BACKGROUND Cardiovascular disease increases with age in both sexes. Treatment can require cardiac surgery, where the hearts are pre-treated with protective cardioplegic solution before ischemia and reperfusion (I/R). While endogenous estrogen is beneficial in I/R, whether testosterone is involved is uncertain and whether age modifies responses to I/R is unclear. We investigated sex- and age-specific differences in I/R injury in the hearts pre-treated with clinically relevant cardioplegic solution. METHODS The hearts were isolated from young (6-9 months) and old (20-28 months) mice of both sexes and perfused (Langendorff) with Krebs-Henseleit buffer (15 min, 37 °C), followed by St. Thomas' two cardioplegia (6 min, 6-7 °C), global ischemia (90 min, 23-24 °C), and reperfusion (30 min, 37 °C). The hearts were perfused with triphenyltetrazolium chloride to quantify infarct area. Testosterone's role was investigated in gonadectomized (GDX, 6-9 months) male mice; serum testosterone and estradiol were measured with ELISA assays. RESULTS Left ventricular developed pressure (LVDP) recovered to 67.3 ± 7.4% in the old compared to 21.8 ± 9.2% in the young male hearts (p < 0.05). Similar results were seen for rates of pressure development (+dP/dt) and decay (-dP/dt). Infarct areas were smaller in the old male hearts (16.6 ± 1.6%) than in the younger hearts (55.8 ± 1.2%, p < 0.05). By contrast, the hearts from young and old females exhibited a similar post-ischemic functional recovery and no age-dependent difference in infarcts. There was a sex difference in the young group, where ventricular function (LVDP, +dP/dt, -dP/dt) recovered better and infarcts were smaller in females than males. Estradiol levels were highest in young females. Testosterone was high in young males but low in females and old males, which suggested beneficial effects of low testosterone. Indeed, the hearts from GDX males exhibited much better recovery of LVDP in reperfusion than that from intact males (values were 64.4 ± 7.5 % vs. 21.8 ± 9.2%; p < 0.05). The GDX hearts also had smaller infarcts than the hearts from intact males (p < 0.05). CONCLUSIONS Although age had no effect on susceptibility to I/R injury after cardioplegic arrest in females, it actually protected against injury in older males. Our findings indicate that low testosterone may be protective against I/R injury following cardioplegic arrest in older males.

中文翻译：

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在雄性小鼠中，心脏停搏后的缺血和再灌注损伤会因年龄和睾酮缺乏而减弱，而雌性小鼠则不会。

背景技术无论男女，心血管疾病都会随着年龄的增长而增加。治疗可能需要进行心脏手术，即在缺血和再灌注 (I/R) 之前用保护性心脏停跳液对心脏进行预处理。虽然内源性雌激素对 I/R 有益，但睾酮是否参与尚不确定，并且年龄是否会改变对 I/R 的反应尚不清楚。我们研究了用临床相关心脏停跳液预处理的心脏 I/R 损伤的性别和年龄特异性差异。方法从年轻（6-9 个月）和年老（20-28 个月）的雌性小鼠中分离心脏，并用 Krebs-Henseleit 缓冲液（15 分钟，37°C）灌注（Langendorff），然后用 St. Thomas'两次心麻痹（6 分钟，6-7°C）、全局缺血（90 分钟，23-24°C）和再灌注（30 分钟，37°C）。用氯化三苯基四唑灌注心脏以量化梗塞面积。在去性腺切除（GDX，6-9 个月）的雄性小鼠中研究了睾酮的作用；通过 ELISA 测定测定血清睾酮和雌二醇。结果 老年男性左心室展开压 (LVDP) 恢复至 67.3 ± 7.4%，而年轻男性心脏为 21.8 ± 9.2%（p < 0.05）。压力发展率 (+dP/dt) 和衰减率 (-dP/dt) 也出现了类似的结果。老年男性心脏的梗塞面积 (16.6 ± 1.6%) 比年轻男性心脏的梗塞面积小 (55.8 ± 1.2%, p < 0.05)。相比之下，年轻和年老女性的心脏表现出相似的缺血后功能恢复，并且梗塞情况没有年龄依赖性差异。年轻组中存在性别差异，其中女性的心室功能（LVDP、+dP/dt、-dP/dt）恢复得更好，并且梗死灶更小。年轻女性的雌二醇水平最高。年轻男性的睾酮水平较高，但女性和老年男性的睾酮水平较低，这表明低睾酮水平的有益作用。事实上，GDX 雄性心脏在再灌注中表现出比完整雄性心脏更好的 LVDP 恢复（值为 64.4 ± 7.5 % 与 21.8 ± 9.2%；p < 0.05）。GDX 心脏的梗塞面积也比完整雄性心脏的梗塞面积小 (p < 0.05)。结论 虽然年龄对女性心脏停跳后 I/R 损伤的易感性没有影响，但它实际上可以保护老年男性免受损伤。我们的研究结果表明，低睾酮水平可能对老年男性心脏停跳后的 I/R 损伤具有保护作用。