Modulation of decompression sickness risk in pigs with caffeine during H(2) biochemical decompression.

In H(2) biochemical decompression, H(2)-metabolizing intestinal microbes remove gas stored in tissues of animals breathing hyperbaric H(2), thereby reducing decompression sickness (DCS) risk. We hypothesized that increasing intestinal perfusion in pigs would increase the activity of intestinal Methanobrevibacter smithii, lowering DCS incidence further. Pigs (Sus scrofa, 17-23 kg, n = 20) that ingested caffeine (5 mg/kg) increased O(2) consumption rate in 1 atm air by ~20% for at least 3 h. Pigs were given caffeine alone or caffeine plus injections of M. smithii. Animals were compressed to 24 atm (20.5-23.1 atm H(2), 0.3-0.5 atm O(2)) for 3 h, then decompressed and observed for signs of DCS. In previous studies, DCS incidence in animals without caffeine treatment was significantly (P < 0.05) lower with M. smithii injections (7/16) than in controls (9/10). However, contrary to our hypothesis, DCS incidence was marginally higher (P = 0.057) in animals that received caffeine and M. smithii (9/10) than in animals that received caffeine but no M. smithii (4/10). More information on gas kinetics is needed before extending H(2) biochemical decompression to humans.     

Increasing activity of H(2)-metabolizing microbes lowers decompression sickness risk in pigs during H(2) dives.

The risk of decompression sickness (DCS) was modulated by varying the biochemical activity used to eliminate some of the hydrogen (H(2)) stored in the tissues of pigs (19.4 +/- 0.2 kg) during hyperbaric exposures to H(2). Treated pigs (n = 16) received intestinal injections of Methanobrevibacter smithii, a microbe that metabolizes H(2) to water and CH(4). Surgical controls (n = 10) received intestinal injections of saline, and an additional control group (n = 10) was untreated. Pigs were placed in a chamber and compressed to 24 atm abs (20.6-22.9 atm H(2)). After 3 h, the pigs were decompressed and observed for symptoms of DCS for 1 h. Pigs with M. smithii had a significantly lower (P < 0.05) incidence of DCS (44%; 7/16) than all controls (80%; 16/20). The DCS risk decreased with increasing activity of microbes injected (logistic regression, P < 0.05). Thus the supplemental tissue washout of the diluent gas by microbial metabolism was inversely correlated with DCS risk in a dose-dependent manner in this pig model.     

On the likelihood of decompression sickness during H(2) biochemical decompression in pigs.

A probabilistic model was used to predict decompression sickness (DCS) outcome in pigs during exposures to hyperbaric H(2) to quantify the effects of H(2) biochemical decompression, a process in which metabolism of H(2) by intestinal microbes facilitates decompression. The data set included 109 exposures to 22-26 atm, ca. 88% H(2), 9% He, 2% O(2), 1% N(2), for 0.5-24 h. Single exponential kinetics described the tissue partial pressures (Ptis) of H(2) and He at time t: Ptis = integral (Pamb - Ptis). tau(-1) dt, where Pamb is ambient pressure and tau is a time constant. The probability of DCS [P(DCS)] was predicted from the risk function: P(DCS) = 1 - e(-r), where r = integral (Ptis(H(2)) + Ptis(He) - Thr - Pamb). Pamb(-1) dt, and Thr is a threshold parameter. Inclusion of a parameter (A) to estimate the effect of H(2) metabolism on P(DCS): Ptis(H(2)) = integral (Pamb - A - Ptis(H(2))). tau(-1) dt, significantly improved the prediction of P(DCS). Thus lower P(DCS) was predicted by microbial H(2) metabolism during H(2) biochemical decompression.     

Short oxygen prebreathing and intravenous perfluorocarbon emulsion reduces morbidity and mortality in a swine saturation model of decompression sickness.

Disabled submarine (DISSUB) survivors will achieve inert gas tissue saturation within 24 h. Direct ascent to the surface when saturated carries a high risk of decompression sickness (DCS) and death, yet may be necessary during rescue or escape. O(2) has demonstrated benefits in decreasing morbidity and mortality resulting from DCS by enhancing inert gas elimination. Perfluorocarbons (PFCs) also mitigate the effects of DCS by decreasing bubble formation and increasing O(2) delivery. Our hypothesis is that combining O(2) prebreathing (OPB) and PFC administration will reduce the incidence of DCS and death following saturation in an established 20-kg swine model. Yorkshire swine (20 +/- 6.5 kg) were compressed to 5 atmospheres (ATA) in a dry chamber for 22 h before randomization into one of four groups: 1) air and saline, 2) OPB and saline, 3) OPB with PFC given at depth, 4) OPB with PFC given after surfacing. OPB animals received >90% O(2) for 9 min at depth. All animals were returned to the surface (1 ATA) without decompression stops. The incidence of severe DCS < 2 h after surfacing was 96%, 63%, 82%, and 29% for groups 1, 2, 3, and 4, respectively. The incidence of death was 88%, 41%, 54%, and 5% for groups 1, 2, 3, and 4, respectively. OPB combined with PFC administration after surfacing provided the greatest reduction in DCS morbidity and mortality in a saturation swine model. O(2)-related seizure activity before reaching surface did not negatively affect outcome, but further safety studies are warranted.     

急性减压病大鼠肺组织粘附分子的变化

目的:探讨急性减压病大鼠肺组织中内粘附分子的改变。方法:雄性SD大鼠置于加压舱内,压缩空气在3 min内匀速加压至0.7 MPa,停留60 min后,3 min内快速减压出舱。观察减压后生存率、减压病症状。在减压后30 min、6 h、24 h取大鼠脑、肺及肝脏组织,甲醛溶液固定、切片、HE染色观测病理改变。免疫组化测定肺组织中细胞间粘附分子-1(ICAM-1)、E-选择素(E-selectin)、主要组织相容性复合体-Ⅱ(MHC-Ⅱ)的表达变化。在减压后6h、24 h前30 min,大鼠尾静脉注射2%evans blue溶液。30 min后行生理盐水灌注,收集肺组织,观测肺组织蓝染程度,酶标仪测定血浆中evans blue含量。结果:肺、肝及脑组织在减压后30 min出现水肿、淤血等病理表现。和正常组比较,肺组织中ICAM-1、E-selectin、MHC-Ⅱ在减压后明显上升,并呈现动态变化。相对于正常组,减压后6 h、24h肺组织血浆中evans blue含量明显增加。结论:气泡导致的,粘附分子介导的血管内皮受损是减压病的发病机制之一。     

Bubble formation in crabs induced by limb motions after decompression

In vivo bubble formation was studied in the megalopal stage of the crab Pachygrapsus crassipes. The animals were equilibrated with elevated argon, nitrogen, or helium pressures then rapidly decompressed to atmospheric pressure. Voluntary motions induced bubble nucleation in leg joints after exposures to as low as 2 atm nitrogen (gauge pressure). Delays of several minutes sometimes passed between decompression and bubble formation. Mechanically stimulating the animals to move their legs increased this bubble formation, whereas immobilizing the legs before gas equilibration prevented it, even in animals decompressed from 150 atm nitrogen. We conclude that preformed nuclei are not responsible for bubbles developing in the legs of this animal. Instead, tribonucleation of bubbles apparently occurs as a result of limb motions at relatively low gas supersaturations.     

Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness

Decompression sickness (DCS) with alterations in coagulation system and formation of platelet thrombi occurs when a subject is subjected to a reduction in environmental pressure. Blood platelet consumption after decompression is clearly linked to bubble formation in humans and offers an index for evaluating DCS severity in animal models. Previous studies highlighted a predominant involvement of platelet activation and thrombin generation in bubble-induced platelet aggregation (BIPA). To study the mechanism of the BIPA in DCS, we examined the effect of acetylsalicylic acid (ASA), heparin (Hep), and clopidogrel (Clo), with anti-thrombotic dose pretreatment in a rat model of DCS. Male Sprague-Dawley rats (n = 208) were randomly assigned to one experimental group treated before the hyperbaric exposure and decompression protocol either with ASA (3×100 mg·kg(-1)·day(-1), n = 30), Clo (50 mg·kg(-1)·day(-1), n = 60), Hep (500 IU/kg, n = 30), or to untreated group (n = 49). Rats were first compressed to 1,000 kPa (90 msw) for 45 min and then decompressed to surface in 38 min. In a control experiment, rats were treated with ASA (n = 13), Clo (n = 13), or Hep (n = 13) and maintained at atmospheric pressure for an equivalent period of time. Onset of DCS symptoms and death were recorded during a 60-min observation period after surfacing. DCS evaluation included pulmonary and neurological signs. Blood samples for platelet count (PC) were taken 30 min before hyperbaric exposure and 30 min after surfacing. Clo reduces the DCS mortality risk (mortality rate: 3/60 with Clo, 15/30 with ASA, 21/30 with Hep, and 35/49 in the untreated group) and DCS severity (neurological DCS incidence: 9/60 with Clo, 6/30 with ASA, 5/30 with Hep, and 12/49 in the untreated group). Clo reduced fall in platelet count and BIPA (-4,5% with Clo, -19.5% with ASA, -19,9% with Hep, and -29,6% in the untreated group). ASA, which inhibits the thromboxane A2 pathway, and Hep, which inhibits thrombin generation, have no protective effect on DCS incidence. Clo, a specific ADP-receptor antagonist, reduces post-decompression platelet consumption. These results point to the predominant involvement of the ADP release in BIPA but cannot differentiate definitively between bubble-induced vessel wall injury and bubble-blood component interactions in DCS.     

VCO2 and VE kinetics during moderate- and heavy-intensity exercise after acetazolamide administration.

The effect of carbonic anhydrase inhibition with acetazolamide (Acz) on CO2 output (VCO2) and ventilation (VE) kinetics was examined during moderate- and heavy-intensity exercise. Seven men [24 +/- 1 (SE) yr] performed cycling exercise during control (Con) and Acz (10 mg/kg body wt iv) sessions. Each subject performed step transitions (6 min) in work rate from 0 to 100 W [below ventilatory threshold (VET)]. VE and gas exchange were measured breath by breath. The time constant (tau) was determined for exercise VET by using a three-component model (fit from the start of exercise). VCO2 kinetics were slower in Acz (VET, MRT = 75 +/- 10 s) than Con (VET, MRT = 54 +/- 7 s). During VET kinetics were faster in Acz (MRT = 85 +/- 17 s) than Con (MRT = 106 +/- 16 s). Carbonic anhydrase inhibition slowed VCO2 kinetics during both moderate- and heavy-intensity exercise, demonstrating impaired CO2 elimination in the nonsteady state of exercise. The slowed VE kinetics in Acz during exercise 相似文献   

Effect of inert gas switching at depth on decompression outcome in rats

The present investigation was performed to determine whether inert gas sequencing at depth would affect decompression outcome in rats via the phenomenon of counterdiffusion. Unanesthetized rats (Rattus norvegicus) were subjected to simulated dives in either air, 79% He-21% O2, or 79% Ar-21% O2; depths ranged from 125 to 175 feet of seawater (4.8-6.3 atmospheres absolute). After 1 h at depth, the dive chamber was vented (with depth held constant) over a 5-min period with the same gas as in the chamber (controls) or one of the other two inert gas-O2 mixtures. After the gas switch, a 5- to 35-min period was allowed for gas exchange between the animals and chamber atmosphere before rapid decompression to the surface. Substantial changes in the risk of decompression sickness (DCS) were observed after the gas switch because of differences in potencies (He less than N2 less than Ar) for causing DCS and gas exchange rates (He greater than Ar greater than N2) among the three gases. Based on the predicted gas exchange rates, transient increases or decreases in total inert gas pressure would be expected to occur during these experimental conditions. Because of differences in gas potencies, DCS risk may not directly follow the changes in total inert gas pressure. In fact, a decline in predicted DCS risk may occur even as total inert gas pressure in increasing.     

Bubble formation in crustaceans following decompression from hyperbaric gas exposures

In vivo bubble formation was studied in various crustaceans equilibrated with high gas pressures and rapidly decompressed to atmospheric pressure. The species varied widely in susceptibility to bubble formation, and adults were generally more susceptible than larval stages. Bubbles did not form in early brine shrimp larvae unless equilibration pressures of at least 175 atm argon or 350 atm helium were used; for adult brine shrimp, copepods, and the larvae of crabs and shrimps, 100-125 atm argon or 175-225 atm helium were required. In contrast, bubbles formed in the leg joints of megalopa and adult crabs following decompression from only 3-10 atm argon; stimulation of limb movements increased this bubble formation, whereas inhibition of movements decreased it. High hydrostatic compressions applied before gas equilibration or slow compressions did not affect bubble formation. We concluded that circulatory systems, musculature, and storage lipids do not necessarily render organisms susceptible to bubble formation and that bubbles do not generally originate as preformed nuclei. In some cases, tribonucleation appears to be the cause of the bubbles.     

Influence of priming exercise on pulmonary O2 uptake kinetics during transitions to high-intensity exercise from an elevated baseline.

It has been suggested that the slower O2 uptake (VO2) kinetics observed when exercise is initiated from an elevated baseline metabolic rate are linked to an impairment of muscle O2 delivery. We hypothesized that "priming" exercise would significantly reduce the phase II time constant (tau) during subsequent severe-intensity cycle exercise initiated from an elevated baseline metabolic rate. Seven healthy men completed exercise transitions to 70% of the difference between gas exchange threshold (GET) and peak VO2 from a moderate-intensity baseline (90% GET) on three occasions in each of the "unprimed" and "primed" conditions. Pulmonary gas exchange, heart rate, and the electromyogram of m. vastus lateralis were measured during all tests. The phase II VO2 kinetics were slower when severe exercise was initiated from a baseline of moderate exercise compared with unloaded pedaling (mean+/-SD tau, 42+/-15 vs. 33+/-8 s; P<0.05), but were not accelerated by priming exercise (42+/-17 s; P>0.05). The amplitude of the VO2 slow component and the change in electromyogram from minutes 2 to 6 were both significantly reduced following priming exercise (VO2 slow component: from 0.47+/-0.09 to 0.27+/-0.13 l/min; change in integrated electromyogram between 2 and 6 min: from 51+/-35 to 26+/-43% of baseline; P<0.05 for both comparisons). These results indicate that the slower phase II VO2 kinetics observed during transitions to severe exercise from an elevated baseline are not altered by priming exercise, but that the reduced VO2 slow component may be linked to changes in muscle fiber activation.     

Muscle capillary blood flow kinetics estimated from pulmonary O2 uptake and near-infrared spectroscopy.

The near-infrared spectroscopy (NIRS) signal (deoxyhemoglobin concentration; [HHb]) reflects the dynamic balance between muscle capillary blood flow (Q(cap)) and muscle O(2) uptake (Vo(2)(m)) in the microcirculation. The purposes of the present study were to estimate the time course of Q(cap) from the kinetics of the primary component of pulmonary O(2) uptake (Vo(2)(p)) and [HHb] throughout exercise, and compare the Q(cap) kinetics with the Vo(2)(p) kinetics. Nine subjects performed moderate- (M; below lactate threshold) and heavy-intensity (H, above lactate threshold) constant-work-rate tests. Vo(2)(p) (l/min) was measured breath by breath, and [HHb] (muM) was measured by NIRS during the tests. The time course of Q(cap) was estimated from the rearrangement of the Fick equation [Q(cap) = Vo(2)(m)/(a-v)O(2), where (a-v)O(2) is arteriovenous O(2) difference] using Vo(2)(p) (primary component) and [HHb] as proxies of Vo(2)(m) and (a-v)O(2), respectively. The kinetics of [HHb] [time constant (tau) + time delay [HHb]; M = 17.8 +/- 2.3 s and H = 13.7 +/- 1.4 s] were significantly (P < 0.001) faster than the kinetics of Vo(2) [tau of primary component (tau(P)); M = 25.5 +/- 8.8 s and H = 25.6 +/- 7.2 s] and Q(cap) [mean response time (MRT); M = 25.4 +/- 9.1 s and H = 25.7 +/- 7.7 s]. However, there was no significant difference between MRT of Q(cap) and tau(P)-Vo(2) for both intensities (P = 0.99), and these parameters were significantly correlated (M and H; r = 0.99; P < 0.001). In conclusion, we have proposed a new method to noninvasively approximate Q(cap) kinetics in humans during exercise. The resulting overall Q(cap) kinetics appeared to be tightly coupled to the temporal profile of Vo(2)(m).     

Continuous measurement of gas uptake and elimination in anesthetized patients using an extractable marker gas.

Measurement of pulmonary gas uptake and elimination is often performed, using nitrogen as marker gas to measure gas flow, by applying the Haldane transformation. Because of the inability to measure nitrogen with conventional equipment, measurement is difficult during inhalational anesthesia. A new method is described, which is compatible with any inspired gas mixture, in which fresh gas and exhaust gas flows are measured using carbon dioxide as an extractable marker gas. A system was tested in eight patients undergoing colonic surgery for automated measurement of uptake of oxygen, nitrous oxide, isoflurane, and elimination of carbon dioxide with this method. Its accuracy and precision were compared with simultaneous measurements made with the Haldane transformation and corrected for predicted nitrogen excretion by the lungs. Good agreement was obtained for measurement of uptake or elimination of all gases studied. Mean bias was -0.003 l/min for both oxygen and nitrous oxide uptake, -0.0002 l/min for isoflurane uptake, and 0.003 l/min for carbon dioxide elimination. Limits of agreement lay within 30% of the mean uptake rate for nitrous oxide, within 15% for oxygen, within 10% for isoflurane, and within 5% for carbon dioxide. The extractable marker gas method allows accurate and continuous measurement of gas uptake and elimination in an anesthetic breathing system with any inspired gas mixture.     

Acclimatization to neurological decompression sickness in rabbits

Diving acclimatization refers to a reduced susceptibility to acute decompression sickness (DCS) in individuals undergoing repeated compression-decompression cycles. We demonstrated in a previous study that the mechanism responsible for this acclimatization is similar to that of stress preconditioning. In this study, we investigated the protective effect of prior DCS preconditioning on the severity of neurological DCS in subsequent exposure to high pressure in rabbits. We exposed the rabbits (n = 10) to a pressure cycle of 6 absolute atmospheres (ATA) for 90 min, which induced signs of neurological DCS in 60% of the animals. Twenty-four hours after the pressure cycle, rabbits with DCS expressed more heat-shock protein 70 (HSP70) in the lungs, liver, and heart than rabbits without signs of disease or those in the control group (n = 6). In another group of rabbits (n = 24), 50% of animals presented signs of neurological DCS after exposure to high pressure, with a neurological score of 46.5 (SD 19.5). A course of hyperbaric oxygen therapy alleviated the signs of neurological DCS and ensured the animals' survival for 24 h. Experiencing another pressure cycle of 6 ATA for 90 min, 50% of 12 rabbits with prior DCS preconditioning developed signs of DCS, with a neurological score of 16.3 (SD 28.3), significantly lower than that before hyperbaric oxygen therapy (P = 0.002). In summary, our results show that the occurrence of DCS in rabbits after rapid decompression is associated with increased expression of a stress protein, indicating that the stress response is induced by DCS. This phenomenon was defined as "DCS preconditioning." DCS preconditioning attenuated the severity of neurological DCS caused by subsequent exposure to high pressure. These results suggest that bubble formation in tissues activates the stress response and stress preconditioning attenuates tissue injury on subsequent DCS stress, which may be the mechanism responsible for diving acclimatization.     

Biophysical basis for inner ear decompression sickness.

Isolated inner ear decompression sickness (DCS) is recognized in deep diving involving breathing of helium-oxygen mixtures, particularly when breathing gas is switched to a nitrogen-rich mixture during decompression. The biophysical basis for this selective vulnerability of the inner ear to DCS has not been established. A compartmental model of inert gas kinetics in the human inner ear was constructed from anatomical and physiological parameters described in the literature and used to simulate inert gas tensions in the inner ear during deep dives and breathing-gas substitutions that have been reported to cause inner ear DCS. The model predicts considerable supersaturation, and therefore possible bubble formation, during the initial phase of a conventional decompression. Counterdiffusion of helium and nitrogen from the perilymph may produce supersaturation in the membranous labyrinth and endolymph after switching to a nitrogen-rich breathing mixture even without decompression. Conventional decompression algorithms may result in inadequate decompression for the inner ear for deep dives. Breathing-gas switches should be scheduled deep or shallow to avoid the period of maximum supersaturation resulting from decompression.     

Secretagogue-induced changes in system A amino acid transport in the rat exocrine pancreas: stimulation of 2-methylaminoisobutyric acid efflux by carbachol

Secretagogue-induced changes in exocrine pancreatic amino acid transport are poorly understood. In this study uptake of the specific non-metabolized System A amino acid analogue 2-methylaminoisobutyric acid (2-MeAIB) was measured in the isolated perfused rat pancreas during 60 min loading with D-[3H]mannitol (extracellular tracer) and 2-[14C]MeAIB. Tracer 2-MeAIB reached a maximal uptake of 37 +/- 4% (n = 4) after 3 min of loading and gradually decreased to a steady-state uptake of 13 +/- 1%. Infusion of carbachol (3.10(-7) M) during the tracer loading period abolished net tracer 2-MeAIB uptake, and reperfusion in the absence of carbachol restored net uptake to the prestimulus value. Less than 41% of the arterial 2-[14C]MeAIB or D-[3H]mannitol activity appeared in the basal pancreatic secretion. Carbachol evoked a 4.8-fold increase in pancreatic juice flow and appeared to reduce the activity of both tracers in the exocrine secretion. During washout of the pancreas with an isotope-free medium 2-[14C]MeAIB cleared from a rapidly exchanging pool with a time constant (tau 1) of 1.4 +/- 0.3 min (n = 4) and a more slowly exchanging pool with a time constant (tau 2) of 20.7 +/- 1.1 min. Carbachol accelerated efflux of 2-[14C]MeAIB from the epithelium but had no effect on the slow phase of D-[3H]mannitol washout. Our findings suggest that activation of cholinergic receptors modifies Na+-dependent System A amino acid transport in the basolateral membrane of the exocrine pancreatic epithelium.     

Assessing recruitment of lung diffusing capacity in exercising guinea pigs with a rebreathing technique.

Noninvasive techniques for assessing cardiopulmonary function in small animals are limited. We previously developed a rebreathing technique for measuring lung volume, pulmonary blood flow, diffusing capacity for carbon monoxide (Dl(CO)) and its components, membrane diffusing capacity (Dm(CO)) and pulmonary capillary blood volume (Vc), and septal volume, in conscious nonsedated guinea pigs at rest. Now we have extended this technique to study guinea pigs during voluntary treadmill exercise with a sealed respiratory mask attached to a body vest and a test gas mixture containing 0.5% SF(6) or Ne, 0.3% CO, and 0.8% C(2)H(2) in 40% or 98% O(2). From rest to exercise, O(2) uptake increased from 12.7 to 25.5 ml x min(-1) x kg(-1) while pulmonary blood flow increased from 123 to 239 ml/kg. The measured Dl(CO), Dm(CO), and Vc increased linearly with respect to pulmonary blood flow as expected from alveolar microvascular recruitment; body mass-specific relationships were consistent with those in healthy human subjects and dogs studied with a similar technique. The results show that 1) cardiopulmonary interactions from rest to exercise can be measured noninvasively in guinea pigs, 2) guinea pigs exhibit patterns of exercise response and alveolar microvascular recruitment similar to those of larger species, and 3) the rebreathing technique is widely applicable to human ( approximately 70 kg), dog (20-30 kg), and guinea pig (1-1.5 kg). In theory, this technique can be extended to even smaller animals provided that species-specific technical hurdles can be overcome.     

Predicting risk of decompression sickness in humans from outcomes in sheep.

In animals, the response to decompression scales as a power of species body mass. Consequently, decompression sickness (DCS) risk in humans should be well predicted from an animal model with a body mass comparable to humans. No-stop decompression outcomes in compressed air and nitrogen-oxygen dives with sheep (n = 394 dives, 14.5% DCS) and humans (n = 463 dives, 4.5% DCS) were used with linear-exponential, probabilistic modeling to test this hypothesis. Scaling the response parameters of this model between species (without accounting for body mass), while estimating tissue-compartment kinetic parameters from combined human and sheep data, predicts combined risk better, based on log likelihood, than do separate sheep and human models, a combined model without scaling, and a kinetic-scaled model. These findings provide a practical tool for estimating DCS risk in humans from outcomes in sheep, especially in decompression profiles too risky to test with humans. This model supports the hypothesis that species of similar body mass have similar DCS risk.     

Ventilatory and gas exchange kinetics during exercise in chronic airways obstruction

The influence of chronic obstructive pulmonary disease (COPD) on exercise ventilatory and gas exchange kinetics was assessed in nine patients with stable airway obstruction (forced expired volume at 1 s = 1.1 +/- 0.33 liters) and compared with that in six normal men. Minute ventilation (VE), CO2 output (VCO2), and O2 uptake (VO2) were determined breath-by-breath at rest and after the onset of constant-load subanaerobic threshold exercise. The initial increase in VE, VCO2, and VO2 from rest (phase I), the subsequent slow exponential rise (phase II), and the steady-state (phase III) responses were analyzed. The COPD group had a significantly smaller phase I increase in VE (3.4 +/- 0.89 vs. 6.8 +/- 1.05 liters/min), VCO2 (0.10 +/- 0.03 vs. 0.22 +/- 0.03 liters/min), VO2 (0.10 +/- 0.03 vs. 0.24 +/- 0.04 liters/min), heart rate (HR) (6 +/- 0.9 vs. 16 +/- 1.4 beats/min), and O2 pulse (0.93 +/- 0.21 vs. 2.2 +/- 0.45 ml/beat) than the controls. Phase I increase in VE was significantly correlated with phase I increase in VO2 (r = 0.88) and HR (r = 0.78) in the COPD group. Most patients also had markedly slower phase II kinetics, i.e., longer time constants (tau) for VE (87 +/- 7 vs. 65 +/- 2 s), VCO2 (79 +/- 6 vs. 63 +/- 3 s), and VO2 (56 +/- 5 vs. 39 +/- 2 s) and longer half times for HR (68 +/- 9 vs. 32 +/- 2 s) and O2 pulse (42 +/- 3 vs. 31 +/- 2 s) compared with controls. However, tau VO2/tau VE and tau VCO2/tau VE were similar in both groups. The significant correlations of the phase I VE increase with HR and VO2 are consistent with the concept that the immediate exercise hyperpnea has a cardiodynamic basis. The slow ventilatory kinetics during phase II in the COPD group appeared to be more closely related to a slowed cardiovascular response rather than to any index of respiratory function. O2 breathing did not affect the phase I increase in VE but did slow phase II kinetics in most subjects. This confirms that the role attributed to the carotid bodies in ventilatory control during exercise in normal subjects also operates in patients with COPD.