Voluntary exercise protects against acute doxorubicin cardiotoxicity in the isolated perfused rat heart

2005 ◽  
Vol 289 (2) ◽  
pp. R424-R431 ◽  
Author(s):  
Adam J. Chicco ◽  
Carole M. Schneider ◽  
Reid Hayward
Keyword(s):  
Exercise Training ◽  
Rat Heart ◽  
Left Ventricular ◽  
Voluntary Exercise ◽  
Sprague Dawley ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Sprague Dawley Rats ◽  
Developed Pressure ◽  
Running Wheels

The clinical use of doxorubicin (DOX) is limited by a dose-dependent cardiotoxicity. The purpose of this study was to determine whether voluntary exercise training would confer protection against DOX cardiotoxicity in the isolated perfused rat heart. Female Sprague-Dawley rats were randomly assigned to standard holding cages or cages with running wheels for 8 wk. Twenty-four hours after the sedentary (SED) or voluntary exercise (VEX) running period, rats were anesthetized with pentobarbital sodium, and hearts were isolated and perfused with oxygenated Krebs-Henseleit (KH) buffer at a constant flow of 15 ml/min. After a 20-min stabilization period, hearts were paced at 300 beats per minute and perfused with KH buffer containing 10 μM DOX for 60 min. A set of control hearts from SED and VEX rats were perfused under identical conditions without DOX for the same period. DOX perfusion led to significant decreases in left ventricular developed pressure, +dP/d t, and −dP/d t, and significant increases in LV lipid peroxidation in sedentary rats compared with non-DOX controls ( P < 0.05). Prior voluntary exercise training attenuated these DOX-induced effects and was associated with a significant increase (78%, P < 0.05) in heat shock protein (HSP72), but not mitochondrial isoform of SOD (MnSOD) or CuZnSOD protein expression in the hearts of wheel-run animals. These data indicate that chronic physical activity may provide resistance against the cardiac dysfunction and oxidative damage associated with DOX exposure and provide novel evidence of HSP72 induction in the heart after voluntary exercise.

Location of epicardial pacemaker electrodes and myocardial contractility

1969 ◽  
Vol 47 (3) ◽  
pp. 267-271 ◽  
Author(s):  
G. M. Tremblay ◽  
M. Nahas
Keyword(s):  
Rat Heart ◽  
Myocardial Contractility ◽  
Calcium Concentration ◽  
Cardiac Contractility ◽  
Sprague Dawley ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Pacemaker Electrodes

Effects of pacing from different epicardial sites on cardiac contractility were studied in the isolated perfused rat heart. An indwelling balloon containing a known volume of saline was used to record intracavitary pressure (LVP), force, and maximum dp/dt during isovolumic paced contraction. Coronary flow was kept constant, and the adequacy of oxygenation was verified by lactate extraction. Forty male Sprague–Dawley rats weighing 250–300 g were divided into two groups, according to the rate of pacing, and stimulated. Pacing from four different epicardial sites failed to show any statistically significant difference in LVP, force, or maximum dp/dt at either different heart rate or calcium concentration. The present study suggests that myocardial contractility in the isolated perfused rat heart is not affected by the pacing site of the epicardial pacemaker.

scholarly journals Differential expression of stress proteins in rat myocardium after free wheel or treadmill run training

1999 ◽  
Vol 86 (5) ◽  
pp. 1696-1701 ◽  
Author(s):  
Earl G. Noble ◽  
Albert Moraska ◽  
Robert S. Mazzeo ◽  
David A. Roth ◽  
M. Charlotte Olsson ◽  
...  
Keyword(s):  
Exercise Training ◽  
Stress Proteins ◽  
Citrate Synthase ◽  
Treadmill Exercise ◽  
Stress Protein ◽  
Critical Factor ◽  
Voluntary Exercise ◽  
Similar Response ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

High-intensity treadmill exercise increases the expression of a cardioprotective, inducible 72-kDa stress protein (SP72) in cardiac muscle. This investigation examined whether voluntary free wheel exercise training would be sufficient to confer a similar response. Male Sprague-Dawley rats were randomly assigned to either treadmill (TM-Tr) or free wheel (FW-Tr) training groups. By the end of the 8-wk training period, TM-Tr animals ran 1 h/day, 5 days/wk up a 10% grade, covering a distance of 8,282 m/wk. FW-Tr rats ran, on average, 5,300 m/wk, with one-third of the animals covering distances similar to those for the TM-Tr group. At the time of death, hearts of trained and caged sedentary control (Sed) animals were divided into left (LV) and right (RV) ventricles. Citrate synthase activity and the relative immunoblot contents of SP72, SP73 (the constitutive isoform of the SP70 family), and a 75-kDa mitochondrial chaperone (SP75) were subsequently determined. LV and RV did not differ on any measure, and SP73, SP75, and citrate synthase were not affected by training. Cardiac SP72 levels were elevated over fourfold in both ventricles of TM-Tr compared with RV of FW-Sed rats. Despite the animals having run a similar total distance, cardiac SP72 content in FW-Tr rats was not different from that in Sed animals. These data indicate that voluntary exercise training is insufficient to elicit an elevation of SP72 in rat heart and suggest that exercise intensity may be a critical factor in evoking the cardioprotective SP72 response.

scholarly journals Use of the Isolated Perfused Heart for Evaluation of Cardiac Toxicity

1990 ◽  
Vol 18 (4a) ◽  
pp. 497-510 ◽  
Author(s):  
Peter G. Anderson ◽  
Stanley B. Digerness ◽  
Jerald L. Sklar ◽  
Paul J. Boor
Keyword(s):  
Rat Heart ◽  
Coronary Flow ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Heart Weight ◽  
Isolated Perfused Heart ◽  
Heart Model ◽  
Perfused Heart ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart

The isolated perfused rat heart model can be used to evaluate cardiotoxicity, and is especially useful in distinguishing direct vs indirect cardiac injury. Various perfusion systems can be used to characterize the pathophysiologic as well as morphologic changes induced by drugs or chemicals of interest. The isolated perfused heart was used in the studies described herein to characterize the mechanism of allylamine cardiotoxicity. Rat hearts were perfused with Krebs-Henseleit buffer containing 10 mm allylamine and a latex balloon was inserted into the left ventricle to monitor pressure. Coronary flow in hearts perfused with 10 mm allylamine was similar to control hearts at 5, 10, and 30 min, but was reduced by 1 hr (11.5 ± 0.6 ml/min/g wet heart weight vs 16.0 ± 0.7, p < 0.01). Peak left ventricular systolic pressure increased in hearts perfused with allylamine for 5 min (156 ± 8 mm Hg vs 103 ± 9, p < 0.01), but by 2 hr was decreased compared to controls (89 ± 6 vs 105 ± 5, p < 0.05). End diastolic pressure was markedly increased at 2 hr (58 ± 3 vs 4 ± 0.8, p < 0.01). Morphologically, allylamine perfused hearts exhibited significant contraction band changes as well as numerous cells with marked swelling of the sarcoplasmic reticulum. The findings in this study suggest that allylamine produces direct myocardial damage that appears to be independent of coronary flow. These studies demonstrate that the isolated perfused rat heart model can be used to evaluate mechanisms of acute cardiotoxicity.

Glibenclamide improves postischemic recovery of myocardial contractile function in trained and sedentary rats

2001 ◽  
Vol 91 (4) ◽  
pp. 1545-1554 ◽  
Author(s):  
Korinne N. Jew ◽  
Russell L. Moore
Keyword(s):  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Diastolic Stiffness ◽  
Pressure Development ◽  
Increased Sensitivity ◽  
Developed Pressure

In this study, we sought to determine whether there was any evidence for the idea that cardiac ATP-sensitive K+ (KATP) channels play a role in the training-induced increase in the resistance of the heart to ischemia-reperfusion (I/R) injury. To do so, the effects of training and an KATP channel blocker, glibenclamide (Glib), on the recovery of left ventricular (LV) contractile function after 45 min of ischemia and 45 min of reperfusion were examined. Female Sprague-Dawley rats were sedentary (Sed; n = 18) or were trained (Tr; n = 17) for >20 wk by treadmill running, and the hearts from these animals used in a Langendorff-perfused isovolumic LV preparation to assess contractile function. A significant increase in the amount of 72-kDa class of heat shock protein was observed in hearts isolated from Tr rats. The I/R protocol elicited significant and substantial decrements in LV developed pressure (LVDP), minimum pressure (MP), rate of pressure development, and rate of pressure decline and elevations in myocardial Ca2+ content in both Sed and Tr hearts. In addition, I/R elicited a significant increase in LV diastolic stiffness in Sed, but not Tr, hearts. When administered in the perfusate, Glib (1 μM) elicited a normalization of all indexes of LV contractile function and reductions in myocardial Ca2+content in both Sed and Tr hearts. Training increased the functional sensitivity of the heart to Glib because LVDP and MP values normalized more quickly with Glib treatment in the Tr than the Sed group. The increased sensitivity of Tr hearts to Glib is a novel finding that may implicate a role for cardiac KATP channels in the training-induced protection of the heart from I/R injury.

Mitogenic response of T-lymphocytes to exercise training and stress

1991 ◽  
Vol 70 (6) ◽  
pp. 2535-2538 ◽  
Author(s):  
G. D. Tharp ◽  
T. L. Preuss
Keyword(s):  
Exercise Training ◽  
Sprague Dawley ◽  
Mitogenic Response ◽  
Con A ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Spleen Lymphocytes ◽  
Cell Mitogen ◽  
Running Wheels ◽  
The Impact

The impact of exercise training and stress on the immune response was examined by measuring the mitogenic response of spleen lymphocytes to the T-cell mitogen concanavalin A (Con-A). Male Sprague-Dawley rats were divided into four groups: sedentary controls (n = 11), handled controls (n = 12), treadmill runners (n = 10), and voluntary runners (n = 11) housed in running wheels. The treadmill group ran at 22 m/min (0.8 mph) for 45 min, 5 days/wk for 8 wk. After the training period, spleen lymphocytes isolated from each rat were incubated with Con-A for 54 h, pulsed with radiolabeled thymidine for 18 h, and counted for tritium activity. Counts per minute per group (means +/- SE) were as follows: sedentary, 6,839 +/- 1,461; handled, 8,959 +/- 1,576; voluntary runners, 13,126 +/- 2,069; and treadmill runners, 18,950 +/- 5,975. One-way analysis of variance and Tukey's highly significant difference test found the counts per minute of the treadmill runners to be significantly different from the counts per minute of the sedentary animals. These results indicate that the responsiveness of spleen lymphocytes to Con-A increases as the level of stress and exercise increases.

Role of prostaglandins in exercise-induced core temperature elevation in female Sprague-Dawley rats

1993 ◽  
Vol 265 (5) ◽  
pp. R1121-R1125
Author(s):  
P. J. Rowsey ◽  
K. T. Borer ◽  
M. J. Kluger
Keyword(s):  
Body Temperature ◽  
Sodium Salicylate ◽  
Voluntary Exercise ◽  
Female Rats ◽  
Temperature Elevation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Exercise Induced ◽  
Running Wheels

Female Sprague-Dawley rats (12:12-h photoperiod; body temperature, BT, measured with biotelemetry) with access to running wheels for 6 wk have an elevated BT (compared with rats with no access to exercise wheels, i.e, sedentary) both during the period of voluntary exercise (nighttime) (0.5 degree C, P = 0.0001) and the nonexercise period (daytime) (0.3 degree C, P = 0.002). To determine whether prostaglandin (PG) E was responsible for any portion of this daytime rise in BT, we injected a dose of sodium salicylate (300 mg/kg), which was shown to produce complete antipyresis in rats injected with lipopolysaccharide (LPS), into exercised and sedentary rats 4 h after the onset of the lights-on period. The injections of sodium salicylate led to a fall in body temperature in both the exercised and sedentary rats of similar amounts (-0.88 degree C vs. -0.61 degree C at 2 h postinjection, P = 0.59). We conclude that the increase in daytime BT of exercised female rats is not mediated by prostaglandins.

scholarly journals Exercise training initiated after the onset of diabetes preserves myocardial function: effects on expression of β-adrenoceptors

2008 ◽  
Vol 105 (3) ◽  
pp. 907-914 ◽  
Author(s):  
Keshore R. Bidasee ◽  
Hong Zheng ◽  
Chun-Hong Shao ◽  
Sheeva K. Parbhu ◽  
George J. Rozanski ◽  
...  
Keyword(s):  
Exercise Training ◽  
Cardiac Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Western Blots ◽  
Sprague Dawley Rats ◽  
Function Loss ◽  
Onset Of Diabetes ◽  
Exercise Induced

The present study was undertaken to assess cardiac function and characterize β-adrenoceptor subtypes in hearts of diabetic rats that underwent exercise training (ExT) after the onset of diabetes. Type 1 diabetes was induced in male Sprague-Dawley rats using streptozotocin. Four weeks after induction, rats were randomly divided into two groups. One group was exercised trained for 3 wk while the other group remained sedentary. At the end of the protocol, cardiac parameters were assessed using M-mode echocardiography. A Millar catheter was also used to assess left ventricular hemodynamics with and without isoproterenol stimulation. β-Adrenoceptors were assessed using Western blots and [3H]dihydroalprenolol binding. After 7 wk of diabetes, heart rate decreased by 21%, fractional shortening by 20%, ejection fraction by 9%, and basal and isoproterenol-induced dP/d t by 35%. β1- and β2-adrenoceptor proteins were reduced by 60% and 40%, respectively, while β3-adrenoceptor protein increased by 125%. Ventricular homogenates from diabetic rats bound 52% less [3H]dihydroalprenolol, consistent with reductions in β1- and β2-adrenoceptors. Three weeks of ExT initiated 4 wk after the onset of diabetes minimized cardiac function loss. ExT also blunted loss of β1-adrenoceptor expression. Interestingly, ExT did not prevent diabetes-induced reduction in β2-adrenoceptor or the increase of β3-adrenoceptor expression. ExT also increased [3H]dihydroalprenolol binding, consistent with increased β1-adrenoceptor expression. These findings demonstrate for the first time that ExT initiated after the onset of diabetes blunts primarily β1-adrenoceptor expression loss, providing mechanistic insights for exercise-induced improvements in cardiac function.

Temporal dynamics of inotropic, chronotropic, and metabolic responses during β1- and β2-AR stimulation in the isolated, perfused rat heart

2005 ◽  
Vol 289 (3) ◽  
pp. E412-E418 ◽  
Author(s):  
P. McConville ◽  
R. G. Spencer ◽  
E. G. Lakatta
Keyword(s):  
Rat Heart ◽  
Temporal Dynamics ◽  
High Energy ◽  
Left Ventricular ◽  
Metabolic Responses ◽  
Inotropic Response ◽  
Functional Responses ◽  
Perfused Rat Heart ◽  
Chronotropic Response ◽  
Isolated Perfused Rat Heart

During the β-adrenergic receptor (β-AR)-mediated stress response in the heart, the relations between functional responses and metabolism are ill defined, with the distinction between β1- and β2-AR subtypes creating further complexity. Specific outstanding questions include the temporal relation between inotropic and chronotropic responses and their metabolic correlates. We sought to elucidate the relative magnitudes and temporal dynamics of the response to β1- and β2-AR stimulation and the energy expenditure and bioenergetic state related to these responses in the isolated perfused rat heart. Inotropic [left ventricular developed pressure (LVDP) and dP/d t], chronotropic [heart rate (HR)], and metabolic responses were measured during β1- ( n = 9; agonist: norepinephrine) and β2- ( n = 9; agonist: zinterol) AR stimulation. Myocardial oxygen consumption (MV̇o2) was measured using fiber-optic oximetry, and high-energy phosphate levels and intracellular pH were measured using 31P NMR spectroscopy. A multiple-dose protocol was used, with near-maximal β-AR stimulation at the highest doses. In both β1 and β2 groups, there were dose-dependent increases in LVDP, dP/d t, HR, and MV̇o2. The inotropic response showed more rapid onset, washout, and variation during dose than did the chronotropic response and was closely correlated with MV̇o2. This suggests that the myocardial bioenergetic state is more closely related to the inotropic response than to the chronotropic response. In addition, β1-AR stimulation resulted in a greater magnitude and rate of onset of inotropic and MV̇o2 responses than did β2-AR stimulation during maximal stimulation. However, a similar decrease in intracellular energy charge was seen in the two groups, consistent with a greater rate of oxidative phosphorylation during β1- than during β2-AR stimulation.

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