title: Ventricular function and Na+,K(+)-ATPase activity and distribution with chronic supraventricular tachycardia.
abstract: OBJECTIVE
  The molecular and cellular mechanisms responsible for the dilated cardiomyopathy associated with chronic supraventricular tachycardia are not well understood. The purpose of this study was to examine Na+,K(+)-ATPase activity and distribution in a pacing induced model of dilated cardiomyopathy.
  
  
  METHODS
  Left ventricular function and Na+,K(+)-ATPase activity and distribution were examined in two groups of pigs: (1) atrially paced for 3 weeks (supraventricular tachycardia, 240 beats.min-1); (2) sham operated controls.
  
  
  METHODS
  10 Yorkshire male swine (23-25 kg) were randomly assigned to the control group or the supraventricular tachycardia group.
  
  
  RESULTS
  Left ventricular function was examined using simultaneous pressure echocardiography. Na+,K(+)-ATPase activity was determined in tissue homogenates by measuring the rate of p-nitrophenol-phosphate (pNPP) hydrolysis. Changes in content and distribution of Na+,K(+)-ATPase were examined immuno-histochemically in tissue sections. Left ventricular fractional shortening decreased significantly with supraventricular tachycardia as compared to controls, at 15 (SEM 3)% v 31(3)%, respectively p less than 0.05. Supraventricular tachycardia resulted in a significant increase in end diastolic dimension [5.0(0.3) cm v 3.5(0.2) cm, respectively p less than 0.05] and pressure [22(4)mm Hg v 6(2)mm Hg, respectively p less than 0.05]. Maximal Na+,K(+)-ATPase activity (microgram pNPP.mg-1 protein.h-1) was significantly lower with supraventricular tachycardia than in controls, at 0.45(0.12) v 0.64(0.06), respectively p less than 0.05. In the presence of 7 microM digitalis, Na+,K(+)-ATPase activity was inhibited by 68% in control and by 45% in supraventricular tachycardia homogenates (p less than 0.05). In control sections all left ventricular myocytes showed a uniform immunostaining pattern along the sarcolemma for Na+,K(+)-ATPase, whereas a focal loss of staining was observed in myocytes from the supraventricular tachycardia group.
  
  
  CONCLUSIONS
  The congestive cardiomyopathy produced by supraventricular tachycardia was associated with a reduction in sarcolemmal Na+,K(+)-ATPase activity and changes in enzyme distribution. The findings also suggest a reduction in digitalis sensitivity with chronic supraventricular tachycardia. These alterations in Na+,K(+)-ATPase activity may be one potential mechanism responsible for the depressed left ventricular function associated with chronic supraventricular tachycardia.
authors.affiliation: Medical University of South Carolina, Charleston 29425.
authors.forename: F G
authors.initials: FG
authors.lastname: Spinale
authors.forename: A P
authors.initials: AP
authors.lastname: Pearce
authors.forename: B A
authors.initials: BA
authors.lastname: Schulte
authors.forename: F A
authors.initials: FA
authors.lastname: Crawford
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002908:Chronic Disease; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis*; D013552:Swine; D013617:Tachycardia, Supraventricular / Q000201:enzymology / Q000503:physiopathology*; D016277:Ventricular Function, Left
chemical_list: D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium