ischemic conditioning and endothelial function todd anderson libin cardiovascular institute
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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
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