Perioperative Myocardial Infarction Myocardial... · at reducing perioperative acute myocardial infarction. ... βBlockers Increase Perioperative Stroke? Bangalore Lancet 2008 β-Blockers

Gregory M.T. Hare, MD, PhD, FRCPC Professor

Depts. of Anesthesia and Physiology

ScientistThe Keenan Research Centre

Li Ka Shing Knowledge Institute

St. Michael’s HospitalUniversity of Toronto

Perioperative Myocardial InfarctionWhich β- Blocker is More Protective?

CAS 2014St. John’s

Disclosures

1) Forest Laboratories Inc. Operating grant to study the impactof Nebivolol on Cerebral Perfusion During Anemia

2) Johnson & Johnson Medical Companies:Academic Salary SupportCo-Director of Center of Excellence for Patient BloodManagement at St. Michael’s Hospital

Talk Outline

1) Mechanism of Perioperative MI2) Is there a belter β-blocker?3) Anemia as a Diagnostic Interoperative Stress Test

Incidence of Perioperative MI

Postoperative Days

Why is Perioperative Myocardial Ischemia Feared?

High Mortality ~ 30 to 50%

Nagele P. Anesthesiology, 2011Ghaferi A.A. NEJM, 2009

Unknown or Unpredictable Mechanism

Demand Ischemia~55%Thrombotic ~26%

Non-obstructive ~19%

Duvall W.L. Catheter Cardiovasc. Interv. 2012

Clinical Question

A 73 yo Woman Present in the PAF for THA tomorrow!Very limited exercise tolerance (< 4 METS)EKG-nonspecific ST changes; Hb 110 g/L

The Optimal Approach Includes:

A) Proceed to surgery tomorrow.B) Prescribe metoprolol 25 BID; proceed to surgery tomorrow.C) Prescribe metoprolol 25 BID and delay surgery for 1 week.D) Prescribe bisoprolol 2.5 OD and delay surgery for 1 week.E) Delay surgery, get a dobutamine echo, consider

appropriate β-blockade; diagnose and treat anemia.

Clinical Question

The 73 yo Woman has chest pain in the PACU after THATroponin-T > 0.03, HR 105; lateral ST depression; Hb 78 g/L

The optimal Treatment Includes:

A) Admission to the CCU/ICU for monitoringB) Consider anti-platelet therapy (ASA)C) Transfusion of 1 U PRBCsD) Consider acute beta-blockadeE) All of the above

Which β-Blocker Should We Use? Drug Solubility Rec.

Spec.1/2-Life

Metab. Indication Dose (Start/Max)

Metoprolol β1>β2+

3-7 hrs.

BP,HF CAD, Post-MI,

12.5-25 BID(400 BID)

Atenolol β1>β2++

6-14 hrs.

BP, Angina, Post-MI

12.5-25 OD(200 OD)

Bisoprolol β1>β2+++

10-12 hrs.

BP 1.25-2.5 OD20 OD

Carvedilol β1/β2α

6-8 hrs.

Heart Failure 3.125 BID(50 BID)

Labetalol β1/β2α

6-8 hrs.

BP, AnginaPreclampsia

100 OD (600 BID)

Nebivolol β1>β2+++++

12-19hrs.

BP 2.5 OD(40 OD)

-Liver-Kidney-Water Soluble-Lipid Soluble

Clinical Question

After transfusion to Hb 100 g/L, a dobutamine stress echo demonstrated a lateral wall motion abnormality. You have decided to start a β-blocker for HR control and to minimize risk of ongoing ischemia.

Which drug would you choose?

A) Atenolol 12.5 mg/kg ODB) Metoprolol 25 mg BIDC) Carvedilol 6.5 mg ODD) Bisoprolol 2.5 mg ODE) Nebivolol 2.5 mg OD

de Lemos JAMA 2013

The Cardiac Myocyte is the Source of Troponin

Universal Definition of a Myocardial Infarction

Circulation, JACC; 2012

A rise in Troponin:

And one of-i) Symptoms of myocardial ischemiaii) New ST-T wave changes or LBBBiii) New pathological Q waveiv) Imaging showing new loss of myocardial functionv) Intracoronary thrombus on angiogram

Universal Definition of a Myocardial Infarction

JACC Vol 60 2012

A rise in Troponin:

And one of-i) Symptoms of myocardial ischemia

Landesberg G Circulation 2013

Perioperative MI Caused by:1) Plaque Rupture and 2) Demand Ischemia



Revascularization



Treat the Underlying Cause


Focal MI (Type I)Plaque Rupture

Global Ischemia (Type II)Troponin Leak?

TROPONIN TROPONIN

Perioperative MI Defined by Increased Troponin? Demand Ischemia (Type II)

Troponin Leak

êOxygen Supply

éOxygen Demand

Perioperative Ischemia leads to MI and Death??

Oxygen Supply/Demand Imbalance (Ischemia)

ST Depression

Troponin Leak

Myocardial Infarction

Sympathetic Nervous System Activation

Surgery and Blood Loss

Death

The Vascular Events in Noncardiac SurgeryPatients Cohort Evaluation (VISION)

Devereaux PJ JAMA 2012

Peak TnT level was associated with 30 Day Mortality

Anesthesiology 2014

Re-evaluation of the Definition of Myocardial InjuryAfter Noncardiac Surgery (MINS)

Utilized the VISION data to determine if:Myocardial injury caused by ischemia (+/- necrosis)Has a prognostic relevance within 30 Days of surgery

Definition of MINS-TnT >0.03 due to myocardial ischemia

30 Day Mortality with MINS ~9.8% vs. 1.1% MINS predicted: nonfatal Cardiac arrest (OR 14.6 [CI 5-37])CHF (OR 10.3 [CI 8-13]), Stroke (OR 4.6 [CI 2-7])

Non-vascular Death 46%; Vascular death 54%

POISE 1, 2- Goal of Perioperative Treatment: To Reduce Risk of Perioperative MI and Death

Pre-Cellular Injury CellularInjury Post-Cellular injury

Treat Risk:(POISE-1:β-Blockade)(POISE-2: Clonide)

Supportive Interventions to Optimize Perfusion and Reduce the Risk of Organ Injury & Mortality

Optimal Pointof Intervention

Devereaux PJ NEJM 2014

POISE-2

POISE 2-Clonidine in Patients UndergoingNon-cardiac Surgery


Assumptions-

Activation of the sympathetic nervous systemDuring surgery leads to O2 supply demand imbalance and MI.

Clonidine can prevent the increased sympathetic outflow.

Hypothesis-Perioperative clonidine can prevent 30 day MI and death

Is it a Good Idea to Impair the Brains Sympathetic Signaling to the Body???

Heart

Brain

Liver

Kidney

Troponin

S100

Hepcidin

KIM

Rationale for POISE-2

Anesthesiology 2004

POISE 2-Clonidine Did Not Reduce MI + Death


POISE 2-Clonidine Outcomes

Hypotension and Major Bleeding Increase the Risk of MI

β Blockers in General Medicine: the GOODβ-blockers are GOOD at reducing mortality after an acute myocardial infarction

MIAMI Trial (Metoprolol)Eur Heart J 1985

MIAMI- Metoprolol in acute myocardial infarction

POISE 1-Metoprolol in Patients UndergoingNon-cardiac Surgery

Are β-blockers GOOD at reducing perioperativeacute myocardial infarction?

Non-Fatal MIComposite Outcome

Beta Blocker

Beta Blocker

PlaceboPlacebo

Time, days

0 10 20 30 0 10 20 30

Ris

k, %

Devereaux PJ Yang H, POISE 2008

β Blockers in Perioperative Medicine: the GOOD

β-blockers are GOOD at reducing perioperativeacute myocardial infarction

Perioperative MI Defined by Increased Troponin:Beta-Blockers Prevent Perioperative MIMyocardial IschemiaTroponin Leak?

Beta-BlockadePrevents MI

β Blockers Protect Against Perioperative MI

Favors β-Blockade Favors ControlBangalore Lancet 2008

β-Blockers ↓ Non-Fatal MI

Lindenauer, NEJM 2005;353:349

Perioperative β-Blocker Therapy and MortalityAfter Major Noncardiac Surgery

Patients atHigh risk for MI

Benefit fromβ-Blockade.

London MJ et al. JAMA 2013

Current β Blocker Recommendations + GuidelinesClass I (Benefit>>>Risk)

Do Not Discontinueβ-Blocker Therapy

ACCF/AHAContinue in patients using

β blockers for otherAHA Class I Guidelines

(Level C)

ESCKnown IHD or myocardialIschemia on stress testing

(Level B)

Class II (Benefit>Risk)

β Blocker TherapyIndicated for Patients

with ↑Cardiac Risk

ACCF/AHAVascular or Intermediate

risk surgery with apositive stress test or more than 1 risk factor

(Level C to B)

ESCIntermediate risk surgery

(Level B)

Class III (Risk>>Benefit)

Do Not Routinely Treat Low Risk Patients with High Dose β Blockers

ACCF/AHAHigh dose β blockers

without titration(Level B)

ESCHigh dose β blockers

without titration(Level A)

Fleishmann KE, Circulation 2009;120:2123-51, London M, Can J Anesth 2010

Level of Evidence A (Gold); B (Silver); C (Bronze)

Stroke Death

Time, days

Beta Blocker

Beta Blocker

Placebo

Placebo

Devereaux PJ Yang H, POISE 2008

β Blockers in Perioperative Medicine: the BADβ-blockers are BAD because they may impair cardiovascular responses (cardiac output) required for organ perfusion

Ris

k, %

BMJ 2005

β Blockers Increase Bradycardia, Hypotension, Perioperative Stroke?

β Blockers Increase Perioperative Stroke?

Bangalore Lancet 2008

β-Blockers ↓ Non-fatal MI

β-Blockers ↑ Non-fatal Stroke

Favors β-Blockade Favors Control


Beattie WS 2014

Heart

Brain

The Job of The Heart is to Perfuse the Brain

Heart

Brain

β-Blockade

Risk vs. Benefit with β Blockade: Summary of Clinical Trial Outcomes

Yang and Beattie CJA 2008

Trial Intervention Benefit Cost

CIBIS-II Bisoprolol vs. Placebo-CHF

Reduced Mortality (11.8 vs. 17.3%)

Increased Stroke Rate (31 vs. 16)

ASCOT-BPLA

Amlodipine + Periindopril vs.

Atenolol + Thiazide-HT

Reduce MAPIncreased Stroke

Rate (327 vs. 423)

NOR-DIL Beta Blocker vs. Diltiazem Reduce MAP Increased Stroke

Rate (159 vs. 196)

COMMIT Metoprolol vs. Placebo-Early MI

Reduced Re-Infarction, VT

Increased Cardiogenic Shock

(1141 vs. 885)

COMET Carvedilol vs. Metoprolol-CHF

Increased Survival with Carvedilol

Increased Mortality with Metoprolol(512 vs. 600)

Lancet 2003

Is there a Problem with Metoprolol?

Is there a Problem with Metoprolol?

Wallace A, Anesthesiology , 2011

Anemia Associated with Increased Mortalityin Non-Cardiac Surgical Patients

Beattie WS, Anesthesiology 2009

Pre-operative Hemoglobin Concentration

Prob

abilit

y of

Mor

talit

y

Beattie WS, Anesthesiology 2009

β Blockers Increase Risk Associated with Perioperative Anemia

β-Blockade + Anemia Increases Incidence of MI

β-Blocked Group

Relative Risk of Major Adverse Cardiac Event with β-blockade: 2.38 (1.43-3.96) p=0.0009

Anesthesiology 2010

Hemoglobin < 100 g/L

Acute β-Blocker Withdrawal Increases MI Risk

Van Kei WA, Anesthesiology 2009

β Blocker withdrawal Increased MI incidence

β Blocker treatmentincreased MI incidencein low risk patients

Increased Stroke Risk In Perioperative Patients

Beatiie WS TGH

Clinical Question




Which β-Blocker Should We Use? Drug Solubility Rec.

Spec.1/2-Life

Metab. Indication Dose (Start/Max)

Metoprolol β1>β2+

3-7 hrs.

BP,HF CAD, Post-MI,

12.5-25 BID(400 BID)

Atenolol β1>β2++

6-14 hrs.

BP, Angina, Post-MI

12.5-25 OD(200 OD)

Bisoprolol β1>β2+++

10-12 hrs.

BP 1.25-2.5 OD20 OD

Carvedilol β1/β2α

6-8 hrs.

Heart Failure 3.125 BID(50 BID)

Labetalol β1/β2α

6-8 hrs.

BP, AnginaPreclampsia

100 OD (600 BID)

Nebivolol β1>β2+++++

12-19hrs.

BP 2.5 OD(40 OD)

-Liver-Kidney-Water Soluble-Lipid Soluble

Metoprolol Has Lowest β1-Adrenergic Receptor Specificity of Commonly Used β1-Blockers

β1 antagonist fold selectivity β1/β2

CGP 20712A 501.2ICI 89406 69.2Practolol 14.1Xamoterol 14.1Bisoprolol 13.5Betaxolol 6.8AtenololICI 215001 3.2Acebutolol 2.4Metoprolol 2.3

Baker, Br J Pharmacol, 2005

Cross-reactivity with β2-ARs may inhibit adrenergic mediated vasodilation.

4.1

-0.5

0

0.5

0 5 10 15

LOG

OD

DS

RAT

IO F

OR

PO

ST O

PER

ATIV

E ST

RO

KE

RATIO BETA 1 TO BETA 2 ACTIVITY

BISOPROLOL

ATENOLOL

METOPROLOL

OTHERS


Beattie et al TGH

Sufgery(Adrenergic

Stress)

Anemia(Blood Loss)

β-Blockade

What is the Interaction Between SurgeryAnemia and β-Blockade?

Systemic Effect of Surgery Acute Blood Loss

Medical Intervention

How Does Anemia (Acute Blood loss) ImpactPerioperative MI and Stroke?

POISE-2 –Acute Blood loss ↑ the Risk of MI

POISE-1 –Acute Blood loss ↑ the Risk of Stroke

Lancet 2008

Anemiaê Blood Oxygen Contenté Cardiac Output

é Coronary Blood Flow(çè Oxygen Extraction)

BloodO2

Content

CardiacOutput

AndMyocardialO2 Demand

Anemia-The Ultimate Cardiac and Brain Stress Test!!!!

O2 Supply-Demand Un-Balanced

Troponin Leak?

JAMA 1998

Anemia-The Ultimate Cardiac and Brain Stress Test!!!!

Hemoglobin Concentration

Met

abol

ic C

onsu

mpt

ion

of O

2

HighLow

Total BodyBrain

Myocardium

Gut, Kidney andOther Tissue

Anemia-The Ultimate Cardiac Stress Test!!!!

Hare GM, Tsui AKY et al., Best Pract Res Clin Anesth 2013

Haemoglobin Concentration (g/L)

MAP CBF

CO Brain PO2

Cardiovascular Responses to Acute Anemia in Mice

Fan F-C et al, Am J Physiol 1980

Increased Cardiac Output is Preferentially Diverted to the Brain and Heart During Anemia

Heart

Brain

Anemia-Brain Oxygen Delivery Bioassay

Heart

BrainHypoxia

Anemia +/-β-Blockade

The Impact of β-BlockadeOn Cerebral O2 Delivery

CAS Richard Knill Award 2005Hare et al Brit J Anaesth 2006

Anemia ≈ MortalityéWith MetoprololBeattie et al. Anesthesiol 2009

Anemia + Metoprolol ≈ éCerebral Hypoxia

Ragoonana et al. Anesthesiol 2009

Anemia + β-Blockade ≈ éMACE

Beattie et al. Anesthesiol 2011

β2-Blockade ≈ êCerebral Vasodilation

El Beheiry et al. J Appl. Physiol 2011

Low Dose β1-Blockade Maintained Cerebral O2

Hu et al. Anesth & Analg 2013

β-Blockade + Anemia ≈ éStroke (not nebivolol)

Beattie et al. Anesthesiol 2013

Potential Mechanisms by which Perfusion Limited by β-Blockade During Anemia

Cardiac Output

Pump Regulated Blood Flow

Resistance Aertry

InadequateTissue PO2

BrainHeart

Kidneyβ1 Receptor

Β2 Receptor

Β1,2 ReceptorBeta Blocker

Central Nervous System

Interrupted Oxygen Delivery to Tissue

~30 torr ~20-30 torr

~10-20 torr?

O2

O2

O2

Capillary Tissue Brain Cell

Mitochondriaβ-Blockade

Inhibit CO Response to Anemia

Cardiac Output

Mouse Brain Perfusion is Limited by MetoprololHeart Rate MAP

Cerebral Blood Flow Brain PO2

Baseline Saline vs. Drug Baseline Saline vs. Drug

Baseline Saline vs. DrugEl Beheiry J Appl Physiol 2011

Adrenergic Stress Anemia

β-blockade

Why are Patients at High Risk ofPoor Outcomes Following Surgery?

Systemic Effect of Surgery Acute Blood Loss

Associated Medical Therapy

POISEAnemia ↑ Stroke

Risk by 2X


Cardiac Output


Resistance Aertry


BrainHeart

Kidneyβ1 Receptor

Β2 Receptor

Β1,2 ReceptorMetoprolol


Metoprolol Impairs the Cardiac Response to Anemia

Ragoonanan T et al, Anesthesiology 2009

Cardiac Output Carotid Blood Flow

-Anemia

-Anemia + β-Blockade

Ragoonanan T, Anesthesiology 2009

Metoprolol Dramatically Reduces Brain Tissue PO2During Acute Hemodilution

0 20 40 60 80 100

Hip

poca

mpa

l Tis

sue

Oxy

gen

Tens

ion,

mm

Hg

10

20

30

40

* #

Hemodilutionβ1 Blocker or Saline

DMicrovascular PO2 Tissue PO2

-Anemia

-Anemia + β-Blockade


Cardiac Output


Resistance Aertry


BrainHeart

Kidneyβ1 Receptor

Β2 Receptor

Β1,2 ReceptorICI 118,551

Autonomic Nervous System

β2 Mediated Cerebral Vasodilation

Cerebral Vasodilation and Increased CBF

Vascular Smooth Muscle

NO

NO

nNOS

NO

Nitric Oxide Synthase (NOS)

NitrogenergicNeuron

β2 Adrenergic Receptor

NE

GTP cGMPGC

Lee et al Am J Physiol 2000;279: H808-16

NoradrenergicPerivascular

Neurons

β2

Inhibition of the β2-AdrenoreceptorAccentuated Cerebral Perfusion In Anemic Rats

Hare GMT. Brit J Anaesth 2006

CAS Richard Knill Research Award 2005

β2-Adrenoreceptor Antagonist – ICI 118, 551

Cerebral Blood Flow Cerebral Cortical PO2

β1

β2 VasodilationVASOCONSTRICTION Organ

Ischemia

Metoprolol Impairs Cardiovascular Functionβ-blockers may be UGLY because they could impair global perfusion and microvascular vascular function

metoprolol

β1

β2

↑Cardiac Output

Assessment of Resistance Artery Functionby Pressure Myography

Metoprolol Impairs Resistance Artery Dilation to β-Adrenergic Agonists

-9 -8 -7 -6 -5 -40

20

40

60

80Control, n=750µM Metoprolol, n=7

log [isoproterenol (mol/L)]

% d

ilatio

n

-7 -6 -5 -4 -30

20

40

60

80 Control50µM Metoprolol

*#

##

##

#

log [isoproterenol (mol/L)]

% d

ilatio

n

Mesenteric Artery Posterior Cerebral Artery

El Beheiry et al J Appl Physiol 2010β1

β2

β1

β2Metoprolol

Perfusion Limited by β-Blockade During Anemia

Cardiac Output


Resistance Aertry


BrainHeart

Kidneyβ Receptor

β Receptor

β ReceptorMetoprolol


0

10

20

30

0 1 2 3 4 5 6 7

POSTOPERATIVE DAY

NU

MBE

R O

F ST

ROKE

S

Temporally similar to POISE

Ashes et al Anesthesiology 2013


Date of download: mm/dd/yyyy

Copyright © 2012 American Medical Association. All rights reserved.

0.0%

0.5%

1.0%

80 100 120 140 160

Lowest recorded Haemoglobin

Prob

abili

ty o

f Pos

tope

rati

ve s

trok

e

METOPROLOL

BISOPROLOL

Ashes C, Anesthesiology 2013

Relationship Between β-blockade, Anemia, Stroke

Metoprolol was associated with a 4.2 ↑ in stroke incidence.

Mashour GA et al Anesthesiol 2013

Metoprolol Associated with Perioperative Stroke


Cardiac Output


Resistance Aertry


BrainHeart

Kidneyβ1 Receptor

Β2 Receptor



Clinical Question




Nebivolol has the Highest β1-Adrenergic Receptor Specificity of Available β1-Blockers

β1 antagonist fold selectivity β1/β2

CGP 20712A 501.2ICI 89406 69.2Practolol 14.1Xamoterol 14.1Bisoprolol 13.5Betaxolol 6.8AtenololICI 215001 3.2Acebutolol 2.4Metoprolol 2.3

Baker, Br J Pharmacol, 2005Bristow et al. 2005

Cross-reactivity with β2-ARs may inhibit adrenergic mediated vasodilation.

4.1

Nebivolol ~40

Metoprolol has Relatively Poor β1 SelectivityWhile Nebivolol is much more β1 Selective

Compound β1/β2Selectivit

y

Propranolol 1.0

Metoprolol 74

Bisoprolol 103

Nebivolol 321

Bristow et al. (2005)

Hypothesis:

A highly β1 specific antagonist (nebivolol) will

NOT attenuate the increase in cerebral blood flow needed to maintain cerebral oxygen delivery

during anemia.

Can Treatment with Nebivolol Preserve Cerebral Perfusion During Anemia?

β1: ~0.7 nMβ2: ~225 nM

Results nebivolol drug levels areproportional to dose

# p<0.05 vs. baselinep<0.05 vs. 1.25 Nebivolol

Vehicle Control 1.25 Nebivolol2.5 Nebivolol

Time (minutes)10 60 120

Neb

ivol

ol C

once

ntra

tion

(nM

)

0

50

100

150

200

250

Vehicle orNebivolol

No detecteddrug levels

Hemodilution#

#

#

#β2 Affinity Threshold

Affinity (Ki) for β1 and β2

Levels

Hu et al A&A 2013

Time (minutes)10 40 90 120

Car

diac

Out

put (

mL/

min

ute)

50

100

150

200

250

300

Vehicle orNebivolol

Administration

Hemodilution#

#

# ###

Cardiac Output Effect

n = 5 per group

# p<0.05 vs. baseline


Hu et al A&A 2013

Time (minutes)0 20 40 60 80 100

Mic

rova

scul

ar C

ereb

ral C

ortic

al

Oxy

gen

Tens

ion

(mm

Hg)

0

20

40

60

80

100

120 Vehicle orNebivolol

Administration

Hemodilutionp=0.01 for 1.25 Nebivolol

vs. 2.5 Nebivolol (2-way repeated measures ANOVA)

n = 5 – 11 per group


Cerebral Oxygen Tension Effect

Hu et al A&A 2013

Only High Dose Nebivolol Increases HIF-1αLevels

GSNORHIF-2αHIF-1α

α-tubulin (55 kDa)

Nebivolol(2.5 mg/kg)

Nebivolol (1.25 mg/kg)

VehicleControl

Hemodilution

HIF-1α(120 kDa)

HIF-2α(120 kDa)

GSNOR(40 kDa)

α-tubulin (55 kDa)

α-tubulin (55 kDa)



VehicleControl

Hemodilution



VehicleControl

Hemodilution

Treatment GroupVehicle Control 1.25 Nebivolol 2.5 Nebivolol

Cer

ebra

l Cor

tical

GS

NO

R P

rote

inLe

vel N

orm

aliz

ed to

Alp

ha-T

ubul

in

0.0

0.2

0.4

0.6

0.8

1.0

1.25 1.25

Treatment Group Vehicle Control 1.25 Nebivolol 2.5 NebivololC

ereb

ral C

ortic

al H

IF-1

alp

ha P

rote

in

Leve

l Nor

mal

ized

to A

lpha

-Tub

ulin

0.0

0.2

0.4

0.6

0.8#

1.25

Treatment GroupVehicle Control 1.25 Nebivolol 2.5 NebivololC

ereb

ral C

ortic

al H

IF-2

alp

ha P

rote

inLe

vel N

orm

aliz

ed to

Alp

ha-T

ubul

in

0.0

0.2

0.4

0.6

0.8

#

#

* p<0.05 vs. baseline# p<0.05 vs. control group

Vehicle Control 1.25 mg/kg Nebivolol 2.5 mg/kg Nebivolol

Hu et al A&A 2013

Control Nebivolol Bisoprolol Atenolol

Control Nebivolol Bisoprolol Atenolol

β-2

Med

iate

d Po

tass

ium

Shi

ft β-

2 M

edia

ted

Glu

cose

Res

pons

e

Perfusion Limited by β-Blockade During Anemia

Cardiac Output


Resistance Aertry


BrainHeart

Kidneyβ 1-Receptor

β Receptor

β ReceptorNebivolol


Clinical Question




What about Other Vasodilating β-Blockers?

DeNicolantonioAm J Col Cardiol 2013

Dea

thN

on-F

atal

MI

What is the Next Step for β-Blocker Therapy?

Patients on Chronic β-Blocker Therapy (metoprolol)

Randomization

ContinueMetoprolol

Convert toBisoprolol

Assess Composite Clinical Outcome(Stroke-Hypotension-MI-Death)

Protected Heart

Brain

Hypoxic Brain

+Peri-Operative β Blockade

Non-Stressed β-Blockade β-Blockade + Anemia

Brain

+

Brain

VeryHypoxic Brain

+

Protected Heart

Acknowledgements:

Acknowledgements:

Dept. of AnesthesiaSt. Michael’s HospitalUniversity of Toronto

SMH Anesthesiologists

Dr. A. BakerDr. R. ByrickDr. P. HoustonDr. J. LaffeyDr. P. LeungDr. C.D. Mazer

Research Collaboration

Dr. W.S. BeattieDr. S.S. BolzDr. K. ConnellyDr. P. DorianDr. S. HeximerDr. B. KavanaghD. H Leong-PoiDr. P.A. MarsdenDr. D. Wilson

Canadian Anesthesiologists SocietyPhysicians Services Incorporated FoundationSociety of Cardiovascular Anesthesiologists

Research Associates & Students

Neil DattaniMostafa El Beheiry (MSc)Tina Hu (MSc)Elaine Liu (MD)Tim MakAnya McLaren (MSc)Tenille Ragoonanan (MSc)Albert Tsui (PhD)Julie Yu

Trinity College, University of Toronto

Acknowledged Funding Support:


Cardiac Output


Resistance Aertry


BrainHeart

Kidneyβ1 Receptor

Β2 Receptor



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Perioperative Myocardial Infarction Myocardial... · at reducing perioperative acute myocardial infarction. ... βBlockers Increase Perioperative Stroke? Bangalore Lancet 2008 β-Blockers