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Ann Thorac Surg 1996;62:38-39
© 1996 The Society of Thoracic Surgeons
DR IRVIN KRUKENKAMP (Boston, MA): This was an excellent study! The blood-perfused rabbit Langendorff preparation is a very difficult model, and you are to be congratulated for bringing this study to fruition.
As you know, we presented our data using an intact sheep model at the American Heart Association meeting just a few months ago. We reported on the use of pinacidil in a cold blood cardioplegia model, and I note several differences of which I am sure you are aware.
We noticed that the time to either electrical or mechanical arrest was very quick, about 90 seconds, compared with your data of 4 minutes for mechanical arrest and 12 minutes for electrical arrest. I would be curious to hear your thoughts about this. In the cold cardioplegia study we noted 100% recovery of function compared with your data with a 69% functional recovery. Do you think the hearts in your study were "protected"? I also noticed that your pinacidil dosage was 50 µmol/L and ours was 200 µmol/L. We also observed less ventricular fibrillation in the cold versus warm models. I would be curious to hear your comments about these issues.
DR LAWTON: Thank you for your comments. Regarding your first comment about cold cardioplegia giving rapid mechanical and electrical arrest, the rapid arrest may not only reflect the cardioplegia, but the temperature of the cardioplegia. Using these agents in cold cardioplegia in our model, we also found a very rapid mechanical and electrical arrest.
Second, the 100% recovery using pinacidil in cold cardioplegia that you found may be related to the protective effect of the temperature during ischemia. Our experiments were performed using normothermic ischemia at 37°C, and previous work from our laboratory has demonstrated significant improvement (and therefore protection) in recovery with pinacidil when compared with the control group.
Regarding your third comment, the 50 µmol/L dose of pinacidil was chosen after a careful dose-response curve was performed in this model, which demonstrated this to be the optimal dose and a decline in recovery, or toxicity, with the 200 µmol/L concentration.
Finally, potassium-channel openers are known to be proarrhythmic, and this is manifested in our experiments with warm ischemia. In our experience with these agents in cold cardioplegia in this model, we also noted no ventricular fibrillation upon reperfusion.
DR RICHARD M. ENGELMAN (Springfield, MA): I certainly enjoyed this very excellently presented paper. I question about the proarrhythmic effects of the potassium agents. They are clearly species specific, and when we have used these agents in the isolated rat model, they are clearly very proarrhythmic. In the event of ventricular fibrillation, was this a repetitive episode of fibrillation; did it occur once only to be defibrillated, not to appear again; or did the same isolated model have repetitive episodes of fibrillation?
And secondarily, was not only fibrillation a problem but did ventricular tachycardia occur and could these hearts be appropriately paced?
DR LAWTON: The ventricular fibrillation noted upon reperfusion occurred only immediately upon release of the column clamp in the potassium-channel opener groups. Fibrillation did not occur again for the full 30 minutes of reperfusion, and for 60 minutes of reperfusion in other experiments previously performed. The arrhythmia noted was always ventricular fibrillation, never ventricular tachycardia, and we did not have any difficulty pacing these hearts after reperfusion.
DR ROBERT A. GUYTON (Atlanta, GA): I enjoyed the paper. I am somewhat disturbed by your use of normothermic St. Thomas' solution; I do not think that Dr Hearse would endorse this.
Second, because your dose-response curve seems to indicate a fairly tight dose response, and clinical cardioplegia is very heterogeneous, with some regions of the heart receiving ten times as much cardioplegia as other regions in coronary disease, do you think that a cardioplegia solution with this tight a dose-response curve can be clinically useful?
DR LAWTON: It is well known that St. Thomas' solution is not efficacious as warm cardioplegia, and that is one of the reasons why the addition of cold arrest and ischemia is practiced today. We chose to examine these agents in a series of experiments using warm cardioplegia first to examine their effectiveness before adding the additional variable of hypothermia.
Second, the tight pinacidil dose-response curve is very disturbing. We found a similar dose-response relationship with aprikalim in this model with toxicity at higher doses. You pose a very good question, and I do not know if these agents will ever become clinically relevant because of that reason. Perhaps there is one agent that does not have this dose-response relationship that we are yet to discover. However, these agents are potent vasodilators and would probably reach all areas of the myocardium during the time of administration. This may be beneficial compared with other forms of cardioplegia.
Related Article
Ann. Thorac. Surg. 1996 62: 31-38.
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