title: Bypass conduit vessel wall biology substantially influences downstream myocardial contractile response to injury from ischemia and reperfusion.
abstract: Coronary vascular intraluminal release of endogenous endothelium-derived substances, such as prostacyclin, may affect downstream cardiac myocyte contractile function. With a "chronic" canine model of endothelialized and deendothelialized internal thoracic artery coronary grafts, we tested the hypothesis that higher basal release of endothelium-derived prostacyclin in internal thoracic artery bypass conduit effluent accelerates functional recovery of postischemic stunned myocardium in the intact circulation. Eleven dogs underwent left internal thoracic artery-left circumflex artery bypass, and the proximal circumflex artery was then ligated. Internal thoracic artery conduit endothelium was denuded by balloon catheter in five dogs before grafting and left intact in six dogs. After 7 days, awake dogs were studied to measure myocardial segment length in the circumflex region with ultrasonic dimension transducers, left ventricular pressure with micromanometers, and circumflex artery flow with an ultrasonic flow probe. Regional contractile function was quantified by the area beneath the linear preload recruitable stroke work relationship at baseline and at intervals after a 15-minute circumflex graft occlusion followed by 3 hours of reperfusion. Heart rate, left ventricular peak pressure, left ventricular end-diastolic pressure, left ventricular peak first derivative of pressure (dP/dt), and circumflex flow were similar (all p not significant) in endothelialized and nonendothelialized dogs during ischemia and reperfusion. Ischemia reduced the preload recruitable stroke work relationship to 44% +/- 35% of control values (p < 0.01) in endothelialized dogs and to 47% +/- 18% of control values in nonendothelialized dogs (p < 0.01) at 15 minutes of reperfusion, indicating a similar (p not significant) initial degree of injury. During 3 hours of reperfusion, the preload recruitable stroke work relationship returned to 51% +/- 17% of control values in endothelialized dogs but to only 35% +/- 20% of control values in nonendothelialized dogs (p < 0.02). Basal intraluminal release of endogenous prostanoids in excised internal thoracic artery conduits was subsequently quantified by ex vivo bioassay of vasoactive properties of conduit effluent on normal coronary artery smooth muscle. Endothelialized conduits induced greater smooth muscle relaxation than did nonendothelialized conduits (67% vs 23%), and this increased relaxation by endothelialized conduits was eliminated by indomethacin, a blocker of prostanoid synthesis. These data indicate that coronary bypass conduit endothelium-derived substances, such as prostacyclin, significantly influence downstream myocardial contractile response to ischemia and reperfusion, independent of alterations in coronary flow in the intact circulation.
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Mayo Clinic and Foundation, Rochester, Minn 55905, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Robinson
authors.forename: T
authors.initials: T
authors.lastname: Morita
authors.forename: K
authors.initials: K
authors.lastname: Fujita
authors.forename: M
authors.initials: M
authors.lastname: Chow
authors.forename: H V
authors.initials: HV
authors.lastname: Schaff
authors.forename: J J
authors.initials: JJ
authors.lastname: Morris
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D007387:Internal Mammary-Coronary Artery Anastomosis; D008855:Microscopy, Electron, Scanning; D009200:Myocardial Contraction / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013895:Thoracic Arteries / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure
chemical_list: D011464:Epoprostenol