Worsening of left ventricular diastolic function during long-term correction of anemia with erythropoietin in chronic hemodialysis patients – an assessment by radionuclide ventriculography at rest and exercise

We studied the effect of correction of anemia with erythropoietin on left ventricular systolic and diastolic function at rest and exercise in 17 chronic hemodialysis patients by means of maximum exercise testing and equilibrium gated radionuclide angiocardiography on three occassions: 1) initial–before erythropoietin administration, 2) intermediate–at the time when the target hemoglobin level reached 100 g/l, and 3) long-term–after 12 months of therapy. After correction of anemia, the patients showed a significant improvement in their response to exercise regarding maximal work load achieved, exercise duration and recovery time. Ejection fraction and peak ejection rate remained unchanged during therapy. At rest, peak filling rate was reduced from 2.62 ± 1.0 (baseline) to 2.28 ± 0.9 (intermediate) end-diastolic volume per second, p < 0.01, while no significant difference was observed during exercise. The time to peak filling rate was prolonged significantly during EPO therapy from 157 ± 30 to 177 ± 28 ms at rest, p < 0.05, and from 101 ± 24 to 130 ± 27 ms during exercise, p < 0.01. By the time of the late study, there were no significant differences between the late and intermediate study. In conclusion, amelioration of anemia with erythropoietin in hemodialysis patients produced improvement in exercise capacity, but diastolic function worsened with therapy and this effect was maintained during the long-term treatment, while systolic function at rest and exercise remained unchanged.     

Sustained (rh)VEGF165 release from a sprayed fibrin biomatrix induces angiogenesis, up-regulation of endogenous VEGF-R2, and reduces ischemic flap necrosis

This study investigated (1) the release of recombinant human vascular endothelial growth factor ([rh]VEGF₁₆₅) from an in vitro fibrin matrix, (2) the effects of (rh)VEGF₁₆₅ released from an in vivo fibrin matrix on ischemic flap necrosis in the rat dorsal skin flap model, and (3) the effects of (rh)VEGF₁₆₅ released from an in vivo fibrin matrix on VEGF-R2 expression in transgenic VEGF-R2/luc mice. In vitro fibrin matrices were spiked with (rh)VEGF₁₆₅ and demonstrated (rh)VEGF₁₆₅ release over 88 hours with 66% recovery. Ischemic dorsal flaps were treated with a fibrin sealant (FS), FS spiked with (rh)VEGF₁₆₅, or left untreated. Flaps treated with FS spiked with (rh)VEGF₁₆₅ showed greater viability than controls as measured by planimetric analysis. Immunohistochemical analyses revealed stronger neovascularization than that exhibited by controls. Transgenic mice implanted with FS spiked with (rh)VEGF₁₆₅ had significant increases in VEGF-R2 expression relative to controls at days 5–13 after implantation. Conclusions drawn from this work are that (1) (rh)VEGF₁₆₅ is released from an in vitro fibrin matrix at clinically appropriate times, (2) (rh)VEGF₁₆₅ increases the viability of tissue flaps in vivo, and (3) (rh)VEGF₁₆₅ induces the expression of VEGF-R2 expression. This work demonstrates the clinical ability of sprayed FS to locally deliver growth factors to ischemic tissue of patients.     

Spontaneous contractions of isolated rat portal vein under temperature perturbations

We studied nonlinear dynamics underlying spontaneous rhythmical contractions of isolated rat portal vein. The signals were acquired at four different temperatures important in isolated blood vessels preparations: 4, 22, 37 and 40°C. To characterize the system’s nonlinearity, we calculated the largest Lyapunov exponent, sample entropy and scaling exponents. Evidence for nonlinearity was provided by analysis of surrogate data generated from the phase-randomized Fourier transform of the original sequences. Positive values of the largest Lyapunov exponent were obtained for the time series recorded under applied conditions, indicating that the system preserves its chaotic deterministic nature even far from the physiological temperature range. Scaling exponents revealed three distinctive regions with different correlation properties. The calculated measures that characterize the time series obtained at 4°C were significantly different from those derived from data obtained at higher temperatures. System’s dynamics becomes more complex or less predictable as temperature approaches physiological value. The computation of the largest Lyapunov exponent, sample entropy and correlation measures gave an insight into the complex dynamics of the isolated blood vessels rhythmicity. We identified different modes of rhythmical contractions of isolated rat portal vein which could improve understanding of possible control mechanisms in vivo.     

Prognostic factors in patients who have survived myocardial infarction

Patients who have survived myocardial infarction (MI), compared to the general population, have an increased risk of reinfarction, myocardial revascularization, and death. In this study we investigated the prognostic significance of the predictors of the risk for adverse coronary events in 118 patients, both male and female, with a confirmed diagnosis of MI in the last 3 years. The predictors of reinfarction, revascularization and death in patients who survived MI were: poor adherence to hypolipemics (hazard ratio [HR] 3.06, p=0.006), physical inactivity (HR 2.22, p=0.056), the number of variable risk factors (HR 1.29, p=0.025), and age (HR 1.06, p=0.007). After the inclusion of the invariable risk factors in the model of multivariant analysis, the following factors were singled out as significant predictors of the risk: gender (HR 3.86, p=0.0015), physical inactivity (HR 2.38, p=0.007), change in the level of triglycerides (HR 1.49, p=0.040), change in the number of variable risk factors (HR 1.41, p=0.0007), and age (HR 1.05, p=0.009). A 3-year follow-up of the patients who survived the first MI and who were enrolled in this study of secondary prevention demonstrated that physical inactivity, the number of variable risk factors and age significantly contributed to an increased risk of reinfarction, revascularization, and death.