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PubMed1994

Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography.

BACKGROUND: Experimental studies have shown that fractional flow reserve (defined as the ratio of maximal achievable flow in a stenotic area to normal maximal achievable flow) can be calculated from coronary pressure measurements only. The objectives of this study were to validate fractional flow reserve calculation in humans and to compare this information with that derived from quantitative coronary angiography. METHODS AND RESULTS: Twenty-two patients with an isolated, discrete proximal or mid left anterior descending coronary artery stenosis and normal left ventricular function were studied. Relative myocardial flow reserve, defined as the ratio of absolute myocardial perfusion during maximal vasodilation in the stenotic area to the absolute myocardial perfusion during maximal vasodilation (adenosine 140 micrograms.kg-1 x min-1 intravenously during 4 minutes) in the contralateral normally perfused area, was assessed by 15O-labeled water and positron emission tomography (PET). Myocardial and coronary fractional flow reserve were calculated from mean aortic, distal coronary, and right atrial pressures recorded during maximal vasodilation. Distal coronary pressures were measured by an ultrathin, pressure-monitoring guide wire with minimal influence on the trans-stenotic pressure gradient. Minimal obstruction area, percent area stenosis, and calculated stenosis flow reserve were assessed by quantitative coronary angiography. There was no difference in heart rate, mean aortic pressure, or rate-pressure product during maximal vasodilation during PET and during catheterization. Percent area stenosis ranged from 40% to 94% (mean, 77 +/- 13%), myocardial fractional flow reserve from 0.36 to 0.98 (mean, 0.61 +/- 0.17), and relative flow reserve from 0.27 to 1.23 (mean, 0.60 +/- 0.26). A close correlation was found between relative flow reserve obtained by PET and both myocardial fractional flow reserve (r = .87) and coronary fractional flow reserve obtained by pressure recordings (r = .86). The correlations between relative flow reserve obtained by PET and stenosis measurements derived from quantitative coronary angiography were markedly weaker (minimal obstruction area, r = .66; percent area stenosis, r = -.70; and stenosis flow reserve, r = .68). CONCLUSIONS: Fractional flow reserve derived from pressure measurements correlates more closely to relative flow reserve derived from PET than angiographic parameters. This validates in humans the use of fractional flow reserve as an index of the physiological consequences of a given coronary artery stenosis.

Coronary Angiography↗
PubMed1997

Dependency of contractile reserve on myocardial blood flow: implications for the assessment of myocardial viability with dobutamine stress echocardiography.

BACKGROUND: Contractile reserve, improvement in contractile function during inotropic stimulation, is a proposed marker of viable myocardium. This study was designed to address, in patients with left ventricular dysfunction due to chronic coronary artery disease, whether contractile reserve depends on myocardial blood flow. METHODS AND RESULTS: We studied 19 patients, at rest and during dobutamine, with 2D echocardiography for regional mechanical function and PET for regional myocardial blood flow ([(15)O]water) and oxygen consumption ([11C]acetate). Of 166 myocardial segments, 21 had normal systolic function, 56 were dysfunctional but contractile reserve-positive, and 89 were dysfunctional and contractile reserve-negative. Myocardial blood flow at rest was lower in contractile reserve-negative (0.41+/-0.18 mL x g(-1) x min(-1)) than in contractile reserve-positive (0.50+/-0.22 mL x g(-1) x min(-1)) and normal segments (0.55+/-0.20 mL x g(-1) x min(-1), P<.009). After dobutamine infusion, blood flow increased less in contractile reserve-negative (0.63+/-0.38 mL x g(-1) x min(-1)) than in contractile reserve-positive (1.28+/-0.65 mL x g(-1) x min(-1)) and normal segments (1.93+/-0.83 mL x g(-1) x min(-1), P<.0001). Likewise, myocardial oxygen consumption was lower at rest in contractile reserve-negative (clearance rate of [11C]acetate, 0.043+/-0.012 min(-1)) than in contractile reserve-positive (0.048+/-0.01 min(-1)) and normal segments (0.058+/-0.008 min(-1), P<.02). Myocardial oxygen consumption with dobutamine increased less in contractile reserve-negative (0.060+/-0.013 min(-1)) than in contractile reserve-positive (0.077+/-0.016 min(-1)) and normal segments (0.092+/-0.024 min(-1), P<.0001). Of segments defined as viable by PET, 54% were contractile reserve-negative and exhibited lower blood flow with dobutamine (0.72+/-0.36 mL x g(-1) x min(-1)) than with viable, contractile reserve-positive segments (1.29+/-0.70 mL x g(-1) x min(-1), P<.0001). CONCLUSIONS: Contractile reserve depends, in part, on the level of myocardial blood flow at rest and during inotropic stimulation.

Aged↗
PubMed2002

The effects of dispersal patterns on marine reserves: does the tail wag the dog?

The concept of marine reserves as a method of improving management of fisheries is gaining momentum. While the list of benefits from reserves is frequently promoted, precise formulations of theory to support reserve design are not fully developed. To determine the size of reserves and the distances between reserves an understanding of the requirements for persistence of local populations is required. Unfortunately, conditions for persistence are poorly characterized, as are the larval dispersal patterns on which persistence depends. With the current paucity of information regarding meroplanktonic larval transport processes, understanding the robustness of theoretical results to larval dispersal is of key importance. From this formulation a broad range of dispersal patterns are analyzed. Larval dispersal is represented by a probability distribution that defines the fraction of successful settlers from an arbitrary location, the origin of the distribution, to any other location along the coast. While the effects of specific dispersal patterns have been investigated for invasion processes, critical habitat size and persistence issues have generally been addressed with only one or two dispersal types. To that end, we formulate models based on integrodifference equations that are spatially continuous and temporally discrete. We consider a range of dispersal distributions from leptokurtic to platykurtic. The effect of different dispersal patterns is considered for a single isolated reserve of varying size receiving no external larvae, as well as multiple reserves with varying degrees of connectivity. While different patterns result in quantitative differences in persistence, qualitatively similar effects across all patterns are seen in both single- and multiple reserve models. Persistence in an isolated reserve requires a size that is approximately twice the mean dispersal distance and regardless of the dispersal pattern the population in a patch is not persistent if the reserve size is reduced to just the mean dispersal distance. With an idealized coastline structure consisting of an infinite line of equally spaced reserves separated by regions of coastline in which reproduction is nil, the relative settlement as a function of the fraction of coastline and size of reserve is qualitatively very similar over a broad range of dispersal patterns. The upper limit for the minimum fraction of coastline held in reserve is about 40%. As the fraction of coastline is reduced, the minimum size of reserve becomes no more than 1.25 times the mean dispersal distance.

Animals↗
PubMed1993

Effect of increases in heart rate and arterial pressure on coronary flow reserve in humans.

OBJECTIVES: The objective of this study was to determine the effect of increases in heart rate and arterial pressure on maximal pharmacologic coronary blood flow reserve. BACKGROUND: Coronary flow reserve measurements are useful in assessment of the physiologic significance of coronary lesions. However, animal studies suggest that alterations in hemodynamic status may influence coronary flow reserve independent of coronary stenosis. METHODS: Coronary flow reserve was measured during cardiac catheterization with the use of a 3F coronary Doppler catheter and intracoronary papaverine. Flow reserve was measured under control conditions and during increases in heart rate produced by atrial pacing (18 patients) or during elevation of arterial pressure by intravenous phenylephrine infusion (9 patients) with intracoronary alpha-adrenergic blockade by phentolamine. RESULTS: Coronary flow reserve progressively decreased from 3.7 +/- 0.9 (mean +/- SD) at the rate of 71 +/- 8 beats/min at rest to 3.0 +/- 0.6 during pacing at 100 beats/min and to 2.6 +/- 0.5 during pacing at 120 beats/min. Flow reserve decreased because of a progressive increase in rest coronary flow velocity during pacing (122 +/- 16% of control value at 100 beats/min, 139 +/- 16% of control value at 120 beats/min), whereas papaverine hyperemia peak velocity remained unchanged. Flow reserve decreased with pacing tachycardia whether the initial flow reserve was normal or depressed. Mean arterial pressure increased from 95 +/- 12 mm Hg to 130 +/- 8 mm Hg during intravenous phenylephrine infusion and to 123 +/- 10 mm Hg during combined intravenous phenylephrine and intracoronary phentolamine infusions. Coronary flow reserve was not affected by the blood pressure increases (control value 4.3 +/- 1.0, phenylephrine 4.4 +/- 1.5, phenylephrine and phentolamine 4.4 +/- 2.0). CONCLUSIONS: Sudden increases in heart rate but not mean arterial pressure lead to a substantial reduction in maximal coronary blood flow reserve. These data suggest that the diagnostic utility of all flow reserve measurement techniques might be improved by standardization of heart rate during measurement or extrapolation of the measured flow reserve to that expected at a reference heart rate.

Blood Flow Velocity↗
PubMed2003

Beneficial impact of term labor: nonenzymatic antioxidant reserve in the human fetus.

OBJECTIVE: Oxidative stress occurs when the production of damaging free radicals and other oxidative molecules exceeds the capacity of the body's antioxidant defenses. Oxidative stress is implicated in diseases that are associated with prematurity (such as retinopathy, cerebral palsy, intraventricular hemorrhage, and necrotizing enterocolitis). Nonenzymatic antioxidant reserve is the first line of defense against free radicals. We hypothesized that an in utero redox imbalance because of stress would diminish the fetal antioxidant reserve. We tested aspects of this hypothesis by investigating whether the presence of labor or gestational age at delivery (term vs preterm) alters the maternal/fetal nonenzymatic antioxidant reserve peripartum. STUDY DESIGN: Fetal redox consumption was calculated from the difference in the nonenzymatic antioxidant reserve that was measured in umbilical venous and arterial blood that was collected prospectively at delivery from 39 newborn infants. Eight women were delivered at term by elective cesarean delivery in the absence of labor; 31 women labored either at term (n = 20) or preterm (<37 weeks, n = 11). Maternal venous blood was collected on admission and within 1 hour of delivery. Nonenzymatic antioxidant reserve was measured in the plasma and red blood cells of each specimen by the quantitation of glutathione content (glutathione in red blood cell lysate) and the plasma total free radical-trapping antioxidant potential. Glutathione was measured with the use of a colorimetric assay and expressed in nanomoles per milligram of hemoglobin. The plasma total radical-trapping antioxidant potential was estimated with the use of a controlled, kinetic assay based on the time that was required to inhibit peroxyl-free radical generated under controlled conditions. The differences between both umbilical venous and umbilical arterial total radical-trapping antioxidant potential and glutathione were computed to estimate fetal nonenzymatic antioxidant reserve consumption. The differences between maternal total radical-trapping antioxidant potential and glutathione before and after delivery were computed to estimate maternal peripartal nonenzymatic antioxidant reserve consumption. RESULTS: Fetal red blood cell glutathione content was significantly greater than maternal red blood cell glutathione content, independent of delivery route. The calculation of the fetal nonenzymatic antioxidant reserve consumption and maternal peripartal nonenzymatic antioxidant reserve consumption revealed that women who labored at term experienced an up-regulation in red blood cell glutathione content, while their fetuses had significantly lower red blood cell glutathione consumption. In contrast, there was consumption of plasma antioxidants in preterm fetuses, as illustrated by a doubling of the fetal nonenzymatic antioxidant reserve consumption (elective cesarean delivery in the absence of labor, 0.9 +/- 0.5 min/microL; term labor, 1.0 +/- 0.1 min/microL; preterm labor, 2.0 +/- 0.4 min/microL; one-way analysis of variance; P =.04). This was mostly due to a lower umbilical arterial total radical-trapping antioxidant potential in preterm versus term fetuses (umbilical arterial, 3.3 min/microL versus umbilical venous 5.4 min/microL; paired t test; P =.001; power, 0.98). Generally, maternal total radical-trapping antioxidant potential remained unchanged peripartum. CONCLUSION: Term labor triggers a compensatory up-regulation of nonenzymatic antioxidant reserve in the fetal red blood cell compartment that may act to protect against the relative hyperoxia that is experienced by the newborn infant at birth. In contrast, the decreased nonenzymatic antioxidant reserve in the fetal red blood cell and plasma compartments after preterm labor and delivery would enhance the vulnerability to free radical damage of the preterm neonate. These findings suggest that the two compartments of nonenzymatic antioxidant reserve have distinct physiologic roles in the peripartal defense against free radicals and that their development is, in some fashion, ontogenes, in some fashion, ontogenetically regulated.

Antioxidants↗
PubMed1995

Effect of diltiazem on coronary flow reserve in patients with microvascular angina.

Microvascular angina is characterized by ischemia-like symptoms in patients with normal coronary arteries and reduced coronary flow reserve. Clinical observations suggested an improvement in clinical symptomatology and exercise tolerance after treatment with calcium antagonists. The effect of diltiazem on coronary flow reserve was evaluated in controls and in patients with microvascular angina. Coronary flow reserve was measured in 16 normotensive patients (7 females, 9 males, mean age 51 +/- 10 years) with angiographically normal coronary arteries. Coronary blood flow was determined at rest, after dipyridamole (0.5 mg/kg) and following intravenous administration of diltiazem (10 mg) using coronary sinus thermodilution technique. Coronary flow reserve was calculated as coronary blood flow after dipyridamole divided by coronary blood flow at rest. Patients with normal coronary flow reserve (coronary flow reserve > 2.0) received either dipyridamole alone (group 1, controls, n = 6) or dipyridamole and diltiazem (group 2, n = 5), whereas patients with reduced coronary flow reserve (coronary flow reserve < 2.0) obtained dipyridamole and diltiazem (group 3, n = 5). Resting coronary flow was identical in the three groups, but after maximal vasodilation with dipyridamole, coronary flow increased significantly more in groups 1 and 2 than in group 3 (P < 0.05, analysis of variance (ANOVA)). Coronary flow reserve was 2.5 in group 1 and 2.3 in group 2, but was significantly reduced in group 3 (1.3; P < 0.05, ANOVA). Intravenous diltiazem failed to increase coronary blood flow in groups 2 and 3. Therefore, diltiazem does not improve reduced coronary flow reserve in patients with microvascular angina, but leaves coronary flow reserve unaffected. The failure to ameliorate impaired coronary flow reserve with diltiazem is in contrast to the reported clinical improvement after calcium channel blockade in these patients. Thus, other factors such as structural abnormalities in the microcirculation or functional abnormality in smooth muscle relaxation not responsive to calcium channel blockade are probably responsible for the occurrence of myocardial ischemia in patients with microvascular angina.

Analysis of Variance↗
PubMed1993

Myocardial contrast echocardiography for the assessment of coronary blood flow reserve: validation in humans.

OBJECTIVES: The aim of this study was to validate the use of myocardial contrast echocardiography to determine coronary blood flow reserve in humans. BACKGROUND: Although myocardial contrast echocardiography has been used to accurately quantify coronary flow reserve in animals, validation for its use in humans to measure flow reserve is lacking. METHODS: We analyzed the time-intensity curve from the anteroseptal region of the left ventricular short axis produced after a left main coronary artery injection of sonicated albumin before and after intracoronary administration of papaverine in 16 patients without angiographically significant coronary artery disease. The ratio of half-time of video intensity disappearance from peak intensity, variable of curve width, area under the time-intensity curve and corrected peak contrast intensity after papaverine compared with baseline were correlated with coronary flow reserve measured simultaneously with an intracoronary Doppler probe in the left anterior descending coronary artery. RESULTS: There was a strong inverse correlation with half-time of contrast washout and coronary flow reserve (r = -0.76, p = 0.0007) and a strong positive correlation between the variable of curve width (which is inversely proportional to curve width) and coronary flow reserve (r = 0.71, p = 0.002). There was a weak but significant inverse correlation between area under the time-intensity curve and coronary flow reserve (r = -0.54, p = 0.03) but no correlation between corrected peak contrast intensity and coronary flow reserve (r = -0.36, p = NS). Despite the strong correlation for the ratios for half-time of contrast washout and variable of curve width and actual coronary flow reserve measured with intracoronary Doppler probe, the transit time ratios consistently underestimated coronary flow reserve. CONCLUSIONS: Myocardial contrast echocardiography performed with left main coronary artery injections of sonicated albumin can be utilized to measure coronary flow reserve in humans. Transit time variable ratios (half-time of contrast washout and variable of curve width) derived from the time-intensity curve correlate most strongly with coronary flow reserve.

Adult↗
PubMed1996

Efficacy of selection criteria for ovarian reserve screening using the clomiphene citrate challenge test in a tertiary fertility center population.

OBJECTIVE: To examine selection criteria for ovarian reserve screening. DESIGN: Retrospective study. PATIENTS: Two hundred nineteen women underwent testing for ovarian reserve for woman's age > 35 years, any age with unexplained infertility, one ovary, or a poor response to hMG. INTERVENTIONS: Clomiphene citrate challenge test. MAIN OUTCOME MEASURES: Frequency of abnormal ovarian reserve screening, menstrual cycle parameters, response to hMG, and pregnancy outcome by screening criteria. RESULTS: One hundred eighty-four (84.0%) women had a normal ovarian reserve screening test; 35 (16.0%) had an abnormal ovarian reserve screening test. Twenty-six had abnormal ovarian reserve screening when screened by age, 14 for unexplained infertility, 5 for poor response to hMG, and 6 for one ovary. Fifteen women with abnormal ovarian reserve screening had more than one indication for screening. For women attempting pregnancy (n = 182), 49 of 148 (33.1%) with normal ovarian reserve screening became pregnant compared with 2 of 34 (5.9%) with abnormal ovarian reserve screening. Within each screening category, women with abnormal ovarian reserve had menstrual cycle parameters associated with a short follicular phase, required more hMG, and responded poorly to hMG. CONCLUSIONS: One of six women undergoing ovarian reserve screening had an abnormal test, which was associated a poor reproductive outcome. Age was the most important single criteria. Selected ovarian reserve screening is simple and inexpensive and should be offered to all fertility patients meeting the specific screening criteria listed above.

Adult↗
PubMed1997

Contractile reserve of dysfunctional myocardium after revascularization: a dobutamine stress echocardiography study.

OBJECTIVES: We sought to investigate the effects of revascularization on the contractile reserve of dysfunctional myocardium. BACKGROUND: The improvement in dysfunctional but viable myocardium after revascularization is frequently less than expected from the amount of contractile reserve detected on dobutamine stress echocardiography. The fate of the contractile reserve, when it does not result in an adequate contractile recovery, is unknown. METHODS: Basal contraction and contractile reserve of infarct zones were assessed by dobutamine stress echocardiography in 21 postinfarction male patients before and > 3 months after revascularization (30 infarct zones; mean +/- SD left ventricular ejection fraction 35 +/- 8%). An infarct zone wall motion score index (WMSI) was calculated. RESULTS: Before revascularization, contractile reserve was present in 14 infarct zones (12 patients) and absent in 16 (9 patients). After revascularization, ejection fraction increased by 5 +/- 4% (p < 0.01) in patients classified as positive for contractile reserve and remained unchanged in those classified as negative. New York Heart Association classification improved in 58.3% and 22.2% of patients, respectively. Basal contraction improved in eight zones with previous contractile reserve (57.1%) and in one zone without (6.3%) (p < 0.01). Contractile reserve was still evident in 13 zones with previous contractile reserve (93%; 8 with contractile recovery), and it developed in 6 zones without (38%; none with contractile recovery). WMSI values after revascularization were decreased from values before revascularization during low dose dobutamine in zones with and without previous contractile reserve (p < 0.01 and < 0.05, respectively). CONCLUSIONS: After revascularization, contractile reserve is maintained or even increases in viable infarct zones that do not recover as expected. It may also develop in some infarct zones judged not to be viable before revascularization. This increased contractile reserve may play a role in the functional improvement of patients after revascularization.

Aged↗
PubMed1998

Influence of receptor reserve on beta-adrenoceptor-mediated responses in human lung mast cells.

1. The effects of the beta-adrenoceptor agonists isoprenaline and salbutamol on IgE-mediated histamine release from human lung mast cells (HLMC) were evaluated. Both agonists (10(-10)-10(-5) M) inhibited histamine release in a dose-dependent manner and isoprenaline (pD2, 8.3+/-0.1, mean+/-s.e.mean) was more potent than salbutamol (7.3+/-0.1). Moreover, the mean data indicated that salbutamol was a partial agonist when compared with isoprenaline. However, there was a large degree of interexperimental variability because, in 11 of 32 experiments, salbutamol was a full agonist and, in 21 of 32 experiments, a partial agonist relative to isoprenaline. These data suggest that different HLMC preparations possess variable receptor reserves. 2. The effect of the irreversible beta-adrenoceptor antagonist, bromoacetylalprenolol menthane (BAAM), on the inhibition of IgE-mediated histamine release by both isoprenaline and prostaglandin E2 (PGE2) was assessed. Whereas BAAM (100 nM) antagonized the isoprenaline inhibition of histamine release from activated HLMC, BAAM had no effect on the PGE2 inhibition. Pretreatment of HLMC with the beta2-selective competitive antagonist, ICI 118551 (100 nM), protected against the loss in responsiveness to isoprenaline following treatment with BAAM. 3. Concentrations of 1, 10 and 100 nM of BAAM caused dose-dependent rightward shifts in the dose-response curve for the isoprenaline inhibition of histamine release. Furthermore, there was a dose-dependent reduction in the maximal inhibitory response obtained with isoprenaline following treatments with increasing concentrations of BAAM. Although the rightward shifts in the isoprenaline dose-response curves, with a given concentration of BAAM, were similar in all experiments, there was some variability in the depression of the maximal response in individual experiments. Thus, in 6 of 16 experiments, BAAM (1 nM) did not depress the maximal response to isoprenaline, whereas in 10 of 16 experiments there was a depression (7 to 49% reduction) in the maximal response. These data suggest that different HLMC preparations possess variable receptor reserves. 4. Isoprenaline was more potent as an inhibitor in those HLMC preparations in which there was a larger receptor reserve (i.e. preparations in which the maximal inhibitory response to isoprenaline was unaffected by pretreatment with 1 nM BAAM). 5. The influence of receptor reserve on the inhibition by salbutamol of histamine release from HLMC was evaluated. There was a good correlation (r=0.77) between receptor reserve and the maximal response (relative to isoprenaline) obtained with salbutamol. Thus, HLMC preparations with larger receptor reserves were more responsive to salbutamol. 6. Receptor reserve influenced the desensitization of beta-adrenoceptor-mediated responses in HLMC. Cells were incubated (24 h) with isoprenaline (1 microM), washed and then the ability of a second isoprenaline (10(-10)-10(-5) M) exposure to inhibit histamine release was assessed. The pretreatment caused a reduction in the isoprenaline inhibition of histamine release although the extent of desensitization was highly variable, ranging from essentially negligible levels in some preparations to substantial reductions (93% desensitization) in the ability of isoprenaline to inhibit histamine release. There was a reasonable correlation (r=0.59) between receptor reserve and desensitization. Preparations that possessed a larger receptor reserve were more resistant to desensitization. 7. Collectively, these data suggest that a receptor reserve exists for the beta-adrenoceptor-mediated inhibition of histamine release from HLMC but that the size of this reserve varies between HLMC preparations. Moreover, the size of this receptor reserve may influence the sensitivity of HLMC to beta-adrenoceptor agonists and the susceptibility of individual HLMC preparations to desensitization.

Adrenergic beta-Agonists↗
PubMed2001

[Calf flow reserve measured by venous-occlusion near-infrared spectroscopy: relationship to exercise tolerance].

OBJECTIVES: The correlations between calf flow reserve evaluated with venous-occlusion near-infrared spectroscopy, air plethysmography or skin laser Doppler flowmetry were investigated in patients with cardiovascular diseases. The relationships to exercise tolerance during upright bicycle exercise were also examined. METHODS: The calf flow reserve (blood flow after 5 min of arterial occlusion/basal blood flow) evaluated by the above three methods and peak oxygen uptake (peak VO2) on bicycle exercise were measured in 24 male patients (mean age 65.0 +/- 7.7 years, left ventricular ejection fraction 24-86%). RESULTS: There was a good correlation between flow reserve by near-infrared spectroscopy (8.0 +/- 3.8) and air plethysmography (7.9 +/- 3.1; r = 0.90). However, there was a weak correlation between flow reserve by near-infrared spectroscopy and skin laser Doppler flowmetry (3.4 +/- 1.7; r = 0.42). There was a good correlation between flow reserve by near-infrared spectroscopy and peak VO2 (r = 0.69), or flow reserve by air plethysmography and peak VO2 (r = 0.53). However, there was no significant correlation between flow reserve by skin laser Doppler flowmetry and peak VO2 (r = 0.18). CONCLUSIONS: Calf flow reserve evaluated by venous-occlusion near-infrared spectroscopy relates to the flow reserve in the muscle tissue and is minimally affected by the flow reserve in the skin. The flow reserve in the muscle tissue is related to exercise tolerance, but the flow reserve in the skin is not, in patients with cardiovascular diseases.

Aged↗
PubMed1994

[Immunohistochemical study on keratin expression of uterine reserve cells].

An immunohistochemical expression in the reserve cells of the uterine cervix using monoclonal antibodies of cytokeratin which detected the different subtypes of keratin was studied. Although the reserve cells were positive for all the four cytokeratin antibodies (CAM5.2, M-20, M-888, M-630), different immunoreactivity was found as follows: CAM5.2 reacted uniformly and intensely in the cervical glands, but weak in the reserve cells. M-20 reacted similar to that of CAM5.2 in the cervical glands, but was weaker stained in the reserve cells than with CAM5.2. M-888 reacted uniformly and intensely in both the cervical glands and reserve cells. M-630 reacted only in the reserve cells, but seldom in the cervical glands. Hence, CAM5.2 and M-20, which detected No.8 and No.18 of antiserum for low-molecular weight cytokeratin, reacted more weakly in the reserve cells than in the cervical glands, and M-630, which detected No.5 and No.14 of antiserum for high-molecular weight cytokeratin, reacted uniformly and intensely in the reserve cells. That results suggested the reserve cells revealed the expression as the stratified squamous epithelium. As for cell proliferation on the cervical glands and reserve cells, the positive nuclear staining for proliferating cell nuclear antigen (PCNA) was found in both of them, especially in the cervical glands just above the reserve cells. Therefore, the reserve cells had characteristics of squamous cell epithelium and developed to metaplastic cells.

Antibodies, Monoclonal↗
PubMed1992

Tachycardia, contractility and volume loading alter conventional indexes of coronary flow reserve, but not the instantaneous hyperemic flow versus pressure slope index.

OBJECTIVES AND BACKGROUND: Because measurements of flow reserve are often made in the setting of fluctuating hemodynamic variables that cause alterations in basal or hyperemic coronary blood flow, traditional flow reserve indexes may be difficult to interpret. Prior work in this laboratory has suggested that the instantaneous hyperemic flow versus pressure slope index is a more hemodynamically stable alternative to measures of flow reserve. Although this index has no hemodynamic dependence on changes in aortic pressure, the extent to which it is affected by other factors that alter myocardial work is unknown. Therefore, the purpose of this investigation was to analyze the effects of tachycardia (induced by atrial pacing at 10 beats/min above the basal heart rate), dobutamine infusion (10 micrograms/kg per min) and saline solution volume loading (500 ml) on measurements of traditional coronary flow reserve, the resistance reserve ratio and the instantaneous hyperemic flow versus pressure slope index. METHODS: Twenty-nine open chest anesthetized dogs were studied in four sequential stages: baseline, tachycardia, dobutamine infusion and saline solution volume loading. Traditional coronary flow reserve was defined as the ratio of hyperemic coronary blood flow to basal coronary blood flow, the resistance reserve ratio as the ratio of basal coronary resistance to hyperemic coronary resistance and the instantaneous hyperemic flow versus pressure slope index as the slope of the instantaneous relation between diastolic hyperemic coronary blood flow and diastolic aortic pressure normalized by perfusion bed weight. Hyperemia was induced by intravenous adenosine infusion (1 mg/kg per min). Mean aortic pressure was kept nearly constant during the interventions by manipulation of an aortic clamp or a vena caval snare. RESULTS: The final study group comprised 18 open chest dogs. Coronary flow reserve was significantly decreased by tachycardia (3.7 +/- 1.2 to 3.0 +/- 1.2, p < 0.0001), decreased by saline solution volume loading (3.2 +/- 1.3 vs. 2.7 +/- 0.8, p = 0.06) and significantly increased by dobutamine infusion (3.2 +/- 1.3 to 4.3 +/- 1.5, p < 0.0005). In contrast, the instantaneous hyperemic flow versus pressure slope index was not affected by the three interventions (7.4 +/- 3.1 vs. 7.3 +/- 3.3, 7.4 +/- 3.2 vs. 7.4 +/- 3.4 and 7.5 +/- 3.1 vs. 7.3 +/- 3.4, respectively, all p = NS). The changes observed in the resistance reserve ratio were of similar or greater magnitude and significance to the changes in coronary flow reserve. CONCLUSIONS: The instantaneous hyperemic flow versus pressure slope index offers a hemodynamically stable alternative to measures of vascular reserve because it is independent of moderate changes in heart rate, contractility and volume loading that may occur commonly in clinical situations.

Analysis of Variance↗
PubMed2005

Marine reserves with ecological uncertainty.

To help manage the fluctuations inherent in fish populations scientists have argued for both an ecosystem approach to management and the greater use of marine reserves. Support for reserves includes empirical evidence that they can raise the spawning biomass and mean size of exploited populations, increase the abundance of species and, relative to reference sites, raise population density, biomass, fish size and diversity. By contrast, fishers often oppose the establishment and expansion of marine reserves and claim that reserves provide few, if any, economic payoffs. Using a stochastic optimal control model with two forms of ecological uncertainty we demonstrate that reserves create a resilience effect that allows for the population to recover faster, and can also raise the harvest immediately following a negative shock. The tradeoff of a larger reserve is a reduced harvest in the absence of a negative shock such that a reserve will never encompass the entire population if the goal is to maximize the economic returns from harvesting, and fishing is profitable. Under a wide range of parameter values with ecological uncertainty, and in the 'worst case' scenario for a reserve, we show that a marine reserve can increase the economic payoff to fishers even when the harvested population is not initially overexploited, harvesting is economically optimal and the population is persistent. Moreover, we show that the benefits of a reserve cannot be achieved by existing effort or output controls. Our results demonstrate that, in many cases, there is no tradeoff between the economic payoff of fishers and ecological benefits when a reserve is established at equal to, or less than, its optimum size.

Algorithms↗
PubMed2002

Coronary patency and its relation to contractile reserve in hibernating myocardium.

OBJECTIVES: Recent clinical studies suggest that contractile reserve may occur in a minority of viable, chronically dysfunctional segments with reduced resting flow (hibernating myocardium). We hypothesized that epicardial artery patency might predict which segments have critically reduced subendocardial flow reserve and limited contractile reserve. METHODS: Pigs were chronically instrumented with a fixed stenosis on the left anterior descending coronary artery (LAD) to produce hibernating myocardium. At least 3 months later, flow at rest and during adenosine vasodilation (microspheres), ventricular function and contractile reserve (contrast ventriculography), and (18)F-2-deoxyglucose (FDG) deposition (ex vivo tissue counting) were quantified. RESULTS: Hibernating myocardium (regional dysfunction with reduced resting perfusion) was present in animals with an occluded (n=40) or patent (n=19) LAD. Viability was confirmed by histology and FDG deposition. In collateral-dependent hibernating myocardium, subendocardial flow did not increase above baseline levels during epinephrine or adenosine stimulation, consistent with exhausted subendocardial flow reserve at rest. This was associated with limited contractile reserve and regionally increased FDG deposition. In contrast, subendocardial flow reserve was present in hibernating myocardium distal to a patent artery. Contractile reserve during epinephrine infusion in this group was significantly greater than in animals with an occluded artery. CONCLUSIONS: The physiology and metabolism of hibernating myocardium was dependent upon stenosis severity and its effects on subendocardial flow reserve. In collateral-dependent hibernating myocardium, contractile reserve was limited in the setting of exhausted subendocardial flow reserve, thus supporting the hypothesis that metabolic imaging may be preferable for determining viability distal to a complete occlusion.

Adenosine↗
PubMed1998

Inhibin-B: the physiologic basis of the clomiphene citrate challenge test for ovarian reserve screening.

OBJECTIVE: To determine inhibin-B concentrations during ovarian reserve screening in women with normal and diminished ovarian reserve as determined by the clomiphene citrate challenge test. DESIGN: Retrospective. SETTING: Tertiary fertility center. PATIENT(S): Women undergoing ovarian reserve screening for a routine fertility evaluation. INTERVENTION(S): Clomiphene citrate challenge test. MAIN OUTCOME MEASURE(S): Inhibin-B concentrations on menstrual days 3 and 10. RESULT(S): Nineteen patients with normal ovarian reserve and 15 with diminished ovarian reserve had serum inhibin-B concentrations determined during ovarian reserve screening. For all patients, day 10 inhibin-B concentrations were higher than day 3. Women with normal ovarian reserve had higher inhibin-B concentrations on both days 3 and 10 than women with diminished ovarian reserve. Inhibin-B concentrations demonstrated a negative correlation with FSH levels on both cycle days 3 and 10 and a positive correlation with E2 on cycle day 10. CONCLUSION(S): Women with diminished ovarian reserve during ovarian reserve screening had reduced granulosa cell inhibin-B production compared with women with normal ovarian reserve. The lower inhibin-B concentrations may be responsible for the elevated FSH concentrations and may be indicative of the aging follicular apparatus.

Adult↗
PubMed1986

Comparative study of coronary flow reserve, coronary anatomy and results of radionuclide exercise tests in patients with coronary artery disease.

A comparative assessment of regional coronary flow reserve, quantitative percent diameter coronary stenosis and exercise-induced perfusion and wall motion abnormalities was performed in 39 patients with coronary artery disease. Coronary flow reserve was determined by a digital angiographic technique utilizing contrast medium as the hyperemic agent. Percent diameter stenosis was calculated by an automated quantification program applied to orthogonal cineangiograms. Thallium-201 scintigraphy and radionuclide ventriculography were used to assess regional perfusion and wall motion abnormalities, respectively, at rest and during exercise. In Group A, 19 patients without transmural infarction or collateral vessels, coronary flow reserve was inversely related to percent diameter stenosis (r = -0.61, p less than 0.0001), and scintigraphic abnormalities occurred only in vascular distributions with a coronary flow reserve of less than 2.00. There was a strong relation among abnormal regional exercise results, stenoses greater than 50% and reactive hyperemia of less than 2.00. Patients with multivessel disease, however, often had normal exercise scintigrams in regions associated with greater than 50% stenosis and low coronary flow reserve when other regions had a lower coronary flow reserve or higher grade stenosis, or both. In Group B, 20 patients with angiographically visible collateral vessels, 12 of whom had prior myocardial infarction, coronary flow reserve correlated less well with percent diameter stenosis than in Group A (r = -0.47, p less than 0.004). As in Group A patients, there was a significant relation between abnormal exercise test results and stenoses greater than 50%. However, reactive hyperemia values were generally lower than in Group A, and positive exercise stress results were strongly correlated only with highly impaired flow reserves of 1.3 or less. In Group B patients, the coronary flow reserve of vessels with less than 50% stenosis was significantly lower than that of similar vessels in Group A patients (2.40 +/- 0.79 versus 1.56 +/- 0.43; p less than 0.0002). It is concluded that: there is a general relation between quantitative percent diameter stenosis and reactive hyperemia that is not of sufficient precision to allow accurate prediction of coronary flow reserve in individual cases; exercise scintigraphic abnormalities are usually associated with low coronary flow reserve, and the relation between these two functional tests is stronger than the relation between exercise test results and quantitative percent diameter stenosis.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed2006

Logic for designing nature reserves for multiple species.

We examine the logic of designing nature reserves to understand better how to integrate the concepts of representativeness and persistence. Simple models of viability are used to evaluate how the expected number of species in the reserve system changes with variation in the risk of extinction among species, their rate of occurrence, and the distribution of species. The optimal size of individual reserves increased with the mean and variance of the probability of extinction among species and with the rate at which the risk of extinction declines with the cost of each reserve. In contrast, the rate of occurrence of species within reserves and their rate of accumulation with increasing reserve area had a relatively minor influence on the optimal size of reserves. Patterns of endemism were most important for the location of reserves. Including differences among species in the analysis reduced the optimal number of individual reserves (and increased the size of each) when operating under a fixed budget compared with reserve designs based on single species. A case study in the city of Melbourne, Australia, demonstrates the conservation value of small (approximately 1 ha) grassland reserves and the underrepresentation of Melbourne's volcanic plains in the region's conservation network.

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