Cholesterol homeostasis and cell proliferation by mitogenic homologs: insulin, benzo-α-pyrene and UV radiation.

Low-Density Lipoprotein (LDL) is known to promote the unregulated proliferation of cells that is progression of cancer. We aimed to investigate the effect of mitogens on the expression of cell cycle proteins, nuclear cholesterol and cell proliferation. We observed that insulin and benzo-α-pyrene (BaP) induced the expression of Low-Density Lipoprotein receptor (LDLR) on HepG2 cells, thereby enhancing the uptake of LDL. The internalized LDL increased the concentration of cholesterol in the cytoplasm and nucleus of the cell. At the same time, insulin and BaP also stimulated the expression of cell cycle proteins viz., Cyclin E and Cdk2, and thus induced more incorporation of Bromodeoxyuridine (BrdU) in cultured cells indicating increased DNA synthesis. Increased expression of cell cycle proteins and DNA synthesis are the indications of DNA replication and new cell synthesis. This suggests a link between the enhanced nuclear cholesterol concentration and new cell formation. On the other hand, UV irradiation with selectively given dose of cell death eventually decreases nuclear cholesterol concentration and LDLR expression. Reduced LDLR shows low functional activity. This, again, repeated the plausibility of the same link between intracellular cholesterol concentration and cell population. The biasness of adverse effect observed by UV irradiation has been compromised by inactivating LDLR with anti-LDLR antibody, resulting in similar effects on Cyclin E expression in the cultured cells. Hence, we concluded that in all the conditions, LDLR expression was found to be a translational event of its transcription factor, SREBP-2, by the induction of insulin, BaP and UV irradiation.

Differential Expressions of p53, p53R2, hRRM2 and PBR in Chronic Lymphocytic Leukemia: A Correlation with Intracellular Cholesterol.

Regulation of intracellular cholesterol homeostasis exists under balance between intracellular biosynthesis and uptake from extracellular origin by cell surface transport proteins. Expected role of cholesterol on either tumor suppressor gene and/or DNA synthesis has been aimed in the present study to explore intracellular cholesterol homeostasis in CLL subjects. Higher expressions of p53R2 (p53 dependent subunit of ribonucleotide reductase) and p53 were found in lymphocytes of chronic human lymphocytic leukemia as comparison to their normal counterparts. Inverse relation was found with p53 independent R2 subunit (in human hRRM2) of ribonucleotide reductase, which was found to be decreased from its control group. More expression of peripheral type benzodiazepine receptor, a cholesterol transporter, was noticed in isolated nuclear fraction with simultaneous increase of cholesterol concentration in cytoplasmic and nuclear compartments. A parallel increase of cholesterol in cell nucleus with increased p53R2 expression shows priority of the involvement of cholesterol in the process of cell replication.

Estradiol regulates insulin dependent stimulation of LDL-receptor expression in HepG(2) cells.

The low density lipoprotein, one of the major vehicle for extraneous cholesterol, internalizes into the cells through the process of LDL-receptor mediated endocytosis. The expression of LDL-receptor on the cell surface is a function of various hormone regulated transcription of the receptor gene. The present study elucidates the differential expression pattern of LDL-receptor protein in human hepatoma HepG(2) cells by the influence of two hormones, insulin and estrogen (ß-estradiol), as compared to the basal level expression of the receptor protein. The combined effect of insulin and ß-estradiol reveals that ß-estradiol is the ultimate regulator between these two hormones and supershades the message of insulin on LDL-receptor expression. The receptor protein level immunobloted by anti LDL-receptor antibody after treating cells with insulin, ß-estradiol and mixture of both also reflects the same phenomena. This comparative study makes it consistent that cell saturation with sterol (ß-estradiol) is the prime regulator of LDL-receptor expression between the two hormones, insulin and estrogen.

Seasonal pattern of acute myocardial infarction in the National Registry of Myocardial Infarction.

OBJECTIVES: The purpose of this study was to determine whether the rate of hospital admission for acute myocardial infarction (AMI) varies seasonally in a large, prospective U.S. registry. BACKGROUND: Identification of specific patterns in the timing of the onset of AMI is of importance because it implies that there are triggers external to the atherosclerotic plaque. Using death certificate data, most investigators have noted a seasonal pattern to the death rate from AMI. However, it is unclear whether this observation is due to variation in the prevalence of AMI or to other factors that may alter the likelihood of a fatal outcome. METHODS: We examined the seasonal mean number of cases of AMI (adjusted for the length of days in each season) that were submitted to the National Registry of Myocardial Infarction (NRMI) by 138 high volume core hospitals over a 3-year period (December 21, 1990 through December 20, 1993) during which the number of hospitals participating in the Registry was stable. Data were analyzed using general linear modeling and analysis of variance. RESULTS: High volume core hospitals reported 83,541 cases of AMI to the Registry during the study period. Approximately 10% more such cases were entered into the Registry in winter or spring than in summer (p < 0.05). The same trends were seen in both northern and southern states, men and women, patients < 70 versus > or = 70 years of age and those with Q wave versus non-Q wave AMI. CONCLUSIONS: We conclude that there is a seasonal pattern to the reporting rate of cases of AMI in the NRMI. This observation further supports the hypothesis that acute cardiovascular events may be triggered by events that are external to the atherosclerotic plaque.

Clinical experience with primary percutaneous transluminal coronary angioplasty compared with alteplase (recombinant tissue-type plasminogen activator) in patients with acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2).

OBJECTIVES: We sought to compare outcomes after primary percutaneous transluminal coronary angioplasty (PTCA) or thrombolytic therapy for acute myocardial infarction (MI). BACKGROUND: Primary PTCA and thrombolytic therapy are alternative means of achieving reperfusion in patients with acute MI. The Second National Registry of Myocardial Infarction (NRMI-2) offers an opportunity to study the clinical experience with these modalities in a large patient group. METHODS: Data from NRMI-2 were reviewed. RESULTS: From June 1, 1994 through October 31, 1995, 4,939 nontransfer patients underwent primary PTCA within 12 h of symptom onset, and 24,705 patients received alteplase (recombinant tissue-type plasminogen activator [rt-PA]). When lytic-ineligible patients and patients presenting in cardiogenic shock were excluded, baseline characteristics were similar. The median time from presentation to initiation of rt-PA in the thrombolytic group was 42 min; the median time to first balloon inflation in the primary PTCA group was 111 min (p < 0.0001). In-hospital mortality was higher in patients in shock after rt-PA than after PTCA (52% vs. 32%, p < 0.0001). In-hospital mortality was the same in lytic-eligible patients not in shock: 5.4% after rt-PA and 5.2% after PTCA. The stroke rate was higher after lytic therapy (1.6% vs. 0.7% after PTCA, p < 0.0001), but the combined end point of death and nonfatal stroke was not significantly different between the two groups (6.2% after rt-PA and 5.6% after PTCA). There was no difference in the rate of reinfarction (2.9% after rt-PA and 2.5% after PTCA). CONCLUSIONS: These findings suggest that in lytic-eligible patients not in shock, PTCA and rt-PA are comparable alternative methods of reperfusion when analyzed in terms of in-hospital mortality, mortality plus nonfatal stroke and reinfarction.

Influence of payor on use of invasive cardiac procedures and patient outcome after myocardial infarction in the United States. Participants in the National Registry of Myocardial Infarction.

OBJECTIVES: We sought to determine the influence of payor status on the use and appropriateness of cardiac procedures. BACKGROUND: The use of invasive procedures affects the cost of cardiovascular care and may be influenced by payor status. METHODS: We compared treatment and outcomes of myocardial infarction among four payor groups: fee for service (FFS), health maintenance organization (HMO), Medicaid and uninsured. Multivariate comparison was performed on the use of invasive cardiac procedures, length of hospital stay and in-hospital mortality in 17,600 patients <65 years old enrolled in the National Registry of Myocardial Infarction from June 1994 to October 1995. To determine the appropriateness of coronary angiography, we compared its use in patients at low and high risk for cardiac events. RESULTS: Angiography was performed in 86% of FFS, 80% of HMO, 61% of Medicaid and 75% of uninsured patients. FFS patients were more likely to undergo angiography than HMO (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.13 to 1.42), Medicaid (OR 2.43, 95% CI 2.11 to 2.81) and uninsured patients (OR 1.99, 95% CI 1.76 to 2.25). Similar patterns for the use of coronary revascularization were found. Among those at low risk, FFS patients were as likely to undergo angiography as HMO patients but more likely than Medicaid and uninsured patients. For those at high risk, FFS patients were more likely to undergo angiography than patients in other payor groups. Adjusted mean length of stay (7.3 days) was similar among all payor groups, but adjusted mortality was higher in the Medicaid group (Medicaid vs. FFS: OR 1.55, 95% CI 1.19 to 2.01). CONCLUSIONS: Payor status is associated with the use and appropriateness of invasive cardiac procedures but not length of hospital stay after myocardial infarction. The higher in-hospital mortality in the Medicaid cohort merits further study.

Aortic diameter and pressure-flow sequence identify mechanism of blood flow during external chest compression in dogs.

Aortic flow and pressure relations and aortic diameter were examined during sinus rhythm, internal cardiac massage, vest cardiopulmonary resuscitation, conventional manual cardiopulmonary resuscitation and high impulse manual cardiopulmonary resuscitation in 14 anesthetized large dogs. During sinus rhythm and during internal cardiac massage, ascending aortic flow and pressure increased simultaneously and the rise in ascending aorta pressure preceded the rise in descending aortic pressure by (mean +/- SEM) 28 +/- 4 and 30 +/- 1 ms, respectively. In contrast, during vest, conventional and high impulse cardiopulmonary resuscitation, ascending aortic flow lagged behind the initial rise in aortic pressure by 40 +/- 4 to 46 +/- 4 ms and ascending and descending aortic pressure increased simultaneously (p less than 0.001 for each external compression mode versus sinus rhythm and internal massage). The ratio of pulse pressure to stroke volume increased by an order of magnitude during all modes of external chest compression (p less than 0.001 versus sinus rhythm and internal massage) and aortic diameter decreased during vest and high impulse cardiopulmonary resuscitation (p less than 0.05 versus sinus rhythm and internal massage). The hemodynamics of external chest compression depart from the normal physiologic sequence of stroke volume-induced increase in aortic pressure and diameter. The rise in aortic pressure precedes flow into the aorta, stroke volume does not fully account for pulse pressure, and aortic diameter decreases during chest compression. These data support the hypothesis that blood flow is due to fluctuations in intrathoracic pressure for high impulse as well as vest and conventional cardiopulmonary resuscitation.

Factors influencing the time to thrombolysis in acute myocardial infarction. Time to Thrombolysis Substudy of the National Registry of Myocardial Infarction-1.

BACKGROUND: The Time to Thrombolysis Substudy of the National Registry for Myocardial Infarction provided the opportunity to identify factors that delay thrombolytic treatment of patients with ST-segment elevation acute myocardial infarction. PARTICIPANTS: Forty-two participating registry hospitals volunteered for the Time to Thrombolysis Substudy. METHODS: A case report form was developed to collect time points for emergency department arrival (door), recording of the electrocardiogram (ECG) (data), entry of the order to give a thrombolytic drug (decision), and initiation of the thrombolytic infusion (drug) as defined by the National Heart Attack Alert Program. The impact of mode of transportation to the hospital, sex, policy-driven cardiology consultation and/or contact of the primary care physician on door-to-drug time, and each component interval were determined in 1755 patients who were treated with recombinant tissue-type plasminogen activator (A1-teplase). The t test was used for comparison of means and the nonparametric sign test was used for medians. RESULTS: A minority of patients arrived at the hospital by ambulance, although more women (49.6%) arrived by ambulance than men (40.9%). However, women arrived at hospitals significantly later after onset of symptoms than men. It took half as long for patients arriving by ambulance to be seen by the physician than those who transported themselves to the hospital. It took longer for women to have the initial 12-lead ECG recorded than men. The decision to order a thrombolytic agent was delayed by 22 minutes and median door-to-drug time by 21 minutes in those patients who had a cardiac consultation over those in whom the drug was ordered and infusion was initiated by the emergency physician. Although the initial 12-lead ECG showed ST-segment elevation in 86% of patients who received the thrombolytic drugs, with no difference between men and women and no difference in the rate of cardiology consultation between men and women (77%), door-to-decision time and door-to-drug time were substantially longer for women having consultation than men. There was no significant difference in door-to-decision time between men and women when no consultation was performed, but it still took longer for a drug infusion to be initiated in women. Contacting the primary care physician delayed the decision to give a thrombolytic drug by 18 minutes and the administration of the drug by 20 minutes, but there were no differences between men and women. Preparation of the drug in the pharmacy resulted in significant delay compared with mixing it in the emergency department. CONCLUSIONS: Hospital practices and policies, including contacting the primary care physician prior to the initiation of a lytic drug, cardiology consultation, and preparation of the drug in the pharmacy rather than in the emergency department, significantly delay the goal of early treatment of patients with ST segment elevation acute myocardial infarction. Delays in hospital arrival for women are compounded by delays in the decision to treat them with a thrombolytic drug and initiation of the drug therapy in those women who receive consultation compared with men. Other delays in acquiring the first ECG and initiating the drug infusion in women are not explained.

Payer status and the utilization of hospital resources in acute myocardial infarction: a report from the National Registry of Myocardial Infarction 2.

BACKGROUND: Prior studies have suggested that payer status may be an important determinant of medical resource utilization and outcome in acute myocardial infarction (AMI). METHODS: A national cohort of 332,221 patients with AMI enrolled from June 1994 to July 1996 were compared within 5 payer groups to ascertain the influence of payer status on hospital resource allocation for AMI in the United States. RESULTS: Medicare comprised the largest proportion (56%), followed by commercial insurance (25%), health maintenance organization (HMO) (10%), uninsured (6%), and Medicaid (3%). Compared with commercially insured patients, Medicare and Medicaid patients received fewer reperfusion therapies, underwent fewer invasive cardiac procedures, and had longer hospitalizations. After adjusting for differences in clinical characteristics, Medicare recipients were as likely as commercially insured patients to receive acute reperfusion therapies or any invasive cardiac procedure. Uninsured and HMO patients tended to utilize hospital resources with intermediate frequency. Medicare recipients aged 65 years or older and the HMO group had similar hospital mortality rates compared with the commercial group (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.96-1.20 and OR, 0.93; 95% CI, 0.83-1.04, respectively), but Medicaid and uninsured groups had higher hospital mortality rates compared with the commercial group (OR, 1.30; 95% CI, 1.14-1.48 and OR, 1.29; 95% CI, 1.12-1.48, respectively). CONCLUSION: This report suggests significant variation by payer status in the management of AMI throughout the United States, but no important differences in mortality among the 3 largest payer groups.

Observations of the treatment of women in the United States with myocardial infarction: a report from the National Registry of Myocardial Infarction-I.

BACKGROUND: To determine whether there are sex differences in the demographics, treatment, and outcome of patients with acute myocardial infarction in the United States, data from the National Registry of Myocardial Infarction-I from September 1990 to September 1994 were examined. METHODS: The National Registry of Myocardial Infarction-I is a national observational database consisting of 1234 US hospitals in which each hospital submits data from each patient with acute myocardial infarction to a central data collection center. For these analyses, the following variables were examined in 354 435 patients with acute myocardial infarction: demographics; use of medical therapy including thrombolytic agents; use of procedures including cardiac catheterization, percutaneous transluminal coronary angioplasty, and coronary artery bypass surgery; length of hospital stay; adverse events (stroke, major bleeding, or recurrent myocardial infarction); and causes of death. RESULTS: In comparison with men, women experiencing acute myocardial infarction in the United States are older, with 55.7% older than 70 years. Women have a higher mortality rate than men even when controlled for age and die less often from arrhythmia but more often from cardiac rupture whether or not thrombolytic therapy is used. Treatment with aspirin, heparin, or beta-blockers is less frequent in women. When thrombolytic therapy is used, women are treated an average of almost 14 minutes later than men and experience a greater incidence of major bleeding. Cardiac catheterization, percutaneous transluminal coronary angioplasty, and coronary artery bypass surgery are used less often in women. CONCLUSIONS: Observations from the National Registry of Myocardial Infarction-I document important sex differences in demographics, treatment, and outcome of patients with acute myocardial infarction in the United States.

Assessment of early post-infarction ischemia: correlation between ambulatory electrocardiographic monitoring and exercise treadmill testing.

PURPOSE: Demand-related myocardial ischemia detected by treadmill testing is commonly used to identify high-risk patients after myocardial infarction (MI). Although ischemia detected by ambulatory electrocardiographic monitoring (AECG) has also been shown to predict poor outcome in some patient groups, the relationship between AECG-detected ischemic ST changes and post-MI treadmill ischemia is unknown. PATIENTS AND METHODS: We screened 94 patients after MI with 24-hour AECG monitoring and a Naughton treadmill test. Forty-two patients were excluded because of left bundle branch block, left ventricular hypertrophy, abnormal baseline ST segments, or digoxin therapy. In the remaining 52 patients, AECG was performed 5.1 +/- 2.2 days after MI (mean +/- SD) and the treadmill test 8.4 +/- 2.2 days after MI. Each patient was taking the same drugs for both studies, had no interim revascularization procedures, and all studies were interpreted blindly. RESULTS: The treadmill test (ETT) was positive for ST changes and/or thallium reperfusion defects in 19 of 52 patients (36%). The AECG was positive for ischemia (ST depression greater than 1 mm, for more than 1 minute) in 14 of 52 patients (27%) (Group I), with 9.9 +/- 8.2 ischemic episodes per patient lasting 13.5 +/- 7.5 minutes per episode. The AECG was negative for ischemia in the remaining 38 patients (73%) (Group II). The ETT and AECG correlation was as follows: 9 patients with AECG-detected ischemic ST changes had positive ETT results; 10 patients without AECG-detected ischemic ST changes had positive ETT results; 5 patients with AECG-detected ischemic ST changes had negative ETT results; and 28 patients without AECG-detected ischemic ST changes had negative ETT results (p < 0.02 by chi 2). The predictive accuracy of a positive AECG identifying a positive ETT was 65% (specificity 85%, sensitivity 47%), and the predictive accuracy of a negative AECG identifying a negative ETT was 74%. Group I patients were older than Group II patients (63.6 +/- 8.2 years versus 53.2 +/- 10.6 years p < 0.02), more commonly had painless ETT ischemia (43% versus 18% p = 0.08), and tended to have positive ETT results at a lower level of exercise (366 +/- 210 seconds versus 588 +/- 212 seconds, p = 0.04). CONCLUSION: Ischemic ST changes as detected by AECG monitoring correlate significantly with post-MI treadmill test results with a high specificity, albeit a low sensitivity. In patients without baseline ST-segment abnormalities and limited exercise capability, AECG monitoring may be of limited use in identifying early post-MI ischemia.

Frequency and importance of silent myocardial ischemia identified with ambulatory electrocardiographic monitoring in the early in-hospital period after acute myocardial infarction.

The incidence and clinical significance of silent myocardial ischemia occurring in the early period after acute myocardial infarction (AMI) was studied in 59 patients who had an uncomplicated early course after admission for AMI. Calibrated 2-lead ambulatory electrocardiographic monitoring performed for 39 +/- 2 hours starting 4 +/- 1 days after AMI identified silent myocardial ischemia, defined as greater than or equal to 1 mm ST-segment change lasting greater than or equal to 2 minutes, in 27 patients. These patients had 5 +/- 1 episodes lasting a median of 11 minutes/episode (range 2 to 36 minutes/episode). Patients with and without silent ischemia had comparable baseline demographics, were receiving similar anti-ischemic medications and had similar severity of coronary disease by angiography. No reinfarctions occurred during the in-hospital period. Fourteen of 27 patients (52%) with silent ischemia had greater than or equal to 1 in-hospital clinical ischemic event (pulmonary edema, n = 5, cardiac death, n = 1, and postinfarction angina, n = 11). In contrast, only 7 of 32 patients without silent ischemia (22%) had greater than or equal to 1 in-hospital event (pulmonary edema, n = 1, cardiac death, n = 1, and postinfarction angina, n = 6). The frequency of ischemic events was significantly greater in patients with silent ischemia compared to those without silent ischemia, p less than 0.02. Silent ischemia occurs frequently very early after AMI and identifies a group of patients who are at increased risk for adverse in-hospital clinical outcomes.

An angiographic and functional comparison of patients with silent and symptomatic treadmill ischemia early after myocardial infarction.

Sixty consecutive patients were studied who had positive responses to Naughton exercise treadmill testing (at least 1.5 mm of ST-segment shift in at least 2 leads or thallium reperfusion abnormalities) with or without symptoms of angina 11 +/- 1 days after acute myocardial infarction (AMI). All patients had undergone coronary angiography 24 +/- 4 days after infarction. Thirty-eight patients (63%) had no treadmill angina (silent ischemia, group I) and 22 patients had typical treadmill angina (symptomatic ischemia, group II). Use of beta-blocking drugs, calcium antagonists and nitrates at the time of exercise testing did not differ in the 2 groups. All 9 patients with diabetes mellitus were in the asymptomatic group (p less than 0.40) and group I had a greater proportion of inferior wall AMI (30 of 38) than group II (11 of 22, p = 0.02). Total exercise treadmill test duration (group I 422 +/- 31 seconds, group II 400 +/- 46 seconds) and rate-pressure product were not different in the 2 groups. The number of patients unable to exercise 5 minutes (12 in group I and 7 in group II), the number with diffuse electrocardiographic changes (9 in group I and 7 in group II), and the number with inadequate blood pressure response (8 in group I and 4 in group II) were also similar. At coronary arteriography the mean number of arteries with at least 70% diameter stenosis was 2.0 +/- 0.2 in group I and 2.2 +/- 0.2 in group II (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Reperfusion therapy in patients with acute myocardial infarction and prior coronary artery bypass graft surgery (National Registry of Myocardial Infarction-2).

We reviewed data from the National Registry of Myocardial Infarction-2 to determine the differences in characteristics and outcomes in patients with acute myocardial infarction (AMI) who have undergone previous coronary artery bypass grafting (CABG), and those who have not, and between post-CABG patients who were treated with alteplase (recombinant tissue-type plasminogen activator [rt-PA]) and those who were treated with primary percutaneous transluminal coronary angioplasty (PTCA). Demographic, therapeutic, and outcome data from patients with AMI were collected at > 1,000 hospitals in the United States in collaboration with National Registry of Myocardial Infarction-2. Of the 45,925 patients receiving reperfusion therapy, 2,544 of the 39,574 treated with rt-PA (6.4%) had a history of CABG, and 375 of the 6,351 treated with primary PTCA (5.9%) had a history of CABG. Patients with a history of CABG were older, more likely to be men, and had more comorbidities, but prior CABG was still an independent predictor of mortality after multivariate regression analysis (odds ratio 1.23; 95% confidence interval 1.05 to 1.44). Among the post-CABG patients who received rT-PA or underwent PTCA, there was no significant difference in in-hospital mortality rate or the combined end point of death and nonfatal stroke. Thus, (1) prior CABG is an independent predictor of mortality, and (2) for post-CABG patients with AMI who are not in shock and who are lytic-eligible, reperfusion therapy with rt-PA and PTCA result in similar outcomes with regard to in-hospital mortality and the combined end point of death and nonfatal stroke.

Effect of early enalapril therapy on left ventricular function and structure in acute myocardial infarction.

Infarct expansion starts within hours to days after transmural myocardial injury. Previous echocardiographic and left ventriculographic studies demonstrated that angiotensin-converting enzyme (ACE) inhibitor therapy limits left ventricular dilatation, particularly in patients with anterior wall acute myocardial infarction (AMI) or impaired left ventricular function. Forty-three patients with an acute Q-wave AMI were randomized within 24 hours of symptom onset to intravenous enalaprilat (1 mg) or placebo. Patients were then given corresponding oral therapy and followed for 1 month. Predrug and 1-month gated blood pool scans were obtained in 32 patients to evaluate changes in cardiac volumes and ejection fraction. Twenty-three patients underwent magnetic resonance imaging at 1 month to evaluate left ventricular infarct expansion. Blood pressure decreased at 6 hours but returned to baseline in both groups after 1 month of therapy. The change in cardiac volumes from baseline to 1 month differed between the placebo (end-diastolic volume +16 +/- 5 ml, end-systolic volume +8 +/- 6 ml), and enalapril (end-diastolic volume -8 +/- 9 ml and end-systolic volume -14 +/- 7 ml) groups (p < 0.05 vs placebo). Global and infarct zone ejection fractions improved significantly at 1 month in the enalapril group (+6 +/- 3% and 19 +/- 5%, respectively) but did not change over 1 month in the placebo group. Infarct segment length and infarct expansion index by magnetic resonance imaging were significantly less in those treated with enalapril, suggesting less infarct expansion in this group. Thus, early administration of enalaprilat to patients presenting with a first Q-wave AMI prevents cardiac dilatation and infarct expansion.

Manipulation of external pressure as a method to assist the failing heart.

The development and state of the art in circulatory assistance using external pressure variations is reviewed. All of these techniques use the principle that by cyclic external pressure waves properly timed to the cardiac cycle, hemodynamic energy can be noninvasively transmitted to assist the circulation. Cyclic pressure waves to the lower body require that the high pressure phase occurs in diastole in order to augment cardiac output or coronary flow. In contrast, pressure waves to the chest would optimally augment cardiac output if they begin at the onset of ventricular systole. Manipulation of lung pressure by synchronized ventilation may be also utilized to augment cardiac output. The above methods are discussed in detail in the manuscript with special emphasis on the pathophysiology and mechanisms of cardiac assistance.

Conservative treatment of paroxysmal ventricular tachycardia during pregnancy.

Paroxysmal ventricular tachycardia during pregnancy presents a therapeutic dilemma for the treating physician. The clinical course of two otherwise healthy pregnant patients with this arrhythmia in whom treatment was withheld is outlined. The indications and guidelines for treatment in relatively asymptomatic patients is discussed.

The association between the on-site availability of cardiac procedures and the utilization of those services for acute myocardial infarction by payer group. The National Registry of Myocardial Infarction 2 Investigators.

BACKGROUND: Prior studies have suggested that in-hospital availability may be an important determinant for the use of invasive cardiac services; however, whether this association is influenced by payer status remains unclear. HYPOTHESIS: The interaction of payer status and the on-site availability of coronary arteriography is associated with increased utilization of this procedure. METHODS: In-hospital availability and utilization of coronary arteriography was ascertained in 275,046 patients with acute myocardial infarction (AMI) enrolled in the National Registry of Myocardial Infarction 2 from June 1994 to April 1996. Logistic regression analyses were performed to determine the association between the on-site availability of cardiac catheterization at the initial hospital and subsequent utilization of coronary arteriography. Similar analyses were performed within Medicare, Medicaid, Commercial, Health Maintenance Organization (HMO), and Uninsured payer groups. RESULTS: Patients initially admitted to hospitals having on-site cardiac catheterization facilities were almost twice as likely to receive coronary arteriography as patients admitted to hospitals without such facilities and later transferred out [un-adjusted odds ratio (OR) = 1.69, 95% confidence interval (CI) 1.66-1.73, p < 0.0001; adjusted OR = 2.08, 95% CI 2.01-2.15, p < 0.0001]. Furthermore, this relationship of increased utilization with greater availability was evident within each payer group, but was highest among those with Commercial insurance and lowest among Medicaid recipients: [Commercial insurance (OR = 2.19, 95% CI 2.07-2.31, p < 0.0001); Uninsured (OR = 1.74, 95% CI 1.57-1.92, p < 0.0001); HMO (OR = 1.67, 95% CI 1.54-1.82, p < 0.0001); Medicare 1.60, 95% CI 1.55-1.64, p < 0.0001); Medicaid (1.46, 95% CI 1.29-1.65, p < 0.0001)]. CONCLUSIONS: Our results show a strong association between in-hospital availability and subsequent utilization of invasive cardiac procedures following AMI among all patients, but the strength of these associations varied among payer status.

Refining the treatment of women with unstable angina--a randomized, double-blind, comparative safety and efficacy evaluation of Integrelin versus aspirin in the management of unstable angina.

BACKGROUND: Although women typically develop coronary artery disease several years after men, once they have symptomatic disease their thromboembolic complications are worse than in men. The mechanism mediating this gender difference in outcome after thromboembolic events is unknown. We previously studied platelet functions in siblings from patients with premature coronary artery disease. We observed that platelets from women are responsive than their male counterparts. In particular, platelets from women stimulated ex vivo with various agonists bind more fibrinogen molecules than platelets from men. HYPOTHESIS: We hypothesized that in patients with acute coronary events, the control of platelet activity might require stronger antagonists in women than in men. METHODS: To test this hypothesis, we investigated retrospectively the results of a trial on Integrelin in unstable angina. RESULTS: We report that platelet aggregation and Holter-detected ischemic episodes are significantly reduced in women with unstable angina treated with the specific GPIIb-IIIa inhibitor, Integrelin, compared with the standard platelet inhibitor aspirin. In contrast, both platelet aggregation and Holter-detected ischemic events are well controlled in men with unstable angina treated with standard therapy including aspirin. CONCLUSION: Integrelin does provide protection in men, but, in contrast with women, not beyond what can be achieved with aspirin. Our data are consistent with the concept that the platelets from women require stronger and more specific inhibitors to limit their activity, and that platelets may play a more important role in women with acute coronary syndromes than in men. Most important, specific GPIIb-IIIa inhibitors may represent a therapeutic option which provides as much suppression of ischemic events in women as they do in men with coronary artery disease.