Effect of experimental diabetes on isolated rat heart responsiveness to isoproterenol

1984 ◽  
Vol 62 (1) ◽  
pp. 124-131 ◽  
Author(s):  
Rao V. S. V. Vadlamudi ◽  
John H. McNeill
Keyword(s):  
Rat Heart ◽  
Experimental Diabetes ◽  
Isolated Rat Heart ◽  
Energy Utilization ◽  
Diabetic Rat ◽  
Noradrenaline Content ◽  
Relaxant Effect ◽  
Rat Hearts ◽  
Relaxing Effect ◽  
Working Rat Heart

The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the sensitivity and responsiveness of the myocardium to the effects of isoproterenol. Experimental diabetes was induced by intravenous administration of either 65 mg/kg alloxan or 60 mg/kg streptozotocin. The positive inotropic and cardiac relaxant effects of isoproterenol were studied at various time points after the induction of diabetes. There were no changes either in the sensitivity or in the maximum responses of diabetic rat hearts to the positive inotropic effect of isoproterenol at any time point studied. However, the cardiac relaxant effect of isoproterenol was depressed in acute as well as chronic diabetic rat hearts when compared with age-matched controls. Ventricular noradrenaline content was unchanged in 180-day diabetic rat hearts indicating the absence of a diabetes-induced sympathetic neuropathy in the heart. The depressed relaxing effect of isoproterenol may have resulted from alterations in energy utilization and sarcoplasmic reticular function in diabetic rat hearts.

Effect of experimental diabetes on rat cardiac cAMP, phosphorylase, and inotropy

1983 ◽  
Vol 244 (6) ◽  
pp. H844-H851 ◽  
Author(s):  
R. V. Vadlamudi ◽  
J. H. McNeill
Keyword(s):  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Phosphorylase Activity ◽  
Camp Content ◽  
Rat Hearts ◽  
Underlying Causes ◽  
Camp Levels ◽  
Working Rat Heart ◽  
Time Point

The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the effect of isoproterenol on adenosine 3',5'-cyclic monophosphate (cAMP) content, inotropy, and phosphorylase activity. Experimental diabetes was induced by intravenous injection of either alloxan (40 mg/kg) or streptozotocin (50 mg/kg). There were no changes in either basal cAMP levels or in isoproterenol-induced cAMP levels in hearts from diabetic rats at either 3 days or 100-120 days after induction of diabetes. Maximum changes produced by isoproterenol in positive and negative dP/dt developments of diabetic rat hearts were also not different from control at either time point. However, phosphorylase was activated to a significantly greater extent by isoproterenol in hearts obtained from acute as well as chronic diabetic rats. Chronic diabetic rat hearts exhibited significantly higher total phosphorylase activity. Diabetic rat hearts had slightly but not significantly higher basal phosphorylase a activity. Furthermore, prostaglandin E1 activated phosphorylase in diabetic rat hearts but not in control rat hearts. Acute metabolic derangements and alterations in Ca2+ homeostasis caused by diabetes could be the underlying causes for this phosphorylase response. Thyroid hormone levels were depressed in diabetic rats. However, hypothyroidism is probably not responsible for the alterations in phosphorylase activity.

Reduced high-energy phosphate levels in rat hearts. I. Effects of alloxan diabetes

1976 ◽  
Vol 230 (6) ◽  
pp. 1744-1750 ◽  
Author(s):  
TB Allison ◽  
SP Bruttig ◽  
Crass MF ◽  
RS Eliot ◽  
JC Shipp
Keyword(s):  
Oxidative Metabolism ◽  
Oxygen Delivery ◽  
Rat Heart ◽  
High Energy ◽  
Diabetic Rat ◽  
High Energy Phosphate ◽  
Atp Production ◽  
Rat Hearts

Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.

Methylamine does not inhibit rates of endogenous lipolysis in isolated myocardial cells from rat heart

1987 ◽  
Vol 65 (2) ◽  
pp. 226-229 ◽  
Author(s):  
Albert Kryski Jr. ◽  
Terje S. Larsen ◽  
Ignasi Ramírez ◽  
David L. Severson
Keyword(s):  
Fatty Acids ◽  
Lipase Activity ◽  
Rat Heart ◽  
Diabetic Rat ◽  
Myocardial Cells ◽  
Acid Lipase ◽  
Ph Optimum ◽  
Triacylglycerol Lipase ◽  
Rat Hearts ◽  
Lysosomotropic Agent

Triacylglycerol lipase activity with a pH optimum of 5 was present in homogenates of myocardial cells from rat heart. Acid lipase activity was inhibited by serum, heparin, and increased ionic strength. Methylamine, a lysosomotropic agent, did not inhibit the basal or isoproterenol-stimulated rate of endogenous lipolysis as measured by glycerol output from control myocytes. Similarly, accelerated rates of glycerol output that are a consequence of an elevation in the intracellular stores of triacylglycerols in myocytes from diabetic rat hearts and from myocytes prepared with free fatty acids in the isolation solutions were not reduced by methylamine. Therefore, the acid lysosomal triacylglycerol lipase must not be involved in the mobilization of endogenous triacylglycerols in myocardial cells from rat heart.

Detection of Cardiac Variability in the Isolated Rat Heart

2006 ◽  
Vol 8 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Autumn M. Schumacher ◽  
Joseph P. Zbilut ◽  
Charles L. Webber ◽  
Dorie W. Schwertz ◽  
Mariann R. Piano
Keyword(s):  
Rat Heart ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Rat Hearts ◽  
Before And After ◽  
Quantification Analysis ◽  
Physical Attributes ◽  
Cardiac Variability ◽  
Isolated Rat

Cardiac variability can be assessed from two perspectives: beat-to-beat performance and continuous performance during the cardiac cycle. Linear analysis techniques assess cardiac variability by measuring the physical attributes of a signal, whereas nonlinear techniques evaluate signal dynamics. This study sought to determine if recurrence quantification analysis (RQA), a nonlinear technique, could detect pharmacologically induced autonomic changes in the continuous left ventricular pressure (LVP) and electrographic (EC) signals from an isolated rat heart—a model that theoretically contains no inherent variability. LVP and EC signal data were acquired simultaneously during Langendorff perfusion of isolated rat hearts before and after the addition of acetylcholine (n = 11), norepinephrine (n = 12), or no drug (n = 12). Two-minute segments of the continuous LVP and EC signal data were analyzed by RQA. Findings showed that%recurrence,%determinism, entropy, maxline, and trend from the continuous LVP signal significantly increased in the presence of both acetylcholine and norepinephrine, although systolic LVP significantly increased only with norepinephrine. In the continuous EC signal, the RQA trend variable significantly increased in the presence of norepinephrine. These results suggest that when either the sympathetic or parasympathetic division of the autonomic nervous system overwhelms the other, the dynamics underlying cardiac variability become stationary. This study also shows that information concerning inherent variability in the isolated rat heart can be gained via RQA of the continuous cardiac signal. Although speculative, RQA may be a tool for detecting alterations in cardiac variability and evaluating signal dynamics as a nonlinear indicator of cardiac pathology.

scholarly journals Decrease in cardiac phosphatidylglycerol in streptozotocin-induced diabetic rats does not affect cardiolipin biosynthesis: evidence for distinct pools of phosphatidylglycerol in the heart

1995 ◽  
Vol 306 (3) ◽  
pp. 759-764 ◽  
Author(s):  
G M Hatch ◽  
S G Cao ◽  
A Angel
Keyword(s):  
Rat Heart ◽  
Specific Radioactivity ◽  
Fold Increase ◽  
Mitochondrial Fraction ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Rat Hearts ◽  
Perfused Hearts ◽  
Continuous Pulse ◽  
Pool Sizes

Biosynthesis of phosphatidylglycerol (PG) and cardiolipin (CL) were investigated in perfused hearts of diabetic rats 4 days or 28 days after streptozotocin injection. Sham-injected and insulin-treated diabetic rats were used as controls. In addition, another group of rats fasted for 54 h was examined. Isolated rat hearts from these groups were perfused for 30 min with [32P]P(i), and the radioactivity incorporated into PG and CL and their pool sizes were determined in heart ventricles. There was no difference in the amount of radioactivity incorporated into CL, PG or other phospholipids between all groups. In addition, the pool sizes of CL and other phospholipids were unaltered. However, a striking decrease in the pool size of PG was observed in both diabetic and fasted rats compared to sham- and insulin-treated controls at 4 days after streptozotocin injection. The decrease in PG mass in diabetic rats was rapid (within 24-48 h) and was localized to cardiac membranes. Diabetes did not affect the activity of the enzymes of PG and CL biosynthesis in the mitochondrial fraction, or phospholipase A activity in subcellular fractions prepared from rat heart homogenates. In addition, pulse-chase experiments confirmed that diabetes did not affect the rate of new PG or CL biosynthesis. Since radioactivity associated with PG was unaltered in continuous-pulse perfusion experiments, a calculated 1.8-fold increase in the specific radioactivity of cardiac PG was observed in the hearts of acute diabetic rats compared with controls. Since the radioactivity incorporated into PG and CL, and the rate of CL biosynthesis, were unaltered in diabetic-rat hearts compared with controls, new CL was probably synthesized from newly synthesized PG. We postulate the existence of distinct pools of PG in the heart, and that the pool of newly synthesized PG used for CL biosynthesis does not appear to mix immediately with the pre-existing pool of PG in the isolated intact rat heart.

The effect of chronic alloxan- and streptozotocin-induced diabetes on isolated rat heart performance

1982 ◽  
Vol 60 (7) ◽  
pp. 902-911 ◽  
Author(s):  
Rao V. S. V. Vadlamudi ◽  
Robert L. Rodgers ◽  
John H. McNeill
Keyword(s):  
Left Ventricular Pressure ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Cardiac Performance ◽  
Diabetic Rat ◽  
Heart Performance ◽  
Rat Hearts ◽  
Female Wistar Rats ◽  
Streptozotocin Induced Diabetes

Cardiac disease is a common secondary complication appearing in chronic diabetics. Isolated perfused working hearts obtained from both acute and chronic diabetic rats have also been shown to exhibit cardiac functional abnormalities when exposed to high work loads. We studied cardiac performance at various time points after induction of diabetes in rats to determine exactly when functional alterations appeared and whether these alterations progressed with the disease state. Female Wistar rats were made diabetic by a single i.v. injection of either alloxan (65 mg/kg) or streptozotocin (STZ 60 mg/kg). Cardiac performance was assessed at 7, 30, 100, 180, 240, and 360 days after induction of diabetes using the isolated perfused working heart technique. No changes were observed in the positive and negative dP/dt development at various atrial filling pressures in the diabetic hearts 7 days after treatment. Alloxan diabetic rat hearts exhibited depressed left ventricular pressure and positive and negative dP/dt development when perfused at high atrial filling pressures, at 30. 100, and 240 days after treatment. STZ diabetic rat hearts exhibited depressed cardiac performance at high atrial filling pressures at 100, 180, and 360 days after treatment, but not at 30 days after treatment. Control hearts exhibited slight but significant depressions in cardiac function with age. These results suggest that cardiac functional alterations appear in diabetic rats about 30 days after induction and progress with the disease. These alterations may indicate the development of a cardiomyopathy.

scholarly journals Investigation of cardiotoxic effect of A-1 apo + D actinomycin complex on isolated rat heart

2016 ◽  
Vol 20 (4) ◽  
pp. 88
Author(s):  
R. A. Knyazev ◽  
N. V. Trifonova ◽  
A. R. Kolpakov ◽  
L. M. Polyakov
Keyword(s):  
Anticancer Drug ◽  
Conflict Of Interest ◽  
Rat Heart ◽  
Actinomycin D ◽  
Isolated Rat Heart ◽  
Protein Component ◽  
Solution Temperature ◽  
Apolipoprotein A ◽  
Rat Hearts ◽  
Isolated Rat

<p><strong>Aim.</strong> Chemotherapy is one of the main methods of treating malformations. However, this technique causes a great deal of side effects, among which are complications related to cardiac toxicity. Development of new anticancer drugs is directly related to a decrease in the general toxic effect on the organism and the cardiovascular system in particular. The aim of the study was to investigate the capability of apolipoprotein A-1 together with an anticancer drug, actinomycin D, to induce functional disturbances in the performance of an isolated rat heart and to compare the effect with that of pure actinomycin D. <br /><strong>Methods.</strong> For experiments use was made of Wistar male rats weighing 220-250 g. A modified Krebbs-Henseleit buffer saturated with carbogene (95 % O2 and 5 % CO2, solution temperature 37.5 °C) was used as perfusate. Experiments were conducted on isolated rat hearts. The isolated rat hearts were perfused retrogradely by a standard procedure, with isovolumic pressure registered in the left ventricle. Apolipoprotein A-I was isolated of human high-density lipoprotein by delipidating followed by separation of the proteins mix by means of column chromatography. In the experiment, apolipoprotein A-I- was mixed with actinomycin D, with concentration of the anticancer drug in the complex being 0.1 µg/ml.<br /><strong>Results</strong>. Actinomycin D with concentration 1 µg/ml aggravates the functional indicators of the heart and enhances energy load on the myocardium. Decreasing the concentration of cytostatic down to 0.1 µg/ml of perfusate brings the indicators to the baseline values. Apolipoprotein A-I combined with actinomycin D offsets the changes introduced by the cytostatic without a carrier. The complex improves hemodynamics, which can be interpreted by the presence of a protein component.<br /><strong>Conclusion.</strong> An isolated rat heart model shows that apolipoprotein A-I in combination with 0.1 µg/ml actinomycin D does not cause cardio toxicity. The complex improves myocardial efficiency through the use of the protein component as a carrier of the anticancer drug.</p><p>Received 15 November 2016. Accepted 30 November 2016.</p><p><strong>Funding:</strong> The research was supported by the federal budget project implemented by Research Institute of Biochemistry, Reg. R-085.<br /><strong>Conflict of interest:</strong> The authors declare no conflict of interest.<br /><strong>Author contributions</strong><br />Conceptualization and study design: Kolpakov AR. <br />Сбор и обработка материала: Knyazev R.A., Trifonova N.V.<br />Statistical data processing: Knyazev R.A.<br />Article writing: Knyazev R.A.<br />Review &amp; editing: Polyakov L.M.</p>

Ischemic preconditioning attenuates acidosis and postischemic dysfunction in isolated rat heart

1992 ◽  
Vol 263 (3) ◽  
pp. H887-H894 ◽  
Author(s):  
G. K. Asimakis ◽  
K. Inners-McBride ◽  
G. Medellin ◽  
V. R. Conti
Keyword(s):  
Rat Heart ◽  
Diastolic Pressure ◽  
Isolated Heart ◽  
Isolated Rat Heart ◽  
Rate Pressure Product ◽  
Anaerobic Glycolysis ◽  
Rat Hearts ◽  
Ischemic Period ◽  
Tissue Acidosis ◽  
Isolated Rat

The hypothesis that brief ischemia (preconditioning) protects the isolated heart from prolonged global ischemia was tested. Isovolumic rat hearts were preconditioned with either 5 min of ischemia followed by 5 min of perfusion (P1) or two 5-min episodes of ischemia separated by 5 min of perfusion (P2). Control hearts received no preconditioning. All hearts received 40 min of sustained ischemia and 30 min of reperfusion. Preconditioning (P1 or P2) significantly (P less than 0.0005) improved recovery of the rate-pressure product; percentage recoveries were 17.8 +/- 3.2 (n = 14), 59.9 +/- 5.5 (n = 6), and 46.4 +/- 4.7 (n = 8) for control, P1, and P2, respectively. Improved functional recovery of preconditioned hearts was associated with reduced end-diastolic pressure and improved myocardial perfusion. During the 40-min ischemic period, myocardial pH decreased from approximately 7.4 to 6.3 +/- 0.1 (n = 7) in the control hearts and to 6.7 +/- 0.1 (n = 7) in the preconditioned hearts (P less than 0.01). Also during the 40-min ischemic period, myocardial lactate (expressed as nmol/mg protein) increased to 146 +/- 11 (n = 7) and 101 +/- 12 (n = 8) in control and preconditioned hearts, respectively (P less than 0.02). The results demonstrate that a brief episode of ischemia can protect the isolated rat heart from a prolonged period of ischemia. This protection is associated with decreased tissue acidosis and anaerobic glycolysis during the sustained ischemic period.

Abstract 3894: Inhibition of iNOS Uncoupling by Tetrahydrobiopterin Confers Cardioprotection through Protein S- Nitrosylation in Streptozotocin-Induced Diabetic Rat

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Toru Okazaki ◽  
Hajime Otani ◽  
Koji Yamashita ◽  
Hiromi Jo ◽  
Kei Yoshioka ◽  
...  
Keyword(s):  
Infarct Size ◽  
Rat Heart ◽  
Ischemia Reperfusion ◽  
Protein S ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Diabetic Rat ◽  
Lv Function ◽  
Oxide Synthase

Although expression of inducible nitric oxide synthase (iNOS) and oxidative stress are increased in diabetic (DM) hearts, the role of iNOS uncoupling in ischemia/reperfusion (IR) injury remains unknown. Because iNOS-derived NO is known to play a crucial role in cardioprotection against IR injury in non-DM hearts, we hypothesized that iNOS uncoupling may compromise tolerance to IR injury in the DM heart by decreasing the bioavailability of NO. The expression and activity of iNOS but not n/eNOS were increased in the streptozotocin-induced DM rat heart. Under Langendorff perfusion, superoxide generation as evaluated by dihydroethidium accumulation in the nucleus was significantly increased in cardiomyocytes of the DM heart, but it was inhibited by treatment with the NOS co-factor tetrahydrobiopterin (BH4; 10 μM) or an iNOS selective inhibitor 1400W (10 μM). BH4 increased NOx, a marker of NO bioavailability, and cGMP in the DM heart. The increase in cGMP by BH4 was abrogated by co-treatment with 1400W or a NO-sensitive guanylyl cyclase inhibitor ODQ (10 μM). BH4 significantly decreased nitrotyrosin formation but increased protein S -nitrosylation in the DM heart. The increase in protein S -nitrosylation by BH4 was abolished by co-treatment with a thiol reducing agent dithiothreitol (DTT; 5 mM). The isolated rat heart was subjected to 30 min global ischemia followed by 120 min reperfusion. Post-ischemic recovery of left ventricular (LV) function and infarct size was comparable between the non-DM and the DM hearts. Pre-ischemic treatment with BH4 significantly improved post-ischemic LV function and reduced infarct size only in the DM heart. Co-treatment with BH4 and 1400W, ODQ, or DTT had no significant effect on post-ischemic LV function and infarct size in the non-DM heart. However, co-treatment with BH4 and 1400W or DTT but not ODQ abolished BH4-induced improvement of post-ischemic LV function and reduction of infarct size in the DM heart. These results suggest that inhibition of iNOS uncoupling by BH4 confers cardioprotection against IR injury in the streptozotocin-induced DM rat heart by increasing the bioavailability of NO and this cardioprotective effect is mediated by protein S -nitrosylation but not cGMP.

Reduction of tissue noradrenaline content in the isolated perfused rat heart during ischemia: importance of monoamine oxidation

1991 ◽  
Vol 69 (8) ◽  
pp. 1190-1195 ◽  
Author(s):  
Daniel Lamontagne ◽  
Nobuharu Yamaguchi ◽  
Christophe Ribuot ◽  
Jacques de Champlain ◽  
Réginald Nadeau
Keyword(s):  
Monoamine Oxidase ◽  
Rat Heart ◽  
Interventricular Septum ◽  
Isolated Rat Heart ◽  
Coronary Artery Ligation ◽  
Noradrenaline Content ◽  
Artery Ligation ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Noradrenaline Concentration

The effect of ischemia on myocardial noradrenaline concentration and endogenous noradrenaline output was studied in the isolated perfused rat heart. Following a 15-min stabilization period, regional ischemia was produced by coronary artery ligation. After 60 min of ischemia, noradrenaline concentrations were significantly reduced in the interventricular septum and left ventricle but not in the right ventricle. The reduction in tissue noradrenaline concentration was not prevented when the 60-min ischemia was replaced by a 10-min ischemia followed by a 50-min perfusion. No modification in noradrenaline output was observed during a 60-min ischemia. In contrast, reperfusion was accompanied by a washout of noradrenaline in the coronary effluent, corresponding to only 2% of the amount lost by the tissue. The effect of monoamine oxidase inhibition during the whole ischemic period was studied by perfusing the preparation with pargyline starting 10 min before the artery ligation. Although the administration of pargyline did not alter the noradrenaline output, it did prevent a reduction in myocardial noradrenaline concentration. It was concluded that monoamine oxidase may contribute to the elimination of the noradrenaline lost by the cardiac tissue during ischemia.Key words: tissue noradrenaline, myocardial ischemia, monoamine oxidase, isolated rat heart.

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