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.

Clinical and echocardiographic observations in pulmonary valve endocarditis.

Clinical and echocardiographic data from 12 patients with pulmonary valve endocarditis are described. Seven patients had isolated pulmonary endocarditis and in 5 patients other valves were infected (aortic, tricuspid, mitral or all 3). Two patients were heroin addicts and 4 had underlying heart disease (congenital heart disease in 3 and aortic regurgitation in 1 patient). The organisms involved were alpha streptococci in 3 patients (all with underlying heart disease), Staphylococcus aureus in 4, Streptococcus D bovis in 1 patient and Candida guillermondii in 1. M-mode and 2-dimensional echocardiography was performed in 10 patients and revealed vegetations in 8. Pulsed Doppler echocardiography was performed in 6 patients and revealed pulmonary regurgitation in all 6. Seven patients had pulmonary emboli. Four patients underwent surgery. Four patients died, including 1 after cardiac surgery. Five patients, including the patient infected with Candida guillermondii, recovered with antibiotic treatment.

Tandem coarctation of the thoracic aorta. An unusual congenital anomaly.

The coarctation involving the aortic isthmus, with hypoplasia of the upper aortic segment, was satisfactorily repaired in a 15-year-old girl. The technique used was subclavian flap arterioplasty followed by reimplantation of the distal subclavian artery into the left carotid artery. Suprisingly weak femoral pulses were noted postoperatively and prompted a control angiogram. This showed an intraluminal diaphragm 2 cm below the site of the previous repair, with a 100 mm Hg gradient. At reoperation, a centrally performed fibrous diaphragm was excised, and the aorta was enlarged with a small Dacron patch. The postoperative course was uneventful.

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.

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.

Early isonitrile SPECT in acute myocardial infarction: feasibility and results before and after fibrinolysis.

Early 99Tcm-labelled methoxy-isobutyl-isonitrile (MIBI) SPECT was performed in 14 patients with suspected acute myocardial infarction (AMI). The radiopharmaceutical was administered immediately upon admission to the intensive care unit and before any diagnostic confirmation. Then, if decided, thrombolytic therapy was started. Cardiac imaging was performed 1 h later, and as there is no significant re-distribution, the pictures still showed the pre-treatment MIBI uptake. In three cases acute myocardial infarction was not confirmed. For one of them, the result was normal and this patient was ultimately considered to have had a transient ischaemic event. The two other cases had acute chest pain with a previous history of myocardial infarction (MI) and a pathological MIBI SPECT. In the 11 cases with confirmed first AMI significant perfusion defect was seen. For every patient a new MIBI injection with a control SPECT was repeated 72 h after admission. Eight patients were seen 1 h 15 min to 3 h 15 min after the onset of chest pain and had thrombolytic therapy. Defects were always in agreement with coronary angiography and 2D echocardiography performed in the same period. After thrombolysis, control SPECT showed no recovery in three cases, partial recovery in four, and nearly complete recovery in one. Using this technique, it was then possible to get high quality myocardial perfusion imaging without delaying treatment of AMI. This preliminary series suggests that MIBI SPECT may be useful in accurately showing the size and location of the immediate perfusion defect, and in assessing the response to emergency therapy of AMI, especially thrombolysis.

[Pericarditis in recent myocardial infarct]. / Le pericarditi dell'infarto miocardico recente

Epistenocardial pericarditis, usually associated with anterior infarct, was noted in 64/400 myocardial infarct subjects admitted to an intensive care unit. No significant difference was observed with respect to this group in the case of mortality (20.6% as opposed to 26.2% in the controls) or complications of the acute stage, such as cardiac insufficiency and arrhythmia, though atrial fibrillation was more frequent (25% as against 15%). In all but one case, anticoagulant management was suspended on the appearance of pericarditis. In spite of the high frequency of atrial fibrillation, thromboembolic complications were not more frequent during brief (48-72 hr) suspension of anticoagulants. Dressler's syndrome was noted in 7 cases (1.7%), with epistenocardial pericarditis (4/7) or ventricular ectasia (3/7). Haemopericardium occurred in the case where anticoagulant management was not suspended.

[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.

[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.

[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.

[Second degre Wenckebach phenomenon. Electrocardiographic and clinical study apropos of 10 cases]. / Le phénomène de Wenckebach du 2e degré. Etude clinique et électrocardiographique à propos de 10 cas

Study of atrio-ventricular conduction across the atrio-ventricular node using rapid atrial stimulation revealed a particular kind of block in 10 patients; the characteristics of the Wenckebach phenomenon were associated with a 2/1 block. One P wave was blocked, and the PR interval of the conducting sequence became progressively longer until the cycle was broken by two consecutive blocked P waves. By recording the potentials in the bundle of His, it proved possible to localise the conduction defect to the A/V node in 9 cases. The defect appeared in various clinical forms: atrial tachysystole, incomplete atrio-ventricular block, both chronic and acute, and atrio-ventricular conduction that was apparently normal. Study of the transmission through the node of progressively increasing atrial stimuli showed that there was a strong tendency towards diminishing conductivity which appeared to favour dispersion of the incoming impulses centrally within the node.

[Identification of the sino-atrial potential in the dog by epicardial electrocardiography]. / Identification du potentiel sinusal chez le chien par électrocardiographie épicardique.

The electrical activity of the sino-atrial node has been recorded in the dog through a thoracotomy and using both unipolar and bipolar electrodes. Amiodarone was used to establish that the pre-artial potential which was registered was indeed originating in the sinus, as it allowed us to produce various degrees of sino-atrial block in a reliable and reproducable manner. The fact that the sinus potential can be recorded in the presence of intermittent abnormalities of the surface P wave suggests that the abnormalities may be associated with intra-sinus displacement of the pacemaker and not with ectopic depolarisation of the atrium.

[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.

[Recording of the electrical activity of the sino-atrial node area during an experimental sinoatrial block in dogs. Arguments in favor of its sino-atrial origin]. / Enregistrement de l'activité électrique de la région sinusale au cours d'un bloc sino-auriculaire expérimental chez le chien. Arguments en faveur de son origine sinusale

The electrical activity of the sino-atrial node appears to be difficult to detect, and has not until now been recorded from the heart in situ. Recording of the electrical activity from the area of the sino-atrial node area was carried out in the dog after thoracotomy, using a unipolar electrode placed in the epicardium at the cavo-atrial junction area; it enabled us to demonstrate a slow potential, of low amplitude, preceding the atrial deflection. The particular relationships between this slow potential and atrial activity under differing degrees of sino-atrial block have led us to believe that this potential does indeed originate in the sinoatrial node. In the light of this experimental observation, an explanation is put forward for the difficulty which is usually experienced in obtaining any recording of the sino-atrial node potential, and for the ease with which this potential could be recorded in this case, and indeed in future cases with similar pathological problems.

[Aortic insufficiency in certain so-called systemic diseases]. / Insuffisance aortique au cours de certaines maladies dites systémiques.

The authors present a retrospective study of all the patient followed up for systemic disease in the rheumatology Department of Bichat hospital between 1975 and 1984 in whom aortic regurgitation developed. Only rare or previously undescribed associations were retained: two MacDuffie syndromes, one adult form of Still's disease, one Takayashu's disease, one association of rheumatoid arthritis and Takayashu's disease, one rheumatoid arthritis, one Cogan's syndrome and two cases of disseminated lupus erythematosis. The authors use these cases and a review of the literature to discuss the possible physiopathological mechanisms of the aortic regurgitation. This study confirms the value of regular clinical cardiovascular examination with echocardiography in cases with progressive symptoms. The evolution of the vascular disease seems to be more or less parallel to that of the systemic disease and in a significant number of cases it becomes sufficiently severe to become the main clinical problem. In our series, there was one sudden death, one death due to cardiogenic pulmonary oedema and three patients required aortic valve replacement.

[Echocardiographical study of 2 cases of aortic dissection]. / Etude echocardiographicque de deux cas de dissection aortique

The authors report two cases of acute dissection of the ascending aorta and aortic arch. An urgent ultrasonic investigations showed, in both cases, signs of reduplication of the parietal image, which is highly suggestive of the condition; this was confirmed by angiography. These two cases enable us to discuss the criteria for this diagnosis, the limitations of the method, and its very real application in problems of differential diagnosis of acute chest pain.

[Studies of nodal conduction]. / Etudes sur la conduction nodale

Nodal conduction has been studied in 44 normal subjects, 21 cases of 1st or 2nd degree AV block, 16 cases of LGL syndrome, and 19 patients with a distal infra-His AV block, by means of stimulation which was increased in regular steps of 5 beats per minute, and of extra-systolic stimulation. These two techniques demonstrate that the nodal response to an extrasystole or a regular tachycardia is not the same, and that different mechanisms are probably at play. With regular stimulation, the normal limits of 1/1 conduction lie between 140 and 200 per minute. A nodal block for a rate less than 130 per minute can be taken as indicative of a nodal defect. Delayed AH conduction is a much less precise criterion. It may reach a high level in normal subjects, and it is not certain that the finding of a PR interval of more than 200 msec. (AH of more than 140 msec.) at a normal rate is neccessarily indicative of nodal pathology. Cases of LGL syndrome are associated with short-circuits which are usually partial. The diverse responses observed in these different groups can be explained by modifications of structure within the A/V node itself.

[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.

[Significance of exercise-induced arrhythmias]. / Signification des troubles de conduction apparaissant à l'effort.

Four personal cases of exercise-induced conduction defects occurring during stress testing are reported. The significance of these changes is discussed in the light of the authors' observations and of the cases published in the literature. The development of atrioventricular block is usually related to pre-existing disease of the conduction system, whilst left anterior or posterior hemiblock is usually due to transient ischaemia related to significant stenosis of the coronary artery responsible for the vascularisation of the relevant bundle branch (usually a proximal stenosis of the left anterior descending artery). Complete left bundle branch block may be due to a number of conditions (including chronic ischaemic heart disease).