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  • 1
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    Online Resource
    Functional Effects of Endothelin and Regulation of Endothelin Receptors in Isolated Human Nonfailing and Failing Myocardium
    Ovid Technologies (Wolters Kluwer Health) ; 1999
    In:  Circulation Vol. 99, No. 14 ( 1999-04-13), p. 1802-1809
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 14 ( 1999-04-13), p. 1802-1809
    Abstract: Background —An activated endothelin (ET) system may be of pathophysiological relevance in human heart failure. We characterized the functional effects of ET-1, ET receptors, and ET-1 peptide concentration in left ventricular myocardium from 10 nonfailing hearts (NF) and 27 hearts in end-stage failure due to idiopathic dilative cardiomyopathy (DCM). Methods and Results —Inotropic effects were characterized in isolated muscle strips (1 Hz; 37°C). ET-1 0.0001 to 0.3 μmol/L significantly ( P 〈 0.05) increased twitch force by maximally 59±10% in NF and by 36±11% in DCM ( P 〈 0.05 versus NF). Preincubation with propranolol 1 μmol/L and prazosin 0.1 μmol/L did not affect the response to ET-1, but the mixed ET receptor antagonist bosentan and the ET A receptor antagonist BQ-123 shifted the concentration-response curves for ET-1 rightward. The ET B receptor agonist sarafotoxin S6c 0.001 to 0.3 μmol/L had no functional effects. The inotropic response to ET-1 was not associated with increased intracellular Ca 2+ transients, as assessed in aequorin-loaded muscle strips. ET receptor density (B max ; radioligand binding) was 62.5±12.5 fmol/mg protein in NF and 122.4±24.3 fmol/mg protein in DCM ( P 〈 0.05 versus NF). The increase in B max in DCM resulted from an increase in ET A receptors without change in ET B receptors. ET-1 peptide concentration (radioimmunoassay) was higher in DCM than in NF (14 447±2232 versus 4541±1340 pg/mg protein, P 〈 0.05). Conclusions —ET-1 exerts inotropic effects in human myocardium through ET A receptor–mediated increases in myofibrillar Ca 2+ responsiveness. In DCM, functional effects of ET-1 are attenuated, but ET A receptor density and ET-1 peptide concentration are increased, indicating an activated local cardiac ET system and possibly a reduced postreceptor signaling efficiency.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.99.14.1802
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1999
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  • 2
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    Online Resource
    Relationship Between Na + -Ca 2+ –Exchanger Protein Levels and Diastolic Function of Failing Human Myocardium
    Ovid Technologies (Wolters Kluwer Health) ; 1999
    In:  Circulation Vol. 99, No. 5 ( 1999-02-09), p. 641-648
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 5 ( 1999-02-09), p. 641-648
    Abstract: Background —In the failing human heart, sarcoplasmic reticulum (SR) calcium handling is impaired, and therefore, calcium elimination and diastolic function may depend on the expression of sarcolemmal Na + -Ca 2+ exchanger. Methods and Results —Force-frequency relations were studied in ventricular muscle strip preparations from failing human hearts (n=29). Protein levels of Na + -Ca 2+ exchanger and SR Ca 2+ -ATPase were measured in the same hearts. Hearts were divided into 3 groups by discriminant analysis according to the behavior of diastolic function when stimulation rate of muscle strips was increased from 30 to 180 min −1 . At 180 compared with 30 min −1 , diastolic force was increased by 160%, maximum rate of force decline was decreased by 46%, and relaxation time was unchanged in group III. In contrast, in group I, diastolic force and maximum rate of force decline did not change, and relaxation time decreased by 20%. Na + -Ca 2+ exchanger was 66% higher in group I than in group III. Na + -Ca 2+ exchanger was inversely correlated with the frequency-dependent rise of diastolic force when stimulation rate was increased ( r =−0.74; P 〈 0.001). Compared with nonfailing human hearts (n=6), SR Ca 2+ -ATPase was decreased and Na + -Ca 2+ exchanger unchanged in group III, whereas Na + -Ca 2+ exchanger was increased and SR Ca 2+ -ATPase unchanged in group I. Results with group II hearts were between those of group I and group III hearts. Conclusions —By discriminating failing human hearts according to their diastolic function, we identified different phenotypes. Disturbed diastolic function occurs in hearts with decreased SR Ca 2+ -ATPase and unchanged Na + -Ca 2+ exchanger, whereas increased expression of the Na + -Ca 2+ exchanger is associated with preserved diastolic function.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.99.5.641
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1999
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  • 3
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    Online Resource
    Alterations in Intracellular Calcium Handling Associated With the Inverse Force-Frequency Relation in Human Dilated Cardiomyopathy
    Ovid Technologies (Wolters Kluwer Health) ; 1995
    In:  Circulation Vol. 92, No. 5 ( 1995-09), p. 1169-1178
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 92, No. 5 ( 1995-09), p. 1169-1178
    Abstract: Background The present study was performed to test the hypothesis that the altered force-frequency relation in human failing dilated cardiomyopathy may be attributed to alterations in intracellular calcium handling. Methods and Results The force-frequency relation was investigated in isometrically contracting ventricular muscle strip preparations from 5 nonfailing human hearts and 7 hearts with end-stage failing dilated cardiomyopathy. Intracellular calcium cycling was measured simultaneously by use of the bioluminescent photoprotein aequorin. Stimulation frequency was increased stepwise from 15 to 180 beats per minute (37°C). In nonfailing myocardium, twitch tension and aequorin light emission rose with increasing rates of stimulation. Maximum average twitch tension was reached at 150 min −1 and was increased to 212±34% ( P 〈 .05) of the value at 15 min −1 . Aequorin light emission was lowest at 15 min −1 and was maximally increased at 180 min −1 to 218±39% ( P 〈 .01). In the failing myocardium, average isometric tension was maximum at 60 min −1 (106±7% of the basal value at 15 min −1 , P =NS) and then decreased continuously to 62±9% of the basal value at 180 min −1 ( P 〈 .002). In the failing myocardium, aequorin light emission was highest at 15 min −1 . At 180 min −1 , it was decreased to 71±7% of the basal value ( P 〈 .01). Including both failing and nonfailing myocardium, there was a close correlation between the frequencies at which aequorin light emission and isometric tension were maximum ( r =.92; n=19; P 〈 .001). Action potential duration decreased similarly with increasing stimulation frequencies in nonfailing and end-stage failing myocardium. Sarcoplasmic reticulum 45 Ca 2+ uptake, measured in homogenates from the same hearts, was significantly reduced in failing myocardium (3.60±0.51 versus 1.94±0.18 (nmol/L) · min −1 · mg protein −1 , P 〈 .005). Conclusions These data indicate that the altered force-frequency relation of the failing human myocardium results from disturbed excitation-contraction coupling with decreased calcium cycling at higher rates of stimulation.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.92.5.1169
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1995
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  • 4
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    Online Resource
    Influence of Enoximone on Myocardial Energetics in Patients with Idiopathic Dilated Cardiomyopathy : Comparison with Nitroprusside
    Ovid Technologies (Wolters Kluwer Health) ; 1989
    In:  Journal of Cardiovascular Pharmacology Vol. 14, No. Supplement ( 1989), p. S75-
    Details
    In: Journal of Cardiovascular Pharmacology, Ovid Technologies (Wolters Kluwer Health), Vol. 14, No. Supplement ( 1989), p. S75-
    Type of Medium: Online Resource
    ISSN: 0160-2446
    URL: Article
    DOI: 10.1097/00005344-198900141-00012
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1989
    detail.hit.zdb_id: 2049700-3
    SSG: 15,3
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  • 5
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    Online Resource
    Influence of the Novel Inotropic Agent Levosimendan on Isometric Tension and Calcium Cycling in Failing Human Myocardium
    Ovid Technologies (Wolters Kluwer Health) ; 1998
    In:  Circulation Vol. 98, No. 20 ( 1998-11-17), p. 2141-2147
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 20 ( 1998-11-17), p. 2141-2147
    Abstract: Background —Levosimendan was shown to increase calcium sensitivity by a novel mechanism and to inhibit phosphodiesterase III activity in animal myocardium. Methods and Results —We investigated the influence of levosimendan on isometric contractions and calcium transients (aequorin method) in muscle strips from human hearts with end-stage failing dilated or ischemic cardiomyopathy (n=27). Data were compared with the effects of the phosphodiesterase inhibitor milrinone (n=9). The average maximum increase in twitch tension was 47±14% (range, 6% to 150%) at a levosimendan concentration of 0.8±0.3 μmol/L ( P 〈 0.01). This was associated with significant increases in maximum rates of tension rise and fall and decreases in times to peak tension, to 50% relaxation, and to 95% relaxation. In aequorin-loaded muscles, levosimendan 10 −6 mol/L increased average tension by 50% ( P 〈 0.02), associated with a nonsignificant increase in aequorin light (16%). With milrinone 10 −5 mol/L, average tension increased by 58% and aequorin light by 49% ( P 〈 0.05). In those muscle strips with pronounced inotropic effects ( 〉 50% increase in tension), there was a comparable and pronounced increase in aequorin light with both agents. However, in muscle strips with weak inotropic responses ( 〈 50% increase in tension), the increase in light was significantly higher with milrinone than with levosimendan. Conclusions —Levosimendan has inotropic and lusitropic actions in failing human myocardium. Comparison with the phosphodiesterase inhibitor milrinone indicates that in case of pronounced inotropic stimulation, the modes of action of the two agents may be similar (phosphodiesterase inhibition), whereas small inotropic effects of levosimendan may result predominantly from calcium sensitization.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.98.20.2141
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1998
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  • 6
    Online Resource
    Online Resource
    Influence of Enoximone on Myocardial Energetics in Patients with Idiopathic Dilated Cardiomyopathy : Comparison with Nitroprusside
    Ovid Technologies (Wolters Kluwer Health) ; 1989
    In:  Journal of Cardiovascular Pharmacology Vol. 14 ( 1989), p. S75-
    Details
    In: Journal of Cardiovascular Pharmacology, Ovid Technologies (Wolters Kluwer Health), Vol. 14 ( 1989), p. S75-
    Type of Medium: Online Resource
    ISSN: 0160-2446
    URL: Article
    DOI: 10.1097/00005344-198906141-00012
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1989
    detail.hit.zdb_id: 2049700-3
    SSG: 15,3
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  • 7
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    Online Resource
    Alterations of Sarcoplasmic Reticulum Proteins in Failing Human Dilated Cardiomyopathy
    Ovid Technologies (Wolters Kluwer Health) ; 1995
    In:  Circulation Vol. 92, No. 4 ( 1995-08-15), p. 778-784
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 92, No. 4 ( 1995-08-15), p. 778-784
    Abstract: Background Previous studies provide considerable evidence that excitation-contraction coupling may be disturbed at the level of the sarcoplasmic reticulum (SR) in the failing human heart. Disturbed SR function may result from altered expression of calcium-handling proteins. Methods and Results Levels of SR proteins involved in calcium release (ryanodine receptor), calcium binding (calsequestrin, calreticulin), and calcium uptake (calcium ATPase, phospholamban) were measured by Western blot analysis in nonfailing human myocardium (n=7) and in end-stage failing myocardium due to dilated cardiomyopathy (n=14). The levels of the ryanodine receptor, calsequestrin, and calreticulin were not significantly different in nonfailing and failing human myocardium. Phospholamban protein levels (pentameric form) normalized per total protein were decreased by 18% in the failing myocardium ( P 〈 .05). However, phospholamban protein levels were not significantly different in failing and nonfailing myocardium when normalization was performed per calsequestrin. Protein levels of SR calcium ATPase, normalized per total protein or per calsequestrin, were decreased by 41% ( P 〈 .001) or 33% ( P 〈 .05), respectively, in the failing myocardium. Furthermore, SR calcium ATPase was decreased relative to ryanodine receptor by 37% ( P 〈 .05) and relative to phospholamban by 28% ( P 〈 .05). Conclusions Levels of SR proteins involved in calcium binding and release are unchanged in failing dilated cardiomyopathy. In contrast, protein levels of calcium ATPase involved in SR calcium uptake are reduced in the failing myocardium. Moreover, SR calcium ATPase is decreased relative to its inhibitory protein, phospholamban. These findings support the concept that reduced capacity of the SR to accumulate calcium may reflect a major defect in excitation-contraction coupling in human heart failure.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.92.4.778
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1995
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  • 8
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    Online Resource
    Association Between Thrombolytic Treatment and the Prognosis of Hemodynamically Stable Patients With Major Pulmonary Embolism : Results of a Multicenter Registry
    Ovid Technologies (Wolters Kluwer Health) ; 1997
    In:  Circulation Vol. 96, No. 3 ( 1997-08-05), p. 882-888
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 3 ( 1997-08-05), p. 882-888
    Abstract: Background Thrombolytic treatment has been shown to accelerate resolution of major pulmonary embolism and lead to a rapid improvement of right-side hemodynamics. However, the association between these favorable effects and the clinical outcome of patients who have no severe hemodynamic compromise at presentation remains unknown. Methods and Results The present multicenter registry included 719 consecutive patients with major pulmonary embolism according to clinical, echocardiographic, scintigraphic, and cardiac catheterization criteria. Symptom onset was acute ( 〈 48 hours) in 63% of patients. All patients were hemodynamically stable (ie, without evidence of cardiogenic shock) at presentation. Primary thrombolytic treatment (within 24 hours of diagnosis) was given to 169 patients (23.5%), whereas the remaining 550 patients were initially treated with heparin alone. Overall 30-day mortality was significantly lower in the patients who received thrombolytic agents (4.7 versus 11.1%, P =.016). Clinical factors associated with a higher death rate were syncope ( P =.012), arterial hypotension ( P =.021), history of congestive heart failure ( P =.013), and chronic pulmonary disease ( P =.032). However, only primary thrombolysis was found by multivariate analysis to be an independent predictor of survival (odds ratio for in-hospital death, 0.46; 95% confidence interval, 0.21 to 1.00). Patients who underwent early thrombolytic treatment had a reduced rate of recurrent pulmonary embolism (7.7 versus 18.7%, P 〈 .001) but also a higher frequency of major bleeding episodes (21.9% versus 7.8%, P 〈 .001). Cerebral bleeding occurred in 2 patients in each treatment group, and 1 patient in each group died of a bleeding complication. Conclusions The results of our study suggest that thrombolysis may favorably affect the clinical outcome of hemodynamically stable patients with major pulmonary embolism.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.96.3.882
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1997
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  • 9
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    Online Resource
    Patent Foramen Ovale Is an Important Predictor of Adverse Outcome in Patients With Major Pulmonary Embolism
    Ovid Technologies (Wolters Kluwer Health) ; 1998
    In:  Circulation Vol. 97, No. 19 ( 1998-05-19), p. 1946-1951
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 97, No. 19 ( 1998-05-19), p. 1946-1951
    Abstract: Background —Right-to-left shunt through a patent foramen ovale is frequently diagnosed by contrast echocardiography and can be particularly prominent in the presence of elevated pressures in the right side of the heart. Its prognostic significance in patients with pulmonary thromboembolism, however, is unknown. Methods and Results —The present prospective study included 139 consecutive patients with major pulmonary embolism diagnosed on the basis of clinical, echocardiographic, and cardiac catheterization criteria. All patients underwent contrast echocardiography at presentation. The end points of the study were overall mortality and complicated clinical course during the hospital stay defined as death, cerebral or peripheral arterial thromboembolism, major bleeding, or need for endotracheal intubation or cardiopulmonary resuscitation. Patent foramen ovale was diagnosed in 48 patients (35%). These patients had a death rate of 33% as opposed to 14% in patients with a negative echo-contrast examination ( P =.015). Logistic regression analysis demonstrated that the only independent predictors of mortality in the study population were a patent foramen ovale (odds ratio [OR], 11.4; P 〈 .001) and arterial hypotension at presentation (OR, 26.3; P 〈 .001). Patients with a patent foramen ovale also had a significantly higher incidence of ischemic stroke (13% versus 2.2%; P =.02) and peripheral arterial embolism (15 versus 0%; P 〈 .001). Overall, the risk of a complicated in-hospital course was 5.2 times higher in this patient group ( P 〈 .001). Conclusions —In patients with major pulmonary embolism, echocardiographic detection of a patent foramen ovale signifies a particularly high risk of death and arterial thromboembolic complications.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.97.19.1946
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1998
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  • 10
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    Online Resource
    Arterial dilatory reserve in congestive heart failure
    Ovid Technologies (Wolters Kluwer Health) ; 1992
    In:  Journal of Hypertension Vol. 10, No. Suppliment ( 1992-08), p. S65???S68-
    Details
    In: Journal of Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. Suppliment ( 1992-08), p. S65???S68-
    Type of Medium: Online Resource
    ISSN: 0263-6352
    URL: Article
    DOI: 10.1097/00004872-199208001-00017
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1992
    detail.hit.zdb_id: 2017684-3
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