Hyperventilation alters colonic motor and sensory function: effects and mechanisms in humans

BACKGROUND & AIMS. Hyperventilation-induced hypocapnia affects hemodynamic function and enhances colonic motility. The aims of this study were to determine the effects of hypocapnic hyperventilation on colonic motility and sensation in health and to explore the putative neurohumoral mechanisms. METHODS: In experiment 1, colonic tone, sensation, plasma levels of cortisol, beta-endorphin, selected gut neuropeptides, norepinephrine, epinephrine, and splanchnic blood volume were measured during two sequences of hypocapnic hyperventilation. In experiment 2, colonic tone and sensation were assessed during eucapnic hyperventilation and abdominal compression. RESULTS: Hypocapnic hyperventilation, but not eucapnic hyperventilation or abdominal compression, significantly increased colonic tone and sensitivity to balloon distention (P = 0.017) without altering humoral mediators or splanchnic blood volume. Plasma norepinephrine level increased (P = 0.017) and splanchnic blood volume decreased (P = 0.028) during 5 minutes after hyperventilation, consistent with homeostatic responses. CONCLUSIONS: Increased colonic tone and sensation during hypocapnic hyperventilation are not caused by colonic compression. These effects of hyperventilation are not mediated humorally but may result from direct metabolic effects of hypocapnia on colonic muscle or from changes in central autonomic control of colonic smooth muscle.     

Diagnosis of hyperventilation for elimination of false-positive results of physical exercise test

The study was conducted in 55 patients with cardiac pains. Electrocardiography was used successively prior to, during and following physical exercises, followed by Seldinger selective coronary angiography, and electrocardiography prior to, during and following hyperventilation tests. In 2 of 55 patients the result of the exercise test was interpreted as false-positive, since the coronary angiography demonstrated intact vessels, and during hyperventilation ECG recorded a decreased ST segment. To avoid false-positive results in patients with suspected angina pectoris the physical exercises tests can be considered positive only in cases in which hyperventilation caused no ECG changes typical for angina pectoris.     

Hyperventilation and mannitol administration during surgery in patients with space-occupying intracranial lesions

The aim of this work was to evaluate the effect of hyperventilation and mannitol on brain volume during neurosurgical operations. The material comprises 30 cases of supratentorial tumours. pO2, pCO2, pH and lactate concentration were determined in the arterial blood and in 7 cases also in the CSF. It was established that hyperventilation sometimes fails to decrease ICP; it was observed that hyperventilation was more effective in decreasing brain volume of the pCO2 level decreased by 14,6 mm Hg on the average. The joint use of hyperventilation and hypertonic mannitol was found to be more effective. Neither of the above methods was effective in the case of cystic tumors.     

Tetany, spasmophilia, hyperventilation syndrome: theoretical and therapeutic synthesis

The hyperventilation syndrome (HVS), characterised by multiple somatic symptoms induced by inappropriate hyperventilation, constitutes the physiopathological manifestation of a common disorder in general medicine. As a synonym of spasmophilia or tetany, it has the advantage of offering diagnostic criteria, even though the latter are still vaguely defined. But its definition allows for objective measurements: indeed, a decrease in PCO2 during a hyperventilation provoking test and an abnormally low PCO2 rate at rest can be easily quantified. Moreover, the HVS concept offers a treatment which is both structured (respiratory reeducation, psychotherapy and pharmacology) and efficient. Yet, a number of scientific uncertainties still exist. There is no general agreement regarding the criteria which should be taken into account in a hyperventilation provoking test in order to diagnose an hyperventilation syndrome; the specificity of such a test is weak and a placebo can induce as many symptoms as can a HVS. Respiratory reeducation has good results but does not necessarily have an effect on PCO2. Some therapists see in it no more than a mechanism of relaxation and a rational explanation of frightening symptoms. This has led some authors to reject the term "hyperventilation syndrome" and to prefer the expression "chronic hyperventilation of unknown origin".     

Effects of hyperventilation and hypocapnic/normocapnic hypoxemia on renal function and lithium clearance in humans

BACKGROUND: Using the renal clearance of lithium as an index of proximal tubular outflow, this study tested the hypothesis that acute hypocapnic hypoxemia decreases proximal tubular reabsorption to the same extent as hypocapnic normoxemia (hyperventilation) and that this response is blunted during normocapnic hypoxemia. METHODS: Eight persons were studied on five occasions: (1) during inhalation of 10% oxygen (hypocapnic hypoxemia), (2) during hyperventilation of room air leading to carbon dioxide values similar to those with hypocapnic hypoxemia, (3) during inhalation of 10% oxygen with the addition of carbon dioxide to produce normocapnia, (4) during normal breathing of room air through the same tight-fitting face mask as used on the other study days, and (5) during breathing of room air without the face mask. RESULTS: Hypocapnic and normocapnic hypoxemia and hyperventilation increased cardiac output, respiratory minute volume, and effective renal plasma flow. Glomerular filtration rate remained unchanged on all study days. Calculated proximal tubular reabsorption decreased during hypocapnic hypoxemia and hyperventilation but remained unchanged with normocapnic hypoxemia. Sodium clearance increased slightly during hypocapnic and normocapnic hypoxemia, hyperventilation, and normocapnic normoxemia with but not without the face mask. CONCLUSIONS: The results indicate that (1) respiratory alkalosis with or without hypoxemia decreases proximal tubular reabsorption and that this effect, but not renal vasodilation or natriuresis, can be abolished by adding carbon dioxide to the hypoxic gas; (2) the increases in the effective renal plasma flow were caused by increased ventilation rather than by changes in arterial oxygen and carbon dioxide levels; and (3) the natriuresis may be secondary to increased renal perfusion, but application of a face mask also may increase sodium excretion.     

Nocturnal panic: Response to hyperventilation and carbon dioxide challenges.

To examine the role of ventilatory response in nocturnal panic, subjects experiencing nocturnal panic were compared with those who experienced daytime panic attacks only. In particular, measures of chronic hyperventilation (baseline pCO?) and CO? hypersensitivity (response to ventilatory challenges) were assessed. Subjective and psychophysiological measures were obtained during baseline, forced hyperventilation, and carbon dioxide inhalation phases of a standardized laboratory-based assessment. The groups did not differ with respect to subjective or physiological measures or to the frequency with which panic occurred during the assessment. The results do not lend support to models that emphasize central CO? hypersensitivity and chronic hyperventilation as primary mechanisms underlying nocturnal panic. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of anxiety sensitivity on the response to hyperventilation.

We tested the hypothesis that anxiety sensitivity enhances responses to biological challenge by exposing college students who scored either high or low on the Anxiety Sensitivity Index (ASI) to 5 min of voluntary hyperventilation. The ASI is a validated self-report instrument that measures the fear of anxiety symptoms. Following hyperventilation, high-anxiety-sensitivity (HAS) subjects reported more frequent and more intense hyperventilation sensations and a higher level of subjective anxiety than did low-anxiety-sensitivity (LAS) subjects. Analyses of covariance controlling for baseline differences indicated that the magnitude of increase (i.e., reactivity) in hyperventilation symptoms remained greater in the HAS than in the LAS group, whereas the magnitude of increase in anxiety did not. HAS subjects also exhibited a bias for reporting bodily sensations in general. These findings parallel those obtained when panic patients and normal controls are biologically challenged with hyperventilation, lactate infusion, and other anxiogenic agents. Taken together, these results suggest that anxiety sensitivity may also enhance the anxiety responses of panic patients during biological challenge tests. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in blood flow velocity and diameter of the middle cerebral artery during hyperventilation: assessment with MR and transcranial Doppler sonography

PURPOSE: To compare blood flow velocity changes within the middle cerebral artery (MCA) during hyperventilation, as measured with by both transcranial Doppler sonography and MR imaging, with the diameter of the MCA as measured with MR imaging alone. METHODS: The studies were performed in six healthy volunteers ranging in age from 22 to 31 years (mean, 27 years). Transcranial Doppler sonography was carried out with a range-gated 2-MHz transducer. MR examinations were done on a 1.5-T imaging unit. MR angiography was performed using the time-of-flight technique. MR flow measurements were carried out by using the phase-mapping technique with an ECG-triggered phase-contrast sequence. RESULTS: During hyperventilation, the mean blood flow velocity of the proximal MCA declined by 49.6% +/- 5.7 (mean +/- standard deviation) as measured with Doppler sonography, and by 47% +/- 4.6 as measured with MR flow calculation. The diameter of the MCA (3.4 +/- 0.3 mm) remained unchanged on MR imaging studies (3.3 +/- 0.3 mm). CONCLUSION: We found a good correlation between relative flow velocity changes measured by transcranial Doppler sonography and MR techniques. MR imaging revealed no significant changes in the diameter of the proximal MCA during normal versus hyperventilation. Relative changes in flow velocity in the MCA would thereby reflect relative changes in cerebral blood flow, at least during hyperventilation.     

Regional dynamic signal changes during controlled hyperventilation assessed with blood oxygen level-dependent functional MR imaging

PURPOSE: To quantitate the amplitude changes and temporal dynamics of regional functional MR imaging signals during voluntary hyperventilation using blood oxygen level-dependent contrast echo-planar imaging. METHODS: Seven male subjects were studied during voluntary hyperventilation (PetCO2 = 20 mm Hg) regulated by capnometry. Measurements were made on multisection echo-planar MR images obtained with parameters of 1000/66 (repetition time/echo time), flip angle of 30 degrees, and voxel size of 3 x 3 x 5 mm3. Sensitivity of the functional MR imaging signal to changes in PetCO2, time delays in relation to PetCO2 changes, and time constants of functional MR imaging signal changes were assessed on a region-by-region basis. RESULTS: Within 20 seconds of starting hyperventilation, rapid and substantial decreases in the functional MR imaging signal (by as much as 10%) were measured in areas of gray matter, which were significantly greater than the modest changes observed in white matter. Regional-specific effects in areas of the frontal, occipital, and parietooccipital cortex were stronger than in subcortical regions or in the cerebellum. Signal decreases measured with functional MR imaging were significantly delayed with respect to the reduction in PetCO2. Apparent differences between regional time constants did not reach statistical significance. CONCLUSION: Regional and gray-white matter differences in functional MR imaging signal changes during controlled hyperventilation may reflect differences in metabolic activity, vascular regulation, and/or capillary density. When measuring brain activation with functional MR imaging, arterial PCO2 differences due to unregulated respiration may confound interpretation of activation-related functional MR imaging signal changes.     

Bulging iris-lens in cataract extraction

The basic cause of iris-lens diaphragm bulging during cataract extraction is thought to be increased choroidal venous congestive pressure. This is shown to be controlled by hyperventilation under general anesthesia.     

Starch granulomas after transurethral resection of bladder tumors

Cerebrovascular reactivity to CO2 inhalation and voluntary hyperventilation was studied in seven normotensive subjects and nine hypertensive patients without clinical or angiographical signs of arteriosclerosis. Cerebral blood flow (CBF) was measured by the intracarotid 133Xe clearance method and calculated as the initial slope index. Three to five CBF measurements were made in each patient in the PaCO2 range of 20 to 55 mm Hg. No difference was observed in reactivity between hypertensive and normotensive patients, either during CO2 inhalation or during hyperventilation. The shape of the CBF:PaCO2 curve suggested a decrease in reactivity below a PaCO2 of 30 to 35 mm Hg in both groups. Above a PaCO2 of 35 mm Hg, exponential regression analysis yielded a mean reactivity of 6 +/- 2%, whereas below a PaCO2 of 30 mm Hg it was about 2%. The rise in CBF during CO2 inhalation was not influenced by the intravenous infusion of a small dose of trimethaphan which blocked the concomitant rise in blood pressure.     

Factors which alter the relationship between ventilation and carbon dioxide production during exercise in normal subjects

The slope of the linear relationship between ventilation (V(E)) and carbon dioxide production (VC0(2)) has been thought to indicate that VC0(2) is one of the major stimuli to V(E). A group of 15 normal subjects undertook different incremental treadmill exercise protocols to explore the relationship between V(E) and VCO(2). An incremental protocol using 1 instead of 3-min stages of exercise resulted in an increase in the V E to VCO(2) ratio [26.84 (SEM 1.23) vs 31.08 (SEM 1.36) (P <0.008) for the first stage, 25.24 (SEM 0.86) vs 27.83 (SEM 0.91) (P <0.005) for the second stage and 23.90 (SEM 0.86) vs 26.34 (SEM 0.81) (P = 0.001) for the third stage]. Voluntary hyperventilation to double the control level of V(E) during exercise resulted in an increase in the V(E) to VCO(2) slope [from 21.3 (SEM 0.71) for the control run to 35.1 (SEM 1.2) for the hyperventilation run (P <0.001)]. Prolonged hyperventilation (5 min) during exercise at stage 2 of the Bruce protocol resulted in a continued elevation of VCO(2) and the V(E)/VCO(2) slope. A steady state of V(E) and metabolic gas exchange can only be said to have been present after at least 3 min of exercise. Voluntary hyperventilation increased the slope of the relationship between V(E) and VCO(2). End-tidal carbon dioxide fell, but remained within the normal range. These results would suggest that a non-carbon dioxide factor may have been responsible for the increase we found in V(E) during exercise, and that factors other than increased dead space ventilation can cause an increased ventilation to VCO(2) slope, such as that seen in some pathophysiological conditions, such as chronic heart failure.     

White cell-reduced red cells prepared by filtration: a critical evaluation of current filters and methods for counting residual white cells

Atrial natriuretic peptide (ANP) is reported to dilate a major coronary artery in both experimental animals and humans. Spasm of a major coronary artery is the cause of variant angina pectoris and can be induced by hyperventilation. The effect of the ANP infusion on anginal attack induced by hyperventilation was studied in patients with variant angina pectoris. The study was performed in the early morning on 3 consecutive days in 11 patients with variant angina pectoris in whom the attacks were reproducibly induced by hyperventilation. On days 1 and 3 (saline solution infusion), and day 2 (ANP infusion), hyperventilation was started 14 minutes after beginning infusion of ANP (0.1 microgram/kg/min) or saline solution for 6 minutes. The attacks were induced in all 11 patients by hyperventilation on days 1 and 3. However, the attacks were not induced in any patient on day 2 of the ANP infusion. The plasma ANP level increased from 33 +/- 7 pg/ml to the peak level of 2,973 +/- 479 pg/ml (p < 0.01) at the end of the ANP infusion, and the plasma level of cyclic guanosine monophosphate (cGMP) increased from 5 +/- 1 pmol/ml to the peak level of 58 +/- 6 pmol/ml (p < 0.01) 5 minutes after the ANP infusion. The plasma levels of ANP and cGMP did not change after hyperventilation on days 1 and 3. It is concluded that the ANP infusion suppresses the attacks induced by hyperventilation in patients with variant angina pectoris, and cGMP is related to the mechanisms of suppression of the attacks.     

Biological challenge of PCO? levels: A test of Klein's (1993) suffocation alarm theory of panic.

D. F. Klein (see record 1993-37796-001) proposed that patients with panic disorder ( PD) have a hypersensitive suffocation monitor that predisposes them to experience panic attacks under certain conditions. The suffocation alarm theory predicts differential emotional responding to biological challenges that affect arterial partial pressure of carbon dioxide ( PCO? ). These PD patients should exhibit (a) lower fear and less likelihood of panic in response to biological challenges that lower PCO? levels (e.g., hyperventilation), and (b) increased fear and greater likelihood of panic in response to biological challenges that raise PCO? levels (e.g., inhalation of 35% CO? gas). The following indicators of the suffocation monitor were assessed: (a) severity of dyspnea symptoms, (b) frequency of dyspnea symptoms, (c) heightened respiration rate, and (d) lowered PCO? levels. Ratings of physiological and subjective responding, as well as panic, were obtained during both a hyperventilation and a 35% CO? challenge. None of the classification methods predicted differential emotional responding to hyperventilation versus 35% CO? challenge. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of the milieu on the rate of neutralisation of herpes simplex virus 1

Minimizing secondary injury after severe traumatic brain injury (TBI) is the primary goal of cerebral resuscitation. For more than two decades, hyperventilation has been one of the most often used strategies in the management of TBI. Laboratory and clinical studies, however, have verified a post-TBI state of reduced cerebral perfusion that may increase the brain's vulnerability to secondary injury. In addition, it has been suggested in a clinical study that hyperventilation may worsen outcome after TBI. OBJECT: Using the controlled cortical impact model in rats, the authors tested the hypothesis that aggressive hyperventilation applied immediately after TBI would worsen functional outcome, expand the contusion, and promote neuronal death in selectively vulnerable hippocampal neurons. METHODS: Twenty-six intubated, mechanically ventilated, isoflurane-anesthetized male Sprague-Dawley rats were subjected to controlled cortical impact (4 m/second, 2.5-mm depth of deformation) and randomized after 10 minutes to either hyperventilation (PaCO2 = 20.3 +/- 0.7 mm Hg) or normal ventilation groups (PaCO2 = 34.9 +/- 0.3 mm Hg) containing 13 rats apiece and were treated for 5 hours. Beam balance and Morris water maze (MWM) performance latencies were measured in eight rats from each group on Days 1 to 5 and 7 to 11, respectively, after controlled cortical impact. The rats were killed at 14 days postinjury, and serial coronal sections of their brains were studied for contusion volume and hippocampal neuron counting (CA1, CA3) by an observer who was blinded to their treatment group. Mortality rates were similar in both groups (two of 13 in the normal ventilation compared with three of 13 in the hyperventilation group, not significant [NS]). There were no differences between the groups in mean arterial blood pressure, brain temperature, and serum glucose concentration. There were no differences between groups in performance latencies for both beam balance and MWM or contusion volume (27.8 +/- 5.1 mm3 compared with 27.8 +/- 3.3 mm3, NS) in the normal ventilation compared with the hyperventilation groups, respectively. In brain sections cut from the center of the contusion, hippocampal neuronal survival in the CA1 region was similar in both groups; however, hyperventilation reduced the number of surviving hippocampal CA3 neurons (29.7 cells/hpf, range 24.2-31.7 in the normal ventilation group compared with 19.9 cells/hpf, range 17-23.7 in the hyperventilation group [25th-75th percentiles]; *p < 0.05, Mann-Whitney rank-sum test). CONCLUSIONS: Aggressive hyperventilation early after TBI augments CA3 hippocampal neuronal death; however, it did not impair functional outcome or expand the contusion. These data indicate that CA3 hippocampal neurons are selectively vulnerable to the effects of hyperventilation after TBI. Further studies delineating the mechanisms underlying these effects are needed, because the injudicious application of hyperventilation early after TBI may contribute to secondary neuronal injury.     

Continuous monitoring of brain tissue PO2: a new tool to minimize the risk of ischemia caused by hyperventilation therapy

Secondary ischemic events worsen the outcome of patients with severe head injury. Such a secondary ischemic event may be caused by a forced hyperventilation. A consequence of the induced vasoconstriction is the risk of ischemia with an adverse effect on outcome. As a reliable and on-line technique, brain tissue pO2 (p(ti)O2) is used for monitoring regional microcirculation, to detect critical hypoperfusion. On 22 patients with a severe head injury 70 hyperventilation tests were performed from day 0-9 after trauma, calculating TCD-CO2-reactivity (% change of mean flow velocity per mm Hg paCO2 change). Additionally brain p(ti)O2-CO2-reactivity (% change of brain p(ti)O2 per mm Hg paCO2 change) was calculated and introduced. Group A +2 (p(ti)O2 < or = 15 mm Hg, TCD-CO2-reactivity > or = 2.5%, p(ti)O2-CO2-reactivity > 0%) and group B +2 (p(ti)O2 > 15 mm Hg, TCD-CO2-reactivity > or = 2.5%. p(ti)O2-CO2-reactivity > 0%) was formed. P(ti)O2 values in group A+2 decreased to an ischemic level or ischemia aggravated during hyperventilation. In group B+2 no ischemic events occurred. TCD-CO2-reactivity, p(ti)O2-CO2-reactivity and decrease of paCO2 were not significantly different in both groups. 6 out of 22 patients showed, from day 0-9, at least once a risk of (aggravating) ischemia by hyperventilation therapy.     

Dynamic changes in cerebrospinal fluid pressure during neurosurgical operations

The effects of hyperventilation, osmotic and diuretic agents (urea, frusemide), thiopentone and succinylcholine chloride on the intracranial pressure were studied in neurosurgical patients with brain tumours. We have shown that hyperventilation together with osmotic and diuretic agents is very useful for reducing increased intracranial pressure.     

Posthyperventilatory steal response in chronic cerebral hemodynamic stress: a positron emission tomography study

BACKGROUND AND PURPOSE: The alteration of regional cerebral blood flow (CBF) during and after hyperventilation was measured using positron emission tomography (PET) to determine the circulatory response induced by daily respiratory changes in the cerebral area under chronic hemodynamic stress. METHODS: Three normal volunteers and 12 patients with an obstruction of major cerebral arteries underwent PET measurements of the CBF after an injection of H2(15)O: (1) in the resting condition, (2) during hyperventilation (HV scan), (3) 1 to 3 minutes after hyperventilation (post-HV scan), (4) during the inhalation of 5% CO2, and (5) after an injection of acetazolamide. Eleven patients also underwent a 15O gas study to measure CBF, oxygen extraction fraction (OEF), and cerebral blood volume (CBV). RESULTS: (1) In 9 patients, the CBF value in the post-HV scan was lower than that in the HV scan in 1 or more regions in the area of the obstructed arteries, although the PaCO2 level during the post-HV scan was higher than that during the HV scan in all patients. All control regions in the patients and in the normal volunteers showed an elevated CBF in the post-HV scan compared with the HV scan. (2) The negative post-HV response (posthyperventilatory steal) was prominent in 4 patients with moyamoya vessels and in another 5 patients with atherosclerotic disease who had PET evidence of hemodynamic stress (elevated CBV or OEF). (3) The regional pre- to post-HV change in CBF was significantly correlated with the CBF responses to acetazolamide and CO2. CONCLUSIONS: Vasodilatation after the termination of hyperventilation in the normal areas induces a steal response in the cerebral area suffering from hemodynamic stress and may cause profound hypoperfusion in everyday situations. This phenomenon may be important to our understanding of the clinical symptoms and the natural course of chronic cerebral occlusive disease bearing hemodynamic stress.     

Changes in EEG induced by prolonged hyperventilation in humans

The data obtained revealed a significant augmentation of the EEG slow-wave activity following a 32-minute hyperventilation in neurologically healthy subjects. In 43% of the subjects, on the 8th minute of the hyperventilation a generalised paroxysm of the delta-activity occurred.     

Eucapnic hypoxia lowers human cold thermoregulatory response thresholds and accelerates core cooling

Hypoxia lowers the basic thermoregulatory responses of animals and humans. In cold-exposed animals, hypoxia increases core temperature (Tco) cooling rate and suppresses shivering thermogenesis. In humans, the experimental effects of hypoxia on thermoregulation are equivocal. Also, the effect of hypoxia has not been separated from that of hypocapnia consequent to hypoxic hyperventilation. To determine the isolated effects of hypoxia on warm and cold thermoregulatory responses and core cooling during mild cold stress, we examined the Tco thresholds for sweating, vasoconstriction, and shivering as well as the core cooling rates of eight subjects immersed in 28 degrees C water under eucapnic conditions. On 2 separate days, subjects exercised on an underwater cycle ergometer to elevate Tco above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects inspired humidified room air during the control trial. For the eucapnic hypoxia trial, they inspired 12% O2-balance N2 with CO2 added to maintain eucapnia. Eucapnic hypoxia lowered the Tco thresholds for vasoconstriction and shivering by 0.14 and 0.19 degrees C, respectively, and increased core cooling rate by 33% (1.83 vs. 1.38 degrees C/h). These results demonstrate that eucapnic hypoxia enhances the core cooling rate in humans during mild cold stress. This may be attributed in part to a delay in the onset of vasoconstriction and shivering as well as increased respiratory heat loss during hypoxic hyperventilation.