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Decreased cardiac output at the onset of diabetes: renal mechanisms and peripheral vasoconstriction.

Recently we reported that hindquarter blood flow, measured 24 h/day, decreased progressively over the first 6 days of type 1 diabetes in rats. That response, coupled with the tendency of mean arterial pressure to increase, suggested a vasoconstrictor response. The purpose of this study was to measure the changes in cardiac output together with the renal hemodynamic and excretory responses to allow integrative determination of whether vasoconstriction likely accompanies the onset of type 1 diabetes. Rats were instrumented with a Transonic flow probe on the ascending aorta and with artery and vein catheters, and cardiac output and mean arterial pressure were measured continuously, 24 h/day, throughout the study. The induction of diabetes, by withdrawing intravenous insulin-replacement therapy in streptozotocin-treated rats, caused a progressive decrease in cardiac output that was 85 +/- 5% of control levels by day 7. This was associated with significant increases in glomerular filtration rate, renal blood flow, and microalbuminuria as well as urinary fluid and sodium losses, with a negative cumulative sodium balance averaging 15.7 +/- 1.6 meq by day 7. Restoring insulin-replacement therapy reversed the renal excretory responses but did not correct the negative sodium balance, yet cardiac output returned rapidly to control values. Increasing sodium intake during the diabetic and recovery periods also did not significantly affect the cardiac output response during any period. These results indicate that cardiac output decreases significantly at the onset of type 1 diabetes without glycemic control, and although volume loss may contribute to this response, there also is a component that is not volume or sodium dependent. We suggest this may be due to vasoconstriction, but to what extent local blood flow autoregulation or active vasoconstriction may have mediated that response is not known.

Albuminuria↗

Validation of the CO2 rebreathing method for measuring cardiac output in patients with hypertension or heart failure.

The CO2 rebreathing method, a noninvasive indirect Fick procedure, has been previously validated in normal subjects at supine rest and during exercise. In the present study 29 nearly simultaneous measurements of cardiac output were made by CO2 rebreathing and dye dilution in 17 patients with cardiovascular disease, 11 with hypertension, and six with congestive heart failure. Cardiac output at supine rest averaged 5.52 +/- 0.31 L. per minute by CO2 and 5.62 +/- 0.32 L. per minute by dye dilution (r = 0.93). Successive cardiac output measurements by rebreathing varied 6.0 +/- 1.1 per cent (r = 0.96) and by dye dilution, 6.5 +/- 0.9 per cent. Changes in cardiac output during exercise or after beta-adrenergic blockade were reflected by the CO2 method. It is concluded that the CO2 method provides reliable measurements of cardiac output both at rest and during exercise in patients with hypertension or congestive heart failure. Further validation of the method is needed in various disease states before it can be widely applied.

Carbon Dioxide↗

Cardiac output and tissue blood flow in the abalone, Haliotis cracherodii (Mollusca, Gastropoda).

Little is known about the characteristics of hemolymph (blood) flow in animals with open circulatory systems. We measured cardiac output and blood flow to specific tissues in the black abalone, Haliotis cracherodii, a gastropod mollusk. The use of thermodilution allowed us to make repeated measurements of cardiac output and cardiac stroke volume over relatively short time intervals (5-10 heart beats) in resting, unrestrained abalone while disturbing the animals minimally. Anatomical studies of the abalone circulation showed that the arterial system terminated in small diameter (approaching 10-20 micron in some cases) lacunar tissue spaces. Because of this, we used radioactive microspheres (which must be trapped in the tissue vasculature) to measure blood flow rates to selected tissues. The major findings of our study were that 1) cardiac output in the black abalone ranged from about 100 to 150 ml X kg-1 X min-1, and was highly correlated with body size; 2) weight-specific cardiac stroke volume was about 5 ml X kg-1, considerably larger than that of a mammal; 3) tissue blood flow rates ranged from 10 ml X 100 g-1 X min-1 (foot muscle) to 80 ml X 100 g-1 X min-1 (nephridial tissue), similar to typical tissue blood flow rates in mammals. Our data suggest that the blood in the abalone is directed to the tissues not in proportion to percent total body weight the tissues represent (as might be expected in an open vascular system), but apparently in proportion to tissue metabolic rate.

Animals↗

Valve area and cardiac output in aortic stenosis: quantification by magnetic resonance velocity mapping.

Valve area and cardiac output were determined with magnetic resonance (MR) velocity mapping in 12 patients with aortic stenosis. Heart catheterization, Doppler echocardiography, and indicator dilution were performed for comparison. Left ventricle could be catheterized in only nine patients; in these cases, MR measured a mean valve area of 1.2 cm2 compared with 0.9 cm2 derived from catheterization data, with a mean difference of 0.2 cm2 between the 2 methods. The limits of agreement were [0.0, +0.5] cm2, less in patients with an important degree of concomitant regurgitation. In the whole material, MR measured a mean area of 1.1 cm2 compared with 1.2 cm2 derived from Doppler echocardiography data, with a mean difference of 0.1 cm2 and [-0.5, +0.6] cm2 as limits of agreement. In 11 patients the cardiac output was quantified by MR to a mean of 4.9 L/min and by indicator dilution to 5.0 L/min, with a mean difference of 0.2 L/min, and [-0.6, +0.8] L/min as limits of agreement. In addition, MR offers the major advance of simultaneous quantification of regurgitant volume in cases of concomitant regurgitation. In conclusion, because the two important prognostic determinants in aortic stenosis--the valvular area and the cardiac output--may be quantified, MR has potential to become a clinical tool in assessment of severity in aortic stenosis.

Aged↗

Contribution of lung stretch depressor reflex to nonlinear fall in cardiac output during PEEP.

The hypothesis that lung stretch reflexes elicit negative cardiovascular effects during positive end-expiratory pressure (PEEP) application in a ramp procedure up to 15 cmH2O was tested in piglets under steady-state anesthesia and muscle relaxation. The effects of lung stretch on hemodynamics were studied by comparing the differences in responses during PEEP application with two different tidal volumes. In both ventilatory conditions cardiac output and aortic pressure decreased nonlinearly in three phases with the rise of PEEP: a gradual decrease in phase I, a sharp decrease in phase II, and again a more gradual decrease in phase III. Heart rate decreased significantly in phase II. In the series with the larger tidal volume, implying more lung stretch during insufflation, phase II was between a PEEP of 2.6 and 9 cmH2O. In the series with the smaller tidal volume, phase II occurred between 5.7 and 10.5 cmH2O. To assess the contribution of lung stretch reflexes to the decrease in cardiac output we also related cardiac output to the changes in central venous pressure. Again a nonlinear response was observed, indicating that an additional effect besides the rise in mean central venous pressure was involved in the decrease in cardiac output. During ventilation with the smaller tidal volume, phase II of the decrease in cardiac output was also shifted to higher values of mean central venous pressure, which only could be ascribed to the differences in lung stretch at insufflation. It appeared that under circumstances of artificial ventilation the onset of the reflex is determined by a characteristic threshold of lung stretch.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The reason for cardiac output reduction after aortic cross-clamping.

The hypothesis that a decrease in cardiac output during infrarenal aortic cross-clamping is related to a decrease in oxygen consumption in the perfused tissues (cross-clamp-adapted oxygen consumption) rather than to deterioration of myocardial performance has been tested. Twenty-two patients undergoing excision of an aortic abdominal aneurysm were randomly divided into two groups of equal number. During aortic cross-clamping, Group 1 patients received nitroglycerin infusion, 1 to 2 micrograms.kg-1.min-1, whereas Group 2 patients did not receive a nitroglycerin infusion. During aortic cross-clamping, cross-clamp-adapted body oxygen consumption decreased equally in both groups by 40 to 42 percent of baseline values, whereas cardiac output decreased by 17 percent in Group 2 but did not change significantly in Group 1. Mixed venous oxygen content increased significantly after induction of anesthesia and prior to aortic cross-clamping in both groups. During cross-clamping, the values of mixed venous oxygen content remained increased in Group 2 and increased further in Group 1. The data support our hypothesis since a decrease in cardiac output was not associated with an increase in filling pressures during aortic cross-clamping, but was instead associated with an increase in mixed venous oxygen content and a decrease in the arteriovenous oxygen content difference. Nitroglycerin infusion was associated with a further increase in mixed venous oxygen content during aortic cross-clamping and a decrease in the arteriovenous oxygen content difference, without a concomitant increase in oxygen utilization.

Aorta, Abdominal↗

Continuous Fick cardiac output measurement during exercise by monitoring of mixed venous oxygen saturation and oxygen uptake.

To determine whether continuous Fick cardiac output measurement is applicable to exercise testing, cardiac output data obtained by the continuous Fick method (Qcf) during exercise were compared with data obtained by the thermodilution method (Qth). Seventeen patients with old myocardial infarction underwent a 1-min or 3-min incremental exercise test (protocols 1 and 2, respectively). During exercise, the oxygen consumption (VO2), arterial oxygen saturation (SaO2), and mixed venous oxygen saturation (SvO2) were monitored continuously. Qcf was calculated at 12-s intervals by the Fick equation. The SaO2 remained almost constant during exercise. The SvO2 showed four characteristic phases during exercise protocol 1. SvO2 values changed rapidly in phases 2 and 4, but only slightly during phase 3. In exercise protocol 2, SvO2 almost reached a steady-state by the end of each stage. The correlation between Qcf and Qth was good in protocol 1 (r = 0.86), except in phases 2 and 4, and was also good in protocol 2 (r = 0.80). We conclude that the continuous Fick method may be applicable for determining the cardiac output during exercise provided that the variation in SvO2 is slight.

Adult↗

Increasing tidal volumes and pulmonary overdistention adversely affect pulmonary vascular mechanics and cardiac output in a pediatric swine model.

OBJECTIVES: In a pediatric swine model, the effects of increasing tidal volumes and the subsequent development of pulmonary overdistention on cardiopulmonary interactions were studied. The objective was to test the hypothesis that increasing tidal volumes adversely affect pulmonary vascular mechanics and cardiac output. An additional goal was to determine whether the effects of pulmonary overdistention are dependent on delivered tidal volume and/or positive end-expiratory pressure (PEEP, end-expiratory lung volume). DESIGN: Prospective, randomized, controlled laboratory trial. SETTING: University research laboratory. SUBJECTS: Eleven 4- to 6-wk-old swine, weighing 8 to 12 kg. INTERVENTIONS: Piglets with normal lungs were anesthetized, intubated, and paralyzed. After median sternotomy, pressure transducers were placed in the right ventricle, pulmonary artery, and left atrium. An ultrasonic flow probe was placed around the pulmonary artery. MEASUREMENTS AND MAIN RESULTS: The swine were ventilated and data were collected with delivered tidal volumes of 10, 15, 20, and 25 mL/kg and PEEP settings of 5 and 10 cm H2O in a random order. Pulmonary overdistention was defined as a decrease in dynamic compliance of > or =20% when compared with a compliance measured at a baseline tidal volume of 10 mL/kg. At this baseline tidal volume, airway pressure-volume curves did not demonstrate pulmonary overdistention. Tidal volumes and airway pressures were measured by a pneumotachometer and the Pediatric Pulmonary Function Workstation. Inspiratory time (0.75 sec), FIO2 (0.3), and minute ventilation were held constant. We evaluated the pulmonary vascular and cardiac effects of the various tidal volume and PEEP settings by measuring pulmonary vascular resistance, pulmonary characteristic impedance, and cardiac output. When compared with a tidal volume of 10 mL/kg, a tidal volume of 20 mL/kg resulted in a significant decrease in dynamic compliance from 10.5 +/- 0.9 to 8.4 +/- 0.6 mL/cm H2O (p = .02) at a constant PEEP of 5 cm H2O. The decrease in dynamic compliance of 20% indicated the presence of pulmonary overdistention by definition. As the tidal volume was increased from 10 to 20 mL/kg, pulmonary vascular resistance (1351 +/- 94 vs. 2266 +/- 233 dyne x sec/cm5; p = .004) and characteristic impedance (167 +/- 12 vs. 219 +/- 22 dyne x sec/cm5; p = .02) significantly increased, while cardiac output significantly decreased (951 +/- 61 vs. 708 +/- 48 mL/min; p = .001). Each of these effects of pulmonary overdistention were further magnified when the tidal volume was increased to 25 mL/kg. The tidal volume-induced alterations in pulmonary vascular mechanics, characteristic impedance, and cardiac output occurred to a greater degree when the PEEP was increased to 10 cm H2O. Pulmonary vascular resistance and characteristic impedance were significantly increased and cardiac output significantly decreased for all tidal volumes studied at a PEEP of 10 cm H2O as compared with 5 cm H2O. CONCLUSIONS: Increasing tidal volumes, increasing PEEP levels, and the development of pulmonary overdistention had detrimental effects on the cardiovascular system by increasing pulmonary vascular resistance and characteristic impedance while significantly decreasing cardiac output. Delivered tidal volumes of >15 mL/kg should be utilized cautiously. Careful monitoring of respiratory mechanics and cardiac function, especially in neonatal and pediatric patients, is warranted.

Animals↗

Measuring cardiac output in one-lung ventilation: a comparison of pulmonary artery and transpulmonary aortic measurements in pigs.

OBJECTIVE: The agreement between cardiac output measurements via pulmonary artery thermodilution (CO[PA]) and transpulmonary aortic thermodilution (CO[AT]) during one-lung ventilation was studied. DESIGN: Animal study with repeated simultaneous measurements comparing 2 cardiac output measurement techniques. SETTING: Experimental animal facility of a university department. PARTICIPANTS: Forty-eight female pigs (26-42 kg). INTERVENTIONS: The pigs were anesthetized, tracheally intubated, and mechanically ventilated. After placement of an aortic thermistor catheter via the femoral artery and a pulmonary artery catheter, a double-lumen tube was placed via tracheotomy. During one-lung ventilation in each animal, 3 measurements with pulmonary artery thermodilution and transpulmonary aortic thermodilution were performed in different hemodynamic states. Both thermistors were connected to 1 computer system, and 144 simultaneous cardiac output measurements were analyzed. MEASUREMENTS AND MAIN RESULTS: Linear regression analyses revealed a close relationship between the 2 methods: CO(AT) = 0.81 CO(PA) + 1.04 (L/min) (r = 0.96, p < 0.0001). Bland-Altman analysis showed that CO(AT) was slightly higher than the CO(PA) with a bias of 0.2 +/- 0.5 L/min. However, in higher CO states, an inversion of this relationship was found, possibly because of indicator loss and recirculation. CONCLUSIONS: The pulmonary artery thermodilution and the transpulmonary aortic thermodilution techniques both accurately measure cardiac output during one-lung ventilation.

Animals↗

Theory and application of thermodilution cardiac output measurement: a review.

The thermodilution method of measuring cardiac output has a firm scientific basis and provides data to assist clinicians in assessing the hemodynamic function of patients and evaluating therapeutic interventions. Most of the research that validated this method of measurement was conducted from 1954 to 1979. Research in the 1980s focuses primarily on refining measurement techniques evaluating protocols that will simplify measurements in the clinical setting, and testing new devices that have the potential for affecting the accuracy of measurements. Although discrepancies between theory and application took years to resolve resulting in initial resistance to this method, thermodilution cardiac output measurement is now well accepted by researchers and clinicians as safe, simple, and accurate.

Animals↗

Cardiac output determinations with ear piece densitometry.

The results of cardiac output determinations by a dye dilution technique were compared using (a) a dichromatic earpiece which was calibrated as a flow-through cuvette, but also permitted automatic computing by virtue of a pressure capsule, and (b) an ordinary flow-through densitometer. Eleven subjects, some with cardio-pulmonary disease, were investigated. Cardiac outputs were systematically overestimated when automatically computed. The results obtained by manual calculation with the ear-piece corresponded more nearly with those derived from the flow-through cuvette, but still with a deviation from the identity line and with a residual standard deviation of 0.8 l/min. Double determinations had a residual standard deviation of 0.7 l/min. Despite its ease of handling, an earpiece densitometer seems to be too unreliable to be suitable for routine use.

Adult↗

Effects of vasopressin on cardiac output and its distribution in the subhuman primate.

The effects of vasopressin, when administered as intravenous bolus injections and infusions, on cardiac output and the distribution of blood flow to the splanchnic vascular beds were studied in six anesthetized rhesus monkeys. Vasopressin as bolus injections caused dose-dependent decreases in superior mesenteric arterial blood flow. However, small reductions in cardiac output were observed only at the highest doses concomitant with increases in systemic arterial pressure. When vasopressin was infused at the highest dose (5 X 10(-2) units kg-1 min-1) for 10 minutes, cardiac output was unaffected; but sustained reductions in superior mesenteric arterial blood flow and increases in arterial pressure and total peripheral resistance were observed. Infusions of vasopressin (5 X 10(-3) units kg-1 min-1) caused significant and sustained reductions in superior mesenteric arterial blood flow and increases in arterial pressure but no measurable effects on cardiac output or total peripheral resistance. However, there was a significant redistribution of blood flow away from the stomach, small and large intestines, spleen, and pancreas toward the liver (hepatic artery), with no statistically significant change in renal blood flow. On the assumption that comparable responses exist among primates, these data support the clinical use of vasopressin to control gastrointestinal hemorrhage and to offer a probably ideal dose and route of administration.

Animals↗

Effects of thyroxine and growth hormone treatment of dairy cows on milk yield, cardiac output and mammary blood flow.

Four cows received thyroxine injections (T4; 20 mg/d) and three cows received growth hormone injections (GH; 44 mg/d) for 4 d during successive 16-d experimental periods. Measurement was made of milk yield, protein yield, mammary tyrosine and phenylalanine uptake, blood plasma hormone concentrations, mammary blood flow and cardiac output. Milk yield increased by 25% with T4 and 21% with GH treatment. Milk protein content tended to decline during T4 treatment and increase following GH treatment. Cardiac output increased by 8.9 liter/min (20%) and 4.6 liter/min (10%) with T4 and GH injection. Mammary blood flow (half-udder) increased from 3.6 to 4.9 liter/min (35%) and from 3.3 to 4.4 liter/min (33%) with T4 and GH treatment, respectively. These increases calculated on a whole-udder basis, accounted for 28% (T4) and 48% (GH) of the increases in cardiac output. The proportion of cardiac output perfusing the (whole) udder increased to 19.1% (T4) and 18.7% (GH), increases of 17 and 30%, respectively. Heart rate increased with T4 (but not GH treatment) from 80 to 115/min. Ratio of blood flow to milk yield was not changed by either treatment. The proportion of cardiac output perfusing the udder likely plays a major role in facilitating the partitioning of nutrients for milk synthesis.

Animals↗

In vivo correlation of thermodilution cardiac output and videodensitometric indicator-dilution curves obtained from contrast two-dimensional echocardiograms.

In previous studies, indicator-dilution curves obtained by videodensitometry of contrast two-dimensional echocardiograms have shown close correlation with measurements of blood flow in vitro. In this study the technique was extended and contrast indicator-dilution curves obtained in vivo were correlated with simultaneous cardiac output measurements determined by thermodilution in eight dogs. Two-dimensional echocardiograms of the left ventricle were performed with the transducer on the myocardium during left atrial-pulmonary vein injection of 10 cc of a 1 X 10(-4) concentration of 30 mu diameter microballoons. A total of 148 injections were performed at 37 levels of cardiac output (1.70 to 7.90 liters/min) induced by alterations of left ventricular preload, isoproterenol and propranolol. Indicator-dilution curves were obtained from recordings of the analog signal of a linear videodensitometer focused on the left ventricle. Linear regression analysis between total area of the indicator-dilution curves and cardiac output yielded correlation coefficients (r) of 0.77 to 0.96 (mean 0.90) for individual dogs, and 0.65 for all cardiac output determinations in all dogs. Analysis of indicator-dilution curve area by the forward triangle-exponential decay method yielded enhanced individual coefficients of 0.90 to 0.97 (mean 0.94) with cardiac output and 0.61 for the group of animals. It is concluded that echographic indicator-dilution curves obtained from uniform size microballoons and videodensitometry may be obtained in vivo and correlate with cardiac output measurements.

Animals↗

Effects of propranolol and pindolol on cardiac output during extended periods of low-intensity physical activity.

The effects of a nonselective beta-adrenergic blocking agent with (pindolol) and without (propranolol) intrinsic sympathomimetic activity properties, compared with placebo-controlled conditions, on metabolic and cardiorespiratory function during long-duration (2 hours) physical activity were examined. After initial cardiorespiratory testing, subjects performed 2-hour walks at 25 and 45% of maximal oxygen consumption (VO2max) under each of the following 3 treatments: pindolol, propranolol and placebo. Medication distribution was randomized and double-blinded. A supine resting blood pressure and electrocardiogram were obtained before each exercise trial. Oxygen consumption, heart rate, stroke volume, cardiac output and blood pressure were determined after 5 minutes of quiet sitting and every 30 minutes during each 2-hour exercise trial. Cardiac output was not significantly different at rest or during exercise, comparing pindolol and propranolol with placebo conditions. Cardiac output tended to decrease over time earlier during propranolol treatment for the 25% VO2max trials in trained normotensive subjects than for the other treatments. Cardiac output decreased at approximately the same time across treatments during the 45% VO2max trials in trained normotensive and untrained hypertensive groups. Finally, owing to the observation that a reduction in cardiac output was delayed or prevented in trained normotensive subjects when compared with that in untrained hypertensives while exercising at 25% VO2max, developing a subject's cardiovascular fitness level may be important in the maintenance of cardiac output during extended periods of low-to-moderate physical activities while under the influence of beta-adrenergic blockade.

Adolescent↗

Cerebral blood flow velocity and cardiac output in infants of insulin-dependent diabetic mothers.

Cardiac output and cerebral blood flow velocity in the anterior cerebral and internal carotid arteries were investigated in eight large-for-date infants of insulin-dependent diabetic mothers and 12 healthy term infants during the first four days of life using two-dimensional/pulsed Doppler ultrasound. Temporal mean flow velocity was used as an indicator of changes in cerebral blood flow. Six of the eight infants of diabetic mothers had ventricular septal hypertrophy with reduced cardiac outputs and stroke volumes. Mean flow velocity in both cerebral vessels showed a comparable pattern in both groups throughout the study period and was independent of mean arterial pressure, suggesting unaltered cerebral hemodynamics in the infants of diabetic mothers.

Adult↗

The effects of maternal position and cardiac output on intrapulmonary shunt in normal third-trimester pregnancy.

OBJECTIVE: To assess the effect of pregnancy, maternal position, and cardiac output on intrapulmonary shunting (Qs/Qt) in normotensive nulliparous women near term. METHODS: Ten normotensive nulliparas between 36 and 38 weeks' gestation underwent pulmonary artery catheterization (via the subclavian route) and radial artery canalization. Baseline assessments were made with subjects in the left lateral recumbent position after a 30-minute stabilization period. Measurements were obtained sequentially in the left lateral, right lateral, supine, knee-chest, sitting, and standing positions. Each position change was followed by a 10-minute pre-measurement stabilization period. Cardiac output was measured via the thermodilution technique. Blood samples were obtained simultaneously from the pulmonary and radial arteries and analyzed in duplicate for oxygen content with a blood gas analyzer. Qs/Qt was calculated using the classic shunt equation. Statistical analysis was performed by analysis of variance of repeated measures of Qs/Qt and maternal position. The relationship of Qs/Qt to maternal cardiac output was evaluated by the correlation coefficient. Significance was defined as P < .05. RESULTS: Directly measured Qs/Qt averaged 15.3% in left lateral, 15.2% in right lateral, 13.9% in supine, 12.8% in knee-chest, 13.8% in sitting, and 13.0% in standing positions. There was no statistically significant correlation between Qs/Qt and cardiac output (R2 = 0.11, not significant). CONCLUSION: This is the first report of directly measured Qs/Qt in normal pregnant women in the third trimester. Qs/Qt values reported in pregnancy are higher than those reported in nonpregnant individuals.

Adult↗

A comparative study of cardiac output measurement by dye dilution and pulsed Doppler ultrasound.

Dye dilution was compared with pulsed doppler for the measurement of cardiac output in eighteen children being ventilated after cardiac surgery. The mean difference between the two techniques was -0.04/min (dye minus doppler) with 95% confidence limits of 0.25 l/min and -0.33 l/min over a cardiac output range 0.27-6.12 l/min; this difference is not significant. Calculation of the product-moment correlation coefficient showed a close relationship between the dye dilution and doppler methods with r = 0.97. Pulsed doppler is a new noninvasive technique that can be used instead of dye dilution for the measurement of cardiac output in co-operative or anaesthetised children.

Aorta↗