Blood volume and body fluid compartments in lambs with aortopulmonary left-to-right shunts.

A left-to-right shunt is accompanied by an increased plasma and blood volume. Since this is likely realized through renin/aldosterone-mediated salt and water retention, other body fluid compartments may be changed too. Therefore, we studied blood volume and body fluid compartments by a single-injection, triple-indicator dilution technique in nine 8-wk-old lambs with an aortopulmonary left-to-right shunt (55 +/- 3% of left ventricular output; mean +/- SEM) and in 11 control lambs, 2.5 wk after surgery. Systemic blood flow was maintained at the same level as in control lambs, but the aortic pressure of the shunt lambs was lower. Blood volume in shunt lambs was larger than in control lambs (110 +/- 6 vs. 84 +/- 7 ml/kg, P < 0.001) through an increase in plasma volume, which correlated significantly with the magnitude of the left-to-right shunt (r = 0.81, P < 0.01). Red blood cell volume was equal to that of control lambs. Evidence was obtained that the increase in plasma volume was induced by a transient increase in renin (8.0 +/- 2.2 vs. 1.6 +/- 0.2 nmol.l-1.h-1; P < 0.02) and aldosterone (0.51 +/- 0.14 vs. 0.24 +/- 0.09 nmol/liter) concentrations. Interstitial water volume, however, was not significantly different from that in control lambs. The amount of intravascular protein was significantly higher than in control lambs (5.0 +/- 0.3 vs. 3.5 +/- 0.2 g/kg body mass, P < 0.001). There were no significant differences in intracellular and total body water volumes between the two groups. We conclude that the increased amount of intravascular protein confines the fluid retained by the kidneys to the vascular compartment.

Myocardial lactate metabolism in fetal and newborn lambs.

BACKGROUND: Around birth, myocardial substrate supply changes from carbohydrates before birth to primarily fatty acids after birth. Parallel to these changes, the myocardium is expected to switch from the use of primarily lactate before birth to fatty acids thereafter. However, myocardial lactate uptake and oxidation around birth has not been measured in vivo. METHODS AND RESULTS: We measured myocardial lactate uptake, oxidation, and release with infusion of [1-13C]lactate and myocardial flux of fatty acids and glucose in chronically instrumented fetal and newborn (1 to 15 days) lambs. Myocardial lactate oxidation was the same in newborn (81.7+/-14.7 micromol. min-1. 100 g-1, n=11) as in fetal lambs (60.7+/-26.7 micromol. min-1. 100 g-1, n=7). Lactate uptake was also the same in newborn as in fetal lambs. Lactate uptake was higher than lactate flux, indicating lactate release simultaneously with uptake. In the newborn lambs, lactate uptake declined with age. Lactate uptake was strongly related to lactate supply, whereas lactate oxidation was not. The supply of fatty acids or glucose did not interfere with lactate uptake, but the flux of fatty acids was inversely related to lactate oxidation. CONCLUSIONS: We show that lactate is an important energy source for the myocardium before birth as well as in the first 2 weeks after birth in lambs. We also show that there is release of lactate by the myocardium simultaneously with uptake of lactate. Furthermore, we show that lactate oxidation may be attenuated by fatty acids but not by glucose, probably at the level of pyruvate dehydrogenase.

Perinatal changes in myocardial metabolism in lambs.

BACKGROUND: Lactate accounts for a third of myocardial oxygen consumption before and in the first 2 weeks after birth. It is unknown how the remainder of myocardial oxygen is consumed. Glucose is thought to be important before birth, whereas long-chain fatty acids (LC-FA) are the prime substrate for the adult. However, the ability of the myocardium of the newborn to use LC-FA has been doubted. METHODS AND RESULTS: We measured the myocardial metabolism of glucose and LC-FA with [U-(13)C]glucose and [1-(13)C]palmitate in chronically instrumented fetal and newborn lambs. In fetal lambs, myocardial oxidation of glucose was high and that of LC-FA was low. Glucose and LC-FA accounted for 48+/-4% and 2+/-2% of myocardial oxygen consumption, respectively. In newborn lambs, oxidation of glucose decreased, whereas oxidation of LC-FA increased. Glucose and LC-FA accounted for 12+/-3% and 83+/-19% of myocardial oxygen consumption. To test whether near-term fetal lambs could use LC-FA, we increased the supply of LC-FA with a fat infusion. In fetal lambs during fat infusion, the oxidation of LC-FA increased 15-fold. Although the oxidation of LC-FA was still lower than in newborn lambs, the contribution to myocardial oxygen consumption (70+/-13%) was the same as in newborn lambs. CONCLUSIONS: These data show that glucose and lactate account for the majority of myocardial oxygen consumption in fetal lambs, whereas in newborn lambs, LC-FA and lactate account for the majority of myocardial oxygen consumption. Moreover, we showed that the fetal myocardium can use LC-FA as an energy substrate.

Comparative effects of isoproterenol and dopamine on myocardial oxygen consumption, blood flow distribution and total body oxygen consumption in conscious lambs with and without an aortopulmonary left to right shunt.

OBJECTIVES: We sought to study the effects of catecholamines on myocardial oxygen consumption (VO2), regional blood flows and total body VO2 in lambs with circulatory congestion. BACKGROUND: Catecholamines are often used to support cardiovascular function in children with circulatory congestion because they increase contractility as well as heart rate. However, these changes increase myocardial oxygen demand and thus can lead to a mismatch between myocardial oxygen supply and demand. Catecholamines can also change regional blood flows and VO2 unfavorably. METHODS: We infused isoproterenol (0.1 microg/kg body weight per min) and dopamine (10 microg/kg per min) and measured myocardial and total body VO2 and regional blood flows in chronically instrumented 7-week old lambs with and without a left to right shunt. RESULTS: Isoproterenol increased myocardial VO2, parallel to the increase in heart rate. However, myocardial blood flow and, consequently, oxygen supply also increased. This increase outweighed the increase in myocardial VO2, so that myocardial oxygen extraction decreased. Isoproterenol did not change blood flow distribution. Isoproterenol increased total body VO2; however, systemic oxygen supply increased even more, so that oxygen extraction decreased and mixed venous oxygen saturation increased. In contrast, dopamine had no or little effect on myocardial VO2 or blood flow distribution. CONCLUSIONS: We conclude that the catecholamines isoproterenol and dopamine do not lead to a mismatch between myocardial oxygen supply and demand, nor do they change blood flow distribution unfavorably in 7-week old lambs with a left to right shunt. We demonstrated that isoproterenol is superior to dopamine, because it shifts the balance between oxygen supply and consumption toward supply so that systemic oxygen extraction reserve increases.

Investigation of the origin of the impedance cardiogram by means of exchange transfusion with stroma free haemoglobin solution in the dog.

PURPOSE OF INVESTIGATION - To determine the contribution of variations in orientation of erythrocytes (orientation effect) to the heart synchronous variations in thoracic impedance in impedance cardiography. DESIGN - The blood of four dogs was gradually replaced by stroma free haemoglobin solution, causing a decrease in resistivity and orientation effect. The decrease in orientation effect was used to determine the contribution of the orientation effect using an extended form of the "parallel conductor" model of the thorax (parallel connection of a tissue admittance Yt and a blood conductance Gb). SUBJECTS - Four adult splenectomised mongrel dogs. MEASUREMENTS and RESULTS - Packed cell volume and resistivity at body temperature of every volume of circulating fluid removed was measured. Real and imaginary parts of the transthoracic impedance and the modulus of the heart synchronous impedance variations were measured just before each exchange. The parallel conductor model was extended to account for the influence on Gb of packed cell volume and orientation of erythrocytes. Applying this extended model, the average variations in Gb at a packed cell volume of 40% were estimated to be 7.46%:3.03% due to volume variations, 4.43% due to orientation effect. After further extending the model to account for the influence of small changes in blood pressure and heart rate, the average volume variations were estimated to range from 2.8% to 3.3% and the average orientation effect from 4.1% to 4.7% at a packed cell volume of 40%. CONCLUSION - Resistivity of the blood is far from constant and the contributions of variations in blood conductivity and volume to the heart synchronous thoracic impedance are of comparable magnitude. The contribution of the volume variations is the sum of the volume variations in the contributing intrathoracic vessels. The effects of variations in orientation are added up in proportion to the relative volumes of the contributing vessels. The extensions of the parallel conductor model brought out all physiological factors determining the heart synchronous thoracic impedance variations: pulse pressures and flows, mean pressures and flows, compliances of all contributing blood vessels, packed cell volume and heart rate, as well as the relevant properties of blood: the relations between volume, flow and orientation effect and the change in orientation effect during decelerating flow.

Investigation of the parallel conductor model of impedance cardiography by means of exchange transfusion with stroma free haemoglobin solution in the dog.

To test one of the assumptions underlying the calculation of stroke volume--namely, that the transthoracic impedance consists of a parallel connection of a tissue impedance and a blood resistance--experiments were carried out on four dogs in which blood was gradually replaced by a stroma free haemoglobin solution, with the purpose of changing the blood resistance while leaving the tissue impedance unchanged. This was accomplished by exchange transfusion in such a way that the volume of the circulating fluid remained constant and the distribution of fluid volume between the fluid compartments was not altered. During the exchange transfusions the mean decrease in resistivity of the circulating fluid was 54%. The packed cell volume and resistivity of every volume of removed circulating fluid were measured. Just before each exchange the real and imaginary parts of the transthoracic impedance were measured. The packed cell volume decreased exponentially with the number of exchanges. This indicates that the circulating fluid volume remained constant during the exchange transfusion. From the packed cell volumes an estimate of the circulating fluid volume was made. Because of the parallel connection all calculations were based on the use of admittance, which is the reciprocal value of impedance. The real and imaginary parts of the transthoracic admittance were calculated from the measured values of the real and imaginary parts of the transthoracic impedance.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary valve incompetence. I. Evaluation using electromagnetic flow velocity catheters and a new valve insufficiency analyser.

In animal experiments regurgitant flow through competent and incompetent pulmonary valves was evaluated with electromagnetic flow velocity catheters by using the ratio of the separately integrated backward and forward flow velocity signals. This ratio was obtained with a special purpose analog computing circuit set by an in-vitro zero flow reference signal, which was in good agreement with in-vivo zero flow signals.

Pulmonary valve incompetence. II. Application of electromagnetic flow velocity catheters in children.

During cardiac catheterization in 49 children regurgitant flow through competent and incompetent pulmonary valves was evaluated with electromagnetic flow velocity catheters using the ratio of the separately integrated backward and forward flow velocity signals (vb/vf). When the pulmonary valve was normal, vb/vf was less than or equal to 0.10. After operation for pulmonary valve stenosis or tetralogy of Fallot larger values were often found. In patients with an outflow patch across the pulmonary valve ring vb/vf values of up to 0.54 were found.

Effects of vasoactive intestinal polypeptide on heart rate in relation to vagal cardioacceleration in conscious dogs.

OBJECTIVE: The vagal cardiac accelerator (VCA) system takes part in the nervous control of the heart rate. In the present study we tried to adduce evidence that vasoactive intestinal polypeptide (VIP) contributes to vagally induced cardioaccelerations. METHODS: The effect of VIP on heart rate and arterial blood pressure was investigated after unmasking the inherent VCA activity by blocking the sympathetic accelerator and vagal decelerator influences on heart rate in conscious dogs. RESULTS: Following intravenous administration of VIP (10 micrograms i.v.) the heart rate increased by 43.6 +/- 6.7 (28.1 +/- 4.7%), from 165.6 +/- 8.5 to 209.1 +/- 7.0 beats/min (P < 0.001) and the mean arterial blood pressure decreased by 47.5 +/- 3.2 (37.9 +/- 3.0%), from 126.6 +/- 2.6 to 79.1 +/- 4.9 mmHg (P < 0.001) (n = 11). After VCA activity was reflexly enhanced by alpha 1-adrenoceptor stimulation with methoxamine, VIP increased heart rate by 36.9 +/- 7.3 (21.5 +/- 4.6%), from 179.8 +/- 5.2 to 216.7 +/- 5.8 beats/min (P < 0.001) and decreased mean arterial pressure by 79.1 +/- 6.4 (46.7 +/- 3.5%), from 168.2 +/- 4.1 to 89.1 +/- 5.0 mmHg (P < 0.001). Hence, the VIP-induced tachycardia, expressed in relative values, shows a significant attenuation after the administration of methoxamine (P < 0.05). The increase in heart rate induced by VIP appeared to be inversely related to the prevailing VCA activity, both before (r = -0.744, P = 0.009) and after methoxamine (r = -0.689, P = 0.019). The VIP-induced tachycardia is certainly not reflexly induced by the fall in arterial pressure, because intracoronary administration of VIP (0.5 microgram i.c.) caused an appreciable increase in the heart rate by 63.7 +/- 13.0 (46.4 +/- 10.4%), from 143.0 +/- 8.1 to 208.7 +/- 12.0 beats/min (P < 0.005), whereas the mean arterial pressure only slightly changed (-7.7 +/- 2.0 mmHg) (P < 0.05) (n = 6). In addition, VIP (10 micrograms i.v.) also caused a tachycardia in vagotomized dogs with blocked beta-adrenergic and muscarinic receptors. The administration of the VIP antagonists [D-p-CI-Phe6, Leu17]-VIP (50-150 micrograms i.c.) and [Lys1, Pro2,5, Leu17]-VIP (20 micrograms i.c.) did not result in alterations in VCA activity nor did the VIP antagonists block the VCA reflex response to a rise in arterial pressure. However, none of the VIP antagonists reduced the VIP-induced tachycardia either. CONCLUSION: Vasoactive intestinal polypeptide is likely to play a part in the vagal cardiac accelerator system. However, conclusive evidence for its role as the terminal transmitter in the VCA pathway will have to wait for the availability of a specific cardiac VIP receptor antagonist.

Spectrophotometric determination of oxygen saturation of blood independent of the presence of indocyanine green.

The strong absorbance of indocyanine green in a broad band around lambda = 800 nm invalidates the usual spectrophotometric two-wavelength methods for measuring oxygen saturation operating in the red and near infrared region. By proper wavelength selection, however, the effect of the dye can be eliminated. With the two-wavelength method utilising lambda = 660 and 860 nm oxygen saturation is measured virtually independent of the presence of indocyanine green.

Inbreeding depression and genetic load in laboratory metapopulations of the butterfly Bicyclus anynana.

We investigated the effects of inbreeding on various fitness components and their genetic load in laboratory metapopulations of the butterfly Bicyclus anynana. Six metapopulations each consisted of four subpopulations with breeding population sizes of N = 6 or N = 12 and migration rate of m = 0 or m = 0.33. Metapopulations were maintained for seven generations during which coancestries and pedigrees were established. Individual inbreeding coefficients at the F7 were calculated and ranged between 0.01 and 0.51. Even though considerable purging had occurred during inbreeding, the genetic load remained higher than that of many outbreeding species: approximately two lethal equivalents were detected for egg sterility, one for zygote survival, one for juvenile survival, and one for longevity. Severe inbreeding depression occurred after seven generations of inbreeding, which jeopardized the metapopulation survival. This finding suggests that the purging of genetic load by intentional inbreeding cannot be recommended for the genetic conservation of species with a high number of lethal equivalents.

Metabolic and hormonal responses to adrenoceptor antagonists in 48-hour-starved exercising rats.

The influence of 48 hours of starvation on sympathoadrenal regulation of nutrient utilization was investigated in rats. To assess the role of alpha- and beta-adrenoceptors, rats were studied during alpha- and beta-blockade. Energy metabolism was measured using indirect calorimetry before, during, and after moderate swimming exercise (approximately 60% maximal O2 consumption [VO2max]). Additionally, blood samples were taken for determination of nutrient and hormone concentrations. In 48-hour-starved rats, under baseline conditions, there was a reduction in energy expenditure (EE) accompanied by a shift toward fat oxidation (fat-ox) in comparison to fed rats. Exercise-induced responses in EE, fat-ox, and carbohydrate oxidation (CHO-ox) did not differ from those in fed rats. In starved rats, a stronger response to exercise of the sympathoadrenal system was observed. In comparison to control 48-hour-starved rats, blockade of alpha- and beta-adrenoceptors led to a reduction in the exercise-induced increase in EE and fat-ox. The rate of CHO-ox was slightly reduced after blockade of either adrenoceptor type. Alpha-blockade prevented the exercise-induced increase in blood glucose. Plasma free fatty acid (FFA) was not affected. Blood lactate, plasma insulin, norepinephrine (NOR), and epinephrine (EPI) were increased after alpha-blockade. Due to beta-blockade, exercise-induced increases in glucose and FFA were prevented. Blood glucose even declined below the baseline value. EPI showed an exaggerated increase, and NOR showed a smaller increase. Results obtained in starved rats support the idea that alpha-adrenoceptor blockade-induced changes in energy metabolism are the result of a diminished oxygen supply due to diminished circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic and hormonal responses to adrenoceptor antagonists in exercising rats.

alpha- and beta-adrenoceptors play a key role in the regulation of nutrient supply to working muscles during exercise. To assess their influence in the regulation of substrate utilization, rats were studied during alpha- or beta-adrenoceptor blockade. Energy metabolism was studied by means of indirect calorimetry before, during, and after moderate swimming exercise. Blood samples were taken for the determination of nutrient and hormone concentrations. In addition, central venous blood samples were withdrawn for determination of blood gases, pH, and total hemoglobin concentration (c/Hb). alpha- and beta-adrenoceptor blockade decreased the rates of energy expenditure (EE) and fat oxidation (fat-ox) during and after swimming in comparison to swimming without adrenoceptor blockade. The oxidation of carbohydrates (CHO-ox) was increased in both cases. alpha-Blockade prevented the exercise-induced increase in blood glucose, plasma free fatty acids (FFA) were not affected, and plasma insulin, norepinephrine (NOR), epinephrine (EPI), and lactate were markedly increased. beta-adrenoceptor blockade prevented the exercise-induced increases in blood glucose and FFA. EPI increased slightly more than and NOR less than in the control experiment. The exercise-induced decrease in insulin was more pronounced after beta-blockade. alpha-Blockade caused a less pronounced decrease in venous oxygen saturation (SO2) and tension (PO2) than in the control experiment. The exercise-induced increase in carbon dioxide tension (PCO2) was almost absent. After beta-blockade, venous SO2 and PO2 decreased more and PCO2 increased more than in the control experiment. It is concluded that both alpha and beta-blockade restrict the rate of EE during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic responses to moderate exercise in lambs with aortopulmonary shunts.

In a previous study we found, after an overnight fast of 18 hours, a lower arterial glucose concentration and a depressed glycogenolysis in lambs with aortopulmonary left-to-right shunts. During exercise, glucose and free fatty acids (FFA) concentrations normally increase. The aim of this study was to investigate whether the shunt lambs could compensate for a depressed glycogenolysis by increasing gluconeogenesis and by increasing levels of blood substrates such as FFA and glycerol during exercise. Therefore, we investigated glucose kinetics, with [U-(13)C]glucose, in five 7-week-old shunt and 7 control lambs of a similar age, at rest and during moderate exercise (treadmill; 50% of VO(2) peak). The glucose production rate and the rate of disappearance of glucose were lower in shunt than in control lambs, both at rest and during exercise. We found no difference in metabolic clearance rate of glucose, glucose recycling, or gluconeogenesis between both groups of lambs. Glycogenolysis was at rest lower in shunt than in control lambs and tended to be lower during exercise. The arterial concentrations of pyruvate, lactate, FFA, and total and free glycerol increased during exercise in both groups of lambs. In conclusion, shunt lambs have lower arterial glucose concentrations than control lambs, both at rest and during moderate exercise. This was due to a lower glucose production rate, in particular a lower glycogenolysis. In addition, the reduced glycogenolysis rate was not offset by an increase in gluconeogenesis nor by an increase in other substrates that can be utilized by working muscles.

Lower arterial glucose concentrations in lambs with aortopulmonary shunts after an 18-hour fast.

Spontaneously occurring hypoglycemia has been described in children with severe acute congestive heart failure. Hypoglycemia may be the result of an increase in glucose utilization in tissues, a decrease in glucose production, or a decrease in the dietary intake of nutrients. To determine whether hypoglycemia may also occur in congenital heart disease with volume overloading, we investigated glucose metabolism during and after an 18-hour fast in nine lambs with an aortopulmonary left-to-right shunt and nine control lambs. Plasma levels of hormones involved in the endocrine control of glucose metabolism were determined. The glucose production rate (rate of appearance [Ra]) was studied using [U-13C]glucose. Gluconeogenesis through the Cori cycle was estimated by measuring glucose 13C recycling. The arterial glucose concentration (3,409 +/- 104 v 4,338 +/- 172 micromol/L, P < .001) and Ra of glucose (16.97 +/- 0.89 v 25.49 +/- 4.28 micromol x min(-1) x kg(-1), P < .05) were lower in shunt versus control lambs. There were no differences in hormone levels between control and shunt lambs. Fractional glucose 13C recycling via the Cori cycle (6.9% +/- 2.8% v 7.1% +/- 2.5%) and gluconeogenesis from pyruvate and lactate (1.24 +/- 0.58 v 1.95 +/- 0.67 micromol x min(-1) x kg(-1)) were similar in both groups of lambs. The sum of glycogenolysis and gluconeogenesis from precursors other than pyruvate and lactate was lower in shunt versus control lambs (15.73 +/- 1.07 v 23.54 +/- 4.27 micromol x min(-1) x kg(-1), P < .05). In conclusion, after an 18-hour fast, the arterial glucose concentration is lower in lambs with aortopulmonary shunts. This lower glucose concentration is associated with a decreased glucose production rate. In shunt lambs, glycogenolysis is decreased, while there is no difference in gluconeogenesis or hormonal control.

Respiration and measurement of cardiac output by thermodilution and central or peripheral dye dilution.

Cardiac output as measured by indicator dilution methods during artificial ventilation shows differences up to +/- 35%. We studied the influence of spontaneous breathing on measurement of cardiac output by thermodilution (TD) and central (CDD) and peripheral dye dilution (PDD) in seven anesthetized dogs. Injection of indicator was timed at one of five chosen moments in a respiratory cycle. The indicator for TD was also used as solvent for indocyanine green. Results were normalized by the value obtained with injection at inspiratory onset. Results of the central dilution methods showed a slight but not significant difference between values measured with injection at 25 and 75% of the respiratory cycle: 105.7 and 98.0%, respectively, (TD) and 102.3 and 97.2% (CDD). Mean cardiac output determined by TD, CDD, or PDD was not significantly different. We conclude that 1) a reasonable estimate of cardiac output may be obtained by means of a single indicator-dilution curve and 2) the choice of the dilution method may be determined by practical considerations.

Human whole-blood O2 affinity: effect of CO2.

The proton Bohr factor (phi H = alpha log PO2/alpha pH), the carbamate Bohr factor (phi C = alpha log PO2/alpha log PCO2), the total Bohr factor (phi HC = d log PO2/dpH[base excess) and the CO2 buffer factor (d log PCO2/dpH) were determined in the blood of 12 healthy donors over the whole O2 saturation (SO2) range. All three Bohr factors proved to be dependent on SO2, although to a lesser extent than reported in some of the recent literature. At SO2 = 50% and 37 degrees C, we found phi H = -0.428 +/- 0.010 (SE), phi C = 0.054 +/- 0.006, and phi HC = -0.488 +/- 0.007. The values obtained for phi H, phi C, and d log PCO2/dpH were used to calculate phi HC. Calculated and measured values of phi HC proved to be in good agreement. In an additional series of 12 specimens of human blood we determined the influence of PCO2 on phi H and the influence of pH on phi C. At SO2 = 50%, phi H varied from -0.49 +/- 0.009 at PCO2 = 15 Torr to -0.31 +/- 0.010 at PCO2 = 105 Torr and phi C from 0.157 +/- 0.015 at pH = 7.80 to 0.006 +/- 0.009 at pH = 7.00. When on the basis of these data a second-order term is taken into account, a still slightly better agreement between measured and calculated values of phi HC can be attained.

Myocardial substrate uptake in lambs with and without aortopulmonary shunts during strenuous exercise.

Increased myocardial fatty acid uptake during acute exercise could adversely affect myocardial O2 consumption in lambs with left-to-right shunts, which would be unfavorable in view of their decreased coronary blood flow reserve. Therefore, we studied myocardial substrate uptake (glucose, lactate, pyruvate, free fatty acids, triglycerides, beta-hydroxybutyrate, and acetoacetate) in 10 7-wk-old lambs with an aortopulmonary left-to-right shunt [61 +/- 3% (SE) of left ventricular output] and 9 control lambs during strenuous treadmill exercise. The hemodynamic reaction to exercise was similar in shunt and control lambs. The peripheral metabolic response to exercise was also similar in the two groups: glucose free fatty acids, and, most prominently, lactate concentrations increased. Myocardial O2 consumption increased but less in shunt than in control lambs because of a smaller increase in heart rate. In both groups myocardial lactate uptake increased substantially at the cost of other substrates, providing the heart with 40% of its oxidative metabolism. Fatty acid uptake was not different between the two groups. In conclusion, our data reveal no essential differences in myocardial substrate uptake between shunt and control lambs during a substantial circulatory load.

Maximal exercise capacity and oxygen consumption of lambs with an aortopulmonary left-to-right shunt.

We determined maximal exercise capacity and measured hemodynamics in 10 6-wk-old lambs with an aortopulmonary left-to-right shunt [S, 57 +/- 11%, (SD)] and in 9 control lambs (C) during a graded treadmill test 8 days after surgery. Maximal exercise capacity (3.7 +/- 0.2 km/h and 10 +/- 5% inclination vs. 4.0 +/- 0.9 km/h and 15 +/- 0% inclination, P less than 0.02) and peak oxygen consumption (25 +/- 7 vs. 34 +/- 8 ml O2.min-1.kg-1, P less than 0.02) were both lower in the shunt than in the control lambs. This was due to a lower maximal systemic blood flow in the shunt lambs (271 +/- 38 vs. 359 +/- 71 ml.min-1.kg-1, P less than 0.01). Despite their high maximal left ventricular output, which was higher than in the control lambs (448 +/- 87 vs. 359 +/- 71 ml.min-1.kg-1, P less than 0.05), the left-to-right shunt could not be compensated for during maximal exercise because of a decreased reserve in heart rate (S: 183 +/- 22 to 277 +/- 38 beats/min; C: 136 +/- 25 to 287 +/- 29 beats/min) and in left ventricular stroke volume (S: 1.8 +/- 0.3 to 1.6 +/- 0.4 ml/kg; C: 1.0 +/- 0.3 to 1.3 +/- 0.2 ml/kg). We conclude that exercise capacity of shunt lambs is lower than that of control lambs, despite a good left ventricular performance, because a part of the reserves for increasing the left ventricular output is already utilized at rest.

Effects of exercise and isoproterenol on hemodynamics and myocardial VO2 in lambs with aortopulmonary shunts.

To compare hemodynamic changes induced by isoproterenol and exercise stress tests in individuals with and without left ventricular volume load, we studied 10 lambs with an aortopulmonary shunt [58 +/- 4% (SE) of left ventricular output] 2 wk after the shunt was created. Two studies, isoproterenol infusion at 0.1 microgram.kg-1.min-1 and treadmill exercise at 76 +/- 4% of predetermined maximal O2 consumption (VO2) were performed in each lamb in random order on different days. Identical experiments were performed in nine lambs without shunts. Isoproterenol and exercise induced similar changes in heart rate (43 +/- 5%); systemic (72 +/- 7%), pulmonary (35 +/- 3%), and shunt blood flows (8 +/- 6%); and stroke volume (NS) in shunt lambs. Aortic systolic pressure increased less during isoproterenol infusion than during exercise (7 +/- 3 vs. 27 +/- 5%), and left atrial pressure decreased during isoproterenol infusion (-23 +/- 4%) but changed in an opposite direction during exercise (7 +/- 6%). These changes were accompanied by a smaller increase in myocardial VO2 during isoproterenol infusion than during exercise (5.0 +/- 0.7 to 5.3 +/- 0.6 and 5.3 +/- 0.8 to 7.3 +/- 0.9 mumol.beat-1 x 100 g-1, respectively). In control lambs, stroke volume decreased during isoproterenol infusion despite an equal decrease in left atrial pressure as in shunt lambs. In conclusion, isoproterenol better stimulates the blood flow changes during exercise in shunt than in control lambs probably because of their higher ventricular filling pressures. In interpreting isoproterenol stress tests it should, however, be kept in mind that these changes are realized at a lower work load for the heart.