Physical examination for exclusion of hemodynamically important right ventricular infarction

Fifty-three consecutive patients with inferior myocardial infarction were evaluated prospectively, by physical examination and right heart catheterization within 36 hours of the onset of symptoms, to determine whether physical findings can separate such patients into those with and without associated right ventricular infarction. Hemodynamic findings consistent with right ventricular infarction were defined as right atrial pressure of 10 mm Hg or greater and a right atrial: pulmonary artery wedge pressure ratio of 0.80 or greater. Eight patients (Group 1) had hemodynamic evidence of right ventricular infarction, whereas 45 patients (Group 2) did not meet these criteria. Group 1, compared with Group 2, had a lower cardiac index (1.8 +/- 0.3 versus 2.6 +/- 0.6 L/min X m2, p less than 0.001), and a lower right ventricular stroke work index (4.1 +/- 3.6 versus 7.3 +/- 3.2 g X m/m2, p less than 0.05). An elevated jugular venous pressure of 8 cm H2O or more was seen in 7 of 8 Group 1 and 14 of 45 Group 2 patients (p less than 0.01). In addition, a Kussmaul's sign, substantiated by hemodynamic findings, was seen in all 8 Group 1 and in no Group 2 patients (p less than 0.001). The absence of both an elevated jugular venous pressure and a Kussmaul's sign in patients with inferior myocardial infarction makes the presence of a hemodynamically significant right ventricular infarction highly unlikely.     

Increased susceptibility of peripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro

Peripheral mononuclear cells (MNC) collected from 12 healthy donors and 44 leukemic patients at various stages of the disease were tested for natural killer (NK) activity and for their susceptibility to HTLV-I infection in vitro, measured in terms of percentage of p19 positive cells. MNC from leukemic donors at any stage of leukemia (ie, onset or relapse, ON/REL; complete remission or off-therapy, CR/OT donors) were highly susceptible to HTLV-I infection. This was true for acute leukemias of lymphoblastic (ALL) or nonlymphoblastic (ANLL) type. MNC of ON/REL patients were more susceptible to HTLV-I than those of CR/OT donors. In addition, leukemic blasts were more rapidly infected (ie, within five to seven days) than the HTLV-I-susceptible normal cord- blood lymphocytes. However, the presence of circulating blasts was not essential to virus susceptibility, since CR/OT MNC, presumably free of leukemic blasts, were still more susceptible to HTLV-I than normal cells. Basal NK function of MNC from leukemic patients was significantly lower than that detectable in healthy controls. However, no correlation was found between susceptibility to HTLV-I infection and NK activity.     

Suppression of apoptosis in hematopoietic factor-dependent progenitor cell lines by expression of the FAC gene

Fanconi anemia (FA) is a genetically heterogeneous, inherited blood disorder characterized by bone marrow failure, congenital malformations, and a predisposition to leukemias. Because FA cells are hypersensitive to DNA cross-linking agents and have chromosomal instability, FA has been viewed as a disorder of DNA repair. However, the exact cellular defect in FA cells has not been identified. Sequence analysis of the gene defective in group C patients (FAC) has shown no significant homologies to other known genes. The FAC protein has been localized to the cytoplasm, indicating that FAC may either play an indirect role in DNA repair or is involved in a different cellular pathway. Recent evidence has indicated that FA cells may be predisposed to apoptosis, especially after treatment with DNA cross-linking agents. The demonstration that genes can suppress apoptosis has been accomplished by overexpression of such genes in growth factor-dependent cell lines that die by apoptosis after factor withdrawal. Using retroviral-mediated gene transfer, we present evidence that expression of FAC in the hematopoietic factor-dependent progenitor cell lines 32D and MO7e can suppress apoptosis induced by growth factor withdrawal. Flow cytometry and morphologic analysis of propidium iodide stained cells showed significantly lower levels of apoptosis in FAC-retroviral transduced cells after growth factor deprivation. Expression of FAC in both cell lines promoted increased viability rather than proliferation, which is consistent with other apoptosis-inhibiting genes such as Bcl- 2. These findings imply that FAC may act as a mediator of an apoptotic pathway initiated by growth factor withdrawal. Furthermore, the congenital malformations and hematologic abnormalities characterizing FA may be related to an increased predisposition of FA progenitor cells to undergo apoptosis, particularly in the absence of extracellular signals.     

Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells

Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis.     

Relation between maximum time-varying elastance pressure-volume areas and myocardial oxygen consumption in dogs

To establish whether pressure-volume areas (PVAs) calculated using the maximum time-varying elastance (Emax) have a relation with myocardial oxygen consumption (MVO2) that improves on other indexes of myocardial oxygen demand, we studied nine dogs of either sex weighing 19-39 kg, which were instrumented with a micromanometer left ventricular (LV) catheter and a Wilton-Webster coronary sinus flow catheter and had red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamics, coronary sinus flow determinations, and radionuclide angiograms were obtained under control conditions and during three to five steady-state loading conditions (mean +/- SD, 5.6 +/- 0.7). Isochronal pressure-volume data points from each pressure-volume loop were subjected to linear regression analysis to calculate Emax. The Emax relations, diastolic curves, and systolic portions of each pressure-volume loop were used to obtain calibrated PVAs. The Emax PVA (mm Hg.ml.beat-1.100 g-1) and MVO2 (ml O2.beat-1.100 g-1) values correlated in each animal (r = 0.77 to 0.99). Their slopes averaged (3.48 +/- 1.68) x 10(-5) ml O2.mm Hg-1.ml-1, and their y-axis intercepts averaged 0.07 +/- 0.04 ml O2.beat-1.100 g-1. When the MVO2 relations were compared with Emax PVA, LV systolic pressure-rate product, LV stroke work, and a modification of the LV pressure-work index, the Emax PVA, LV systolic pressure-rate product, and LV pressure-work index had similar relations with MVO2, whereas LV stroke work was a weaker index of MVO2 (p less than 0.05 versus Emax PVA). This occurred because the Emax PVA:MVO2 slopes and y-axis intercepts differed in each dog, which was due to differences in basal LV contractility. The Emax PVA:MVO2 slopes correlated with Emax (r = 0.73, p less than 0.05), and the y-axis intercepts were also weakly related to Emax (r = 0.48, p = 0.19). We conclude that the Emax PVAs calculated using data acquisition techniques that are clinically applicable have relations with MVO2 that in general do not improve on other indexes of myocardial oxygen demand in this animal preparation.     

Accuracy of biplane axial oblique and oblique cineangiographic left ventricular cast volume determinations using a modification of Simpson''s rule algorithm

In order to compare biplane left ventricular cast volume determinations from orthogonal and nonorthogonal axial oblique and standard orthogonal oblique cineangiograms to those that were obtained by water (H2O) displacement, we evaluated 14 human heart specimens in the following projections: 30-degree right anterior oblique and 60-degree left anterior oblique/20-degree cranial (LVa), 45-degree left posterior oblique and 60-degree left anterior oblique/30-degree cranial (LVb), and 30-degree right anterior oblique and 60-degree left anterior oblique (LVc). The correlation coefficients and standard errors of the estimate (SEEs) for the biplane orthogonal and nonorthogonal axial oblique (LVa and LVb, respectively) and standard orthogonal oblique (LVc) cineangiographic left ventricular volume determinations compared with the left ventricular cast volumes obtained by H2O displacement were similar (each r = 0.99 with SEEs = 5 to 7 milliliters (ml)). However, the mean biplane cineangiographic cast volume of 69 +/- 43 ml (SD) by LVa exceeded the average left ventricular cast volume of 60 +/- 35 ml by H2O displacement (p less than 0.01), while the average left ventricular cast volumes obtained with LVb and LVc (63 +/- 35, and 60 +/- 34 ml, respectively) did not differ significantly from the mean left ventricular cast volume obtained by H2O displacement. We concluded that the biplane orthogonal and nonorthogonal axial oblique cineangiographic views of the left ventricle, which have been reported to improve the delineation of cardiac anatomy, left ventricular regional wall motion, and the assessment of mitral regurgitation, also provide accurate determinations of left ventricular volume that are similar to those calculated from standard biplane orthogonal oblique cineangiograms.     

Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function?

OBJECTIVES: This study sought to determine whether changes in intra-abdominal pressure (IAP) with aggressive diuretic or vasodilator therapy are associated with improvement in renal function in acute decompensated heart failure (ADHF). BACKGROUND: Elevated IAP (>or=8 mm Hg) is associated with intra-abdominal organ dysfunction. There is potential for ascites and visceral edema causing elevated IAP in patients with ADHF. METHODS: Forty consecutive patients admitted to a specialized heart failure intensive care unit for management of ADHF with intensive medical therapy were studied. The IAP was measured using a simple transvesical technique at time of admission and before removal of the pulmonary artery catheter. RESULTS: In our study cohort (mean age 59 +/- 13 years, mean left ventricular ejection fraction 19 +/- 9%, baseline serum creatinine 2.0 +/- 0.9 mg/dl), the mean baseline IAP was 8 +/- 4 mm Hg, with 24 (60%) patients having elevated IAP. Elevated IAP was associated with worse renal function (p = 0.009). Intensive medical therapy resulted in improvement in both hemodynamic measurements and IAP. A strong correlation (r = 0.77, p < 0.001) was observed between reduction in IAP and improved renal function in patients with baseline elevated IAP. However, changes in IAP or renal function did not correlate with changes in any hemodynamic variable. CONCLUSIONS: Elevated IAP is prevalent in patients with ADHF and is associated with impaired renal function. In the setting of intensive medical therapy for ADHF, changes in IAP were better correlated with changes in renal function than any hemodynamic variable.