title: Impairment of diastolic function by lack of frequency-dependent myofilament desensitization rabbit right ventricular hypertrophy.
abstract: BACKGROUND
  Ventricular hypertrophy is a physiological response to pressure overload that, if left untreated, can ultimately result in ventricular dysfunction, including diastolic dysfunction. The aim of this study was to test the hypothesis that frequency-dependent myofilament desensitization, a physiological response of healthy myocardium, is altered in hypertrophied myocardium.
  
  
  RESULTS
  New Zealand white rabbits underwent a pulmonary artery banding procedure to induce pressure overload. After 10 weeks, the animals were euthanized, hearts removed, and suitable trabeculae harvested from the free wall of the right ventricle. Twitch contractions, calibrated bis-fura-2 calcium transients, and myofilament calcium sensitivity (potassium contractures) were measured at frequencies of 1, 2, 3, and 4 Hz. The force frequency response, relaxation frequency response, and calcium frequency relationships were significantly blunted, and diastolic tension significantly increased with frequency in the pulmonary artery banding rabbits compared with sham-operated animals. Myofilament calcium sensitivity was virtually identical at 1 Hz in the treatment versus sham group (pCa 6.11 + or - 0.03 versus 6.11 + or - 0.06), but the frequency-dependent desensitization that takes place in the sham group (DeltapCa 0.14 + or - 0.06, P<0.05) was not observed in the pulmonary artery banding animals (DeltapCa 0.02 + or - 0.05). Analysis of myofilament protein phosphorylation revealed that the normally observed frequency-dependent phosphorylation of troponin-I is lost in pulmonary artery banding rabbits.
  
  
  CONCLUSIONS
  The frequency-dependent myofilament desensitization is significantly impaired in right ventricular hypertrophy and contributes to the frequency-dependent elevation of diastolic tension in hypertrophy.
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, Ohio State University, Columbus, Ohio, USA.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Varian
authors.forename: Anusak
authors.initials: A
authors.lastname: Kijtawornrat
authors.forename: Subash C
authors.initials: SC
authors.lastname: Gupta
authors.forename: Carlos A A
authors.initials: CA
authors.lastname: Torres
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Monasky
authors.forename: Nitisha
authors.initials: N
authors.lastname: Hiranandani
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Delfin
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rafael-Fortney
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hamlin
authors.forename: Paul M L
authors.initials: PM
authors.lastname: Janssen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D024722:Cardiac Myosins / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D002352:Carrier Proteins / Q000378:metabolism; D003971:Diastole; D004195:Disease Models, Animal; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D053580:Muscle Strength; D009200:Myocardial Contraction; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism; D018497:Ventricular Dysfunction, Right / Q000378:metabolism / Q000503:physiopathology*; D000099211:Phospholamban; D000099163:Myosin Binding Protein C
chemical_list: D000199:Actins; D009320:Atrial Natriuretic Factor; D002135:Calcium-Binding Proteins; D024722:Cardiac Myosins; D002352:Carrier Proteins; D018994:Myosin Light Chains; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D019210:Troponin I; D020107:Troponin T; D000099211:Phospholamban; D000099163:Myosin Binding Protein C; C107184:myosin light chain 2