Related Experiment Video
Updated: Aug 23, 2026

Murine Isolated Heart Model of Myocardial Stunning Associated with Cardioplegic Arrest
Published on: August 6, 2015
Cyclic GMP reduces myocardial stunning through non-cyclic GMP protein kinase mechanisms
Qihang Zhang1, Michael Lazar, Lin Yan
1Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, 08903, USA.
Abstract:
We tested the hypothesis that myocardial stunning would be reduced by increased cyclic GMP and cGMP protein kinase activity. Hearts were instrumented in eight open-chest anesthetized dogs. The left anterior descending coronary artery (LAD) was occluded for 15 minutes followed by a 30-minute recovery and infusion of 8-Bromo-cGMP (0.1 and 1 microg/kg/min) during functional and metabolic data collection. Myocytes from circumflex and LAD regions were then used to obtain data at baseline, with 8-Br-cGMP (10(-7, -6, -5) M) and KT5823 10(-6) M, cGMP protein kinase inhibitor. The in vivo time delay of regional shortening increased significantly from 55 +/- 12 to 99 +/- 3 msec following stunning, but was reduced to 81 +/- 2 by 1 microg/kg/min 8-Br-cGMP. The % regional work during systole decreased during stunning (93 +/- 2 to 76 +/- 8%), but was restored by 8-Br-cGMP (91 +/- 7). Stunning lengthened the time of myocyte contraction and relaxation and reduced baseline shortening. 8-Br-cGMP reduced myocyte shortening in both regions. However, KT5823 only restored myocyte shortening in controls. These data indicated that regional myocardial stunning could be reduced by cyclic GMP but this appeared to be through non-cGMP protein kinase mechanisms.
Insights
Myocardial stunning, a heart condition, was improved by cyclic GMP (cGMP). However, the protective effects of cGMP were not mediated by cGMP-dependent protein kinase.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
Background:
- Myocardial stunning is a post-ischemic dysfunction.
- Cyclic guanosine monophosphate (cGMP) plays a role in cardiac function.
Purpose of the Study:
- To investigate if increased cyclic GMP and cGMP protein kinase activity can reduce myocardial stunning.
- To explore the mechanisms by which cGMP affects myocardial stunning.
Main Methods:
- Open-chest anesthetized dogs underwent left anterior descending coronary artery occlusion followed by reperfusion.
- 8-Bromo-cGMP (8-Br-cGMP) was infused to increase cGMP levels.
- Myocytes were isolated to assess the effects of 8-Br-cGMP and KT5823 (a cGMP protein kinase inhibitor).
Main Results:
- 8-Br-cGMP administration reduced the time delay of regional shortening and restored regional work during systole in stunned hearts.
- cGMP reduced myocyte shortening, while the cGMP protein kinase inhibitor KT5823 only restored myocyte shortening in control (non-stunned) conditions.
- These findings suggest that the beneficial effects of cGMP on myocardial stunning may involve pathways independent of cGMP protein kinase.
Conclusions:
- Regional myocardial stunning can be attenuated by elevated cyclic GMP levels.
- The protective mechanisms of cyclic GMP against myocardial stunning appear to be independent of cGMP protein kinase activation.
Related Concept Videos
GPCRs Regulate Adenylyl Cylase Activity
Two...
cAMP-dependent Protein Kinase Pathways
G-Protein Gated Ion Channels
Sensory organs,...
Nitric Oxide Signaling Pathway
GPCR Desensitization
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...

