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Murine Isolated Heart Model of Myocardial Stunning Associated with Cardioplegic Arrest
Published on: August 6, 2015
Differences in ischemic damage between young and old hearts--Effects of blood cardioplegia
Andreas Böning1, Susanne Rohrbach2, Lukas Kohlhepp1
1Department of Cardiovascular Surgery, Justus-Liebig University Gießen, Germany.
Insights
Senescent hearts show higher risk of cardiac dysfunction. Buckberg
Area of Science:
- Cardiovascular Science
- Geriatric Medicine
- Cardiothoracic Surgery
Background:
- Senescent patients face increased perioperative cardiac risks.
- Current cardioplegic strategies are not age-specific.
- Octogenarians represent a growing segment of cardiac surgery patients.
Purpose of the Study:
- Compare hemodynamic and metabolic performance of adult vs. senescent rat hearts post-ischemia.
- Evaluate age-related differences in myocardial function and cellular ultrastructure after blood cardioplegia (BCP).
Main Methods:
- Isolated Langendorff perfusion of adult and senescent rat hearts.
- Application of Buckberg's blood cardioplegia (BCP) with repeated doses.
- Assessment of ex vivo cardiac function (LVDP, +/-dp/dt, coronary blood flow).
- Measurement of myocardial oxygen consumption and lactate production.
- Transmission electron microscopy for ultrastructural analysis (edema, mitochondria).
Main Results:
- Senescent hearts showed impaired recovery after unprotected ischemia.
- BCP provided similar functional recovery in both adult and senescent hearts.
- Mitochondrial ultrastructure was preserved in BCP-treated hearts of both age groups.
- Senescent hearts exhibited higher oxygen consumption and lower lactate production.
Conclusions:
- Senescent hearts are more vulnerable to ischemia/reperfusion injury without protection.
- BCP effectively protects senescent hearts, yielding hemodynamic performance comparable to adult hearts.
- Age-independent myocardial protection is achievable with BCP.
Objective:
Senescent patients exhibit an elevated perioperative risk for cardiac dysfunction, hemodynamic depression and subsequent cardiac death compared to young patients. Despite the fact that a growing proportion of cardiac surgery patients are octogenarians, cardioplegic regimes remain comparable across patients of all ages. We compared the hemodynamic performance, metabolic parameters and ultrastructural changes in adult and senescent rat hearts after application of Buckberg's blood cardioplegia (BCP) to evaluate differences between the age groups regarding postischemic myocardial function and cellular ultrastructure.
Methods:
Hearts of adult (young adult group, 3-4 months) and senescent (old group, 24 months) male Wistar rats were excised and inserted into a blood perfused isolated heart apparatus (Langendorff perfusion). After a stabilization period of 30 min, in 16 adult and 16 senescent hearts, Buckberg BCP was administered antegradely and repeated every 20 min. Six young adult and 3 senescent hearts served as ischemia control. After an aortic clamping time of 90 min an antegrade hot shot was administered. During reperfusion ex vivo cardiac functional parameters were recorded, including coronary blood flow, left ventricular developed pressure (LVDP) and velocity of myocardial contraction or relaxation (+/-dp/dt). Oxygen consumption and lactate production of the hearts were calculated. After perfusion fixation, the hearts of five rats in each BCP group and 3 rats in each ischemia group were investigated for cellular edema and mitochondrial damage by morphometry using transmission electron microscopy.
Results:
While recovery of cardiac function after 90 min of unprotected ischemia was significantly impaired in senescent hearts, functional recovery after ischemia protected by BCP was similar in adult and senescent hearts. Mitochondrial ultrastructure was severely damaged in both age groups after 90 min ischemia, but well preserved in both BCP groups. The qualitative analysis was confirmed by the morphometric cellular edema index and the volume-to-surface ratio of the mitochondria. Myocardial oxygen consumption was highest and lactate production was lowest in senescent hearts.
Conclusion:
Senescent rat hearts were more susceptible to unprotected ischemia/reperfusion injury than young adult hearts. When protected by BCP, we found no difference in hemodynamic performance between adult and senescent hearts indicating preserved myocardial protection even in senescent individuals.
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