Effect of Endothelin on the Function of the Isolated Perfused Working Rat Heart

1. The effect of endothelin on the performance of the isolated perfused working rat heart has been examined. 2. A low concentration of endothelin (60 pmol/l) produced a gradual but sustained increase in cardiac output; coronary vascular resistance was unaffected. 3. A high concentration of endothelin (600 pmol/l) produced a rapid increase in cardiac output, followed by a marked fall in cardiac output as progressive, severe coronary vasoconstriction developed. 4. The coronary vasoconstriction induced by endothelin (600 pmol/l) was partially blocked by nicardipine (0.5 pmol/l) 5. In the presence of either nicardipine (0.5 μmol/l) or verapamil (0.2 μmol/l), the increment in cardiac output induced by endothelin (600 pmol/l) was greater than that induced by the addition of the same concentration of endothelin to hearts which had not been exposed to calcium-entry blockers. 6. The effect of endothelin on myocardial contractility has a different time course, concentration dependence and response to calcium-entry blockade than the effect on the coronary vasculature. This suggests that different mechanisms are involved in the generation of the myocardial and vascular responses to endothelin.

Download Full-text

Calcium-accentuated ischemic damage during reperfusion: The time course of the reperfusion injury in the isolated working rat heart model

Journal of Surgical Research ◽

10.1016/0022-4804(87)90064-3 ◽

1987 ◽

Vol 42 (1) ◽

pp. 51-55 ◽

Cited By ~ 14

Author(s):

Yoh Yano ◽

Thomas R. Riggs ◽

Douglas F. Milam ◽

John C. Alexander

Keyword(s):

Reperfusion Injury ◽

Rat Heart ◽

Time Course ◽

Ischemic Damage ◽

Heart Model ◽

Working Rat Heart

Download Full-text

Effect of insulin and lack of effect of workload and hypoxia on protein degradation in the perfused working rat heart

Biochemical Journal ◽

10.1042/bj2100055 ◽

1983 ◽

Vol 210 (1) ◽

pp. 55-61 ◽

Cited By ~ 6

Author(s):

D M Smith ◽

P H Sugden

Keyword(s):

Cardiac Output ◽

Protein Degradation ◽

Rat Heart ◽

Acute Hypoxia ◽

Aortic Pressure ◽

Partial Replacement ◽

The Stability ◽

Increased Pressure ◽

Working Rat Heart

1. Protein degradation was studied in the glucose (5 mM)-perfused working rat heart preparation of Taegtmeyer, Hems & Krebs [(1980) Biochem. J. 186. 701-711]. 2. The effects of cardiac workload were investigated in three different preparations: (a) control (low workload), (b) increased pressure workload (simulating conditions of aortic pressure in vivo) and (c) increased volume workload. There was no effect of increased workload on protein degradation in preparation (b) or (c) when compared with preparation (a). Insulin inhibited protein degradation in all three preparations. Significantly greater inhibition by insulin was observed in the increased-pressure-workload preparation (b). 3. Hypoxia was induced by the partial replacement of O2 in the gaseous phase by N2. Hearts maintained their cardiac output when O2 content was decreased from 95% to 55% by volume, but the stability of the preparation was less at 50% O2. Lactate output was significantly increased at O2 contents of 65% or less. The rate of protein degradation was not different from control values (95% O2) in perfusions with 65, 55 or 50% O2. 4. We conclude that acutely increased workload or acute hypoxia does not affect protein degradation in the perfused working rat heart when cardiac output is relatively stable.

Download Full-text

Effect of global ischemia & dietary lipids on cardiac output, O2 extraction & consumption in the erythrocyte perfused working rat heart

Journal of Molecular and Cellular Cardiology ◽

10.1016/0022-2828(90)91046-a ◽

1990 ◽

Vol 22 (9) ◽

pp. i ◽

Cited By ~ 1

Author(s):

S Pepe

Keyword(s):

Cardiac Output ◽

Rat Heart ◽

Dietary Lipids ◽

Global Ischemia ◽

O2 Extraction ◽

Working Rat Heart

Download Full-text

Carnitine stimulation of glucose oxidation in the fatty acid perfused isolated working rat heart.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)50590-7 ◽

1992 ◽

Vol 267 (6) ◽

pp. 3758-3763 ◽

Cited By ~ 2

Author(s):

T.L. Broderick ◽

H.A. Quinney ◽

G.D. Lopaschuk

Keyword(s):

Fatty Acid ◽

Rat Heart ◽

Glucose Oxidation ◽

Working Rat Heart ◽

Stimulation Of

Download Full-text

A new class of calcium entry blockers defined by 1,3-diphosphonates

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)84748-8 ◽

1989 ◽

Vol 264 (28) ◽

pp. 16598-16607

Author(s):

J R Rossier ◽

J A Cox ◽

E J Niesor ◽

C L Bentzen

Keyword(s):

Calcium Entry ◽

Calcium Entry Blockers ◽

New Class

Download Full-text

Decline of contractility during ischemia-reperfusion injury: actin glutathionylation and its effect on allosteric interaction with tropomyosin

AJP Cell Physiology ◽

10.1152/ajpcell.00419.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. C719-C727 ◽

Cited By ~ 70

Author(s):

Frank C. Chen ◽

Ozgur Ogut

Keyword(s):

Reperfusion Injury ◽

Posttranslational Modifications ◽

Actin Polymerization ◽

Time Course ◽

Troponin I ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

High Concentration ◽

Cross Sectional ◽

The Impact

The severity and duration of ischemia-reperfusion injury is hypothesized to play an important role in the ability of the heart subsequently to recover contractility. Permeabilized trabeculae were prepared from a rat model of ischemia-reperfusion injury to examine the impact on force generation. Compared with the control perfused condition, the maximum force (Fmax) per cross-sectional area and the rate of tension redevelopment of Ca2+-activated trabeculae fell by 71% and 44%, respectively, during ischemia despite the availability of a high concentration of ATP. The reduction in Fmax with ischemia was accompanied by a decline in fiber stiffness, implying a drop in the absolute number of attached cross bridges. However, the declines during ischemia were largely recovered after reperfusion, leading to the hypothesis that intrinsic, reversible posttranslational modifications to proteins of the contractile filaments occur during ischemia-reperfusion injury. Examination of thin-filament proteins from ischemic or ischemia-reperfused hearts did not reveal proteolysis of troponin I or T. However, actin was found to be glutathionylated with ischemia. Light-scattering experiments demonstrated that glutathionylated G-actin did not polymerize as efficiently as native G-actin. Although tropomyosin accelerated the time course of native and glutathionylated G-actin polymerization, the polymerization of glutathionylated G-actin still lagged native G-actin at all concentrations of tropomyosin tested. Furthermore, cosedimentation experiments demonstrated that tropomyosin bound glutathionylated F-actin with significantly reduced cooperativity. Therefore, glutathionylated actin may be a novel contributor to the diverse set of posttranslational modifications that define the function of the contractile filaments during ischemia-reperfusion injury.

Download Full-text