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Metabolism of arrhythmogenic lysophosphatides in rabbit myocardium
ABSTRACTS
EFFICACY OF AFTERLOAD REDUCTION IN AORTIC REGURGITATION: ASSESSMENT BY TWO-DIMENSIONAL ECHO Martin St. John Sutton, MD, Nathaniel Reichek, MD, Ted Plappert, John A. Eastor, MD, FACC, Hospital of the University of Pennsylvania, Philadelphia, PA
To determine the effects of afterload reduction in the treatment of chronic aortic regurgitation(AR), we developed a method of assessing LV cavity size, wall thickness, and end-systolic wall stress using 2-dimensional echo and systolic cuff blood pressure(P). High-quality echoes of the LV short axis at,mitral valve level and simultaneous systolic blood P were obtained in 12 patients with severe AR before and after 0.4 mg sublingual nitroglycerin. LV echograms were digitized to obtain cavity area( and myocardial area and these results were corrected with a regression equation previously validated in vitro. Endsystolic wall stress was calculated as 1.334 x P x CA/MA before and after nitroglycerin(NTG): P.(mm) CA.(cn/) MA.(cm2) Wall Stress.(dynes/cr&) Before: -15.5fp.o 32.2k6.5 79.0225.8 X 103 (NTG) 69.0+24.8 X lo3 After: 121+17 14.6+8.6 32.156.5 (NTG) Nitroglycerin significantly reduced P (p<.Ol), CA (p< .005), and end-systolic wall stress (pc.02) without any changed in MA or heart rate. In conclusion, we describe a new, reproducible and non-invasive method of assessing end-systolic wall stress, 2) demonstrate that in patients with AR nitroglycerin significantly reduced end-systolic LV size and wall stress, 3) since end-systolic wall stress is the critical factor limiting LV emptying, afterload reduction appears efficacious in the treatment of patients with chronic severe aortic regurgitation.
TWO DIMENSIONAL ECHOCARDIOGRAPHIC EVALUATION OF BRANCH PULMONARY ARTERY STENOSIS Navin C. Nanda, MO, FACC; Mark S. Rosenzweig, MD; James E. Hodsden, MD; James A. Manning, MD; Shirley Santelli, Univ. of Rochester Medical Center--Rochester, New York Real time two dimensional echocardiographic studies were performed in 6 patients (ages 5-25 years; 3 females, 3 males) with branch pulmonary artery stenosis proven by cardiac catheterization and angiography. The suprasternal
approach was utilized using a commercially availabletransducer specially suited for this technique. The right pulmonary artery was visualized behind the aortic arch, and angling the transducer leftward brought the main and left pulmonary arteries into view. Discrete narrowing of the lumen at the origin of the left pulmonary artery was seen in one patient with an atria1 septal defect, and at the origin of both right and left pulmonary arteries in another patient with tetrology of Fallot and atria1 septal deTubular narrowing of the right pulmonary artery was fect. seen in one patient who had pulmonary valvotcmy for pulThe main pulmonary artery waslarge monary valve stenosis.
and prominently pulsatile. Tubular narrowing of the right pulmonary artery with post-stenotic dilatation of its distal portion was identified in one patient who had no other cardiac lesions. Diffuse narrowing of both the right and left pulmonary arteries was seen in one patient with mild 'pulmonary valve stenosis. A large left pulmonary artery with absent right pulmonary artery was identified in one patient with tricuspid atresia. All findings were confirmed at angio-cardiography. Abnormalities of the pulmonary artery branches could not be identified in any patient using the precordial or subcostal approach. Suprasternal two dimensional echocardiographic examinationtechnique is useful in the evaluation of branch pulmonary artery stenosis and this represents a newer extension raoabilitv of this non-invasive method.
of the
MONDAY, MARCH 16, 1987 PM MYOCARDIAL METABOLISM P:OO-530
PHOSPHORYLATION OF CARDIAC SARCOPLASMIC RETICULUM (SR) BY A CALCIUM-ACTIVATED, PHOSPHOLIPID-DEPENDENT PROTEIN KINASE. Constantinos J. Limas, M.D.; University of Minnesota School of Medicine; Minneapolis, Minnesota A novel cyclic nucleotide-independent protein kinase (PK-C) has been isolated from rat heart cytosol. PK-C can phosphorylate cardiac SR (1.6kO.4 nmol/mg/lO min) in the presence of Ca2+ (10-7-10-4 M CaC12) and phospholipids (2-20 ng/ml). Phosphatidylserine is most effective, followed by phosphatidylinositol and phosphatidyl-choline. Diacylglycerols containing unsaturated fatty acids (diolein,dilinolein,diarachidonin) stimulate PK-C by SO75% by increasing its Ca2+ sensitivity. Saturated diacyl-glycerols, mono- and triacylglycerols, on the other hand, are ineffective. PK-C dependent phosphorylation of cardiac SR results in enhanced Ca2+ uptake (128f16 nmol Ca2+) mg/min vs 82?9 nmol/mg/min in controls, p
METABOLISM OF ARRHYTHMOGENIC LYSOPHOSPHATIDES IN RABBIT MYOCARDIUM Richard W. Gross, MD; Burton E. Sobel, MD, FACC, Washington University, St. Louis, Missouri Cardiac
metabolism of lysophosphatidyl choline (LPC), implicated as a mediator of dysrhythmia induced by ischemia, has not been elucidated. To determine whether LPC transacylase acitivity, analogous to that in liver, is present in heart muscle, rabbit heart extracts were prepared by mincing; homogenization in 0.25 M sucrose (25X w/v), 1 mM DTT, 10 mM phosphate, pH 7.4; and centrifugation at 3,000, 8,000, 20,000 g for 10 min and 100,000 g for 1 hr. LPC-transacylase in the supernate was assayed in 800 ~1 of media containing 75 mM buffer, pH 5 to 9; 3 mM MgCl; 120 FM I-T4C-LPC; and 600 fig protein incubated at 37O for 15 min; products extracted in 750 @ butanol and separated by HPLC; and radioactivity quantified. Transacylation, manifested as synthesis of l,2-'4Cphosphatidylcholine (PC) occurred at a high rate (0.61 f .07 (SE) nmols/mg protein/min (n : 6), displayed a sharp pH ,optimum at pH 7.0, and was linear with respect to incubation time and protein concentration. To identify the position of incorporated label, PC synthesized was isolated by HPLC and treated with snake venom phospholipase A2. The ratio of labeled fatty acid to labeled LPC was 1.09 f .I1 (n I 4), demonstrating the initial presence of PC labeled in both the I- and 2-positions. To detect other reactions such as direct acylation (LPC acyl transferase), cytosol was incubated under the same 14C-palmitoyl CoA and unlabeled LPC. conditions with PC synthesis was < 10% of that seen with labeled LPC.
Thus, rabbit heart cytosolic extracts exhibit considerable LPC transacylase activity (but not LPC acyl transferase) that does not require acyl CoA and that appears to contribute substantially to LPC metabolism.
February 1981
The American Journal of CARDIOLOGY
Volume 47
413
EFFICACY OF AFTERLOAD REDUCTION IN AORTIC REGURGITATION: ASSESSMENT BY TWO-DIMENSIONAL ECHO Martin St. John Sutton, MD, Nathaniel Reichek, MD, Ted Plappert, John A. Eastor, MD, FACC, Hospital of the University of Pennsylvania, Philadelphia, PA
To determine the effects of afterload reduction in the treatment of chronic aortic regurgitation(AR), we developed a method of assessing LV cavity size, wall thickness, and end-systolic wall stress using 2-dimensional echo and systolic cuff blood pressure(P). High-quality echoes of the LV short axis at,mitral valve level and simultaneous systolic blood P were obtained in 12 patients with severe AR before and after 0.4 mg sublingual nitroglycerin. LV echograms were digitized to obtain cavity area( and myocardial area and these results were corrected with a regression equation previously validated in vitro. Endsystolic wall stress was calculated as 1.334 x P x CA/MA before and after nitroglycerin(NTG): P.(mm) CA.(cn/) MA.(cm2) Wall Stress.(dynes/cr&) Before: -15.5fp.o 32.2k6.5 79.0225.8 X 103 (NTG) 69.0+24.8 X lo3 After: 121+17 14.6+8.6 32.156.5 (NTG) Nitroglycerin significantly reduced P (p<.Ol), CA (p< .005), and end-systolic wall stress (pc.02) without any changed in MA or heart rate. In conclusion, we describe a new, reproducible and non-invasive method of assessing end-systolic wall stress, 2) demonstrate that in patients with AR nitroglycerin significantly reduced end-systolic LV size and wall stress, 3) since end-systolic wall stress is the critical factor limiting LV emptying, afterload reduction appears efficacious in the treatment of patients with chronic severe aortic regurgitation.
TWO DIMENSIONAL ECHOCARDIOGRAPHIC EVALUATION OF BRANCH PULMONARY ARTERY STENOSIS Navin C. Nanda, MO, FACC; Mark S. Rosenzweig, MD; James E. Hodsden, MD; James A. Manning, MD; Shirley Santelli, Univ. of Rochester Medical Center--Rochester, New York Real time two dimensional echocardiographic studies were performed in 6 patients (ages 5-25 years; 3 females, 3 males) with branch pulmonary artery stenosis proven by cardiac catheterization and angiography. The suprasternal
approach was utilized using a commercially availabletransducer specially suited for this technique. The right pulmonary artery was visualized behind the aortic arch, and angling the transducer leftward brought the main and left pulmonary arteries into view. Discrete narrowing of the lumen at the origin of the left pulmonary artery was seen in one patient with an atria1 septal defect, and at the origin of both right and left pulmonary arteries in another patient with tetrology of Fallot and atria1 septal deTubular narrowing of the right pulmonary artery was fect. seen in one patient who had pulmonary valvotcmy for pulThe main pulmonary artery waslarge monary valve stenosis.
and prominently pulsatile. Tubular narrowing of the right pulmonary artery with post-stenotic dilatation of its distal portion was identified in one patient who had no other cardiac lesions. Diffuse narrowing of both the right and left pulmonary arteries was seen in one patient with mild 'pulmonary valve stenosis. A large left pulmonary artery with absent right pulmonary artery was identified in one patient with tricuspid atresia. All findings were confirmed at angio-cardiography. Abnormalities of the pulmonary artery branches could not be identified in any patient using the precordial or subcostal approach. Suprasternal two dimensional echocardiographic examinationtechnique is useful in the evaluation of branch pulmonary artery stenosis and this represents a newer extension raoabilitv of this non-invasive method.
of the
MONDAY, MARCH 16, 1987 PM MYOCARDIAL METABOLISM P:OO-530
PHOSPHORYLATION OF CARDIAC SARCOPLASMIC RETICULUM (SR) BY A CALCIUM-ACTIVATED, PHOSPHOLIPID-DEPENDENT PROTEIN KINASE. Constantinos J. Limas, M.D.; University of Minnesota School of Medicine; Minneapolis, Minnesota A novel cyclic nucleotide-independent protein kinase (PK-C) has been isolated from rat heart cytosol. PK-C can phosphorylate cardiac SR (1.6kO.4 nmol/mg/lO min) in the presence of Ca2+ (10-7-10-4 M CaC12) and phospholipids (2-20 ng/ml). Phosphatidylserine is most effective, followed by phosphatidylinositol and phosphatidyl-choline. Diacylglycerols containing unsaturated fatty acids (diolein,dilinolein,diarachidonin) stimulate PK-C by SO75% by increasing its Ca2+ sensitivity. Saturated diacyl-glycerols, mono- and triacylglycerols, on the other hand, are ineffective. PK-C dependent phosphorylation of cardiac SR results in enhanced Ca2+ uptake (128f16 nmol Ca2+) mg/min vs 82?9 nmol/mg/min in controls, p
METABOLISM OF ARRHYTHMOGENIC LYSOPHOSPHATIDES IN RABBIT MYOCARDIUM Richard W. Gross, MD; Burton E. Sobel, MD, FACC, Washington University, St. Louis, Missouri Cardiac
metabolism of lysophosphatidyl choline (LPC), implicated as a mediator of dysrhythmia induced by ischemia, has not been elucidated. To determine whether LPC transacylase acitivity, analogous to that in liver, is present in heart muscle, rabbit heart extracts were prepared by mincing; homogenization in 0.25 M sucrose (25X w/v), 1 mM DTT, 10 mM phosphate, pH 7.4; and centrifugation at 3,000, 8,000, 20,000 g for 10 min and 100,000 g for 1 hr. LPC-transacylase in the supernate was assayed in 800 ~1 of media containing 75 mM buffer, pH 5 to 9; 3 mM MgCl; 120 FM I-T4C-LPC; and 600 fig protein incubated at 37O for 15 min; products extracted in 750 @ butanol and separated by HPLC; and radioactivity quantified. Transacylation, manifested as synthesis of l,2-'4Cphosphatidylcholine (PC) occurred at a high rate (0.61 f .07 (SE) nmols/mg protein/min (n : 6), displayed a sharp pH ,optimum at pH 7.0, and was linear with respect to incubation time and protein concentration. To identify the position of incorporated label, PC synthesized was isolated by HPLC and treated with snake venom phospholipase A2. The ratio of labeled fatty acid to labeled LPC was 1.09 f .I1 (n I 4), demonstrating the initial presence of PC labeled in both the I- and 2-positions. To detect other reactions such as direct acylation (LPC acyl transferase), cytosol was incubated under the same 14C-palmitoyl CoA and unlabeled LPC. conditions with PC synthesis was < 10% of that seen with labeled LPC.
Thus, rabbit heart cytosolic extracts exhibit considerable LPC transacylase activity (but not LPC acyl transferase) that does not require acyl CoA and that appears to contribute substantially to LPC metabolism.
February 1981
The American Journal of CARDIOLOGY
Volume 47
413