Right ventricular pressure-volume loops using simultaneous radionuclide angiography with a multiwire gamma camera and right heart catheterization

BACKGROUND: The purpose of this study was to generate right ventricular (RV) pressure-volume loops (PVLs) from time-activity curves obtained by first-pass radionuclide angiography (RNA) and RV pressures obtained by right heart catheterization. METHODS AND RESULTS: Short-lived tantalum 178 was used to obtain first-pass RNA at baseline (n = 31), after nitroglycerin (n = 5), or after the conclusion of cardiac catheterization (n = 13). From the radionuclide-derived RV ejection fraction and thermodilution stroke volume, the RV end-diastolic volume and end-systolic volume were measured. Special proprietary software was developed and used to integrate the pressure and the RNA data. The mean heart rate was 80 +/- 17 beats/min; RV ejection fraction, 39% +/- 12%; RV end-diastolic volume, 217 +/- 79 mL; RV end-systolic volume, 142 +/- 74 mL; and RV end-diastolic pressure, 10 +/- 7 mm Hg. The RV PVLs were of high quality and reproducible. CONCLUSIONS: This study provides proof of concept of the feasibility of generating RV PVL; the short half-life (10 minutes) and low energy (59 keV) of Ta-178 allow the generation of multiple loops at low radiation exposure. Such studies could be performed at the bedside and provide a wealth of information that may have clinical and research merits.     

Assessment of left ventricular function during upright treadmill exercise with tantalum 178 and multiwire gamma camera

BACKGROUND: Prior studies with first-pass radionuclide angiography (RNA) during treadmill exercise used a single-crystal (Anger) or multicrystal gamma camera and technetium 99m tracers. Motion correction, when done, used point sources, which limited correction to only plane movement. METHODS AND RESULTS: We examined the performance of a multiwire gamma camera (MWGC), generator-produced tantalum 178, and a novel method of motion correction during treadmill exercise testing. We studied 100 patients in whom rest and stress gated tomographic myocardial perfusion images were obtained. Eight patients were excluded because of incomplete data. There were 53 men and 39 women aged 52 +/- 12 years. The resting left ventricular (LV) ejection fraction (EF) was 61% +/- 12% by gated single photon emission computed tomography. Stress myocardial perfusion was normal in 83 patients and abnormal in 9 patients. The resting RNA EF in the upright position was 57% +/- 12% (r = 0.52, P = .0001 vs gated EF). At peak exercise, the EF by MWGC was 60% +/- 26% if uncorrected and 69% +/- 13% after motion correction. Among the 80 patients with normal perfusion and normal resting EF by gated single photon emission computed tomography, a normal response to exercise was seen in 52 (63%) without motion correction and 74 (89%) with motion correction (P < .05). CONCLUSION: Assessment of LV function is feasible with MWGC. The motion-corrected images significantly improved the results.     

Fluorescent microspheres are reliable for serial bone blood flow measurements

The fluorescent microsphere method is one of the current techniques to determine regional blood flow in various organs. The purpose of this study was to examine the suitability of fluorescent microspheres for serial measurement of regional bone blood flow. Six anesthetized female New Zealand rabbits received five left ventricular injections of fluorescent microspheres in 20-minute intervals. To test the precision of the measurement two types of fluorescent microspheres were injected simultaneously at the first and last injections. Blood flow was calculated in the kidneys, lungs, brain, femurs, and tibias after measuring the fluorescence intensity in each reference blood and tissue sample. Comparison of blood-flow values obtained by simultaneously injected microspheres showed an excellent correlation and a minimal percentage difference at the first and last injections, indicating valid measurements of regional bone blood flow. No significant differences were observed when comparing blood flow in the corresponding regions of bones on the right side and left side. Mean blood flow in the femur and tibia significantly increased at the fourth injection whereas flow distribution within the femur and tibia essentially remained unchanged throughout the experiment. Comparison of blood flow values obtained by simultaneously injected microspheres showed moderate agreement for the kidneys and lungs at the last injections. Because this finding might be attributable to disturbances of microcirculation caused by accumulation of spheres in high-flow organs, the increase in regional bone blood flow observed in our experiments has to be interpreted carefully. This study showed that bone blood flow can be determined reliably in anesthetized rabbits by as many as three serial injections of fluorescent microspheres.     

In vitro assessment of dose-dependent platelet activation by polyclonal antithymocyte globulins: a flow-cytometric analysis

Polyclonal antithymocyte globulins (ATGs) are immunosuppressive drugs widely used in transplantation and hematologic disorders. Treatment with ATGs can induce side effects such as neutropenia and thrombocytopenia because of unspecific antibodies directed against nonmyeloid cells present in these preparations. Depletion, activation, and expression of adhesion molecules on platelets in vitro were studied in the whole blood of healthy volunteers by means of flow cytometry after incubation with different doses of three polyclonal ATGs. Our data show no ATG-mediated cytotoxic activity against platelets. ATGs are able to induce activation of platelets through increased expression of P-selectin and hLAMP-1 and higher percentages of gated thrombocytes expressing these molecules. Furthermore, increased expression of hLAMP-1 presented a dose-dependent pattern. ATGs induced activation and enhanced expression of adhesion molecules in unstimulated platelets. Increased adhesion may be responsible for undesirable side effects such as thrombocytopenia and reticulopenia.     

Impact of small variations of ischemia time after polyclonal antithymocyte globulins in a nonhuman primate model of ischemia-reperfusion injury

Ischemia-reperfusion injury leads to increased leukocyte adherence enhancing acute cellular rejection, causing microvascular dysfunction and tissue damage. The length of the ischemic time is important in clinical transplantation. Polyclonal antithymocyte globulins (pATGs) induce T-cell depletion and functional impairment of nondepleted lymphocytes. In this study cynomolgus monkeys were used to evaluate the impact of three different pATGs on the microcirculation, on leukocyte behavior and infiltration, as well as on tissue damage after two different periods of ischemia (60 and 150 minutes). pATGs were administered 30 minutes before ex vivo reperfusion. Using intravital fluorescence microscopy, the postreperfusion microcirculation was visualized in vivo. Morphologic analyses were performed on biopsies obtained after the experiments. Significant differences were observed between the two periods of ischemia in both the ATG-treated and control groups. Minimizing ischemia time, even in short intervals, improves the outcome of ischemia-reperfusion injury by reducing leukocyte adherence to the antigen-presenting endothelial cells, improving the microcirculation, and reducing tissue damage.     

Polyclonal anti-thymocyte globulins influence apoptosis in reperfused tissues after ischaemia in a non-human primate model

Reperfusion triggers the expression of inflammatory cytokines and adhesion molecules that increase the rate of apoptosis in the reperfused tissues after ischaemia, thus worsening the outcome of the grafts. Polyclonal anti-thymocyte globulins (pATGs) are able to reduce the number of lymphocytes as well as block adhesion molecules and induce apoptosis in T-lymphocytes through Fas-ligand. The aims of this study were to investigate the influence of pATGs on the prevention of apoptosis of reperfused tissues after ischaemia and to monitor their capability to enhance lymphocyte apoptosis thus decreasing the deleterious effects of ischaemia/reperfusion injury (IRI). Extremities of cynomolgus monkeys (n=8) were flushed via either the femoral or the brachial artery. After 60 min of ischaemia the limbs were reperfused with human blood. ATG was added to the blood in a therapeutic dose 20 min prior to reperfusion of the extremities. Surgically available limbs (n=20) were assigned to the following groups: ATG group (n=10) and control group (without ATG; n=10). DNA fragmentation analysis was performed in situ to detect apoptosis at the single-cell level. Our study shows an increased rate of muscle and connective tissue apoptosis in the control group compared with the ATG-treated group. Cells found in the vascular areas present different rates of apoptosis, with enhanced cellular death of endothelium and connective perivascular areas being observed in the control group. The group treated with ATG shows an increased rate of white blood cell (WBC) apoptosis in vascular and perivascular areas. Previous studies have shown that pATGs are able to induce apoptosis as well as complement-mediated cell death in peripheral T-lymphocytes in vitro. Our results confirm that pATGs not only increase the rate of apoptosis of WBCs in vivo but also have a protective effect on the reperfused tissue. This may alleviate the damage after reperfusion of solid-organ transplantation.     

Chondroinduction of mouse mesenchymal stem cells in three-dimensional highly porous matrix scaffolds

Porous polyvinyl formal (PVF) resin and poly(lactide-caprolactone) [P(LA/CL)] sponges were examined as three-dimensional matrices for chondroinduction of cultured bone marrow mesenchymal stem cells (MSCs). Approximately 5 x 10(5) mouse MSCs were seeded in porous PVF resin or P(LA/CL) sponges and were cultured for up to 1 month in serum-free high-glucose Dulbecco's modified Eagle's medium containing 10 ng/mL transforming growth factor-beta3 and 100 nM dexamethasone for chondroinduction. After the 1-month culture period, the PVF resin and P(LA/CL) sponges contained approximately twice the amount of glycosaminoglycans compared with the control pellet. Safranin-O staining of PVF and P(LA/CL) after 1 month of culture revealed a cartilage-like extracellular matrix containing glycosaminoglycans and collagen. When implanted into nude mice, PVF and P(LA/CL) seeded with MSCs were found to be both biocompatible and chondroinductive. These highly porous scaffolds can maintain a large number of cells in a three-dimensional structure. Both are potentially promising for the chondroinduction of bone marrow MSCs for research and clinical applications.     

The influence of periarterial papaverine application on intraoperative renal function and blood flow during laparoscopic donor nephrectomy in a pig model

Background: The transplantation of live donor kidneys harvested laparoscopically is associated with a higher incidence of delayed graft function than the transplantation of grafts harvested via the open technique. The delay is believed to be due to a decrease in renal blood flow during laparoscopic donor nephrectomy (LDN). The aim of this study was to evaluate whether renal function and blood perfusion can be enhanced by the periarterial application of papaverine during LDN. Methods: Renal function and blood flow were studied in a porcine model that included a total of 24 pigs (20–30 kg). In 12 of the pigs, urine output and creatinine clearance were determined as measures of renal function. In the other 12 pigs, renal blood flow was determined using fluorescent-labeled microspheres. In each group, the pigs were randomized into two subgroups, one with and one without a perivascular injection of 50 mg papaverine. Results: As compared to the controls, the animals receiving papaverine had a significantly higher urine output (3.1 ± 1.6 vs 0.9 ± 0.45 ml/h/kg; p = 0.02), superior creatinine clearance (2.22 ± 0.5 vs 0.95 ± 0.1 ml/min/kg; p = 0.038), and enhanced renal blood flow (4.9 ± 2.2 vs 2.1 ± 0.8 ml/min/g; p = 0.008). Conclusions: When applied to the tissue surrounding the renal artery, papaverine substantially improves renal function and blood flow during laparoscopic live kidney donation. Whether graft optimization during kidney procurement also translates into improved posttransplantation function remains to be established. Presented at the 8th World Congress of Endoscopic Surgery, Society of American Gastrointestinal Endoscopic Surgeons (SAGES) meeting, New York, NY, USA, 13–16 March