Early increase in left ventricular compliance after myocardial infarction.

The left ventricular (LV) pressure-volume (P-V) relationship is a resultant of several determinants, including initial ventricular volume, geometry, and wall stiffness. A quantitative index of one of these determinants, LV wall stiffness, was developed from a mathematical analysis of the isolated P-V relationship. Since this relationship was exponential, stiffness (dP/dV) could be expressed by the equation dP/dV = aP + b, where a and b are constants. The a constant, termed the passive elastic modulus, was independent of both pressure and volume, was modified only slightly by changes in geometry, and thus was primarily affected by changes in wall stiffness. LV wall stiffness was assessed by determination of the passive elastic modulus in eight normal canine hearts and in five hearts 1 hr after acute myocardial infarction. The value of the passive elastic modulus for the normal canine LV was found to be 0.099+/-0.006 cc(-1). In the five infarcted hearts there was a modest, but statistically insignificant, shift of the P-V curves from control, such that for the same pressure the infarcted hearts contained greater volume. However, the passive elastic modulus decreased 41% to 0.057+/-0.006 cc(-1) (P < 0.001). Thus, although LV wall stiffness may increase later in the course of myocardial infarction, it is concluded that it was significantly decreased 1 hr after infarction. Calculation of the passive elastic modulus provided a sensitive means of detecting such changes, whereas P-V curves alone were generally insensitive.

Nicotine does not influence arterial lipid deposits in rabbits exposed to second-hand smoke.

BACKGROUND: Second-hand smoke (SHS) accelerates atherogenesis and impairs vascular function. The role of nicotine in this process has not been defined. METHODS AND RESULTS: To examine the potential effects of nicotine on atherogenesis and vascular function, 48 rabbits receiving a 0.5% cholesterol diet were randomized to control (cholesterol diet only), SHS from nicotine-standard research cigarettes (SHS-ST), and SHS from nicotine-free research cigarettes (SHS-NF). The SHS rabbits were exposed to 48 nicotine-standard (12 animals) or nicotine-free (12 animals) cigarettes/d, 5 d/wk for 10 weeks. Air carbon monoxide and particulates and plasma carboxyhemoglobin were significantly higher in the 2 SHS groups than the control group (P<0.001). The SHS-ST group had significant increases in plasma nicotine and cotinine compared with the other groups (P<0.001). There was no difference in serum lipids. Lipid lesions were increased in both SHS groups (54+/-5% [SEM] aorta and 66+/-4% pulmonary artery, 53+/-7% and 69+/-4%, and 39+/-4% and 43+/-3% in the SHS-ST, SHS-NF, and control groups, respectively; P=0.049 aorta and P<0.001 pulmonary artery). CONCLUSIONS: SHS exposure increased arterial lipid lesions, but nicotine did not contribute significantly to this effect. This effect is presumably due to other combustion products in the smoke.

Magnetic resonance-based assessment of global coronary flow and flow reserve and its relation to left ventricular functional parameters: a comparison with positron emission tomography.

BACKGROUND: Measurement of coronary sinus blood flow (CSF) by phase-contrast magnetic resonance (PC-MR) imaging at rest and during hyperemia may allow noninvasive assessment of global coronary hemodynamics. METHODS AND RESULTS: Sixteen healthy volunteers (age, 22 to 32 years) were examined with MR and PET in random order within 1 to 2 days. At rest and during hyperemia (dipyridamole 0.56 mg/kg), CSF was measured by a cine PC-MR technique (temporal resolution, 40 ms; spatial resolution, 1.25x0.8 mm(2)), and myocardial blood flow (MBF) was measured by [(13)N]NH(3) PET. PET and MR agreed closely for coronary flow reserve (CFR; mean difference, 2.2+/-14.7%; Bland-Altman method). CSF divided by either total left ventricular mass or an estimate of drained myocardium (LVM(drain)) correlated highly with PET flow data (r=0.93 and 0.95, respectively) and with measures of oxygen demand, ie, heart rate, afterload-corrected fiber shortening, and peak systolic stress determined by MR (overall correlation coefficients, 0.81 and 0.87, respectively, multivariate analysis). CSF/LVM(drain) did not differ significantly from PET-derived MBF (difference, 3.6+/-16.6%). In orthotopic heart transplant recipients (n=9), CFR was reduced and blood supply-demand relationships at rest were shifted toward higher flows (P<0.0001). CONCLUSIONS: This integrated MR approach allows comprehensive assessment of autoregulated and hyperemic coronary flow and is suitable for serial measurements in patients. In transplanted hearts, elevated resting flow is the major cause of reduced CFR.

Pathophysiology and current therapy of congestive heart failure.

Congestive heart failure is a common clinical syndrome, with a relatively poor prognosis in its advanced stages. During the development of heart failure, there is a decline in myocardial contractility and activation of neurohormonal systems. An overshoot of some of these compensatory mechanisms sets the stage for therapeutic interventions. Any of the three therapeutic classes of drugs (inotropic drugs, diuretics or vasodilators) can be used as first-line therapy. Other classes can be added to produce additive effects on ventricular function. Because vasodilators have been shown to prolong life, they should be used routinely in patients with heart failure. Arrhythmias and sudden death are relatively common in heart failure, although the value of antiarrhythmic therapy is less certain. Although current therapy is very helpful in patients with heart failure, it is clear that preventive approaches will be more effective in decreasing morbidity and mortality.

Vasodilator therapy for acute myocardial infarction and chronic congestive heart failure.

Vasodilator therapy is useful adjunctive therapy in the management of both acute and chronic heart failure. Arteriolar dilators, such as hydralazine, increase cardiac output by decreasing the elevated peripheral vascular resistance that occurs in heart failure. Venodilators, such as nitrates, decrease ventricular filling pressures by redistributing blood so that more is pooled in peripheral veins. Vasodilators that produce both effects (nitro-prusside, prazosin, captopril, for example) are usually helpful in short-term improvement of hemodynamics. Long-term treatment with nonparenteral vasodilators often reduces symptoms and increases exercise tolerance, although there is inconclusive evidence regarding the effects of these agents on mortality. In acute myocardial infarction, intravenous vasodilators frequently improve cardiac performance. Evidence regarding their beneficial effects on infarct size and immediate mortality is encouraging but inconclusive. There is little evidence that they prolong life in patients who survive cardiogenic shock and leave the hospital. Thus, vasodilators can improve hemodynamics and lessen symptoms, but more evidence is needed regarding their long-term effects on survival.

Eighteen-hour preservation of rat hearts with hexanol and pyruvate cardioplegia.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of 1-hexanol as an arresting agent and pyruvate as a substrate in a cardioplegic solution. BACKGROUND: Heart transplantation is limited in part by the short preservation time of donor hearts. Better preservation techniques would improve patient survival and the time and geographic area for using donor hearts. We previously showed that a cardioplegic solution containing ethanol and pyruvate was superior to a conventional high potassium cardioplegic solution in 24-h cold storage of hamster hearts. Hexanol, a more potent arresting agent than ethanol, might be a more suitable alcohol. METHODS: Rat hearts were arrested and stored for 18 h at 4 degrees C with an ethanol (3 vol% = 510 mmol/liter) or 1-hexanol (4 mmol/liter) and pyruvate (10 mmol/liter) cardioplegic solution, St. Thomas' Hospital solution and Stanford solution and subsequently reperfused for 1 h at 35 degrees C. In other groups of hearts, basal oxygen consumption and rest intracellular calcium (Indo 1 technique) were evaluated during ethanol-, hexanol- and potassium-induced cardiac arrest. RESULTS: The percent recovery of left ventricular developed pressure and rate-pressure product were significantly better with the hexanol cardioplegic solution (67 +/- 21% and 58 +/- 19%, respectively; p < 0.05 for all comparisons) compared with the ethanol (10 +/- 7% and 5 +/- 4%), St. Thomas' Hospital (14 +/- 6% and 10 +/- 5%) and Stanford solutions (2 +/- 2% and 2 +/- 1%, respectively). Exclusion of ethanol and hexanol from storage solutions did not influence functional recovery. Values for oxygen consumption after 15- and 30-min ethanol- and hexanol-induced arrest were significantly lower than those after potassium-induced cardiac arrest. There was no difference in the rest intracellular calcium during cardiac arrest induced by the three arresting agents. CONCLUSIONS: A hexanol and pyruvate cardioplegic solution was more favorable than ethanol or conventional solutions for long-term cold storage of rat hearts. The beneficial effects of hexanol may have been provided in part by lower energy consumption during hexanol-induced cardiac arrest. These results may have implications for preservation of hearts for heart transplantation.

Evaluation of clinical competence in cardiovascular disease.

The American Board of Internal Medicine has called on directors of cardiology training programs to establish systems to evaluate, document and substantiate those components of overall clinical competence considered essential for certification in the subspecialty. Many of these can be assessed only by repeated direct observations. In particular, proficiency is now required in advanced cardiac life support including cardioversion, electrocardiography (including ambulatory electrocardiographic monitoring) and exercise testing, echocardiography, insertion of arterial lines and right heart catheterization (including insertion of temporary pacemakers). The goal of this expanded evaluation program is to ensure that the public and the profession can identify, through certification, physicians with demonstrated excellence in cardiovascular disease.

Safety and efficacy of esmolol (ASL-8052: an ultrashort-acting beta-adrenergic blocking agent) for control of ventricular rate in supraventricular tachycardias.

Esmolol (ASL-8052) is a new intravenous beta-adrenergic blocking agent that has exhibited both cardiac selectivity and an extremely short half-life in animal studies. To assess its clinical efficacy, 16 patients were studied with a rapid ventricular rate associated with atrial flutter (n = 2), atrial fibrillation (n = 10), atrial tachycardia (n = 2) and multifocal atrial tachycardia (n = 2). During a 30 minute control period of observation, the ventricular rate ranged from 121 to 150 beats/min (mean 133.2 +/- 10.6). Using a double blind crossover method, esmolol was infused intravenously for a maximum of 60 minutes. Infusions of 50, 100, 150, 200, 250 and 300 micrograms/kg per min were given in consecutive 5 minute periods (during the first minute of each period, a loading dose of 500 micrograms/kg was given). Not all patients received the maximal dose. A response was defined as conversion to sinus rhythm or a 20% reduction in ventricular rate. One patient with atrial fibrillation associated with the Wolff-Parkinson-White syndrome did not respond. In the remaining 15 patients, their highest esmolol infusion rate was maintained for an additional 30 minutes. This resulted in a reduction in ventricular rate to a mean of 97.8 +/- 12.9 beats/min (range 72 to 119) (p less than 0.001). Conversion from flutter/fibrillation to sinus rhythm occurred in two patients. During the infusion, six had transient asymptomatic hypotension that was mild and manageable. After infusion, ventricular rate and blood pressure returned rapidly toward control values within 25 minutes in patients without conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary angioplasty and thrombolysis for acute myocardial infarction: an evidence summary.

Coronary angioplasty is being increasingly used as the primary treatment for patients with acute myocardial infarction, but controversy remains over its potential adoption in preference to thrombolysis as standard care. This report summarizes the published evidence on health outcomes after primary angioplasty compared with thrombolysis or no intervention for patients with acute myocardial infarction. The data tables presented provide the scientific groundwork to assist physicians and other policy-makers in deciding which interventions to provide for broad populations of patients.

Attenuation of the circadian patterns of myocardial ischemia with nifedipine GITS in patients with chronic stable angina. N-CAP Study Group.

The Nifedipine Gastro-Intestinal Therapeutic System (GITS) Circadian Anti-ischemia Program (N-CAP) was designed to test the effect of nifedipine GITS as monotherapy or in combination with a beta-adrenergic blocking agent on the circadian pattern of angina and silent ischemia in patients with chronic stable angina. At 118 sites in the United States, 1,174 patients were screened for entry into this study. To be eligible for participation patients were required to have at least two episodes of angina a week and at least two episodes of myocardial ischemia during 48-h ambulatory electrocardiographic (ECG) monitoring during the baseline placebo period. A total of 207 patients completed all phases of the study. Beta-blockers were continued in those patients already receiving them. In this 7- to 10-week single-blind placebo withdrawal study, a 1-week placebo run-in was followed by up to 5 weeks of single-blind titration with nifedipine GITS, a 4-week efficacy phase with an established dose and a final single-blind 2-week placebo withdrawal period. Ambulatory ECG monitoring was performed at the end of each placebo phase and at the end of the efficacy phase with a digital monitoring device that was validated in a pilot study. Overall, nifedipine GITS significantly reduced the weekly number of anginal episodes from 5.7 to 1.8 (p = 0.0001) and the number of ischemic events from 7.3 to 4 (p = 0.0001) reported during the 48-h monitoring periods, with a significant increase in both during the placebo withdrawal period. The baseline circadian pattern of ischemia showed an early morning peak and a secondary peak in the afternoon. Nifedipine GITS significantly reduced ischemia during the 48-h period when administered as monotherapy or in combination with a beta-blocker. Patients were also randomized to receive nifedipine GITS in either a morning or an evening dose. The two regimens resulted in equal anti-ischemic benefit. The primary side effect of nifedipine GITS was edema, which was dose related. In summary, nifedipine GITS reduced the number of anginal and ischemic episodes when given alone or in combination with a beta-blocker. Nifedipine GITS had a sustained effect: a single daily dose was effective over 24 h regardless of whether it was administered in the morning or evening. This study also suggests that combination therapy with nifedipine GITS and a beta-blocker is especially efficacious in reducing ischemia.

Verapamil prevents the development of alcoholic dysfunction in hamster myocardium.

Ethanol causes depression of cardiac function. A new model in hamsters was developed for studying ethanol-induced myocardial dysfunction and the effects of verapamil in preventing the functional and metabolic derangements caused by ethanol ingestion were evaluated. Ethanol was added to the drinking water of hamsters in increasing amounts, reaching 50% from 5 weeks on. A control group received plain water only. A third group had verapamil (1.75 mg/cc) added to the ethanol-water mixture to evaluate its potential protective effect. After 5, 7 and 12 weeks, the animals were killed and the hearts perfused using a Langendorff heart preparation. Pressures were recorded and metabolic analysis was performed by the freeze-clamp technique. Compared with control hearts, the hearts from hamsters ingesting ethanol showed significant depression of developed pressure and maximal rate of rise in pressure. There was also significant depression of high energy phosphates and adenosine. The animals drinking the ethanol-verapamil mixture had preservation of left ventricular performance and high energy phosphates, with measurements indistinguishable from those of the control group. In summary, verapamil prevented the development of myocardial depression and preserved normal energy metabolism in hearts of hamsters drinking 50% ethanol.

Inhibition of atherosclerosis by fish oil in cholesterol-fed rabbits.

To evaluate the effects of dietary fish oil on cholesterol-induced atherosclerosis, 36 New Zealand rabbits in four groups were fed a 0.3% cholesterol diet for 10 weeks. One group served as control, whereas groups I, II and III received 1, 2 and 3 ml/day, respectively, of fish oil (Protochol, eicosapentaenoic acid, 180 mg, and docosahexaenoic acid [DHA], 120 mg/ml). The percent of aortic and pulmonary atherosclerosis was measured by planimetry of sudanophilic lesions. The percent of aortic lesions in the control group was 59 +/- 22%. The two higher dose fish oil groups showed a significant reduction in aortic lesions: group I (40 +/- 26%, p = NS), group II (18 +/- 11%, p less than 0.01) and group III (36 +/- 22%, p less than 0.05). Area of pulmonary artery lesions was significantly higher in the control group (48 +/- 22%) as compared with group I (15 +/- 13%, p less than 0.01), group II (4 +/- 3%, p less than 0.01) and group III (8 +/- 9%, p less than 0.01). The high cholesterol diet in the control group decreased bleeding time from 82 +/- 17 to 59 +/- 22 s (p less than 0.05). Groups II and III showed an increased bleeding time (62 +/- 15 to 84 +/- 17 s and 66 +/- 22 to 95 +/- 27 s; p less than 0.05, respectively). Fish oil did not significantly alter total serum cholesterol and high density lipoprotein (HDL) cholesterol. In group II triglyceride decreased from 128 +/- 22 to 64 +/- 25 mg/dl (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Enalaprilat, a new parenteral angiotensin-converting enzyme inhibitor: rapid changes in systemic and coronary hemodynamics and humoral profile in chronic heart failure.

Systemic and coronary hemodynamic, metabolic and humoral effects of a new intravenous angiotensin-converting enzyme inhibitor, enalaprilat, were evaluated in 14 patients with chronic heart failure. Onset of hemodynamic action occurred within 15 minutes and persisted for 6 hours. At the time of peak effect, there was a significant reduction in mean arterial pressure (-21%) and pulmonary capillary wedge pressure (-33%). Systemic vascular resistance decreased by 32% and stroke volume index increased by 20%. These systemic hemodynamic changes indicate improved left ventricular function. There was a substantial sustained reduction in rate-pressure product initially without a change in coronary sinus blood flow or myocardial oxygen consumption. There was also reduced myocardial oxygen extraction and augmented coronary sinus oxygen saturation at 30 minutes and 1 hour. In three patients, abnormal myocardial lactate extraction, present before enalaprilat, changed to uptake after enalaprilat, indicating amelioration of myocardial ischemia that was not clinically manifest. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma renin activity increased and plasma aldosterone decreased. These findings suggest that enalaprilat produces inhibition of the angiotensin-converting enzyme and consequent beneficial systemic hemodynamic changes in heart failure. In some patients with heart failure, silent myocardial ischemia at rest can occur and can be alleviated with enalaprilat. Decreased myocardial oxygen extraction, increased coronary sinus oxygen saturation and lack of expected decrease in coronary sinus blood flow despite reduced rate-pressure product suggest transient coronary vasodilation by enalaprilat.

Variability in coronary hemodynamics in response to ergonovine in patients with normal coronary arteries and atypical chest pain.

Because an increase in coronary vascular resistance in response to ergonovine maleate has been suggested as a possible diagnostic aid for variant angina, changes were evaluated in coronary hemodynamics and serial myocardial thallium-201 perfusion scans in 15 patients without angina and with normal coronary arteries in response to ergonovine (0.05, 0.10 and 0.20 mg intravenously). For the group, heart rate-blood pressure product increased significantly (p less than 0.001) without any change in coronary sinus flow, coronary vascular resistance, myocardial oxygen extraction, arterial-coronary sinus oxygen difference and lactate extraction. In 7 of 15 patients, however, coronary vascular resistance increased (mean 39%, range 11 to 75%, probability [p] less than 0.001), and coronary sinus flow decreased (14%, p less than 0.001), despite an increase in heart rate-blood pressure product (36%, p less than 0.02). No electrocardiographic, metabolic or thallium-201 scan abnormalities occurred. Therefore, significant increases in coronary vascular resistance in response to ergonovine may occur in patients with normal coronary arteries and atypical chest pain.

Enalapril: a new angiotensin-converting enzyme inhibitor in chronic heart failure: acute and chronic hemodynamic evaluations.

Hemodynamic effects of the new oral angiotensin-converting enzyme inhibitor, enalapril, were evaluated acutely in 15 patients with chronic heart failure and in 7 patients after 4 weeks of maintenance therapy. Initial hemodynamic effects were characterized by a significant increase in cardiac index (from 2.1 +/- 0.7 to 2.6 +/- 0.7 liters/min per m2) and a decrease in pulmonary capillary wedge pressure (from 30 +/- 6 to 24 +/- 7 mm Hg), right atrial pressure (from 14 +/- 5 to 11 +/- 4 mm Hg), mean arterial pressure (from 96 +/- 16 to 80 +/- 17 mm Hg) and systemic vascular resistance (from 1,820 +/- 480 to 1,200 +/- 410 dynes . s . cm-5) without any significant change in heart rate, pulmonary artery pressure and pulmonary vascular resistance. During maintenance therapy, the dose of diuretic drugs had to be increased because of systemic venous hypertension. Repeat hemodynamic study showed that after chronic therapy, cardiac index (2.1 +/- 0.7 vs. 3.0 +/- 0.08 liters/min per m2) and stroke volume index (24 +/- 10 vs. 36 +/- 7 ml/m2) remained elevated and pulmonary capillary wedge pressure was lower than control (30 +/- 6 vs. 16 +/- 6 mm Hg), indicating sustained improvement in left ventricular performance. Plasma renin activity increased and plasma norepinephrine levels decreased after enalapril therapy and these humoral changes persisted during maintenance therapy. All patients receiving chronic therapy had symptomatic improvement. Significant hypotension, which occurred in five patients at the initiation of therapy, appears to be the major side effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous and oral MDL 17043 (a new inotrope-vasodilator agent) in congestive heart failure: hemodynamic and clinical evaluation in 38 patients.

To evaluate the potential benefit of MDL 17043, a new inotrope-vasodilator agent, in the short- and long-term management of severe heart failure, its hemodynamic effects were determined after both intravenous (cumulative average dose 3.7 mg/kg) and oral (average 18.4 mg/kg) administration in 38 patients with severe intractable heart failure. After both intravenous and oral therapy, cardiac index increased from a control value of 2.1 +/- 0.4 to 3.6 +/- 0.9 liters/min per m2, p less than 0.001 (intravenous) and from 2.2 +/- 0.5 to 3.4 +/- 0.6 liters/min per m2, p less than 0.001 (oral). Pulmonary capillary wedge pressure decreased from 26 +/- 6 to 14 +/- 7 mm Hg (p less than 0.001) and from 26 +/- 7 to 18 +/- 8 mm Hg (p less than 0.001) after intravenous and oral routes, respectively. Stroke volume index and stroke work index increased, and right atrial and pulmonary arterial pressures and systemic vascular resistance decreased by similar magnitude after both intravenous and oral MDL 17043 (all p less than 0.001). The hemodynamic effects persisted during 4 hours of observation. Thirty-seven patients were discharged while receiving MDL 17043 therapy and were followed up for a mean of 5.6 months (range 0.5 to 13). Thirty-three of the 37 patients had short-term improvement clinically by at least one New York Heart Association functional class. Undesirable effects, including nausea (35%), anorexia (27%), fluid retention (24%) and thrombocytopenia (less than 1%), necessitated discontinuation of therapy in 11 patients (30%) who were receiving multiple drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Regression of atherosclerosis in cholesterol-fed rabbits: effects of fish oil and verapamil.

Previous studies have shown that either fish oil or verapamil can attenuate the development of atherosclerosis in the lipid-fed rabbit. The present study was designed to evaluate the individual and combined effects of these two interventions on regression. Seventy New Zealand rabbits in seven groups (10 each) were fed a 0.3% cholesterol diet for 10 weeks. Control group C10 was then killed. Control group C20 was fed a 0.3% cholesterol diet and the other five groups were fed a normal diet for an additional 10 weeks. Group F in three treated groups received 2 ml/day of fish oil (Proto-Chol, eicosapentaenoic acid, 180 mg/ml and docosahexaenoic acid, 120 mg/ml) by gavage. Group V received verapamil, 2 g/1,000 ml drinking water, and group FV received both fish oil and verapamil for an additional 10 weeks. Group CF (control for fish oil) received 2 ml/day of water by gavage and group CV (control for verapamil) received water without gavage for an additional 10 weeks. The percent of aortic and pulmonary atherosclerosis was measured by planimetry of sudanophilic lesions. The percent of aortic lesions in the four control groups (C20, C10, CF and CV) was 57 +/- 22, 40 +/- 15, 40 +/- 14 and 33 +/- 25%, respectively. The fish oil or verapamil groups (F, V, FV) showed a significant reduction in aortic lesions: 15 +/- 17%, p less than 0.05; 16 +/- 12%, p less than 0.05; and 26 +/- 24%, p = NS, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Application of cine nuclear magnetic resonance imaging for sequential evaluation of response to angiotensin-converting enzyme inhibitor therapy in dilated cardiomyopathy.

Cine nuclear magnetic resonance (NMR) imaging was used to serially measure cardiovascular function in 17 patients with New York Heart Association class II or III heart failure and left ventricular ejection fraction less than or equal to 45% who were treated for 3 months with benazepril hydrochloride, a new angiotensin-converting enzyme inhibitor, while continuing treatment with diuretic agents and digoxin. Interobserver reproducibilities for ejection fraction (r = 0.94, SEE 3.3%), end-systolic volume (r = 0.98, SEE 10.6 ml), end-diastolic volume (r = 0.99, SEE 8.29 ml), end-systolic mass (r = 0.96, SEE 15.4 g), end-systolic wall stress (r = 0.91, SEE 10 dynes.s.cm-5) and end-systolic stress/volume ratio (r = 0.85, SEE 0.13) demonstrated applicability of cine NMR imaging for the serial assessment of cardiovascular function in response to pharmacologic interventions in patients with heart failure. During 12 weeks of treatment with benazepril, ejection fraction increased progressively from 29.7 +/- 2.2% (mean +/- SEM) to 36 +/- 2.2% (p less than 0.05), end-diastolic volume decreased from 166 +/- 14 to 158 +/- 12 ml (p = NS), end-systolic volume decreased from 118 +/- 12 to 106 +/- 11 ml (p less than 0.05), left ventricular mass decreased from 235 +/- 13 to 220 +/- 12 g (p less than 0.05), end-systolic wall stress decreased 29% from 90 +/- 5 to 64 +/- 5 dynes.s.cm-5 (p less than 0.05), end-systolic pressure decreased from 92.6 +/- 3.7 to 78.8 +/- 5.3 (p less than 0.05) and end-systolic stress/volume ratio, a load-independent index of contractility, decreased from 0.83 +/- 0.05 to 0.67 +/- 0.06 (p less than 0.05), demonstrating that improved ejection fraction is due to afterload reduction.

Passive smoking increases experimental atherosclerosis in cholesterol-fed rabbits.

OBJECTIVES: We evaluated the influence of passive smoking on experimental atherosclerosis in cholesterol-fed rabbits. BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been epidemiologically linked to death from ischemic heart disease in nonsmokers. METHODS: New Zealand male rabbits were randomly divided into three groups after 2 weeks of a 0.3% cholesterol diet. Sixteen rabbits were exposed to a high and 16 rabbits to a low dose of ETS; 32 rabbits located in another room served as an unexposed control group. After 10 weeks of ETS exposure, all rabbits were killed, and the percent of aortic and pulmonary artery endothelial surfaces covered by lipid lesions was measured by staining and planimetry. RESULTS: Average air nicotine, carbon monoxide and total particulate concentrations were 1,040 micrograms/m3, 60.2 ppm and 32.8 mg/m3 for the high dose ETS group, 30 micrograms/m3, 18.8 ppm and 4.0 mg/m3 for the low dose ETS group and < 1 microgram/m3, 3.1 ppm and 0.13 mg/m3 for the control group. The percent atherosclerotic involvement of the aorta and pulmonary artery increased significantly with ETS exposure (for the aorta, 30 +/- 19% [mean +/- SD] for the control group, 36 +/- 14% for the low dose ETS group and 52 +/- 21% for the high dose ETS group, p < 0.001; for the pulmonary artery, 22 +/- 15% for the control group, 29 +/- 25% for the low dose ETS group, and 45 +/- 12% for the high dose ETS group, p < 0.001). Bleeding time was significantly shorter in the two ETS groups than in the control group (86 +/- 17 vs. 68 +/- 15, 68 +/- 18 s, p < 0.001). There were no significant differences in serum triglycerides, cholesterol and high density lipoprotein cholesterol at the end of the study. CONCLUSIONS: Environmental tobacco smoke affects platelet function and increases aortic and pulmonary artery atherosclerosis. This increase of atherosclerosis was independent of changes in serum lipids and exhibited a dose-response relation. These results are consistent with data from epidemiologic studies demonstrating that ETS increases the risk of death due to heart disease.

Initial cost of primary angioplasty for acute myocardial infarction.

OBJECTIVES: We sought to evaluate the initial economic cost of primary angioplasty for acute myocardial infarction under varying assumptions about whether a cardiac catheterization laboratory exists, whether services are provided during night and weekend hours and how cardiovascular surgical backup is arranged. BACKGROUND: Primary angioplasty for acute myocardial infarction has resulted in clinical outcomes superior or equal to those obtained with thrombolysis in recent studies, but its future implementation depends greatly on its cost and cost-effectiveness. There is a gap in knowledge about the true economic costs of this procedure, and understanding costs under a variety of hypothetic scenarios is important in planning whether and how the procedure should be offered to broad groups of patients. METHODS: A generalizable spreadsheet model was constructed to calculate the cost of primary angioplasty at a single hospital with assumptions based on data from a large nonprofit health maintenance organization (Kaiser Permanente). The following baseline assumptions were made: 1) A total of 200 patients with myocardial infarction presented to the hospital each year; 2) primary angioplasty was offered for 10 years; 3) the hospital had a cardiac catheterization laboratory; 4) costs of night call for technical personnel and cardiovascular surgical backup were already covered. Other scenarios were modeled to represent different assumptions about existing resources. RESULTS: Under the baseline assumptions, primary angioplasty cost $1,597/procedure. If night call for technical personnel were a new expense, the average cost would be > or = $3,206. If a new cardiac catheterization laboratory needed to be built, costs would range from $3,866 to $14,339/procedure, depending on how cardiovascular surgical backup was provided. Results were sensitive to assumptions about the annual volume of myocardial infarctions, the number of years the procedure was offered and the costs of labor, construction and equipment. CONCLUSIONS: The initial cost of providing primary angioplasty for acute myocardial infarction varies greatly, depending on the setting in which it is provided. To provide information for clinical policy decisions, a cost-effectiveness model is needed that combines these initial costs with data on survival, quality of life and rates and costs of subsequent cardiac procedures.