Acute effect of thyroid hormone in the rat heart: role of calcium

1996 ◽  
Vol 149 (1) ◽  
pp. 73-80 ◽  
Author(s):  
J Segal ◽  
S Masalha ◽  
H Schwalb ◽  
G Merin ◽  
J B Borman ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Thyroid Hormone ◽  
Rat Heart ◽  
Systolic Pressure ◽  
Acute Effect ◽  
Left Ventricular ◽  
Acute Effects ◽  
Calcium Blockers ◽  
Calcium Dependent

Abstract Several observations provide some clues as to the possible mode of the regulatory action of thyroid hormone (TH) in the heart, indicating delayed action at the level of the nucleus and acute effects on the plasma membrane. Here we present evidence for a direct and rapid stimulatory effect of TH in the intact normal heart. In the isolated perfused rat heart, 3,5,3′-tri-iodothyronine (T3) produced a positive inotropic effect increasing both the left ventricular peak systolic pressure (P) and +dP/dt values, but had no significant effect on heart rate. This effect of T3 was: (1) very rapid in onset (starting after 15 s) and transient, increasing gradually to reach a maximum (80% above control) at about 20 min, and declining progressively 20 to 30 min later; (2) dose-related and biphasic, occurring at physiological concentrations as low as 1 pm (+dP/dt) and 10 pm (P), reaching a maximum at 1 nm, and decreasing at higher concentrations; and (3) thyroid hormone specific, as shown by the effects of several TH analogs (l-T3>l-thyroxine (T4)=d-T3>d-T4; 3,3′,5′-tri-iodothyronine (rT3), 3,5,-l-di-iodothyronine and dl-thyronine had no effect). The calcium blockers nifedipine and verapamil, at concentrations of 10−8–10−5 m given before or after the addition of T3 (10−9–10−6 m), inhibited the T3-induced increase in cardiac inotropic activity in a time- and dose-related fashion. We suggest that the acute effect of TH in the heart is plasma membrane-mediated and calcium-dependent. Journal of Endocrinology (1996) 149, 73–80

scholarly journals Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH

2009 ◽  
Vol 297 (1) ◽  
pp. H153-H162 ◽  
Author(s):  
Sabrina Serpillon ◽  
Beverly C. Floyd ◽  
Rakhee S. Gupte ◽  
Shimran George ◽  
Mark Kozicky ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Rat Heart ◽  
Mitochondrial Respiratory Chain ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Posterior Wall Thickness ◽  
Patients With Diabetes ◽  
Protein Kinase C Inhibitor ◽  
Glucose 6 Phosphate Dehydrogenase

Increased oxidative stress is a known cause of cardiac dysfunction in animals and patients with diabetes, but the sources of reactive oxygen species [e.g., superoxide anion (O2−)] and the mechanisms underlying O2− production in diabetic hearts are not clearly understood. Our aim was to determine whether NADPH oxidase (Nox) is a source of O2− and whether glucose-6-phosphate dehydrogenase (G6PD)-derived NADPH plays a role in augmenting O2− generation in diabetes. We assessed cardiac function, Nox and G6PD activities, NADPH levels, and the activities of antioxidant enzymes in heart homogenates from young (9–11 wk old) Zucker lean and obese (fa/fa) rats. We found that myocardial G6PD activity was significantly higher in fa/fa than in lean rats, whereas superoxide dismutase and glutathione peroxidase activities were decreased ( P < 0.05). O2− levels were elevated (70–90%; P < 0.05) in the diabetic heart, and this elevation was blocked by the Nox inhibitor gp-91ds-tat (50 μM) or by the mitochondrial respiratory chain inhibitors antimycin (10 μM) and rotenone (50 μM). Inhibition of G6PD by 6-aminonicotinamide (5 mM) and dihydroepiandrosterone (100 μM) also reduced ( P < 0.05) O2− production. Notably, the activities of Nox and G6PD in the fa/fa rat heart were inhibited by chelerythrine, a protein kinase C inhibitor. Although we detected no changes in stroke volume, cardiac output, or ejection fraction, left ventricular diameter was slightly increased during diastole and systole, and left ventricular posterior wall thickness was decreased during systole ( P < 0.05) in Zucker fa/fa rats. Our findings suggest that in a model of severe hyperlipidema and hyperglycemia Nox-derived O2− generation in the myocardium is fueled by elevated levels of G6PD-derived NADPH. Similar mechanisms were found to activate O2− production and induce endothelial dysfunction in aorta. Thus G6PD may be a useful therapeutic target for treating the cardiovascular disease associated with type 2 diabetes, if second-generation drugs specifically reducing the activity of G6PD to near normal levels are developed.

Role of reflexes following myocardial necrobiosis

1965 ◽  
Vol 209 (6) ◽  
pp. 1081-1088 ◽  
Author(s):  
G. Ascanio ◽  
F. Barrera ◽  
E. V. Lautsch ◽  
M. J. Oppenheimer
Keyword(s):  
Peripheral Resistance ◽  
Systolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Hemodynamic Changes ◽  
Ventricular Systolic Pressure ◽  
Arterial Blood ◽  
Bilateral Vagotomy ◽  
Left Ventricular Systolic Pressure

Intracoronary administration of hexachlorotetrafluorobutane (Hexa) into non-thoracotomized dogs produced a statistically significant decrease in left ventricular systolic pressure (LVSP), mean femoral arterial blood pressure (MFAP), first derivative of left ventricular pressure pulse (dP/d t), total peripheral resistance (TPR), and cardiac output (C.O.) lasting up to 1 hr after injection. Femoral vascular resistance decreased during the first 3 min after production of necrobiosis. Fifty percent of the dogs died of ventricular fibrillation (VF) after Hexa infarction. Prereserpinized dogs did not show significant changes in the parameters which were significantly changed in normal dogs after Hexa necrobiosis except in the case of VF which was almost absent in this group. Bilateral vagotomy prior to Hexa administration prevented most hemodynamic changes after necrobiosis whereas atropine did not. Bilateral vagotomy and atropine 1 hr after necrobiosis increased MFAP, dP/d t, LVSP, C.O., and TPR. Apparently excitatory efferent sympathetic activity on heart and femoral arterial vessels is reflexly inhibited by the effects of intracoronary injection of Hexa. The afferent pathway is via the vagus nerve.

scholarly journals Use of the Isolated Perfused Heart for Evaluation of Cardiac Toxicity

1990 ◽  
Vol 18 (4a) ◽  
pp. 497-510 ◽  
Author(s):  
Peter G. Anderson ◽  
Stanley B. Digerness ◽  
Jerald L. Sklar ◽  
Paul J. Boor
Keyword(s):  
Rat Heart ◽  
Coronary Flow ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Heart Weight ◽  
Isolated Perfused Heart ◽  
Heart Model ◽  
Perfused Heart ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart

The isolated perfused rat heart model can be used to evaluate cardiotoxicity, and is especially useful in distinguishing direct vs indirect cardiac injury. Various perfusion systems can be used to characterize the pathophysiologic as well as morphologic changes induced by drugs or chemicals of interest. The isolated perfused heart was used in the studies described herein to characterize the mechanism of allylamine cardiotoxicity. Rat hearts were perfused with Krebs-Henseleit buffer containing 10 mm allylamine and a latex balloon was inserted into the left ventricle to monitor pressure. Coronary flow in hearts perfused with 10 mm allylamine was similar to control hearts at 5, 10, and 30 min, but was reduced by 1 hr (11.5 ± 0.6 ml/min/g wet heart weight vs 16.0 ± 0.7, p < 0.01). Peak left ventricular systolic pressure increased in hearts perfused with allylamine for 5 min (156 ± 8 mm Hg vs 103 ± 9, p < 0.01), but by 2 hr was decreased compared to controls (89 ± 6 vs 105 ± 5, p < 0.05). End diastolic pressure was markedly increased at 2 hr (58 ± 3 vs 4 ± 0.8, p < 0.01). Morphologically, allylamine perfused hearts exhibited significant contraction band changes as well as numerous cells with marked swelling of the sarcoplasmic reticulum. The findings in this study suggest that allylamine produces direct myocardial damage that appears to be independent of coronary flow. These studies demonstrate that the isolated perfused rat heart model can be used to evaluate mechanisms of acute cardiotoxicity.

Role of gp91phox-containing NADPH oxidase in left ventricular remodeling induced by intermittent hypoxic stress

2008 ◽  
Vol 294 (5) ◽  
pp. H2197-H2203 ◽  
Author(s):  
Tetsuya Hayashi ◽  
Chika Yamashita ◽  
Chika Matsumoto ◽  
Chol-Jun Kwak ◽  
Kiwako Fujii ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Nadph Oxidase ◽  
Intermittent Hypoxia ◽  
Sleep Apnea Syndrome ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Hypoxic Stress ◽  
Wild Type ◽  
Lv Remodeling

Intermittent hypoxia due to sleep apnea syndrome is associated with cardiovascular diseases. However, the precise mechanisms by which intermittent hypoxic stress accelerates cardiovascular diseases are largely unclear. The aim of this study was to investigate the role of gp91 phox-containing NADPH oxidase in the development of left ventricular (LV) remodeling induced by intermittent hypoxic stress in mice. Male gp91 phox-deficient (gp91−/−) mice ( n = 26) and wild-type ( n = 39) mice at 7–12 wk of age were exposed to intermittent hypoxia (30 s of 4.5–5.5% O2 followed by 30 s of 21% O2 for 8 h/day during daytime) or normoxia for 10 days. Mean blood pressure and LV systolic and diastolic function were not changed by intermittent hypoxia in wild-type or gp91−/− mice, although right ventricular systolic pressure tended to be increased. In wild-type mice, intermittent hypoxic stress significantly increased the diameter of cardiomyocytes and interstitial fibrosis in LV myocardium. Furthermore, intermittent hypoxic stress increased superoxide production, 4-hydroxy-2-nonenal protein, TNF-α and transforming growth factor-β mRNA, and NF-κB binding activity in wild-type, but not gp91−/−, mice. These results suggest that gp91 phox-containing NADPH oxidase plays a crucial role in the pathophysiology of intermittent hypoxia-induced LV remodeling through an increase of oxidative stress.

scholarly journals Acute effects of nandrolone decanoate on cardiodynamic parameters in isolated rat heart

2016 ◽  
Vol 94 (10) ◽  
pp. 1048-1057 ◽  
Author(s):  
Tamara R. Nikolic ◽  
Vladimir I. Zivkovic ◽  
Ivan M. Srejovic ◽  
Dragan S. Radovanovic ◽  
Nevena S. Jeremic ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Rat Heart ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Albino Rats ◽  
Coronary Perfusion ◽  
Nandrolone Decanoate ◽  
Acute Effects ◽  
Isolated Rat

Despite worldwide use of anabolic steroids in last decades, there is still contradictory information about their acute influence on myocardium. The aim of this study was to examine the acute effects of nandrolone decanoate (ND) on cardiodynamics and coronary flow in isolated rat heart. The hearts of male Wistar albino rats (n = 48, 12 per group, age 8 weeks, body mass 180–200 g) were excised and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40–120 cmH2O). After the control sets of experiments, the hearts in different groups were perfused with different doses of ND (1, 10, or 100 μmol/L separately). Using a sensor placed in the left ventricle, we registered maximum and minimum rate of pressure development in the left ventricle (dP/dtmax and dP/dtmin), systolic and diastolic left ventricular pressure (SLVP and DLVP), and heart rate (HR). Coronary flow (CF) was measured flowmetrically. The results clearly show the depression in cardiac function caused by higher doses of ND. The highest concentration of ND (100 μmol/L) induced the most deleterious impact on the myocardial function and perfusion of the heart (coronary circulation), which could be of clinical significance.

scholarly journals The Acute Effects of Esmolol in Intact and Infarcted Myocardium–Experimental Study

2020 ◽  
pp. 1-7
Author(s):  
Savvas Toumanidis ◽  
John Agrios ◽  
Anna Kaladaridou ◽  
Dimitrios Bramos ◽  
Elias Skaltsiotes ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Speckle Tracking ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Short Axis ◽  
Acute Effects ◽  
Anterior Myocardial Infarction ◽  
Infarcted Myocardium ◽  
Lv Ejection Fraction

Aim: Early intravenous use of b-blockers within the first hours of STEMI is less firmly established. The aim of this study was to evaluate the effect of esmolol on left ventricular (LV) haemodynamic, rotational and strain parameters in intact myocardium and early post an experimental acute anterior myocardial infarction (MI). Methods: In 20 healthy pigs LV torsional and strain parameters were calculated from basal and apical short axis epicardial planes with speckle tracking technique using EchoPAC platform. LV measurements at baseline and during esmolol infusion (0.5 mg/kg for 1 min, then 0.05 mg/kg/min for 5 min) were compared in intact myocardium and repeated without b-blocker and during esmolol infusion 2 hours post LAD ligation. Results: LV function was highly dependent on the esmolol infusion, in the intact and even more in the infarcted myocardium. LV ejection fraction, LV dP/dtmax and LV end-systolic pressure decreased significantly, a deterioration produced by the administration of esmolol. Torsion-twist and untwisting rate also presented significant reduction in correlation with ejection fraction and cardiac output, appearing to affect especially the apex torsional and strain parameters. Conclusion: Esmolol infusion significantly reduces LV haemodynamic, torsional and strain parameters in intact myocardium and early post MI. These results suggest that early intravenous use of esmolol in patients with STEMI is risky and it is prudent to wait for the patient to stabilize before starting esmolol.

The inotropic effect of digoxin on an isolated rat heart in hypercapnia and (or) hypoxia

1990 ◽  
Vol 68 (3) ◽  
pp. 455-461
Author(s):  
M. Allam ◽  
C. Saunier ◽  
A. Sautegeau ◽  
D. Hartemann
Keyword(s):  
Rat Heart ◽  
Myocardial Contractility ◽  
Diastolic Pressure ◽  
Isolated Heart ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Gas Mixture ◽  
Constant Frequency

The explanation for the increased frequency of troubles with digoxin therapy in patients with chronic pulmonary diseases is debated. The reported effects of hypoxia in vivo on myocardial levels of digoxin are contradictory, and there have been few studies on the effects of hypercapnia. In the past, it has been shown in rat myocardial tissue at rest in vitro that hypoxia decreased and hypercapnia acidosis increased the digoxin uptake. We performed a new study in vitro in an isolated beating rat heart perfused at constant flow (37 °C) and stimulated at a constant frequency (6 Hz). The performances were recorded with an intraventricular balloon equipped with a tip-manometer catheter. The action of digoxin was studied by recording systolic pressure (PS) and diastolic pressure (PD), the left ventricular developed pressure (LVDP = PS − PD), the (dP/dt)max, and the ratio (dP/dt)max/PS. First, the heart was perfused for 30 min with a modified Tyrode's solution perfusate aerated with carbogen (pH = 7.40; [Formula: see text]; [Formula: see text]) (1 mmHg = 133.32 Pa). Various parameters of contractions were recorded (initial control values). Then the heart was perfused for 15 min with Tyrode's solution aerated either with a hypoxic gas mixture (pH = 7.41; [Formula: see text]; [Formula: see text]), a hypercapnic gas mixture (pH = 7.08; [Formula: see text]; [Formula: see text]), or a hypoxic–hypercapnic gas mixture (pH = 7.09; [Formula: see text]; [Formula: see text]). Control hearts were continuously perfused with Tyrode's solution aerated with carbogen. During heart perfusion with hypercapnic, hypoxic, or hypoxic–hypercapnic Tyrode's solution, a decrease in LVDP and (dP/dt)max was observed. Finally, the heart was perfused with the same Tyrode's solution plus 1.75 × 10−5 M digoxin. The increase in myocardial contractility produced by digoxin was enhanced by hypercapnia and abolished by hypoxia. The addition of hypercapnia to hypoxia in Tyrode's solution seems to enhance the depressor action of the hypoxia.Key words: isolated heart, digoxin, hypoxia, hypercapnia, myocardial contractility.

Ventricular pacing attenuates but does not reverse cardiac atrophy and an isomyosin shift in the rat heart

1994 ◽  
Vol 267 (6) ◽  
pp. H2149-H2154 ◽  
Author(s):  
D. L. Geenen ◽  
A. Malhotra ◽  
P. M. Buttrick ◽  
J. Scheuer
Keyword(s):  
Protein Synthesis ◽  
Protein Content ◽  
Rat Heart ◽  
Left Ventricular ◽  
Synthesis Rate ◽  
Fractional Synthesis Rate ◽  
Cardiac Atrophy ◽  
Wet Weight ◽  
Fractional Synthesis

The heterotopically transplanted rat heart (TH) undergoes rapid muscle atrophy and a concurrent shift from alpha- to beta-myosin heavy chain (MHC) by 1 wk after surgery. In the current experiments, TH were continuously paced (420 beats/min) for 1 wk beginning 24 h after surgery or for 1 wk beginning 14 days after surgery to determine the role of increased heart rate in preventing or reversing cardiac atrophy. Left ventricular (LV) wet weight (283 vs. 256 mg paced vs. nonpaced) and protein content (32 vs. 23 mg paced vs. nonpaced, P < 0.05) were significantly elevated in TH paced 1 wk after surgery but were unchanged (211 vs. 198 mg and 24 vs. 23 mg LV wet wt and protein content, respectively) in TH paced 2 wk after surgery. Total cardiac protein synthesis in the TH paced immediately after surgery was increased compared with the corresponding nonpaced hearts (5.6 vs. 4.0 mg.mg LV wet wt-1.day-1, P < 0.05), while in the TH, where pacing was initiated 2 wk after surgery, it was unchanged (3.6 vs. 3.7 mg.mg LV wet wt-1.day-1). Fractional synthesis rate was elevated in TH and was not altered by pacing. Pacing the TH also attenuated the shift in alpha-MHC in the first 7 days after surgery but did not reverse the shift 2 wk later. The increase in protein synthesis combined with an unchanged fractional synthesis rate suggests that pacing attenuates cardiac mass by decreasing protein degradation and that once the atrophic process is established, neither synthesis rate nor isomyosin shift can be altered by continuous pacing.

scholarly journals Expression and regulation of pyruvate dehydrogenase kinase isoforms in the developing rat heart and in adulthood: role of thyroid hormone status and lipid supply

2000 ◽  
Vol 352 (3) ◽  
pp. 731-738 ◽  
Author(s):  
Mary C. SUGDEN ◽  
Maria L. LANGDOWN ◽  
Robert A. HARRIS ◽  
Mark J. HOLNESS
Keyword(s):  
Thyroid Hormone ◽  
Pyruvate Dehydrogenase ◽  
Rat Heart ◽  
Glucose Oxidation ◽  
Pyruvate Dehydrogenase Kinase ◽  
Glucose Disposal ◽  
Hormone Status ◽  
Isoform Expression ◽  
Developing Rat

Activation of the pyruvate dehydrogenase (PDH) complex (PDHC) promotes glucose disposal, whereas inactivation conserves glucose. The PDH kinases (PDHKs) regulate glucose oxidation through inhibitory phosphorylation of PDHC. The adult rat heart contains three PDHK isoforms PDHK1, PDHK2 and PDHK4. Using Western-blot analysis, with specific antibodies raised against individual recombinant PDHK1, PDHK2 and PDHK4, the present study investigated PDHK isoform expression in the developing rat heart and adulthood. We identified clear differences in the patterns of protein expression of each of these PDHK isoforms during the first 3 weeks of post-natal development, with most marked up-regulation of isoforms PDHK1 and PDHK4. Distinctions between the three cardiac PDHK isoforms were also demonstrated with respect to post-neonatal maturational up-regulation; with greatest up-regulation of PDHK1 and least up-regulation of PDHK4 from the post-neonatal period until maturity. The study also examined the role of thyroid hormone status and lipid supply on PDHK isoform expression. We observed marked selective increases in the amount of PDHK4 protein present relative to total cardiac protein in both hyperthyroidism and high-fat feeding. Overall, our data identify PDHK isoform PDHK1 as being of more potential regulatory importance for glucose oxidation in the adult compared with the neonatal heart, and cardiac PDHK4 as a PDHK isoform whose expression is specifically responsive to changes in lipid supply, suggesting that its up-regulation during early post-natal life may be the perinatal switch to use fatty acids as the energy source. We also identify regulation of pyruvate sensitivity of cardiac PDHK as a physiological variable, a change in which requires factors in addition to a change in lipid supply.

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.

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