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Increased resting metabolic rate in patients with congestive heart failure.

OBJECTIVE: To examine resting metabolic rate in patients with congestive heart failure as a cause of cardiac cachexia and associated weight loss. DESIGN: Cross-sectional study. SETTING: Baltimore Veterans Affairs Medical Center. PATIENTS: 20 men with heart failure (mean age +/- SD, 69 +/- 7 years) and reduced ejection fraction (mean, 0.24 +/- 0.10) and 40 healthy men (mean age, 69 +/- 7 years). RESULTS: Patients with heart failure had smaller fat-free mass than did controls (53 +/- 8 kg compared with 56 +/- 6 kg; P < 0.09), but no difference in fat mass existed (21 +/- 8 kg compared with 19 +/- 8 kg). Measured resting metabolic rate was 18% higher in patients with heart failure than in controls (1828 +/- 275 kcal/d compared with 1543 +/- 219 kcal/d; P < 0.01); no difference in caloric intake existed (2144 +/- 479 kcal/d compared with 2174 +/- 826 kcal/d). The difference in resting metabolic rate between the two groups was even more striking when indexed per kilogram of fat-free mass. CONCLUSIONS: Higher resting metabolic rate in patients with heart failure at least partially accounts for otherwise unexplained weight loss. Present caloric guidelines, which were established in healthy elderly persons, substantially underestimate the resting caloric needs of elderly persons with heart failure.

Aged↗

Efficacy of nifedipine in rest angina refractory to propranolol and nitrates in patients with obstructive coronary artery disease.

Nineteen patients with recurrent rest angina were given oral nifedipine. All patients had chest discomfort refractory to propranolol and oral or topical nitrates given to tolerance. The addition of nifedipine, 30 to 120 mg daily, abolished rest angina in 14 patients, decreased its frequency in two, and had no effect in three patients. Five of seven patients on long-term nifedipine (mean, 6.2 +/- 3.4 months) remained free of rest pain. Of seven patients who had their nifedipine dose decreased or discontinued, five had recurrent rest angina. Of the 19 patients, 16 had coronary angiography. Five had three- vessel obstructive disease (greater than 75% lesion), six had two-vessel obstructive disease, and five had one-vessel obstructive disease. The remaining three unstudied patients had pathologic Q waves in the ECG. Thus nifedipine appears to be an efficacious agent in the treatment of refractory rest angina in patients with obstructive coronary artery disease.

Adult↗

Effects of peritoneal rest on peritoneal transport and peritoneal membrane thickening in continuous ambulatory peritoneal dialysis rats.

OBJECTIVE: To evaluate the effects of peritoneal rest on peritoneal transport and morphology in a rat model of peritoneal dialysis. DESIGN: Twenty-four rats (Sprague-Dawley, male, 250-300 g) were divided into three groups: group 1 (control, n = 6) without dialysis, group 2 (n = 9) sacrificed immediately after 3 weeks of dialysis, and group 3 (n = 9) sacrificed after 4 weeks of peritoneal rest after 3 weeks of dialysis. Both dialysis groups were dialyzed twice daily with an intraperitoneal instillation volume of 25 mL of 3.86% dextrose solution for 3 weeks. Peritonitis was induced by supplementing the dialysis fluid with lipopolysaccharide (5 microg/mL) on days 8, 10, and 12 in both dialysis groups. Peritoneal equilibration tests were performed on each animal at baseline. The equilibration tests were repeated at the 4th and the 8th week of dialysis. Morphometric analyses of the peritoneal membrane were carried out in tissue specimens obtained at the time of sacrifice. RESULTS: The D/D0 ratio for glucose at two hours in groups 2 and 3 at the beginning of week 4 was significantly lower than at baseline, indicating an increase in peritoneal permeability to glucose after 3 weeks of dialysis. D/D0 in group 3 at the beginning of week 8, after 4 weeks of peritoneal rest, was significantly higher than at week 4. The drain volume in groups 2 and 3 at week 4 was significantly lower than at baseline; however, the drain volume in group 3 at week 8 was significantly higher than at week 4. The thickness of the parietal peritoneal membrane in group 3 was significantly greater than in group 1 and less than in group 2 (group 1, 11.4+/-7.6 microm; group 2, 37.5+/-18.4 microm; group 3, 21.4+/-12.1 microm). CONCLUSIONS: Peritoneal rest improves ultrafiltration in rats by decreasing the hyperpermeability of glucose and also reduces the degree of peritoneal thickening. These data suggest that dialysis-induced changes in peritoneal transport and morphology are reversible under the conditions of peritoneal rest in this experimental model.

Animals↗

Lack of prognostic value of 99mTc MIBI rest, 18F FDG and 201TL rest/redistribution on PTCA outcome of patients with moderate left ventricle dysfunction.

BACKGROUND: The clinical work-out of patients undergoing coronary revascularization includes the assessment of myocardial viability. This approach has to be defined in the different classes of patients. The aim of this study was to evaluate the predictive prognostic value of different techniques on outcome following PTCA in patients with moderate left ventricle dysfunction (left ventricle EF > or = 40%). METHODS: Seventeen patients with EF > or = 40% and undergoing PTCA were studied by 201Tl rest/redistribution, 18F-FDG and 99mTc-MIBI rest. Regional kinesis was scored by echo, dividing left ventricle in 11 segments. The echo evaluation was repeated at 1 and 6 months after revascularization. RESULTS: Global EF was 52.5 +/- 7% and 69 segments had abnormal kinesis. Patients underwent stress/rest 99mTc-MIBI SPET, rest/redistribution 201Tl SPET and rest 18F-FDG PET. Among the 11 segments defined on echo-matched tomographic images, the one with the highest activity at stress was assumed as reference (activity = 100%). If > 50% of reference segment, 18F-FDG and 201Tl uptakes were considered significant. After PTCA, the echo-follow-up did not demonstrated significant improvement of left ventricle function at 30 days after PTCA (EF 56 +/- 6%) as well as at 6 months (EF 56 +/- 9%). The positive predictive value under these conditions resulted: 46.5% with 99mTc-MIBI rest, 47.4% with 201Tl rest-redistribution and 45.7% with 18F-FDG. CONCLUSIONS: In summary, in the class of patients with moderately compromised function, considering as reference the improved regional kinesis after PTCA, 99mTc-MIBI at rest, 201Tl rest/redistribution and 18F-FDG do not exhibit a clear predictive value; patient population is then a highly relevant point to establish the accuracy of these diagnostic procedures.

Adult↗

Myocardial viability assessment after acute myocardial infarction: low-dose dobutamine echocardiography versus rest-redistribution thallium-201 SPECT.

BACKGROUND: The presence of tissue viability is of great importance in the prognostic work-up of patients recovering from acute myocardial infarction. However, uncertainty still exists concerning the optimal tool for its assessment. The present study was undertaken in order to compare low-dose dobutamine echocardiography and rest-redistribution thallium SPECT for predicting late improvement of regional left ventricular function after acute myocardial infarction. METHODS: Fifteen patients undergoing coronary angiography, low-dose dobutamine echocardiography and rest-redistribution thallium SPECT after thrombolyzed anterior acute myocardial infarction were studied. A 3 month follow-up echocardiogram was performed in all patients and 9 underwent coronary revascularization. RESULTS: A significant (> or = 70%) residual stenosis of the infarct-related artery was present in 14 patients, whilst a total occlusion was observed in 1. At 3 month follow-up, 41% of the dyssynergic segments improved. The sensitivity, specificity and accuracy for late wall motion improvement was 61, 89 and 77% for low-dose dobutamine echocardiography and, respectively, 76, 45 and 58% for rest-redistribution thallium SPECT. Tissue viability was detected in 65 and 31% of dyssynergic segments by rest-redistribution thallium SPECT and low-dose dobutamine echocardiography, respectively (p < 0.001). The agreement between the two techniques was 48%. CONCLUSIONS: Low-dose dobutamine echocardiography is more accurate than rest-redistribution thallium SPECT for predicting 3 month wall motion improvement in patients with acute anterior myocardial infarction, mainly due to its significantly better specificity.

Adult↗

Ethnicity and socioeconomic status: impact on cardiovascular activity at rest and during stress in youth with a family history of hypertension.

OBJECTIVE: The purpose of the present study was to examine the potential interaction of ethnicity and SES on hemodynamic functioning at rest and during acute stress in normotensive adolescents with a family history of essential hypertension (EH). DESIGN: The influences of ethnicity and socioeconomic status (SES) on cardiovascular function were evaluated at rest and in response to five different laboratory stressors. METHODS: 110 (50 female) Caucasian and 162 (85 female) African-American normotensive youth (initial age 11.2+/-2.4 years) with a family history of essential hypertension (EH) were tested on two occasions, an average of 2.5 years apart. Based on previous findings, it was predicted that African Americans, particularly those of low SES, would exhibit higher resting blood pressure (BP) and greater cardiovascular reactivity to acute laboratory stressors than would Caucasians. RESULTS: As predicted, African-American youth exhibited higher resting diastolic blood pressure (DBP) and total peripheral resistance (TPR) than Caucasians on both visits (both Ps<.04). African Americans exhibited greater systolic blood pressure (SBP) reactivity than did Caucasians to the video game stressor during both lab visits (both Ps<.02) and greater heart rate reactivity during the first lab visit (P<.01). African Americans exhibited greater SBP and/or DBP, and TPR reactivity to the cold pressor during the first lab visit and the parent-child discussion during the second visit (all Ps<.03). CONCLUSION: As predicted, African Americans exhibited higher resting BP and TPR, and greater cardiovascular reactivity than Caucasians. Although not in the predicted direction, a pattern of interactions began to emerge on the second evaluation. For example, upper SES youth exhibited greater heart rate reactivity compared to all other groups on the social competence interview and parent-child discussion stressors. Further study is needed to clarify the role cardiovascular reactivity may play in the link between ethnicity, SES, and cardiovascular disease risk.

Adolescent↗

[Relation of serum leptin levels and regulation of resting energy expenditure].

Leptin is a protein hormone produced by adipocytes. Its serum concentrations in the most of cases positively correlate with total body fat content and body mass index (BMI). Leptin plays a role in the food intake regulation. It also increases resting energy expenditure in hypoleptinaemic ob/ob mice. Its relationship to resting energy expenditure in human is less clear. The aim of our study was to follow the serum leptin levels in healthy females (n = 12) and males (n = 14) and their relationship to resting energy expenditure, body fat content, other antropometric and nutritional biochemical parameters. It was found that serum leptin levels were significantly higher in females comparing to males (6.8 +/- 3 ng.ml-1 vs. 2.6 +/- 1 ng.ml-1, p < 0.05). The serum leptin levels correlated positively with body fat content and body mass index in both groups. In females the positive correlation between body weight and serum leptin levels was found. No statistically significant relationship between serum leptin levels and resting energy expenditure, serum total protein, albumin or prealbumin concentration was found in any of studied groups. The results of our study do not testify to direct relationship between serum leptin levels and resting energy expenditure in young healthy individuals.

Adult↗

The marginal-ridge rest seat.

Natural canine crowns are preferred as abutments for removable partial dentures because of their root morphology and bony support. However, preparing the rest seat on the lingual surface of a mandibular canine risks perforating the enamel. An alternative rest-seat preparation, on the marginal ridge of the canine crown, conserves tooth structure and provides a rest seat of adequate length and depth to ensure support for a cast framework. To illustrate why this little-discussed rest-seat preparation has endured locally, the rationale and preparation of the marginal-ridge rest seat is discussed from both historical and clinical perspectives.

Cuspid↗

Effect of oral contraceptives on peripheral blood flow in untrained women at rest and during exercise.

BACKGROUND: Endothelium-derived nitric oxide is an important mediator of exercise-induced changes in skeletal muscle blood flow. Given the recently documented effects of estrogens on nitric oxide synthase, it is hypothesized that oral contraceptives (OC) containing estrogen would increase nitric oxide production at rest and after endurance exercise. Further, we postulated that OC use would augment skeletal muscle blood flow at rest and during exercise. METHODS: Fourteen women (non-smokers) were divided into two groups: control (CON; sedentary, normal menstrual-cycling women who have not used oral contraceptives for > or = 12 mons; 18-38 yrs old; n = 7), and oral contraceptive users (OC; sedentary women who have been using low-dose estrogen/progestin oral contraceptives for > or = 12 mons; 19-38 yrs old; n = 7). Measurements of forearm blood flow were obtained from each group, using strain gauge plethysmography, at rest and during an exercise protocol in which intermittent handgrip exercise was performed at 15%, 30%, and 45% of maximum voluntary contraction (MVC). Additionally, venous blood samples were taken before and after a 90 min treadmill walk for measurement of serum nitrate/nitrite, an indirect assessment of steady-state nitric oxide production. RESULTS: There was no difference in forearm blood flow (ml/min/ 100 cc tissue) at rest (CON = 2.7; OC = 2.8); however, the hyperemic response to handgrip exercise was significantly (p < 0.05) lower in the OC group at 30% (9.0 vs CON = 14.2) and 45% (12.0 vs CON=17.0) of MVC. Serum nitrate values at rest and following 90 min of treadmill walking did not differ between groups (p > 0.05). CONCLUSIONS: Contrary to our hypotheses, these data indicate a compromised hyperemic response in the forearm of OC users. Further, chronic OC use may not affect nitric oxide production during low intensity treadmill exercise.

Adolescent↗

[Change of pulmonary diffusing capacity, membrane diffusing capacity and pulmonary capillary blood volume in patients with COPD and connective tissue disease at rest and post-exercise].

OBJECTIVE: Studying the changes of pulmonary diffusing capacity (DL), alveolar capillary membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc) in patients with COPD and connective tissue disease (CTD) at rest and post-exercise; evaluating the diagnostic values of DL, Dm and Vc in early stage of pulmonary involvement of CTD. METHOD: Spirometry was performed in the sit position. Several measurements of diffusing capacity of the lung for carbon monoxide (DLCO) were measured by single-breath method at increasing alveolar oxygen tension. The estimations of Dm and Vc were done by the method of Roughton and Forster. RESULT: (1) In COPD group, the values of DL were lower than that of the control group at rest. The decreases were due to the reduction of Dm, but Vc were normal. In CTD group, all the value of DL, Dm and Vc were lower than that of its control group at rest. (2) COPD patients had the higher DL, Dm and Vc after the end of exercise than that of at rest. But the changes of DL Dm and Vc in COPD patients were lower compared with the control group. In contrast to the control group, DL, Dm and Vc did not increase or even decreased after the end of exercise in CTD group. (3) There was no significant differences of DL, Dm and Vc between the 7 CTD patients with normal pulmonary volume and DLCO and the control subjects at rest. But after the end of exercise, DL, Dm and Vc of CTD patients kept unchanging or even decreasing. The difference between CTD patients and its control group was found significant. CONCLUSION: The measurements of post-exercise Dm and Vc are sensitive tests for pulmonary involvement in of CTD patients. The results are abmormal much earlier in subject with minimal dyspnea and roentgenologic change. They are useful tests for early stage CTD.

Aged↗

Expression of aquaporin-1 in human trabecular meshwork cells: role in resting cell volume.

PURPOSE: Drainage of aqueous humor from the human eye appears dependent on intracellular volume of trabecular meshwork (TM) cells, the predominant cell type of the human outflow pathway. Thus, the modulation of water and solute flux across the plasma membrane of TM cells is predicted to be an important factor in regulating outflow facility. Aquaporin (AQP)-1 is a hexahelical integral membrane protein that functions as a regulated channel for water and cations in fluid-secreting and -absorbing tissues. AQP1 is present in many tissues of the human eye, including the TM; however, its role in outflow facility is unknown. The purpose of the present study was twofold: to evaluate the prospect of manipulating AQP1 protein levels in TM cells using sense and antisense mRNA and to investigate the functional role of AQP1 in TM cells. METHODS: An adenovirus (AV) expression system was used to alter AQP1 protein levels. AQP1 protein expression was monitored using immunoblot analysis, and resting cell volume was measured by forward light scatter, electronic cell sizing, and [(14)C]-sucrose/urea equilibration. Permeability of TM monolayers to [(14)C]-sucrose was also assessed as an indirect evaluation of cell volume. RESULTS: AV-mediated gene transfer of AQP1 cDNA to TM cells resulted in a titer-dependent increase in recombinant AQP1, whereas transfer of antisense cDNA decreased native AQP1 protein by 71.7% +/- 5.5% (P < 0.01) after 5 days. A novel finding of this study is that mean resting volumes of AQP1(s) AV-infected TM cells in suspension were 8.7% +/- 3.0% greater (P < 0.05) than control cells. Conversely, AQP1 antisense (as) AV-infected cells had resting volumes 7.8% +/- 2.9% less than control cells (P < 0.05). Similar effects of AQP1 expression on resting cell volume were observed in TM monolayers. Consistent with this finding, paracellular permeability of AQP1(s) AV-infected TM monolayers to [(14)C]-sucrose decreased by 8.0% +/- 1.4% (P < 0.001). CONCLUSIONS: In addition to influencing the osmotic permeability of TM plasma membranes, the level of AQP1 protein expression influences resting intracellular volume and thus paracellular permeability of TM cell monolayers in vitro. These data suggest that AQP1 expression may affect outflow facility in vivo.

Adenoviruses, Human↗

Correlation between left ventricular mass and the resting and post-exercise release of ANP in healthy men.

BACKGROUND: The goal of our study was to assess the impact of left ventricular mass on the resting and post-exercise release of atrial natriuretic peptide (ANP) in healthy young men. MATERIAL AND METHODS: The study involved 36 young men divided into two groups. Group I consisted of 18 healthy untrained men 20-24 years old (mean 22.1). Group II included 18 healthy men aged 22-27 years (mean 23.4 years) who had been taking regular dynamic and static physical exercise for at least 2 years. Echocardiograms were performed in both groups. The thickness of the posterior wall (PW-d), the thickness of the interventricular septum (IV-d), and the left ventricular end-diastole dimension (DdLV) were measured and used to calculate the left ventricular mass. Subsequently, all the patients underwent an exercise test on a cycloergometer. The workload in both groups was 2 Watts/kg at 60 rpm. The anticipated age-adjusted heart rate values at this workload were 170/min in Group I and 155/min in Group II. Blood samples were collected before the exercise test and 1 minute afterwards. The concentrations of ANP and sodium ions and the hematocrit index were measured. RESULTS: In Group I the mean left ventricular mass was 193.1 +/- 51.8 g; in Group II, 248.1 x 91.91 g, which is a statistically significant difference. The resting ANP concentration in Group I was higher than in Group II (24.44 +/- 12.35 pg/ml vs 21.39 +/- 11.03 pg/ml), but the difference was not statistically significant. After exercise there was a significant increase in ANP concentration in both groups: 53.89 +/- 39.98 pg/ml and 47.50 +/- 26.67 pg/ml respectively. There was no correlation between the ANP concentration before and after exercise and the left ventricular mass in either group. There were also no differences between the two groups in resting hematocrit: 48% in Group I and 49.5% in Group II. A significant increase in hematocrit was observed in both groups after exercise. Exertion induced a significant decrease in the plasma sodium concentration in both groups. The ratio of mean plasma ANP concentration at rest to left ventricular mass, corrected according to hematocrit values, was 6.10 in Group I and 4.25 in Group II; after exercise, 14.06 and 9.72 respectively. The ratio of post-exercise increase in ANP concentration to left ventricular mass was 7.6 in Group I and 5.32 in Group II. The average left ventricular mass in Group II, although 30% greater than in Group I, did not exceed 259 g, which is considered the upper limit of normal. Despite this difference the ANP concentration in Group II was ca. 20% lower than in Group II, without cardiac hypertrophy. In both groups a significant increase in ANP concentration was observed when the subjects were exposed to submaximal workload. In Group II, however, the increase was markedly lower. No correlation was found between left ventricular mass at rest and post-exercise ANP release, nor between left ventricular mass and ANP secretion. By contrast, a tendency towards lower ANP release was found in Group II, despite the markedly larger left ventricular mass. CONCLUSIONS: In the evaluation of risk related to left ventricular hypertrophy, both the mass index and cardiac functional efficiency should be taken into account.

Adult↗

The influence of varied rest interval lengths on depth jump performance.

The purpose of this study was to measure the effects of varied rest interval lengths on the vertical jump heights and ground reaction forces during the execution of a depth jump from a predetermined optimal height. The subjects were 12 men with a mean (SD) age of 25.08 +/- 2.43 years. Each subject's optimal depth jump height was determined by executing depth jumps from 10-80 cm. After determining their optimal depth jump height, the subjects performed 3 sets of 10 depth jumps, each set with a different rest interval duration. The 3 rest intervals between depth jumps were 15, 30, and 60 seconds and were counterbalanced for each subject. Maximal vertical jump height and vertical ground reaction forces were calculated for each depth jump trial. The Peak Performance Motion Measurement System was used to measure vertical jump height and the Kistler force platform was used to measure ground reaction forces. Two-way analyses of variance revealed that rest interval length did not affect (p > 0.05) vertical jump height or vertical ground reaction forces. Therefore, this study demonstrated a 15-second rest interval was sufficient for recovery during the performance of depth jumps.

Adult↗

[Effect of initial population density on resting egg formation of rotifer Brachionus calyciflorus].

With the method of population accumulative culture, the effect of initial population density on the formation of resting eggs of freshwater rotifer(Brachionus calyciflorus), and on the rates of mictic female and fertilization was studied. During 11 days culture, the productivity and the formation efficiency of resting eggs, and the mean rate of mictic female were the biggest when the initial population density was 1.0-10.0 ind.ml-1, second by the density of 20.0 ind.ml-1, and the lowest by the density of 50.0 ind.ml-1. There was no significant effect of initial population density on the fertilization rate. Statistical analysis on maximum formation efficiency of resting eggs, their emergence and productivity showed that when the production of resting eggs was large-scaled proceeded, the feasible initial population density should be 10.0 ind.ml-1, and the corresponding time should be 6 days to obtain a higher yield of resting eggs and a higher formation efficiency.

Animals↗

Resting potential and submembrane calcium concentration of inner hair cells in the isolated mouse cochlea are set by KCNQ-type potassium channels.

Cochlear inner hair cells (IHCs) transduce sound-induced vibrations into a receptor potential (RP) that controls afferent synaptic activity and, consequently, frequency and timing of action potentials in the postsynaptic auditory neurons. The RP is thought to be shaped by the two voltage-dependent K+ conductances, I(K,f) and I(K,s), that are carried by large-conductance Ca2+- and voltage-dependent K+ (BK)- and K(V)-type K+ channels. Using whole-cell voltage-clamp recordings in the acutely isolated mouse cochlea, we show that IHCs display an additional K+ current that is active at the resting membrane potential (-72 mV) and deactivates on hyperpolarization. It is potently blocked by the KCNQ-channel blockers linopirdine and XE991 but is insensitive to tetraethylammonium and 4-aminopyridine, which inhibit I(K,f) and I(K,s), respectively. Single-cell PCR and immunocytochemistry showed expression of the KCNQ4 subunit in IHCs. In current-clamp experiments, block of the KCNQ current shifted the resting membrane potential by approximately 7 to -65 mV and led to a significant activation of BK channels. Using BK channels as an indicator for submembrane intracellular Ca2+ concentration ([Ca2+]i), it is shown that the shift in IHC resting potential observed after block of the KCNQ channels leads to an increase in [Ca2+]i to values > or =1 microm. In conclusion, KCNQ channels set the resting membrane potential of IHCs in the isolated organ of Corti and thus maintain [Ca2+]i at low levels. Destabilization of the resting potential and increase in [Ca2+]i, as may result from impaired KCNQ4 function in IHCs, provide a novel explanation for the progressive hearing loss (DFNA2) observed in patients with defective KCNQ4 genes.

Animals↗

[Relationship between sexual reproduction, population growth and resting egg production of freshwater rotifer Brachionus calyciflorus].

Using exponential and logistic growth models, the effects of sexual reproduction frequency and the proportion of a female's daughters reproducing sexually on population growth rate and resting egg production of freshwater rotifer Brachionus calyciflorus were examined by computer simulation. Within the parameters of the simulation, the percentage of micitc females in the offspring required for maximum resting egg production increased from 9% to 69%, when the frequency of sexual reproduction decreased from 100% to 20%. The increase of density-dependent limitation (the value of K decreased from 1000 to 100) made this percentage increase from 18% to 69%, and resting egg production decrease from 1072.10 to 133.67. The relationship between the population growth rate (r) and the optimum percentage of mictic females in the offspring required for maximum resting egg production was best described by curvilinear regression. When sexual reproduction became more frequent and density-dependent decreased, The population with the percentage of mictic females in the offspring in 10-30% had a bigger resting egg production.

Animals↗

Effect of antianginal medication on resting myocardial perfusion and pharmacologically induced hyperemia.

Background. Patients scheduled for myocardial perfusion imaging are often taking several antianginal drugs. There is presently no consensus concerning a regimen of discontinuation before either rest or pharmacologic stress myocardial perfusion imaging. Whether antianginal treatment affects diagnostic sensitivity and specificity is not well documented. Methods and Results. The effect of the three most commonly used antianginal drugs (nitroglycerin, 400 micro g [NTG]; metoprolol, 50 mg [MET]; and amlodipine, 5 mg [AML]) on myocardial perfusion was tested in 49 patients (age, 63 +/- 8 years; 43 men) allocated prospectively to one of the treatments (NTG, n = 25; MET, n = 14; and AML, n = 10). All patients had documented coronary artery disease and were scheduled for elective percutaneous coronary intervention. Patients were studied once on treatment and once off treatment with an interval of 1 to 3 weeks. For NTG, the measurements were performed on the same day with an interval of 1 hour. The MET and AML groups were also studied during dipyridamole-induced hyperemia (0.56 mg. kg(-1). min(-1) for 4 minutes). So that a quantitative value of myocardial perfusion in milliliters per gram per minute could be obtained, myocardial perfusion was quantified with nitrogen 13 ammonia positron emission tomography as an average of the midventricular perfusion in each of the 3 vascular territories. NTG treatment increased the overall resting perfusion (0.75 +/- 0.18 vs 0.86 +/- 0.22, P <.05), whereas resting perfusion was reduced after MET treatment (0.92 +/- 0.14 vs 0.82 +/- 0.17, P <.05). AML treatment did not alter resting perfusion (0.87 +/- 0.22 vs 0.87 +/- 0.23, P = NS). Dipyridamole-induced hyperemia was reduced after treatment with MET (2.02 +/- 0.66 vs l.57 +/- 0.52, P <.001), whereas the hyperemic response was unchanged after treatment with AML (1.54 +/- 0.49 vs 1.86 +/- 0.91, P = NS). Conclusions. Antianginal medication can alter both resting and hyperemic myocardial perfusion and might affect the ability to detect flow-limiting stenosis. NTG increases perfusion, MET reduces perfusion, and AML does not affect perfusion. Larger-scale trials are warranted to establish a consensus for optimal antianginal medication for patients undergoing perfusion imaging.

Journal Article↗

Membrane association of active 5-lipoxygenase in resting cells. Evidence for novel regulation of the enzyme in the rat alveolar macrophage.

The enzyme 5-lipoxygenase (5-LO) catalyzes the first two steps in the metabolism of arachidonic acid to leukotrienes, substances which play pivotal roles both in normal host defense and in pathologic states of inflammation. Recent studies in granulocytic cells have shown that activation of 5-LO involves its Ca(2+)-dependent translocation from cytosol to membrane compartments. However, little information exists about the molecular regulation of 5-LO in macrophages, even though these cells comprise the resident effector cell population of most organs. We therefore examined the levels of 5-LO activity and immunoreactive protein in cytosol and membrane fractions of resident rat alveolar (AM) and peritoneal macrophages (PM) and compared them with the well studied human neutrophil (polymorphonuclear leukocyte). In the resting state, PM resembled polymorphonuclear leukocyte in that most of their cell-free 5-LO activity, as well as protein content, were localized to the cytosol fraction. By contrast, resting AM contained most of their activity and almost half of their immunoreactive protein in the crude membrane fraction. The inability of the drug MK-886 to reverse this membrane association suggested that the 5-LO-activating protein was not the site of binding in the resting cell; however, this drug completely inhibited leukotriene B4 synthesis in ionophore A23187-stimulated AM, indicating that an interaction between 5-LO and 5-LO-activating protein was nonetheless required for product synthesis upon stimulation. Translocation of cytosolic 5-LO protein could not be convincingly demonstrated in A23187-stimulated AM, suggesting that the pool of 5-LO enzyme responsible for product formation originated in the membrane rather than the cytosol fraction of the resting cell. The AM therefore represents the first mammalian cell in which 5-LO has been recovered from the membrane fraction (a) of a resting cell and (b) in active form. These novel findings extend our understanding of the molecular regulation of 5-LO and may be of importance in designing strategies to limit inflammation in the lung and other sites.

Animals↗