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January 16, 1991, Vol 265, No. 3 >
ARTICLE | January 16, 1991

Circadian Variations in Myocardial Ischemia: Title and subTitle BreakImplications for Management FREE

Carl J. Pepine, MD
[+] Author Affiliations

This article is one of a series sponsored by the American Heart Association.

Presented, in part, at a satellite symposium at the Annual Scientific Session of the American College of Cardiology, New Orleans, La, March 17,1990.

Reprint requests to Department of Medicine, Division of Cardiology, University of Florida, Box J-277, Gainesville, FL 32610-0277 (Dr Pepine).


JAMA. 1991;265(3):386-390. doi:10.1001/jama.1991.03460030092036
Text Size: A A A
Published online
Article
References

Extended ambulatory electrocardiographic monitoring in the patient's customary environment provides clear evidence of circadian patterns in myocardial ischemic episodes. In patients with effort angina, the highest activity occurs between 6 AM and noon. This coincides with peaks in diurnal variation of frequency of acute myocardial infarction, stroke, and sudden death. A number of potential underlying common triggering mechanisms, including catecholamine secretion, sympathetic nervous system activity, blood pressure, heart rate, cortisol secretion, and aggregability of platelets, exhibit similar surges. As a result of these coinciding morning peaks, myocardial oxygen demand is increased and oxygen supply reduced after a person arises in the morning. Attention to this vulnerable period is merited in the timing and choice of medication, both to prevent or reduce ischemia and to modify potential disease-triggering mechanisms.

(JAMA. 1991;265:386-390)

REFERENCES

1 +
Lambert CR, Coy K, Imperi G, Pepine CJ.  Influence of beta-adrenergic blockade defined by time series analysis on circadian variations of heart rate and ambulatory ischemia . Am J Cardiol. 1989;;64: 835-839.
2 +
Stern S, Tzivoni D.  Early detection of silent ischemic heart disease by 24-hour electrocardiographic monitoring of active subjects . Br Heart J. 1974;;36:481-486.
3 +
Schang SJ, Pepine C.  Transient asymptomatic ST segment depression during daily activity . Am J Cardiol. 1977;;39:396-402.
4 +
Deanfield JE, Maseri A, Selwyn AP, et al.  Myocardial ischaemia during daily life in patients with stable angina: its relation to symptoms and heart rate changes . Lancet . 1983;;2:753-758.
5 +
Muller JE, Stone PH, Turi ZG, et al.  Circadian variation in the frequency of acute myocardial infarction . N Engl J Med. 1985;;313:1315-1322.
6 +
Rocco MB, Barry J, Campbell S, et al.  Circadian variation of transient myocardial ischemia in patients with coronary artery disease . Circulation . 1987;;75:395-400.
7 +
Rocco MB, Nadel EG, Selwyn AP.  Circadian rhythms and coronary artery disease . Am J Cardiol. 1987;;59( (suppl 1) ):13C-17C.
8 +
Gottlieb SO.  Circadian patterns of myocardial ischemia: pathophysiologic and therapeutic considerations . J Cardiovasc Pharmacol. 1988;;12( (suppl 7) ):S18-S21.
9 +
Muller JE, Tofler GH, Stone PH.  Circadian variation and triggers of onset of acute cardiovascular disease . Circulation . 1989;;79:733-743.
10 +
Pepine CJ, Lambert CR.  Coronary artery spasm: pathophysiology, natural history, recognition and treatment . In: Hurst JW, ed. The Heart . 7th ed. New York, NY: McGraw-Hill International Book Co; 1989;.
11 +
Turton MB, Deegan T.  Circadian variations of plasma catecholamine, cortisol and immunoreactive insulin concentrations in supine subjects . Clin Chim Acta. 1974;;55:389-397.
12 +
Wertheimer L, Hassen AZ, Delman AJ.  The 24-hour (circadian) rhythm of the cardiovascular system . Clin Res. 1972;;20:404. Abstract.
13 +
Millar-Craig MW, Bishop CN, Raftery EB.  Circadian variation of blood pressure . Lancet . 1978;;1:795-797.
14 +
Floras JS, Jones JV, Johnston JA, et al.  Arousal and the circadian rhythm of blood pressure . Clin Sci Mol Med. 1978;;55:395-397.
15 +
Davies AB, Bala-Subramanian V, Cashman PMM, Raftery EB.  Simultaneous recording of continuous arterial pressure, heart rate, and ST segment in ambulant patients with stable angina pectoris . Br Heart J. 1983;;50:85-91.
16 +
Nademanee K, Christenson PD, Robertson HA, et al.  Role of parasympathetic activity in the diurnal variation of heart rate in man: heart rate spectrum analysis of Holter monitoring . Circulation . 1988;;78( (suppl II) ):610. Abstract.
17 +
Nademanee K, Intarachot V, Josephson MA, Singh BN.  Circadian variation in occurrence of transient overt and silent myocardial ischemia in chronic stable angina and comparison with Prinzmetal angina in men . Am J Cardiol. 1987;;60:494-498.
18 +
Yasue H, Omote S, Takizawa A, Nagao M, Miwa K, Tanaka S.  Circadian variation of exercise capacity in patients with Prinzmetal's variant angina: role of exercise-induced coronary arterial spasm . Circulation . 1979;;59:938-948.
19 +
Imperi GA, Lambert CR, Coy K, Lopez L, Pepine CJ.  Effects of titrated beta blockade (metoprolol) on silent myocardial ischemia in ambulatory patients with coronary artery disease . Am J Cardiol. 1987;;60:519-524.
20 +
Quyyumi AA, Panza JA, Lakatos E, et al.  Circadian variation in ischemic events: causal role of variation in ischemic threshold due to changes in vascular resistance . Circulation . 1988;;78( (suppl II) ):331. Abstract.
21 +
Weitzman ED, Fukushima D, Nogeire C, Roffwarg H. Gallagher TF, Hellman L.  Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects . J Clin Endocrinol Metab. 1971;;33:14-22.
22 +
Tofler GH, Brezinski D, Schafer AI, et al.  Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death . N Engl J Med. 1987;;316:1514-1518.
23 +
Willich SN, Sintonen SP, Bhatia SS, et al.  Morning increase of platelet aggregability in patients with coronary artery disease . J Am Coll Cardiol. 1988;;11:204. Abstract.
24 +
Angleton P, Chandler WL, Schmer G.  Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1) . Circulation . 1989;; 79:101-106.
25 +
Ogawa H, Yasue H, Oshima S.  Circadian variation of plasma fibrinopeptide A levels in patients with variant angina . Circulation . 1988;;78( (suppl II) ):331. Abstract.
26 +
Petralito A, Mangiafico RA, Gibino S, Cuffari MA, Miano, MF, Fiore CE.  Daily modifications of plasma fibrinogen, platelets, aggregation, Howell's time, PTT, TT and antithrombin III in normal subjects and in patients with vascular disease . Chronobiologia. 1982;;9:195-201.
27 +
Rosing DR, Brakman P, Redwood DR, et al.  Blood fibrinolytic activity in man: diurnal variation and the response to varying intensities of exercise . Circ Res. 1970;;27:171-184.
28 +
Andreotti F, Davies GJ, Hackett DR, et al.  Major circadian fluctuations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardiac death, and stroke . Am J Cardiol. 1988;;62:635-637.
29 +
Ehrly AM, Jung G.  Circadian rhythm of human blood viscosity . Biorheology . 1973;;10:577-583.
30 +
Kruskal JB, Commerford PJ, Franks JJ, Kirsch RE.  Fibrin and fibrinogen-related antigens in patients with stable and unstable coronary artery disease . N Engl J Med. 1987;;317:1361-1365.
31 +
Davies MJ, Thomas AC.  Plaque fissuring—the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina . Br Heart J. 1985;;53:363-373.
32 +
Quyyumi AA, Crake T, Wright CM, Mockus LJ, Fox KM.  Medical treatment of patients with severe exertional and rest angina: double-blind comparison of β-blocker, calcium antagonist, and nitrate . Br Heart J. 1987;;57:501-511.
33 +
Nabel EG, Barry J, Rocco MB, Mead K, Selwyn AP.  Effects of dosing intervals on the development of tolerance to high-dose transdermal nitroglycerin . Am J Cardiol. 1989;;63:663-669.
34 +
Barry J, Campbell S, Nabel EG, Mead K, Selwyn AP.  Ambulatory monitoring of the digitized electrocardiogram for detection and early warning of transient myocardial ischemia in angina pectoris . Am J Cardiol. 1987;;60:483-488.
35 +
Abrams J.  The use of nitroglycerin and long-acting nitrates in angina pectoris . In: Weiner D, Frishman WH, eds. Therapy of Angina Pectoris . New York, NY: Marcel Dekker Inc; 1986;:53-82.
36 +
McGregor M.  Pathogenesis of angina pectoris and role of nitrates in relief of myocardial ischemia . Am J Med. 1983;;74( (6B) ):21-27.
37 +
Needleman P, Corr PB, Johnson EM Jr.  Drugs used for the treatment of angina: organic nitrates, calcium channel blockers and β-adrenergic antagonists . In: Gilman AG, Goodman LS, Rall TW, et al, eds. The Pharmacological Basis of Therapeutics . New York, NY: Macmillan Publishing Co Inc; 1985;:806-826.
38 +
Cohen MV, Downey JM, Sonnenblick EH, Kirk ES. The effects of nitroglycerin on coronary collaterals and myocardial contractility . J Clin Invest. 1973;;52:2836-2847.
39 +
Horwitz LD, Gorlin R, Taylor WJ, Kemp HJ.  Effects of nitroglycerin on regional myocardial blood flow in coronary artery disease . J Clin Invest. 1971;;50:1578-1584.
40 +
Luscher TF.  Endothelium-derived relaxing and contracting factors: potential role in coronary artery disease . Eur Heart J. 1989;;10:847-857.
41 +
Pelc LR, Gross GJ, Warltier DC.  Preferential increase in subendocardial perfusion produced by endothelium-dependent vasodilators . Circulation . 1987;;76:191-200.
42 +
Hoekenga D, Abrams J.  Rational medical therapy for stable angina pectoris . Am J Med. 1984;;76:309-314.
43 +
Frishman WH.  Beta-adrenergic blockade for the treatment of angina pectoris . In: Weiner D, Frishman WH, eds. Therapy of Angina Pectoris . New York, NY: Marcel Dekker Inc; 1986;:83-144.
44 +
Frishman WH.  Multifactorial actions of β-adrenergic blocking drugs in ischemic heart disease: current concepts . Circulation . 1983;;67( (suppl I) ):I-11-I-18.
45 +
Kloner RA, Reimer K, Jennings R.  Distribution of coronary collateral flow in acute myocardial ischemic injury: effect of propranolol . Cardiovasc Res. 1976;;10( (1) ):81-90.
46 +
Frishman WH, Weksler BB.  Effects of β-adrenoceptor blocking drugs on platelet function in normal subjects and patients with angina pectoris . In: Roskamm H, Graefe KH, eds. Advances in β-Blocker Therapy: Proceedings of an International Symposium . Princeton, NJ: Excerpta Medica; 1980;:165.
47 +
Weiner DA, Klein MD.  Calcium antagonists for the treatment of angina pectoris . In: Weiner D, Frishman WH, eds. Therapy of Angina Pectoris . New York, NY: Marcel Dekker Inc; 1986;:145-204.
48 +
Lambert CR, Pepine CJ.  Effects of intravenous and intracoronary nicardipine . Am J Cardiol. 1989;;64:8H-15H.
49 +
Kirk ES, Sonnenblick EH.  Newer concepts in the pathophysiology of ischemic heart disease . Am Heart J. 1982;;103:756-767.
50 +
Brown BG, Pierce CD, Petersen RB, et al.  Verapamil, a mild epicardial dilator, inhibits sympathetic and ergonovine-induced coronary constriction in humans . Circulation . 1981;;64( (suppl IV) ):150. Abstract.
51 +
Feldman RL, Macdonald RG, Hill JA, Pepine CJ.  Effect of nicardipine on determinants of myocardial ischemia occurring during acute coronary occlusion produced by percutaneous transluminal coronary angioplasty . Am J Cardiol. 1987;;60: 267-270.
52 +
Braunwald E.  Control of myocardial oxygen consumption: physiologic and clinical considerations . Am J Cardiol. 1971;;27:416-432.
53 +
Mulcahy D, Keegan J, Cunningham D, et al.  Circadian variation of total ischaemic burden and its alteration with anti-anginal agents . Lancet . 1988;;2:755-759.
54 +
Fazzini P, Multino D, Zambaldi G.  Il diltiazem nell' angina spontaneo: studio doppio cieco, crossover, sotto controllo Holter . G Ital Cardiol. 1985;;15:1085-1089.
55 +
Raehl CL, Nolan PE Jr.  Angina pectoris . In: Katcher BS, Young LY, eds. Applied Therapeutics: The Clinical Use of Drugs . San Francisco, Calif: Applied Therapeutics Inc; 1983;:271-295.
56 +
Cairns JA, Gent M, Singer J, et al.  Aspirin, sulfinpyrazone or both in unstable angina: results of a Canadian multicenter trial . N Engl J Med. 1985;;313:1369-1374.
57 +
Moschos CB, HaiderB, De La Cruz C Jr, Lyons MM, Regan TJ.  Antiarrhythmic effects of aspirin during nonthrombotic coronary occlusion . Circulation . 1978;;57:681-684.
58 +
Williams JK, Heistad DD.  Modulation of vascular growth by endothelial denudation and aspirin . Circulation . 1987;;76( (suppl IV) ):294. Abstract.
59 +
Yousefi S, Chui J, Carandang G, Archibeque EG, Vaziri N, Cesario TC.  Effect of acetyl salicylic acid on production and action of leukocyte-derived interferons . Antimicrob Agents Chemother . 1987;;31:114-116.
60 +
Zamarron C, Lijnen HR, Collen P.  Kinetics of the activation of plasminogen by natural and recombinant tissue-type plasminogen activator . J Biol Chem. 1984;;259:2080-2083.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Lambert CR, Coy K, Imperi G, Pepine CJ.  Influence of beta-adrenergic blockade defined by time series analysis on circadian variations of heart rate and ambulatory ischemia . Am J Cardiol. 1989;;64: 835-839.
2 +
Stern S, Tzivoni D.  Early detection of silent ischemic heart disease by 24-hour electrocardiographic monitoring of active subjects . Br Heart J. 1974;;36:481-486.
3 +
Schang SJ, Pepine C.  Transient asymptomatic ST segment depression during daily activity . Am J Cardiol. 1977;;39:396-402.
4 +
Deanfield JE, Maseri A, Selwyn AP, et al.  Myocardial ischaemia during daily life in patients with stable angina: its relation to symptoms and heart rate changes . Lancet . 1983;;2:753-758.
5 +
Muller JE, Stone PH, Turi ZG, et al.  Circadian variation in the frequency of acute myocardial infarction . N Engl J Med. 1985;;313:1315-1322.
6 +
Rocco MB, Barry J, Campbell S, et al.  Circadian variation of transient myocardial ischemia in patients with coronary artery disease . Circulation . 1987;;75:395-400.
7 +
Rocco MB, Nadel EG, Selwyn AP.  Circadian rhythms and coronary artery disease . Am J Cardiol. 1987;;59( (suppl 1) ):13C-17C.
8 +
Gottlieb SO.  Circadian patterns of myocardial ischemia: pathophysiologic and therapeutic considerations . J Cardiovasc Pharmacol. 1988;;12( (suppl 7) ):S18-S21.
9 +
Muller JE, Tofler GH, Stone PH.  Circadian variation and triggers of onset of acute cardiovascular disease . Circulation . 1989;;79:733-743.
10 +
Pepine CJ, Lambert CR.  Coronary artery spasm: pathophysiology, natural history, recognition and treatment . In: Hurst JW, ed. The Heart . 7th ed. New York, NY: McGraw-Hill International Book Co; 1989;.
11 +
Turton MB, Deegan T.  Circadian variations of plasma catecholamine, cortisol and immunoreactive insulin concentrations in supine subjects . Clin Chim Acta. 1974;;55:389-397.
12 +
Wertheimer L, Hassen AZ, Delman AJ.  The 24-hour (circadian) rhythm of the cardiovascular system . Clin Res. 1972;;20:404. Abstract.
13 +
Millar-Craig MW, Bishop CN, Raftery EB.  Circadian variation of blood pressure . Lancet . 1978;;1:795-797.
14 +
Floras JS, Jones JV, Johnston JA, et al.  Arousal and the circadian rhythm of blood pressure . Clin Sci Mol Med. 1978;;55:395-397.
15 +
Davies AB, Bala-Subramanian V, Cashman PMM, Raftery EB.  Simultaneous recording of continuous arterial pressure, heart rate, and ST segment in ambulant patients with stable angina pectoris . Br Heart J. 1983;;50:85-91.
16 +
Nademanee K, Christenson PD, Robertson HA, et al.  Role of parasympathetic activity in the diurnal variation of heart rate in man: heart rate spectrum analysis of Holter monitoring . Circulation . 1988;;78( (suppl II) ):610. Abstract.
17 +
Nademanee K, Intarachot V, Josephson MA, Singh BN.  Circadian variation in occurrence of transient overt and silent myocardial ischemia in chronic stable angina and comparison with Prinzmetal angina in men . Am J Cardiol. 1987;;60:494-498.
18 +
Yasue H, Omote S, Takizawa A, Nagao M, Miwa K, Tanaka S.  Circadian variation of exercise capacity in patients with Prinzmetal's variant angina: role of exercise-induced coronary arterial spasm . Circulation . 1979;;59:938-948.
19 +
Imperi GA, Lambert CR, Coy K, Lopez L, Pepine CJ.  Effects of titrated beta blockade (metoprolol) on silent myocardial ischemia in ambulatory patients with coronary artery disease . Am J Cardiol. 1987;;60:519-524.
20 +
Quyyumi AA, Panza JA, Lakatos E, et al.  Circadian variation in ischemic events: causal role of variation in ischemic threshold due to changes in vascular resistance . Circulation . 1988;;78( (suppl II) ):331. Abstract.
21 +
Weitzman ED, Fukushima D, Nogeire C, Roffwarg H. Gallagher TF, Hellman L.  Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects . J Clin Endocrinol Metab. 1971;;33:14-22.
22 +
Tofler GH, Brezinski D, Schafer AI, et al.  Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death . N Engl J Med. 1987;;316:1514-1518.
23 +
Willich SN, Sintonen SP, Bhatia SS, et al.  Morning increase of platelet aggregability in patients with coronary artery disease . J Am Coll Cardiol. 1988;;11:204. Abstract.
24 +
Angleton P, Chandler WL, Schmer G.  Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1) . Circulation . 1989;; 79:101-106.
25 +
Ogawa H, Yasue H, Oshima S.  Circadian variation of plasma fibrinopeptide A levels in patients with variant angina . Circulation . 1988;;78( (suppl II) ):331. Abstract.
26 +
Petralito A, Mangiafico RA, Gibino S, Cuffari MA, Miano, MF, Fiore CE.  Daily modifications of plasma fibrinogen, platelets, aggregation, Howell's time, PTT, TT and antithrombin III in normal subjects and in patients with vascular disease . Chronobiologia. 1982;;9:195-201.
27 +
Rosing DR, Brakman P, Redwood DR, et al.  Blood fibrinolytic activity in man: diurnal variation and the response to varying intensities of exercise . Circ Res. 1970;;27:171-184.
28 +
Andreotti F, Davies GJ, Hackett DR, et al.  Major circadian fluctuations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardiac death, and stroke . Am J Cardiol. 1988;;62:635-637.
29 +
Ehrly AM, Jung G.  Circadian rhythm of human blood viscosity . Biorheology . 1973;;10:577-583.
30 +
Kruskal JB, Commerford PJ, Franks JJ, Kirsch RE.  Fibrin and fibrinogen-related antigens in patients with stable and unstable coronary artery disease . N Engl J Med. 1987;;317:1361-1365.
31 +
Davies MJ, Thomas AC.  Plaque fissuring—the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina . Br Heart J. 1985;;53:363-373.
32 +
Quyyumi AA, Crake T, Wright CM, Mockus LJ, Fox KM.  Medical treatment of patients with severe exertional and rest angina: double-blind comparison of β-blocker, calcium antagonist, and nitrate . Br Heart J. 1987;;57:501-511.
33 +
Nabel EG, Barry J, Rocco MB, Mead K, Selwyn AP.  Effects of dosing intervals on the development of tolerance to high-dose transdermal nitroglycerin . Am J Cardiol. 1989;;63:663-669.
34 +
Barry J, Campbell S, Nabel EG, Mead K, Selwyn AP.  Ambulatory monitoring of the digitized electrocardiogram for detection and early warning of transient myocardial ischemia in angina pectoris . Am J Cardiol. 1987;;60:483-488.
35 +
Abrams J.  The use of nitroglycerin and long-acting nitrates in angina pectoris . In: Weiner D, Frishman WH, eds. Therapy of Angina Pectoris . New York, NY: Marcel Dekker Inc; 1986;:53-82.
36 +
McGregor M.  Pathogenesis of angina pectoris and role of nitrates in relief of myocardial ischemia . Am J Med. 1983;;74( (6B) ):21-27.
37 +
Needleman P, Corr PB, Johnson EM Jr.  Drugs used for the treatment of angina: organic nitrates, calcium channel blockers and β-adrenergic antagonists . In: Gilman AG, Goodman LS, Rall TW, et al, eds. The Pharmacological Basis of Therapeutics . New York, NY: Macmillan Publishing Co Inc; 1985;:806-826.
38 +
Cohen MV, Downey JM, Sonnenblick EH, Kirk ES. The effects of nitroglycerin on coronary collaterals and myocardial contractility . J Clin Invest. 1973;;52:2836-2847.
39 +
Horwitz LD, Gorlin R, Taylor WJ, Kemp HJ.  Effects of nitroglycerin on regional myocardial blood flow in coronary artery disease . J Clin Invest. 1971;;50:1578-1584.
40 +
Luscher TF.  Endothelium-derived relaxing and contracting factors: potential role in coronary artery disease . Eur Heart J. 1989;;10:847-857.
41 +
Pelc LR, Gross GJ, Warltier DC.  Preferential increase in subendocardial perfusion produced by endothelium-dependent vasodilators . Circulation . 1987;;76:191-200.
42 +
Hoekenga D, Abrams J.  Rational medical therapy for stable angina pectoris . Am J Med. 1984;;76:309-314.
43 +
Frishman WH.  Beta-adrenergic blockade for the treatment of angina pectoris . In: Weiner D, Frishman WH, eds. Therapy of Angina Pectoris . New York, NY: Marcel Dekker Inc; 1986;:83-144.
44 +
Frishman WH.  Multifactorial actions of β-adrenergic blocking drugs in ischemic heart disease: current concepts . Circulation . 1983;;67( (suppl I) ):I-11-I-18.
45 +
Kloner RA, Reimer K, Jennings R.  Distribution of coronary collateral flow in acute myocardial ischemic injury: effect of propranolol . Cardiovasc Res. 1976;;10( (1) ):81-90.
46 +
Frishman WH, Weksler BB.  Effects of β-adrenoceptor blocking drugs on platelet function in normal subjects and patients with angina pectoris . In: Roskamm H, Graefe KH, eds. Advances in β-Blocker Therapy: Proceedings of an International Symposium . Princeton, NJ: Excerpta Medica; 1980;:165.
47 +
Weiner DA, Klein MD.  Calcium antagonists for the treatment of angina pectoris . In: Weiner D, Frishman WH, eds. Therapy of Angina Pectoris . New York, NY: Marcel Dekker Inc; 1986;:145-204.
48 +
Lambert CR, Pepine CJ.  Effects of intravenous and intracoronary nicardipine . Am J Cardiol. 1989;;64:8H-15H.
49 +
Kirk ES, Sonnenblick EH.  Newer concepts in the pathophysiology of ischemic heart disease . Am Heart J. 1982;;103:756-767.
50 +
Brown BG, Pierce CD, Petersen RB, et al.  Verapamil, a mild epicardial dilator, inhibits sympathetic and ergonovine-induced coronary constriction in humans . Circulation . 1981;;64( (suppl IV) ):150. Abstract.
51 +
Feldman RL, Macdonald RG, Hill JA, Pepine CJ.  Effect of nicardipine on determinants of myocardial ischemia occurring during acute coronary occlusion produced by percutaneous transluminal coronary angioplasty . Am J Cardiol. 1987;;60: 267-270.
52 +
Braunwald E.  Control of myocardial oxygen consumption: physiologic and clinical considerations . Am J Cardiol. 1971;;27:416-432.
53 +
Mulcahy D, Keegan J, Cunningham D, et al.  Circadian variation of total ischaemic burden and its alteration with anti-anginal agents . Lancet . 1988;;2:755-759.
54 +
Fazzini P, Multino D, Zambaldi G.  Il diltiazem nell' angina spontaneo: studio doppio cieco, crossover, sotto controllo Holter . G Ital Cardiol. 1985;;15:1085-1089.
55 +
Raehl CL, Nolan PE Jr.  Angina pectoris . In: Katcher BS, Young LY, eds. Applied Therapeutics: The Clinical Use of Drugs . San Francisco, Calif: Applied Therapeutics Inc; 1983;:271-295.
56 +
Cairns JA, Gent M, Singer J, et al.  Aspirin, sulfinpyrazone or both in unstable angina: results of a Canadian multicenter trial . N Engl J Med. 1985;;313:1369-1374.
57 +
Moschos CB, HaiderB, De La Cruz C Jr, Lyons MM, Regan TJ.  Antiarrhythmic effects of aspirin during nonthrombotic coronary occlusion . Circulation . 1978;;57:681-684.
58 +
Williams JK, Heistad DD.  Modulation of vascular growth by endothelial denudation and aspirin . Circulation . 1987;;76( (suppl IV) ):294. Abstract.
59 +
Yousefi S, Chui J, Carandang G, Archibeque EG, Vaziri N, Cesario TC.  Effect of acetyl salicylic acid on production and action of leukocyte-derived interferons . Antimicrob Agents Chemother . 1987;;31:114-116.
60 +
Zamarron C, Lijnen HR, Collen P.  Kinetics of the activation of plasminogen by natural and recombinant tissue-type plasminogen activator . J Biol Chem. 1984;;259:2080-2083.

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