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Biomedical subjects

E G Lakatta

Publications and source records attributed to E G Lakatta.

16 recordsLinked to original sources
PubMed1979

Alterations in the cardiovascular system that occur in advanced age.

Recent information appears to solidify the concept that the left ventricle hypertrophies with age in normal adult man. The stimulus for this moderate increase in wall thickness has not been precisely determined but an attractive hypothesis suggests that the stimulus may be an increased load imposed by the peripheral vascular resistance. The mechanism for the well-documented diminished cardiovascular response to maximal exercise in normal aged man still remains unclear. Evidence in the canine model indicates that a diminished chronotropic response to catecholamines could in part explain a limitation in maximal heart rate response. The reflex change in heart rate in respone to hypercapnia, hypoxia, and sustained isometric handgrip in normal man is diminished with age. The precise mechanism of this age-associated phenomenon remains to be elucidated, but the chronotropic responsiveness to catecholamines is likely a contributing factor. Finally, there is evidence of slowed myocardial relaxation in hearts of aged animals and man. A decrement in the speed at which the sarcoplasmic reticulum from hearts of aged rats accumulates calcium has been demonstrated and appears to be involved in the mechanism of prolonged contraction in aged myocardium.

Adult↗
PubMed1979

Calcium overload and mechanical function in posthypoxic myocardium: biphasic effect of pH during hypoxia.

Mechanical function and calcium accumulation in the myocardium during and after hypoxia were examined in the isolated but arterially perfused interventricular rabbit septum. The pH of the perfusate during hypoxia was varied from 7.4 to 6.6 by increase of the pCO2. All septa were reoxygenated for 30 min at pH 7.4. In the posthypoxic period the recovery of developed tension was greatest and the magnitude of contracture least in those septa perfused at pH 6.8 during hypoxia; calcium overload did not occur. By contrast, marked calcium overload (3.5 mumol/g wet wt) occurred in septa perfused at pH 7.4 during hypoxia. Reduction of pH to 6.6 during hypoxia did not result in a greater degree of recovery of developed tension or complete reversal of contracture in the posthypoxic period, and marked calcium overload was not prevented. These results indicate that: (1) partial recovery of mechanical function in the posthypoxic period can occur concurrent with a net gain of calcium; (2) the beneficial effects on recovery in the posthypoxic period in septa perfused at pH 6.8 during hypoxia may be in part released to prevention of calcium overload; (3) the beneficial effects of acidosis are lost when the perfusate pH is reduced to 6.6 during hypoxia.

Acid-Base Equilibrium↗
PubMed1977

Distance correction for precordial electrocardiographic voltage in estimating left ventricular mass: an echocardiographic study.

This study was undertaken to assess both the relation between echocardiographic measurement of left ventricular (LV) mass and commonly used electrocardiographic criteria for LV hypertrophy and the effect of the distance from the center of LV mass to the anterior chest wall on precordial voltage. Echocardiograms and standard 12-lead electrocardiograms were obtained on 100 persons, ages 3 to 79. The correlation coefficients of echocardiographically determined LV mass with ECG precordial voltage (SV1 + RV5 or V6), the Estes point score system, and a VL4 wave voltage were .686, .721, and .531, respectively. Extrapolating from the dipole nature of the heart, the precrodial voltage was multiplied by the square of the chest wall to mid-LV distance to correct for the loss of energy across the distance from LV to recording electrode. Utilizing this correction, a much improved precordial voltage estimation of LV mass (r = .846) was obtained. We conclude that the distance of the center of LV mass from the chest wall influences the amplitude of recorded precordial voltage and that correction for this influence improved the correlation of precordial voltage with LV mass.

Adolescent↗
PubMed1977

Echocardiographic assessment of a normal adult aging population.

Echocardiograms were performed on 105 male participants in the National Institutes on Aging's volunteer Longitudinal Study Program. All subjects (25--84 years of age) were physically active and had no evidence of hypertension or cardiovascular disease. Measurements were made of the initial diastolic (E-F) slope of the anterior mitral valve leaflet, the aortic and left ventricular cavity dimensions, and the thickness of the posterior left ventricular wall. Fractional shortening of the minor semi-axis of the left ventricle and the velocity of circumferential fiber shortening were also determined. It was found that increasing age correlated with a decrease mitral valve E-F slope and increased aortic root diameter and left ventricular wall thickness. Aging did not affect left ventricular cavity dimension, fractional shortening of the minor semi-axis, and velocity of circumferential fiber shortening. These findings suggest that aging in the normal male is associated with altered left ventricular diastolic filling, increased aortic root diameter and left ventricle hypertrophy but little change in contractile ability in the resting state.

Adult↗
PubMed1977

Length-dependent activation: its effect on the length-tension relation in cat ventricular muscle.

In cat papillary muscles at 30 degrees C, bathed with Tyrode's solution containing 2.25 mM Ca2+, the effect of various inotropic interventions (varying the stimulus frequency and continual paired stimulation) on the shape of the steady state length-tension relation was examined at lengths from Lmax, where tension production is maximal, to 0.87 Lmax. The relative steepness of the length-tension curves for peak tension developed (DT) and for maximum rate of tension development (dT/dT) varied inversely with the degree of potentiation. Thus, during paired pulse stimulation the relative decline in DT and dT/dT for a given change in muscle length was significantly less than the decline observed during stimulation at 5 min-1. When a muscle was stretched DT did not reach its final steady level for several minutes, and this slow increase in DT contributed significantly to the steepness of the steady state length-tension relation. The half-time of the slow increase in DT exhibited beat-dependency, and conditions that reduce the transsarcolemmal influx of calcium (reduction in bathing [Ca2+] or the presence of verapamil) significantly prolonged the time course of the slow increase and reduced its magnitude. These results support the hypothesis (1) that there is length-dependence of the excitation-contraction coupling process, such that an increase in muscle length is accompanied by greater activation of the contractile system; and (2) that this is due at least in part to an increased influx of calcium into the muscle cells. The implication of this hypothesis is that the influence of muscle length on myocardial performance (the Frank-Starling relation) should not be regarded as fundamentally different in character from other inotropic interventions.

Animals↗
PubMed1975

Diminished inotropic response of aged myocardium to catecholamines.

The effect of advanced age on the response of active tension, maximal rate of tension development (dT/dt), and contraction duration to catecholamines and to calcium was evaluated in isometric trabeculae carneae from young adult (6-month-old), middle-aged (12-month-old), and aged (25-month-old) rats. Control values were not age dependent except for that for contraction duration which was prolonged in the aged group. At a norepinephrine concentration of 8 times 10-5M, dT/dt increased to 163.8 plus or minus 5.3% of control in the young adult group and to 125.9 plus or minus 6.3% of control in the aged group (P smaller than 0.001). Active tension increased to 121.3 plus or minus 4.0% of control in the young adult muscles but did not increase in the aged muscles (P smaller than 0.01). Contraction duration shortened proportionately in both age groups. Similar results were obtained with isoproterenol. In contrast to the response to catecholamines, there was no age difference in the response of active tension and dT/dt to increasing concentrations of calcium. It is concluded that the intrinsic inotropic response to catecholamines is diminished in the aged myocardium. This finding does not appear to result from differences in tachyphylaxis, tissue uptake of catecholamines, or the ability of the contractile proteins to respond to increasing concentrations of calcium but instead may result from a decreased ability of catecholamines to increase the intracellular calcium available for contraction.

Aging↗
PubMed1975

Prolonged contraction duration in aged myocardium.

Isometric performance at 29degreesC was measured in left ventricular trabeculae carneae from young adult (6-mo) and aged (25-mo) rats (n equals 18 in each group). Active tension and maximal rate of tension development did not differ with age, but contraction duration was 255plus or minus6 ms in the young adult and 283plus or minus6 ms in the aged group (P less than0.001). Although catecholamine content per gram heart weight was less in the aged myocardium, additional experiments showed that neither 1 times 10-6 M propranolol nor pretreatment with 6-hydroxydopamine eliminated the age difference in contraction duration. To determine if this age difference resulted from a prolonged active state, electromechanical dissociation and the overshoot of contraction duration during recovery from hypoxia were measured. During paired stimulation greater mechanical refractoriness was found in aged muscles (P less than0.01), but intracellular action potential recordings showed no age difference in the electrical refractory period. On recovery from hypoxia, contraction duration overshoot was 117plus or minus 4percent of control in the young and 138plus or minus 4percent of control in the aged muscles (P less than0.01). The greater electromechanical dissociation and greater overshoot in contraction duration following hypoxia in aged myocardium suggests that prolonged contraction duration in aged myocardium results from a prolonged active state rather than changes in passive properties or myocardial catecholamine content.

Action Potentials↗