The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and corresponding changes in cerebral blood flow velocity (CBFV) is studied in a population of 83 neonates. Static and dynamic methods are used to identify two subgroups showing either normal (group A, n = 23) or impaired (group B, n = 21) cerebral autoregulation. An FFT algorithm is used to estimate the coherence and transfer function between CBFV and ABP. The significance of the linear dependence between these two variables is demonstrated by mean values of squared coherence > 0.50 for both groups in the frequency range 0.02-0.50 Hz. However, group A has significantly smaller coherences than group B in the frequency ranges 0.02-0.10 Hz and 0.33-0.49 Hz. The phase response of group A is also significantly more positive than that of group B, with slopes of 9.3 +/- 1.05, and 1.80 +/- 1.2 rad Hz-1, respectively. The amplitude frequency response is also significantly smaller for group A in relation to group B for the frequency range 0.25-0.43 Hz. These results suggest that transfer function analysis may be able to identify different components of cerebral autoregulation and also provide a deeper understanding of recent findings by other investigators.

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Computerized coherent averaging of the cerebral blood flow velocity response to spontaneous blood pressure transients offers a promising new method for noninvasive bedside assessment of autoregulation in patients undergoing intensive care. The time course for autoregulation, when present, is in agreement with that reported in adults.

Angiogenesis is essential for the replacement of cartilage by bone during growth and repair. In order to obtain a better understanding of the mechanisms regulating vascular invasion at sites of endochondral ossification we have investigated the expression of the endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF), by chondrocytes in human neonatal growth plates. VEGF was absent from chondrocytes in the resting zone and only weakly expressed by occasional chondrocytes in the proliferating region. In the hypertrophic zone the number of chondrocytes stained and the intensity of staining for VEGF increased with chondrocyte hypertrophy, maximum expression of VEGF being observed in chondrocytes in the lower hypertrophic and mineralised regions of the cartilage. These observations provide the first demonstration of the presence of VEGF in situ in developing human bone and are consistent with in vitro observations demonstrating the upregulation of proangiogenic growth factor production with increasing chondrocyte hypertrophy. The presence of numerous small blood vessels and vascular structures in the subchondral region where VEGF expression was maximal indicates that VEGF produced by hypertrophic chondrocytes may play a key role in the regulation of vascular invasion of the growth plate.

The dynamic response of cerebral autoregulation to spontaneous changes in arterial blood pressure (ABP) is described by the relationship between cerebral blood flow velocity (CBFV) and resistance-area product (RAP). CBFV was measured with Doppler ultrasound in the middle cerebral artery and ABP with an intra-arterial catheter in 66 neonates. Spontaneous changes in mean ABP were automatically detected and the maximum derivative was used to synchronize the coherent averaging of corresponding CBFV and RAP transients. These were classified into two groups corresponding to intact (group A) or impaired (group B) autoregulation. The cross correlation between RAP and CBFV indicates a significant relationship with a time delay of 5 s for group A. The frequency response of RAP was estimated by the cross spectra with CBFV. Groups A and B present a similar amplitude spectra but the phase spectra of group A lags that of group B. The impulse responses of the two groups are also markedly different and were used to simulate the velocity response to a 5% step change in ABP. Impulse responses were also obtained for four different levels of pCO2 showing that hypercapnia leads to an impulse response similar to that of group B (impaired autoregulation). This method can be used to extend the usual dichotomic classification adopted in clinical studies of autoregulation.

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