Biomedical subjects

D Sapoznikov

Publications and source records attributed to D Sapoznikov.

At least 19 recordsLinked to original sources

PubMed2001

Power spectral analysis of heart rate variability in rats as a quantitative tool in the PK-PD analysis of the parasympatholytic activity of atropine.

PURPOSE: To utilize power spectral analysis (PSA) of heart rate variability (HRV) as a pharmacodynamic (PD) measure of atropine parasympathetic effect, and to model the kinetics of action. METHODS: Heart rate data was collected following atropine administration to rats and was analyzed off-line for high frequency peaks by PSA of HRV as a measure of parasympathetic tone. A temporal cumulative approach (TCA) detected transient changes in parasympathetic activity. The pharmacokinetics (PK) was analyzed and linked to both direct and indirect PK-PD models. RESULTS: TCA enabled a quantitative measure of atropine parasympathetic activity. A simultaneous fit of the indirect PK-PD model to the experimental data of all three atropine doses successfully captured the experimental data. CONCLUSIONS: TCA can be used as a quantitative measure of parasympathetic tone. Our work has established a preclinical model to investigate the kinetics of drug action on the autonomic nervous system.

Animals↗

PubMed2001

Variability in repeated pattern ventricular arrhythmia: application of a reentry model.

Repeated pattern ventricular arrhythmia (RPVA) is often observed in electrocardiogram recordings as a repeated sequence of a fixed number of normal sinus QRS complexes interposed between ventricular ectopic beats. The number of interposed sinus complexes is defined as the order of the repeated pattern ventricular arrhythmia. Regions of orders as a function of sinus RR and coupling intervals and duration of refractory periods of normal conduction and reentry pathways were derived from a computer model that simulates a reentry mechanism. Refractory periods of both the normal and reentry conduction pathways could be estimated from electrocardiogram measured time intervals. A variable relationship of RR intervals for different orders was found among patients. According to the reentry model, these order changes were more likely to occur with changes in the reentry refractory period than with heart rate changes. The longer RR intervals of interpolated beats in some patients were also explained by the model.

Adult↗

PubMed2001

Electrogastrographic norms in children: toward the development of standard methods, reproducible results, and reliable normative data.

BACKGROUND: Surface electrogastrography (EGG) is a noninvasive technique that detects gastric myoelectrical electric activity, principally the underlying pacemaker activity generated by the specialized interstitial cells of Cajal. Interest in the use of this methodology has grown because of its potential applications in describing functional gastrointestinal disorders, particularly as a tool in the evaluation of nausea, anorexia, and other dyspeptic symptoms. METHODS: Fifty-five healthy volunteers (27 female), ranging in age from 6 to 18 years (mean, 11.7 years), were studied for a 1-hour baseline preprandial period and a 1-hour postprandial period after consumption of a standard 448-kcal meal. Recordings were obtained with an EGG Digitrapper or modified Polygraph (Medtronic-Synectics, Shoreview, MN). Spectral analysis by an autoregressive moving average method was used to extract numerical data on the power and frequency of gastric electrical activity from the EGG signal. RESULTS: The authors present normative data for healthy children and adolescents studied under a standardized protocol. Mean dominant frequency was found to be 2.9 +/- 0.40 cycles per minute preprandially and 3.1 +/- 0.35 postprandially, with 80% +/- 13% of test time spent in the normogastric range (2-4 cycles per minute) before and 85% +/- 11% after the test meal. The response of several key parameters to meal consumption was considered, and the effects of age, gender, and body mass index (BMI) on the EGG were sought. CONCLUSIONS: There is a postprandial increase in the rhythmicity and amplitude of gastric slow waves, as other investigators have shown in adults. Key normative values are not dependent on age, gender, or BMI. The authors discuss limitations in the data set and its interpretability. The authors establish a normative data set after developing a standardized recording protocol and test meal and show that EGG recordings can be obtained reliably in the pediatric population. Development of similar norms by investigators using the EGG is crucial for future exploration of the validity and clinical application of the EGG. Differences in test conditions of signal detection and analytic methods influence EGG results substantially, and caution should be used when comparing results across centers.

Adolescent↗

PubMed2001

Determinants of short-period heart rate variability in the general population.

Decreased heart rate variability (HRV) is associated with a worse prognosis in a variety of diseases and disorders. We evaluated the determinants of short-period HRV in a random sample of 149 middle-aged men and 137 women from the general population. Spectral analysis was used to compute low-frequency (LF), high-frequency (HF) and total-frequency power. HRV showed a strong inverse association with age and heart rate in both sexes with a more pronounced effect of heart rate on HRV in women. Age and heart rate-adjusted LF was significantly higher in men and HF higher in women. Significant negative correlations of BMI, triglycerides, insulin and positive correlations of HDL cholesterol with LF and total power occurred only in men. In multivariate analyses, heart rate and age persisted as prominent independent predictors of HRV. In addition, BMI was strongly negatively associated with LF in men but not in women. We conclude that the more pronounced vagal influence in cardiac regulation in middle-aged women and the gender-different influence of heart rate and metabolic factors on HRV may help to explain the lower susceptibility of women for cardiac arrhythmias.

Age Factors↗

PubMed2000

Restenosis and progression of coronary disease after balloon angioplasty in patients with diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus (D) (both insulin-requiring D [IRD] and non-IRD) who undergo angioplasty have worse long-term outcome than do non-D patients. Few data are available in the literature that explain these findings. HYPOTHESIS: The study was undertaken to compare restenosis and progression of coronary disease after angioplasty in IRD patients, in non-IRD patients, and in non-D patients. METHODS: Diabetic patients who underwent coronary angioplasty were separated into two subgroups: IRD and non-IRD patients. Their angiographic outcome was compared with non-D patients. We examined retrospectively 353 coronary angiograms of patients who were referred for diagnostic angiography > 1 month after successful angioplasty. Quantitative angiography was used to determine the outcome in dilated narrowings (restenosis) and in nondilated narrowings (disease progression). RESULTS: Baseline clinical and angiographic characteristics were similar in all groups. Restenosis rate was higher in IRD (61%) than in non-IRD (36%) and non-D (35%) patients (p = 0.04). Late luminal loss after angioplasty was two times greater in IRD patients than in the other two groups (p = 0.01). Disease progression of nondilated narrowings was significantly more prominent in non-IRD than in non-D patients: Diameter stenoses were similar in the initial angiogram, but narrowings were significantly more severe (p = 0.02) in the final angiogram (70 +/- 27% and 60 +/- 33%, respectively). New narrowings were more common in non-IRD than in non-D patients: there was a 23% increase in the number of narrowings in the follow-up angiogram in non-IRD patients compared with only 12% in non-D patients (p < 0.003). These new narrowings were more common (p = 0.01) in angioplasty arteries (57 narrowings on 420 arteries--13.6%) than in nonangioplasty arteries (54 narrowings on 639 arteries--8.5%). CONCLUSION: Restenosis is more common in IRD patients and explains the high rate of adverse cardiac events within the first year after coronary intervention in these patients (mainly target lesion revascularization). Disease progression (including new narrowings) is the main determinant of patient outcome > 1 year after coronary intervention and is accelerated in non-IRD compared with non-D patients.

Aged↗

PubMed2000

Enhancing long-term ECG monitoring with graphic analysis of coupling intervals.

By graphically identifying patterns of ventricular ectopic beat (VEB) interval characteristics, we sought to enhance arrhythmia analysis, especially in long-term ECG monitoring. Coupling intervals as a function of preceding sinus RR intervals (CI/RR diagrams) with the aid of coupling interval and interectopic interval histograms were analyzed in 172 patients with frequent VEBs. Four distinct types of CI/RR diagrams were observed: horizontal-elongated (25 patients), linear (4 patients), triangular (37 patients), and clusters separated by dot-sparse areas (17 patients). In 89 patients, no definite pattern was discerned. The patients with elongated diagrams were significantly younger, had fixed coupling, uniform QRS complexes, and lacked periodicities in their interectopic interval histograms. The linear pattern was detected in a small group with rate-related VEBs. In the group with a triangular pattern, 30% of the patients exhibited interectopic periodicities suggesting parasystole. The patients with dot-sparse areas in the CI/RR diagrams had more variable coupling and predominantly more multiform QRS complexes. We conclude that CI/RR diagrams in conjunction with coupling interval and interectopic interval histograms enhance arrhythmia analysis by identifying patterns, such as those consistent with either fixed coupling, rate dependence, parasystole, or multiform VEBs.

Electrocardiography, Ambulatory↗

PubMed2000

Reduction of congestive heart failure symptoms by very early fibrinolytic therapy in acute myocardial infarction: a long-term follow-up.

BACKGROUND: In patients with acute myocardial infarction (MI), early fibrinolytic therapy results in improved survival and preservation of ventricular function. The purpose of the study was to determine whether very early treatment also reduces the development of congestive heart failure. METHODS AND RESULTS: During the years 1984 to 1989, 358 consecutive patients with acute MI were treated with streptokinase, 161 within the first 1.5 hours from the onset of chest pain (group A) and 197 within 1.5 to 4.0 hours (group B). In 68, fibrinolysis was initiated in the prehospital setting pioneered by our group. Symptoms related to heart failure including dyspnea on exertion, fatigue, orthopnea, paroxysmal nocturnal dyspnea, nocturia, and peripheral edema, in addition to pulmonary edema events, were assessed during 5 years of follow-up. The evaluation was based on medical records and a detailed questionnaire, which was filled in by the investigators. A favorable significant effect of very early thrombolysis on the development of most of these limiting symptoms appeared 3 months after hospital discharge and persisted thereafter (P <.05). During hospitalization, pulmonary edema attacks occurred less frequently in patients from group A (23% vs 36.5%, P <.01). This difference persisted during 4 years of follow-up (13% vs 36%, P <.001). CONCLUSIONS: Our data demonstrate that very early fibrinolytic therapy results in a significant long-term reduction of congestive heart failure-related symptoms and thereby improves the quality of life in patients after MI.

Dyspnea↗

PubMed1999

Changes in sinus RR interval patterns preceding ventricular ectopic beats: assessment with rate enhancement and dynamic heart rate trends.

Changes in heart rate preceding ventricular ectopic beats may be used to identify clinical subsets of patients. We evaluated RR interval patterns preceding ventricular ectopic beats with a rate enhancement method which estimates ventricular ectopic beat dependence on the sinus RR interval preceding the ventricular ectopic beat and the dynamic heart rate trend, which is based on the slope of the five RR intervals preceding the ventricular ectopic beat. Using these two methodologies in 176 patients with frequent ventricular ectopic beats we identified several unique subsets of patients: (1) bradycardia-enhanced patients were younger with a high proportion of males and longer, more variable coupling intervals; (2) tachycardia-enhanced patients exhibited sleep suppression of ventricular ectopic beats and had shorter, less variable coupling intervals; (3) patients with predominantly no change in RR preceding the ventricular ectopic beat were significantly older, with greater prevalence of cardiovascular disease and reduced sinus RR variability, indicating decreased autonomic nervous system activity. These two methods may serve as a basis for further investigations regarding the treatment and prognosis of ventricular ectopic beats.

Age Factors↗

PubMed1999

Inheritance of heart rate variability: the kibbutzim family study.

Heart rate variability (HRV) measures are associated with coronary heart disease incidence and mortality. Therefore insight into the genetic and environmental determinants of these measures may have clinical relevance. We assessed the role of genetic and environmental factors of time domain and frequency domain HRV indices. Participants were 451 kibbutz members, aged 15 and up, belonging to 80 families. HRV indices were calculated from Holter recordings measured over 5 min. Our data indicate that for the two time- and four frequency domain indices, a mixture of two normal distributions fit the data significantly better than a single normal distribution (P<0.05). We used complex segregation analysis to infer the modes of inheritance of these HRV measures. We found evidence for possible involvement of a recessive major gene in the inheritance of the root mean square of successive differences in RR intervals (RMSSD), which is predominantly vagally mediated. A putative major gene explains 28%-34% of the adjusted inter-individual variability. The SD, determined by a mixture of mechanisms, is influenced by environmental and polygenic effects, but not by a major gene. The findings regarding the heritability of the frequency domain indices were not conclusive. However, the involvement of genetic factors was not rejected. Additional studies in extended families are needed to confirm the involvement of major genes in the determination of the autonomic activity.

Adolescent↗

PubMed1999

Simulation of ventricular arrhythmias using a re-entry model algorithm.

The present study employs a computer simulation of the timing of normal and abnormal ventricular activation according to a re-entry model. A wide variety of arrhythmia patterns similar to those obtained in clinical settings may be simulated by using an algorithm which is based on parameters such as the sinus RR interval (RR), the refractory period, the coupling interval between normal activation and re-entry and the coupling interval between one re-entry and a subsequent re-entry (CV). By varying RR and CV the results of the simulation may show transition between different types of arrhythmia such as ventricular tachycardia, bigeminy, trigeminy and more widely separated ventricular ectopic beats such as in concealed bigeminy. The algorithm provides a basis for the study of re-entry, a major mechanism in the genesis of ventricular arrhythmias.

Algorithms↗

PubMed1999

Heart rate variability during chronic hemodialysis and after renal transplantation: studies in patients without and with systemic amyloidosis.

The present study was undertaken to compare heart rate variability (HRV) values in patients on maintenance hemodialysis with no evidence of ischemic or hypertensive heart diseases to those of age- and gender-matched healthy individuals and those of patients after renal transplantation. To assess the effects of a common confounding factor, HRV values were also determined in patients with systemic amyloidosis, in chronic hemodialysis, and after successful renal transplantation. Spectral analyses of RR intervals from continuous electrocardiogram recordings were performed to quantify ultra low frequency, very low frequency, low frequency, and high frequency powers. HRV determinations were all significantly reduced in uremic patients undergoing hemodialysis compared with the healthy control subjects, especially in those with systemic amyloidosis. Renal transplantation normalized HRV in most patients; HRV, however, remained reduced in isolated amyloidosis patients with cardiac or adrenal involvement. HRV circadian day/night differences were preserved in hemodialysis patients and after renal transplantation in those without amyloidosis but not in those with amyloidosis. These data suggest that reduced HRV in chronic hemodialysis patients may precede other manifestations of cardiovascular disease. In uremic patients with amyloidosis, a more severe form of autonomic failure may occur. Successful transplantation corrects HRV abnormalities in most patients, suggesting that the autonomic dysfunction of uremia is caused by humoral factors reversed by the normalization of the renal function.

Adolescent↗

PubMed1998

Prevention of congestive heart failure by early, prehospital thrombolysis in acute myocardial infarction: a long-term follow-up study.

The long term impact of pre-hospital thrombolysis in acute myocardial infarction on the subsequent development of heart failure symptoms was investigated in 362 consecutive patients. The pre hospital strategy, used in 61 patients, allowed for very early administration of streptokinase, within 1.2+/-0.6 (mean+/-S.D.) hours from pain onset. In contrast, 294 patients treated in hospital received lytic treatment within 2.0+/-0.9 hours. The pre hospital group showed faster reperfusion, as measured by the time to peak creatine kinase and to ST segment recovery, but only a slightly better ventricular function, as compared to hospital treated patients. Heart failure symptoms were significantly reduced in the pre hospital group during hospitalization and at long term follow up: there were less dyspnea, fatigue, orthopnea, nocturnal dyspnea, nocturia, peripheral edema and episodes of pulmonary edema. Angina was reduced as well. We conclude that the initial benefit of prehospital thrombolysis translates into long term reduction of heart failure symptoms, thus improving quality of life.

Female↗

PubMed1998

Familial aggregation of heart rate variability based on short recordings--the kibbutzim family study.

The objective of this study was to assess the familial aggregation of heart rate variability (HRV), a readily measurable noninvasive reflection of cardiac autonomic function. Familial correlations were analyzed in 451 kibbutz members aged 15-97 years belonging to 80 kindreds. Five-minute duration Holter recordings made during silent supine spontaneous breathing and metronomic breathing were analyzed in the time and frequency domains. The present analysis considers the familial correlations and the heritability estimates of two time-domain indices, the standard deviation (SD) of the R-R interval (RR), reflecting total variability, and the root mean square of successive differences in RR intervals (RMSSD), reflecting vagal (parasympathetic) tone. During free breathing, age- and sex-adjusted correlations between parents and their children (r=0.24 for both indices) and between adult siblings above 30 years of age (r=0.24 and t=0.34 for SD and RMSSD, respectively) were statistically significant, whereas spouse correlations (r=-0.04, r=-0.02 for SD and RMSSD, respectively) and correlations in younger siblings (r=-0.22 and r=0.01, respectively) were not. Significant heritability estimates were demonstrated for the two indices (h2=0.41 for SD and h2=0.39 for RMSSD). These findings suggest that familial aggregation of HRV characteristics is determined mostly by genetic factors and less so by environmental factors and provide a basis for continuing the investigation into the underlying genetic influences on HRV.

Adolescent↗

PubMed1998

Five minute recordings of heart rate variability for population studies: repeatability and age-sex characteristics.

OBJECTIVE: To evaluate the stability of short recordings of heart rate variability (HRV) with time, and the association of HRV with age and sex. DESIGN: Five minute Holter recordings were made twice over a two month interval (tracking study). In addition, HRV was measured in a cross sectional study. SETTING: Residents of 11 Israeli kibbutzim were examined in their settlements. SUBJECTS: 32 men and 38 women (aged 31-67) participated in the tracking study and 294 (aged 35-65) were involved in the cross sectional study. MAIN OUTCOME MEASURES: Time and frequency domain analyses on Holter recordings were undertaken in two breathing conditions: spontaneous and controlled breathing (15 respirations per minute). Regression was used to assess the relations of sex, age, heart rate, and logarithmically transformed HRV indices. RESULTS: HRV measures were highly consistent with time with correlations of 0.76-0.80 for high frequency and total power. Geometric mean total power declined with age by 45% in men and 32% in women, and was lower by 24% among women than among men (all p < or = 0.005). Men had a 34% higher very low and low frequency power and a higher ratio of low to high frequency power (p < 0.001). Conversely, high frequency power in women represents a greater proportion of total power than in men. CONCLUSION: Short recordings of HRV in a non-laboratory setting are stable over months and therefore characteristic of an individual. Strong age and sex effects were evident. HRV derived from short recordings can be informative in population based studies.

Adult↗

PubMed1998

Heart rate variability as a marker of myocardial perfusion.

RR variability (HRV), an independent predictor of death following myocardial infarction, may also be related to other features of coronary artery disease. We evaluated its ability to differentiate among sedentary patients with chest pain >/=45 years of age demonstrating either normal or abnormal myocardial perfusion with rest and exercise thallium-210 tomographic imaging. The major HRV difference between 48 men and 50 women with normal perfusion was a significantly higher high frequency power in women. No significant differences in mean HRV values were found between the 57 men with abnormal perfusion scans and the 48 men with normal perfusion. In both men and women with normal perfusion scans, duration of exercise was significantly related to age. In men with abnormal scans, impaired myocardial perfusion alters the relationship between exercise duration and age, and a group of individuals with diminished HRV and low levels of physical fitness, regardless of age, can be identified. Despite these latter selective findings, we conclude that HRV is not a sensitive indicator to differentiate patients with normal and abnormal myocardial perfusion.

Age Factors↗

PubMed1997

Long-term angiographic follow-up of coronary balloon angioplasty in patients with diabetes mellitus: a clue to the explanation of the results of the BARI study. Balloon Angioplasty Revascularization Investigation.

OBJECTIVES: We sought to compare the angiographic outcome of diabetic patients (treated with insulin or oral hypoglycemic agents) after successful coronary angioplasty with that in nondiabetic patients. The analysis included the outcome of the dilated (restenosis) and nondilated narrowings (disease progression). BACKGROUND: Recent data have confirmed that diabetes mellitus is an important risk factor for long-term adverse events. These adverse events are more common after balloon angioplasty than after bypass surgery (Bypass Angioplasty Revascularization Investigation [BARI]). METHODS: We examined retrospectively 353 coronary angiograms of 248 patients (55 diabetic, 193 nondiabetic) who were referred for diagnostic angiography >1 month after successful angioplasty (1.4 +/- 0.6 [mean +/- SD] repeat angiograms/patient). Restenosis and disease progression/regression were compared between groups by means of quantitative angiography. RESULTS: Baseline clinical and angiographic characteristics were similar in both groups. There was a nonsignificant trend for a higher restenosis rate of dilated narrowings in diabetic patients. There were no significant changes between diabetic and nondiabetic patients in the rates of progression and regression of narrowings that were not dilated during the initial angioplasty. The main difference was in the rate of appearance of new narrowings: There was a 22% increase in the number of narrowings on the follow-up angiogram in diabetic patients (38 new, 174 preexisting narrowings) compared with 12% (86 new, 734 preexisting narrowings) in nondiabetic patients (p < 0.004). Diabetes mellitus and the performance of angioplasty in the artery had an additive risk for development of new narrowings, which were identified in 15 (16.9%) of 89 arteries with and 16 (13.2%) of 121 without angioplasty in diabetic patients and in 42 (12.7%) of 331 arteries with and 38 (7.3%) of 518 without angioplasty in nondiabetic patients (p = 0.009). CONCLUSIONS: The combination of diabetes mellitus and an artery that was instrumented during balloon angioplasty is additive and increases the risk of formation of new narrowing in that artery. This finding may explain the high adverse event rates observed in diabetic patients in the angioplasty arm of the BARI study, most of whom had angioplasty performed in at least two arteries.

Aged↗

PubMed1997

Analysis of the onset and termination of repeated pattern ventricular arrhythmias.

A group of algorithms has been developed to investigate the characteristics of beat-to-beat intervals preceding and following the onset and termination of repeated pattern ventricular arrhythmias (RPVA) such as bigeminy and trigeminy. Eighty-five patients, each with more than 3000 ventricular ectopic beats in a 24-hour Holter recording and with more than 10 episodes of RPVA, were evaluated. A statistically significant prolongation of sinus intervals preceding the onset of bigeminy and trigeminy and shortening of postectopic intervals after the onset were observed. In addition, shortening of postectopic intervals before the termination of bigeminy and trigeminy and lengthening of sinus intervals following their termination were also seen. A significant presence of these characteristics was not observed in arrhythmias with a greater number of sinus beats between ectopic beats. These dynamics provide information which may be utilized in the assessment of mechanisms involved in the onset and termination of RPVA.

Algorithms↗

PubMed1997

Angiographic deterioration of target coronary artery narrowing as a result of percutaneous balloon angioplasty.

We evaluated the long-term angiographic outcome of balloon angioplasty by comparing original and follow-up target coronary narrowing. Rather than using restenosis to determine outcome, as in most angioplasty studies, we took an unusual approach and analyzed outcome in terms that are commonly used in progression and regression studies after medical interventions. Quantitative angiographic measurements were undertaken in 315 narrowings with an initial diameter stenosis <90% before and after angioplasty and at follow-up. Angiographic deterioration (>10% increase in follow-up diameter stenosis) was identified in 44 (14%) narrowings. Angiographic deterioration was not influenced by age, sex, risk factors, lipid profile, or the indication for angioplasty. Deterioration was also not predicted by the severity, length, or the location of the narrowing. The deteriorating narrowings had a higher recoil after dilatation compared with narrowings with angiographic improvement (21% +/- 31% vs 12% +/- 17%, p = 0.006); the residual stenosis after angioplasty was therefore higher. The late loss was also significantly increased compared with narrowings with angiographic improvement (65% +/- 26% vs 8% +/- 24%, p < 0.001). We conclude that the incidence of angiographic deterioration of coronary disease as a result of restenosis is uncommon but not negligible. Interventional cardiologists should resist the temptation to dilate mild, silent coronary narrowings because the procedure might have an unfavorable angiographic (and probably clinical) effect.

Angioplasty, Balloon, Coronary↗