RATIONALE: Functional reinnervation of the transplanted human heart by the autonomic nervous system has not been demonstrated. A lack of autonomic control of the transplanted allograft is reflected by an increased resting heart rate, a sluggish heart rate response to dynamical exercise and a reduced heart rate variability. Recent evidence suggests that a measure of deterministic chaos in the heartbeat interval series (point correlation dimension, PD2i) is superior to the conventional power spectrum or other stochastic measures in detecting changes in the mechanism underlying heartbeat generation. METHODS: The PD2i is based on the presumption that the variability is determined and patterned, whereas the stochastic measures all assume that the variability is around a stationary mean and is noise. The PD2i reconstructs the degrees of freedom (number of independent variables) in the system that generates the time series examined, and does this irrespective of whether the system is stochastic or deterministic and is stationary in time. RESULTS: PD2i was determined for heartbeat intervals (RR, ECG digitized at 1200 Hz; supine posture) of 23 heart transplant recipients (HTR: 9 adults, 14 children; 0.04-7.7 years after transplantation) and 21 healthy control subjects (CTL; 13 adults, 8 children). The PD2i (+/-SD) averaged 5.4 +/- 0.7 for the CTL adults and 5.4 +/- 0.6 for the CTL children. Mean PD2i was reduced after transplantation to 1.1 +/- 0.1 in 6 HTRs recorded within 1 year after surgery; in one HTR recorded 2 weeks after surgery the mean PD2i was 3.7. Between 1 to 2 years PD2i was found increased in 2 of 3 subjects and between 2 to 8 years it was increased in 13 of 13, but not to control levels. In normal hearts the QT subinterval of each heartbeat cycle is associated with inotropy and the RR-QT remainder with chronotropy (i.e., the dyastolic interval during which RR is primarily regulated). To examine more closely the residual and returning heartbeat dynamics of the HTR subjects, these subinterval series were examined during mild exercise (40 to 90 Watts) and its recovery. In recent HTRs, resting QT and RR-QT were moderately reduced and modulated by exercise and recovery, but with an approximate 100 beat latency. In long-term (7-8 years) HTR subjects there was a rapid and larger response to exercise/recovery, but compared to normal the range was smaller and the complexity of the subinterval trajectories in time was simpler. CONCLUSIONS: Recurrence of low-dimensional deterministic dynamics after transplantation suggests recovery of neurocardiac control attributable to 1) reorganization of the viable intrinsic cardiac nervous system, 2) reinnervation by the extrinsic autonomic nervous system, or 3) both.

Adult↗

PubMedDate not supplied

Factors limiting maximal oxygen consumption in humans.

The factors limiting VO2max in humans are analyzed according to a multifactorial model derived from the O2 conductance equation. In this context, alveolar ventilation (VA) and lung O2 transfer (GL) are not considered to be limiting, at least at sea level, because changes in VA and/or in GL are not accompanied by changes in VO2max due to the shape of the O2 dissociation curve. Thus, the limits to VO2max are shared between blood O2 transport (FQ') and a peripheral factor. This last includes tissue O2 transfer (Ft') and mitochondrial O2 utilization (Fm'). In untrained subjects at sea level, blood O2 transport is found to be responsible for approximately 70% of the overall limits to VO2max (FQ' = 0.7), the rest depending on the peripheral factors. FQ', as well as the sum of Ft' and Fm', are unchanged after training or upon return to sea level following exposure to chronic hypoxia (altitude higher than 5000 m). In the latter condition, however, since tissue O2 transfer, which sets Ft', is facilitated, and mitochondrial O2 utilization, which sets Fm', is impaired, Ft' is reduced and Fm' increased as compared to control condition and/or after training.

Humans↗

PubMedDate not supplied

Diacetylrhein and rhein: in vivo and in vitro effect on lymphocyte membrane fluidity.

The effect of diacetylrhein on lymphocyte membrane fluidity in osteoarthritis patients before and after 10 and 30 days of treatment was studied using the 1,6-diphenyl-1,3,5-hexatriene fluorescence polarization. Moreover we studied the in vitro effect of rhein, the active metabolite of diacetylrhein, on lymphocyte membrane fluidity of controls using the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene and its cationic derivative 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene. Our results showed that the patients with active osteoarthritis have higher fluorescence polarization values than those in the other osteoarthritis patients and in the controls. Moreover after 10 days of diacetylrhein treatment, we observed a significant decrease of fluorescence polarization values only in lymphocytes of the patients who showed active osteoarthritis before therapy. However after 30 days of treatment, significant changes of fluorescence polarization values were observed also in those patients who did not show painful osteoarthritis before diacetylrhein treatment. We observed that in vitro rhein also induces an increase in lymphocyte membrane fluidity, more evident with 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene with respect to 1,6-diphenyl-1,3,5-hexatriene.

Aged↗

PubMedDate not supplied

Molecular adsorbent recirculating system treatment for acute hepatic failure in patients with hepatitis B undergoing chemotherapy for non-Hodgkin's lymphoma.

Hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface (HBsAg) antigen-positive patients treated with chemotherapy. Because the hepatitis is related to HBV virological reactivation, application of effective antiviral therapy, such as Lamivudine, has been attempted. Despite the use of these antiviral agents at the time of clinical hepatitis, some HBsAg-positive patients still develop hepatic failure and die. We used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock, Germany) to treat 5 HBsAg-positive lymphoma patients with acute hepatic failure due to chemotherapy despite lamivudine treatment. Before and after each treatment we monitored the parameters of neurological status (EEG, cerebral CT and Glasgow coma score), hemodynamic parameters, acid-base equilibrium and blood gases as well as hepatic and renal function. The inclusion criteria were these of the King's College Hospital. Statistical analysis by Student t method showed significant results (P < .01). Three of 5 patients are alive without signs of reactivation of viral or hematological diseases at 1 year follow-up. The 2 patients died because MARS treatment was started too late, with Glascow coma score grade IV, hemodynamic instability, and mechanical ventilator assistance. Despite the limited number of cases, we believe that MARS can be applied to patients with a high tolerance and yield good results, but the treatment has to start at the first signs of hepatic failure.

Adult↗