Related Experiment Videos
Influence of oxygenation on endothelial modulation of coronary vasomotor function during hyperkalemic cardioplegia
N Matsuda1, M Tofukuji, K G Morgan
1Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Insights
Oxygenation of hyperkalemic cardioplegic solution (K-CP) affects vascular tone by influencing endothelial nitric oxide production and intracellular calcium, impacting smooth muscle function during cardiac surgery.
Area of Science:
- Cardiovascular Physiology
- Endothelial Function
- Myocardial Protection
Background:
- Hyperkalemic cardioplegic solutions (K-CP) are used to arrest the heart during surgery.
- The role of oxygenation in K-CP and its effect on vascular tone is not fully understood.
- Endothelial modulation of vasomotor tone is critical for maintaining blood flow.
Purpose of the Study:
- To investigate how oxygenation of K-CP influences endothelial control of vasomotor tone.
- To correlate these vascular changes with intracellular calcium concentration ([Ca++]i) in microvascular smooth muscle.
- To elucidate the mechanisms of endothelial modulation during K-CP.
Main Methods:
- Rat coronary arterioles were studied in a pressurized, normothermic, no-flow state.
- Simultaneous measurements of luminal diameter and intracellular calcium ([Ca++]i) using fura-2.
- Vessels were exposed to either oxygenated or hypoxic K-CP, followed by reperfusion.
Main Results:
- Oxygenated K-CP caused increased contraction and [Ca++]i in endothelium-denuded vessels, similar to nitric oxide synthase inhibition.
- Hypoxic K-CP led to attenuated contraction in endothelium-denuded vessels without significant [Ca++]i changes.
- Indomethacin did not influence endothelium-dependent contraction under hypoxic K-CP.
Conclusions:
- Endothelium-derived nitric oxide regulates vascular tone during oxygenated K-CP by controlling smooth muscle [Ca++]i.
- Endothelium-derived contracting factors, not primarily from cyclo-oxygenase, may increase vascular smooth muscle Ca++ sensitivity under hypoxic K-CP.
- Oxygenation status of K-CP significantly alters endothelial modulation of vascular tone.
Background:
The purpose of this study was to determine the influence of oxygenation of a hyperkalemic cardioplegic solution (K-CP) on endothelial modulation of vasomotor tone and to correlate these changes with the intracellular calcium concentration ([Ca++]i) in microvascular smooth muscle.
Methods:
Rat coronary arterioles were studied in a pressurized, no-flow normothermic state. Simultaneous monitoring of luminal diameter and [Ca++]i (fura-2) was performed with use of microscopic image analysis. Vessels were subjected to 60 minutes of oxygenated or hypoxic K-CP (K+ = 25.0 mmol/L) and were then reperfused with oxygenated Krebs-physiologic saline solution for 60 minutes.
Results:
In oxygenated K-CP, the K-CP-induced contraction and [Ca++]i accumulation were significantly increased in endothelium-denuded (ED) vessels compared with endothelium-intact vessels. The effect of ED in oxygenated K-CP was mimicked by administration of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine. Conversely, in hypoxic K-CP the contraction was significantly attenuated in ED vessels compared with endothelium-intact vessels, although there was no significant difference in [Ca++]i. Indomethacin did not affect the endothelium-dependent contraction during hypoxic K-CP.
Conclusions:
Endothelium-derived nitric oxide modulates the vascular tone during K-CP by regulating the vascular smooth muscle [Ca++]i, whereas endothelium-derived contracting factor(s), which is not predominantly a product of cyclo-oxygenase, may play a prominent role under hypoxic K-CP by increasing vascular smooth muscle Ca++ sensitivity.