73 research outputs found
Models in orthotopic canine cardiac allotransplantation
Since human orthotopic allotransplantation of the heart became a reality
in 1968, clinical experience has consolidated the knowledge obtained experimentally
in the previous period. According to some investigators nothing
more than this has been achieved. In an early comment on clinical
heart transplantation, Dempster et a!. ( 43) declared "Nothing new was
proved by the incursion into human heart transplantation". The same authors
continued "None-the-less experimental work must continue in the
quite relentless way it has in the past"
Arterial switch for pulmonary venous obstruction complicating mustard procedure
Two patients underwent an arterial switch procedure for the relief of severe pulmonary venous obstruction complicating a Mustard procedure. Without preparatory pulmonary banding, both patients had adequate left ventricular function due to secondary pulmonary hypertension. At 8 and 4 years after the procedure, both patients are in New York Heart Association functional class I, with echocardiographic evidence of good left and right ventricular function
Different pharmacological responses of atrium and ventricle: Studies with human cardiac tissue
It has been recently reported that 5-hydroxytryptamine (5-HT) increases force of contraction in atrial tissue but not in ventricular tissue. In the present study with trabeculae obtained from non-diseased human hearts, we investigated whether this difference in the contractile response is specific for 5-HT or is also observed for other substances: calcitonin gene-related peptide (CGRP), angiotensin II, adenosine, somatostatin and acetyllcholine. CGRP (10β9 to 10β7 M) and angiotensin II (10β9 to 10β5 M) caused concentration-dependent increases in force of contraction in atrial trabeculae (up to36 Β± 8%and42 Β± 8% of the response to 10β5 M noradrenaline, respectively). Similar to 5-HT, no effects were observed with CGRP and angiotensin II in ventricular trabeculae. Adenosine (10β8 to 10β5 M) and somatostatin (10β8 to 10β6 M) caused concentration-dependent negative inotropic effects on baseline atrial contractility (β54 Β± 17%andβ51 Β± 25%, respectively, but no response was found on baseline ventricular contractility. Adenosine, but not somatostatin, reduced force of contraction after pre-stimulation with 10β5 M noradrenaline in atrial tissue and, to a lesser extent, in ventricular tissue. Acethlcholine exhibited a biphasic concentration-response curve in the atrial tissue, consisting of an initial negative inotropic response (10β9 to 10β7 M, from 120 Β± 41mg at baseline to48 Β± 16mg at 10 β7 M, fol lowed by a positive inotropic response (10β6 to 10β3 M, from 48 Β± 16 mg at 10β7 M to77 Β± 55mg). On the baseline ventricular for foce of contraction, acetylcholine (10β9 to 10β4 M) induced only a positive inotropic effect, starting at 10β9 M (from 252 Β± 65mg at baseline to353 Β± 71mg at 10β4M). After pre-stimulation with 10β5 M noradrenaline, acethylcholine reduced force of contraction in both tissue at 10β3 M(atrium: β14 Β± 4%,ventricle: β61 Β± 5%). The data indicate that, in atrial tissue, force of contraction can be affected by either postive or negative inotropic agents. However, in ventricular tissue only positive inotropic effects could be detected. Since atrial and ventricular tissues display different responses to the above biogenic substances, a different mechnism of regulation of contractility seems feasible
Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium
In the human isolated myocardium, acetylcholine (10β9 to 10β3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised contractility achieved by exposure to noradrenaline (10β5 M), only negative inotropic effects were observed in both atria and ventricles. Atropine (10β6 M), but not propranolol (10β6 M), antagonized both positive and negative inotropic effects of acetylcholine, thus showing that the responses were mediated by muscarinic acetylcholine receptors. The use of subtype selective muscarinic receptor antagonists (10β7 to 10β5 M), pirenzepine (M1 > M3 > M2), AF-DX 116 (11-({2-[(diethylamino)-methyl]-1-piperidyl}acetyl)-5,11-dihydro-6H-pyridol[2,3-b][1,4]benzodiazepine-6-one base; M2 > M1 > M and HHSiD (p-fluorohexahydro-siladifenidol hydrochloride; M3 β₯ M1 βͺ’ M2) revealed that the negative inotropic effect of acetylcholine in atrial as well as the positive inotropic effect in ventricular trabeculae were best antagonized by AF-DX 116 and not by pirenzepine, suggesting the involvement of the muscarinic M2 receptor subtype, possibly linked to different second messenger systems. On the other hand, the positive inotropic effect of acetylcholine (10β6 to 10β3 M) in the atrial tissue, observed only in preparation with depressed contractility, was not effectively antagonized by either AF-DX 116 or HHSiD, but was significantly reduced by pirenzepine. Furthermore, the selective muscarinic M1 receptor agonist McN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethyl ammonium chloride; 10β9 to 10β3 M), which failed to significantly change the baseline contractility in either atrial or ventricular trabeculae, produced a positive inotropic effect in atrial preparations when contractility had been depressed by prior treatment with acetylcholine (10β9 to 10β7 M). This effect of McN-A-343 was effectively antagonized by pirenzepine (10β5 M). These data show that, besides the muscarinic M2 receptor mediating both negative (atria) and positive (ventricle) inotropic effects, muscarinic M1 receptors, capable of reversing depressed atrial contractility, are present in the human heart
Cardiac status and health-related quality of life in the long term after surgical repair of tetralogy of Fallot in infancy and childhood
The long-term results of surgical repair of tetralogy of Fallot were assessed by means of extensive cardiologic examination of 77 nonselected patients 14.7 +/- 2.9 years after surgical repair of tetralogy of Fallot in infancy and childhood. Because of the frequent use of a transannular patch (56%) for the relief of right ventricular outflow tract obstruction, the prevalence of elevated right ventricular systolic pressure was low (8%), but the prevalence of substantial right ventricular dilation with severe pulmonary regurgitation was high (58%). The exercise capacity of patients with a substantially dilated right ventricle proved to be significantly decreased (83% +/- 19% of predicted) when compared with that of patients with a near normal sized right ventricle (96% +/- 13%). Eight out of 10 patients who had needed treatment for symptomatic arrhythmia had supraventricular arrhythmia, which makes supraventricular arrhythmia--in numbers--a more important sequela in the long-term survivors than ventricular arrhythmia. Older age at the time of the operation and longer duration of follow-up were not associated with an increase in prevalence or clinical significance of sequela
Human tissue valves in aortic position: determinants of reoperation and valve regurgitation
BACKGROUND: Human tissue valves for aortic valve replacement have a
limited durability that is influenced by interrelated determinants.
Hierarchical linear modeling was used to analyze the relation between
these determinants of durability and valve regurgitation measured by
serial echocardiography. METHODS AND RESULTS: In adult patients, 218
cryopreserved aortic allografts were implanted with the subcoronary (85)
or the root replacement technique (133), and 81 patients had root
replacement with a pulmonary autograft. Mean follow-up was 4.2 years (SD
2.7; range, 0 to 10.5). Patient age, operator experience with subcoronary
implantation, and allograft diameter were independent predictors for
reoperation. With repeated color Doppler echocardiography, the severity of
aortic regurgitation was assessed by the jet length method and the jet
diameter ratio. Multilevel hierarchical linear modeling was used to
estimate initial aortic regurgitation (intercept), its change over time
(slope), and the effect of 11 potential determinants of durability on
aortic regurgitation. With the jet length method, the intercept was 0.94
grade and the slope was 0.11 grade per year. With the jet diameter ratio,
the intercept was 0.34 and the annual increase was 0.01. Subcoronary
implanted valves had more initial aortic regurgitation, but progression of
aortic valve regurgitation did not differ from root replacement. At
midterm follow-up, recipient age <40 years was the only independent
predictor of aortic regurgitation. CONCLUSIONS: Subcoronary implantation
has a learning curve, resulting in more initial aortic regurgitation and
early reoperation compared with root replacement. In both techniques,
progression of aortic regurgitation over time is small but accelerated in
young adults
Collagen content and distribution in the normal and transplanted human heart: A postmortem quantitative light microscopic analysis
Endomyocardial biopsies in heart transplant patients offer the opportunity to study the myocardial interstitium in the context of myocardial function. For that purpose endomyocardial biopsies should reliably reflect the composition of the entire myocardium. We determined whether the collagen content in the subendocardial region of the right side of the interventricular septum (site of right ventricular endomyocardial biopsy), in 16 normal and 30 transplanted human hearts, is representative for the entire myocardium. Moreover we determined whether or not the mean collagen content of the myocardium is altered along with the posttransplantation survival time and which factors might contribute to the development of interstitial myocardial fibrosis. Transmural sections of the right and left ventricular free wall and interventricular septum were stained with Sirius red, which specifically stains collagen fibers. Collagen in the subendocardial region and central parts of the myocardium was quantified using a digital image analyzer. In normal hearts the mean collagen content of the subendocardial region of the right side of the interventricular septum (site of right ventricular endomyocardial biopsy) correlates well with the mean collagen content of the right ventricular wall and the center of the interventricular septum, but it does not reliably reflect the mean collagen content of the left ventricular free wall. In transplanted hearts the collagen content at the site of right ventricular endomyocardial biopsy correlates highly with the mean collagen content of the entire myocardium. In transplanted hearts the increase in collagen content is a result mainly of an increase in collagen of the left ventricular free wall. We conclude that in heart transplant patients, right ventricular endomyocardial biopsies have potential value in the analysis of the causes of left ventricular dysfunction. In transplanted human hearts, the posttransplantation survival time correlates positively with the collagen content, and this is attributable mainly to an increase in the collagen of the left ventricular free wall
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