The measurement of cardia output by the thoracic impedance method

The aim of our experiments was to study the thoracic electrical impedance method as a method for measuring cardiac output in anesthetized dogs. Four electrodes were placed around the neck and thorax. A 50 kHz, 1 mA electric current was applied to the outer two electrodes and the two inner electrodes were used to measure impedance changes related to the stroke volume during the cardiac cycle at end-expiratory apnea. The cardiac output obtained by the impedance method was compared to the cardiac output measured by isotope dilution and by the electromagnetic flowmeter. Either mean cardiac output or cardiac output determined beat-to-beat from the pulsatile flow was measured with the latter method. Significant correlations were obtained between the impedance and the isotope dilution method (r = 0.8799), and between the impedance and the electromagnetic (mean) flow measurements (r = 0.7330). The comparison of impedance cardiac output to that determined from the pulsatile flow (beat-to-beat) also showed a good correlation (r = 0.7618). The effect of changing the fluid and air contents in the chest on the basal thoracic impedance was also studied.     

Non-invasive assessment of cardiac output and stroke volume in patients during exercise. Evaluation of a CO2-rebreathing method

A one-step CO2 rebreathing method for the determination of cardiac output and stroke volume (SV) has been evaluated by comparison with the direct Fick technique during recumbent exercise (10-90 W) in 13 patients. In an initial analysis, the influence of different rebreathing times and of correction for haemoglobin concentration was studied. The best correlation with the direct Fick technique was obtained with the longest analysis time, i.e. 21 s, and correction for variations in haemoglobin concentration further improved the correlation. Consequently, an analysis time of 21 s and correction for haemoglobin have been used. At low cardiac outputs, the CO2-rebreathing method overestimated the flow compared to the Fick technique. The correlation between the methods, however, was so good that a valid estimate of cardiac output could be obtained from the CO2 rebreathing method with appropriate corrections (Cardiac output, CO2 method = 2.7 + 0.77. Cardiac output, Fick; r = 0.91; Residual Standard deviation (SD res) = 0.77 l X min-1). Stroke volumes measured with the CO2 rebreathing method did not differ significantly from those obtained with the direct Fick technique, although there was a tendency to overestimate stroke volume with the CO2 rebreathing method (SV, CO2 method = 12 + 0.89 X SV, Fick; r = 0.82; SD res = 11 ml).     

CARDIAC OUTPUT DURING CARDIOPULMONARY BYPASS—Animal Experiments as a Guide to Flow Rate

Superior total body perfusion during cardiopulmonary bypass in dogs is achieved by duplicating, in each individual case, the actual operative cardiac output, rather than by relying on the currently recommended perfusion flow rates.A highly accurate method of measuring the cardiac output is presented using the gated sinewave electromagnetic flowmeter. Simplicity and sensitivity of the method enable the operator to measure the flow in situ (in the intact canine ascending aorta) and thus to determine a truly representative cardiac output before the cardiopulmonary bypass is effected.An adjustable hydraulic pump in conjunction with the electromagnetic flowmeter is used to substitute the natural cardiac action in order to maintain the normal hemodynamic state by providing a pulsatile flow of proper magnitude. The procedure is technically simple and, supported by favorable experimental evidence, is recommended for clinical use in open heart operations.     

New method of cardiac output measurement using ultrasound velocity dilution in rats.

The aim of this study was to validate a new technique for the measurement of cardiac output (CO) based on ultrasound and dilution (COUD) in anesthetized rats. A transit time ultrasound (TTU) probe was placed around the rat carotid artery, and ultrasound velocity dilution curves were generated on intravenous injections of saline. CO by COUD were calculated from the dilution curves for normal and portal hypertensive rats in which CO was known to be increased. COUD was compared with the radiolabeled microsphere method and with direct aortic TTU flowmetry for baseline CO and drug-induced CO variations. CO in direct aortic TTU flowmetry was the ascending aorta blood flow measured directly by TTU probe (normal use of TTU flowmetry). The reproducibility of COUD within the same animal was also determined under baseline conditions. COUD detected the known CO increase in portal hypertensive rats compared with normal rats. CO values by COUD were correlated with those provided by microsphere technique or direct aortic TTU flowmetry (adjusted r = 0.76, P < 10(-4) and r = 0.79, P < 0.05, respectively). Baseline CO values and terlipressin-induced CO variations were detected by COUD and the other techniques. Intra- and interobserver agreements for COUD were excellent (intraclass r = 0.99 and 0.98, respectively). COUD was reproducible at least 10 times in 20 min. COUD is an accurate and reproducible method providing low-cost, repetitive CO measurements without open-chest surgery. It can be used in rats as an alternative to the microsphere method and to direct aortic flowmetry.     

Evidence for increased hepatic sympathetic nerve activity resulting in hyperglycemia in response to hemorrhage-induced reflex stimulation in anesthetized dogs

To investigate the role of the sympathoadrenal system in glucose mobilization by the liver during hemorrhage, catecholamine (CA) output from both adrenal glands was determined in anesthetized dogs. Venous blood draining from both adrenal glands was combined in a Y-tube that was connected to an electromagnetic flow probe to measure total adrenal venous blood flow. Plasma concentrations of norepinephrine (NE), epinephrine (E), dopamine (DA), and glucose (GL) were determined in various vascular regions. Adrenal CA output (nanograms per minute) under basal conditions was 50.2 +/- 13.6, 181.4 +/- 41.9, and 13.7 +/- 4.8 for NE, E, and DA, respectively. These values were found to increase significantly (P less than 0.05) in response to 5 min of hemorrhage, reaching a maximum output (nanograms per minute) of 663.6 +/- 160.6 (NE), 2503.4 +/- 607.8 (E), and 141.7 +/- 43.7 (DA). Aortic CAs (nanograms per millilitre) increased significantly with a predominant increase in E (0.33 +/- 0.08 to 3.75 +/- 1.03, P less than 0.05). In contrast, increases in portal and hepatic venous CAs (nanograms per millilitre) were characterized by a predominant increase in NE (0.30 +/- 0.06 to 0.64 +/- 0.11 and 0.17 +/- 0.02 to 0.31 +/- 0.07, respectively, P less than 0.05). Hepatic venous and aortic GL concentrations also increased significantly during hemorrhage. Among the various correlations between plasma CA and GL concentrations, the strongest correlation was found between hepatic venous NE and hepatic venous GL (r = 0.804, P less than 0.001). Correlation coefficients obtained with aortic NE and E were weaker but significant (r = 0.603 and r = 0.608, respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the method of blood extraction on plasma levels of renin in the Wistar rat

To investigate the influence of blood extraction conditions on the renin-angiotensin system in rats, plasma renin activity (PRA) and plasma renin concentration (PRC) were measured in blood samples obtained by different methods. PRA and PRC in samples obtained by chronic catheterization, cardiac puncture without anesthesia, and decapitation immediately following light ether anesthesia were not significantly different from those obtained by simple decapitation (control group). In contrast, PRA and PRC in samples obtained by cardiac puncture and cavernous sinus puncture after light ether anesthesia were significantly (p less than 0.01) higher than those obtained in the control group. There was a significant direct correlationship between PRA and PRC in all samples studied (r = 0.87, p less than 0.001). The present results suggest that light ether anesthesia increases renin levels, except when blood samples are taken by decapitation, and that chronic catheterization and cardiac puncture are the choice blood extraction methods to evaluate the renin-angiotensin system in rats.     

Separate hemodynamic roles for chloride and sodium in deoxycorticosterone acetate-salt hypertension

It has been reported that both sodium and chloride ions must be ingested to induce the elevated blood pressure of deoxycorticosterone acetate (DOCA)-salt-sensitive hypertension. This study was designed to determine the separate roles of the sodium and chloride ions in the altered hemodynamics underlying the high blood pressure. DOCA pellets (75 mg) were implanted in uninephrectomized rats and the animals were then fed one of four diets: (i) high sodium chloride, (ii) high sodium-low chloride, (iii) high chloride-low sodium, or (iv) low sodium chloride. Blood pressures were measured weekly by tail-cuff plethysmography for 5 weeks and the animals were then subjected to a terminal experiment to measure cardiac output by thermodilution technique, renal blood flow by electromagnetic flow probe, and direct arterial pressure. Blood pressure in the DOCA-high NaCl group was significantly greater (P less than 0.05) compared with that of the DOCA-low NaCl group (160 +/- 3 mm Hg vs 124 +/- 2 mm Hg, respectively) at 5 weeks after treatment; all other groups were not significantly different from the DOCA-low NaCl group. Cardiac output was significantly greater in DOCA-treated rats consuming diets high in sodium (44 +/- 2 ml/min/100 g) or sodium chloride (40 +/- 2 ml/min/100 g) compared with animals consuming low sodium chloride (31 +/- 2 ml/min/100 g; P less than 0.01 for each comparison). Direct intraarterial blood pressure and renal blood flow were used to calculate renal vascular resistance. Renal vascular resistance was increased in those DOCA-treated rats consuming diets high in chloride (42 +/- 3 mm Hg/ml/min/100 g) and high sodium chloride (54 +/- 3 mm Hg/ml/min/100 g) compared with rats consuming low sodium chloride (30 +/- 3 mm Hg/ml/min/100 g; P less than 0.01 for each). It appears that elevations in cardiac output are associated with increased dietary sodium and act in synergy with the elevations in renal vascular resistance associated with increased dietary chloride. Increases in both cardiac output and renal vascular resistance are involved in the maintenance of elevated blood pressure in the DOCA-salt-sensitive model of hypertension.     

Increased plasma brain natriuretic peptide levels in DOCA-salt hypertensive rats: relation to blood pressure and cardiac concentration

Four experimental groups of rats treated with (1) DOCA-salt, (2) DOCA or (3) salt, and (4) controls were used to study the participation of brain natriuretic peptide (BNP) in the development of hypertension. Plasma and cardiac tissue concentrations of BNP as well as atrial natriuretic peptide (ANP) were measured in each group by using radioimmunoassays specific to rat BNP or ANP. Plasma BNP levels in DOCA-salt hypertensive group were higher than those in control (p less than 0.01), salt (p less than 0.01) and DOCA (p less than 0.01) groups. A positive correlation was observed between plasma BNP levels and blood pressure (r = 0.70, p less than 0.001) and between plasma ANP levels and blood pressure (r = 0.62, p less than 0.001). Plasma BNP/ANP ratio increased parallel with elevation of blood pressure. Plasma BNP levels correlated negatively with atrial BNP concentration (r = -0.33, p less than 0.05), but positively with ventricular BNP (r = 0.76, p less than 0.001). Compared with controls, tissue BNP-45/gamma-BNP ratio in the DOCA-salt rats was lower in atrium, but higher in ventricle. Thus, in DOCA-salt hypertension atrial BNP decreased with exhaustion of stored BNP-45, while ventricular BNP increased as BNP-45 accumulated. These results suggest that BNP is a novel cardiac hormone, synthesized, processed and secreted in response to changes in blood pressure. BNP may play different roles in controlling blood pressure than those assumed by ANP.     

Noninvasive Doppler determination of cardiac output during submaximal and peak exercise

We compared pulsed Doppler (PD) measurements of stroke volume (SV) and cardiac output (CO) as a function of work load with previously reported values that were obtained by standard invasive methods. Suprasternal notch measurements of Doppler-shifted frequency (delta f) were obtained from the ascending aorta and SV calculated with the Doppler equation and an independent measurement of aortic diameter. Motion artifacts were minimized with the aid of a restraining table cycle ergometer. Signal aliasing was accommodated with manual summation of delta f waveforms. A total of 207 determinations were made in 10 sitting subjects exercising to exhaustion. Linear regression analysis of CO vs. work load was significant (P less than 0.001). The correlation coefficient (r = 0.95) and standard error of estimate value (1.21 1/min) were similar to values from the literature. Absolute values of CO and SV underestimated the literature values across all work loads. Technical reproducibility was assessed by comparing with paired t tests the differences between 65 duplicate serial measurements of CO and SV at rest and exercise. No significant differences (P less than 0.001) were found. We concluded that PD-determined SV and CO are reproducible and correlate linearly with work load in a manner consistent with reported invasive techniques. Thus the PD method appears suitable for use during submaximal and peak exercise.     

Cardiac content of brain natriuretic peptide in DOCA salt-hypertensive rats

The cardiac content of immunoreactive rat brain natriuretic peptide (ir-rBNP) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats was measured by radioimmunoassay (RIA). The atrial content of ir-rBNP was significantly lower in the DOCA-salt group than in the control group (p less than 0.01). However, the ventricular content of ir-rBNP was markedly increased in the DOCA-salt group as compared to the other groups. Ir-rBNP level in the atria was negatively correlated with other groups. Ir-rBNP level in the atria was negatively correlated with blood pressure (r = -0.49, p less than 0.01), while that in the ventricle was positively correlated with blood pressure (r = 0.79, p less than 0.001). A significant correlation was observed between tissue levels of ir-rBNP and ir-rat atrial natriuretic peptide (rANP) both in atrium and ventricle (atrium, r = 0.63, p less than 0.001; ventricle, r = 0.95, p less than 0.001). These results raise the possibility that rBNP as well as rANP functions as a cardiac hormone, the production of which probably changes in response to increased of body fluid and blood pressure.     

Recent Advances in Hypertension

The possible relationship between the renal mechanism of volume control and blood pressure regulation is discussed. Expansion of the extracellular fluid (ECF) and plasma volumes was demonstrated following renal artery constriction in the rat; after about one month ECF volume returned to normal although hypertension persisted. Measurements of cardiac output in the unanesthetized rat by an implanted electromagnetic flowmeter showed an initial rise in cardiac output after renal artery constriction, returning to normal in 10 to 15 days. A homeostatic hypothesis for the production of renal hypertension is put forward in which changes in ECF volume, capacity vessel tone and myocardial contractility participate in the development of hypertension by elevating cardiac output. Autoregulation of peripheral flow then occurs and the consequent restoration of blood pressure at a renal pressure receptor results in return to normal of cardiac output by negative feedback. Thus in chronic hypertension the high peripheral resistance is maintained by autoregulation.     

Blood selenium and glutathione peroxidase activity of populations in New Zealand, Oregon, and South Dakota

The relationship of whole blood selenium (Se) to glutathione peroxidase (GPX) activity was examined for individuals in New Zealand, Oregon, and South Dakota who represented, respectively, populations with exposure to low, medium, and high amounts of Se. The mean (respective) blood Se levels were 60, 200, and 400 ng/ml. Intergroup differences in blood Se levels were highly significant (P less than 0.001). GPX assays were performed using two variations of an enzyme-coupled procedure to assess the equivalence of the two methods. Despite a fourfold difference in absolute activities measured by these methods, the GPX activities were highly correlated (r = .86) between procedures. Average blood GPX activity was significantly lower (P less than 0.001) for the New Zealand group compared with the other two groups, but there was no difference in GPX activities between the Oregon and South Dakota groups. Linear regression of GPX vs. Se values within each group indicated a significant correlation of these parameters only in the New Zealand group (r = .46, P less than 0.01). Comparison of these parameters for combined data from all three groups also showed a significant positive correlation (r = .60, P less than 0.001). A saturation model (In GPX = k1 + k2 (Se)-1)) fits the combined data better (r = .80, P less than 0.01) than does direct comparison of the two parameters. These results suggest that GPX activity is an appropriate indicator of human Se status only in populations with below normal exposure to Se, as activity of this enzyme is saturated at relatively low levels.     

Advantages of perfluorochemical perfusion in the isolated working rabbit heart preparation using 31P-NMR

Quantitative 31P-NMR and enzymatic analysis of high-energy phosphates were used to characterize an isolated perfused working rabbit heart preparation. In this model, the left side of the heart works against a physiological after-load. Two perfusates, Krebs-Henseleit saline and the perfluorocarbon emulsion FC-43 (perfluorotributylamine), were evaluated in their ability to maintain cardiac function and high-energy phosphate metabolites over a period of 2-3 h. Adenine nucleotides ATP, ADP, phosphocreatine and inorganic phosphate (Pi) were measured by 31P-NMR while monitoring cardiac output and coronary flow. Intracellular pH was determined using the chemical shift of Pi. At the end of each experiment, hearts were freeze clamped and enzymatically assayed for adenine nucleotides, phosphocreatine and Pi. In every experiment, hearts perfused with FC-43 emulsion maintained the same rate of cardiac output as hearts perfused with Krebs-Henseleit saline, but with half the coronary flow rate: FC-43, 22 +/- 2.5 (n = 5), Krebs-Henseleit saline 42 +/- 2.7 (n = 6) ml/min, P less than 0.001. Hearts perfused with FC-43 emulsion showed higher [phosphocreatine] and [ATP] measured by 31P-NMR. For [phosphocreatine]: FC-43 3.2 +/- 0.7 (n = 5), Krebs-Henseleit saline 1.7 +/- 0.2 (n = 6) mumol/g wet wt., P less than 0.01. For [ATP]: FC-43 1.8 +/- 0.7 (n = 5), Krebs-Henseleit saline 0.9 +/- 0.2 (n = 6) mumol/g wet wt., P less than 0.02. [phosphocreatine] and [ATP] determined by 31P-NMR values were identical within experimental error to those values obtained by enzymatic analysis. Comparing [Pi] determined by both methods, 36% of Pi in FC-43-perfused hearts, and only 24% of Pi in Krebs-Henseleit saline-perfused hearts were visible by NMR, indicating that a large proportion of Pi is bound in the intact functioning heart. Similar results were obtained for [ADP]. Using the combined techniques of 31P-NMR and enzymatic assay, we have shown in this model of the isolated working rabbit heart preparation, that FC-43 emulsion maintains significantly better function and high-energy phosphate levels than Krebs-Henseleit saline.     

Cardiac output in exercise by impedance cardiography during breath holding and normal breathing

Estimation of cardiac output by impedance cardiography (QZ) in exercise during normal breathing (NB) has been limited by motion artifact. Our objective was to obtain readable impedance cardiograms on five subjects during upright cycle exercise at 0, 50, 100, 150, and 200 W to permit comparisons of QZ during NB, expiratory breath hold (EXP) and inspiratory breath hold (INSP). Q was also determined using an equilibration CO2 rebreathing method [Q(RB)]. QZ during NB exceeded EXP QZ at 100, 150, and 200 W, and exceeded INSP QZ at 100 W (P less than 0.05). The low EXP QZ values were due to a significantly lower stroke volume at 100, 150, and 200 W (P less than 0.05). For the INSP QZ at 100 W, heart rate was lower than during EXP (P less than 0.05). Regression of QZ (NB) against Q(RB) resulted in a linear relationship (r = 0.93) over the range of Q = 7-26 1/min. The slope of the regression differed significantly from 1.0 (P less than 0.05). We conclude that QZ values obtained during EXP or INSP should not be assumed to represent QZ during NB, at least at work rates greater than 50 W. A consequence of the linear relationship between QZ(NB) and Q(RB) over the range of 0-200 W is that estimates of CO2 rebreathing cardiac output can be obtained by impedance cardiography if QZ is adjusted using an appropriate empirical factor.     

Organ blood flow and cardiac contractility in anaesthetized cats at 5 bar (500 kPa) ambient pressure

Previous in vivo and in vitro experiments have demonstrated increased cardiac contractility and increased total myocardial blood flow (Qmyocardial) when rats were exposed to normoxic 5-bar (500 kPa) ambient pressure. In the present study, regional blood flow was measured using the microsphere method on nine anaesthetized cats at surface and normoxic 5-bar (500 kPa) ambient pressure. Left ventricular pressure (LVP) and cardiac contractility, measured as peak left ventricular +dP/dt and -dP/dt were measured in six of the cats. Arterial pressure, heart rate and cardiac output remained unchanged after compression, but total Qmyocardial increased by 29% (P less than 0.01) and cerebral blood flow increased by 66% (P less than 0.05). At the same time +dP/dt and -dP/dt was increased by 83% and 102%, respectively (P less than 0.01), while LVP was enhanced by 14% (P less than 0.05). Except for a moderate decrease in partial pressure of oxygen, acid base status in arterial blood remained unchanged. The results indicate that the effects of increased ambient pressure on the heart are general physiological phenomena, which are not only limited to the laboratory rat.     

Cardiac output of marmots by the thoracic impedance technique.

Baseline impedance (Z₀) and resistivity of blood were higher for marmots than reported for other species. The transthoracic impedance method was compared to dye dilution and electromagnetic flowmeter procedures for estimation of cardiac output of seven marmots at a range of flows from 40 to 400 ml/min. There was a low, positive, but significant correlation (r = 0.566) found in comparison to dye dilution at outputs measured by the impedance method exceeding 120 ml/min. Correlation was better (r = 0.905) in the comparison between impedance and flowmeter methods.It was concluded that transthoracic impedance provides data that are sufficiently accurate for chronic measurements of stroke volume and cardiac output of this species. The method has the additional advantage of supplying EGG and respiratory data without supplemental connections to the animal preparations.     

A technique of measuring cardiac output and peripheral resistance in the conscious rat

A technique for the measurement of cardiac output in the conscious rat by cardiac catherization and application of the Fick principle, with simultaneous measurement of oxygen consumption and aortic pressure, is described. In conscious rats, the cardiac index was found to be 1.5 1/min/m² and the total peripheral resistance 0.8 mm Hg/ml/min per 100g body weight.     

Plasmodium berghei: malaria infection causes increased cardiac output in rats, Rattus rattus

Thirty-two 4-week-old male Wistar rats were infected with Plasmodium berghei malaria. On Days 12 through 14, blood volume, arterial blood pressure, right ventricular pressure, heart rate, cardiac output, stroke volume, hematocrit, and vascular resistances were determined. All of the cardiovascular parameters measured, with the exception of calculated pulmonary vascular resistance, changed progressively as the peripheral blood parasitemia increased. With a rising parasitemia, cardiac output increased, despite a reduced heart rate. The highest parasitemia of 63% was accompanied by a doubling of the normal cardiac output. The relationship between parasitemia and cardiac output can be described by the equation, cardiac output = (6.14) x % parasitemia + 452 ml/min/kg. The mean arterial blood pressure was lower than controls when parasitemia exceeded 20%, whereas systolic right ventricular pressure was elevated only at the highest parasitemias. When noninfected control rats were compared with those animals having parasitemias greater than 40%, in the infected animals, mean arterial pressure was 28% lower (P less than 0.01) and systolic right ventricular pressure rose by 21% (P less than 0.02). A 50% decline was observed in the total peripheral vascular resistance (P less than 0.01), although the pulmonary resistance was apparently unchanged. With P. berghei infection, there is also a marked anemia, an increase in plasma volume, and a 16% increase in blood volume (% body weight). It is concluded from these results that although the hemodynamic changes previously reported in the literature indicate that infection with malaria may result in focal blockages in microvessels and poor tissue perfusion, the total systemic effect, in the rat, is an increase in cardiac output secondary to a reduced peripheral resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pressure-flow relations of diaphragm and vital organs with nitroprusside-induced vasodilatation

We determined maximal conductance in the diaphragm and other vital organs in 14 anesthetized dogs, weighing 22.8 +/- 4.2 kg, which were given maximal vasodilating doses of nitroprusside (mean dose 13.9 +/- 4.3 micrograms X kg-1 X min-1) and the blood pressure was lowered in stages by hemorrhage. Blood flow in the diaphragm, brain, heart, kidney, gut, and quadriceps was measured with radiolabeled microspheres. To ensure maximal vasodilatation of diaphragmatic vessels, we stimulated the phrenic nerves to produce diaphragmatic contractions at 0.3 Hz. The mean cardiac output was 2.13 +/- 0.42 l/min (thermodilution) before nitroprusside and 4.68 +/- 1.45 after (P less than 0.001). Nitroprusside failed to break the autoregulation of the brain. Pressure-flow relations (P-F) in other regions were linear (r = 0.70 +/- 0.03, P less than 0.001) and blood pressure at zero flow (X-intercept) was always greater than venous pressure (diaphragm = 11, kidney = 19, heart = 8, gut = 8, quadriceps = 32 mmHg). The flow to the diaphragm (Qdi) could be predicted by Qdi (ml X min-1 X g-1) = [(3.13 +/- 0.56) X Pa X 10(-2)] -0.52 (r = 0.71), where Pa is mean arterial pressure. The maximal vascular conductance (i.e., slope of the P-F relation) of the diaphragm was 27% of the conductance in the kidney, 87% of the value in the gut, and 42% of that in the heart. In conclusion the maximal diaphragmatic blood flow at a given blood pressure is much larger when the muscle is stimulated than is observed in spontaneously breathing animals.     

Linkage between brain blood flow and respiratory drive during rapid-eye-movement sleep

The correlation between brain blood flow (BBF) and respiratory neuromotor output, as reflected by diaphragmatic electromyogram (EMG) activity (EMGdi), was studied during wakefulness, rapid-eye-movement (REM) sleep, and non-REM sleep (NREM). Compared with the awake state, mean BBF increased by 4.7% during NREM and by 32.6% during REM (P less than 0.001). Also, surges of BBF during REM occurred during periods of intense phasic activity. EMGdi [peak and peak/inspiratory time (TI)] was highly variable within REM periods but fluctuated as a reciprocal function of simultaneously measured BBf (r = -0.49, P less than 0.001). Furthermore, mean EMGdipeak decreased from NREM to REM in a manner reciprocally related to the corresponding change in BBF (r = -0.77, P = 0.015). These findings suggest that a component of the reduction of respiratory neuromotor output during REM is attributable to increased BBF with consequent relative hypocapnia in the central chemoreceptor environment.