Downregulation of ventricular contractile function during early ischemia is flow but not pressure dependent

1998 ◽  
Vol 275 (5) ◽  
pp. H1520-H1523 ◽  
Author(s):  
Miao-Xiang He ◽  
H. Fred Downey
Keyword(s):  
Coronary Artery ◽  
Perfusion Pressure ◽  
Contractile Function ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Rat Hearts ◽  
Myocardial Contractile Force ◽  
Myocardial Contractile ◽  
Artery Obstruction

The mechanism responsible for the abrupt fall in myocardial contractile function following coronary artery obstruction is unknown. The “vascular collapse theory” hypothesizes that the fall in coronary perfusion pressure after coronary artery obstruction is responsible for contractile failure during early ischemia. To test the role of vascular collapse in downregulating myocardial contractile force at the onset of ischemia, coronary flow of isolated rat hearts was abruptly decreased by 50, 70, 85, and 100% of baseline, and subsequent changes in coronary perfusion pressure and ventricular function were recorded at 0.5-s intervals. At 1.5 s after flow reductions ranging from 50 to 100%, decreases in contractile function did not differ, although perfusion pressure varied significantly from 45 ± 1 to 20 ± 2 mmHg. When function fell to 50% of baseline, perfusion pressures ranged from 35 ± 0.5 to 2.5 ± 1 mmHg for flow reductions ranging from 50 to 100%. Identical contractile function at widely differing coronary perfusion pressures is incompatible with the vascular collapse theory.

Correlation between myocardial contractile force and cytosolic inorganic phosphate during early ischemia

1997 ◽  
Vol 272 (3) ◽  
pp. H1333-H1341 ◽  
Author(s):  
M. X. He ◽  
S. Wang ◽  
H. F. Downey
Keyword(s):  
Inorganic Phosphate ◽  
Contractile Force ◽  
Left Ventricular ◽  
Resonance Spectroscopy ◽  
Rat Hearts ◽  
Initial Control ◽  
Myocardial Contractile Force ◽  
Myocardial Contractile ◽  
Developed Pressure

To test the role of inorganic phosphate (Pi) in downregulation of myocardial contractile force at the onset of ischemia, Pi of rat hearts was determined with 31P nuclear magnetic resonance spectroscopy. Forty cycles of brief hypoperfusion (30% of baseline flow for 33 s) were used to achieve a time resolution of 0.512 s for comparing dynamic changes in Pi and contractile force. Initial control values of left ventricular developed pressure (LVP), heart rate, and oxygen consumption were 136 +/- 11 mmHg, 236 +/- 4 beats/min, and 95 +/- 3 microl O2 x min(-1) x g(-1); these values were unchanged at the end of the experiment. During the first 10 s of hypoperfusion, Pi increased at a rate (percentage of the total observed change) faster than the decrease in LVP; Pi and LVP then changed at the same rate during the remainder of the hypoperfusion. ADP did not change in advance of LVP. Intracellular pH did not change. The results indicate that Pi plays an important role in initiating the downregulation of myocardial contractile force at the onset of ischemia. Perfusion pressure also declined faster than LVP at the onset of ischemia, indicating potential importance of vascular collapse in contractile downregulation during early ischemia.

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.

Role of myocardial oxygen and carbon dioxide in coronary autoregulation

1992 ◽  
Vol 262 (4) ◽  
pp. H1231-H1237 ◽  
Author(s):  
T. P. Broten ◽  
E. O. Feigl
Keyword(s):  
Carbon Dioxide ◽  
Left Main Coronary Artery ◽  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Vascular Conductance ◽  
Anesthetized Dogs ◽  
Coronary Conductance ◽  
A Prospective Study

Myocardial oxygen (PO2) and carbon dioxide tensions (PCO2) are likely mediators of the local control of coronary blood flow. A previous study demonstrated that myocardial PO2 and PCO2, estimated by coronary venous values, interact synergistically to determine coronary flow. This synergistic relation was used in a prospective study to test the hypothesis that myocardial PO2 and PCO2 mediate changes in coronary vascular conductance during autoregulation. The left main coronary artery was pump perfused at controlled pressures in closed-chest anesthetized dogs. Autoregulation curves were obtained by increasing coronary perfusion pressure from 80 to 160 mmHg in 20-mm increments. Steady-state measurements of coronary venous PO2 and PCO2 and coronary conductance were obtained at each perfusion pressure. The coronary venous PO2 and PCO2 were used in the previously determined synergistic relation to predict the coronary vascular conductance during autoregulation. The predicted changes in coronary vascular conductance were compared with the actual changes in coronary vascular conductance for the pressure range of 80-160 mmHg. The data indicate that the synergistic interaction of oxygen and carbon dioxide accounts for approximately 23% of the change in coronary vascular conductance during autoregulation. These results suggest that other factors are also involved in autoregulation.

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.

Mechanism of mechanical alternans in ischemia-reperfusion: role of deficient relaxation of the strong twitch

1995 ◽  
Vol 269 (1) ◽  
pp. H169-H175 ◽  
Author(s):  
O. N. Nwasokwa
Keyword(s):  
Papillary Muscle ◽  
Perfusion Pressure ◽  
Isometric Force ◽  
Ischemia Reperfusion ◽  
Coronary Perfusion Pressure ◽  
Peak Force ◽  
Coronary Perfusion ◽  
Myocardial Relaxation

We tested the hypothesis that impaired and incomplete relaxation of the strong twitch of mechanical alternans causes the peak force deficit (PFD) of the weak twitch and that, by decreasing the relaxation deficit (RD) of the strong twitch, dobutamine would diminish the PFD. We studied isometric twitches of the in situ blood-perfused canine papillary muscle (n = 8). To produce mechanical alternans, we paced the heart at 110-155 beats/min and decreased mean coronary perfusion pressure (MCPP) stepwise to produce ischemia and then increased it to produce reperfusion. We measured the RD and PFD and fit each curve of isometric force [F(t)] with the relation F(t) = F0 + C(t/A)Be1-(t/A)B, where F0 is force at twitch onset, to obtain the parameters A, B, and C. B is a dimensionless index of myocardial relaxation; it decreases with impaired (delayed) relaxation. At each MCPP, we averaged B for the strong and weak twitches. The PFD showed a positive correlation with the RD. At each MCPP, mean B was lower for the strong twitch than for the weak twitch, indicating impaired relaxation of the strong twitch. Dobutamine increased B from 1.83 +/- 0.14 to 2.12 +/- 0.16 (P = 0.00002) in the strong twitch and decreased B from 4.15 +/- 2.42 to 2.19 +/- 0.18 (P = 0.05) in the weak twitch. Dobutamine thus equalized the relaxation of the strong and weak twitches. Consequently it decreased the RD from 2.57 +/- 2.14 to 0.16 +/- 0.24 g (P = 0.01) and the PFD from 5.50 +/- 3.67 to 1.04 +/- 1.15 g (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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