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Relationship between the release of thromboxane and the occurrence and extent of myocardial ischemia during exercise
ABSTRACTS
RELATIONSHIP BETWEEN THE RELEASE OF THROMPOXANE AND THE OCCURRENCE AND EXTENT OF MYOCARDIAL ISCHEMIA DURING EXERCISE. Peter P. Steele, MD; Joel Sklar, MD; Veterans Administration Medical Center, Denver, CO. Exercise (EX) is associated with activation of the platelet release reaction and stimulation of arachidonic acid metabolism with release of thromboxane (TRX). TBX and myocardial blood flow distribution (MBFD) (201TL) were measured during maximal (MAX), angina-limited EX and EX to Z/3 of maximal workload (SUB-MAX) in 20 men with TBX was measured in systemic venous coronary disease. blood as TBX B2 at rest and within one minute of completion of EX by radioimmunoassay and MRFD was measured using tomographic imaging and computer reconstruction. During MAX EX all men had ST segment depression and abnormal and reversible MBFD (acquisition of 201TL normalized counts from EX to two hours post-EX). During MAX EX TBX averaged 13.?18. pQ/ml (*SD) (normal 0.) and was detected in 17 of 20 men. Eleven men also had abnormal MBFD during SUB-MAX EX and TBX averaged 10.+16. pg/ml (detected in 6 of 11); whereas 9 had normal SUB-MAX Another 20 MBFD and TBX was not detected in any man. men with coronary disease underwent MAX EX before and after treatment with sulfinpyrazone (SFP). SFP inhibited TBX release during MAX EX (control 19.+17. pg/ml; SFP 0.) and improved MBFD (AVE+403. normalized counts; range +137. to +874.; control vs placebo AVE+24.; range -119. to +142.; integrated differences in EX myocardial count-rate for sum of 3 central planes). SFP did not alter heart rate, blood pressure, ST change, or the occurrence of angina during MAX EX. Results suggest that TBX is detectable in venous blood during EX associated with abnormal MBFD and inhibited by SFP. SFP decreases the extent of abnormal MBFD, but does not alter the occurrence of ischemia.
INFLUENCE OF BLOOD SAMPLING SITE AND TECHNIQUE DN THROMBOXANE AND PROSTACYCLIN LEVELS IN PATIENTS WITH CORONARY ARTERY DISEASE Paul Hirsh, MD; Brian Firth, MD, D Phil; William Campbell, PhD; James T. Willerson, MD, FACC; L. David Hillis, MD, FACC; University of Texas Health Science Center, Dallas, TX. The role of thromboxane (Tx)A2 and prostacyclin in ischemic This study was heart disease is under intense Investigation. performed to determine (1) if blood withdrawal through long TxB catheters (C) alters their stable metabolite concentrations, and 6-keto PGFh, respectively, and (2) if peripheral levels o3 these prostanoids reflect their coronary sinus (CS) levels or their intracoronary production. Paired blood samples were obtained through an 18 gauge needle (N) and a N7 or 8 Fr 110-125cm catheter from the arterial (14 pts) and venous (16 pts) circulations; paired CS and peripheral venous (16 pts) with ascending Samples were aortic (14 pts) samples were also obtained. analyzed by radioimmunoassay after extraction and chromatographic separation. Arterial TxB levels (in pg/ml) were similar via N (86+68; mean+SD) and C (6;?+41) (p&20), as were venous TxB levels~N:183+17’; (3:521+1536)7~=0.39). Likewise, arterial 6-ket z PGFh levels were similar via N (135+75) and C (117252) (p&16), as were venous 6-keto PGF levels (N:102+71; C:114+134) (PZO.73). levels did no: correlate-with Peripheral venous TX% levels in CS (r=O.Ol) or with the fxB CS/eortic ratios (r=0.21). Peripheral 6-keto PGF levels cor?elated with levels in CS CS/aortic ratios (r=0.85, pcO.001) but notI%ith the 6-keto PGF (r=0.22). Thus, (1) blood sampling through Iong’&theters does not levels, and (2) there is no relationship alter Tx8 or L-keto PGF between Jeripheral and, t&cardiac levels of these prostanoids. Hence, blood sampling through long catheters across the coronary bed is both a reliable and necessary method for assessing intracoronary prostanoid production in patients with coronary artery disease.
March
CIGARETTE SMOKING INCREASES TllE RELEASE OF PROSTACYCLIN INTO THE CORONARYCIRCULATION IN PATIENTS WITH ISCHEYIC HEART DISEASE. I. Stoel, ?iD; P.W. Serrups, YD; W.J. v.d. Giessen, MD; P.G. Hugenholtz, LID, FACC; P.W. de Leeuw, YD; G. Defreyn, MD; J. Vermylen, MD, Thoraxcenter, Erasmus University, Rotterdam, The Netherlands. The effect of cigarette smoking on the release of thromboxane A2 (TXA ) prostacyclin (PC), catecholamines and platelet functso: in the coronary circulation (CS) and aorta (AO) was studied in 7 patients with coronary artery disease. Blood samples were obtained before (b) and after (a) smoking 2 cigarettes. TXA2 and PC were indirectly measured by radio immune assay of their stable metabolites PGF 1 aloha (6PGF). thromboxane B (TXB2) and 6-keto ( H) and Norepineohrine (NE)were measured by Epinephrine a conversion reaction after they were oretreated with a radioactive marker. Results: CS TXB2
b
25 + 2.2
CS
a
A0
b
30 + 1.8
20 + 3
A0
a
Units
30 + 3
llglml
6PGF
56+14
83 + _ 25
87 _+ 26
65 + 21
pg/ml
E
37 + 9
91 +_ 28
69 + 6
132 + 34
og/ml
312 t
pg/ml
NE
152 + 66
388 _+ 56
- 43 307 _+
45
Judging by their metabolites in A0 and CS, TXA2 is released under the influence of cigarette smoking, whereas PC production is decreased in the AO, but increased in the CS. This stimulation of PC oroduction in the coronary circulation might be a defense mechanism against the aggregatory and vasoconstrictor effects of TXA 2’
LIMITATIONS OF PLATELET FACTOR 4 ASSAY IN ASSESSING .MYOCARDIAL ISCHEMIA IN PATIENTS WITH CORONARY DISEASE. Kenneth 5. Korr, MD, Robert Raglini, James Srowley, MD, Albert S. Most, MD, FACC, David 0. \X’llliams, MD, FACC. Rhode IslandHospi&l, Providence, RI The plasma concentration of platelet factor 4 (PF4), an index of platelet activation, has been shown to be elevated followIn? exercise induced myocardial ischemia. Little data are avaIlable, however, as to the mechanism of PF4 increase and the influence of indwelling vascular catheters on PF4 assay. Thus we assessed the plasma concenrration of PF4 in 19 normals (NLS), 18 patients (Pts) with coronary artery disease (CAD) undereoine cardiac catheterization (CC) and 7 additional CAD Pts undergoing CC, subjected to pacing tachycardia. V&puncture samples were obtained in NLS. CAD Pts had venipuncture samples before (A) and during (8) CC and through an indwelling catheter CC). Pacing Pts had paired arterial (ART) and coronary sinus (0) samples obtained prior to (PRE) and durinp pacing tachycardia. Percent PF4 generation (%PF4C) across the coronary circulation was calculated. NLS CAD Pts A R C PF4 24+26x 90+56Y 71+57* (ng/ml) 9+5 ?? P< 0.005 VS-NLS +P<0.05 vs A Values : mean + I5D Prior to CC, PF4 levels were greater in CAD Pts (A) than is NL5 and rose further with CC. Five of 7 paced Pts demonstrated abnormal lactate metabolism but only one of these showed an increase in %PF$G. Thus PF4 is elevated in CAD Pts. CC results in an additional increase in PF4. Increased PF4G could not be demonstrated across the coronary circulation suggesting that either changes were masked by the effect of CC or that platlet activation occurs at an extra cardiac site in the setting of myocardial ischemia.
1982
The American
Journal
of CARDIOLOGY
Volume
49
903
RELATIONSHIP BETWEEN THE RELEASE OF THROMPOXANE AND THE OCCURRENCE AND EXTENT OF MYOCARDIAL ISCHEMIA DURING EXERCISE. Peter P. Steele, MD; Joel Sklar, MD; Veterans Administration Medical Center, Denver, CO. Exercise (EX) is associated with activation of the platelet release reaction and stimulation of arachidonic acid metabolism with release of thromboxane (TRX). TBX and myocardial blood flow distribution (MBFD) (201TL) were measured during maximal (MAX), angina-limited EX and EX to Z/3 of maximal workload (SUB-MAX) in 20 men with TBX was measured in systemic venous coronary disease. blood as TBX B2 at rest and within one minute of completion of EX by radioimmunoassay and MRFD was measured using tomographic imaging and computer reconstruction. During MAX EX all men had ST segment depression and abnormal and reversible MBFD (acquisition of 201TL normalized counts from EX to two hours post-EX). During MAX EX TBX averaged 13.?18. pQ/ml (*SD) (normal 0.) and was detected in 17 of 20 men. Eleven men also had abnormal MBFD during SUB-MAX EX and TBX averaged 10.+16. pg/ml (detected in 6 of 11); whereas 9 had normal SUB-MAX Another 20 MBFD and TBX was not detected in any man. men with coronary disease underwent MAX EX before and after treatment with sulfinpyrazone (SFP). SFP inhibited TBX release during MAX EX (control 19.+17. pg/ml; SFP 0.) and improved MBFD (AVE+403. normalized counts; range +137. to +874.; control vs placebo AVE+24.; range -119. to +142.; integrated differences in EX myocardial count-rate for sum of 3 central planes). SFP did not alter heart rate, blood pressure, ST change, or the occurrence of angina during MAX EX. Results suggest that TBX is detectable in venous blood during EX associated with abnormal MBFD and inhibited by SFP. SFP decreases the extent of abnormal MBFD, but does not alter the occurrence of ischemia.
INFLUENCE OF BLOOD SAMPLING SITE AND TECHNIQUE DN THROMBOXANE AND PROSTACYCLIN LEVELS IN PATIENTS WITH CORONARY ARTERY DISEASE Paul Hirsh, MD; Brian Firth, MD, D Phil; William Campbell, PhD; James T. Willerson, MD, FACC; L. David Hillis, MD, FACC; University of Texas Health Science Center, Dallas, TX. The role of thromboxane (Tx)A2 and prostacyclin in ischemic This study was heart disease is under intense Investigation. performed to determine (1) if blood withdrawal through long TxB catheters (C) alters their stable metabolite concentrations, and 6-keto PGFh, respectively, and (2) if peripheral levels o3 these prostanoids reflect their coronary sinus (CS) levels or their intracoronary production. Paired blood samples were obtained through an 18 gauge needle (N) and a N7 or 8 Fr 110-125cm catheter from the arterial (14 pts) and venous (16 pts) circulations; paired CS and peripheral venous (16 pts) with ascending Samples were aortic (14 pts) samples were also obtained. analyzed by radioimmunoassay after extraction and chromatographic separation. Arterial TxB levels (in pg/ml) were similar via N (86+68; mean+SD) and C (6;?+41) (p&20), as were venous TxB levels~N:183+17’; (3:521+1536)7~=0.39). Likewise, arterial 6-ket z PGFh levels were similar via N (135+75) and C (117252) (p&16), as were venous 6-keto PGF levels (N:102+71; C:114+134) (PZO.73). levels did no: correlate-with Peripheral venous TX% levels in CS (r=O.Ol) or with the fxB CS/eortic ratios (r=0.21). Peripheral 6-keto PGF levels cor?elated with levels in CS CS/aortic ratios (r=0.85, pcO.001) but notI%ith the 6-keto PGF (r=0.22). Thus, (1) blood sampling through Iong’&theters does not levels, and (2) there is no relationship alter Tx8 or L-keto PGF between Jeripheral and, t&cardiac levels of these prostanoids. Hence, blood sampling through long catheters across the coronary bed is both a reliable and necessary method for assessing intracoronary prostanoid production in patients with coronary artery disease.
March
CIGARETTE SMOKING INCREASES TllE RELEASE OF PROSTACYCLIN INTO THE CORONARYCIRCULATION IN PATIENTS WITH ISCHEYIC HEART DISEASE. I. Stoel, ?iD; P.W. Serrups, YD; W.J. v.d. Giessen, MD; P.G. Hugenholtz, LID, FACC; P.W. de Leeuw, YD; G. Defreyn, MD; J. Vermylen, MD, Thoraxcenter, Erasmus University, Rotterdam, The Netherlands. The effect of cigarette smoking on the release of thromboxane A2 (TXA ) prostacyclin (PC), catecholamines and platelet functso: in the coronary circulation (CS) and aorta (AO) was studied in 7 patients with coronary artery disease. Blood samples were obtained before (b) and after (a) smoking 2 cigarettes. TXA2 and PC were indirectly measured by radio immune assay of their stable metabolites PGF 1 aloha (6PGF). thromboxane B (TXB2) and 6-keto ( H) and Norepineohrine (NE)were measured by Epinephrine a conversion reaction after they were oretreated with a radioactive marker. Results: CS TXB2
b
25 + 2.2
CS
a
A0
b
30 + 1.8
20 + 3
A0
a
Units
30 + 3
llglml
6PGF
56+14
83 + _ 25
87 _+ 26
65 + 21
pg/ml
E
37 + 9
91 +_ 28
69 + 6
132 + 34
og/ml
312 t
pg/ml
NE
152 + 66
388 _+ 56
- 43 307 _+
45
Judging by their metabolites in A0 and CS, TXA2 is released under the influence of cigarette smoking, whereas PC production is decreased in the AO, but increased in the CS. This stimulation of PC oroduction in the coronary circulation might be a defense mechanism against the aggregatory and vasoconstrictor effects of TXA 2’
LIMITATIONS OF PLATELET FACTOR 4 ASSAY IN ASSESSING .MYOCARDIAL ISCHEMIA IN PATIENTS WITH CORONARY DISEASE. Kenneth 5. Korr, MD, Robert Raglini, James Srowley, MD, Albert S. Most, MD, FACC, David 0. \X’llliams, MD, FACC. Rhode IslandHospi&l, Providence, RI The plasma concentration of platelet factor 4 (PF4), an index of platelet activation, has been shown to be elevated followIn? exercise induced myocardial ischemia. Little data are avaIlable, however, as to the mechanism of PF4 increase and the influence of indwelling vascular catheters on PF4 assay. Thus we assessed the plasma concenrration of PF4 in 19 normals (NLS), 18 patients (Pts) with coronary artery disease (CAD) undereoine cardiac catheterization (CC) and 7 additional CAD Pts undergoing CC, subjected to pacing tachycardia. V&puncture samples were obtained in NLS. CAD Pts had venipuncture samples before (A) and during (8) CC and through an indwelling catheter CC). Pacing Pts had paired arterial (ART) and coronary sinus (0) samples obtained prior to (PRE) and durinp pacing tachycardia. Percent PF4 generation (%PF4C) across the coronary circulation was calculated. NLS CAD Pts A R C PF4 24+26x 90+56Y 71+57* (ng/ml) 9+5 ?? P< 0.005 VS-NLS +P<0.05 vs A Values : mean + I5D Prior to CC, PF4 levels were greater in CAD Pts (A) than is NL5 and rose further with CC. Five of 7 paced Pts demonstrated abnormal lactate metabolism but only one of these showed an increase in %PF$G. Thus PF4 is elevated in CAD Pts. CC results in an additional increase in PF4. Increased PF4G could not be demonstrated across the coronary circulation suggesting that either changes were masked by the effect of CC or that platlet activation occurs at an extra cardiac site in the setting of myocardial ischemia.
1982
The American
Journal
of CARDIOLOGY
Volume
49
903