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.

Activation of PKC decreases myocardial O2consumption and increases contractile efficiency in rats

2001 ◽  
Vol 281 (5) ◽  
pp. H2191-H2197 ◽  
Author(s):  
Teruo Noguchi ◽  
Zengyi Chen ◽  
Stephen P. Bell ◽  
Lori Nyland ◽  
Martin M. LeWinter
Keyword(s):  
Perfusion Pressure ◽  
Diastolic Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Regulatory Proteins ◽  
Basal Metabolism ◽  
Coronary Perfusion ◽  
Kinase C ◽  
Rat Hearts ◽  
Pkc Activation

The effect of protein kinase C (PKC) activation on cardiac mechanoenergetics is not fully understood. To address this issue, we determined the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) on isolated rat hearts. Hearts were exposed to PMA with or without pretreatment with the PKC inhibitor chelerythrine. Contractile efficiency was assessed as the reciprocal of the slope of the linear myocardial O2consumption (V˙o 2) pressure-volume area (PVA) relation. PMA decreased contractility ( E max; −30 ± 8%; P < 0.05) and increased coronary perfusion pressure (+58 ± 11%; P < 0.01) without altering left ventricular end-diastolic pressure. Concomitantly, PMA decreased PVA-independentV˙o 2 [nonmechanical energy expenditure for excitation-contraction (E-C) coupling and basal metabolism] by 28 ± 8% ( P < 0.05) and markedly increased contractile efficiency (+41 ± 8%; P < 0.05) in a manner independent of the coronary vascular resistance. Basal metabolism was not affected by PMA. Chelerythrine abolished the PMA-induced vasoconstriction, negative inotropy, decreased PVA-independent V˙o 2, and increased contractile efficiency. We conclude that PKC-mediated phosphorylation of regulatory proteins reduces V˙o 2 via effects on both the contractile machinery and the E-C coupling.

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.

Inorganic phosphate and coronary perfusion pressure mediate contractile dysfunction during mild ischemia

1997 ◽  
Vol 273 (2) ◽  
pp. H566-H572 ◽  
Author(s):  
M. Miyamae ◽  
S. A. Camacho ◽  
W. D. Rooney ◽  
G. Modin ◽  
H. Z. Zhou ◽  
...  
Keyword(s):  
Perfusion Pressure ◽  
Atp Hydrolysis ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Resonance Spectroscopy ◽  
Coronary Perfusion ◽  
Contractile Dysfunction ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
The Relationship

During mild graded ischemia in perfused rat hearts, we (V.M. Figueredo, R. Brandes, M. W. Weiner, B. M. Massie, and S. A. Camacho. J. Clin. Invest 90: 1794-1802, 1992) previously found a relationship between decreased left ventricular developed pressure (LVDP) and increased Pi, in which intracellular pH, cytosolic Ca2+ concentration ([Ca2+]i), ATP, and free-energy change of ATP hydrolysis were not altered enough to affect contractility. However, the contribution of decreased coronary perfusion pressure (CPP) to decreased LVDP could not be determined. Thus, in the present study, graded hypoxia in perfused rat hearts (95-37.5% O2) was used to increase Pi to similar levels produced during mild ischemia without altering CPP and minimizing changes of other potential mediators of contractile dysfunction. 31P-magnetic resonance spectroscopy and indo 1 fluorescence were used to assess energy metabolites and [Ca2+]i, respectively. The relationship between LVDP and Pi during graded hypoxia was fit to a monoexponential (LVDP = 105 x e-0.04Pi). These data were compared with the relationship of LVDP and Pi during mild ischemia (LVDP = 106 x e-0.08Pi) (V. M. Figueredo, R. Brandes, M. W. Weiner, B. M. Massie, and S. A. Camacho. J. Clin. Invest 90: 1794-1802, 1992). The exponential constant, which describes the effect of Pi on LVDP, was 50% lower during graded hypoxia relative to mild ischemia. This suggests that another mediator, which accounted for approximately 50% of the decrease of LVDP during mild ischemia, was not present during hypoxia. Because CPP decreased during ischemia but not hypoxia, these data suggest that CPP and Pi contribute similarly in mediating contractile dysfunction during mild ischemia.

scholarly journals Cardiovascular Activity of Labdane Diterpenes fromAndrographis paniculatain Isolated Rat Hearts

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Khalijah Awang ◽  
Nor Hayati Abdullah ◽  
A. Hamid A. Hadi ◽  
Yew Su Fong
Keyword(s):  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Cardiovascular Activity ◽  
Aerial Parts ◽  
Rat Hearts ◽  
Plant Bioassay ◽  
Coronary Vasodilatation ◽  
Labdane Diterpene ◽  
Isolated Rat

The dichloromethane (DCM) extract ofAndrographis paniculataNees was tested for cardiovascular activity. The extract significantly reduced coronary perfusion pressure by up to24.5±3.0 mm Hg at a 3 mg dose and also reduced heart rate by up to49.5±11.4 beats/minute at this dose. Five labdane diterpenes, 14-deoxy-12-hydroxyandrographolide (1), 14-deoxy-11,12-didehydroandrographolide (2), 14-deoxyandrographolide (3), andrographolide (4), and neoandrographolide (5), were isolated from the aerial parts of this medicinal plant. Bioassay-guided studies using animal model showed that compounds, (2) and (3) were responsible for the coronary vasodilatation. This study also showed that andrographolide (4), the major labdane diterpene in this plant, has minimal effects on the heart.

Effects of Ketamine and Its Isomers on Ischemic Preconditioning in the Isolated Rat Heart

2001 ◽  
Vol 94 (4) ◽  
pp. 623-629 ◽  
Author(s):  
Andrei Molojavyi ◽  
Benedikt Preckel ◽  
Thomas Comfère ◽  
Jost Müllenheim ◽  
Volker Thämer ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Katp Channels ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Protective Effects ◽  
Treatment Groups ◽  
Rat Hearts ◽  
Developed Pressure ◽  
And Control ◽  
Isolated Rat

Background Ischemic preconditioning protects the heart against subsequent ischemia. Opening of the adenosine triphosphate-sensitive potassium (KATP) channel is a key mechanism of preconditioning. Ketamine blocks KATP channels of isolated cardiomyocytes. The authors investigated the effects of ketamine and its stereoisomers on preconditioning. Methods Isolated rat hearts (n = 80) underwent 30 min of no-flow ischemia and 60 min of reperfusion. Two groups with eight hearts each underwent the protocol without intervention (control-1 and control-2), and, in eight hearts, preconditioning was elicited by two 5-min periods of ischemia before the 30 min ischemia. In the six treatment groups (each n = 8), ketamine, R(-)- or S(+)-ketamine were administered at concentrations of 2 or 20 microg/ml before preconditioning. Eight hearts received 20 microg/ml R(-)-ketamine before ischemia. Left ventricular (LV) developed pressure and creatine kinase (CK) release during reperfusion were determined as variables of ventricular function and cellular injury. Results Baseline LV developed pressure was similar in all groups: 104 +/- 28 mmHg (mean +/- SD). Controls showed a poor recovery of LV developed pressure (17 +/- 8% of baseline) and a high CK release (70 +/- 17 IU/g). Ischemic preconditioning improved recovery of LV developed pressure (46 +/- 14%) and reduced CK release (47 +/- 17 IU/g, both P &lt; 0.05 vs. control-1). Ketamine (2 microg/ml) and 2 or 20 microg/ml S(+)-ketamine had no influence on recovery of LV developed pressure compared with preconditioning (47 +/- 18, 43 +/- 8, 49 +/- 36%) and CK release (39 +/- 8, 30 +/- 14, 41 +/- 25 IU/g). After administration of 20 microg/ml ketamine and 2 or 20 microg/ml R(-)-ketamine, the protective effects of preconditioning were abolished (LV developed pressure-recovery, 16 +/- 14, 22 +/- 21, 18 +/- 11%; CK release, 67 +/- 11, 80 +/- 21, 82 +/- 41 IU/g; each P &lt; 0.05 vs. preconditioning). Preischemic treatment with R(-)-ketamine had no effect on CK release (74 +/- 8 vs. 69 +/- 9 IU/g in control-2, P = 0.6) and functional recovery (LV developed pressure 12 +/- 4 vs. 9 +/- 2 mmHg in control-2, P = 0.5). Conclusion Ketamine can block the cardioprotective effects of ischemic preconditioning. This effect is caused by the R(-)-isomer.

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%.

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.

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.

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