Prevention of lipid peroxidation does not prevent oxidant-induced myocardial contractile dysfunction

1994 ◽  
Vol 267 (6) ◽  
pp. H2371-H2377 ◽  
Author(s):  
Y. Kong ◽  
E. J. Lesnefsky ◽  
J. Ye ◽  
L. D. Horwitz
Keyword(s):  
Lipid Peroxidation ◽  
Coronary Flow ◽  
Systolic Function ◽  
Lipid Peroxide ◽  
Left Ventricular Pressure ◽  
Lipid Peroxides ◽  
Left Ventricular ◽  
Contractile Dysfunction ◽  
Myocardial Contractile ◽  
Generating System

We tested whether, with exposure to an extraneous iron-catalyzed free radical-generating system, prevention of lipid peroxidation with U74006F, a 21-aminosteroid, could also prevent myocardial contractile dysfunction. Rabbits received either U74006F (10 mg/kg iv) or vehicle (V). Thirty minutes later the hearts were excised and perfused by a non-recirculating Langendorff technique. Six U74006F- and six V-treated hearts were exposed for 7.5 min to a .OH-generating system (H2O2 and Fe(2+)-ADP chelate). Myocardial lipid peroxides were measured by glutathione peroxidase-catalyzed oxidation of exogenous glutathione. With exposure to .OH, cytosolic lipid peroxide levels were increased threefold in V-treated hearts, but there was no increase in U74006F-treated hearts. After 30 min of recovery, developed pressure and maximum first derivative of left ventricular pressure were greater in U74006F-treated hearts than in V-treated hearts but were still 50 and 44% of levels in saline hearts, respectively. Coronary flow was markedly reduced after exposure to free radicals and was only slightly less depressed when U74006F was administered. When coronary flow following oxidant exposure was increased by nitroglycerin, U74006F again only modestly improved systolic function. Thus, although U74006F blocked lipid peroxidation, it only slightly improved the ventricular dysfunction caused by .OH. Therefore, factors other than lipid peroxidation play a major role in oxidant-induced myocardial stunning.

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.

Regional Left Ventricular Systolic Function in Humans During Off-Pump Coronary Bypass Surgery

Circulation ◽  
1999 ◽  
Vol 100 (suppl_2) ◽  
Author(s):  
Philip M. Brown ◽  
Victor B. Kim ◽  
Bret J. Boyer ◽  
Robert M. Lust ◽  
W. Randolph Chitwood ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Stenosis ◽  
Systolic Function ◽  
Coronary Bypass ◽  
Inverse Correlation ◽  
Left Ventricular Pressure ◽  
Left Ventricular Systolic Function ◽  
Left Ventricular ◽  
Off Pump ◽  
Clinically Significant

Background —Controversy exists as to whether off-pump CABG with local occlusion results in clinically significant myocardial ischemia during the occlusion period. This study was undertaken to delineate the effects of transient local coronary artery occlusion on regional systolic function. Methods and Results —Eight consenting patients undergoing left internal mammary to left anterior descending coronary artery (LAD) bypass were instrumented with a left ventricular pressure catheter and 2 subepicardial cylindrical ultrasonic dimension transducers placed in the minor axis dimension in the region served by the LAD. A digital sonomicrometer was used to collect data before, during, and after coronary occlusion from which percent systolic shortening and pressure-dimension loops were derived. Measuring devices were removed immediately after the final time point. All patients tolerated the procedure well, and there were no complications. Average duration of local occlusion needed for CABG was 15.9±4.4 minutes (range, 12 to 26 minutes). Local occlusion was associated with a decrease in peak systolic shortening from 5.8±0.8% to 1.8±0.8%. In all cases, function returned to baseline after restoration of flow. Pressure-dimension loops confirmed these findings and no evidence of diastolic creep. Linear repression analysis of degree of stenosis versus change in segmental shortening revealed a significant inverse correlation. Conclusions —Local occlusion of the LAD resulted in a transient decrease in myocardial function during occlusion with complete recovery during reperfusion. This change was less significant with increasing degrees of coronary stenosis. These data suggest that local occlusion is not associated with permanent myocardial injury but that ischemic changes do occur that may be clinically significant, especially in patients with lesser degrees of coronary stenosis.

Myocardial substrate metabolism influences left ventricular energetics in vivo

2000 ◽  
Vol 278 (4) ◽  
pp. H1345-H1351 ◽  
Author(s):  
Christian Korvald ◽  
Odd Petter Elvenes ◽  
Truls Myrmel
Keyword(s):  
Fatty Acid ◽  
Coronary Flow ◽  
Left Ventricular Pressure ◽  
Random Order ◽  
Left Ventricular ◽  
Acid Oxidation ◽  
Left Ventricular Volumes ◽  
Acid Consumption ◽  
Myocardial Substrate

The myocardial oxygen consumption (MV˙o 2) to left ventricular pressure-volume area (PVA) relationship is assumed unaltered by substrates, despite varying phosphate-to-oxygen ratios and possible excess MV˙o 2 associated with fatty acid consumption. The validity of this assumption was tested in vivo. Left ventricular volumes and pressures were assessed with a combined conductance-pressure catheter in eight anesthetized pigs. MV˙o 2 was calculated from coronary flow and arterial-coronary sinus O2 differences. Metabolism was altered by glucose-insulin-potassium (GIK) or Intralipid-heparin (IH) infusions in random order and monitored with [14C]glucose and [3H]oleate tracers. Profound shifts in glucose and fatty acid oxidation were observed. Contractility, coronary flow, and slope of the MV˙o 2-PVA relationship were unchanged during GIK and IH infusions. MV˙o 2 at zero PVA (unloaded MV˙o 2) was 0.16 ± 0.13 J ⋅ beat− 1 ⋅ 100 g− 1 higher during IH compared with GIK infusion ( P = 0.001), a 48% increase. The study demonstrates a marked energetic advantage of glucose oxidation in the myocardium, profoundly affecting the MV˙o 2-PVA relationship. This may in part explain the “oxygen-wasting” effect of lipid-enhancing interventions such as adrenergic drugs and ischemia.

Myocardial relaxant effect of exogenous nitric oxide in isolated ejecting hearts

1994 ◽  
Vol 266 (5) ◽  
pp. H1699-H1705 ◽  
Author(s):  
R. Grocott-Mason ◽  
S. Fort ◽  
M. J. Lewis ◽  
A. M. Shah
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Coronary Flow ◽  
Systolic Function ◽  
Myocardial Contraction ◽  
Left Ventricular ◽  
Nitric Oxide Donor ◽  
Vasodilator Activity ◽  
Exogenous Nitric Oxide ◽  
Whole Heart

In isolated myocytes and papillary muscles, both nitric oxide, acting through guanosine 3',5'-cyclic monophosphate (cGMP), and cGMP analogues exert a novel effect on myocardial contraction, influencing mainly the onset of relaxation. We studied the effect of the exogenous nitric oxide donor, sodium nitroprusside (0.1-10 microM), in isolated ejecting guinea pig hearts at constant filling pressure, afterload, and heart rate to identify its direct myocardial effects in the whole heart. Sodium nitroprusside induced concentration-dependent increases in coronary flow as well as premature and faster early left ventricular (LV) pressure decline, but did not change end-diastolic or peak LV pressure or peak rate of rise of LV pressure. There was no correlation between changes in coronary flow and LV pressure decline. Sodium nitroprusside effects were inhibited by hemoglobin, which inactivates nitric oxide. The cGMP-independent vasodilator nicardipine also increased coronary flow but did not influence early LV pressure fall. Thus exogenous nitric oxide exerts novel direct myocardial relaxant effects in the isolated ejecting heart, independent of its known vasodilator activity, and without compromising systolic function.

Anesthetic Preconditioning

2003 ◽  
Vol 99 (2) ◽  
pp. 385-391 ◽  
Author(s):  
Leo G. Kevin ◽  
Peter Katz ◽  
Amadou K. S. Camara ◽  
Enis Novalija ◽  
Matthias L. Riess ◽  
...  
Keyword(s):  
Coronary Flow ◽  
Vascular Dysfunction ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Ischemic Time ◽  
Langendorff Preparation ◽  
Anesthetic Preconditioning ◽  
Structural Variables ◽  
Serious Injury

Background Anesthetic preconditioning (APC) is protective for several aspects of cardiac function and structure, including left ventricular pressure, coronary flow, and infarction. APC may be protective, however, only if the duration of ischemia is within a certain, as yet undefined range. Brief ischemia causes minimal injury, and APC would be expected to provide little benefit. Conversely, very prolonged ischemia would ultimately cause serious injury with or without APC. Previous investigations used a constant ischemic time as the independent variable to assess ischemia-induced changes in dependent functional and structural variables. The purpose of the study was to define the critical limits of efficacy of APC by varying ischemic time. Methods Guinea pig hearts (Langendorff preparation; n = 96) underwent pretreatment with sevoflurane (APC) or no treatment (control), before global ischemia and 120 min reperfusion. Ischemia durations were 20, 25, 30, 35, 40, and 45 min. Results At 120 min reperfusion, developed (systolic-diastolic) left ventricular pressure was increased by APC compared with control for ischemia durations of 25-40 min. Infarction was decreased by APC for ischemia durations of 25-40 min, but not 20 or 45 min. APC improved coronary flow and vasodilator responses for all ischemia durations longer than 25 min, and decreased ventricular fibrillation on reperfusion for ischemia durations longer than 30 min. Conclusions Although APC protects against vascular dysfunction and dysrhythmias after prolonged ischemia, protection against contractile dysfunction and infarction in this model is restricted to a range of ischemia durations of 25-40 min. These results suggest that APC may be effective in a subset of patients who have cardiac ischemia of intermediate duration.

Lipid peroxidation contributes to cardiac deficits after ischemia and reperfusion of the small bowel

1993 ◽  
Vol 264 (5) ◽  
pp. H1686-H1692 ◽  
Author(s):  
J. W. Horton ◽  
D. J. White
Keyword(s):  
Lipid Peroxidation ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Contractile Function ◽  
Langendorff Preparation ◽  
Cardiac Contractile ◽  
Intestinal Ischemia Reperfusion

Our previous studies showed that intestinal ischemia-reperfusion (IR) impairs cardiac contractile function. The present study examined the contribution of oxygen free radicals and lipid peroxidation of cardiac cell membrane to cardiac dysfunction after intestinal IR in a rat model of superior mesenteric artery (SMA) occlusion (atraumatic clip for 20 min) and collateral arcade ligation. Controls were sham operated (group 1, n = 25). In group 2, 30 rats with SMA occlusion were killed 3-4 h after reperfusion without treatment. Aminosteroid (U-74389F), a pharmacological agent known to inhibit lipid peroxidation of membranes, was given 1 min before occlusion of the SMA (group 3, n = 19). All rats were killed 3-4 h after reperfusion of the ischemic intestine, and the hearts were harvested for in vitro assessment of cardiac function (Langendorff preparation). Cardiac contractile depression occurred in the untreated group as indicated by a fall in left ventricular pressure (from 76 +/- 3 to 64 +/- 3 mmHg, P = 0.01), maximum +dP/dt (from 1,830 +/- 60 to 1,577 +/- 64 mmHg/s, P = 0.05), and maximum -dP/dt (from 1,260 +/- 50 to 950 +/- 60 mmHg/s, P = 0.005). Lipid peroxidation of cardiac membranes occurred after untreated IR as indicated by the rise in cardiac malondialdehyde levels (MDA) (from 0.203 +/- 0.046 to 0.501 +/- 0.044 nM/mg protein, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in lipid peroxidation and free radical scavengers in the brain of hyper- and hypothyroid aged rats

1995 ◽  
Vol 147 (2) ◽  
pp. 361-365 ◽  
Author(s):  
T Mano ◽  
R Sinohara ◽  
Y Sawai ◽  
N Oda ◽  
Y Nishida ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Free Radical ◽  
Lipid Peroxide ◽  
Lipid Peroxides ◽  
Thiobarbituric Acid ◽  
Free Radical Scavengers ◽  
Aged Rats ◽  
Radical Scavengers ◽  
Old Rats ◽  
The Brain

Abstract To determine how lipid peroxides and free radical scavengers are changed in the brain of hyper- or hypothyroid rats, we examined the behavior of lipid peroxide and free radical scavengers in the cerebral cortex of aged (1·5 years old) rats that had been made hyper- or hypothyroid by the administration of thyroxine or methimazol for 4 weeks. Concentrations of catalase, Mn-superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in hyperthyroid rats compared with euthyroid rats. Concentrations of total SOD, Cu,Zn-SOD and GSH-PX were increased but that of Mn-SOD was decreased in hypothyroid animals. There were no differences among hyperthyroid, hypothyroid and euthyroid rats in the levels of coenzymes 9 or 10. The concentration of lipid peroxides, determined indirectly by the measurement of thiobarbituric acid reactants, was decreased in hyperthyroid rats but not in hypothyroid rats when compared with euthyroid animals. These findings suggest that free radicals and lipid peroxides are scavenged to compensate for the changes induced by hyper- or hypothyroidism. Journal of Endocrinology (1995) 147, 361–365

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