Prediction of circulatory equilibrium in response to changes in stressed blood volume

Accurate prediction of cardiac output (CO), left atrial pressure (PLA), and right atrial pressure (PRA) is a prerequisite for management of patients with compromised hemodynamics. In our previous study (Uemura et al. Am J Physiol Heart Circ Physiol 286: H2376-H2385, 2004), we demonstrated a circulatory equilibrium framework, which permits the prediction of CO, PLA, and PRA once the venous return surface and integrated CO curve are known. Inasmuch as we also showed that the surface can be estimated from single-point CO, PLA, and PRA measurements, we hypothesized that a similar single-point estimation of the CO curve would enable us to predict hemodynamics. In seven dogs, we measured the PLA-CO and PRA-CO relations and derived a standardized CO curve using the logarithmic function CO = SL[ln(PLA - 2.03) + 0.80] for the left heart and CO = SR[ln(PRA - 2.13) + 1.90] for the right heart, where SL and SR represent the preload sensitivity of CO, i.e., pumping ability, of the left and right heart, respectively. To estimate the integrated CO curve in each animal, we calculated SL and SR from single-point CO, PLA, and PRA measurements. Estimated and measured CO agreed reasonably well. In another eight dogs, we altered stressed blood volume (-8 to +8 ml/kg of reference volume) under normal and heart failure conditions and predicted the hemodynamics by intersecting the surface and the CO curve thus estimated. We could predict CO [y = 0.93x + 6.5, r2 = 0.96, standard error of estimate (SEE) = 7.5 ml.min(-1).kg(-1)], PLA (y = 0.90x + 0.5, r2= 0.93, SEE = 1.4 mmHg), and PRA (y = 0.87x + 0.4, r2= 0.91, SEE = 0.4 mmHg) reasonably well. In conclusion, single-point estimation of the integrated CO curve enables accurate prediction of hemodynamics in response to extensive changes in stressed blood volume.     

The relationship between O2 saturation mixed venous blood and pressure in the trunk of the pulmonary artery for healthy people and patients with heart defects

Investigated the relationship between pulmonary artery pressure (P(LA)) and the oxygen saturation of mixed venous blood (S(V)) in 12 group's of surveyed individuals (1750 men and 1026 women). We have identified a function (P(LA)) between P(LA) = f(S(V)), and a function (S(V)) S(V) = f(P(LA)) was estimated for each group based on direct measurements of P(LA) and S(V). We found, that factors were subordinated to the dependences for a P(LA) = f(S(V)), P(LA) = a x (S(V))(-b), where b = = -0.2284a + 0.6564 men - and b = -0.285a + 1.2947 in women and the other for -S(V) = f(P(LA)), S(V) = c x (P(LA))(-d) where d = -0.251311n(c) + 1.0212; (R2 = 0.8993) men and d = -1.96451n(c) + 2.852; (R2 = 0.9674) women. Each group occupies a position on the curves represented by equations. The subjects with a diagnosis of functional murmur in the heart and patients with congenital stenos is of the aortic valve form a group, provisionally designated as "group norms", which is characterized by its dependence P(LA) = f(S(V)), and -S(V) = f(P(LA)). The men in "group norms" additionally include patients with coronary heart disease. The equation - CO = Cons.O2/(KEK(S(A) - (c x (P(LA))(-d). It relates the P(LA), caused by different reasons, with the corresponding saturation of mixed venous blood, and when the saturation of mixed venous blood is also caused by various factors, set the corresponding P(LA). Interdependent changes in physiological parameters of blood circulation and gas exchange in humans is established equilibrium between systemic and pulmonary circulation.     

Changes in venous return parameters associated with univentricular Fontan circulations

To clarify the physiology of venous return (Q(vr)) in Fontan circulations, venous return conductance (G(vr)) and mean circulatory filling pressure (P(mcf)) were determined in pentobarbital sodium-anesthetized pigs. Relationships between Q(vr) and right (biventricular, n = 8) or left (Fontan, n = 8) filling pressures are described by straight lines with significant correlation coefficients. Estimated P(mcf) values were correlated with observed P(mcf) values in either circulations (P 相似文献   

Progesterone, 17-OH-progesterone, androstenedione and testosterone plasma levels in spermatic venous blood of normal men and varicocele patients

Progesterone (P), 17-OH-progesterone (17-OH-P), Androstenedione (delta 4) and testosterone (T) plasma levels were measured in spermatic venous blood of twenty-nine varicocele patients (V) and in twelve normal subjects (N). Our data reveal a significant decrease of the mean testosterone in the spermatic blood of varicocele patients with respect to normal controls: (N = 1708.7 +/- 223.8 (SEM) nmol/l, n = 10. V = 1190.9 +/- 101.1 (SEM) nmol/l, n = 29. P less than 0.03). An inverse correlation has been observed between the age of varicocele patients and 17-OH-P (n = 29. y = -33.38x + 1384.70, r = -0.59, P less than 0.01) and delta 4 values (n = 23, y = -1.62x + 85.65, r = -0.49, P less than 0.05). The 17-OH-P/delta 4 ratio appears significantly augmented in varicocele patients with respect to normal controls (n = 4.80 +/- 0.86 (SEM), n = 12. V = 9.65 +/- 1.21 (SEM), n = 23.0.02 greater than P greater than 0.01). This indicates a deficiency in varicocele patients of 17-20 lyase activity. The positive correlation between the P/17-OH-P ratio and age of varicocele patients (n = 28, y = 0.007 x -0.090, r = 0.45, P less than 0.03) suggests a progressive impairment of 17-alpha-hydroxylase in such patients as they grow relatively older. These data demonstrated that the reduced spermatic levels of testosterone in varicoceles are due to the enzymatic impairment of testosterone biosynthesis, concerning firstly 17-20 lyase activity and secondly 17-alpha-hydroxylase activity. The latter enzymatic impairment is age related as is seen from the significant increase of the P/17-OH-P ratio in older patients.     

Doppler echo evaluation of pulmonary venous-left atrial pressure gradients: human and numerical model studies

The simplified Bernoulli equation relates fluid convective energy derived from flow velocities to a pressure gradient and is commonly used in clinical echocardiography to determine pressure differences across stenotic orifices. Its application to pulmonary venous flow has not been described in humans. Twelve patients undergoing cardiac surgery had simultaneous high-fidelity pulmonary venous and left atrial pressure measurements and pulmonary venous pulsed Doppler echocardiography performed. Convective gradients for the systolic (S), diastolic (D), and atrial reversal (AR) phases of pulmonary venous flow were determined using the simplified Bernoulli equation and correlated with measured actual pressure differences. A linear relationship was observed between the convective (y) and actual (x) pressure differences for the S (y = 0.23x + 0.0074, r = 0.82) and D (y = 0.22x + 0.092, r = 0.81) waves, but not for the AR wave (y = 0. 030x + 0.13, r = 0.10). Numerical modeling resulted in similar slopes for the S (y = 0.200x - 0.127, r = 0.97), D (y = 0.247x - 0. 354, r = 0.99), and AR (y = 0.087x - 0.083, r = 0.96) waves. Consistent with numerical modeling, the convective term strongly correlates with but significantly underestimates actual gradient because of large inertial forces.     

Deciphering the metabolic and mechanical contributions to the exercise-induced circulatory response: insights from eccentric cycling

Metabolic demand and muscle mechanical tension are closely coupled during exercise, making their respective drives to the circulatory response difficult to establish. This coupling being altered in eccentric cycling, we implemented an experimental design featuring eccentric vs. concentric constant-load cycling bouts to gain insights into the control of the exercise-induced circulatory response in humans. Heart rate (HR), stroke volume (SV), cardiac output (Q), oxygen uptake (V(.-)(O(2))), and electromyographic (EMG) activity of quadriceps muscles were measured in 11 subjects during heavy concentric (heavy CON: 270 +/- 13 W; V(.-)(O(2)) = 3.59 +/- 0.20 l/min), heavy eccentric (heavy ECC: 270 +/- 13 W, V(.-)(O(2)) = 1.17 +/- 0.15 l/min), and light concentric (light CON: 70 +/- 9 W, V(.-)(O(2)) = 1.14 +/- 0.12 l/min) cycle bouts. Using a reductionist approach, the circulatory responses observed between heavy CON vs. light CON (difference in V(.-)(O(2)) and power output) was ascribed either to metabolic demand, as estimated from heavy CON vs. heavy ECC (similar power output, different V(.-)(O(2))), or to muscle mechanical tension, as estimated from heavy ECC vs. light CON (similar V(.-)(O(2)), different power output). 74% of the Q response was determined by the metabolic demand, also accounting for 65% and 84% of HR and SV responses, respectively. Consequently, muscle mechanical tension determined 26%, 35%, and 16% of the Q, HR, and SV responses, respectively. Q was significantly related to V(.-)(O(2)) (r(2) = 0.83) and EMG activity (r(2) = 0.82; both P < 0.001). These results suggest that the exercise-induced circulatory response is mainly under metabolic control and support the idea that the level of muscle activation plays a role in the cardiovascular regulation during cycle exercise in humans.     

Dynamic cerebral autoregulation during exhaustive exercise in humans

We investigated whether dynamic cerebral autoregulation is affected by exhaustive exercise using transfer-function gain and phase shift between oscillations in mean arterial pressure (MAP) and middle cerebral artery (MCA) mean blood flow velocity (V(mean)). Seven subjects were instrumented with a brachial artery catheter for measurement of MAP and determination of arterial Pco(2) (Pa(CO(2))) while jugular venous oxygen saturation (Sv(O(2))) was determined to assess changes in whole brain blood flow. After a 10-min resting period, the subjects performed dynamic leg-cycle ergometry at 168 +/- 5 W (mean +/- SE) that was continued to exhaustion with a group average time of 26.8 +/- 5.8 min. Despite no significant change in MAP during exercise, MCA V(mean) decreased from 70.2 +/- 3.6 to 57.4 +/- 5.4 cm/s, Sv(O(2)) decreased from 68 +/- 1 to 58 +/- 2% at exhaustion, and both correlated to Pa(CO(2)) (5.5 +/- 0.2 to 3.9 +/- 0.2 kPa; r = 0.47; P = 0.04 and r = 0.74; P < 0.001, respectively). An effect on brain metabolism was indicated by a decrease in the cerebral metabolic ratio of O(2) to [glucose + one-half lactate] from 5.6 to 3.8 (P < 0.05). At the same time, the normalized low-frequency gain between MAP and MCA V(mean) was increased (P < 0.05), whereas the phase shift tended to decrease. These findings suggest that dynamic cerebral autoregulation was impaired by exhaustive exercise despite a hyperventilation-induced reduction in Pa(CO(2)).     

Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.

To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.     

A ventricular-vascular coupling model in presence of aortic stenosis

In patients with aortic stenosis, the left ventricular afterload is determined by the degree of valvular obstruction and the systemic arterial system. We developed an explicit mathematical model formulated with a limited number of independent parameters that describes the interaction among the left ventricle, an aortic stenosis, and the arterial system. This ventricular-valvular-vascular (V(3)) model consists of the combination of the time-varying elastance model for the left ventricle, the instantaneous transvalvular pressure-flow relationship for the aortic valve, and the three-element windkessel representation of the vascular system. The objective of this study was to validate the V(3) model by using pressure-volume loop data obtained in six patients with severe aortic stenosis before and after aortic valve replacement. There was very good agreement between the estimated and the measured left ventricular and aortic pressure waveforms. The total relative error between estimated and measured pressures was on average (standard deviation) 7.5% (SD 2.3) and the equation of the corresponding regression line was y = 0.99x - 2.36 with a coefficient of determination r(2) = 0.98. There was also very good agreement between estimated and measured stroke volumes (y = 1.03x + 2.2, r(2) = 0.96, SEE = 2.8 ml). Hence, this mathematical V(3) model can be used to describe the hemodynamic interaction among the left ventricle, the aortic valve, and the systemic arterial system.     

Peroxynitrite-derived carbonate and nitrogen dioxide radicals readily react with lipoic and dihydrolipoic acid

Alpha-lipoic acid (LA) and dihydrolipoic acid (DHLA) may have a role as antioxidants against nitric oxide-derived oxidants. We previously reported that peroxynitrite reacts with LA and DHLA with second-order rate constants of 1400 and 500 M(-1) s(-1), respectively, but indicated that these direct reactions are not fast enough to protect against peroxynitrite-mediated damage in vivo. Moreover, the mechanism of the reaction of peroxynitrite with LA has been recently challenged (J. Biol. Chem.279:9693-9697; 2004). Pulse radiolysis studies indicate that LA and DHLA react with peroxynitrite-derived nitrogen dioxide (*NO2) (k2 = 1.3 x 10(6) and 2.9 x 10(7) M(-1) s(-1), respectively) and carbonate radicals (CO(3-)) (k2 = 1.6 x 10(9) and 1.7 x 10(8) M(-1) s(-1), respectively). Carbonate radical-mediated oxidation of LA led to the formation of the potent one-electron oxidant LA radical cation. LA inhibited peroxynitrite-mediated nitration of tyrosine and of a hydrophobic tyrosine analog, N-t-BOC L-tyrosine tert-butyl ester (BTBE), incorporated into liposomes but enhanced tyrosine dimerization. Moreover, while LA competitively inhibited the direct oxidation of glutathione by peroxynitrite, it was poorly effective against the radical-mediated thiol oxidation. The mechanisms of reaction defined herein allow to rationalize the biochemistry of peroxynitrite based on direct and free radical-mediated processes and contribute to the understanding of the antioxidant actions of LA and DHLA.     

Preload-adjusted right ventricular maximal power: concept and validation

Right ventricular (RV) maximal power (PWR(mx)) is dependent on preload. The objective of this study was to test our hypothesis that the PWR(mx) versus end-diastolic volume (EDV) relationship, analogous to the load-independent stroke work (SW) versus EDV relationship (preload-recruitable SW, PRSW), is linear, with the PWR x-axis intercept (V(0PWR)) corresponding to the PRSW intercept (V(0SW)). If our hypothesis is correct, the preload sensitivity of PWR(mx) could be eliminated by adjusting for EDV and V(0PWR). Ten dogs were instrumented with a pulmonary flow probe, micromanometers, and RV conductance catheter. Data were obtained during bicaval occlusions under various conditions and fitted to PWR(mx) = a.(EDV - V(0PWR))(beta), where a is the slope of the relationship. The PWR(mx) versus EDV relationship did not deviate from linearity (beta = 1.09, P = not significant vs. 1), and V(0PWR) correlated with V(0SW) (r = 0.93, P <0.0001). V(0PRW) was related to steady-state EDV and left ventricular end-diastolic pressure, allowing for estimation of V(0PWR) (V(0Est)) and single-beat PWR(mx) preload adjustment. Dividing PWR(mx) by the difference of EDV and V(0PWR) (PAMP(V0PWR)) eliminated preload dependency down to 50% of the baseline EDV. PWR(mx) adjustment using V(0Est) (PAMP(V0Est)) showed similar preload independency. Enhancing contractility increased PAMP(V0PWR) and PAMP(V0Est) from 176 +/- 52 to 394 +/- 205 W/ml x 10(4) and 145 +/- 51 to 404 +/- 261 W/ml x 10(4), respectively, accompanied by an increase of PRSW from 13.0 +/- 4.5 to 29.7 +/- 16.4 mmHg (all P <0.01). PAMP(V0PWR) and PAMP(V0Est) correlated with PRSW (r = 0.85; r = 0.77; both P <0.001). Numerical modeling confirmed the accuracy of our experimental data. Thus preload adjustment of PWR(mx) should consider a linear PWR(mx) versus EDV relationship with distinct V(0PWR). PAMP(V0PWR) is a preload-independent estimate of RV contractility that may eventually be determined noninvasively.     

Mechanisms of increase in cardiac output during acute weightlessness in humans

Based on previous water immersion results, we tested the hypothesis that the acute 0-G-induced increase in cardiac output (CO) is primarily caused by redistribution of blood from the vasculature above the legs to the cardiopulmonary circulation. In seated subjects (n = 8), 20 s of 0 G induced by parabolic flight increased CO by 1.7 ± 0.4 l/min (P < 0.001). This increase was diminished to 0.8 ± 0.4 l/min (P = 0.028), when venous return from the legs was prevented by bilateral venous thigh-cuff inflation (CI) of 60 mmHg. Because the increase in stroke volume during 0 G was unaffected by CI, the lesser increase in CO during 0 G + CI was entirely caused by a lower heart rate (HR). Thus blood from vascular beds above the legs in seated subjects can alone account for some 50% of the increase in CO during acute 0 G. The remaining increase in CO is caused by a higher HR, of which the origin of blood is unresolved. In supine subjects, CO increased from 7.1 ± 0.7 to 7.9 ± 0.8 l/min (P = 0.037) when entering 0 G, which was solely caused by an increase in HR, because stroke volume was unaffected. In conclusion, blood originating from vascular beds above the legs can alone account for one-half of the increase in CO during acute 0 G in seated humans. A Bainbridge-like reflex could be the mechanism for the HR-induced increase in CO during 0 G in particular in supine subjects.     

Repeated pregnancies (multiparity) increases venous tone and reduces compliance

In humans, multiparity (repeated pregnancy) is associated with increased risk of cardiovascular disease. In rats, multiparity increases the pressor response to phenylephrine and to acute stress, due in part to changes in tone of the splanchnic arterial vasculature. Given that the venous system also changes during pregnancy, we studied the effects of multiparity on venous tone and compliance. Cardiovascular responses to volume loading (2 ml/100 g body wt), and mean circulatory filling pressure (MCFP, an index of venomotor tone) were measured in conscious, repeatedly bred (RB), and age-matched virgin rats. In addition, passive compliance and venous reactivity of isolated mesenteric veins were measured by pressure myography. There was a greater increase in mean arterial pressure after volume loading in RB rats (+7.2 +/- 2.5 mmHg, n = 8) than virgin rats (-1.4 +/- 1.7 mmHg, n = 7) (P < 0.05). The increase in MCFP in response to norepinephrine (NE) was also greater in RB rats [half maximal effective dose (ED(50)) 3.1 +/- 0.5 nmol.kg(-1).min(-1), n = 6] than virgins (ED(50): 12.1 +/- 2.7 nmol.kg(-1).min(-1), n = 6) (P < 0.05). Pressure-induced changes in passive diameter were lower in isolated mesenteric veins from RB rats (29.3 +/- 1.8 microm/mmHg, n = 6) than from virgins (36.9 +/- 1.3 microm/mmHg, n = 6) (P < 0.05). Venous reactivity to NE in isolated veins was also greater in RB rats (EC(50): 2.68 +/- 0.37x10(-8) M, n = 5) than virgins (EC(50): 4.67 +/- 0.93 x 10(-8) M, n = 8). We conclude that repeated pregnancy induces a long-term reduction in splanchnic venous compliance and augments splanchnic venous reactivity and sympathetic tonic control of total body venous tone. This compromises the ability of the capacitance (venous) system to accommodate volume overloads and to buffer changes in cardiac preload.     

Two-breath CO(2) test detects altered dynamic cerebrovascular autoregulation and CO(2) responsiveness with changes in arterial P(CO(2))

The new two-breath CO(2) method was employed to test the hypotheses that small alterations in arterial P(CO(2)) had an impact on the magnitude and dynamic response time of the CO(2) effect on cerebrovascular resistance (CVRi) and the dynamic autoregulatory response to fluctuations in arterial pressure. During a 10-min protocol, eight subjects inspired two breaths from a bag with elevated P(CO(2)), four different times, while end-tidal P(CO(2)) was maintained at three levels: hypocapnia (LoCO(2), 8 mmHg below resting values), normocapnia, and hypercapnia (HiCO(2), 8 mmHg above resting values). Continuous measurements were made of mean blood pressure corrected to the level of the middle cerebral artery (BP(MCA)), P(CO(2)) (estimated from expired CO(2)), and mean flow velocity (MFV, of the middle cerebral artery by Doppler ultrasound), with CVRi = BP(MCA)/MFV. Data were processed by a system identification technique (autoregressive moving average analysis) with gain and dynamic response time of adaptation estimated from the theoretical step responses. Consistent with our hypotheses, the magnitude of the P(CO(2))-CVRi response was reduced from LoCO(2) to HiCO(2) [from -0.04 (SD 0.02) to -0.01 (SD 0.01) (mmHg x cm(-1) x s) x mmHg Pco(2)(-1)] and the time to reach 95% of the step plateau increased from 12.0 +/- 4.9 to 20.5 +/- 10.6 s. Dynamic autoregulation was impaired with elevated P(CO(2)), as indicated by a reduction in gain from LoCO(2) to HiCO(2) [from 0.021 +/- 0.012 to 0.007 +/- 0.004 (mmHg x cm(-1) x s) x mmHg BP(MCA)(-1)], and time to reach 95% increased from 3.7 +/- 2.8 to 20.0 +/- 9.6 s. The two-breath technique detected dependence of the cerebrovascular CO(2) response on P(CO(2)) and changes in dynamic autoregulation with only small deviations in estimated arterial P(CO(2)).     

Quantitative assessment of changes in blood CO(2) tension mediated by the haldane effect.

Adequate assessment of circulatory and gas-exchange interactions may involve the quantification of the Haldane effect (HE) and of the changes in blood PCO(2) mediated by changes in Hb-O(2) saturation and O(2)-linked CO(2) binding. This is commonly prevented by the complexity of the involved calculations. To simplify the task, a large series of patient measurements has been processed by regression analysis, thus developing an accurate fit for this quantification (v-a) PCO(2)HE + 0.460 [(a-v) HbO(2)]0.999e0.015(PvCO(2))-0.852(Hct) (n = 247, r(2) = 0. 99, P < 0.001), where (v-a)PCO(2 HE) is the reduction in venous PCO(2) (Pv(CO(2)), Torr) allowed by the chemical binding of CO(2) in blood due to the HE (Torr), (a-v)HbO(2) is the arteriovenous difference in Hb-bound O(2) (ml/dl), and Hct is hematocrit fraction. Values of (v-a)PCO(2 HE) estimated by this expression compared well with the results of previously published experiments. This formula is useful in assessing the impact of HE on Pv(CO(2)) and venoarterial PCO(2) gradient and the survival advantage offered by HE in extreme conditions. Use may be extended to all investigative and clinical settings in which changes in blood O(2) saturation and O(2)-linked CO(2) binding must be converted into the corresponding changes in dissolved CO(2) and PCO(2).     

Cross-validation of ventilatory threshold prediction equations on aerobically trained men and women

The purpose of this investigation was to determine the validity of the non-exercise-based equations of Davis et al. (13), Jones et al. (20), and Neder et al. (30) for estimating the ventilatory threshold (VT) in samples of aerobically trained men and women. One hundred and forty-four aerobically trained men (mean +/- SD age, 41.0 +/- 11.6 years; N = 83) and women (37.1 +/- 9.0 years, N = 61) performed a maximal incremental test to determine VO2max and observed VT on a cycle ergometer. The observed VT was determined by gas exchange measurements using the V-slope method (VCO2/VO2) in conjunction with analyses of the ventilatory equivalents (i.e., minute ventilation VE/VO2 and VE/VCO2) and end-tidal gas tensions (i.e., P(ET)O2 and P(ET)CO2) for oxygen and carbon dioxide. The predicted VT values from 14 equations were compared to the observed VT values by examining the constant error (CE), standard error of estimate (SEE), Pearson correlation coefficient (r), and total error (TE). The results of this investigation indicated that all 14 equations resulted in significant (p < 0.008) CE values ranging from 1.13 to 1.72 L x min(-1) for the men and from 0.58 to 1.12 L x min(-1) for the women. Furthermore, the SEE, r, and TE values ranged from 0.37 to 0.54, from 0.36 to 0.53, and from 0.68 to 1.81 L x min(-1), respectively. The lowest TE values for the men and women represented 45 and 36% of the mean of the observed VT values, respectively. The results of this study indicated that the errors associated with all 14 equations were too large to be of practical value for estimating VT in aerobically trained men and women.     

Right atrial pressure as measure of ventricular constraint in newborn lambs

Although the lungs and pericardium constrain the heart and limit cardiac output, no method exists to assess this constraint in sick newborns. We hypothesize that a useful estimate of ventricular constraint may be obtained by measuring right atrial pressure (P(RA)) in the newborn. To test this hypothesis, we measured P(RA), thoracic inferior vena caval pressure (P(IVC); saline-filled catheters), and ventricular constraint (pericardial pressure, P(PER); liquid-containing balloon) in 4-wk-old (neonatal, n = 12) and 3-day-old (newborn, n = 6) anesthetized lambs. The measurements were made while LV filling pressure was altered (0-20 mmHg) and while positive end-expiratory pressure (PEEP) was maintained at 2.5 or 15 cmH2O. In all of the lambs, a strong linear relationship (r) existed between P(RA) and P(PER) (P(RA) = 1.19 P(PER) + 0.0, r = 0.99) and between P(IVC) and P(PER) (P(IVC) = 1.24 P(PER) + 0.1, r = 0.99; PEEP of 2.5 cmH2O). Similar relationships were also observed with increased PEEP (P(RA) = 1.29 P(PER)-1.2, r = 0.98 and P(IVC) = 1.32 P(PER)-1.2, r = 0.97). Because P(RA) provides an accurate measure of ventricular constraint in the normal lamb, it may be a useful measure of ventricular constraint in the sick newborn.     

Deceleration time of systolic pulmonary venous flow: a new clinical marker of left atrial pressure and compliance.

The curvilinearity of the atrial pressure-volume curve implies that atrial compliance decreases progressively with increasing left atrial (LA) pressure (LAP). We predicted that reduced LA compliance leads to more rapid deceleration of systolic pulmonary venous (PV) flow. With this rationale, we investigated whether the deceleration time (t dec) of PV systolic flow velocity reflects mean LAP. In eight patients during coronary surgery, before extracorporeal circulation, PV flow by ultrasonic transit time and invasive LAP were recorded during stepwise volume loading. The t dec was calculated using two methods: by drawing a tangent through peak deceleration and by drawing a line from peak systolic flow through the nadir between the systolic and early diastolic flow waves. LA compliance was calculated as the systolic PV flow integral divided by LAP increment. Volume loading increased mean LAP from 11 +/- 3 to 20 +/- 5 mmHg (P < 0.001) (n = 40), reduced LA compliance from 1.16 +/- 0.42 to 0.72 +/- 0.40 ml/mmHg (P < 0.004) (n = 40), and reduced t dec from 320 +/- 50 to 170 +/- 40 ms (P < 0.0005) (n = 40). Mean LAP correlated well with t dec (r = 0.84, P < 0.0005) (n = 40) and LA compliance (r = 0.79, P < 0.0005) (n = 40). Elevated LAP caused a decrease in LA compliance and therefore more rapid deceleration of systolic PV flow. The t dec has potential to become a semiquantitative marker of LAP and an index of LA passive elastic properties.     

Mechanism of electroporative dye uptake by mouse B cells.

The color change of electroporated intact immunoglobulin G receptor (Fc gammaR-) mouse B cells (line IIA1.6) after direct electroporative transfer of the dye SERVA blue G (Mr 854) into the cell interior is shown to be dominantly due to diffusion of the dye after the electric field pulse. Hence the dye transport is described by Fick's first law, where, as a novelty, time-integrated flow coefficients are introduced. The chemical-kinetic analysis uses three different pore states (P) in the reaction cascade (C <==> P1 <==> P2 <==> P3), to model the sigmoid kinetics of pore formation as well as the biphasic pore resealing. The rate coefficient for pore formation k(p) is dependent on the external electric field strength E and pulse duration tE. At E = 2.1 kV cm(-1) and tE = 200 micros, k(p) = (2.4 +/- 0.2) x 10(3) s(-1) at T = 293 K; the respective (field-dependent) flow coefficient and permeability coefficient are k(f)0 = (1.0 +/- 0.1) x 10(-2) s(-1) and P0 = 2 cm s(-1), respectively. The maximum value of the fractional surface area of the dye-conductive pores is 0.035 +/- 0.003%, and the maximum pore number is Np = (1.5 +/- 0.1) x 10(5) per average cell. The diffusion coefficient for SERVA blue G, D = 10(-6) cm2 s(-1), is slightly smaller than that of free dye diffusion, indicating transient interaction of the dye with the pore lipids during translocation. The mean radii of the three pore states are r(P1) = 0.7 +/- 0.1 nm, r(P2) = 1.0 +/- 0.1 nm, and r(P3) = 1.2 +/- 0.1 nm, respectively. The resealing rate coefficients are k(-2) = (4.0 +/- 0.5) x 10(-2) s(-1) and k(-3) = (4.5 +/- 0.5) x 10)(-3) s(-1), independent of E. At zero field, the equilibrium constant of the pore states (P) relative to closed membrane states (C) is K(p)0 = [(P)]/[C] = 0.02 +/- 0.002, indicating 2.0 +/- 0.2% water associated with the lipid membrane. Finally, the results of SERVA blue G cell coloring and the new analytical framework may also serve as a guideline for the optimization of the electroporative delivery of drugs that are similar in structure to SERVA blue G, for instance, bleomycin, which has been used successfully in the new discipline of electrochemotherapy.     

Effect of phentolamine on the relationship between O2 consumption and delivery in sheep.

The oxygen flux challenge test (OFT) has recently been used in critically ill patients as a dynamic test for assessment of the response in oxygen consumption (VO2) to an increase in O2 delivery (QO2). Such a test may indicate whether a patient demonstrates delivery-dependent VO2. However, the increase in whole body VO2 following an increase of QO2 might be due to the agents used for the OFT. In this study, we examined the possibility of obtaining false positive OFT with an alpha-adrenergic antagonist. Five normothermic thiopentone-anaesthetised and mechanically-ventilated (inspired O2 fraction, 0.3; expired CO2 fraction, 0.045-0.055) adult sheep (25-31 kg) were investigated. The QO2 was increased in a stepwise fashion from 200 to 850 ml.min-1 by vasodilatation with intravenous infusion of phentolamine. The VO2 was calculated at each step from the product of arteriovenous. O2 content difference (CO2, a-v) and cardiac output (Qc), the latter being continuously measured with a transit-time ultrasonic flow probe placed around the main pulmonary artery. The VO2 (y) was linearly related to QO2 (x), y = 0.034 (SD 0.024) x + 29.3 (SD 3.9). The relationship between Qc (y) and CO2, a-v (x) was y = 4.6x(-1.12) (n = 69; r2 = 0.75; P = NS compared to the expected relationship for isoconsumption conditions, i.e. where Qc = VO2.(CO2, a-v)(-1). Our data suggested that under stable conditions, an infusion of phentolamine did not sufficiently alter the relationship between Qc and CO2, a-v to invalidate its use for OFT in normal sheep.