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Biomedical subjects

L A Mulieri

Publications and source records attributed to L A Mulieri.

At least 37 records · Page 2Linked to original sources
PubMed1992

The reorganization of the human and rabbit heart in response to haemodynamic overload.

A myothermal/mechanical analysis on non-failing and failing human hearts and normal and pressure overloaded rabbit hearts is reported. Heat production is partitioned into tension-dependent and tension-independent components together with force measurements to provide information about calcium and cross-bridge cycling. In the non-failing human heart the cross-bridge force-time integral is 0.51 +/- 0.06 (ns). This value is increased to 0.97 +/- 0.09 (P less than 0.05 s) in failing hearts. In control as compared to pressure-overload rabbit hearts the cross-bridge force-time integral increases from 0.36 +/- 0.02 to 0.96 +/- 0.11 (P less than 0.05 s). The increase in force-time integral allows the heart muscle to develop force with greater economy (less high energy phosphate hydrolysis) but at the expense of velocity and power. The amount of calcium cycled following activation in non-failing human hearts is 32.2 +/- 8.17 nmoles.g-1.-beat-1. In the failing preparations calcium cycling is reduced to 16.7 +/- 1.72 nmoles.g-1.-beat-1. In pressure-overloaded hypertrophied, as compared with control rabbit hearts, the calcium cycled per beat is reduced from 43.0 +/- 7.3 to 17.6 +/- 3.4 nmoles.g-1. It is suggested that the alterations in cross-bridge cycling are more likely to be related to isoenzyme shifts in light chains or troponin T than to myosin isoforms. The calcium cycling changes are well correlated with changes in the sarcoplasmic reticular and sarcolemmal calcium transport proteins. The alterations in the contractile and excitation contractions coupling systems contribute to the functional changes observed in the failing human and pressure-overload rabbit hearts.

Animals↗
PubMed1992

Cellular basis of negative inotropic effect of 2,3-butanedione monoxime in human myocardium.

2,3-Butanedione monoxime (BDM) exerts a marked negative inotropic effect and has been shown to have protective actions on human myocardial force production that may be of clinical use. To determine the underlying mechanisms, we studied the effects of BDM on chemically skinned and aequorin-loaded myopathic human myocardium from transplant recipients. Eighteen muscles were chemically skinned with saponin (250 micrograms/ml) and then subjected to activation-relaxation cycles, with and without 5 mM BDM. Contracture force vs. Ca2+ data were fitted to a modified Hill equation, and values for 50% maximal activation (pCa50) and maximal Ca(2+)-activated force (Fmax) were obtained. pCa50 was decreased by 0.2 pCa units, indicating myofilament Ca2+ desensitization, and Fmax was reduced by 48% in 5 mM BDM. A second group of intact muscles (n = 8) was loaded with aequorin to monitor intracellular calcium (Cai2+) transients (peak light) and twitch force in the presence of BDM (1-30 mM). Over a range of 1-20 mM, BDM depressed peak light by 3-49% while force was depressed by 10-82%. This was accompanied by an abbreviation of the duration of the twitch but not of the Cai2+ transient. At a concentration of 30 mM, BDM completely inhibited force generation, but an Cai2+ transient was still present. We conclude that in human myocardium, 5 mM BDM predominantly affects cross-bridge force production and Ca2+ sensitivity and has a less pronounced effect on Cai2+.

Aequorin↗
PubMed1992

Altered myocardial force-frequency relation in human heart failure.

BACKGROUND: In congestive heart failure (idiopathic dilated cardiomyopathy), exercise is accompanied by a smaller-than-normal decrease in end-diastolic left ventricular volume, depressed peak rates of left ventricular pressure rise and fall, and depressed heart-rate-dependent potentiation of contractility (bowditch treppe). We studied contractile function of isolated left ventricular myocardium from New York Heart Association class IV-failing and nonfailing hearts at physiological temperature and heart rates in order to identify and quantitate abnormalities in myocardial function that underlie abnormal ventricular function. METHODS AND RESULTS: The isometric tension-generating ability of isolated left ventricular strips from nonfailing and failing human hearts was investigated at 37 degrees C and contraction frequencies ranging from 12 to 240 per minute (min-1). Strips were dissected using a new method of protection against cutting injury with 2,3-butanedione monoxime (BDM) as a cardioplegic agent. In nonfailing myocardium the twitch tension-frequency relation is bell-shaped developing 25 +/- 2 mN/mm2 at a contraction frequency of 72 min-1 and peaking at 44 +/- 3.7 mN/mm2 at a contraction frequency of 174 +/- 4 min-1. In failing myocardium the peak of the curve occurs at lower frequencies between 6 and 120 min-1 averaging 81 +/- 22 min-1, and it develops 48% (p less than 0.001) and 80% (p less than 0.001) less tension than in nonfailing myocardium at 72 and 174 min-1, respectively. Between 60 and 150 min-1 tension increases by 107% in nonfailing myocardium, but it does not change significantly in failing myocardium. Peak rates of rise and fall of isometric twitch tension vary in parallel with twitch tension as stimulation frequency rises in nonfailing myocardium but not in failing myocardium. CONCLUSIONS: The quantitative agreement between these results from isolated myocardium and those from catheterization laboratory measurements on intact humans suggest that alterations of myocardial origin, independent of systemic factors, may contribute to the above mentioned abnormalities in left ventricular function seen in dilated cardiomyopathy.

Adult↗
PubMed1992

Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy.

Myocardial failure in dilated cardiomyopathy may result from subcellular alterations in contractile protein function, excitation-contraction coupling processes, or recovery metabolism. We used isometric force and heat measurements to quantitatively investigate these subcellular systems in intact left ventricular muscle strips from nonfailing human hearts (n = 14) and from hearts with end-stage failing dilated cardiomyopathy (n = 13). In the failing myocardium, peak isometric twitch tension, maximum rate of tension rise, and maximum rate of relaxation were reduced by 46% (p = 0.013), 51% (p = 0.003), and 46% (p = 0.018), respectively (37 degrees C, 60 beats per minute). Tension-dependent heat, reflecting the number of crossbridge interactions during the isometric twitch, was reduced by 61% in the failing myocardium (p = 0.006). In terms of the individual crossbridge cycle, the average crossbridge force-time integral was increased by 33% (p = 0.04) in the failing myocardium. In the nonfailing myocardium, the crossbridge force-time integral was positively correlated with the patient's age (r = 0.86, p less than 0.02), whereas there was no significant correlation with age in the failing group. The amount and rate of excitation-contraction coupling-related heat evolution (tension-independent heat) were reduced by 69% (p = 0.24) and 71% (p = 0.028), respectively, in the failing myocardium, reflecting a considerable decrease in the amount of calcium released and in the rate of calcium removal. The efficiency of the metabolic recovery process, as assessed by the ratio of initial heat to total activity-related heat, was similar in failing and nonfailing myocardium (0.54 +/- 0.03 versus 0.50 +/- 0.02, p = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1991

Energetics of isometric force development in control and volume-overload human myocardium. Comparison with animal species.

Alteration in crossbridge behavior and myocardial performance have been associated with myosin isoenzyme composition in animal models of myocardial hypertrophy or atrophy. In the hypertrophied human heart, myocardial performance is altered without significant changes in myosin isoenzymes. To better understand this discrepancy, isometric heat and force measurements were carried out in 1) control and volume-overload human myocardium, 2) control, pressure-overload, and hyperthyroid rabbit myocardium, and 3) control and hypothyroid rat myocardium. In control human myocardium, peak isometric twitch tension was 44.0 +/- 11.7 mN/mm2, and maximum rate of tension rise was 69.2 +/- 21.0 mN/sec.mm2. In volume-overload human myocardium, peak twitch tension and maximum rate of tension rise were reduced by 55% (p less than 0.05) and 65% (p less than 0.05), respectively. The average force-time integral of the individual crossbridge cycle, calculated by myothermal techniques, was increased by 85% (p less than 0.005) in volume-overload human myocardium. In control and hormonally altered myocardium, both across and within species (control human, control rat, control rabbit, hypothyroid rat, and hyperthyroid rabbit), there was a close relation between the crossbridge force-time integral and the percentage of V3-type myosin isoenzyme in the myocardium. However, hemodynamically altered (volume-overload human and pressure-overload rabbit) myocardium did not follow this relation. Across and within species, there were significant correlations between maximum rate of tension rise and average tension-dependent heat rate (r = 0.97, p less than 0.001) and between maximum rate of tension fall and average tension-independent heat rate (r = 0.82; p less than 0.025). Furthermore, there were close inverse relations between these heat rates and the crossbridge force-time integral. In addition, there was an inverse relation between tension-independent heat and the crossbridge force-time integral. Across and within species total myocardial energy turnover was significantly correlated with the crossbridge force-time integral (relative total heat, r = -0.84, p less than 0.02; relative total-activity related heat, r = -0.88, p less than 0.01). The present findings indicate that 1) factors separate from myosin isoenzymes account for the altered crossbridge cycle in volume-overload human and pressure-overload rabbit myocardium, 2) changes in excitation-contraction coupling processes accompany changes in the crossbridge cycle within and across species, and 3) the force-time integral of the crossbridge cycle is a major determinant of total myocardial energy turnover.

Animals↗
PubMed1990

Dynamic calcium requirements for activation of rabbit papillary muscle calculated from tension-independent heat.

The heat generated by right ventricular papillary muscles of rabbits was measured after adenosine triphosphate (ATP) splitting by the contractile proteins was chemically inhibited. This tension-independent heat (TIH) (1 mJ/g wet weight) was used to calculate the total calcium (Ca) cycled in a muscle twitch by assuming that 87% of TIH was due to Ca2+ transport by the sarcoplasmic reticulum with a coupling ratio of 2 Ca2+/ATP split; the enthalpy of creatine phosphate hydrolysis buffering ATP was taken as -34 KJ/mol. The estimated Ca turnover per muscle twitch at 21 degrees C, 0.2 Hz pacing rate, and 2.5 mM Ca in the Krebs solution was approximately equal to 50 nmol/g wet weight. There was a tight positive correlation between TIH and mechanical activation during steady-state measurements but no correlation during the sharp increase in mechanical activation (treppe) when stimulation was resumed after a rest period. It is suggested that while total Ca cycling remains unchanged during the initial period of tension treppe, the free Ca2+ transient and mechanical activation increase sharply due to resaturation of high affinity Ca2+ buffers, other than troponin C, depleted of Ca2+ during the rest period.

Actin Cytoskeleton↗
PubMed1990

Modulation of myothermal economy of isometric force generation by positive inotropic interventions in the guinea pig myocardium.

Isometric force development has been measured simultaneously with liberated heat in papillary muscles from the right ventricle of the guinea pig, using rapid antimony-bismuth thermopiles. The following components of the contractile cycle and their relation to energy consumption were evaluated: (1) basal metabolism; (2) crossbridge cycling; (3) calcium cycling; and (4) recovery processes. The influences of isoproterenol, high calcium and UDCG-115, a calcium-sensitizing substance, on these four energy compartments of the muscle were studied relative to their positive inotropic effects. Isoproterenol increased initial heat per peak developed tension or per tension-time integral from 7.4 +/- 1.55 to 11.65 +/- 1.15 mucal/g cm (p less than 0.02) or from 4.52 +/- 0.79 to 8.14 +/- 0.77 mucal/g cm sec (p less than 0.01), respectively. In contrast, these ratios were unchanged from control values by positive inotropic interventions with 11 mM calcium or UDCG-115. The increase of initial heat for a unit of mechanical activity due to isoproterenol is attributable to activation and contractile protein processes, i.e. the activation heat increased from 0.24 +/- 0.05 to 0.68 +/- 0.13 mcal/g (p less than 0.01) and tension-dependent heat per tension-time integral increased from 2.24 +/- 0.60 to 5.18 +/- 0.89 mucal/g cm sec (p less than 0.01). We conclude that isoproterenol increases the number of calcium ions released into the sarcoplasm during each activation cycle. It also alters the rate of crossbridge cycling associated with a decreased economy of force generation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Genetic and non-genetic control of myocardial calcium.

Some aspects of the genetic and non-genetic control of the amount and rate of calcium cycled during steady-state activation of papillary muscles from right ventricular rabbit myocardium are presented. Genetic reorganization of the intracellular structure of the myocardium is achieved by producing right ventricular pressure overload and thyrotoxic hypertrophy. The mechanical performance of the pressure overload heart is slowed while time to peak tension is increased. These changes are associated with an increase in myothermal economy. In thyrotoxic hypertrophy the rate of mechanical performance is increased while time to peak tension is decreased. These alterations are associated with a decrease in myothermal economy. Tension-independent heat is used as an index of calcium cycling. In pressure overload hearts the amount and rate of calcium cycling is decreased. In contrast in thyrotoxic hypertrophy the amount of calcium cycled is unchanged while the rate is increased. In the pressure overload hearts there is a decrease in sarcoplasmic reticular (SR) Ca++ ATPase, whereas in the thyrotoxic preparations the message is increased. The change in the rate of calcium uptake in pressure overload and thyrotoxic hearts is correlated with a change in the amount of SR Ca++ ATPase mRNA. Calcium cycling was also altered by non-genetic inotropic intervention. Isoproterenol (1 microM) increases the amount of calcium cycled during each contraction relaxation cycle and the rate at which it is removed. These alterations are associated with an increase in force and a foreshortened twitch. Incubating the papillary muscle in high calcium (11 mM) also increases the force and the amount of calcium released into the cytosol. Under these circumstances the rate of uptake is not significantly increased and, accordingly, the isometric twitch is not foreshortened. In the presence of verapamil (14 microM) the peak twitch force is decreased and the isometric myogram is foreshortened. These changes are associated with a decrease in the amount of calcium released during activation and the rate at which it is removed.

Animals↗
PubMed1989

Influence of isoproterenol on myocardial energetics. Experimental and clinical investigations.

The influence of isoproterenol on myocardial performance and energetics was investigated in normal guinea pig myocardium and in patients with normal left ventricular function. The in vitro experiments were performed by simultaneous isometric force and heat measurements using sensitive antimony-bismuth thermopiles. Following the application of isoproterenol (10(-8) M) isometric peak twitch tension and tension-time integral increased significantly by 185% and 142%, respectively. Tension-independent heat which reflects high energy phosphate hydrolysis of excitation-contraction coupling increased by 183%. Tension-dependent heat reflecting the high energy phosphate hydrolysis of the crossbridges increased by 417%. The ratio of tension-dependent heat to tension-time integral increased by 131%. The recovery/initial heat ratio, reflecting the efficiency of the recovery metabolism, and the resting metabolism did not significantly change. In the patients the effect of isoproterenol on myocardial energetics was evaluated in terms of myocardial efficiency. Following isoproterenol administration, left ventricular systolic stress-time integral decreased by 49% due to reductions in end-diastolic pressure, end-diastolic volume and duration of systole. Pressure-volume work remained unchanged. Myocardial oxygen consumption per minute increased in proportion to heart rate. The ratio of myocardial oxygen consumption per beat to left ventricular systolic stress-time integral increased significantly by 95%. External myocardial efficiency was unaltered. Thus, isoproterenol increases the energy turnover of excitation-contraction coupling and increases the energy consumption of the crossbridges disproportionately to developed tension-time integral in the guinea pig heart.

Adult↗
PubMed1989

Tension-independent heat in rabbit papillary muscle.

1. Heat and force were measured from isometrically contracting (0.2 Hz) rabbit papillary muscles at 21 degrees C during a single contraction-relaxation cycle using antimony-bismuth thermopiles and a capacitance force transducer. 2. Tension-independent heat (TIH) associated with excitation-contraction coupling was isolated from the initial heat by eliminating tension and tension-dependent heat with a Krebs-Ringer solution containing 2,3-butanedione monoxime (BDM) and mannitol. 3. A strategy for testing the validity of this new method for measuring TIH in heart muscle is described and the test confirms that the BDM-hypertonic solution partitioning method properly estimates the magnitude of the TIH component of initial heat. 4. TIH at the time of complete mechanical relaxation is 1.00 +/- 0.17 mJ/g wet weight and the data suggest that calcium cycling is complete by this time. Conversion of TIH to calcium cycled, assuming that 87% of TIH is due to calcium pumping by the sarcoplasmic reticulum, indicates that approximately 52 nmol calcium/g wet weight are required to support a single cycle of mechanical activity (0.2 Hz, 21 degrees C). 5. The length and frequency dependence of excitation-contraction coupling were demonstrated. TIH is reduced by shortening muscle length and by increasing the interval between stimuli. These steady-state data suggest that only a portion (approximately 40%) of TIH is directly related to activation of the contractile apparatus. 6. TIH in the first twitch following a 45 min rest period is significantly reduced by approximately 30%. 7. With subsequent twitches in the positive treppe following the rest period, TIH does not increase as steeply as expected suggesting that tension rise in twitches 1-10 may be modulated by competitive binding of calcium rather than increased calcium delivery.

Animals↗
PubMed1989

Protection of human left ventricular myocardium from cutting injury with 2,3-butanedione monoxime.

To prevent dissection injury when cutting strip preparations from human left ventricular papillary muscle tissue, dissections were carried out with 2,3-butanedione monoxime (30 mM) added to Krebs-Ringer solution and followed by washout with normal solution. Eleven muscle strip preparations were dissected from left ventricular papillary muscle tissue of five patients undergoing mitral valve replacement surgery. The average muscle strip length was 6.8 +/- 1.4 mm, and cross-section area was 0.49 +/- 0.16 mm2. Peak twitch tension was 2.02 +/- 1.33 g/mm2 and ranged from 0.67 to 5.5 g/mm2 at an extracellular calcium concentration of 2.5 mM (21 degrees C, 0.16 Hz). In one muscle strip, which was stored in Krebs-Ringer plus 2,3-butanedione monoxime solution for 20 hours, peak twitch tension in normal Krebs-Ringer solution was 1.85 g/mm2. When temperature was increased from 21 degrees C, there was a continuous increase in peak twitch tension (by 38%) up to about 28 degrees C; then peak twitch tension decreased so that at 37 degrees C (n = 3) average peak twitch tension was lower than at 21 degrees C by 47%. The force-frequency relation exhibited a broad force plateau between 40 and 120 beats/min at 37 degrees C. The plateau was markedly narrowed at 30 degrees C and 24 degrees C. Thermopile heat measurements revealed appropriate waveform characteristics in high-resolution single-beat heat records indicating minimal surface cell damage. Thus, cardioplegia with 2,3-butanedione monoxime protects human left ventricular myocardium from dissection injury facilitating dissection and preservation of strip preparations with extraordinarily low cross-sectional areas and high peak twitch tensions. These preparations are suitable for myothermal and mechanical measurements.

Animals↗
PubMed1989

Influence of the positive inotropic substance pimobendan (UD-CG 115 BS) on contractile economy of guinea pig papillary muscles.

Using antimony-bismuth myothermal equipment, we measured simultaneously the initial heat liberated from and the stress-time integral developed by guinea pig papillary muscles before and after application of UD-CG 115 BS (200 microM) at an experimental temperature of 21 degrees C. By means of the shortening method, the initial heat was subdivided into the activation heat, which is associated with the calcium turnover, and the tension-dependent heat, which represents the ATP splitting by contractile proteins. The activation heat increased slightly but not significantly from 0.24 +/- 0.05 to 0.34 +/- 0.09 mcal/g. The increase in the tension-dependent heat (from 0.23 +/- 0.07 to 0.49 +/- 0.22 mcal/g) was directly proportional to the increase in the developed stress-time integral (from 0.95 +/- 0.24 to 2.37 +/- 0.76 g.s/mm2). The data indicate that the economy of force generation by contractile proteins is unchanged by UD-CG 115 BS, whereas the activation heat may be slightly increased by this compound. A comparison of UD-CG 115 BS with other substances like isoproterenol or classic phosphodiesterase inhibitors reveals that UD-CG 115 BS increases myocardial force in a more economical way that may have clinical implications. The mode of action of this compound is attributed to its calcium-sensitizing effect on the contractile proteins.

Animals↗
PubMed1989

Influence of enoximone on mechanics and energetics of right ventricular guinea pig papillary muscles.

Using highly sensitive antimony-bismuth thermopiles, the heat that is liberated during isometric contraction (initial heat) was measured simultaneously with the force signal in right ventricular papillary muscles of guinea pigs (n = 10). Measurements were taken before and after application of enoximone in a concentration of 10(-5) M. Enoximone increased peak developed tension from 1.92 +/- 0.98 to 2.81 +/- 1.11 g/mm2 (p less than 0.01) and the tension-time integral from 1.52 +/- 0.87 to 1.86 +/- 0.86 g.s/mm2 (p less than 0.05). Initial heat was increased from 0.50 +/- 0.13 to 0.79 +/- 0.24 mcal/g (p less than 0.01). The ratio between initial heat and tension-time integral, which is an inverse measure of myocardial economy of force generation, was increased from 3.77 +/- 1.17 to 4.66 +/- 1.49 mucal/g.s.cm (p less than 0.05). To study the potential changes induced by enoximone on an intracellular level, the initial heat was separated into tension-dependent heat (cross-bridge cycling) and tension-independent heat (calcium cycling). The latter increased from 0.20 +/- 0.05 to 0.28 +/- 0.09 mcal/g (p less than 0.05). The tension-dependent heat as normalized for a unit of developed tension-time integral increased from 2.17 +/- 0.63 to 2.86 +/- 0.79 mucal/g.s.cm (p less than 0.01). From these data, we conclude that enoximone decreases the economy of myocardial force generation by (a) increasing the number of calcium ions cycling during one twitch and (b) by altering the fundamental mechanisms of the contractile proteins with respect to force generation, i.e., faster contraction velocity and decreased economy of force generation.

Animals↗
PubMed1987

The effects of acute and chronic inotropic interventions on tension independent heat of rabbit papillary muscle.

We have used the myothermal method to noninvasively monitor the amount of calcium cycled during a single isometric twitch of rabbit papillary muscle. Experiments were designed to test the working hypothesis that changes in peak twitch tension caused by pharmacological agents or changing haemodynamic conditions are accompanied by parallel changes in the tension independent heat (TIH) signal associated with Ca2+ cycling. We isolated the TIH signal by eliminating the tension dependent component of initial heat with a hyperosmotic Krebs solution containing 2,3-butanedione monoxime. Contrary to the working hypothesis, positive or negative inotropic effects on twitch tension caused by pressure overload hypertrophy, thyrotoxic hypertrophy, isoproterenol, and UDCG115 were not accompanied by parallel changes in TIH. Alternative explanations for the relation between peak twitch tension and TIH are explored.

Animals↗
PubMed1987

Energetic aspects of inotropic interventions in rat myocardium.

Contractile force of the myocardium can be increased by different molecular mechanisms, and therefore different energetic consequences may result. The influence of the inotropic substances isoproterenol and UDCG-115 on myocardial energetics in isometrically contracting left ventricular rat papillary muscles was investigated by means of highly sensitive antimony bismuth thermopiles. Isoproterenol increased total heat and initial heat by 147% (p less than 0.01) and 69% (p less than 0.02) when normalized to tension-time integral, respectively. No significant change of both heat terms occurred due to UDCG-115. Initial heat was separated into tension-independent heat ("calcium cycling") and tension-dependent heat ("cross-bridge cycling") by means of a new method using 2,3-butanedione monoxime. Both tension-dependent heat per tension-time integral and tension-independent heat increased significantly, due to isoproterenol, from 4.9 +/- 1.17 to 7.6 +/- 2.72 mu cal/g.cm.s (p less than 0.05) and from 0.15 +/- 0.06 to 0.22 +/- 0.04 mcal/g (p less than 0.01). UDCG-115 influenced neither tension-independent heat nor tension-dependent heat per tension-time integral significantly. Thus, the economy of force development was not significantly altered due to UDCG-115 whereas isoproterenol significantly increased the energy necessary for activation, i.e. calcium cycling, and the energy necessary for force production, i.e. cross-bridge cycling. The basic mechanisms of these energetic changes are discussed.

Animals↗
PubMed1987

The response of the heart to stress: a biological view of myocardial adaptation and failure.

The response of the myocardium to persistent stress involves an increase in mass and a restructuring of the cellular and subcellular elements. The experiments described in this article are designed to test the hypothesis that the restructuring of the various systems (contractile, excitation-contraction coupling, recovery, etc.) that occurs in adaptive hypertrophy is a coordinated (matched) process. When the restructuring of the systems in response to stress occurs in an uncoordinated fashion, congestive heart failure results. In addition to controls, three heart models with normal pump performance are used (control, C; pressure overload, P; thyrotoxic, T; and pressure overload plus thyrotoxic, PT4) and one with inadequate pump performance (pressure overload plus thyrotoxic, PT2). In this analysis the contractile and excitation-contraction coupling systems are evaluated. The former is assessed by sensitive myothermal measurement of tension dependent heat (TDH) normalized for the isometric tension time integral (integral of Pdt). The latter is assessed from measurement of the time to peak isometric tension (TPT). The TDH/integral of Pdt (mu cal/g.cm.s) and TPT (ms) for the C, P, T, PT4, and PT2 hearts are 2.4, 1.8, 5.2, 5.1, and 0.1, mu cal/g.cm.s and 627, 816, 352, 484, and 465 ms, respectively. According to the coordination or matching hypothesis, if TDH/integral of Pdt is low, then TPT should be increased, or if TDH/integral of Pdt is high, then TPT should be decreased. Relative to control hearts, matched restructuring of the contractile and excitation-contraction coupling systems occurred for the P, T, and PT4 preparations. In these animals the hypertrophy has been adaptive and the pump performance is adequate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗