Catecholamines and preconditioning: studies of contraction and function in isolated rat hearts

1999 ◽  
Vol 277 (1) ◽  
pp. H136-H143 ◽  
Author(s):  
David J. Hearse ◽  
Fiona J. Sutherland
Keyword(s):  
Ischemic Preconditioning ◽  
Untreated Control ◽  
Vehicle Control ◽  
Left Ventricular ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Developed Pressure ◽  
And Function ◽  
Postischemic Recovery ◽  
Isolated Perfused Rat Hearts

The aims of this study were to determine whether 1) like ischemic preconditioning, transient exposure to norepinephrine before ischemia exacerbates contracture during ischemia and 2) protection afforded by norepinephrine is stereospecific (receptor mediated). Isolated perfused rat hearts were randomized into five groups ( n = 6/group): 1) ischemic preconditioning (3 min of ischemia + 3 min of reperfusion + 5 min of ischemia + 5 min of reperfusion), 2) untreated control, 3) vehicle control (ascorbic acid), 4) substitution of preconditioning ischemia by perfusion with d-norepinephrine, and 5) substitution of preconditioning ischemia by perfusion with l-norepinephrine. This was followed by 40 min of zero-flow ischemia and 50 min of reperfusion. Ischemic preconditioning and l-norepinephrine exacerbated contracture (time to 50% contracture = 9.2 ± 1.1 and 9.0 ± 1.1 vs. 13.3 ± 0.3, 12.4 ± 0.5, and 13.2 ± 0.4 min for untreated control, vehicle control, and d-norepinephrine, respectively, P < 0.05). Postischemic left ventricular developed pressure was poor in untreated control (23.0 ± 2.2%), vehicle control (26.9 ± 2.3%), and d-norepinephrine (19.8 ± 2.8%) groups but good in preconditioned (52.4 ± 5.1%) and l-norepinephrine (52.5 ± 1.1%) groups ( P < 0.05). Thus norepinephrine preconditioning, like ischemic preconditioning, causes a paradoxical exacerbation of contracture coupled with enhanced postischemic recovery; both effects are stereospecific.

Thermodynamic limitation for Ca2+ handling contributes to decreased contractile reserve in rat hearts

1998 ◽  
Vol 275 (6) ◽  
pp. H2064-H2071 ◽  
Author(s):  
Rong Tian ◽  
Jessica M. Halow ◽  
Markus Meyer ◽  
Wolfgang H. Dillmann ◽  
Vincent M. Figueredo ◽  
...  
Keyword(s):  
Atp Hydrolysis ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Contractile Reserve ◽  
Rat Hearts ◽  
Intracellular Ca ◽  
Perfused Rat Hearts ◽  
Thermodynamic Driving Force ◽  
Developed Pressure ◽  
Isolated Perfused Rat Hearts

The free energy release from ATP hydrolysis (‖ΔG∼p‖) is decreased by inhibiting the creatine kinase (CK) reaction, which may limit the thermodynamic driving force for the sarcoplasmic reticulum (SR) Ca2+ pumps and thereby cause a decrease in contractile reserve. To determine whether a decrease in ‖ΔG∼p‖ results in decreased contractile reserve by impairing Ca2+ handling, we measured left ventricular pressure and cytosolic Ca2+concentration ([Ca2+]c; by indo 1 fluorescence) in isolated perfused rat hearts, with >95% inhibition of CK with 90 μmol iodoacetamide. Iodoacetamide did not directly alter SR Ca2+-ATPase activity, baseline left ventricular developed pressure, or baseline [Ca2+]c. When perfusate Ca2+ concentration was increased from 1.2 to 3.3 mM, LV developed pressure increased from 67 ± 6 to 119 ± 8 mmHg in control hearts ( P < 0.05) but did not significantly increase in CK-inhibited hearts. Similarly, the amplitude of the [Ca2+]ctransient increased from 548 ± 54 to 852 ± 140 nM in control hearts ( P < 0.05) but did not significantly increase in CK-inhibited hearts. We conclude that decreased ‖ΔG∼p‖ limits intracellular Ca2+ handling and thereby limits contractile reserve.

Effects of perfusion pressure on intracellular calcium, energetics, and function in perfused rat hearts

1993 ◽  
Vol 264 (1) ◽  
pp. H183-H189 ◽  
Author(s):  
S. Kojima ◽  
S. T. Wu ◽  
T. A. Watters ◽  
W. W. Parmley ◽  
J. Wikman-Coffelt
Keyword(s):  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Myocardial Contraction ◽  
Left Ventricular ◽  
Left Ventricular Geometry ◽  
Fluorescence Ratio ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Developed Pressure ◽  
And Function

Effects of perfusion pressure in a range from 50 to 140 cmH2O on intracellular Ca2+ concentration ([Ca2+]i) were evaluated along with cardiac function, energy metabolism, and left ventricular geometry in a concentration of 2 or 4 mM of extracellular Ca2+ ([Ca2+]o) in isovolumic perfused rat hearts. [Ca2+]i was evaluated with a surface fluorometry technique in hearts loaded with indo-1/AM. The systolic and diastolic values and the amplitude (difference between systolic and diastolic values) of indo-1 fluorescence ratio (an index of [Ca2+]i) were linearly related to perfusion pressure. Changes in the fluorescence ratio were harmonious with rapid changes in left ventricular pressure and stabilized within 30-40 s after changes in perfusion pressure. Developed pressure and O2 consumption were closely, linearly correlated with the fluorescence ratio irrespective of [Ca2+]o. Left ventricular end-diastolic wall thickness, measured by 2-dimensional echocardiography, paralleled perfusion pressure and showed a good correlation with the fluorescence ratio. Diastolic myocardial adenosine 3',5'-cyclic monophosphate significantly decreased only at the lowest perfusion pressure. The ln[phosphocreatine]/[Pi] also changed with altered perfusion pressure. In conclusion, perfusion pressure modulates [Ca2+]i, which in turn regulates myocardial contraction and associated O2 utilization.

Heat stress protects aged hypertrophied and nonhypertrophied rat hearts against ischemic damage

1997 ◽  
Vol 273 (3) ◽  
pp. H1333-H1341 ◽  
Author(s):  
R. N. Cornelussen ◽  
A. V. Garnier ◽  
M. M. Vork ◽  
P. Geurten ◽  
R. S. Reneman ◽  
...  
Keyword(s):  
Heat Stress ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Control Treatment ◽  
Sham Operation ◽  
Hsp 70 ◽  
Rat Hearts ◽  
Developed Pressure ◽  
And Control ◽  
Postischemic Recovery

To explore the effects of heat stress (HS) in aged hypertrophied and nonhypertrophied rat hearts, postischemic recovery was investigated 15 mo after aortic constriction (AoB) or sham operation (Sham). Twenty-four hours after HS (42 degrees C; 15 min) or control treatment (normothermia), global ischemia was induced for 20 min in isolated AoB hearts and for 20 or 30 min in Sham hearts. After HS, postischemic recovery after 20-min ischemia in AoB hearts and 30-min ischemia in Sham hearts, respectively, was significantly better than in corresponding controls. In AoB hearts, cardiac output (CO), left ventricular developed pressure (LVDP), and the positive maximal first derivative of left ventricular pressure (+dP/dtmax) recovered to 33 +/- 26 (means +/- SD), 87 +/- 5, and 72 +/- 12%, respectively, after HS and to 5 +/- 8, 22 +/- 39, and 17 +/- 29% of preischemic values, respectively, in controls. Postischemic arrhythmias were significantly reduced in HS hypertrophied hearts, but creatine kinase (CK) loss was not reduced. In Sham hearts subjected to 30 min ischemia, CO, LVDP, and +dP/dtmax recovered to 20 +/- 20, 75 +/- 8, and 59 +/- 15%, respectively, after HS and to 3 +/- 8, 21 +/- 32, and 16 +/- 32% of preischemic values, respectively, in controls. Duration of arrhythmias and CK loss were not reduced in the heated hearts. When Sham hearts were subjected to only 20-min ischemia, functional recovery was not different in HS and control hearts, indicating that HS pretreatment extends the ischemic interval before irreversible injury occurs in the heart. In all HS Sham hearts, the myocardial 72-kDa HS protein (HSP 70) content was significantly increased. However, in HS AoB hearts, HSP 70 levels were not significantly different from the values in the control hearts. These results indicate that HS pretreatment induces cardioprotection in aged hypertrophied and nonhypertrophied rat hearts, which, however, cannot be unequivocally related to increased HSP 70 tissue contents.

Inhibition of nitric oxide synthesis does not affect ischemic preconditioning in isolated perfused rat hearts

1995 ◽  
Vol 268 (1) ◽  
pp. H242-H249 ◽  
Author(s):  
E. O. Weselcouch ◽  
A. J. Baird ◽  
P. Sleph ◽  
G. J. Grover
Keyword(s):  
Nitric Oxide ◽  
Ischemic Preconditioning ◽  
Coronary Flow ◽  
Constant Pressure ◽  
Contractile Function ◽  
No Synthase ◽  
Constant Flow ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Isolated Perfused Rat Hearts

Endothelium-derived nitric oxide (NO) has recently been reported to be a mediator of ischemic preconditioning in dog hearts. The aim of the present study was to determine the role of NO in ischemic preconditioning in isolated perfused rat hearts. Rat hearts were perfused at either constant pressure (80 mmHg) or constant flow. After aerobic perfusion (37 degrees C) for 10 min, hearts were treated with N omega-nitro-L-arginine methyl ester (L-NAME; 30 microM), which is an inhibitor of NO synthase, or vehicle. Ten minutes later, the hearts were preconditioned (4 episodes of 5 min of global ischemia and 5 min of reperfusion) or perfused normally before a 30-min global ischemic period. All hearts were reperfused for 30 min. Coronary flow or perfusion pressure plus heart rate and contractile function were measured continuously. Hearts perfused at constant pressure and treated with 30 microM L-NAME, a concentration that effectively inhibits endogenous NO synthesis, exhibited decreased coronary flow after 10 min, and flow remained decreased throughout the experiment. Ischemic preconditioning before 30 min of global ischemia resulted in a doubling of contractile function and a reduction of lactate dehydrogenase release at the end of the 30-min reperfusion period compared with nonpreconditioned hearts. The protective effect of preconditioning was not different in L-NAME-treated hearts. In addition, inhibition of NO synthase had no effect on the severity of ischemia in nonpreconditioned hearts. Similar results were obtained in preconditioned hearts that were perfused at constant flow, indicating that the flow reductions caused by L-NAME did not influence the results.(ABSTRACT TRUNCATED AT 250 WORDS)

NMR measurements of Na+ and cellular energy in ischemic rat heart: role of Na(+)-H+ exchange

1993 ◽  
Vol 265 (6) ◽  
pp. H2017-H2026 ◽  
Author(s):  
M. M. Pike ◽  
C. S. Luo ◽  
M. D. Clark ◽  
K. A. Kirk ◽  
M. Kitakaze ◽  
...  
Keyword(s):  
Ph Regulation ◽  
Left Ventricular ◽  
Atp Depletion ◽  
Low Flow ◽  
Cellular Energy ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Ischemic Period ◽  
Developed Pressure ◽  
Zero Flow

Interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectra were continuously collected on perfused rat hearts subjected to low-flow ischemia (30 min, 10% flow) or zero-flow ischemia (21 min) followed by reperfusion. During untreated low-flow and zero-flow ischemia, intracellular Na+ (Nai+) increased by 53 +/- 11 (+/- SE) and 78 +/- 8%, respectively, and remained elevated for zero-flow hearts. However, during both low- and zero-flow ischemia, Nai+ did not increase in hearts treated with the Na(+)-H+ exchange inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). The pH decreases during ischemia were unchanged. EIPA treatment reduced ATP depletion during ischemia. During reperfusion from zero-flow ischemia, EIPA-treated hearts displayed more rapid and extensive recoveries of phosphocreatine and ATP. Recovery of left ventricular developed pressure was improved for zero-flow hearts treated with EIPA during the ischemic period exclusively (104 +/- 13%) compared with untreated hearts (36 +/- 21%). These data indicate that Na(+)-H+ exchange is an important mechanism for Nai+ accumulation, but not for pH regulation, during myocardial ischemia. Additionally, Nai+ homeostasis plays an important role in the postischemic recovery of cellular energy and ventricular function.

Effect of diazoxide on flavoprotein oxidation and reactive oxygen species generation during ischemia-reperfusion: a study on Langendorff-perfused rat hearts using optic fibers

2008 ◽  
Vol 294 (5) ◽  
pp. H2088-H2097 ◽  
Author(s):  
Philippe Pasdois ◽  
Bertrand Beauvoit ◽  
Liliane Tariosse ◽  
Béatrice Vinassa ◽  
Simone Bonoron-Adèle ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Reactive Oxygen Species Generation ◽  
Left Ventricular ◽  
Rate Pressure Product ◽  
Control Group ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Optic Fibers ◽  
The One ◽  
Isolated Perfused Rat Hearts

This study analyzed the oxidant generation during ischemia-reperfusion protocols of Langendorff-perfused rat hearts, preconditioned with a mitochondrial ATP-sensitive potassium channel (mitoKATP) opener (i.e., diazoxide). The autofluorescence of mitochondrial flavoproteins, and that of the total NAD(P)H pool on the one hand and the fluorescence of dyes sensitive to H2O2 or O2•− [i.e., the dihydrodichlorofluoroscein (H2DCF) and dihydroethidine (DHE), respectively] on the other, were noninvasively measured at the surface of the left ventricular wall by means of optic fibers. Isolated perfused rat hearts were subjected to an ischemia-reperfusion protocol. Opening mitoKATP with diazoxide (100 μM) 1) improved the recovery of the rate-pressure product after reperfusion (72 ± 2 vs. 16.8 ± 2.5% of baseline value in control group, P < 0.01), and 2) attenuated the oxidant generation during both ischemic (−46 ± 5% H2DCF oxidation and −40 ± 3% DHE oxidation vs. control group, P < 0.01) and reperfusion (−26 ± 2% H2DCF oxidation and −23 ± 2% DHE oxidation vs. control group, P < 0.01) periods. All of these effects were abolished by coperfusion of 5-hydroxydecanoic acid (500 μM), a mitoKATP blocker. During the preconditioning phase, diazoxide induced a transient, reversible, and 5-hydroxydecanoic acid-sensitive flavoprotein and H2DCF (but not DHE) oxidation. In conclusion, the diazoxide-mediated cardioprotection is supported by a moderate H2O2 production during the preconditioning phase and a strong decrease in oxidant generation during the subsequent ischemic and reperfusion phases.

Effect of perfusate Ca2+ on the relation between metabolism and mechanical performance in the rat heart

1980 ◽  
Vol 58 (5) ◽  
pp. 570-573 ◽  
Author(s):  
T. Russell Snow ◽  
Gabor Rubanyi ◽  
Tunde Dora ◽  
Eörs Dora ◽  
Arisztid G. B. Kovach
Keyword(s):  
Respiratory Chain ◽  
Mechanical Performance ◽  
Left Ventricular ◽  
Perfused Heart ◽  
Exogenous Substrate ◽  
Rat Hearts ◽  
Nadh Fluorescence ◽  
Perfused Rat Hearts ◽  
Developed Pressure ◽  
Contractile Performance

Langendorf perfused rat hearts (n = 25) were used to study the effects of changes in perfusate Ca2+ concentration ([Ca2+p]) on the relation between metabolism and mechanical performance with either glucose or pyruvate as the exogenous substrate. Increased [Ca2+p] (from 1.3 to 3.9 mM) produced an increase (243 ± 38%) in left ventricular developed pressure regardless of the substrate. With glucose as the substrate, the NADH fluorescence intensity increased by 11.8 ± 1.2% (n = 17) relative to control indicating a more reduced state of the respiratory chain. Increasing [Ca2+p] in the pyruvate perfused heart produced the expected NADH oxidation (−6.2 ± 1.1%; n = 8). Hence the change in NADH fluorescence associated with increased [Ca2+p] is substrate dependent. The data show that, with glucose as the substrate but not with pyruvate, increases in [Ca2+p] increase the availability of reducing equivalents to the respiratory chain above the level necessary to compensate for the increased demand resulting from the greater contractile performance.

scholarly journals Rutin trihydrate attenuated cisplatin- induced cardiac toxicity in isolated perfused rat’s hearts

2020 ◽  
Author(s):  
Ishfaq Bukhari ◽  
Osama Yousif Mohamed ◽  
Rahmathunnisa Lateef ◽  
Sabiha Fatima ◽  
Fahim Vohra ◽  
...  
Keyword(s):  
Mechanical Performance ◽  
Left Ventricular ◽  
Dependent Manner ◽  
Protective Effects ◽  
Time Index ◽  
Pressure Time ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Dose Dependent ◽  
Isolated Perfused Rat Hearts

Abstract Background The present study aims to investigate the protective effect of rutin against cisplatin induced toxic effects on the mechanical performance of the myocardium, histopathology, and oxidative stress in isolated perfused rat hearts. Methods Cardiotoxicity of cisplatin was assessed at three dosage levels (1, 7, and 14 mg/l) in the isolated perfused rat hearts. The toxic effect of cisplarin was assessed on left ventricular pressure (LVP), heart rate (HR), dp/dt(max), dp/dt (min), perfusion pressure, pressure-time index, contractility index and duration of diastole. Measurements were carried out one minute before perfusion of cisplatin and 60 minutes after perfusion. Results Cisplatin reduced significantly (p < 0.05) in a dose-dependent manner LVP, dp/dt(max), dp/dt(min) and pressure- time index. Perfusion of rutin trihydrate (1 µM/l), 10 minutes before administration of cisplatin and throughout the experiment significantly (p < 0.05) attenuated the detrimental effects of cisplatin on cardiac parameters. Cisplatin caused degeneration and necrosis of cardiac muscle cells, while rutin reduced these changes and restored normal heart histology. Moreover, cisplatin reduced the myocardium concentration of reduced glutathione and increased the level of malondialdehyde, whereas rutin almost reversed these changes. Conclusion Cisplatin-induced dose-dependent impairment of several parameters of cardiac function and produced histopathological alterations in isolated rat hearts. These harmful effects of cisplatin were ameliorated by rutin trihydrate. These findings suggest the potential protective effects of rutin trihydrate against cisplatin-induced cardiotoxicity.

scholarly journals Hemidesmus indicusandHibiscus rosa-sinensisAffect Ischemia Reperfusion Injury in Isolated Rat Hearts

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Vinoth Kumar Megraj Khandelwal ◽  
R. Balaraman ◽  
Dezider Pancza ◽  
Táňa Ravingerová
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Moderate Increase ◽  
Dependent Manner ◽  
Hemidesmus Indicus ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Developed Pressure

Hemidesmus indicus(L.) R. Br. (HI) andHibiscus rosa-sinensisL. (HRS) are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R). Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure), reperfusion arrhythmias, and infarct size (TTC staining) served as the endpoints. A transient increase in LVDP (32%–75%) occurred at all concentrations of HI, while coronary flow (CF) was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55%) and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions.

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