title: Gadolinium attenuates the upward shift of the left ventricular diastolic pressure-volume relation during pacing-induced ischemia in dogs.
abstract: BACKGROUND
  The mechanism of the reversible upward shift of the left ventricular diastolic pressure-volume relation during demand ischemia is controversial. To assess the possibility that cation influx through stretch-activation channels may contribute to the upward shift, we asked whether gadolinium, a blocker of the stretch-activated channels, attenuates the upward shift of the diastolic pressure-volume relation during pacing-induced ischemia in 5 dogs.
  
  
  RESULTS
  To produce pacing-induced ischemia, we constricted the left anterior descending and circumflex coronary arteries to reduce their flows by approximately 30% and paced the left atrium at 150 to 180 beats per minute for 3 minutes. We measured left ventricular pressure, volume, and two segment lengths with micromanometers, a conductance catheter, and ultrasonic crystals, respectively. We recorded these variables during baseline, coronary stenosis, and pacing-induced ischemia (immediately after rapid pacing). After injecting 20 mg/kg (76 mumol/kg) gadolinium, we repeated the measurements during coronary stenosis (gadolinium experiment) and pacing-induced ischemia (pacing-induced ischemia plus gadolinium experiment). For each measurement, we recorded the variables in steady state to obtain diastolic pressure-volume and pressure-segment length loops and then during a brief (within 25 seconds) inferior vena caval occlusion to obtain the left ventricular end-diastolic pressure-volume relation. We found that left ventricular diastolic pressure-volume and pressure-segment length loops in steady-state beats shifted upward from coronary stenosis to pacing-induced ischemia. After injection of gadolinium, the upward shift from gadolinium to pacing-induced ischemia plus gadolinium was smaller than the shift from coronary stenosis to pacing-induced ischemia. Similarly, the left ventricular end-diastolic pressure-volume relation obtained during vena caval occlusion shifted upward (by 2.2 +/- 0.6 [SE] mm Hg) from coronary stenosis to pacing-induced ischemia. After injection of gadolinium, the upward shift from gadolinium to pacing-induced ischemia plus gadolinium was smaller (by -2.1 +/- 0.4 mm Hg).
  
  
  CONCLUSIONS
  These results indicate that gadolinium, a blocker of stretch-activated channels, attenuates the upward shift of the diastolic pressure-volume relation during pacing-induced ischemia, suggesting that the cation influx through stretch-activated channels may contribute to this upward shift.
authors.affiliation: Department of Medicine, University of California, San Francisco 94143-0124.
authors.forename: H
authors.initials: H
authors.lastname: Takano
authors.forename: S A
authors.initials: SA
authors.lastname: Glantz
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000503:physiopathology; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D005682:Gadolinium / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000209:etiology / Q000503:physiopathology*; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
chemical_list: D007473:Ion Channels; D005682:Gadolinium