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Biomedical subjects

D S Sheps

Publications and source records attributed to D S Sheps.

At least 19 recordsLinked to original sources
PubMed1992

Relation between systemic hypertension and pain perception.

To test the hypothesis that hypertension diminishes pain perception, a study was made that evaluated the relation between arterial blood pressure and thermal pain perception in human subjects. The average mean arterial pressure in all 20 men studied (10 hypertensive, 10 normotensive) proved to be significantly related to both thermal pain threshold (p = 0.05) and tolerance (p = 0.003). The difference between normotensive and hypertensive groups in baseline and posttest plasma levels of beta endorphin was also significant (p = 0.02) and indicated an interaction between endogenous opioids and blood pressure. Other recent studies of hypertension in relation to hypalgesia were also reviewed. An increased pain threshold was found in hypertensive versus normotensive rats. In cats, electrical stimulation of vagal afferent nerves (cardiopulmonary baroreceptors) suppresses nociceptive responses, and both pharmacologic elevation of blood pressure and vascular volume expansion produce antinociception. Together with preliminary findings in human studies, these results indicate an interaction between pain-controlling and cardiovascular regulatory functions that is probably mediated by the baroreceptor system.

Adult↗
PubMed1992

The relationship between plasma beta-endorphin, opioid receptor activity, and silent myocardial ischemia.

OBJECTIVE: To investigate the role of the opioid system in the pathophysiology of silent ischemia through opiate antagonism with naloxone, and to determine the reproducibility of resting and postexercise beta-endorphin levels in predominantly asymptomatic patients with coronary artery disease. DESIGN: Randomized, double-blind, placebo-controlled crossover trial. SETTING: A University hospital referral center. PATIENTS: Ten patients with prior evidence of silent exercise-induced ischemia were studied. INTERVENTION: An infusion of saline placebo or naloxone at two dose regimens of 0.015 mg/kg or 0.15 mg/kg before supine exercise testing during three separate occasions for each patient. OUTCOME MEASURES: Plasma beta-endorphin was measured at rest, immediately after exercise, and 5 min poststress. Timing and severity of angina and exercise hemodynamics were also determined. RESULTS: Seven of 10 patients reported no angina, whereas the other three experienced angina with placebo and after administration of naloxone at both doses. The severity and duration of angina was consistently noted to decrease in these patients after naloxone administration, especially after low-dose naloxone relative to placebo. There were no apparent correlations between beta-endorphin levels and the characteristics of angina in these three patients, nor between beta-endorphin and hemodynamic responses in all patients in the study. CONCLUSIONS: (a) naloxone failed to precipitate angina in this population of patients with silent ischemia; (b) naloxone appears to exert an analgesic effect at low doses; and (c) a variability of 5 pM at rest and 13 pM after exercise might be expected in predominantly asymptomatic patients due to random variation, which is comparable with results found in normal subjects.

Aged↗
PubMed1992

Interrelationships between left ventricular volume and output during exercise in healthy subjects.

To better characterize the relationship between left ventricular volume response and improved ventricular ejection and output during supine exercise in normal subjects, 36 healthy asymptomatic volunteers (age 39 +/- 17 yr) were studied with radionuclide ventriculography during recumbent bicycle ergometry. Relative changes in left ventricular end-diastolic and end-systolic volume were measured at rest and during exercise by a modification of the radionuclide counts-based method that accounted for variability in stress blood pool counts. A biphasic response was noted in left ventricular end-diastolic volume with an initial increase in early exercise (8.5 +/- 11% at 200 kpm/min and 11 +/- 12% at 300 kpm/min) followed by a progressive and significant decline at peak exercise (-3.3 +/- 18% at 547 +/- 140 kpm/min; P < 0.05). There was substantial variation in end-diastolic volume response at peak exercise in the group as a whole, which could be more closely related to changes in end-systolic volume (r = 0.84, P < 0.0001) than in heart rate (r = -0.57, P < 0.01) or age (r = 0.36, P < 0.05) of the study subjects. Despite the decline in ventricular filling, systolic function appeared to improve dramatically at peak exercise (change in left ventricular ejection fraction 15.5 +/- 6.4, P < 0.0001). Although not directly related to increasing systolic ejection, end-diastolic volume was directly related to the percent change in stroke volume at peak exercise among the study subjects (r = 0.88, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effects of 4 percent and 6 percent carboxyhemoglobin on arrhythmia production in patients with coronary artery disease.

In this study, we assessed the effects of exposure to 4 percent and 6 percent carboxyhemoglobin on ventricular arrhythmias in 41 subjects (nonsmokers) with documented coronary artery disease. We used a randomized, double-blind, crossover design. On day 1, a training session with no exposure, the baseline carboxyhemoglobin level was measured, and a supine bicycle exercise test was done. On days 2 through 4, subjects were exposed to room air, 100 parts per million (ppm)2 carbon monoxide (target, 4 percent blood carboxyhemoglobin), or 200 ppm carbon monoxide (target, 6 percent blood carboxyhemoglobin), and they then did a supine bicycle exercise test. Radionuclide ventriculography was performed at rest and during exercise. Ambulatory electrocardiogram recordings were made during the four consecutive days to determine the frequency of premature ventricular contractions at various intervals. The frequency of single premature ventricular contractions per hour during exercise was significantly greater on the 6 percent carboxyhemoglobin day than on the room air day (167.72 +/- 37.99 for 6 percent carboxyhemoglobin compared with 127.32 +/- 28.22 for room air, p = 0.03). The frequency of multiple premature ventricular contractions per hour was also significantly greater during exercise on the 6 percent carboxyhemoglobin day compared with the room air day (9.59 +/- 3.70 for the 6 percent carboxyhemoglobin day compared with 3.18 +/- 1.67 for the room air day, p = 0.02). Patients who developed increased arrhythmias during exercise on the 6 percent carboxyhemoglobin day were significantly older than those who had no increased arrhythmia, and, in addition, exercised longer and had a higher peak workload during exercise. No effect of carbon monoxide exposure was seen on the 4 percent carboxyhemoglobin day.

Aged↗
PubMed1990

Production of arrhythmias by elevated carboxyhemoglobin in patients with coronary artery disease.

OBJECTIVE: To assess the effects of exposure to 4% and 6% carboxyhemoglobin on ventricular arrhythmias in patients with coronary artery disease. DESIGN: Randomized, double-blind, crossover design. SETTING: Exercise laboratory with an environmentally controlled exposure. PATIENTS: Forty-one nonsmokers with documented coronary artery disease. INTERVENTION: On day 1, a training session with no exposure, the baseline carboxyhemoglobin level was measured, and a supine bicycle exercise test was done. On days 2 to 4, patients were exposed to room air, 100 ppm carbon monoxide (target, 4% carboxyhemoglobin) or 200 ppm carbon monoxide (target, 6% carboxyhemoglobin), and they then did supine bicycle exercise with radionuclide ventriculography. Ambulatory electrocardiogram recordings were made during the 4 consecutive days to determine the frequency of ventricular premature depolarization (VPD) at various intervals. MEASUREMENTS AND MAIN RESULTS: The frequency of single VPD/h was significantly greater on the 6% carboxyhemoglobin day than on the room air day during the exercise period (167.72 +/- 37.99 for 6% carboxyhemoglobin compared with 127.32 +/- 28.22 for room air, P = 0.03). During exercise, the frequency of multiple VPD/h was greater on the 6% carboxyhemoglobin day compared with room air (9.59 +/- 3.70 on the 6% carboxyhemoglobin compared with 3.18 +/- 1.67 on room air, P = 0.02). Patients who developed increased single VPD during exercise on the 6% carboxyhemoglobin day were significantly older than those who had no increased arrhythmia, whereas patients who developed complex arrhythmias were also older and, in addition, exercised longer and had a higher peak workload during exercise. CONCLUSION: The number and complexity of ventricular arrhythmias increases significantly during exercise after carbon monoxide exposure producing 6% carboxyhemoglobin compared with room air but not after exposure producing 4% carboxyhemoglobin.

Age Factors↗
PubMed1990

Aging and pain perception in ischemic heart disease.

Age is a recognized risk factor for coronary artery disease, but the relationship between age and silent ischemia is not well understood. We analyzed the data from 35 rest/stress radionuclide ventriculography examinations in patients with documented ischemic coronary artery disease who had experienced 1 mm ST segment depression accompanied by angina during exercise testing. An index of ischemic cardiac pain perception (PPI) was calculated by subtracting the time of onset of 1 mm ST segment depression from the time of onset of angina. The mean value of PPI was -97 +/- 311 seconds. PPI was significantly correlated with age (r = 0.37, p = 0.03). This suggests that as age increases, perception of pain during myocardial ischemic episodes becomes muted. This relationship remained significant when we controlled for the presence of medication and severity of disease (change in ejection fraction from rest to peak exercise). These findings suggest that age is an independent risk factor for a decreased perception of ischemic cardiac pain, and thus for silent myocardial ischemia.

Adult↗
PubMed1989

Prevalence of silent myocardial ischemia in survivors of cardiac arrest.

The prevalence and type of ischemia (silent vs painful) in survivors of cardiac arrest not associated with acute myocardial infarction were studied to test the hypothesis that survivors may have an increased prevalence of silent ischemia. Of 48 survivors of cardiac arrest over a 4-year period who had undergone exercise testing, 24 met inclusion criteria. These 24 subjects had documented ventricular fibrillation and coronary artery disease proven by cardiac catheterization or a previous electrocardiographic pattern of myocardial infarction. Thirteen of 24 (54%) had a positive treadmill stress test (greater than or equal to 1.0 mm flat or downsloping ST depression). The mean resting left ventricular ejection fraction was 43%. Nine of 11 patients (82%) who had exercise radionuclide studies performed had ischemic abnormalities (less than 5% increase in left ventricular ejection fraction with new or worsened wall motion abnormalities). Thus, 16 of 24 (67%) had a positive treadmill stress test or radionuclide ventriculogram. Only 1 of 16 (6%) had painful ischemia (p less than 0.001 relative to an even distribution of painful vs painless ischemia). Thus, survivors of cardiac arrest have a high prevalence of exercise-induced ischemia, and in most the ischemia is silent.

Coronary Disease↗
PubMed1989

A comparison of amplitude-modulated and frequency-modulated ambulatory monitoring systems.

To compare the results of monitoring for ischemia with amplitude-modulated (AM) and frequency-modulated (FM) ambulatory recorders, 22 patients with coronary artery disease were monitored during exercise and during 24 to 48 hours of daily activities. Simultaneous recordings were obtained with Oxford Medilog 4000-II and Medilog MR-35 systems from the same 2 bipolar leads. Each potential ischemic episode was interpreted blindly by 2 investigators. Significant ST depression was strictly defined as greater than or equal to 1 mm of horizontal or down-sloping ST depression persisting for 0.06 second beyond the J point and lasting greater than or equal to 1 minute. Of 82 episodes reviewed, 63 (77%) were either positive (37) or negative (26) for ischemia by both systems. However, 17 episodes were interpreted as positive on AM tracings but negative on FM tracings; the converse was true for only 2 episodes (p less than 0.01). For episodes read as positive with both systems, there were close correlations between recorders for duration (r = 0.80) and magnitude (r = 0.90) of ST depression. Because of the greater number of positive AM events, however, the mean total duration of ST depression for patients with ischemia during daily activities was greater on AM than on FM recordings (74 +/- 77 vs 39 +/- 42 minutes, p less than 0.10). Discrepancies between AM and FM tracings were invariably due to small differences in ST-segment morphology or in the magnitude of ST-segment depression. In summary, AM monitors generate complexes similar in appearance to those produced by FM devices in most instances.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1989

Sudden death and silent myocardial ischemia.

Recent research indicates that silent myocardial ischemia may play a role in sudden cardiac death. To what extent treatment can reduce occurrence of silent ischemia remains to be assessed. Three classes of silent ischemia patients are identified: type 1--totally asymptomatic; type 2--post myocardial infarction; and type 3--noninfarcted with both silent ischemia and angina. An index of prognostic risk (PR), showing the percent of adverse events attributable to silent ischemia, is calculated to measure the potential impact of successful treatment of silent ischemia on population mortality. Type 1 individuals' PR is estimated at a low 3.8%, suggesting that screening the general asymptomatic population would be unproductive. Type 2 patients exhibit an 80% PR. We lack the empirical information to estimate type 3 patients' PR, but silent ischemia is a recognized adverse prognostic factor in the subgroup exhibiting unstable angina. These results suggest that successful treatment of silent ischemia might favorably influence coronary artery disease patient outcomes.

Coronary Disease↗
PubMed1988

Physical fitness as a predictor of cardiovascular mortality in asymptomatic North American men. The Lipid Research Clinics Mortality Follow-up Study.

Limited data are available on the relation between physical fitness and mortality from cardiovascular disease. We examined this question in a study of 4276 men, 30 to 69 years of age, whom we followed for an average of 8.5 years. Examinations at base line included assessment of conventional coronary risk factors and treadmill exercise testing. The heart rate during submaximal exercise (stage 2 of the exercise test) and the duration of exercise were used as measures of physical fitness. Men with incomplete data (n = 308) or who were using cardiovascular drugs (n = 213) were excluded from the analysis. Men who had clinical evidence of cardiovascular disease at base line (n = 649) were analyzed separately. Forty-five deaths from cardiovascular causes occurred among the remaining 3106 men. A lower level of physical fitness was associated with a higher risk of death from cardiovascular and coronary heart disease, after adjustment for age and cardiovascular risk factors. The relative risk of death from cardiovascular causes was 2.7 (95 percent confidence interval, 1.4 to 5.1; P = 0.003) for healthy men with an increment of 35 beats per minute in the heart rate during stage 2, and 3.0 (95 percent confidence interval, 1.6 to 5.5; P = 0.0004) for those with a decrement of 4.4 minutes in the exercise time spent on the treadmill. The corresponding values for death from coronary heart disease were 3.2 (95 percent confidence interval, 1.5 to 6.7; P = 0.003) and 2.8 (95 percent confidence interval, 1.3 to 6.1; P = 0.007), respectively. We conclude that a lower level of physical fitness is associated with a higher risk of death from coronary heart disease and cardiovascular disease in clinically healthy men, independent of conventional coronary risk factors.

Adult↗
PubMed1988

Endorphins and pain perception in silent myocardial ischemia.

Evidence suggests that endogenous opioids, particularly the beta-endorphins and met-enkephalins, are closely involved in stress-induced analgesia and nociceptive pain control. Numerous investigations have been conducted to evaluate the role of opioids in silent vs symptomatic myocardial disease. There is good evidence to suggest that patients with asymptomatic ischemia have defective pain perception compared with those with angina; however, the precise role of the endorphin and enkephalin systems in this phenomenon remains to be elucidated. Possible sources for disparate study results include variation in patient populations, insensitive or improperly timed assay techniques, and differences in amount of ischemia.

Angina Pectoris↗
PubMed1988

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↗
PubMed1988

Acute elevation of blood carboxyhemoglobin to 6% impairs exercise performance and aggravates symptoms in patients with ischemic heart disease.

Acute exposure to carbon monoxide has the potential to impair exercise capacity in patients with ischemic heart disease. The effect of sufficient inhalation of this compound to gradually produce a level of 6% carboxyhemoglobin was studied in 30 nonsmoking patients with obstructive coronary artery disease and evidence of exercise-induced ischemia. After an initial training session, subjects were exposed to air or carbon monoxide on successive days in a randomized double-blind crossover fashion. Cardiac function and exercise capacity were assessed during symptom-limited supine radionuclide ventriculography. On the carbon monoxide day, mean postexposure carboxyhemoglobin was 5.9 +/- 0.1% compared with 1.6 +/- 0.1% (p less than 0.01) after air exposure. The mean duration of exercise was significantly longer after air compared with carbon monoxide exposure (626 +/- 50 s for air versus 585 +/- 49 s for carbon monoxide, p less than 0.05). Actuarial methods suggested that subjects were likely to experience angina earlier during exercise on the day of carbon monoxide exposure (p less than 0.05). Both the level (62 +/- 2.4 versus 60 +/- 2.4%, p = 0.05) and change in left ventricular ejection fraction at submaximal exercise (1.6 +/- 1.6 versus -1.2 +/- 1.6%, p = 0.05) were greater on the air exposure day compared with the carbon monoxide day. The peak exercise left ventricular ejection fraction was not different for the two exposures (57 +/- 2.5% for both). These results demonstrate earlier onset of ventricular dysfunction, angina and poorer exercise performance in patients with ischemic heart disease after acute carbon monoxide exposure sufficient to increase blood carboxyhemoglobin to 6%.

Aged↗
PubMed1987

Endorphins are related to pain perception in coronary artery disease.

Plasma beta-endorphin levels were measured by radioimmunoassay before and after exercise in 25 patients with coronary artery disease. Eighteen patients were men and 7 were women; age range was 36 to 75 years (mean 60). All patients had angina pectoris, a positive treadmill test response or positive exercise radionuclide findings. The mean preexercise plasma endorphin level was 4.9 +/- 3.0 pmol/liter (range 0.7 to 13.5). The mean postexercise plasma endorphin level of 6.6 +/- 4.6 mol/liter (range 0 to 19.5) was significantly higher (p less than 0.05). A significant positive correlation was seen between postexercise endorphin levels and time to onset of angina (r = 0.4, p = 0.03). There were negative correlations between postexercise endorphin levels and occurrence (r = -0.4, p = 0.04) and duration of angina (r = -0.4, p = 0.05). No association was found for maximal heart rate-blood pressure product, workload, time to ST-segment depression or stress ejection fraction. A positive correlation was found between rest left ventricular ejection fraction and postexercise endorphin levels (r = 0.5, p = 0.02). In conclusion, in patients with exercise-induced myocardial ischemia, plasma beta-endorphin levels are increased after exercise; postexercise endorphin levels are related to timing and occurrence (presence or absence) of angina; and endorphins may alter the perception of pain caused by myocardial ischemia.

Adult↗
PubMed1987

The influence of age and gender on left ventricular response to supine exercise in asymptomatic normal subjects.

The performance of normal subjects during radionuclide ventriculography has been related to age, but the combined effects of age and sex on exercise ventricular function are not well described. We studied 55 normal volunteers, 27 men (age = 30 +/- 10 years) and 28 women (age = 33 +/- 14 years), free of chest pain syndromes, during supine rest/exercise radionuclide ventriculography performed to fatigue. Resting left ventricular ejection fraction did not differ between male and female subjects (64 +/- 5.4 vs 64 +/- 6.1; p = NS). Both the peak left ventricular ejection fraction (78 +/- 4.4 vs 72 +/- 9.2; p less than 0.001) and the change in ejection fraction with exercise (14 +/- 4.0 vs 7.9 +/- 7.0; p less than 0.001) were significantly greater in men compared to respective values in women. Regression analysis showed that sex (r = 0.51; p less than 0.001) but not age (r = -0.18; p = 0.19) was a significant predictor of change in ejection fraction with exercise. Data on left ventricular volume response to exercise, available in 43 subjects, revealed that men had a greater percentage of decline in end-systolic volume with exercise than women (-47 +/- 15 vs -24 +/- 26; p less than 0.001). It is concluded that sex exerts a significant influence on normal left ventricular response to fatigue-limited supine exercise and that the gender difference is mediated, in part, by left ventricular end-systolic volume response to exercise.

Adolescent↗