ischemic conditioning and endothelial function todd anderson libin cardiovascular institute
DESCRIPTION
Ischemic Conditioning and Endothelial Function Todd Anderson Libin Cardiovascular Institute University of Calgary. Disclosures. Department of Cardiac Sciences and Libin Cardiovascular Institute – U of Calgary Grant support by Alberta Innovates Merck, Amgen, Abbott. BASELINE (3.65 mm). - PowerPoint PPT PresentationTRANSCRIPT
Ischemic Conditioning and
Endothelial Function
Todd Anderson
Libin Cardiovascular Institute
University of Calgary
Disclosures
• Department of Cardiac Sciences and Libin
Cardiovascular Institute – U of Calgary
• Grant support by Alberta Innovates
– Merck, Amgen, Abbott
BASELINE(3.65 mm)
REACTIVE HYPEREMIA (4.08 mm)
Flow-Mediated Vasodilation
FMD = 10.5 %
Microvasculature
Philpott et al. ATVB 2007;27:2065
Ischemic Conditioning
• Ischemia-reperfusion injury
– Kloner JCI 1974:54:1496 – No reflow in dogs
– Reimer et al. Circulation 1977; 56:786 – wavefront of ischemic death
– Braunwald and Kloner. JCI 1985;76:1713 – double edged sword and
concept of stunned myocardium Circulation 1982
• Ischemic conditioning
– Murry et al. Circulation 1986; 74:1174 – IPC
Ischemic Conditioning
Vinten-Johansen JAP 2007;103:1441
Significant parallelism between pre and post-conditioning
Ischemic Conditioning and Endothelial Function
• Ischemia-reperfusion injury causes injury and acute conduit
and NO dependent micro-vessel endothelial dysfunction
• Pre and post-conditioning with IPC bouts of transient ischemia
attenuate this abnormality
• Pharmacological conditioning prevents IR endothelial
dysfunction acutely but less reliably chronically
• IPC improves LV function during acute myocardial infarction in
some but not all studies
• Remote IPC also results in variable outcomes
• IPC may also have favorable effects on other outcomes including
blood pressure
Ischemic Conditioning
Kharbanda Circ 2001; 103:1624
Ischemic Conditioning
Kharbanda Circ 2001; 103:1624
Attenuation of NO dependent increases inFBF post IR injury with activation of neutrophils as well
Attenuation of FMD with pre-conditioning attenuating this abnormality
Remote Ischemic Conditioning
Kharbanda Circ 2002; 106:2881
20 minutes of ischemia with and without 3 cycles of 5 minutes of IPC on the contra-lateral arm
Remote Ischemic Post-Conditioning
Loukogeorgakis et al. Circulation 2007;116:1386
19 healthy subjectsRIPC and RPostC20 minutes of ischemiaWith and without glibenclamide to assess K+ ATP channelsBoth prevented the ↓ FMD with IR (PostC in leg but not arm) and this was blocked by glibenclamide
Ischemia-Reperfusion Injury
Alhejily et al. Microcirculation 2013
45 normal subjects with 15 minutes of ischemia
Attenuation of FMD but no change in hyperemic stimulus or PAT-index
IR doesn’t impair microvascular function
Pharmacologic Conditioning - Statins
Liuni et al. Clin Hemorheol 2010;45:161
Ischemic Conditioning
Luca et al. JAHA 2013;2(1)
30 healthy subjectsIR alone vs 1 day IPC vs 7 d IPC protocol
3 cycles of 5 min of ischemia and reperfusion
Celecoxib did not change results.
Both 1 and 7 days of IPC attenuated IR decrease in FMD
Ischemic Conditioning
Luca et al. JAHA 2013;2(1)
30 healthy subjectsIR alone vs 1 day IPC vs 7 d IPC protocol
3 cycles of 5 min of ischemia and reperfusion
Celecoxib did not change results.
Both 1 and 7 days of IPC attenuated IR decrease in FMD
Ischemic Conditioning and Endothelial Function
• Effect of acute or repeated episodes of IPC in patients with
endothelial dysfunction is unknown
• Acute and 7 days of IPC can ameliorate the IR-induced
decreases in FMD with no effect on measures of microvascular
response (hyperemic velocity or PAT)
• Pre-conditioning may be more effective than post-conditioning
in the forearm acute endothelial dysfunction model (and
studies are mixed with AMI)
• Further studies are needed to assess the effects of longer term
IPC on endothelial function and cardiovascular
pathophysiology