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Platelet aggregation in angina pectoris: Effect of exercise induced stress
ABSTRACTS
LATE RESULTS OF THE BAFFLE REPAIR FOR TRANSPOSITION OF THE GREAT ARTERIES Beat Friedli, MD, MSc; Michael .I. Godman, MB; B.S. Langford Ridd, MD, FACC; Andre Pasternac, MB; George A. Trusler, MD; William T. Mustard, MB, FACC, Hospital for Sick Children, Toronto, Ontario, Canada. Fourteen unselected patients have been assessed hemodynamically 4 to 10 years (mean 5.5 years) after the Mustard operation for transposition of the great arteries Investigations were directed principally at, @GA). i) detection of baffle obstruction by pressure measurements in the pulmonary veins (PV) and venae cavae and by recording simultaneously right ventricular (RV) and pulii) detection of baffle monary wedge (PCW) pressures; leaks by dye curves and by selective angiography; iii) assessment of RV and LV function by calculating peak VCE (dp/dt/28 p) from high fidelity recordings in 11 patients. Severe baffle obstruction to the PV return was found in 1 patient. The others had no or minimal gradients between the RV end-diastolic and PCW pressures (mean 1.3 f 0.69 After Isuprel infusion cardiac output rose from mm Hg). 4.1 +_ .22 to 7.1 f .62 l/min/m2 (+73%), but the gradient between RV end-diastolic and PCW pressures remained insignificant (2.2 + 1.13 sun Hg). There was no caval obstruction. Baffle leaks were found in 5 patients with mild Mild tricuspid regurgitation bi-directional shunting. was demonstrated in 2 patients by RV angiography and was absent in 12 others. The contractility index peak VCE averaged 1.87 +_ .122 set-1 for the RV and was significantly lower for the LV (1.53 +_ .135 set-1, P< 0.01). Only 1 patient presented significantly decreased contractility with a peak VCE of 1.07 set-1 and poor contractility on These data indicate that the longterm the RV angiogram. outlook after the Mustard operation should be optimistic in most patients and that the RV is able to function at the level of contractility of a normal LV.
NON-INVASIVE ASSESSMENT OF CLINICAL RESPONSE TO ORAL PROPRANOLOL William Frishman, MD; Charles Smithen, MD; Thomas Killip, MD, FACC, The New York Hospital-Cornell Medical Center, New York, N.Y. Nineteen patients (pts) with severe angina pectoris entered a double blind controlled study to evaluate the effect of oral propranolol (P) on exercise tolerance measured with a bicycle ergometer, and left ventricular (LV) function measured by echocardiography and systolic time intervals. In the P treated group dosage was increased from 80 to 320mg/day. Studies , which included blood P levels, were obtained before treatment and at each P dose. On P 80mg/day total work increased by 128% from 765*125 to 1,785*285 kpm when compared to pre-treatment performance (pc.01). At dose levels of Pg160mg total work performance decreased, but remained higher than at control levels. In the P treated group LV function decreased progressively with increasing drug dose. As measured from the echocardiogram, maximum endocardial posterior wall velocity fell 35% from 62i15 to 40511 mm/set, ejection fraction fell by 12% from .68*.05 to .60*.04, and end diastolic volume increased from 90*23 to 111*28 PEP/LVET significantly increased ml/m2, (all pc.05). with each dose increment and correlated with the decrease in ejection fraction measured from the echocardiogram, There was no correlation between blood (r=.75, p*.Oi). level of P and improved work performance. Thus exercise tolerance was maximally improved with dosages of 8Dmg/ daily. At higher dose levels LV function deteriorated and exercise work fell. Non-invasive assessment of LV function proved more valuable than drug levels in management of patients with angina pectoris and provides a guide to optimal adJustment of dosage.
ANx9DAL INFLUENCE ON VENTRICULAR FIBRILLATION Seymour Furman, M.D., FACC Rahul Mehra, B.S., Montefiore Hospital and Medical Center, Bronx, New York
PLATELET AGGREGATION IN ANGINA PECTORIS: EFFECT OF EXERCISE INDUCED STRESS William Frishman, MD; James Christodoulou, MD; Dabette Weksler, MD; Charles Smithen, MD;Simon Horwitz, MD; Thomas Killip, MD, FACC, The New York Hospital-Cornell Medical Center, New York, N.Y. Several observers have suggested that platelet dysfunction may be important in the pathogenesis of symptomatic coroPlatelet aggregates have been demonnary artery disease. strated in the coronary microvasculature of animal models following catecholamine infusions or the production of severe stress. To test the hypothesis that stress may lead to altered platelet function in man, exercise tolerance tests (ETT) were performed on 10 patients (pts) with angina pectoris and 10 age matched normals (nls) using a Six angina pts had repeat ETT while bicycle ergometer. receiving 80mg/day of oral propranolol (P). Exercise endpoint was either chest pain, severe fatigue or a heart rate of 16D/min. Platelet aggregation (agg) studies were obtained at rest and immediately after exercise. Eiphasic agg threshold in response to ADP and epinephrine was measured in fresh platelet rich plasma. At rest, minimum concentration of ADP for full agg response was 2.7f 0.6 uM in pts and 6.Dt1.4 in nls (p-05); with epinephrine, 8.6i3.1 uM in pts and 2Ok4.6 uM in nls (pr.05). However, following exercise with significant increase in heart rate and blood pressure, no change in agg threshold was found in either the nl or pt groups. P.t rest, P treated pts required an increased concentration of ADP to induce agg, 4.5tO.5 uM (pCD1); after exercise, this effect was maintained or further increased concomitant with improvement in work performance. Thus, exercise induced stress does not acutely alter resting platelet agg in nls or pts with angina pectoris. Angina pts show increased platelet agg at rest which is restored towards normal by P, an effect which persists despite submaximal exercise.
January
The difference between cathodal, anodal and bipolar fibrillation threshold was investigated in open chest anesthetized dogs with SA nodal destruction and ventricular pacing at lSO/min. Constant current 2 msec duration rectangular cathodal, anodal or bipolar pulse trains of 100 Hz were applied via the pacing electrode($) for 500 msec to the left ventricular apex with the onset of the R wave during interruption of ventricular pacing. The current required to fibrillate using cathodal trains was 2.5 times larger than that required for anodal or bipolar trains, both of which had equal fibrillation thresholds. Electrograms indicated shorter refractory periods with more rapid ventricular responses for anodal or bipolar trains than for cathodal. Fibrillation threshold was also determined after two consecutive premature ventricular contractions by a 2 msec pulse. Starting from total refractory, a time range of vulnerability was determined in which anodal fibrillation threshold was less than cathodal. It is hypothesized that lower anodal or bipolar fibrillation threshold is due to their shorter refractory period and lower threshold in relative refractory. These data support the observed greater relative frequency of ventricular fibrillation in the presence of bipolar cardiac stimulation than unipolar, and suggest that unipolar cathodal stimulation is intrisically safer than bipolar, especially when fibrillation threshold is reduced as with myocardial ischemia.
1974
The American
Journal
of CARDIOLOGY
Volume
33
137
LATE RESULTS OF THE BAFFLE REPAIR FOR TRANSPOSITION OF THE GREAT ARTERIES Beat Friedli, MD, MSc; Michael .I. Godman, MB; B.S. Langford Ridd, MD, FACC; Andre Pasternac, MB; George A. Trusler, MD; William T. Mustard, MB, FACC, Hospital for Sick Children, Toronto, Ontario, Canada. Fourteen unselected patients have been assessed hemodynamically 4 to 10 years (mean 5.5 years) after the Mustard operation for transposition of the great arteries Investigations were directed principally at, @GA). i) detection of baffle obstruction by pressure measurements in the pulmonary veins (PV) and venae cavae and by recording simultaneously right ventricular (RV) and pulii) detection of baffle monary wedge (PCW) pressures; leaks by dye curves and by selective angiography; iii) assessment of RV and LV function by calculating peak VCE (dp/dt/28 p) from high fidelity recordings in 11 patients. Severe baffle obstruction to the PV return was found in 1 patient. The others had no or minimal gradients between the RV end-diastolic and PCW pressures (mean 1.3 f 0.69 After Isuprel infusion cardiac output rose from mm Hg). 4.1 +_ .22 to 7.1 f .62 l/min/m2 (+73%), but the gradient between RV end-diastolic and PCW pressures remained insignificant (2.2 + 1.13 sun Hg). There was no caval obstruction. Baffle leaks were found in 5 patients with mild Mild tricuspid regurgitation bi-directional shunting. was demonstrated in 2 patients by RV angiography and was absent in 12 others. The contractility index peak VCE averaged 1.87 +_ .122 set-1 for the RV and was significantly lower for the LV (1.53 +_ .135 set-1, P< 0.01). Only 1 patient presented significantly decreased contractility with a peak VCE of 1.07 set-1 and poor contractility on These data indicate that the longterm the RV angiogram. outlook after the Mustard operation should be optimistic in most patients and that the RV is able to function at the level of contractility of a normal LV.
NON-INVASIVE ASSESSMENT OF CLINICAL RESPONSE TO ORAL PROPRANOLOL William Frishman, MD; Charles Smithen, MD; Thomas Killip, MD, FACC, The New York Hospital-Cornell Medical Center, New York, N.Y. Nineteen patients (pts) with severe angina pectoris entered a double blind controlled study to evaluate the effect of oral propranolol (P) on exercise tolerance measured with a bicycle ergometer, and left ventricular (LV) function measured by echocardiography and systolic time intervals. In the P treated group dosage was increased from 80 to 320mg/day. Studies , which included blood P levels, were obtained before treatment and at each P dose. On P 80mg/day total work increased by 128% from 765*125 to 1,785*285 kpm when compared to pre-treatment performance (pc.01). At dose levels of Pg160mg total work performance decreased, but remained higher than at control levels. In the P treated group LV function decreased progressively with increasing drug dose. As measured from the echocardiogram, maximum endocardial posterior wall velocity fell 35% from 62i15 to 40511 mm/set, ejection fraction fell by 12% from .68*.05 to .60*.04, and end diastolic volume increased from 90*23 to 111*28 PEP/LVET significantly increased ml/m2, (all pc.05). with each dose increment and correlated with the decrease in ejection fraction measured from the echocardiogram, There was no correlation between blood (r=.75, p*.Oi). level of P and improved work performance. Thus exercise tolerance was maximally improved with dosages of 8Dmg/ daily. At higher dose levels LV function deteriorated and exercise work fell. Non-invasive assessment of LV function proved more valuable than drug levels in management of patients with angina pectoris and provides a guide to optimal adJustment of dosage.
ANx9DAL INFLUENCE ON VENTRICULAR FIBRILLATION Seymour Furman, M.D., FACC Rahul Mehra, B.S., Montefiore Hospital and Medical Center, Bronx, New York
PLATELET AGGREGATION IN ANGINA PECTORIS: EFFECT OF EXERCISE INDUCED STRESS William Frishman, MD; James Christodoulou, MD; Dabette Weksler, MD; Charles Smithen, MD;Simon Horwitz, MD; Thomas Killip, MD, FACC, The New York Hospital-Cornell Medical Center, New York, N.Y. Several observers have suggested that platelet dysfunction may be important in the pathogenesis of symptomatic coroPlatelet aggregates have been demonnary artery disease. strated in the coronary microvasculature of animal models following catecholamine infusions or the production of severe stress. To test the hypothesis that stress may lead to altered platelet function in man, exercise tolerance tests (ETT) were performed on 10 patients (pts) with angina pectoris and 10 age matched normals (nls) using a Six angina pts had repeat ETT while bicycle ergometer. receiving 80mg/day of oral propranolol (P). Exercise endpoint was either chest pain, severe fatigue or a heart rate of 16D/min. Platelet aggregation (agg) studies were obtained at rest and immediately after exercise. Eiphasic agg threshold in response to ADP and epinephrine was measured in fresh platelet rich plasma. At rest, minimum concentration of ADP for full agg response was 2.7f 0.6 uM in pts and 6.Dt1.4 in nls (p-05); with epinephrine, 8.6i3.1 uM in pts and 2Ok4.6 uM in nls (pr.05). However, following exercise with significant increase in heart rate and blood pressure, no change in agg threshold was found in either the nl or pt groups. P.t rest, P treated pts required an increased concentration of ADP to induce agg, 4.5tO.5 uM (pCD1); after exercise, this effect was maintained or further increased concomitant with improvement in work performance. Thus, exercise induced stress does not acutely alter resting platelet agg in nls or pts with angina pectoris. Angina pts show increased platelet agg at rest which is restored towards normal by P, an effect which persists despite submaximal exercise.
January
The difference between cathodal, anodal and bipolar fibrillation threshold was investigated in open chest anesthetized dogs with SA nodal destruction and ventricular pacing at lSO/min. Constant current 2 msec duration rectangular cathodal, anodal or bipolar pulse trains of 100 Hz were applied via the pacing electrode($) for 500 msec to the left ventricular apex with the onset of the R wave during interruption of ventricular pacing. The current required to fibrillate using cathodal trains was 2.5 times larger than that required for anodal or bipolar trains, both of which had equal fibrillation thresholds. Electrograms indicated shorter refractory periods with more rapid ventricular responses for anodal or bipolar trains than for cathodal. Fibrillation threshold was also determined after two consecutive premature ventricular contractions by a 2 msec pulse. Starting from total refractory, a time range of vulnerability was determined in which anodal fibrillation threshold was less than cathodal. It is hypothesized that lower anodal or bipolar fibrillation threshold is due to their shorter refractory period and lower threshold in relative refractory. These data support the observed greater relative frequency of ventricular fibrillation in the presence of bipolar cardiac stimulation than unipolar, and suggest that unipolar cathodal stimulation is intrisically safer than bipolar, especially when fibrillation threshold is reduced as with myocardial ischemia.
1974
The American
Journal
of CARDIOLOGY
Volume
33
137