1. Bradykinin protects the rabbit heart after cardioplegic ischemia via NO-dependent pathways 
Jun Feng, MD, PhD, Hongling Li, MD, MSc, Eliot R Rosenkranz, MD 
The Annals of Thoracic Surgery 
Volume 70, Issue 6, Pages (December 2000)
DOI: /S (00)

2. Fig 1
Protocol. All hearts received a 20-minute period of pretreatment before 50 minutes of normothermic cardioplegic arrest. After 60 minutes of reperfusion, recovery of LV performance and CF was recorded. See Material and Methods for details. (STCP = St. Thomas’ cardioplegia solution.)
The Annals of Thoracic Surgery  , DOI: ( /S (00) )

3. Fig 2
LV developed pressure. Bradykinin-treated hearts had significantly better recovery of LVDP during reperfusion compared with control hearts. Pretreatment with HOE 140 or L-NAME blocked the beneficial effect of BK pretreatment.
The Annals of Thoracic Surgery  , DOI: ( /S (00) )

4. Fig 3
CF. Pretreatment with bradykinin caused a slight increase in CF before ischemia. During reperfusion, BK hearts had significantly higher CF than control hearts. Pretreatment with HOE 140 or L-NAME blocked the beneficial effect of BK pretreatment.
The Annals of Thoracic Surgery  , DOI: ( /S (00) )

5. Fig 4
LV contractility. Bradykinin-treated hearts had significantly better recovery of contractility than control hearts. Pretreatment with HOE 140 or L-NAME blocked the benefit of bradykinin pretreatment.
The Annals of Thoracic Surgery  , DOI: ( /S (00) )

6. Fig 5
LV end diastolic pressure. Although LVEDP rose in all hearts during ischemia, bradykinin-treated hearts had significantly lower LVEDP at the end of reperfusion compared with control hearts. Pretreatment with HOE 140 or L-NAME blocked the beneficial effect of BK pretreatment.
The Annals of Thoracic Surgery  , DOI: ( /S (00) )

7. Fig 6
LV compliance. Bradykinin-treated hearts had significantly better recovery of compliance than control hearts. Pretreatment with HOE 140 or L-NAME blocked the benefit of bradykinin pretreatment.
The Annals of Thoracic Surgery  , DOI: ( /S (00) )

8. Fig 7
Proposed molecular mechanisms. BK activates eNOS via the bradykinin B2 receptor, resulting in the production of NO. NO then activates the signal transduction cascade, leading to early and late preconditioning by forming reactive oxygen species (ROS). ROS activate discrete PKC isoforms, leading to opening of the ATP-sensitive potassium (KATP) channel and induction of the early preconditioned state. Simultaneously, inducible NOS (iNOS) is activated and iNOS mRNA transcripts are produced by the activation of nuclear factors such as NFκB, resulting in “amplification” of the signal transduction cascade, leading to the late preconditioned state. HOE 140 can block these signal transduction pathways by preventing the activation of the bradykinin B2 receptor. L-NAME can block these pathways by preventing activation of both eNOS and iNOS.
The Annals of Thoracic Surgery  , DOI: ( /S (00) )