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Prevention of myocardial intracellular edema induced by St. Thomas' Hospital cardioplegic solution
K Drewnowska1, H F Clemo, C M Baumgarten
1Department of Physiology, Medical College of Virginia, Richmond 23298-0551.
Insights
Cold cardioplegic solutions used in heart surgery can cause cell swelling due to hypotonicity, not just hypothermia. This swelling is linked to KCl influx and impacts cell volume, affecting cardiac surgery outcomes.
Area of Science:
- Cardiology
- Cell Biology
- Biochemistry
Background:
- Cardiac surgery frequently uses cold crystalloid cardioplegic solutions like St. Thomas' Hospital (StT) solution.
- These solutions contain high K+ and Mg2+ to arrest the heart and reduce oxygen consumption.
- Myocardial edema and post-operative issues are often attributed to ischemia, reflow, or hypothermia.
Purpose of the Study:
- To investigate the causes of myocardial edema and cell swelling during cardiac surgery.
- To determine the specific mechanisms behind cell volume changes induced by cold cardioplegic solutions.
- To clarify the role of solution composition and temperature in cardioplegia-induced cell alterations.
Main Methods:
- Isolated ventricular cells were exposed to cold (9 degrees C) St. Thomas' Hospital solution.
- Experiments involved manipulating anion composition (replacing Cl- with impermeant anions).
- Cell volume changes were monitored during hypothermia and subsequent rewarming in Tyrode's solution, with and without ouabain.
Main Results:
- Cold StT solution (9 degrees C) was hypotonic and induced cell swelling independent of ischemic injury.
- Cell swelling was primarily caused by KCl influx, preventable by using impermeant anions.
- Upon rewarming, cells transiently shrank, an effect blocked by ouabain, indicating Na+ loading and Na+-K+ pump activation.
Conclusions:
- Cold, hypotonic cardioplegic solutions can cause cell swelling through KCl influx, irrespective of ischemia.
- Rewarming depolarized, hypothermic cells leads to transient shrinkage mediated by Na+ loading and pump activation.
- The product of [K+] x [Cl-] in cardioplegic solutions significantly influences cell volume in hypothermic conditions.
Abstract:
During cardiac surgery, the heart is infused with cold crystalloid cardioplegic solutions such as St. Thomas' Hospital (StT) solution, which contains high concentrations of K+ and Mg2+. The high K+ and Mg2+ block impulse conduction and inhibit Ca2+ influx, thereby arresting the heart and reducing cardiac oxygen consumption. Nevertheless, myocardial edema and post-operative abnormalities have been noted after cardioplegia and attributed to ischemia and reflow or to hypothermia. We found, however, that cold StT (9 degrees C) was hypotonic and induced cell swelling in the absence of ischemic injury. Cell swelling in cold StT was not due to hypothermia alone, but rather was caused by KCl influx and was prevented by partially replacing Cl- with an impermeant anion. After exposure to cold StT, cells transiently shrank to less than control volume on rewarming in physiological saline (Tyrode's solution, 37 degrees C). The transient shrinkage was blocked by ouabain suggesting that Na+ loading of depolarized hypothermic cells and Na(+)-K+ pump activation on rewarming were responsible. Hypothermic ventricular cells seem to follow Donnan equilibrium, and the product of [K+] x [Cl-] in cardioplegic solutions affects cell volume in the absence of ischemic injury.