[Time course of the myocardial infarction in the rabbit]. / Cronodinamia del infarto de miocardio en el conejo.

The histopathologic evolution of myocardial infarct and of areas distant from infarct in rabbit hearts was studied. The left coronary artery of 55 rabbits was ligated, and rabbits were sacrificed at 2, 4, 6, 8, 12, 14, 16, 18, 26, 35 and 56 days post-ligature (n = 5 per group). Two rabbits were used as control and two were sham operated. The hearts were excised, cut in slices and stained with hematoxilin-eosin, Masson's trichrome and picrosirius red. Histological evaluation was semi-quantitative (scale: 0 to +++). At day 2, presence of neutrophils was +++, disappearing completely at day 6. Fibroblast proliferation increased from day 4 to day 14 post-occlusion. Coagulation necrosis in medial myocardium during the first week was +++. Subendocardic myocytolysis was evident from day 2 up to day 56 post-infarction. During the second week, proliferation of lymphocytes and macrophages (+++), granulation tissue formation (+++), and incipient traces of fibrosis that peaked at day 35 were observed. Cicatrization was complete at day 56 (+++). In areas far from infarction (right ventricle and septum), proliferation of fibroblasts was observed at day 2, and perivascular, interstitial and endocardic fibrosis at day 16. In conclusion, myocardial infarction in rabbits, unlike myocardial infarction in human beings, is characterized by early presence of fibroblasts and subendocardic fibrosis, and quick increase and precocious disappearance of neutrophils. An interesting finding was the early proliferation of fibroblasts in normal areas far from infarct.

Cronodinamia del infarto de miocardio en el conejo. / [Time course of the myocardial infarction in the rabbit]

The histopathologic evolution of myocardial infarct and of areas distant from infarct in rabbit hearts was studied. The left coronary artery of 55 rabbits was ligated, and rabbits were sacrificed at 2, 4, 6, 8, 12, 14, 16, 18, 26, 35 and 56 days post-ligature (n = 5 per group). Two rabbits were used as control and two were sham operated. The hearts were excised, cut in slices and stained with hematoxilin-eosin, Massons trichrome and picrosirius red. Histological evaluation was semi-quantitative (scale: 0 to +++). At day 2, presence of neutrophils was +++, disappearing completely at day 6. Fibroblast proliferation increased from day 4 to day 14 post-occlusion. Coagulation necrosis in medial myocardium during the first week was +++. Subendocardic myocytolysis was evident from day 2 up to day 56 post-infarction. During the second week, proliferation of lymphocytes and macrophages (+++), granulation tissue formation (+++), and incipient traces of fibrosis that peaked at day 35 were observed. Cicatrization was complete at day 56 (+++). In areas far from infarction (right ventricle and septum), proliferation of fibroblasts was observed at day 2, and perivascular, interstitial and endocardic fibrosis at day 16. In conclusion, myocardial infarction in rabbits, unlike myocardial infarction in human beings, is characterized by early presence of fibroblasts and subendocardic fibrosis, and quick increase and precocious disappearance of neutrophils. An interesting finding was the early proliferation of fibroblasts in normal areas far from infarct.

Exercise training and heparin pretreatment in patients with coronary artery disease.

The purpose of this study was to evaluate whether combined treatment with a cardiovascular exercise rehabilitation program and low doses of heparin can induce changes in ergometric parameters of ischemia in patients with coronary artery disease (CAD). Heparin may potentiate the development of new vessels promoted by ischemia and therefore may produce important clinical improvement. Thirty-six patients with stable CAD and evidence of myocardial ischemia on exercise testing were randomized into three groups: a control group (n = 11) received the usual medical treatment; another group (n = 11) underwent three exercise sessions per week during 12 weeks; and a third group (n = 14) undertook this exercise program and also received calcium heparin 12,500 IU subcutaneously 20 to 30 minutes before each exercise session. Pretreatment and posttreatment exercise tests were compared. Patients who underwent the rehabilitation program had an increase in exercise duration and workload at the onset of 1 mm ST-segment depression, but only patients who received calcium heparin showed a significant increase in rate-pressure product at the ST-segment ischemic threshold (p = 0.035). This result suggests that higher levels of myocardial oxygen consumption were now tolerated, a change that may be related to an improvement in myocardial perfusion.

Prognostic value of clinical variables for recurrent ischemic events after acute myocardial infarction.

Recurrent ischemia after acute myocardial infarction (AMI) has been largely associated with a poor prognosis. This study was carried out to analyze the relationship among different clinical variables and both postinfarction angina and reinfarction after AMI. A total of 452 consecutive patients (mean age 58.2 +/- 12 years) were admitted to the coronary care unit and were studied prospectively. More than half of the patients received some type of thrombolytic therapy. Death occurred in 45 patients (9.9%) during hospital stay. Postinfarction angina was diagnosed in 81 patients (17.9%) and reinfarction in 22 (4.9%). Patients who developed reinfarction had a high mortality rate (45.5%) compared with those who did not develop such an event (8.1%) (p < 0.0001; odds ratio: 9.4; 95% confidence interval 3.5-25.4). On the other hand, postinfarction angina had no significant association with mortality. Multivariate analysis revealed that a history of angina (> 1 week) was predictive of the occurrence of postinfarction angina and that the use of fibrinolytic treatment, prodromal symptoms, and postinfarction angina were significantly related to reinfarction. We conclude that several simple clinical variables are clear independent predictors of postinfarction angina and reinfarction following AMI and should be taken into account in routine clinical practice or when planning intervention trials.

The clinical presentation of acute myocardial infarction predicts the severity of the lesion in the infarct-related artery.

The purpose of this study was to correlate the clinical presentation of acute myocardial infarction with the patency rate and degree of residual stenosis of the infarct-related artery. One hundred and forty-five patients who underwent angiography after acute myocardial infarction were divided into two groups according to the time of onset of anginal pain prior to infarction. Group A comprised 119 patients, (109 men, 10 women, aged 53 +/- 9 years) who did not experience any symptoms before infarction or with anginal pain of less than 5 days preceding myocardial infarction, and group B 26 patients (all men, aged 54 +/- 12 years) with previous stable angina for greater than or equal to 1 year. Twenty-two days after acute myocardial infarction, 68 of the 145 patients (47%) had a patent infarct-related artery: 64 patients in group A (54%) and four patients in group B (15.4%) (P less than 0.006). Furthermore, 19 patients in group A (16%) and none in group B had less than 70% stenosis in the infarct-related artery (P less than 0.02). The mean residual stenosis in group A was 83.3 +/- 27% whereas in group B it was 98.1 +/- 4% (P less than 0.001). These results indicate that a long-standing history of angina before acute myocardial infarction is often related to a severe pre-existing atheromatous obstruction, which would account for the higher incidence of total coronary occlusion observed in group B. Thus angina of recent onset preceding acute myocardial infarction is associated with a higher patency rate of the infarct-related artery and frequent less than 70% residual lesions.

[Treatment of paroxysmal supraventricular tachycardia with a single oral doses of diltiazem and propranolol]. / Tratamiento de la taquicardia paroxística supraventricular con doses única oral de diltiazem y propranolol.

Chronic antiarrhythmic therapy for the prevention of episodes of paroxysmal supraventricular tachycardia is limited by its elevated cost, the development of side effects and lack of patients' collaboration. In this study the efficacy and safety of a single oral dose of diltiazem (180 mg) and propranolol (80 mg) were assessed. Eighteen episodes of supraventricular tachycardia were treated in 17 patients, 9 female and 8 male, aged between 19 and 60 years old (mean 45.3 +/- 11.4). The episodes had begun 3 months to 40 years before. They were divided in 3 groups: group I (placebo), 6 episodes; group II (diltiazem-propranolol), 12 episodes; and group III (patients from the placebo group without spontaneous recovery of sinus rhythm who were given active drug), 6 episodes. There were no spontaneous conversions in group I (placebo) within 80 minutes. In group II, ten out of 12 episodes responded to the combination after 38.8 +/- 20.8 minutes (seven episodes were converted to sinus rhythm within the first 45 minutes). In group III (non-responders to placebo who were subsequently given active drugs), four out of 6 episodes were suppressed after 50.7 +/- 16.7 minutes. The cycle of the tachycardia lengthened before conversion to sinus rhythm both in groups II and III. Neither systolic nor diastolic blood pressure changed significantly in any group. Seven out of 14 patients who successfully converted to sinus rhythm in groups II and III, suffered mild to moderate sweat between 3 and 5 minutes before the end of the episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Tratamiento de la taquicardia paroxistica supra ventricular con dosis unica oral de diltiazem y propranolol / Treatment of paroxysmal supraventricular tachycardia with a single oral dosis of diltiazem and propranolol

El tratamiento crónico para prevenir la recurrencia de episodios de taquicardia supraventricular presenta el incoveniente del elevado costo, aparición de efectos adversos y escasa adherencia de los pacientes. En el presente estudio se evaluó la seguridad y eficacia de la combinación de ditiazem (180 mg) y propranolol (80 mg) en dosis única oral. Fueron incluidos 18 episodios de taquicardia supraventricular en 17 pacientes. La población fue dividida en 3 grupos I (placebo), 6 episodios; grupo II (droga activa), 12 episodios y grupo III (pacientes del grupo placebo en quienes, al no existir reversión a ritmo sinusal, se indicó diltiazem-propranolol), 6 episodios. No hubo ceses epontáneos de la arritmia en el grupo I (placebo) dentro de los 80 minutos. En el grupo II, 10 e 12 episodios fueron convertidos a ritmo sinusal a los 38,8 ñ 20,8 minutos post-droga. En el grupo III, 4 de 6 episodios fueron convertidos a ritmo sinusal a los 50,7 ñ 16,7 minutos post-droga activa. Dos pacientes tuvieron hipotensión arterial que no requirió tratamento específico. Es decir que 14 de 18 episodios revirtieron a ritmo sinusal con la combinación oral. Se concluye que el tratamiento episódico puede ser de utilidad en pacientes sin cardiopatía severa y con aceptable tolerancia hemodinámica durante las crisis

Tratamiento de la taquicardia paroxística supraventricular con doses única oral de diltiazem y propranolol. / [Treatment of paroxysmal supraventricular tachycardia with a single oral doses of diltiazem and propranolol]

Chronic antiarrhythmic therapy for the prevention of episodes of paroxysmal supraventricular tachycardia is limited by its elevated cost, the development of side effects and lack of patients collaboration. In this study the efficacy and safety of a single oral dose of diltiazem (180 mg) and propranolol (80 mg) were assessed. Eighteen episodes of supraventricular tachycardia were treated in 17 patients, 9 female and 8 male, aged between 19 and 60 years old (mean 45.3 +/- 11.4). The episodes had begun 3 months to 40 years before. They were divided in 3 groups: group I (placebo), 6 episodes; group II (diltiazem-propranolol), 12 episodes; and group III (patients from the placebo group without spontaneous recovery of sinus rhythm who were given active drug), 6 episodes. There were no spontaneous conversions in group I (placebo) within 80 minutes. In group II, ten out of 12 episodes responded to the combination after 38.8 +/- 20.8 minutes (seven episodes were converted to sinus rhythm within the first 45 minutes). In group III (non-responders to placebo who were subsequently given active drugs), four out of 6 episodes were suppressed after 50.7 +/- 16.7 minutes. The cycle of the tachycardia lengthened before conversion to sinus rhythm both in groups II and III. Neither systolic nor diastolic blood pressure changed significantly in any group. Seven out of 14 patients who successfully converted to sinus rhythm in groups II and III, suffered mild to moderate sweat between 3 and 5 minutes before the end of the episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Tratamiento de la taquicardia paroxistica supra ventricular con dosis unica oral de diltiazem y propranolol / Treatment of paroxysmal supraventricular tachycardia with a single oral dosis of diltiazem and propranolol

El tratamiento crónico para prevenir la recurrencia de episodios de taquicardia supraventricular presenta el incoveniente del elevado costo, aparición de efectos adversos y escasa adherencia de los pacientes. En el presente estudio se evaluó la seguridad y eficacia de la combinación de ditiazem (180 mg) y propranolol (80 mg) en dosis única oral. Fueron incluidos 18 episodios de taquicardia supraventricular en 17 pacientes. La población fue dividida en 3 grupos I (placebo), 6 episodios; grupo II (droga activa), 12 episodios y grupo III (pacientes del grupo placebo en quienes, al no existir reversión a ritmo sinusal, se indicó diltiazem-propranolol), 6 episodios. No hubo ceses epontáneos de la arritmia en el grupo I (placebo) dentro de los 80 minutos. En el grupo II, 10 e 12 episodios fueron convertidos a ritmo sinusal a los 38,8 ñ 20,8 minutos post-droga. En el grupo III, 4 de 6 episodios fueron convertidos a ritmo sinusal a los 50,7 ñ 16,7 minutos post-droga activa. Dos pacientes tuvieron hipotensión arterial que no requirió tratamento específico. Es decir que 14 de 18 episodios revirtieron a ritmo sinusal con la combinación oral. Se concluye que el tratamiento episódico puede ser de utilidad en pacientes sin cardiopatía severa y con aceptable tolerancia hemodinámica durante las crisis (AU)

Acute myocardial infarction-related coronary artery residual narrowing after intravenous streptokinase: relationship with previous coronary symptoms.

In 72 patients who received streptokinase within 6 hours of the onset of an acute myocardial infarction (AMI), the relationship between the presence of a previous coronary event and the severity of the residual coronary artery stenosis was studied. Fifty-five patients were either asymptomatic or had recent onset angina (less than 5 days) before AMI (group A) and 17 patients had chronic angina (greater than 1 year) before AMI (group B). Coronary angiograms were performed at 20 days (range 15 to 25 days). Patency of the infarct-related artery was greater in group A: 43 of 55 patients (78%) versus 8 of 17 patients (47%) in group B (p less than 0.05). Residual stenosis was less than 70% in 21 patients of group A (49% of patent arteries), whereas it manifested in none of eight patients with patent arteries in group B (p less than 0.01). This suggests that thrombosis was a major component of the coronary artery narrowing in group A patients, while it is more likely that thrombus only completes a previously severe (greater than 70%) coronary artery stenosis in patients with long-standing angina before AMI.

A double-blind study to compare the efficacy, tolerance and safety of two doses of the angiotensin converting enzyme inhibitor ramipril with placebo.

In a randomized, double-blind trial, 2 doses of ramipril (2.5 and 5 mg once daily) were compared with placebo in patients with mild to moderate essential hypertension. A 2-week placebo run-in phase was followed by 4 weeks of treatment. Eighty-six patients entered the study and 17 withdrew during the course of the study. Both doses of ramipril appeared to be more effective than placebo in reducing blood pressure, but significant differences between 2.5 mg of ramipril and placebo were not found in any statistical analyses. In the endpoint analyses (taking the last measurement from each patient), the patients receiving 5 mg of ramipril had significantly larger decreases in blood pressure than the patients receiving placebo (t tests: standing systolic, p less than 0.001; supine diastolic, p less than 0.05; standing diastolic, p less than 0.05) and also than the patients receiving 2.5 mg of ramipril (standing systolic, p less than 0.05). It appears from the results of this study that the minimum effective dosage of ramipril is 5 mg once daily. No clinically relevant side effects or clinically relevant changes in laboratory values were observed.

Efficacy of flecainide in the management of ventricular arrhythmias: comparative study with amiodarone.

The effects on ventricular arrhythmias of a new class IA drug, flecainide, were compared with those of amiodarone in 10 patients with frequent, chronic, and stable ventricular ectopic beats (VEBs). The study consisted of an initial 1-week, placebo-controlled, baseline period followed by two 12-day, randomized, crossover, double-blind treatment periods with incremental dosage and 1 month of placebo between drug periods. Frequent VEBs, which were present in all 10 patients during both placebo control periods (30 or more VEBs/hour every hour, during 24-hour Holter monitoring), were markedly suppressed (reduction greater than 80%) in nine patients with both drugs (p less than 0.01). There was almost total abolition of the VEBs in six patients with flecainide, and the satisfactory results with a minimal dose in three demonstrate its fast onset of action. Side effects from either agent were infrequent and no discontinuation was necessary. We conclude from our study that flecainide is a highly effective antiarrhythmic agent.

Los beta bloqueadores en la década del 80: su perspectiva en America Latina

En este simposio se presentaron trabajos sobre hipertensión arterial, sus consecuencias patológicas, tratamientos con beta bloqueadores. Respuesta antihipertensiva e importancia terapéutica de los beta bloqueadores, su compatibilidad con otros hipotensores. Fisiopatología de la isquemia miocárdica, farmacología de los beta bloqueadores y su función en el tratamiento de la angina. Infarto de miocardio y falla de bomba. Tratamiento del infarto y reinfarto del miocardio

Los beta bloqueadores en la década del 80: su perspectiva en America Latina

En este simposio se presentaron trabajos sobre hipertensión arterial, sus consecuencias patológicas, tratamientos con beta bloqueadores. Respuesta antihipertensiva e importancia terapéutica de los beta bloqueadores, su compatibilidad con otros hipotensores. Fisiopatología de la isquemia miocárdica, farmacología de los beta bloqueadores y su función en el tratamiento de la angina. Infarto de miocardio y falla de bomba. Tratamiento del infarto y reinfarto del miocardio

Clinical spectrum of "unstable angina".

In order to determine the natural evolution of different clinical types of "unstable angina", 167 patients were included in a prospective study. After angiography, 11 (6.5%) were excluded because they had no significant coronary lesions. The remaining 156 were sorted into different groups according to their clinical characteristics and were followed up for a period of 24 months at least. After that follow-up period, mortality and incidence of acute myocardial infarction (AMI) were as follows: angina of recent onset (Class III--IV NYHA): 8.5% (3/35) and 34.2% (12/35). Progressive angina: 7.4% (2/27) and 7.4% (2/27). Intermediate syndrome: 41.6% (10/24) and 37.5% (9/24). Prinzmetal's angina: 10% (1/10) and 10% (1/10). Post acute myocardial infarction angina: 35% (7/20) and 10% (2/20). Acute persistent ischemia: 2.5% (1/40) and 20% (8/40). Comparison of these figures pointed out significant differences (p less than 0.001 for mortality and p less than 0.03 for AMI incidence respectively). We conclude that it is clinically possible to identify different groups within the so-called unstable angina. Such a division not only allows for the creation of more homogeneous groups, but it contributes to a more rational therapeutic approach and also permits identification of high risk prodromes of greater complications, such as myocardial infarction or sudden death.

Natural history of unstable angina with medical or surgical therapy.

In order to establish the natural evolution of unstable angina under medical treatment and to determine the possible benefits of revascularization surgery, 113 patients were studied; 51 received medical treatment (24 with intermediate syndrome and 27 with progressive angina), and 62 others received surgical treatment (28 with intermediate syndrome and 34 with progressive angina). After a mean follow-up of 32 months, the mortality in the medically treated groups was 46 percent (11/24) with intermediate syndrome and 7 percent (2/27) with progressive angina (P less than 0.005), and the incidence of myocardial infarction was 38 percent (9/24) and 7 percent (2/27), respectively (P less than 0.01). Moreover, in comparing cases treated medically or surgically, the mortality was as follows: intermediate syndrome treated medically, 46 percent (11/24) vs 11 percent (3/28) in those treated surgically (P less than 0.005); and progressive angina treated medically, 7 percent (2/27) vs 9 percent (3/34) in those treated surgically (P = 0.85). The incidence of myocardial infarction was as follows: intermediate syndrome treated medically, 38 percent (9/24) vs 14 percent (4/28) in those treated surgically (P less than or equal to 0.056); and progressive angina treated medically, 7 percent (2/27) vs 12 percent (4/34) in those treated surgically (P greater than 0.55).