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Beat by beat variations in rate and extent of mechanical restitution during mechanical alternans
.J Mol Cell Cardiol 24 (Supplement IV) (1992)
P-40 COMPARISON
OF THE RATIO BETWEEN RYANODINEAND DHP-RECEPTORS IN CONTROL AND HYPERTROPHIED HEARTS FROM GUINEA PIG AND RAT. F. Rahnou, C. Sainte-Beuve, I. Primot, P. Oliviero, D. Charlemagne. INSERM U 127, Hopital Laribdisikre, 75010 Paris, France. Abnormal calcium handling and depressed contractility have been observed in the hypertrophied heart whatever the species. To determine whether the adaptation of the number or ratio of Dihvdropvridine and Rvanodine receptors (DHP-R and Rva-R) in the hvuertrouhied heart is an overall procedure or varied wiih the species; we have compared the density of ihese ieceptors in control and hypertrophied guinea pig and rat hearts. Binding assays were performed with [3H]PN 200-l 10 and [3H]Ryanodine on crude membrane preparations. The n&s were expressed in pmol of receptors per g of left ventricle (LV). In control and hypertrophied guinea pig LV the ratio between DHP and Rya-R was significantly increased (0.33 and 0.40) at 52% hypertrophy according to the number of DHP-R (13.!kbO.8 and 11.6k0.7, respectively) and of Rya-R (42.1k5.2 and 28.9~b4.5, respectively). In the rat LV, this ratio remained identical in control and 40-60 % hypertrophy (0.32 and 0.31) and was only increased at hypertrophy > 60% (0.43) due to a similar number of DHP-R whatever the hvoertroohv (14.2+3.2) anda decrease in the number of Rva-R at 69% hvoertroohv f44.5k7.8 andil.M?.<. respectively). In conclusion, adaptation of the guinea pig heart o&&d ailo’wer hypertrophy than in the rat and the decrease observed in the ratio DHP-R/Rva-R even at mild hvoertrouhv. emohasized the role of the membrane functions in the depressed contra&y of the guinea pig hearf. 1 I
P-41 BEAT BY BEAT VARIATIONS
IN RATE AND EXTENT OF MECHANICAL RESTITUTICrN DURING ~ECBANICAL ALTERWAWS. C. Ian Spencer, Max J. Lab*, W. Anthony Seed. Departments of Medicine and Physiology*, Charing Cross and Westminster Medical School, London W6 SRF. Mechanical alternans is regular alternation of contractility on but constant successive beats in myocardium stimulated at a high frequency. We have obtained sustained alternans in isolated papillary muscles under predisposing conditions, i.e. temperature reduced to 27oC. We studied the muscles by constructing mechanical restitution curves and fitting the curves with monoexponentials. The mea.n restitution rate constants for the beat 3 following the i$rge and small s and 8.9+1.3 alternans contractions were 7.3~1.4 s resnectivelv The difference between the meanrate const-ants wasil (SEM, n=ll). significant at the 95% level. In addition to the slishtlv accelerated rate of restitution following a small contraction, -ful iy restitutecj force tended to be higher. This could imply either that enhanced Cal with a small beat, or that a fraction of the total1 inf h ux is associated [Ca Ii is unreleasable following a large contraction.
P-42
THE EFFECT OF HYPOCHLORITE ON CHEMICALLY ‘SKINNED’ CARDIAC MUSCLE Nial G MacFarkme and DavidJ Miller. Institute of Physiology, Glasgow University, G12 SQO, UK. Neuuophil accumulation and activation occurs after periods of ischaemia and myocardiil infarction and may contriblute to conaactile dysfunction upon reperfnsion. Neutrophil myeloperoxidase catalyses the formation of hypochlorous acid (HOCI) from cytoplasmic Cl-. HOC1 is highly reactive and can oxidise many biological molecules (especially SH groups). We have studied the effects of HOC1 on calcium sensitivity and force production by the myofilamenta. We used T&on-treated trabeculae (dia. 75-120bm, sarcomere length 2.1-2.2pm) from rat right ventricle. At physiologically relevant concentrations, and after an application as brief as 1 minute, si oificant effects occur in a dose-dependent fashion. At 10pM (pH 7), callcium rose by 0.091M.021, from 5.23 to 5.32), but maximum sensitivity increases (mean ?r SD, n=5: log [Ca 3 +1 for half activation Ca-activated force (Cm,) is reduced (by 18.8f5.8%). Resting tension increases from nominally zero to 15.4?8 % of Cmax. We have examined the nature of These actions, apart from the fall in Cmax, contrast with those we obtained with superoxide.
the resting tension increaseby allowing HOC1to act in the presenceof 20mM Pi or 20mM caffeine,both mance~vres expected to affect rigor tension. Neither intervention was effective, suggesting that rigor bridges are not involved. However, relatively small length changes (-1% of resting length) dissipate the resting tension increase, as would be the case for dgor. Dithiothreitol(2OmM) does not protect The Ca sensitivity and peak force changes do not depend upon altered resting tension. against, or reverse, the effects of HOCl, suggesting that thiol reduction is not the primary cawe of the effects described. These data demonstrate that the ftmdamentat units of force production in the myocardium are sensitive to HOC1 at concentrations that could occur physiologically. The effects described would contribute to the depression of contractile function seen clinically in reperfwd myocardiam.
s.49
P-40 COMPARISON
OF THE RATIO BETWEEN RYANODINEAND DHP-RECEPTORS IN CONTROL AND HYPERTROPHIED HEARTS FROM GUINEA PIG AND RAT. F. Rahnou, C. Sainte-Beuve, I. Primot, P. Oliviero, D. Charlemagne. INSERM U 127, Hopital Laribdisikre, 75010 Paris, France. Abnormal calcium handling and depressed contractility have been observed in the hypertrophied heart whatever the species. To determine whether the adaptation of the number or ratio of Dihvdropvridine and Rvanodine receptors (DHP-R and Rva-R) in the hvuertrouhied heart is an overall procedure or varied wiih the species; we have compared the density of ihese ieceptors in control and hypertrophied guinea pig and rat hearts. Binding assays were performed with [3H]PN 200-l 10 and [3H]Ryanodine on crude membrane preparations. The n&s were expressed in pmol of receptors per g of left ventricle (LV). In control and hypertrophied guinea pig LV the ratio between DHP and Rya-R was significantly increased (0.33 and 0.40) at 52% hypertrophy according to the number of DHP-R (13.!kbO.8 and 11.6k0.7, respectively) and of Rya-R (42.1k5.2 and 28.9~b4.5, respectively). In the rat LV, this ratio remained identical in control and 40-60 % hypertrophy (0.32 and 0.31) and was only increased at hypertrophy > 60% (0.43) due to a similar number of DHP-R whatever the hvoertroohv (14.2+3.2) anda decrease in the number of Rva-R at 69% hvoertroohv f44.5k7.8 andil.M?.<. respectively). In conclusion, adaptation of the guinea pig heart o&&d ailo’wer hypertrophy than in the rat and the decrease observed in the ratio DHP-R/Rva-R even at mild hvoertrouhv. emohasized the role of the membrane functions in the depressed contra&y of the guinea pig hearf. 1 I
P-41 BEAT BY BEAT VARIATIONS
IN RATE AND EXTENT OF MECHANICAL RESTITUTICrN DURING ~ECBANICAL ALTERWAWS. C. Ian Spencer, Max J. Lab*, W. Anthony Seed. Departments of Medicine and Physiology*, Charing Cross and Westminster Medical School, London W6 SRF. Mechanical alternans is regular alternation of contractility on but constant successive beats in myocardium stimulated at a high frequency. We have obtained sustained alternans in isolated papillary muscles under predisposing conditions, i.e. temperature reduced to 27oC. We studied the muscles by constructing mechanical restitution curves and fitting the curves with monoexponentials. The mea.n restitution rate constants for the beat 3 following the i$rge and small s and 8.9+1.3 alternans contractions were 7.3~1.4 s resnectivelv The difference between the meanrate const-ants wasil (SEM, n=ll). significant at the 95% level. In addition to the slishtlv accelerated rate of restitution following a small contraction, -ful iy restitutecj force tended to be higher. This could imply either that enhanced Cal with a small beat, or that a fraction of the total1 inf h ux is associated [Ca Ii is unreleasable following a large contraction.
P-42
THE EFFECT OF HYPOCHLORITE ON CHEMICALLY ‘SKINNED’ CARDIAC MUSCLE Nial G MacFarkme and DavidJ Miller. Institute of Physiology, Glasgow University, G12 SQO, UK. Neuuophil accumulation and activation occurs after periods of ischaemia and myocardiil infarction and may contriblute to conaactile dysfunction upon reperfnsion. Neutrophil myeloperoxidase catalyses the formation of hypochlorous acid (HOCI) from cytoplasmic Cl-. HOC1 is highly reactive and can oxidise many biological molecules (especially SH groups). We have studied the effects of HOC1 on calcium sensitivity and force production by the myofilamenta. We used T&on-treated trabeculae (dia. 75-120bm, sarcomere length 2.1-2.2pm) from rat right ventricle. At physiologically relevant concentrations, and after an application as brief as 1 minute, si oificant effects occur in a dose-dependent fashion. At 10pM (pH 7), callcium rose by 0.091M.021, from 5.23 to 5.32), but maximum sensitivity increases (mean ?r SD, n=5: log [Ca 3 +1 for half activation Ca-activated force (Cm,) is reduced (by 18.8f5.8%). Resting tension increases from nominally zero to 15.4?8 % of Cmax. We have examined the nature of These actions, apart from the fall in Cmax, contrast with those we obtained with superoxide.
the resting tension increaseby allowing HOC1to act in the presenceof 20mM Pi or 20mM caffeine,both mance~vres expected to affect rigor tension. Neither intervention was effective, suggesting that rigor bridges are not involved. However, relatively small length changes (-1% of resting length) dissipate the resting tension increase, as would be the case for dgor. Dithiothreitol(2OmM) does not protect The Ca sensitivity and peak force changes do not depend upon altered resting tension. against, or reverse, the effects of HOCl, suggesting that thiol reduction is not the primary cawe of the effects described. These data demonstrate that the ftmdamentat units of force production in the myocardium are sensitive to HOC1 at concentrations that could occur physiologically. The effects described would contribute to the depression of contractile function seen clinically in reperfwd myocardiam.
s.49