Executive Function Predicts the Validity of Subjective Memory Complaints in Older Adults beyond Demographic, Emotional, and Clinical Factors.

BACKGROUND: Although evidence suggests that subjective memory complaints (SMCs) could be a risk factor for dementia, the relationship between SMCs and objective memory performance remains controversial. Old adults with or without mild cognitive impairment (MCI) may represent a highly heterogeneous group, based partly on the demonstrated variability in the level of executive function among those individuals. It is reasonable to speculate that the accuracy of the memory-monitoring ability could be affected by the level of executive function in old adults. OBJECTIVE: This study investigated the effects of executive function level on the consistency between SMCs and objective memory performance while simultaneously considering demographic and clinical variables in nondemented older adults. SETTING: Participants were recruited from both the memory clinics and local communities. PARTICIPANTS: Participants comprised 65 cognitively normal (CN) older adults and 54 patients with MCI. MEASUREMENTS: Discrepancy scores between subjective memory evaluation and objective memory performance were calculated to determine the degree and directionality of the concordance between subjective and objective measures. Demographic, emotional, genetic, and clinical information as well as several executive function measurements were collected. RESULTS: The CN and MCI groups exhibited similar degrees of SMC; however, the patients with MCI were more likely to overestimate their objective memory ability, whereas the CN adults were more likely to underestimate their objective memory ability. The results also revealed that symptoms of depression, group membership, and the executive function level together predicted the discrepancy between the subjective and objective measures of memory function; however, the executive function level retained its unique predictive ability even after the symptoms of depression, group membership, and other factors were controlled for. CONCLUSION: Although both noncognitive and cognitive factors were necessary for consideration, the level of executive function may play a unique role in understanding the equivocal relationship of the concurrence between subjective complaints and objective function measures. Through a comprehensive evaluation, high-risk individuals (i.e., CN individuals heightened self-awareness of memory changes) may possibly be identified or provided with the necessary intervention during stages at which objective cognitive impairment remains clinically unapparent.

Effects of amino acids on substrate selection, anaplerosis, and left ventricular function in the ischemic reperfused rat heart.

The effect of aspartate and glutamate on myocardial function during reperfusion is controversial. A beneficial effect has been attributed to altered delivery of carbon into the citric acid cycle via substrate oxidation or by stimulation of anaplerosis, but these hypotheses have not been directly tested. 13C isotopomer analysis is well suited to the study of myocardial metabolism, particularly where isotopic and metabolic steady state cannot be established. This technique was used to evaluate the effects of aspartate and glutamate (amino acids, AA) on anaplerosis and substrate selection in the isolated rat heart after 25 min of ischemia followed by 30 or 45 min of reperfusion. Five groups of hearts (n = 8) provided with a mixture of [1,2-13C]acetate, [3-13C]lactate, and unlabeled glucose were studied: control, control plus AA, ischemia followed by 30 min of reperfusion, ischemia plus AA followed by 30 min of reperfusion, and ischemia followed by 45 min of reperfusion. The contribution of lactate to acetyl-CoA was decreased in postischemic myocardium (with a significant increase in acetate), and anaplerosis was stimulated. Metabolism of 13C-labeled aspartate or glutamate could not be detected, however, and there was no effect of AA on functional recovery, substrate selection, or anaplerosis. Thus, in contrast to earlier reports, aspartate and glutamate have no effect on either functional recovery from ischemia or on metabolic pathways feeding the citric acid cycle.

Characteristics of ventricular function in severe hemorrhagic shock.

Although left ventricular (LV) function appears altered by severe hemorrhagic shock (HS), the mechanisms of this dysfunction have been difficult to characterize. Depression in the LV function curve could be caused by altered diastolic or systolic function. It has been difficult to assess the systolic function, but the use of the rate and load independent index of contractility, Emax (the slope of the end-systolic pressure-dimension relationship), offers a new approach to the quantification of systolic mechanical performance. Emax and the LV diastolic pressure-strain relationship were measured in 15 chronically instrumented dogs by sonomicrometric and micromanometric techniques. Gradual LV unloading was obtained from transient vena caval occlusion. After control study, each dog underwent 2 hours of HS (mean aortic pressure 40 mm Hg), followed by reinfusion of all shed blood. Upon reinfusion, Emax was not decreased; however, all dogs had a significant decrease in LV compliance. During the next 4 days, the LV compliance of the eight survivors progressively returned toward control, while Emax remained stable. All seven nonsurvivors demonstrated progressive loss of LV compliance, and Emax was significant decreased prior to death. Cardiac contractility appeared improved immediately after shock, but a consistent decrease in compliance was observed. Reversal of abnormal diastolic function was demonstrated in all survivors and progressive depression in all nonsurvivors. Depression in systolic function was observed only in nonsurvivors immediately prior to death.

Effects of storage and reperfusion oxygen content on substrate metabolism in the isolated rat lung.

BACKGROUND: Lung transplantation requires a period of storage and ischemia; we examined the largely unknown effects of that period on intermediary metabolism. METHODS: Two groups of isolated rat lung blocks (n = 16 each) were flushed with Euro-Collins solution and harvested. The lung blocks were immediately ventilated and either perfused for 30 minutes with an erythrocyte-based solution containing carbon 13 labeled substrates (group 1) or stored for 6 hours at 1 degree C and then reperfused (group 2). Half of each group was reperfused at a physiologic Po2 the other half at high Po2. Analysis of carbon 13 isotopomers was performed to determine substrate utilization through aerobic pathways in lung tissue. RESULTS: Lungs from both groups oxidized all major substrates. The contribution of fatty acids to acetylcoenzyme acid oxidized in the citric acid cycle was significantly higher in group 2 than in group 1 (31.3% +/- 2.2% versus 22.0% +/- 2.1%, p < 0.05). Perfusate Po2 did not affect substrate preference. Gas exchange was worse in stored lungs. CONCLUSIONS: After a period of hypothermic ischemia and storage, substrate preference in lung tissue exhibits a switch towards fatty acids. As fatty acid oxidation occurring after ischemia is deleterious in other organs, strategies to inhibit this process in stored lungs may warrant further investigation.

Effect of extracorporeal membrane oxygenation flow on pulmonary capillary blood flow.

OBJECTIVE: To validate a new application of the modified acetylene rebreathing method for pulmonary capillary blood flow in a swine extracorporeal membrane oxygenation (ECMO) model. DESIGN: Prospective, sequential measurements of pulmonary capillary blood flow, using a rebreathing technique, as affected by different flows through the ECMO circuit. SETTING: A cardiovascular hemodynamic research laboratory at a university medical center. SUBJECTS: Fifteen young mature farm swine (48 to 52 kg). INTERVENTIONS: Pulmonary capillary blood flow was measured using a modified rebreathing technique, and this measurement repeated at different flow rates through the extracorporeal membrane oxygenation circuit. Pulmonary artery flow rates were measured using both thermodilution and echo-Doppler techniques for comparison purposes. MEASUREMENTS AND MAIN RESULTS: Pulmonary capillary blood flow measurements, as assessed by modified acetylene rebreathing, compared well with both the thermodilution cardiac output measurement during normal circulation and the pulmonary artery flow probe measurement while the subjects received ECMO. Mean pulmonary capillary blood flow measured by acetylene rebreathing decreased from 89.72 +/- 6.97 (baseline) to 43.59 +/- 5.66 mL/kg/min as ECMO flow was maximized to 56.22 +/- 3.62 mL/kg/min. Decreasing the ECMO flow rate by half (to 28.23 +/- 3.45 mL/kg/min) caused an increase in mean pulmonary capillary blood flow to 53.79 +/- 6.16 mL/kg/min. When ECMO flow was discontinued, pulmonary capillary blood flow returned to a near baseline value of 71.68 +/- 7.05 mL/kg/min (mean values of pooled data for both closed- and open-chest animals [n = 15]). These measurements correlated well with both thermodilution cardiac output and pulmonary artery ultrasonic flow probe measurements. CONCLUSIONS: The modified acetylene rebreathing method is a valid and accurate method for the measurement of pulmonary capillary blood flow in the presence of ECMO flows. Pulmonary blood flow decreases as ECMO flow is increased, and the extent of decrease is directly proportional to the amount of flow through the extracorporeal circulation.

An extracorporeal perfusion system to bridge pediatric liver transplant candidates.

An extracorporeal liver perfusion system was designed to maintain cadaver livers in an oxygenated, normothermic state for bridging procedures for hepatic transplantation. Nonpulsatile high flow and pulsatile low flow blood are supplied to the portal venous (PV) and hepatic arterial (HA) circulations. Controlled low blood flow (5-10 cc/kg [patient]/min) is exchanged between the high flow extracorporeal perfusion circuit (1 cc/g [liver]/min) and the patient. The system was evaluated in perfusions of fresh, excised pig livers (n = 5). The average oxygen consumption was 9 +/- 3 microliters/g/min, and bile production averaged 4.7 microliters/g/hr. Perfusion pressures and flows were normal in both the HA and PV circulations for about 4 hr. Pressures then gradually rose, especially in the HA circulation, causing flow to decrease, with subsequent mottling and discoloration of the liver. Red blood cell, platelet, and white blood cell counts fell continuously. Maintenance of liver function was assessed by clearance of an 80 mg taurocholic acid challenge. An average of 56% of injected acid was cleared from the perfused livers (n = 5) in the first half hour, compared with 90% and 25% for the in situ (n = 3) and unperfused (n = 3) control livers, respectively. The system consistently maintained livers in a moderately well functioning state through the first 4 hr of perfusion. Adequate support of animals with induced hepatic failure must now be demonstrated.

Early mechanical function in the heterotopic heart transplant.

The characteristics of left ventricular (LV) function in the nonimmunosuppressed heterotopic heart transplant (TX) with less than 3 hr of cold preservation, were studied in 12 awake chronically instrumented dogs prior to TX (control), 1-12 hr post TX (P1), 12-24 hr post TX (P2), and 24-48 hr post TX (P3). Micromanometers measured LV transmural pressure and ultrasonic transducers measured ventricular dimension in order to allow calculations of myocardial mechanical properties. Immediately after transplant (P1) there was significant (P less than 0.05) depression noted in both diastolic function and systolic function (peak LV pressure, 137 +/- 5 vs 80 +/- 10 mm Hg; dp/dtmax, 2642 +/- 170 vs 1038 +/- 98 mm Hg/sec; maximum velocity of minor axis shortening, 4.46 +/- 0.50 vs 2.41 +/- 0.56; and Emax, 6.5 +/- 1.2 vs 2.0 +/- 1.4 mm Hg/ml). However, the contractility reserve (studied in six dogs) as estimated by postextrasystolic potentiation ratio was maintained (1.41 +/- 0.07 vs 1.37 +/- 0.15), suggesting reversibility of the depressed function. Over the next 2 days the diastolic function and the systolic function (at P3: 109 +/- 6 mm Hg, 1842 +/- 450 mm Hg/sec, 5.54 +/- 0.77 cm/sec, and 4.5 +/- 1.3 mm Hg/ml, respectively) gradually improved toward control. Microscopic examination of the autopsied hearts did not show significant evidence of rejection. Thus, the early depression of function in the heart TX appeared to be the result of ischemia from preservation and surgical trauma.(ABSTRACT TRUNCATED AT 250 WORDS)