Biomedical subjects

Patrick S McQuillen

Publications and source records attributed to Patrick S McQuillen.

8 recordsLinked to original sources

PubMed2006

Balloon atrial septostomy is associated with preoperative stroke in neonates with transposition of the great arteries.

BACKGROUND: Preoperative brain injury is common in neonates with transposition of the great arteries (TGA). The objective of this study is to determine risk factors for preoperative brain injury in neonates with TGA. METHODS AND RESULTS: Twenty-nine term neonates with TGA were studied with MRI before cardiac surgery in a prospective cohort study. Twelve patients (41%) had brain injury on preoperative MRI, and all injuries were focal or multifocal. None of the patients had birth asphyxia. Nineteen patients (66%) required preoperative balloon atrial septostomy (BAS). All patients with brain injury had BAS (12 of 19; risk difference, 63%; 95% confidence interval, 41 to 85; P=0.001). As expected on the basis of the need for BAS, these neonates had lower systemic arterial hemoglobin saturation (Sao2) (P=0.05). The risk of injury was not modified by the cannulation site for septostomy (umbilical versus femoral, P=0.8) or by the presence of a central venous catheter (P=0.4). CONCLUSIONS: BAS is a major identifiable risk factor for preoperative focal brain injury in neonates with TGA. Imaging characteristics of identified brain injuries were consistent with embolism; however, the mechanism is more complex than site of vascular access for BAS or exposure to central venous catheters. These findings have implications for the indications for BAS, timing of surgical repair, and use of anticoagulation in TGA.

Catheterization↗

PubMed2006

Pyramidal tract maturation after brain injury in newborns with heart disease.

OBJECTIVE: Our objective was to quantify white matter tract development in term newborns with congenital heart disease, a population at high risk for perioperative brain injury, using magnetic resonance imaging diffusion tensor tractography (DTT). METHODS: Twenty-five newborns with congenital heart disease were imaged before and after surgery, with a median of 2 weeks between serial magnetic resonance imaging examinations. DTT was performed to segment bilateral pyramidal tracts using semiautomated fiber tracking software, and manual region of interest measurements were taken for comparison. RESULTS: Significant maturational rates of increasing fractional anisotropy (median, 4.4% per week) and decreasing mean diffusivity (D(av)) (median, -2.0% per week) in the pyramidal tract were measured in infants without brain injury. Fractional anisotropy maturation rates were highest in newborns with normal scans, intermediate (median, 2.4% per week) in those with postoperative injury, and lowest (median, 0.9% per week) in those with preoperative injury, indicating a significant trend across brain injury groups (p = 0.015). D(av) maturation rates did not differ across injury groups (p = 0.15). Manual region of interest measures showed greater variability in serial measurements, and no significant differences were identified between injury groups, suggesting that DTT may provide more sensitive measures. INTERPRETATION: DTT is feasible in term newborns and may help to characterize abnormal white matter tract development following acquired brain injury.

Brain Injuries↗

PubMed2005

Erythropoietin improves functional and histological outcome in neonatal stroke.

Neonatal stroke is a condition that leads to disability in later life, and as yet there is no effective treatment. Recently, erythropoietin (EPO) has been shown to be cytoprotective following brain injury and may promote neurogenesis. However, the effect of EPO on functional outcome and on morphologic changes in neonatal subventricular zone (SVZ) following experimental neonatal stroke has not been described. We used a transient focal model of neonatal stroke in P10 rat. Injury was documented by diffusion weighted MRI during occlusion. Immediately upon reperfusion, either EPO (5U/gm) or vehicle was administered intraperitoneally and animals were allowed to grow for 2 wk. Sensorimotor function was assessed using the cylinder rearing test and then brains were processed for volumetric analysis of the SVZ. Stroke induced SVZ expansion proportional to hemispheric volume loss. EPO treatment markedly preserved hemispheric volume and decreased the expansion of SVZ unilaterally. Furthermore, EPO treatment significantly improved the asymmetry of forelimb use following neonatal stroke. This functional improvement directly correlated with the amount of preserved hemispheric volume. These results suggest EPO may be a candidate in the treatment of neonatal stroke.

Animals↗

PubMed2005

Cerebral oxygen balance is impaired during repair of aortic coarctation in infants and children.

OBJECTIVE: During repair of aortic coarctation through a left thoracotomy without cardiopulmonary bypass, clamping the proximal transverse aortic arch occludes antegrade flow to the left carotid and vertebral arteries. It is assumed that flow through the right carotid and vertebral arteries is adequate for cerebral perfusion. The study objective is to determine whether aortic occlusion impairs left hemispheric cerebral oxygen balance measured by near-infrared spectroscopy. METHODS: In 18 children having repair of aortic coarctation, we measured the maximum change and integral for hemoglobin D (difference of oxyhemoglobin and deoxyhemoglobin), total oxygenation index, and the redox state of cytochrome aa3. Thirteen subjects had recordings from the left hemisphere to test the hypothesis that aortic occlusion impairs left hemispheric oxygen balance. Five subjects had recordings from the right hemisphere for comparison. RESULTS: After aortic clamping, a significant decrease in hemoglobin D was observed in recordings from the left hemisphere compared with those from the right hemisphere (P = .03, maximum change in hemoglobin D). Total oxygenation index and cytochrome aa3 were generally preserved. There was an inverse linear relationship for the change in hemoglobin D during clamp application and after removal (Spearman rho = -0.74), with increased hemoglobin D after clamp removal in those subjects with the greatest decrease of hemoglobin D during arch occlusion. Linear regression analysis identified nitroprusside administration as significantly associated with a decrease in hemoglobin D (P < .001). CONCLUSIONS: Significant impairment in left hemispheric cerebral oxygen balance was identified during arch clamping. The neurodevelopmental significance of impaired cerebral oxygen balance detected by near-infrared spectroscopy during aortic coarctation repair remains to be elucidated.

Aorta, Thoracic↗

PubMed2004

Preoperative brain injury in newborns with transposition of the great arteries.

BACKGROUND: The objective was to determine the timing and mechanism of brain injury using preoperative and postoperative magnetic resonance imaging (MRI) and three-dimensional MR spectroscopic imaging (MRSI) in newborns with transposition of the great arteries (TGA) repaired with full-flow cardiopulmonary bypass. METHODS: Ten term newborns with TGA undergoing an arterial switch operation were studied with MRI, MRSI, and neurologic examination preoperatively and postoperatively at a median of 5 days (2 to 9 days) and 19 days (14 to 26 days) of age, respectively. Five term historical controls were studied at a median of 4 days (3 to 9 days). Lactate/choline (marker of cerebral oxidative metabolism) and N-acetylaspartate (NAA)/choline (marker of cerebral metabolism and density) were measured bilaterally from the basal ganglia, thalamus, and corticospinal tracts. RESULTS: Four TGA newborns had brain injury on the preoperative MRI. The only new lesion detected on the postoperative study was a focal white matter lesion in one newborn with a normal preoperative MRI. The MRSI of age-adjusted lactate/choline was quantitatively higher in newborns with TGA compared with those without heart disease (p < 0.0001), even in newborns without MRI evidence of preoperative brain injury. Lactate/choline decreased after surgery but remained elevated compared with controls. In newborns with TGA, those with preoperative brain injury on MRI had lower NAA/choline globally (p = 0.04) than those with normal preoperative MRI. Five newborns had a decline in NAA/choline from the preoperative to postoperative studies. CONCLUSIONS: Abnormal brain metabolism and injury was observed preoperatively in newborns with TGA. Brain injury is not solely related to the operative course.

Brain Injuries↗

PubMed2004

Selective vulnerability in the developing central nervous system.

Selective patterns of cerebral injury are observed after a variety of insults at different ages during development. Distinct populations of cells demonstrate selective vulnerability during these specific developmental stages, which may account for the observed patterns of injury. We review the evidence that injury to preoligodendrocytes and subplate neurons contributes to periventricular white matter injury in preterm infants, whereas thalamic neuronal cell vulnerability and neuronal nitric oxide synthase-expressing striatal interneurons resistance result in deep gray nuclei damage in the term infant. The unique roles of particular mechanisms including oxidative stress, glutamatergic neurotransmission, and programmed cell death are discussed in the context of this selective vulnerability.

Animals↗

PubMed2003

Selective vulnerability of subplate neurons after early neonatal hypoxia-ischemia.

Neonatal hypoxia-ischemia in the preterm human leads to selective injury to the subcortical developing white matter, which results in periventricular leukomalacia (PVL), a condition associated with abnormal neurodevelopment. Maturation-dependent vulnerability of late oligodendrocyte progenitors is thought to account for the cellular basis of this condition. A high frequency of cognitive and sensory deficits with decreasing gestational age suggests pervasive abnormalities of cortical development. In a neonatal rat model of hypoxic-ischemic injury that produces the characteristic pattern of subcortical injury associated with human PVL, selective subplate neuron death is seen. The premature subplate neuron death occurs after thalamic axons have reached their targets in cortex. Thus, as expected, thalamocortical connections form normally, including patterned connections to somatosensory cortex. However, deficits in motor function still occur, as in babies with PVL. Subplate neuron cell death in PVL provides another mechanism for abnormal neurodevelopment after neonatal hypoxia-ischemia.

Animals↗

PubMed2002

A novel role for p75NTR in subplate growth cone complexity and visual thalamocortical innervation.

In cortical development, subplate axons pioneer the pathway from neocortex to the internal capsule, leading to the proposal that they are required for subsequent area-specific innervation of cortex by thalamic axons. A role for p75 neutrophin receptor (NTR) in area-specific thalamic innervation of cortex is suggested by the observation that p75NTR expression is restricted to subplate neurons in a low-rostral to high-caudal gradient throughout the period of thalamocortical innervation. In vitro, neurotrophin 3 binding to p75NTR increases neurite length and filopodial formation of immunopurified subplate neurons, suggesting a role for p75NTR in subplate growth cone morphology and function in vivo. Consistent with this idea, subplate growth cones have markedly fewer filopodia in mice lacking p75NTR than in wild type mice. Despite this gross morphologic defect, many subplate axons in knock-out mice pioneer the projection to the internal capsule as they do in wild-type mice. However a few subplate axons in the knock-out mice make ectopic projections rostral in the intermediate zone and frontal cortex. Concomitant with the altered morphology of subplate growth cones, mice lacking p75NTR have diminished innervation of visual cortex from the lateral geniculate nucleus, with markedly reduced or absent connections in 48% of knock-out mice. Thalamic projections to auditory and somatosensory cortex are normal, consistent with the gradient of p75NTR expression. Our present results are unusual in that they argue that p75NTR functions in a novel way in subplate neurons, that is, in growth cone morphology and function rather than in axon extension or neuronal survival.

Aging↗