Genetically determined mitochondrial preservation and cardioprotection against myocardial ischemia-reperfusion injury in a consomic rat model.

Cardioprotection may be genome dependent. One example is the increased tolerance to cardiac ischemia-reperfusion (IR) in Brown Norway (BN) compared with Dahl salt-sensitive (SS) rats. By narrowing the genetic difference to chromosome 6 only, we found the consomic SS(6BN) to be similarly IR tolerant as BN. We hypothesized that better preserved mitochondrial structure and function are genetically determined and therefore critically linked to myocardial IR tolerance associated with BN chromosome 6. Langendorff-prepared BN, SS, and SS(6BN) rat hearts were subjected to IR, while corresponding controls were continuously perfused. Though largely equal in nonischemic controls, assessment of functional data and ventricular infarct size in IR experiments confirmed that BN and SS(6BN) have an equally higher tolerance to IR than SS hearts. This was complemented by equally better preserved mitochondrial structure, oxidative phosphorylation, and calcium retention capacity in BN and SS(6BN) vs. SS hearts. For the first time, our data indicate that SS(6BN) are as resistant to IR injury as BN hearts in mitochondrial and myocardial function and viability compared with SS hearts. These findings not only link myocardial and mitochondrial protection in a genetic model but also suggest that genetic information on rat chromosome 6 is critical for mitochondrial preservation and IR tolerance.

Refractory hypotension during general anesthesia despite preoperative discontinuation of an angiotensin receptor blocker.

Due to their beneficial reduction in morbidity and mortality angiotensin receptor blockers (ARBs) have become increasingly popular to treat hypertension. However, similar to angiotensin converting enzyme inhibitors, they can lead to severe hypotension in conjunction with general anesthesia and thus have been recommended to be withheld in the morning of surgery. Here, we present a 51 year old female who developed severe refractory hypotension after induction of general anesthesia, although she had discontinued her medication 24 hours preoperatively as instructed. Therefore, halting ARBs for more than 24 hours before surgery may be necessary. Heightened awareness of this potential interaction and recognizing the need to treat with vasopressin is required when ARB-induced hypotension occurs.