Hypoxia In Rabbits Research Articles

Can R2 ' mapping evaluate hypoxia in renal ischemia reperfusion injury quantitatively? An experimental study.

To explore if R2 ' mapping can assess renal hypoxia in rabbits with ischemia reperfusion injury (IRI). Forty rabbits were randomly divided into 4 groups according to the clipping time: the sham group and 45 min, 60 min, and 75 min for the mild, moderate, and severe groups (with n = 10 each group), respectively. Intravenous furosemide (FU) was administered 24 h after IRI. All rabbits were performed 5 times (IRIpre , IRI24h , FU5min , FU12min , and FU24min ) with a 3.0 Tesla MR. The R2 ' values and the hypoxic scores were then recorded. The repeated measurement analysis of variance and Spearman correlation analysis was used for statistical analysis. Compared to the baseline, the medullary R2 ' values increased significantly 24 h after the IRI (baseline 19.31 ± 1.21 s-1 , mild group 20.05 ± 1.26 s-1 , moderate group 25.38 ± 1.38 s-1 , and severe group 25.79 ± 1.10 s-1 ; each P < .001). FU led to a significant decrease in the medullary R2 ' value (sham group 11.17 ± 4.33 s-1 , mild group 7.80 ± 0.74 s-1 , moderate group 3.92 ± 0.28 s-1 , and severe group 3.82 ± 0.23 s-1 ; each P < .05). Quantitative hypoxic scores revealed significant differences among the 4 groups in the outer medulla (P < .001 each). The medullary R2 ' differences (before and after intravenous FU) were significantly correlated with the hypoxic scores, respectively (P < .001). R2 ' mapping can evaluate the renal hypoxia in the procession of IRI in rabbits and might serve as a quantitative biomarker for IRI.

Prone Position Impairs Oxygen Supply-Demand Balance During Systemic Hypoxia in Rabbits

Ventilation in the prone position improves the prognosis of patients with severe acute respiratory distress syndrome (ARDS). Contraindications to ventilation in this position include unstable systemic circulation. Only a few reports exist on the effects of prone ventilation in respiratory failure on systemic circulation. This animal study compared systemic hemodynamic changes between supine and prone positions in anesthetized rabbits under acute systemic hypoxia (breathing 15% O2). Cardiac output and the systemic O2 extraction ratio increased under the hypoxia, but only in the supine group. Besides, the rate pressure product was higher in the prone group than in the supine group. This study showed that prone ventilation increases myocardial O2 consumption and suppresses compensatory mechanisms to maintain aerobic metabolism during systemic hypoxia. First of all, it will be necessary to examine the effect of prone ventilation on the O2 supply-demand balance in the ARDS model.

Differential responses of sympathetic premotor neurons in the RVLM on a defense response and hypoxia in rabbits

Differential responses of sympathetic premotor neurons in the RVLM on a defense response and hypoxia in rabbits

NO and CO have got to GO for enhanced chemoreceptor sympathoexcitation in heart failure

arterial chemoreceptors located in the carotid body are an important defense mechanism against systemic hypoxemia. Activation of arterial chemoreceptors increases alveolar ventilation and sympathetic outflow to most vascular beds. During acute exposures to hypoxia, the sympathoexcitatory responses

Rabbit Models of Contact Lens–Associated Corneal Hypoxia: A Review of the Literature

To provide a review of the literature on rabbit models of contact lens-associated corneal hypoxia. The literature was searched for articles describing corneal hypoxia in the rabbit coincident with contact lens wear. The articles were identified by key word searches for rabbit models, contact lens, hypoxia, and cornea. Designing a rabbit model of contact lens-associated corneal hypoxia requires identification of the key determinants of the physiologic response. The retention of soft contact lenses, particularly high-water content lenses, is problematic in the rabbit eye, in which blink frequency is on the order of minutes. An intact nictitating membrane may be beneficial in the hydration and, therefore, retention of soft contact lenses. Although tarsorrhaphy improves lens retention, lid closure also enhances the hypoxic response and may obscure the benefits of the greater oxygen transmissibility of soft contact lenses. The duration of lens wear in most reviewed studies was 24 hours or less, with only a few studies evaluating the hypoxic effect of lens wear of 1 week or more. Methods commonly used to characterize corneal hypoxia in rabbits include pachymetry, tear film lactate dehydrogenase measurements, clinical observations of limbal hyperemia, and more invasive methods of assessing cell proliferation and apoptosis. In summary, the ideal rabbit model of contact lens-associated corneal hypoxia depends on the question to be answered. This review tabulates the known studies, highlights key considerations in study design, and describes useful methods in characterization of the hypoxic response.

Respiratory Alterations Due to Chronic Long-Term Intermittent Hypobaric Hypoxia in Rabbits: Importance of Peripheral Chemoreceptors

None of the studies carried out so far investigated the effect of denervation of peripheral chemoreceptors on basal ventilation and respiratory responses to acute hypoxia in subjects exposed to chronic long-term intermittent hypobaric hypoxia (CLTIHH). We aimed to research (i) the effect of CLTIHH (430 mmHg, 5 h/day, 5 days/week, 5 weeks) on basal ventilation and respiratory responses to hypoxia and (ii) the effects of CLTIHH on central respiratory mechanisms after peripheral chemodenervation. Sixteen adult albino rabbits were divided into two groups: CLTIHH (n = 8) and control (n = 8). The tidal volume (V(T)) and respiratory frequency (f/min) were initially recorded in both groups and respiratory minute volume (V(E)) was calculated. PaO(2), PaCO(2), and pHa values were determined. The initial values of f/min and V(E) in CLTIHH group were significantly higher than that of control group. After exposure to hypoxic gas mixture (8% O(2)-92% N(2)), the elevations in f/min, V(T), and V(E) in CLTIHH group were significantly higher than those of control group. After denervation of peripheral chemoreceptors, the decrease in V(E) in CLTIHH group was found to be significantly less than that of control group. When the animals in control group were allowed to breathe hypoxic gas mixture, f/min, V(T,) and V(E) decreased significantly and hypoxic depression was obtained. In contrast, hypoxic depression did not occur in the CLTIHH group. Our results suggested that CLTIHH increases the basal ventilation and hypoxic respiratory responses and that enhanced ventilatory responses were due not only to the augmentation of peripheral chemoreceptor activity but also to the augmentation of central respiratory activity.

Animal Models of Acute Moderate Hypoxia Are Associated with a Down-Regulation of CYP1A1, 1A2, 2B4, 2C5, and 2C16 and Up-Regulation of CYP3A6 and P-glycoprotein in Liver

In humans, indirect evidence suggests that hypoxia reduces the rate of biotransformation of drugs cleared by cytochrome P450 (P450) subfamilies CYP1A, 2B, and 2C. The aim of this study was to assess whether acute moderate hypoxia modulates the expression of CYP2B4, 2C5, and 2C16 in vivo, and to determine whether the changes in hepatic P450 are conveyed by serum mediators. Moreover, because hypoxia increases the expression of P-glycoprotein in vitro, we examined whether in vivo acute moderate hypoxia modulates the expression of several membrane transporters in the liver. Rabbits and rats were exposed to a fractional concentration of oxygen of 8% for 48 h to generate a stable arterial partial pressure of O2 of 34 +/- 1 mm Hg. Compared with rabbits breathing room air, hypoxia in rabbits reduced the amount of CYP1A1, 1A2, 2B4, 2C5, and 2C16 proteins and increased the expression of CYP3A6. Sera of rabbits with hypoxia were fractionated by size exclusion chromatography, the fractions were tested for their ability to modify the expression of P450 isoforms, and serum mediators were identified through neutralization experiments. The serum mediators responsible for the down-regulation of P450 isoforms were interferon-gamma, interleukin-1beta (IL-1beta), and IL-2. In vivo, in rats, hypoxia increased the mRNA and protein expression of P-glycoprotein but did not affect the mRNA of breast cancer resistance protein and organic anion-transporting polypeptide 2. It is concluded that in vivo, hypoxia down-regulates rabbit hepatic CYP1A1, 1A2, 2B4, 2C5, and 2C16 and up-regulates CYP3A6. CYP3A11 and P-glycoprotein were up-regulated in the livers of hypoxic rats.

Differential responsiveness of RVLM sympathetic premotor neurons to hypoxia in rabbits

To determine whether differential sympathetic nerve responses to hypoxia are explained by opposing effects of hypoxia upon sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM), the cardiac sympathetic nerve and the renal sympathetic nerve were recorded in anesthetized and vagotomized rabbits. Renal sympathetic nerve was activated by the injection of sodium cyanide solution close to the bifurcation of the common carotid artery and/or by inhalation of hypoxic gas (3% oxygen-97% nitrogen). On the other hand, cardiac sympathetic nerve was inhibited by these stimuli. Barosensitive (inhibited by the stimulation of baroreceptor afferents) reticulospinal (antidromically activated by the stimulation of the spinal cord) neurons in the RVLM were divided into three groups according to their responses to hypoxic stimulation: neurons (Type I, n = 25), the activity of which was inhibited by the injection of sodium cyanide solution close to the bifurcation of the common carotid artery and/or by inhalation of hypoxic gas, neurons (Type II, n = 99), the activity of which was facilitated by the same stimulation, and neurons (Type III, n = 11), the activity of which was not changed. These data indicated that the differential responses of cardiac and renal sympathetic nerves might be due to opposing effects of hypoxia on individual RVLM neurons.

Simultaneous measurement of electrocochleography and cochlear blood flow during cochlear hypoxia in rabbits

In this study, a new monitoring system is developed to measure cochlear blood flow (CBF) and electrocochleography (ECochG) during transient ischemic episodes of the cochlea. A newly designed otic probe was used for the simultaneous recordings of laser-Doppler CBF and ECochG directly from the round window (RW). The probe enabled the recording of high amplitude compound action potentials (CAP) and cochlear microphonics (CM) with few averages. Experiments were conducted on rabbits to generate episodes of cochlear ischemia by using timed compressions of the internal auditory artery (IAA). The computer monitoring system extracted and measured CAP and CM components from ECochG in real-time. Results indicate that CM and CAP generally followed CBF during compressions and releases of IAA. Both CBF values and CAP amplitudes showed an overshoot following the reperfusion. CAP amplitude measures were found to be very sensitive to ischemia showing very rapid amplitude, latency and morphological changes. CM amplitude decreased more slowly than the CAP and CBF. Simultaneous recordings of CBF and ECochG using the otic probe provide a valuable neuromonitoring tool to investigate the dynamic behavior of the cochlea during ischemia.

Olprinone, a phosphodiesterase III inhibitor, reduces gut mucosal injury and portal endotoxin level during acute hypoxia in rabbits.

Preservation of gut integrity has become a therapeutic goal to obviate bacterial translocation in the critically ill. The authors examined whether olprinone, a phosphodiesterase III inhibitor, protected functional and structural integrity of gut mucosa against acute progressive hypoxia. Thirty-two animals were randomly allocated to a control group (n = 12), a low-dose group (0.2 microg x kg-1 x min-1 olprinone; n = 10), or a high-dose group (0.6 microg x kg-1 x min-1 olprinone; n = 10) after preparatory surgery. Ascending aortic and portal blood flow, intramural pH of the ileum, and portal endotoxin levels were measured at normoxia and through three stages of progressive hypoxia (fraction of inspired oxygen = 0.17, 0.13, and 0.10). At normoxia, ascending aortic flow in the high-dose group was approximately 20% higher than in the control and low-dose groups. During progressive hypoxia, both ascending aortic and portal flow in the control group were depressed, whereas olprinone infusion attenuated such alterations and redistributed blood to the splanchnic area in a dose-dependent manner. On the contrary, the reduction of intramural pH of the ileum and the elevation of portal endotoxin levels observed in the control group were significantly minimized in both the low- and high-dose groups to a similar extent during acute hypoxia. Histopathologic alterations of gut mucosa observed in the control group were minimized by olprinone infusion dose-independently, accompanied by reduction of mortality rate of the animals. Olprinone slows progression of intestinal mucosal acidosis and gut barrier dysfunction, concurrently with preservation of microscopic structures, through both flow-dependent and -independent mechanisms under acute hypoxia. Such properties of olprinone may serve to protect the host under insult.

Downregulation of hypoxic vasoconstriction by chronic hypoxia in rabbits: effects of nitric oxide.

Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion to ventilation for optimizing pulmonary gas exchange. Chronic alveolar hypoxia results in vascular remodeling and pulmonary hypertension. Previous studies have reported conflicting results of the effect of chronic alveolar hypoxia on pulmonary vasoreactivity and the contribution of nitric oxide (NO), which may be related to species and strain differences as well as to the duration of chronic hypoxia. Therefore, we investigated the impact of chronic hypoxia on HPV in rabbits, with a focus on lung NO synthesis. After exposure of the animals to normobaric hypoxia (10% O(2)) for 1 day to 10 wk, vascular reactivity was investigated in ex vivo perfused normoxic ventilated lungs. Chronic hypoxia induced right heart hypertrophy and increased normoxic vascular tone within weeks. The vasoconstrictor response to an acute hypoxic challenge was strongly downregulated within 5 days, whereas the vasoconstrictor response to the thromboxane mimetic U-46619 was maintained. The rapid downregulation of HPV was apparently not linked to changes in the lung vascular NO system, detectable in the exhaled gas and by pharmacological blockage of NO synthesis. Treatment of the animals with long-term inhaled NO reduced right heart hypertrophy and partially maintained the reactivity to acute hypoxia, without any impact on the endogenous NO system being noted. We conclude that chronic hypoxia causes rapid downregulation of acute HPV as a specific event, preceding the development of major pulmonary hypertension and being independent of the lung vascular NO system. Long-term NO inhalation partially maintains the strength of the hypoxic vasoconstrictor response.

Epidural anesthesia retards intestinal acidosis and reduces portal vein endotoxin concentrations during progressive hypoxia in rabbits.

Because it is postulated that gut is important via bacterial translocation in the development of the systemic inflammatory response and multiple organ dysfunction, the preservation of gut integrity is a therapeutic goal for physicians who care for critically ill patients. The aim of the current study was to evaluate whether epidural anesthesia prevented gut injury and subsequent translocation of endotoxin during acute progressive hypoxia in rabbits. After the placement of an epidural catheter, 18 male rabbits, anesthetized with buprenorphine-midazolam, were allocated randomly to two groups: 0.5% lidocaine (group E) and saline (group C) groups. The solutions (0.4 ml/kg) were injected epidurally, followed by continuous infusion (0.1 ml x kg(-1) x h(-1)) during the study period. Portal blood flow, portal endotoxin concentrations, and intramucosal pH (pHi) of the ileum were measured at baseline and during two stages of progressive hypoxia (fraction of inspired oxygen [Fio2] = 0.15 and 0.10). In both study groups, the portal blood flow was preserved to a similar extent during acute hypoxia. However, pHi was reduced to a lesser extent in group E (7.33 +/- 0.12 versus 7.22 +/- 0.12 at an Fio2 of 0.15 and 7.13 +/- 0.15 versus 7.03 +/- 0.12 at an Fio2 of 0.10; mean +/- SD, P < 0.01), concurrently with lower portal endotoxin concentrations (P < 0.05) compared with group C. The current study showed that epidural anesthesia slowed the progression of intestinal ischemia during acute hypoxia, subsequently preventing translocation of endotoxin through the gut mucosa.

The earliest histopathological response to hypobaric hypoxia in rabbits in the rifugio torino (3370 M) on Monte Bianco

Twelve Dutch rabbits were kept on Monte Bianco at an altitude of 3370 m. Half of the animals were killed after 3 months, the remainder after 6 months, and a further six animals maintained at sea-level acted as controls. The carotid bodies of all the rabbits were processed for light and electron microscopy and examined qualitatively and quantitatively. The lungs were processed for light microscopical assessment of small pulmonary arterial vessels; the thickness of the pulmonary trunks and aortas were measured; and the hearts were dissected to obtain ratios of the ventricular weight. There was a slight increase in the right ventricular weight in the hypoxic rabbits but no change in the thickness of the pulmonary trunk compared with that of the aorta. In particular, there was no hypoxic remodelling of the pulmonary vasculature such as muscularization of pulmonary arterioles or intimal longitudinal muscle in pulmonary arteries. The earliest histopathological response to hypoxia occurred in the carotid bodies in the form of an increase in the count of the dark variant of chief cell after 3 months which returned to normal after 6 months. It is concluded that the carotid body of the rabbit responds with a change in its population of dark chief cells to a level of hypoxia which is insufficient to affect the pulmonary arterioles. Changes in the cardiopulmonary system can no longer be considered to be the earliest histopathological response to hypobaric hypoxia.

The inhibitory effect of halothane on mesenteric venoconstriction and related reflex responses during acute graded hypoxia in rabbits.

Systemic hypoxia is a common abnormality encountered frequently in the clinical setting that produces compensatory cardiopulmonary changes affecting heart rate, blood pressure, peripheral vascular resistance, and respiratory drive. These changes are known to be inhibited or reversed by inhaled anesthetics. More recently, chemoreflex-mediated constriction of capacitance veins has been identified as a mechanism that contributes significantly to the hemodynamic adjustments during hypoxia. However, the effects of anesthetics on this response have not been clarified. The current study was designed to quantify sympathetically mediated mesenteric venoconstriction as well as heart rate and blood pressure responses to acute graded hypoxia; to identify the inhibitory effects of inhaled halothane on these responses; and to estimate the contribution of the peripheral chemoreceptors in mediating these changes. Changes in mesenteric vein diameter were measured in alpha-chloralose anesthetized rabbits in situ with simultaneous changes in heart rate and blood pressure during 40-s periods of 10%, 5%, 2.5%, and 0% inspired O2 administered sequentially before, during, and after 1% or 1.25% inhaled halothane. Sympathetic efferent nerve activity also was measured, and, in a separate group of animals, measurements were preceded by carotid chemoreceptor denervation. Hypoxia-mediated venoconstriction, bradycardia, and hypertension were attenuated almost equally by both 1% and 1.25% inhaled halothane (the higher dose produced only slightly greater inhibition). These responses were inhibited significantly in chemoreceptor-denervated animals, and the subsequent 1% inhaled halothane added only minimal additional attenuation. Increases in chemoreflex-mediated sympathetic efferent nerve activity also were reduced significantly by (1.25%) inhaled halothane. These results indicate that halothane impairs capacitance vein responses and other hemodynamic adjustments during hypoxia. Inhibition of these compensatory changes appears to be mediated, at least in part, via attenuation of peripheral chemoreflex responses and suppression of the resultant reflex increases in sympathetic efferent nerve activity.

Maturation of Respiratory Responses to Graded Hypoxia in Rabbits

The respiratory effects of graded hypoxia were determined in 8 rabbits on postnatal days 1, 6 and 21. Ventilation was measured in the unanesthetized state by plethysmography. Graded hypoxia was produced by reducing the fraction of inspired O2 to 0.15 (mild hypoxia) for 15 min and then lowering it further to 0.10 (moderate hypoxia) for another 15 min. Mild hypoxia initially stimulated breathing to the same extent in all 3 groups; however, with moderate hypoxia, the percent increase in ventilation was greater for older rabbits. The rise in ventilation was due to an increase in tidal volume and frequency in 1- and 21-day-old rabbits, and it was almost entirely the result of changes in frequency in 6-day-old rabbits. After 2-3 min of hypoxia (mild or moderate), a decline in ventilation was observed in all 3 groups. This reduction of respiration was greater in younger animals and with moderate hypoxia. Decreases in frequency and tidal volume contributed significantly to this fall in ventilation for 1- and 2-day-old rabbits. However, the fall in ventilation for 6-day-old pups occurred almost entirely by changes in tidal volume. It is concluded that the magnitude of phase 1 (increased ventilation) and phase 2 (decreased ventilation) responses to hypoxia depend upon the level of hypoxia and the age of the rabbit.

Effect of urea-hydrogen peroxide on hypoxia in rabbits.

PaO2 in hypoxemic rabbits was raised 30 min after intravenous administration of urea-hydrogen peroxide (U-H2O2). Peak levels appeared 2 h after administration of the drug and the effect continued up to 4 h. The treatment was effective and no side effects in the rabbits were observed. A new technique is described to produce hypoxemia in rabbits using a special mask. In contrast to previously described techniques the rabbits in this study could be kept alive with a stable hypoxemia for at least 4-5 h. This model may be useful for future studies requiring similar hypoxemic conditions in experimental animals.

Ventilatory acclimatization to hypoxia in rabbits after denervation of peripheral chemoreceptors.

Ventilatory acclimatization to hypoxia in rabbits after denervation of peripheral chemoreceptors.

Bulbar and suprabulbar control of the cardiovascular autonomic effects during arterial hypoxia in the rabbit.

The autonomic effects on heart rate, portal, renal, cutaneous and muscle blood flows were studied during approximately constant severe arterial hypoxia in unanesthetized sham-operated, thalamic and pontine rabbits, 3 hours after operations conducted under halothane anesthesia. Neural and adrenal effects were estimated by comparing the responses of different groups of animals: (a) with all neural effectors intact, (b) after adrenalectomy, (c) after selective and (d) after complete pharmacological block of neural effector mechanisms. In pontine animals hypoxia greatly increased cardiac sympathetic activity and seemed to evoke a greater release of adrenal catecholamine (epinephrine) than in other preparations, but caused significant neural peripheral sympathetic constrictor effects in only the portal bed. In thalamic animals, hypoxia caused reflex bradycardia, striking neural constrictor effects in the portal, renal and muscle beds, and cutaneous dilatation. There was little evidence of an increase in epinephrine secretion. It is suggested that there is an inhibitory pathway between diencephalon and bulb that limits the release of epinephrine. Sham-operated animals exposed to hypoxia secreted epinephrine which played an important role in the total reflex response; this group had similar cardioinhibitory and cutaneous effects to thalamic animals, but a more rapid onset of portal and renal constriction and a marked increase in muscle blood flow. The sympathetic responses of the different preparations resulted in different rates of metabolic H + ion production.

EFFECTS OF HYPOTHALAMIC LESIONS ON THE ERYTHROPOIETIC RESPONSE TO HYPOXIA IN RABBITS.

AbstractPrevious studies have indicated that electrical stimulation of the hypothalamus increases erythropoiesis (Seip et al. 1961) and erythropoietin production (Halvorsen 1961). The effects of hypothalamic lesions on the erythropoietic response to hypoxia have been investigated in the present study. The lesioned rabbits were exposed to low oxygen and the erythropoietic response evaluated by means of reticulocyte counts. Eleven out of 26 rabbits showed a normal response to hypoxia while 15 showed a reduced response. Of these 15 rabbits, 6 showed a normal response when ACTH was given prior to the hypoxic test indicating that the reduced response to hypoxia in these rabbits was due to ACTH deficiency following the hypothalamic lesion. The lesions in these 6 rabbits were in the ventral and median part of hypothalamus. Seven out of the 15 rabbits neither responded normally to hypoxia alone nor to hypoxia following ACTH injections. The lesions in these 7 rabbits were in the posterior part of the hypothalamus. It is concluded that an extra‐pituitary influence on erythropoiesis may be exerted from this region.

Transaminase activity after experimental hypoxia in rabbits.

Transaminase activity after experimental hypoxia in rabbits.