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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).

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Ischemic conditioning and endothelial function todd anderson libin cardiovascular institute

Ischemic Conditioning and

Endothelial Function

Todd Anderson

Libin Cardiovascular Institute

University of Calgary


Disclosures
Disclosures

  • Department of Cardiac Sciences and Libin Cardiovascular Institute – U of Calgary

  • Grant support by Alberta Innovates

    • Merck, Amgen, Abbott


Ischemic conditioning and endothelial function todd anderson libin cardiovascular institute

BASELINE

(3.65 mm)

REACTIVE HYPEREMIA

(4.08 mm)

Flow-Mediated Vasodilation

FMD = 10.5 %


Ischemic conditioning and endothelial function todd anderson libin cardiovascular institute

Microvasculature

Philpott et al. ATVB 2007;27:2065


Ischemic conditioning
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 and endothelial function todd anderson libin cardiovascular institute

Ischemic Conditioning

Significant parallelism between pre and post-conditioning

Vinten-Johansen JAP 2007;103:1441


Ischemic conditioning and endothelial function
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 conditioning1
Ischemic Conditioning

Kharbanda Circ 2001; 103:1624


Ischemic conditioning2
Ischemic Conditioning

Attenuation of NO dependent increases in

FBF post IR injury with activation of neutrophils as well

Attenuation of FMD with pre-conditioning attenuating this abnormality

Kharbanda Circ 2001; 103:1624


Remote ischemic conditioning
Remote Ischemic Conditioning

20 minutes of ischemia with and without 3 cycles of 5 minutes of IPC on the contra-lateral arm

Kharbanda Circ 2002; 106:2881


Remote ischemic post conditioning
Remote Ischemic Post-Conditioning

19 healthy subjects

RIPC and RPostC

20 minutes of ischemia

With and without glibenclamide to assess K+ ATP channels

Both prevented the ↓ FMD with IR (PostC in leg but not arm) and this was blocked by glibenclamide

Loukogeorgakis et al. Circulation 2007;116:1386


Ischemia reperfusion injury
Ischemia-Reperfusion Injury

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

Alhejily et al. Microcirculation 2013


Pharmacologic conditioning statins
Pharmacologic Conditioning - Statins

Liuni et al. Clin Hemorheol 2010;45:161


Ischemic conditioning3
Ischemic Conditioning

30 healthy subjects

IR 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

Luca et al. JAHA 2013;2(1)


Ischemic conditioning4
Ischemic Conditioning

30 healthy subjects

IR 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

Luca et al. JAHA 2013;2(1)


Ischemic conditioning and endothelial function1
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