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At least 415 records · Page 23Linked to original sources
PubMed1999

Gated Tc-99m sestamibi SPECT versus stress-rest SPECT in detecting coronary artery disease: correlation with coronary angiography in patients without myocardial infarction.

PURPOSE: It is possible to simultaneously evaluate wall thickening and perfusion abnormalities with radionuclide techniques that use tracers such as Tc-99m MIBI. We presumed that detection of wall thickening by gated MIBI SPECT imaging in the presence of a stress-induced perfusion defect correlates with reversibility of that defect on resting images. Therefore, the aim of our study was to analyze, in patients without myocardial infarction, resting wall thickening and stress perfusion imaging as an alternative to conventional stress-rest imaging. METHODS AND RESULTS: The patients (n = 44) underwent an exercise (n = 37) or pharmacologic (n = 7) stress protocol. All patients had previous coronary angiography within 3 months. Stress-rest MIBI SPECT and gated MIBI SPECT studies were analyzed by visual scoring. The sensitivity and specificity of segmental analysis of both stress-rest MIBI SPECT perfusion and gated MIBI SPECT studies for the overall detection of coronary artery disease were, respectively, 71% and 96%. For patient evaluation for detection of coronary artery disease, stress-rest MIBI SPECT perfusion and gated MIBI SPECT studies showed a sensitivity rate of 96% for both and specificity rates of 84% and 79%, respectively. CONCLUSIONS: Our data revealed close agreement between reversible perfusion defects on stress-rest MIBI SPECT scans and significant wall thickening on gated MIBI SPECT stress images in patients without previous myocardial infarction (95%). Gated MIBI SPECT stress, without resting studies, which provide an assessment of wall motion and wall thickening, potentially allows stress defect reversibility to be evaluated in patients without previous myocardial infarction.

Adult↗
PubMed1997

Relationship between ambulatory and resting blood pressure responses to dietary salt restriction in normotensive men.

OBJECTIVE: To examine the relationship between changes in resting and ambulatory blood pressures induced by dietary salt restriction in 90 young normotensive men. METHODS: Subjects were given a standardized low-salt diet containing 20 mmol sodium chloride per day for 14 days. To this diet, a daily supplement of 20 tablets of slow sodium (10 mmol NaCl per tablet) or placebo was added in a randomized single-blind cross-over fashion for 7 days. The ambulatory blood pressure was measured on the sixth day and the resting blood pressure was measured on the seventh day of each dietary period. RESULTS: Although salt intake did not affect blood pressure levels in the whole group, the response of the blood pressure was quite variable among individual subjects. Salt-induced changes in resting systolic (r = 0.30, P = 0.006) and mean (r = 0.27, P = 0.014) blood pressures, but not diastolic blood pressure, were correlated positively to changes in daytime ambulatory blood pressure. The changes in resting systolic and mean blood pressures were also correlated significantly to the nocturnal falls in systolic (r = 0.26, P = 0.015) and mean (r = 0.27, P = 0.012) blood pressure levels and heart rate (r = 0.26, P= 0.015) under the high-salt diet. Diet-induced changes in resting mean blood pressure were correlated significantly to the daytime ambulatory blood pressure (r = 0.30, P < 0.005) and the resting heart rate (r = 0.24, P < 0.02) under the high-salt diet. CONCLUSION: Salt-induced changes in resting blood pressure in young normotensive men are correlated positively to changes in ambulatory daytime blood pressure levels as well as to the daytime ambulatory blood pressure and the nocturnal fall in blood pressure under a high-salt diet. These findings suggest that dietary salt-intake restriction can lower both resting and daytime ambulatory blood pressure levels in some normotensive individuals who may be predisposed to the development of hypertension.

Adult↗
PubMedDate not supplied

Relationship between pain sensitivity and resting arterial blood pressure in patients with painful temporomandibular disorders.

OBJECTIVE: Patients experiencing temporomandibular disorders (TMD) show greater sensitivity to painful stimuli than age- and gender-matched control subjects. This enhanced pain sensitivity may result, at least in part, from an alteration in pain regulatory systems that are influenced by resting arterial blood pressure. In this study, we examined the relationship between resting systolic blood pressure and pain perception in 64 female TMD and 23 age-matched pain-free female subjects. METHOD: Resting arterial blood pressure and measures of thermal and ischemic pain threshold and tolerance were determined for each participant. Subjective ratings of thermal pain evoked by suprathreshold noxious thermal stimuli (45-49 degrees C) using a magnitude matching procedure were also obtained for both groups. RESULTS: TMD patients had lower thermal and ischemic pain thresholds and tolerances than pain-free subjects (ps < .05). Both groups provided equivalent intensity ratings to suprathreshold noxious thermal stimuli. A median split of each group based on resting systolic blood pressure revealed an influence of blood pressure on both thermal and ischemic pain perception for the Pain-Free group. The Pain-Free high resting blood pressure subgroup had higher thermal pain tolerances, higher ischemic pain thresholds, and provided lower magnitude estimates of the intensity of graded heat pulses compared with the Pain-Free low blood pressure subgroup. A trend toward a significant effect of blood pressure level on ischemic pain tolerance was also observed for the Pain-Free group. In contrast to the Pain-Free group, blood pressure level did not influence ischemic or thermal pain perception for TMD patients. Similar to the lack of effect of resting blood pressure on experimental pain perception in TMD patients, resting blood pressure was not related to measures of clinical orofacial pain in TMD patients. CONCLUSIONS: These findings confirm our previous findings that TMD patients are more sensitive to noxious stimuli and suggest that painful TMD may result, at least in part, from an impairment in central pain regulatory systems that are influenced by resting arterial blood pressure.

Adult↗
PubMed2006

The role of stress hormones in the relationship between resting blood pressure and coagulation activity.

BACKGROUND: Systemic hypertension confers a hypercoagulable state. We hypothesized that resting mean blood pressure (MBP) interacts with stress hormones in predicting coagulation activity at rest and with acute mental stress. METHODS: We measured plasma clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, epinephrine and norepinephrine, and saliva cortisol in 42 otherwise healthy normotensive and hypertensive medication-free men (mean age 43 +/- 14 years) at rest, immediately after stress, and twice during 60 min of recovery from stress. RESULTS: At rest, the MBP-by-epinephrine interaction predicted FVII:C (beta = -0.33, P < 0.04) and D-dimer (beta = 0.26, P < 0.05), and the MBP-by-cortisol interaction predicted D-dimer (beta = 0.43, P = 0.001), all independent of age and body mass index (BMI). Resting norepinephrine predicted fibrinogen (beta = 0.42, P < 0.01) and D-dimer (beta = 0.37, P < 0.03), both independent of MBP. MBP predicted FVIII:C change from rest to immediately post-stress independent of epinephrine (beta = -0.37, P < 0.03) and norepinephrine (beta = -0.38, P < 0.02). Cortisol change predicted FVIII:C change (beta = -0.30, P < 0.05) independent of age, BMI and MBP. Integrated norepinephrine change from rest to recovery (area under the curve, AUC) predicted D-dimer AUC (beta = 0.34, P = 0.04) independent of MBP. The MBP-by-epinephrine AUC interaction predicted FVII:C AUC (beta = 0.28) and fibrinogen AUC (beta = -0.30), and the MBP-by-norepinephrine AUC interaction predicted FVIII:C AUC (beta = -0.28), all with borderline significance (Ps < 0.09) and independent of age and BMI. CONCLUSIONS: MBP significantly altered the association between stress hormones and coagulation activity at rest and, with borderline significance, across the entire stress and recovery interval. Independent of MBP, catecholamines were associated with procoagulant effects and cortisol reactivity dampened the acute procoagulant stress response.

Adult↗
PubMed2007

Determination of simian immunodeficiency virus production by infected activated and resting cells.

OBJECTIVE: To determine the relative amount of virus produced by activated and resting CD4+ T cells. DESIGN: The total quantity of virus produced by an activated cell relative to a resting cell in vivo was estimated from 'snap-shots' of virus production by infected cells at one time point. METHODS: Bayesian statistical methods were used to determine a credible interval for the desired ratio. RESULTS: The posterior mean of the ratio of virus produced by a typical activated cell to a typical resting cell is 0.82 to 4.28, depending on the half-lives of the resting infected cells. Simian immunodeficiency virus-infected resting cells could accordingly be responsible for 70 to 93% of peak virus production in the acute stage of infection. CONCLUSIONS: Whereas in 'snap-shots' the infected resting cells apparently produce much less virus than infected activated CD4+ T cells, the coincidence of peak SIV production with predominant infection of resting cells along with longer half-lives for productively infected resting cells point to a major contribution to virus production in early infection.

Animals↗
PubMed1995

Transient inhibition of protein synthesis induces expression of proto-oncogenes and stimulates resting cells to enter the cell cycle.

There is evidence that resting cells are able to produce molecules with antiproliferative activity, some of which behave as short-lived repressor proteins. We suggest that transient inhibition of protein synthesis in resting cells would lead to a decrease in the levels of these negative growth regulators and might, therefore, promote mitogenic responses. We report that treatment of resting (serum-deprived) NIH 3T3 cells with cyclocheximide (CH) or puromycin induces expression of c-fos, c-jun and c-myc proto-oncogenes in a manner similar to that of platelet-derived growth factor (PDGF). Actinomycin D (Act D) abrogates the induction of proto-oncogene expression. Transient inhibition of protein synthesis by CH or puromycin also induces the resting NIH 3T3 and C3H 1OT1/2 cells to enter the cell cycle. Inhibition of new RNA or protein synthesis abolishes the proliferative response. These findings show that control mechanisms at both transcriptional and translational levels are operative in the resting cells treated with protein synthesis inhibitors. Cell fusion experiments with resting and serum-stimulated NIH 3T3 cells revealed that brief pre-incubation of resting cells with either PDGF, CH or puromycin abrogates their ability to suppress the onset of DNA synthesis in the nuclei of stimulated cells in heterodikaryons. However, the abrogative effect of PDGF disappeared in the presence of Act D, whereas the effects of protein synthesis inhibitors did not, indicating their independence of the induction of transcription. The data suggest that the observed effects of protein synthesis inhibitors are connected with elimination of some short-lived negative growth regulators, since a brief translational arrest is sufficient for the resumption of DNA synthesis in the nuclei of stimulated cells blocked by resting cells in heterodikaryons.

3T3 Cells↗
PubMedDate not supplied

Arytenoid cartilage movement in resting and exercising horses.

Endoscopic examinations of the larynx were recorded on 49 horses at rest and while exercising on a 5% inclined high-speed treadmill for 8 minutes at a maximum speed of 8.5 m/sec. Subjective laryngeal function scores at rest and while exercising were based on the degree and synchrony of arytenoid abduction. Arytenoid abduction was expressed as a left:right ratio of rima glottidis measurements. Horses with arytenoid cartilage asynchrony at rest (grade 2) could not be distinguished from normal horses (grade 1) when exercising because full abduction was maintained throughout the exercise period. Five horses with incomplete left arytenoid abduction at rest (grade 3) maintained full abduction during exercise; one grade 3 horse had dynamic collapse of the left side of the larynx. All horses with laryngeal hemiplegia at rest (grade 4) had dynamic collapse of the left side of the larynx during exercise. Forty-two horses with a resting left:right arytenoid abduction ratio greater than or equal to .71 consistently had complete arytenoid abduction at exercise. Seven horses with a left:right ratio less than .71 consistently showed dynamic collapse at exercise. There was no significant difference in the exercising left:right ratio between normal horses (grade 1) and grade 2 or grade 3 horses. These results suggest that horses with arytenoid asynchrony at rest do not suffer progressive collapse of the rima glottidis during exercise, and that incomplete arytenoid abduction at rest is an unreliable predictor of such collapse. Surgical treatment of all grade 2 horses and some grade 3 horses may be inappropriate.

Animals↗
PubMed2001

The transcriptional repressor REST determines the cell-specific expression of the human MAPK8IP1 gene encoding IB1 (JIP-1).

Islet-brain 1 (IB1) is the human and rat homologue of JIP-1, a scaffold protein interacting with the c-Jun amino-terminal kinase (JNK). IB1 expression is mostly restricted to the endocrine pancreas and to the central nervous system. Herein, we explored the transcriptional mechanism responsible for this preferential islet and neuronal expression of IB1. A 731-bp fragment of the 5' regulatory region of the human MAPK8IP1 gene was isolated from a human BAC library and cloned upstream of a luciferase reporter gene. This construct drove high transcriptional activity in both insulin-secreting and neuron-like cells but not in unrelated cell lines. Sequence analysis of this promoter region revealed the presence of a neuron-restrictive silencer element (NRSE) known to bind repressor zinc finger protein REST. This factor is not expressed in insulin-secreting and neuron-like cells. By mobility shift assay, we confirmed that REST binds to the NRSE present in the IB1 promoter. Once transiently transfected in beta-cell lines, the expression vector encoding REST repressed IB1 transcriptional activity. The introduction of a mutated NRSE in the 5' regulating region of the IB1 gene abolished the repression activity driven by REST in insulin-secreting beta cells and relieved the low transcriptional activity of IB1 observed in unrelated cells. Moreover, transfection in non-beta and nonneuronal cell lines of an expression vector encoding REST lacking its transcriptional repression domain relieved IB1 promoter activity. Last, the REST-mediated repression of IB1 could be abolished by trichostatin A, indicating that deacetylase activity is required to allow REST repression. Taken together, these data establish a critical role for REST in the control of the tissue-specific expression of the human IB1 gene.

3T3 Cells↗
PubMed1992

Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations.

BACKGROUND: Current treatment of patients with pulmonary arteriovenous malformations requires serial embolisations by means of steel coils or balloons. Measurement of right to left shunt is the most specific index of response to treatment. A new method of measuring shunt has been developed that is less invasive than traditional methods. METHODS: Right to left pulmonary shunt (expressed as percentage of cardiac output) was measured at rest in 19 patients with pulmonary arteriovenous malformations and six normal subjects by using intravenously injected albumin microspheres labelled with technetium-99m. The technique was compared with a simultaneous shunt measurement in subjects breathing 100% oxygen while they rested. The microsphere technique was adapted to measure the right to left shunt during exercise in 12 patients and five normal subjects with a new method of quantification. RESULTS: The mean (SD) shunt at rest as measured by the microsphere method was 23.2% (15.6%) in the patients and 2.7% (1.2%) in the normal subjects. When these values were compared with those of the 100% oxygen method the difference in mean values was 1% and the limits of agreement between the two methods -32% to +45%. The microsphere method is less invasive (arterial blood gas sampling is not required), quicker, and more comfortable for patients than the 100% oxygen method. In five of the normal subjects the mean (SD) 99mTc microsphere shunt increased from 2.9% (1.3%) at rest to 5.1% (2.9%) during exercise. In the 12 patients studied during exercise the shunt increased from 33.7% (12.7%) at rest to 41.7% (13.3%) during exercise in eight but decreased from 22.6% (2.4%) at rest to 17.6% (2.2%) during exercise in four. Arterial desaturation during exercise correlated with change in the size of the right to left shunt during exercise (r = +0.80). CONCLUSIONS: The microsphere method allows measurement of right to left shunt at rest and during exercise. Serial measurements at rest provide a simple, safe assessment of the physiological response to embolisation in patients with pulmonary arteriovenous malformations.

Adolescent↗
PubMed1989

Inhibition of rest potentiation in canine ventricular muscle by BAY K 8644: comparison with caffeine.

Rest potentiation, believed to be due to increased utilization of sarcoplasmic reticular calcium, was converted to rest depression by BAY K 8644 (1 microM). Plateau height and duration of the postrest beat were enhanced by BAY K 8644, suggesting an enhancement of extracellular calcium entry. Caffeine (3 mM) also produced depression at all rest intervals, although to a lesser extent than BAY K 8644. Compared with BAY K 8644, treatment with caffeine resulted in an elevation of plateau amplitude and a shortening of action potential duration. Action potential configuration changes induced by rest were unaltered by caffeine despite reduction in rest potentiation. Caffeine-induced rest depression was associated with an increase in the time to peak tension. This was not observed with BAY K 8644. Treatment with both caffeine (3 mM) and BAY K 8644 (1 microM) greatly prolonged time to peak tension. Action potential duration and plateau height were either maintained or increased. Less rest depression was observed with the combination than with either agent alone. These results suggest that 1) BAY K 8644 and caffeine inhibit rest potentiation by different mechanisms, and 2) caffeine-induced inhibition of calcium uptake by the sarcoplasmic reticulum may enhance the effect of BAY K 8644-induced increase in calcium influx on the contractile apparatus.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress.

Our aim was to determine whether the adaptation to simulated microgravity (microG) impairs regulation of cerebral blood flow (CBF) during orthostatic stress and contributes to orthostatic intolerance. Twelve healthy subjects (aged 24 +/- 5 yr) underwent 2 wk of -6 degrees head-down-tilt (HDT) bed rest to simulate hemodynamic changes that occur when humans are exposed to microG. CBF velocity in the middle cerebral artery (transcranial Doppler), blood pressure, cardiac output (acetylene rebreathing), and forearm blood flow were measured at each level of a ramped protocol of lower body negative pressure (LBNP; -15, -30, and -40 mmHg x 5 min, -50 mmHg x 3 min, then -10 mmHg every 3 min to presyncope) before and after bed rest. Orthostatic tolerance was assessed by using the cumulative stress index (CSI; mmHg x minutes) for the LBNP protocol. After bed rest, each individual's orthostatic tolerance was reduced, with the group CSI decreased by 24% associated with greater decreases in cardiac output and greater increases in systemic vascular resistance at each level of LBNP. Before bed rest, mean CBF velocity decreased by 14, 10, and 45% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. After bed rest, mean velocity decreased by 16% at -30 mmHg and by 21, 35, and 39% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. Compared with pre-bed rest, post-bed-rest mean velocity was less by 11, 10, and 21% at -30, -40, and -50 mmHg, respectively. However, there was no significant difference at maximal LBNP. We conclude that cerebral autoregulation during orthostatic stress is impaired by adaptation to simulated microG as evidenced by an earlier and greater fall in CBF velocity during LBNP. We speculate that impairment of cerebral autoregulation may contribute to the reduced orthostatic tolerance after bed rest.

Adult↗
PubMed1975

Physiologic characteristics of vestibular first-order canal neurons in the cat. I. Response plane determination and resting discharge characteristics.

The response plane and resting rate characteristics of first-order, vestibular, semicircular canal neurons were studied in 67 cats under sodium pentobarbital anesthesia using single-unit recording techniques in the eighth nerve. Five hundred fifty-nine units were classified as to the canal they were associated with by employing an identification technique based on physiologic response patterns to brief, high-level (up to 250 degrees/S2) angular accelerations delivered in various head positions. All horizontal canal neurons had increased firing rates to ampullopetal and all vertical canal units to ampullofugal endolymph flow. The average observed roll and pitch null points for each canal were used to determine the average sensitivity vectors for the right horizontal, anterior, and posterior canals. These sensitivity vectors were at a variance of 4.6-10.2 degrees from those predicted by anatomical measurements (3). The mean resting discharge characteristics of 318 first-order neurons was 36.0 spikes/s (range 0.50-114 spikes/s). No significant difference was noted between horizontal and anterior canal neurons on horizontal and anterior canal neurons on the basis of resting rate. The resting rate of the posterior canal neuron population was significantly lower. The regularity of the resting discharge varied in all three canals and the average coefficient of variation was 0.238 for the population, with a range of 0.298-1.030. The population distribution of all resting-rate statistical parameters appeared to be unimodal, indicating that first-order canal neurons may not be broken into discrete populations on the basis of resting-rate characteristics. Of 47 adequately examined first-order canal neurons, 25 demonstrated a repeatable and predictable alteration in their resting discharge as their position to gravity was reoriented. This alteration was usually nonadapting and varied in magnitude according to the degree of tilt and original starting position. Of 25 canal gravity units, 4 had nearby units from the same canal which were unresponsive to gravity, suggesting the effect was due to a limited distortion of the crista or cupula rather than an overall displacement of the cupula.

Acceleration↗
PubMed1989

Patterns of resting discharge in neurons of the raccoon main cuneate nucleus.

1. The presence and pattern of resting discharge were examined in 100 single neurons of the raccoon main cuneate nucleus (MCN). Of these, 66 were activated, either antidromically or synaptically, by electrical stimulation of the contralateral thalamic ventrobasal complex (VB), and 34 were activated by stimulation of the ipsilateral cerebellum (CB). 2. Forty-one percent of VB-activated neurons displayed a resting discharge, whereas 32% of CB-activated neurons did. Most neurons activated from VB and showing a resting discharge fired in bursts of 2-5 spikes, whereas those activated from CB and showing a resting discharge generally fired as single, irregularly spaced spikes, with occasional bursts in some neurons. 3. All neurons antidromically activated from VB were histologically localized within the clusters region of the MCN, whereas those antidromically activated from CB were confined to its polymorphic region. Neurons synaptically activated from either VB or CB were located in either of these regions. 4. Differences in the proportions of neurons displaying a resting discharge did not vary significantly as a function of type of preparation: methoxyflurane anesthesia, pentobarbital sodium anesthesia, decerebrate (the latter CB-activated only). 5. Although the sample sizes were too small to demonstrate statistical significance, neurons exhibiting a resting discharge were more likely to show a bursting pattern in methoxyflurane-anesthetized preparations than were neurons in pentobarbital sodium-anesthetized preparations. 6. The probability of having no resting discharge, firing in bursts, or firing in single spikes was not related to cutaneous submodality [rapidly adapting (RA), slowly adapting (SA), Pacinian (Pc)], or to receptive field (RF) locus (glabrous versus hairy skin). 7. The overall mean rate of firing (11.8 Hz) was not significantly different for bursting versus nonbursting neurons. 8. In bursting neurons, median interspike intervals (ISIs) varied between 1.3 and 2.3 ms. Most bursting neurons also had a range of short or minimal interburst intervals (MIBIs), characteristic for each neuron, whose medians varied from neuron to neuron between 34 and 90 ms. Distributions of within-burst ISIs and MIBIs had comparable coefficients of variation, varying between 0.031 and 0.223. 9. The application of a mechanical stimulus to a neuron's peripheral RF led to a decrease in interburst intervals, accompanied, depending upon the unit, by either an increase or a decrease in the number of spikes per burst. 10. Results are discussed in terms of the functional significance of resting discharge, including bursting, and possible roles in somatosensory information

Animals↗
PubMed2000

HERG-Like potassium current regulates the resting membrane potential in glomus cells of the rabbit carotid body.

Direct evidence for a specific K(+) channel underlying the resting membrane potential in glomus cells of the carotid body has been absent. The product of the human ether-a-go-go-related gene (HERG) produces inward rectifier currents that are known to contribute to the resting membrane potential in other neuronal cells. The goal of the present study was to determine whether carotid body glomus cells express HERG-like K(+) current, and if so, to determine whether a HERG-like current regulates the resting membrane potential. Freshly dissociated rabbit glomus cells under whole cell voltage clamp exhibited slowly decaying outward currents that activated 20-30 mV positive to the resting membrane potential. Raising extracellular K(+) revealed a slowly deactivating inward tail current indicative of HERG-like K(+) current. HERG-like currents were not found in cells resembling type II cells. The HERG-like current was blocked by dofetilide (DOF) in a concentration-dependent manner (IC(50) = 13 +/- 4 nM, mean +/- SE) and high concentrations of Ba(2+) (1 and 10 mM). The biophysical and pharmacological characteristics of this inward tail current suggest that it is conducted by a HERG-like channel. The steady-state activation properties of the HERG-like current (V(h) = -44 +/- 2 mV) suggest that it is active at the resting membrane potential in glomus cells. In whole cell, current-clamped glomus cells (average resting membrane potential, - 48 +/- 4 mV), DOF, but not tetraethylammonium, caused a significant (13 mV) depolarizing shift in the resting membrane potential. Using fluorescence imaging, DOF increased [Ca(2+)](i) in isolated glomus cells. In an in-vitro carotid body preparation, DOF increased basal sensory discharge in the carotid sinus nerve in a concentration-dependent manner. These results demonstrate that glomus cells express a HERG-like current that is active at, and responsible for controlling the resting membrane potential.

Animals↗
PubMed1982

Effects of verapamil and propranolol on left ventricular systolic function and diastolic filling in patients with coronary artery disease: radionuclide angiographic studies at rest and during exercise.

To determine the effects of verapamil on left ventricular (LV) systolic function and diastolic filling in patients with coronary artery disease (CAD), we performed gated radionuclide angiography at rest and during exercise in 16 symptomatic patients before and during oral verapamil therapy (480 mg/day). Twelve patients were also studied during oral propranolol (160--320 mg/day). LV ejection fraction at rest was normal in 13 patients, but abnormal diastolic filling at rest, defined as peak filling rate (PFR) less than 2.5 end-diastolic volumes (EDV)/sec or time to PFR greater than 180 msec, was present in 15. During verapamil, resting ejection fraction decreased (control 50 +/- 10% [+/- SD), verapamil 45 +/- 12%, p less than 0.005), but resting diastolic filling improved: PFR increased (control 1.9 +/- 0.6 EDV/sec, verapamil 2.3 +/- 0.9 ECV/sec, p less than 0.005) and time to PFR decreased (control 185 +/- 38 msec, verapamil 161 +/- 27 msec, p less than 0.05). Exercise ejection fraction did not change during verapamil (control 42 +/- 13%, verapamil 43 +/- 12%, NS), but exercise PFR increased (control 3.1 +/- 0.9 EDV/sec, verapamil 3.6 +/- 1.1 EDV/sec, p less than 0.05) and exercise time to PFR decreased (control 108 +/- 30 msec, verapamil 91 +/- 17 msec, p less than 0.05). In contrast, propranolol did not alter ejection fraction, PFR, or time to PFR at rest or during exercise. Thus, LV ejection fraction is decreased by verapamil at rest but is unchanged during exercise. While LV systolic function is not improved by verapamil, LV diastolic filling is enhanced by verapamil, both at rest and during exercise. These mechanisms may account in part for the symptomatic improvement in many patients during verapamil therapy.

Adult↗
PubMed1993

Concordance and discordance between stress-redistribution-reinjection and rest-redistribution thallium imaging for assessing viable myocardium. Comparison with metabolic activity by positron emission tomography.

BACKGROUND: Stress thallium scintigraphy provides important diagnostic and prognostic information in patients with coronary artery disease by demonstrating regional myocardial ischemia. However, if the clinical question being addressed is whether a region is viable and not whether there is inducible ischemia, then it may be more reasonable to perform rest-redistribution imaging rather than stress-redistribution imaging followed by either reinjection or late redistribution. Therefore, we determined whether stress-redistribution-reinjection and rest-redistribution imaging provide the same information regarding myocardial viability. METHODS AND RESULTS: Both stress-redistribution-reinjection and rest-redistribution thallium single photon emission computed tomographic imaging was performed in 41 patients with chronic stable coronary artery disease, with quantitative analysis of regional thallium activity. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution images were completed. Of the 155 myocardial regions with perfusion defects on the stress images, 91 (59%) were irreversible on conventional 3- to 4-hour redistribution images. When the outcomes of these irreversible regions were assessed after reinjection and compared with rest-redistribution images, there was concordance of data regarding myocardial viability (normal/reversible or irreversible) in 72 of the 91 (79%) irreversible defects. Twenty of the 41 patients also underwent positron emission tomography at rest with [18F]fluorodeoxyglucose and [15O]water. In these patients, stress-redistribution-reinjection and rest-redistribution imaging provided concordant information regarding myocardial viability in 427 (72%) of 594 myocardial regions and discordance in 167 regions. However, when irreversible thallium defects were further analyzed according to the severity of the thallium defect in these discordant regions, 149 of 167 (89%) demonstrated only mild-to-moderate reduction in thallium activity (51% to 85% of normal activity), and positron emission tomography verified 98% of these regions to be metabolically active and viable. Thus, when the severity of thallium activity was considered within irreversible thallium defects, the concordance between stress-redistribution-reinjection and rest-redistribution imaging regarding myocardial viability increased to 94%. CONCLUSIONS: These data indicate that one of two imaging modalities, either stress-redistribution-reinjection or rest-redistribution imaging, may be used for identifying viable myocardium. However, if there are no contraindications to stress testing, stress-redistribution-reinjection imaging provides a more comprehensive assessment of the extent and severity of coronary artery disease by demonstrating regional myocardial ischemia without jeopardizing information on myocardial viability.

Coronary Angiography↗
PubMed1990

Profound spatial heterogeneity of coronary reserve. Discordance between patterns of resting and maximal myocardial blood flow.

We examined the ability of individual regions of the canine left ventricle to increase blood flow relative to baseline rates of perfusion. Regional coronary flow was measured by injecting radioactive microspheres over 90 seconds in seven anesthetized mongrel dogs. Preliminary experiments demonstrated a correlation between the regional distributions of blood flow during asphyxia and pharmacological vasodilatation with adenosine (mean r = 0.75; 192 regions in each of two dogs), both of which resulted in increased coronary flow. Subsequent experiments, during which coronary perfusion pressure was held constant at 80 mm Hg, examined the pattern of blood flow in 384 regions (mean weight, 106 mg) of the left ventricular free wall during resting flow and during maximal coronary flow effected by intracoronary adenosine infusion. We found that resting and maximal flow patterns were completely uncorrelated to each other in a given dog (mean r = 0.06, p = NS; n = 3 dogs). Furthermore, regional coronary reserve, defined as the ratio of maximal to resting flow, ranged from 1.75 (i.e., resting flow was 57% of maximum) to 21.9 (resting flow was 4.5% of maximum). Thus, coronary reserve is spatially heterogeneous and determined by two distinct perfusion patterns: the resting (control) pattern and the maximal perfusion pattern. Normal hearts, therefore, contain small regions that may be relatively more vulnerable to ischemia. This may explain the patchy nature of infarction with hypoxia and at reduced perfusion pressures as well as the difficulty of using global parameters to predict regional ischemia. Despite the wide dispersion of coronary reserve, we found, by autocorrelation analysis, that reserve in neighboring regions (even when separated by a distance of several tissue samples) was significantly correlated. This also applied to patterns of resting myocardial flow. Thus, both resting coronary blood flow and reserve appear to be locally continuous and may define functional zones of vascular control and vulnerability, respectively.

Adenosine↗
PubMed2002

Resting oxygen consumption and in vivo ADP are increased in myopathy due to complex I deficiency.

BACKGROUND: Patients with isolated complex I deficiency (CID) in skeletal muscle mitochondria often present with exercise intolerance as their major clinical symptom. OBJECTIVE: To study the in vivo bioenergetics in patients with complex I deficiency in skeletal muscle mitochondria. METHODS: In vivo bioenergetics were studied in three of these patients by measuring oxygen uptake at rest and during maximal exercise, together with forearm ADP concentrations ([ADP]) at rest. Whole-body oxygen consumption at rest (VO(2)) was measured with respiratory calorimetry. Maximal oxygen uptake (VO(2)max) was measured during maximal exercise on a cycle ergometer. Resting [ADP] was estimated from in vivo (31)P MRS measurements of inorganic phosphate, phosphocreatine, and ATP content of forearm muscle. RESULTS: Resting VO(2) was significantly increased in all three patients: 128 +/- 14% (SD) of values in healthy control subjects. VO(2)max in patients was on average 2.8 times their VO(2) at rest and was only 28% of VO(2)max in control subjects. Resting [ADP] in forearm muscle was significantly increased compared with healthy control subjects (patients 26 +/- 2 microM, healthy controls 9 +/- 2 microM). CONCLUSION: In patients with CID, the increased whole-body oxygen consumption rate at rest reflects increased electron transport through the respiratory chain, driven by a decreased phosphorylation potential. The increased electron transport rate may compensate for the decreased efficiency of oxidative phosphorylation (phosphorylation potential).

Adenosine Diphosphate↗