Ischemic Conditioning and Endothelial Function Todd Anderson Libin Cardiovascular Institute

16
Ischemic Conditioning and Endothelial Function Todd Anderson Libin Cardiovascular Institute University of Calgary

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 Presentation

Transcript of Ischemic Conditioning and Endothelial Function Todd Anderson Libin Cardiovascular Institute

Page 1: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

Ischemic Conditioning and

Endothelial Function

Todd Anderson

Libin Cardiovascular Institute

University of Calgary

Page 2: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

Disclosures

• Department of Cardiac Sciences and Libin

Cardiovascular Institute – U of Calgary

• Grant support by Alberta Innovates

– Merck, Amgen, Abbott

Page 3: 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 %

Page 4: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

Microvasculature

Philpott et al. ATVB 2007;27:2065

Page 5: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

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

Page 6: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

Ischemic Conditioning

Vinten-Johansen JAP 2007;103:1441

Significant parallelism between pre and post-conditioning

Page 7: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

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

Page 8: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

Ischemic Conditioning

Kharbanda Circ 2001; 103:1624

Page 9: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

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

Page 10: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

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

Page 11: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

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

Page 12: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

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

Page 13: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

Pharmacologic Conditioning - Statins

Liuni et al. Clin Hemorheol 2010;45:161

Page 14: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

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

Page 15: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

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

Page 16: Ischemic Conditioning and  Endothelial Function Todd Anderson Libin Cardiovascular Institute

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