Zinc improves postischemic recovery of isolated rat hearts through inhibition of oxidative stress

1994 ◽  
Vol 266 (6) ◽  
pp. H2497-H2507 ◽  
Author(s):  
S. R. Powell ◽  
D. Hall ◽  
L. Aiuto ◽  
R. A. Wapnir ◽  
S. Teichberg ◽  
...  
Keyword(s):  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Isolated Rat Heart ◽  
Essentially Normal ◽  
Rat Hearts ◽  
Absorption Studies ◽  
Reperfusion Period ◽  
Postischemic Recovery ◽  
Krebs Henseleit Buffer ◽  
Isolated Rat

We studied the cardiac protective qualities of zinc in the postischemic isolated rat heart. Hearts, perfused with Krebs-Henseleit buffer with or without zinc-bis-histidinate, were subjected to 20 min of "no-flow" normothermic global ischemia. Pre- and postischemic treatment with 0, 10, 20, or 30 microM zinc resulted in concentration-dependent enhancement of postischemic function as evidenced by decreased end-diastolic pressure (37 +/- 3, 25 +/- 5, 17 +/- 5, and 8 +/- 2 mmHg, respectively) and increased recovery of developed systolic pressure (41 +/- 6, 59 +/- 17, 76 +/- 18, and 87 +/- 16 mmHg, respectively) and maximum rate of rise in pressure (+dP/dtmax; 823 +/- 141, 1,413 +/- 396, 1,700 +/- 450, and 2,157 +/- 407 mmHg/s, respectively) as well as decreased lactate dehydrogenase efflux from the hearts (peak: 1,002%, 840%, 580%, and 440%, respectively). Only preischemic treatment resulted in an intermediate protective effect, whereas treatment starting at reperfusion worsened postischemic damage. In hearts perfused with zinc throughout the experiment, prolongation of the preischemic treatment interval further enhanced postischemic recovery. With the use of salicylate as a trap for .OH, it was determined that zinc virtually eliminated the early postischemic "burst" of this species normally observed in this preparation. Atomic absorption studies demonstrated that hearts treated with 30 microM zinc contained 27% less copper than control hearts by the end of the reperfusion period. In control hearts, electron microscopy revealed swollen mitochondria with marked loss of inner matrix density, whereas morphology of postischemic zinc-treated hearts was essentially normal. These studies indicate that zinc possesses cardiac cytoprotective qualities and support the concept that this metal can decrease .OH formation by affecting copper reactivity.

Promotion of copper excretion from the isolated rat heart attenuates postischemic cardiac oxidative injury

1999 ◽  
Vol 277 (3) ◽  
pp. H956-H962 ◽  
Author(s):  
Saul R. Powell ◽  
Ellen M. Gurzenda ◽  
Mark A. Wingertzahn ◽  
Raul A. Wapnir
Keyword(s):  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Oxidative Injury ◽  
Isolated Rat Heart ◽  
Protein Carbonyls ◽  
Rate Pressure Product ◽  
Beneficial Effects ◽  
Rat Hearts ◽  
Postischemic Period ◽  
Isolated Rat

This study examined the role of Cu as a mediator of cardiac postischemic oxidative injury. Isolated rat hearts were subjected to 20 min of normothermic global ischemia, followed by 30 min of reperfusion; after 20 min of preischemic loading with Krebs-Henseleit buffer ± 20 or 30 μM zinc-bis-histidinate (Zn-His2), 0.5 mM deferoxamine (DEF) or 42 μM neocuproine (NEO). Postischemic developed systolic pressure and rate-pressure product were highest and postischemic end-diastolic pressure was lowest in hearts treated with 20 or 30 μM Zn-His2 and 0.5 mM DEF. Cu efflux was significantly increased by 225 and 290% (end of preischemic loading), and 325 and 375% (immediate postischemic period) of control basal rates in hearts treated with 30 μM Zn-His2 and 0.5 mM DEF, respectively. NEO did not effect any of these parameters. By the end of ischemia, protein carbonyls were lowest in Zn-His2-treated hearts and highest in DEF-treated hearts when compared with control hearts. The results of this study suggest that removal of redox-active Cu before ischemia has beneficial effects, indicating a mediatory role in postischemic cardiac oxidative injury.

Transient hypothermic reperfusion and postischemic recovery in isolated rat heart

1990 ◽  
Vol 259 (3) ◽  
pp. H879-H888
Author(s):  
R. D. Kempsford ◽  
T. Murashita ◽  
D. J. Hearse
Keyword(s):  
Creatine Kinase ◽  
Cardiac Output ◽  
Potential Benefit ◽  
Recovery Of Function ◽  
Isolated Rat Heart ◽  
Ischemia And Reperfusion ◽  
Cardioplegic Solution ◽  
Rat Hearts ◽  
Postischemic Recovery ◽  
Isolated Rat

The potential benefit of transient hypothermic reperfusion of the ischemic myocardium was investigated in isolated working rat hearts (n = 6/group) subjected to 25 min of global ischemia at 37 degrees C. Hearts were reperfused in the Langendorff mode at 5, 10, 20, 30, or 37 degrees C for 10 min plus 5 min at 37 degrees C before assessment of functional recovery (working mode). Compared with normothermic reperfusion (recovery of cardiac output = 42.3 +/- 6.1%), transient hypothermia failed to improve the recovery of cardiac output, which was 47.9 +/- 12.7 (P = NS), 54.3 +/- 11.5 (P = NS), 25.3 +/- 2.7 (P = NS), and 6.4 +/- 3.8% (P less than 0.05) in the 30, 20, 10, and 5 degrees C groups, respectively. Reduced recovery in the 5 degrees C group was reflected in increased creatine kinase leakage from 0.26 +/- 0.04 IU.ml-1.g dry wt-1 (37 degrees C reperfusion) to 0.62 +/- 0.12 IU. ml-1.g dry wt-1 (5 degrees C reperfusion; P less than 0.05). Brief periods (3 x 1 min) of hypothermic (5 degrees C) perfusion during normothermic Langendorff reperfusion (15 min) also reduced recovery of cardiac output to 12.1 +/- 7.2% (P less than 0.01). In additional studies, hearts were subjected to a 2-min preischemic infusion with the St. Thomas' Hospital cardioplegic solution before either 25 or 35 min of normothermic ischemia and reperfusion with transient hypothermia at 5, 10, 20, or 30 degrees C. Once again hypothermic reperfusion failed to improve recovery but detrimental effects were not observed in the 5 degrees C group. These results indicate no beneficial effect of transient hypothermic reperfusion on recovery of function measured following global normothermic ischemia.

Ischemic preconditioning attenuates acidosis and postischemic dysfunction in isolated rat heart

1992 ◽  
Vol 263 (3) ◽  
pp. H887-H894 ◽  
Author(s):  
G. K. Asimakis ◽  
K. Inners-McBride ◽  
G. Medellin ◽  
V. R. Conti
Keyword(s):  
Rat Heart ◽  
Diastolic Pressure ◽  
Isolated Heart ◽  
Isolated Rat Heart ◽  
Rate Pressure Product ◽  
Anaerobic Glycolysis ◽  
Rat Hearts ◽  
Ischemic Period ◽  
Tissue Acidosis ◽  
Isolated Rat

The hypothesis that brief ischemia (preconditioning) protects the isolated heart from prolonged global ischemia was tested. Isovolumic rat hearts were preconditioned with either 5 min of ischemia followed by 5 min of perfusion (P1) or two 5-min episodes of ischemia separated by 5 min of perfusion (P2). Control hearts received no preconditioning. All hearts received 40 min of sustained ischemia and 30 min of reperfusion. Preconditioning (P1 or P2) significantly (P less than 0.0005) improved recovery of the rate-pressure product; percentage recoveries were 17.8 +/- 3.2 (n = 14), 59.9 +/- 5.5 (n = 6), and 46.4 +/- 4.7 (n = 8) for control, P1, and P2, respectively. Improved functional recovery of preconditioned hearts was associated with reduced end-diastolic pressure and improved myocardial perfusion. During the 40-min ischemic period, myocardial pH decreased from approximately 7.4 to 6.3 +/- 0.1 (n = 7) in the control hearts and to 6.7 +/- 0.1 (n = 7) in the preconditioned hearts (P less than 0.01). Also during the 40-min ischemic period, myocardial lactate (expressed as nmol/mg protein) increased to 146 +/- 11 (n = 7) and 101 +/- 12 (n = 8) in control and preconditioned hearts, respectively (P less than 0.02). The results demonstrate that a brief episode of ischemia can protect the isolated rat heart from a prolonged period of ischemia. This protection is associated with decreased tissue acidosis and anaerobic glycolysis during the sustained ischemic period.

Abstract P144: Effects of Alamandine in Post-ischemic Function

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Jonathas F Almeida ◽  
Robson A Santos
Keyword(s):  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Baseline Period ◽  
Left Ventricular ◽  
Biologically Active ◽  
Ventricular Systolic Pressure ◽  
Infarcted Area ◽  
Rat Hearts ◽  
Ischemic Period ◽  
Isolated Rat

Alamandine, a biologically active peptide of the renin-angiotensin system (RAS), was recently described and characterized. Further it has been shown to present effects similar to those elicited by Ang-(1-7). It has been described that Ang-(1-7) decreases the incidence and duration of ischemia-reperfusion arrhythmias and improved the post-ischemic function in isolated perfused rat hearts. In this study we aimed to evaluate the effects of Alamandine in isolated rat hearts subjected to myocardial infarction (MI). Wistar rats weighing between 250-300g were euthanized and their hearts were placed on Langendorff apparatus to evaluate the cardiac parameters. Hearts were submitted to 30min of stabilization, 30min of partial ischemia by occlusion of the left descending coronary artery and 30min of reperfusion. Drugs (alamandine 22pM, d-pro7-ang-(1-7) 220pM) were added to the perfusion setting from the beginning of the experiment until the end. 2,3,5-trypheniltetrazolium chloride were used to evaluate the extension of infarcted area. In control hearts (CON), there was a decrease on the left ventricular systolic pressure (LVSP) on ischemic period (54,6 ± 6,9mmHg) compared to the baseline period (84,6 ± 11,6mmHg). Alamandine (ALA) attenuated that decrease in the ischemic period (66,9 ± 7,9mmHg) vs (82,3 ± 8,9mmHg). Further, ischemia led to a decrease in the left ventricular developed pressure (dLVP), dP/dt maximum and minimum when compared to baseline values. ALA, once more, kept the ischemic parameters of dLVP and dP/dt max and min (58,9 ± 8mmHg; 1629 ± 202,2mmHg/s; 1101 ± 130mmHg/s, respectively) similar to those of baseline period (68,9 ± 8,92; 1682 ± 248,8; 1179 ± 118,6 mmHg, respectively). Ischemia/reperfusion induced an arrhythmia severity index (ASI) in control hearts (4,9 ± 1,26) higher than in hearts treated with ALA (1,10 ± 0,58). ALA also reduced infarcted area (19,64 ± 2,61%) compared with CON (33,85 ± 4,55%). All those effects were blocked by D-PRO7-Ang-(1-7). In conclusion, our data shown that Alamandine exert cardioprotective effects in post-ischemic function in isolated rat hearts by preventing LVSP, dLVP , dP/dt max and min decrease. Furthermore it reduced the infarcted area and I/R arrhythmias, apparently involving MrgD receptor participation.

Left ventricular function of isoproterenol-induced hypertrophied rat hearts perfused with blood: mechanical work and energetics

2009 ◽  
Vol 297 (5) ◽  
pp. H1736-H1743 ◽  
Author(s):  
Chikako Nakajima-Takenaka ◽  
Guo-Xing Zhang ◽  
Koji Obata ◽  
Kiyoe Tohne ◽  
Hiroko Matsuyoshi ◽  
...  
Keyword(s):  
Relaxation Rate ◽  
Diastolic Pressure ◽  
Mechanical Energy ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Mechanical Work ◽  
Linear Relations ◽  
Rat Hearts ◽  
Total Mechanical Energy ◽  
Heart Preparation

We investigated left ventricular (LV) mechanical work and energetics in the cross-circulated (blood-perfused) isoproterenol [Iso 1.2 mg·kg−1·day−1 for 3 days (Iso3) or 7 days (Iso7)]-induced hypertrophied rat heart preparation under isovolumic contraction-relaxation. We evaluated pressure-time curves per beat, end-systolic pressure-volume and end-diastolic pressure-volume relations, and myocardial O2 consumption per beat (V̇o2)-systolic pressure-volume area (PVA; a total mechanical energy per beat) linear relations at 240 beats/min, because Iso-induced hypertrophied hearts failed to completely relax at 300 beats/min. The LV relaxation rate at 240 beats/min in Iso-induced hypertrophied hearts was significantly slower than that in control hearts [saline 24 μl/day for 3 and 7 days (Sa)] with unchanged contraction rate. The V̇o2-intercepts (composed of basal metabolism and Ca2+ cycling energy consumption in excitation-contraction coupling) of V̇o2-PVA linear relations were unchanged associated with their unchanged slopes in Sa, Iso3, and Iso7 groups. The oxygen costs of LV contractility were also unchanged in all three groups. The amounts of expression of sarcoplasmic reticulum Ca2+-ATPase, phospholamban (PLB), phosphorylated-Ser16 PLB, phospholemman, and Na+-K+-ATPase are significantly decreased in Iso3 and Iso7 groups, although the amount of expression of NCX1 is unchanged in all three groups. Furthermore, the marked collagen production (types I and III) was observed in Iso3 and Iso7 groups. These results suggested the possibility that lowering the heart rate was beneficial to improve mechanical work and energetics in isoproterenol-induced hypertrophied rat hearts, although LV relaxation rate was slower than in normal hearts.

scholarly journals Staircase, rest contractions, and potentiation in the isolated rat heart

1962 ◽  
Vol 202 (4) ◽  
pp. 636-640 ◽  
Author(s):  
F. L. Meijler
Keyword(s):  
Cycle Length ◽  
Rest Period ◽  
Isolated Rat Heart ◽  
Stimulation Rate ◽  
Rat Hearts ◽  
Constant Rate ◽  
Theoretical Evidence ◽  
The Relationship ◽  
Isotonic Contractions ◽  
Isolated Rat

Variation in amplitude of isotonic contractions of intact isolated rat hearts, following changes in cycle length, were studied. It was found that a staircase-like phenomenon resembling the original Bowditch effect cannot be evoked in a intact mammalian heart without special measures, such as adding acetylcholine to the perfusion fluid. A steady state relation of rate to amplitude of isotonic contractions was demonstrated. Potentiation of contractility can be originated by sudden changes in stimulation rate. A rest period preceding the changes in stimulation rate does not change the potentiation found originally. At a constant rate the amplitude of a contraction is determined by the preceding cycle length. This relation has been called restitution. Theoretical evidence is presented in an attempt to demonstrate that restitution and potentiation are due to the same process. It can be concluded that Bowditch's staircase does not play a role in the relationship between cycle length and contractility in intact hearts and the statement that restitution and potentiation are due to the same process offers an opportunity to describe all effects of changes in cycle length on isotonic contractions as one phenomenon.

Detection of Cardiac Variability in the Isolated Rat Heart

2006 ◽  
Vol 8 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Autumn M. Schumacher ◽  
Joseph P. Zbilut ◽  
Charles L. Webber ◽  
Dorie W. Schwertz ◽  
Mariann R. Piano
Keyword(s):  
Rat Heart ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Rat Hearts ◽  
Before And After ◽  
Quantification Analysis ◽  
Physical Attributes ◽  
Cardiac Variability ◽  
Isolated Rat

Cardiac variability can be assessed from two perspectives: beat-to-beat performance and continuous performance during the cardiac cycle. Linear analysis techniques assess cardiac variability by measuring the physical attributes of a signal, whereas nonlinear techniques evaluate signal dynamics. This study sought to determine if recurrence quantification analysis (RQA), a nonlinear technique, could detect pharmacologically induced autonomic changes in the continuous left ventricular pressure (LVP) and electrographic (EC) signals from an isolated rat heart—a model that theoretically contains no inherent variability. LVP and EC signal data were acquired simultaneously during Langendorff perfusion of isolated rat hearts before and after the addition of acetylcholine (n = 11), norepinephrine (n = 12), or no drug (n = 12). Two-minute segments of the continuous LVP and EC signal data were analyzed by RQA. Findings showed that%recurrence,%determinism, entropy, maxline, and trend from the continuous LVP signal significantly increased in the presence of both acetylcholine and norepinephrine, although systolic LVP significantly increased only with norepinephrine. In the continuous EC signal, the RQA trend variable significantly increased in the presence of norepinephrine. These results suggest that when either the sympathetic or parasympathetic division of the autonomic nervous system overwhelms the other, the dynamics underlying cardiac variability become stationary. This study also shows that information concerning inherent variability in the isolated rat heart can be gained via RQA of the continuous cardiac signal. Although speculative, RQA may be a tool for detecting alterations in cardiac variability and evaluating signal dynamics as a nonlinear indicator of cardiac pathology.

scholarly journals Molecular hydrogen potentiates beneficial anti-infarct effect of hypoxic postconditioning in isolated rat hearts: a novel cardioprotective intervention

2017 ◽  
Vol 95 (8) ◽  
pp. 888-893 ◽  
Author(s):  
Marek Zálešák ◽  
Branislav Kura ◽  
Ján Graban ◽  
Veronika Farkašová ◽  
Ján Slezák ◽  
...  
Keyword(s):  
Molecular Hydrogen ◽  
Redox Reactions ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Area At Risk ◽  
Rat Hearts ◽  
Hypoxic Postconditioning ◽  
Cardioprotective Effects ◽  
Krebs Henseleit Buffer ◽  
Isolated Rat

Generation of free radicals through incomplete reduction of oxygen during ischemia–reperfusion (I/R) is well described. On the other hand, molecular hydrogen (H2) reduces oxidative stress due to its ability to react with strong oxidants and easily penetrate cells by diffusion, without disturbing metabolic redox reactions. This study was designed to explore cardioprotective potential of hypoxic postconditioning (HpostC) against I/R (30 min global I – 120 min R) in isolated rat hearts using oxygen-free Krebs-Henseleit buffer (KHB). Furthermore, the possibility to potentiate the effect of HpostC by H2using oxygen-free KHB saturated with H2(H2+ HpostC) was tested. HPostC was induced by 4 cycles of 1-minute perfusion with oxygen-free KHB intercepted by 1-minute perfusion with normal KHB, at the onset of reperfusion. H2+ HPostC was applied in a similar manner using H2-enriched oxygen-free KHB. Cardioprotective effects were evaluated on the basis of infarct size (IS, in % of area at risk, AR) reduction, post-I/R recovery of heart function, and occurrence of reperfusion arrhythmias. HPostC significantly reduced IS/AR compared with non-conditioned controls. H2present in KHB during HPostC further decreased IS/AR compared with the effect of HPostC, attenuated severe arrhythmias, and significantly restored heart function (vs. controls). Cardioprotection by HpostC can be augmented by molecular hydrogen infusion.

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