Sex and the migraine brain.

The brain responds differently to environmental and internal signals that relate to the stage of development of neural systems. While genetic and epigenetic factors contribute to a premorbid state, hormonal fluctuations in women may alter the set point of migraine. The cyclic surges of gonadal hormones may directly alter neuronal, glial and astrocyte function throughout the brain. Estrogen is mainly excitatory and progesterone inhibitory on brain neuronal systems. These changes contribute to the allostatic load of the migraine condition that most notably starts at puberty in girls.

The enigma of the dorsolateral pons as a migraine generator.

In this editorial, we integrate improved understanding of functional and structural brain stem anatomy with lessons learned from other disciplines on brainstem function to provide an alternative interpretation to the data used to support the brainstem migraine generator theory.

Painful heat reveals hyperexcitability of the temporal pole in interictal and ictal migraine States.

During migraine attacks, alterations in sensation accompanying headache may manifest as allodynia and enhanced sensitivity to light, sound, and odors. Our objective was to identify physiological changes in cortical regions in migraine patients using painful heat and functional magnetic resonance imaging (fMRI) and the structural basis for such changes using diffusion tensor imaging (DTI). In 11 interictal patients, painful heat threshold + 1°C was applied unilaterally to the forehead during fMRI scanning. Significantly greater activation was identified in the medial temporal lobe in patients relative to healthy subjects, specifically in the anterior temporal pole (TP). In patients, TP showed significantly increased functional connectivity in several brain regions relative to controls, suggesting that TP hyperexcitability may contribute to functional abnormalities in migraine. In 9 healthy subjects, DTI identified white matter connectivity between TP and pulvinar nucleus, which has been related to migraine. In 8 patients, fMRI activation in TP with painful heat was exacerbated during migraine, suggesting that repeated migraines may sensitize TP. This article investigates a nonclassical role of TP in migraineurs. Observed temporal lobe abnormalities may provide a basis for many of the perceptual changes in migraineurs and may serve as a potential interictal biomarker for drug efficacy.

Heart rate monitoring as a reliable tool for assessing energy expenditure in obese individuals.

Previous studies have suggested the use of the FlexHR method for predicting daily energy expenditure in various populations. We investigated the stability of the relation between oxygen consumption (VO2) and heart rate (HR) in obese subjects undergoing a fitness and weight reduction program. Eleven obese (BMI>30) healthy subjects (6 males, 5 females) were recruited from a Wellness program. Subjects performed a laboratory calibration procedure between HR and VO2 in resting and exercising conditions, before starting the Wellness program (Stage I) and after reducing 10% of their initial body weights (BW) within 6 months (Stage II). Mean BW, BMI and % body fat were reduced by 13.1±4.4 kg, 4.2±1.4 kg.m-2 and 6.8±4.1%, respectively, for all parameters (P<0.001). Mean peak VO2 increased from 31.3±7.1 at the beginning to 37.2±7.3 mL.kg-1.min-1 at the end of the intervention period (P<0.01). The mean flex HR point changed from 96±14 to 86±15 beats.min-1 (P<0.05). There were no significant individual differences in the HR-VO2 prediction equations derived from the laboratory calibrations in either stage. In conclusion, the relationship between HR and VO2 consumption remains stable during a time period of weight reduction. The use of the FlexHR method for predicting energy expenditure by heart rate monitoring is recommended for subjects undergoing a weight-reduction program. It should be taken in account, however, that an increase in aerobic capacity, in parallel to changes in body weight and composition, might cause a decrease in the flex point.

Sensitisation of spinal cord pain processing in medication overuse headache involves supraspinal pain control.

Medication overuse could interfere with the activity of critical brain regions involved in the supraspinal control of pain signals at the trigeminal and spinal level, leading to a sensitisation phenomenon responsible for chronic pain. We hypothesised that medication-overuse headache (MOH) patients might display abnormal processing of pain stimuli at the spinal level and defective functioning of the diffuse noxious inhibitory controls. We tested 31 MOH patients before (bWT) and after (aWT) standard inpatient withdrawal treatment, 28 episodic migraine (EM) patients and 23 healthy control subjects. We measured the threshold, the area and the temporal summation threshold (TST) of the nociceptive withdrawal reflex before, during and after activation of the diffuse noxious inhibitory controls by means of the cold pressor test. A significantly lower TST was found in both the MOH (bWT and aWT) and the EM patients compared with the controls, and in the MOH patients bWT compared with both the MOH patients aWT and the EM patients. In the MOH bWT patients the cold pressor test induced a TST increase significantly lower than that found in the MOH aWT, EM and control groups. Abnormal spinal cord pain processing and a decrease of the antinociceptive activity of the supraspinal structures in MOH patients can be hypothesised. These abnormalities could, in part, be related to the medication overuse, given that the withdrawal treatment was related to an improvement in the neurophysiological findings.

Hormonal response to Taekwondo fighting simulation in elite adolescent athletes.

Exercise training efficiency depends on the training load, as well as on the athlete's ability to tolerate it. The aim of the present study was to evaluate the effect of fighting simulation (3 fights, 6 min each, 30 min rest between fights) on anabolic (IGF-I, LH, FSH, estradiol, and testosterone) and catabolic hormones (cortisol) in elite, male (n = 10) and female (n = 10) adolescent (12-17 years) Taekwondo fighters. Blood samples were collected before the first and immediately after the third fight. The fighting simulation practice led to significant (p < 0.05) decreases in IGF-I (males -27.1 ± 25.6, females -22.4 ± 36.3 ng/ml), LH (males -0.7 ± 1.2, females -2.3 ± 3.3 U/L), and FSH (males -0.9 ± 0.5, females -1.5 ± 1.1 U/L), and to a significant increase (p < 0.05) in cortisol (males 141.9 ± 30.1, females 64.1 ± 30.6 mcg/dL) in both genders. Fighting simulation decreases in testosterone (males -1.9 ± 1.6, females -0.02 ± 0.06 ng/mL), and free androgen index (males -20.1 ± 21.5, females -0.3 ± 0.5) were significant (p < 0.05) only in male fighters. Exercise had no significant effect on estradiol, sex-hormone-binding globulins or thyroid function tests. Our data demonstrate that the physiologic and psychologic strain of a Taekwondo fighting simulation day led to a catabolic-type circulating hormonal response.

Biological and behavioral markers of pain following nerve injury in humans.

The evolution of peripheral and central changes following a peripheral nerve injury imply the onset of afferent signals that affect the brain. Changes to inflammatory processes may contribute to peripheral and central alterations such as altered psychological state and are not well characterized in humans. We focused on four elements that change peripheral and central nervous systems following ankle injury in 24 adolescent patients and 12 age-sex matched controls. Findings include (a) Changes in tibial, fibular, and sciatic nerve divisions consistent with neurodegeneration; (b) Changes within the primary motor and somatosensory areas as well as higher order brain regions implicated in pain processing; (c) Increased expression of fear of pain and pain reporting; and (d) Significant changes in cytokine profiles relating to neuroinflammatory signaling pathways. Findings address how changes resulting from peripheral nerve injury may develop into chronic neuropathic pain through changes in the peripheral and central nervous system.

Sensitization of central trigeminovascular neurons: blockade by intravenous naproxen infusion.

We have previously observed that migraine attacks impervious to triptan therapy were readily terminated by subsequent i.v. administration of the non-steroidal anti-inflammatory drug (NSAID) ketorolac. Since such attacks were associated with periorbital allodynia--a symptom of central sensitization--we examined whether infusion of the NSAID naproxen can block sensitization of central trigeminovascular neurons in the medullary dorsal horn, using in vivo single-unit recording in the rat. Topical exposure of the cerebral dura to inflammatory soup (IS) for 5 min resulted in a short-term burst of activity (<8 min) and a long-lasting (>120 min) neuronal hyper-responsiveness to stimulation of the dura and periorbital skin (group 1). Infusion of naproxen (1 mg/kg) 2 h after IS (group 1) brought all measures of neuronal responsiveness back to the baseline values recorded prior to IS, and depressed ongoing spontaneous activity well below baseline. When given preemptively 1 h before IS (group 2), naproxen blocked the short-term burst of activity and every long-term measure of neuronal hyper-responsiveness that was studied in the central neurons. The same preemptive treatment, however, failed to block IS-induced short-term bursts of activity in C-unit meningeal nociceptors (group 3). The results suggest that parenteral administration of naproxen, unlike triptan therapy, can exert direct inhibition over central trigeminovascular neurons in the dorsal horn. Though impractical as a routine migraine therapy, parenteral NSAID administration should be useful as a non-narcotic rescue therapy for migraine in the setting of the emergency department.

A 'complex' of brain metabolites distinguish altered chemistry in the cingulate cortex of episodic migraine patients.

Despite the prevalence of migraine, the pathophysiology of the disease remains unclear. Current understanding of migraine has alluded to the possibility of a hyperexcitable brain. The aim of the current study is to investigate human brain metabolite differences in the anterior cingulate cortex (ACC) during the interictal phase in migraine patients. We hypothesized that there may be differences in levels of excitatory neurotransmitters and/or their derivatives in the migraine cohort in support of the theory of hyperexcitability in migraine. 2D J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired on a 3 Tesla (3 T) MRI from a voxel placed over the ACC of 32 migraine patients (MP; 23 females, 9 males, age 33 ± 9.6 years) and 33 healthy controls (HC; 25 females, 8 males, age 32 ± 9.6 years). Amplitude correlation matrices were constructed for each subject to evaluate metabolite discriminability. ProFit-estimated metabolite peak areas were normalized to a water reference signal to assess subject differences. The initial analysis of variance (ANOVA) was performed to test for group differences for all metabolites/creatine (Cre) ratios between healthy controls and migraineurs but showed no statistically significant differences. In addition, we used a multivariate approach to distinguish migraineurs from healthy subjects based on the metabolite/Cre ratio. A quadratic discriminant analysis (QDA) model was used to identify 3 metabolite ratios sufficient to minimize minimum classification error (MCE). The 3 selected metabolite ratios were aspartate (Asp)/Cre, N-acetyl aspartate (NAA)/Cre, and glutamine (Gln)/Cre. These findings are in support of a 'complex' of metabolite alterations, which may underlie changes in neuronal chemistry in the migraine brain. Furthermore, the parallel changes in the three-metabolite 'complex' may confer more subtle but biological processes that are ongoing. The data also support the current theory that the migraine brain is hyperexcitable even in the interictal state.

Acute reversal of the enhanced insulin action in trained athletes. Association with insulin receptor changes.

We studied the effect of aerobic training and detraining on insulin-stimulated glucose disposal and on erythrocyte insulin receptor binding. Seven endurance-trained athletes were studied at 12 h, 60 h, and 7 days after cessation of training and compared with three untrained, age- and weight-matched controls. The metabolic clearance rate of glucose as measured by the euglycemic clamp technique was 15.6 +/- 1.8 ml/kg/min (mean +/- SEM) in the trained subjects 12 h after the last bout of exercise compared with 7.8 +/- 1.2 ml/kg/min in the untrained control group. When the trained subjects refrained from physical training, the metabolic clearance rate decreased to 10.1 +/- 1.0 ml/kg/min at 60 h and further to 8.5 +/- 0.5 ml/kg/min after 7 days of detraining. The percentage of specific insulin binding to young erythrocytes (density 1.089-1.092), isolated by density gradient centrifugation, decreased from 10.4 +/- 0.9 at 12 h after the last exercise to 8.1 +/- 0.7%/3 X 10(9) cells after 60 h of detraining (P less than 0.001). The decrease in insulin binding to erythrocytes was almost entirely accounted for by a decrease in the number of insulin receptors. We conclude that the increase in peripheral insulin action seen in trained athletes is rapidly reversed, possibly by a mechanism separate from other phenomena associated with chronic training. The parallel findings of decreased in vivo insulin action and decreased insulin binding in young erythrocytes suggest that modulation of in vivo insulin response by detraining may be at least partially mediated by changes in insulin receptor number.(ABSTRACT TRUNCATED AT 250 WORDS)

Immune changes in male homosexuals--predisposing factors for HIV seroconversion.

Israel is still a low incidence country for AIDS and thus the temporal relationships between various cofactors and HIV infection can be more easily determined. We have studied a cohort of 243 asymptomatic male homosexuals (MHS) during the last 4 years. At the beginning of the study, 40% had significant decreases in the peripheral blood lymphoid populations, signs for reactivation of CMV and EBV infections, and elevated serum levels of interferon. There was no difference in the prevalence of these immune derangements between seropositive and seronegative individuals. In the course of 4 years' follow-up, the prevalence of these immune derangements has remained the same though being significantly more severe in the HIV seropositive subjects. HIV seroconversion did not exceed 8% (about 2% annually) and was related to the immune impairments found when first seen at the beginning of the study. The results suggest that immune impairments are common among asymptomatic MHS, precede HIV infection, and probably contribute to the increased risk for AIDS among male homosexuals.

Stress-induced regulation of a human proenkephalin-beta-galactosidase fusion gene in the hypothalamus of transgenic mice.

Transgenic mice expressing an Escherichia coli beta-galactosidase reporter gene under the control of 3 kilobases of human proenkephalin gene 5'-flanking sequence and 1.2 kilobases of 3'-flanking sequence exhibited an anatomically correct pattern of basal and stress-regulated transgene expression within the hypothalamus. Acute osmotic stress and hypovolemia induced transgene expression in neurons within both the paraventricular and supraoptic nuclei. Chronic osmotic stress resulted in dramatic induction of transgene expression in both nuclei. These results demonstrate that the information required for correct hypothalamic expression and stress regulation of the proenkephalin gene is contained within our fusion construct.

Effects of sensitization of trigeminovascular neurons to triptan therapy during migraine.

Migraine is a neurological disorder which leads to recurring, unilateral, throbbing headache, associated with variable incidence of aura (i.e., visual, sensory and motor function disturbances), nausea and vomiting, photophobia and phonophobia, fatigue, and enhanced irritability. We have recently shown that migraine headache is also associated with high incidence of ipsilateral cutaneous allodynia, particularly in periorbital and temporal skin areas. Patients who experience cutaneous allodynia during migraine feel that their skin hurts in response to otherwise innocuous activities such as combing, shaving, taking a shower, or wearing glasses or earrings. Here, we present evidence to support the view that the development of throbbing in the initial phase of migraine is mediated by sensitization of peripheral trigeminovascular neurons that innervate the meninges, and that the development and maintenance of cutaneous allodynia later in the attack is propelled by sensitization of central trigeminovascular neurons which receive converging sensory input from the meninges as well as from the scalp and facial skin. We also present evidence that the development of cutaneous allodynia during migraine is detrimental to termination of acute migraine attacks using triptans (5HT1B/1D receptor agonist).

Age-related maximal heart rate: examination and refinement of prediction equations.

AIM: The aim of this study was to establish the maximal heart rate (HRmax)-age relation with minimal error rate. METHODS: The records of 28,137 participants (20,691 male and 7446 female, age range between 10 and 80 yrs) who performed a maximal stress test were used in this study. Linear regressions between HRmax and age were used for the entire sample, for the male and female samples, separately, and for each section of the gender-by-age category. The equations were then contrasted to a number of equations reported in the literature. The best fitted equations were then tested on a new sample of 2449 subjects (2091 males and 358 females) for validation purposes. RESULTS: Mean HRmax values were found to decrease at a faster rate in women than in men with age increase. The linear regression functions within each age category were found to be less reliable than the equations derived for the entire sample and for the female and male samples, respectively. The new and updated HRmax prediction equations are as follows: HRmax=208.609-0.716age and 209.273-0.804age for males and females, respectively, and 208.852-0.741age for the entire sample. Those equations along with the other four best equations for predicting HRmax were found to be correlated with the observed HRmax values (validation sample): 0.64 and 0.664 for males and females, respectively. CONCLUSION: Our equations were derived from a large data set and were found to be highly sensitive for both genders. Therefore, we propose that these new formulas, with their improved accuracy, be used in healthy active and clinical populations.

Retrograde labeling of neurons in the spinal cord that project directly to the amygdala or the orbital cortex in the rat.

The amygdala and orbital cortex are thought to play an important role in the regulation of autonomic functions, hormonal secretion, and behavioral expression in response to sensory stimulation. The responsiveness of neurons in these regions to stimulation of cutaneous and visceral organs indicates that sensory information reaches the amygdala and orbital cortex. In the past, a large number of studies have thoroughly documented multiple neural pathways by which sensory information can reach these regions via relay nuclei in the brainstem and diencephalon. Recent studies reported that the amygdala and orbital cortex also receive direct input from the spinal cord. The aim of this study was to determine the magnitude and the origin of these projections in the rat. Injections of the retrograde tracer Fluoro-Gold (FG), restricted to the amygdala, labeled several hundred neurons bilaterally (60% contralateral) throughout the length of the spinal cord. More than 60% of labeled neurons were found in the lateral reticulated area of the deep dorsal horn and the gray matter surrounding the central canal. Many neurons were also found in the lateral spinal nucleus. Labeled neurons were concentrated in upper lumbar and upper cervical segments. Injections of Fluoro-Gold that were centered in the orbital cortex labeled only a small number of neurons (73% contralateral) within the spinal cord. Most labeled neurons were found in the lateral reticulated area. Neurons located in the intermediate zone and the gray matter surrounding the central canal were found mainly in upper lumbar and upper cervical segments. These findings, together with the anterograde tracing observations, provide evidence for direct projections of spinal cord neurons to the amygdala and orbital cortex. Their laminar distribution in the spinal cord and the involvement of the amygdala and orbital cortex in limbic functions suggest that these pathways may play a role in neuronal circuits that enable somatosensory information, including pain, to affect autonomic, endocrine and behavioral functions.

Cells of origin of the trigeminohypothalamic tract in the rat.

Recent studies have demonstrated that a large number of spinal cord neurons convey somatosensory and visceral nociceptive information directly from cervical, lumbar, and sacral spinal cord segments to the hypothalamus. Because sensory information from head and orofacial structures is processed by all subnuclei of the trigeminal brainstem nuclear complex (TBNC) we hypothesized that all of them contain neurons that project directly to the hypothalamus. In the present study, we used the retrograde tracer Fluoro-Gold to examine this hypothesis. Fluoro-Gold injections that filled most of the hypothalamus on one side labeled approximately 1,000 neurons (best case = 1,048, mean = 718 +/- 240) bilaterally (70% contralateral) within all trigeminal subnuclei and C1-2. Of these neurons, 86% were distributed caudal to the obex (22% in C2, 22% in C1, 23% in subnucleus caudalis, and 18% in the transition zone between subnuclei caudalis and interpolaris), and 14% rostral to the obex (6% in subnucleus interpolaris, 4% in subnucleus oralis, and 4% in subnucleus principalis). Caudal to the obex, most labeled neurons were found in laminae I-II and V and the paratrigeminal nucleus, and fewer neurons in laminae III-IV and X. The distribution of retrogradely labeled neurons in TBNC gray matter areas that receive monosynaptic input from trigeminal primary afferent fibers innervating extracranial orofacial structures (such as the cornea, nose, tongue, teeth, lips, vibrissae, and skin) and intracranial structures (such as the meninges and cerebral blood vessels) suggests that sensory and nociceptive information originating in these tissues could be transferred to the hypothalamus directly by this pathway.

Distinct lateral and medial projections of the spinohypothalamic tract of the rat.

We recently described a direct nociceptive projection from the spinal cord to the hypothalamus in the rat. Several electrophysiological studies of this projection indicated that the axons of some spinohypothalamic tract neurons (SHT) reach the hypothalamus either by a lateral or by a medial route. The purpose of this study was to determine the origin of all SHT neurons that reach the hypothalamus through the lateral and the medial projections, and to investigate the possibility of ablating the SHT without damaging other important sensory and motor tracts by combining retrograde tracing techniques with axonal ablation. As compared with control cases, significant (P < .05) reductions in the number of labeled SHT neurons were encountered, 26% in the ipsilateral spinal cord following lesions of the medial projection, 67% in the contralateral spinal cord following lesions of the lateral projection, and 94% in both contra- and ipsilateral sides following lesions of both the medial and lateral projections. Bilateral lesions of the lateral projections had no effect on the distribution of labeled neurons in the spinal cord and dorsal column nuclei following injections of Fluoro-Gold (FG) into the thalamus, and a small unilateral lesion of the lateral projection reduced the ipsilateral labeling in the motor cortex following injections of FG into the pyramidal decussation. These findings suggest that most SHT neurons ascend through the contralateral lateral projection and that less than half continue in the medial projection to the ipsilateral side. They also suggest a site that can be lesioned without affecting other ascending sensory spinal pathways.

The cells of origin of the spinohypothalamic tract in cats.

Various cutaneous and visceral stimuli alter the discharge rates of neurons in the hypothalamus. Changes in the activity of hypothalamic neurons are thought to play important roles in eliciting neuroendocrine, autonomic, and affective responses to somatosensory and visceral stimuli. Information from peripheral structures has been considered generally to reach the hypothalamus via multisynaptic ascending pathways. Recently, a direct projection from the spinal cord to the hypothalamus was demonstrated in rats. The goal of this study was to determine whether a similar projection exists in cats. Either wheat germ agglutinin conjugated to horseradish peroxidase, a mixture of this tracer and the B subunit of cholera toxin conjugated to horseradish peroxidase, or fast blue was injected into the hypothalamus of cats. Injections were centered in the hypothalamus in seven cats and did not spread to the thalamus, zona incerta or midbrain. After these injections, retrogradely labeled neurons were observed bilaterally in each of the 17 spinal segments that were examined. A total of approximately 400-500 labeled neurons was observed in alternate sections through these segments in the most effective cases. Roughly 70% of the labeled neurons were located contralaterally. Labeled neurons were found predominantly in the deep dorsal horn, the intermediate zone/ventral horn and in the area surrounding the central canal. A few were also noted in the superficial dorsal horn. The first and second sacral segments contained the largest numbers of retrogradely labeled neurons in the spinal cord. The number of spinohypothalamic tract neurons observed in this study in cats was roughly an order of magnitude smaller than that previously reported for rats. This finding suggested either that the spinohypothalamic tract is relatively small in cats or that our tracing techniques did not label many spinohypothalamic tract neurons in cats. To test the sensitivity of one of our tracing techniques, control injections of wheat germ agglutinin conjugated to horseradish peroxidase that filled the ventrobasal thalamus were made in two cats. In both cases, thousands of spinal cord neurons were labeled. In summary, our results indicate that a spinohypothalamic tract exists in cats. However, our findings also suggest that the total number of spinohypothalamic tract neurons in cats may be an order of magnitude smaller than it is in rats.

Cells of origin of the spinohypothalamic tract in the rat.

We recently demonstrated that large numbers of neurons in the spinal cord of rats project directly to the hypothalamus. In the present study, we used the retrograde tracer Fluoro-Gold (FG) to examine this projection more completely. In the first series of studies, we attempted to label the entire population of spinal cord neurons that project to the hypothalamus. Injections that virtually filled the hypothalamus on one side without spreading into any other diencephalic area labeled a large number of neurons (estimated to be more than 9,000 in the case with the most neurons labeled) bilaterally at all levels of the spinal cord. Approximately 60% of the labeled neurons were contralateral to the injection. The greatest number of labeled neurons was found within the deep dorsal horn. Many were also found within the lateral spinal nucleus, the superficial dorsal horn, and the gray matter surrounding the central canal. A small number of labeled cells was located in the intermediate zone and ventral horn of the spinal gray matter. Labeled neurons were distributed bilaterally within the sacral parasympathetic nucleus and trigeminal nucleus caudalis. Injections of FG restricted to the medial hypothalamus labeled neurons within the spinal cord in a distribution similar to that produced by injections that filled the hypothalamus. However, fewer neurons were labeled in the spinal cord (estimated to be more than 6,200) and trigeminal nucleus caudalis. Injections of FG restricted to the lateral hypothalamus also labeled fewer neurons (approximately 3,300) than did injections that filled the hypothalamus. In these cases, also, the pattern of labeled neurons within the spinal cord was similar to that produced by injections within either medial or both medial and lateral hypothalamus. However, few neurons were labeled in the sacral parasympathetic nucleus following injections into the lateral hypothalamus. These findings show the distribution of a large number of spinal cord neurons that project directly to medial or lateral hypothalamic regions that are involved in autonomic, neuroendocrine, and emotional responses to somatosensory stimulation, including painful stimuli.

Evaluation of infants with bronchopulmonary dysplasia using cardiac catheterization.

Nine infants with bronchopulmonary dysplasia underwent cardiac catheterization to define thier circulatory status. In room air, the mean cardiac index was normal (3.4 liters/min/sq m), but pulmonary arterial pressure (39 mm Hg, mean) and pulmonary vascular resistance (8.6 Wood units . sq m) were elevated. Preejection period/right ventricular ejection time ratios determined echocardiographically correlated well with values obtained at catheterization, but did not correlate well with hemodynamic values. Administration of 40% and 88% oxygen caused variable responses in hemodynamic measurements. Studies of left ventricular function were normal in all patients. These findings raise questions about the long-term prognosis of infants with bronchopulmonary dysplasia.