)-6- tellurapentadecanoic acid ( TPDA ) was studied in dogs during coronary occlusion and after reperfusion. In eight dogs with a 3 hour occlusion (Group A) with (n = 5) and without (n = 3) 30 minutes of reperfusion, iodine-125 TPDA uptake correlated well with microsphere myocardial blood flow over a wide range of flow levels (n = 111, r = 0.94). In six dogs with a 20 minute occlusion of the left anterior descending coronary artery and 1 hour of reperfusion (Group B), iodine-125 TPDA uptake correlated equally well with myocardial blood flow (n = 37, r = 0.90). There was no difference between the slopes of regression lines for Groups A and B, indicating no release from the myocardium of radioiodinated TPDA . Dual radiolabeling of TPDA was employed in five Group A animals by intravenous injection of iodine-125 TPDA during coronary occlusion and iodine-131 TPDA after reperfusion. In 63 myocardial samples, microsphere reperfusion flow and iodine-131 TPDA uptake were closely correlated (r = 0.91). As with monovalent cations, at myocardial flows higher than control flows, iodine-131 TPDA uptake was flow-limited. It is concluded that: 1) radioiodinated TPDA accurately reveals severely ischemic areas of myocardium without myocardial release of the radionuclide in coronary occlusions lasting 20 to 180 minutes and followed by reperfusion, and 2) double radiolabeled TPDA allows assessment of both occlusion and reperfusion flows. This compound may find an application in the measurement of infarct size and the evaluation of interventional therapies in acute myocardial infarction.

Biochemical characterization of a unique canine myeloid antigen.

In marrow transplantation, radioisotope-labeled monoclonal antibodies may provide a way to selectively deliver high doses of radiation to target tissues (marrow in the case of myeloid malignancies) without significant toxicity to other normal organs. This paper describes the production and characterization of a novel monoclonal antibody, DM5, that we have developed for use in an animal model of radiotherapy targeted to the marrow. DM5 recognizes three glycosylation variants, gp19,21,23DM5, of a polypeptide core that is expressed on canine cells of the myeloid lineage, but not on lymphoid cells. The antigen recognized by DM5 is not present on most progenitor cells as determined by CFU-GM assays of DM5 positive and negative cell populations.

Diastolic function of the heart in clinical cardiology.

During the last six years, there has been increased interest in the detection of abnormalities of left ventricular diastolic function in patients with heart disease. Before 1981, most studies on diastolic function were performed in the catheter laboratory using invasive techniques and complex methods. Recently, radionuclide angiograms and Doppler echocardiography have been employed to measure the dynamics of filling in normal individuals and in patients with heart disease. These methods are noninvasive, easy to perform, accurate, and reproducible. It is now clear that diastolic function may be altered globally and regionally, at rest and perhaps during exercise, in many patients with ischemic heart disease, hypertension, and hypertrophic cardiomyopathy. Interestingly, these diastolic abnormalities may even appear before systolic abnormalities are identified in these patients. Thus, diastolic abnormalities may permit assessment of presence of disease early in its evolution. Whether detection and quantitation of diastolic abnormalities will permit grading of disease severity or evaluation of therapeutic efficacy remains an important research question. At the present time, it appears that the decision to employ either radionuclide angiography or Doppler echocardiography for the assessment of diastolic abnormalities will depend on the local expertise to carry out the investigation. Both diagnostic modalities require standardization of accuracy and reproducibility with proper selection of control values from the appropriate populations of normal individuals. It is also important to remember that left ventricular diastolic abnormalities have to be identified after the elimination of the confounding influence of variables such as ejection fraction, heart rate, age, and preload (end-diastolic volume). Automation of the derivation of indexes of diastolic filling should provide an objective assessment of the dynamics of left ventricular filling. Although the value of measurement of diastolic filling in the individual patient remains controversial, we believe that the practice of cardiology is incomplete without consideration of the second half of cardiac function.

Pulmonary embolism from a venous thrombus located below the knee.

A patient with bronchogenic carcinoma developed acute thrombophlebitis below the knee followed by pulmonary embolism. Sequential nuclear venograms, perfusion lung scans, bilateral impedance plethysmography, and the patient's clinical course indicated that the below-knee thrombus had embolized in its entirety, causing clinically significant disease. This case demonstrates that below-knee thrombi are not always benign and, in certain circumstances, merit anticoagulation.

Specific marrow localization of an 131I-labeled anti-myeloid antibody in normal dogs: effects of a "cold" antibody pretreatment dose on marrow localization.

Tumor recurrence and regimen-related toxicity remain major obstacles in the successful use of marrow transplantation as therapy for hematologic malignancies. By attaching radionuclides to monoclonal antibodies (MoAbs) targeted at myeloid-associated antigenic determinants, a more effective and directed delivery of therapy may be possible without increasing toxicity. We investigated the biodistribution over time of an anti-myeloid antibody (DM-5) labeled with trace amounts of 131I in normal dogs. This study demonstrates the ability to target marrow with a high degree of selectivity, achieving marrow/blood ratios of 25-30:1 with the greatest concentration in any other organ being a tissue/blood ratio of 1.4:1 for stomach at 48 h. A pretreatment dose of unlabeled antibody effectively reduced early hepatic uptake by 80%, resulting in improved marrow localization with an estimated 58.6% of the injected dose localized in marrow within 2 h following infusion, compared to 32.8% without pretreatment. The marrow concentration clearance curve for the radioimmunoconjugate revealed an initial short half-life (4.75 h), suggesting rapid internalization, digestion, and release of free iodine (dehalogenation). This view was supported by a corresponding rise in trichloroacetic acid-non-precipitable activity during this period. Methods aimed at decreasing dehalogenation may result in longer residence time of the radionuclide within the marrow space, resulting in more effective tumor cell kill. This approach may provide a way to improve upon the current results obtained with marrow transplantation as treatment for patients with leukemia and other hematologic malignancies.

Prevalence of clinically relevant bacteremia after upper gastrointestinal endoscopy in bone marrow transplant recipients.

PURPOSE: To determine the prevalence of clinically relevant bacteremia after upper endoscopy in patients undergoing bone marrow transplantation. PATIENTS AND METHODS: We retrospectively reviewed the records of 151 patients who received an HLA-identical allogeneic bone marrow transplant (BMT) at the Seattle Veterans Affairs Medical Center between September 1983 and December 1988. Forty-seven patients who required esophago-gastroduodenoscopy (EGD) during their first 100 days after transplant were selected for evaluation. Clinically relevant bacteremia was defined as the development of hypotension, temperature greater than 38.5 degrees C, and a positive blood culture occurring within 24 hours after endoscopy. The presence of acute graft-versus-host disease (GVHD) at the time of endoscopy and the use of prednisone prior to endoscopy were considered possible risk factors for the development of bacteremia. The proportion of subjects who became bacteremic were compared using Fisher's exact test. RESULTS: Within 24 hours following endoscopy, nine patients (19%) developed clinically evident bacteremia (hypotension, temperature greater than 38.5 degrees C, and a positive blood culture). Eight of 14 patients receiving prednisone at the time of endoscopy developed bacteremia, compared to one of 33 not receiving prednisone (p less than 0.01). Nineteen patients had acute GVHD of at least grade 2 at the time of EGD, six of whom developed bacteremia. Although acute GVHD alone did not increase the risk of post-EGD bacteremia in patients not receiving prednisone (one of 21 versus zero of 12, p greater than 0.9), the risk of bacteremia was particularly high in patients with acute GVHD treated with prednisone at the time of EGD (six of seven). CONCLUSION: Allogeneic BMT recipients receiving prednisone for immunoprophylaxis after grafting or for treatment of acute GVHD are at high risk for clinically relevant bacteremia following EGD. Such patients are candidates for antibiotic prophylaxis prior to endoscopy.

Preferential radiosensitization of G1 checkpoint-deficient cells by methylxanthines.

PURPOSE: To develop a checkpoint-based strategy for preferential radiosensitization of human tumors with deficient and/or mutant p53. METHODS AND MATERIALS: A549 human lung adenocarcinoma cell lines differing in their expression of the p53 tumor suppressor gene were produced by transduction with the E6 oncogene from human papilloma virus type 16. The cells expressing E6 (E6+) lack a G1 arrest in response to ionizing radiation, are deficient in p53 and p21 expression, and exhibit a fivefold greater clonogenic survival following 10 Gy radiation. RESULTS: Postirradiation incubation with millimolar concentrations of the methylxanthine pentoxifylline (PTX) results in preferential radiosensitization of the E6+ cells compared to the LXSN+ vector transduced controls. There is a threefold sensitization of the LXSN+ cells and a 15-fold sensitization of the E6+ cells, which results in equal clonogenic survival of the two lines. Flow cytometry reveals PTX abrogation of the radiation induced G2 arrest for both cell lines. PTX also prolongs G1 transit for both cell lines. Preliminary results are presented using a novel methylxanthine, lisofylline (LSF), which has similar cell cycle effects on G1 and G2 and achieves differential radiosensitization at micromolar concentrations that are sustainable in humans. CONCLUSION: This checkpoint-based strategy is a promising approach for achieving preferential radiosensitization of p53- tumors relative to p53+ normal tissues.

Thallium myocardial scintigraphy in congenitally-corrected transposition of the great arteries.

A case of congenitally-corrected transposition of the great arteries is presented with the correlation of thallium scintigraphic results with catheterization data. The essential features of the thallium scintigrams were marked counterclockwise rotation of the heart with perfusion abnormalities of the inferior wall and apex. Since patients with congenitally-corrected transposition of the great arteries may present with the symptom of chest pain, the diagnosis of transposition of the great arteries should be considered in patients with marked counterclockwise rotation of the heart and segmental perfusion abnormalities on thallium scintigraphy.

Digital restoration of indium-111 and iodine-123 SPECT images with optimized Metz filters.

A number of radiopharmaceuticals of great current clinical interest for imaging are labeled with radionuclides that emit medium- to high-energy photons either as their primary radiation, or in low abundance in addition to their primary radiation. The imaging characteristics of these radionuclides result in gamma camera image quality that is inferior to that of 99mTc images. Thus, in this investigation 111In and 123I contaminated with approximately 4% 124I were chosen to test the hypothesis that a dramatic improvement in planar and SPECT images may be obtainable with digital image restoration. The count-dependent Metz filter is shown to be able to deconvolve the rapid drop at low spatial frequencies in the imaging system modulation transfer function (MTF) resulting from the acceptance of septal penetration and scatter in the camera window. Use of the Metz filter was found to result in improved spatial resolution as measured by both the full width at half maximum and full width at tenth maximum for both planar and SPECT studies. Two-dimensional, prereconstruction filtering with optimized Metz filters was also determined to improve image contrast, while decreasing the noise level for SPECT studies. A dramatic improvement in image quality was observed with the clinical application of this filter to SPECT imaging.

Resting early peak diastolic filling rate: a sensitive index of myocardial dysfunction in patients with coronary artery disease.

Resting first-pass radionuclide angiocardiography (RNA) was used to derive left-ventricular (LV) peak diastolic filling rates (PFR) in normals (Group 1:N = 12) and in patients with coronary artery disease (CAD), both without (Group 2:N = 27) and with previous myocardial infarction (Group 3:N = 23). Resting peak filling rates were significantly depressed in both Group 2 (1.61 +/- 0.36; p less than 0.01) and Group 3 (1:35 +/- 0.26; p less than 0.001) patients when compared with Group 1, normals (2.14 +/- 0.63). Even though LV systolic function of Group 2 patients was normal and comparable to that in Group 1 (EF = 0.55 +/- 0.06 against EF 0.55 +/- 0.06 NS), diastolic dysfunction [PFR less than 1.61 end diastolic volume/sec (EDV/sec)] was present at rest in 14 of 27 (52%). Depressed PFR values was also seen in 20 of 23 Group 3 patients (87%). It appears that (a) resting PFR is a sensitive and easily obtainable parameter of the diastolic dysfunction associated with CAD; (b) abnormal PFR values are seen in almost all patients with previous myocardial damage, and (c) a significant proportion of CAD patients without any evidence of abnormal systolic function have depressed resting PFR of the LV.

Technetium-99m(Sn2+)pyrophosphate in ischemic and infarcted dog myocardium in early stages of acute coronary occlusion: histochemical and tissue-counting comparisons.

We have investigated the pattern of accumulation of Tc-99m(Sn2+)pyrophosphate (Tc-99m PPi) in myocardial tissue of dogs during the early stages of acute occlusion of the left anterior descending coronary artery. Three groups were studied after: (a) 40 min occlusion followed by 6 hr reperfusion (n = 6); (b) 6 hr occlusion followed by one hour reperfusion (n = 5); and (c) 7 hr occlusion with no reperfusion (n = 4). Areas of myocardial infarction were defined with triphenyl-tetrazolium chloride (TTC) staining, and blood flow was determined with 9-mu radioactive microspheres. In Group C uptake in infarcted and peri-infarct areas was not enhanced, most likely owing to low flow. In Group B, with late reperfusion, Tc-99m PPi sequestration was increased in both infarcted and peri-infarcted tissues. In Group A, areas ischemic during occlusion but with normal flow and viability by TTC after 6 hr of reperfusion showed significant uptake of Tc-99m PPi (twice the uptake of nonischemic regions).

Radionuclide left ventricular dV/dt for the assessment of cardiac function in patients with coronary disease.

To investigate potential uses of left-ventricular (LV) systolic ejection rate (LV dV/dt) in the evaluation of LV function, we examined the effect of exercise, angiotensin, and leg raising on LV ejection fraction and LV dV/dt in patients with coronary-artery disease. The following observations were made: a) LV ejection fraction and dV/dt changed proportionately, but in opposite directions, during supine exercise; b) LV ejection fraction and dV/dt decreased to a similar extent during angiotensin infusions; and c) LV ejection fraction and dV/dt were unchanged by leg raising. The changes in peak and mean LV dV/dt were similar. Regardless of the physiologic state, peak LV dV/dt occurred during the first third of systole. These data imply that in this population there were no specific advantages of LV dV/dt over LV ejection fraction in the evaluation of LV performance.

Effects of propylthiouracil on the biodistribution of an iodine-131-labeled anti-myeloid antibody in normal dogs: dosimetry and clinical implications.

Despite the use of near maximal doses of chemoradiotherapy, tumor recurrence remains the most frequent cause of treatment failure following marrow transplantation for leukemia. We have previously demonstrated that it is possible to selectively deliver radiation to the marrow space. In that study an initial short half-life of the radionuclide was observed. In this study we attempted to prolong the retention of the radioiodine in marrow through the use of propylthiouracil (PTU). When administered to normal dogs, PTU pretreatment resulted in improved marrow localization of 131I-labeled DM-5. There was no appreciable loss of activity from the marrow during the 2-4 hr postinjection time interval; a finding in contrast to the control animals where marrow activity declined a mean 45 +/- 0.5% over the same time period. Additionally, in contrast to controls, a rise in plasma trichloroacetic acid (TCA) nonprecipitable activity was not demonstrated in the PTU treated group during this 2-4 hr period. These results suggest that PTU's inhibition of deiodinases resulted in longer residence time of the radionuclide in its target tissue without adversely affecting distribution to non-target organs.

CT-1501R selectively inhibits induced inflammatory monokines in human whole blood ex vivo.

The effect of (R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine (CT-1501R; the nonproprietary name for CT-1501R approved by the United States Name Council is lisofylline), an inhibitor of second messenger signaling through phosphatidic acid, on release of endogenous mediators important in the systemic inflammatory response syndrome (SIRS) was studied using the human whole blood ex vivo assay system. Human blood was stimulated with various endotoxin preparations, zymosan, or protein A, and the levels of secreted monokines were measured by enzyme-linked immunosorbent assay. CT-1501R inhibited tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6 release in a dose-dependent manner and was active with all stimuli tested including Salmonella and Escherichia coli-derived endotoxin, endotoxin from both rough and smooth E. coli strains, as well as zymosan and protein A. CT-1501R inhibited monokine release by approximately 50% at 200 microM and 30% at 50 microM and was independent of the relative potency of stimulus. CT-1501R also inhibited IL-1 alpha or IL-1 beta induction of either TNF-alpha or IL-1 beta and inhibited the synergistic effects of stimulation with both human IL-1 beta and murine TNF-alpha on release of human TNF-alpha. Inhibition of monokine release following stimulation with monokine(s) was, in general, greater than that achieved with lipopolysaccharide (LPS) stimulation. Northern blot analysis showed decreased mRNA accumulation of TNF-alpha and IL-1 beta in CT-1501R-treated samples following LPS stimulation suggesting that CT-1501R acts at least in part, at the pretranslational level. In contrast, CT-1501R does not inhibit LPS-stimulated IL-8 or IL-1 receptor antagonist (IL-1ra) release in human whole blood or IL-1 alpha-induced release of PGE2 in human foreskin fibroblast cells. These data suggest that CT-1501R may be of use for clinical intervention in SIRS.

Assessment of cardiac reserve in patients with hyperthyroidism.

Radionuclide multigated cardiac imaging was performed to assess functional cardiac reserve in patients with hyperthyroidism. In 11 normal individuals, submaximl supine exercise increased heart rate (HR) by 60 percent, systolic blood pressure (BP) by 54 percent, and the left ventricular ejection fraction (LVEF) by 13 percent. All of these increments were statistically significant (p < 0.001). Eight patients with hyperthyroidism were studied. Their mean +/- standard error of the mean (SEM) serum thyroxine level was 17.7 +/- 0.5 micrograms percent. There was a negative correlation between serum thyroxine levels and LVEF, both at rest and during exercise, in the patients with hyperthyroidism. Our data suggest that hyperthyroidism is associated with impaired functional cardiac reserve.

Comparison of gated radionuclide scans and chest radiographs. Assessment of left ventricular impairment in patients with coronary disease.

Diagnostic efficacy of gated cardiac blood pool imaging was studied in 41 consecutive patients with LV ejection fractions (LVEF) less than or equal to 0.50. Eighty percent of patients were receiving therapy for LV failure at the time of the study. All patients had documented coronary-artery disease (CAD). Chest x-ray films were interpreted blindly by a senior radiologist. Cardiothoracic ratio of less than or equal to 0.50 was recorded as normal. Radionuclide assessment of LV function contributes importantly to the diagnostic and screening value of chest x-ray films. Patients with coronary disease and clinical evidence of heart failure should have radioisotopic studies even if chest x-ray film findings are normal. In patients with coronary artery disease and enlarged LV on chest films, radionuclide study of left ventricular performance aids in defining LV impairment, and in the prognostication of subsequent clinical course.