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PubMed2005

Tissue edema does not change gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced T1 relaxation times of viable myocardium.

PURPOSE: To determine whether tissue edema changes gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced T1 relaxation times of the viable myocardium. MATERIALS AND METHODS: A total of 16 isolated pig hearts were divided into four groups (N=4/group) and perfused in a Langendorff apparatus. Gd-DTPA was injected into the aortic perfusion line. Tissue edema was then induced by two hours of simultaneous arterial/venous perfusion (SAVP). Myocardial water content and T1 relaxation times were monitored throughout SAVP. The volumes of the extracellular and intracellular compartments were assessed using 31P MRS-detectable markers, phenylphosphonic acid (PPA) and dimethyl methylphosphonate (DMMP). RESULTS: Tissue water content in both viable and infarcted myocardium increased significantly during two-hour SAVP. However, Gd-DTPA-enhanced T1 relaxation times of the viable myocardium remained relatively unchanged. Infarcted myocardium, on the other hand, exhibited significant T1 shortening during SAVP. Furthermore, SAVP resulted in significant expansions of both extracellular and intracellular compartments, but the ratio of the volumes of the two compartments remained relatively constant. CONCLUSION: Tissue edema in the viable myocardium does not increase the relative distribution volume of the contrast agent. As a result, edema does not change Gd-DTPA-enhanced T1 relaxation times of the viable myocardium.

Analysis of Variance↗
PubMed1991

Optical properties of normal, diseased, and laser photocoagulated myocardium at the Nd: YAG wavelength.

Laser photocoagulation of the myocardium effectively destroys arrhythmogenic foci. The purpose of this study was 1) to compare the optical properties of canine myocardium before and after photocoagulation, 2) to compare the canine model with clinical cases by measuring the optical properties of human myocardium, and 3) to assess the optical properties of human myocardial scar and epicardial fat tissue. Measured optical properties were the absorption coefficient, mu a; scattering coefficient, mu s; and scattering anisotropy factor, g. Optical measurements were performed at 1064 nm wavelength on thin plane parallel tissue slices using the integrating sphere method with glass hemispheres on either side of the sample. The study showed 1) an increase of the scattering coefficient by 40% and a two- to threefold increase in reduced scattering coefficient as a result of photocoagulation; 2) that the mu a (0.035 +/- 0.024 mm-1) and mu s (17.9 +/- 3.8 mm-1) of human myocardium were not significantly different from mu a (0.043 +/- 0.021 mm-1) and mu s (17.3 +/- 2.2 mm-1) of canine myocardium, whereas the human g (0.964 +/- 0.005) was slightly different from the canine g (0.974 +/- 0.008); and 3) that the mu a (0.021 +/- 0.016 mm-1) of epicardial fat and mu s (13.8 +/- 1.1 mm-1) of myocardial scar were significantly lower than those of normal myocardium. A dynamic model of laser-tissue interaction incorporating these changes and inhomogeneities is necessary to better describe light distribution during laser photocoagulation.

Animals↗
PubMed1998

Expression of major gap junction connexin types in the working myocardium of eight chordates.

The alpha1 connexin (connexin43) is regarded as the major gap junction protein of the myocardium because it predominates there in mammals. Here, we show that it is not the major connexin of the working myocardium in non-mammalian vertebrates, which instead express beta1-like connexins homologous to mammalian connexin32. A phylogenetic series of hearts was immunostained with seven antibodies raised against peptide sequences specific for three distinct members of the gap junction connexin family: alpha1, beta1 and alpha5 (mammalian connexin40/avian connexin42). Working myocardium from two ascidian chordates (Ciona and Mogula), a teleost (Carassius), a frog (Xenopus) and two reptiles (Anolis and Alligator) was found to express a beta1-like connexin, rather than an alpha1-like connexin. An alpha1-like connexin was nevertheless often detected in other cardiac tissues. In the chicken (by ancestry a reptile), the developing myocardium expressed a beta1-like connexin strongly on embryonic day 6 but less strongly at hatching, and minimally in the adult. Myocardial expression of alpha5 connexin increased during development, but remained strongest in the coronary vascular endothelial and cardiac conduction tissues. The arteriolar smooth muscle of the chicken expressed alpha1 connexin throughout development, but its myocardium did not. In contrast, the working myocardium of a marsupial mammal (the opossum Trichosurus) strongly expressed an alpha1 connexin just like placental mammals. These results imply that a shift from beta1 to alpha1 connexin expression in the heart occurred prior to the evolution of the opossums. The beta and alpha connexin subfamilies have different permeabilities and gating properties, and we discuss factors that might have made this shift beneficial.

Animals↗
PubMed1999

Regional expression and functional characterization of the L-type Ca2+-channel in myocardium from patients with end-stage heart failure and in non-failing human hearts.

The purpose of the present study was to investigate the expression and functional relevance of sarcolemmal L-type Ca2+-channels in failing and non-failing human myocardium. The protein expression of sarcolemmal L-type Ca2+-channels was determined with 3H-(+)-PN 200-110-binding experiments and Western blot analysis using a specific antibody against the alpha1-subunit in membrane preparations of ventricular and atrial myocardium from both failing (n = 15) and non-failing hearts (n = 8). The gene expression of the ion conducting pore of the L-type Ca2+-channel was examined with Northern blot technique in human failing and non-failing RNA. For normalization the RNA expression of calsequestrin was used. In electrically driven ventricular papillary muscle strips and auricular trabeculae, the responses to nifedipine and Ca2+ as parameters of myocardial function were studied. The protein expression as measured by 3H-(+)-PN 200-110-binding (Bmax) and Western Blot analysis with calsequestrin as reference was similar in left ventricular failing and non-failing myocardium. However, both were reduced in atrial compared to ventricular tissue in failing and non-failing hearts. The KD remained unchanged. Calsequestrin levels were unaltered in failing and non-failing hearts. The gene expression of the alpha1-subunit was similar in human failing and non-failing hearts. The L-type Ca2+-channel antagonist nifedipine reduced force of contraction with the same potency and efficiency in ventricular failing and non-failing myocardium. In contrast, the potency of nifedipine was higher in atrial than in ventricular tissue. Consistently, atrial myocardium from patients with dilated cardiomyopathy was more sensitive towards Ca2+ than those of the control group. In conclusion, the altered Ca2+-homeostasis in failing human myocardium may be less due to changes in sarcolemmal L-type Ca2+-channel expression or function than due to an altered intracellular Ca2+-handling.

Adolescent↗
PubMed2002

Evidence for calcineurin-mediated regulation of SERCA 2a activity in human myocardium.

Compromised SERCA 2a activity is a key malfunction leading to the Ca(2+) cycling alterations in failing human myocardium. SERCA 2a activity is regulated by the Ca(2+)/calmodulin-dependent protein kinase (CaM-kinase) but alterations of the CaM-kinase pathway regarding SERCA 2a in heart failure are unresolved. Therefore we investigated the CaM-kinase and phosphatase calcineurin mediated regulation of SERCA 2a in failing and non-failing human myocardium. We studied human myocardial preparations from explanted hearts from non-failing organ donors (NF, n=8) and from patients with terminal heart failure undergoing cardiac transplantation (dilated cardiomyopathy, DCM, n=8). SERCA 2a activity was determined using a NADH-coupled enzyme assay [expressed in nmol ATP/(mg protein x min)] and by(45)Ca(2+) uptake. Protein expression of SERCA 2a, phospholamban, calsequestrin and calcineurin was assessed by Western blotting (expressed as densitometric units/microg protein); phosphorylation of cardiac proteins was detected with specific phospho-antibodies for phospholamban at threonine-17 (PT17) or by incorporation of [gamma -(32)P] (expressed as pmol(32)P/mg). Maximal(45)Ca(2+) uptake (in pmol/mg/min) (NF: 3402+/-174; DCM: 2488+/-189) and maximal SERCA 2a activity were reduced in DCM compared to NF (V(max): NF: 125+/-9; DCM: 98+/-5). The V(max) reduction could be mimicked by calcineurin in vitro in NF (NF(control): 72.1+/-3.7; NF(+calcineurin): 49.8+/-2.9) and restored in DCM by CaM-kinase in vitro (DCM(control): 98+/-5; DCM(+CaM-kinase): 120+/-6). Protein expression of SERCA 2a, phospholamban and calsequestrin remained similar, but calcineurin expression was significantly increased in failing human hearts (NF: 11.6+/-1.5 v DCM: 17.1+/-1.6). Although the capacity of endogenous CaM-kinase to phosphorylate PT17 was significantly higher in DCM (DCM(control): 128+/-36; DCM(+endogenous CaM-kinase): 205+/-20) compared to NF myocardium (NF(control): 273+/-37; NF(+endogenous CaM-kinase): 254+/-31), net phosphorylation at threonine-17 phospholamban was significantly lower in DCM (DCM 130+/-11 v NF 170+/-11). A calcineurin-dependent dephosphorylation of phospholamban could be mimicked in vitro by incubation of NF preparations with calcineurin (NF(control) 80.7+/-4.4 v NF(+calcineurin) 30.7+/-4.1, P<0.05). In human myocardium, the V(max) of SERCA 2a and the phosphorylation of phospholamban is modulated by CaM-kinase and calcineurin, at least in vitro. In failing human myocardium, despite increased CaM-kinase activity, calcineurin dephosphorylation leads to decreased net phosphorylation of threonine-17 phospholamban in vivo. Increased calcineurin activity contributes to the impaired V(max) of SERCA 2a in failing human myocardium and the disorder in Ca(2+)-handling in heart failure.

Adult↗
PubMed1992

Hibernating myocardium in patients with coronary artery disease: identification and clinical importance.

The term hibernating myocardium describes a particular outcome of myocardial ischemia in which myocytes show a chronically depressed contractile ability but remain viable. Revascularization of hibernating tissue causes a recovery of mechanical function that correlates with long-term survival. Therefore it is important clinically to distinguish hibernating from infarcted myocardium, since asynergies due to hibernation will improve on reperfusion, whilst those due to infarct will not. One suggested technique to identify hibernating myocardium is to stimulate the myocytes acutely, but briefly, by administration of inotropic agents while monitoring contractile function by echocardiography. We report our experience on the use of low dosages of dobutamine. Myocardial viability was validated by measuring the recovery in contraction of the akinetic areas after coronary artery bypass surgery by means of intraoperative epicardial echocardiography. The test has a sensitivity of 93% and a specificity of 78%. It is useful for identification of viable myocardium and also for quantification of intraoperative risk in individual patients. Limitations of this test are related to the presence of downregulation of beta receptors and to the impossibility of differentiating hibernating from stunned myocardium. Another useful technique of identifying hibernating myocardium is the use of radionuclear markers for viability. In our experience the two most important tests are (1) rest-redistribution imaging of thallium 201 (which has a high sensitivity of 93% but a low specificity of 44%) and (2) 99mTc-Sestamibi imaging, which provides information on both perfusion and function with a single injection. This latter technique allows differentiation between stunning and hibernating on the basis of coronary flow which is preserved in stunning and reduced in hibernation.

Cell Survival↗
PubMed1990

Ultrastructural effects induced by global ischaemia on the AV node compared with the working myocardium. A qualitative and morphometric investigation on the canine heart.

The cardiac conduction system is considered to be particularly resistant to ischaemia. Nevertheless, following open heart surgery with short periods of ischaemia disturbances in AV conduction or ventricular arrhythmia have been reported. We compared the ultrastructure of AV node and working myocardium following 30 min global ischaemia at 25 degrees C, during pure ischaemia and with HTK cardioplegia qualitatively and morphometrically. After 30 min of pure ischaemia, interstitial and intracellular oedema together with considerable changes in organelles in AV nodes predominate over mainly cellular oedema in working myocardium. Sometimes irregular overcontractions of sarcomeres occur in the AV node, though very seldom in working myocardium. In pure ischaemia, mitochondrial swelling is comparable in both types of tissue. Following HTK cardioplegia and 30 min ischaemia, cellular oedema and mitochondrial swelling are significantly reduced in AV nodal cells and working myocardium, but remain more extensive in the AV nodes. Irregularities in the contractile state of sarcomeres are not observed. The extent of the ultrastructural alterations corresponds to the degree of metabolic change in the working myocardium. Thus, despite considerable differences during pure ischaemia and HTK cardioplegia, ultrastructurally the AV nodal cells do not display a greater resistance to ischaemia than working myocardium.

Animals↗
PubMed1990

Occurrence and prevention of contraction bands in Purkinje fibres, transitional cells and working myocardium during global ischaemia.

Contraction bands usually occur in the intramural working myocardium following post-ischaemic reperfusion. In the subendocardium, however, they are found during ischaemia. Thus, we ascertained the contraction states of Purkinje fibres, transitional cells, subendocardial and intramural parts of the working myocardium during 30 min global ischaemia at 25 degrees C. The effects with and without myocardial protection were compared. At the onset of pure ischaemia contraction bands are completely lacking in all cell types. During pure ischaemia contraction bands are found in all subendocardial cell types but not in the intramural working myocardium. A peak of pathological contraction states is found in the intramural working myocardium at the onset (0 min), in the subendocardial working myocardium at 10 min, in the transitional cells and Purkinje fibres at 30 min of pure ischaemia. Histidine-, tryptophan-, ketoglutarate-enriched (HTK) cardioplegia prevents contraction bands completely at the onset of ischaemia and prevents both contraction bands and pathological contraction states during ischaemia almost completely. Striking differences in the physiological contraction states are seen only in the working myocardium: HTK cardioplegia brings about dominance of relaxation during ischaemia. These findings may be due mainly to the effects of global ischaemia on the one hand and to catecholamines, calcium and oxygen on the other.

Animals↗
PubMedDate not supplied

The oxygen consumption paradox of "stunned myocardium" in dogs.

The contractile state of the heart is a major determinant of myocardial oxygen consumption. Since regional myocardial contractility can be severely impaired following a transient coronary occlusion, post-ischemic myocardium is frequently assumed to consume less oxygen. To test this assumption, regional myocardial function and oxygen consumption were studied in anesthetized dogs during 2 h of myocardial reperfusion following either a 15-min (Group I) or 4-h (Group II) left anterior descending coronary artery occlusion. Both groups developed similar post-ischemic regional dysfunction characterized by paradoxical motion (negative shortening). Measured as a percent of baseline segment shortening, anterior wall function in Group I (n = 8) and Group II (n = 5) at 30 min of reperfusion was -33 +/- 11% and -34 +/- 16% (p = NS) and at 120 min was -23 +/- 9% and -40 +/- 16% (p = NS). However, the two groups showed a marked difference in regional myocardial oxygen consumption during reperfusion. Despite the abnormal wall motion, regional oxygen consumption in Group I at 30 and 120 min of reperfusion was unchanged from pre-ischemic levels as measured as a percent of baseline: 104 +/- 20% (p = NS) and 111 +/- 21% (p = NS). In contrast, regional oxygen consumption in Group II was markedly depressed from baseline at 30 and 120 min of reperfusion: 42 +/- 7% (p less than .01) and 40 +/- 8% (p less than .01). To determine whether the dissociation between regional myocardial oxygen consumption and function in Group I was related to mitochondrial uncoupling, six additional dogs were studied. Tissue samples were obtained from post-ischemic myocardium after 120 min of reperfusion following a 15-min coronary artery occlusion, and compared to non-ischemic myocardium. There were no differences in the in vitro mitochondrial respiratory rates or oxidative phosphorylation capacity between the post-ischemic and non-ischemic myocardium. Therefore, in the post-ischemic myocardium, significant depressions in regional contractility may not be associated with falls in oxygen consumption. Following a 15-min coronary artery occlusion, the injured myocardium maintains a paradoxically high oxygen consumption with normal mitochondrial function despite decreased contractility and abnormal wall motion.

Animals↗
PubMedDate not supplied

Effect of coronary hyperperfusion on regional myocardial function and oxygen consumption of stunned myocardium in pigs.

The "Gregg phenomenon" implies that myocardial function and oxygen consumption (MVO2) increase when coronary perfusion is enhanced within or above the autoregulatory range. We have recently demonstrated that the "Gregg phenomenon" has no significance for regional myocardial function and MVO2 in anesthetized swine in situ. There is, however, some evidence that the "Gregg phenomenon" may exist within stunned myocardium. To test whether coronary hyperperfusion increases regional myocardial function and MVO2 in stunned myocardium, in six anesthetized swine the left anterior descending coronary artery (LAD) was cannulated and perfused at constant pressure (CAP) using an extracorporal circuit. The coronary vein which parallels the LAD was cannulated to allow measurement of regional MVO2 and regional systolic wall thickening (WT%) of the anterior myocardium was assessed using sonomicrometry. Blood flow (CBF) to the LAD was increased by increasing CAP within the extracorporal circuit or by intracoronary adenosine infusion (150 micrograms/min). In normal myocardium, increasing CBF from 71.4 +/- 19.7 (SD) to 156.7 +/- 48.8 ml/min/100 g by increasing CAP from 100 +/- 10 to 190 +/- 10 mm Hg or increasing CBF from 75.1 +/- 29.1 to 189.2 +/- 45.8 ml/min/100 g by intracoronary adenosine infusion did not increase WT% (34.3 +/- 12.2% vs 32.1 +/- 10.6% and 32.3 +/- 10.7% vs 30.1 +/- 13.2%, respectively). MVO2 was not changed during enhanced CAP (6.94 +/- 1.05 vs 8.10 +/- 1.08 ml/min/100 g) and during intracoronary adenosine infusion (6.67 +/- 1.45 vs 7.30 +/- 2.23 ml/min/100 g). Twenty min of hypoperfusion followed by 30 min of reperfusion depressed WT% by 47% (p less than 0.05). However, MVO2 was only decreased by 23% (NS). In the stunned myocardium, increasing CBF from 62.1 +/- 36.4 to 157.1 +/- 60.0 ml/min by increasing CAP was not associated with an increase in WT%. MVO2, however, increased from 5.14 +/- 1.07 to 8.88 +/- 1.83 ml/min/100 g (p less than 0.05). Comparable results were achieved when CBF was increased from 60.3 +/- 28.7 to 176.9 +/- 48.5 ml/min by intracoronary adenosine infusion. WT% was unaffected, while MVO2 increased from 4.69 +/- 0.92 to 9.46 +/- 3.39 ml/min/100 g (p less than 0.05). Thus, increasing coronary perfusion within or above the autoregulatory range increases MVO2 in stunned myocardium, but without a simultaneous increase in regional myocardial function.

Adenosine↗
PubMed1998

[Regulation of myocardium beta-adrenoceptors pathway in ventricular remodeling of heart failure patients].

To study the role of myocardium beta-adrenoceptors pathway in ventricular remodeling of heart failure patients. beta-adrenegic receptor density (Bmax) and the content of cAMP were measured in the papillae of left ventricle and blood lymphocyte of 20 patients suffered from heart failure (CHF) (NYHZ classification II to III) Bmax were investigated using 3H-dihydroalpheolol as ligand. cAMP were assessed by competitive immunoassay. Left ventricle mass index (LVMI) were measured using echocardiogram. The results showed that the Bmax and cAMP in failing myocardium significantly negatively correlated with LVMI (r = -0.77, P < 0.01 and r = -0.46 P < 0.05 respectively); the Bmax of myocardium and blood lymphocyte in CHF patients with NYHA III (63 +/- 12 fmol/mgpro and 514 +/- 115 fmol/10(7) cell) significantly lowered than that of NYHA II patients (94 +/- 20 fmol/mgpro and 702 +/- 138 fmol/10(7) cell); and the Bmax of myocardium and blood lymphocyte in patients with abnormal LVMI (62 +/- 12 fmol/mgpro and 516 +/- 122 fmol/10(7) cell) decreased more significantly than that with normal LVMI patients; even in nromal LVMI patients (92 +/- 21 fmol/mgpro and 682 +/- 146 fmol/10(7) cell), the Bmax of blood lymphocyte was already decreased (P < 0.01), when comparing with controls. The intralymphocyte cAMP content sygnificantly decreased than that of controls (P < 0.05). These results indicated that Bmax could reflect the severity of ventricle remodeling and the impairment of myocardium. The regulation of myocardium intracellular messenger transduction was earlier than the pathologic structural change of LV remodeling.

Adult↗
PubMed2006

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin-angiotensin system.

AIMS/HYPOTHESIS: The angiotensin II (type 1) (AT1) receptor mediates many biological effects of the renin-angiotensin system (RAS), leading to remodelling of cardiac tissue. The present study was designed to analyse changes in the function and expression of the AT1 receptor as principal effector of the RAS in myocardium from type 2 diabetic patients compared with non-diabetic myocardium as control. In addition, we determined the effect of treatment with ACE inhibitors or AT1 receptor blockers on expression levels of the receptor in diabetic patients. METHODS: Gene expression of the AT1 receptor was analysed by quantitative RT-PCR and protein expression was determined by immunoblot analysis in human right atrial myocardium. We investigated functional coupling of the receptors by measuring contractility in isolated trabeculae stimulated with increasing concentrations of angiotensin II. RESULTS: Diabetic myocardium showed a significant increase in protein expression (170 +/- 16% of control) and median mRNA expression (186% of control) of the AT1 receptor. The additional receptors were functionally coupled, resulting in a stronger inotropic response upon stimulation with angiotensin II (89 +/- 5.5% vs 29 +/- 1.6% in controls), whereas receptor affinity was similar in both groups. However, myocardium from diabetic patients treated with ACE inhibitors or AT1 receptor blockers showed no increase in AT1 receptor expression. CONCLUSIONS/INTERPRETATION: AT1 receptor expression in myocardium of type 2 diabetic patients is dynamic, depending on the level of glycaemic control and the activity of the RAS. These findings could at least in part explain the strong therapeutic benefit of RAS inhibition in diabetic patients.

Aged↗
PubMed1998

Frequency dependent force generation correlates with sarcoplasmic calcium ATPase activity in human myocardium.

OBJECTIVE: In congestive heart failure both a decreased function of the sarcoplasmic Ca(2+)-ATPase and a negative force-frequency relationship have been shown. This study aimed to investigate a possible relationship between frequency potentiation, sarcoplasmic Ca(2+)-ATPase activity, and SERCA2 protein expression in human myocardium. METHODS: Frequency potentiation was studied in electrically stimulated, isometric, left ventricular papillary muscle strip preparations (37 degrees C, 0.5-3.0 Hz) from terminally failing (NYHA i.v.; n = 5, dilated cardiomyopathy) and nonfailing (donor hearts, n = 5) human myocardium. In the identical samples the Ca(2+)-ATPase activity (NADH coupled assay) and the protein expression of sarcoplasmic Ca(2+)-ATPase (SERCA2), phospholamban, and calsequestrin (western blot) were determined. The frequency dependent change in the force of contraction and Vmax of the Ca(2+)-ATPase activity and the protein expression of SERCA2 were correlated with each other. RESULTS: In terminally failing myocardium the force-frequency relationship was negative (2.0 Hz vs. 0.5 Hz: -0.2 +/- 0.1 delta mN) contrasting a positive rate dependent potentiation of force in nonfailing tissue (2.0 Hz vs. 0.5 Hz: +0.8 +/- 0.2 delta mN; p < 0.01). In failing myocardium the corresponding maximal sarcoplasmic Ca(2+)-ATPase activity (Vmax) was reduced significantly compared to nonfailing myocardium (174 +/- 24 vs. 296 +/- 31 nmol ATP/mg.min, p < 0.01). The protein expression of SERCA2, phospholamban, and calsequestrin remained unchanged in failing myocardium. The maximal Ca(2+)-ATPase activity significantly correlated with the frequency dependent change in force of contraction (2 Hz vs. 0.5 Hz: r = 0.88, p = 0.001; 3 Hz vs. 0.5 Hz: r = 0.84, p = 0.004). No correlation between protein expression of SERCA2 and Ca(2+)-ATPase activity or change in force of contraction was observed. CONCLUSION: Due to a significant correlation between sarcoplasmic Ca(2+)-ATPase activity and frequency potentiation, the negative rate dependent force potentiation in human heart failure could be at least in part be attributed to decreased function of the sarcoplasmic Ca(2+)-ATPase.

Adult↗
PubMed2001

Correlation between heterogeneous myocardial flow and oxidative metabolism in normoxic and stunned myocardium.

Myocardial blood flow exhibits considerable heterogeneity. Consequently, oxygen supply to the myocardium is also heterogeneous, as is myocardial metabolism. Many lines of evidence show a close correlation between local flow and local metabolism in the normoxic myocardium. So far, myocardial metabolism has predominantly been assessed indirectly by using labeled substrates. We used the (18)O isotope, permitting analytical separation of H2(18)O from the (18)O isotope, as well as quantification of regional oxidative metabolism by measuring the tissue residue of oxidation water in the rabbit myocardium. Correlation of local flow with oxidative metabolism was significant in the normoxic myocardium. This correlation was lost in the postischemic/reperfused myocardium. Apart from the established mechanisms underlying myocardial stunning, a mismatch between local flow and oxidative metabolism might thus also contribute to the postischemic dysfunction. In the normoxic myocardium, function should correlate with metabolism and blood flow. For technical reasons, function has not been assessed on a very local scale. Nevertheless, some considerations are presented on the heterogeneity of function as well as on the scale on which heterogeneity should be investigated to convey physiologically meaningful information on regulatory cardiac mechanisms.

Animals↗
PubMed2003

Reduced length-dependent cross-bridge recruitment in skinned fiber preparations of human failing myocardium.

A depressed activity of myosin ATPase has been described in human failing myocardium. Since alterations in cross-bridge kinetics may affect both systolic and diastolic cardiac function, the present study simultaneously investigated Ca(2+)-dependent tension and actomyosin ATPase activity (MYO) in triton X-skinned fiber preparations of human non-failing (donor hearts, n=8) and failing (dilated cardiomyopathy, n=11) left ventricular myocardium at increasing sarcomeric length (1.9 and 2.1 microm, alpha-actinin staining). The MYO/tension ratio was analyzed as a parameter characterizing myofibrillar energetics. At a sarcomere length of 1.9 microm, the Ca(2+) sensitivity of tension was significantly increased in human failing compared to non-failing myocardium. In human non-failing myocardium, maximal Ca(2+)-activated tension [1.9 microm vs. 2.1 microm, 23.7 (1.9) vs. 28.3 (1.9) mN/mm(2)] and the Ca(2+) sensitivity of tension [EC(50)Ca(2+ )(pCa): 5.67 (0.06) vs. 7.07 (0.11)] were increased by increasing sarcomere length. This was accompanied by an enhancement in Ca(2+)-dependent MYO [+72 (11) vs. +101 (9) microM ADP/s] as well as an increase in the Ca(2+)-sensitivity of MYO [EC(50)Ca(2+ )(pCa): 5.84 (0.08) vs. 6.86 (0.08)]. In human failing myocardium, only Ca(2+) sensitivity of tension (but not of MYO) increased. Tension cost was increased in failing vs. non-failing tissue [1.9 microm: 4.18 (0.06) vs. 3.53 (0.06) (mN.s)/(mm(2). microM ADP); 2.1 microm: 4.28 (0.13) vs. 3.52 (0.05) (mN.s)/(mm(2). microM ADP)]. We concluded that, in human failing myocardium, the length-dependent force generation may be blunted due to an already increased Ca(2+) affinity of troponin C as well as an impairment of length-dependent cross-bridge recruitment.

Adult↗
PubMedDate not supplied

Cine and tagged magnetic resonance imaging in short-term stunned versus necrotic myocardium.

We investigated the potential of Cine and 2D Tagged Cardiac Magnetic Resonance (CMR) Imaging to distinguish stunned from necrotic left ventricular (LV) myocardium in the early postischemic phase in an open-chest animal model (N = 12). Reversible and permanent occlusion of the LAD coronary artery resulted in global LV dysfunction in both groups without significant differences. LAD perfused segments revealed significant higher values for end systolic wall thickening (ESWT) and percentual systolic wall thickening in animals with stunned myocardium. Analysis of strain parameters showed significant regional differences (maximal principal strain lambda1, deviation angle beta) between postischemic and remote myocardium within both groups, however results were not significantly different comparing animals with stunned myocardium to animals with myocardial necrosis. In conclusion, at rest neither global LV functional nor regional strain parameters derived from Cine and 2D Tagged CMR Imaging can distinguish animals with short-term stunned myocardium from respective animals with necrotic myocardium. Diagnostic value of ESWT is limited due to the spatial resolution of the gradient-echo sequence used.

Animals↗
PubMed1990

Effects of xamoterol on inotropic and lusitropic properties of the human myocardium and on adenylate cyclase activity.

The purpose of the present study was to characterize the effects of xamoterol in the human myocardium. In the presence of forskolin or milrinone, xamoterol increased isometric force of contraction, contraction velocity, and relaxation velocity in isolated, electrically driven preparations from human myocardium, but had no effect alone. There was no difference in the effect of xamoterol between right atrial myocardium and left ventricular myocardium from nonfailing (NF), moderately failing (NYHA II-III), and severely failing (NYHA IV) human hearts. The positive inotropic and lusitropic effects of isoprenaline were reduced depending on the severity of heart failure in left ventricular myocardium (i.e., NF greater than NYHA II-III greater than NYHA IV). In the presence of norepinephrine, xamoterol produced negative inotropic effects similar to those of the beta-adrenoceptor antagonists pindolol and propranolol. Xamoterol alone had no effects on force of contraction, whereas pindolol and propranolol markedly reduced contractile force. In NYHA class IV, isoprenaline stimulated adenylate cyclase about twofold but xamoterol, like pindolol or propranolol, had no effect. Experiments with the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively, showed that the positive inotropic and lusitropic effects of xamoterol were mediated by beta 1-adrenoceptors. Consistently, xamoterol had a selectivity of 13.8 at beta 1-adrenoceptors as measured in radioligand binding experiments. It is concluded that xamoterol acts as a beta 1-adrenoceptor antagonist with a selectivity of 13.8 in human ventricular myocardium. The compound has an intrinsic sympathomimetic activity, as it produces beta 1-adrenoceptor-mediated positive inotropic and lusitropic effects in the presence of forskolin. The beneficial effects of xamoterol in patients with heart failure could be due to prevention of the detrimental effects of norepinephrine such as beta 1-adrenoceptor downregulation of an increase of Gi (inhibitory guanine-nucleotide binding protein).

Adenylyl Cyclases↗
PubMed1991

Energy metabolism in preconditioned and control myocardium: effect of total ischemia.

Myocardium which has been preconditioned by one or several brief episodes of ischemia has much slower energy utilization during a subsequent sustained episode of ischemia. Since preconditioned tissue also is 'stunned', the reduced energy utilization of preconditioned tissue may be due to reduced contractile effort. This study was done to assess whether differences in energy utilization persisted or disappeared under conditions of total ischemia, in vitro, when contractile activity was abolished in both control and preconditioned regions by hyperkalemic cardiac arrest. Preconditioned myocardium was produced in open-chest anesthetized dogs by exposing the circumflex bed to four 5-min episodes of ischemia each followed by 5 min of arterial reperfusion. Non-preconditioned anterior descending bed was used as control myocardium. Hearts were arrested with hyperkalemia after the last reperfusion period in order to reduce or eliminate the effects of contractile activity. Metabolite content was measured in sequential biopsies of the tissue. Large differences in the rate of energy metabolism of the two regions were noted during the first 15 minutes of ischemia. During this time, the preconditioned tissue utilized less glycogen, and produced less lactate, glucose-6-phosphate (G6P), glucose-1-phosphate (G1P), and alpha-glycerol phosphate (alpha GP), than did control myocardium. Moreover, there was a much smaller decrease in net tissue ATP in the preconditioned than in the control tissue. Thus, the decrease in the demand of preconditioned tissue for energy, which has been observed in vivo, persisted despite the elimination of differences in contractile effort between control and preconditioned myocardium. Although the cause of this decrease in energy demand in preconditioned myocardium remains unknown, the present results suggest that it is not due to concomitant stunning.

Adenine Nucleotides↗