Systemic hypoxia increases leukocyte emigration and vascular permeability in conscious rats.

We recently observed that acute systemic hypoxia produces rapid increases in leukocyte adherence in the mesenteric microcirculation of the anesthetized rat Wood JG, Johnson JS, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 1734-1740, 1999; Wood JG, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 873-881, 1999. Hypoxia-induced leukocyte adherence is associated with an increase in reactive oxygen species (ROS) generation and is attenuated by antioxidants or interventions that increase tissue levels of nitric oxide (NO). These results suggest that the acute effects of hypoxia on leukocyte-endothelial interactions are caused by a change in the ROS-NO balance. The present experiments were designed to extend our observations of the initial microcirculatory response to hypoxia; specifically, we wanted to determine whether the response to systemic hypoxia involves increased microvascular permeability and leukocyte emigration and whether ROS generation and decreased NO levels contribute to these responses. At this time, there is conflicting evidence, from in vitro studies, regarding the effect of hypoxia on these indexes of vascular function. Our studies were carried out in the physiological setting of the conscious animal, in which a prolonged hypoxic exposure is possible without the adverse effects that may develop under anesthesia. The central observation of these studies is that conscious animals exposed for 4 h to environmental hypoxia show increased microvascular permeability and emigration of leukocytes into the extravascular space of the mesenteric circulation. Furthermore, these events are dependent on increased ROS generation and, possibly, a subsequent decrease in tissue NO levels during systemic hypoxia. Our results show that systemic hypoxia profoundly affects vascular endothelial function through changes in the ROS-NO balance in the conscious animal.

Systemic hypoxia promotes leukocyte-endothelial adherence via reactive oxidant generation.

We recently demonstrated that systemic hypoxia during reduced inspired PO(2) produces a rapid increase in leukocyte adherence to rat mesenteric venules. Evidence suggests that the mechanism of this response involves decreased nitric oxide (NO) levels. One possible pathway for NO depletion could involve increased reactive oxygen species (ROS) generation resulting in inactivation of NO. The overall goal of the present study was to examine the role of ROS in promoting leukocyte-endothelial adherence during systemic hypoxia. Experiments were designed to 1) evaluate changes in ROS generation in the mesenteric microcirculation during systemic hypoxia, 2) determine how the ROS signal changes when PO(2) levels return to normal after a period of systemic hypoxia, 3) assess the effect of antioxidants on ROS generation during hypoxia, and 4) utilize antioxidants to examine the functional relationship between ROS generation and leukocyte adherence during hypoxia. The major findings from this study are that systemic hypoxia increases ROS generation within the mesenteric microcirculation and that antioxidants prevent the increase in leukocyte-endothelial adhesive interactions observed in hypoxia.

Hypoxia causes leukocyte adherence to mesenteric venules in nonacclimatized, but not in acclimatized, rats.

Although the effects of ischemia-reperfusion have received considerable attention, few studies have directly evaluated the microcirculatory response to systemic hypoxia. The overall objective of this study was to assess the effect of environmental hypoxia on adhesive interactions of circulating leukocytes with rat mesenteric venules by using intravital microscopy. Experiments were designed to 1) characterize the adhesive interactions of circulating leukocytes to venules during acute hypoxia produced by a reduction in inspired PO(2), 2) evaluate the role of nitric oxide in these adhesive interactions, 3) determine whether the effect of hypoxia on leukocyte adhesive interactions differs between acclimatized and nonacclimatized rats, and 4) assess whether compensatory changes in nitric oxide formation contribute to this difference. The results showed that acute hypoxia promotes leukocyte-endothelial adherence in mesenteric venules of nonacclimatized rats. The mechanism of this response is consistent with depletion of nitric oxide within the microcirculation. In contrast, no leukocyte-endothelial adherence occurred during hypoxia in rats acclimatized to hypobaric hypoxia. The results are consistent with increased nitric oxide formation due to expression of inducible nitric oxide synthase during the acclimatization period. Further studies are needed to establish the cause of nitric oxide depletion during acute hypoxia as well as to define the compensatory responses that attenuate hypoxia-induced leukocyte-endothelial adherence in the microvasculature of acclimatized rats.

Evaluation of remote stethoscopy for pediatric telecardiology.

OBJECTIVE: To investigate the interobserver reliability and diagnostic validity of a commercial electronic stethoscope for pediatric telecardiology. MATERIALS AND METHODS: Pairs of blinded pediatric cardiologists made independent diagnoses, recommendations concerning follow-up echocardiography, and specific judgments regarding heart sounds, murmurs, and congenital heart disease using an electronic (ES) or an acoustic (AS) stethoscope on 78 pediatric cardiology outpatients and at a distance of 450 km (280 miles) with 38 telemedicine cardiology outpatients. The kappa statistic (K) indexed the instruments' interexaminer reliabilities. The validity of ES was measured by K for ES versus AS and by the percentage of cases where the findings for ES and AS differed sufficiently to suggest an important ES screening error. RESULTS: For heart disease, AS, ES, and tele-ES reliabilities were satisfactory (K = 0.80, 0.67, and 0.80, respectively), as were AS agreement with hands-on ES (K = 0.65) and with tele-ES (K = 0.64). The AS and ES reliabilities and ES/AS agreement were also satisfactory for systolic regurgitant and diastolic pulmonic murmurs (K = 0.63-0.78) but were unsatisfactory for evaluable heart sounds and other murmurs (K = 0.16-0.60). The ES yielded clinically important disagreements with AS in 5.4% of the clinic cases and 10.5% of the telemedicine cases (P = 0.67). In determining the need for additional work-up (echocardiography) or follow-up appointments, hands-on ES and tele-ES had a combined accuracy of 92%, with a sensitivity of 88% and a specificity of 97%. CONCLUSIONS: Hands-on ES provided reliable and valid screening for congenital heart disease. Tele-ES was highly reliable but had reduced diagnostic validity. Examiner blinding, bandwidth limitations, and artificial restrictions on the remote assistant may have contributed to this reduced performance. As these factors are easily correctable, we regard the ES as a highly promising tool for pediatric telecardiology.

Cerebrovascular stenoses with cerebral infarction in a child with Williams syndrome.

We report on a patient with Williams syndrome who suffered a cerebrovascular accident. Clinical evaluation demonstrated the presence of carotid and cerebral arterial stenoses. We believe these lesions led to acute cerebrovascular ischemia and a non-hemorrhagic cerebral infarction. It is possible the stenoses were exacerbated by a vasculitis. The stenoses were identified by both invasive and noninvasive imaging studies. These studies may have a role in the evaluation of persons with Williams syndrome.