Effects of sustained low-flow ischemia on myocardial function and calcium-regulating proteins in adult and senescent rat hearts.

OBJECTIVE: Both aging and myocardial ischemia are associated with alterations of calcium-regulating proteins. We investigated the effects of graded levels of low-flow ischemia on myocardial function and on SR Ca(2+)-ATPase (SERCA2), Na(+)-Ca2+ exchanger (NCX) and ryanodine receptor (RyR2), at mRNA and protein levels in both adult and senescent myocardium. METHODS: Isolated hearts from 4 and 24 month old (mo) rats were retrogradely perfused during 180 min at 100% (100% CF, n = 11 and n = 11 respectively. 30% (30% CF, n = 10 and n = 12) or 15% (15% CF, n = 13 and n = 8) of their initial coronary flow, and active tension and coronary resistance (in % of their baseline value) were recorded. After 180 min of perfusion. NCX, RyR2 and SERCA2 mRNAs (in % of age-matched 100% CF group value) and protein levels were quantitated in the left ventricles by slot blot and Western blot analysis, respectively. RESULTS: In 24 mo hearts, low-flow ischemia induced a greater fall in active tension (-65 +/- 7% vs. -40 +/- 4% in 4 mo 30% CF, p, 0.01 and -82 +/- 2% vs. -60 +/- 5% in 4 mo 15% CF groups, p < 0.05 after 15 min of ischemia) and a greater increase in coronary resistance (+357 +/- 44% vs. +196 +/- 39% in 4 mo 30% CF, p < 0.05 and +807 +/- 158% vs. +292 +/- 61% in 4 mo 15% CF groups, p < 0.001 after 15 min of ischemia). An increased accumulation of SERCA2 (+36% and NCX (+46%) transcripts, but not RyR2, already occurred in 24 mo 30% CF group while the 3 transcripts accumulated in 24 mo 15% CF group. In 4 mo rats SERCA2 (+26%), NCX (+35%) and RyR2 (+81%) mRNA levels only increased in the 15% CF group. Corresponding calcium-regulating protein levels were unaltered whatever the degree of flow reduction in both 4 mo and 24 mo hearts. CONCLUSION: Low-flow ischemia does not induce calcium-regulating protein loss in both adult and senescent hearts. The increase in mRNAs coding for calcium-handling proteins and the impairment of myocardial function which occur at a lesser degree of coronary flow reduction in senescent hearts, indicate a higher vulnerability to low-flow ischemia during aging.

Senescent heart compared with pressure overload-induced hypertrophy.

Although systolic left ventricular (LV) function is normal in the elderly, aging is associated in rat papillary muscle with mechanical and sarcoplasmic reticulum Ca2+ ATPase alterations similar to those observed in the hypertrophied heart. However, alterations in the other calcium-regulating proteins implicated in contraction and relaxation are still unknown. To investigate alterations in LV function and calcium-regulating proteins, we measured hemodynamics and Na(+)-Ca2+ exchanger (NCx), ryanodine receptor (RyR2), and sarcoplasmic reticular Ca2+ ATPase (SERCA2) mRNA levels (expressed in densitometric scores normalized to that of poly(A+) mRNA) in left ventricle from 4-month-old (adult, n = 13) and 24-month-old (senescent, n = 15) rats. For ex vivo contractile function, active tension was measured during isolated heart perfusion in adult (n = 11) and senescent (n = 11) rats. For comparison of age-dependent effects of moderate hypertension on both hemodynamics and calcium proteins, renovascular hypertension was induced or a sham operation performed at 2 (n = 11 and n = 6) and 22 (n = 26 and n = 5) months of age. In senescent rats, LV systolic pressure and maximal rates of pressure development were unaltered, although active tension was depressed (4.7 +/- 0.4 versus 8.3 +/- 0.7 g/g heart weight in adults, P < .0001). SERCA2 mRNA levels were decreased in senescent left ventricle (0.98 +/- 0.05 versus 1.18 +/- 0.05 in adults, P < .01), without changes in NCx and RyR2 mRNA accumulation. Renovascular hypertension resulted in 100% mortality in aged rats; in adults, renovascular hypertension resulted, 2 months later, in an increase of LV systolic pressure (170 +/- 7 versus 145 +/- 3 mm Hg in sham-operated rats, P < .05) and in mild LV hypertrophy (+18%, P < .01) associated with a decrease in SERCA2 mRNA levels (1.02 +/- 0.03 versus 1.18 +/- 0.03 in sham-operated rats, P < .001). Contractile dysfunction in senescent isolated heart and decreased SERCA2 mRNA levels were associated with in vivo normal LV function at rest, indicating the existence of in vivo compensatory mechanisms. RyR2 and NCx gene expressions were not implicated in the observed contractile dysfunction. In aged rats, renovascular hypertension resulted in 100% mortality, probably related to elevated levels of circulating angiotensin II, whereas in adult rats, renovascular hypertension induced a mild LV hypertrophy associated with a selective alteration in SERCA2 gene expression.

Screening of renal artery stenosis: assessment with magnetic resonance angiography at 1.0 T.

The results of MR angiography at 1.0 T with digital intraarterial angiography in the screening of patients with suspected renal hypertension were compared. In this first phase of the study, 10 volunteers underwent examination with both two-dimensional (2D) with traveling saturation time-of-flight (TOF) magnetic resonance angiography (MRA) with various parameters to develop a protocol for evaluation of the renal arteries. In the second phase, 36 patients with suspected renovascular hypertension underwent both 2D TOF MRA and intraarterial digital angiography to evaluate the clinical value of MRA. The degree of stenosis was graded with a two-point scale. In volunteers, using 2D acquisitions C/N ratios indicated the best flip angle as being 55 degrees (p = .02). MRA showed 100% (70/70) of all main arteries and 86% (6/7) of all accessory renal arteries seen on angiography. MRA had a sensitivity of 94% (15/16) and a specificity of 98% (60/61) for detection of stenoses of greater than 50% present in 14 patients. 2D-TOF MRA at 1.0 T shows promise in the noninvasive diagnosis of patients with suspected renovascular hypertension.

[Unstable angina. Physiopathology, clinical course and therapeutic principles]. / Angor instable. Physiopathologie, clinique et principes du traitement.

The pathogenic mechanism of unstable angina, a clinical expression of coronary heart disease, is similar to that of myocardial infarction. The main event is the instability of the atheromatous plaque adhering to the coronary intima leading to thrombosis and occlusion. Clinical manifestations can be severe since fatal or non-fatal myocardial infarction occurs in 3.9% and 5.4% of the case respectively. Adapted medical treatment can stabilize the situation in most patients, justifying early preventive treatment. Moreover, it has been estimated that a premonitory phase of angina had gone unnoticed or undiagnosed in one-half of all myocardial infarcts. In nearly all patients with unstable angina, coronarography is of major importance for rapidly defining an adapted therapeutic strategy. Myocardial revascularization (especially by angioplasty) is often needed to limit the risk of major cardiac events occurring within a short or moderate delay. Unfortunately, these procedures carry a supplementary risk of thrombosis. Thus the emphasis placed on measures capable of improving the anti-thrombotic risk in unstable angina by using new antiplatelet agents, or for certain patients at high risk of a major cardiac event, antithrombosis agents. Finally, the search for compounds capable of stabilizing the previously formed atheromatous plaque (and thus avoiding rupture) is a prime objective for an overall management strategy for patients with coronary heart disease.

[Stress ultrasonography with dobutamine in the diagnosis of coronary disease]. / L'échographie de stress sous dobutamine dans le diagnostic de la maladie coronaire.

Digital stress echocardiography (DSE) with dobutamine infusion has recently emerged as an attractive alternative to exercise stress testing for evaluating coronary artery disease. DSE seems particularly useful in the diagnosis or the assessment of ischemia in patients unable to exercise or when the test is difficult to interpret. DSE has also proved to be useful in patients undergoing preoperative evaluation of cardiac risk. The assessment of residual myocardial viability in patients with previous myocardial infarction is another promising development. After a description of the methodology of dobutamine stress echocardiography, this article reviews the experience obtained to date with this technique in the diagnosis and the evaluation of coronary artery disease.

[Hemiblocks: electrocardiographic diagnosis]. / Les hémiblocs; diagnostic électrocardiographique.

Left hemiblocks or fascicular blocks are conduction defects which lead to asynchronous left ventricular activation. The classical diagnostic criteria must be respected, especially the degree of left axial deviation in complete forms. Other, less well-known criteria, which include the widening of the QRS complex opposite the myocardial walls showing delayed activation, seem very useful for making the diagnosis. The real diagnostic difficulties lie in incomplete forms because the inferior limits of axial deviation in this type of conduction defect are not known and clinical progression is usually the decisive factor. Precise understanding of the clinical signs of hemiblock is useful in clinical practice for the discussion of the significance of Q waves in the right precordial leads or for explaining sudden changes in QRS axis or amplitude.

Pulmonary time-of-flight MR angiography at 1.0 T: comparison between 2D and 3D tone acquisitions.

The purpose of this study was to compare the performance of 2D vs. 3D time-of-flight (TOF) methods in imaging the normal pulmonary arteries with commercially available 1.0 T equipment. The study was conducted in 20 volunteers and 7 patients with suspected pulmonary embolism (PE). To reduce artifacts caused by cardiac and respiratory motion, MR images were acquired in volunteers using two-dimensional (2D), gradient-recalled echo (GRE), breath-hold techniques, and three-dimensional (3D) acquisitions. Sagittal thin (6-MM) segmented k-space 2D sections obtained with cardiac gating during systole (turboFLASH, TR/TE9/6 ms, 14 segments of 9 lines) and incremented flip-angles (TONE), and 50-mm 3D volume TONE acquisitions with 32 partitions (FISP, TR/TE34/10ms) were successively performed. In the second phase of the study, patients were examined only with the 3D technique. Images of volunteers were qualitatively and quantitatively analyzed. S/N ratios were statistically compared by means of the paired-sample Wilcoxon ranked-signed test, a value of p < .05 being significant. In volunteers, 3D acquisitions displayed significantly more segment-order pulmonary arteries on average than did 2d acquisitions displayed significantly more segment-order pulmonary arteries on average than did 2D acquisitions (2.95 +/- 0.64 vs. 2.2 +/- 0.85, respectively; p < .01). Moreover, the signal intensity of arteries within the lungs was less homogeneous in the 2D than in the 3D technique, with a signal intensity ratio between peripheral and proximal arteries of 63% +/- 7% and 73% +/- 2%, respectively (p < .05). In patients, no erroneous diagnoses were obtained using the 3D technique. 3D images of normal lungs provide MR angiograms of better quality than do 2D images, and require less contribution from subjects because they are performed in free breathing. Ongoing improvements in MR sequences and further studies are now necessary to assess the value of 3D TONE MRA in the diagnosis of PE.

[Treatment of chronic ventricular extrasystole by propafenone (600 mg/d) in 2 or 3 daily doses]. / Traitement des extrasystoles ventriculaires chroniques par la propafénone (600 mg/j), en deux ou trois prises journalières.

The efficacy of propafenone by oral route in the treatment of chronic ventricular extrasystoles (VES) was investigated in 14 subjects in the context of a multicenter evaluation carried out double blind and using a crossover sequence. The purpose of this study was to compare the antiarrhythmic efficacy of a dose of 600 mg/d of propafenone randomly divided into two or three subdoses. After carrying out two Holter recordings (< 15 days) the patients presenting with chronic (< or = 100 VES/H) and stable (interindividual variability > or = 30%) ventricular extrasystoles were included. The treatment period consisted of two 8-day courses divided by a placebo period and carried out following a crossover mode. The efficacy of treatment was defined as a reduction in the VES by at least 70% relative to the second Holter during the inclusion period which was used as the reference period. Fourteen patients (57.2 +/- 18.2 years) from eight cardiological centers (eight with heart disease) were included. In general, propafenone at a dose of 600 mg/d bid or tid significantly reduced the total number of VES by about 65%: 15,239 +/- 2,663 VES/24 h (baseline) to 5,238 +/- 2,746 VES/24 h (bid) and 5,765 +/- 2683 VES/24 h (tid); p < 0.0001, with no significant difference between the bid and tid treatments. Individually, 8 patients (57%) responded during the bid treatment, 7 patients (50%) during the tid treatment and 6 patients during both treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cardiac metastasis disclosed by ventricular tachycardia. Diagnosis by echocardiography and ultrafast tomodensitometry]. / Métastase cardiaque révélée par une tachycardie ventriculaire. Diagnostic par échocardiographie et tomodensitométrie ultrarapide.

The authors report the case of a right ventricular metastasis presenting with ventricular tachycardia and underline the usual diagnostic problems of secondary cardiac tumours, the symptoms of which are often unspecific and late. The appearance of a cardiac arrhythmia in the absence of known cardiac disease should raise the possibility of a cardiac metastasis in patients with malignant disease. The reported case also illustrates the diagnostic value of non-invasive cardiac imaging techniques (echocardiography and ultra-fast computerised tomography) in this context.

[Arteriovenous fistula following surgery of intervertebral disk]. / Fistule artério-veineuse dans les suites de la chirurgie du disque intervertébral.

Vascular damage during intervertebral disc surgery is uncommon. It sometimes leads to the formation of an arteriovenous fistula and about one hundred cases have been reported in the literature. The diagnosis is often early, with signs of venous hypertension predominating. The authors report a case of arteriovenous fistula presenting late as apparently primary congestive cardiac failure. The mechanisms of this condition were demonstrated during preoperative instrumental manoeuvres. Surgical correction is the only treatment alternative. Repair must be arterial and venous, most often using prosthetic material. This generally enables total and permanent recovery, but overall mortality in pathology of this type is not nil.

[Elements of choice of thrombolytic agents in myocardial infarction]. / Eléments du choix d'un agent thrombolytique dans l'infarctus du myocarde.

Five thrombolytic agents have been used in the acute phase of myocardial infarction: streptokinase, recombinant tissue plasminogen activator (rt-PA) and its acyl enzyme (APSAC), urokinase and pro-urokinase. Experience with the latter two agents is much more limited. The antigenicity, biological half-life, fibrino-specificity and cost are important parameters to be taken into account when choosing a therapeutic agent. The doses expressed in different units or in milligrams vary with the product used. Large scale clinical trials have not shown improved efficacy of new thrombolytic agents. The role of associated treatments, aspirin and/or heparin and their respective doses, the timing of their administration are also important elements in the evaluation of efficacy judged by the frequency of coronary recanalisation and early reocclusion. The haemorrhagic risk is difficult to assess and seems more related to heparin therapy than the prescription of aspirin. Mutants of rt-PA obtained by genetic engineering and other new thrombolytics are currently under evaluation to try and obtain new, more effective and safer thrombolytic agents.

[Contribution of sequential voluntary ambulatory monitoring in the diagnosis of arrhythmia. A multicenter study of 1287 symptomatic patients]. / Apport de l'enregistrement ambulatoire séquentiel volontaire à la détection des arythmies. Etude multicentrique sur 1,287 patients symptomatiques.

Voluntary sequential ambulatory recording is a diagnostic method of recording per-critical electrocardiographs in symptomatic patients with the aid of a portable solid-state technology recorder. In order to assess the value of this technique in the detection of arrhythmias, a multicenter study was performed in 1,287 symptomatic patients suspected of having paroxysmal arrhythmias (palpitations in 86.5% of cases). The quality of the sequential ambulatory recording was judged to be good in 54.9% and mediocre in 40.2% of cases: only 4.9% of recordings were uninterpretable. This technique allowed identification of a cardiac arrhythmia related to symptoms in 42.5% of the 1,091 cases which were analysed; sustained supraventricular tachycardia (11.7%), ventricular extrasystoles (14.9%) and simple sinus tachycardia (9.5%) were the principal abnormalities. The per-critical recording was negative in 57.5% of patients, suggesting a purely functional origin of symptoms in these cases. Atrial fibrillation was more common in hypertensive patients (11.3% vs 5.5% in normotensives, p less than 0.01) as were ventricular extrasystoles (23.1% vs 13% in normotensives, p less than 0.001). Voluntary sequential ambulatory recording seems to be a technique well adapted to the detection of symptomatic arrhythmias and a useful complement to Holter recording.

[Pericardial manifestations of toxoplasmosis]. / Manifestations péricardiques de la toxoplasmose.

A case of pericarditis due to toxoplasmosis in a 20 year old non-immune depressed man with a favourable outcome with specific antiparasitic treatment is reported. Pericarditis is rare in toxoplasmosis and does not require an associated immune deficiency. The clinical presentation is that of acute benign pericarditis, the diagnosis depending on positive toxoplasmosis serology (positive IgM or increasing IgG antibody titres) and the absence of another obvious cause. Isolation of the parasite by direct examination or animal inoculation is very rare. The spontaneous evolution is to pericardial constriction whilst specific antibiotic therapy (sulfadiazine-pyrimethamine) leads to a rapid cure in most cases. This underlines the necessity of searching for toxoplasmosis in patients with unexplained pericarditis.

[Sudden syncope and myocardial ischemia. Apropos of a case]. / Syncope à l'emporte-pièce et ischémie myocardique. A propos d'une observation.

It is unusual to carry out a systematic search for myocardial ischemia in patients who have suffered a sudden syncopy with no known history of angina. We report a case involving loss of consciousness (LC) in the context of sub-hissian atrioventricular block (AVB) which required the installation of a pacemaker, with the detection of angina pectoris immediately after its installation. Coronary artery angiography confirmed a diagnosis of severe, multitrunk coronary disease characterized by a tight stenosis of the common trunk. If consciousness is lost by a patient suffering from baseline conduction impairment with no chest pain, the first thought is 3rd degree degenerative paroxysmal AVB but the possibility of an ischemic origin of this AVB should not be overlooked.

[Significance of hemiblock of the left branch during exercise]. / Signification des hémiblocs de branche gauche survenant à l'effort.

There have been few reports of exercise induced left branch hemiblock. In order to assess its frequency and significance, a retrospective study of 8684 patients was undertaken: 24 cases (11 anterior and 13 posterior) were recensed. Nineteen of these patients had typical effort angina, 3 had a history of myocardial infarction and 3 had aortiocoronary bypass surgery. Twenty patients developed ST-T wave abnormalities included 11 ST segment depressions. Four patients refused coronary angiography: 3 of these patients had probable coronary artery disease (typical effort angina, positive exercise stress tests and in 1 case, inferior wall hypofixation during myocardial scintigraphy). Twenty patients underwent coronary angiography. In 2 patients, the exercise stress test was performed under Class IC antiarrhythmic therapy; 1 had a normal coronary angiogram and the other had patient coronary bypass graft. A control exercise stress test after withdrawal of drug therapy was negative in these 2 cases. The other 18 patients had significant coronary artery disease. The recording of left branch hemiblock during exercise stress testing would seem to indicate severe coronary artery narrowing (greater than or equal to 90% in 15 cases; greater than or equal to 80% in 3 cases) and left anterior hemiblock is indicative of left main coronary or proximal left anterior descending artery disease. In this series, medical therapy did not make exercise-induced left branch hemiblock regress, in contrast to aortocoronary bypass surgery and angioplasty.

[Ventricular arrhythmia following thioridazine poisoning]. / Troubles du rythme ventriculaires secondaires à une intoxication par thioridazine.

The authors report a case of acute thioridazine (Melleril) poisoning with manifestations of polymorphous ventricular rhythm disturbances in the form of torsades de pointes, with an impaired conscious level. The opportunity is taken to review the electrocardiographic changes and cardiac complications linked to the quinidine-like effect of Melleril.

[Unstable angina: from physiopathology to therapeutics]. / Angor instable: de la physiopathologie à la thérapeutique.

Unstable angina is a term which encompasses several clinical syndromes (crescendo angina, angina de novo, resting angina, postinfarction angina), intermediary between stable angina and myocardial infarction. The results of coronary angioscopy have allowed differentiation of accelerated effort angina which seems related to ulceration of an atheromatous plaque from resting angina, more commonly associated with intraluminal thrombosis. The diagnosis of unstable angina is clinical and justifies immediate hospital admission to a coronary care unit because of the risk of myocardial infarction and/or sudden death. Medical management comprises triple anti-ischemic therapy (nitrate derivatives, betablockers, calcium antagonists), anticoagulants and platelet antiagregants. Randomised therapeutic trials versus placebo have shown that this treatment decreases the incidence of refractory angina and myocardial infarction. Several studies are under way to assess the role of thrombolytic therapy in unstable angina. When unstable angina is refractory to maximal medical therapy, emergency coronary angiography should be performed. However the outcome is usually favourable and coronary angiography can be performed several days after the acute event. The coronary lesion responsible for unstable angina is often "complex", an eccentric, irregular, severe stenosis or appearances of thrombosis. Whenever possible, depending on the coronary lesion, myocardial revascularisation by coronary angioplasty or aorto-coronary bypass should be proposed. Surgical treatment has been shown to be more effective (symptomatic relief, improved survival) than medical therapy in patients with triple vessel disease. However, the results of studies comparing medical or surgical treatment with coronary angioplasty are not yet available.

[Detection of coronary disease before valve surgery. Contribution of myocardial scintigraphy with dipyridamole]. / Détection d'une maladie coronarienne avant chirurgie valvulaire. Apport de la scintigraphie myocardique sous dipyridamole.

The detection of coronary disease before valve surgery remains difficult in the absence of coronary arteriography. The contribution of myocardial scintigraphy with dipyridamole (MS-DP) was studied in 34 consecutive patients with valve disease (11 mitral and 23 aortic) with a mean age of 63 +/- 11 years having undergone coronary arteriography before valve surgery. Coronary arteriography was performed because of angina (21 cases) or age (women greater than 50, men greater than 40). Positive criteria of coronary disease were the presence of at least one frank and clearly visible fault of myocardial perfusion (MS-DP positive) and at least one stenosis of greater than 70 per cent by coronary arteriography. Coronary disease existed in 13 patients (38 per cent). Ten patients (29 per cent) had a positive MS-DP. The sensitivity and specificity of MS-DP in detecting coronary disease were 69 per cent and 95 per cent respectively. Its positive predictive value was 90 per cent. MS-DP was negative in all asymptomatic patients (19 per cent of them having coronary disease) and in 11 symptomatic patients (18 per cent of them having coronary disease). The low positive predictive value of angina (52 per cent) increased to 90 per cent when combined with a positive MS-DP. Because of relatively low sensitivity, basing indications for coronary arteriography before valve surgery on the results of MS-DP cannot be advised.

Coronary to bronchial artery anastomosis with bronchial steal syndrome demonstrated by thallium-201 myocardial tomoscintigraphy.

A case study is presented in which the bronchial steal syndrome is demonstrated by stress thallium-201 myocardial perfusion imaging. The various aspects of the syndrome are discussed. We conclude that bronchial steal syndrome may provoke severe myocardial ischaemia even in the absence of coronary artery stenosis.