Loss of adenosine-induced negative inotropic effect in hyperexcited rabbit hearts: relationship to PKC

1995 ◽  
Vol 268 (3) ◽  
pp. H1037-H1044 ◽  
Author(s):  
C. Cano ◽  
K. J. Slavik ◽  
K. U. Malik
Keyword(s):  
Perfusion Pressure ◽  
Negative Inotropic Effect ◽  
Coronary Perfusion Pressure ◽  
Inotropic Effect ◽  
Coronary Perfusion ◽  
Ang Ii ◽  
Calphostin C ◽  
Kinase C ◽  
Alarm Behavior ◽  
Pkc Activation

Adenosine produced a negative inotropic effect in hearts isolated from calm rabbits but not from those exhibiting alarm behavior during handling. This study was conducted to determine whether protein kinase C (PKC) activation is responsible for the loss of adenosine-induced negative inotropism in the hearts of hyperexcited rabbits. Adenosine (10 microM) decreased myocardial contractility (dP/dtmax) in the hearts of calm, but not hyperexcited, rabbits but decreased heart rate (HR) and coronary perfusion pressure (PP) in the hearts of both calm and hyperexcited animals. During infusion of calphostin C (200 nM), a PKC inhibitor, adenosine also decreased dP/dtmax in the hearts of hyperexcited rabbits. Calphostin C did not alter the actions of adenosine in the hearts of calm rabbits. Agents that stimulate PKC directly [phorbol 12,13-dibutyrate (PDBu), 1 nM] or indirectly [norepinephrine (NE), 3 nM; angiotensin II (ANG II), 5 nM] abolished the adenosine-induced decrease in dP/dtmax but not HR or PP in the hearts of calm rabbits. During calphostin C, infusion of PDBu, NE, and ANG II failed to prevent the adenosine-induced decrease in dP/dtmax. These data suggest that the lack of a negative inotropic effect of adenosine in hyperexcited rabbits is due to an increase in 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.

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.

Abstract 17334: The Detrimental Effect of Chest Compression Interruptions on Coronary Perfusion Pressure Dynamics

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Norman A Paradis ◽  
Karen L Moodie ◽  
Christopher L Kaufman ◽  
Joshua W Lampe
Keyword(s):  
Blood Flow ◽  
Chest Compression ◽  
Detrimental Effect ◽  
Perfusion Pressure ◽  
Vena Cava ◽  
Coronary Perfusion Pressure ◽  
Right Atrial ◽  
Coronary Perfusion ◽  
Chest Compressions ◽  
Over Time

Introduction: Guidelines for treatment of cardiac arrest recommend minimizing interruptions in chest compressions based on research indicating that interruptions compromise coronary perfusion pressure (CPP) and blood flow and reducing the likelihood of successful defibrillation. We investigated the dynamics of CPP before, during, and after compression interruptions and how they change over time. Methods: CPR was performed on domestic swine (~30 Kg) using standard physiological monitoring. Blood flow was measured in the abdominal aorta (AAo), the inferior vena cava, the right common carotid and external jugular. Ventricular fibrillation (VF) was electrically induced. Mechanical chest compressions (CC) were started after four minutes of VF. CC were delivered at a rate of 100 compressions per minute (cpm) and at a depth of 2” for a total of 12 min. CPP was calculated as the difference between aortic and right atrial pressure at end-diastole per Utstein guidelines. CPP was determined for 5 compressions prior to the interruption, every 2 seconds during the CC interruption, and for 7 compressions after the interruption. Per protocol, 12 interruptions occurred at randomized time points. Results: Across 12 minutes of CPR, averaged CPP prior to interruption was significantly greater than the averaged CPP after the interruption (22.4±1.0 vs. 15.5±0.73 mmHg). As CPR continued throughout the 12 minutes, CPP during compressions decreased (First 6 min = 24.1±1.4 vs. Last 6 min = 20.1±1.3 mmHg, p=0.05), but the effect of interruptions remained constant resulting in a 20% drop in CPP for every 2 seconds irrespective of the prior CPP. The increase (slope) of CPP after resumption of compressions was significantly reduced over time (First 6 min = 1.47±0.18 vs. Last 6 min = 0.82±0.13 mmHg/compression). Conclusions: Chest compression interruptions have a detrimental effect on coronary perfusion and blood flow. The magnitude of this effect increases over time as a resuscitation effort continues. These data confirm the importance of providing uninterrupted CPR particularly in long duration resuscitations.

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