Biochemical changes as a result of prolonged strenuous exercise.

OBJECTIVE: To briefly review biochemical changes that may result from prolonged strenuous exercise and to relate these changes to health risk. METHODS: Medline and Sports Discus databases were searched for relevant articles. Additional articles were found using cross referencing and the authors' knowledge of the subject area. RESULTS: Prolonged strenuous exercise may result in a series of biochemical changes that are of concern from a health point of view. Generally, these changes are benign, but some, especially hyponatraemia, are potentially life threatening occurrences. CONCLUSION: Doctors and athletes should be aware of the potentially adverse biochemical changes, especially hyponatraemia, that may result from prolonged strenuous exercise.

Increased circulating monocyte activation in patients with unstable coronary syndromes.

OBJECTIVES: The primary objective of this research was to assess the activation level of circulating monocytes in patients with unstable angina. BACKGROUND: Markers of systemic inflammatory responses are increased in patients with unstable coronary syndromes, but the activation state and invasive capacity of circulating monocytes have not been directly assessed. METHODS: Peripheral blood mononuclear cell (MC) activation in blood samples isolated from patients with stable and unstable coronary artery disease was measured in two studies. In study 1, a modified Boyden chamber assay was used to assess spontaneous cellular migration rates. In study 2, optical analysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a cellular activation marker. RESULTS: Increased rates of spontaneous monocyte migration (p < 0.01) were detected in patients with unstable angina (UA) (Canadian Cardiovascular Society [CCS] angina class IV) on comparison to patients with acute myocardial infarction (MI), stable angina (CCS angina classes I to III) or normal donors. No significant increase in lymphocyte migration was detected in any patient category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparison with MCs from normal volunteers (p < 0.001). A concomitant reduction in the MC response to activation was detected (p < 0.05). CONCLUSIONS: Using two complementary assays, activated monocytes with increased invasive capacity were detected in the circulation of patients with unstable angina. This is the first demonstration of increased monocyte invasive potential in unstable patients, raising the issue that systemic inflammation may both reflect and potentially drive plaque instability.

Impaired left ventricular systolic function after a half-ironman race.

OBJECTIVE: To assess the effects of prolonged strenuous exercise in the form of a half-ironman (HI) race (2 km swim, 90 km bike ride and a 21 km run) on left ventricular systolic function. METHODS AND RESULTS: The study participants consisted of nine male triathletes (mean age +/- SD 32+/-5 years) who competed in the Great White North HI race. Two-dimensional transthoracic echocardiograms were obtained two to three days before the HI (prerace), immediately after completion of the HI (postrace) and 24 h after cessation of exercise. Compared with before the race, performing an HI was associated with a decline in systolic blood pressure (prerace 127.2+/-15.0 mmHg compared with after the race 116.1+/-10.2 mmHg, P<0.05), the systolic blood pressure to end-systolic cavity area ratio (a surrogate for left ventricular contractility - prerace 14.3+/-3.0 mmHg/cm(2) compared with postrace 11.0+/-2.2 mmHg/cm(2), P<0.05) and the fractional area change (prerace 54.1+/-3.8% compared with postrace 47.4+/-5.5%, P<0.05). There was also a concomitant increase in heart rate (prerace 56.3+/-9.4 beats/min compared with postrace 74.1+/-10.7 beats/min, P<0.05), the end-systolic cavity area (prerace 9.2+/-2.2 cm(2) compared with postrace 10.8+/-1.9 cm(2), P<0.05) and the end-systolic cavity area to end-systolic myocardial area ratio (prerace 0.39+/-0.08 compared with postrace 0.51+/-0.1, P<0.05), which returned toward baseline values 24 h after cessation of the HI. CONCLUSIONS: Performing an HI appears to be associated with a transient impairment in left ventricular contractility and a subsequent decline in left ventricular systolic function that tends to return toward normal values within 24 h after cessation of exercise.

Predicting and explaining cardiac rehabilitation attendance.

BACKGROUND: A variety of factors influence patients' health behaviour; these are patterns of practitioner practice, patient characteristics and availability of resources. OBJECTIVES: To examine patient-related factors (demographic, health, psychosocial characteristics) that may influence patients' attendance at cardiac rehabilitation programs and their subsequent behaviour change. PATIENTS AND METHODS: A prospective cohort design was used. Three hundred four acute myocardial infarction and/or coronary artery bypass graft surgery patients from a tertiary care centre in a Western Canadian city were enrolled to participate in telephone interviews at two weeks and again at approximately six months after their hospital discharge. Measures of self-efficacy and behaviour performance for cardiac health maintenance and role resumption, motivation and social support were used at both interview times. A survey focusing on factors influencing patients' choices to attend cardiac rehabilitation programs was also administered at the interview six months after discharge. RESULTS: Attendance at cardiac rehabilitation programs is not associated with patients' risk factor status, and elderly and rural-living patients are at particular risk for nonattendance. CONCLUSIONS: Systematic mechanisms to guide the appropriate referral of patients to this health care resource and administer secondary prevention initiatives to those with limited access to resources need to be a priority in cardiovascular health care.

Left ventricular wall stress during leg-press exercise performed with a brief Valsalva maneuver.

STUDY OBJECTIVES: To assess the effects of leg-press (LP) exercise performed with a brief (2 to 3 s) Valsalva maneuver on left ventricular (LV) systolic function and LV wall stress in five healthy men (mean +/- SD age, 27.6 +/- 2.9 years). METHODS AND MEASUREMENTS: Subjects performed submaximal (80% one repetition maximum [1RM], 337.9 +/- 109.1 kg; 95% 1RM, 400.6 +/- 129.8 kg) and maximal LP exercise (420 +/- 118.6 kg) during which central arterial pressure, intrathoracic pressure, and two-dimensional echocardiographic analysis of LV systolic function and LV wall stress were measured. RESULTS: Compared with baseline, LP exercise resulted in an increase in intrathoracic pressure (baseline, 1.7 +/- 2.9 mm Hg; 80% 1RM, 111.7 +/- 20.2 mm Hg; 95% 1RM, 112.2 +/- 21.1 mm Hg; 100% 1RM, 111.0 +/- 21.3 mm Hg; p < 0.05) and LV end-systolic pressure (baseline, 120.0 +/- 13.2 mm Hg; 80% 1RM, 251.6 +/- 15.3 mm Hg; 95% 1RM, 255.3 +/- 12.2 mm Hg; 100% 1RM, 242.8 +/- 16.5 mm Hg; p < 0.05) with no changes in LV end-systolic transmural pressure (baseline, 118.3 +/- 12.6 mm Hg; 80% 1RM, 140.0 +/- 6.1 mm Hg; 95% 1RM, 143.1 +/- 16.1 mm Hg; 100% 1RM, 131.8 +/- 29.7 mm Hg; p > 0.05), LV end-systolic wall stress (baseline, 91.7 +/- 20.2 kilodyne/cm(2); 80% 1RM, 78.0 +/- 24.4 kilodyne/cm(2); 95% 1RM, 81.4 +/- 25.3 kilodyne/cm(2); 100% 1RM, 85.9 +/- 20.1 kilodyne/cm(2); p > 0.05), or LV fractional area change (baseline, 0.48 +/- 0.03; 80% 1RM, 0.52 +/- 0.11; 95% 1RM, 0.53 +/- 0.06; 100% 1RM, 0.52 +/- 0.05; p > 0.05). CONCLUSION: LP exercise performed with a brief Valsalva maneuver is not associated with an alteration in LV wall stress or LV systolic function in healthy young men.

Psychosocial components of cardiac recovery and rehabilitation attendance.

OBJECTIVE: To examine the relations between demographic factors, specific psychosocial factors, and cardiac rehabilitation attendance. DESIGN: Cohort, repeated measures design. SETTING: A large tertiary care centre in western Canada PATIENTS: 304 consecutive consenting patients discharged following acute myocardial infarction and/or coronary artery bypass graft surgery. MAIN OUTCOME MEASURES: The Jenkins self-efficacy expectation scales and activity checklists of behaviour performance for maintaining health and role resumption, modified version of the self-motivation inventory, and the shortened social support scale. RESULTS: Those who had higher role resumption behaviour performance scores at two weeks after discharge were significantly less likely to attend cardiac rehabilitation programmes. At six months after discharge, those who attended cardiac rehabilitation demonstrated higher health maintenance self-efficacy expectation and behaviour performance scores. Health maintenance self-efficacy expectation and behaviour performance improved over time. Women reported less social support but showed greater improvement in health maintenance self-efficacy expectation. Changes in self-efficacy scores were unrelated to-but changes in health maintenance behaviour performance scores were strongly associated with-cardiac rehabilitation attendance. CONCLUSIONS: Cardiac patients and practitioners may have misconceptions about the mandate and potential benefits of rehabilitation programmes. Patients who resumed role related activities early and more completely apparently did not see the need to "rehabilitate" while those who attended cardiac rehabilitation programmes enhanced their secondary prevention behaviours.

Effects of half ironman competition on the development of late potentials.

OBJECTIVES: The primary purpose was to evaluate the prevalence of late potentials (LPs) in triathletes before and after a half ironman triathlon. The secondary purpose was to examine whether LPs are the electrocardiographic expression of a greater myocardial mass. METHODS: Nine asymptomatic male triathletes (mean age +/- SD, 32 +/- 5 yr) were examined using signal-averaged ECG (SAECG) 48-72 h before (PRE), immediately after (POST), and 24-48 h after the completion (RECOVERY) of a half ironman triathlon. Late potentials were considered to be present if two of the following SAECG anomalies were observed: 1) a prolonged filtered QRS (/QRS) complex (> or = 114 ms), 2) a lengthened low amplitude signal (LAS) duration (>38 ms), and/or 3) a low root mean square (RMS) voltage of the last 40 ms of the fQRS (<20 microV). Left ventricular dimensions were determined at PRE using M-mode echocardiography. RESULTS: There were no significant differences between PRE, POST, and RECOVERY in the fQRS duration, the LAS duration, or the RMS voltage. Two athletes displayed a single SAECG abnormality during PRE and two SAECG anomalies (i.e., LPs) during POST. Late potentials remained in one of the two athletes during RECOVERY. A moderate relationship existed between fQRS and left ventricular mass (r = 0.67, P < 0.05). CONCLUSIONS: Ultra-endurance training and/or events do not lead to LPs in the majority of triathletes who do not possess ventricular arrhythmias. However, a small subset of triathletes do display SAECG anomalies, which are augmented by an ultra-endurance event and may persist even after recovery from the event. Left ventricular mass does not affect overall SAECG parameters.

Effects of 16 weeks of resistance training on left ventricular morphology and systolic function in healthy men >60 years of age.

Resistance training (RT) has gained popularity as an effective form of exercise for older adults. However, the effects of RT on left ventricular (LV) morphology and systolic function in older persons is not well known. The purpose of this study was to assess the effects of 16 weeks of RT on LV morphology and systolic function in healthy older men. Subjects were randomly assigned into a RT group (n = 10; mean+/- SD age, 68 +/- 3 years) or a nonexercise control group (n = 10; age 68 +/- 4 years). RT was performed 3 times per week for 16 weeks at a mean intensity between 60% and 80% of 1 repetition maximum. Leg and bench press 1 repetition maximum and 2-dimensional echocardiography were performed at baseline and after 4, 8, 12, and 16 weeks of training in the RT group. Sixteen weeks of RT was associated with an increase in leg press maximal strength (baseline, 285 +/- 48 kg; after 16 weeks, 367 +/- 47 kg; p <0.05) and bench press maximal strength (baseline, 59 +/- 11 kg; after 16 weeks, 69 +/- 11 kg; p <0.05). No change in leg press maximal strength (baseline, 291 +/- 59 kg; after 16 weeks, 290 +/- 53 kg; p >0.05) or bench press maximal strength (baseline, 60 +/- 9 kg; after 16 weeks, 61 +/- 13 kg; p > .05) was found in control subjects during the same time. RT was not associated with changes in LV cavity size, wall thickness, mass, or systolic function after 4, 8, 12, and 16 weeks of exercise. Thus, 16 weeks of RT was sufficient to increase leg press and bench press maximal strength but did not alter the size or systolic function of the senescent left ventricle.

Effects of long term resistance training on left ventricular morphology.

OBJECTIVES: To assess the effects of long term (mean +/- SD 10+/-5 years, range three to 25 years) resistance training on left ventricular (LV) dimensions and mass. METHODS AND RESULTS: The study participants were 21 elite male power-lifters (age 33.4+/-5.9 years) and 10 sedentary male control subjects (age 30.9+/-4.2 years). Two-dimensionally guided transthoracic M-mode echocardiograms were obtained at rest to quantify LV diastolic cavity dimension, posterior wall thickness, ventricular septal wall thickness and LV mass. Long term resistance training was not associated with an alteration in LV diastolic cavity dimension (resistance trained 54. 4+/-4.3 mm versus control 51.8+/-5.6 mm), ventricular septal wall thickness (resistance trained 9.7+/-1.0 mm versus control 10.1+/-0.7 mm), posterior wall thickness (resistance trained 9.6+/-1.5 mm versus control 9.3+/-1.4 mm) or LV mass (resistance trained 200. 3+/-32.5 g versus control 186.5+/-39.6 g). In addition, no resistance-trained athlete was found to have an LV mean wall thickness above clinical normal limits (12 mm or less). CONCLUSION: Contrary to common beliefs, long term resistance training as performed by elite male power-lifters does not alter LV morphology.

ARCTIC: assessment of haemodynamic response in patients with congestive heart failure to telmisartan: a multicentre dose-ranging study in Canada.

BACKGROUND: The aim of this study was to examine the acute hemodynamic and neurohormonal effects of the angiotensin II antagonist telmisartan relative to placebo in patients with chronic symptomatic (New York Heart Association class II to III) congestive heart failure and to explore the dose-response relation for these effects. METHODS AND RESULTS: After baseline hemodynamic and neurohormonal measurements made with the use of a pulmonary artery and radial arterial catheter, 82 patients were randomly assigned to placebo or 10, 20, 40, or 80 mg of telmisartan in a double-blind fashion. Hemodynamic and neurohormonal measurements were carried out over 24 hours. Telmisartan caused significant decreases in systemic arterial, pulmonary arterial, and pulmonary capillary wedge pressures with evidence of a dose-response relation for each of these parameters. The drug had no significant effects on heart rate, cardiac index, or systemic vascular resistance. Telmisartan did not have consistent effects on either plasma norepinephrine or plasma atrial natriuretic peptide levels, although it did cause significant increases in both plasma renin activity and angiotensin II levels at higher doses. CONCLUSIONS: The acute administration of the angiotensin II antagonist telmisartan was associated with significant dose-dependent reductions in systemic arterial blood pressure and pulmonary pressures. Long-term follow-up studies are required to translate changes in hemodynamic parameters into a clinical benefit.

Cardiac rehabilitation: the forgotten intervention.

OBJECTIVE: To examine the influence of cardiac patients' demographic and health characteristics on physicians' cardiac rehabilitation (CR) referral practice and patients' attendance at such programs. DESIGN: A retrospective, systematic review of consecutive health records. SETTING: A tertiary care centre and the two associated CR programs in a Western Canadian city. PATIENTS: One thousand, three hundred and twenty-eight adult patients (21 years of age or older) discharged following acute myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) and/or coronary artery bypass graft surgery between September 1, 1996 and August 31, 1997. MAIN RESULTS: There were 1245 surviving patients. Evidence of attendance at a CR program was 28.4%, while auditable evidence of referral to a CR program was 23.9%. Stepwise logistic regression revealed that ability to speak English (OR 9.56) living in a city (OR 3.97) and current smoking (OR 1.51) were associated with an increased likelihood, whereas having a history of chronic obstructive pulmonary disease or asthma (OR 0.53), being 70 years of age or older (OR 0.42), having a current admission for PTCA (OR 0.32) and having a history of neurological or cognitive impairment (OR 0.26) were associated with a decreased likelihood of CR attendance. Sex, nature of coronary artery disease risk factors, incidence of postevent complications and pre-event cardiac status (including New York Heart Association status and number of previous events) were not associated with patients' CR attendance. CONCLUSIONS: This study suggests that there is an inconsistent and poorly documented approach to referral of patients to CR programs for reasons that remain unclear. These findings provide a foundation for development and testing of enhanced referral mechanisms and of innovative means to provide rehabilitation services to patients who are at risk for not being referred to or attending CR programs.

Insights into the contemporary epidemiology and outpatient management of congestive heart failure.

OBJECTIVES: To evaluate the epidemiology, prognosis, and patterns of practice in patients with chronic congestive heart failure (CHF) treated and followed at a specialized clinic. METHODS: Prospective cohort study of consecutive patients referred to and followed up in a specialized heart failure clinic between September 1989 and March 1996. RESULTS: Of the 628 patients referred, 566 were confirmed to have CHF. Mean duration of follow-up was 518 +/- 490 days (range 1 to 2192 days). Vital status was available for 99.3% of patients. Mean age at enrollment was 66 years, 68% were men, 67% had an ischemic cause of heart disease, and 78% had systolic dysfunction. Patients with preserved systolic function were older, more often female, had higher mean systolic blood pressures, and a lower prevalence of ischemic heart disease, ventricular arrhythmias, or impaired renal function when compared with those with systolic dysfunction (all P

Reliability and validity of measures of cardiac output during incremental to maximal aerobic exercise. Part II: Novel techniques and new advances.

For exercise physiologists and sport cardiologists, one of the greatest challenges is to develop a valid, reliable, noninvasive and affordable measure of cardiac output (Q). There are several techniques available to measure Q during exercise conditions. These procedures generally provide accurate and reliable determinations of Q during submaximal exercise, but may be limited during maximal exercise conditions. The most commonly used noninvasive measures are the acetylene (C2H2) and carbon dioxide (CO2) rebreathe methods as reviewed in part I of this article. Only the foreign gas rebreathe method, using C2H2, meets all of the criteria of being noninvasive, easy to use, reliable and valid for use during maximal exercise. New methodologies have recently been developed to measure Q during exercise conditions. Although not as popular as the C2H2 and CO2 rebreathe methods, these methods have increasingly gained favour in exercise physiology and sport cardiology settings. The majority of these measures (if performed meticulously), with the exception of impedance cardiography, provide reasonably accurate and reliable determinations of Q. However, the cost of usage and technological limitations during maximal exercise have prevented these techniques from replacing the conventional measures of Q during exercise conditions. Doppler echocardiography and the modified C2H2 methods hold promise for the assessment of Q during maximal exercise. With further advances in these technologies their use in exercise physiology and sport cardiology setting may become more common.

Reliability and validity of measures of cardiac output during incremental to maximal aerobic exercise. Part I: Conventional techniques.

The assessment of cardiac function, particularly cardiac output (Q) during heavy exercise is essential for the evaluation of cardiovascular factors that might limit oxygen transport. A series of invasive and noninvasive techniques has been developed for the assessment and monitoring of Q during resting and submaximal exercise conditions. However, very few techniques have been found to give accurate and reliable determinations of Q during vigorous to maximum exercise. For exercise physiologists and sport cardiologists, maximal exercise data are of primary importance. The 'gold standard' measures of cardiac function are considered to be the direct Fick and dye-dilution methods. These have been widely shown to give accurate and reliable determinations of Q during resting and submaximal exercise conditions; however, their use during maximal exercise conditions is debatable due to the inherent risks involved with each and their increasing inaccuracy during the later stages of vigorous exercise. Thermodilution has also been considered to be a relatively good method for the determination of Q during rest and exercise conditions, but recent authors have questioned its use due to the nature of the measure and its inaccuracy during strenuous exercise. Various noninvasive measures of cardiac function have been developed to overcome the problems associated with the 'gold standard' measures. The first part of this article discusses conventional techniques used in exercise physiology settings. The majority of these provide accurate and reliable determinations of Q during rest and submaximal exercise. However, very few techniques are suitable for maximal exercise conditions. Perhaps only the foreign gas rebreathe using acetylene (C2H2) meets all the criteria of being noninvasive, simple to use, reliable over repeated measurements, accurate and useful during maximal exercise.

Limitation of left ventricular hypertrophy and dysfunction by ACE inhibition after anterior Q-wave myocardial infarction.

To determine whether limitation of left ventricular (LV) hypertrophy with angiotensin-converting enzyme inhibition after myocardial infarction (MI) is associated with improved systolic and diastolic function, quantitative two-dimensional echocardiograms and Doppler of 40 patients, who were randomized on day 3 after a first Q-wave anterior MI to receive therapy with captopril (12.5 mg t.i.d.) or placebo for 6 weeks, were analyzed for LV volumes (Simpson's rule) and mass (3D reconstruction), remodeling parameters and peak early (E) and late (A) transmitral flow velocities and deceleration times (DT) at 3 days, 6 weeks, 6 months and 1 year. Compared to placebo over 1 year, captopril limited (p < 0.001) the increase in diastolic volume and mass, increased LV ejection fraction and diastolic E/A ratio, and decreased DT, the frequency of E and A reversal, infarct expansion and aneurysm frequency but volume/ mass ratio was unchanged. Captopril over the first 6 weeks after a first Q-wave anterior MI limited LV remodeling and hypertrophy and improved both systolic and diastolic function up to 1 year.

Prognostic value of myocardial perfusion imaging with exercise and/or dipyridamole hyperemia in patients with preexisting left bundle branch block.

UNLABELLED: The detection of myocardial ischemia in patients with preexisting left bundle branch block (LBBB) remains problematic. Pharmacologic hyperemia with dipyridamole is now used routinely in such patients for detection of significant coronary artery disease. Little data exists on the prognostic value of cardiac nuclear scintigraphy in patients with preexisting LBBB. The purpose of our study was to determine the prognostic value of cardiac nuclear scintigraphy in patients with preexisting LBBB. METHODS: Ninety-six patients with preexisting LBBB underwent perfusion imaging between July 1987 and June 1995. Thirty-seven underwent planar 201Tl imaging, and 59 underwent SPECT sestamibi imaging. Images were interpreted by consensus of two experienced observers and classified as normal, abnormal low risk and abnormal high risk. Outcomes measured were survival, cardiac and noncardiac death. The final study group included 43 women and 53 men, aged 42-83 (mean 66 +/- 9). Average follow-up was 3.4 +/- 2.1 yr. RESULTS: Of the 96 patients examined, 31 had normal scans, 39 had low-risk scans and 26 had high-risk scans. At the end of the study period, 27 patients with normal scans were still alive while 2 suffered cardiac death and 2 suffered noncardiac death. Of those with low-risk scans, 36 survived while 2 suffered cardiac death and 1 suffered noncardiac death. Finally, of those with high-risk scans, 17 survived while 8 suffered cardiac death and 1 suffered noncardiac death (chi-square test, p = 0.020). CONCLUSION: Dipyridamole imaging is an important prognostic tool for predicting future cardiac events in patients with preexisting LBBB and aids in their risk stratification for coronary artery disease.

Safety and efficacy of monotherapy with fantofarone, a novel calcium channel antagonist, in patients with chronic stable angina pectoris. Fantofarone Study Group.

Fantofarone is a calcium channel antagonist of a class (sulfone indolizine) that is structurally different from the existing classes. The primary cardiac action of fantofarone is on the sinus node, although it is also a potent peripheral and coronary vasodilator. This is a multicenter, double-blind, randomized, placebo-controlled, dose-ranging study evaluating the efficacy and safety of fantofarone. Three hundred and thirty patients were included as intent-to-treat, and 299 patients completed the entire protocol. Doses of fantofarone studied were 50, 100, 150, and 200 mg twice daily. The 100- and 150-mg groups demonstrated antianginal activity, prolonging exercise time walking on a treadmill by 38 and 45 seconds to the endpoint of moderate angina, compared with the placebo group. Sinus bradycardia occurred in 23 patients and was somewhat dose-related. Systolic blood pressure at rest and while exercising was not altered by therapy. No deaths occurred in the treated group. Of the 20 patients in the treatment group who did not complete the protocol (compared with 23 in the placebo group) 6 were dropped because of symptomatic bradycardia, 5 because of increased angina, and 9 for miscellaneous reasons. In doses of 100 mg to 150 mg twice daily, monotherapy fantofarone was effective and safe in the treatment of patients with chronic, stable angina pectoris.

Virus-encoded serine proteinase inhibitor SERP-1 inhibits atherosclerotic plaque development after balloon angioplasty.

BACKGROUND: Recurrent atherosclerotic plaque growth, restenosis, is a significant clinical problem after interventional procedures. Initiation of restenosis involves activation of inflammatory and thrombotic cascades, which are regulated by serine proteinase enzymes and inhibitors. We have investigated the use of a viral serine proteinase inhibitor, SERP-1, to reduce plaque development after primary balloon angioplasty. This is the first experimental report of the use of a viral anti-inflammatory protein for the prevention of atherosclerosis. METHODS AND RESULTS: Seventy-four cholesterol-fed rabbits were treated with either local or systemic infusions of SERP-1 protein (or control solutions) after balloon-mediated injury. Sites of SERP-1 infusion in rabbits had dramatically reduced plaque compared with control infusions at the 4-week follow-up. At low-dose infusions (30 to 300 pg), only the primary infusion site had a demonstrable decrease in plaque, whereas at higher-dose infusions (> 3000 pg), a generalized reduction in plaque development was detected. An associated decrease in mononuclear cell infiltration of the arterial wall was detected after SERP-1 infusion within the first 24 hours. Infusion of an active-site mutant of SERP-1 (P1-P1', ala-ala) lacking serine proteinase inhibitory activity failed to prevent plaque growth. CONCLUSIONS: Purified SERP-1, a virus-encoded secreted glycoprotein, reduces plaque growth after primary balloon-mediated injury. Plaque development is decreased by inhibition of serine proteinase activity and is associated with a focal reduction in macrophage infiltration immediately after injury. Investigation of serine proteinase inhibitors may provide new insight into the regulation of arterial responses to injury.