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At least 19 recordsLinked to original sources

Comprehensive assessment of vasospastic angina using coronary computed tomography angiography: synergistic value of the presence of myocardial bridge, perivascular inflammation, and myocardial extracellular volume fraction.

AIMS: Coronary computed tomography angiography (CCTA) has evolved beyond anatomical assessment to include sophisticated tissue characterization. While an elevated perivascular fat attenuation index around the right coronary artery (FAI-RCA) is known to reflect coronary inflammation in vasospastic angina (VSA), recurrent vasospasms may also induce chronic subclinical myocardial injury and subsequent remodelling, potentially associated with an increased myocardial extracellular volume fraction (ECV). However, the diagnostic integration of ECV and FAI-RCA for identifying VSA in patients with angina with non-obstructive coronary arteries (ANOCA) remains to be elucidated. METHODS AND RESULTS: This study included consecutive ANOCA patients who underwent CCTA with a dedicated ECV protocol, followed by an invasive spasm provocation test. Comprehensive CCTA analysis quantified both FAI-RCA and the transmural ECV gradient (the difference between endocardial and epicardial ECV: ECVEndo - ECVEpi). Of the 100 patients analysed (mean age: 65.3 &#xb1; 11.8 years; 55% male), 27 were diagnosed with VSA. Multivariable logistic regression analysis identified transmural ECV gradient [odds ratio (OR): 1.12, 95% confidence interval (CI): 1.01-1.25], presence of myocardial bridging (MB) (OR: 3.49, 95% CI: 1.25-9.74), and high FAI-RCA (> -70.95 Hounsfield units [HU]) (OR: 5.79, 95% CI: 2.06-16.30) as significant independent predictors of VSA (all P < 0.05). Notably, the integration of transmural ECV gradient provided incremental diagnostic value beyond FAI-RCA and MB, as assessed by the Net Reclassification Improvement and Integrated Discrimination Improvement. CONCLUSION: A multi-parametric CCTA approach potentially identifies patients at high risk for VSA. The significant association of the transmural ECV gradient with VSA suggests that myocardial remodelling imaging provides a novel diagnostic window into the cumulative myocardial impact of vasospasm, independent of active adipose tissue inflammation and the presence of MB.

Humans

Myocardial bridges in man: clinical correlations and angiographic accentuation with nitroglycerin.

Little is known of the clinical significance of myocardial bridges, which may be recognized angiographically as systolic coronary artery narrowing (SCAN). A retrospective review of a 1 year's experience (313 consecutive coronary arteriograms) revealed 5 patients with SCAN, an incidence of 1.6%. SCAN involved the proximal and/or middle segments of the left anterior descending coronary artery in all patients. It is of particular note that the administration of nitroglycerin noticeably accentuated the SCAN phenomenon in each of 3 patients to whom it was administered. Four of the 5 patients had left ventricular hypertrophy due to hypertrophic cardiomyopathy (2), aortic stenosis (1), and hypertension (1). All 5 patients with the SCAN phenomenon had anginal chest pains, and critical obstructive coronary atherosclerosis was observed in only 2 cases. The other 3 patients showed, otherwise normal coronary arteriograms. Thus, myocardial bridges appear to be angiographically manifest predominantly in patients with cardiac hypertrophy. Nitroglycerin, which accentuates SCAN, might be useful as a provocative test to enhance the angiographic recognition of this phenomenon. The possible role of myocardial bridges in the production of myocardial ischemia warrants further investigation.

Adult

[Myocardial "bridges". A new pathogenetic problem in angina without coronary obstruction (author's transl)].

Six patients showing at coronary angiography normal coronary arteries during dyastole, but a segmental constriction of the left anterior descending artery during systole, were studied. Four of these patients in which the degree of systolic artery narrowing was more evident had typical angina and positive stress test. In two of these cases, a probable idiopathic cardiac hypertrophy was present. The pathogenetic significance of the angiographic findings are discussed, on the basis of common knowledge of coronary physiology and of pathophysiology of angina with normal coronary arteries.

Adult

[Muscle bridges over the left anterior descending coronary artery: their influence on arterial disease (author's transl)].

A total of 711 hearts was studied and examined for coronary muscle bridges of the left anterior descending (LAD) macroscopically, angiographically and histologically. A muscular overbridging of the LAD was found in 22.9% of all hearts. The average distance from left artery bifurcation was 33.6 mm, the average length was 22.5 mm and the average thickness 2.8 mm. A thin layer of fat tissue is mostly to be found between the overbridged coronary artery and the myocardial bridge. The patient group with and without myocardial overbridging showed no difference in sex or age nor in average stature and the average heart weight. Statistically, there is significantly more atherosclerosis of the coronary artery proximal to the muscle bridge than there is under and distal to the bridge. A difference in frequency and extent of atherosclerosis in hearts with and without coronary muscle bridge could not be shown for this portion of the LAD. Nevertheless, there is a tendency for fewer anterior-wall infarctions in the patient group with a coronary muscle bridge of the LAD, because, when the whole branch is considered, there is a significantly lower incidence of atherosclerosis in hearts with myocardial overbridging of the LAD. The reason for the protective effect of a coronary muscle bridge is yet not clear.

Adipose Tissue

[Reentry tachycardia with complete atrioventricular dissociation probably connected with the right Mahaïm bundle].

A case of reentrant tachycardia with narrow and wide ventricular complexes without appearances of preexcitation is reported. Electrophysiological investigation showed complete retrograde atrioventricular block during tachycardia; left bundle branch block did not show the tachycardia rate. The reentry loop probably comprised: the His bundle, the right bundle branch, a right Mahaïm bundle and possibly a myocardial bridge. Possible intra-hisian reentry is discussed. The initiation of the tachycardia is analysed together with the possible consequences of permanent cardiac pacing.

Bundle of His

[Unloaded shortening velocity of the myocardium as an index of contractility (author's transl)].

An experimental study attempts to clarify the reasons for a fashionable over- or underestimation of the unloaded shortening velocity of the myocardium (Vmax) as an index of "contractility" in international cardiological literature. Long-term investigations on the isolated myocardial preparation as well as on the heart in situ support our own position: 1. Vmax of the myocardium is, without doubt, a value of greater relevance in muscle physiology independent of the interpretation related to the fundamental processes. 2. Vmax cannot be exclusively regarded as a function of the rate of cross-bridge movements, but is influenced by the Ca2+-concentration and consequently by the conditions of electromechanical coupling. 3. Vmax is not a reliable measure for myocardial power capacity under all conditions as this value on the one hand and the developed tension on the other are influenced to different degrees. 4. If the amount of contractile material per cross sectional unit is changed (changed relation of fibrils/mitochondria), Vmax can give better indications on the contractile elementary process than the developed tension. 5. Increased content of connective tissue and scars influence both the developed tension and Vmax. 6. A reduction in Vmax under long-term increased hemodynamic loading of the heart is not to be considered a priori as an expression of cellular damage.

Animals

Effect of Ca++ on Vmax measured in absence of external or internal load.

Myofibrils 1 sarcomere wide (single myofibrils) were prepared from rat heart. Mean initial sarcomere length was 2.68 mu. Contraction was initiated with 20, 25 or 100 muM MgATP and terminated with EGTA and EDTA. Single fibrils shortened at the theoretical Vmax for the in vitro conditions until sarcomere length reached 2.05 mu. At this length they encountered a significant internal afterload. Reaction time, substrate, and temperature were adjusted so that final sarcomere length was greater than or equal to 2.05 mu in most experiments. Ca++ increased Vmax of single fibrils 2- 4-fold. Results were similar at 20 and 100 muM MgATP, and in reaction mixture containing 100 or 140 mM KCI. We conclude that Ca++ controls not only the number of cross-bridges, but also the rate at which the cross-bridges turn over.

Animals

A needleless liquid jet injection delivery method for cardiac gene therapy: a comparative evaluation versus standard routes of delivery reveals enhanced therapeutic retention and cardiac specific gene expression.

This study evaluates needleless liquid jet method and compares it with three common experimental methods: (1) intramuscular injection (IM), (2) left ventricular intracavitary infusion (LVIC), and (3) LV intracavitary infusion with aortic and pulmonary occlusion (LVIC-OCCL). Two protocols were executed. First (n&#x2009;=&#x2009;24 rats), retention of dye was evaluated 10&#xa0;min after delivery in an acute model. The acute study revealed the following: significantly higher dye retention (expressed as % myocardial cross-section area) in the left ventricle in both the liquid jet [52&#x2009;&#xb1;&#x2009;4] % and LVIC-OCCL [58&#x2009;&#xb1;&#x2009;3] % groups p&#x2009;<&#x2009;0.05 compared with IM [31&#x2009;&#xb1;&#x2009;8] % and LVIC [35&#x2009;&#xb1;&#x2009;4] %. In the second (n&#x2009;=&#x2009;16 rats), each animal received adeno-associated virus encoding green fluorescent protein (AAV.EGFP) at a single dose with terminal 6-week endpoint. In the second phase with AAV.EGFP at 6&#xa0;weeks post-delivery, a similar trend was found with liquid jet [54&#x2009;&#xb1;&#x2009;5] % and LVIC-OCCL [60&#x2009;&#xb1;&#x2009;8] % featuring more LV expression as compared with IM [30&#x2009;&#xb1;&#x2009;9] % and LVIC [23&#x2009;&#xb1;&#x2009;9] %. The IM and LVIC-OCCL cross sections revealed myocardial fibrosis. With more detailed development in future model studies, needleless liquid jet delivery offers a promising strategy to improve direct myocardial delivery.

Animals

[Effect of nitrate derivatives on the contractility and relaxation of papillary muscle in hypoxia and reoxygenation].

The direct action of nitrate derivatives on myocardial contractility is not fully understood. The effects of Glyceryl Trinitrate (1 mM/L.) and Sodium Nitro prussiate (3 X 10(-5) M/L.) on papillary muscle were studied during 30 minutes hypoxia followed by 60 minutes reoxygenation: Both conditions were analysed every 5 minutes: 1. Contractility was assessed by maximal shortening velocity with no load (Vmax), maximal isometric force (PF), number of active cross-bridges and peak time (TPF), a characteristic of the period of activity. 2. Relaxation was assessed by the relaxation velocity (V relax) and the 1/2 relaxation time (THR). The two nitrate derivatives had the same effects: during anoxia, a notable reduction of the maximal force was observed; myocardial depression continued during the first 15 minutes of reoxygenation. After the 30th minute of investigation all parameters increased significantly (107-110 p. 100, p less than 0,01); TPF and THR returned to normal. A positive inotropic effect and improvement of the relaxation phase were observed at the end of reoxygenation. This effect is not attributed to improved segmental performance especially as it occurred at dosages close to those used in therapeutics.

Animals

Regional and systemic haemodynamic effects of some vasopressins: structural features of the hormone which prolong activity.

Cardiac output and regional blood flows to myocardium, gut, uterus and kidney were determined in anaesthetised female rats by a single injection of 86RbCl. The haemodynamic responses were measured at various time intervals up to 2 h after single I.V. injections of lysine-vasopressin and the following of its analogues: a) with extended peptide chains at the N-terminal (including "hormonogens") Nalpha-glycyl-glycyl-lysine-vasopressin, Nalpha-glycyl-glycyl-glycyl-arginine-vasopressin and Nalpha-D-valyl-lysine-vasopressin, b) "carba" modifications desamino-carba6-arginine-vasopressin, desamino-carba6-D-arginine8-vasopressin, desamino-carba6-ornithine8-vasopressin, desamino-dicarba-arginine-vasopressin and c) other steric alterations - desamino-D-arginine8-vasopressin and desamino-N-methylarginine8-vasopressin. Sub-pressor doses of lysine-vasopressin were followed by marked reductions in gut and uterus blood flows which reached a peak at 10 min. and had completely receded by 60 min. The presence of steric alterations in the C-terminal tripeptide of the molecule- D-arginine or N-methylarginine in sequence position 8 - practically completely eliminated vascular activity. The same was true for Nalpha-D-valyl-lysine-vasopressin. None of the latter three analogues showed any inhibitor properties to the action of lysine-vasopressin. The two hormonogens (triglycyl N-terminal extensions) had to be given in doses 10 times greater to obtain a vasoconstrictor effect in gut and uterus equivalent in amplitude to that of a lysine-vasopressin, but this effect was still present to the same degree 2 h later with the hormonogen of lysine-vasopressin, and was only starting to return to baseline values at the same time with the arginine-vasopressin hormonogen. The vascular potency of both mono-carba L-analogues was higher than that of lysine-vasopressin, and the effect was as prolonged as with the hormonogens. The dicarba analogue also showed a prolonged action, but with much reduced potency. No significant changes in renal or myocardial blood flows were observed at all. Molecular features of vasopressin smooth muscle activity were discussed, and a receptor model was proposed. It was suggested that the -S-S-, -CH2CH2-bridges in the above analogues are not directly bound in the peptide-receptor complex and constitute the limiting factor determining complex duration, or persistence of the active peptide in the "receptor compartment". These results provide an experimental basis for possible clinical application of triglycyl-vasopressin and carba-vasopressin in bleeding from both gut and uterus and for induction of menstruation.

Amino Acid Sequence

Myocardial infarct imaging agents. III. Synthesis and evaluation of [203Hg] hydroxymercuriphthaleins.

Four Hg-203-mercurated phthaleins were prepared, purified, and compared with [203Hg] mercuric nitrate, [3H] phenolphthalein [203Hg] hydroxymercurifluorescein and Tc-99m-pyrophosphate in a rat model of myocardial necrosis to determine their specificities for damaged myocardium. The ratios of damaged myocardium to normal myocardium, and to blood, for the [203Hg] hydroxymercuriphthaleins (20.7-34.1 and 12.1-20.1, respectively) were somewhat lower than those reported previously for [203Hg] hydroxymercurifluorescein, but were higher than those found with [203Hg] mercuric nitrate, [3H] phenolphthalein, and Tc-99m pyrophosphate. Both the hydroxymercuri- functional group and the phthalein moiety are required for selectivity. The removal of the oxygen bridge present in fluorescein, and the replacement of carboxylic acid by sulfonic acid, had no significant effects on the sequestration process in damaged tissue.

Animals

Patterns of activation in ventricular arrhythmias of late myocardial infarction in dogs.

Ventricular arrhythmias were produced in 12 dogs 4 to 6 days after coronary artery ligation by programmed ventricular stimulation. The electrocardiogram and 7 composite electrograms from endocardial and epicardial surfaces of the ischemic, border and normal zones, as well as from the right ventricle, were recorded during and after programmed ventricular stimulation. The ventricular arrhythmias were preceded and sustained by delayed, fragmented activity in the ischemic epicardial zone bridging diastole. Efferent pathways from the ischemic epicardium led to direct epicardial spread to adjacent normal epicardium in most instances. Efferent pathways into the endocardial regions were also observed, but to a lesser extent. The efferent reentry pathways led to both ventricles, and produced right and left ventricular arrhythmias in 8 of the 12 dogs; they were exclusively of left ventricular origin in the remaining 5. Classification of right and left ventricular arrhythmias may only be related to the exit points and not necessarily to their origin.

Animals

Intramyocardial pH as an index of myocardial metabolism during cardiac surgery.

At present, a practical method for continuous monitoring of the state of tissue metabolism in the individual patient's heart during cardiac operations is not available. We have explored the use of miniature electrode measurements of myocardial interstitial pH to provide this monitoring capability, making comparisons with intracellular pH in left ventricular biopsy specimens and with tissue PCO2 measured by mass spectrometry. The electrode system consisted of a hydrogen ion-sensitive glass miniature electrode, housed in the beveled end of a 21 gauge (0.8 mm diameter) hypodermic needle, and a 2 mm diameter reference electrode, with an internal silver-silver chloride electrode coupled to tissue through a saline bridge (150 mM/L sodium chloride) saturated with silver chloride. Accuracy in blood at 37 degrees C was compared with conventional instrumentation (Radiometer BMS-3 MK-2 Blood Micro System) over a pH range of 7.4 to 6.4 with linear regression analysis (n = 26) revealing a high correlation (r = 0.997) and a mean difference in paired observations of only 0.01 +/- 0.004 (mean +/- SEM) pH units. In two groups of dogs on cardiopulmonary bypass, the pH needle and reference electrodes were inserted into the anterior wall of the left ventricle. Ischemic arrest of the heart at 37 degrees C was used to vary myocardial pH. In Group 1 (n = 8), intracellular pH was estimated from left ventricular biopsy specimens (400 mg each) taken over a microelectrode pH range of 7.37 to 6.37, snap frozen, and homogenized. In Group II (n = 6), tissue PCO2 in the anterior wall of the left ventricle was determined by mass spectrometry (sampling catheter 1.3 mm diameter). Miniaturized electrode (interstitial) pH exceeded biopsy (intracellular) pH under control conditions by 0.28 +/- 0.025 pH units (p less than 0.001), but below an electrode pH of 6.8 the results of the two techniques did not differ significantly. The tissue PCO2 rose from 69 +/- 2 mm Hg to a final plateau of 419 +/- 25 mm Hg, which was similar to the predicted value of 427 +/- 28 mm Hg calculated from the pH change (7.37 +/- 0.01 to 6.01 +/- 0.07), providing a further independent check on the pH electrode technique. These data indicate that our intramyocardial pH measurements do reflect intracellular metabolism during elective arrest of the heart and may have potential for clinical use.

Animals

Continuous concealed ventricular arrhythmias.

Twenty dogs were studied 3 to 9 days after myocardial infarction. None had ventricular arrhythmias during sinus rhythm, and ventricular automaticity (as revealed by sinus nodal crush procedure or vagal stimulation, or both) was within the normal range. With regular atrial pacing or pacing with long-short cycle sequences it was possible to induce ventricular arrhythmias in all animals. Quadrigeminal and pentageminal rhythms (19 of 20 dogs) and trigeminal (17 of 20) and bigeminal ventricular rhythms (8 of 20) were observed. These rhythms which were manifest or partially or entirely concealed were always associated with delayed and fractionated electrical activity within the "infarcted" subepicardium. Continuous electrical activity (electrical activity that bridged the interval between two or more successive beats) was recorded from the infarct zone. Such activity either was manifest as ventricular arrhythmia during atrial pacing or remained concealed until atrial pacing was stopped and then was manifest as ventricular tachycardia.

Animals

Percutaneous preformed single catheter coronary arteriography and its complications--10,000 cases.

The single preformed catheter has offered an alternative to the conventional approaches to study of the coronary circulation and ventriculography. It has the advantages of being introduced percutaneouly without multiple changes for routine study or for provocative drug testing such as for spasm with Ergonovine maleate or muscular bridges with nitroglycerine. It requires no arteriotomy and has been associated with a low complication rate.

Angiography

A cross-bridge model for inotropism as revealed by stiffness measurements in cardiac muscle.

Stiffness measurements obtained by means of rapid length changes performed according to Huxley and Simmons (23) showed that the series elasticity of the living frog myocardium obeys Hooke's law and alters in proportion to isometric tension. The same results had previously been reported for glycerol-extracted heart muscle (15, 16). Under conditions of postive inotropism caused by application of noradrenaline, adrenaline or increased extracellular Ca++ concentration, the proportionality between tension and stiffness is maintained (13). As there is strong evidence that the series elasticity of heart muscle resides in the cross-bridges (17, 24) this means that systolic force development and positive inotropism are due to the same process, namely a recruitment of "activated" cross-bridges (an increase in the number of cross-bridges attached to actin at any moment). This rules out the two-component model proposed by Sonnenblick in which a non-linear series elastic element was postulated.

Actins