An assessment of wall motion, perfusion and glucose metabolism in recent myocardial infarction: a comparison in patients with and without revascularization.

The aim of this study was to compare the extent and severity of wall motion abnormalities, perfusion and glucose metabolism, in recent myocardial infarction in patients with and without revascularization. Forty-nine patients were studied (82% men; mean age 58 years) by using echocardiography, 201Tl single photon emission computed tomography (SPECT) rest and redistribution, and 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) SPECT at a mean of 9.2 days (range, 1-24 days) after myocardial infarction. Twenty-seven of the 49 patients underwent revascularization while the other 22 received medical therapy before echocardiography and studies using radionuclides. A contrast angiogram was obtained for each patient. A follow-up echocardiogram at 3 months was obtained for 44 patients. Images were read blindly, using a 17 segment model, with semi-quantitative analysis. In the whole group, the extent of hypokinesia was 15%+/-14 (mean+/-SD); the extent of mild defects was determined as 5%+/-6 by using 201Tl at rest, 6%+/-9 by using 201Tl redistribution, and 4%+/-6 by using 18F-FDG (P<0.0005, echocardiogram/radionuclides). Echocardiography showed that the extent of akinesia-dyskinesia was 16%+/-18 in revascularized patients and 28%+/-18 in non-revascularized patients (P=0.017). With regard to moderate and severe defects, 201Tl rest showed 19%+/-16 and 28%+/-17, respectively (P=0.047); 201Tl redistribution 17%+/-15 and 26%+/-15, respectively (P=0.043); and 18F-FDG 17%+/-13 and 24%+/-15, respectively (NS). In echocardiography, the extent of hypokinetic segments decreased from 16%+/-15 at baseline to 10%+/-11 at 3 months (P=0.045), in revascularized patients. It is concluded that, in recent myocardial infarction, hypokinesia extent on echocardiogram is greater than mild perfusion or metabolic defect extent, reflecting stunning and so the use of radionuclide techniques appear more accurate for defining the extent of myocardial infarction. Non-revascularized patients showed a significantly greater extent of akinesia-dyskinesia and moderate-severe perfusion defects than did revascularized patients, which can be considered a result of therapy. It is suggested that 201Tl rest perfusion be used for the assessment of myocardial infarction soon after revascularization.

Vitamin supplementation can markedly reduce the homocysteine elevation induced by fenofibrate.

Elevated homocysteine concentrations are a risk factor for atherosclerotic disease. Recently it was reported that lipid lowering with fibrates increases homocysteine by up to 40%. Since elevated homocysteine concentrations can readily be lowered by vitamin supplementation, a randomized, double-blind crossover study was performed to investigate the effect of fenofibrate plus folic acid, vitamin B6 and B12 versus fenofibrate plus placebo in hyperlipidemic men. The crossover study comprised a run-in period of 6 weeks, a first treatment phase of 6 weeks, a washout phase of 8 weeks and a second treatment phase of 6 weeks. Vitamins were given at doses of 650 microg folic acid, 50 microg vitamin B12 and 5 mg vitamin B6 per day for a period of 6 weeks. After fenofibrate plus placebo the increase in homocysteine concentration was 44+/-47%. After fenofibrate plus vitamins it was 13+/-25%, being significantly lower than without vitamins. The increase in homocysteine in response to fenofibrate may counteract the cardioprotective effect of lipid lowering. The addition of vitamins involved in homocysteine metabolism can prevent most of the homocysteine increase seen after fenofibrate plus placebo. Addition of these vitamins to fenofibrate may therefore be warranted for routine use.

Protective effects of the thiophosphate amifostine (WR 2721) and a lazaroid (U83836E) on lipid peroxidation in endothelial cells during hypoxia/reoxygenation.

Little is known about pharmacological interventions with thiophosphates or lazaroids in endothelial cells injured by hypoxia/reoxygenation with respect to membrane lipid peroxidation (LPO) caused by reactive oxygen species. Therefore, a cell line of bovine aortic endothelial cells was studied after 120-min hypoxia followed by 30-min reoxygenation, resulting in moderate and predominantly reversible injury (energy depression/cytosolic Ca2+-accumulation during hypoxia, which almost normalized during reoxygenation; membrane blebs, an increasing amount of lysosomes, vacuolization, lipofuscin formation, alterations in mitochondria size, some lyzed cells). 18.9 +/- 4.3% of the cells died. Radical-induced LPO measured as malondialdehyde continuously increased to 2.18 +/- 0.17 nmol/mg of protein after reoxygenation vs control (0.41 +/- 0.13, P < 0.05). Simultaneously, the content of 4-hydroxynonenal, a novel indicator of LPO, increased from 0.02 +/- 0.01 to 0.11 +/- 0.02 nmol/mg of protein (P < 0.01). The results support the assumption that reoxygenation injury is accompanied by an increase in membrane LPO, causing structural and functional disturbances in the monolayer. The thiophosphate WR 2721 [S-2-(3-aminopropylamino) ethylphosphorothioic acid] and the lazaroid U83836E [(-)-2-[[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl] methyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol (dihydrochloride)] were effective scavengers of .OH, being more efficient than trolox C (6-hydroxy-2,5,7,8-tetramethylchroman-2-carbon acid) used as standard (EC50: 12, 5 and 15 microM, respectively, measured by electron spin resonance spectroscopy). One mM WR 2721, 10 microM U83836E, and 5 microM trolox C reduced formation of malondialdehyde during hypoxia/reoxygenation to 53 +/- 7, 51 +/- 10 and 48 +/- 6%, respectively (P < 0.05 each, versus control). In general, WR 2721 and U83836E prevent radical-induced membrane LPO in a model of endothelial cells injured by hypoxia/reoxygenation. The use of these two agents is a new approach to protect the endothelium against oxidative stress.

[Comparison of low-molecular-weight heparin and unfractionated heparin in the treatment of unstable angina]. / Heparina de bajo peso molecular versus heparina no fraccionada en el tratamiento de la angina inestable.

BACKGROUND: Low molecular weight heparin can be administered by the subcutaneous route and has a stable and prolonged antithrombotic effect. These features have prompted clinical essays about its use as an alternative to unfractionated heparin in the treatment of unstable angina. AIM: To compare the clinical effects of low molecular weight heparin and unfractionated conventional heparin in patients with unstable angina or non Q infarction. PATIENTS AND METHODS: Seventy patients (47 male) admitted to the hospital with the diagnosis of unstable angina or non Q acute myocardial infarction were randomly assigned to receive unfractionated intravenous heparin or subcutaneous low molecular weight heparin bid. All received aspirin p.o. and i.v. nitroglycerin. The incidence of recurrent angina, acute myocardial infarction or a need for emergency surgical revascularization during hospital stay were assessed in both groups. RESULTS: Compared to patients with low molecular weight heparin, patients receiving unfractionated heparin had a higher incidence of recurrent resting angina (23 and 47.5% respectively, p < 0.04) and higher need for emergency surgical revascularization (3.3 and 17.5% respectively, p < 0.06). Patients treated with unfractionated conventional heparin had a 3 times higher risk of having an adverse cardiovascular event than patients receiving low molecular weight heparin (O.R. 0.33, confidence intervals 0.11-0.58). CONCLUSIONS: Low molecular weight heparin is superior to unfractionated conventional heparin in the treatment of unstable angina and non Q acute myocardial infarction.

[Disability in the private pension system in Chile]. / Invalidez en el sistema privado de pensiones en Chile.

BACKGROUND: The degree of disability of workers ascribed to the private allowances system in Chile, is judged by Medical Commissions that apply norms that establish percentages of incapacity, without considering prognosis. AIM: To communicate the causes of disability among Chilean workers ascribed to the private allowances system, their mortality and to correlate the causes of death with diagnoses. SUBJECTS AND METHODS: We analyzed 13,456 consecutive cases judged between August 1990 and April 1992. Mortality was registered up to 12 months after judgment. RESULTS: Total incapacity was determined in 4,158 cases (30.9%), partial incapacity in 1,340 (9.9%) and minor incapacity in 7,958 (59.1%). Osteoarticular diseases were the main cause of disability in 4,460 patients (33.1%) and 77.8% of patients with malignant tumors were considered as having total incapacity. Mortality was 17% among subjects with total incapacity, 1.5% among those with partial disability and 1% among those with minor disability. The cause of death was related to the main disabling disease in 94% of subjects with total incapacity and 66.6% of those with partial incapacity. CONCLUSIONS: Osteoarticular diseases are the main cause of inability among workers ascribed to a private pension system.

High metabolic rates of 4-hydroxynonenal in brain capillary endothelial cells during hypoxia/reoxygenation.

We measured the accumulation of 4-hydroxynonenal (HNE), a major lipid peroxidation product during hypoxia/reoxygenation of brain capillary endothelial cells (BCEC). The concentration of HNE after 2 h of hypoxia was 0.23 nmol/mg protein and rose up to 0.28 nmol/mg protein after 30 min of reoxygenation. That reflects a 1.5-fold increase, whereas aortic endothelial cells (AEC) increased the HNE level 5-fold, compared to the control. Therefore, the ability of BCEC to degrade exogenously added HNE was tested. The HNE consumption in BCEC achieved a rate of about 600 nmol.min-1.mg protein-1, about two times higher than in AEC. The higher ability of BCEC to degrade HNE is probably the reason of the 2-fold higher IC50 value against the aldehyde. Therefore, we concluded that the high ability of BCEC to degrade HNE is a substantial part of the secondary antioxidative defense of the brain.

[Hospital course of acute myocardial infarction: significance of the therapeutic procedures of early reperfusion]. / Evolución intrahospitalaria del infarto agudo del miocardio: importancia de las medidas terapéuticas de reperfusión precoz.

Reperfusion therapy has contributed to decreased morbidity and mortality in patients with acute myocardial infarction (AMI). Implementation of thrombolytic therapy; primary angioplasty and emergency coronary artery by-pass surgery have proved to be effective in well designed controlled clinical trials. There is little information, however, about the impact of reperfusion therapy in the general clinical population that is usually seen in the coronary care unit. In this paper we have compared the clinical course, morbidity and mortality of patients attended for a first AMI in 2 different periods. Group I comprised 431 patients seen during the period 1981-1986 and group II bad 113 patients seen during the period 1992-1993. Age, gender distribution and AMI location were similar in both groups. Patients in group I had a significantly higher incidence of tobacco use and previous angina pectoris. In group I, 4% of patients received streptokinase, 0.9% of patients had emergency by-pass surgery and none had primary angioplasty, whereas in group II, 29% of patients received trombolytics, 6.5% had primary angioplasty and 6.5% had by-pass surgery. Heart failure Killip class II-III occurred in 35% of patients in group I and in 13% of patients in group II (p < 0.05). Intrahospital mortality was 19.6% in group I and 11.5% in Group II (p < 0.045). There were no differences in the incidence of cardiogenic shock in both groups. Multivariate analysis showed that age and heart failure were significant independent predictors of mortality in both periods. Thus, there has been a significant change in the therapeutic approach to AMI patients in recent years. Widespread utilization of reperfusion therapy appears to be associated with decrease in morbidity and mortality in a general population of patients with a first AMI.

[Diltiazem versus intravenous nitroglycerin in the treatment of unstable angina pectoris. A randomized study]. / Diltiazem versus nitroglicerina por vía endovenosa en el tratamiento de la angina inestable. Estudio randomizado.

Prognosis of unstable angina pectoris is related to admission EKG changes and prompt symptom control. The aim of this study was to compare the clinical effects of intravenous diltiazem (DTZ) or nitroglycerin (NTG) in patients with unstable angina pectoris. We studied 43 patients admitted to the hospital with a history of rest angina within the last 48 hours, associated with EKG evidence of ischemia. All subjects received intravenous heparin and oral aspirin, 23 were randomly assigned to receive intravenous DTZ and 20 to receive intravenous NTG. Both groups had similar baseline features and the endpoints of treatment were recurrence of angina, myocardial infarction, death during hospitalization and secondary side effects. Treatment with DTZ, when compared to NTG, resulted in a significant reduction of recurrent angina (8.7 and 59% respectively; p < 0.005), number of angina episodes per patient (0.18 +/- 0.5 and 0.9 +/- 1.2 respectively; p < 0.05) and lower need for dose increment to control symptoms (3 and 9 patients respectively; p < 0.05). The most common side effects observed were cephalea with NTG (60% of patients) and asymptomatic sinus bradicardia with DTZ (28% of patients). In each group, one patient had a myocardial infarction and one patient died. It is concluded that intravenous DTZ reduces myocardial ischemia to a greater extent than NTG and can be safely used in patients with unstable angina pectoris.

[Characteristics of acute myocardial infarction in patients with diabetes mellitus]. / Caracteristicas del infarto agudo del miocardio en pacientes con diabetes mellitus.

We analyzed retrospectively the clinical course and prognosis of 565 consecutive patients with acute myocardial infarction (AMI), 117 of them with a previous history of diabetes mellitus. Male/female ration was 7.9/2.1 in non diabetics and 7.0/3.0 in diabetics (p < 0.03). Incidence of hypertension and hyperlipidemia was higher in diabetic patients as well as history of congestive heart failure (13.7% vs 6.5 in non diabetics p < 0.01). The type and location of AMI did not differ among groups, however the incidence of congestive heart failure Killip class III-IV was higher in diabetic patients (31.6 vs 21.2%). Peak CPK values were lower in diabetics (1.270 +/- 1.179 vs 1.648 +/- 1.377 U/l p < 0.01). Cardiac mortality was higher one month and one year after AMI in diabetics (17.1 vs 13.6% and 21.4 vs 17.8% respectively, p < 0.01). Univeriate and multivariate analysis identified new bundle branch block, heart failure and advanced age as independent predictors of mortality in both groups of patients. It is concluded that the worst prognosis of diabetic patients with AMI may be related to a previously depressed ventricular function and that appropriate metabolic control and treatment of associated risk factors, could improve the prognosis of diabetics patients with AMI.

[Vasodilator agents in chronic heart failure: which is the best option?]. / Vasodilatadores en la insuficiencia cardíaca crónica: cual es la mejor opción?

Vasodilator therapy has been utilized for the treatment of congestive heart failure in the last 20 years. These drugs contribute to increase cardiac output, decrease peripheral vascular resistance and favour venous dilatation. Recent multicenter trials have addressed the issue of the impact of vasodilator therapy upon survival. Thus, the VHEFT-I and Consensus studies have shown that both the combination of nitrates and hydralazine and ACF inhibitors improve life expectancy in patients with moderate and severe heart failure. Moreover, the SOLVD study showed that ACE inhibitors improve survival and reduce cardiac events in patients with mild heart failure and depressed myocardial function at the end of 2 years of follow-up. The VHEFT II trial compared the effects of the nitrate-hydralazine combination versus ACE inhibitors upon the clinical course of patients with moderate heart failure. This last trial showed that although nitrates and hydralazine exerted a slightly better benefit upon exercise tolerance and left ventricular ejection fraction, patients that were treated with ACE inhibitors had a significantly reduced mortality. Differences in mortality when both groups of vasodilators drugs were compared were due to reduction of arrhythmias and sudden death. It is likely that this greater benefit obtained with ACE inhibitors when compared to nitrates and hydralazine in heart failure might be due to their favourable effects upon the abnormal neurohormonal activation observed in this syndrome. Thus ACE inhibitors have turned out to be one of the cornerstones in the treatment of congestive heart failure.

[Value of electrocardiogram in localization of the coronary artery occlusion in acute inferior wall myocardial infarction]. / Valor del electrocardiograma en la localizacion de la arteria coronaria culpable en el infarto agudo del miocardio de pared inferior.

Early EKG changes may contribute to predict the site of coronary artery occlusion during acute inferior myocardial infarction (MI). Its interpretation is relevant to therapeutic clinical decisions. We have prospectively evaluated early EKG changes of 40 consecutive patients with acute inferior MI and correlated them with the site and location of the coronary artery culprit lesion. Proximal right coronary artery occlusion was characterized by negative ST-T wave changes in leads D1 and aVL and ST segment elevation in leads D3 > D2. However the most distinctive EKG pattern of proximal right coronary artery occlusion was ST segment elevation with positive T wave in V4R (specificity 96%, predictive value 89%, p < 0.001). Distal right coronary artery occlusion was characterized by a positive T wave without ST segment elevation in V4R. Finally circumflex coronary artery occlusion was defined by a positive R/S > 1 relationship in V1, ST segment elevation in V5 and V6. Again lead V4R with flat or negative ST-T wave morphology had the highest predictive value for circumflex coronary artery occlusion (100%). Thus early EKG changes may contribute to precise the site and location of coronary artery occlusion and may help to implement clinical therapeutic strategies in patient with inferior MI. Right precordial leads are most useful in the EKG interpretation of inferior MI.

[Early test of thallium dipyridamole after myocardial infarction: prognostic value and correlation with coronarography]. / Prueba de talio dipiridamol precoz postinfarto del miocardio: valor pronóstico y correlación con coronariografía.

Fifty three patients were studied with dipyridamole thallium myocardial scintigraphy, 4 to 6 days after a first episode of myocardial infarction. Localization of infarction was anterior in 25 and inferior in 28. Infarction was confirmed by myocardial scintigraphy in 87% of cases. A non q wave myocardial infarction was present in 5 of the 7 patients with negative scintigraphy. Residual myocardial ischemia was suggested by myocardial scintigraphy in 68% of patients. Correlated to coronary arteriography, sensitivity for myocardial ischemia was 80%, specificity 82%. After a mean follow up of 11.2 months, 22 of 36 patients with positive myocardial scintigraphy had new coronary events, 15 of them requiring myocardial revascularization. In contrast, only 2 of 17 patients with negative scintigraphy had new events (p < 0.05). Thus dipyridamole thallium myocardial scintigraphy early after myocardial infarction is a valuable prognostic test.

[Early systemic thrombolysis in acute myocardial infarction: clinical and angiographic results]. / Trombólisis sistémica precoz en el infarto agudo del miocardio: resultados clínicos y angiográficos.

Systemic thrombolysis is an effective therapy for acute myocardial infarction, since it restores coronary flow and contributes to preserve left ventricular function. We analyze our experience with intravenous thrombolytic therapy in 45 cases with acute myocardial infarction treated within 6 hours of onset of symptoms. 28 patients had anterior and 17 inferior myocardial infarction. We treated 38 patients with streptokinase 1 to 1.5 million units infused during a 30 to 60 minute period and 7 patients with tissue plasminogen activator factor, 100 mg infused during 2 hours. Regression of chest pain and ST segment elevation and early CPK peaking (less than 4 hours) were utilized as criteria for reperfusion. Accordingly 29 patients (64%) met these criteria. Coronary angiogram was performed within 7 days in 38 patients. It disclosed a patent coronary artery in the infarcted area in 28 cases (74%). Transient hypotension with thrombolytic therapy was observed in 17 patients (38%) and bleeding complications in 3 cases (7%). Two patients (4%) died early after therapeutic failure. In summary we have confirmed that intravenous thrombolytic therapy is safe and effective in the early period of myocardial infarction and that is associated with a high incidence of clinical and angiographic reperfusion.

[Intraventricular conduction disorders in acute myocardial infarction: early and late clinical significance]. / Trastornos de conducción intraventricular en infarto agudo del miocardio: significado clínico precoz y tardío.

The prognostic impact of new bundle branch block (BBB) upon the intra hospital course and long-term prognosis of patients with acute myocardial infarction (MI) was studied in 517 consecutive patients with a recent MI: 449 patients did not have BBB (group I) and 69 developed a new BBB (group II). Age and sex were similar in both groups. Incidence of BBB among patients with anterior wall MI was 61% compared to 8% in patients with inferior wall MI (p less than 0.05). The distribution of RBBB, RBBB + left anterior hemiblock and LBBB was 32%, 30% and 38% among 46 patients with anterior wall MI, compared to 28%, 6% and 68% among 18 patients with inferior wall MI (p less than 0.05). The level of peak CK values (2345 vs 1437 IU/l), presence of Killip grade III or IV (56 vs 18%), complete A-V block (24 vs 6%) and mortality (34 vs 9%) were significantly higher in group II (p less than 0.05). Long-term mortality at 1 and 5 years of follow up was 29% and 51% in group II patients, a three fold increase over group I. We conclude that development of new BBB during myocardial infarction is associated with a poor immediate and long term prognosis. This may be related to larger infarcts rather than the conduction defect itself.