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At least 19 recordsLinked to original sources
PubMed1992

Regional venous outflow, blood volume, and sympathetic nerve activity during hypercapnia and hypoxic hypercapnia.

We examined the changes in systemic blood volume and regional venous outflow from the splanchnic, coronary, and other remaining vascular beds in response to acute hypercapnia or hypoxic hypercapnia in dogs, using cardiopulmonary bypass and a reservoir. Hypercapnia (PCO2 = 105 mmHg) (1 mmHg = 133 Pa) and hypoxic hypercapnia (PO2 = 23 mmHg, PCO2 = 99 mmHg) caused marked decreases in systemic blood volume of 14 +/- 3 and 16 +/- 3 mL/kg in spleen-intact dogs, and 3 +/- 2 and 10 +/- 2 mL/kg in splenectomized dogs, respectively. Splanchnic venous outflow increased by 12% at 3.5 min hypercapnia, whereas it decreased by 60% at 3.5 min hypoxic hypercapnia. Coronary venous outflow increased by 85 and 400% at 3.5 min hypercapnia and hypoxic hypercapnia, respectively. Sympathetic efferent nerve activity revealed a significant augmentation during hypoxic hypercapnia and a relatively smaller increase (30% of the response to hypoxic hypercapnia) during hypercapnia. Carotid and aortic chemoreceptor and baroreceptor denervation attenuated significantly the response of systemic blood volume to hypercapnia and hypoxic hypercapnia. The regional venous outflow responses to hypercapnia were not altered after chemodenervation, but those to hypoxic hypercapnia were significantly attenuated after chemodenervation. These results suggest that acute hypercapnia and hypoxic hypercapnia caused a marked decrease in vascular capacitance owing primarily to an increase in sympathetic efferent nerve activity via chemoreceptor stimulation. They also indicate that blood flow to the splanchnic vascular bed during hypercapnia increased (even though the cardiac output was constant), whereas it increased to the extrasplanchnic and coronary vascular beds during hypoxic hypercapnia.

Animals↗
PubMed1989

Contractility of papillary muscle from rats exposed to 28 days of hypoxia, hypercapnia, and hypoxia with hypercapnia.

The effects of chronic respiratory failure (hypoxia and hypercapnia) on the contractile properties of cardiac muscle are not established. A study was performed of the isometric contractile properties of isolated papillary muscle removed from rats exposed in a normobaric environmental chamber to 28 days of hypoxia (fractional inspired oxygen (FIO2) 10%, fractional inspired carbon dioxide (FICO2) less than 1%), hypercapnia (FIO2 21%, FICO2 5%), and hypoxia with hypercapnia (FIO2 10%, FICO2 5%). Rats exposed to both hypoxia and hypoxia with hypercapnia developed selective right ventricular hypertrophy. Exposure to hypercapnia alone did not alter right ventricular weight. No change in right ventricular papillary muscle contractility per unit muscle mass was observed as measured by maximum active tension, maximum rate of rise or fall of tension, or time to peak tension. Rat cardiac muscle adapts successfully to the altered acid-base environment and increased work load associated with prolonged exposure to hypoxia and mild hypercapnia.

Animals↗
PubMed1990

Reflex control of vascular capacitance during hypoxia, hypercapnia, or hypoxic hypercapnia.

We tested the hypothesis that the changes in venous tone induced by changes in arterial blood oxygen or carbon dioxide require intact cardiovascular reflexes. Mongrel dogs were anesthetized with sodium pentobarbital and paralyzed with veruronium bromide. Cardiac output and central blood volume were measured by indocyanine green dilution. Mean circulatory filling pressure, an index of venous tone at constant blood volume, was estimated from the central venous pressure during transient electrical fibrillation of the heart. With intact reflexes, hypoxia (arterial PaO2 = 38 mmHg), hypercapnia (PaCO2 = 72 mmHg), or hypoxic hypercapnia (PaO2 = 41; PaCO2 = 69 mmHg) (1 mmHg = 133.32 Pa) significantly increased the mean circulatory filling pressure and cardiac output. Hypoxia, but not normoxic hypercapnia, increased the mean systemic arterial pressure and maintained the control level of total peripheral resistance. With reflexes blocked with hexamethonium and atropine, systemic arterial pressure supported with a constant infusion of norepinephrine, and the mean circulatory filling pressure restored toward control with 5 mL/kg blood, each experimental gas mixture caused a decrease in total peripheral resistance and arterial pressure, while the mean circulatory filling pressure and cardiac output were unchanged or increased slightly. We conclude that hypoxia, hypercapnia, and hypoxic hypercapnia have little direct influence on vascular capacitance, but with reflexes intact, there is a significant reflex increase in mean circulatory filling pressure.

Animals↗
PubMed1997

The effect of hypercapnia and hypercapnia associated with central cooling on breathing in unanesthetized fetal lambs.

In utero breathing activity is present periodically, but it must become continuous at birth. We investigated the effect of hypercapnia and of hypercapnia combined with central cooling on fetal breathing in seven chronically instrumented fetal lambs of 131-134-d gestation, using an extracorporeal membrane oxygenation (ECMO) system to control fetal blood gases and fetal temperature. During fetal hypercapnia (from a partial pressure of arterial CO2 (Paco2) 6.18 +/- 0.11 kPa to Paco2 7.39 +/- 0.15 kPa) frequency, amplitude, and incidence of fetal breathing movements during low voltage electrocortical activity (LV ECoG) increased significantly compared with isocapnic control on ECMO, but breathing remained absent during high voltage electrocortical activity (HV ECoG). During hypercapnia accompanied by central cooling (Paco2 7.90 +/- 0.13 kPa, temperature decreased by 2.1 degrees C) there were similar changes in fetal breathing movements during LV ECoG, but in four out of seven fetuses fetal breathing movements continued throughout HV ECoG. Hypercapnia accompanied by central cooling can thus override the inhibitory effects of HV ECoG on fetal breathing movements. This may be due to changes in sensitivity to CO2 produced by an increase in afferent input to the CNS.

Animals↗
PubMed1997

Response to hypercapnia in moyamoya disease. Cerebrovascular response to hypercapnia in pediatric and adult patients with moyamoya disease.

BACKGROUND AND PURPOSE: We have previously reported that cerebral blood flow decreased and oxygen extraction fraction and cerebral blood volume increased in pediatric patients with moyamoya disease, whereas these values did not change significantly in adult patients. In this study, we measured the cerebrovascular response to hypercapnia using 15O H2O positron emission tomography (PET) in each group of patients. These data were also compared with the oxygen extraction fraction and transit time (cerebral blood volume/cerebral blood flow) measured by 15O PET. METHODS: The subjects consisted of 20 patients with moyamoya disease (7 pediatric and 13 adult patients). Cerebral blood flow was measured by the 15O H2O bolus injection method at the resting state and during the inhalation of 5% CO2. Cerebrovascular CO2 response was estimated as the percentage change of cerebral blood flow per 1 mm Hg change of PaCO2. Oxygen extraction fraction and transit time were measured by the 15O steady-state method. RESULTS: Cerebrovascular response to hypercapnia severely decreased over the cerebral cortices in both pediatric and adult patients with moyamoya disease when compared with those of normal control subjects, and there was no significant difference between pediatric and adult patients. A significant correlation was observed between the CO2 response and transit time, whereas no significant correlation was seen between the CO2 response and oxygen extraction fraction. CONCLUSIONS: Our study revealed that the cerebral hemodynamic reserve capacity decreased to an equal degree in both pediatric and adult patients with moyamoya disease. This finding may thus help to explain the occurrence of transient ischemic attack in adult patients.

Administration, Inhalation↗
PubMedDate not supplied

Intracorporeal CO2 removal and permissive hypercapnia to reduce airway pressure in acute respiratory failure. The theoretical basis for permissive hypercapnia with IVOX.

Initial studies have shown that the intravascular oxygenator and carbon dioxide removal device (IVOX, Cardiopulmonics, Inc., Salt Lake City, UT) removes approximately 30% of VCO2. After noting increased CO2 removal with increased venous CO2, we developed a conceptual analytical model based on data obtained from patients and laboratory experiments. Increasing the CO2 gradient across the hollow fiber membranes of IVOX increases the operating efficiency of the device. Using the patient management technique of permissive hypercapnia (limiting tidal volumes, respiratory rates, and airway pressures) serves to increase the CO2 gradient across the membrane. The conceptual analytical model predicts that a PaCO2 of 75-80 mm Hg is required to obtain a CO2 gradient that results in IVOX CO2 removal of approximately 90-100 ml CO2/min. This technique may allow a broader application of both permissive hypercapnia and IVOX in acute respiratory failure.

Acute Disease↗
PubMed2000

Ventilatory responses to hypercapnia and hypoxia following chronic hypercapnia in the rat.

This study investigated the effects of an 18 week exposure to 10% CO(2) in air on minute ventilation (V(E)), breathing pattern and the chemoresponiveness of rats to hypoxic and hyperoxic stimuli. We found that V(E) remained elevated over the 18 weeks. Nonetheless, the breathing pattern changed significantly. Tidal volume increased and the durations of inspiration and the total cycle decreased. After the sustained hypercapnia the mean Pa(CO(2)) was 72.0+/-5.1 (S. D.) mmHg. Every 6 weeks the chemoresponiveness of the CO(2)-exposed rats was tested by an acute exposure sequentially to room air, then a 6% O(2), 10% CO(2) and 84% N(2) gas mixture, and finally a 90% O(2) in 10% CO(2) mixture. On either room air or the hyperoxic-hypercapnic mixture V(E) fell to its pre-hypercapnic level. On the hypoxic-hypercapnic mixture V(E) increased significantly. These results demonstrate that the initial stimulating effect of 10% CO(2) on V(E) persisted for the entire 18 weeks without altering hypoxic or hyperoxic ventilatory responses.

Animals↗
PubMed2000

Chronic hypercapnia inhibits hypoxic pulmonary vascular remodeling.

Chronic hypercapnia is commonly found in patients with severe hypoxic lung disease and is associated with a greater elevation of pulmonary arterial pressure than that due to hypoxia alone. We hypothesized that hypercapnia worsens hypoxic pulmonary hypertension by augmenting pulmonary vascular remodeling and hypoxic pulmonary vasoconstriction (HPV). Rats were exposed to chronic hypoxia [inspiratory O(2) fraction (FI(O(2))) = 0.10], chronic hypercapnia (inspiratory CO(2) fraction = 0.10), hypoxia-hypercapnia (FI(O(2)) = 0.10, inspiratory CO(2) fraction = 0.10), or room air. After 1 and 3 wk of exposure, muscularization of resistance blood vessels and hypoxia-induced hematocrit elevation were significantly inhibited in hypoxia-hypercapnia compared with hypoxia alone (P < 0.001, ANOVA). Right ventricular hypertrophy was reduced in hypoxia-hypercapnia compared with hypoxia at 3 wk (P < 0.001, ANOVA). In isolated, ventilated, blood-perfused lungs, basal pulmonary arterial pressure after 1 wk of exposure to hypoxia (20.1 +/- 1.8 mmHg) was significantly (P < 0.01, ANOVA) elevated compared with control conditions (12.1 +/- 0.1 mmHg) but was not altered in hypoxia-hypercapnia (13.5 +/- 0.9 mmHg) or hypercapnia (11.8 +/- 1.3 mmHg). HPV (FI(O(2)) = 0.03) was attenuated in hypoxia, hypoxia-hypercapnia, and hypercapnia compared with control (P < 0.05, ANOVA). Addition of N(omega)-nitro-L-arginine methyl ester (10(-4) M), which augmented HPV in control, hypoxia, and hypercapnia, significantly reduced HPV in hypoxia-hypercapnia. Chronic hypoxia caused impaired endothelium-dependent relaxation in isolated pulmonary arteries, but coexistent hypercapnia partially protected against this effect. These findings suggest that coexistent hypercapnia inhibits hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy, reduces HPV, and protects against hypoxia-induced impairment of endothelial function.

Animals↗
PubMed1999

Experimental critical care in ventilated rats: effect of hypercapnia on arterial oxygen-carrying capacity.

PURPOSE: We have previously demonstrated an increased arterial O2-carrying capacity in normal ventilated dogs subjected to both acute and prolonged exogenous hypercapnia. In the present study, we tested if arterial hypercapnia, during controlled ventilation, can increase O2-carrying capacity also in rats. MATERIALS AND METHODS: Twenty young male Sprague Dawley rats were anesthetized (60 mg/kg pentobarbital), tracheostomized, intubated, and one femoral vein and artery were cannulated. Anesthesia and paralysis were maintained using 15 mg/kg/h pentobarbital intravenously, and 2 mg/kg/h vecuronium bromide. The fluid balance (5 mL/kg/h saline), normothermia, and minute volume were maintained. The mean arterial blood pressure and heart rate were continuously monitored. Experiments included the following: (1) a control group, ventilated with normoxic air for 150 minutes (n = 5); (2) mild hypercapnia, a group of eight rats ventilated with normoxic air for 30 minutes and then ventilated with a mixture of normoxic air at 60 mm Hg CO2 (8 kPa) for 1 hour; and (3) severe hypercapnia, a group of seven rats were treated exactly as in group II, except a 90 mm Hg (12 kPa) CO2 during hypercapnia. Gas-exchange profile, arterial hemoglobin (Hb) concentration, arterial Hb-oxygen saturation (Hb-O2), and arterial O2 content were periodically determined during normocapnia and 1 hour of hypercapnia. RESULTS: Exposures to mild and severe hypercapnia, in rats with maintained ventilation, significantly reduced the arterial O2 content by 20% and 33%, respectively, without significant changes in the arterial Hb concentration (-2%). Severe hypercapnia generated a significant reduction of -14% in the PaO2, but not in PaO2/ FiO2 ratio. CONCLUSION: Rats subjected to controlled ventilation and permissive hypercapnia, unlike dogs and perhaps humans, show no augmentation of Hb concentration. Hypercapnia in rats also provokes much stronger Bohr effect than in dogs. Hypercapnia-induced Bohr effect in rats is accompanied with extreme desaturations of Hb-O2, and substantial reduction in the O2-carrying capacity. We speculate that the strong hypercapnia-induced Bohr effect in rats may prevent hypoxia at the tissue level. However, to maintain a stable oxygen-carrying capacity in rats used for pulmonary critical care studies with hypercapnia, we suggest to use hyperoxia, with or without a mild hypothermia.

Analysis of Variance↗
PubMed2000

Oxygen-carrying capacity during 10 hours of hypercapnia in ventilated dogs.

OBJECTIVE: To test if a relatively long-term exogenous hypercapnia, equivalent to those maintained during permissive hypercapnia, can persistently increase oxygen-carrying capacity in ventilated dogs. DESIGN: Prospective study. SETTING: Research laboratory in a hospital. SUBJECTS: Six mongrel dogs (3 males; 3 females). INTERVENTIONS: The dogs were anesthetized (30 mg/kg pentobarbital, i.v.), intubated, and cannulated in one femoral artery, one femoral vein, and the right jugular vein. The mean arterial blood pressure, heart rate, and mean pulmonary artery pressure were continuously recorded. Anesthesia, fluid balance, and normothermia were maintained. Arterial hypercapnia was generated by the addition of 60 torr dry CO2 (8 kPa) to the inspired air for 10 hrs, continuously. All subjects were paralyzed (vecuronium bromide) and ventilated with room air, while the ventilator settings were kept constant. MEASUREMENTS AND MAIN RESULTS: Arterial and venous gas exchange profiles, hemoglobin concentration, oxygen saturation, oxygen content, cardiac output, and oxygen consumption were determined, before, during, and after 10 hrs of hypercapnia, periodically. Both hemoglobin concentration and oxygen content were gradually increased during hypercapnia and reached significant levels at 8 and 10 hrs of hypercapnia, respectively. These increases continued up to 2 hrs after termination of hypercapnia. The PaO2/FIO2, as an index of arterial oxygenation, was significantly increased during the first 3 hrs of hypercapnia and then remained at the normoxic level up to 10 hrs of hypercapnia. No significant changes occurred in the mean arterial blood pressure and oxygen consumption. The heart rate and cardiac output were significantly reduced at 4 and 8 hrs of hypercapnia, respectively. The mean pulmonary artery pressure was increased throughout the hypercapnic trial. CONCLUSIONS: A relatively long-term exogenous hypercapnia can significantly increase oxygen-carrying capacity in normal ventilated dogs. Whether this effect can occur during permissive hypercapnia because of controlled ventilation in patients warrants investigation.

Animals↗
PubMed2000

Cerebral blood flow and metabolism during and after prolonged hypercapnia in newborn lambs.

OBJECTIVE: To study the effects of prolonged (6 hrs) hypercapnia on cerebral blood flow and cerebral metabolism in newborn lambs and to evaluate the effects on cerebral blood flow and cerebral metabolism on return to normocapnia after prolonged hypercapnia. DESIGN: Animal studies, using the newborn lamb, with comparison to control group. SUBJECTS: Newborn lambs of mixed breed, 1-7 days of age, were used for the study. Two groups of animals were studied: a hypercapnic group (n = 10) and a normocapnic control group (n = 5). SETTING: Work was conducted in the research laboratories at Children's National Medical Center, Washington, DC. INTERVENTIONS: Animals were anesthetized with pentobarbital, intubated, paralyzed, and mechanically ventilated. After baseline measurements were made, CO2 was blended into the ventilator gas until a PaCO2 of 75-80 torr (10-10.6 kPa) was obtained. Measurements were made 1 hr after the desired PaCO2 was achieved and after 6 hrs of hypercapnia. After 6 hrs of hypercapnia, the ventilator gas was returned to the baseline value, that is, normocapnia. Measurements were made 30, 60, and 90 mins after PaCO2 returned to baseline. MEASUREMENTS: Six measurements were made during the study. For each measurement, blood samples were drawn from the sagittal sinus and brachiocephalic artery catheters and were analyzed for pH, hemoglobin concentration, oxygen saturation, and blood gas values. Cerebral blood flow (CBF) was measured by using the radiolabeled microsphere technique. Cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period. MAIN RESULTS: Increasing PaCO2 from 37 +/- 3 torr to 78 +/- 6 torr (4.9 +/- 0.4 kPa to 10.3 +/- 0.8 kPa) for 1 hr increased CBF by 355%. After 6 hrs of PaCO2 at 78 +/- 3 torr (10.3 +/- 0.4 kPa), CBF remained 195% above baseline. At 30 mins of normocapnia, CBF had returned to baseline and remained at baseline until the conclusion of the study, a total of 90 mins of normocapnia. Cerebral oxygen consumption did not change during hypercapnia or with return to normocapnia. Oxygen transport increased 331% above baseline after 1 hr of hypercapnia and stayed 180% above baseline after 6 hrs of hypercapnia. Fractional oxygen extraction decreased by 55% at 1 hr of hypercapnia and stayed 39% below baseline at 6 hrs of hypercapnia. CONCLUSIONS: Healthy lambs seem to tolerate undergoing hypercapnia for 6 hrs with a return to normocapnia. The return to baseline of CBF and cerebral metabolism at normocapnia seen in our study with lambs may explain why prolonged hypercapnia appears to be well tolerated in mechanically ventilated patients. If these results can be extrapolated to human subjects, our study in lambs supports evidence that patients who have undergone permissive hypercapnia seem to be neurologically unaffected.

Age Factors↗
PubMed1996

Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans.

STUDY OBJECTIVE: The inotropic, lusitropic, and electrophysiologic effects of acute hypercapnia in humans are not known. Although the effects of hypercapnia on the systemic circulation have been well documented, there is still some debate as to whether hypercapnia causes true pulmonary vasoconstriction in vivo. We have therefore evaluated the effects of acute hypercapnia on these cardiac indices and the interaction of hypercapnia with the systemic and pulmonary vascular beds in humans. PARTICIPANTS AND INTERVENTIONS: Eight healthy male volunteers were studied using Doppler echocardiography. After resting for at least 30 min to achieve baseline hemodynamic parameters (T(0)), they were rendered hypercapnic to achieve an end-tidal carbon dioxide (CO2) of 7 kPa for 30 min by breathing a variable mixture of CO2/air (T1). They were restudied after 30 min recovery breathing air (T2). Hemodynamic, diastolic, and systolic flow parameters, QT dispersion (maximum-minimum QT interval measured in a 12-lead ECG), and venous blood samples for plasma renin activity (PRA), angiotensin II (ANG II), and aldosterone (ALDO) were measured at each time point. RESULTS: Hypercapnia compared with placebo significantly increased mean pulmonary artery pressure 14 +/- 1 vs 9 +/- 1 mm Hg and pulmonary vascular resistance 171 +/- 17 vs 129 +/- 17 dyne.s.cm-5, respectively. Heart rate, stroke volume, cardiac output, and mean arterial BP were increased by hypercapnia. Indexes of systolic function, namely peak aortic velocity and aortic mean and peak acceleration, were unaffected by hypercapnia. Similarly, hypercapnia had no effect on lusitropic indexes reflected by its lack of effect on isovolumic relaxation time, mitral E-wave deceleration time, and mitral E/A wave ratio. Hypercapnia was found to significantly increase both QTc interval and QT dispersion: 428 +/- 8 vs 411 +/- 3 ms and 48 +/- 2 vs 33 +/- 4 ms, respectively. There was no significant effect of hypercapnia on PRA, ANG II, or ALDO. CONCLUSION: Thus, acute hypercapnia appears to have no adverse inotropic or lusitropic effects on cardiac function, although repolarization abnormalities, reflected by an increase in QT dispersion, and its effects on pulmonary vasoconstriction may have important sequelae in man.

Adult↗
PubMed1999

The control of blood pressure during external hypercapnia in the rainbow trout (Oncorhynchus mykiss).

Adult freshwater rainbow trout (Oncorhynchus mykiss) were exposed acutely (approximately 20 min) in a stepwise manner to increasing levels of environmental carbon dioxide ranging between 1.7 and 9.0 mmHg (0.23-1.2 kPa). Experiments were performed to examine, for the first time, the influence of hypercapnic acidosis on aspects of cardiovascular physiology including blood pressure, cardiac output and vascular resistance. Fish displayed dose (water CO(2) partial pressure) -dependent increases in ventral aortic (13-39 %) and dorsal aortic (17-54 %) blood pressures that reflected marked increases in systemic vascular resistance (16-78 %); branchial vascular resistance was unaffected by hypercapnia. At the highest level of hypercapnia (9.0 mmHg), central venous pressure was significantly elevated by 54 %. Although cardiac output remained constant, heart rate was significantly lowered by 4-7 beats min(-)(1) at the two highest levels of hypercapnia. To determine whether the cardiovascular responses to hypercapnia were being blunted by the stepwise increase in external P(CO2), a separate group of fish was exposed directly to a single step of hypercapnia (water P(CO2) 8.0 mmHg). The cardiovascular responses were similar to those exhibited by the more gradually exposed fish except that central venous pressure did not increase and the extent of the bradycardia was greater (13 beats min(-)(1)). After confirming the effectiveness of yohimbine in blocking the vasoconstrictory (&agr;)-adrenoreceptors of the systemic vasculature, this antagonist was used as a tool to assess the importance of (&agr;)-adrenoreceptor stimulation in promoting the cardiovascular responses during hypercapnia. Prior treatment of fish with yohimbine prevented the increased blood pressures and systemic vascular resistance during hypercapnia but did not influence the CO(2)-induced bradycardia. Plasma levels of catecholamines did not change during hypercapnia, and therefore the stimulation of the systemic (&agr;)-adrenoreceptors presumably reflected increased sympathetic nerve activity. To determine whether the cardiovascular changes elicited by hypercapnia were related to acidosis-induced hypoxaemia, fish were exposed to hypoxia in a stepwise manner (water P(O2) 65-151 mmHg). The cardiovascular responses to hypoxia were markedly different from those to hypercapnia and consisted of pronounced increases in systemic and branchial vascular resistance, but only at the most severe level of hypoxia; ventral and dorsal aortic pressures were unaffected. The differences between the responses to hypercapnia and hypoxia, coupled with the smaller reductions in blood oxygen content during hypercapnia, support the hypothesis that the cardiovascular responses to CO(2) are direct and are unrelated to hypoxaemia.

Journal Article↗
PubMed2004

Regulation of breathing and body temperature of a burrowing rodent during hypoxic-hypercapnia.

Burrowing mammals usually have low respiratory sensitivity to hypoxia and hypercapnia. However, the interaction between ventilation (V), metabolism and body temperature (Tb) during hypoxic-hypercapnia has never been addressed. We tested the hypothesis that Clyomys bishopi, a burrowing rodent of the Brazilian cerrado, shows a small ventilatory response to hypoxic-hypercapnia, accompanied by a marked drop in Tb and metabolism. V, Tb and O(2) consumption (V?O(2)) of C. bishopi were measured during exposure to air, hypoxia (10% and 7% O(2)), hypercapnia (3% and 5% CO(2)) and hypoxic-hypercapnia (10% O(2)+ 3% CO(2)). Hypoxia of 7% but not 10%, caused a significant increase in V, and a significant drop in Tb. Both hypoxic levels decreased V?O(2) and 7% O(2) significantly increased V/V?O(2). Hypercapnia of 5%, but not 3%, elicited a significant increase in V, although no significant change in Tb, V?O(2) or V/V?O(2) was detected. A combination of 10% O(2) and 3% CO(2) had minor effects on V and Tb, while V?O(2) decreased and V/V?O(2) tended to increase. We conclude that C. bishopi has a low sensitivity not only to hypoxia and hypercapnia, but also to hypoxic-hypercapnia, manifested by a biphasic ventilatory response, a drop in metabolism and a tendency to increase V/V?O(2). The effect of hypoxic-hypercapnia was the summation of the hypoxia and hypercapnia effects, with respiratory responses tending to have hypercapnic patterns while metabolic responses, hypoxic patterns.

Adaptation, Physiological↗
PubMed1994

Inhaled nitric oxide reverses the increase in pulmonary vascular resistance induced by permissive hypercapnia in patients with acute respiratory distress syndrome.

BACKGROUND: The aim of this prospective study was to determine if inhaled nitric oxide (NO) would reverse the increase in pulmonary arterial pressures and in pulmonary vascular resistance induced by acute permissive hypercapnia in patients with acute respiratory distress syndrome. METHODS: In 11 critically ill patients (mean age 59 +/- 22 yr) with acute respiratory distress syndrome (Murray Score > or = 2.5), the lungs were mechanically ventilated with NO 2 ppm during both normocapnic and hypercapnic conditions. Four phases were studied: normocapnia (arterial carbon dioxide tension 38 +/- 6 mmHg, tidal volume (655 +/- 132 ml); normocapnia plus inhaled NO 2 ppm; hypercapnia (arterial carbon dioxide tension 65 +/- 15 mmHg, tidal volume 330 +/- 93 ml); and hypercapnia plus inhaled NO 2 ppm. Continuous recordings were made of heart rate, arterial pressure, pulmonary artery pressure, tracheal pressure, and tidal volume (by pneumotachograph). At the end of each condition, arterial pressure, pulmonary artery pressure, cardiac filling pressures, and cardiac output were measured. Simultaneous arterial and mixed venous blood samples were obtained to measure arterial oxygen tension, arterial carbon dioxide tension, mixed venous oxygen tension, arterial hemoglobin oxygen saturation, mixed venous hemoglobin oxygen saturation, pH, and blood hemoglobin and methemoglobin concentrations (by hemoximeter). In addition, plasma concentrations of catecholamines were measured with a radioenzymatic assay. In 5 patients, end-tidal carbon dioxide tension was measured with a nonaspirative infrared capnometer. Calculations were made of pulmonary vascular resistance index, systemic vascular resistance index, true pulmonary shunt, and alveolar dead space. RESULTS: During hypercapnia, NO decreased pulmonary vascular resistance index from 525 +/- 223 to 393 +/- 142 dyn.s.cm-5.m-2 (P < 0.01), a value similar to that measured in normocapnic conditions (391 +/- 122 dyn.s.cm-5.m-2). It also reduced mean pulmonary artery pressure from 40 +/- 9 to 35 +/- 8 mmHg (P < 0.01). NO increased arterial oxygen tension (inspired oxygen fraction 1) from 184 +/- 67 to 270 +/- 87 mmHg during normocapnia and from 189 +/- 73 to 258 +/- 101 mmHg during hypercapnia (P < 0.01). NO decreased true pulmonary shunt during normocapnia (from 34 +/- 3% to 28 +/- 4%, P < 0.001) but had no significant effect on it during hypercapnia (39 +/- 7% vs. 38 +/- 8.5%). In five patients, NO resulted in a decrease in alveolar dead space from 34 +/- 7% to 28 +/- 10% in normocapnic conditions and from 30 +/- 9% to 22 +/- 10% in hypercapnic conditions (P < 0.05). CONCLUSIONS: Inhaled NO completely reversed the increase in pulmonary vascular resistance index induced by acute permissive hypercapnia. It only partially reduced the pulmonary hypertension induced by acute permissive hypercapnia, probably because the flow component of the increase in pulmonary pressure (i.e., the increase in cardiac output) was not reduced by inhaled NO. A significant increase in arterial oxygenation after NO administration was observed during normocapnic and hypercapnic conditions. A ventilation strategy combining permissive hypercapnia and inhaled NO may reduce the potentially deleterious effects that permissive hypercapnia alone has on lung parenchyma and pulmonary circulation.

Administration, Inhalation↗
PubMed1998

Effects of inhaled nitric oxide during permissive hypercapnia in acute respiratory failure in piglets.

OBJECTIVE: To look for the effects of inhaled nitric oxide on oxygenation and pulmonary hemodynamics during acute hypercapnia in acute respiratory failure. DESIGN: Prospective, randomized, experimental study. SETTING: University research laboratory. SUBJECTS: Ten piglets, weighing 9 to 13 kg. INTERVENTIONS: Acute respiratory failure was induced by oleic acid infusion and repeated lung lavages with 0.9% sodium chloride. The protocol consisted of three randomly assigned periods with different PaCO2 levels. Tidal volume was reduced to induce hypercapnia. Inspiratory time was prolonged to achieve similar mean airway pressures. During permissive hypercapnia, pH was not corrected. At each PaCO2 period, the animals were ventilated with inhaled nitric oxide of 10 parts per million and without nitric oxide inhalation. MEASUREMENTS AND MAIN RESULTS: Continuous hemodynamic monitoring included right atrial, mean pulmonary arterial, and mean systemic arterial pressures, arterial and mixed venous oxygen saturations, and continuous flow recording at the pulmonary artery. In addition, airway pressures, tidal volumes, dynamic lung compliance and airway resistance, end-tidal CO2 concentrations, and arterial and mixed venous blood gases were measured. Data were obtained at baseline and after lung injury, at normocapnia, at two levels of hypercapnia with and without nitric oxide inhalation. Acute hypercapnia resulted in a significant decrease in blood pH and a significant increase in mean pulmonary arterial pressure. There was no significant change in PaO2 during normocapnia and hypercapnia. Inhaled nitric oxide significantly decreased the mean pulmonary arterial pressure during both hypercapnic periods. It significantly improved oxygenation during both normocapnia and hypercapnia. CONCLUSIONS: Acute hypercapnia resulted in a significant increase in pulmonary arterial pressure without influencing oxygenation and cardiac output. Inhaled nitric oxide significantly reduced the pulmonary hypertension induced by acute permissive hypercapnia but did not influence the flow through the pulmonary artery. Inhaled nitric oxide significantly improved oxygenation in this model of acute lung injury during normocapnia and acute hypercapnia.

Administration, Inhalation↗
PubMed2005

Permissive hypercapnia: role in protective lung ventilatory strategies.

PURPOSE OF REVIEW: Hypercapnia is a central component of current protective ventilatory strategies. This review aims to present and interpret data from recent clinical and experimental studies relating to hypercapnia and its role in protective ventilatory strategies. RECENT FINDINGS: Increasing clinical evidence supports the use of permissive hypercapnia, particularly in acute lung injury/acute respiratory distress syndrome, status asthmaticus, and neonatal respiratory failure. However, there are no clinical data examining the contribution of hypercapnia per se to protective ventilatory strategies. Recent experimental studies provide further support for the concept of therapeutic hypercapnia, whereby deliberately elevated PaCO2 may attenuate lung and systemic organ injury. CO2 administration attenuates experimental acute lung injury because of adverse ventilatory strategies, mesenteric ischemia reperfusion, and pulmonary endotoxin instillation. Hypercapnic acidosis attenuates key effectors of the inflammatory response and reduces lung neutrophil infiltration. At the genomic level, hypercapnic acidosis attenuates the activation of nuclear factor-kappaB, a key regulator of the expression of multiple genes involved in the inflammatory response. The physiologic effects of hypercapnia, both beneficial and potentially deleterious, are increasingly well understood. In addition, reports suggest that humans can tolerate extreme levels of hypercapnia for relatively prolonged periods without adverse effects. SUMMARY: The potential for hypercapnia to contribute to the beneficial effects of protective lung ventilatory strategies is clear from experimental studies. However, the optimal ventilatory strategy and the precise contribution of hypercapnia to this strategy remain unclear. A clearer understanding of its effects and mechanisms of action is central to determining the safety and therapeutic utility of hypercapnia in protective lung ventilatory strategies.

Acidosis↗