Severe Arterial Hypoxia Research Articles

Dexmedetomidine Modification of the Chemoreflex Response to Severe Arterial Hypoxia in the Rabbit

The carotid body contains alpha‐2 adrenoceptors but selective agonists given during hypoxia have shown inhibition or enhancement of carotid sinus nerve activity in vivo (1), and in vitro (2). Dexmedetomidine (DM) is a highly‐selective alpha‐2 adrenergic agonist currently used for clinical sedation and analgesia (3,4) but its effects on integrated chemoreflex control during hypoxia are unknown. We examined the hypothesis that DM would selectively alter components of the cardiorespiratory responses to severe arterial hypoxia (PaO2 <35 mm Hg). An ear artery and vein of 6 New Zealand White female rabbits were cannulated (lidocaine 2%). Mean arterial pressure (AP), arterial blood gases, heart rate (HR), minute ventilation (VE), tidal volume (VT), respiratory frequency (f) and oxygen saturation (ear SpO2) were measured breathing room air, followed by 5 minutes of hypoxia (FiO2 7–8%). After a one‐hour recovery period, the measurements were repeated during intravenous DM infusions (4 or 40 mcg/kg/hr), breathing room air followed by exposure to a matched hypoxic stimulus. One dose of DM was studied on each of two experimental days, one week apart. Behavioural responses were recorded before and during DM infusions. Data were analysed using two‐way repeated measures ANOVA. Significant differences were accepted at the p<0.05 level. In the absence of DM, hypoxia alone evoked a reflex fall in HR and f, with increases in VT, VE and AP. In rabbits breathing room air, DM alone caused dose‐dependent falls in f, VE, HR and AP, while VT was unchanged. With DM plus hypoxia, the reflex bradycardia was absent at the higher dose. The increase in VT remained intact during both doses, while the rise in VE was attenuated due to an unchanged f. The AP increased from a lowered baseline. DM produced dose‐dependent sedation. We conclude reflex vagal control of heart rate during severe hypoxia is modified by DM. There are dose‐dependent effects on AP and components of ventilation. The increase in VT in response to hypoxia during DM infusion indicates that chemotransduction at the carotid body is intact. The data suggest the main sites of action of dexmedetomidine on cardiorespiratory control during hypoxia are within the CNS and not at the carotid body.Support or Funding InformationJohn Hunter Hospital Charitable Trust and Hunter Medical Research InstituteThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Effects of Remifentanil on the Cardiorespiratory Responses to Severe Arterial Hypoxia in the Rabbit

We have previously shown that the central vagus is sensitive to several modern anesthetics (Quail et al 2013, 2015). Remifentanil is an ultra‐short acting synthetic opiate widely used in anesthesia, sedation, obstetrics and analgesia. Opiates can act at the carotid body (McQueen and Ribeiro 1980; Mayer, et al., 1989) and at the commissural nucleus of the solitary tract in the CNS (Zhang et al. 2011), but effects on the integrated components of chemoreflex control are unknown. We examined the hypothesis that components of the cardiorespiratory responses evoked by severe arterial hypoxia (PaO2 < 35 mm Hg) are selectively altered by remifentanil. Six female NZ White rabbits were cannulated via an ear artery and vein (lidocaine 1%). Minute ventilation (VE), tidal volume (VT), respiratory frequency (f), heart rate (HR), mean arterial pressure (MAP) and oxygen saturation (ear SpO2) were measured in conscious rabbits breathing room air, followed by 5 minutes of hypoxia (FiO2 7–8%). After one hour recovery, rabbits breathed room air during i.v. remifentanil (0.1, 0.2, 0.3, or 0.4 mcg/kg/min), followed by matched hypoxia, then recovery breathing room air. Two doses of remifentanil were studied on each of two days, one week apart. Arterial blood samples were taken for blood gas analysis. Data were analysed using repeated measures ANOVA. In rabbits breathing room air remifentanil caused a dose‐related fall in f, VE and HR (P<0.01), while VT and MAP were unchanged. During remifentanil and hypoxia, the reflex bradycardia evoked in conscious rabbits was largely preserved (P<0.05) in a dose‐related manner. The increase in VT remained intact, however the increase in VE was attenuated, with f increasing from a lowered baseline. Remifentanil produced dose‐dependent sedation. We conclude that vagal control of heart rate with remifentanil during severe hypoxia is maintained, while the effects on VE, VT and f appear selective. The data suggest the actions of remifentanil on cardiorespiratory control during hypoxia are mainly central, rather than at the carotid body.Support or Funding InformationJohn Hunter Charitable Research Trust and Hunter Medical Research Institute

Central Modulation of Arterial Chemoreceptor Control by Midazolam during Severe Arterial Hypoxia in the Rabbit

The ventilatory response to arterial hypoxia and carotid body chemoreceptor activity are depressed by midazolam but the effects on the integrated chemoreflex arc are unknown. This study tested the postulate that midazolam selectively modifies components of intense autonomic activity evoked by the arterial chemoreflex during severe arterial hypoxia (PaO2 < 35 mm Hg). Female NZ White rabbits (n=10) were cannulated via an ear artery and vein (lidocaine 1%). Minute ventilation (VE), tidal volume (VT), respiratory frequency (f), heart rate (HR), mean arterial pressure (MAP) and SpO2 were measured breathing room air, followed by 5 minutes of hypoxia (FiO2 7-8%). After recovery, rabbits breathed room air during i.v. midazolam, followed by matched hypoxia. Two doses of midazolam (0.78 mg/kg bolus + 0.66 mg/kg/h or 1.56 mg/kg bolus + 1.32 mg/kg/h) were studied, each on separate days. Arterial blood samples were taken for blood gas analysis and drug assay. Data were analysed using repeated measures ANOVA. Midazolam caused a fall in f, VE and MAP while VT and HR increased (P<0.01). During midazolam infusion the hypoxia induced reflex bradycardia observed in conscious rabbits was reversed (P<0.001), whereas MAP, VE and VT responses were maintained. Midazolam produced sedation but rabbits remained responsive. Midazolam is therefore selectively inhibitory on vagal control of heart rate during the response to severe hypoxia, while other reflex components appear functionally intact. We have shown previously the central vagus is sensitive to some anesthetics, suggesting midazolam action is also central, rather than at the carotid body. Funding: ANZCA and HMRI

Effects of sub‐anesthetic sevoflurane on cardiorespiratory responses to severe arterial hypoxia in the rabbit (709.4)

Volatile anesthetics may alter reflexes to hypoxia through actions at the carotid body chemoreceptors. The effects of sevoflurane (Sev) in sub‐anesthetic concentrations on integrated chemoreflex control during hypoxia are unknown. The cardiorespiratory responses to end‐tidal Sev (0.18%, 0.37% or 1.86%) were studied in 7 rabbits. Ventilation (VE), tidal volume (VT), respiratory rate (f), heart rate (HR) and arterial pressure (AP) were measured in awake rabbits breathing room air, then 5 minutes of hypoxia (PaO2 &lt; 35 mm Hg), during Sev alone, and Sev plus hypoxia. In awake rabbits hypoxia produced an increase in VE and VT (p&lt;0.05) while f was unchanged. HR fell and AP rose (p&lt;0.05). During normoxia, VT increased and f decreased with all concentrations of Sev, while VE only fell at 0.37% and 1.86% (p&lt;0.05). HR increased with at all concentrations while AP decreased at 0.37% and 1.86% (p&lt;0.05). With hypoxia and Sev, the increase in VT was the same as awake levels at all concentrations associated with a small rise in f (p&lt;0.05). VE increased to levels seen in the awake state at lower concentrations of Sev but was attenuated at 1.86% (p&lt;0.05). The hypoxia induced bradycardia and rise in AP were attenuated by increasing doses of Sev and abolished at 1.86% (p&lt;0.05). Sub‐anesthetic depressant effects of Sev on the cardiorespiratory responses to hypoxia are selective and therefore unlikely to be the result of carotid body inhibition.Grant Funding Source: Supported by John Hunter Hospital Charitable Trust

Central modulation of arterial chemo‐baroreflex control by propofol during severe arterial hypoxia in the rabbit

During hypoxia specific deficits in neural control caused by propofol (2,6‐diisopropylphenol) anesthesia (Prop) are unknown. Dose‐related effects were analysed in rabbits with and without carotid body denervation (CBD) to partition arterial chemo‐baroreflex control. Minute ventilation (VE), tidal volume (VT), respiratory frequency (f), heart rate (HR), mean arterial pressure (MAP) were measured in 12 awake rabbits mask‐breathing room air, then 15 minutes of low oxygen air (PaO2 &lt; 35 mm Hg), during Prop alone (0.2 and 0.5 mg kg−1min−1i.v.), and during matched Prop plus hypoxia. Prop alone caused dose‐related depression in f and rise in HR. Prop plus hypoxia abolished bradycardia, while MAP, VE and VT effects remained intact. CBD eliminated all chemoreflex responses to hypoxia and MAP fell while HR rose, effects enhanced by Prop in a dose‐related way. It is concluded that during Prop, carotid body function for respiratory and MAP defense is functionally intact. Central activation of the vagus is inhibited selectively, because electrical stimulation of peripheral vagus during Prop evokes normal bradycardia blocked by atropine. By contrast, Prop inhibits arterial baroreflex‐vagosympathetic defense against widespread hypoxic vasodilatation. We speculate that the data reflect dominant central GABAA receptor agonist effects on the arterial chemo‐baroreflex arc. Funding: ANZCA and HMRI.

Hemodynamic, respiratory, and perfusion parameters during asphyxia, resuscitation, and post-resuscitation in a pediatric model of cardiac arrest

To analyze the evolution of hemodynamic, respiratory, and tissue perfusion parameters in an infant animal model of asphyxial cardiac arrest (CA). This was a secondary analysis of a prospective observational study conducted at a laboratory research department of a university hospital. Seventy-one, 2-month-old piglets were studied. CA was induced by removal of mechanical ventilation. Cardiopulmonary resuscitation (CPR) was performed by means of manual external chest compressions, mechanical ventilation, epinephrine and/or terlipressin intravenous administration. The evolution of hemodynamic (heart rate, blood pressure, cardiac index), respiratory (end-tidal CO(2), blood gas analysis), and tissue perfusion (intramucosal gastric pH, central, cerebral, and renal hemoglobin saturation) parameters was analyzed during three periods: asphyxia, CPR, and after return of spontaneous circulation (ROSC). During asphyxia, a severe arterial and tissue hypoxia with hypercapnia and lactic acidosis quickly developed. Bradycardia, hypotension, and increasing of systemic vascular resistances and pulmonary arterial pressure were also observed. During CPR, arterial, cerebral, and tissue oxygenation were low in spite of ventilation with oxygen 100%. After ROSC a rapid restoration of hemodynamic and respiratory parameters was observed. However, 30min after ROSC, lactic acidosis and low intramucosal gastric pH persisted. Asphyxia leads to sudden hypoxia and hypercapnia with tissue hypoxia and progressive bradycardia. Standard CPR is not able to maintain an adequate tissue oxygenation during CPR in this animal model. When ROSC is achieved, a rapid restoration of the normal values of general hemodynamic and respiratory parameters is observed, although lactic acidosis and splanchnic hypoperfusion persist in time.

Cerebral blood flow, cerebrovascular resistance and cerebral metabolic rate of oxygen in severe arterial hypoxia in dogs.

Cerebral blood flow and cerebral oxygen uptake were studied during severe arterial hypoxia in anesthetized dogs. It was shown that the hypoxic vasodilatation in the brain reaches a limit at an arterial oxygen saturation at about 25% and that this vasodilatation is less than that which may be induced by hypercapnia. A further deepening of the arterial hypoxia at a maintained cerebral perfusion pressure is combined with a continuous decrease in cerebral venous oxygen tension and a reduced oxygen uptake.

Cerebral blood flow, cerebrovascular resistance, cerebral metabolic rate of oxygen and intracranial pressure during and after severe prolonged arterial hypoxia in dogs. The role of dopamine in the deep hypoxic state.

The effect of extreme, prolonged arterial hypoxia on cerebral blood flow, oxygen uptake and intracranial pressure was studied in anesthetized dogs. The experiments were performed along two lines. Both started with a period of hypoxia of about 40 minutes to 2 hours. Thereafter normoxia was restituted in one group and the animals were studied for another 1-2 hours. In the other group with continued hypoxia dopamine was administered. During the hypoxic period the cerebral blood flow decreased mainly as a result of vasoconstriction after an initial marked flow increase. Cerebral oxygen uptake was reduced. Intracranial pressure increased, largely in proportion to blood flow changes, and no indication of important brain edema appeared. In the "recovery" period at normoxia the cerebral oxygen uptake showed an increase during the observation time. The blood flow, initially high, returned to the control level within the observation period. Dopamine infusion during continued hypoxia induced a vasodilatation, with reduction of vascular resistance to the values found at the induction of hypoxia, and with an increase of the cerebral oxygen uptake. An important role of endogenous dopamine in the hypoxic vasodilatation is suggested.

Reducing Barriers for Implementation of Immediate CPR with Chest Compressions Alone

It is well known that out-of-hospital sudden cardiac death is a leading public health problem. In the absence of early defibrillation, survival rates of patients with outof-hospital cardiac arrest are dismal and have remained essentially unchanged. The guidelines advocate the same approach for 2 entirely different pathophysiological conditions: respiratory arrest in which severe arterial hypoxia and hypotension eventually lead to secondary cardiac arrest, and primary cardiac arrest in which the arterial blood is fully saturated with oxygen at the time of the arrest. Cardiopulmonary resuscitation (CPR) is traditionally defined as chest compressions plus ventilations. The need for chest compressions is unquestionable, but the need for mouth-to-mouth ventilations for cardiac arrest has been questioned. Recent observational studies underline the paramount role of chest compressions in an alternative way of CPR, compression only CPR. Public education and training in compression only CPR is much simpler. Compression only CPR may significantly increase bystander-initiated resuscitation efforts and thereby give patients a better chance of survival, given the reluctance of lay people to provide mouth to mouth rescue breaths. In view of the above, the principal question is, what barriers are delaying the guidelines from recommending compression only CPR? Perhaps the major problem is the difficulty to change the paradigm. For decades, the “ABCs” (airway, breathing, and circulation) have been advocated for bystander basic life support, making it extremely difficult to transform the so ingrained in the popular understanding “ABC” to “AC” The most important cause of death in the adult population of the industrialized world is sudden cardiac arrest due to coronary disease. The first recorded rhythm in patients presenting with a sudden cardiovascular collapse is ventricular fibrillation (VF) even if its percentage is declining according to recent studies, whereas bradyarrhythmias are thought to be responsible for a minority of sudden cardiac arrests. The actions linking the victim of sudden cardiac arrest with survival are called the Chain of Survival. These actions include four separate steps, early recognition of the emergency and activation of the emergency medical services (EMS), early cardiopulmonary resuscitation (CPR), early defibrillation and early advanced life support. CPR plays a fundamental role in the chain of survival acting as a link between the recognition of cardiac arrest and defibrillation that in fact restores life. In a way CPR buys time while waiting for the defibrillator to arrive. As there is no delay in the AtHENs cArDIOLOGY UPDAtE 2008 First Department of Cardiology Evangelismos General Hospital of Athens HOSPITAL CHRONICLES 2008, SUPPLEMENT: –12 Address for correspondence: Dimosthenis Avramidis, MD First Department of Cardiology Evangelismos General Hospital of Athens Ypsilantou 45-47 Athens 106 76, Greece Phone: +30-210-72

Continuous-Chest-Compression Cardiopulmonary Resuscitation for Cardiac Arrest

It is well known that out-of-hospital sudden cardiac death is a leading public health problem in the industrialized world. In the absence of early defibrillation, survival rates of patients with out-of-hospital cardiac arrest (OHCA) in most areas of the world are dismal and, except for a recent report of an improved rate of survival when their paramedic protocol was changed, have remained essentially unchanged.1,2 Articles p 2900 and 2908 Why have survival rates not improved? One possibility is that the guidelines are not optimal. The guidelines advocate the same approach for 2 entirely different pathophysiological conditions: respiratory arrest in which severe arterial hypoxia and hypotension eventually lead to secondary cardiac arrest, and primary cardiac arrest in which the arterial blood is fully saturated with oxygen at the time of the arrest.1 Mouth-to-mouth ventilations, although appropriate for respiratory arrest, are not, as will be reviewed, essential for survival in the vast majority of patients with OHCA. The recommendation for so-called rescue breathing is a major impediment to performing the crucial first link in the chain of survival.3 Only about a quarter of individuals with OHCA receive bystander resuscitation efforts before the arrival of emergency medical services personnel.4 Cardiopulmonary resuscitation (CPR) is traditionally defined as chest compressions plus ventilations. The need for chest compressions is unquestionable, but the need for or advisability of mouth-to-mouth ventilations for cardiac arrest has been questioned. Two articles in this issue of Circulation , one by Iwami and associates5 from Osaka, Japan, and the other by Bohm and colleagues6 from Sweden, report that the survival rates of patients with OHCA were similar in those who received bystander chest compressions alone and those who received traditional CPR. Although important, these findings are not new. They do, however, add to the previous reports …

Anaphylactic bronchoconstriction in immunized guinea pigs provoked by inhalation and intravenous administration of hexahydrophthalic anhydride and methyltetrahydrophthalic anhydride.

We established a guinea-pig model of anaphylactic bronchoconstriction provoked in immunized animals by inhalation and intravenous administration of 4,4-methyltetrahydrophthalic anhydride (MTHPA) and hexahydrophthalic anhydride (HHPA). Guinea pigs were immunized intradermally with either MTHPA (n = 8) or HHPA (n = 8) suspended in olive oil. Control animals (n = 8) were injected with olive oil alone. After 4 weeks, the animals were challenged during mechanical ventilation by inhalation or intravenous administration of MTHPA or HHPA conjugated with guinea-pig serum albumin (GPSA). Airway flow, and airway and esophageal pressures were measured. Resistance (R) and static compliance (Cst) of the respiratory system (rs), lung (1), and chest wall were studied with the flow-interruption technique. After challenge with MTHPA-GPSA or HHPA-GPSA, R,rs and R,1 increased dramatically while Cst,rs and Cst,1 decreased, and severe arterial hypoxia developed. The reaction occurred at a well-defined dose of anhydride and lasted about 30 min. When the same dose was repeated after 30 min, the response was much attenuated. MTHPA and HHPA can induce asthma in guinea pigs. The dose-response curve at antigen challenge is steep. Once a threshold dose is reached, a severe reaction occurs. The reactivity is then exhausted. This model may be suitable for assessing occupational asthma caused by acid anhydrides and possibly by other low-molecular-weight chemicals.

Short note: The potential of umbilical cord blood to increase tissue oxygenation in adult respiratory distress syndrome

Umbilical blood, consisting mainly of fetal haemoglobin, has an increased oxygen affinity. Adult respiratory distress syndrome may be caused by any acute, diffuse, infiltrative lung lesion of diverse aetiologies and is characterized by severe arterial hypoxia. Mechanical ventilation with high Foe and elevated pressures is used to improve tissue oxygenation in these patients. Nevertheless, adult respiratory distress syndrome may be fatal. Our hypothesis suggests that transfusion of umbilical cord blood to adult respiratory distress syndrome patients may facilitate oxygen transport by increasing oxygen binding in the erythrocytes passing through the damaged lungs. The local hypoxia and the accompanied acidosis in the periphery may accelerate the oxygen unload to the tissues, thus augmenting overall oxygen delivery. Studies with animals and humans show that left-shifted oxyhaemoglobin dissociated curve confers a degree of adaptation to low-oxygen tension ambient. Umbilical cord blood is available in every hospital, and there are no contraindications to its use.

Effects of histamine H1-receptor blockade on respiratory and cardiac manifestation of systemic anaphylaxis

In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to further characterize respiratory and cardiac anaphylactic events. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin together with Freund's adjuvant. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced an initial increase of left ventricular pressure which was followed by a rapid decrease 5 min after antigenic challenge. Enddiastolic left ventricular pressure increased within 3 min, thus indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, heart rate steadily decreased. All animals died within 15 min. Simultaneously with cardiac anaphylactic malfunction, severe arterial hypoxia and carbon dioxide retention occurred, revealing respiratory distress. Histamine is known as a potent bronchoconstrictor via histamine H1-receptor stimulation. Administration of H1-receptor antagonists to improve respiration may therefore provide further information on the contribution of pulmonary malfunction to anaphylactic cardiovascular shock. Therefore, additional experiments were performed with sensitized guinea pigs pretreated with the histamine H1-receptor blocker mepyramine. In these experiments the antigenic challenge induced a dissociation of cardiac and respiratory manifestation of anaphylaxis. Despite inhibition of hypoxia and carbon dioxide retention, left ventricular pump failure and occurrence of myocardial ischemia were delayed but not suppressed. It is concluded that histamine is an important mediator of anaphylactic respiratory distress. However, vasoactive anaphylactic mediators other than histamine are primarily involved in anaphylactic cardiac malfunction occurring during the later phase of systemic anaphylaxis.

Effect of intestinal denervation on intestinal vascular response to severe arterial hypoxia in newborn swine.

We examined the effects of alpha-adrenergic blockade (phentolamine) and intestinal denervation on the circulatory response of the newborn swine intestine to severe arterial hypoxia. Intestinal vascular resistance significantly increased during severe arterial hypoxia in the control group, whereas no change in intestinal vascular resistance was observed in the phentolamine or denervation groups at this time. Intestinal perfusion pressure increased in the control group but decreased in the phentolamine and denervation groups during severe arterial hypoxia. Despite the difference in intestinal vascular resistance, intestinal blood flow decreased in a similar manner in all groups during severe arterial hypoxia. Intestinal arteriovenous O2 content difference [(a-v)O2] and O2 uptake were greater during severe arterial hypoxia in the phentolamine and denervation groups than in the control group. We speculate that the sympathetic stimulation mediates the increase in intestinal vascular resistance in newborn swine during severe arterial hypoxia; and sympathetic stimulation limits the increase in intestinal (a-v)O2, which occurs during severe arterial hypoxia in the newborn swine intestine.

Effect of controlled ventilation on renal and splanchnic blood flows during severe arterial hypoxia.

The present study was undertaken to evaluate the extent that the lung inflation reflex attenuates vasoconstrictor responses in renal cortex and splanchnic beds during severe arterial hypoxia. Hypoxia was induced by inspiration of a 3-5% oxygen gas mixture in three groups of chloralose-anesthetized dogs: Group I, free breathing; Group II, controlled ventilation; Group III, free breathing with arterial PCO2 held constant. Regional vascular conductances (VC) were calculated from regional blood flows measured with 15-microns radioactive microspheres. In Group I, hypoxia caused marked hyperventilation, which was accompanied by no significant change in VC in renal cortex, and by reductions in VC in spleen (-36%), pancreas (-56%), and duodenum (-28%). In Group II, hypoxia caused reduction in VC in renal cortex (-70%), and reductions in VC in spleen, pancreas, and duodenum similar to those in Group I. In Group III, hypoxia again caused marked hyperventilation, but reductions in VC in renal cortex, spleen, pancreas, and duodenum were similar to those in Group II. Results indicate that during severe arterial hypoxia activation of lung inflation reflex does not attenuate or reverse vasoconstriction in renal cortex, spleen, pancreas, and duodenum.

The role of substance P in arterial chemoreflex control of ventilation

The postulate that Substance P (SP) plays a neurotransmitter-like role in the arterial chemo- and thermoreflex control of ventilation was examined in conscious rabbits. The investigation was based on CNS neurotransmitter criteria and involved morphological studies using a monoclonal SP antibody, and functional experiments which compared within-animal responses to severe arterial hypoxia (PaO 2 < 35 mm Hg) and to intracisternal SP infusions. Experiments were performed in normal rabbits, and in rabbits pretreated at birth with capsaicin. The data support a neurotransmitter-like role for SP in the arterial chemo- and the thermoreflex control of ventilation, and there appear to be SP-dependent collateral chemoreflex pathways which block thermoregulatory panting through an inhibitory interneuron system.

Adaptation of Red Blood Cell Function to Hypoxia and Temperature in Ectothermic Vertebrates

function in adaptations of ectothermic ver? tebrates to hypoxia and temperature. The term adaptation, as used in this ar? ticle, means an alteration of physiological function which compensates for a stressful environmental or organismic factor. Two such factors of paramount importance to ectothermic vertebrates are temperature and availability. The physiological function to be examined in terms of adapt? ability is transport by blood from the gas exchange surface to the intracel? lular sites of 02 utilization. Hypoxia is best defined as inadequate uptake of 02 by tissues. The cause may be environmental (reduced 02 content and/or partial pressure in the respiratory medi? um) or organismic. In the latter category there is a hierarchy of sub-causes proceeding down the oxygen cascade, i.e., impaired gas exchange, shunt, ventilation/ perfusion mismatch, hypoperfusion, or inappropriate binding properties of blood. The appropriateness of the oxy? gen binding properties of blood depends, in turn, on environmental conditions, i.e., the partial pressure of 02 (Po2) in the res? piratory medium, and on the efficacy of gas exchange and degree of shunt. The position of the oxyhemoglobin dis? sociation curve (ODC) even with full knowledge about the environmental oxy? gen availability, is inadequate information for conclusions about adaptability of propriateness for tissue oxygenation. Such conclusions are valid only if infor? mation is available on in vivo values of temperature, blood gases (arterial and mixed venous Po2 and Pco2), pH and ca? pacity. Furthermore, the position of the ODC may cause, as well as be affected by, hypoxia. For example, in vertebrates with incompletely separated pulmonary and systemic circulations (lungfishes, amphibi? ans, and reptiles), the arterial hypoxemia due to right-to-left shunting may lead to severe arterial desaturation and hypoxia if the ODC is positioned too far to the right. Conversely, hypoxia caused by environ? mental factors can, by influencing the aerobic metabolism of nucleated red cells (or anaerobic metabolism of mammalian red cells), alter (in opposite directions!) the level of allosteric effectors of hemoglobin function and shift the position of the ODC. Thus, although it is often irresistably tempting (as evidenced below) to assess physiological meaning from shapes and positions of ODCs, Bohr factors, and ap? parent enthalpy (AH) values, such specu? lations should always be recognized and identified as just that.

Studies on the regulation of myocardial blood flow in man. II. Effects of acute arterial hypoxia.

AbstractTo determine whether adjustment of myocardial blood flow (MBF), myocardial oxygen consumption (MVO2) and myocardial substrate uptake (MSU) to acute arterial hypoxia is influenced by training effects on the heart, 7 trained and 7 untrained healthy individuals were investigated. MBF (argon method), MVO2 and MSU of glucose, lactate and free fatty acids were measured at rest during normoxia and two different stages of acute arterial hypoxia: a) 12.82 vol% O2; b) 8.74 vol% O2. Measurements were carried out during hemodynamic and respiratory steady state conditions.Myocardial flow and metabolism of athletes were significantly (p&lt;0.01) lower compared to untrained subjects. In the trained cohort, MBF increased from 65 ± 19 to 73 ± 16 (a) and 98 ± 23 (b) ml/min·100 g. MVO2 remained at normoxic control level of 8.00 ± 2.27 ml/min·100g. In the untrained group, MBF increased from 77 ± 15 to 84 ± 20 (a) and 108 ± 18 (b) ml/min · 100g. Again, there was no significant deviation in MVO2 from the normoxic level of 10.11 ± 1.90 ml/min·100g. Decrease in arterial oxygen content was overcompensated by an increase in coronary conductance resulting in a significantly improved efficiency of myocardial perfusion during severe hypoxia. MSU of glucose, lactate and free fatty acids as well as calculated ATP production did not change significantly during hypoxia.It is concluded that training effects on the heart do not influence regulation of MBF, MVO2 and MSU during moderate or severe acute arterial hypoxia. Reaction of coronary smooth muscle tone to a decrease in oxygen partial pressure is independent from training effects. However, both acute arterial hypoxia and physical training exert synergetic effects on the heart by reducing myocardial oxygen consumption per heart beat. Thus, it is assumed that adaptive properties of myocardial blood flow and metaboüsm to severe hypoxia are more pronounced in trained than in untrained individuals.

Central nervous resetting of baroreceptor reflexes.

SummaryStimulus‐response curves were derived in unanaesthetized rabbits relating menu arterial pressure to heart period (pulse interval). Arterial and atrial pressure were altered by graded inflation of balloons placed around the upper abdominal aorta and inferior vena cava. The stimulus‐response curves differed significantly between sham‐operated, thalamic and pontine rabbits, indicating that suprapontine as well as bulbar heart rate centres normally participated in reflexes arising from circulatory baroreceptors. The stimulus‐response curves were also used to determine whether generalized disturbances acted independently of the input from the baroreceptors on a distinctive part of the heart rate motoneurone pool, or whether they interacted with the baroreceptor input because of convergence on to common autonomic motoneurones. Vagal afferents from lung inflation receptors acted independently of the baroreceptor input on cardiac sympathetic motoneurones. Chemoreceptor stimulation produced by severe arterial hypoxia acted on a distinctive section of the motoneurone pool, but also interacted with the baroreceptor input on common motoneurone sites. This interaction increased the threshold to baroreceptor stimuli in both sham‐operated and pontine animals, thus altering baroreceptor reflex performance from regulator to servomechanism action. Because of this type of interaction, the reflex response to multiple inputs is not the same as the sum of individual reflex effects studied under controlled conditions.

Effects of hypoxia on cerebral autoregulation.

ARTICLESEffects of hypoxia on cerebral autoregulationK Kogure, P Scheinberg, M Fujishima, R Busto, and OM ReinmuthK Kogure, P Scheinberg, M Fujishima, R Busto, and OM ReinmuthPublished Online:01 Nov 1970https://doi.org/10.1152/ajplegacy.1970.219.5.1393MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByPrognostication in Anoxic Brain Injury3 April 2018 | American Journal of Hospice and Palliative Medicine®, Vol. 35, No. 11Cerebrovascular Injury in Premature Infants: Current Understanding and Challenges for Future PreventionClinics in Perinatology, Vol. 35, No. 4Differential effects of acute hypoxia and high altitude on cerebral blood flow velocity and dynamic cerebral autoregulation: alterations with hyperoxiaPhilip N. 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Todd1 October 2000 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. 279, No. 4Cerebral Autoregulation in Subjects Adapted and Not Adapted to High AltitudeStroke, Vol. 31, No. 10Uses of High Altitude for Studies of Effects of HypoxiaIntravenous Fluid Therapy in Neurologic InjuryCritical Care Clinics, Vol. 8, No. 2Cerebrovascular regulation and neonatal brain injuryPediatric Neurology, Vol. 7, No. 1Comparison of carbon-dioxide-enriched, oxygen-enriched, and normal air in treatment of acute mountain sicknessThe Lancet, Vol. 336, No. 8718A mathematical model of cerebral blood flow chemical regulation. II. Reactivity of cerebral vascular bedIEEE Transactions on Biomedical Engineering, Vol. 36, No. 2Regional Anesthesia is Preferable for Patients Undergoing Carotid EndarterectomyNeuroanesthesia: A Review of the Effects of Anesthetic Agents on Cerebral Blood Flow and Intracranial Pressure in the DogVeterinary Surgery, Vol. 14, No. 3Pathophysiologische Grundlagen zerebraler Durchblutungs- und Stoffwechselstörungen unter Berücksichtigung der RisikofaktorenFactors involved in the physiological regulation of the cerebral circulation21 June 2005Preservation of cerebral autoregulation in the unanesthetized hypoxemic newborn dogBrain Research, Vol. 241, No. 2Retinal vascular autoregulation in normal subjects.Stroke, Vol. 13, No. 2The neurology of hypertension, a neurologist viewClinical Neurology and Neurosurgery, Vol. 84, No. 2Physiologie und Pathophysiologie der GehirndurchblutungDelayed sequelae of head injuryJournal of Computed Tomography, Vol. 4, No. 4Autoregulation of cerebral blood flow after experimental fluid percussion injury of the brainJournal of Neurosurgery, Vol. 53, No. 4Survival of the ischemic brain: a progress report.Circulation, Vol. 60, No. 7Cerebral blood flow, cerebrovascular resistance, cerebral metabolic rate of oxygen and intracranial pressure during and after severe prolonged arterial hypoxia in dogs. The role of dopamine in the deep hypoxic state29 January 2009 | Acta Neurologica Scandinavica, Vol. 60, No. 1Cerebral Autoregulation in Unconscious Patients with Brain Injury30 December 2008 | Acta Anaesthesiologica Scandinavica, Vol. 22, No. 3SUMMARY and GENERAL CONCLUSIONSActa Neurologica Scandinavica, Vol. 57LiteraturThe kinetics of extracellular potassium changes during hypoxia and anoxia in the cat cerebral cortexBrain Research, Vol. 123, No. 1Joint Committee for Stroke FacilitiesStroke, Vol. 7, No. 2XIII. Cerebral circulation and metabolism in stroke. Cerebral circulation and metabolism in stroke study group.Stroke, Vol. 7, No. 2Experimental Production of Cerebral Vascular DisordersLiterature29 January 2009 | Acta Neurologica Scandinavica, Vol. 50, No. S57Primary and secondary cerebrospinal fluid acidosis as a manifestation of cerebral lesionsZeitschrift f�r Neurologie, Vol. 206, No. 3REFERENCES29 January 2009 | Acta Neurologica Scandinavica, Vol. 49, No. S52Disorders of the Cerebral CirculationThe influence ofPa O2 on the effects of sinus nerve stimulation with intact and inactivated vagiPfl�gers Archiv European Journal of Physiology, Vol. 341, No. 4Effects of Blood Gases on the Pressure-Flow Relationships in Canine Cerebral CirculationStroke, Vol. 4, No. 1Concepts of Cerebral Perfusion Pressure and Vascular Compression During Intracranial Hypertension More from this issue > Volume 219Issue 5November 1970Pages 1393-1396 Copyright & PermissionsCopyright © 1970 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1970.219.5.1393PubMed5473124History Published online 1 November 1970 Published in print 1 November 1970 Metrics