Mechanism of reversible (99m)Tc-sestamibi perfusion defects during pharmacologically induced vasodilatation

Reversible perfusion defects on (99m)Tc-sestamibi imaging during hyperemia are thought to occur due to myocardial blood flow (MBF) "mismatch" between regions with and without stenosis. We have recently shown that myocardial blood volume (MBV) distal to a stenosis decreases during hyperemia, resulting in a reversible perfusion defect on myocardial contrast echocardiography (MCE). In this study, we hypothesized that a reversible perfusion defect on (99m)Tc-sestamibi imaging during hyperemia results from the same mechanism. We tested our hypothesis under the following conditions: 1) increases in MBF in the absence of changes in MBV by using direct intracoronary infusion of adenosine (group I, n = 10 dogs); 2) decrease in MBV despite an increase in MBF by left main infusion of adenosine proximal to a noncritical coronary stenosis placed on either coronary artery (group II, n = 13 dogs); and 3) reduction in both resting MBF and MBV by placement of a severe stenosis (group III, n = 7 dogs). In group I dogs, no difference in MBV or (99m)Tc-sestamibi uptake was found between the two coronary beds despite an up to fourfold increase in MBF in one bed with adenosine. In group II dogs, MBV distal to the stenosis decreased during hyperemia despite a twofold increase in mean MBF. A good correlation was found between (99m)Tc-sestamibi uptake and MBV ratios from the stenosed versus normal bed (r = 0.91, P < 0.001). In group III dogs, both MBF and MBV were decreased in the stenosed bed at rest with a good correlation noted between (99m)Tc-sestamibi uptake and MBV ratios from the stenosed versus normal bed (r = 0.92, P = 0.004). We conclude that reversible defects on (99m)Tc-sestamibi during vasodilator stress imaging are related to decreases in MBV distal to a stenosis and not to "flow mismatch" between beds. The decrease in MBV results in reduced (99m)Tc-sestamibi uptake during hyperemia.     

Incretion of Insulin by Pancreas and Its Inactivation in Women during Long-Term Head-down Tilt Bed Rest

An increase in insular activity in response to hyperglycemia when performing a glucose tolerance test (GTT) during normal physical activity in eight women volunteers was found to be associated with increased blood concentrations of insulin provided by an increase in secretion rate and a decrease in inactivation rate. After 81 days of stay in long-term –6° head-down tilt bed rest (bed rest), flattened glycemic curves (with low hyperglycemic lifting) observed during the GTT, what was indicated high insular activity. An increase in the insular activity was evidencing also by a smaller peak of the blood concentration of glucose from 5 min after intravenous nfusion of 20 mL of 40% glucose solution at 120 minute of the GTT. In bed rest on empty stomach no significant changes in the concentrations of insulin and C-peptide were observed. The dynamics of hormone during the GTT was showed that the appearance of flattened glycemic curves when performing GTT during bed rest was associated with more pronounced, than under the usual conditions, an increase in insulin concentration in response to hyperglycemia. An increase in the blood insulin concentration when performing GTT in bed rest was mainly provided by increased hormone secretion rate in the pancreas, but not by a decrease in its inactivation rate. If you use regular exercises for prevention of hypokinesia under conditions of bed rest, an increase in insulin concentration during GTT was mainly provided by a decrease in its inactivation rate and not by an increase in secretion rate.     

Mechanisms involving the endothelium in reaction of reactive hyperemia

The experiments on anesthetized dogs and on test-preparations of isolated vascular rings of femoral artery used for detection of appearance of vasoactive substances in venous blood demonstrated that the response of reactive hyperemia is accompanied by the appearance of vasodilation substances in the blood, the concentration of which taking into account the reaction of relaxation of vascular preparation, increases with the occlusion duration. Chemical inhibition of endothelium of a studied bed by saponin essentially decreases the reactive hyperemia and relaxation of test-preparation. The rise of pressure in an overlapped part of a bed and the decrease in the deformation of endothelium with the help of dimerized glutaraldehyde treatment affected the hyperemia and vascular preparation reaction in the similar way. We concluded that the reaction of reactive hyperemia is the result of the vasoactive substances secretion by endothelium in response to a decrease in intravascular pressure.     

Maximal and submaximal forces of slow fibers in human soleus after bed rest.

The effects of 2 and 4 mo of bed rest, with or without exercise countermeasures, on the contractile properties of slow fibers in the human soleus muscle were examined. Mean fiber diameters were 8 and 36% smaller after 2 and 4 mo of bed rest, respectively, than the pre-bed rest level. Maximum tetanic force (P(o)), maximum activated force (F(max)) per cross-sectional area (CSA), and the common-logarithm value of free Ca(2+) concentration required for half-maximal activation (pCa(50)) also decreased after 2 and 4 mo of bed rest. In contrast, maximum unloaded shortening velocity (V(o)) was increased after 2 and 4 mo of bed rest. After 1 mo of recovery, fiber diameters, P(o), F(max) per CSA (P > 0.05), and pCa(50) were increased and V(o) decreased toward pre-bed rest levels. Effects of knee extension/flexion exercise by wearing an anti-G Penguin suit for 10 h daily, and the effects of loading or unloading of the plantar flexors with (Penguin-1) or without (Penguin-2) placing the elastic loading elements of the suit, respectively, were investigated during ~2 mo of bed rest. In the Penguin-1 group, mean fiber diameter, P(o), F(max) per CSA, V(o), and pCa(50) were similar before and after bed rest. However, the responses of fiber size and contractile properties to bed rest were not prevented in the Penguin-2 group, although the degree of the changes was less than those induced by bed rest without any countermeasure. These results indicate that long-term bed rest results in reductions of fiber size, force-generation capacity, and Ca(2+) sensitivity, and enhancement of shortening velocity in slow fibers of the soleus. The data indicate that continuous mechanical loading on muscle, such as stretching of muscle, is an effective countermeasure for the prevention of muscular adaptations to gravitational unloading.     

Heat and water flux in the intrathoracic airways and exercise-induced asthma

To explore the relationship between the flux of heat and water within the respiratory tract during exercise and recovery to the development of exercise-induced asthma (EIA), we recorded airstream temperature at multiple points throughout the tracheobronchial tree in 10 normal and 10 asthmatic subjects before, during, and after cycle ergometry. In both groups, the intra-airway temperature fell progressively as ventilation increased, and there were no significant differences between the thermal profiles of the two populations at rest or during exercise. Calculation of water losses and the osmolality of the airway surface fluid failed to demonstrate significant airway drying in either group. With cessation of the work load, the airstream temperature increased abruptly, rising two times more rapidly in the asthmatics than the normals. Since the major source of heat in these experiments is the bronchial circulation, our findings suggest a reaction sequence consisting of vasoconstriction and airway cooling during exercise followed by a rapid resupply of heat when exercise ceases. The latter may cause the hyperplastic capillary bed in the airways of asthmatics to develop an exaggerated rebound hyperemia which may lead to airway edema and EIA.     

Egg-to-fry survival of the sea trout in some streams of Gotland

The quality of the surface water of Gotland (Sweden) streams was good, and did not limit sea trout egg-to-fry (ETF) survival. The oxygen concentration of the interstitial water was positively correlated to the permeability of the stream bed, and to the geometric mean diameter of the substratum. When the oxygen at 15 cm inside the stream bed was undiminished from surface values, the permeability of the stream bed was at least 6000 cm h^–1 and the geometric mean diameter of the substratum at least 15.0 mm. When the interstitial oxygen concentration increased, the interstitial ammonium concentration decreased, the NO₂ concentration remained stable and the NO₃ concentration increased. The ETF survival up to hatching was highly dependent upon the oxygen concentration of the interstitial water. For survival from hatching to emergence, the geometric mean diameter of the substratum was the most important factor. ETF survival >50% was observed where the interstitial oxygen concentration averaged at least 10mg I-¹, the substratum permeability at least 2000cm h-¹ and the substratum geometric mean diameter at least 15 mm. Other factors, such as overdigging and drying out of the spawning grounds could increase the ETF mortality.     

小麦玉米不同幅宽套作对种群生态关系和作物产量的影响

小麦玉米不同幅宽套作对种群生态关系和作物产量的影响李萍萍陈欣（南京农业大学农学系,２１００１４）ＩｎｆｌｕｅｎｃｅｏｆＤｉｆｅｒｅｎｔＢｅｄＷｉｄｔｈｏｎｔｈｅＩｎｔｅｒｓｐｅｃｉｆｉｃＲｅｌａｔｉｏｎｓｈｉｐａｎｄＹｉｅｌｄｉｎＲｅｌａｙＣｒｏｐｐ...     

Imaging the permeability pore transition in single mitochondria.

In mitochondria the opening of a large proteinaceous pore, the "mitochondrial permeability transition pore" (MTP), is known to occur under conditions of oxidative stress and matrix calcium overload. MTP opening and the resulting cellular energy deprivation have been implicated in processes such as hypoxic cell damage, apoptosis, and neuronal excitotoxicity. Membrane potential (delta psi(m)) in single isolated heart mitochondria was measured by confocal microscopy with a voltage-sensitive fluorescent dye. Measurements in mitochondrial populations revealed a gradual loss of delta psi(m) due to the light-induced generation of free radicals. In contrast, the depolarization in individual mitochondria was fast, sometimes causing marked oscillations of delta psi(m). Rapid depolarizations were accompanied by an increased permeability of the inner mitochondrial membrane to matrix-entrapped calcein (approximately 620 Da), indicating the opening of a large membrane pore. The MTP inhibitor cyclosporin A significantly stabilized delta psi(m) in single mitochondria, thereby slowing the voltage decay in averaged recordings. We conclude that the spontaneous depolarizations were caused by repeated stochastic openings and closings of the transition pore. The data demonstrate a much more dynamic regulation of membrane permeability at the level of a single organelle than predicted from ensemble behavior of mitochondrial populations.     

High-density surface EMG study on the time course of central nervous and peripheral neuromuscular changes during 8 weeks of bed rest with or without resistive vibration exercise

The aim of the present study was to assess the time course and the origin of adaptations in neuromuscular function as a consequence of prolonged bed rest with or without countermeasure. Twenty healthy males volunteered to participate in the present study and were randomly assigned to either an inactive control group (Ctrl) or to a resistive vibration exercise (RVE) group. Prior to, and seven times during bed rest, we recorded high-density surface electromyogram (sEMG) signals from the vastus lateralis muscle during isometric knee extension exercise at a range of contraction intensities (5–100% of maximal voluntary isometric torque). The high-density sEMG signals were analyzed for amplitude (root mean square, RMS), frequency content (median frequency, F_med) and muscle fiber conduction velocity (MFCV) in an attempt to describe bed rest-induced changes in neural activation properties at the levels of the motor control and muscle fibers. Without countermeasures, bed rest resulted in a significant progressive decline in maximal isometric knee extension strength, whereas RMS remained unaltered throughout the bed rest period. In line with observed muscle atrophy, both F_med and MFCV declined during bed rest. RVE training during bed rest resulted in maintained maximal isometric knee extension strength, and a strong increase (～30%) in maximal EMG amplitude, from 10 days of bed rest on. Exclusion of other factors led to the conclusion that the RVE training increased motor unit firing rates as a consequence of an increased excitability of motor neurons. An increased firing rate might have been essential under training sessions, but it did not affect isometric voluntary torque capacity.     

The role of the endothelium in the development of functional hyperemia of the skeletal muscles]

Experiments on anesthesized dogs demonstrated that gastrocnemius muscle vessels working hyperemia substantially decreased after chemical destruction of endothelium by saponin, inhibition of endothelium-derived relaxing factor synthesis by gossypol and inhibition of quanylate cyclase by methylene blue. Reaction was not decreased after cyclooxygenase inhibition by indomethacin. The endothelium-derived relaxing factor predecessor--L-arginine essentially increased working hyperemia. We concluded that endothelium plays an important role in reaction of working hyperemia by endothelium-derived relaxing factor release.     

Effects of the renin-angiotensin-aldosterone system on the cardiovascular system during 20-days bed rest

Long term change of renin-angiotensin-aldosterone system (RAAS) induced by bed rest and its effects on cardiovascular system are still controversial. The purpose of this study was to obtain a general conclusion on these questions by analyzing our two 20-days horizontal bed rest experiments in past two years with 18 subjects. Plasma renin activity and aldosterone were consistently increased during the bed rest, but angiotensin II was increased only during the early days. Decrease in urinary sodium excretion and increase in urinary potassium excretion were observed during day 3-8 and day 7-12, respectively. Mean arterial pressure increased during day 3-8. Pulse pressure was returned to pre-bed rest level by day 10 after an initial decrease. All these results indicated an activated RAAS and its active effects on cardiovascular and overall fluid regulating systems during our horizontal bed rest studies. Direct effect of change in gravitational force on renal pressure-sensitive cells or effects related to physical inactivity may explain our results.     

Mechanism of the development of functional hyperemia in the palatal salivary glands of the rat

At various regimens of the secretory activity in the palatile salivary glands, changes occurring in the transversal profiles of the postcapillary venules, but not of the blood capillaries, are most noticeable. Under food stimulation of secretion, the former dilate essentially, that can demonstrate certain functional hyperemia developing in the palatine salivary glands. Some previous experiments concerning interpretation of principles on the microcirculatory bed spatial organization give a good reason to suggest that dilatation of the postcapillary venules is connected with an increased blood perfusion in the canals of the preferrable blood stream. The postcapillary dilatation is possible because blood from the precapillaries gets into the capacitance blood microvessels and its volume at that moment is greater than the capacity of the venous microvessels. A suggestion is made that filtrative function of the palatile salivary glands depends on development of the functional hyperemia. It is possible, that this mechanism is universal, since owing to it, reflectory reactions of the salivary glands directed to the immediate secure of the oral cavity with a necessary amount of liquor become possible.     

Influence of repetitive Gz acceleration on structural and metabolic profile of m. vastus lateralis in monkeys exposed to 30 day bedrest

It was shown that changes in structural and metabolic indices of extensor muscles of the lower extremities were usually found in man after exposure to space flight or to bed rest. Similar changes were also observed in monkeys, space-flown on "Kosmos" biosatellites. Response to weightlessness and to restraint was found to be different in m. soleus and in m. vastus lateralis. Therefore, it is important to study structural and metabolic changes of m. vastus lateralis fibers under conditions of gravitational unloading in monkeys, who have motor apparatus similar to that of man, and are much more fruitful object of research. It is assumed that artificial gravity can serve as a countermeasure, aimed at diminishing effects of gravitational unloading. We have studied the effect of repeated gravity overloading, created by means of a centrifuge, on structural and metabolic indices of monkey m. vastus lateralis at the background of 30 day head down tilt bed rest (BR).     

Vascular adaptation to deconditioning and the effect of an exercise countermeasure: results of the Berlin Bed Rest study.

Deconditioning is a risk factor for cardiovascular disease. The physiology of vascular adaptation to deconditioning has not been elucidated. The purpose of the present study was to assess the effects of bed rest deconditioning on vascular dimension and function of leg conduit arteries. In addition, the effectiveness of resistive vibration exercise as a countermeasure for vascular deconditioning during bed rest was evaluated. Sixteen healthy men were randomly assigned to bed rest (BR-Ctrl) or to bed rest with resistive vibration exercise (BR-RVE). Before and after 25 and 52 days of strict horizontal bed rest, arterial diameter, blood flow, flow-mediated dilatation (FMD), and nitroglycerin-mediated dilatation were measured by echo Doppler ultrasound. In the BR-Ctrl group, the diameter of the common femoral artery decreased by 13 +/- 3% after 25 and 17 +/- 1% after 52 days of bed rest (P < 0.001). In the BR-RVE group this decrease in diameter was significantly attenuated (5 +/- 2% after 25 days and 6 +/- 2% after 52 days, P < 0.01 vs. BR-Ctrl). Baseline blood flow did not change after bed rest in either group. After 52 days of bed rest, FMD and nitroglycerin-mediated dilatation of the superficial femoral artery were increased in both groups, possibly by increased nitric oxide sensitivity. In conclusion, bed rest deconditioning is accompanied by a reduction in the diameter of the conduit arteries and by an increased reactivity to nitric oxide. Resistive vibration exercise effectively attenuates the diameter decrease of leg conduit arteries after bed rest.     

Alpha-adrenergic vasoconstrictor tone limits right coronary blood flow in exercising dogs

In exercising dogs, increased myocardial O2 consumption (MVO2) of the left ventricle is met primarily by hyperemia, whereas increased O2 extraction makes a greater contribution to right ventricular (RV) O2 supply. We hypothesized that alpha-adrenergic vasoconstrictor tone limits right coronary (RC) blood flow during exercise, forcing increased O2 extraction. This tone might also contribute to lesser RC vascular conductance at rest. Accordingly, RV O2 balance was examined at rest and during graded treadmill exercise before and during alpha-adrenergic blockade with phentolamine (1 mg/kg, i.v., n=6). The transmural distribution of RC flow was measured with radiolabeled microspheres in 4 additional dogs. At rest, alpha-adrenergic receptor blockade did not significantly increase RC flow or conductance. During exercise, alpha-adrenergic blockade increased RC flow and conductance responses to increased RV MVO2 by 25% and 60%, respectively. The transmural distribution of RC flow was not altered by exercise or by alpha-adrenergic blockade. Before alpha-adrenergic blockade, hyperemia provided 39%-66% of the additional O2 consumed by the right ventricle during graded exercise; after alpha-adrenergic blockade, hyperemia contributed 74%-85%. After alpha-adrenergic blockade, the slope of the relationship between RC venous PO2 and RV MVO2 became less steep, reflecting less O2 extraction due to enhanced hyperemia. Additional experiments were conducted on 5 anesthetized, open-chest dogs with constant RC perfusion pressure and beta-adrenergic blockade. The RC flow response to intracoronary norepinephrine was shifted to the left compared with that measured in the left coronary circulation, consistent with observations in the conscious exercising dogs. In conclusion, alpha-adrenergic vasoconstrictor tone does not restrict resting RC blood flow, but during exercise, this tone transmurally blunts RC hyperemia and forces the right ventricle to mobilize its O2 extraction reserve. This effect is more pronounced than has been reported for the left ventricle.     

Effect of simulated microgravity on endocrine response to insulin-induced hypoglycemia in physically fit men.

Adaptation to microgravity is associated with alteration in some endocrine functions. In the present longitudinal study, the counterregulatory hormonal response to insulin-induced hypoglycemia (ITT, 0.1 IU/kg short acting insulin i. v.) was evaluated under simulated microgravity conditions in 15 physically fit subjects. ITT was performed at the beginning of the investigation, and again after completion of 6 weeks of endurance training and after a subsequent period of 4 days of head-down bed rest at a backward tilt of 6 degrees from the horizontal. Endurance training showed a significant increase in maximal aerobic capacity in previously well-trained subjects (increase by 12 %), as well as on attenuation of counterregulatory response of epinephrine to hypoglycemia. After 4 days of bed rest, basal concentrations of plasma norepinephrine was diminished (p < 0.002) and plasma renin activity was enhanced (p < 0.02). After bed rest, decreased responses of the two catecholamines (norepinephrine, p < 0.001; epinephrine, p < 0.001), growth hormone (p < 0.001), and cortisol (p < 0.05) were observed. Response of plasma renin activity after bed rest was increased (p < 0.01). This longitudinal study indicated that 4 days of bed rest in endurance-trained subjects induced increased response of PRA to hypoglycemia and attenuation of other counterregulatory neuroendocrine responses.     

Quantitative analysis of feedforward sympathetic coronary vasodilation in exercising dogs.

Recent experiments demonstrate that feedforward sympathetic beta-adrenoceptor coronary vasodilation occurs during exercise. The present study quantitatively examined the contributions of epinephrine and norepinephrine to exercise coronary hyperemia and tested the hypothesis that circulating epinephrine causes feedforward beta-receptor-mediated coronary dilation. Dogs (n = 10) were chronically instrumented with a circumflex coronary artery flow transducer and catheters in the aorta and coronary sinus. During strenuous treadmill exercise, myocardial oxygen consumption increased by approximately 3.9-fold, coronary blood flow increased by approximately 3.6-fold, and arterial plasma epinephrine concentration increased by approximately 2.4-fold over resting levels. At arterial concentrations matching those during strenuous exercise, epinephrine infused at rest (n = 6) produced modest increases (18%) in flow and myocardial oxygen consumption but no evidence of direct beta-adrenoceptor-mediated coronary vasodilation. Arterial norepinephrine concentration increased by approximately 5. 4-fold during exercise, and coronary venous norepinephrine was always higher than arterial, indicating norepinephrine release from cardiac sympathetic nerves. With the use of a mathematical model of cardiac capillary norepinephrine transport, these norepinephrine concentrations predict an average interstitial norepinephrine concentration of approximately 12 nM during strenuous exercise. Published dose-response data indicate that this norepinephrine concentration increases isolated coronary arteriolar conductance by approximately 67%, which can account for approximately 25% of the increase in flow observed during exercise. It is concluded that a significant portion of coronary exercise hyperemia ( approximately 25%) can be accounted for by direct feedforward beta-adrenoceptor coronary vascular effects of norepinephrine, with little effect from circulating epinephrine.     

Effects of indomethacin on local blood flow regulation in canine heart and kidney.

In two series of experiments we studied the effects of indomethacin on (a) coronary reactive hyperemia and, (b) renal blood flow, autoregulation, and reactive dilation. Coronary blood flow was measured in closed-chest dogs. Reactive hyperemia was induced by coronary occlusion for 5 and 15 sec. Indomethacin, an inhibitor of prostaglandin synthesis, was infused intra-arterially in doses of 90-200 mg over periods ranging from 30-120 min. Coronary reactive hyperemia was not affected by indomethacin. The canine renal vascular bed was studied under conditions of natural flow, controlled flow, and controlled pressure. Intra-arterial infusion of 90 mg of indomethacin over a 30- to 60- min period caused increased renal vascular resistance and an attenuation of reactive dilation (induced by stopping renal blood flow for 90 sec). Indomethacin slightly attenuated the autoregulatory response to decreasing perfusion pressures, but did not affect the respone to increasing pressures. Thus the study fails to provide evidence for participation of the prostaglandins in regulation of coronary blood flow and suggests only minimal participation of prostaglandings in renal blood flow regulation.     

Effect of bed rest on the adenine nucleotides concentration in human blood platelets.

The effect of immobilization in bed on metabolism and function of human blood platelet was studied. Blood platelets taken from patients with bone fractures after long term bed rest (14 days and 28 days) demonstrated significantly reduced concentration of total adenine nucleotides (after 28 days reduction about 30%). This decrease of total platelet adenine nucleotides after immobilization in bed is probably caused by stimulation of platelet secretory process. Thrombin which released from control platelets 58.2% +/- 1.5% of total adenine nucleotides liberated decreased amounts (only 23.1% +/- 3.3% of total) of nucleotides from patient platelets isolated after 28 days of immobilization in bed. Loss of nucleotides from platelets was accompanied by slightly increased extent of platelet aggregation. It is concluded that during bed rest the reactivity of blood platelets (aggregation and release reaction) is stimulated.     

eNOS 894T allele and coronary blood flow at rest and during adenosine-induced hyperemia

The 894T allele of a G894T polymorphism in the endothelial nitric oxide synthase (eNOS) gene is associated with decreased eNOS activity, cleavage of the protein, and endothelial dysfunction. The present study evaluated the association with coronary blood flow (CBF) at rest and during adenosine (ADO)-induced hyperemia. CBF was determined by Doppler flow wire and angiography in 97 left anterior descending arteries of individuals without coronary artery disease. At rest, average peak velocity (APV) was lower and coronary vascular resistance (CVR) was higher in homozygous carriers of the 894T allele than in heterozygotes and individuals without the 894T allele. CBF tended to be lower in eNOS 894T allele carriers. During ADO-induced hyperemia (18 microg ic), APV, CVR, and CBF were not statistically different between the genotypes. The reduced APV at rest in conjunction with an increased CVR indicates a vasomotor dysfunction related to an increased microvascular resting tone in eNOS 894T allele carriers.