Influence of Medication-induced Preconditioning (MIPC) or Remote Ischemic Preconditioning (RIPC) on the Intrinsic Vascular eRNA/RNase System in Cardio-protection

Objectives: The protective effect of the vascular RNase1 on cardiovascular diseases like ischemia-reperfusion injury (IRI), atherosclerosis and thrombotic events has been proven. Knowing that remote ischemic preconditioning (RIPC) can increase the intrinsic RNase level and that medication-induced preconditioning (MIPC) is also a powerful model for cardio-protection, we examined the influence of RIPC and MIPC on vascular extracellular RNA- (eRNA), and RNase-levels in rats and compared their effects in a Langendorff ischemia/reperfusion model.

Methods: In 17 male Lewis rats, RIPC or MIPC were performed under general anesthesia with isoflurane and buprenorphine. 5 rats did not receive RIPC or MIPC (non-MIPC group) serving as a control. After preconditioning, eRNA plasma levels and RNase activity were determined, and the hearts were inserted in a Langendorff ischemia -reperfusion model. Hemodynamic (left ventricular developed pressure (LVDP), coronary flow (CF)), metabolic (oxygen consumption, lactate production) and electron-microscopical (cellular edema index (CEI), volume-to-surface ratio of mitochondria (V/S-ratio(mi)) parameters were recorded and calculated. Further, MIPC with one anesthetic drug only (either isoflurane, buprenorphine or etomidate) was induced in male Wistar rats (n = 5). After 30 minute, eRNA levels and RNase activity were determined.

Results: The plasma of RIPC-treated rats showed significantly higher RNase activity and lower eRNA levels than MIPC-treated rats. RIPC-treated rats showed also a significantly higher RNase activity than rats treated with one drug alone (isoflurane, buprenorphine and etomidate). Between these MIPC-groups, the RNase activity and eRNA levels differed appreciably. MIPC (isoflurane + buprenorphine), in comparison to non-MIPC, was superior to preserve the LVDP and the CF after cardiac ischemia. Accordingly, RIPC-treated hearts had significantly elevated LVDP and CF values after ischemia, compared with non-MIPC hearts. No obvious, differences were noted between MIPC and RIPC rat hearts regarding hemodynamics, metabolism or electron-microscopic parameters.

Conclusions: RIPC in rats did not show functional or metabolic advantage compared with MIPC in the Langendorff ischemia/reperfusion model. MIPC with isoflurane and buprenorphine lead to functional preservation of the heart compared with non-MIPC, and it appears most likely that RIPC does not bear any additional cardio-protective benefit in this experimental system.