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Effects of propranolol on changes in heart rate, heart weight, kidney weight, urinary hydroxyproline and weight gain induced by large doses of thyroxine in the rat.

The effects of the beta-adrenergic receptor blocking agent, DL-propranolol, and of the antithyroid drug, carbimazole, upon some manifestations of thyroxine (T4)-induced changes in peripheral metabolism were studied in rats. Propranolol lowered the heart rate, but did not alter the following changes induced by T4: increment in heart rate, increase in heart or kidney weight, increase in urinary hydroxyproline, decrease in body weight gain or increase in serum T4. Carbimazole administration lowered serum T4 and reduced weight gain, but had no effect upon heart rate or hydroxyproline excretion.

Animals↗

Factors affecting the species-homologous and species-heterologous binding of mitochondrial ATPase inhibitor, IF1, to the mitochondrial ATPase of slow and fast heart-rate hearts.

We examined the effects of a variety of conditions upon the IF1-mediated inhibition of the ATPase in both intact and sonicated mitochondria and in IF1-depleted submitochondrial particles (SMP) in species-homologous and species-heterologous combinations of IF1 and ATPase. IF1-mediated ATPase inhibition occurred in intact rabbit heart mitochondria at low matrix pH and low membrane potential, but not in intact pigeon and rat heart mitochondria under the same conditions. IF1-mediated ATPase inhibition was, however, demonstrable in both the rabbit and pigeon heart systems in sonicated mitochondria incubated at low ionic strength. The rat heart system failed to exhibit significant IF1-mediated ATPase inhibition in either intact or sonicated mitochondria due to the low amount of IF1 present. When rabbit heart IF1-containing extracts were incubated with IF1-depleted rabbit heart SMP over a range of KCl concentrations, increasing the [KCl] to 100 mM had little effect on IF1-mediated ATPase inhibition. When pigeon heart IF1-containing extracts were incubated with IF1-depleted pigeon heart SMP under the same conditions, increasing [KCl] to 100 mM nearly completely blocked IF1-mediated ATPase inhibition. While the species-endogenous level of rat heart IF1 (i.e., 1x IF1) inhibited IF1-depleted rat heart SMP virtually not at all at any [KCl] examined, the 8x rat heart IF1 was nearly as inhibitory as the 1x rabbit heart IF1 at varying ionic strengths. When rabbit, pigeon, or rat heart IF1 was bound to rabbit versus pigeon IF1-depleted SMP, the effect of varying ionic strength on IF1-mediated ATPase inhibition was related to the species source of the IF1, not to the species source of the enzyme; 1x bovine heart IF1 purified to homogeneity behaved much like 1x crude rabbit heart IF1 when binding to either the rabbit or the pigeon heart enzyme. This suggests that an IF1-ATPase complex stabilizing factor such as has been isolated from baker's yeast cells in neither lacking in the pigeon heart system nor required for the more ionic-strength-resistant binding of IF1 observed in slow heart-rate mammalian heart mitochondria.

Adenosine Triphosphatases↗

Temperature effects on ventilatory rate, heart rate, and preferred pedal rate during cycle ergometry.

According to the most customary exercise protocols, core temperature (Tc) rises in parallel with workload (WL) and experimental time. Physiological variables, however, may be related to each of these factors. To investigate effects of WL independent of experimental time and body temperature, we employed four moderate WLs in 4-min steps between 35 and 65% peak O2 uptake (VO2 peak) in randomized order. To investigate independent effects of body temperature, the same work protocol was performed both after resting in comfortable ambient temperature [control test (Cont)] and after a double cold exposure [precooling test (Pret)], where Tc and the temperature set point are decreased by approximately 0.6 and 0.3 degrees C, respectively. Eight male subjects (24 +/- 1.9 yr, VO2 peak 4.9 +/- 0.5 l/min) worked on a cycle ergometer in a climatic chamber. Heart rate (HR) and breathing frequency (BF), but not preferred pedal rate (PR), were positively correlated to Tc, the slopes amounting to 17 and 3.75 min-1/degree C for HR and BF, respectively. The regression appeared linear over the whole temperature range, and the regression lines were not shifted by precooling. PR was increased by time, but Pret-Cont differences of PR and Tc were inversely correlated (r = -0.50, P < 0.01). The effects of WL were highly significant on HR, O2 uptake, and rate of perceived exertion but not on BF, PR, and sweat rate. The relation of rate of perceived exertion to HR was shifted by precooling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Factors affecting the loss of mitochondrial function during zero-flow ischemia (autolysis) in slow and fast heart-rate hearts.

The (uninhibited) mitochondrial ATPase comprises approximately 90% of the total ATP hydrolyzing activity present in quiescent, ischemic canine heart muscle and its inhibition by its natural inhibitor protein plays a pivotal role in the slowing of tissue ATP depletion during ischemia. While dog heart mitochondria contain a full complement of mitochondrial ATPase inhibitor capable of fully down-regulating the enzyme activity present in this species, rat heart mitochondria contain a much lower level of inhibitor, sufficient to inhibit the enzyme activity present in this species by only approximately 20%. Moreover, this fractional complement of inhibitor remains largely inoperative in the ischemic rat heart. As shown in the present study, one apparent result of the lack of a functional complement of mitochondrial ATPase inhibitor in the rat heart is a more rapid rate of cell ATP depletion during zero-flow ischemia. This in turn results in a more rapidly developed and initially more severe cell acidosis in the ischemic rat heart because ATP hydrolysis produces protons. Finally, and consistent with earlier studies by us, the more rapid ATP depletion together with the more severe acidosis appears to result in a marked increase in the rate of loss of mitochondrial respiratory function in the ischemic rat heart compared to the ischemic dog heart. Our findings suggest that slow heart-rate hearts which contain in situ functional mitochondrial ATPase inhibitor, possess an effective mechanism for sparing cell ATP stores during early ischemia, whereas fast heart-rate hearts which lack in situ mitochondrial ATPase inhibitor function, possess a less effective ATP sparing mechanism.

Adenosine Triphosphatases↗

ATP depletion and mitochondrial functional loss during ischemia in slow and fast heart-rate hearts.

In the present study, isolated dog and rat hearts were perfused in the Langendorff mode with Krebs bicarbonate buffer in the absence and presence of 10(-5) M oligomycin. The perfusion protocols employed allowed tissue pH to drop during subsequent ischemic incubations essentially as it would in blood-perfused hearts. Tissue pH, ATP, lactate, and mitochondrial respiratory function were measured during the course of subsequent zero-flow ischemic incubations. The adenosinetriphosphatase (ATPase) activities attributable to both mitochondrial and nonmitochondrial ATPases in sonicated heart homogenates and the actomyosin ATPase in isolated cardiac myofibrils were measured in both species. Consistent with earlier results with a different model in which tissue pH was buffered during the ischemic incubations [W. Rouslin, J. L. Erickson, and R. J. Solaro. Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H503-H508, 1986], the inhibition of the mitochondrial ATPase in situ by oligomycin markedly slowed both tissue ATP depletion and the loss of mitochondrial function during ischemia in the dog. However, oligomycin had only a very small and transient effect on ATP depletion and mitochondrial function in the rat. This was apparently so because of the fivefold higher rate of glycolytic ATP production as well as the nearly threefold higher total nonmitochondrial ATPase activity of ischemic rat compared with ischemic dog heart. These results suggest that although the inhibition of the mitochondrial ATPase makes a major contribution to ATP conservation in ischemic dog heart, it makes only a very small contribution in rat.

Adenosine Triphosphatases↗

Relationship between heart rate turbulence and heart rate, heart rate variability, and number of ventricular premature beats in coronary patients.

INTRODUCTION: Heart rate variability (HRV) illustrates regulation of the heart by the autonomic nervous system whereas heart rate turbulence (HRT) is believed to reflect baroreflex sensitivity. The aim of this study was to determine the association between HRT and HRV parameters and the relationship between HRT parameters and heart rate and number of ventricular premature beats (VPBs) used to calculate HRT parameters. METHODS AND RESULTS: In 146 patients (117 males and 29 females; mean age 62 years) with coronary artery disease, a 24-hour ECG Holter monitoring was performed to calculate mean heart rate (RR interval), number of VPBs, time- and frequency-domain HRV parameters and two HRT parameters: turbulence onset (TO) and turbulence slope (TS). Univariate and multivariate regression analyses were performed to evaluate the association between tested parameters. Significant correlation between TS and mean RR interval was observed (r = 0.42; p < 0.001), while no association for TO vs. RR interval was found. TS values were significantly higher in patients with less than 10 VPBs/24 hours than in patients with more frequent VPBs. Significant associations between HRT and HRV parameters were found with TS showing stronger correlation with HRV parameters than TO (r value ranging from 0.35 to 0.62 for TS vs. -0.16 to -0.38 for TO). CONCLUSION: HRT parameters correlate strongly with HRV parameters indicating that HRT should be considered as a reflection of both baroreceptors response and overall autonomic tone. Heart rate dependence of turbulence slope indicates the need to adjust this parameter for heart rate.

Coronary Disease↗

The effects of specific respiratory rates on heart rate and heart rate variability.

In this study respiratory rates of 3, 4, 6, 8, 10, 12, and 14 breaths per minute were employed to investigate the effects of these rates on heart rate variability (HRV). Data were collected 16 times at each respiratory rate on 3 female volunteers, and 12 times on 2 female volunteers. Although mean heart rates did not differ among these respiratory rates, respiratory-induced trough heart rates at 4 and 6 breaths per minute were significantly lower than those at 14 breaths per minute. Slower respiratory rates usually produced higher amplitudes of HRV than did faster respiratory rates. However, the highest amplitudes were at 4 breaths per minute. HRV amplitude decreased at 3 breaths per minute. The results are interpreted as reflecting the possible effects of the slow rate of acetylcholine metabolism and the effect of negative resonance at 3 cycles per minute.

Adult↗

A point-process model of human heartbeat intervals: new definitions of heart rate and heart rate variability.

Heart rate is a vital sign, whereas heart rate variability is an important quantitative measure of cardiovascular regulation by the autonomic nervous system. Although the design of algorithms to compute heart rate and assess heart rate variability is an active area of research, none of the approaches considers the natural point-process structure of human heartbeats, and none gives instantaneous estimates of heart rate variability. We model the stochastic structure of heartbeat intervals as a history-dependent inverse Gaussian process and derive from it an explicit probability density that gives new definitions of heart rate and heart rate variability: instantaneous R-R interval and heart rate standard deviations. We estimate the time-varying parameters of the inverse Gaussian model by local maximum likelihood and assess model goodness-of-fit by Kolmogorov-Smirnov tests based on the time-rescaling theorem. We illustrate our new definitions in an analysis of human heartbeat intervals from 10 healthy subjects undergoing a tilt-table experiment. Although several studies have identified deterministic, nonlinear dynamical features in human heartbeat intervals, our analysis shows that a highly accurate description of these series at rest and in extreme physiological conditions may be given by an elementary, physiologically based, stochastic model.

Adult↗

Relation of mean heart rate and heart rate variability in patients with left ventricular dysfunction.

The new finding was that mean heart rate and heart rate variability were more closely coupled in patients with more advanced LV dysfunction. Mean heart rate explained a larger portion of variance in heart rate variability in patients in the lowest LVEF quartile than in those in the highest one. These results support our hypothesis that sympathetic activation in patients with more severe LV dysfunction results in closer correlation between heart rate and heart rate variability. Generally, the correlation between mean heart rate and heart rate variability is weak because heart rate and heart rate variability represent different modalities of cardiovascular regulation. Mean heart rate is normally determined by the interactions of both the sympathetic and parasympathetic nervous systems, whereas modulation of these activities, with different gains, determines the magnitude of heart rate variability. This results in great complexity in control of the heart by the autonomic nervous system. However, heart rate is likely to be more dominantly regulated by the sympathetic nervous system because of vagal withdrawal in patients with more severe LV dysfunction. The effect of sympathetic cardiac modulation has been shown to be more sluggish than that of the parasympathetic nervous system in beat-to-beat regulation of heart rate. This may result in more blunted heart rate variability concomitantly with elevated mean heart rate. Thus, variation in heart rate variability in any given mean heart rate is likely to be lower than in patients with more preserved LV function, and hence with more complex cardiac autonomic regulation with involvement of the parasympathetic nervous system. Indeed, even the slopes of regression lines between mean heart rate and heart rate variability were similar in the first and fourth LVEF quartile; the intercept of the regression line was significantly higher in the fourth quartile than in the first one. This further supports our hypothesis.

Adult↗