Effects of allopurinol, propranolol and methylprednisolone on infarct size in experimental myocardial infarction

Shatney, Clayton H.; MacCarter, Dean; Lillehei, Richard C.

doi:10.1016/0002-9149(76)90398-2

Cited by 104 publications

(34 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thirty minutes and again 4 hours after occlusion, dogs received either flurbiprofen, 1 mg/kg, or saline, 1 ml/kg, intravenously. In four dogs in each group, the investigators were blinded to whether flurbiprofen or saline was given.…”

Section: Methodsmentioning

confidence: 99%

Demonstration of lateral and epicardial border zone salvage by flurbiprofen using an in vivo method for assessing myocardium at risk.

Darsee¹,

Kloner²,

Braunwald³

1981

Circulation

View full text Add to dashboard Cite

SUMMARY The purposes of this investigation were (1) to develop an in vivo method of determining the myocardium at risk after experimental coronary occlusion; (2) to define the spatial geometry of the salvageable ischemic border zone; and (3) to assess the ability of flurbiprofen, an antiinflammatory agent, to protect ischemic myocardium from necrosis. Twenty-two open-chest dogs underwent left anterior descending coronary artery occlusion and were randomized to treated (flurbiprofen 1 mg/kg i.v. at 30 minutes and 4 hours after occlusion; n = 11) or control (saline; n = 11) groups. Six hours after occlusion, methylene blue, 3 mI/kg, was injected into the left atrium, and immediately thereafter the hearts were removed and sliced transversely. Areas not perfused by methylene blue (area at risk [Ar]) were traced, planimetered, and compared to the area of necrosis (An) after incubation in triphenyltetrazolium chloride. The Ar for the two groups were similar (control 28.2 + 2.6%; treated 25.2 2.3% of total left ventricle; NS). In control dogs, An/Ar was 96.2 ± 0.7%, with similar values for the epicardium and endocardium. In treated dogs, An/Ar was 66.9 ± 8.9% (p < 0.001), with greater epicardial than endocardial salvage. Topographic superimposition of the An on the Ar showed that salvage occurred both on the epicardial and lateral aspects of the infarct.We conclude that (1) the in vivo methylene blue method of assessing myocardium at risk is useful in standardizing experimental infarct size; (2) flurbiprofen, administered 30 minutes and 4 hours after occlusion, is a potent agent for reducing infarct size; and (3) salvage of myocardium occurs both at the lateral and epicardial borders of the infarct in dogs treated with flurbiprofen.NUMEROUS INTERVENTIONS have been shown in experimental animal studies to preserve myocardium otherwise destined to become necrotic as a result of reduced blood flow.'-" An important omission in many previous studies has been the estimation of the quantity of myocardium that would have been expected to become necrotic without the intervention being tested. The ability to salvage ischemic myocardium has been ascribed to numerous agents, based on a statistically smaller mean infarct size in treated animals compared with the control group. However, the marked variability even in the results of experiments in untreated animals makes this criterion less than adequate. More

show abstract

Section: Methodsmentioning

confidence: 99%

Demonstration of lateral and epicardial border zone salvage by flurbiprofen using an in vivo method for assessing myocardium at risk.

Darsee¹,

Kloner²,

Braunwald³

1981

Circulation

View full text Add to dashboard Cite

show abstract

“…The left ventricle was separated from the rest of the heart and cut in a breadloaf fashion from base to apex. Tissue slices were rinsed in cold tap water and placed in a solution of distilled water (288 ml), phoshate buffer (32 ml, pH 7.4), and nitro blue tetrazolium (100 mg, Sigma) at 37°C for 7 to 12 min.12 17,18 With this method, we verified the location of all sites of drug application in relation to the area of infarction, as well as the transmural nature of the infarction. Data presented in this report were obtained from sites verified to be located above (basal to), within, and below (apical to) the region of latex distribution and transmural myocardial infarction.…”

Section: Methodsmentioning

confidence: 99%

Interruption of sympathetic and vagal-mediated afferent responses by transmural myocardial infarction.

et al. 1985

View full text Add to dashboard Cite

We have demonstrated previously that sympathetic and vagal afferents travel in an apical-to-basal course in the heart, and can be stimulated selectively with epicardial applications of bradykinin and nicotine, respectively. In this study we tested the hypothesis that transmural myocardial infarction interrupts sympathetic and vagal afferent fibers traveling through the infarction and produces regions of afferent denervation in areas apical to the infarction. In open-chest, chloralose-anesthetized dogs, transmural myocardial infarction was created by embolizing a diagonal branch of the left anterior descending coronary artery with a vinyl latex solution that was injected directly into the artery and hardened rapidly. The transmural nature of the infarction was verified by the nitro blue tetrazolium staining technique for dehydrogenase enzymes. Epicardial applications of bradykinin (5 jig) and nicotine (50 ,g) were used to stimulate chemically sensitive sympathetic and vagal afferent nerve endings, respectively. Twenty-nine dogs were studied before and 90 min after creation of transmural myocardial infarction. In 20 dogs, epicardial bradykinin applied before production of transmural myocardial infarction produced a maximal pressor response of 13 3

show abstract

“…6 Presumably, these effects are achieved by improvement in the balance of oxygen supply and demand by inhibition of catecholamine-mediated increases in heart rate, blood pressure and inotropic state. Because an improved balance in oxygen supply and demand would result in reduced regional ischemia, ,B-adrenergic blockade with propranolol might actually improve mechanical performance in ischemic zones despite its negative inotropic effect on nonischemic myocardium.…”

mentioning

confidence: 99%

Effect of oral propranolol on rest, exercise and postexercise left ventricular performance in normal subjects and patients with coronary artery disease.

Marshall¹,

Wisenberg²,

Schelbert³

et al. 1981

Circulation

106

View full text Add to dashboard Cite

SUMMARY The effect of ,B-adrenergic blockade with oral propranolol on resting, exercise and postexercise ventricular performance was evaluated using multiple-gated equilibrium cardiac blood pool images in normal volunteers and patients with coronary artery disease. Propranolol produced no detectable effect on basal left ventricular function in normal subjects at doses producing intermediate (160 mg propranolol/day) and maximal (434 ± 99 mg propranolol/day) # blockade and in patients with coronary artery disease at clinically effective antianginal doses (162 ± 47 mg propranolol/day). During exercise, a dose-related, negative inotropic effect was observed in normal subjects: 160 mg propranolol/day produced a small but statistically insignificant decline in exercise left ventricular performance, whereas maximal , blockade significantly depressed the left ventricular response to exercise. In patients with coronary artery disease, propranolol's effect on exercise ventricular performance depended on the presence or absence of ischemic dysfunction during exercise. In patients with an ischemic functional response to exercise, propranolol significantly improved regional and global performance during and after exercise; in coronary artery disease patients with a normal response to exercise, propranolol had no significant effect on exercise and postexercise ventricular function. These results imply increased sensitivity to the effects of, blockade in ischemic myocardium. In coronary artery disease patients with an abnormal response to exercise and in normal volunteers during , blockade, propranolol's effect on exercise left ventricular performance was independent of changes in ventricular preload and afterload related to heart rate and blood pressure.BETA-ADRENERGIC BLOCKADE with propranolol has been shown to relieve symptomatic ischemic heart disease1'-and limit experimental infarct size.' 6 Presumably, these effects are achieved by improvement in the balance of oxygen supply and demand by inhibition of catecholamine-mediated increases in heart rate, blood pressure and inotropic state. Because an improved balance in oxygen supply and demand would result in reduced regional ischemia, ,B-adrenergic blockade with propranolol might actually improve mechanical performance in ischemic zones despite its negative inotropic effect on nonischemic myocardium. Supportive evidence for this possibility has been obtained from studies tion during acute myocardial ischemia or infarction has yielded contradictory results.'2 14 To date, no studies have been published in man evaluating the effect of fl-adrenergic blockade on mechanical performance in regionally ischemic myocardium. The present study was designed to evaluate the effects of ,B-adrenergic blockade with oral propranolol on resting, exercise and postexercise regional and global left ventricular performance as evaluated by multiple-gated equilibrium cardiac blood pool imaging. The goals of the study were to compare the effects of f-adrenergic blockade on ischemic and nonischemic m...

show abstract

Effects of allopurinol, propranolol and methylprednisolone on infarct size in experimental myocardial infarction

Cited by 104 publications

References 34 publications

Demonstration of lateral and epicardial border zone salvage by flurbiprofen using an in vivo method for assessing myocardium at risk.

Demonstration of lateral and epicardial border zone salvage by flurbiprofen using an in vivo method for assessing myocardium at risk.

Interruption of sympathetic and vagal-mediated afferent responses by transmural myocardial infarction.

Effect of oral propranolol on rest, exercise and postexercise left ventricular performance in normal subjects and patients with coronary artery disease.

Contact Info

Product

Resources

About