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The clearance of circulating catecholamines by the lung in normal man and in patients with pulmonary hypertension
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ABSTRACTS
MITRAL VALVE PROLAPSE AND ADRENERGIC HYPERACTIVITY IN PRIMARY DISORDERS OF SLEEP. Robert W. Clark, MD; Harisios Boudoulas, MD,FACC; Stephen F. Schaal, MD,FACC; Helmut S. Schmldt, MD; Richard P. Lewis, MD,FACC; Ohio State University; Columbus, Ohio. Fifty-three patients (pts) diagnosed as having sleep apnea (n=29), narcolepsy (n=13) or nonspecific excessive drowsiness (n=ll) in our sleep lab were evaluated for evidence of autonomic dysfunction. Night sweats occurred in 2/3. of pts and panic attacks were experience d by 20 of the 53 subjects. Mitral valve prolapse (MVP) was diagnosed by physical and echocardiographic criteria in 59% of pts tested. Twenty-four hour urinary epinephrine (E) and norepinephrine (NE) secretion were significantly greater in the group with sleep disorders as compared to normal (99.2_+6.7 ~g/24 hours vs 39~4, p~0.01). Catecholamine secretion was not significantly different between MVP and non-MVP pts. A shortened electromechanical systole corrected for heart rate (HR)(QS21)(535_+3 vs 548~i, p<0.Ol) also reflected the high adrenergic tone in pts with high catecholamine levels. Intravenous isoproterenol 2 ~g/min for 6 min elicited a significantly greater pulse increase in 8 pts with sleep apnea when compared to 6 normals (34_+2 vs 23_+3, p<0.Ol). Panic attacks during isoproterenol infusion were elicited in 4 pts. Our findings indicate that I) increased adrenergic tone and hypersensitivity to adrenergic stimulation is present in many pts with sleep disorders, 2) MVP is very common in these pts. The paradoxical increase in adrenergic activity in disorders of impaired wakefulness can result in a therapeutic dilemma when either stimulants or beta blocking agents are required. Some MVP symptoms, particularly fatigue, could be related to sleep disorders,
ALTERED EFFECT OF SYMPATHETIC NERVE STIMULATION ON VENTRICULAR FIBRILLATION THRESHOLD DUE TO CORONARY PERFUSION CHANGES Alexandros C. Kralios, MD; Mary Ann McDonnell, MD; William J. Bugni, MD; Theofilos J. Tsagaris, MD; Hiroshi Kuida, MD, University of Utah and VA Hospital, Salt Lake City, Utah. Left cardiac sympathetic nerve stimulation (SNS) reportedly reduces ventricular fibrillation threshold (VFT) in open chest dogs. In view of recent information suggesting that VFT is increased by raising coronary blood flow index (CBFI), the following study was undertaken. VFT was determined before and during stimulation of the ventrolateral nerve (8 Hz, 8V) by the single stimulus scanning technique in i0 open chest dogs with strictly controlled heart rate, cardiac output and systemic arterial pressure. VFT determinations were repeated at different CBFI levels induced either by selective left coronary artery cannulation and perfusion or changes in arterial 02 conte~t. Myocardial 02 consumption index (MVO2I) was continuously monitored via CBFI and coronary sinus saturation recordings along with the ECG and LV dp/dt. SNS resulted in peak increase of LV dp/dt by 180 + 35 ~m Hg/ sec (p<0.001), MV02I by 3.13 + 0.61 ml 02/min---100g-ILv (p<0. 001) and CBFI by 13.8 + 4.3 ml/min- 100g-ILv (p<0.01), but no consistent VFT changes. In the same animal at similar CBFI, 'TFT did not differ before and during SNS. Contrarily, induced larger increases in CBFI either before (39 + 5.5 ml/min.100g-iLV) or during SNS (57.5 + 14.3) were associated with higher VFT by 8.1 + 2.6 mA, p<0.01 and 7.7 ~ 3.0 mA, p<0.05, respectively. Therefore since CBFI represents a strong determinant of VFT and may vary by SNS and/or during the VFT testing procedure, only VFT changes in excess of what can be explained by CBFI variations should be attributed to interventions such as SNS.
THE CLEARANCE OF CIRCULATING CATECHOLAM!NES BY THE LUNG IN NORMAL MAN AND IN PATIENTS WITH PULMONARY HYPERTENSION. Michael J. Sole, MD, FACC; Milutin Drobac, MD; Leonard Schwartz MD; M. Nasir Hussain MSc; Edward F. Vaughan-Neil MD; University of Toronto, Department of Medicine, Toront% Ontario, Canada, M5S 1A8. The lung has been shown to partially inactivate norepinephrine (NE) during its passage through the pulmonary circulation. This inactivation is mediated by the uptake of NE into pre- and post-capillary endothelial cells. The pulmonary extraction of cireulatlng NE, epinephrine (E), and dopamine (DA) has n o t b e e n directly measured in resting man. Using a sensitlve radioenzymatic assay, we examined the pulmonary clearance of these catecholamines in 17 control patients. As it was possible that pulmonary vascular disease may affect this aspect of lung function, we also examined seven patients with primary or secondary pulmonary hypertension. Mixed pulmonary artery NE, E and DA were 314 ± 13 pg/ml, 102 ± 9 pg/ml and 51 ± 5 pg/ml respectively, for the control group; values were similar in the pulmonary hypertensive group. The pulmonary extraction of NE was 25.4 ± 2.6% (clearance 266 ± 62 ng/ min) in control patients; DA and E were not extracted. The presence of a smoking history or an elevation of left atrial pressure and mean pulmonary artery pressure in the absence of an increase in pulmonary vascular resistance d i d not affect norepinephrine clearance. There was no extraction or production of any of the three catecholam i n e s b y the lung in any of the patients with pulmonary hypertension. In conclusion: the lung plays a significant role in the inactivation of circulating NE in man. This metabolic function of the lung appears to be lost in pulmonary hypertension.
EFFECTS OF ACUTE BETARECEPTORBLOCKADE ON MYOCARDIAL NORADRENALINE RELEASE IN CONGESTIVE CARDIOMYOPATHY Karl Swedberq, MD; ~ke Hjalmarson~ MD; Stig Holmberg. MD; Dept, of Med. I, Sahlgrenska Hospltal, G~teborg, Sweden n congestive cardiomyopathy (COCM) with myocardial ailure (MF) improved myocardial function has been observed during longterm treatment with betareceptorblockade (BRB). The purpose of this study was to investigate the hemodynamic effects and noradrenaline (NA) release after acute BRB in COCM. Eight patients (pts) with COCM and 7 volunteers (group N) were investigated in the same way. Another 9 pts with primary valvular disease ~ (group PVD) were studied preoperatively. Cardiac output (CO) was measured by the Fick method at rest and during work before and after metoprolol 15 mg i.v. (grOup PVD without BRB). Blood samples for myocardial arterio-venous differences (MAVD) were taken. NA was determined by an isotop method. Results: After BRB in COCM pts CO decreased at rest from 4.0+0.4 i/rain to 3.0+_0.4 (p~0.01), heart rate from 86+5 to 80+4 (p<0.05). Pulmonary artery diastolic pressures were 21_+4 and 23+3 mm Hg respectively. During work changes in the same direction were observed. NA concentrations in myocardial blood nmol/l (mean+SE): Before BRB After B R B Rest Work Rest Work Group N 2.6+0.3 5.3+0.6 3. i_+0.4 7.4+1.2 Group PVD 4.4+1.1 ii. 7+2.6 -COCM 5.7+1.6 19.5_+6.6 8.2+1.1 27.3+_7.5 Increased values after BRB can be explained by reduced coronary flow and increased sympathetic activity. The arterial NA concentrations increased with exercise and further after BRB. All MAVD for NA were negative. The highest MAVD were seen in COCM pts after exercise during BRB.The degree of MF was negatively related to the arterial NA concentrations. Conclusions: I. Pts with COCM and advanced MF showed a remarkable good tolerance to acute BRB. -- 2. The NA concentrations reflected the degree of MF and do not seem to differ COCM pts from pts with PVD. -- 3. In spite of the supposed low myocardial content of NA in MF the myocardial release of NA was high in COCM pts and could increase further after BRB.
~
February 1979
The American Journal of CARDIOLOGY
Volume 43
345
ABSTRACTS
MITRAL VALVE PROLAPSE AND ADRENERGIC HYPERACTIVITY IN PRIMARY DISORDERS OF SLEEP. Robert W. Clark, MD; Harisios Boudoulas, MD,FACC; Stephen F. Schaal, MD,FACC; Helmut S. Schmldt, MD; Richard P. Lewis, MD,FACC; Ohio State University; Columbus, Ohio. Fifty-three patients (pts) diagnosed as having sleep apnea (n=29), narcolepsy (n=13) or nonspecific excessive drowsiness (n=ll) in our sleep lab were evaluated for evidence of autonomic dysfunction. Night sweats occurred in 2/3. of pts and panic attacks were experience d by 20 of the 53 subjects. Mitral valve prolapse (MVP) was diagnosed by physical and echocardiographic criteria in 59% of pts tested. Twenty-four hour urinary epinephrine (E) and norepinephrine (NE) secretion were significantly greater in the group with sleep disorders as compared to normal (99.2_+6.7 ~g/24 hours vs 39~4, p~0.01). Catecholamine secretion was not significantly different between MVP and non-MVP pts. A shortened electromechanical systole corrected for heart rate (HR)(QS21)(535_+3 vs 548~i, p<0.Ol) also reflected the high adrenergic tone in pts with high catecholamine levels. Intravenous isoproterenol 2 ~g/min for 6 min elicited a significantly greater pulse increase in 8 pts with sleep apnea when compared to 6 normals (34_+2 vs 23_+3, p<0.Ol). Panic attacks during isoproterenol infusion were elicited in 4 pts. Our findings indicate that I) increased adrenergic tone and hypersensitivity to adrenergic stimulation is present in many pts with sleep disorders, 2) MVP is very common in these pts. The paradoxical increase in adrenergic activity in disorders of impaired wakefulness can result in a therapeutic dilemma when either stimulants or beta blocking agents are required. Some MVP symptoms, particularly fatigue, could be related to sleep disorders,
ALTERED EFFECT OF SYMPATHETIC NERVE STIMULATION ON VENTRICULAR FIBRILLATION THRESHOLD DUE TO CORONARY PERFUSION CHANGES Alexandros C. Kralios, MD; Mary Ann McDonnell, MD; William J. Bugni, MD; Theofilos J. Tsagaris, MD; Hiroshi Kuida, MD, University of Utah and VA Hospital, Salt Lake City, Utah. Left cardiac sympathetic nerve stimulation (SNS) reportedly reduces ventricular fibrillation threshold (VFT) in open chest dogs. In view of recent information suggesting that VFT is increased by raising coronary blood flow index (CBFI), the following study was undertaken. VFT was determined before and during stimulation of the ventrolateral nerve (8 Hz, 8V) by the single stimulus scanning technique in i0 open chest dogs with strictly controlled heart rate, cardiac output and systemic arterial pressure. VFT determinations were repeated at different CBFI levels induced either by selective left coronary artery cannulation and perfusion or changes in arterial 02 conte~t. Myocardial 02 consumption index (MVO2I) was continuously monitored via CBFI and coronary sinus saturation recordings along with the ECG and LV dp/dt. SNS resulted in peak increase of LV dp/dt by 180 + 35 ~m Hg/ sec (p<0.001), MV02I by 3.13 + 0.61 ml 02/min---100g-ILv (p<0. 001) and CBFI by 13.8 + 4.3 ml/min- 100g-ILv (p<0.01), but no consistent VFT changes. In the same animal at similar CBFI, 'TFT did not differ before and during SNS. Contrarily, induced larger increases in CBFI either before (39 + 5.5 ml/min.100g-iLV) or during SNS (57.5 + 14.3) were associated with higher VFT by 8.1 + 2.6 mA, p<0.01 and 7.7 ~ 3.0 mA, p<0.05, respectively. Therefore since CBFI represents a strong determinant of VFT and may vary by SNS and/or during the VFT testing procedure, only VFT changes in excess of what can be explained by CBFI variations should be attributed to interventions such as SNS.
THE CLEARANCE OF CIRCULATING CATECHOLAM!NES BY THE LUNG IN NORMAL MAN AND IN PATIENTS WITH PULMONARY HYPERTENSION. Michael J. Sole, MD, FACC; Milutin Drobac, MD; Leonard Schwartz MD; M. Nasir Hussain MSc; Edward F. Vaughan-Neil MD; University of Toronto, Department of Medicine, Toront% Ontario, Canada, M5S 1A8. The lung has been shown to partially inactivate norepinephrine (NE) during its passage through the pulmonary circulation. This inactivation is mediated by the uptake of NE into pre- and post-capillary endothelial cells. The pulmonary extraction of cireulatlng NE, epinephrine (E), and dopamine (DA) has n o t b e e n directly measured in resting man. Using a sensitlve radioenzymatic assay, we examined the pulmonary clearance of these catecholamines in 17 control patients. As it was possible that pulmonary vascular disease may affect this aspect of lung function, we also examined seven patients with primary or secondary pulmonary hypertension. Mixed pulmonary artery NE, E and DA were 314 ± 13 pg/ml, 102 ± 9 pg/ml and 51 ± 5 pg/ml respectively, for the control group; values were similar in the pulmonary hypertensive group. The pulmonary extraction of NE was 25.4 ± 2.6% (clearance 266 ± 62 ng/ min) in control patients; DA and E were not extracted. The presence of a smoking history or an elevation of left atrial pressure and mean pulmonary artery pressure in the absence of an increase in pulmonary vascular resistance d i d not affect norepinephrine clearance. There was no extraction or production of any of the three catecholam i n e s b y the lung in any of the patients with pulmonary hypertension. In conclusion: the lung plays a significant role in the inactivation of circulating NE in man. This metabolic function of the lung appears to be lost in pulmonary hypertension.
EFFECTS OF ACUTE BETARECEPTORBLOCKADE ON MYOCARDIAL NORADRENALINE RELEASE IN CONGESTIVE CARDIOMYOPATHY Karl Swedberq, MD; ~ke Hjalmarson~ MD; Stig Holmberg. MD; Dept, of Med. I, Sahlgrenska Hospltal, G~teborg, Sweden n congestive cardiomyopathy (COCM) with myocardial ailure (MF) improved myocardial function has been observed during longterm treatment with betareceptorblockade (BRB). The purpose of this study was to investigate the hemodynamic effects and noradrenaline (NA) release after acute BRB in COCM. Eight patients (pts) with COCM and 7 volunteers (group N) were investigated in the same way. Another 9 pts with primary valvular disease ~ (group PVD) were studied preoperatively. Cardiac output (CO) was measured by the Fick method at rest and during work before and after metoprolol 15 mg i.v. (grOup PVD without BRB). Blood samples for myocardial arterio-venous differences (MAVD) were taken. NA was determined by an isotop method. Results: After BRB in COCM pts CO decreased at rest from 4.0+0.4 i/rain to 3.0+_0.4 (p~0.01), heart rate from 86+5 to 80+4 (p<0.05). Pulmonary artery diastolic pressures were 21_+4 and 23+3 mm Hg respectively. During work changes in the same direction were observed. NA concentrations in myocardial blood nmol/l (mean+SE): Before BRB After B R B Rest Work Rest Work Group N 2.6+0.3 5.3+0.6 3. i_+0.4 7.4+1.2 Group PVD 4.4+1.1 ii. 7+2.6 -COCM 5.7+1.6 19.5_+6.6 8.2+1.1 27.3+_7.5 Increased values after BRB can be explained by reduced coronary flow and increased sympathetic activity. The arterial NA concentrations increased with exercise and further after BRB. All MAVD for NA were negative. The highest MAVD were seen in COCM pts after exercise during BRB.The degree of MF was negatively related to the arterial NA concentrations. Conclusions: I. Pts with COCM and advanced MF showed a remarkable good tolerance to acute BRB. -- 2. The NA concentrations reflected the degree of MF and do not seem to differ COCM pts from pts with PVD. -- 3. In spite of the supposed low myocardial content of NA in MF the myocardial release of NA was high in COCM pts and could increase further after BRB.
~
February 1979
The American Journal of CARDIOLOGY
Volume 43
345