Myocardial VO2 Research Articles

799 Biventricular dysfunction and lung congestion in athletes on anabolic androgenic steroids: a speckle tracking and stress lung echocardiography analysis

Abstract Aims The real effects of the chronic consumption of anabolic–androgenic steroids (AAS) on cardiovascular structures are subjects of intense debate. Aim of the study was to detect by speckle tracking echocardiography (STE) right ventricular (RV) and left ventricular (LV) dysfunction at rest and during exercise stress echocardiography (ESE) in athletes abusing AAS. Methods and results 115 top-level competitive bodybuilders were selected (70 males), including 65 athletes misusing AAS for at least 5 years (users), 50 anabolic-free bodybuilders (non-users), compared to 50 age- and sex-matched healthy sedentary controls. Standard Doppler echocardiography, STE analysis, and lung ultrasound at rest and at peak supine-bicycle ESE were performed. Athletes showed increased LV mass index, wall thickness, and RV diameters compared with controls, whereas LV ejection fraction was comparable within the groups. LA volume index, LV and RV strain, and LV E/Em were significantly higher in AAS users. Users showed more B-lines during stress (median 4.4 vs. 1.25 in controls and 1.3 in non-users, P < 0.01 vs. users). By multivariable analyses, LV E/Ea (beta coefficient = 0.35, P < 0.01), PASP (beta = 0.43, P < 0.001) at peak effort, and number of weeks of AAS use per year (beta = 0.45, P < 0.001) emerged as the only independent determinants of resting RV lateral wall peak systolic two-dimensional strain. In addition, a close association between resting RV myocardial function and VO2 peak during ESE was evidenced (P < 0.001), with a powerful incremental value with respect to clinical and standard echocardiographic data. Conclusions STE represents a promising technique to assess RV myocardial function in athletes abusing steroids. AAS users showed a more impaired RV deformation, closely associated with reduced functional capacity during physical effort, and—during exercise—more pulmonary congestion.

Biventricular dysfunction and lung congestion in athletes on anabolic androgenic steroids: a speckle tracking and stress lung echocardiography analysis

The real effects of the chronic consumption of anabolic-androgenic steroids (AASs) on cardiovascular structures are subjects of intense debate. The aim of the study was to detect by speckle tracking echocardiography (STE) right ventricular (RV) and left ventricular (LV) dysfunction at rest and during exercise stress echocardiography (ESE) in athletes abusing AAS. One hundred and fifteen top-level competitive bodybuilders were selected (70 males), including 65 athletes misusing AAS for at least 5 years (users), 50 anabolic-free bodybuilders (non-users), compared to 50 age- and sex-matched healthy sedentary controls. Standard Doppler echocardiography, STE analysis, and lung ultrasound at rest and at peak supine-bicycle ESE were performed. Athletes showed increased LV mass index, wall thickness, and RV diameters compared with controls, whereas LV ejection fraction was comparable within the groups. left atrial volume index, LV and RV strain, and LV E/Em were significantly higher in AAS users. Users showed more B-lines during stress (median 4.4 vs. 1.25 in controls and 1.3 in non-users, P < 0.01 vs. users). By multivariable analyses, LV E/Ea (beta coefficient = 0.35, P < 0.01), pulmonary artery systolic pressure (beta = 0.43, P < 0.001) at peak effort and number of weeks of AAS use per year (beta = 0.45, P < 0.001) emerged as the only independent determinants of resting RV lateral wall peak systolic two-dimensional strain. In addition, a close association between resting RV myocardial function and VO2 peak during ESE was evidenced (P < 0.001), with a powerful incremental value with respect to clinical and standard echocardiographic data. In athletes abusing steroids, STE analysis showed an impaired RV systolic deformation, closely associated with reduced functional capacity during physical effort, and-during exercise-more pulmonary congestion.

Left atrial myocardial dysfunction after chronic abuse of anabolic androgenic steroids: a speckle tracking echocardiography analysis.

Anabolic-androgenic steroids (AAS) are used by power athletes to improve performance. However, the real effects of the chronic consumption of AAS on cardiovascular structures are subjects of intense debate. To detect by speckle tracking echocardiography (STE) underlying left atrial (LA) dysfunction in athletes abusing AAS and assess possible correlation between LA myocardial function and exercise capacity during cardiopulmonary stress test. 65 top-level competitive bodybuilders were selected (45 males), including 35 athletes misusing AAS for at least 5 years (users), 30 anabolic-free bodybuilders (non-users), compared to 40 age- and sex-matched healthy sedentary controls. Standard Doppler echocardiography, STE analysis and bicycle ergometric test were performed to assess LA myocardial function and exercise capacity. Athletes showed increased left ventricular (LV) mass index, wall thickness and stroke volume compared with controls, whereas LV ejection fraction, LV end-diastolic diameter and transmitral Doppler indexes were comparable between the three groups. Conversely, LA volume index, LV and LA strain and LV E/Em were significantly increased in AAS users. By multivariate analyses, LV E/Em (beta = - 0.30, p < 0.01), LA volume index (- 0.42, p < 0.001) and number of weeks of AAS use per year (- 0.54, p < 0.001) emerged as the only independent determinants of LA lateral wall peak STE. In addition, a close association between LA myocardial function and VO2 peak during cardiopulmonary exercise testing was evidenced (p < 0.001), showing a powerful incremental value with respect to clinical and standard echocardiographic data. STE represents a promising technique to assess LA myocardial function in athletes abusing steroids. AAS users showed a more impaired LA deformation, associated with reduced functional capacity during physical effort.

Inverse Association Between Myocardial B-Type Natriuretic Peptide Release and Functional Capacity in Healthy Humans

B-type natriuretic peptide (BNP) has been found to be inversely related to peak oxygen consumption (peak VO2) in various patient populations. However, in these studies, circulating plasma BNP, i.e. the net effect of release and elimination, rather than cardiac BNP release has been measured. We assessed the relationship between the transcardiac BNP gradient [ΔBNPCS-A, i.e. the difference between BNP in coronary sinus (BNPCS) and arterial (BNPA) plasma] and peak VO2 in healthy subjects with a view to better understanding the regulation of cardiac BNP release in humans. We studied 10 asymptomatic subjects (age 64±11 years, two females) with preserved left ventricular function (left ventricular ejection fraction 62±5%, averaged early diastolic mitral annular velocity 9±3cm/s) and low BNP (BNP in venous plasma [BNPV] <100ng/l). Subjects underwent measurement of BNPA and BNPCS for the calculation of ΔBNPCS-A, maximal cardiopulmonary exercise testing, echocardiography and resting and submaximal exercise right heart catheterisation. The median (range) BNPV, BNPA, BNPCS, and ΔBNPCS-A were 62 (14, 82), 60 (13, 79), 110 (25, 157), and 44 (1, 103) ng/l. The median peak VO2 during cardiopulmonary exercise testing was 21.5 (18, 54) ml/min/kg. There was an inverse correlation between higher ΔBNPCS-A and lower peak VO2 (r=-0.84; p=0.002) and oxygen pulse (r=-0.64, p=0.049). There was a trend towards an inverse correlation between ΔBNPCS-A and the exercise arteriovenous oxygen content difference (r=-0.58; p=0.08). In healthy humans, there is an inverse association between myocardial BNP release and peak VO2, which may be due to cardiac and non-cardiac mechanisms.

Treadmill exercise in apparently asymptomatic patients with moderate or severe aortic stenosis: relationship between cardiac index and revealed symptoms

ObjectivesTo test whether symptoms revealed on exercise testing in patients with moderate or severe aortic stenosis are associated with changes in left ventricular systolic function and to investigate the ability...

Continuous positive airway pressure decreases myocardial oxygen consumption in heart failure.

The aim of the present study was to investigate the effects of CPAP (continuous positive airway pressure) support on myocardial energetics in patients with CHF (congestive heart failure). CPAP has been shown to decrease left ventricular afterload and to produce favourable short- and long-term haemodynamic and neurohormonal benefits in CHF patients. The mechanisms responsible for these actions are not completely understood. We measured the haemodynamic and myocardial metabolic response to the acute (10 min) application of CPAP in CHF patients. Myocardial VO(2) (O(2) consumption) and VCO(2) (CO(2) production) were measured by simultaneous arterial and coronary sinus blood sampling. The application of CPAP resulted in a significant decrease in left ventricular stroke work (97+/-12 to 83+/-9 g.m; P <0.05) and myocardial VO(2) (0.32+/-0.03 to 0.25+/-0.01 ml of O(2)/beat; P <0.05). Myocardial mechanical efficiency, however, was unchanged. CPAP application decreases myocardial work and VO(2). This effect on myocardial energetics could account for some of the favourable effects of CPAP in CHF patients.

Divergent effects of NO synthase inhibition on systemic and myocardial O2 delivery and consumption during dobutamine infusion in sheep.

It is unknown if nitric oxide (NO) modulates the balance between systemic or myocardial O2 delivery ( DO2) and consumption VO2 during inotropic stimulation with the beta-adrenergic agonist dobutamine. Accordingly, we measured systemic and left ventricular (LV) DO2 and during dobutamine infusion to a peak of 10 microg .kg-1 .min-1, before and after inhibition of NO synthesis with i.v. N(omega)-nitro- L-arginine ( L-NNA, 25 mg.kg-1) in 11 anesthetized ewes instrumented with aortic, pulmonary arterial and coronary sinus catheters, an ultrasonic coronary artery flow probe and a pulmonary arterial thermistor to measure cardiac output. L-NNA reduced systemic DO2 by 19% (2.1+/-0.5 ml.min-1.kg-1, P<0.005) but increased systemic by 13% (0.4+/-0.1 ml.in-1.g-1, P<0.05), whereas LV DO2 and rose by 44% (4.3+/-1.3 ml.min-1).100 g-1, P<0.005) and 47% (3.1+/-0.9.min-1.100 g-1, P<0.025) respectively. Dobutamine increased systemic DO2 by 61% (5.3+/-0.9 ml.min-1.kg-1, P<0.001) and systemic by 10% (0.32+/-0.12 ml.min-1.kg-1, P<0.01), with no effect of L-NNA on either response ( P>0.9). As a result, while was 0.5 ml.min(-1).kg-1 higher at any given level of DO2 ( P<0.001), the slope of the systemic DO2- relation was unchanged after L-NNA. By contrast, LV DO2 increased by 152% (15.6+/-2.2 ml.min-1.100 g-1, P<0.001) and by 184% (12.7+/-1.9 ml.min-1.100 g-1, P<0.001), but because the slope of both dose-response curves was reduced by 48% after L-NNA ( P<0.001), the LV DO2- relationship was unaffected by inhibition of NO synthesis. These results suggest that NO modulated the baseline balance between systemic, but not myocardial, DO2 and. However, NO did not additionally alter dobutamine-related changes in either systemic or myocardial DO2 and balance.

Pacing-Induced Cardiac Failure of Hypertrophic Hearts: Effects of Cyclic GMP Reduction

Background. We tested the hypothesis that pacing-induced cardiac failure of hypertrophic hearts would reduce the functional and metabolic responses of these hearts to guanylate cyclase inhibition and this was associated with alterations in cyclic GMP.Materials and methods. Methylene blue (MB, 2 mg/kg/min, guanylate cyclase inhibitor) was infused into the left anterior descending coronary artery in 5 control, 5 left ventricular hypertrophy (LVH), and 5 LVH pacing-induced failure dogs. Regional myocardial work was calculated as the integrated product of force and segment shortening and regional myocardial O2 consumption (VO2) from coronary blood flow and O2 extraction measurements. Cyclic GMP was determined by radioimmunoassay.Results. MB increased regional work (635 ± 169 vs 1649 ± 500, 781 ± 184 vs 1569 ± 203 g ∗ mm/min) and VO2 (8.3 ± 1.4 vs 10.9 ± 1.4, 7.3 ± 0.7 vs 9.1 ± 0.7 ml O2/min/100 g) in both control and LVH dogs but not in failure dogs (536 ± 234 vs 623 ± 193, 3.6 ± 1.1 vs 4.7 ± 1.9). MB also decreased cyclic GMP in control dogs (1170 ± 142 vs 812 ± 105 pmol/g). LVH dogs had elevated baseline cyclic GMP (5875 ± 949) compared to control dogs but also demonstrated decreased cyclic GMP in response to MB (2820 ± 372). In failure dogs, basal cyclic GMP was also elevated (4650 ± 613) compared to control dogs but there was a lack of response to MB (3670 ± 640).Conclusions. We conclude that the myocardial function, VO2 and cyclic GMP responses to methylene blue are diminished in the transition from hypertrophy to cardiac failure.

Dopexamine Hydrochloride in Septic Shock

To test whether dopexamine hydrochloride, by its beta 2-adrenoreceptor and dopaminergic 1 (DA1) and dopaminergic 2 (DA2) agonistic properties, can improve oxygen consumption (VO2) in hyperdynamic patients with septic shock. Prospective, single-cohort study. ICU, university hospital. Twenty-nine postoperative, hemodynamically stabilized, hyperdynamic patients with septic shock. Short-term application (30 min) of dopexamine hydrochloride at a dose of 2 microgram/kg/min. Complete hemodynamic profile with O2 transport-related variables at baseline, 30 min after starting the dopexamine infusion, and 30 min after stopping the infusion. The dopexamine infusion resulted in significant increases in cardiac index (17%) (p<0.001) and O2 delivery (DO2) (16%) (p<0.001). VO2 increased slightly but significantly about 4% (p<0.001) by respiratory gas exchange measurements and 9% (p<0.001) by cardiovascular Fick calculations. The O2 extraction ratio decreased about 8% (0.001). The addition of dopexamine hydrochloride at a dose of 2 microgram/kg/min resulted in significant increases of DO2 and to a lesser extent VO2. Much of the global DO2 increase was not utilized, because O2 extraction ratio decreased. Direct calorigenic effects of dopexamine and an increase in myocardial VO2 likely account for a large portion of the increase in global VO2. Whether any of the VO2 increase reflects improvement in regions of jeopardized tissue oxygenation remains to be clarified before the definite value of this drug in septic shock can be established.

Myocardial VO2 of mechanically unloaded contraction of rat ventricular slices measured by a new approach

We instituted a new approach of measuring mechanically unloaded myocardial oxygen consumption (VO2) by using rat left ventricular (LV) slices in an air-tight chamber filled with oxygenated Tyrode solution. Myocardial slices (300 microns in thickness) freely shortened without external load by electrical field stimulation (St). VO2 without St (n = 6) was 1.69 +/- 0.41 ml O2.min-1.100 g LV-1. VO2 with St (n = 6) increased to 2.28 +/- 0.36 ml O2.min-1.100 g LV-1. VO2 in Ca(2+)-free Tyrode solution irrespective of St was nearly equal to VO2 without St in normal Tyrode solution, indicating that all these VO2 correspond to basal metabolic VO2. The increment in VO2 by St (delta VO2) increased up to twice normal with the extracellular Ca2+ concentration up to 4 times normal. Inhibition of cross-bridge cycling by 2,3-butanedione monoxime (5 and 10 mM) did not decrease delta VO2. These results suggest that delta VO2 consists of VO2 primarily for excitation-contraction coupling but not for cross-bridge cycling.

Control of oxidative metabolism in volume-overloaded rat hearts: effects of different lipid substrates

The relationship between intracellular energy parameters and myocardial O2 consumption (VO2) was studied in control and volume-overloaded hearts perfused with different lipid substrates and over a range of left ventricular work loads. In control hearts, a unique linear relationship between log of cytosolic [ATP]/[ADPf].[Pi] (where [ADPf] is concentration of free ADP) and myocardial VO2 was observed between low and high work loads for both fatty acids studied. In volume-overloaded hearts perfused in the presence of exogenous palmitate, the slope of the relationship between log [ATP]/[ADPf].[Pi] and myocardial VO2 was considerably depressed. It would seem that, under these conditions, much of the thermodynamic control of respiratory chain function has been lost. When myocardial VO2 was expressed as a function of cytosolic ADPf, the cytosolic ADPf was not regulatory. This may be related to a substrate limitation of the respiratory chain, as suggested by an excessive oxidation of pyridine nucleotides. When octanoate, instead of palmitate, was used, most of the above limitation of the respiration disappeared. With this substrate, the reduction of mitochondrial pyridine nucleotides in volume-overloaded hearts was similar to that in controls, and the linear relationship between log [ATP]/[ADPf].[Pi] and myocardial VO2 reappeared over the range of work loads studied. The above failure of cytosolic phosphate potential and ADPf to drive respiration when mitochondrial NADH is low fits well with the integrated model of kinetic regulation, as proposed by recent nuclear magnetic resonance studies. our results also indicate that, even at high respiratory rates, free-energy change of ATP synthesis of volume-overloaded hearts can be protected by use of an appropriate substrate. This, in turn, prevents contractile failure.

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.

Effects of dopexamine on hemodynamics and oxygen consumption after beta blockade in lambs

Dopexamine is a synthetic catecholamine with predominantly beta 2 and dopaminergic adrenergic receptor activities. We investigated its effects on systemic and myocardial hemodynamics and oxygen consumption (VO2) in a newborn species and studied its predominant mechanism of action. Prospective dose-response study with each animal serving as it own control. Eight chronically instrumented, unanesthetized lambs, 9 to 11 days of age. After surgical instrumentation and recovery for 72 hrs, animals were infused with dopexamine at increasing doses (1, 10, and 100 micrograms/kg/min) for 5 mins each before and after beta 1 (metoprolol) and beta 1, beta 2 (propranolol) adrenergic receptor blockade. All studies were performed during normoxia. Heart rate (HR) increased with increasing infusion rates of dopexamine and systemic arterial pressure and vascular resistance decreased. Cardiac index, left ventricular pressure development, and systemic VO2 were unchanged, as was the rate x pressure product. Left circumflex coronary artery blood flow and myocardial VO2 were unaltered. After beta 1-blockade, dopexamine produced an increase in HR and decreased systemic arterial pressure and vascular resistance. After beta 1-adrenergic receptor blockade, no change was noted in systemic or myocardial VO2, coronary blood flow, or rate x pressure product. After beta 1, beta 2-blockade with propranolol, increasing infusion rates of dopexamine resulted in decreases in systemic pressure and vascular resistance. Dopexamine produced significant cardiovascular effects mediated primarily by beta 2-adrenergic receptors, and also produced residual peripheral arterial vasodilation after combined beta 1- and beta 2-blockade. The latter finding suggests that dopaminergic receptor stimulation may partly mediate dopexamine's effects in newborn lambs.

Metabolic effects of β-adrenergic receptor blockade in advanced alcoholic cirrhosis

It has been postulated that the adverse metabolic effects of beta-adrenergic blockade with propranolol in cirrhosis may be related to altered delivery and utilisation of oxygen, particularly in patients with advanced alcoholic liver disease (ALD). Consequently, in 10 patients with decompensated ALD, we assessed (a) systemic and hepatic oxygen delivery (DO2), extraction ratio (%O2E) and consumption (VO2), (b) myocardial VO2 (assessed by the rate-pressure product [RPP], together with full systemic and splanchnic haemodynamics) and (c) hepatic redox state (HRS), measured indirectly by the arterial ketone body ratio (KBR i.e. ratio of acetoacetate/beta-hydroxybutyrate), prior to and following intravenous propranolol (0.1-2 mg/kg). Results are expressed as mean +/- S.E.M. Propranolol reduced DO2 (700 +/- 33 vs. 583 +/- 32 ml/min/m2, p < 0.05) and myocardial VO2 (RPP 72 vs. 58, p < 0.05). The %O2E increased however, (18.5 +/- 1.3 vs. 22.6 +/- 1.6%, p < 0.05), resulting in unaltered systemic VO2 (127 +/- 7.3 vs. 131 +/- 6.9 ml/min/m2, p > 0.10). Similarly hepatic VO2 did not change. KBR was not altered (0.44 +/- 0.08 vs. 0.48 +/- 0.07), and in fact improved in two patients (Child C12 and C13) from 0.17 to 0.34 and 0.12 to 0.27, respectively. In conclusion, the results of this study suggest that an underlying O2 debt exists in patients with advanced alcoholic cirrhosis and that beta-adrenergic blockade with propranolol 'normalises' the O2 supply-consumption relationship resulting in more efficient O2 utilisation without adversely affecting HRS. The mechanism of this action may be related to the antagonism of beta 2-mediated arteriovenous shunting resulting in appropriate blood redistribution.

Myocardial metabolism and adaptation during extreme hemodilution in humans after coronary revascularization.

This study was designed to evaluate the oxygen transport adjustments and myocardial metabolic adaptation that occurs with different levels of hemodilution during normothermia after cardiopulmonary bypass. Prospective, nonrandomized study. Operating room in a university hospital. Eight patients with ejection fractions (> 40%) undergoing elective coronary artery bypass grafting. Before the institution of cardiopulmonary bypass, blood was withdrawn from patients to a target hematocrit of 15%. After coronary artery bypass grafting, a catheter was inserted directly into the coronary sinus. After the patients were rewarmed to 37 degrees C, they were weaned from cardiopulmonary bypass. Hemodynamic indices were measured, as well as measurements of myocardial oxygen consumption (VO2) and myocardial metabolism (lactate extraction and coronary sinus hypoxanthine). Measurements were made at three different hematocrit values: 15%, 20%, and 25%. Hematocrit was increased by autologous blood transfusion. The three levels of hemodilution (hematocrit: 17.4 +/- 3.4%; 23.0 +/- 3.7%; 27.8 +/- 4.8%) were significantly different from baseline (hematocrit 37 +/- 2.6%; p < .05). Oxygen delivery, which increased with autologous transfusion, exceeded 350 mL/min/m2 at each level of dilution. The myocardial VO2 increased significantly after autologous transfusion compared with the most dilute condition (7.0 +/- 3.7 mL/min at hematocrit 17.4% vs. 11.2 +/- 4.8 mL/min at hematocrit 23.0% and 12.4 +/- 4.0 mL/min at hematocrit 27.8%). This transfusion-induced increase was also true of myocardial oxygen extraction. Lactate extraction and hypoxanthine release were normal and unchanged at each level of hemodilution. Systemic oxygen extraction ratio increased with hemodilution and decreased with autologous transfusion. Hemodilution to a hematocrit of approximately 15% is tolerated in anesthetized humans after coronary artery bypass surgery. There was no evidence of myocardial ischemia, as demonstrated by absence of S-T depression on the electrocardiogram, lactate extraction, or hypoxanthine release. In selected patients, postoperative transfusion may be based on systemic physiologic end-points, such as oxygen extraction ratio, rather than set hematocrit values.

Impaired Myocardial Function and Oxygen Utilization Due to Protamine Sulfate in an Isolated Rabbit Heart Preparation

The myocardial effects of protamine, with and without heparin, were documented in this investigation. Isolated rabbit hearts (n = 30) were retrograde perfused with Krebs-Ringers bicarbonate solution aerated with 95% O2/5% CO2 through the aortic root (37 C, 80 mmHg). Developed left ventricular blood pressure, heart rate, coronary artery flow, contractility as reflected by peak +dp/dt, oxygen extraction (a-vO2), and oxygen consumption (VO2) were measured at baseline and continuously throughout the experiment. Protamine (25 micrograms, 50 micrograms, and 250 micrograms per mL of perfusate) was circulated in the Krebs-Ringers buffer to hearts perfused without heparin (groups I, II, and III) or hearts perfused with heparin added to the buffer solution, 0.1 IU/1.0 microgram protamine (groups IV, V, and VI). Blood pressure 4 minutes after protamine was less in groups III (-23 mmHg) and VI (-28 mmHg) than in groups I (-6 mmHg), II (-18 mmHg), IV (-1 mmHg), and V (-7 mmHg). Heart rate changes (beats/minute) at 4 minutes revealed similar dose-dependent reductions (III and VI: -51, -55; II and V: -36, -36; and I and IV: -20, -16, respectively). Coronary artery flow at 4 minutes was slightly increased in groups III (9 mL/minute) and VI (15 mL/minute), but was relatively unchanged in the other groups. Decreases in contractility were apparent in all groups 4 minutes after protamine was started: group I, -14%; II, -16%; III, -30%; IV, -7%; V, -15%; and VI, -34%. Similarly declines in oxygen extraction and consumption were noted in all groups at the same time period and were greater in groups III (-53%, -44%) and VI (-55%, -49%) than in groups I (-25%, -26%), II (-15%, -12%), IV (-48%, -49%) and V (-15%, -18%), with p less than or equal to 0.05 or p less than or equal to 0.01 compared to baseline. Three of ten hearts exposed to high-dose protamine stopped beating after 5 minutes. This investigation establishes, for the first time, that protamine has dose- and time-specific adverse effects on cardiac contractility. In addition protamine decreases myocardial a-vO2 and VO2. These changes may contribute to certain adverse events accompanying the clinical administration of protamine.

Cardiovascular and metabolic response to red blood cell transfusion in critically ill volume-resuscitated nonsurgical patients

We examined the cardiovascular and metabolic response to RBC transfusion in patients with circulatory shock after volume resuscitation. Data were analyzed from 36 transfusions in 32 patients who were undergoing continuous hemodynamic monitoring. Transfusions were administered for moderate to severe anemia, mean Hgb 8.3 g/dl. The diagnosis were sepsis (19/36), cardiogenic shock (14/36), connective tissue disease (2/36), and severe hypocalcemia (1/36). Benefit from transfusion was defined as an improvement in tissue oxygen utilization (increased oxygen consumption [VO2] or decreased lactate), a decrease in myocardial VO2 (MAP x HR), or a decrease in myocardial work (left ventricular work index). Mean transfusion volume was 577 ml over 4.5 h. Hgb and oxygen delivery (DO2) increased by 27% and 28%, respectively, while pulmonary artery wedge pressure and cardiac index were unchanged. No significant change was noted in VO2, or lactate, after augmentation of red cell mass. An increase occurred in myocardial work indices and MAP x HR. No changes were identified when subgroups were analyzed based on diagnosis, pretransfusion Hgb, lactate, or VO2 levels. We conclude that selective increase in DO2 by augmentation of RBC mass and oxygen-carrying capacity did not improve the shock state in these volume-resuscitated patients, regardless of the etiology of the shock.

Coronary hyperperfusion and myocardial metabolism in isolated and intact hearts.

We determined the independent influence of coronary hyperperfusion on myocardial metabolism in isolated and intact hearts. In an isovolumic blood-perfused rat heart preparation working against a left ventricular (LV) balloon, the effect of increasing coronary perfusion pressure from 100 to 150 mmHg was assessed. In three groups of rat hearts LV volume was fixed to obtain LV peak pressures of 42 +/- 3, 101 +/- 5, and 130 +/- 6 mmHg. With coronary hyperperfusion, LV pressure increased 27, 18, and 16%, LV maximum time derivative of pressure (dP/dt) increased 39, 20, and 22%, and myocardial O2 consumption (VO2) increased 16, 17, and 33%, respectively. In a fourth group, LV peak pressure was held constant at 92 +/- 4 mmHg during coronary hyperperfusion by decreasing LV volume. In this group, despite an increase in coronary blood flow of 48%, there was no significant difference in LV maximum dP/dt or myocardial VO2. Thus, in isolated rat hearts, coronary hyperperfusion was not an independent stimulus to myocardial VO2. To further test this, the effect of coronary hyperperfusion on myocardial metabolism was studied in an intact working swine heart preparation where the cardiac output was fixed with a right heart bypass circuit. Fatty acid oxidation in the left anterior descending bed was assessed by production of 14CO2 from [14C(U)]palmitate. A comparison of coronary perfusion 106 +/- 5 vs. 197 +/- 5 mmHg resulted in no significant change in global LV function, including LV internal diameter. Despite a 70% increase in coronary blood flow, there was no significant change in myocardial VO2 or fatty acid utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

EFFECTS OF INTRA-AORTIC BALLOON PUMPING DURING RIGHT VENTRICULAR INFLOW OBSTRUCTION IN THE NEWBORN LAMB

The intra-aortic balloon pump (IABP), while effective in adults, could be limited in effectiveness in infants because of differences in coronary dynamics, central vascular impedence, heart rate, and the hemodynamic indications for its use. One potential indication is the decreased cardiac output (CO) secondary to right ventricular inflow obstruction (RVIO). In 6 young lambs, catheters were placed in the vena cava, left atrium, coronary sinus, aorta, and pulmonary artery. An IABP was advanced via the femoral artery to the thoracic aorta. RVIO was produced by inflating a Foley catheter in the right atrium, reducing CO by 50%. Studies were performed at rest, rest + IABP, RVIO, and RVIO + IABP. Regional blood flows were measured by the microsphere method. During resting studies, the IABP did not alter CO, heart rate, aortic pressures, systemic or myocardial O2 consumption (VO2) or O2 transport, or regional blood flows. During RVIO, aortic and left atrial pressures decreased, vena caval pressure doubled, and systemic and myocardial VO2 and O2 delivery decreased. Blood flow and O2 delivery to all organs decreased. The IABP had no significant effect on any of these parameters. In conclusion, although the IABP does not interfere with resting hemodynamics or regional blood flows, there is no evidence for its effectiveness in clinical situations where CO is decreased because of RVIO. The utility of the IABP may be affected by the etiology of the reduction in CO, or by the presence of a normal coronary vascular bed.

Myocardial blood flow and VO2 in conscious lambs with an aortopulmonary shunt.

We measured myocardial blood flow (QLVFW) and O2 consumption of the left ventricular free wall (VO2, LVFW) in 13 chronically instrumented, 7-wk-old lambs with an aortopulmonary left-to-right shunt (S) and in 10 control lambs without a shunt (C). The measured VO2, LVFW was compared with the calculated values obtained by two predictive indexes, the rate-pressure product (RPP) and the pressure-work index (PWI). Measured VO2, LVFW in S lambs was significantly higher than in C lambs [983 +/- 104 (SE) vs. 475 +/- 57 mumol X min-1 X 100 g LV-1, P less than 0.001]. This was achieved by the significantly higher QLVFW (294 +/- 33 vs. 145 +/- 15 ml X min-1 X 100 g LV-1, P less than 0.002), since the arteriovenous O2 difference across the left ventricular free wall was similar in both groups of lambs. Total coronary blood flow per unit body mass in S lambs was higher than in C lambs (14.1 +/- 1.5 vs. 5.6 +/- 0.6 ml X min-1 X kg-1, P less than 0.001), not only because of the increased VO2, LVFW per unit muscle mass, but also because of the increased total heart weight (102.4 +/- 6.4 vs. 81.2 +/- 4.9 g, P less than 0.02). Correct estimation of VO2, LVFW by means of the RPP and the PWI was only possible in C lambs. In S lambs the estimated values were significantly lower than the measured ones.(ABSTRACT TRUNCATED AT 250 WORDS)