Physiological Mechanisms of the Effect of Modulated Kinesotherapy on the Circulatory System

A new method of modulated kinesotherapy (MK) involving foot-paced movement (walking and running) with the pace and heart rate synchronized by means of a specially developed Marafon training device is described. In healthy subjects and patients with coronary disease complicated by functional class I or II (FC I–II) angina, the heart rate (HR) decreased by 20–25% during the MK; after the MK, the period of normalization of the HR decreased by 30%, relative to the control. The double product index, an integral representation of the circulatory efficiency, decreased by 15–20%. Normalization of the systolic component (on the average, 62.4 and 64.2% increase in the stroke volume and the end-diastolic volume, respectively) and diastolic function (40 and 43% increase in the peak left ventricular early filling rate and the ratio of the peak early filling rate to the atrial filling rate, respectively) was observed. The indications for and the contraindications to the MK application are specified.     

Reaction of the Cardiovascular System to Local Muscular Activity at Different Ages

Five age groups corresponding to the main stages of human ontogenesis (from 13 to 90 years) were examined during local muscle work with a hand dynamometer. Differences in the adaptive cardiac reactions to static or dynamic loading were revealed. Age-related differences in cardiac reactions were observed, testifying to a beneficial heart functioning during loading at 30–35 years of age and cardiac strain at 18–20 and 60–74 years of age.     

Dynamics of the states of heart rate regulation during 24-h monitoring

An attempt was made to classify the heart rate (HR) regulation states observed during 24-h monitoring of HR variability parameters in patients with essential hypertension and coronary heart disease. A continuous chain of nonoverlapping 5-min intervals was studied, and the cardiointerval mode, the spectral powers in the ranges of respiratory and first-order slow waves, their ratio, and the total spectral power were determined for each interval. Combinations of HR characteristics obtained for 5-min intervals were classified using nonparametric clustering methods. The standard clustering always revealed a limited number (8–13) of classes of HR regulation states. For every patient, the classes of states were numbered and their chronological sequence was studied with a mathematical apparatus for analyzing Markov chains. A set of state-to-state transitions significantly differing in frequency from random transitions was revealed for every patient.Translated from Fiziologiya Cheloveka, Vol. 31, No. 2, 2005, pp. 85–89.Original Russian Text Copyright © 2005 by Dzizinskii, Kuklin, Mikhalevich, Rozhkova.     

Rating of perceived exertion as a tool for prescribing and self regulating interval training: a pilot study

The aim of the present study was to analyse the usefulness of the 6-20 rating of perceived exertion (RPE) scale for prescribing and self-regulating high-intensity interval training (HIT) in young individuals. Eight healthy young subjects (age = 27.5±6.7 years) performed maximal graded exercise testing to determine their maximal and reserve heart rate (HR). Subjects then performed two HIT sessions (20 min on a treadmill) prescribed and regulated by their HR (HR: 1 min at 50% alternated with 1 min at 85% of reserve HR) or RPE (RPE: 1 minute at the 9-11 level [very light-fairly light] alternated with 1 minute at the 15-17 level [hard-very hard]) in random order. HR response and walking/running speed during the 20 min of exercise were compared between sessions. No significant difference between sessions was observed in HR during low- (HR: 135±15 bpm; RPE: 138±20 bpm) and high-intensity intervals (HR: 168±15 bpm; RPE: 170±18 bpm). Walking/running speed during low- (HR: 5.7±1.2 km · h⁻¹; RPE: 5.7±1.3 km · h⁻¹) and high-intensity intervals (HR: 7.8±1.9 km · h⁻¹; RPE: 8.2±1.7 km · h⁻¹) was also not different between sessions. No significant differences were observed in HR response and walking/running speed between HIT sessions prescribed and regulated by HR or RPE. This finding suggests that the 6-20 RPE scale may be a useful tool for prescribing and self-regulating HIT in young subjects.     

Selective effects of adenosine receptor agonists upon coronary resistance and heart rate in isolated working rabbit hearts

Dose dependent changes in heart rate (HR) and coronary resistance (CR) were determined for adenosine, 5'-N-ethylcarboxamide adenosine (NECA) and l-N6-phenylisopropyladenosine (l-PIA) over a dose range of 1 X 10(-9) to 1 x 10(-5) M. Changes in CR were determined under controlled metabolic demand conditions (constant mean aortic pressure, constant mean left atrial pressure, and constant HR). Decreases in HR were determined by allowing the paced hearts to beat spontaneously between doses for 15 seconds. Adenosine significantly decreased CR and HR at greater than or equal to 1 X 10(-5) M. NECA significantly decreased both CR and HR at greater than or equal to 3 X 10(-8) M. l-PIA significantly decreased HR at greater than or equal to 3 X 10(-8) M; however a dose at greater than or equal to 3 X 10(-6) M was required to significantly decrease CR. These results provide evidence that the coronary vasodilator action of adenosine may primarily be mediated by A2 receptors. Furthermore, the data are in support of previous observations that the bradycardic action of adenosine is principally mediated via A1 receptors.     

Restoration of Botshol (The Netherlands) by reduction of external nutrient load: Botshol and the Dutch governmental program of nutrient reduction

In the nature reserve Botshol, the process of eutrophication is very successfully stopped and reversed by hydrological separation of the agricultural area from the nature reserve and by dephosphorizing the inlet-water. The external phosphate loading of about 0.6 g Pm^–2y^–1 decreased 80% to about 0.12 g Pm^–2y^–1. The Dutch governmental program in relation to eutrophication is focussed on the introduction of detergents without phosphates, dephosphorizing the water at sewage purification plants, reduction of fertilization of farming lands and international measures in relation to the discharge of phosphates in the rivers Rhine, Meuse and Scheldt. The effects of the governmental program on the external phosphate loading of Botshol will be a reduction of only 4%.For the average Dutch fresh waters the effect of the governmental program is a decrease of the external loading of about 6 g Pm^–2y^–1 to about 3 g Pm^–2y^–1, a phosphate loading still much to high to push back eutrophication noticeably.As an example also for a number of Dutch fresh waters, sensitive to eutrophication, the effects of the governmental program are calculated. For none of these waters the program will lead to an external phosphate loading that even comes close to the recent phosphate loading of Botshol.     

Effect of crop residues on root growth and phosphorus acquisition of pearl millet in an acid sandy soil in Niger

The effect of long-term (1983–1988) applications of crop residues (millet straw, 2–4 t ha^-1 yr^–1) and/or mineral fertilizer (30 kg N, 13 kg P and 25 kg K ha^-1 yr^-1) on uptake of phosphorus (P) and other nutrients, root growth and mycorrhizal colonization of pearl millet (Pennisetum glaucum L.) was examined for two seasons (1987 and 1988) on an acid sandy soil in Niger. Treatments of the long-term field experiment were: control (–CR–F), mineral fertilizer only (–CR+F), crop residues only (+CR–F), and crop residues plus mineral fertilizer (+CR+F).In both years, total P uptake was similar for +CR–F and –CR+F treatments (1.6–3.5 kg P ha^-1), although available soil P concentration (Bray I P) was considerably lower in +CR–F (3.2 mg P kg^-1 soil) than in –CR+F (7.4) soil. In the treatments with mineral fertilizers (–CR+F; +CR+F), crop residues increased available soil P concentrations (Bray I P) from 7.4 to 8.9 mg kg^-1 soil, while total P uptake increased from 3.6 to 10.6 kg P ha^-1. In 1987 (with 450 mm of rainfall), leaf P concentrations of 30-day-old millet plants were in the deficiency range, but highest in the +CR+F treatment. In 1988 (699 mm), leaf P concentrations were distinctly higher, and again highest in the +CR+F treatment. In the treatments without crop residues (–CR–F; –CR+F), potassium (K) concentrations in the leaves indicated K deficiency, while application of crop residues (+CR–F; +CR+F) substantially raised leaf K concentrations and total K uptake. Leaf concentrations of calcium (Ca) and magnesium (Mg) were hardly affected by the different treatments.In the topsoil (0–30 cm), root length density of millet plants was greater for +CR+F (6.5 cm cm^-3) than for +CR–F (4.5 cm cm^-3) and –CR+F (4.2 cm cm^-3) treatments. Below 30 cm soil depth, root length density of all treatments declined rapidly from about 0.6 cm cm^-3 (30–60 cm soil depth) to 0.2 cm cm^-3 (120–180 cm soil depth). During the period of high uptake rates of P (42–80 DAP), root colonization with vesicular-arbuscular mycorrhizal (VAM) fungi was low in 1987 (15–20%), but distinctly higher in 1988 (55–60%). Higher P uptake of +CR+F plants was related to a greater total root length in 0–30 cm and also to a higher P uptake rate per unit root length (P influx). Beneficial effects of crop residues on P uptake were primarily attributed to higher P mobility in the soil due to decreased concentrations of exchangeable Al, and enhancement of root growth. In contrast, the beneficial effect of crop residues on K uptake was caused by direct K supply with the millet straw.     

Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2

Objective To develop and validate version two of the QRISK cardiovascular disease risk algorithm (QRISK2) to provide accurate estimates of cardiovascular risk in patients from different ethnic groups in England and Wales and to compare its performance with the modified version of Framingham score recommended by the National Institute for Health and Clinical Excellence (NICE).Design Prospective open cohort study with routinely collected data from general practice, 1 January 1993 to 31 March 2008.Setting 531 practices in England and Wales contributing to the national QRESEARCH database.Participants 2.3 million patients aged 35-74 (over 16 million person years) with 140 000 cardiovascular events. Overall population (derivation and validation cohorts) comprised 2.22 million people who were white or whose ethnic group was not recorded, 22 013 south Asian, 11 595 black African, 10 402 black Caribbean, and 19 792 from Chinese or other Asian or other ethnic groups.Main outcome measures First (incident) diagnosis of cardiovascular disease (coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records or linked Office for National Statistics death certificates. Risk factors included self assigned ethnicity, age, sex, smoking status, systolic blood pressure, ratio of total serum cholesterol:high density lipoprotein cholesterol, body mass index, family history of coronary heart disease in first degree relative under 60 years, Townsend deprivation score, treated hypertension, type 2 diabetes, renal disease, atrial fibrillation, and rheumatoid arthritis.Results The validation statistics indicated that QRISK2 had improved discrimination and calibration compared with the modified Framingham score. The QRISK2 algorithm explained 43% of the variation in women and 38% in men compared with 39% and 35%, respectively, by the modified Framingham score. Of the 112 156 patients classified as high risk (that is, ≥20% risk over 10 years) by the modified Framingham score, 46 094 (41.1%) would be reclassified at low risk with QRISK2. The 10 year observed risk among these reclassified patients was 16.6% (95% confidence interval 16.1% to 17.0%)—that is, below the 20% treatment threshold. Of the 78 024 patients classified at high risk on QRISK2, 11 962 (15.3%) would be reclassified at low risk by the modified Framingham score. The 10 year observed risk among these patients was 23.3% (22.2% to 24.4%)—that is, above the 20% threshold. In the validation cohort, the annual incidence rate of cardiovascular events among those with a QRISK2 score of ≥20% was 30.6 per 1000 person years (29.8 to 31.5) for women and 32.5 per 1000 person years (31.9 to 33.1) for men. The corresponding figures for the modified Framingham equation were 25.7 per 1000 person years (25.0 to 26.3) for women and 26.4 (26.0 to 26.8) for men). At the 20% threshold, the population identified by QRISK2 was at higher risk of a CV event than the population identified by the Framingham score.Conclusions Incorporating ethnicity, deprivation, and other clinical conditions into the QRISK2 algorithm for risk of cardiovascular disease improves the accuracy of identification of those at high risk in a nationally representative population. At the 20% threshold, QRISK2 is likely to be a more efficient and equitable tool for treatment decisions for the primary prevention of cardiovascular disease. As the validation was performed in a similar population to the population from which the algorithm was derived, it potentially has a “home advantage.” Further validation in other populations is therefore advised.     

The effect of high energy electron irradiation on blood-brain barrier permeability to haloperidol and stobadin in rats

Summary The heads of rats were irradiated by 4 MeV electrons in doses 90, 180, and 360 Gy. The observed times of deaths ranged 120–600, 60–420, and 150–370 min after 90, 180, and 360 Gy, respectively. A dose dependent decrease of the brain uptake index of haloperidol was observed 1 and 3 h post radiation. On the other hand an increased brain uptake index was found for stobadin after head irradiation with doses of 180 and 360 Gy. Regional cerebral blood flow, blood pressure, and heart rate were not significantly altered in the period following irradiation with 180 Gy. The observed changes in blood-brain barrier (BBB) permeability seem to be the result of the damaged function of morphological structures forming the BBB rather than altered regional blood flow.     

Relationships of Oxygen Consumption, Hemodynamics, and Heart Rate Variability with the Functional Class of Coronary Artery Disease Patients

The functional classes (FCs) established according to the criteria of the New York Heart Association were tested for association with oxygen consumption, the state of central hemodynamics, and heart rate (HR) variability in coronary artery disease (CAD) patients. Oxygen consumption, central hemodynamics, and HR variability at rest and during exercise were assayed in 146 CAD patients and 30 healthy individuals (the control group). It was established that the peak oxygen consumption (VO_2max), anaerobic threshold, pulmonary ventilation, systolic and minute blood volume at the threshold load (TL), and HR variability in a supine position significantly decrease and the total vascular peripheral resistance at rest and during exercise increases with increasing FC in CAD patients. The closest correlation of FC was revealed with physical working capacity, anaerobic threshold, age, and peak oxygen consumption. Moderate correlations were established with the chronotropic function of the heart at the threshold load, HR variability, the high- and low-frequency components of the cardiac rhythm at TL, pulmonary ventilation, stroke volume at rest and at TL, and the carbon dioxide ventilation equivalent at TL. In healthy individuals, the peak oxygen consumption closely correlated with the HR variability, the very low frequency component at TL, and physical capacity. With an increase in FC in CAD patients, peak oxygen consumption became more tightly associated with the chronotropic function and the hemodynamic components at TL than with the HR variability in a supine position or at TL.     

Sympathetic nervous activity and cardiovascular variability after a 3-day tail suspension in rats

The effects of a 3-day tail suspension on central and peripheral sympathetic activity were studied in rats by determining the in vivo noradrenaline (NA) turnover in the brain cell groups involved in central blood pressure control (A1, A2, A5 and A6) and in two peripheral organs, heart and kidneys. In addition, cardiovascular parameters and their variabilities were investigated by recording blood pressure (BP) and heart rate (HR) before and after suspension. These measurements were processed by spectrum analysis to assess the influence of tail suspension on autonomic balance. The NA turnover in the suspended rats was markedly reduced in A2 (–49%, P<0.01) and A5 (–38%, P<0.01) nuclei but unchanged in A1 and A6 cell groups compared with the control rats. Peripheral NA turnover was decreased in cardiac atria (–44%, P<0.001) and ventricles (–27%, P<0.01) while it was unchanged in kidneys after suspension. The BP, HR and their variabilities were similar in both groups of animals and showed no changes after suspension compared with baseline values. Spectrum analysis of BP and HR in our conscious suspended rats revealed no changes in power spectrum density or in peak frequencies. The discrepancy between the decrease in central sympathetic activity and the absence of changes in cardiovascular parameters after tail suspension raises the question of the validity of the tail suspended rat model when studying the cardiovascular deconditioning observed in humans after an exposure to actual or simulated weightlessness.     

Association of Sick Sinus Syndrome with Incident Cardiovascular Disease and Mortality: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study

Background

Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population.

Methods

We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes.

Results

During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14–1.70), coronary heart disease (HR 1.72, 95%CI 1.11–2.66), heart failure (HR 2.87, 95%CI 2.17–3.80), stroke (HR 1.56, 95%CI 0.99–2.46), AF (HR 5.75, 95%CI 4.43–7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9–67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51–2.66), AF (HR 4.25, 95%CI 3.28–5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8–32.1).

Conclusion

Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.     

The development of diving bradycardia in bottlenose dolphins (<Emphasis Type="Italic">Tursiops truncatus</Emphasis>)

Bradycardia is an important component of the dive response, yet little is known about this response in immature marine mammals. To determine if diving bradycardia improves with age, cardiac patterns from trained immature and mature bottlenose dolphins (Tursiops truncatus) were recorded during three conditions (stationary respiration, voluntary breath-hold, and shallow diving). Maximum (mean: 117±1 beats·min^–1) and resting (mean: 101±5 beats·min^–1) heart rate (HR) at the water surface were similar regardless of age. All dolphins lowered HR in response to apnea; mean steady state breath-hold HR was not correlated with age. However, the ability to reduce HR while diving improved with age. Minimum and mean steady state HR during diving were highest for calves. For example, 1.5–3.5-year-old calves had significantly higher mean steady state diving HR (51±1 beats·min^–1) than 3.5–5.5-year-old juveniles (44±1 beats·min^–1). As a result, older dolphins demonstrated greater overall reductions in HR during diving. Longitudinal studies concur; the ability to reduce HR improved as individual calves matured. Thus, although newly weaned calves as young as 1.7 years exhibit elements of cardiac control, the capacity to reduce HR while diving improves with maturation up to 3.5 years postpartum. Limited ability for bradycardia may partially explain the short dive durations observed for immature marine mammals.Abbreviations ADL aerobic dive limit - cADL calculated aerobic dive limit - ECG electrocardiogram - HR heart rate - TDR time–depth recorder Communicated by L.C.-H. Wang     

Autonomic cardiovascular and respiratory control during prolonged spaceflights aboard the International Space Station.

Impaired autonomic control represents a cardiovascular risk factor during long-term spaceflight. Little has been reported on blood pressure (BP), heart rate (HR), and heart rate variability (HRV) during and after prolonged spaceflight. We tested the hypothesis that cardiovascular control remains stable during prolonged spaceflight. Electrocardiography, photoplethysmography, and respiratory frequency (RF) were assessed in eight male cosmonauts (age 41-50 yr, body-mass index of 22-28 kg/m2) during long-term missions (flight lengths of 162-196 days). Recordings were made 60 and 30 days before the flight, every 4 wk during flight, and on days 3 and 6 postflight during spontaneous and controlled respiration. Orthostatic testing was performed pre- and postflight. RF and BP decreased during spaceflight (P < 0.05). Mean HR and HRV in the low- and high-frequency bands did not change during spaceflight. However, the individual responses were different and correlated with preflight values. Pulse-wave transit time decreased during spaceflight (P < 0.05). HRV reached during controlled respiration (6 breaths/min) decreased in six and increased in one cosmonaut during flight. The most pronounced changes in HR, BP, and HRV occurred after landing. The decreases in BP and RF combined with stable HR and HRV during flight suggest functional adaptation rather than pathological changes. Pulse-wave transit time shortening in our study is surprising and may reflect cardiac output redistribution in space. The decrease in HRV during controlled respiration (6 breaths/min) indicates reduced parasympathetic reserve, which may contribute to postflight disturbances.     

Evoked potentials of the human cerebral cortex to perceptible and imperceptible sound stimuli

Evoked potentials averaged with the help of an electronic computer (AEP) to brief sound stimuli of subthreshold (3–10 dB below the threshold of the signal's audibility), threshold, and superthreshold (10–60 dB above the threshold) intensity were recorded from the vertex and occipital region of the cranium in healthy people. The dynamics of the changes in the AEP with an increase in the intensity of the sound from subthreshold to superthreshold (60 dB) values was shown. The time and amplitude parameters of AEP to imperceptible and perceptible sound stimuli differed significantly. The most constant, and in many cases the only component of the AEP to an imperceptible stimulus was a long-latent, low-amplitude, slow positive oscillation. The participation of the cerebral cortex in the neural mechanisms of reactions to imperceptible sound stimuli is discussed.V. P. Serbskii Central Scientific-Research Institute of Forensic Psychiatry, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 2, pp. 115–122, March–April, 1971.     

Evaluation of Changes in Correlation Dimension of a Time Series of RR Intervals during a Functional Exercise Test

Changes in the cardiac rhythm (CR) structure were analyzed from the viewpoint of nonlinear dynamics. The purpose was to evaluate the changes in the chaotic element (the correlation dimension D) of CR during a functional exercise test (the Harvard step test) in ten healthy males aged 17–18. Distinct changes in D of CR were observed during the test. Some general trends and individual differences were revealed. D always decreased in comparison with the background value at the first minutes of exercise and recovery and increased sharply at the third and/or fourth minutes of exercise. The chaotic element of CR changed together with the functional state of the body depending on the stage of exercise.     

Increased diastolic time fraction as beneficial adjunct of alpha1-adrenergic receptor blockade after percutaneous coronary intervention

The effect of alpha1-receptor blockade with urapidil on coronary blood flow and left ventricular function has been attributed to relief of diffuse coronary vasoconstriction following percutaneous coronary intervention (PCI). We hypothesized that an increase in diastolic time fraction (DTF) contributes to the beneficial action of urapidil. In eleven patients with a 63% (SD 13) diameter stenosis, ECG, aortic pressure (Pa) and distal intracoronary pressure (Pd), and blood flow velocity were recorded at baseline and throughout adenosine-induced hyperemia. Measurements were obtained before and after PCI and after subsequent alpha1-receptor blockade with urapidil (10 mg ic). DTF was determined from the ECG and the Pa waveform. Functional parameters such as coronary flow velocity reserve, fractional flow reserve, and an index of hyperemic microvascular resistance (HMR) were assessed. Urapidil administration after PCI induced an upward shift in the DTF-heart rate relationship, resulting in a 3.1% (SD 2.7) increase in hyperemic DTF at a constant heart rate (P < 0.005) due to a shorter duration of systole. Hyperemic Pa and Pd decreased, respectively, by 6.1% (SD 6.6; P < 0.05) and 5.7% (SD 5.8; P < 0.01) after alpha1-blockade. Although epicardially measured functional parameters were on average not altered by alpha1-blockade due to concurrent changes in pressure and heart rate, HMR decreased by urapidil in those patients where coronary pressure remained constant. In conclusion, alpha1-receptor blockade after PCI produced a modest but significant prolongation of DTF at a given heart rate, thereby providing an adjunctive beneficial mechanism for improving subendocardial perfusion, which critically depends on DTF.     

Effects of Verapamil SR and Atenolol on 24-Hour Blood Pressure and Heart Rate in Hypertension Patients with Coronary Artery Disease: An International Verapamil SR-Trandolapril Ambulatory Monitoring Substudy

Elevated nighttime blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged ≥50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies. The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P<0.0001). Atenolol also decreased hourly HR (P<0.0001). Both treatment strategies decreased SBP variability (weighted standard deviation: P = 0.012 and 0.021, respectively). Compared with verapamil SR, atenolol also increased the prevalence of BP and HR nighttime dipping among prior non-dippers (BP: OR = 3.37; 95% CI: 1.26 – 8.97; P = 0.015; HR: OR = 4.06; 95% CI: 1.35-12.17; P = 0.012) and blunted HR morning surge (+2.8 vs. +4.5 beats/min/hr; P = 0.019). Both verapamil SR- and especially atenolol-based strategies resulted in favorable changes in ambulatory monitoring parameters that have been previously associated with increased adverse cardiovascular events.

Trial Registration

Clinicaltrials.gov; NCT00133692     

Reduced cardiac myofibrillar Mg-ATPase activity without changes in myosin isozymes in patients with end-stage heart failure

In this study we tested the hypothesis that reduced myofibrillar ATPase activities in end-stage heart failure are associated with a redistribution of myosin isozymes. Cardiac myofibrils were isolated from left ventricular free wall from normal human hearts and hearts at end-stage heart failure caused by coronary artery diseases, cardiomyopathy or immunological rejection. The hearts had been excised in preparation for a heart transplant. Myofibrillar Ca^2–-dependent Mg-ATPase and myosin Ca^–- and K^–EDTA-ATPase activities were compared. Possible changes in myosin isozyme distribution in the diseased heart were investigated using polyacrylamide gel electrophoresis of native myosin in the presence of pyrophosphate. Significant reduction in myofibrillar Ca²⁺-dependent Mg-ATPase with no changes in the sensitivity of the myofibrils to Ca⁺ was observed in heart with coronary artery diseases (25.2 to 27.1% at pCa 5.83 to pCa 5.05), cardiomyopathy (21.1 to 25.5% at pCa 5.41 to pCa 5.05), and in the immunologically rejected heart (18.4 to 22.8% at pCa 5.41 to pCa 5.05). Significantly lower myosin Ca²⁺-ATPase was observed with coronary artery diseases only and myosin K-EDTA activities did not differ in diseased and normal hearts. Polyacrylamide gel electrophoresis of native myosin from the normal and three models of end-stage heart failure revealed two distinct bands in the human left ventricle and one diffuse band in the human right atria. No apparent differences in myosin isoenzyme pattern were observed between the normal and diseased hearts. Further evaluation is needed to clarify the ATPase nature of the two bands.