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Negative inotropism of ryanodine wastes the excitation-contraction-relaxation-coupling energy for total released calcium handling in the dog heart
J Mol
(314-4
Cell Cardiol
24 (Supplement
HYPEROSMOLALI-IY RIGHT VENTRICULAR
I) (1992)
ENHANCES TRABECULAE
THE RATE OF HEAT OF THE RAT
PRODUCTION
OF ISOLATED,
QUIESCENT,
Denis S. Loiselle, Ger Stienen, Jiirgen Daut, Gijs Elzinga. Laboratorium voor Fysiologie, Vrije Universiteit, Amsterdam, The Netherlands. The rate of heat production of resting rat cardiac trabeculae was measured in a calorimeter. Trabeculae 2 to 3 mm in length and 5 to 50 pg dry weight were mounted in the calorimeter and bathed in isosmotic Tyrode solution containing 2 mM pyruvate and 20 mM glucose (pH 7.4) at 37°C. The resting, isosmotic, heat rate was 105 f 13 rnW/g dry wt (mean k sem, n = 25). When the bathing solution was rendered hyperosmotic by addition of NaCI, KCl, mannitol or sucrose, the rate of resting heat production increased in a dose-dependent fashion. The peak increment occurred between 450 and 500 mOsm and averaged 3.7 + 0.3-fold, often reaching values in excess of those measured during electrical stimulation under isosmotic conditions. Provided that the osmolality did not exceed about 2.5 times normal, the effect was fully reversible. The hyperosmotic response was characterized by a slow time-course of many minutes, independent of osmotic species, and was totally abolished by anoxia. It was unaffected by ouabain, persisted in the absence of extracellular Ca*+ and was variably diminished (and occasionally abolished) by procaine. Since isometric force production was inhibited under all hyperosmotic conditions, we conclude that the thermal response to a hyperosmotic challenge is due to release of Ca 2+ from the sarcoplasmic reticulum with consequent stimulation of its ATPase activity.
(3-14-5
NEOATIVE CO-G
JNOTROP~ ENERGY
FOR
OF RYANODINE WASTES THE E TOTAL RELEASED CXXRJhiHANDLlNGINTHEDOGHEART
Toshiyuki Takasago, Y&hi Goto, Katsuya Hata, Akio Saeki, Takehiko Nihioka, Hiroyuki Suga* Depts. of Cardiovase. Dynamics and Internal Med., Natl. Cardiovase. Ctr., 5 Fajishiro-dai, Suita, Osaka, 565 and *The 2nd Dept. of Physiol., Okayama University Medical School, 2 Shikatacho, Okayama, 700 Japan Ryanodine (RYA) at a low concentration (several teas nM) is known to bid to calcium (Caz’) release channels in sarcoplasmic reticulum (SR) and fix it open. We studied the mechanism of negative inotropism of RYA at a low concentration in terms of cardiac energetics using the isolated, blood-perfused, cross-circulated dog left ventricle (LV). Fit, we enhanced Emax (an index of LV contractility) ia steps with CaClz given into coronary circulation and obtained the LV oxygen consumption (Vod - total mechanical energy (TME) relation at a constant LV volume. Next, we depressed Emaz with RYA (up to 30 aM) and obtained the Vo2-TME relation at the same volume. Both Vq and TME decreased with the gradually decreased Emax. We calculated TME-independent Voz values at varied Emax levels in both CaClz and RYA runs and obtained the relation between TME-independent Voz and Emax. We have already found that TME-independent Voz is primarily related to the total released Ca’+ from SR, and that TMB-independent Voz and Emaz are proportionally altered by general inotropic drxgs such as CaClz, dobutamine and propranolol (Saga: Physiol. Rev. 70: 247, 1990). In contrast, we found that TME-independent Voz remained dispropotionally high despite the gradually decreased Emax in RYA ran. This result indicates that RYA suppresses the force generation of cardiac muscle for a given amount of total released Ca” from SR. We speculate the underlying mechanism that RYA makes SR leaky for Ca ‘+ , decreasing the releasing speed of Ca ‘* from SR to myofihments.
O-14-6
MYOWRDIAL MECHANICS AND ENERGETICS IN HUMANFAILEDHRARTS Hideyuki Takaoka, Motoshi Takeuchi, Michio Odake, Yoshihiko Hayashi, Masuki Mori. Mitsuhiro Yokoyama. Kobe University School of Medicine, Kobe. JAPAN To assess the chemomechanical energy transduction efficiency (EffJ in human failed hearts, we investigated the relation between myocardial oxygen consumption per beat (Vo2) and systolic pressure-volume area PVA) in 11 patients: Group I: ejection fraction (EF) 150% (n=6), Group II: EFc50% (n=5). The reciprocal of the slope of the Vo2-PVA relation represents Eff whereas the Vo2-intercept represents the non-mechanical Vo2. Vo2 was measured by Webster catheter. WA and Emax. the slope of the end-systolic pressure-volume relation, were measured by conductance catheter. Results: We obtained highly linear regression lines in all the patients (r= 0.908 + 0.082). Emax in Group I were higher than Group II (4.0 f 1.5 vs 2.1 + 0.8 mmHg/ml/m2. p < 0.05). However, Eff in Group I (46 f 12 vs 34 + 9 O/6, NS) and Vo2-intercept (0.52 f 0.97 vs 0.75 rt 0.80 J/beat/lOOgLV) were comparable to Group II. Conclusions: These results suggest that. in the failed heart, Eff is similar to the normal heart, but the nonmechanical Vo2 in a given contractility may be higher than the normal heart. 5.82
(314-4
Cell Cardiol
24 (Supplement
HYPEROSMOLALI-IY RIGHT VENTRICULAR
I) (1992)
ENHANCES TRABECULAE
THE RATE OF HEAT OF THE RAT
PRODUCTION
OF ISOLATED,
QUIESCENT,
Denis S. Loiselle, Ger Stienen, Jiirgen Daut, Gijs Elzinga. Laboratorium voor Fysiologie, Vrije Universiteit, Amsterdam, The Netherlands. The rate of heat production of resting rat cardiac trabeculae was measured in a calorimeter. Trabeculae 2 to 3 mm in length and 5 to 50 pg dry weight were mounted in the calorimeter and bathed in isosmotic Tyrode solution containing 2 mM pyruvate and 20 mM glucose (pH 7.4) at 37°C. The resting, isosmotic, heat rate was 105 f 13 rnW/g dry wt (mean k sem, n = 25). When the bathing solution was rendered hyperosmotic by addition of NaCI, KCl, mannitol or sucrose, the rate of resting heat production increased in a dose-dependent fashion. The peak increment occurred between 450 and 500 mOsm and averaged 3.7 + 0.3-fold, often reaching values in excess of those measured during electrical stimulation under isosmotic conditions. Provided that the osmolality did not exceed about 2.5 times normal, the effect was fully reversible. The hyperosmotic response was characterized by a slow time-course of many minutes, independent of osmotic species, and was totally abolished by anoxia. It was unaffected by ouabain, persisted in the absence of extracellular Ca*+ and was variably diminished (and occasionally abolished) by procaine. Since isometric force production was inhibited under all hyperosmotic conditions, we conclude that the thermal response to a hyperosmotic challenge is due to release of Ca 2+ from the sarcoplasmic reticulum with consequent stimulation of its ATPase activity.
(3-14-5
NEOATIVE CO-G
JNOTROP~ ENERGY
FOR
OF RYANODINE WASTES THE E TOTAL RELEASED CXXRJhiHANDLlNGINTHEDOGHEART
Toshiyuki Takasago, Y&hi Goto, Katsuya Hata, Akio Saeki, Takehiko Nihioka, Hiroyuki Suga* Depts. of Cardiovase. Dynamics and Internal Med., Natl. Cardiovase. Ctr., 5 Fajishiro-dai, Suita, Osaka, 565 and *The 2nd Dept. of Physiol., Okayama University Medical School, 2 Shikatacho, Okayama, 700 Japan Ryanodine (RYA) at a low concentration (several teas nM) is known to bid to calcium (Caz’) release channels in sarcoplasmic reticulum (SR) and fix it open. We studied the mechanism of negative inotropism of RYA at a low concentration in terms of cardiac energetics using the isolated, blood-perfused, cross-circulated dog left ventricle (LV). Fit, we enhanced Emax (an index of LV contractility) ia steps with CaClz given into coronary circulation and obtained the LV oxygen consumption (Vod - total mechanical energy (TME) relation at a constant LV volume. Next, we depressed Emaz with RYA (up to 30 aM) and obtained the Vo2-TME relation at the same volume. Both Vq and TME decreased with the gradually decreased Emax. We calculated TME-independent Voz values at varied Emax levels in both CaClz and RYA runs and obtained the relation between TME-independent Voz and Emax. We have already found that TME-independent Voz is primarily related to the total released Ca’+ from SR, and that TMB-independent Voz and Emaz are proportionally altered by general inotropic drxgs such as CaClz, dobutamine and propranolol (Saga: Physiol. Rev. 70: 247, 1990). In contrast, we found that TME-independent Voz remained dispropotionally high despite the gradually decreased Emax in RYA ran. This result indicates that RYA suppresses the force generation of cardiac muscle for a given amount of total released Ca” from SR. We speculate the underlying mechanism that RYA makes SR leaky for Ca ‘+ , decreasing the releasing speed of Ca ‘* from SR to myofihments.
O-14-6
MYOWRDIAL MECHANICS AND ENERGETICS IN HUMANFAILEDHRARTS Hideyuki Takaoka, Motoshi Takeuchi, Michio Odake, Yoshihiko Hayashi, Masuki Mori. Mitsuhiro Yokoyama. Kobe University School of Medicine, Kobe. JAPAN To assess the chemomechanical energy transduction efficiency (EffJ in human failed hearts, we investigated the relation between myocardial oxygen consumption per beat (Vo2) and systolic pressure-volume area PVA) in 11 patients: Group I: ejection fraction (EF) 150% (n=6), Group II: EFc50% (n=5). The reciprocal of the slope of the Vo2-PVA relation represents Eff whereas the Vo2-intercept represents the non-mechanical Vo2. Vo2 was measured by Webster catheter. WA and Emax. the slope of the end-systolic pressure-volume relation, were measured by conductance catheter. Results: We obtained highly linear regression lines in all the patients (r= 0.908 + 0.082). Emax in Group I were higher than Group II (4.0 f 1.5 vs 2.1 + 0.8 mmHg/ml/m2. p < 0.05). However, Eff in Group I (46 f 12 vs 34 + 9 O/6, NS) and Vo2-intercept (0.52 f 0.97 vs 0.75 rt 0.80 J/beat/lOOgLV) were comparable to Group II. Conclusions: These results suggest that. in the failed heart, Eff is similar to the normal heart, but the nonmechanical Vo2 in a given contractility may be higher than the normal heart. 5.82