Adenosine attenuates phorbol ester-induced negative inotropic and vasoconstrictive effects in rat hearts

1994 ◽  
Vol 266 (6) ◽  
pp. H2159-H2166 ◽  
Author(s):  
R. D. Lasley ◽  
M. A. Noble ◽  
K. L. Paulsen ◽  
R. M. Mentzer
Keyword(s):  
Phorbol Esters ◽  
Cardiac Contractility ◽  
Negative Inotropic Effect ◽  
Receptor Activation ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Coronary Vasoconstriction ◽  
Cgs 21680 ◽  
Rat Hearts

Phorbol esters reduce cardiac contractility and produce coronary vasoconstriction presumably by stimulating protein kinase C (PKC). We tested whether adenosine altered the response to phorbol 12-myristate 13-acetate (PMA) in isolated rat hearts. Hearts, perfused at constant flow and constant heart rate, were exposed to PMA (10 nM) for 30 min and then allowed 30 min of recovery. PMA reduced left ventricular developed pressure (LVDP) from 81 +/- 2 to 49 +/- 3 and 40 +/- 2 mmHg (51 +/- 3% of baseline LVDP) after 30 min infusion and 30 min recovery, respectively. PMA also increased coronary perfusion pressure to 224 +/- 13% of baseline after 60 min. The PKC inhibitor bisindolylmaleimide (0.5 microM) blocked the PMA-induced negative inotropy and vasoconstriction. Adenosine (100 microM) and the A1-agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 0.1 microM) significantly attenuated the negative inotropic effect of PMA as LVDP was maintained at 81 +/- 4% and 99 +/- 7% of baseline, whereas CGS-21680, an A2-agonist, had no beneficial effect on function (54 +/- 4% of baseline). Adenosine and CGS-21680 (0.1 microM), but not CCPA, significantly attenuated PMA-induced coronary vasoconstriction. These results suggest that adenosine receptor activation may modulate myocardial PKC activity or attenuate the effects of increased PKC activity.

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.

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.

Direct cardiac effects of vasopressin: role of V1- and V2-vasopressinergic receptors

1988 ◽  
Vol 255 (2) ◽  
pp. H261-H265 ◽  
Author(s):  
B. R. Walker ◽  
M. E. Childs ◽  
E. M. Adams
Keyword(s):  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Coronary Perfusion ◽  
Cardiac Effects ◽  
Coronary Vasoconstriction ◽  
Langendorff Preparation ◽  
Wide Range ◽  
Male Wistar Rats

Experiments were performed to determine the possible direct effects of arginine vasopressin (AVP) on cardiac function in the nonworking Langendorff preparation. Hearts were isolated from male Wistar rats, and the coronary arteries were retrograde perfused at a constant rate through the aorta with a Krebs-Henseleit solution, which was continuously bubbled with 95% O2–5% CO2. The hearts were paced at 280 beats/min and measurements made of peak ventricular pressure (PVP), first derivative of left ventricular pressure (dP/dtmax), and coronary perfusion pressure (CPP). By maintaining constant coronary flow, the direct cardiac effects of AVP could be determined independent of changes in myocardial O2 delivery elicited by potential coronary vasoconstriction. Myocardial function was assessed at AVP concentrations of 0, 10, 25, 50, 100, 200, 400, and 500 pg/ml. Progressive coronary vasoconstriction was observed with increasing AVP concentration. In contrast, PVP and dP/dtmax increased at 50 and 100 pg/ml of AVP but fell at 400 and 500 pg/ml. The maximal PVP and dP/dtmax responses were at 50 pg/ml (+16 +/- 3 and +44 +/- 4%, respectively), whereas at 500 pg/ml both PVP and dP/dtmax were reduced below control (-30 +/- 4 and -34 +/- 5%, respectively). Pretreatment with the specific V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP (40 ng/ml) totally blocked both the coronary vasoconstrictor and contractility responses to AVP. Furthermore, infusion of a specific V2-agonist was without effect even at high doses. These data suggest that although AVP causes dose-related coronary vasoconstriction over a wide range of AVP concentrations, the hormone may exert a positive inotropic effect at doses mimicking circulating levels encountered in a number of pathophysiological situations.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of freeze-dried red wine on cardiac function and ECG of the Langendorff-perfused rat heart

2014 ◽  
Vol 92 (2) ◽  
pp. 171-174 ◽  
Author(s):  
Antonella Ferrara ◽  
Fabio Fusi ◽  
Beatrice Gorelli ◽  
Giampietro Sgaragli ◽  
Simona Saponara
Keyword(s):  
Cardiac Function ◽  
Red Wine ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Rat Hearts ◽  
Freeze Dried ◽  
High Concentrations ◽  
Vasodilating Activity

The effect of freeze-dried red wine (FDRW) on cardiac function and electrocardiogram (ECG) in Langendorff-isolated rat hearts was investigated. FDRW significantly decreased left ventricular pressure and coronary perfusion pressure, the latter being dependent on the activation of both phosphatidylinositol 3-kinase and eNOS. FDRW did not affect the QRS and QT interval in the ECG, although at 56 μg of gallic acid equivalents/mL, it prolonged PQ interval and induced a second-degree atrioventricular block in 3 out of 6 hearts. This is the first study demonstrating that at concentrations resembling a moderate consumption of red wine, FDRW exhibited negative inotropic and coronary vasodilating activity leaving unaltered ECG, whereas at very high concentrations, it induced arrhythmogenic effects.

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.

Intramyocardial pressure gradients in working and nonworking isolated cat hearts

1994 ◽  
Vol 266 (3) ◽  
pp. H1233-H1241 ◽  
Author(s):  
L. S. Mihailescu ◽  
F. L. Abel
Keyword(s):  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Mechanical Resistance ◽  
Coronary Perfusion ◽  
Pressure Gradients ◽  
Intramyocardial Pressure ◽  
Krebs Henseleit Buffer ◽  
Transmural Gradient

This study presents an improved method for the measurement of intramyocardial pressure (IMP) using the servo-nulling mechanism. Glass micropipettes (20-24 microns OD) were used as transducers, coated to increase their mechanical resistance to breakage, and placed inside the left ventricular wall with a micropipette holder and manipulator. IMP was measured at the base of the left ventricle in working and nonworking isolated cat hearts that were perfused with Krebs-Henseleit buffer. In working hearts a transmural gradient of systolic IMP oriented from endocardium toward the epicardium was found; the endocardial values for systolic IMP were slightly higher than systolic left ventricular pressure (LVP), by 11-18%. Increases in afterload induced increases in IMP, without changing the systolic IMP-to-LVP ratio. In nonworking hearts with drained left ventricles, the systolic transmural gradient for IMP described for working hearts persisted, but at lower values, and was directly dependent on coronary perfusion pressure. Systolic IMP-to-LVP ratios were always > 1. The diastolic IMP of both working and nonworking hearts exhibited irregular transmural gradients. Our results support the view that generated systolic IMP is largely independent of LVP development.

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