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Comparative mechanisms of ventricular unloading by systemic vasodilator agents in therapy of cardiac failure: Nitroprusside versus phentolamine
ABSTRACTS
MONITORING TISSUX OXYGENATION OF TUE HEART FOLLOWING MTOCARDIAL RRVASCULARIWTION Leslie Wiener, M.D., FACC; Mario Faola, M.D., FACC; Vcnkataaamy Veluchamy; John Y. Templeton, III. M.D., Thomaa Jefferson University Rospital, Philadelphia, Pa. A polarographic technique for the continuous monitoring of myocardial tissue oxygenation was evaluated in dogs and wed in patients undergoing aorto-coronary bypass surgery. Ihrec precalibrated micro-Clark type electrodes verc implanted at various depths in selected areas and connected to a dual purpose electronic circuit, which allowed simultaneous recording of myocardial tissue oxygen tension (n402) and electrical activity potentials (unipolar electrograma). In 13 doga, MqO2 from 30 areaa was atudied in relation to changes in arterial oxygen content, cardiac output, aortic preaaure, coronary blood flow and myocardial oxygen extraction. The beat correlation was with regional coronary artery blood flow (r-0.92). In 9 patients, XqO2 was measured in 14 areas undergoing revaaeularisation and monitored for two weeks postoperatively. In seven, PlqO2 rose in 12 areas from 4.6 t1.4 to 12 t4 II. Ug (psO.05). paralleling an incraase in regional coronary artery blood flow via an aorta-coronary bypass (108t12 ml./min.). MqO2 recorded from two areas in tuo patienta increased ilrcdiately, but dropped in the third postoperative day, failing to rise in response to oxygen administration. Concomitantly, the ST-segment of the unipolar electrograma rose from 1.2 t 0.4 to 6 t 1 IY. (I% 0.005). This preceded by at least 24 hours subsequent evidence of myocardial infarction by standard ECC and enaymatic methoda. This technique l eema aenaitive and reliable. It appears to be capable of anticipating acutely developing myocardial ischemia during the high riak early postoperative period follwing coronary surgery.
MECHANISM OF IMPAIRED CONTRACTILE PROTEIN FUNCTION IN AORTIC STENOSIS: ALTERATIONS OF MYOSIN ATPASE ACTIVITY IN THE CHRONICALLY PRESSURE OVERLOADED CANINE LEFT VENTRICLE. Joan Wikmann-Coffelt, PhD; John McPherson, BS; Antone F. Salel, MD; Teiko Kamiyama, MD; Dean T. Mason, MD, FACC. Univ. Calif. Davis, Calif. To evaluate the fundamental changes in contractile proteins underlying disturbed left ventricular(LV) performance in clinical aortic stenosis, severe aortic banding was performed in twelve dogs to raise the peak systolic LV pressure 70% above normal as measured at the time of sacrifice. Contrary to mild pulmonary artery bandin?, there was no increase in enzymatic Vmax values of K activated myosin ATPzise. In contrast, 6 weeks following aortic banding, LV myosin was depressed 12% below normal and by 16 weeks postoperatively, enzymatic Vm, values were 60% below normal. Normal LV V, was 0.84 umoles POq!mg.min. Similar decreases in CA* activated myosin Vmax were also observed. The wet weight of the heart relative to body weight increased 30% above normal by 6 weeks postoperatively and was 50% above normal after 16 weeks of aortic stenosis. Mechanical LV V,x was depressed 20% below normal following 16 weeks of severe aortic stenosis. By mass spectrometry analyses of intramyocardial gas tensions, LV tissue was hypoxic at 16 weeks postoperatively: Partial pressure of 02 was 8 while that of CO2 was 94, compared to control measurements of PO2 24 and PC02 45. These experimental studies of severe aortic stenosis demonstrate that marked LV systolic pressure overload results in depressed myosin enzymatic performance in the hypertrophied myocardium. This abnormality in contractile protein function is postulated to be important in the reduction of mechanical contractile state which occurs secondary to the chronic excessive hemodynamic burden on the left ventricle.
TliROWROLYSIN@ TREQMlZNT OF ACUTE MAIN PULMONARY TWROMROEMBOLI W. Curtis Wilcox, M. D.; John F. Carroll, M. D.; Lee I. Schocket, M. D.; Robert M. Anderson, M. D.; Tucson Medical Center, Tucson, Arizona Acute thromboetiboliwithin the main pulmonary arteries and right heart chambers visualized by cardiopulmonary angiography cause two distinct hemodynmaic patterns. ACUTE MAIN, IN EXTREMIS is characterized by clinical shock, a cardiac index of-Zl.6 L/min/M* (Range 1.6-0.85), a right ventricular end-diastolic pressure of>10 mmllg (Range 15-20) a pulmonary vascular resistance of > 750 dyne-cm-sec'5 (Range 750-1326). ACUTE MAIN is characterized by systemic normotension to hypotension, a cardiac index ofH.6 LlminiM2 (Range 1.76-4.0) and a pulmonary vascular resistance of <750 dyne-cm-see-5 (Range 199-652) In six ACUTE MAIN, IN EXTREMIS patients treated wit a one-hour superior vena caval infusion of Tbrombolysin & (streptokinase activated human fibrinolysin and profibrinalysin) shock disappeared within 120 minutes and there was only one hospital death and no late deaths. The cardiopulmonary hemodynamics and angiograms in all five survivors returned to normal prior to discharge. In 16 ACUTE MAIN patients treated with superior vena caval Thrombolysit@there was only one hospital death and no late deaths, with the cardiopulmonary hemodynamics returning to normal in the 15 survivors prior to discharge. The rapid thrombolytic effect of Thrombolysin@ in reversing shock, right ventricular failure, and pulmonary vascular hyperresistance in 22 patients with acute thromboemboli within the main pulmonary arteries is documented by serial cardiopulmonary hemodynamic and angiographic studies.
COMPARATIVE MECHANISMS OF VENTRICULAR UNLOADING BY SYSTEMIC VASODILATOR AGENTS IN THERAPY OF CARDIAC FAILURE: NITROPRUSSIDE VERSUS PHENTOLAMINE. David 0. Williams, MD; General K. Hilliard, MD; Stephen A. Cantor, MD; Richard R. Miller, MD; Dean T. Mason, MD, FACC. Martinez VA Hospital and Sacramento Medical Center, Univ. Calif. Davis, Calif. Since improvement of low cardiac output in pump dysfunction by vasodilators depends on relative actions on left ventricular(LV) impedance and preload, nitroprusside(NP) was compared to phentolamine(PH) in 16 coronary patients (pts). NP(25-100 pgm/min) and PH(l.O-2.5 mg/min) were separately infused IV in each pt to effect equal+ of mean brachial arterial pressure(MAP) with control hemodynamics allowed to return between the two agents; administration sequence was alternated in successive pts. After MAP+ (87 to 71 mmHg) with each agent, eripheral vascular resistance(TPVR 1386 dynes-sec-cm- s ) was unchanged after NP (p>.O5) whereas+ occurred with PH(-350; pc.05). In 16 pts, LV end-diastolic pressure(EDP 14 mmHg) was+ more by NP than PH(-8 versus -5; pc.05); while cardiac index(C1 2.51 L/min/M2)+ with NP butt with PH(-0.32 versus tC.23; pc.01). In 9 normal EDP(sl2 mmHg) pts, NP+ both EDP(-5) and CI (-0.40). whereas PHS only EDP(-3). In 6 high EDP(>lZ) pts, NPC EDP from 21 to 8(-13) without change in low CI(2.26); in contrast EDP+ was less(-9) while CIt (t0.39, pq.02) with PH. Afterload/preload change expressed as APVR/ALVEDP was greater with PH than NP(-190 versus -33; pc.05) in 16 pts. Equal LV afterloadf by NP causes greater preloadt than PH due to NP-venodilation which may counterbalance NP impedance+ effect, thereby inhibiting CI rise. Vaaodepressor-induced reflex competes with direct NP action which impairs impedance+. whereas PH blocks alpha receptor stimulation. PH principally+ afterload and NP has combined pre- and afterload+ actions. Thus PH is more effective than NP in improving pump failure when LV does not remain fully preloaded at apex of its function curve.
January 1975
The American Journal of CARDIOLOGY
Volume 35
177
MONITORING TISSUX OXYGENATION OF TUE HEART FOLLOWING MTOCARDIAL RRVASCULARIWTION Leslie Wiener, M.D., FACC; Mario Faola, M.D., FACC; Vcnkataaamy Veluchamy; John Y. Templeton, III. M.D., Thomaa Jefferson University Rospital, Philadelphia, Pa. A polarographic technique for the continuous monitoring of myocardial tissue oxygenation was evaluated in dogs and wed in patients undergoing aorto-coronary bypass surgery. Ihrec precalibrated micro-Clark type electrodes verc implanted at various depths in selected areas and connected to a dual purpose electronic circuit, which allowed simultaneous recording of myocardial tissue oxygen tension (n402) and electrical activity potentials (unipolar electrograma). In 13 doga, MqO2 from 30 areaa was atudied in relation to changes in arterial oxygen content, cardiac output, aortic preaaure, coronary blood flow and myocardial oxygen extraction. The beat correlation was with regional coronary artery blood flow (r-0.92). In 9 patients, XqO2 was measured in 14 areas undergoing revaaeularisation and monitored for two weeks postoperatively. In seven, PlqO2 rose in 12 areas from 4.6 t1.4 to 12 t4 II. Ug (psO.05). paralleling an incraase in regional coronary artery blood flow via an aorta-coronary bypass (108t12 ml./min.). MqO2 recorded from two areas in tuo patienta increased ilrcdiately, but dropped in the third postoperative day, failing to rise in response to oxygen administration. Concomitantly, the ST-segment of the unipolar electrograma rose from 1.2 t 0.4 to 6 t 1 IY. (I% 0.005). This preceded by at least 24 hours subsequent evidence of myocardial infarction by standard ECC and enaymatic methoda. This technique l eema aenaitive and reliable. It appears to be capable of anticipating acutely developing myocardial ischemia during the high riak early postoperative period follwing coronary surgery.
MECHANISM OF IMPAIRED CONTRACTILE PROTEIN FUNCTION IN AORTIC STENOSIS: ALTERATIONS OF MYOSIN ATPASE ACTIVITY IN THE CHRONICALLY PRESSURE OVERLOADED CANINE LEFT VENTRICLE. Joan Wikmann-Coffelt, PhD; John McPherson, BS; Antone F. Salel, MD; Teiko Kamiyama, MD; Dean T. Mason, MD, FACC. Univ. Calif. Davis, Calif. To evaluate the fundamental changes in contractile proteins underlying disturbed left ventricular(LV) performance in clinical aortic stenosis, severe aortic banding was performed in twelve dogs to raise the peak systolic LV pressure 70% above normal as measured at the time of sacrifice. Contrary to mild pulmonary artery bandin?, there was no increase in enzymatic Vmax values of K activated myosin ATPzise. In contrast, 6 weeks following aortic banding, LV myosin was depressed 12% below normal and by 16 weeks postoperatively, enzymatic Vm, values were 60% below normal. Normal LV V, was 0.84 umoles POq!mg.min. Similar decreases in CA* activated myosin Vmax were also observed. The wet weight of the heart relative to body weight increased 30% above normal by 6 weeks postoperatively and was 50% above normal after 16 weeks of aortic stenosis. Mechanical LV V,x was depressed 20% below normal following 16 weeks of severe aortic stenosis. By mass spectrometry analyses of intramyocardial gas tensions, LV tissue was hypoxic at 16 weeks postoperatively: Partial pressure of 02 was 8 while that of CO2 was 94, compared to control measurements of PO2 24 and PC02 45. These experimental studies of severe aortic stenosis demonstrate that marked LV systolic pressure overload results in depressed myosin enzymatic performance in the hypertrophied myocardium. This abnormality in contractile protein function is postulated to be important in the reduction of mechanical contractile state which occurs secondary to the chronic excessive hemodynamic burden on the left ventricle.
TliROWROLYSIN@ TREQMlZNT OF ACUTE MAIN PULMONARY TWROMROEMBOLI W. Curtis Wilcox, M. D.; John F. Carroll, M. D.; Lee I. Schocket, M. D.; Robert M. Anderson, M. D.; Tucson Medical Center, Tucson, Arizona Acute thromboetiboliwithin the main pulmonary arteries and right heart chambers visualized by cardiopulmonary angiography cause two distinct hemodynmaic patterns. ACUTE MAIN, IN EXTREMIS is characterized by clinical shock, a cardiac index of-Zl.6 L/min/M* (Range 1.6-0.85), a right ventricular end-diastolic pressure of>10 mmllg (Range 15-20) a pulmonary vascular resistance of > 750 dyne-cm-sec'5 (Range 750-1326). ACUTE MAIN is characterized by systemic normotension to hypotension, a cardiac index ofH.6 LlminiM2 (Range 1.76-4.0) and a pulmonary vascular resistance of <750 dyne-cm-see-5 (Range 199-652) In six ACUTE MAIN, IN EXTREMIS patients treated wit a one-hour superior vena caval infusion of Tbrombolysin & (streptokinase activated human fibrinolysin and profibrinalysin) shock disappeared within 120 minutes and there was only one hospital death and no late deaths. The cardiopulmonary hemodynamics and angiograms in all five survivors returned to normal prior to discharge. In 16 ACUTE MAIN patients treated with superior vena caval Thrombolysit@there was only one hospital death and no late deaths, with the cardiopulmonary hemodynamics returning to normal in the 15 survivors prior to discharge. The rapid thrombolytic effect of Thrombolysin@ in reversing shock, right ventricular failure, and pulmonary vascular hyperresistance in 22 patients with acute thromboemboli within the main pulmonary arteries is documented by serial cardiopulmonary hemodynamic and angiographic studies.
COMPARATIVE MECHANISMS OF VENTRICULAR UNLOADING BY SYSTEMIC VASODILATOR AGENTS IN THERAPY OF CARDIAC FAILURE: NITROPRUSSIDE VERSUS PHENTOLAMINE. David 0. Williams, MD; General K. Hilliard, MD; Stephen A. Cantor, MD; Richard R. Miller, MD; Dean T. Mason, MD, FACC. Martinez VA Hospital and Sacramento Medical Center, Univ. Calif. Davis, Calif. Since improvement of low cardiac output in pump dysfunction by vasodilators depends on relative actions on left ventricular(LV) impedance and preload, nitroprusside(NP) was compared to phentolamine(PH) in 16 coronary patients (pts). NP(25-100 pgm/min) and PH(l.O-2.5 mg/min) were separately infused IV in each pt to effect equal+ of mean brachial arterial pressure(MAP) with control hemodynamics allowed to return between the two agents; administration sequence was alternated in successive pts. After MAP+ (87 to 71 mmHg) with each agent, eripheral vascular resistance(TPVR 1386 dynes-sec-cm- s ) was unchanged after NP (p>.O5) whereas+ occurred with PH(-350; pc.05). In 16 pts, LV end-diastolic pressure(EDP 14 mmHg) was+ more by NP than PH(-8 versus -5; pc.05); while cardiac index(C1 2.51 L/min/M2)+ with NP butt with PH(-0.32 versus tC.23; pc.01). In 9 normal EDP(sl2 mmHg) pts, NP+ both EDP(-5) and CI (-0.40). whereas PHS only EDP(-3). In 6 high EDP(>lZ) pts, NPC EDP from 21 to 8(-13) without change in low CI(2.26); in contrast EDP+ was less(-9) while CIt (t0.39, pq.02) with PH. Afterload/preload change expressed as APVR/ALVEDP was greater with PH than NP(-190 versus -33; pc.05) in 16 pts. Equal LV afterloadf by NP causes greater preloadt than PH due to NP-venodilation which may counterbalance NP impedance+ effect, thereby inhibiting CI rise. Vaaodepressor-induced reflex competes with direct NP action which impairs impedance+. whereas PH blocks alpha receptor stimulation. PH principally+ afterload and NP has combined pre- and afterload+ actions. Thus PH is more effective than NP in improving pump failure when LV does not remain fully preloaded at apex of its function curve.
January 1975
The American Journal of CARDIOLOGY
Volume 35
177