Mechanism of physiologic versus pathologic ventricular hypertrophy process: Enhanced or depressed myosin ATPase activity and contractility governed by type, degree and duration of inciting stress

Wikman‐Coffelt, Joan; Laks, Michael M.; Riemenschneider, Th.; Mason, Dean T.

doi:10.1007/bf02001407

Cited by 12 publications

(3 citation statements)

References 14 publications

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“…The aortic-ejecting heart preparation, described in detail elsewhere, 13 consisted of a heart perfused retrogradely through the aorta; the afterload and perfusion pressure were determined by the height of the aortic chamber and set to 110 mm Hg. The preload was determined by the height of the chamber feeding the left atrium, which was set to provide a pressure of 7 mm Hg.…”

Section: Isolated Heart Preparationsmentioning

confidence: 99%

Improved myocardial efficiency in the working perfused heart of the spontaneously hypertensive rat.

et al. 1987

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SUMMARY We assessed the relationship between determinants of myocardial oxygen demandwall stress, peak rate of change of pressure and heart rate-and measured myocardial oxygen consumption over a range of loading conditions in the perfused, working heart of 6-month-old spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY). Two isolated heart preparations, an aortic-ejecting heart and an isovolumically contracting preparation with and without isoproterenol (10~7 M) added, were employed. Under a constant perfusion pressure of 110 mm Hg, the heart rate, developed wall stress, and peak rate of change of pressure were not different between the two groups, but coronary flow and myocardial oxygen consumption were significantly lower in the SHR. Systolic values of myocardial high energy phosphate compounds (adenosine 5-triphosphate, phosphocreatine) and myocardial lactate in the two preparations were not significantly different between SHR and WKY. Following adenosine infusion at maximum developed pressure (isovolumic preparation), both SHR and WKY demonstrated preservation of coronary reserve. These results indicate that cardiac hypertrophy represents a compensatory adaptation with improved mechanical efficiency in the 6-month-old SHR when maximally stressed and may be related to the shift from V, to V 2 and V 3 isomyosin phenotypes that was observed in the hypertensive animals. (Hypertension 10: 396-403, 1987) KEY WORDS • hypertension • spontaneously hypertensive rats • heart enlargement • left ventricular hypertrophy • heart physiology • left ventricular function • oxygen consumption • myosin isoenzymes C ARDIAC hypertrophy secondary to pressure overload is a common finding in the clinical setting. 1 " 5 Experimental studies using papillary muscles from hypertrophied rat hearts have demonstrated improved economy of myocardial contraction.6 ' 7 In contrast, the majority of studies performed in vivo in several animal species and in humans have failed to confirm these findings. 1 -38 "" In vivo, hearts from hypertensive animals not only work against an increased afterload but are also exposed to a higher Received January 30, 1987; accepted March 19, 1987. coronary perfusion pressure, making comparative studies more difficult. Therefore, we studied the relationship between myocardial oxygen consumption (MVo 2 ) and workload in 6-month-old spontaneously hypertensive rats (SHR) and their corresponding controls, Wistar-Kyoto rats (WKY), using isolated, perfused heart preparations, which permit increases in workload while maintaining a constant coronary perfusion pressure. Materials and Methods AnimalsSix-month-old male SHR and WKY were obtained from Taconic Farms (Germantown, NY, USA). Rats were individually caged and fed standard rat chow and water ad libitum. Rats were trained to remain quiet in a restrainer; blood pressure was measured at 28 to 30°C by tail-cuff manometry in the unanesthetized animal. The average of the last three daily measurements before death was used for comparison. Isola...

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Section: Isolated Heart Preparationsmentioning

confidence: 99%

Improved myocardial efficiency in the working perfused heart of the spontaneously hypertensive rat.

et al. 1987

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“…In the atrium, downregulation of multiple members of the Krebs cycle and oxidative phosphorylation chain (including ATP synthase) suggests decreased, or less efficient, ATP generation. Perturbed myocardial energetics are known to occur in the hypertrophic state, and may be reflective of increased tissue acidity or PCO 2 , leading to the classic definition of pathologic hypertrophy as depressed myosin ATPase activity without concordant heart failure [ 26 ]. In the current study, manifest changes in mitochondrial proteins integral to cellular energetics were affected, even with only moderate versus severe elevations in pulmonary artery pressures.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology

et al. 2015

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Background The molecular mechanisms governing right atrial (RA) and ventricular (RV) hypertrophy and failure in chronic pulmonary hypertension (CPH) remain unclear. The purpose of this investigation was to characterize RA and RV protein changes in CPH and determine their adaptive versus maladaptive role on hypertrophic development. Methods Nine dogs underwent sternotomy and RA injection with 3 mg/kg dehydromonocrotaline (DMCT) to induce CPH (n=5) or sternotomy without DMCT (n=4). At 8-10 weeks, RA and RV proteomic analyses were completed after trypsinization of cut 2-D gel electrophoresis spots and peptide sequencing using mass spectrometry. Results In the RV, 13 protein spots were significantly altered with DMCT compared to Sham. Downregulated RV proteins included contractile elements: troponin T and C (-1.6 fold change), myosin regulatory light chain 2 (-1.9), cellular energetics modifier: fatty-acid binding protein (-1.5), and (3) ROS scavenger: superoxide dismutase 1 (-1.7). Conversely, beta-myosin heavy chain was upregulated (+1.7). In the RA, 22 proteins spots were altered including the following downregulated proteins contractile elements: tropomyosin 1 alpha chain (-1.9), cellular energetic proteins: ATP synthase (-1.5), fatty-acid binding protein (-2.5), and (3) polyubiquitin (-3.5). Crystallin alpha B (hypertrophy inhibitor) was upregulated in both the RV (+2.2) and RA (+2.6). Conclusions In early stage hypertrophy there is adaptive upregulation of major RA and RV contractile substituents and attenuation of the hypertrophic response. However, there are multiple indices of maladaptive pathology including considerable cellular stress associated with aberrancy of actin machinery activity, decreased efficiency of energy utilization, and potentially decreased protein quality control.

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“…Finally, it has been shown that there was a close correlation between a functional state of the contractile protein system and ATPase activity value of myofibrils (5,41,50) and myosin (4,7,37,46,53,59). The latter fact was a new argument in favour of myosin hypothesis of the myocardial contractile protein system contractibility decrease.…”

Section: Introductionmentioning

confidence: 90%

Thin myofilament proteins in norm and heart failure I. Polymerizability of myocardial Straub actin in acute and chronic heart failure

Карсанов¹,

Pirtskhalaishvili²,

Semerikova³

et al. 1986

Basic Res Cardiol

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The reduced and intrinsic viscosities of myocardial Straub F-actin from the left ventricle of a practically healthy man were equal to 3.05 +/- 0.2 and 2.4 +/- 0.32 and from the right ventricle were 2.37 +/- 0.2 and 2.1 +/- 0.3 dl/g, respectively (the difference between ventricles was not significant). The average length of filaments measured by flow birefringence technique was equal to 1.3 +/- 0.04 micron, the number-average length (Ln), determined by the electron microscopy was 1.4 micron, the weight-average length (Lw), was 2 microns and the maximal one was 5.5 microns. The histograms showed that the most characteristic length was that of 0.8-1.2 micron. According to the flow birefringence data canine myocardial F-actin had a length similar to that of myocardial F-actin from a practically healthy man, though its reduced and intrinsic viscosities were higher. In acute and especially chronic congestive heart failure the actin polymerizability was sharply reduced. In consequence, in acute heart failure the number-average length of F-actin filaments was decreased by 43% and in congestive heart failure by 65.7%. The characteristic length in acute heart failure shifts to the range of 0.2-0.6 micron, while in congestive heart failure the range is 0.2-0.4 micron. This fact can possibly explain why during preparation of actin from the pathologically changed myocardium according to the methods including purification by the cycles of polymerization-sedimentation-depolymerization, the pathologically changed actin is discarded and the normal actin remains. A definite parallel was observed between the reduction of actin polymerizability and the ability of myocardial glycerinated fiber bundles (MBGF) to generate force. We conclude that the changes of actin properties in heart failure may cause a decrease in contractibility of the myocardial contractile protein system.

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Mechanism of physiologic versus pathologic ventricular hypertrophy process: Enhanced or depressed myosin ATPase activity and contractility governed by type, degree and duration of inciting stress

Cited by 12 publications

References 14 publications

Improved myocardial efficiency in the working perfused heart of the spontaneously hypertensive rat.

Improved myocardial efficiency in the working perfused heart of the spontaneously hypertensive rat.

Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology

Thin myofilament proteins in norm and heart failure I. Polymerizability of myocardial Straub actin in acute and chronic heart failure

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