Key result
Losartan significantly improved survival in the first 24 hours after myocardial infarction in transgenic rats overexpressing AT1R (from 39% to 80%, p<0.05) and decreased total duration of arrhythmia.
Why the study?
Does AT1R blockade with losartan reduce reperfusion-induced arrhythmias and mortality early after myocardial infarction in rats with cardiac AT1R overexpression?
Does AT1R blockade with losartan reduce reperfusion-induced arrhythmias and mortality early after myocardial infarction in rats with cardiac AT1R overexpression?
AT1R blockade with losartan reduces reperfusion-induced arrhythmias and early mortality after myocardial infarction specifically in the setting of AT1R overexpression.
Answers are grounded in this paper and cite their sources.
Losartan may improve early post-MI survival in AT1R-overexpressing models; leaves open human translation.
Angiotensin II induces ischemia/reperfusion (I/R)-induced arrhythmias and blockade of the angiotensin II type 1 receptor (AT1R) may therefore be beneficial in preventing arrhythmias and decreasing mortality after myocardial infarction (MI). Because the AT1R is upregulated after myocardial ischemia, it was hypothesized that the level of AT1R expression would mediate the response to AT1R blockade. Transgenic (TGR) rats that overexpress the human AT1R and Sprague-Dawley rats were used as controls. Total duration of arrhythmia (seconds) after I/R injury was similar in TGR and SD rats (433 +/- 109 vs. 376 +/- 117, p = n.s.). AT1R blockade with losartan decreased total duration of arrhythmia in the TGR rats (433 +/- 110 s-164 +/- 48 s; p < 0.05), whereas it caused a nonsignificant increase in the SD rats (376 +/- 117 s-497 +/- 97). In vivo, survival in the first 24 hours after MI was impaired in TGR rats (39%; SD, 63%). Losartan improved survival significantly in TGR rats (from 39% to 80%, p < 0.05). A smaller, nonsignificant effect was observed in SD rats (63% to 81%). AT1R blockade is beneficial only when the AT1R was overexpressed, both in reducing the reperfusion-induced arrhythmias and mortality early after MI.
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Boer et al. (2002) studied Myocardial infarction and ischemia/reperfusion-induced arrhythmias. Losartan vs. No losartan (control) was evaluated on Survival in the first 24 hours after MI in TGR rats (p=<0.05). Losartan significantly improved survival in the first 24 hours after myocardial infarction in transgenic rats overexpressing AT1R (from 39% to 80%, p<0.05) and decreased total duration of arrhythmia.
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