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Age-related changes in the ability of hypothermia and cardioplegia to protect ischemic rabbit myocardium
J E Baker1, L E Boerboom, G N Olinger
1Department of Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee.
Insights
Immature rabbit hearts show remarkable tolerance to ischemia, with hypothermia alone providing excellent protection. Pharmacologic cardioplegia, however, unexpectedly damages immature hearts, unlike in mature hearts.
Area of Science:
- Cardiology
- Pediatric Cardiology
- Cardiovascular Surgery
Background:
- Hypothermia with cardioplegia protects adult hearts during ischemia.
- This protective effect may not extend to pediatric patients, potentially leading to poor outcomes.
Purpose of the Study:
- To assess the susceptibility of immature and mature rabbit hearts to ischemia-induced injury.
- To compare the protective effects of hypothermia alone versus hypothermia with cardioplegia in different age groups.
Main Methods:
- Isolated perfused immature and mature rabbit hearts were subjected to hypothermic global ischemia.
- Hearts were protected with hypothermia alone or with St. Thomas' Hospital cardioplegic solution No. 2.
- Postischemic recovery of aortic flow was measured as an indicator of myocardial function.
Main Results:
- Hypothermia alone provided excellent protection for immature hearts (93-97% flow recovery).
- Mature hearts showed minimal recovery with hypothermia alone (22% flow recovery).
- St. Thomas' Hospital solution No. 2 improved recovery in mature hearts but significantly damaged immature hearts (86% flow recovery).
Conclusions:
- Immature rabbit hearts are more tolerant to ischemic injury than mature hearts.
- Pharmacologic cardioplegia (St. Thomas' Hospital solution No. 2) is detrimental to immature hearts, contrary to its protective effect in mature hearts.
Abstract:
Hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, but this benefit may not extend to children; poor postischemic recovery of function and increased mortality may result when this method of myocardial protection is used in children. The relative susceptibilities to ischemia-induced injury modified by hypothermia alone and by hypothermia plus cardioplegia were assessed in isolated perfused immature (7- to 10-day-old) and mature (6- to 24-month-old) rabbit hearts. Hearts were perfused aerobically with Krebs-Henseleit buffer in the working mode for 30 minutes, and aortic flow was recorded. This was followed by 3 minutes of hypothermic (14 degrees C) coronary perfusion with either Krebs or St. Thomas' Hospital cardioplegic solution No. 2, followed by hypothermic (14 degrees C) global ischemia (mature hearts 2 and 4 hours; immature hearts 2, 4, and 6 hours). Hearts were reperfused for 15 minutes in the Langendorff mode and 30 minutes in the working mode, and recovery of postischemic function was measured. Hypothermia alone provided excellent protection of the ischemic immature rabbit heart, with recovery of aortic flow after 2 and 4 hours of ischemia at 97% +/- 3% and 93% +/- 4% (mean +/- standard deviation) of the preischemic value. Mature hearts protected with hypothermia alone recovered only minimally, with 22% +/- 16% recovery of preischemic aortic flow after 2 hours; none were able to generate flow at 4 hours. St. Thomas' Hospital solution No. 2 improved postischemic recovery of aortic flow after 2 hours of ischemia in mature hearts from 22% +/- 16% to 65% +/- 6% (p less than 0.05), but actually decreased postischemic aortic flow in immature hearts from 97% +/- 3% to 86% +/- 10% (p less than 0.05). To investigate any dose-dependency of this effect, we subjected hearts from both age groups to reperfusion with either Krebs solution or St. Thomas' Hospital solution No. 2 for 3 minutes every 30 minutes throughout a 2-hour period of ischemia. Reexposure to Krebs solution during ischemia did not affect postischemic function in either age group. Reexposure of immature hearts to St. Thomas' Hospital solution No. 2 caused a decremental loss of postischemic function in contrast to incremental protection with multidose cardioplegia in the mature heart. We conclude that immature rabbit hearts are significantly more tolerant of ischemic injury than mature rabbit hearts and that, unexpectedly, St. Thomas' Hospital solution No. 2 damages immature rabbit hearts.