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G E Taffet

Publications and source records attributed to G E Taffet.

32 records · Page 2Linked to original sources
PubMed1994

Mechanisms for the responses of cardiac muscle to physical activity in old age.

The decline of maximal cardiac output (Qmax) is a major factor responsible for the lower maximal oxygen consumption of elderly mammals. The lower Qmax is associated with aging-related decreases in maximal heart rate (HR-max) and maximal stroke volume (SVmax). The mechanism(s) for the slower HRmax, unchanged by exercise training, is unknown. The decrement in SVmax, however, can be improved, as shown by the enhanced systolic and diastolic properties of the elderly heart after exercise training. One major problem is diastolic dysfunction observed in the absence of disease. Diastolic dysfunction (a decrease in peak ventricular filling after systole or a prolonged relaxation of contracted muscle) results from in part a downregulation of the sarcoplasmic reticulum's (SR) calcium ATPase that sequesters cytosolic calcium via the hydrolysis of ATP. Exercise training of sedentary old mammals produces a faster relaxation and an upregulation of the SR calcium ATPase. Yet the characteristic shift of myosin toward the slower isoform is unaltered by exercise training. The molecular signals and mechanisms underlying these aging-related alterations in sedentary and physically active individuals are unknown. An enhancement of cardiac function by exercise training, though, is preserved in advanced age.

Aged↗
PubMed1993

The calcium uptake of the rat heart sarcoplasmic reticulum is altered by dietary lipid.

Small amounts of dietary n-3 fatty acids can have dramatic physiological effects, including the reduction of plasma triglycerides and an elevation of cellular eicosapentanoic (EPA) and docosahexanoic acids (DHA) at the expense of arachidonic acid (AA). We investigated the effects of alterations in the fatty acid compositions of cardiac sarcoplasmic reticulum (CSR) produced by dietary manipulation on the calcium pump protein that is required for energy dependent calcium transport. CSR was isolated from rats fed menhaden oil, which is rich in n-3 fatty acids, and from control animals that were given corn oil. Relative to control membranes, those isolated from rats fed menhaden oil, had a lower content of saturated phospholipids, an increased DHA/AA ratio, and an increased ratio of n-3 to n-6 fatty acids. These changes were associated with a 30% decrease in oxalate-facilitated, ATP-dependent calcium uptake and concomitant decreased Ca-ATPase activity in the membranes from the animals fed menhaden oil. In contrast, there was no alteration in active pump sites as measured by phosphoenzyme formation. Thus, the CSR Ca-ATPase function can be altered by dietary interventions that change the composition, and possibly structure, of the phospholipid membranes thereby affecting enzyme turnover.

Adenosine Triphosphatases↗
PubMed1993

Mitochondrial metabolism and substrate competition in the aging Fischer rat heart.

OBJECTIVE: The objective was to examine mitochondrial oxidative metabolism of long chain fatty acids and to compare it with glucose uptake and the generation of pressure-volume work in hearts from mature and aged rats. METHODS: Hearts from mature (8 to 15 months of age) and old (28 to 30 months) Fischer 344 rats were perfused as working hearts with either 10 mM glucose or glucose plus 1 mM oleic acid (2% bovine serum albumin) and rates of glucose extraction were determined. Hearts were subjected to a stepwise increase in work load. In separate experiments, mitochondria were isolated from mature and old rat hearts and assayed for respiratory function, carnitine exchange, carnitine palmitoyltransferase activities, and phospholipid content. RESULTS: Although there were no differences in peak work attained between the mature and old rats in the presence of either glucose alone or glucose plus oleic acid, glucose utilisation was significantly decreased by oleate in the mature animals only. No significant changes in either glutamate or succinate (+rotenone) supported respiration were found in heart mitochondria isolated from old rats compared with mature animals. In agreement with prior studies with the Wistar rat model of aging, significant decrements in the rates of palmitoylcarnitine oxidation and carnitine exchange were apparent in the old Fischer animals. A significant lowering of heart mitochondrial carnitine palmitoyltransferase I activity was also found in the old animals. A decrease in the amounts of carnitine loaded in mitochondria from old animals is consistent with reduced carnitine content in both mitochondria and whole hearts from aged Wistar and Fischer rats. A significant (23%) reduction in heart mitochondrial cardiolipin content from 30 month old Fischer rats suggests that this phospholipid may also contribute to the lower rates of carnitine and acylcarnitine transport across the mitochondrial inner membrane. CONCLUSION: The limitation in the delivery of fatty acyl units to beta oxidation as measured in isolated heart mitochondria from old rats has a physiological correlate in the intact heart. The well documented suppression of glucose oxidation by fatty acids seen in the adult rat heart is not seen in old hearts, supporting the in vitro finding of decreased oxidation of palmitoylcarnitine with senescence.

Aging↗
PubMed1993

CaATPase content is lower in cardiac sarcoplasmic reticulum isolated from old rats.

The rate of oxalate-facilitated ATP-dependent calcium uptake by the calcium pump, calcium adenosinetriphosphatase (CaATPase), is 30-40% slower in the sarcoplasmic reticulum (SR) isolated from the hearts of senescent Fischer 344 male rats. To determine the underlying mechanism, cardiac SR was isolated from 11- to 12-mo-old (adult) and 22- to 24-mo-old (senescent) male Fischer 344 rats. The yield of SR and contamination by other membrane organelles were similar between the groups. The rate of calcium uptake by the homogenate and isolated SR was 28-44% slower (P < 0.05) in the senescent group. In the isolated SR the calculated maximal velocity (Vmax) of CaATPase activity as a function of varying concentrations of ATP or calcium was 20-30% lower (P < 0.05) in the senescent group; however, the affinities for both calcium and ATP of CaATPase activity were unaltered. The lower Vmax was matched by a decreased (P < 0.05) content of calcium-dependent phosphoenzyme (EP) in the SR isolated from the senescent rats. Thus the ratio of enzyme activity to phosphoenzyme content (Vmax/EP) was similar between the groups. The immunoreactive CaATPase protein was 22 +/- 2% lower in the SR from the senescent rats. Taken together the data indicate that the major mechanism underlying the slower calcium transport by cardiac SR isolated from old rats is a lower content of the CaATPase protein.

Adenosine Triphosphatases↗
PubMed1992

The MgATPase activity of rat cardiac sarcoplasmic reticulum is a function of the calcium ATPase protein.

Magnesium-dependent ATPase (MgATPase) activity is associated with many E1-E2 or P-type transport ATPases including the sarcoplasmic reticulum (SR) calcium ATPase. The SR isolated from rat heart has a MgATPase activity which is 6-12 times faster than the MgATPase activity of the SR isolated from dog heart. To determine the origin of the high MgATPase activity of rat heart SR, we compared and contrasted cardiac SR isolated from both species. The preparations were similar in the following ways: (i) contamination by other organelles; (ii) the comigration of MgATPase activity with calcium-dependent ATPase (CaATPase) activity through a sucrose gradient; (iii) a similar ATPase activity sensitivity to pH and ATP concentration; (iv) the high and similar of sensitivity of ATPase activity to detergent; and (v) a similar protein profile. In both preparations, a single protein in the 105,000-Da region of polyacrylamide gels was phosphorylated by ATP, and the phosphorylated species was an acylphosphate formed in the presence and absence of calcium. Dimethyl sulfoxide, which slows acylphosphoenzyme breakdown, markedly inhibited both CaATPase and MgATPase activities of both preparations but not other enzyme activities. Importantly, the specific inhibitor of the SR calcium pump, thapsigargin, completely inhibited the CaATPase activity with an I50 of 6-7 nM; however, a higher concentration (I50 of 2 microM) was required to inhibit the MgATPase activity of the rat cardiac SR. These results provide evidence that the MgATPase activity of rat cardiac SR is part of the enzyme cycle of the calcium ATPase protein.

Adenosine Triphosphate↗
PubMed1992

Survival of elderly men with congestive heart failure.

Congestive heart failure (CHF) is the most common discharge diagnosis for elderly patients. The survival of elderly (age greater than or equal to 75 years) patients with CHF has not recently been reported, especially with reference to left ventricular ejection fraction (LVEF). A patient database was searched for the diagnosis of CHF and then screened for age greater than or equal to 75, Framingham Criteria for CHF and an LVEF evaluation. Ninety-four men fitted all criteria, including a minimum potential follow-up of 3 years. Life-table analysis was employed to compare their survival experience to an expected survival based on a sex- and age-equivalent subset of the 1980 Census data. Causes of death were determined from autopsy, medical records or death certificates. Mean age at onset of CHF was 82.5. Forty-three per cent had an LVEF greater than or equal to 0.45. There was no difference in the prevalence of potential aetiologies between those with LVEF greater than or equal to 0.45 versus LVEF less than 0.45. Life-table analysis revealed that CHF patients had a worse survival than controls for the first 5 years after diagnosis, attributable primarily to a high first-year mortality (28%) for the CHF group. There was no difference in survival between the LVEF greater than or equal to 0.45 and LVEF less than 0.45 groups.

Aged↗
PubMed1991

Nucleotide specificity of cardiac sarcoplasmic reticulum. Inhibition of GTPase activity by ATP analogue in fluorescein isothiocyanate-modified calcium ATPase.

Unlike skeletal muscle sarcoplasmic reticulum, canine cardiac sarcoplasmic reticulum hydrolyzes GTP in ways that are similar and different from ATP hydrolysis. Also, ATP and ATP analogues inhibit GTPase activity noncompetitively with a Ki compatible with the high affinity ATP-binding site (c.f. Tate, C.A., Bick, R.J., Blaylock, S., Youker, K., Scherer, N.M., and Entman, M.L. (1989) J. Biol. Chem. 264, 7809-7813). This suggested that ATP and GTP may enter the reaction pathway at separate nucleotide-binding sites on the CaATPase. To test this hypothesis, cardiac sarcoplasmic reticulum was incorporated with fluorescein isothiocyanate (FITC), which apparently binds at or near the ATP-binding site of the enzyme, preventing ATP binding. After FITC incorporation, calcium-dependent ATPase activity, but not GTPase activity, was completely inhibited. Adenyl-5'-yl imidodiphosphate (AMP-P(NH)P), but not guanyl-5'-yl imidodiphosphate, protected against FITC incorporation and the inhibition of calcium-dependent ATPase activity; at least 100 microM AMP-P(NH)P was required for some protection. Despite FITC incorporation, AMP-P(NH)P still inhibited the GTPase activity with a Ki of 3-7 microM. Direct photo-affinity labeling with either 0.2 microM [alpha-32P]ATP or 0.2 microM [alpha-32P]GTP demonstrated that FITC incorporation did not prevent ATP or GTP binding. The mechanism of FITC inhibition of calcium-dependent ATPase activity was related to the prevention of all calcium-dependent, but not calcium-independent, reactions with both nucleotides.

Adenosine Triphosphate↗
PubMed1991

The role of calcium in the energetics of contracting skeletal muscle.

In its second messenger role in skeletal muscle, calcium coordinates the function of muscle (contractile activity) with its overall energetics, thereby controlling the provision of ATP in a time of need. Not only is ATP required for crossbridge turnover in the myofibrils, but it is also needed for the maintenance of ion pumps, nuclear activity, and so forth. When oxygen is limiting, the sustained contractions of both fast and slow muscle (after the immediate burst of activity) is primarily supported by glycogenolysis and the glycolytic pathway (anaerobic). Calcium is important to this process, and the compartmentation of the glycogen particle and some of the enzymes associated with the glycolytic pathway in the terminal cisternae of the sarcoplasmic reticulum ensures that the provision of glucose-6-phosphate to the glycolytic pathway for the generation of the needed ATP proceeds rapidly. The activation of phosphorylase and glycogenolysis by calcium-troponin-C is another example of the tight control of cellular energetics deemed possible by compartmentation within the cell. The regulation by calcium, therefore, is only dependent on the diffusion of calcium rather than diffusion of substrate. When oxygen is not limiting (i.e. when a new steady-state is reached), the aerobic metabolism of pyruvate and fatty acids may be regulated in part by calcium at least in slow skeletal muscle. Oxidative phosphorylation, where ADP is phosphorylated to ATP, is though to be controlled by the concentration of ADP in skeletal muscle. However, because of the obvious compartmentation of the mitochondria within the slow muscle fibre and the higher free calcium required for peak force development (5 mumol/L), the kinetics are theoretically favourable for the calcium cycle in slow muscle mitochondria to play an important role in the regulation of aerobic substrate oxidation, as it does in the heart. Although this hypothesis is attractive based on the available data, the direct demonstration of a major role for calcium as a regulator of substrate oxidation in slow muscle awaits experimentation.

Adenosine Triphosphate↗
PubMed1990

Enhanced calcium uptake of cardiac sarcoplasmic reticulum in exercise-trained old rats.

To determine whether endurance exercise training initiated during senescence improves the slower calcium transport of cardiac sarcoplasmic reticulum in senescent rats, three groups of male Fischer 344 rats were used: sedentary mature (SM), 11-12 mo of age; sedentary old (SO), 23-24 mo of age; and exercised old (EO), 23-24 mo of age. The EO rats ran on a motor-driven treadmill 5 days/wk for 8-10 wk while two other groups remained sedentary. The contraction duration of isometrically contracting papillary muscle was prolonged in the SO rats compared with the SM group, resulting from both a longer time-to-peak tension and a longer half-relaxation time. Chronic exercise improved the papillary muscle contractile function of the EO group to that observed in the younger SM rats. More importantly, the exercise regime ameliorated the slower oxalate-supported, ATP-dependent calcium transport observed in the SO group so that the EO and SM groups were the same. In contrast, the calcium-activated myosin adenosinetriphosphatase activity, which was slower in the SO group, was not altered after exercise training, so that both senescent groups were slower than the SM rats. Thus the increased calcium transport by the cardiac sarcoplasmic reticulum may be one of the potential mechanisms underlying the improvement of myocardial performance with chronic exercise initiated during senescence.

Aging↗
PubMed1989

The regulatory role of calcium in striated muscle.

Calcium plays numerous roles in striated muscle, including excitation-contraction coupling and the stimulation of substrate oxidation by the mitochondria. These two topics are considered in this symposium. The purpose of this introductory paper is to present a conceptual framework about the control of calcium movements in striated muscle. Additionally, we provide a brief historical perspective regarding the key research observations leading to our current understanding of the various cellular systems controlling calcium flux in the muscle cell.

Calcium↗
PubMed1988

In-hospital cardiopulmonary resuscitation.

A retrospective review of 399 cardiopulmonary resuscitation (CPR) efforts in 329 veterans was performed to evaluate the observation that few geriatric patients were discharged alive after they underwent CPR. Cardiopulmonary resuscitation efforts with witnessed arrests were more frequently successful than efforts with unwitnessed arrests (47.7% vs 29.9%) and resulted in live discharge more often than efforts with unwitnessed arrests. Cardiopulmonary resuscitation efforts that resulted in a live discharge were more brief and involved a lower mean number of medication doses. Of the 77 CPR efforts in patients 70 years of age or older who had arrests, 24 (31%) were successful, and in 22 (92%), patients were alive after 24 hours. None lived to discharge. There were 322 CPR efforts in the younger cohort; 137 (43%) were successful, in 124 (91%) of these 137 efforts, patients were alive after 24 hours, and in 22 (16%), patients were discharged alive. Older patients were significantly less likely to live to discharge both at the time of arrest and 24 hours after successful resuscitation. When a multivariate analysis was used, the presence of sepsis, cancer, increased age, increased number of medication doses administered, and absence of witness were all "predictive" of poor outcome. Cardiopulmonary resuscitation should be administered only to those who have the greatest potential benefit from this emotionally and physically traumatic procedure.

Adult↗
PubMed1988

Urinary incontinence in a community-residing elderly population.

A self-administered postal questionnaire was presented to all attending members (843) of local summer meetings of a national association for retired persons. A 71% response rate (599) revealed that 33% of the total sample population experienced some form of urinary incontinence. Twenty-three and seven-tenths percent (142) experienced occasional urine dribbling, 2.3% (14) were unable to prevent involuntary emptying of their bladder, and 7.3% (44) suffered both problems. Eighty-three percent of the respondents were between the ages of 65 and 85 years. Females accounted for 75% of all respondents. Respondents 75 years of age or older had a higher occurrence of all forms of urinary incontinence (P = 0.57), and a strong association existed with the same age-group and uncontrolled emptying of the bladder (P = .02). Thirty-seven percent of the females and 22% of the males reported having had an incontinent episode (P = .002). High parity (four or more births) was significantly associated with incontinence in females (P = .04). These survey findings provide prevalence estimates of urinary incontinence that are greater than those previously reported and show statistical differences by age and gender. The study population is not representative of all the noninstitutionalized elderly, but consists primarily of individuals who are active, ambulatory, generally healthy and may underestimate the magnitude of the problem. Urinary incontinence is substantiated as a major health problem in even the most functional community-residing elderly citizens.

Activities of Daily Living↗