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Sleep apnea in hypoxic and normal kittens.

Frequency and characteristics of apneas were studied in 10-, 20-, and 40-day old kittens during several days of exposure to 21%, 10%, or 7% oxygen atmospheres. Ninety-seven percent of all apneas occurred during sleep or at transitions between sleep and waking states. Hypoxic kittens, compared to controls, had greatly decreased apnea frequency, but other characteristics of apneas did not differ significantly. Apneas in both control and hypoxic kittens were normal, stereotyped events and were not considered to represent pathological processes. Evaluation of events preceding apneas indicated that a majority of apneas followed augmented breaths and/or brief arousals. We suggest that apnea, heart rate changes during apnea, and frequently concurrent transitions in sleep-waking state may be causally related to these pre-apnea events. The results of this study and a parallel study of human infants suggest that below-normal apnea frequency may indicate hypoxemia and may be associated with higher risk for Sudden Infant Death Syndrome.

Age Factors↗

South Carolina's suicide mortality in the 1970s.

In an epidemiologic study of suicide mortality among South Carolina residents for the years 1970--78, death certificates for 2,763 persons were reviewed. The overall suicide rates were lower than those observed in the same period for the United States. As expected, the highest rates were among white males; females and nonwhite males had rates with intermediate values, and nonwhite females, the lowest rates. Rates for white males increased up to age 75. All other race-sex groups peaked at much younger ages. An increase in suicide rates over time appeared in those under 25 years, and a slight decline was observed in residents aged 50--74. Age-race-sex-adjusted rates proved relatively stable over the 9 years. Geographically, race-adjusted rates by county varied from calculated expected values, with some suggestion of a pattern for the counties with the highest rates. However, no urban-rural differences were seen. Examination of methods used to commit suicide reveals that firearms were the most common means in all race-sex groups, accounting for 78.7 percent of deaths. The percentage of firearm users was almost identical among white males and white females, differing markedly from the country as a whole. Females of both race groups were more likely to have used poisons than males, but the percentage of those who used poisons was much less than would be expected from national data. This study confirms previous findings of sex and race differentials, rate changes with age, increasing rates in young people, and lower overall rates in the Southeast compared with the entire country. Interpretation of race-sex specific rates, together with suicide methods, lends support to the assertion that suicide rates are independent of methods. Rate trends by age groups over time are believed to have important implications.

Adolescent↗

Electrocardiographic accompaniments of temporal lobe epileptic seizures.

74 spontaneous seizures in 26 patients with a clinical diagnosis of temporal lobe epilepsy (complex partial seizures) were recorded by simultaneous ambulatory cassette monitoring of the electrocardiogram and the electroencephalogram (EEG). In 24 patients (92%) seizures were associated with an increased heart rate. The maximum heart rates exceeded 120 beats/min in 67% of seizures, 140 beats/min in 30%, and 160 beats/min in 12%. The acceleration of heart rate was greater in patients under than in those over 25 years old (p less than 0.01) and in those not treated with than in those on anticonvulsant drugs (p less than 0.01). Ictal cardiac arrhythmias occurred in 42% of the patients and the commonest was an irregular series of abrupt rate changes which occurred towards the end of the EEG seizure discharge. Asymptomatic (clinically silent) arrhythmias occurred no more frequently in the patients than in age and sex matched healthy subjects. These secondary autonomic effects of epilepsy may lead to diagnostic errors if their cerebral origins are not suspected. They seem to be reduced in severity by anticonvulsant drugs (ACD) and they may account for sudden unexplained deaths in epileptics.

Adolescent↗

Kidney transplantation: Improvement in patient and graft survival.

Patient and graft survival were reviewed in a series of 249 kidney transplants done from 1963 to March 1973. Patient survival was calculated by the life table method for the periods 1963-1970, and 1970-1973, since in 1970 a formal Kidney Center was established and mortality rates changed. Graft survival was analyzed in terms of donor source, HL-A matching and immune responsiveness to HL-A antigens. Three-year predicted mortality for cadaver kidney recipients was 62% between 1963 and 1969 (42 patients) and 8% between 1970 anid 1973 (67 patients). Similar predicted mortality for related living donors was 30% between 1963 and 1969 (52 patients) and 14% between 1970 and 1973 (85 patients). Mortality has continued to decrease and there has been only one death in the last 87 consecutive transplants, including 57 consecutive cadaver transplants. Oneyear predicted kidney survival for the 10-year period is 44% for cadaveric, 60% for non HL-A identical related living and 90% for HL-A identical sibling donors. In the cadaver group, those sharing 2 or more HL-A antigens had the same kidney survival as the non HL-A identical related living donor grafts. Since cadaver graft recipients are on dialysis for a longer period of time, immune responsiveness can be detected by their response to blood transfusions, whereas this determination could not be made in our related living donor group. Non-responsive cadaver kidney recipients had 80% one year kidney survival. We conclude that transplant mortality can be reduced to less than 10% by the Center approach to treatment of renal disease, dialysis does not adversely affect future transplantation, and excellent (80%) kidney survival can be expected in properly selected cadaver graft recipients.

Blood Transfusion↗

Cognitive stress and cardiovascular reactivity. II. Relationship to atherosclerosis, arrhythmias, and cognitive control.

This is the second of a two-part series on the effects of cognitive stress on cardiovascular disease. This paper reviews the relationship between cognitive stress and cardiovascular reactivity as it relates to the development of atherosclerosis and arrhythmias. In addition, the moderation of cardiovascular reactivity by the opportunity to exercise control over the stressor is discussed. The findings may be summarized as follows. First, recent animal work has suggested that the magnitude of heart rate change in the presence of a conditioned aversive stimulus is positively correlated with the extent of coronary atherosclerosis under diets high and low in atherogenic potential. Second, cardiovascular reactivity in humans may be related to several factors that could have an influence on the pathogenesis of atherosclerosis. These factors include: increased beta-adrenergic driving, increased shearing force on the intimal lining of the vessels, changes in pulsatile flow and the subsequent smooth muscle reparatory process. Cognitive (psychological) stress has also been related to ST segment depression, rate-pressure product changes, and changes in cardiac contractility. Animal studies have shown that the susceptibility to ventricular fibrillation may be enhanced by the presence of a conditioned aversive stimulus and may be reduced through adaptation to the aversive environment. The balance between sympathetic and parasympathetic influences on the myocardium may also play a critical role in the susceptibility of an already diseased heart to succumb to fatal arrhythmias during a behavioral stressor. Finally, studies in which subjects may exercise some control over an aversive stimulus suggest that cardiovascular reactivity may be pronounced and sustained in situations requiring frequent adjustment to changes in the criteria for successful performance, and/or the presence of positive incentives.

Arrhythmias, Cardiac↗

Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study.

To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo-controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid-Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo.

Autonomic Nervous System Diseases↗

Maternal-fetal outcomes in prolonged pregnancy.

The intrapartum fetal heart rate changes, type of labor, mode of delivery, and neonatal outcome were evaluated in 379 consecutive continuously monitored prolonged pregnancies (greater than 42 weeks by history and early examination). These represent only a fraction of the total prolonged gestation population. There were 56% multiparous women, 33% less than 20 years of age, and 95% with cephalic presentation. Oxytocin was given to 76% (48% induced, 28% enhanced). Delivery was by cesarean section in 13% of patients (9% of induced cases), and 15% had forceps deliveries. Fetal heart rate alterations were observed in high proportion. Cesarean section for cephalopelvic disproportion was indicated in 60% of operations, and 13% of the fetuses weighed greater than 4000 gm. Depression occurred in 15% of infants at 1 minute and in 4% at 5 minutes. Prolonged hospital stay was seen in 9%, and postmaturity syndrome in 19%. There were four perinatal deaths (two corrected). Active induction does not appear to increase the cesarean section rate. The durations of predelivery observation may be longer because the cervices are frequently unripe. There is a high incidence of fetal heart rate alterations. Induction appears justified as an active intervention to prevent some sudden unexplained deaths.

Adolescent↗

The effect of intracerebroventricular D-ALA2 methionine enkephalinamide and naloxone on cardiovascular parameters in the cat.

Lathers and Schraeder (1) have shown that autonomic dysfunction is associated with epileptogenic activity induced by pentylenetetrazol while Vindrola et al (2) found increased D-ALA2 methionine-enkephalinamide (DAME) levels in the rat brain after pentylenetetrazol-induced epileptogenic activity. Thus, this study was designed to determine whether DAME could have contributed, at least in part, to the autonomic dysfunction associated with pentylenetetrazol-induced epileptogenic activity in the study of Lathers and Schraeder (1). DAME (500 micrograms/kg, icv) was given to 9 cats anesthetized with alpha chloralose. Epileptogenic activity and hypotension occurred in all cats (maximum fall ranging from 6 to 46 mmHg; duration of 6 to 35 min). In 6 cats the heart rate decreased, in 2 it increased, and in 1 it showed little or no change. The duration of heart rate changes varied from 18 to 76 min. Naloxone (100 micrograms/kg, iv) was given to 6 cats after DAME. Naloxone suppressed or abolished the epileptogenic activity in all 6 cats, reversed the DAME-induced hypotension and increased the heart rate in 3 cats, decreased it in 2, and produced no change in 1. These results indicate that DAME may produce epileptogenic activity and cardiovascular changes through an action on central opiate receptors. It is hypothesized that: 1) increased levels of DAME inhibit the release of gamma aminobutyric acid; 2) this then increases vagal bradycardia and hypotension; and 3) step 2 causes an imbalance in peripheral autonomic cardiac neural discharge which may cause arrhythmias and/or sudden unexplained death in the epileptic person.

Animals↗

Tumor sensitization and protection: influence of stromal injury on estimates of dose modification.

Tumor regrowth delay is an assay which reflects tumor cell kill but can be modified by growth rate changes resulting from damage to the stroma (tumor bed effects). If the stromal damage is modified by radiosensitizers and radioprotectors to a different degree from the tumor cells, the overall measurement of dose modifying factors may be influenced by the choice of a regrowth size for the growth delay analysis. We have studied the response of two mouse tumors; a fibrosarcoma which showed only a small TBE and a carcinoma which showed a very large TBE. Sensitizer enhancement ratios and protection factors have been obtained by assessing regrowth to a variety of endpoint sizes. The dose modifying effects on the stroma have then been determined by analyzing the regrowth rates of tumors after irradiation. The choice of endpoint size modified both the sensitizer enhancement ratio and the protection factor for both tumors. It appears that stromal damage may be the cause of the radioprotection observed in the carcinoma, whereas direct tumor cell radioprotection is indicated in the fibrosarcoma. Both direct tumor cell killing and cell death secondary to stromal damage will play an important role in determining the local control of irradiated tumors.

Amifostine↗

Cardiac asystole: a manifestation of neurally mediated hypotension-bradycardia.

It has been proposed that prolonged cardiac asystole mimicking an episode of sudden cardiac death may occur as a manifestation of neurally mediated hypotension-bradycardia syndrome. To assess this possibility, electrocardiographic and hemodynamic findings during upright tilt testing were evaluated in six survivors of suspected asystolic sudden cardiac arrest with normal conventional electrophysiologic evaluation (Group I). These observations were compared with findings in two control groups: six patients with syncope but without evident asystole and with normal conventional electrophysiologic evaluation but demonstrable neurally mediated hypotension-bradycardia (Group II), and six patients with syncope in whom conventional electrophysiologic evaluation provided a presumptive diagnosis (Group III). Patients in all three groups ranged in age from 16 to 59 years. During head-up tilt testing (either alone or with isoproterenol infusion), patients in both Groups I and II developed syncope in less than or equal to 5 min, whereas patients in Group III remained asymptomatic. Patients in Groups I and II exhibited a similar tilt-induced decrease in mean arterial pressure (-46 +/- 9 and -40 +/- 9 mm Hg, respectively, p = NS) and heart rate (-44 +/- 28 and -49 +/- 12 beats/min, respectively, p = NS). In contrast, patients in Group III manifested only a moderate decrease in mean arterial pressure (-14 +/- 5 mm Hg) and had an increase in heart rate (+14 +/- 8 beats/min). Both mean arterial pressure and heart rate changes in Group I and Group II patients differed significantly (p less than 0.001) from values in Group III patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Impaired vagal heart rate control in aortic valve stenosis.

Impaired reflex control of heart rate seems to be associated with increased risk of sudden cardiac death. To assess the effect of aortic valve stenosis on parasympathetic heart rate control we measured the heart rate responses to deep breathing and to standing up, non-invasive measures of cardiac parasympathetic activity, in 24 patients with valvular aortic stenosis and in 24 healthy asymptomatic subjects of the same age group. All but one of the patients were symptomatic and the mean aortic valve pressure gradients ranged from 32 to 114 mmHg. The heart rate response to deep breathing was significantly (P less than 0.05) lower in valve patients than in the healthy subjects. The heart rate changes evoked by standing up, however, did not differ significantly between the groups. The heart rate response to deep breathing was inversely weakly related to the left ventricular end-diastolic pressure (r = -0.41, P less than 0.05), but not significantly to the aortic valve pressure gradient, valve area, left ventricular ejection fraction or presence of coronary artery disease. Our results suggest that the impairment of reflex heart rate control is common in patients with significant aortic valve stenosis.

Adult↗

Protective action of cimetidine against ouabain-induced pressor effects, arrhythmias, and lethality in guinea pigs.

The effect of the H2-receptor antagonist cimetidine on ouabain cardiotoxicity was studied in anesthetized guinea pigs. Ouabain, infused intravenously at 3.0 micrograms X kg-1 X min-1, was lethal in a dose of 44.0 +/- 3.5 micrograms (n = 6). All control animals died in ventricular fibrillation. Cimetidine, infused concurrently at 10, 30, and 100 micrograms X kg-1 X min-1, significantly increased the lethal dose of ouabain and delayed the onset of various arrhythmias and fibrillation. Cimetidine abolished ouabain-induced pressor effects that have been reported to be neurally mediated; the course of heart-rate changes in ouabain-treated animals, however, was unaffected by cimetidine. In vitro, cimetidine had no effect on the inotropic action of ouabain at concentrations as high as 10(-4) M, whereas serum levels of cimetidine in protected animals did not exceed this concentration. When the ouabain infusion rate was reduced by 50% (to 1.5 microgram X kg-1 X min-1), the lethal dose increased to 72.7 +/- 4.7 micrograms (n = 6), the predominant mode of death changed from fibrillation to cardiac standstill, ouabain-induced pressor effects were absent, and cimetidine no longer exhibited a protective action. Taken together, these findings support the hypothesis that cimetidine acts primarily against indirect components of digitalis toxicity, and so may be potentially valuable for increasing the margin of safety of the cardiac glycosides.

Animals↗

Fetal responses to vibrotactile stimulation, a possible predictor of fetal and neonatal outcome.

This study measured the antenatal fetal heart rate changes in response to a single vibrotactile stimulus. In a group of 11 normal patients, this resulted in a significant change in the fetal heart rate (P less than 0.001). Sixty-eight high risk patients were also tested. In the group of 25 patients whose fetuses showed no response to the stimulus, there were 4 stillbirths and 4 neonatal deaths; 23 of these 25 infants were small for gestational age (SGA) compared to only 15 of the 43 that showed a response to the stimulus. Fetal habituation to a repeated vibrotactile stimulus was measured in a control group of 40 patients who had a normal antepartum and intrapartum course and delivered infants in an optimal condition. The same was done in a study group of 48 patients who delivered infants that were SGA. These infants were assessed at 1 year of age by the Griffiths Mental Developmental Scale (GMDS). Infants that were SGA did not differ significantly from the control group. However, infants who had a normal antenatal habituation pattern had a significantly better performance (P less than 0.01) compared to infants who had an abnormal antenatal habituation pattern.

Electrocardiography↗

Changes in obstetric practice in our time.

In the years since 1939 there has been a marked change in the nature and results of obstetric practice at the Royal Women's Hospital, Melbourne. The noteworthy changes have been a reduction in the number of maternal deaths (from 12.2 per 1,000 in the 1940's to 0.2 per 1,000 in the 1980's), especially those due to septic abortion, and an increase in the Caesarean section rate (from 2% to 14%). The increase in the operative delivery rate has been matched by a decrease in mortality in patients thus delivered, the maternal and perinatal mortality rates changing from 5.5 and 88.9 per 1,000 to 0 and 7.6 per 1,000 respectively in the case of forceps delivery and from 24.7 and 162.5 per 1,000 to 0.15 and 10.6 per 1,000 respectively in the case of Caesarean delivery.

Adult↗

Autonomic reflexes in preterm infants.

Some autonomic nervous reflexes often tested in adult medicine have been studied in 21 preterm infants (25-37 gestational weeks). The aim was to develop such tests for preterm infants and see if there were any differences in babies with recurrent apnea and bradycardia and babies who had been exposed to sympathicolytic drugs before birth. To test sympathetic nervous activity the peripheral vascular resistance was measured before and during 45 degrees of head-up tilting. To test parasympathetic nervous activity the degree of bradycardia was measured in response to cold face test (application of an ice-cube on the fore-head) and laryngeal stimulation with saline. Finally the heart rate changes after a sudden noise (85 dB) were studied as an indicator of both sympathetic and vagal activity. The peripheral resistance was found to be relatively low in these preterm infants, particularly in some infants tested at the postnatal age of about two months. Heart rate and mean blood pressure did not change during tilting, while the peripheral resistance increased significantly mainly due to lowered limb blood flow. The median decrease of the heart rate during the cold face test was 20.0% and during laryngeal receptor stimulation 23.7%. The sudden noise usually caused a biphasic heart rate response. An autonomic nervous reflex score was calculated and found to be negative (parasympathetic) in infants with recurrent prolonged apnea and bradycardia and positive in infants with clinical signs of increased sympathetic nervous activity.

Apnea↗

Relationship between fluorescein diacetate-stained hyphae and oxygen utilization, glucose utilization, and biomass of submerged fungal batch cultures.

The relationship between fungal activity and staining with fluorescein diacetate (FDA) was investigated by growing Penicillium citrinum and Rhizoctonia solani in submerged batch cultures at different initial glucose concentrations and aeration rates. A modified FDA staining method, similar to the Jones and Mollison technique (P. Jones and J. Mollison, J. Gen. Microbiol. 2:54-69, 1948), was developed to assess both total and FDA-stained hyphae. In previous studies, soil hyphae stained with FDA were considered viable. However, determination of a quantitative relationship between FDA staining and fungal activity is necessary before such an assumption can be made. Growth rates and the rate of change in the percentage of FDA-stained hyphae were significantly correlated. The regression equation calculated for the relationship was: growth rate (mg . ml-1 . h-1) = 0.34 + 1.1 (rate of change in the percentage of FDA-stained hyphae [. ml-1 . h-1]). Changes in activity as measured by O2 utilization, glucose utilization, and biomass correlated significantly with changes in the percentage of FDA-stained hyphae, although the relationships among these parameters were different for each fungal species. Fungal growth stage was also correlated with the percentage of FDA-stained hyphae. Staining was 10% or greater during fungal growth and less than 10% during the late growth, stationary, and death phases. Thus, the rate of change in the percentage of FDA-stained hyphae can be used to predict fungal activity rate changes for single fungal cultures and growth rates for mixed fungal cultures, and the growth stage can be assessed by the percentage of FDA-stained hyphae.

Aerobiosis↗

Dynamic analysis of cardiac R-R intervals in normal infants and in infants who subsequently succumbed to the sudden infant death syndrome.

Infants who subsequently succumb to the sudden infant death syndrome (SIDS) have higher heart rates and reduced heart rate variation compared with other infants. We examined dynamic changes in cardiac interbeat intervals to explore these differences in cardiac control. Recordings of electrocardiographic activity and respiratory movement were acquired from 13 SIDS victims before their deaths. Moment-to-moment changes in R-R intervals during quiet sleep, rapid eye movement sleep, and waking were compared with values of 13 matched control infants. For each sleep-waking state, every R-R interval was plotted against the previous interval (Poincaré plots), and each change in interbeat interval was plotted against the previous change. Dispersion of interbeat intervals at different heart rates was reduced in SIDS victims, resulting in Poincaré plots markedly different from those of controls. The dispersion, sampled at the 10th and 90th percentiles of heart rates, was reduced across all sleep-waking states in SIDS victims. At high heart rates, the difference between groups disappeared after correcting for basal rate; however, the reduced range at low heart rates was independent of basal rate. SIDS victims also showed smaller beat-to-beat changes in heart rate and fewer sustained runs of consistent heart rate changes during waking relative to controls. The differences in cardiac rate dynamics suggest altered autonomic control in infants who succumb to SIDS. We speculate that the autonomic disturbance may lead to cardiac instability or may indicate CNS alterations with the potential to affect other vital functions.

Autonomic Nervous System↗

Circadian variation of myocardial ischemia in patients with stable coronary artery disease.

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression greater than or equal to 1 mm and duration greater than or equal to 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low--28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.

Adult↗