Influence of age on cardiac baroreflex function during dynamic exercise in humans

We investigated the influence of aging on cardiac baroreflex function during dynamic exercise in seven young (22 +/- 1 yr) and eight older middle-aged (59 +/- 2 yr) healthy subjects. Carotid-cardiac baroreflex function was assessed at rest and during moderate-intensity steady-state cycling performed at 50% heart rate reserve (HRR). Five-second pulses of neck pressure and neck suction from +40 to -80 Torr were applied to determine the operating point gain (G(OP)) and maximal gain (G(MAX)) of the full carotid-cardiac baroreflex function curve and examine baroreflex resetting during exercise. At rest, mean arterial pressure (MAP) and heart rate were similar between the younger and older subjects. In contrast, the resting G(OP) and G(MAX) were significantly lower in the older subjects. The increase in MAP from rest to exercise was greater in the older subjects (Delta +20 +/- 2 older vs. Delta +6 +/- 3 younger mmHg; P < 0.001). However, the G(OP) was similar in both groups during exercise because of a reduction in the younger subjects. In contrast, G(MAX) was unchanged from rest and therefore remained lower in older subjects (-0.19 +/- 0.05 older vs. -0.42 +/- 0.05 younger beats.min(-1).mmHg(-1); 50% HRR; P < 0.001). Furthermore, exercise resulted in an upward and rightward resetting of the cardiac baroreflex function curve in both groups. Collectively, these findings suggest that the cardiac baroreflex function curve appropriately resets during exercise in older subjects but operates at a reduced G(MAX) primarily because of age-related reductions in carotid-cardiac control manifest at rest.     

Aging and physical activity determine cardiac structure and function in the older athlete.

To evaluate the effects of age and physical activity on cardiac structure and function, 45 ultra-endurance athletes were compared with 24 sedentary control subjects. Two-dimensionally guided M-mode echocardiograms and pulsed Doppler studies of left ventricular inflow velocity were obtained. Both older and younger athletes differed from age-similar sedentary control subjects in having lower heart rates (56 vs. 72 beats/min, younger; 53 vs. 74 beats/min, older), larger left ventricular cavities at end diastole (5.4 vs. 4.9 cm younger; 5.4 vs. 4.9 cm older), and higher ratios of early to atrial inflow velocities (2.14 vs. 1.37, younger; 1.32 vs. 0.83, older; all P less than 0.05). Older athletes differed from younger athletes in having higher systolic and diastolic blood pressures (131/79 vs. 122/71 mmHg), greater posterior wall thickness (1.1 vs. 0.9 cm), lower rapid filling velocity (52 vs. 70 cm/s), higher atrial systolic velocity (41 vs. 34 cm/s), and lower early-to-atrial inflow velocity ratios (1.32 vs. 2.14, all P less than 0.05). Thus the aging heart manifests structural and functional changes in response to physical activity that are similar but not identical to those seen in younger subjects. The expected pattern of cardiac alterations normally seen in response to age is modified in the older athlete, suggesting that exercise training, as well as aging, is an effective stimulus in shaping left ventricular structure and function in the older heart.     

Aging and cardiac responses to epinephrine in humans: role of neuronal uptake

In healthy humans, ganglionic blockade unmasks a clear age-related decrease in cardiac responses to isoproterenol but not to epinephrine. We postulated that an age-related decrease in neuronal uptake (which affects epinephrine but not isoproterenol) may offset a parallel decrease in beta-receptor-mediated responses. To test this concept, nine young (mean 29 +/- 2 yr) and eight older (mean 61 +/- 2 yr) healthy subjects were infused on three different study mornings with epinephrine at increasing rates either alone or combined with desipramine to eliminate differences in neuronal uptake or with desipramine and trimetaphan to induce ganglionic blockade and thereby also eliminate differences in arterial baroreflex activity. Epinephrine caused the expected rate-related increases in systolic blood pressure, heart rate, stroke volume, ejection fraction, and cardiac index. Except for the systolic blood pressure, the extent of the changes was similar in young and older subjects. After desipramine, cardiac responsiveness to epinephrine was markedly enhanced, although more (P < 0.01) in young vs. older subjects for heart rate and cardiac index (+14 vs. 7 beats/min and +1.6 vs. 1.1 l.min(-1).m(-2), respectively, at 20 ng.kg(-1).min(-1)). Combined with desipramine and trimetaphan, cardiac responses to epinephrine were further enhanced, again more (P < 0.01) in young subjects, resulting in large differences in heart rate and ejection fraction increases (+29 vs. 17 beats/min and +14 vs. 7%, respectively, at 20 ng.kg(-1).min(-1)). Here, we show that "healthy aging" in humans is associated with decreased cardiac responsiveness to the beta-agonist epinephrine; however, this decrease can be balanced by concomitant decreases in buffering of these responses by neuronal uptake and the arterial baroreflex.     

Hemodynamic and plasma atrial natriuretic factor responses to cardiac volume loading in young versus older normotensive humans.

To assess the effects of age on responsiveness of atrial natriuretic factor (ANF) release, and the possible contribution of cardiac sympathetic activity, in young (n = 8) and older normotensives (n = 7), the effects of cardiac volume load on plasma ANF, central venous pressure, and general hemodynamics were evaluated. Studies were performed after pretreatment with placebo or 80 mg propranolol. Cardiac volume loading increased central venous pressure by 3-5 mmHg (1 mmHg = 133.3 Pa); beta-blockade did not affect this response. Cardiac volume load caused significant increases in heart rate (10-15 beats/min) and cardiac index (by 0.7-0.8 L.min-1.m-2) and decreases in plasma catecholamines. Propranolol attenuated the increases in heart rate and cardiac index. These hemodynamic responses did not differ significantly between the two groups of subjects. Cardiac volume load significantly increased plasma ANF, by 87 +/- 21 pg/mL in the young normotensives and by 212 +/- 33 pg/mL in the older normotensives (p < 0.01, young vs. older). beta-Blockade did not affect this different response. Our results show that the plasma ANF response to volume loading is potentiated by aging. Although differences in atrial stretch cannot be excluded, this effect may relate to the decrease in clearance of plasma ANF occurring with aging.     

Cardiovascular responses to lower body negative pressure in trained and untrained older men.

To determine whether aerobic conditioning alters the orthostatic responses of older subjects, cardiovascular performance was monitored during graded lower body negative pressure in nine highly trained male senior athletes (A) aged 59-73 yr [maximum O2 uptake (VO2 max) = 52.4 +/- 1.7 ml.kg-1 x min-1] and nine age-matched control subjects (C) (VO2 max = 31.0 +/- 2.9 ml.kg-1 x min-1). Cardiac volumes were determined from gated blood pool scintigrams by use of 99mTc-labeled erythrocytes. During lower body negative pressure (0 to -50 mmHg), left ventricular end-diastolic and end-systolic volume indexes and stroke volume index decreased in both groups while heart rate increased. The decreases in cardiac volumes and mean arterial pressure and the increase in heart rate between 0 and -50 mmHg were significantly less in A than in C. For example, end-diastolic volume index decreased by 32 +/- 4 ml in C vs. 14 +/- 2 ml in A (P < 0.01), mean arterial pressure declined 7 +/- 5 mmHg in C and increased by 5 +/- 3 mmHg in A (P < 0.05), and heart rate increased 13 +/- 3 beats/min in C and 7 +/- 1 beats/min in A (P < 0.05). These data suggest that increased VO2 max among older men is associated with improved orthostatic responses.     

Orthostatic hypotension in aging humans

We tested the hypothesis that hypotension occurred in older adults at the onset of orthostatic challenge as a result of vagal dysfunction. Responses of heart rate (HR) and mean arterial pressure (MAP) were compared between 10 healthy older and younger adults during onset and sustained lower body negative pressure (LBNP). A younger group was also assessed after blockade of the parasympathetic nervous system with the use of atropine or glycopyrrolate and after blockade of the beta(1)-adrenoceptor by use of metoprolol. Baseline HR (older vs. younger: 59 +/- 4 vs. 54 +/- 1 beats/min) and MAP (83 +/- 2 vs. 89 +/- 3 mmHg) were not significantly different between the groups. During -40 Torr, significant tachycardia occurred at the first HR response in the younger subjects without hypotension, whereas significant hypotension [change in MAP (DeltaMAP) -7 +/- 2 mmHg] was observed in the elderly without tachycardia. After the parasympathetic blockade, tachycardiac responses of younger subjects were diminished and associated with a significant hypotension at the onset of LBNP. However, MAP was not affected after the cardiac sympathetic blockade. We concluded that the elderly experienced orthostatic hypotension at the onset of orthostatic challenge because of a diminished HR response. However, an augmented vasoconstriction helped with the maintenance of their blood pressure during sustained LBNP.     

Heart rate and extrasystolic arrhythmias in active subjects aged over 90. A chronobiological study

We analyzed the circadian rhythm of heart rate (HR), of simple atrial premature beats (APB) and of simple ventricular premature beats (VPB) in very old subjects undergoing dynamic ECG for 24 h. The 18 subjects under study (11 women and 7 men) were aged 90 or more (mean +/- SD 92.3 +/- 2.3, range 90-98), did not complain of acute cardiac pathologies, were not taking any medication and were synchronized as to time schedules. The mean duration of DECG recording was of 23 h and 54 min. The collection of data concerning the hourly mean of HR (6 ten-sec samples taken every 10 min) and of the number/hour of APB and VPB was carried out manually. A significant rhythm (single cosinor) was detected for heart rate in 14 subjects out of 18 and in the group (population cosinor); it was also detected for APB (9 subjects out of 15) and for VPB (5 subjects out of 15) also by the single cosinor. It was not detected for the group (population cosinor). No significant correlations, either direct or inverted, were revealed between HR and premature beats. We demonstrate therefore that, even in very old subjects, the circadian rhythm of HR still exists as in younger subjects.     

Long-term effect of dietary {alpha}-linolenic acid or decosahexaenoic acid on incorporation of decosahexaenoic acid in membranes and its influence on rat heart in vivo

The present study was designed to evaluate whether long-term intake of dietary alpha-linolenic acid (ALA), supplied as whole grain-extruded linseed, can increase endogenous production of n-3 long-chain polyunsaturated fatty acids (FAs) in healthy adult rats and influence the heart rate (HR) and adrenergic response in the same way as docosahexaenoic acid (DHA)-rich diets. DHA enrichment was evaluated using FA analysis of tissue phospholipids after 8, 16, 24, and 32 wk of feeding in male Wistar rats randomly assigned to three dietary groups (n = 8 in each group): a reference fat diet (RFD), an ALA-rich (ALA) diet, and a DHA-rich (DHA) diet. At 1 wk before the animals were killed, under anesthesia, HR was measured from ECG recordings during an adrenergic stimulation challenge (n = 8). There was a significant increase of DHA in the cardiac membrane in the ALA group compared with the RFD group. DHA content in the cardiac membrane was approximately 10% in the ALA group vs. 20% in the DHA group and 4% in the RFD group. The cardiac FA profile was established after 2 mo and remained essentially unchanged thereafter. Regardless of the diet, DHA in the heart decreased with age. Nevertheless, DHA content in the heart remained at >15% in the DHA group and remained greater in older rats fed the ALA diet than in younger RFD-fed rats. Basal HR decreased in the ALA group (395 +/- 24.9 beats/min) to a level between that of the DHA and RFD groups (375 +/- 26.4 and 407 +/- 36.7 beats/min, respectively). Both n-3 dietary intakes contribute to enhancement of the chronotropic response to adrenergic agonist stimulation. Regulation of HR by neurohumoral mediators may be controlled by lower content of DHA, e.g., by a dietary supply of extruded linseed (ALA).     

Leg vasoconstriction during dynamic exercise with reduced cardiac output.

We evaluated whether a reduction in cardiac output during dynamic exercise results in vasoconstriction of active skeletal muscle vasculature. Nine subjects performed four 8-min bouts of cycling exercise at 71 +/- 12 to 145 +/- 13 W (40-84% maximal oxygen uptake). Exercise was repeated after cardioselective (beta 1) adrenergic blockade (0.2 mg/kg metoprolol iv). Leg blood flow and cardiac output were determined with bolus injections of indocyanine green. Femoral arterial and venous pressures were monitored for measurement of heart rate, mean arterial pressure, and calculation of systemic and leg vascular conductance. Leg norepinephrine spillover was used as an index of regional sympathetic activity. During control, the highest heart rate and cardiac output were 171 +/- 3 beats/min and 18.9 +/- 0.9 l/min, respectively. beta 1-Blockade reduced these values to 147 +/- 6 beats/min and 15.3 +/- 0.9 l/min, respectively (P < 0.001). Mean arterial pressure was lower than control during light exercise with beta 1-blockade but did not differ from control with greater exercise intensities. At the highest work rate in the control condition, leg blood flow and vascular conductance were 5.4 +/- 0.3 l/min and 5.2 +/- 0.3 cl.min-1.mmHg-1, respectively, and were reduced during beta 1-blockade to 4.8 +/- 0.4 l/min (P < 0.01) and 4.6 +/- 0.4 cl.min-1.mmHg-1 (P < 0.05). During the same exercise condition leg norepinephrine spillover increased from a control value of 2.64 +/- 1.16 to 5.62 +/- 2.13 nM/min with beta 1-blockade (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Leg crossing improves orthostatic tolerance in healthy subjects: a placebo-controlled crossover study

Vasovagal syncope is the most common cause of transient loss of consciousness, and recurrent vasovagal fainting has a profound impact on quality of life. Physical countermaneuvers are applied as a means of tertiary prevention but have so far only proven useful at the onset of a faint. This placebo-controlled crossover study tested the hypothesis that leg crossing increases orthostatic tolerance. Nine na?ve healthy subjects [6 females, median age 25 yr (range 20-41 yr), mean body mass index 23 (SD 2)] were subjected to passive head-up tilt combined with a graded lower body negative pressure challenge (20, 40, and 60 mmHg) determining orthostatic tolerance thrice, in randomized order: 1) control, 2) with leg crossing, and 3) with oral placebo. Blood pressure (Finometer), heart rate, and changes in thoracic blood volume (impedance), stroke volume, and cardiac output (Modelflow) were followed during orthostatic stress. Primary outcome was time to presyncope (systolic blood pressure /=140 beats/min). With leg crossing, orthostatic tolerance increased from 26 +/- 2 to 34 +/- 2 min (placebo 23 +/- 3 min, P < 0.001). During leg crossing, mean arterial pressure (81 vs. 81 mmHg) and cardiac output (95 vs. 94% supine) remained unchanged; heart rate increase was lower (13 vs. 18 beats/min, P < 0.05); stroke volume was higher (79 vs. 74% supine, P < 0.05); and there was a trend toward lower thoracic impedance. Leg crossing increases orthostatic tolerance in healthy human subjects. As a measure of prevention, it is a worthwhile addition to the management of vasovagal syncope.     

Decreased RhoA expression in myocardium of diabetic rats

Diabetic cardiomyopathy is 1 of the major causes of death in diabetic patients, but the pathogenesis is unclear. There is evidence that RhoA, a small GTPase, might be involved in cardiac function. This study, therefore, analyzed RhoA expression and activation in hearts of diabetic rats. Male Sprague-Dawley rats were divided into control and diabetic groups of 18 each. Diabetes was induced by intravenous injection of streptozotocin (55 mg/kg). Rats were studied 3 weeks after induction of diabetes. Heart rate, which was measured 24 h/day, decreased by 93 +/- 7 beats/min in diabetic rats. There was a 62% decrease (p < 0.01) in RhoA mRNA expression in heart tissues (left ventricle) of diabetic rats (38.5 +/- 6.7 x 106 molecules/microg total RNA) compared with controls (101 +/- 10.3 x 106 molecules/microg total RNA). Western blot showed a 33% decrease in total RhoA protein expression in heart tissues of diabetic rats compared with controls (p < 0.05). A reduced RhoA translocation in heart tissues of diabetic rats was determined by a 64% decrease in membrane-bound RhoA (p < 0.01 vs. control group), indicating that the activation of RhoA is markedly reduced in diabetic myocardium. Our data suggest that down-regulated RhoA may be involved in cardiomyopathy in diabetic rats.     

Cardiac vagal modulation of heart rate during prolonged submaximal exercise in animals with healed myocardial infarctions: effects of training

The present study investigated the effects of long-duration exercise on heart rate variability [as a marker of cardiac vagal tone (VT)]. Heart rate variability (time series analysis) was measured in mongrel dogs (n = 24) with healed myocardial infarctions during 1 h of submaximal exercise (treadmill running at 6.4 km/h at 10% grade). Long-duration exercise provoked a significant (ANOVA, all P < 0.01, means +/- SD) increase in heart rate (1st min, 165.3 +/- 15.6 vs. last min, 197.5 +/- 21.5 beats/min) and significant reductions in high frequency (0.24 to 1.04 Hz) power (VT: 1st min, 3.7 +/- 1.5 vs. last min, 1.0 +/- 0.9 ln ms(2)), R-R interval range (1st min, 107.9 +/- 38.3 vs. last min, 28.8 +/- 13.2 ms), and R-R interval SD (1st min, 24.3 +/- 7.7 vs. last min 6.3 +/- 1.7 ms). Because endurance exercise training can increase cardiac vagal regulation, the studies were repeated after either a 10-wk exercise training (n = 9) or a 10-wk sedentary period (n = 7). After training was completed, long-duration exercise elicited smaller increases in heart rate (pretraining: 1st min, 156.0 +/- 13.8 vs. last min, 189.6 +/- 21.9 beats/min; and posttraining: 1st min, 149.8 +/- 14.6 vs. last min, 172.7 +/- 8.8 beats/min) and smaller reductions in heart rate variability (e.g., VT, pretraining: 1st min, 4.2 +/- 1.7 vs. last min, 0.9 +/- 1.1 ln ms(2); and posttraining: 1st min, 4.8 +/- 1.1 vs. last min, 2.0 +/- 0.6 ln ms(2)). The response to long-duration exercise did not change in the sedentary animals. Thus the heart rate increase that accompanies long-duration exercise results, at least in part, from reductions in cardiac vagal regulation. Furthermore, exercise training attenuated these exercise-induced reductions in heart rate variability, suggesting maintenance of a higher cardiac vagal activity during exercise in the trained state.     

Thr164Ile polymorphism of the human beta2-adrenoceptor exhibits blunted desensitization of cardiac functional responses in vivo

In subjects heterozygous for Thr164Ile beta2-adrenoceptor (beta2AR) polymorphism, cardiac responses to beta2AR agonist stimulation are blunted. In this study, we investigated agonist-induced desensitization of Thr164Ile beta2ARs. For this purpose, we assessed in six subjects with heterozygous Thr164Ile beta2ARs and in 10 subjects with homozygous wild-type (WT) beta2ARs the effects of 2-wk oral treatment with 3 x 5 mg/day terbutaline on terbutaline infusion-induced increases in heart rate (HR) and contractility [measured as shortening of HR-corrected duration of electromechanical systole (QS2c)]. Compared with WT beta2AR subjects, Thr164Ile subjects exhibited a blunted terbutaline-induced maximum increase in HR (WT 32 +/- 4 beats/min, Thr164Ile 19 +/- 3 beats/min, P < 0.05) and contractility (WT -54 +/- 2 ms, Thr164Ile -37 +/- 6 ms, P < 0.05). Two-week oral terbutaline treatment desensitized cardiac beta2AR responses to terbutaline infusion (increase in HR: WT 10 +/- 2 beats/min, Thr164Ile 8 +/- 4 beats/min; increase in contractility: WT -22 +/- 5 ms Thr164Ile: -17 +/- 6 ms); however, the extent of desensitization was larger in WT than Thr164Ile beta2AR subjects. Thus, after 2-wk oral terbutaline treatment cardiac, beta2AR responses did not differ anymore between WT and Thr164Ile beta2AR subjects. We conclude that agonist-induced desensitization of cardiac beta2ARs is more pronounced in WT than Thr164Ile subjects. Thus cardiac Thr164Ile subjects appear to be somewhat protected against agonist-induced desensitization.     

Sinus versus nonsinus tachycardia in the emergency department: Importance of age and heart rate

Background

The emergency department diagnosis of sinus versus nonsinus tachycardia is an important clinical challenge. The objective of this study was to identify subjects with a high prevalence of nonsinus tachycardia.

Methods

Heart rate and cardiac rhythm were prospective reviewed in 500 consecutive patients with heart rate ≥ 100 beats/min in a busy emergency department. A predictive model based on age and heart rate was then developed to identify the probability of nonsinus tachycardia.

Results

As age and heart rate increased, nonsinus tachycardias became more frequent. The probability of nonsinus tachycardia in a subject ≥ 71 years with heart rate ≥ 141 beats/minute was 93%, compared to only three percent in a subject ≤ 50 years with heart rate 100–120 beats/minute. A simple point score system based on age and heart rate helps predict the probability of sinus tachycardia versus nonsinus tachycardia.

Conclusion

Nonsinus tachycardia is significantly more common than sinus tachycardia in elderly patients in the emergency department. The diagnosis of sinus tachycardia becomes much less likely as age and heart rate increase.     

Heart mechanical and hemodynamic parameters of a beetle,Tenebrio molitor,at selected ages

The physiological processes that occur during the aging of insects are poorly understood. The aim of this study was to describe the changes in contractile activity and hemodynamic parameters of the heart that take place as the coleopteran beetle, Tenebrio molitor, ages. The frequency of heart contractions in beetles that had just undergone metamorphosis (median 24.7 beats/min) was significantly lower than the frequency of heart contractions in older beetles. In 56% of beetles that were < 1 week of age, a pattern of contractile activity with alternating periods of higher and lower contraction frequency was detected, suggesting that some posteclosion developmental processes occur during the first week of adulthood. All beetles that were 1 week of age showed a regular rhythm of heart contractions (median 72 beats/min). In older beetles, abnormalities such as heart arrhythmias or heart arrest were observed. The incidence of arrhythmia as well as the arrhythmicity index was highest in beetles that were 8–18 weeks old. The calculated stroke volume (SV) was also found to increase from eclosion to 12 weeks of age, and then decreased as adults aged further. Interestingly, cardiac output increased gradually, but the ejection fraction did not change significantly with age.     

Effects of altitude on exercise level and heart rate in patients with coronary artery disease and healthy controls

Background. To evaluate the safety and effects of high altitude on exercise level and heart rate in patients with coronary artery disease compared with healthy controls. Methods. Eight patients with a history of an acute myocardial infarction (ejection fraction >5%) with a low-risk score were compared with seven healthy subjects during the Dutch Heart Expedition at the Aconcagua in Argentina in March 2007. All subjects underwent a maximum exercise test with a cycle ergometer at sea level and base camp, after ten days of acclimatisation, at an altitude of 4200 m. Exercise capacity and maximum heart rate were compared between groups and within subjects. Results. There was a significant decrease in maximum heart rate at high altitude compared with sea level in both the patient and the control group (166 vs. 139 beats/min, p<0.001 and 181 vs. 150 beats/min, p<0.001). There was no significant difference in the decrease of the exercise level and maximum heart rate between patients and healthy controls (-31 vs. -30%, p=0.673). Conclusion. Both patients and healthy controls showed a similar decrease in exercise capacity and maximum heart rate at 4200 m compared with sea level, suggesting that patients with a history of coronary artery disease may tolerate stay and exercise at high altitude similarly to healthy controls. (Neth Heart J 2010;18:118-21.)     

Cardiovascular risk factors in a small urban community in central Croatia

The aim of this study was to determine in Karlovac (southern part of central Croatia) the most important risk factors for coronary heart diseases in men and women according to age < or = 59 and > or = 60 on the basis of their prevalence in 558 non-coronary patients and 442 symptomatic coronary patients. In younger male coronary patients (< or = 59 years of age) in relation to the control study, the statistically significant more frequent risk factors were hypercholesterolemia (p < 0.001), smoking (p < 0.01) and diabetes (p < 0.01). In older male patients (> or = 60 years of age) there was no statistically significant difference in a single risk factor. In younger female coronary patients, the statistically significant more frequent risk factors were hypercholesterolemia (p < 0.001) and diabetes (p < 0.001) and in older female patients diabetes (p < 0.05). This population sample showed higher prevalence of cardiovascular risk factors in younger coronary patients. The most frequent risk factors were diabetes, hypercholesterolemia and smoking. The difference is slighter in older coronary patients where it is diabetes, which is the most important for women.     

The effect of selective umbilical embolization on the common umbilical artery pulsatility index and umbilical vascular resistance in fetal sheep.

In eight anaesthesized fetal sheep (gestational age 112-127 days; term 147 days), embolization of the umbilical placental circulation was performed in order to evaluate the response of the umbilical artery pulsatility index to an exclusive increase in umbilical vascular resistance. Measurements were performed using a 20 MHz pulsed Doppler transducer and an electromagnetic flow meter mounted on the common umbilical artery and catheters at the aortic trifurcation and in one of the umbilical veins. Umbilical vascular resistance was calculated according the Poiseuille equation as the ratio of aortic to umbilical venous pressure gradient and umbilical blood flow. Microspheres were administered at 15-min intervals through a catheter in one of the cotyledonary arteries, until fetal heart rate had decreased beneath 100 beats/min or had become arrhythmic. The period of examination per fetus varied between 60 and 120 min, after which cardiac decompensation occurred. During this period, umbilical perfusion pressure increased from 20.3 +/- 4.9 to 28.1 +/- 4.7 mmHg (SD; P less than 0.01), umbilical blood flow (ml/min) decreased from 342 +/- 127 to 115 +/- 99 mmHg (SD; P less than 0.01), umbilical vascular resistance increased from 0.065 +/- 0.022 to 0.342 +/- 0.150 mmHg.min/ml (P less than 0.01) and common umbilical artery pulsatility index increased from 0.97 +/- 0.23 to 4.03 +/- 1.69 (P less than 0.01). Fetal heart rate did not change significantly (168 +/- 33 prior to cardiac decompensation versus 178 +/- 19 beats/min at baseline condition). The linear correlation between common umbilical artery pulsatility index and umbilical vascular resistance varied between 0.83 and 0.99 and the average correlation was 0.93 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related augmentation of plasma catecholamines during dynamic exercise in healthy males

Although plasma norepinephrine (NE) increases with age in response to a variety of submaximal adrenergic stimuli, the effect of age on plasma catecholamine levels during maximal aerobic effort and during submaximal work at a fixed percent of peak O2 consumption (VO2) is unknown. We therefore measured NE, epinephrine (E), and VO2 at rest and during graded maximal treadmill exercise in 24 healthy male volunteers (ages 22-77 yr) from the Baltimore Longitudinal Study of Aging who were rigorously screened to exclude the presence of cardiovascular disease. At rest neither heart rate (HR) nor VO2 were age related. Resting NE (pg/ml) was not age related, but resting E (pg/ml) was higher in male subjects 68-77 yr old (group III) than in those aged 22-37 (group I) or 44-55 yr (group II), P less than 0.01. Maximal HR (beats/min) showed a strong inverse relationship to age (203.5 - 0.65 age, r = -0.80, P less than 0.001). Peak VO2 in milliliters per kilogram total body weight per minute decreased with age (47.7 - 0.23 age, r = -0.71, P less than 0.001). At maximal effort both NE (P less than 0.01) and E (P less than 0.05) were higher in group III than in either of the younger groups. At submaximal work levels NE and E also increased with age, and when normalized for relative effort at loads between 45 and 80% of peak VO2 both NE and E were higher in the group III male subjects, although statistical significance was reached for NE (P less than 0.01) but not for E (P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)     

Age Dimorphism in the Association between Growth‐Hormone Status and the Respiratory Quotient

Objective: To investigate the impact of age on the association between the respiratory quotient (RQ) and growth‐hormone (GH) secretion and to investigate the acute lipolytic response to an exogenous GH bolus. Research Methods and Procedures: A cross‐sectional study of 36 non‐obese healthy subjects (18 women and 18 men) from two age groups was used: “younger” (mean age, 29.5 years; range, 27 to 34 years) and “older” (mean age, 50.8 years; range, 47 to 59 years). Endogenous GH secretion by means of deconvolution analysis of 24‐hour serum GH concentrations was measured every 20 minutes. Resting RQ was measured after a 12‐hour overnight fast. The lipolytic response to an intravenous exogenous GH bolus (200 μg) was assessed by measuring serum levels of free fatty acids as well as changes in RQ. Additional measurements included body composition (regional computed tomography scan and DXA) and physical fitness (Vo ₂max). Results: Resting RQ did not differ between the two age groups: 0.81 ± 0.01 (young) vs. 0.82 ± 0.01 (older; not significant). Several estimates of GH release correlated positively with RQ in the younger group, whereas a negative correlation was detected in the older subjects [GH production rate (μg/liter × kg) vs. RQ: r = 0.62, p < 0.01 (younger); r = ?0.53; p = 0.02 (older)]. By regression analysis, 52% to 58% of the variation in RQ could be explained by GH status. After an exogenous GH bolus, the incremental response in nonesterified fatty acid was slightly higher in younger individuals (p = 0.09). Discussion: Resting RQ is significantly correlated with GH status. This association is positive in younger individuals and negative in older individuals. The lipolytic response to exogenous GH is moderately higher in younger compared with older individuals. GH status should be taken into account when investigating the residual variation in RQ.