Superoxide and nitroglycerin stimulate release of PGF2 alpha and TxA2 in isolated rat heart

1996 ◽  
Vol 271 (6) ◽  
pp. H2447-H2453
Author(s):  
S. A. Gupte ◽  
T. Okada ◽  
R. Ochi
Keyword(s):  
Rat Heart ◽  
Perfusion Pressure ◽  
Control Period ◽  
Coronary Perfusion Pressure ◽  
Isolated Rat Heart ◽  
Coronary Perfusion ◽  
No Donor ◽  
Heart Perfusion ◽  
Txa2 Receptor ◽  
Pg Release

The aim of this study was to investigate the effects of nitroglycerin (NTG), a nitric oxide (NO) donor used as a vasodilating agent, on prostanoid [e.g., prostaglandin (PG)] release in the O2(-)-pretreated rat heart. Perfusion of O2-, generated by a xanthine oxidase-purine coupling, caused elevation (P < 0.05) of the coronary perfusion pressure (CPP) after 20 min (from 57.1 +/- 3.9 during the control period to 72.2 +/- 3.9 mmHg, P < 0.05). O2- caused increased release of PGF2 alpha from 3.6 +/- 0.7 to 20.6 +/- 4.4 pmol.min-1.g-1 and of thromboxane A2 (TxA2) from 2.4 +/- 0.4 to 9.6 +/- 1.6 pmol.min-1.g-1 (P < 0.001) with no significant changes in PGE2 and PGI2 release. During the 20-min washout of O2- from the heart with normal Krebs solution, release of PGF2 alpha and TxA2 decreased to 8.7 +/- 1.4 and 6.3 +/- 1.7 pmol.min-1.g-1, respectively, and the release of PGE2 and PGI2 markedly increased from 11.1 +/- 2.9 to 25.4 +/- 3.6 and 157.2 +/- 16.4 to 413.2 +/- 41.4 pmol.min-1.g-1, respectively (P < 0.05), without lowering the elevated CPP. Administration of 4 microM NTG during the washout period paradoxically augmented the elevated CPP to 133.3 +/- 0.6% and was associated with a doubling (P < 0.05) of PGF2 alpha and TxA2 release with no significant changes in PGE2 and PGI2 release. The NTG-induced CPP elevation was inhibited (P < 0.05) by indomethacin, a cyclooxygenase inhibitor, or ONO-3708, a TxA2 receptor blocker, whereas arachidonic acid, a substrate for PG synthesis, augmented the CPP elevation. These results indicate that NTG stimulates the synthesis of vasoconstrictive PG in the O2(-)-pretreated rat heart, inducing a paradoxical elevation in CPP.

P561Acute effects of dronedarone and amiodarone on functional, morphological and oxidative stress parameters in isolated rat heart with hypertension

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
S Simovic ◽  
J Jeremic ◽  
G Davidovic ◽  
I Srejovic ◽  
S Mitrovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Heart ◽  
Structural Changes ◽  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Isolated Rat Heart ◽  
Coronary Perfusion ◽  
Acute Administration ◽  
Isolated Hearts ◽  
Isolated Rat

Abstract Introduction Amiodarone represents the most widely used antiarrhythmic drug, even though it has been shown that it has negative inotropic and lusitropic effect in healthy hears. On the other hand, dronedarone reduces the risk of recurrent atrial fibrillation, but with increased early mortality related to the worsening of heart failure. However, the mechanisms responsible for these fatal outcomes remain unclear and require further examinations.  Purpose To investigate acute, direct effects of Dronedarone and Amiodarone on cardiac contractility, coronary flow and oxidative stress parameters in isolated rat heart with hypertension. Methods  The present study was carried out on 18 isolated hearts of spontaneously hypertensive Wistar Kyoto male rats (6 weeks old, bodyweight 200 ± 10 g). After isolation, all hearts were retrogradely perfused according to Langendorff technique with a gradually increment of coronary perfusion pressure (CPP from 40 to 120 cm H2O) and randomly divided into 3 groups: Control (n = 6), Amiodarone (n = 6, isolated hearts perfused with Amiodarone in dose of 3 umol), Dronedarone (n = 6, isolated hearts perfused with Dronedarone in dose of 1.8 umol). During ex vivo protocol continuously were registered cardiac contractility parameters and coronary flow, while from collected coronary venous effluent markers of oxidative stress were measured. All hearts were then fixated and stained with Hematoxylin/eosin. Results  Dronedarone severely depressed the function of all cardiodynamic parameters of the heart compared with Amiodarone or Control while Amiodarone intensified the function of the isolated rat heart with hypertension compared to Control (dp/dt max mmHg/s at coronary perfusion pressure 120cmH2O Dronedarone vs. Amiodarone vs. Control 579.733 ± 202.27 vs. 3063.65 ± 467.93 vs. 2682.88 ± 368.75; p &lt; 0.001. dp/dt min mmHg/s 120cmH2O -352.13 ± 204.65 vs. 1960 ± 242.21 vs. -1858.83 ± 118.23; p &lt; 0.001. SLVP mmHg at CPP 120cmH20 27.8 ± 3.46 vs. 98.95 ± 11.78 vs. 71.45 ± 7.56; p &lt; 0.001. DLVP mmHg at CPP 120cmH2O 6.32 ± 0.49 vs. 4.83 ± 0.54 vs. 0.85 ± 0.35; p &lt; 0.001). Acute administration of Dronedarone decreased the level of NO2- and increased the level of H2O2 , while Amiodarone heightens O2- levels (O2- nmol/min g wt at coronary perfusion pressure 120cmH2O Dronedarone vs. Amiodarone vs. Control  28.62 ± 2.54 vs. 77.3 ± 8.86 vs. 31.72 ± 4.56; p &lt; 0.001. H2O2 nmol/min g wt at CPP 120cmH2O 92.56 ± 11.65 vs. 48.63 ± 10.11 vs. 42.84 ± 84; p &lt; 0.001. NO2- nmol/min g wt at CPP 120cmH2O 38.61 ± 4.94 vs.  82.28 ± 5.76 vs.  64.71 ± 3.51; p &lt; 0.001). Pathohistological, structural changes were observed in both, experimental groups. Conclusions  Acute administration of Dronedarone depresses cardiac function in isolated, working rat heart with hypertension, with decreasing the NO2- levels, increasing the level of H2O2 and enhanced structural changes when compared to Amiodarone.

scholarly journals Glucagon Effects on Ischemic Vasodilatation in the Isolated Rat Heart

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Mirko Rosic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Aleksandra Tomic-Lucic ◽  
Tatjana Labudovic ◽  
...  
Keyword(s):  
Rat Heart ◽  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Isolated Rat Heart ◽  
Myocardial Reperfusion ◽  
Coronary Perfusion ◽  
Vasoactive Substances ◽  
Significant Attenuation ◽  
Biphasic Release ◽  
Isolated Rat

The myocardial reperfusion following ischemia leads to the ischemic vasodilation by affecting the release of various vasoactive substances, such as free radicals, NO, and histamine. In addition, some evidences suggest that glucagon itself may alter the release of those substances. In this study, we investigated the ischemic vasodilation of the isolated rat heart, as well as the concentrations of NO, TBARS, and histamine in the coronary venous effluent either in the presence or in the absence of glucagon. Our results showed that in the presence of glucagon, there was a faster restoration of coronary perfusion pressure during ischemic vasodilation compared to the absence of glucagon ( versus  s) with no apparent changes in TBARS concentration. The glucagon's administration leads to the decreased release of histamine by approximately 35%. Biphasic release of NO in the presence of glucagon initially showed augmentation by 60%, followed by the significant attenuation of 45%.

scholarly journals The Effects of Chronic Administration of Cisplatin on Oxidative Stress in the Isolated Rat Heart

2017 ◽  
Vol 0 (0) ◽  
Author(s):  
Jelena Smigic ◽  
Isidora Stojic ◽  
Vladimir Zivkovic ◽  
Ivan Srejovic ◽  
Tamara Nikolic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Heart ◽  
Chronic Administration ◽  
Coronary Perfusion Pressure ◽  
Isolated Rat Heart ◽  
Control Group ◽  
Albino Rats ◽  
Coronary Perfusion ◽  
Cellular Mechanisms ◽  
Isolated Rat

Abstract Taken into consideration that molecular and cellular mechanisms involved in cardiotoxicity are still not clear the aim of this study was to compare the production of oxidative stress parameters in the isolated rat heart between animals chronically treated with cisplatin and saline. Th e hearts of male Wistar albino rats (n = 24, 12 per group, age 8 weeks, body mass 250±50 g) were excised and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmH2O). We followed the production of superoxide anion radicals, hydrogen peroxide, and nitrites and also index of lipid peroxidation during the changes of coronary perfusion pressure (CPP) (from 40 to 120 cm H2O) in coronary venous effluent. Modifications CPP were performed in order to determined if oxidative stress is involved in coronary endothelium response in conditions of hypoxia (lower than 60 cm H2O) and hyperoxia (higher than 80 cm H2O). Based on the results of this research we can conclude that with enhancement of CPP the values of oxidative stress statistically increased. However, this increment is more prominent in control group as a result of preserved endothelium and its more powerful response to hyperoxia. On the other hand, damaged endothelium of cisplatin-treated animals had weaker response to hyperoxia, and also lower antioxidant capacity.

Mechanism of action of arachidonic acid in the isolated perfused rat heart

1984 ◽  
Vol 62 (5) ◽  
pp. 551-558 ◽  
Author(s):  
Joel E. Shaffer ◽  
Kafait U. Malik
Keyword(s):  
Heart Rate ◽  
Arachidonic Acid ◽  
Mechanism Of Action ◽  
Rat Heart ◽  
Perfusion Pressure ◽  
Nordihydroguaiaretic Acid ◽  
Isolated Rat Heart ◽  
Coronary Perfusion ◽  
Coronary Vasodilation ◽  
Lipoxygenase Inhibitors

The purpose of this study was to elucidate the mechanism of action of arachidonic acid in the isolated rat heart perfused with Krebs solution at a constant flow. Administration of arachidonic acid, 3.3–33 nmol, into the heart caused a small transient increase followed by a pronounced decrease in coronary perfusion pressure and increased myocardial tension, heart rate, and the output of prostaglandins (6-keto-PGF1α, PGE2, and PGF2α). Administration of structurally similar fatty acids, dihomo-γ-linolenic acid, and 8,14,17-eicosatrienoic acid, produced vasoconstriction and decreased myocardial tension without affecting heart rate or the output of prostaglandins. Infusion of PGI2, PGF2α, or PGE2 produced coronary vasodilation and increased myocardial tension, whereas PGF2α increased heart rate, an effect which was not prevented by propranolol. Indomethacin blocked the effect of arachidonic acid on myocardial tension and heart rate, but only reduced the duration of coronary vasodilation. The initial component of arachidonic acid induced coronary vasodilation which was unaffected by indomethacin and also remained unaltered during the infusion of three structurally dissimilar lipoxygenase inhibitors, eicosatetraynoic acid, nordihydroguaiaretic acid, and 1-phenyl-3-pyrazolidone. Indomethacin did not alter the effects of the exogenously administered prostaglandins on perfusion pressure or myocardial tension; however, it blocked the effect of PGF2α on heart rate. The effect of arachidonic acid or PGF2α to increase heart rate was not blocked by thromboxane synthetase inhibitors, imidazole, or OKY-1581. We conclude that the cardiac effects of arachidonic acid are mediated primarily through its conversion to cyclooxygenase products. However, the initial biphasic component of the coronary vascular response, vasoconstriction, and subsequent vasodilation produced during the first 3-min period following arachidonic acid administration appears to be unrelated to prostaglandins, whereas the duration of the coronary vasodilation depends upon the formation of cyclooxygenase products.

scholarly journals The Effects of Chronic Administration of Cisplatin on Oxidative Stress in the Isolated Rat Heart

2018 ◽  
Vol 19 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Jelena Smigic ◽  
Isidora Stojic ◽  
Vladimir Zivkovic ◽  
Ivan Srejovic ◽  
Tamara Nikolic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Heart ◽  
Chronic Administration ◽  
Coronary Perfusion Pressure ◽  
Isolated Rat Heart ◽  
Control Group ◽  
Albino Rats ◽  
Coronary Perfusion ◽  
Cellular Mechanisms ◽  
Isolated Rat

Abstract Taken into consideration that molecular and cellular mechanisms involved in cardiotoxicity are still not clear the aim of this study was to compare the production of oxidative stress parameters in the isolated rat heart between animals chronically treated with cisplatin and saline. The hearts of male Wistar albino rats (n = 24, 12 per group, age 8 weeks, body mass 250±50 g) were excised and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cm H2O). We followed the production of superoxide anion radicals, hydrogen peroxide, and nitrites and also index of lipid peroxidation during the changes of coronary perfusion pressure (CPP) (from 40 to 120 cm H2O) in coronary venous effluent. Modifications CPP were performed in order to determined if oxidative stress is involved in coronary endothelium response in conditions of hypoxia (lower than 60 cm H2O) and hyperoxia (higher than 80 cm H2O). Based on the results of this research we can conclude that with enhancement of CPP the values of oxidative stress statistically increased. However, this increment is more prominent in control group as a result of preserved endothelium and its more powerful response to hyperoxia. On the other hand, damaged endothelium of cisplatin-treated animals had weaker response to hyperoxia, and also lower antioxidant capacity.

Effect of perfusion pressure at reoxygenation on reflow and function in isolated rat hearts

1992 ◽  
Vol 262 (4) ◽  
pp. H1029-H1035
Author(s):  
K. S. Seiler ◽  
J. P. Kehrer ◽  
J. W. Starnes
Keyword(s):  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Coronary Perfusion ◽  
Vascular Compression ◽  
Rat Hearts ◽  
Developed Pressure ◽  
And Function ◽  
Isolated Rat

The effect of coronary perfusion pressure during reoxygenation on recovery of endocardial flow, arrhythmogenesis, and mechanical function was investigated in the isolated rat heart. Hearts were subjected to 30 min of substrate-free hypoxia followed by 30 min reoxygenation at either 80 or 150 cmH2O perfusion pressure. No flow areas were quantified by 0.3% phthalocyanine blue injection after 30 min of hypoxia, 30 min reoxygenation at 80 cmH2O, or 30 min reoxygenation at 150 cmH2O. After hypoxia, 31 +/- 2% of the myocardium was unperfused. After 80 cmH2O reoxygenation, 13 +/- 4% of the heart remained unperfused. Ten of 12 (83%) 80-cmH2O hearts were in sustained fibrillation after 10 min of reoxygenation. Reoxygenation at 150 cmH2O resulted in complete reperfusion of the myocardium. Fibrillation was absent in all hearts reoxygenated at this higher pressure. Functional recovery after 30 min reoxygenation (% of normoxic heart rate x left ventricular developed pressure) was significantly (P less than 0.05) higher in 150 cmH2O vs. 80 cmH2O (60 +/- 5 vs. 42 +/- 8%). Elevating perfusion pressure upon reoxygenation appears to counter the vascular compression caused by contracture and leads to a more rapid and homogeneous restoration of coronary flow during the transition from the hypoxic to the normoxic state.

Contribution of extravascular compression to reduction of maximal coronary blood flow

1992 ◽  
Vol 262 (1) ◽  
pp. H68-H77
Author(s):  
F. L. Abel ◽  
R. R. Zhao ◽  
R. F. Bond
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Coronary Perfusion ◽  
Storage Site

Effects of ventricular compression on maximally dilated left circumflex coronary blood flow were investigated in seven mongrel dogs under pentobarbital anesthesia. The left circumflex artery was perfused with the animals' own blood at a constant pressure (63 mmHg) while left ventricular pressure was experimentally altered. Adenosine was infused to produce maximal vasodilation, verified by the hyperemic response to coronary occlusion. Alterations of peak left ventricular pressure from 50 to 250 mmHg resulted in a linear decrease in total circumflex flow of 1.10 ml.min-1 x 100 g heart wt-1 for each 10 mmHg of peak ventricular to coronary perfusion pressure gradient; a 2.6% decrease from control levels. Similar slopes were obtained for systolic and diastolic flows as for total mean flow, implying equal compressive forces in systole as in diastole. Increases in left ventricular end-diastolic pressure accounted for 29% of the flow changes associated with an increase in peak ventricular pressure. Doubling circumferential wall tension had a minimal effect on total circumflex flow. When the slopes were extrapolated to zero, assuming linearity, a peak left ventricular pressure of 385 mmHg greater than coronary perfusion pressure would be required to reduce coronary flow to zero. The experiments were repeated in five additional animals but at different perfusion pressures from 40 to 160 mmHg. Higher perfusion pressures gave similar results but with even less effect of ventricular pressure on coronary flow or coronary conductance. These results argue for an active storage site for systolic arterial flow in the dilated coronary system.

scholarly journals Cardiac arrest complicating cardiogenic shock: from pathophysiological insights to Impella-assisted cardiopulmonary resuscitation in a pheochromocytoma-induced Takotsubo cardiomyopathy—a case report

2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Filippo Zilio ◽  
Simone Muraglia ◽  
Roberto Bonmassari
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Left Ventricle ◽  
Cardiogenic Shock ◽  
Takotsubo Cardiomyopathy ◽  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Refractory Cardiac Arrest

Abstract Background A ‘catecholamine storm’ in a case of pheochromocytoma can lead to a transient left ventricular dysfunction similar to Takotsubo cardiomyopathy. A cardiogenic shock can thus develop, with high left ventricular end-diastolic pressure and a reduction in coronary perfusion pressure. This scenario can ultimately lead to a cardiac arrest, in which unloading the left ventricle with a peripheral left ventricular assist device (Impella®) could help in achieving the return of spontaneous circulation (ROSC). Case summary A patient affected by Takotsubo cardiomyopathy caused by a pheochromocytoma presented with cardiogenic shock that finally evolved into refractory cardiac arrest. Cardiopulmonary resuscitation was performed but ROSC was achieved only after Impella® placement. Discussion In the clinical scenario of Takotsubo cardiomyopathy due to pheochromocytoma, when cardiogenic shock develops treatment is difficult because exogenous catecholamines, required to maintain organ perfusion, could exacerbate hypertension and deteriorate the cardiomyopathy. Moreover, as the coronary perfusion pressure is critically reduced, refractory cardiac arrest could develop. Although veno-arterial extra-corporeal membrane oxygenation (va-ECMO) has been advocated as the treatment of choice for in-hospital refractory cardiac arrest, in the presence of left ventricular overload a device like Impella®, which carries fewer complications as compared to ECMO, could be effective in obtaining the ROSC by unloading the left ventricle.

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