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Lack of importance of the slow component of the response of force to increase of cardiac muscle length
J Mol Cell Cardiol 24 (Supplement IV) (1992) p-46
THE DETERMINANTS OF MYOCARDIAL FORCE VARIATION IN AN ISOMETRIC MODEL OF ATRIAL FIBRILLATION S.M.C.Hardman, W.A. Seed, T Biggs, M.I.M. Noble Dept of Medicine, and Academic Unit of Cardiovascular Medicine, Charing Cross and Westminster Medical School, London W6. Isolated right ventricular trabeculae from 2 patients and 5 guinea pigs were stimulated to contract isometrically in response to (a) sequences of stimuli derived from ECG recordings from 6 patients in jatrial fibrillation (AF) and (b) protocols where all intervals except a single variable interval were held constant. In the AF patients, contractility was recorded as the maximum rate of rise of left ventricular pressure (LVdP/dtmax). During isometric coutraction the maximum rate of rise of force (dF/dtmax) demonstrated a positive relationship with preceding interval typical of mechanical restitution (Spearman Rank correl,ation (rs) = 0.69 - 0.89, p
p-47
LACK OF IMPORTANCE OF THE SLOW COMPONENT OF THE RESPONSE OF FORCE TO INCREASE OF CARDIAC MUSCLE LENGTH M. I.M. Noble, J W Kreuger, N Westerhof, A J Drake-Holland, M Main, K Petterson. Academic Unit of Cardiovascular Medicine, Charing Cross and Westminster Medical School, London UK; Cardiovascular Research Laboratories, Dept of Medicine, Albert Einstein College, Bronx, USA: Laboratorv for Physiology, Free University,-Amsterdam, The Netherlands; Hassle, M&&l, Sweden. An increase in length in isolated preparations is accompanied by an immediate increase in contractile force and followed by a slower fur&r progressive incrcasc - the slow component which is accompanied by an increase in calcium release. Four preparations were used to assess the physiological role of this phenomenon- (1) isolated rat or guixzea pig trabeculae, (2) isolated blood perfused cat heart, (3) isovoltic dog heart on cardiopulmonary bypass and, (4) intact humans undergoing left heart catheterisation for clinical indications. In (1) slow components of force increase reached 20-30%, but change of diastolic length alone resulted in contractile force variations which never exceeded 15%; the slow component was a function of muscle thickness, no component being discernable at diameters ofcO.2mm. In (2) the increases in volume varied from 25 to 850%, but the slow component never exceeded 10%; in one case, the slow component was negative. There was no relationship between the magnitude of the slow component and the magnitude of the volume increase, in contrast to the relationship found fm the immediate component. In (3) there was, if anything a slight dropping back of isovolumic pressure after the initial increase. In (4), no evidence for any slow component was elicited, as judged by constancy of the maximum rate of rise of left ventricular pressure followed for five minutes.
METABOLIC PRODUCTS OF ISCHAFMIA AFFECT RIGOR TENSION DEVELOPMENT IN CARDIAC SKINNED FIBERS. Vladimir Veksler, Rem& Ventura-Clapier. U-241 INSERM, Universite Paris-Sud 91405 Orsay, FrallU?. The effects of ischaemic factors on rigor tension development were studied in rat vent&&r TribDn X-100 treated fip. All solutions were calculated to contain (mM$ imidazole 30, Mg 1, EGTA 10 (pCa 7), Na 30.6, D’IT 0.3, ionic strength 160 adjusted with K-acetate, in the presence or in the absence of phosphocreatine (PCr) 12, and variable MgATP concentrations. In control conditio’ns @H 7.1, and no added inorganic phosphate (Pi) or MgADP), the pMgATP for half-maximal rigor tension @MgATP was 3.47 + 0.04 in the absence and 5.09 + 0.02 in the presence of PCr. The addition of 20 miiP Pi did not change the pMgATP5 in the absence of PCr but slightly decreased pMgATP50 (5.01 + 0.02) in the presence of PCr. 8..a&c pH (6.6) strongly increased pMgATP both in the absence (3.90 + 0.03) and in the presence (5.45 + 0.02) of PCr. Conversely, Mg Ad (250 PM) decreased pMgATP50 to 3.26 It: 0.06 in the absence of PCr; no rigor tension was observed in the presence of PCr. At acidic pH, maximal rigor tension was lower by 29% compared to control conditions while in the presence of MgADP, maximal rigor tension developed to 143 % of control value; Pi had no effect. Thus, in addition to their known effects on active tension, MgADP and protons affect rigor tension and may influence ischaemic contracture development. s.51
THE DETERMINANTS OF MYOCARDIAL FORCE VARIATION IN AN ISOMETRIC MODEL OF ATRIAL FIBRILLATION S.M.C.Hardman, W.A. Seed, T Biggs, M.I.M. Noble Dept of Medicine, and Academic Unit of Cardiovascular Medicine, Charing Cross and Westminster Medical School, London W6. Isolated right ventricular trabeculae from 2 patients and 5 guinea pigs were stimulated to contract isometrically in response to (a) sequences of stimuli derived from ECG recordings from 6 patients in jatrial fibrillation (AF) and (b) protocols where all intervals except a single variable interval were held constant. In the AF patients, contractility was recorded as the maximum rate of rise of left ventricular pressure (LVdP/dtmax). During isometric coutraction the maximum rate of rise of force (dF/dtmax) demonstrated a positive relationship with preceding interval typical of mechanical restitution (Spearman Rank correl,ation (rs) = 0.69 - 0.89, p
p-47
LACK OF IMPORTANCE OF THE SLOW COMPONENT OF THE RESPONSE OF FORCE TO INCREASE OF CARDIAC MUSCLE LENGTH M. I.M. Noble, J W Kreuger, N Westerhof, A J Drake-Holland, M Main, K Petterson. Academic Unit of Cardiovascular Medicine, Charing Cross and Westminster Medical School, London UK; Cardiovascular Research Laboratories, Dept of Medicine, Albert Einstein College, Bronx, USA: Laboratorv for Physiology, Free University,-Amsterdam, The Netherlands; Hassle, M&&l, Sweden. An increase in length in isolated preparations is accompanied by an immediate increase in contractile force and followed by a slower fur&r progressive incrcasc - the slow component which is accompanied by an increase in calcium release. Four preparations were used to assess the physiological role of this phenomenon- (1) isolated rat or guixzea pig trabeculae, (2) isolated blood perfused cat heart, (3) isovoltic dog heart on cardiopulmonary bypass and, (4) intact humans undergoing left heart catheterisation for clinical indications. In (1) slow components of force increase reached 20-30%, but change of diastolic length alone resulted in contractile force variations which never exceeded 15%; the slow component was a function of muscle thickness, no component being discernable at diameters ofcO.2mm. In (2) the increases in volume varied from 25 to 850%, but the slow component never exceeded 10%; in one case, the slow component was negative. There was no relationship between the magnitude of the slow component and the magnitude of the volume increase, in contrast to the relationship found fm the immediate component. In (3) there was, if anything a slight dropping back of isovolumic pressure after the initial increase. In (4), no evidence for any slow component was elicited, as judged by constancy of the maximum rate of rise of left ventricular pressure followed for five minutes.
METABOLIC PRODUCTS OF ISCHAFMIA AFFECT RIGOR TENSION DEVELOPMENT IN CARDIAC SKINNED FIBERS. Vladimir Veksler, Rem& Ventura-Clapier. U-241 INSERM, Universite Paris-Sud 91405 Orsay, FrallU?. The effects of ischaemic factors on rigor tension development were studied in rat vent&&r TribDn X-100 treated fip. All solutions were calculated to contain (mM$ imidazole 30, Mg 1, EGTA 10 (pCa 7), Na 30.6, D’IT 0.3, ionic strength 160 adjusted with K-acetate, in the presence or in the absence of phosphocreatine (PCr) 12, and variable MgATP concentrations. In control conditio’ns @H 7.1, and no added inorganic phosphate (Pi) or MgADP), the pMgATP for half-maximal rigor tension @MgATP was 3.47 + 0.04 in the absence and 5.09 + 0.02 in the presence of PCr. The addition of 20 miiP Pi did not change the pMgATP5 in the absence of PCr but slightly decreased pMgATP50 (5.01 + 0.02) in the presence of PCr. 8..a&c pH (6.6) strongly increased pMgATP both in the absence (3.90 + 0.03) and in the presence (5.45 + 0.02) of PCr. Conversely, Mg Ad (250 PM) decreased pMgATP50 to 3.26 It: 0.06 in the absence of PCr; no rigor tension was observed in the presence of PCr. At acidic pH, maximal rigor tension was lower by 29% compared to control conditions while in the presence of MgADP, maximal rigor tension developed to 143 % of control value; Pi had no effect. Thus, in addition to their known effects on active tension, MgADP and protons affect rigor tension and may influence ischaemic contracture development. s.51