[The viable myocardium: metabolic, diagnostic and therapeutic aspects]. / Il miocardio vitale: aspetti metabolici, diagnostici e terapeutici.

The term stunned myocardium is used to indicate a reversible post-ischemic dysfunction of the ventricular mechanism which may persist for hours, days or weeks after the restoration of coronary flow following spontaneous or pharmacological thrombolysis, transluminal coronary angioplasty, aorto-coronary bypass and ischemic attacks. Hibernating myocardium is used to describe a depression of ventricular contractility in the presence of chronic hypoperfusion which may be reversed following revascularization as a result of aorto-coronary by-pass surgery. Three biochemical and physiopathological hypotheses are currently acknowledged to explain the phenomenon of stunning: the hypothesis of free oxygen radicals, the hypothesis related to an energy deficit and that involving a calcium overload. It is possible that oxydizing stress induced by free radicals may modify the activity of one or more sarcolemmic proteins which regulate the flow of calcium or other ions. Alterations in the transport and accumulation of calcium ions due to a Na+/Ca++ pump deficit and calcium-ATPase of the sarcoplasmatic reticle appear to be responsible for contractile dysfunction. The hypothesis concerning an energy deficit appears to be least probable since even if ATP levels are low the intracellular energy status does not appear to be a factor which limits mechanical function which may be stimulated in the absence of further variations in the content of highly energetic phosphates. There is also reduced myofibrillar creatinkinase activity. In hibernating myocardium the mechanical dysfunction is due to a metabolic and therefore contractile "down-regulation' with low myocardial energy and oxygen consumption to ensure the survival of chronically hypoperfused areas.(ABSTRACT TRUNCATED AT 250 WORDS)

[A critical review of the stable changes in ventricular repolarization in ischemic cardiopathy. A correlation with the angiographic findings]. / Revisione critica delle alterazioni stabili della ripolarizzazione ventricolare nella cardiopatia ischemica. Correlazione con i reperti angiografici.

Unknown is the significance of the abnormalities of repolarization observed at rest in patients with coronary artery disease (CAD) demonstrated by coronary angiography, except for ischemic episodes, myocardial infarction, left ventricular hypertrophy, electrolyte changes or pharmacological interactions. The chronic T wave inversion and ST segment depression are usually considered as an alteration due to ischemia ("chronic myocardial ischemia"); this definition is, in our opinion, erroneous, because myocardial ischemia is an acute episode caused by a sudden lack of balance between demand and availability of myocardial oxygen, corresponding to transient electrocardiographic alterations. Thus, the definition of "chronic myocardial ischemia" referred to stable abnormalities of repolarization is incorrect, because a "chronic" lack of balance between MVO2 and O2 availability would produce necessarily irreversible myocardial damage (necrosis). To contribute to the comprehension of the stable ECG changes at rest, we have selected a group of patients with CAD demonstrated by coronary angiography, presenting stable T wave alterations and ST depression at rest. We have studied the main and regional left ventricular function through radionuclide angiocardiography (ACS). Comparing the abnormalities of repolarization (ECG) on the one hand with angio, EFR and VER on the other, we have obtained different positive correlations, according to the functional parameters considered (EFR and VER). In our study, the lowest positive correlation has been noticed comparing ECG versus angio, VER and EFR (37.5%), while the highest correlation was obtained when ECG was considered versus angio and VER (56.25%). Evaluating ECG versus angio and EFR we have obtained a positive correlation equal to 43.75%. So we have deduced that VER is the functional parameter that better relates to angio and ECG.(ABSTRACT TRUNCATED AT 250 WORDS)

Ergometric evaluation of the effects of enalapril maleate in normotensive patients with stable angina.

The anti-ischemic effect of a single oral dose of 10 mg of enalapril maleate (E) was investigated in 14 normotensive patients with coronary artery disease (CAD) and stable effort-induced angina pectoris. An exercise stress test was performed three times in each patient at the same clock hour on three successive days: with no treatment (baseline), 6 h after administration of placebo (P), and 6 h after oral administration of a single 10 mg dose of E. The multistage nonstop effort tests were performed in the sitting position. Workload started at 25 W and was increased by 25 W every 2 min until an ischemic ST depression of more than 1.5 mm was observed. The following parameters were measured: heart rate (HR), systolic blood pressure (BP), rate-pressure product (RPP), workload sustained (WS), elapsed time of effort (ET), and millimeters of ischemic ST depression. The values of the parameters observed with baseline, P, and E were compared at the moment of appearance of chest pain or ischemic ST depression, at the moment of maximal effort, maximal common WS (MCWS), and maximal common RPP (MCRPP). Enalapril delayed the appearance of the ischemic ST depression. At the MCWS, the RPP was significantly lower under E and the ST depression was less marked; this effect was the result of a lower BP level, in the absence of any significant change in HR response. The acute effects of E observed in normotensive patients with effort-induced angina pectoris seems to be related to the inhibition of angiotensin at the coronary level and to its antiadrenergic action.

Does placebo lower blood pressure in hypertensive patients? A noninvasive chronobiological study.

Placebo controlled trials have generally been used in order to evaluate the antihypertensive efficacy of drugs. There is some evidence, though, that blood pressure might not be influenced by placebo. Non-invasive devices for automatic blood pressure monitoring are likely to provide a better assessment of blood pressure response to drugs, as well as to different physiologic and pathologic conditions, than the traditional sphygmomanometric devices. The aim of this study was to investigate the effect of placebo on blood pressure recorded automatically and non-invasively. For this purpose, a chronobiologic approach to the collection, evaluation and interpretation of data seemed most appropriate. A group of 12 patients with a clinical diagnosis of essential hypertension underwent automatic blood pressure monitoring in hospital for 4 days. Measurements were taken every 15 min by an oscillometric instrument with an automatically inflated cuff. After a washout period during which the patients received no treatment, pressure recording was undertaken under basal conditions for 2 days. On the third and fourth days of study, the patients received 2 tablets of placebo, one at 10 a.m. and one at 10 p.m. In each patient a highly significant circadian rhythm was documented for systolic and diastolic pressure, both under basal conditions and during placebo administration. Blood pressure mesors were higher than reference standards and were not significantly affected by placebo. The circadian amplitudes and acrophases did not differ significantly before and during placebo. Our data indicate that automatically recorded blood pressure is not influenced by placebo.

Creatine and membrane sialic acid contents of erythrocytes in patients with heart valve prostheses.

The red cell damage induced by heart valve prostheses was investigated in 2 groups of patients with different heart valve replacements (mechanical or biological devices) by the determination of the creatine and membrane sialic acid contents in the erythrocytes. Red cell creatine did not increase, whereas sialic acid was lowered in both groups of patients, when compared with healthy controls. These findings were briefly discussed.

Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension.

Sixty patients were treated for 1 year for essential uncomplicated hypertension, 30 with beta-blockers alone (BB) and 30 with BB and chlorthalidone (CTD). BB did not affect serum K+ or Mg++. In the BB-group there was a statistically significant trend towards retention of Mg++ in a loading test, but the effect was clinically marginal. BB + CTD reduced serum K+ and Mg++ and caused significant Mg++ depletion, as shown by the Mg++ loading test. All the effects were highly significant and were clinically important. The metabolic perturbations due to CTD are potentially dangerous and make this drug unattractive as 'first choice' treatment for hypertension.

Slow-release nifedipine: effect on the circadian rhythm of blood pressure in essential hypertension.

The aim of this study was to investigate the effect of orally administered, slow-release, nifedipine tablets on the circadian rhythm of blood pressure and heart rate, in hospital patients with clinical diagnosis of hypertension validated by a chronobiologic inferential statistic method. A group of 14 patients (nine women and five men, 47 to 71 years old) with clinical diagnosis of "essential hypertension" underwent automatic blood pressure and heart rate monitoring in a hospital room for 48 hours. Measurements were taken every 15 min by an oscillometric instrument with automatically inflated cuff. The patients received no treatment during the two proceeding weeks and the first day of the study. On the second day, slow-release nifedipine tablets were administered, one at 10 a.m. and one at 10 p.m. A highly significant circadian rhythm was documented for systolic and diastolic blood pressure, mean arterial pressure and heart rate, both in basal conditions and after nifedipine. Blood pressure mesors were higher than reference standards in basal conditions, and were lowered (average decrease = 20 mmHg for systolic and 9 mmHg for diastolic mesor) by nifedipine. A significant, though minor, elevation of heart rate mesor (from 70 to 75 b.p.m.) was also noted during treatment. The circadian amplitudes of blood pressure and heart rate did not differ significantly before and during treatment. In conclusion, the circadian rhythm of blood pressure is still present with the same amplitude after slow-release nifedipine, but is set at a lower pressure level. Heart rate rhythm is also preserved, with only a minor elevation of its mesor.

Effects of captopril on the physical work capacity of normotensive patients with stable-effort angina pectoris.

Twelve normotensive patients with coronary artery disease and stable effort-induced angina pectoris were selected: the antiischemic effect of captopril was studied. A maximal cycloergometer effort test was obtained before (base) and after administration of placebo or captopril (50 mg p.o.). The following parameters were measured: heart rate (HR), blood pressure (BP), maximal rate/pressure product (MRPP), maximal workload sustained, (MWS), maximal working time (MWT), and S-T depression at MRPP. The base and placebo were similar. Compared to them captopril augmented the MWT, increased the MWS, reduced S-T depression at MRPP, and decreased the number of patients with effort-induced angina pectoris. The antiischemic effect of captopril seems related both to its effect on HR and BP, and to a local enhancement of coronary blood flow.

Reduced membrane sialic acid contents of the erythrocytes after heart valve replacement with prosthetic devices.

Mild traumatic hemolysis due to heart valve prosthesis was investigated in three groups of patients with different prosthesis device (tilting disc, ball valve) inserted in aortic area, or in mitral area. By routine laboratory tests, an increased but not remarkable erythrocyte destruction was evidenced. On the other hand, the content of membrane sialic acid of the erythrocytes was determined in patient and control groups in order to give evidence of membrane damage induced by the prosthetic device. The mean value of sialic acid in the patient groups was significantly lower than in controls. These findings may suggest that mechanical damage on the red blood cell (RBC) membrane could be associated with the decrease of the membrane sialic acid content. It is briefly discussed whether the observed low contents of RBC sialic acid may somehow explain the decreased RBC lifespan which is frequently reported in these patients.

Ergometric evaluation of the effects of captopril in hypertensive patients with stable angina.

The antihypertensive and anti-ischaemic effects of methyldopa and captopril were compared in 12 hypertensive patients with coronary artery disease. The antihypertensive effect of alpha-methyldopa (A) and captopril (C) were significant and similar. On the other hand, while methyldopa did not increase the product of systolic pressure and heart rate and did decrease the effort-induced S-T segment depression, C increased the double product (DP) and decreased the ischaemic S-T changes. Captopril might be useful in the treatment of hypertensive patients with coronary artery disease.

Incidence of complex ventricular arrhythmias in asymptomatic patients with recent myocardial infarction.

The incidence of ventricular extrasystoles (VES) was documented in 50 patients with recent uncomplicated myocardial infarction, with a 72-h two-channel ambulatory electrocardiogram. All patients were free of symptoms of arrhythmias; unstable angina pectoris and heart failure were absent. A total of 82% of the patients had VES: 23/50 patients had multiform or complex VES, 8/50 patients had ventricular tachycardia. VES were independent of heart rate and stable angina pectoris. Thus, frequent and complex VES are common in asymptomatic patients with uncomplicated recent myocardial infarction. Even in the absence of symptoms, ambulatory electrocardiography is useful. The prognostic significance of asymptomatic complex VES in these patients remains unsettled.

Noninvasive index of cardiac contractility during stress testing: a collaborative study.

The present study was conducted in parallel in three different institutions with a similar purpose but using different technical setups. Based on the experimental demonstration that the external phonocardiogram is similar to the rate of acceleration (d3P/d3t) of the left ventricular pressure, and that catecholamines in a similar way increase the early positive wave of the left ventricular pressure and the first heart sound (S1) of the external phonocardiogram; knowing that exercise causes secretion of catecholamines and sympathetic reflexes, we have studied the S1 changes as a result of exertion in 34 normal young subjects. Blood pressure, heart rate, electrocardiograph, and phonocardiograph recordings of each subject were taken. In 10 subjects, cardiac output was also recorded by impedance cardiography. The result of the study was that the first heart sound increased routinely 4-5 times the normal amplitude; in a few subjects the increase was up to 15 times greater. While the extent of increase of S1 was proportional to the severity and duration of the effort and was usually proportional to the increase of other parameters, exceptions were noted as having marked increase of S1 with moderate increase of either blood pressure or heart rate. This was explained by the different receptors activated by the catecholamines and by the complexity of hormonal and neural influences acting on various organs in a stress test. The amplitude of S1 was found to be a reasonably reliable index for following changes of cardiac contractility during exercise, and the suggestion was made that this parameter should be studied in parallel with the others in routine stress tests.