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Query: UNIPROT:P06889 (Mol)
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To test the hypothesis that stunning is due to a decreased sensitivity of the myofibrils for calcium, we compared the isometric force-Ca2+ relation in skinned trabeculae from stunned and control hearts. Hearts were made ischemic for 40 min followed by 30 min reperfusion. In one group (Group 1) changes in left ventricular systolic and diastolic pressure were monitored. From another group (Group 2), trabeculae were isolated to determine the relation between force and Ca2+ concentration. Trabeculae isolated from hearts (Group 3) perfused aerobically for 90 min served as controls. Left ventricular developed pressure and end diastolic pressure were 5.9 +/- 0.7 kPa and 5.8 +/- 0.7 kPa, respectively in stunned hearts as compared to 9.9 +/- 1.2 kPa and 1.2 +/- 0.1 kPa prior to ischemia. The nucleotide content decreased from 24.9 +/- 3.4 mumol.g-1(dw) in control hearts to 9.3 +/- 0.8 mumol.g-1(dw) after ischemia and reperfusion while the creatine kinase levels were about the same. Force-Ca2+ relations obtained from trabeculae from control and stunned hearts were fitted to the Hill equation. Maximal isometric force, the midpoint and the steepness of the curves estimated for the two groups were not significantly different. We conclude that the maximum isometric force and the sensitivity of the contractile apparatus of skinned myocardium of stunned hearts do not differ from that of control hearts. This suggests that structural changes of the contractile proteins leading to a decreased sensitivity of the myofibrils to calcium are not involved in the mechanism responsible for stunning.
J Mol Cell Cardiol 1993 May
PMID:Stunning does not change the relation between calcium and force in skinned rat trabeculae. 837 14

The relationship between myocardial triglyceride content and 1H NMR visible fatty acid resonance intensity was investigated. Hearts from rats fed a 20% rapeseed oil diet contained markedly increased levels of triglycerides as judged by thin layer chromatographic analysis. This elevation in cardiac triglycerides was associated with sharp increases in the cell volume occupied by lipid droplets and in 1H NMR visible fatty acid resonances. Spin-lattice and spin-spin relaxation times of the 1H NMR visible fatty acid resonances from myocardium of rapeseed oil-fed rats were similar in value to those measured for neat triolein. Additionally, the fatty acids constituting these enhanced 1H NMR visible resonances were metabolically active. Perfusion of triglyceride enriched hearts in the presence or absence of glucose caused a time-dependent decrease in the intensity of their 1H NMR visible fatty acid resonances. In contrast, perfusion with glucose+acetate essentially prevented this time-dependent decrease in 1H NMR visible fatty acid resonances. Morphometric analysis of these hearts demonstrated that the decrease in 1H NMR resonance intensity correlated with changes in the cell volume of triglyceride-enriched lipid droplets. These results demonstrate that metabolically active stores of cardiac fatty acids, presumably triglycerides, are 1H NMR visible. Further, they indicate the possible utility of 1H NMR spectroscopy in the future study of myocardial triglyceride metabolism.
J Mol Cell Cardiol 1993 May
PMID:Morphometric analysis demonstrates that metabolically active cardiac triglycerides are 1H NMR visible. 839 4

In contrast to cardiac purine metabolism, little is known about pyrimidine catabolism in heart. We therefore investigated uridine and uracil formation in ischemic rat and human hearts. Human donor hearts accumulated uridine 3 x (P < 0.05) before implantation. Hearts released this pyrimidine during implantation or correction of cardiac defects. During the former systemic blood uridine rose 38% (P < 0.05). In explanted human hearts, uridine was the only pyrimidine released during reperfusion; isolated, perfused rat hearts produced initially 3 x more uracil than uridine. Uridine phosphorylase activity in human heart homogenate was 3.4 mU/g wet weight, i.e. 60 x lower than that in rat myocardium (198 mU/g, P < 0.02); its purine counterpart, nucleoside phosphorylase, differed much less in activity (0.32 and 1.12 U/g, respectively; P < 0.001). Thus human heart is virtually devoid of uridine phosphorylase, contrasting rat heart. Consequently uridine accumulates in ischemic human heart while uracil production predominates in rat heart.
J Mol Cell Cardiol 1993 Jan
PMID:Formation and breakdown of uridine in ischemic hearts of rats and humans. 844 Nov 82

The present study was undertaken to assess whether [32P]uptake and autoradiography could be used as an indicator of regional myocardial oxygen consumption. Rat hearts were perfused in the Langendorff mode with medium containing [32P]orthophosphate (32Pi) and the incorporation of label into ATP, perchloric acid-insoluble and soluble material and total tissue was determined. Oxygen uptake and perfusion pressure were continuously monitored. For control hearts the rate of incorporation of radioactivity into all four fractions was linear. Isoproterenol and pressure loading each increased total 32Pi uptake rate and the incorporation rate of 32Pi into ATP. Significant positive correlations were noted between the rates of total 32Pi uptake and oxygen uptake (r = 0.895; P < 0.001) and between the rates of 32P incorporation into ATP and oxygen uptake (r = 0.890; P < 0.001). Autoradiography of diffusible radioactive material (representing total 32Pi uptake) indicated that label correlated with oxygen uptake (r = 0.850; P < 0.001) and was distributed uniformly across the ventricle wall. Hearts subjected to 30 min of regional ischemia followed by reperfusion were indistinguishable from the control group in terms of either total 32Pi uptake or total oxygen uptake, but showed a marked necrotic area that was unlabeled surrounded by an area that was intensely labeled. It is concluded that autoradiography of diffusible radioactive material representing total 32Pi uptake may be applicable for assessing regional myocardial oxygen uptake. The technique has identified a region of tissue in reperfused ischemic hearts that surrounds necrotic tissue and which may have a compensatory increase in a oxidative metabolism.
J Mol Cell Cardiol 1993 Mar
PMID:[32P]phosphate autoradiography as an indicator of regional myocardial oxygen consumption? 851 Jan 70

Chronic activation of the circulating renin-angiotensin-aldosterone system (RAAS), as can occur with unilateral renal ischemia (URI), is associated with an adverse structural remodeling of the right and left ventricles characterized by reparative (i.e., microscopic scars) and reactive (i.e., perivascular/interstitial) fibrosis. The time course and cells involved in fibroplastic and fibrogenic phases of these events are unclear. Hearts were examined over the course of 8 weeks in rats infused with either angiotensin II or aldosterone, and compared to rats with URI. Tissue sections from the same heart were stained with hematoxylin and eosin, collagen specific picrosirius red, or immunolabeled with PCNA or alpha smooth muscle actin antibody. With angiotensin II or renal ischemia, fibroblast proliferation, presenting as focal accumulations at both sites of myocyte necrosis and widespread perivascular locations, was present in each ventricle on days 2 and 4, but not thereafter, alpha-Smooth muscle actin containing cells (myofibroblasts) appeared at day 2 and persisted through week 2 with renal ischemia and week 6 with angiotensin II. Macrophages, neutrophils and lymphocytes were transiently found at sites of necrosis between day 2-4 of renal ischemia. AngII-induced necrotic sites were characterized by macrophages and lymphocytes from day 2 through week 6, and neutrophils at day 2-4. Increased collagen volume fraction, presenting as immature scars associated with fibroblast clusters and interstitial/perivascular fibrosis, was evident on day 14 in both ventricles. In contrast, fibroblast proliferation during aldosterone infusion did not appear in both ventricles until week 3 and was associated with a subsequent reparative and reactive fibrosis as early as 4 weeks. Myofibroblasts became evident between 3-6 weeks; macrophages and lymphocytes were seen between 3-8 weeks. Neutrophils were not seen at any time point with aldosterone. Thus, the temporal cellular response and appearance of myocardial fibrosis associated with chronic elevations in angiotensin II and/or aldosterone differ. We conclude that separate pathogenic mechanisms are operative with these effector hormones of the RAAS.
J Mol Cell Cardiol 1995 Aug
PMID:Temporal differences in fibroblast proliferation and phenotype expression in response to chronic administration of angiotensin II or aldosterone. 852 18

It is well known that ischaemic preconditioning delays infarct size during regional ischaemic insults. However, the extent of this protective effect against different ischaemia periods has not been established, and any reduction in stunning has been difficult to demonstrate with regional models. In this study we have investigated ischaemic preconditioning in a buffer-perfused isolated rabbit heart model with a global ischaemic insult, and measured both infarct volume and functional recovery. Experiments were performed with three ischaemia time periods of 15, 20 and 30 min at 37 degrees C. Infarct volume (expressed as a percentage of left ventricular volume) was measured by tetrazolium staining after 2 hours reperfusion, and left ventricular developed pressure with an intraventricular balloon. Hearts preconditioned with 5 min ischaemia and 10 min reperfusion were compared with a control group. In this model, preconditioning resulted in a 57% reduction in infarct volume compared with control hearts (P = 0.02) subjected to 20 min of global ischaemia, but the degree of this infarct delaying effect was dependent on the ischaemia time and was only 37% (P = 0.02) and 11% (N.S.) with a 30 min and 15 min ischaemic challenge respectively. Recovery of post-ischaemic left ventricular developed pressure as a percentage of the pre-ischaemic value correlated very well with infarct volume in control r = -0.82 (P < 0.001) and preconditioned r = -0.78 (P < 0.001) groups, and the slope of the regression lines was similar for both groups. These results demonstrate that the degree of protection produced by preconditioning is not uniform but varies with the length of the ishaemic insult. By measuring both infarct volume and functional recovery we have been able to confirm that any post-ischaemic improvement in global left ventricular function produced by preconditioning is secondary to reduced infarction, and hence that preconditioning does not attenuate stunning.
J Mol Cell Cardiol 1995 Aug
PMID:Ischaemic preconditioning in a model of global ischaemia: infarct size limitation, but no reduction of stunning. 852 25

We investigated changes in pHi during ischaemia-reperfusion of isolated rat hearts using phosphorus nuclear magnetic resonance spectroscopy (31P NMR). Hearts were separated into three groups according to the perfusion buffer: bicarbonate-buffered Krebs solution, HEPES-buffered Krebs solution, or bicarbonate-buffered Krebs solution plus 10(-6) M 5-(N-ethyl-N-isopropyl) amiloride (EIPA). In HEPES buffer and in bicarbonate buffer plus EIPA, pH at the end of 30 min of ischaemia and pH oscillations observed during early reperfusion were lower than in bicarbonate buffer. Thus, the presence of two pH regulation mechanisms (Na(+)-H+ antiport and Na(+)-HCO3- symport) was confirmed in the isolated rat heart, while in HEPES buffer, pH was regulated by Na(+)-H+ antiport, and in bicarbonate buffer plus EIPA, by Na(+)-HCO3- symport. When cardiac contraction was inhibited by 10 mM 2, 3-butanedione 2-monoxime (BDM), we observed, in all cases, a less pronounced decrease in pHi at the end of ischaemia, and in pHi oscillations at the onset of reperfusion. These effects were similar to those observed with 150 x 10(-8) M verapamil and might thus be related to a decrease in intracellular calcium. However, with BDM, a greater reduction in the pH recovery rate was observed only in HEPES buffer, suggesting a possible phosphatase-like effect affecting the Na(+)-H+ exchange. Whatever the buffer used, the protective effect of BDM was reflected by an increase in the rate pressure product, which was not observed with verapamil.
J Mol Cell Cardiol 1995 Aug
PMID:pH regulation during ischaemia-reperfusion of isolated rat hearts, and metabolic effects of 2,3-butanedione monoxime. 852 32

The effects of single- and multi-dose cardioplegia on post-ischaemic vascular function and contractile activity were compared in 69 blood-perfused neonatal pig hearts, as were the protective properties of two different cardioplegic solutions. Hearts (n = 6 or 9 per group) from neonatal (3-5 days old) pigs were excised, arrested with a 2 min infusion (at 15 degrees C) of St Thomas' Hospital cardioplegic solution number 1 (STH1) or number 2 (STH2), and then maintained in a state of hypothermic (15 degrees C) ischaemia for 6 or 8 h. Hearts in the multi-dose groups received cardioplegia every hour (2 min at 15 degrees C). At the end of ischaemia all hearts were reperfused (60 +/- 2 mmHg perfusion pressure) for 40 min with blood from a support pig. Systolic and diastolic functions were assessed with an intraventricular balloon, and endothelial and smooth muscle functions by measuring the response to infusions of defined concentrations of acetylcholine (8, 16 and 32 micrograms/min) and glyceryl trinitrate (40, 80 and 160 micrograms/min). Hearts (n = 9) not subjected to ischaemia were perfused for the same duration to act as aerobic controls. At the end of the perfusion period, hearts were frozen and taken for metabolite analysis. After 8 h ischaemia, the recovery of left ventricular developed pressure was greatest in the multi-dose STH1 and single-dose STH2 groups (113 +/- 6 and 117 +/- 6 mmHg, respectively, v 128 +/- 9 mmHg in aerobic controls, at an end-diastolic pressure of between 3 and 9 mmHg; P = N.S.) and the poorest in the single-dose STH1 group (92 +/- 5 mmHg; P < 0.05 v controls). The recovery of diastolic function was greatest in the multi-dose STH2 group and again poorest in the single-dose STH1 group (left ventricular end-diastolic pressure 1 +/- 2 and 30 +/- 10 mmHg, at a ventricular volume of 3.0 ml, v -1 +/- 1 mmHg in aerobic controls). Vascular responses to acetylcholine and glyceryl trinitrate and the myocardial high-energy phosphates content were better preserved in multi-dose groups and with STH2. Inter-group differences were less when the duration of ischaemia was reduced to 6 h. In conclusion, the neonatal pig heart was best preserved with multi-dose cardioplegia and STH2 was more efficacious than STH1. However, not all indices were optimally protected by multi-dose STH2. Thus, the best protection of systolic function was obtained with multidose STH1 and this was followed by single-dose STH2. Diastolic function was best preserved with multi-dose STH2 as were vascular function and high-energy phosphates.
J Mol Cell Cardiol 1995 Sep
PMID:Vascular and contractile function and tissue metabolites after prolonged hypothermic ischaemia and reperfusion: comparison of single- versus multi-dose infusions with two cardioplegic solutions in blood-perfused neonatal pig hearts. 852 52

The purpose of this study was to compare coronary and interstitial endothelin-1 (ET-1) levels in perfused rat hearts under several experimental conditions, because the cardiac tissue concentration of ET-1 is not clear. Hearts were perfused in an upside-down position with a colloid-free buffer at a constant flow rate of 9 ml/min/g heart wet weight, and immunoreactive ET-1 was determined in timed collections of coronary effluent and interstitial transudate produced by the ventricles and appearing on their surface. Basal ET-1 release into effluent was 0.26 +/- 0.007 pg/min/g, and 0.005 +/- 0.0012 pg/min/g in transudate. Basal ET-1 concentration was 0.11 +/- 0.005 pg/ml (transudate) and 0.03 +/- 0.002 pg/ml (effluent), indicating four-fold higher transudate than effluent levels (P < 0.05). Following perfusion of hearts with collagenase to remove endothelial cells, ET-1 release into effluent was reduced to one-third and completely abolished in transudate, indicating that the peptide originated from the vascular endothelium. Perfusion of hearts with angiotensin II (0.1 mumol/l) or thrombin (5 U/ml) increased coronary perfusion pressure and ET-1 secretion, but little affected the transudate/effluent ET-1 concentration ratio (5.5 and 3.2, respectively). When coronary flow was reduced to ischaemic level (1 ml/min/g over several hours), ET-1 secretion rates into effluent were decreased by 55-65%, but increased three- to four-fold on reperfusion at normal flow (P < 0.05). The ET-1 concentrations in both fluids were still always below 1 pg/ml. No change in coronary perfusion pressure compared to time-matched normoxic controls was observed. In the presence of the ET-1 converting enzyme inhibitor, phosphoramidon (1.7 mumol/l), ischaemia-induced increases of ET-1 secretion were attenuated, and this was accompanied by a time-dependent rise in coronary perfusion pressure up to 60% (P < 0.05). These are the first measurements of endogenous cardiac tissue ET-1 levels; they do not support a vasoconstrictor (pro-ischaemic) action of endogenous ET-1 in rat hearts following ischaemia/reperfusion, but rather point to a possible vasodilator role of the peptide under these conditions.
J Mol Cell Cardiol 1995 Sep
PMID:Tissue endothelin-1 levels in perfused rat heart following stimulation with agonists and in ischaemia and reperfusion. 852 55

Sprague-Dawley rat hearts were perfused under constant flow conditions, and a balloon was inserted into the left ventricle to measure heart rate (HR) and left ventricular pressures. Left ventricular generated pressure (LVGP) was calculated as peak systolic minus end diastolic pressure. Three substrate groups, pyruvate (5 mM), glucose (15 mM) and octanoate (0.5 mM), were employed. Oxidative stress was induced by perfusion with tertiary-butyl hydroperoxide (tBHP, 0.35 mM, 12 min) followed by 25 min of perfusion with control buffer. Hearts perfused with pyruvate showed no significant decrease in contractile function following tBHP treatment (HR x LVGP = 17666 +/- 585 mmHg/min, initial: 16414 +/- 2083 post-tBHP treatment). Glucose-perfused hearts had an intermediate decrease in function (19174 +/- 828 mmHg/min, initial; 4379 +/- 2083 post-tBHP), while octanoate-perfused hearts recovered no contractile function. Peak release of LDH was lowest in hearts perfused with pyruvate (115 +/- 17 mU/g wet wt/min), intermediate in glucose-perfused hearts (1575 +/- 380) and highest in octanoate-perfused hearts (3074 +/- 499). Thiobarbituric acid reactive substances (TBARS) were unchanged in hearts perfused with pyruvate (16.2 +/- 5 nmoles/g wet wt), but increased significantly in glucose-perfused hearts (36.1 +/- 1) and in octanoate-perfused hearts (45.5 +/- 9). Total glutathione levels were unchanged in hearts perfused with pyruvate (753 +/- 68 nmoles/g wet wt), but significantly decreased in glucose-perfused hearts (594 +/- 68) and in octanoate-perfused hearts (445 +/- 38) following tBHP-treatment. Pyruvate significantly reduced oxidative injury. In contrast, glucose provided a small reduction in injury while octanoate-perfused hearts had the most severe injury.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1995 Sep
PMID:Antioxidant effects of pyruvate in isolated rat hearts. 852 65


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