Serum leptin levels increase following acute myocardial infarction.

Leptin is secreted into the circulation and communicates the peripheral nutritional status to specific hypothalamic centers. Recent studies suggest that leptin may be involved in the acute response to stress, and that its interaction with the hypothalamo-pituitary-adrenal axis and the inflammatory cytokine system may be of clinical importance. Since these systems are activated during acute myocardial infarction (AMI), we studied leptin and cortisol levels during hospitalization in 30 consecutive patients admitted for AMI. The results show that leptin reached its peak on the second day of hospitalization, with a 2-fold increase from its baseline level on admission (p < 0.02). On day 3, leptin levels declined, and were 46%, 9%, and 6% above baseline on days 3, 4 and 5, respectively. The mean cortisol level was elevated on day 1 and decreased toward normal levels thereafter (p < 0.001). The cortisol level did not correlate with leptin concentration throughout the study. These findings suggest that leptin may have a role in the metabolic changes taking place during the first days after an AMI.

Peripheral monocytosis following acute myocardial infarction: incidence and its possible role as a bedside marker of the extent of cardiac injury.

Infiltration by mononuclear cells, mostly monocytes, into necrotic myocardial tissue can be detected beyond the 3rd day after the onset of infarction. These monocytes, mobilized by an unknown mechanism, initiate phagocytosis of necrotic tissue. We observed in patients having sustained an acute myocardial infarction (AMI) a significant increase in monocyte count 2-3 days following presentation, possibly representing peripheral recruitment of monocytes to the injured myocardium. To establish this observation, we prospectively documented monocyte and neutrophil counts throughout hospitalization in 186 consecutive patients (118 patients having sustained an AMI, 34 patients with angina, and 34 patients admitted for nonischemic reasons). Average monocyte count, which rose on the 2nd day and reached a peak on day 3, was significantly elevated in these patients compared with control subjects (p < 0.001). Neutrophil count exhibited a similar phase-shifted response. Peak monocyte count exceeded 800/mm3 (upper limit of normal range) in 69 (58%) of AMI patients but in only 3 of the 68 (4%) non-AMI patients, yielding a sensitivity and specificity of 58 and 95%, respectively, for the diagnosis of AMI by this criterion. A significant correlation between maximal creatine kinase (CK) representing the extent of myocardial necrosis and peak monocyte count was shown (r = 0.51, p < 0.0001). A correlation between CK and monocyte count sum of days 1-3 (r = 0.51, p < 0.001) was found in a substudy of 25 patients with AMI. Similarly, a correlation was shown with cardiac function score as evaluated by 2-dimensional echocardiography (p < 0.001 and p < 0. 008 for difference between CK sum and monocyte count sum of high and low echo score groups, respectively). Hence, the peak monocyte count recorded during the immediate postinfarction period provides a bedside marker of the extent of myocardial damage that is the preponderant prognostic determinant. If validated in future studies this phenomenon may have diagnostic and prognostic implications.

Increased expression of neutrophil and monocyte adhesion molecules LFA-1 and Mac-1 and their ligand ICAM-1 and VLA-4 throughout the acute phase of myocardial infarction: possible implications for leukocyte aggregation and microvascular plugging.

OBJECTIVES: This study sought to evaluate expression of adhesion molecules on neutrophils and monocytes throughout the acute phase of myocardial infarction. BACKGROUND: Neutrophil and monocyte counts increase within days from onset of acute myocardial infarction. Because leukocytes are recruited to the involved myocardial region, we postulated that these activated cells would display an increased expression of adhesion molecules necessary for effective endothelial transmigration. METHODS: We measured the expression of neutrophil and monocyte lymphocyte function associated antigen-1 (LFA-1), Mac-1, very late after activation antigen-4 (VLA-4) and intercellular adhesion molecule-1 (ICAM-1) by flow cytometry throughout the acute phase of acute myocardial infarction in 25 patients and 10 age-matched control subjects. RESULTS: Expression of Mac-1 on neutrophils increased significantly, whereas no expression of VLA-4 and ICAM-1 was detected. The expression of LFA-1, Mac-1, VLA-4 and ICAM-1 on the monocyte cell membrane in patients with an acute myocardial infarction was increased compared with that in control subjects by 22% (on day 7), 67%, 13% and 44% (all on day 4), respectively (all p < 0.001). Elevated density of monocyte-specific CD14 in the AMI versus the control group was also shown (30%, p < 0.001). CONCLUSIONS: Increased expression of neutrophil and monocyte adhesion molecules may contribute to their adhesion to endothelium in the ischemic territory. This adhesion could feasibly precipitate vasoconstriction or add a local thrombotic effect due to tissue factor expression secondary to Mac-1 engagement. In addition, the manifestation of increased density of LFA-1 and Mac-1 by activated leukocytes with monocytes also expressing ICAM-1 suggests that leukocytes may form microaggregates that could cause microvascular plugging. This mechanism may facilitate the occurrence of the "no-reflow" phenomenon or slow coronary filling after acute myocardial infarction.

The outcome of patients with acute myocardial infarction ineligible for thrombolytic therapy. Israeli Thrombolytic Survey Group.

PURPOSE: The aim of this study was to determine the proportion of patients with acute myocardial infarction (AMI) excluded from thrombolytic therapy on a national basis and to evaluate the prognosis of these patients by reasons of ineligibility and according to the alternative therapies that they received during hospitalization. PATIENTS AND METHODS: During a national survey, 1,014 consecutive patients with AMI were hospitalized in all the 25 coronary care units operating in Israel. RESULTS: Three hundred and eighty-three patients (38%) were treated with a thrombolytic agent and included in the GUSTO study. Ineligible patients for GUSTO were treated: (1) without any reperfusion therapy (n = 449), (2) by mechanical revascularization (n = 97), or (3) given 1.5 million units of streptokinase (n = 85) outside of the GUSTO protocol. The inhospital and 1-year post-discharge mortality rates were 6% and 2% in patients included in the GUSTO study; 6% and 5% in those mechanically reperfused; 15% and 10% in those treated with thromoblysis despite ineligibility for the GUSTO trial, and 15% and 13% among patients not treated with any reperfusion therapy. CONCLUSIONS: Ineligibility for thrombolysis among patients with AMI remains high. Patients ineligible for thrombolysis according to the GUSTO criteria, but nevertheless treated with a thrombolytic agent were exposed to an increased risk.

On-site catheterization laboratory and prognosis after acute myocardial infarction. Israeli Thrombolytic Survey Group.

BACKGROUND: Since the introduction of thrombolytic therapy for patients with acute myocardial infarction, the use of coronary angiography has substantially increased. We sought to determine whether the presence of on-site coronary angiographic facilities influenced the utilization of coronary procedures in patients with acute myocardial infarction hospitalized in Israel's coronary care units. METHODS: A prospective survey was conducted in January and February 1992 in the 25 coronary care units operating in Israel, 15 of which had on-site catheterization facilities. Data on demographics, clinical features, thrombolytic therapy, and the type of coronary diagnostic or therapeutic procedures performed during the current in-hospital stay were recorded. Mortality, both in-hospital and 1 year after discharge, was assessed for all patients in the survey. RESULTS: One thousand fourteen consecutive patients with acute myocardial infarction were hospitalized during the survey, 307 (30%) of whom were admitted to 10 coronary care units without and 707 of whom were treated in hospitals with on-site coronary angiography facilities. Demographic and baseline characteristics were similar in both groups. Thrombolytic therapy was provided equally (46%) to patients admitted to hospital with and without catheterization laboratories. Patients admitted to hospitals with these laboratories underwent coronary angiography (26%) and percutaneous transluminal angioplasty and/or coronary artery bypass grafting (12%) in greater numbers than counterparts admitted to hospitals without such laboratories (10% and 5%, respectively). Hospital and cumulative 1-year mortality rates were 11% and 18%, respectively, in patients admitted to hospitals with on-site catheterization facilities vs 10% and 17%, respectively, in the patient group admitted to the other hospitals. Patients receiving thrombolytic therapy had similar hospital mortality rates unrelated to the availability of coronary catheterization laboratories. CONCLUSION: This national survey showed that the availability of invasive coronary facilities led to increased use of diagnostic and therapeutic coronary procedures among patients with acute myocardial infarction. There was no difference in hospital or 1-year mortality rates in patients admitted to hospitals with or without on-site coronary angiographic facilities.

[Do on-site coronary angiographic facilities influence management and prognosis of acute myocardial infarction?].

Whether the presence of on-site coronary angiographic facilities (CAF) influences the use of invasive coronary procedures and the outcome of acute myocardial infarction in coronary care units was studied. A prospective survey was conducted early in 1992 when 1014 consecutive patients with acute infarction were admitted. Of them 707 (70%) were admitted to coronary care units of hospitals with, and 307 (30%) without CAF. Thrombolytic therapy was given to 46% in both groups. Those admitted to hospitals with CAF underwent more coronary angiographies (26%) and percutaneous transluminal angiography and/or coronary artery bypass grafting (12%) than those without CAF (10 and 5%, respectively--p < 0.005). In-hospital and 1-year mortality were 11 and 18% respectively in those with CAF, vs 10 and 11%, respectively, in those without CAF. All patients treated with a thrombolytic agent had similar mortality, unrelated to the availability of CAF. The survey showed that the availability of on-site coronary angiography facilities led to greater use of invasive coronary procedures in cases of acute myocardial infarction, but there was no significant difference in mortality.

Influence of gender in the therapeutic management of patients with acute myocardial infarction in Israel. The Israeli Thrombolytic Survey Group.

A national study was performed in early 1992 in the 25 operating coronary care units in Israel, which enabled the assessment of whether the therapeutic management of patients with acute myocardial infarction was affected by patient gender. During a 2-month period, 1,014 consecutive patients with acute myocardial infarction were hospitalized. Thrombolytic therapy was given to 47% of men (362 of 769), and 43% of women (106 of 245) (p = NS). After adjustment for age, no gender differences in the administration of thrombolytic therapy were noted (odds ratio 0.95; 95% confidence interval 0.73-1.23). Coronary angiography was more frequently performed in men (22%) than in women (16%) (p < 0.05). However, no gender differences in the use of angioplasty or coronary bypass surgery performed during the index hospitalization were found (10% in men, and 8% in women). The main reasons for ineligibility for thrombolytic therapy were: late hospital arrival, absence of qualifying ST-T changes on admission electrocardiogram, and contraindications to thrombolytic therapy. Hospital death was significantly lower in patients receiving thrombolytic therapy (37 of 456; 8%) than in those excluded from thrombolysis (70 of 540;13%) (p < 0.01). This difference was significant for men, but not for women. The 1-year postdischarge mortality was 4% in patients treated compared with 12% in those ineligible for thrombolysis (p < 0.01). This significant difference persisted among men and women.

Effect of Iraqi missile war on incidence of acute myocardial infarction and sudden death in Israeli civilians.

The Iraqi missile attack on Israel provided a unique opportunity to study the effects of fright due to a perceived threat of annihilation on the incidence of acute myocardial infarction (MI) and sudden death among the civilian population. During the first days of the Gulf war we noted a sharp rise in the incidence of acute MI and sudden death in our area compared with five control periods. Patient population in the various study periods did not differ significantly in age, sex ratio, hospital mortality, or proportion of patients in whom the acute event was the first presentation of coronary disease. However, during the first period of the war there were more cases of anterior wall MI and more patients received thrombolytic therapy than during control periods. Despite the continuing missile threat, the incidence of acute MI reverted to normal after the initial phase of the Gulf war.

The beneficial effects of verapamil in chronic atrial fibrillation.

Digitalis preparations frequently fail to control heart rate in many patients who have chronic atrial fibrillation, particularly during physical exertion. The effects of orally administered verapamil, 160 to 240 mg/day, on the heart rate at rest and during mild exercise were studied in 23 digitalized patients with chronic atrial fibrillation of various causes. Verapamil substantially reduced the excessive heart rate response to exercise in well-digitalized patients who had chronic atrial fibrillation.