Effects of aging on cardiac output, regional blood flow, and body composition in Fischer-344 rats

1998 ◽  
Vol 85 (5) ◽  
pp. 1813-1822 ◽  
Author(s):  
Michael D. Delp ◽  
Marina V. Evans ◽  
Changping Duan

The purpose of this study was to determine the effects of maturation and aging on cardiac output, the distribution of cardiac output, tissue blood flow (determined by using the radioactive-microsphere technique), and body composition in conscious juvenile (2-mo-old), adult (6-mo-old), and aged (24-mo-old) male Fischer-344 rats. Cardiac output was lower in juvenile rats (51 ± 4 ml/min) than in adult (106 ± 5 ml/min) or aged (119 ± 10 ml/min) rats, but cardiac index was not different among groups. The proportion of cardiac output going to most tissues did not change with increasing age. However, the fraction of cardiac output to brain and spinal cord tissue and to skeletal muscle was greater in juvenile rats than that in the two adult groups. In addition, aged rats had a greater percent cardiac output to adipose tissue and a lower percent cardiac output to cutaneous and reproductive tissues than that in juvenile and adult rats. Differences in age also had little effect on mass-specific perfusion rates in most tissues. However, juvenile rats had lower flows to the pancreas, gastrointestinal tract, thyroid and parathyroid glands, and kidneys than did adult rats, and aged rats had lower flows to the white portion of rectus femoris muscle, spleen, thyroid and parathyroid glands, and prostate gland than did adult rats. Body mass of juvenile rats was composed of a lower percent adipose mass and a greater fraction of brain and spinal cord, heart, kidney, liver, and skeletal muscle than that of the adult and aged animals. Relative to the young adult rats, the body mass of aged animals had a greater percent adipose tissue mass and a lower percent skeletal muscle and skin mass. These data demonstrate that maturation and aging have a significant effect on the distribution of cardiac output but relatively little influence on mass-specific tissue perfusion rates in conscious rats. The old-age-related alterations in cardiac output distribution to adipose and cutaneous tissues appear to be associated with the increases in percent body fat and the decreases in the fraction of skin mass, respectively, whereas the decrease in the portion of cardiac output directed to reproductive tissue of aged rats appears to be related to a decrease in mass-specific blood flow to the prostate gland.

1978 ◽  
Vol 56 (1) ◽  
pp. 97-109 ◽  
Author(s):  
David O. Foster ◽  
M. Lorraine Frydman

The technique of using γ-labeled plastic microspheres (15 ± 5 μm) to measure cardiac output (CO) and its fractional distribution (FD) to individual tissues and organs was judged by various criteria to give valid data when applied to barbital-sedated warm-acclimated or cold-acclimated (CA) white rats, which were either resting or responding calorigenically to infused noradrenaline (NA). The FD of CO to each of 16 tissues or organs of CA rats at rest or responding to NA was then estimated both with 86Rb+ and with microspheres, the two tracers being injected simultaneously. For only seven of the tissues examined in resting rats and only one in NA-infused rats was the FD of CO estimated with 86Rb+ not significantly different from that estimated with microspheres. 86Rb+ to microsphere ratios of the FD of CO to individual tissues ranged from 3.5 and 3.0 for liver and skeletal muscle, respectively, down to 0.09 and 0.07 for brown adipose tissue (BAT) and brain. Since microsphere-based estimates of blood flow to the interscapular BAT of CA rats responding to NA were corroborated by direct measurements of venous efflux from the tissue, it is unequivocal that the 86Rb+-based estimate of the fraction of CO directed to interscapular BAT was highly erroneous. When considered along with data from the literature, the present findings support a conclusion that the uptake of 86Rb+ by a tissue frequently does not provide a valid measure of the FD of CO to the tissue. Some of the factors that are likely responsible for this situation are discussed, and it is suggested that only by a fortuitous combination of circumstances does the uptake of 86Rb+ by a tissue sometimes match the FD of CO to the tissue.


1978 ◽  
Vol 55 (3) ◽  
pp. 317-320 ◽  
Author(s):  
C. R. Hiley ◽  
M. S. Yates

1. Radioactive 15 μm and 50 μm diameter microspheres were used to determine cardiac output, its regional distribution and tissue blood flow in adult normotensive Wistar and Okamoto spontaneously hypertensive rats. 2. Cardiac output in the spontaneously hypertensive rats was the same as in Wistar normotensive rats, but its distribution in the hypertensive rats appeared to differ: there was a significant increase in the proportion of microspheres trapped in the liver whereas fewer were found in the gastrointestinal tract. This indicates that a greater fraction of the cardiac output passes along the hepatic artery and less through the splanchnic bed. 3. Blood flow in skin and skeletal muscle in spontaneously hypertensive rats was approximately 50% of that in Wistar normotensive rats.


1991 ◽  
Vol 71 (5) ◽  
pp. 1674-1678 ◽  
Author(s):  
P. A. Van Leeuwen ◽  
J. R. Bading ◽  
N. A. Vydelingum ◽  
R. N. Younes ◽  
P. de Rooij ◽  
...  

Although blood flow is central to systemic metabolism, little is known about the effect of tumor on the perfusion of host tissues. This study evaluated the effects of a methylcholanthrene-induced sarcoma on blood flow to intra-abdominal organs and skeletal muscle of Fischer-344 rats anesthetized with pentobarbital sodium. Animals were studied by aortic injection of radiolabeled microspheres when the tumors reached 20% of body weight. Total-organ arterial flows in spleen, liver, small intestine, and pancreas were each increased to 50–150% in tumor bearers relative to controls (P less than 0.05). Portal venous flow and flow per gram to hindlimb muscle were 60 +/- 20 and 300 +/- 100% greater, respectively, in tumor-bearing animals (P less than 0.005). This study shows that tumor growth can be associated with large changes in organ flow and distribution of cardiac output. The increase in skeletal muscle flow in the tumor bearers, which lost normal tissue weight relative to pair-fed controls (P less than 0.05), is in marked contrast to decreased muscle flow previously observed in simple starvation.


2002 ◽  
Vol 282 (5) ◽  
pp. H1843-H1854 ◽  
Author(s):  
Judy Muller-Delp ◽  
Scott A. Spier ◽  
Michael W. Ramsey ◽  
Lisa A. Lesniewski ◽  
Anthony Papadopoulos ◽  
...  

Exercise capacity and skeletal muscle blood flow during exercise are reduced with advancing age. This reduction in blood flow capacity may be related to increased reactivity of skeletal muscle resistance vessels to vasoconstrictor stimuli. The purpose of this study was to test the hypothesis that aging results in increased vasoconstrictor responses of skeletal muscle resistance arterioles. First-order (1A) arterioles (90–220 μm) from the gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-344 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasoconstriction in response to increases in norepinephrine (NE; 1 × 10−9–1 × 10−4 M) and KCl (20–100 mM) concentrations and increases in intraluminal pressure (10–130 cmH2O) were evaluated in the absence of flow. Responses to NE and KCl were similar in both soleus and gastrocnemius muscle arterioles from young and aged rats. In contrast, active myogenic responses to changes in intraluminal pressure were diminished in soleus and gastrocnemius arterioles from aged rats. To assess whether alterations in the mechanical properties of resistance arterioles underlie altered myogenic responsiveness, passive diameter responses to pressure and mechanical stiffness were evaluated. There was no effect of age on the structural behavior (passive pressure-diameter relationship) or stiffness of arterioles from either the soleus or gastrocnemius muscles. These results suggest that aging does not result in a nonspecific decrease in vasoconstrictor responsiveness of skeletal muscle arterioles. Rather, aging-induced adaptations of vasoreactivity of resistance arterioles appear to be limited to mechanisms that are uniquely involved in the signaling of the myogenic response.


1998 ◽  
Vol 85 (3) ◽  
pp. 1024-1029 ◽  
Author(s):  
Jennifer M. Salter ◽  
Vincent M. Cassone ◽  
M. Keith Wilkerson ◽  
Michael D. Delp

Vascular remodeling and changes in vascular responsiveness occur in the rat cerebrum with old age. This includes reductions in cerebral arteriolar numerical density, cross-sectional area, distensibility, the relative proportion of distensible elements in the cerebral arteriolar wall, and reduced endothelium-dependent relaxation. The purpose of this study was to test the hypothesis that old age results in an increase in vascular resistance and, correspondingly, a decrease in blood flow to ocular, regional cerebral, and spinal tissue in the rat. Blood flow was measured in the eye, olfactory bulb, left and right cerebrum, pituitary gland, midbrain, pons, cerebellum, medulla, and spinal cord of juvenile (2-mo-old, n = 6), adult (6-mo-old, n = 7), and aged (24-mo-old, n = 7) male Fischer-344 rats. Arterial pressure and blood flow were used to calculate vascular resistance. Vascular resistance in the eye of aged rats (6.03 ± 1.08 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g) was higher than that in juvenile (3.83 ± 0.38 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g) and adult rats (3.12 ± 0.24 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g). Similarly, resistance in the pons of older rats (2.24 ± 0.55 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g) was greater than in juvenile (0.66 ± 0.06 mmHg ⋅ml−1 ⋅ min ⋅ 100 g) and adult rats (0.80 ± 0.11 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g). In contrast, vascular resistance in the pituitary gland was lower in the aged rats (juvenile, 3.09 ± 0.22; adult, 2.79 ± 0.42; aged, 1.73 ± 0.32 mmHg ⋅ ml−1 ⋅ min ⋅ 100 g, respectively). Vascular resistance was not different in other cerebral tissues or in the spinal cord in the aged rats. These data suggest that regional cerebral and spinal blood flow and vascular resistance remain largely unchanged in conscious aged rats at rest but that elevations in ocular vascular resistance and, correspondingly, decreases in ocular perfusion with advanced age could have serious adverse effects on visual function.


2011 ◽  
Vol 110 (3) ◽  
pp. 695-704 ◽  
Author(s):  
Danielle J. McCullough ◽  
Robert T. Davis ◽  
James M. Dominguez ◽  
John N. Stabley ◽  
Christian S. Bruells ◽  
...  

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O2 delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O2 delivery to O2 uptake, evidenced through improved microvascular Po2 (PmO2), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ∼6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify PmO2 in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline PmO2 (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting PmO2 and the time-delay before PmO2 fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the PmO2 in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.


1996 ◽  
Vol 271 (6) ◽  
pp. E1061-E1066 ◽  
Author(s):  
D. Meynial-Denis ◽  
M. Mignon ◽  
A. Miri ◽  
J. Imbert ◽  
E. Aurousseau ◽  
...  

Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid induction of GS could be altered in aged rats, because alterations in the responsiveness of some genes to glucocorticoids were reported in aging. We compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6-8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex) in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and aged rat, respectively) for 5 days. Dex caused an increase in both GS activity and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged rats. In contrast, Dex increased GS activity in heart of adult rats, without any concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is preserved in skeletal muscle but not in heart from aged animals.


1999 ◽  
Vol 277 (3) ◽  
pp. H1036-H1044 ◽  
Author(s):  
Shaolong Yang ◽  
Mian Zhou ◽  
Douglas J. Koo ◽  
Irshad H. Chaudry ◽  
Ping Wang

The cardiovascular response to sepsis includes an early, hyperdynamic phase followed by a late, hypodynamic phase. Although administration of pentoxifylline (PTX) produces beneficial effects in sepsis, it remains unknown whether this agent prevents the transition from the hyperdynamic to the hypodynamic response during the progression of sepsis. To study this, male adult rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). At 1 h after CLP, PTX (50 mg/kg body wt) or vehicle was infused intravenously over 30 min. At 20 h after CLP (i.e., the late stage of sepsis), cardiac output and organ blood flow were measured by radioactive microspheres. Systemic and regional (i.e., hepatic, intestinal, and renal) oxygen delivery (Do 2) and oxygen consumption (V˙o 2) were determined. Moreover, plasma levels of lactate and alanine aminotransferase (ALT) were measured, and histological examinations were performed. In additional animals, the necrotic cecum was excised at 20 h after CLP, and mortality was monitored for 10 days thereafter. The results indicate that cardiac output, organ blood flow, and systemic and regional Do 2decreased by 36–65% ( P < 0.05) at 20 h after CLP. Administration of PTX early after the onset of sepsis, however, prevented reduction in measured hemodynamic parameters and increased systemic and regional Do 2 andV˙o 2 by 50–264% ( P < 0.05). The elevated levels of lactate (by 173%, P < 0.05) and ALT (by 718%, P < 0.05), as well as the morphological alterations in the liver, small intestine, and kidneys during sepsis were attenuated by PTX treatment. In addition, PTX treatment decreased the mortality rate from 50 to 0% ( P < 0.05) after CLP and cecal excision. Because PTX prevents the occurrence of hypodynamic sepsis, this agent appears to be a useful adjunct for maintaining hemodynamic stability and preventing lethality from sepsis.


1979 ◽  
Vol 236 (2) ◽  
pp. H218-H224 ◽  
Author(s):  
S. C. Crayton ◽  
R. Aung-Din ◽  
D. E. Fixler ◽  
J. H. Mitchell

Studies were designed to characterize the distribution of cardiac output during induced isometric exercise in anesthetized dogs. The response to isometric exercise involved significant increases in heart rate (+12 +/- 3%(SE)), mean arterial pressure (+13 +/- 2%), cardiac output (+26 +/- 8%), and respiratory minute volume (+75 +/- 26%); total peripheral resistance did not change significantly. Significant changes in blood flow were observed during isometric exercise in kidneys (-18 +/- 6%) and contracting limb muscles (+453 +/- 154%). Flow to liver (hepatic artery), spleen, brain, and myocardium remained near control values. Section of spinal dorsal roots L6-L7 abolished the responses to isometric exercise except for the increase in flow to exercising limb muscles. Alpha-adrenergic receptor blockade abolished the decrease in renal blood flow during isometric exercise; however, the increase in flow to exercising limb muscles was not affected by either alpha- or beta-adrenergic blockade.


1985 ◽  
Vol 249 (3) ◽  
pp. H485-H491 ◽  
Author(s):  
R. F. Tuma ◽  
G. L. Irion ◽  
U. S. Vasthare ◽  
L. A. Heinel

The purpose of this investigation was to characterize the changes in regional blood flow and central hemodynamic measures that occur in the rat as a result of the aging process. The isotope-labeled microsphere technique was used to measure cardiac output and regional blood flows in conscious and anesthetized adult (12 mo) and senescent (24 mo) Fischer 344 virgin female rats. No significant changes were observed in central hemodynamic measurements or regional blood flows in conscious rats with the exception of a 25% reduction in splenic blood flow. Pentobarbital anesthesia significantly reduced cardiac index and heart rate but elevated total peripheral resistance and mean arterial blood pressure. There was a decrease in blood flow to skeletal muscle, spleen, duodenum, stomach, and brain tissue samples and increased hepatic arterial blood flow in both age groups. The use of anesthesia caused a greater reduction in the cardiac index and brain blood flow in the senescent anesthetized rats than in the adult rats. Heart and kidney blood flows were decreased by anesthesia in the senescent rats but not in the adult rats. Skeletal muscle blood flow, however, was significantly greater in the senescent anesthetized rats than in the younger anesthetized animals. Although body weight and organ weights of the liver, spleen, kidneys, stomach, heart, and brain were significantly greater for the senescent rats, no differences could be demonstrated in tibial length or lean body mass.


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