Reproducibility and relation to mean heart rate of heart rate variability in normal subjects and in patients with congestive heart failure secondary to coronary artery disease.

Before heart rate (HR) variability can be used for predictive purposes in the clinical setting, day-to-day variation and reproducibility need to be defined as do relations to mean HR. HR variability and mean HR were therefore determined in 2 successive 24-hour ambulatory electrocardiograms obtained from 33 normal subjects (age 34 +/- 7 years, group I), and 22 patients with coronary disease and stable congestive heart failure (CHF) (age 59 +/- 7 years, group II). Three measures were used: (1) SDANN (standard deviation of all mean 5-minute normal sinus RR intervals in successive 5-minute recording periods over 24 hours); (2) SD (the mean of the standard deviation of all normal sinus RR intervals in successive 5-minute recording periods over 24 hours); and (3) CV (coefficient of variation of the SD measure), a new measure that compensates for HR effects. Group mean HR was higher and HR variability lower in group II than in group I (80 +/- 10 vs 74 +/- 9 beats/min, p less than 0.04). Mean group values for HR and HR variability showed good correlations between days 1 and 2 (mean RR, r = 0.89, 0.97; SDANN, r = 0.87, 0.87; SD, r = 0.93, 0.97; CV, r = 0.95, 0.97 in groups I and II, respectively). In contrast, considerable individual day-to-day variation occurred (group I, 0 to 46%; group II, 0 to 51%). Low HR variability values were more consistent than high values. SDANN and SD correlated moderately with HR in both groups (r = 0.50 to 0.64). The CV measure minimizes HR effects on HR variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Low heart rate variability and sudden cardiac death.

Our results indicate the following. 1. HRV is markedly depressed in inducible SCD survivors, a group at high risk of a subsequent episode of SCD. 2. Studies on patients who developed SCD during Holter monitoring indicate that HRV is depressed prior to SCD. 3. HRV is markedly depressed in inducible "asymptomatic ventricular ectopy" patients, with the degree of reduction paralleling that observed in inducible SCD survivors. In contrast, HRV of noninducible "asymptomatic ventricular ectopy" patients did not differ statistically from normal. 4. The findings provide additional evidence that cardiac parasympathetic function is depressed in patients prone to development of SCD and that altered autonomic function contributes to the development of electrical instability in such individuals. This accords with findings that such risk factors for sudden death as coronary artery disease, myocardial infarction, congestive failure, and hypertension all have been associated with reduced parasympathetic activity or attenuation of parasympathetically mediated reflexes. It is tempting to believe that diminished cardiac parasympathetic activity, perhaps by failing to counter excess sympathetic activity, contributes to SCD. 5. It may be inferred that HRV measurements have potential for serving as an independent predictor of inducibility in response to programmed ventricular stimulation and that they could represent a noninvasive screen for patients referred for evaluation of risk of SCD because of asymptomatic ventricular ectopy or other causes. In a larger sense, the data suggest that HRV measurements may provide information pertinent to the identification of individuals at increased risk of SCD that is independent of that provided by other risk factors. Given the human and economic stakes, further study is clearly warranted.

Heart rate variability and sudden death secondary to coronary artery disease during ambulatory electrocardiographic monitoring.

Data are analyzed from 5 patients who died suddenly during ambulatory electrocardiographic monitoring. Three of the patients were also assessed in terms of 2 recently developed indexes of heart rate (HR) variability. One of these, the standard deviation of RR intervals during successive 5-minute segments averaged over 24 hours, has been reported to be a putative index of vagal tone. Comparisons were made with HR variability findings in 20 normal volunteers. Sudden death was due to ventricular tachycardia degenerating into ventricular fibrillation in all cases. Both early (3 patients) and late cycle (2 patients) ventricular premature complexes initiated the terminal dysrhythmia. An increased density of ventricular ectopic activity was noted in the hour before onset of ventricular fibrillation. HR variability as measured by the standard deviation was significantly (p less than 0.01) lower in the patients who died suddenly (30 +/- 10 ms) than in the normal subjects (76 +/- 14 ms). These findings support suggestions that HR variability analysis may be useful in identifying patients at a higher risk of sudden death.

Dominant lethality in Xenopus laevis induced with triethylenemelamine (TEM).

Adult male South African clawed toads, Xenopus laevis, were injected intraperitoneally with triethylenemelamine (TEM) dissolved in water over a dose range of 13-1,300 micrograms/kg or with water (controls). Mating of the treated males with untreated females was induced seven days later by injection of human chorionic gonadotropic hormone (HCG). Accumulated lethality one week after fertilization among progeny was dose related. Morphological abnormalities among embryos that survived to hatching were similarly dose related. Because anatomically anomalous embryos may have impaired behavior, swimming capacity was tested, and anomalies in swimming behavior were also found to be dose related. Finally, short-term cell cultures were made on minced embryos to obtain chromosome spreads. Structural aberrations, rings, dicentrics, etc of somatic chromosomes were also dose related.

Reduced prevalence of the Lucké renal adenocarcinoma in populations of Rana pipiens in Minnesota.

Northern leopard frogs (Rana pipiens) afflicted with the Lucké renal adenocarcinoma virtually disappeared from Minnesota in the autumn of 1977. Frogs from four sites in Minnesota counties (Polk, Otter Tail, Kandiyohi, and Scott) with a previously high prevalence of Lucké renal tumor were studied. In the past decade, prevalence averaged 4.2% in 29 collections (total, 1,870 frogs). No tumors were detected in 685 frogs autopsied in the autumn of 1977 by the method of previous studies. Frog collections, each comprised of 20 or more individuals, were compared for the presence or absence of tumor-bearing frogs. Significantly fewer collections contained tumor-bearing frogs in the autumn of 1977 than did collections of previous years.

Increased prevalence of mature females bearing pigmented oocytes from populations of Minnesota Rana pipiens.

Mature female leopard frogs, Rana pipiens, collected from several sites in Minnesota from 1967 through 1977, were examined for the presence of pigmented oocytes. An increase in the percent of mature females with pigmented oocytes was observed in the frogs captured in 1977 compared to those captured earlier. Coincident with the increase in prevalence of females with pigmented oocytes, there was a decline in abundance of the frogs.

Dominant lethality in frog embryos after paternal treatment with triethylenemelamine: cytogenetics, morphology, and swimming capability.

Male frogs (Rana pipiens) were injected intraperitoneally with triethylenemelamine (TEM). The injected males were held for seven days to permit TEM interaction with sperm. The TEM-treated males were then spermiated with human chorionic gonadotropin (HCG) and the ova of normal females were inseminated with the sperm. Direct observation was made of in vitro fertilized ova, cleavage, blastulation, and subsequent embryonic development. No differences were detected between the controls and treated animals from any experimental group for fertilization, cleavage, and blastulation. Dose-related morphologic abnormalities first became apparent at the time of gastrulation; the capability of hatched embryos to swim was affected by TEM. Metaphase chromosomes were studied from randomly selected embryos, and the prevalence of chromosomal structural abnormalities increased with dose over a range of 13--1,300 microgram TEM per kilogram frog.