摘要:

BackgroundThe mechanism by which small amounts of myofiber shortening lead to extensive wall thickening is unknown. When isolated fibers shorten, they thicken in the two orthogonal directions. In situ fibers, however, vary in their orientation through the wall, and each is tethered to near or distant neighbors, which allows shortening to occur both in the direction of the fibers and also perpendicular to them. This “cross-fiber” shortening may enable the wall to shorten in two directions and thereby thicken extensively in the third.Methods and ResultsNuclear magnetic resonance tagging is a noninvasive method of labeling and tracking myocardium of the entire heart in three dimensions that does not interfere with myocardial motion. To investigate the presence and importance of cross-fiber shortening in the intact left ventricle, 10 closed-chest dogs were studied by nuclear magnetic resonance tagging. Five short-axis and four long-axis images were acquired to reconstruct 32 cubes of myocardium in each dog at end diastole and end systole. Pathological dissection was performed to determine the fiber direction at the epicardium, midwall, and endocardium of each cube. Strain was computed from the three-dimensional cube coordinates in the fiber and cross-fiber directions for epicardial and endocardial surfaces, and thickening of the full wall and its epicardial and endocardial halves was determined. Shear deformations were also calculated. Fiber strain at the epicardium and endocardium was −6.4±0.7% and −8.5±0.6% (mean±SEM), respectively (difference,P> .05). Cross-fiber strain at epicardium and endocardium was −0.6±0.5% and −25±0.6%, respectively (difference,P< .05). Thickening of the full wall reached 32.5±1.0%, composed of epicardial thickening of 25.5±0.6% and endocardial thickening of 43.3±1.0% (difference,P< .05). Fiber/cross-fiber shear strain was small (<3%). Significant regional differences were present in all strains. A significant correlation was found between the extents of regional thickening and cross-fiber shortening.ConclusionsCross-fiber shortening at the endocardium, therefore, far exceeds cross-fiber shortening at the epicardium and fiber shortening at both epicardium and endocardium. Since no active shortening can occur locally in cross-fiber direction, the extensive endocardial cross-fiber shortening must result from interaction with differently aligned fibers at a distance. The correlation between regional thickening and cross-fiber shortening supports the hypothesis that this interaction is the mechanism for amplifying small amounts of fiber shortening to cause extensive endocardial thickening.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundVasodilator function was determined in patients with Raynaud's phenomenon during intra-arterial infusions of the endothelium-dependent and -independent vasodilators, methacholine and sodium nitroprusside, respectively. Reactive hyperemia, induced by 5 minutes of arterial occlusion with exercise, was also measured.Methods and ResultsTotal blood flow was measured in the fingertip and forearm by venous occlusion plethysmography, and blood flow in the forearm skin was determined with laser Doppler flowmetry. Basal fingertip blood flow was not significantly different between control subjects and patients with Raynaud's phenomenon. Infusions of methacholine had no significant effect on fingertip blood flow in control subjects, whereas patients with Raynaud's phenomenon showed a significant increase in fingertip blood flow. Basal total forearm blood flow was significantly lower in patients with Raynaud's phenomenon than in control subjects. Infusions of methacholine and sodium nitroprusside produced dose-related increases in total forearm blood flow that were of similar magnitudes in the two groups, as were the reactive hyperemic responses. Laser Doppler measurements of forearm skin blood flow, however, showed a significantly greater vasodilator response to methacholine in patients with Raynaud's phenomenon than in control subjects. Infusions of sodium nitroprusside produced a relatively small vasodilator response in the skin of the forearm that was smaller than that to methacholine and not significantly different between the two groups.ConclusionsIn Raynaud's phenomenon, a greater vasodilator response to infusions of methacholine in the fingertip, where changes in blood flow mainly reflect those of skin, and in the skin of the forearm may reflect increased responsiveness of cutaneous blood vessels to stimulation of the endothelium. The mechanism involved is unclear but may result from a general abnormality of blood vessels in the skin, which is related to the pathophysiology of cutaneous vasospasm.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundA physiological third heart sound (S3) is common in youth but allegedly very rare after the age of 40 years. The mechanism of its disappearance is not known. The aim of this work was to study the prevalence and predictors of physiological S3in a population-based sample of persons approaching 40 years of age.Methods and ResultsA random sample of 120 persons born in 1954 was invited; 93 (42 men) entered the study. Their physical activity, alcohol and tobacco consumption, and salt intake were quantified by diary follow-up. The presence of an S3was determined by auscultation and confirmed by phonocardiography. Left ventricular (LV) size, mass, and systolic function were assessed by M-mode echocardiography and LV filling by Doppler velocimetry of transmitral flow. An audible S3was detected in 22 subjects, 1 of whom had heart disease. The prevalence of physiological S3was 23.1%. Subjects with physiological S3 had a lower body mass index (22.3 ±2.8 versus 24.6±4.1 kg/m2[mean±SD],P= .005), lower heart rate (63±7 versus 68±10 beats per minute,P= .015), higher peak early diastolic transmitral velocity (67±10 versus 58±8 cm/s,P= .002), and higher acceleration of early diastolic velocity (717±148 versus 622±122 cm/s2,P= .012) than those without S3. No differences were noted in the lifestyle characteristics, blood pressure, or LV mass and systolic function. Body mass index and peak early diastolic transmitral velocity were independent predictors of physiological S3in logistic regression analysis.ConclusionsNearly one fourth of persons approaching their forties still have an audible physiological S3. The presence of S3is predicted by leanness and a high early diastolic LV inflow velocity; the disappearance of S3is unlikely to be secondary to increasing blood pressure and relative LV hypertrophy, as is widely presented, but reflects a more primary age-related alteration of LV early diastolic function.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe outcome of the Fontan operation largely depends on the selection of patients because this procedure is a physiological correction. Among the several selection criteria for the Fontan operation, the importance of adequate size of the pulmonary artery remains controversial. In this series, in order to clarify whether the pulmonary artery size is indispensable or not as one of the selection criteria for the Fontan operation, we considered the physiological meaning of pulmonary artery size and investigated how it influenced postoperative hemodynamics of the Fontan operation.Methods and ResultsIn congenital heart disease of decreasing pulmonary blood flow, 40 patients were examined for this analysis. Pulmonary artery indexes (cross-sectional area of the right and left pulmonary arteries divided by body surface area) were measured as the expression of pulmonary artery size, and the relations of pulmonary artery index (PAI) to pulmonary vascular resistance (Rp) and compliance (Cp) were studied. There was no significant correlation between PAI and Rp, whereas a significant correlation was found between PAI and Cp (r= .71,P= .001). Furthermore, Cp influenced postoperative hemodynamics of the Fontan operation by affecting the peak central venous pressure (pCVP) and total impedance, which was the afterload to the ventricle. Impedance increased abruptly when PAI was < ≈ 100 mm2/m2.ConclusionsThe smaller pulmonary artery size causes more disadvantageous hemodynamics after the Fontan operation, with resultant effects of the rise in pCVP and the increase in afterload to the single ventricle.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundEndothelin (ET)-1 has potent vascular effects. Two endothelin receptors have been cloned, namely, the ETAreceptor, which preferentially binds ET-1, and the ETBreceptor, which equally binds ET-1 and ET-3 and preferentially sarafotoxin S6c. We characterized endothelin receptor subtypes on vascular smooth muscle and endothelium of isolated human internal mammary artery (IMA) and vein (IMV) and porcine coronary artery (PCA) using the ETA antagonists FR139317 and BQ-123, the ETBligand sarafotoxin S6c, and the ETA/ETBantagonist Ro 47-0203 (bosentan).Methods and ResultsIn endothelium-denuded IMA and PCA and less so in IMV, FR139317 and BQ-123 (in PCA only) shifted the concentration-contraction curves to ET-1 parallel to the right. However, even at 10−5mol/L, FR139317 did not inhibit a high-sensitivity portion of the concentration-contraction curve. Moreover, the ETBreceptor agonist sarafotoxin S6c induced contraction in vessels preincubated with FR139317. IMV was significantly more sensitive to the contractile effect of ET-1 and sarafotoxin S6c than was IMA (P< .05). Prolonged incubation with sarafotoxin S6c (to downregulate ETBreceptors) and FR139317 eliminated the contraction resistant to FR139317. The ETA/ETBreceptor antagonist bosentan caused a parallel shift of the concentration-contraction curve to the right at all concentrations of endothelin. ETBreceptor mRNA was detected by Northern blot analysis in IMA and aortic smooth muscle cells. In precontracted IMA and PCA with endothelium, sarafotoxin S6c did not cause endotheliumdependent relaxations, whereas transient responses occurred in IMV.ConclusionsVascular smooth muscle cells of human IMA, IMV, and PCA contain both ETAand ETBreceptors, whereas the endothelium of IMA and PCA does not express functional ETB receptors linked to nitric oxide and/or prostacyclin production. Hence, inhibition of endothelin-induced contraction in patients requires the use of combined ETA/ETBantagonists.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe activation of ATP-sensitive K+(K+ATP) channels by K+ATPopeners, eg, pinacidil, hypoxia, and ischemia, is known to shorten the ventricular action potential. Since adenosine is released in increased amounts during cardiac hypoxia and ischemia, the hypothesis that endogenous adenosine activates K+ATPchannels was tested in vivo in a guinea pig model.Methods and ResultsAnesthetized animals (n=37) were subjected to transient acute global hypoxia by ventilation with 100+ N2. Monophasic action potentials (MAP) were recorded in ventricular and atrial myocardium by use of custom-made Ag/AgCl electrode catheters. In addition, right atrial and left ventricular electrograms as well as systemic arterial blood pressure were monitored throughout the experiments. Under normoxic conditions, pinacidil (1.8μg/kg IV, n=8), a K+ATPchannel opener, shortened ventricular MAP duration (APD); this effect was reversed by glibenclamide, a potent K+ATPchannel blocker, but not by 8-cyclopentyl-1,3-dimethylxanthine (CPT), a potent A1-selective adenosine antagonist. Global hypoxia shortened atrial and ventricular APD. Glibenclamide but not CPT reversed this effect of hypoxia on ventricular but not atrial MAP. CPT but not glibenclamide reversed the effect of hypoxia on atrial MAP. In addition, CPT delayed the appearance of the atrioventricular (AV) nodal conduction block associated with global hypoxia. Finally, the ability of CPT to selectively attenuate A,-adenosine receptormediated effects of adenosine agonists in ventricular and supraventricular tissues was confirmed in 17 animals. CPT reversed the negative dromotropic effect of adenosine on AV nodal conduction and the antiadrenergic effect ofN6-cyclopentyladenosine (CPA) mediated by A1-adenosine receptor but not the adenosine-induced decrease in systemic blood pressure caused by the vasodilatory action of the nucleoside mediated by A2-adenosine receptor.Conclusions(1) Endogenous adenosine released during global cardiac hypoxia mediates, in part, AV nodal conduction delay and shortening of atrial but not ventricular APD. (2) The action of adenosine on atrial APD is mediated by A, adenosine receptors, probably via IK, AdoAch.(3) Endogenous adenosine apparently does not play an important role in the early stages of acute global hypoxia-induced activation of K+ATPchannels. The present results are consistent with the hypothesis that the shortening of ventricular APD in the hypoxic heart is due, in part, to activation of K+ATPchannels.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundVarious myocardial cell surface and intracellular antigens have been associated with autoimmune myocarditis. Since sarcoplasmic calcium overload is a recognized pathobiochemical finding in cardiomyopathy, we reasoned that there might be a causal relation between inhibition of sarcoplasmic calcium exclusion and pathogenesis of the disease and that immunization with sarcoplasmic reticulum calcium ATPase (SRATPase) or antibody specific for SR-ATPase, which can interfere with the regulation of the intracellular calcium content and the myocardial contractility, should lead to the development of cardiomyopathy and possibly myocarditis.Methods and ResultsMonoclonal antibody 4C11-20.21 (IgM class) specific for canine cardiac SR-ATPase (Mr≈110 kD) was generated by immunization of CAF1/J mice with dog heart sarcoplasmic reticulum. Antibody 4C11-20.21 inhibits 75+ of the enzymatic activity of the cardiac SR-ATPase. This antibody also cross-reacts with the higher Mrsubunit of canine skeletal SR-ATPase, but the skeletal muscle SR-ATPase activity is unaffected. This antibody does not cross-react with sarcolemmal calcium ATPase (134 kD). Antibody 4C11-20.21 was used for affinity purification of cardiac muscle SRATPase, which did not contain sarcolemmal calcium ATPase antigen. Nine of 11 CAF1/J mice injected with purified canine cardiac SR-ATPase protein demonstrated myocardial lesions: 3 of 4 mice had occasional perivascular and/or interstitial mononuclear cell infiltrates after 3 weeks, 3 of 4 had borderline myocarditis after 6 weeks, and 3 of 3 had focal myocarditis after 12 weeks. No mononuclear infiltrates were seen in any other organ. To identify the independent effect of 4C11-20.21 antibody on cardiac muscle, 2×106hybridoma cells producing the antibody were injected intraperitoneally into 12 severe combined immunodeficiency (SCID) mice. Eleven of 12 SCID mice showed variable cardiac myocyte degeneration without cellular infiltration between 8 and 19 days. Three control SCID mice, which received equivalent injections of hybridoma cells producing IgM anti–myosin light chain antibody, did not show any pathological lesions. Immunoperoxidase staining and/or immunoperoxidase transmission electron microscopy for detection of in vivo localization of 4C11-20.21 demonstrated staining of the subsarcolemmal myotubular system and focal staining of immediately adjacent sarcolemma in animals that received either 4C11-20.21 hybridoma cells or purified canine cardiac SR-ATPase antigen but not in controls. Immunofluorescence staining with goat anti-mouse C3 antibody revealed focal deposition of complement in the cardiac myocytes.ConclusionsThe time-dependent association between immunization with SR-ATPase antigen and the development of myocarditis in mice suggests that cardiac SR-ATPase constitutes one of several autoimmunogens capable of inducing autoimmune myocarditis. Besides antigenic specificity, since antibody to cardiac SR-ATPase also inhibits energy-dependent processes in the myocardium, it is reasonable to associate the pathological evidence of myonecrosis with the interference of calcium regulation, which controls myocardial contractility.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundAdenosine has been proposed to be an important mediator of ischemic preconditioning. Intracoronary administration of adenosine has recently been shown to mimic the effects of preconditioning in isolated rabbit hearts. However, it is not known whether this agent can duplicate the effects of preconditioning in vivo or in other species. Thus, the first objective of the present study was to determine whether adenosine can limit myocardial necrosis to the same extent as preconditioning in anesthetized dogs. A second objective was to determine whether the duration of the adenosine-induced cardioprotection persisted as long as that of ischemic preconditioning. Finally, a third aim was to determine whether adenosine mediates its cardioprotection via the KATPchannel, which has been shown to be an important mediator of preconditioning in several animal species, including dogs. Methods and Results Barbital-anesthetized open-chest dogsMethods and ResultsBarbital-anesthetized open-chest dogs were subjected to 60 minutes of left anterior descending coronary artery (LAD) occlusion followed by 4 hours of reperfusion. Preconditioning was elicited by 10 minutes of LAD occlusion followed by 10 or 60 minutes of reperfusion before the 60-minute occlusion period. Adenosine (400 μg/ min) or an equivalent volume of saline was infused into the LAD for 10 minutes, followed by a 10- or 60-minute drug-free period before the 60-minute ischemic insult. Glibenclamide (0.3 mg/kg IV), a selective KATPchannel blocker, was given 15 minutes before adenosine administration, and another selective KATPchannel blocker, 5-hydroxydecanoate (5-HD, 3 mg/ min IC) was infused concomitantly with adenosine into the LAD for 10 minutes. Transmural myocardial blood flow was measured at 5 minutes of occlusion, and infarct size was determined by triphenyltetrazolium staining and expressed as a percent of the area at risk (AAR). There were no significant differences in hemodynamics, collateral blood flow, or AAR between groups. Preconditioning with either 10 or 60 minutes of reperfusion produced a marked reduction (P< .05) in infarct size (6.7±2.5% and 8.7±2.6%, respectively, versus 26.9±4.3% in controls). Administration of adenosine with a 10-minute drug-free period before 60 minutes of occlusion resulted in a marked decrease in infarct size similar to that seen with preconditioning (9.6±1.7% versus 26.9±4.3% in controls); however, the protection disappeared when a 60-minute drugfree period was allowed after adenosine administration (23.0±2.4% versus 26.9±4.3% in controls). In addition, treatment with either glibenclamide or 5-HD completely abolished the protective effects of adenosine (26.4±6.8 and 25.0±4.4%, respectively, versus 26.9±4.3% in controls).ConclusionsThese results clearly reveal that (1) a 10- minute intracoronary infusion of adenosine exhibits the same efficacy as ischemic preconditioning in reducing myocardial necrosis in dogs; (2) similar to preconditioning, adenosine mediates its cardioprotection via a cardiac KATPchannellinked mechanism; and (3) adenosine-induced cardioprotection is transient (disappearing within 60 minutes), whereas ischemic preconditioning persists for at least 60 minutes. These data support the hypothesis that endogenous adenosine released during ischemia is an important mediator of ischemic preconditioning; however, important differences exist between the time course of effects of exogenously administered adenosine and preconditioning, which suggests that other factors may also be involved.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundWe have previously reported that ischemic preconditioning increases 5′-nucleotidase activity and adenosine release during ischemia and reperfusion. However, its direct cause-and-effect relation has not been proven. To test the idea that the infarct size-limiting effect of ischemic preconditioning is blunted by inhibition of ectosolic 5′-nucleotidase activity, we assessed 5′-nucleotidase activity, adenosine release, and infarct size caused by sustained ischemia with and without an exposure to α,β,-methylene adenosine 5′-diphosphate (AOPCP) in the ischemia-preconditioned myocardium.Methods and ResultsIn 67 open-chest dogs, the left anterior descending coronary artery was cannulated and perfused with an extracorporeal bypass tube from the carotid artery. After hemodynamic stabilization, the coronary artery was occluded four times for 5 minutes separated by 5 minutes of reperfusion (ischemic preconditioning, n=10). After this procedure, the coronary artery was occluded for 90 minutes followed by 6 hours of reperfusion. Infarct size normalized by the risk area was smaller than the control group (n=8, 41.0±2.6% versus 6.8±1.9%), although there were no significant differences in the endomyocardial collateral flow measured at 80 minutes of ischemia (8.5±1.1 versus 9.4±1.0 mL/100 g per minute). Ectosolic and cytosolic 5′-nucleotidase activity and adenosine release were increased during reperfusion in the ischemic preconditioning group compared with the control group, and the activity of ectosolic 5′-nucleotidase was markedly reduced by AOPCP (n=10). AOPCP affected neither adenosine-induced coronary vasodilation nor increases in myocardial oxygen consumption during an intracoronary infusion of isoproterenol n= 10). To test whether the increase in 5′-nucleotidase activity decreases infarct size, we infused AOPCP 10 minutes before the ischemic preconditioning procedure and continued for 60 minutes after the onset of reperfusion (n=8). AOPCP blunted the infarct size–limiting effect (infarct size, 38.8±4.9%). AOPCP without ischemic preconditioning did not increase infarct size n=9). Furthermore, when AOPCP was infused during the ischemic preconditioning procedure (n=6) or during 60 minutes of reperfusion (n=6), the infarct size-limiting effect was partially blunted (infarct size, 21.3±2.5% and 19.5±2.4%, respectively).ConclusionsIncreases in ectosolic 5′-nucleotidase activity and adenosine release are primarily responsible for the infarct size–limiting effect of ischemic preconditioning. Exposures to adenosine during the ischemic preconditioning procedure and enhanced release of adenosine during reperfusion synergistically contribute to the infarct size–limiting effects.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID