scholarly journals A DEVICE FOR RECORDING LEFT VENTRICULAR CONTRACTION AND ELECTROCARDIOGRAM IN NONWORKING ISOLATED PERFUSED RAT HEART

1978 ◽  
Vol 28 (2) ◽  
pp. 223-229 ◽  
Author(s):  
Kazushige SAKAI ◽  
Yasuyuki SHIRAKI
Keyword(s):  
Rat Heart ◽  
Left Ventricular ◽  
Ventricular Contraction ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart

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.

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.

Effect of extracellular pH on function and metabolism of isolated perfused rat heart

1965 ◽  
Vol 209 (6) ◽  
pp. 1075-1080 ◽  
Author(s):  
Lionel H. Opie
Keyword(s):  
Glucose Uptake ◽  
Flow Rate ◽  
Rat Heart ◽  
Left Ventricular ◽  
Extracellular Ph ◽  
Mechanical Activity ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Oxidation Rates ◽  
Lactate And Pyruvate

The extracellular pH of the isolated perfused rat heart was varied from 6.9 to 8.0 usually by altering the bicarbonate content of the buffer. Isovolumic left ventricular contractility was measured by an intraventricular balloon. The peak systolic pressure was dependent on the coronary flow rate. At a constant flow rate the peak pressure and cardiac rate were unchanged at 7.4–8.0 but declined at about pH 7.1. The uptake and fate of pyruvate-1-C14 (6 mm) and palmitate-1-C14 (0.7 mm) were similar at pH 7.1–8.0. Compared with pH 7.4, oxidation rates of glucose-U-C14 (5 mm) and acetate-2-C14 (5 mm) were unchanged at pH 7.1, but were greater at pH 8.0. Other increases at pH 8.0 (glucose 5 mm) were in glucose uptake, lactate and pyruvate formation, and the percentage of the glucose uptake accounted for by the sum of C14O2, lactate, and pyruvate formed. It is concluded that in spite of decreased mechanical activity at pH 7.1, Krebs cycle activity is unaltered by pH changes from 7.1 to 8.0, whereas glycolysis and acetate oxidation increase above pH 7.4.

scholarly journals Anthrax edema toxin has cAMP-mediated stimulatory effects and high-dose lethal toxin has depressant effects in an isolated perfused rat heart model

2011 ◽  
Vol 300 (3) ◽  
pp. H1108-H1118 ◽  
Author(s):  
Caitlin W. Hicks ◽  
Yan Li ◽  
Shu Okugawa ◽  
Steven B. Solomon ◽  
Mahtab Moayeri ◽  
...  
Keyword(s):  
Rat Heart ◽  
Left Ventricular ◽  
Lethal Toxin ◽  
Heart Model ◽  
In Vivo Models ◽  
Inotropic Effects ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Edema Toxin

While anthrax edema toxin produces pronounced tachycardia and lethal toxin depresses left ventricular (LV) ejection fraction in in vivo models, whether these changes reflect direct cardiac effects as opposed to indirect ones related to preload or afterload alterations is unclear. In the present study, the effects of edema toxin and lethal toxin were investigated in a constant pressure isolated perfused rat heart model. Compared with control hearts, edema toxin at doses comparable to or less than a dose that produced an 80% lethality rate (LD80) in vivo in rats (200, 100, and 50 ng/ml) produced rapid increases in heart rate (HR), coronary flow (CF), LV developed pressure (LVDP), dP/d tmax, and rate-pressure product (RPP) that were most pronounced and persisted with the lowest dose ( P ≤ 0.003). Edema toxin (50 ng/ml) increased effluent and myocardial cAMP levels ( P ≤ 0.002). Compared with dobutamine, edema toxin produced similar myocardial changes, but these occurred more slowly and persisted longer. Increases in HR, CF, and cAMP with edema toxin were inhibited by a monoclonal antibody blocking toxin uptake and by adefovir, which inhibits the toxin's intracellular adenyl cyclase activity ( P ≤ 0.05). Lethal toxin at an LD80 dose (50 ng/ml) had no significant effect on heart function but a much higher dose (500 ng/ml) reduced all parameters ( P ≤ 0.05). In conclusion, edema toxin produced cAMP-mediated myocardial chronotropic, inotropic, and vasodilatory effects. Vasodilation systemically with edema toxin could contribute to shock during anthrax while masking potential inotropic effects. Although lethal toxin produced myocardial depression, this only occurred at high doses, and its relevance to in vivo findings is unclear.

scholarly journals ω-3 Polyunsaturated Fatty Acid Postconditioning Protects the Isolated Perfused Rat Heart from Ischemia-Reperfusion Injury

2018 ◽  
Vol 8 (3) ◽  
pp. 173-182 ◽  
Author(s):  
Fu-wei Zhang ◽  
Jian Tong ◽  
Yu-sheng Yan ◽  
Qun-qing Chen ◽  
Xiao-ping Zhao
Keyword(s):  
Infarct Size ◽  
Rat Heart ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Mitochondrial Damage ◽  
Myocardial Infarct Size ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Cardioprotective Effects

Aims: This study aimed to evaluate the cardioprotective effects of ω-3 polyunsaturated fatty acids (PUFAs) postconditioning against ischemia-reperfusion (I/R) injury. Methods: Sixty Sprague-Dawley rats were randomly divided into 4 groups (n = 15 for each) and used to generate the Langendorff isolated perfused rat heart model. The sham group received a continuous perfusion of 150 min. The remaining three I/R-treated groups sequentially received a 30-min perfusion, a 30-min cardioplegia, and a 90-min reperfusion. The I/R-ischemic preconditioning (IP) group additionally received three cycles of 20-s reperfusion and 20-s coronary reocclusion preceded the 90 min of reperfusion. The I/R-ω group were perfused with ω-3 PUFAs for 15 min before the 90 min of reperfusion. The myocardial infarct size, the degree of mitochondrial damage, the antioxidant capacity of the myocardium, and the cardiac functions during reperfusion were compared among groups. Results: Compared with the I/R group, the I/R-ω group had significantly reduced myocardial infarct size, reduced levels of lactate dehydrogenase and malondialdehyde, elevated superoxide dismutase level, and elevated rising (+dp/dtmax) and descending (–dp/dtmax) rate of left ventricular pressure. The I/R-ω group had a significantly lower rate of mitochondrial damage in myocardial tissue compared with the I/R and I/R-IP groups. Conclusion: ω-3 PUFA postconditioning possesses good cardioprotective effects and may be developed into a therapeutic strategy for myocardial I/R injury.

Greater glycogen utilization during β1- than β2-adrenergic receptor stimulation in the isolated perfused rat heart

2007 ◽  
Vol 293 (6) ◽  
pp. E1828-E1835 ◽  
Author(s):  
Patrick McConville ◽  
Edward G. Lakatta ◽  
Richard G. Spencer
Keyword(s):  
Rat Heart ◽  
Adrenergic Receptor ◽  
Left Ventricular ◽  
Rate Pressure Product ◽  
Lv Function ◽  
Adrenergic Stimulation ◽  
Functional Responses ◽  
Perfused Rat Heart ◽  
Phosphorylation Potential ◽  
Isolated Perfused Rat Heart

Differences in energy metabolism during β1- and β2-adrenergic receptor (AR) stimulation have been shown to translate to differences in the elicited functional responses. It has been suggested that differential access to glycogen during β1- compared with β2-AR stimulation may influence the peak functional response and modulation of the response during sustained adrenergic stimulation. Interleaved 13C- and 31P-NMR spectroscopy was used during β1- and β2-AR stimulation at matched peak workload (2.5 times baseline) in the isolated perfused rat heart to monitor glycogen levels, phosphorylation potential, and intracellular pH. Simultaneous measurements of left ventricular (LV) function [LV developed pressure (LVDP)], heart rate (HR), and rate-pressure product (RPP = LVDP × HR) were also performed. The heart was perfused under both substrate-free (SF) conditions and with exogenous glucose (G). The greater glycogenolysis was observed during β1- than β2-AR stimulation with G (54% vs. 38% reduction, P = 0.006) and SF (92% vs. 79% reduction, P = 0.04) perfusions. The greater β1-AR-mediated glycogenolysis was correlated with greater ability to sustain the initial contractile response. However, with SF perfusion, the duration of this ability was limited: excessive early glycogen depletion caused an earlier decline in LVDP and phosphorylation potential during β1- than β2-AR stimulation. Therefore, endogenous glycogen stores are depleted earlier and to a greater extent, despite a slightly weaker overall inotropic response, during β1- than β2-AR stimulation. These findings are consistent with β1-AR-specific PKA-dependent glycogen phosphorylase kinase signaling.

scholarly journals Distinction between major chloroquine-inhibitable and adrenergic-responsive pathways of protein degradation and their relation to tissue ATP content in the Langendorff isolated perfused rat heart

1988 ◽  
Vol 251 (2) ◽  
pp. 341-346 ◽  
Author(s):  
T D Lockwood
Keyword(s):  
Protein Degradation ◽  
Rat Heart ◽  
Degradation Rate ◽  
Contractile Function ◽  
Left Ventricular ◽  
Atp Content ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Ventricular Tissue ◽  
Lysosomal Protein

In the Langendorff isolated perfused rat heart, 36% of total basal protein degradation was inhibited by the lysosomal inhibitor chloroquine (30 microM), after elimination of rapid turnover proteins during a 3 h preliminary degradation period. Prior inhibition of degradation with chloroquine was additive to the 30% inhibition caused by simultaneous infusion of 50-200 nM-isoprenaline. This additivity suggests that the adrenergic-controlled process is independent of the lysosomal degradative pathway. After discontinuation of drug infusions, the isoprenaline-inhibited degradation rate returned to the previous baseline; however, the chloroquine-inhibited degradation rate transiently exceeded the previous baseline. NaN3 (0.3 mM) caused a decrease of left-ventricular myocardial ATP content of approx. 60% at 14 min and extreme impairment of contractile function; however, the total lysosomal and non-lysosomal protein degradation was not changed at this time. Conversely, left-ventricular tissue ATP content was not changed during proteolytic inhibition by 10 nM-isoprenaline or 10 microM-chloroquine at 14 min. The results indicate that depletion of myocardial energy stores in this preparation is neither necessary nor sufficient to cause inhibition of the total of lysosomal and non-lysosomal protein degradation.

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.

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