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Increased platelet prostaglandin generation and abnormal platelet sensitivity to prostacyclin and thromboxane A2 in angina pectoris
ABSTRACTS
WEDNESDAY, MARCH 72, 1980 AM CORONARY ARTERY DISEASE: ROLE Of 8:30- 10:00
INCREASED PLATELET PROSTAGLANDIN GENERATION AND ABNORMAL PLATELET SENSITIVITY TO PROSTACYCLIN AND THROMBOXANE A2 IN ANGINA PECTORIS Jawahar Mehta, MD, FACC; Paulette Mehta, MD, University of Florida and VA Medical Center, Gainesville, Fl.
VASOSPASM
INCREASED LEVELS OF THROMBOXANE AZ IN PERIPHERAL AND CORONARY CIRCULATION IN PATIENTS WITH ANGINA PECTORIS T. Kuzuya, MD; M. Tada, MD; M. Inoue, MD; K. Kodama, MD; H. Takeda, MD; M. Mishima, MD; M. Inui, MD; H. Abe, MD, FACC, Osaka University School of Medicine, Osaka, Japan
To define the role of platelet function in myocardial ischemia, we studied 22 patients (pts) with angina pectoris (AP) and 14 normal subjects. Of 22 pts, 10 were studied during episode of AP (group A) and 12 several hours after AP (group B). Platelet prostaglandin generation (malondialdehyde levels) (MDA) was measured as index of thromboxane A2 (TXA) synthesis. Platelet sensitivity to vasodilater-platelet aggregation inhibitor prostaeyclin (PGI2) and vasoconstrictor-platelet aggregation stimulant TXA analog EMA were also evaluated. MDA production was significantly higher in AP ts compared to controls (2.50+ 8 0.30 and 1.70+0.13 nM/lO platelets, respectively, P/0102). _ AP pts required more PGI for 50% platelet aggregation inhibition than controls (1 .90+0.35 and 0.68+0.04 ng, P< Group A AP pts required more PGI than group B 0.001). pts for similar degree of aggregation inhibition (2.90+ 0.60 and 1.30+0.12 ng P
Thromboxane AZ (TXAz),a vasoconstrictive prostanoid, is known to induce spasm of isolated coronary vessels and to increase platelet aggregability. Todefine role of TXAzin the pathogenesis of angina pectoris,plasma levelsof TXB2, a biologically inactive product of TXA~,were determinedin coronary sinus (CS) and aorta (AO)as well as antecubital (peripheral) vein of angina1 patients by radioimmunoassay employing anti-TXBz antisera and [3H]TXB, after acidic lipids were extracted from plasmaof EDTA- and indomethacinOf 18 patients with effort angina whose treated blood. stenotic lesions (2 75 %)were angiographically documented, 12 exhibited a marked increase in peripheral TXB2 (494f compared with normal subjects 191 pg/ml plasma, P
RESPONSIVENESS OF ATHEROSCLEROTIC RABBIT AORTA TO ADRENERGIC AND CHOLINERGIC STIMULATION Mitsuhiro Yokoyama, M.D.; Philip D. Henry, M.D., FACC, Washington University, St. Louis, MO. Both adrenergic and cholinergic agents can induce coroTo denary spasm in patients with Prinzmetal's angina. termine whether altered autonomic responsiveness is related to atherosclerosis, helical strips from aortae of control rabbits and rabbits fed a 2% cholesterol diet were mounted in an organ bath for the recording of isometric force under basal conditions and in response to Concentrations of norepinephrine and selected agonists. ergonovine evoking half-maximum contractions (EDso) averaged 4 x lO_'M (n=lO) and 10w6M (n=lO) in normal arteries. corresponding values for the In atherosclerotic arteries, two a-agonists were significantly (P < 0.01) lower, averaging 1O“M (n=ll) and 2 x 10e7M (n=lZ). Acetylcholine and methacholine evoked minor relaxations at low conccnand contractions at higher conccntrations (< 5.10-‘M), tratlons in both control and atherosclerotic arteries. EDso for acetylcholine- and methacholine-induced contractions averaged 2 x 10e6M and 10m6M in atherosclerotic arteries (n=20) and did not differ significantly from valIn both groups ues obtained in control arteries ("~20). of arteries, muscarinic blockade with 10-7W atropine abolished all responses, whereas prejunctional nicotinic blockade with 10T7M 8-bungarotoxin or postjunctional aadrcnergic blockade with 10e7M prazosin had no inhibitory produced by nicotine I” contrast, contractions effect. an agent that acts by releasing norepinoph(lo-5 -lO-‘M), rine from vascular nerves, were abolished by lo-'M 8Thus, bungarotoxin or lO_'H prazosin in all arteries. compared to control arteries, atherosclerotic aortae were supersensitive to a-adrenerglc agonists but exhibited normal muscarinic responses to acetylcholine.
454
February
1990
The American
Journal
of CARDIOLOGY
FREQUENCY OF MYOCARDIAL INFARCTION AND SUDDEN DEATH IN 44 VARIANT ANGINA PATIENTS: A HIGH RISK ISCHEMIC HEART DISEASE SUBSET R. Charles Curry,Jr., MD,FACC; Carl J. Pepine, MD, FACC; Robert L. Feldman, MD; James L. Whittle, MD; C. Richard Conti, MD, FACC, University of Florida, Gainesville, FL. Variant angina is thought to be associated with an increased risk of myocardial infarction and death. To test this hypothesis we tabulated the clinical course of 44 patientscpts) with variant angina documentedby transient episodesof rest pain with ST segment elevation occurring spontaneously(28 pts)or following ergonovine(l6 pts). The group consisted of 36men andBwomen, age 51 years (mean, range 19-69 years). Chest pain was present for 15 months (mean, range l-100 months). All pts underwent coronary angiography with significant (>50% diameter narrowing) coronary artery disease(CAD) present in 29 pts (multivessel in 19 pts, single vessel in 10 pts). Treatment included: short and long-acting nitrates(44 pts), propranolol(37 pts), perhexiline(21 pts), and coronary artery bypass graft surgery(l3 pts). FREQUENCY OF CLINICAL EVENTS IN VARIANT ANGINA MI No. Pts. SUDDEN DEATH 11(38%) CAD 29 7(24%) No CAD 15 3(20%) 2(13%) Totals 44 14(31%) 9(21%) MI = myocardial infarction Conclusion: Patients withvariantangina, especially those with CAD, appear to be at high risk for MI and sudden death. These results supportaneed for improved treatment.
Volume
45
WEDNESDAY, MARCH 72, 1980 AM CORONARY ARTERY DISEASE: ROLE Of 8:30- 10:00
INCREASED PLATELET PROSTAGLANDIN GENERATION AND ABNORMAL PLATELET SENSITIVITY TO PROSTACYCLIN AND THROMBOXANE A2 IN ANGINA PECTORIS Jawahar Mehta, MD, FACC; Paulette Mehta, MD, University of Florida and VA Medical Center, Gainesville, Fl.
VASOSPASM
INCREASED LEVELS OF THROMBOXANE AZ IN PERIPHERAL AND CORONARY CIRCULATION IN PATIENTS WITH ANGINA PECTORIS T. Kuzuya, MD; M. Tada, MD; M. Inoue, MD; K. Kodama, MD; H. Takeda, MD; M. Mishima, MD; M. Inui, MD; H. Abe, MD, FACC, Osaka University School of Medicine, Osaka, Japan
To define the role of platelet function in myocardial ischemia, we studied 22 patients (pts) with angina pectoris (AP) and 14 normal subjects. Of 22 pts, 10 were studied during episode of AP (group A) and 12 several hours after AP (group B). Platelet prostaglandin generation (malondialdehyde levels) (MDA) was measured as index of thromboxane A2 (TXA) synthesis. Platelet sensitivity to vasodilater-platelet aggregation inhibitor prostaeyclin (PGI2) and vasoconstrictor-platelet aggregation stimulant TXA analog EMA were also evaluated. MDA production was significantly higher in AP ts compared to controls (2.50+ 8 0.30 and 1.70+0.13 nM/lO platelets, respectively, P/0102). _ AP pts required more PGI for 50% platelet aggregation inhibition than controls (1 .90+0.35 and 0.68+0.04 ng, P< Group A AP pts required more PGI than group B 0.001). pts for similar degree of aggregation inhibition (2.90+ 0.60 and 1.30+0.12 ng P
Thromboxane AZ (TXAz),a vasoconstrictive prostanoid, is known to induce spasm of isolated coronary vessels and to increase platelet aggregability. Todefine role of TXAzin the pathogenesis of angina pectoris,plasma levelsof TXB2, a biologically inactive product of TXA~,were determinedin coronary sinus (CS) and aorta (AO)as well as antecubital (peripheral) vein of angina1 patients by radioimmunoassay employing anti-TXBz antisera and [3H]TXB, after acidic lipids were extracted from plasmaof EDTA- and indomethacinOf 18 patients with effort angina whose treated blood. stenotic lesions (2 75 %)were angiographically documented, 12 exhibited a marked increase in peripheral TXB2 (494f compared with normal subjects 191 pg/ml plasma, P
RESPONSIVENESS OF ATHEROSCLEROTIC RABBIT AORTA TO ADRENERGIC AND CHOLINERGIC STIMULATION Mitsuhiro Yokoyama, M.D.; Philip D. Henry, M.D., FACC, Washington University, St. Louis, MO. Both adrenergic and cholinergic agents can induce coroTo denary spasm in patients with Prinzmetal's angina. termine whether altered autonomic responsiveness is related to atherosclerosis, helical strips from aortae of control rabbits and rabbits fed a 2% cholesterol diet were mounted in an organ bath for the recording of isometric force under basal conditions and in response to Concentrations of norepinephrine and selected agonists. ergonovine evoking half-maximum contractions (EDso) averaged 4 x lO_'M (n=lO) and 10w6M (n=lO) in normal arteries. corresponding values for the In atherosclerotic arteries, two a-agonists were significantly (P < 0.01) lower, averaging 1O“M (n=ll) and 2 x 10e7M (n=lZ). Acetylcholine and methacholine evoked minor relaxations at low conccnand contractions at higher conccntrations (< 5.10-‘M), tratlons in both control and atherosclerotic arteries. EDso for acetylcholine- and methacholine-induced contractions averaged 2 x 10e6M and 10m6M in atherosclerotic arteries (n=20) and did not differ significantly from valIn both groups ues obtained in control arteries ("~20). of arteries, muscarinic blockade with 10-7W atropine abolished all responses, whereas prejunctional nicotinic blockade with 10T7M 8-bungarotoxin or postjunctional aadrcnergic blockade with 10e7M prazosin had no inhibitory produced by nicotine I” contrast, contractions effect. an agent that acts by releasing norepinoph(lo-5 -lO-‘M), rine from vascular nerves, were abolished by lo-'M 8Thus, bungarotoxin or lO_'H prazosin in all arteries. compared to control arteries, atherosclerotic aortae were supersensitive to a-adrenerglc agonists but exhibited normal muscarinic responses to acetylcholine.
454
February
1990
The American
Journal
of CARDIOLOGY
FREQUENCY OF MYOCARDIAL INFARCTION AND SUDDEN DEATH IN 44 VARIANT ANGINA PATIENTS: A HIGH RISK ISCHEMIC HEART DISEASE SUBSET R. Charles Curry,Jr., MD,FACC; Carl J. Pepine, MD, FACC; Robert L. Feldman, MD; James L. Whittle, MD; C. Richard Conti, MD, FACC, University of Florida, Gainesville, FL. Variant angina is thought to be associated with an increased risk of myocardial infarction and death. To test this hypothesis we tabulated the clinical course of 44 patientscpts) with variant angina documentedby transient episodesof rest pain with ST segment elevation occurring spontaneously(28 pts)or following ergonovine(l6 pts). The group consisted of 36men andBwomen, age 51 years (mean, range 19-69 years). Chest pain was present for 15 months (mean, range l-100 months). All pts underwent coronary angiography with significant (>50% diameter narrowing) coronary artery disease(CAD) present in 29 pts (multivessel in 19 pts, single vessel in 10 pts). Treatment included: short and long-acting nitrates(44 pts), propranolol(37 pts), perhexiline(21 pts), and coronary artery bypass graft surgery(l3 pts). FREQUENCY OF CLINICAL EVENTS IN VARIANT ANGINA MI No. Pts. SUDDEN DEATH 11(38%) CAD 29 7(24%) No CAD 15 3(20%) 2(13%) Totals 44 14(31%) 9(21%) MI = myocardial infarction Conclusion: Patients withvariantangina, especially those with CAD, appear to be at high risk for MI and sudden death. These results supportaneed for improved treatment.
Volume
45