Remote ischemic preconditioning (RIPC) may limit myocardial infarction by improving microvascular function and maintaining myocardial blood flow. We hypothesized that a RIPC stimulus would reduce coronary microvascular resistance and improve coronary blood flow during elective percutaneous coronary intervention (PCI).
Method
We prospectively recruited 54 patients with multi-vessel disease (MVD = 32) or single vessel disease awaiting elective PCI. Patients with MVD had non-target vessel (NTV) index of micro-circulatory resistance (IMR) determined, before and after target vessel (TV) PCI (cardiac RIPC). The effect of arm RIPC on serial microvascular resistance (Rp) was assessed in patients with single vessel disease.
Results
TV balloon occlusion did not alter the NTV IMR: 16.5 (12.4) baseline vs. 17.6 (11.6) post cardiac RIPC, P = 0.65 or hyperaemic transit time. Arm RIPC did not alter Rp in patients with single vessel disease: Rp, mmHg.cm-1.s-1: 3.5 (1.9) baseline vs. 4.1 (3.0) post arm RIPC, P = 0.19 and coronary flow velocity remained constant.
Conclusion
RIPC stimuli during elective PCI do not affect coronary microvascular resistance or coronary flow in humans.
MurryC.E., JenningsR.B., ReimerK.A.Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.Circulation.1986; 74: 1124–1136.
BirnbaumY., HaleS.L., KlonerR.A.Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit.Circulation.1997; 96: 1641–1646.
4.
CheungM.M., KharbandaR.K., KonstantinovI.E.Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans.J Am Coll Cardiol.2006; 47: 2277–2282.
5.
HausenloyD.J., MwamureP.K., VenugopalV.Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial.Lancet.2007; 370: 575–579.
6.
AliZ.A., CallaghanC.J., LimE.Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair: a randomized controlled trial.Circulation.2007; 116(11 suppl): I98–I105.
ShimizuM., KonstantinovI.E., KharbandaR.K., CheungM.H., RedingtonA.N.Effects of intermittent lower limb ischaemia on coronary blood flow and coronary resistance in pigs.Acta Physiol (Oxf).2007; 190: 103–109.
9.
ZhouK., YangB., ZhouX.M.Effects of remote ischemic preconditioning on the flow pattern of the left anterior descending coronary artery in normal subjects.Int J Cardiol.2007; 122: 250–251.
PijlsN.H., BruyneB., SmithL.Coronary thermodilution to assess flow reserve: validation in humans.Circulation.2002; 105: 2482–2486.
12.
FearonW.F., FarouqueH.M., BalsamL.B.Comparison of coronary thermodilution and Doppler velocity for assessing coronary flow reserve.Circulation.2003; 108: 2198–2200.
13.
BarbatoE., AarnoudseW., AengevaerenW.R.Validation of coronary flow reserve measurements by thermodilution in clinical practice.Eur Heart J.2004; 25: 219–223.
14.
FearonW.F., BalsamL.B., FarouqueH.M.Novel index for invasively assessing the coronary microcirculation.Circulation.2003; 107: 3129–3132.
15.
FearonW.F., AarnoudseW., PijlsN.H.Microvascular resistance is not influenced by epicardial coronary artery stenosis severity: experimental validation.Circulation.2004; 109: 2269–2272.
16.
KharbandaR.K., PetersM., WaltonB.Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo.Circulation.2001; 103: 1624–1630.
17.
LoukogeorgakisS.P., WilliamsR., PanagiotidouA.T.Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a KATP channel dependent mechanism.Circulation.2007; 116: 1386–1395.
18.
LoukogeorgakisS.P., PanagiotidouA.T., BroadheadM.W., DonaldA., DeanfieldJ.E., MacAllisterR.J.Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans: role of the autonomic nervous system.J Am Coll Cardiol.2005; 46: 450–456.
19.
KonstantinovI.E., LiJ., CheungM.M.Remote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism.Transplantation.2005; 79: 1691–1695.
20.
BroadheadM.W., KharbandaR.K., PetersM.J., MacAllisterR.J.KATP channel activation induces ischemic preconditioning of the endothelium in humans in vivo.Circulation.2004; 110: 2077–2082.
21.
GattulloD., LindenR.J., LosanoG., PagliaroP., WesterhofN.Ischaemic preconditioning changes the pattern of coronary reactive hyperaemia in the goat: role of adenosine and nitric oxide.Cardiovasc Res.1999; 42: 57–64.
22.
KawasujiM., IkedaM., SakakibaraN., FujiiS., TomitaS., WatanabeY.Near-infrared monitoring of myocardial oxygenation during ischemic preconditioning.Ann Thorac Surg.2000; 69: 1806–1810.
23.
PagliaroP., ChiribiriA., RastaldoR.Ischemic preconditioning changes the pattern of coronary reactive hyperemia regardless of mitochondrial ATP-sensitive K(+) channel blockade.Life Sci.2002; 71: 2299–2309.
24.
MansarayM., HyndJ.W., VergroesenI., BelcherP.R., Drake-HollandA.J., NobleM.I.Thrombosis in one coronary artery causes generalized coronary vasoconstriction in a dog model of unstable angina.Clin Sci (Lond).2001; 100: 405–410.
25.
GregoriniL., MarcoJ., FarahB.Effects of selective alpha1– and alpha2-adrenergic blockade on coronary flow reserve after coronary stenting.Circulation.2002; 106: 2901–2907.
26.
WesterhofN., BoerC., LambertsR.R., SipkemaP.Crosstalk between cardiac muscle and coronary vasculature.Physiol Rev.2006; 86: 1263–1308.
27.
MatsubaraT., MinatoguchiS., MatsuoH.Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease.J Am Coll Cardiol.2000; 35: 345–351.
28.
EdwardsR.J., RedwoodS.R., LambiaseP.D., TomsetE., RakhitR.D., MarberM.S.Antiarrhythmic and anti-ischaemic effects of angina in patients with and without coronary collaterals.Heart.2002; 88: 604–610.
29.
BillingerM., FleischM., EberliF.R., GarachemaniA., MeierB., SeilerC.Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment?J Am Coll Cardiol.1999; 33: 1027–1035.
30.
DeutschE., BergerM., KussmaulW.G., HirshfeldJWJr., HerrmannH.C., LaskeyW.K.Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolic features.Circulation.1990; 82: 2044–2051.
31.
TomaiF., CreaF., GaspardoneA.Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+ channel blocker.Circulation.1994; 90: 700–705.
32.
PiekJ.J., van LiebergenR.A., KochK.T., PetersR.J., DavidG.K.Clinical, angiographic and hemodynamic predictors of recruitable collateral flow assessed during balloon angioplasty coronary occlusion.J Am Coll Cardiol.1997; 29: 275–282.
33.
SeilerC., FleischM., GarachemaniA., MeierB.Coronary collateral quantitation in patients with coronary artery disease using intravascular flow velocity or pressure measurements.J Am Coll Cardiol.1998; 32: 1272–1279.
34.
SiebesM., VerhoeffB.J., MeuwissenM., WinterR.J., SpaanJ.A., PiekJ.J.Single-wire pressure and flow velocity measurement to quantify coronary stenosis hemodynamics and effects of percutaneous interventions.Circulation.2004; 109: 756–762.
