Role of Nitric Oxide in the Mechanism of Preclamping and Remote Ischemic Preconditioning of Adipocutaneous Flaps in a Rat Model

Abstract

The purpose of this study was to determine whether nitric oxide (NO) plays a role in the mechanism of acute ischemic preconditioning (IP). Fifty-eight male Wistar rats were divided into seven experimental groups. An extended epigastric flap was raised in one of the control groups (C, n = 8), and a 3-hr flap ischemia was induced. Another group served as a non-ischemic control (CO, n = 8). The animals of group S (n = 9) received 500 nmol/kg of Spermine/Nitric Oxide Complex (Sper/NO) intravenously 30 min prior to ischemia. The group N+P (L-NAME + preclamping, n = 8) received 10 mg/kg Nomega-Nitro-L-Arginine Methyl Ester (L-NAME) intravenously before preclamping of the flap pedicle (10-min cycle length, 30-min reperfusion). Ten mg/kg L-NAME were administered in group N+T (L-NAME + tourniquet, n = 9) before ischemia of the right hindlimb was induced using a tourniquet for 10 min after flap elevation. Flap ischemia was induced after 30 min of limb reperfusion. A similar protocol was used in the groups N+P+S (L-NAME + preclamping+Sper/NO, n = 8) and N+T+S (L-NAME + tourniquet + Sper/NO, n = 8). In both groups Sper/NO was administered 30 min prior to flap ischemia, additionally to the protocol of the groups N+P and N+T. Mean flap necrosis area was assessed on the fifth postoperative day using a planimetry software. Average flap necrosis area was 67 +/- 16 percent in the control group C, 28 +/- 13.3 percent in the non-ischemic controls (CO), 10 +/- 5.9 percent in group S, 77.5 +/- 10.2 percent in group N+P, 76 +/- 6.9 percent in group N+T, 71.5 +/- 9.4 percent in group N+P+S, and 78 +/- 9.9 percent in group N+T+S. The animals of group S and CO demonstrated a significantly lower area of flap necrosis than all other groups ( p < 0.001). No significant difference could be shown between the groups C, N+P, N+T, N+P+S and N+T+S. Group S showed a significantly lower flap necrosis area than group CO ( p < 0.01). The data showed, that NO plays an important role in the mechanism of IP since the administration of an NO-donor previous to ischemia simulates the effect of IP, while the unspecific blocking of NO synthesis by L-NAME eliminates the protective effect of flap preconditioning by preclamping as well as by remote IP. Exogenous NO application is insufficient to provide protection once the endogenous NO synthesis is blocked.

Remote ischaemic preconditioning of the hind limb reduces experimental liver warm ischaemia–reperfusion injury

“…Nitric oxide has an important role in delayed remote cardioprotection 22 and in the early protection of adipocutaneous flaps with limb RIPC 11 . The role of nitric oxide in early remote cardioprotection is controversial.…”

“…RIPC of the limb in humans 8 and animals 9 reduces IRI to the heart, lungs and other organs 10 . A putative role for nitric oxide has been suggested 11 . The present study investigated the possible effect of RIPC of the hind limb in reducing the adverse effects of warm liver IRI, and the underlying mechanisms.…”

Remote Ischemic Preconditioning: A Novel Protective Method From Ischemia Reperfusion Injury—A Review

“…Eight studies have demonstrated the beneficial effect of skeletal preconditioning on adipocutaneous, muscle, and cremasteric muscle flaps as well as remote skeletal tissue [47][48][49][50][51][52][53][54]. Moses et al [47] demonstrated reduced LD muscle flap infarct size in a pig model following RIPC (3 ϫ 10 min).…”

Remote or Conventional Ischemic Preconditioning –Local Liver Metabolism in Rats Studied with Microdialysis

“…The role of NO in IPC has been proposed in several studies, although the exact mechanism is unknown [23,[40][41][42][43]. On the other hand, in R-IPC the role of NO is more debatable; although it has been proposed as the mechanism for R-IPC in the heart and adipo-cutaneous flaps, others have rejected this [44][45][46]. In the settings of liver IRI, only one study has found evidence for the role of NO in the protective effect of R-IPC [15].…”