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Acute effects of alcohol on left ventricular function in healthy subjects at rest and during upright exercise.

Six healthy men, aged 23 to 30 years, were studied by radionuclide angiocardiography at rest and at 2 submaximal exercise levels in the upright position during increasing alcohol intoxication. At light intoxication (serum ethanol 23 mmol/liter), the median value of left ventricular (LV) ejection fraction (EF) at rest decreased by 5%. At heavy intoxication (serum ethanol 45 mmol/liter), the median LVEF decreased at rest by 11% and during 75% submaximal exercise by 6%, heart rate at rest increased (median 81 vs 62 beats/min), and systolic blood pressure decreased during 50% submaximal exercise (median 145 vs 163 mm Hg). No significant changes of plasma epinephrine concentrations were recorded, whereas plasma norepinephrine concentrations were increased by 24% at rest during light intoxication and by 30 to 38% during heavy intoxication. No changes of LVEF and plasma catecholamine levels were recorded after ingestion of isovolumic, isocaloric drinks as compared with values obtained before intake. Thus, influences of ingestion per se and repeated investigations of LV function were excluded. These findings suggest that in healthy subjects alcohol intoxication causes a dose-dependent impairment of cardiac contractility. Compensatory mechanisms may account for a reduced influence during exercise.

Adult↗

Effect of timolol on mortality and reinfarction after acute myocardial infarction: prognostic importance of heart rate at rest.

Long-term timolol treatment after acute myocardial infarction is associated with a significant reduction in mortality and nonfatal reinfarction. To evaluate whether the reduction in mortality and morbidity is exclusively or partly dependent on a reduction in heart rate (HR), cardiac events in the Norwegian Timolol Multicenter Study were analyzed according to resting HR at baseline and at 1 month of follow-up Resting HR at baseline was a significant predictor of total death and all events (total death plus nonfatal reinfarction) both in placebo- and in timolol-treated patients. In the placebo group the median resting HR was unchanged from baseline to 1 month control (72 beats/min), but was reduced from 72 beats/min to 56 beats/min in the timolol group. Resting HR during follow-up remained a significant predictor of total death. Further, mortality at a given HR during treatment was not markedly different whether the HR was spontaneous or caused by timolol. Timolol treatment was related to a significant reduction in mortality, and this study suggests that the major effect of timolol treatment on mortality after acute myocardial infarction may be attributed to the reduction in HR. Timolol treatment was also associated with an overall reduction in nonfatal reinfarction. However, nonfatal reinfarction was inversely related to resting HR during follow-up, indicating that although coronary artery occlusion in low-risk patients may cause nonfatal reinfarction, the outcome in high-risk patients is more likely to be death. When analyzing mortality and nonfatal reinfarction combined, timolol treatment was related to a reduction in cardiac events at any given HR, suggesting that factors in addition to HR reduction are important in the protective effects of timolol.

Clinical Trials as Topic↗

Effects of metoprolol on rest and exercise cardiac function and plasma catecholamines in chronic congestive heart failure secondary to ischemic or idiopathic cardiomyopathy.

To define the effects of 2 months of metoprolol therapy on cardiac function, aerobic performance and sympathetic nervous system activity, metoprolol (75 to 100 mg/day) was administered to 10 patients with chronic congestive heart failure (CHF). Metoprolol was discontinued in 2 patients because of worsening CHF. In the remaining 8 patients, peak oxygen uptake increased significantly (14.8 +/- 3.0 to 16.1 +/- 2.5 ml/kg/min, p less than 0.05) as did the oxygen pulse (9.0 +/- 2.2 to 12.6 +/- 1.8 ml/beat, p less than 0.02). Resting heart rate (87 +/- 18 to 62 +/- 9 beats/min, p less than 0.05) and peak exercise heart rate (133 +/- 13 to 105 +/- 30 beats/min, p less than 0.02) were both reduced. Mean resting ejection fraction increased from 0.15 +/- 0.06 to 0.25 +/- 0.11 and peak exercise ejection fraction also tended to increase (0.19 +/- 0.11 to 0.28 +/- 0.15, difference not significant). Both resting plasma norepinephrine (613 +/- 706 to 303 +/- 142 pg/ml, p less than 0.05) and epinephrine (71 +/- 50 to 40 +/- 21 pg/ml, p less than 0.05) were reduced. Circulating lymphocyte beta-adrenergic receptor number was unchanged (1,334 +/- 292 to 1,344 +/- 456 receptors/cell, difference not significant). It is concluded that metoprolol therapy is associated with improvements in rest and exercise ventricular performance and maximal aerobic capacity. These improvements are associated with a decline in resting sympathetic nervous system activity.

Aged↗

Impaired left ventricular filling and regional diastolic asynchrony at rest in coronary artery disease and relation to exercise-induced myocardial ischemia.

Impaired left ventricular (LV) diastolic filling at rest is frequently observed in patients with coronary artery disease (CAD) who have normal LV systolic function and no previous infarction. To test the hypothesis that abnormal diastolic function at rest might reflect the functional severity of CAD, as estimated by exercise-induced ischemia, the relation between regional and global LV diastolic function at rest and during exercise-induced ischemia was evaluated in 49 patients with radionuclide angiography. All patients had normal systolic function at rest. Group 1 (n = 26) patients manifested a normal ejection fraction response to exercise and group 2 (n = 23) patients an abnormal response. Data obtained from 22 age-comparable normal volunteers were used for comparison. Although regional and global diastolic function were not different between normal subjects and group 1 patients, peak filling rate was lower in group 2 patients than in normal subjects (2.5 +/- 0.8 vs 3.2 +/- 0.6 end-diastolic counts/s; p less than 0.01). Moreover, regional diastolic asynchrony, as assessed from the radionuclide data by using a regional sector analysis of the LV region of interest, was greater in group 2 patients (46 +/- 44 ms) than in both normal subjects (25 +/- 16 ms; p less than 0.05) and group 1 patients (23 +/- 16 ms; p less than 0.05). Thus, among patients with CAD and with normal LV systolic function at rest, impaired LV filling and regional asynchrony predict a greater degree of exercise-induced ischemia, suggesting a greater extent of jeopardized myocardium.

Coronary Circulation↗

Effect of work-rest schedules on spinal shrinkage in the sedentary worker.

The relationship between duration and frequency of rest intervals and spinal shrinkage was investigated. The objective was to determine whether the amount of spinal shrinkage can be significantly reduced by rest breaks during which the individual is either walking or standing rather than sitting. Seven subjects were studied during 4-h sessions for four consecutive days. During each session the subject sat and typed for a total of 3 h 20 min. Forty minutes of rest breaks were dispersed throughout the 4-h period. One condition was administered during each day with either eight breaks of 5 min, four breaks of 10 min, two breaks of 20 min or a single break of 40 min at the end of the work session. Using a stadiometer, changes in stature were measured with an accuracy of about 0.2 mm. Measurements were taken at the beginning of each work period and before and after each rest break. For the conditions with rest breaks of 20 or 40 min, there was significantly less shrinkage at the end of the 4-h work session.

Journal Article↗

Estimation of blood flow by 133Xe clearance in human masseter muscle during rest, endurance of isometric contraction, and recovery.

Sixty-four measurements of 133Xe clearance from the masseters of 9 individuals, who had no facial or oral pain, were used to evaluate changes in intramuscular blood flow (IMBF) caused by endurance of isometric contraction at approx. 50 per cent of maximum voluntary EMG activity. On average, the IMBF during endurance increased by 4.2 times in 6 individuals and decreased 62 per cent of the rest flow in 3 individuals. Overall, the group average of endurance flow was 2.5 times higher than the initial rest flow. The group average of post-endurance hyperaemia was 27 times higher than the initial rest flow and 11 times higher than the endurance flow. IMBF during the final rest was 1.7 times higher than the initial rest flow. The relative IMBF during endurance was negatively correlated to muscle effort, and the post-endurance flow in relation to the endurance flow presented a compensatory positive correlation to the muscle effort. Although the average IMBF tended to increase during endurance, it was insufficient to meet the demand of the much higher relative increase in muscle activity, as indicated by the pronounced post-endurance hyperaemia, especially after long endurance.

Adult↗

Contribution of electrogenic sodium-potassium ATPase to resting membrane potential of cultured rat skeletal myotubes.

The contribution of electrogenic Na+ -K+ ATPase to resting membrane potential (Em) of mature and developing rat skeletal myotubes in culture was determined by examining effects of inhibition of this enzyme on Em. Ouabain, a specific Na+-K+ ATPase inhibitor, caused resting Em to decrease within 30 s by 5-8 mV and reach a minimum value of about -60 mV after 5 min. The decrease in Em was not accompanied by a decrease in input resistance for up to 15 min after application. Resting Em was found to be dependent on the temperature of the recording medium with maximum values of Em ranging from -85 to -90 mV at a temperature of 35-37 degrees C and minimum values about -60 mV at 10-15 degrees C. Ouabain (1 mM), added to cultures at low temperature (10-15 degrees C) did not further decrease Em but did prevent the increase in Em that occurs with increasing temperature up to 37 degrees C. Resting Em of cultured myotubes was reduced to about -60 mV by reducing the supply of ATP either with 2,4 dinitrophenol (DNP), which inhibits oxidative phosphorylation or with fluorodinitrobenzene (FDNB), which inhibits creatine phosphokinase. Neither of these compounds, when added to cultures in the presence of ouabain, reduced resting Em to a value lower than that obtained with ouabain alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of barium and some channel blockers on sensory discharge of the frog labyrinth posterior canal recorded at rest and during rotation.

The effect on the afferent synaptic transmission of Ba2+, Sr2+, tetraethylammonium (TEA) and 4-aminopyridine (4-AP) has been investigated in the isolated frog labyrinth by intracellularly recording the posterior canal resting and evoked receptor discharge. BaCl2 (0.3 mM) or SrCl2 (1.8 mM) substitution for normal external CaCl2 restored the afferent activity without affecting the membrane potential of the sensory fibres. On further increasing Ba2+ concentration (0.5-5 mM) a dose-dependent increase in the EPSP and spike discharges was observed in all the units examined. Ba2+ (1.8-4 mM) removed the depression of the sensory activity operated by CoCl2 (3 mM), while its facilitatory effect was completely antagonized by raising Ca2+ concentration (up to 10 mM). TEA (20 mM) elicited a clear-cut increase in the EPSP and spike discharges which, however, was less consistent than that produced by Ba2+ (1 mM). The increment in spike frequency produced by TEA and Ba2+ proved to be inversely related to the initial resting firing level of the different units. The 4-AP (4-20 mM) effect resulted in a decrease of the sensory activity, which was fully restored by TEA or Ba2+. In normal saline a linear relationship was found between the mean unit resting discharge and the respective excitatory peak response during sinusoidal rotation (0.1-0.3 Hz). This result suggest that the mechanical response is mainly determined by the unit resting level. Consistent evoked responses were obtained under TEA and Ba2+ treatment which proved to depend linearly on the new mean resting discharge of the different units. Conversely, a reduced evoked response was invariably observed in all the fibres tested in the presence of 4-AP. The present results suggest that Ba2+ and Sr2+ may substitute for Ca2+ in the transmitter release process at the cyto-neural junction, the ability of Ba2+ being even larger than that of Sr2+ and Ca2+ itself. The effects of TEA and 4-AP are discussed in the light of their possible interaction with the presynaptic K+-currents recently described in hair cells.

4-Aminopyridine↗

Biochemical analysis of inhibitory effects of a lymphokine suppressive B-cell factor on the activation process of resting B cells.

Suppressive B-cell factor (SBF) is elaborated by FcR gamma (Fc receptor for IgG)-bearing small, resting B cells after the stimulation of immune complexes and is known to inhibit humoral immune responses by acting on resting B cells. In order to elucidate where and how SBF interferes with B-cell activation in the course of transmembrane signaling, we examined the effect of SBF on the several sequential events which B cells undergo after crosslinking surface immunoglobulin (sIg). Hyper-Ia expression, plasma membrane depolarization, and activation of phosphatidylinositol (PI) hydrolysis of resting B cells, all of which were induced by the stimulation with anti-mu antibody, were significantly suppressed by the pretreatment of cells with SBF. However, SBF had no effect on the intracytoplasmic cyclic AMP level of either activated or resting B cells. Another inhibitory effect of SBF on the activation process of resting B cells by anti-mu antibody was to suppress the transient elevation of intracytoplasmic free Ca2+ only in the initial phase after triggering with anti-mu antibody. This seems to be due to a decrease in the release of inositol triphosphate into the cytoplasm by suppressing the activation of PI hydrolysis. Considering all the data, the suppressive effect of SBF on the transmembrane signaling by sIg crosslinking is ascribed to the selective suppression of the activation of PI hydrolysis. This provides a concept on a molecular basis that feedback regulation of humoral immune response is, at least partly, regulated by SBF.

Animals↗

Induction of interleukin-5 responsiveness in resting B cells by engagement of the antigen receptor and perception of a second polyclonal activation signal.

Experiments were performed to examine the nature of agents which could induce IL-5 responsiveness in small, resting splenic B lymphocytes. First, IL-5 increased plaque forming cell responses to the TI-1 antigen TNP-LPS. A second set of experiments using anti-IgM + LPS which allowed limiting dilution analysis showed induction of IL-5 responsiveness in about 20% of the resting B cell population. In the same system, IL-4 increased the percentage of proliferating cells by about 40%. A third system using the TI-2 analog conjugate anti-IgD-dextran (anti-delta-dextran) also rendered small, resting B cells responsive to IL-5. An additional system employing anti-IgM plus dextran sulfate, which also allowed limiting dilution analysis, induced IL-5 responsiveness in at least 10% of resting B cells. The features common to all four systems inducing B cell IL-5 responsiveness are at least twofold. Each system directly accesses the B cell antigen receptor and causes crosslinking. Second, each system also provides an additional polyclonal activating moiety, some of which may be similar to those in thymus independent antigens. These results suggest that some resting B cells may become IL-5 receptive after perception of at least two kinds of signals one of which perturbs sIg and the second being nonspecific and polyclonally activating.

Animals↗

Vasodilating actions of cromakalim in resting and contracting states of carotid arteries from spontaneously hypertensive rats.

To determine the properties of cromakalim-opened K+ channels in arterial smooth muscle of spontaneously hypertensive rats (SHR), the effects of cromakalim on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). The addition of cromakalim or of nifedipine to resting strips caused a relaxation only in SHR. When strips from both strains were contracted with 15.9 mM K+, the magnitude of the precontraction was greater in SHR than in WKY. Under these conditions, relaxant responses to lower concentrations of cromakalim were decreased and those to higher concentrations of cromakalim were increased in SHR. When strips from both strains were contracted with a different concentration of K+ to an equivalent magnitude (78% of the maximum) relaxant responses to cromakalim were greater in SHR than in WKY. When strips were contracted with 10(-7) M norepinephrine, the precontraction was similar between SHR and WKY, and relaxant responses to cromakalim were greater in SHR. In both strains, the relaxant responses to cromakalim were competitively antagonized by glibenclamide, a blocker of ATP-sensitive K+ (KATP) channels, with a pA2 value of approximately 7.3. Charybdotoxin (10(-7) M), a blocker of Ca(2+)-activated K+ (KCa) channels, did not inhibit the relaxant responses to cromakalim in both strains. Charybdotoxin alone elicited a contraction, which was greater in SHR than in WKY. In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was higher in SHR than in WKY. The addition of cromakalim (10(-5) M) to the resting strips increased the 86Rb efflux rate constant in both strains to a similar peak value. The addition of nifedipine (10(-7) M) to the resting strips decreased the basal 86Rb efflux rate constant only in SHR, and concomitantly affected the action of cromakalim in SHR. The results suggest that (1) cromakalim caused arterial relaxation via the opening of KATP channels in both SHR and WKY, (2) although the relaxant effects of cromakalim tended to be greater in SHR than in WKY, the differences were rather small, depended on the precontraction tone and varied with the concentration of the vasoconstrictors, and (3) there was an increased basal Ca2+ influx and a high activation of KCa channels in the resting state of SHR arteries, and these changes might influence the effects of cromakalim.

Animals↗

Detection of late potentials on the averaged QRS signal recorded at rest and during a standardized stress test after acute myocardial infarction.

The high-amplification signal-averaged ECG (SAECG) allows the detection and analysis of late potentials (LP), which are related to a higher risk of severe ventricular arrhythmias in patients with myocardial disease and coronary artery disease. Because of excessive noise, this technique is usually performed at rest and occasionally immediately after interruption of exercise. Until now, however, it has not been used during exercise. The authors relate in this paper the method and results of the SAECG recorded at rest and during a standard stress test on 30 patients with a recent first myocardial infarction (day 10-14), in good condition, without ECG evidence of significant residual ischemia or bundle branch block. The SAECG was recorded during the steady state of a standardized stress test when a heart rate (HR) corresponding to 80% of the maximal HR was reached during a first test. Three patients had three criteria for LP, three others had two criteria, and two had only one. It has been impossible to analyze the SAECG during exercise because of excessive noise. One patient out of 30 in our study, 21 subjects had normal SAECG at rest and during exercise. None of the 6 patients with more than 1 abnormal criterion at rest became normal during the stress test despite a decrease of the duration criteria in all and an increase of the amplitude (root mean square) the terminal 40 ms (RMS40), as opposed to the 2 patients with just one positive criterion at rest (RMS 40 less than 25 muV) who became normal during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

Calcium in the in situ mitochondria of rested and stimulated myocardium.

Calcium is believed to provide feedback between myocardial energy consumption and production. Calcium content was proved to increase in mitochondria (MT) isolated from (1) stimulated hearts, and (2) hearts of increased contractility. In this work we compared Ca2+ content in the intact MT of skinned strips excised at 0 degrees C from previously stimulated or rested guinea-pig ventricles equilibrated with 45Ca and in single rested or stimulated myocytes. In both preparations Ca2+ was released from MT by means of CCCP (carbonyl cyanide m-chlorophenyl-hydrazone; 100 microM). CCCP released 1.58 +/- 0.55 nmol Ca2+/mg of MT protein from the strips of rested hearts and 3.86 +/- 1.12 nmol Ca2+/mg of MT protein from the stimulated muscles. Stimulated myocytes responded to the close micro-injection of CCCP with transient contracture which was not inhibited by caffeine (10 mM) or ryanodine (0.1 microM, 45 min), although the time-course of the contracture was changed. Contracture could not be initiated in rested cells. It is suggested that in rested myocytes MT contain much less Ca2+ than in stimulated ones.

Animals↗

Removable partial dentures without rests.

Ever since Bonwill recommended the use of rests on removable partial dentures in 1899, rests have been universally considered inviolate and have gone unchallenged and untested. The author claims that removable partial dentures without rests may not cause the adverse conditions usually predicted, such as gingival stripping, gingival inflammation, mutilated residual ridges, or extensive and rapid resorption of the alveolar ridges. In removable partial dentures made by the author for several patients, the residual ridge remained stable and in physiologic equilibrium when rests were not used. A history of the long-term effect on patients wearing partial dentures with and without rests is presented.

Adult↗

The reproducibility of resting and post exercise plasma beta-endorphins.

This investigation examined the reproducibility of resting and post exercise plasma beta-endorphin levels. Twenty subjects (10 men and 10 women) had their resting endorphin levels measured under controlled conditions on four separate occasions. Concomitantly, the endorphin response of eight trained runners completing three similar ten mile runs was also determined. For the resting data, there was no significant overall variation among trials, but the intra-subject variability was substantial; the within subject variance was 6.16, and it corresponded to an intra-class reliability coefficient of r = 0.239. No gender effect was noted for the average beta-endorphin values for the four occasions (men = 4.6 +/- 1.7; women = 4.4 +/- 2.1 pM/l); however, the males' within-subject variance of 8.548 (r = 0.080) was significantly larger than that of 3.719 (r = 0.485) for females. Of the runners, one outlier subject had a uniquely high average beta endorphin level of 85.67. Analysis including and excluding the outlier subject yielded within-subject variances of 29.61 (r = 0.960) and 34.47 (r = 0.176), respectively; variances for differences in confidence limits for random variation, they must exceed 7 pM/l at rest, 17 pM/l post exercise, and 20 pM/L difference from rest to post exercise.

Female↗

The pH of stimulated and resting saliva in different morphologic forms of the tongue surface in a young population.

Salivary condition and its correlation to tongue morphology was studied in 149 dental students. The students were divided according to the morphologic form of the tongue. The salivary pH and the buffer capacity of resting and stimulated saliva were determined. The pH values in the resting saliva of the fissured tongue group were more alkaline than those in the control group. The difference in pH values of stimulated saliva in the fissured tongue and control groups was only indicative. The stimulated saliva values of the normal tongue and the geographic tongue groups were similar. The pH valves of resting saliva in the geographic tongue group were more acidic than those in the normal tongue group. The salivary pH values of the filiform atrophy group were more acidic than those of the control group: resting salivar highly significantly and stimulated saliva significantly. The pH values of the hairy tongue group were also more acidic than those of the control group: both resting saliva and stimulated saliva highly significantly. No differences were observed in salivary buffer capacity, although buffer capacity in the hairy tongue group seemed to be lower than in the other groups.

Adult↗

DNA repair by articular chondrocytes. III. Unscheduled DNA synthesis following ultraviolet light irradiation of resting cartilage.

Unscheduled DNA synthesis (UDS) was demonstrated both in fresh slices of rabbit articular cartilage and in resting chondrocytes dissociated from it. Uptake of [3H]thymidine by chondrocytes treated with 10 mM hydroxyurea and irradiated with 254 nm ultraviolet light (20 J/m2) was measured by autoradiography. The UDS in the resting chondrocytes was minuscule compared with that of chondrocytes growing in monolayer culture. It was greater in resting cells from 3- than in 18-month old rabbits but persisted in animals up to 52 months of age. In both resting and cultured chondrocytes, UDS was greatly inhibited by aphidicolin (5 micrograms/ml). The finding of age-related decrease in UDS of resting chondrocytes, contrasted with previously demonstrated lack of it in dividing ones, raises questions about in vitro artefacts in studies of cellular senescence.

Aging↗

Characterization of adhesion of "resting" and stimulated platelets to fibrinogen and its fragments.

Adhesion of resting and stimulated platelets to immobilized fibrinogen (Fg) was characterized using various forms of Fg, receptor peptide mimics, and antibodies to glycoprotein (GP) IIb/IIIa and Fg. Resting platelets adhered to Fg, but to less than half the extent of the same platelets stimulated with epinephrine/ADP. The adhesion of resting and stimulated platelets to Fg was inhibited by a receptor peptide mimic (G13, a peptide corresponding to residues 300-312 of GPIIb), anti-GPIIb/IIIa antibodies, and a monoclonal antibody (4A5) against the carboxyl terminus of the gamma chain of Fg. The results presented here demonstrate that the alpha chain RGD platelet recognition sites are not required to mediate the adhesion of either stimulated or resting platelets to immobilized Fg. Although stimulated platelets can adhere extensively to monomeric Fg containing one functional gamma chain, resting platelets require bivalent Fg containing two functional gamma chains to mediate irreversible adhesion to Fg.

Amino Acid Sequence↗