technetium-tc-99m-pyrophosphate and Reperfusion-Injury

Topics: Animals; Diphosphates; Heart; Humans; Myocardial Ischemia; Myocardium; Necrosis; Radionuclide Imaging; Reperfusion Injury; Technetium Tc 99m Pyrophosphate

The mechanism of testicular ischemia-reperfusion injury has not been well delineated. We determined the efficacy of a biocompatible surfactant (tetronic 1107) to reduce tissue injury and evaluated cell membrane integrity as reflected by calcium ion permeability in an in vivo animal model of testicular ischemia-reperfusion.. Three groups of male Sprague-Dawley rats (6 per group) were studied. Group 1 was the nonoperative control, and groups 2 and 3 underwent 4 hours of unilateral testicular ischemia followed by 4 hours of reperfusion. Ten minutes after reperfusion 0.4 ml. saline was administered intravenously to group 2 and 180 mg./kg. surfactant tetronic 1107 to group 3. 99mTechnetium pyrophosphate was used to monitor calcium ion uptake by the ipsilateral and contralateral testicles. Both testicles were also examined histologically.. The surfactant treated animals had markedly diminished hemorrhagic discoloration and vascular congestion compared to saline treated animals. These results were confirmed microscopically with improved nuclear chromicity and disarray of germ cell layers of the seminiferous tubules. The surfactant treated group also had a statistically significant (p <0.05) reduction in radiotracer uptake compared to the saline treated animals, confirming a reduction in calcium ion permeability.. The results of this study suggest that tetronic 1107 is effective in reducing tissue damage in a testicular ischemia-reperfusion animal model.

Topics: Animals; Calcium; Disease Models, Animal; Ethylenediamines; Male; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Seminiferous Tubules; Spermatic Cord Torsion; Surface-Active Agents; Technetium Tc 99m Pyrophosphate; Testis

To study the relationship between ischaemia-reperfusion and multiple organ dysfunction syndrome (MODS), a new anaesthesia method was required to be applied to C57BL/6 mice. These mice are also used in a well accepted, standardized model for MODS using intraperitoneally administered zymosan (zymosan induced general inflammation, ZIGI). The aim was to develop a new model for ischaemia-reperfusion with 6 h of anaesthesia. This and further specific requirements for the combination of ischaemia-reperfusion and the ZIGI method, made us select inhalational anaesthesia using isoflurane in oxygen. This study evaluates whether long-term anaesthesia confounds the results of ischaemia-reperfusion and the ZIGI model. In addition the benefits of using the analgesic buprenorphine were evaluated. Ischaemia was induced with a tourniquet around the hindlimb. Ischaemia and reperfusion were verified by imaging a radioactive tracer with a gamma-camera. It was established that anaesthesia with isoflurane in oxygen caused little perturbation of body temperature and respiratory rate. A survival rate of 89% without noteworthy influence on organs was obtained. Buprenorphine proved to provide adequate analgesia and had no influence on measured parameters. In our experimental setting, this model with long duration anaesthesia allowed us to induce ischaemia and reperfusion of the hindlimb without perturbation of measurements. It also allowed good exposure of the abdomen and facilitated combination with the ZIGI model.

Topics: Analgesics, Opioid; Anesthesia; Anesthetics, Inhalation; Animals; Body Temperature; Buprenorphine; Disease Models, Animal; Isoflurane; Male; Mice; Mice, Inbred C57BL; Organ Size; Radionuclide Imaging; Radiopharmaceuticals; Reperfusion Injury; Respiration; Technetium Tc 99m Pyrophosphate

Because the three distinct fiber types of skeletal muscle have significant metabolic differences, the predominant fiber type in a muscle may influence its sensitivity to injury from ischemia and reperfusion. The few studies to address this issue have been conflicting. We explored possible differences in the sensitivity of fiber types to ischemia/reperfusion injury with an isolated rat hindlimb preparation perfused with an albumin-enriched Krebs buffer. Following 120 min of ischemia and 60 min of reperfusion, the tibialis anteriorwhite, tibialis anteriorred, soleus, and plantaris muscles were assessed for injury by examining three parameters: skeletal muscle injury (via 99Tc-pyrophosphate), microvascular injury (via 125I-albumin), and tissue water content. There was no consistent correlation between fiber type and sensitivity to postischemic injury. Both the soleus (slow twitch) and plantaris (fast twitch) muscles sustained similar significant injury: muscle damage was 133 and 167% greater than controls, and microvascular damage 96 and 91% greater than controls, respectively. However, other fast twitch muscles (tibialis anteriorwhite and tibialis anteriorred) exhibited no significant injury. Both injured muscles were in the posterior compartment while the uninjured muscles were in the anterior compartment. Regional flow as measured by microspheres revealed no correlation between postischemic flow and muscle injury, microvascular injury, or compartmental location. Skeletal muscle fiber type was not consistently predictive of its sensitivity to ischemia/reperfusion-induced injury. Compartmental location may have played an as yet unknown role in modulating vulnerability to postischemic damage.

Topics: Animals; Body Water; Capillary Permeability; Ischemia; Male; Microcirculation; Microspheres; Muscles; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Reperfusion Injury; Serum Albumin, Radio-Iodinated; Technetium Tc 99m Pyrophosphate

Reperfusion-induced vascular endothelial cell dysfunction may exacerbate skeletal muscle damage after an ischemic insult. Although concurrent endothelial and skeletal muscle injury has been documented after ischemia and reperfusion, their temporal relationship has not been well characterized. An isolated rat hindlimb model was used to measure the effect of progressive ischemia and reperfusion on both endothelial cell function and skeletal muscle damage. Endothelial cell dysfunction as reflected by changes in permeability was measured by protein clearance techniques with use of albumin labeled with iodine 125 (125I-albumin). Skeletal muscle damage was assessed by tissue uptake of technetium 99m pyrophosphate (99mTc-pyrophosphate). The soleus muscle was used for evaluation of endothelial and skeletal muscle damage throughout the study. Significant increases in vascular permeability preceded skeletal muscle damage. The protein leak index increased after 60 minutes of ischemia and reperfusion (7.5 +/- 1.2 vs 4.1 +/- 0.9 control), whereas the muscle injury index did not change until 120 minutes of ischemia and 60 minutes of reperfusion (10.5 +/- 0.6 vs 4.5 +/- 0.5 control). Significant graded increases in both indexes were noted with longer intervals of ischemia. Electron microscopy revealed ultrastructural evidence of endothelial and skeletal muscle damage after 120 minutes of ischemia and 60 minutes of reperfusion but not after 60 minutes of ischemia and reperfusion. These studies indicate that microvascular injury precedes skeletal muscle damage after ischemia and reperfusion. This temporal relationship may have important implications in designing strategies to minimize ischemia-reperfusion injury.

Topics: Analysis of Variance; Animals; Capillary Permeability; Endothelium, Vascular; Hindlimb; In Vitro Techniques; Male; Muscles; Rats; Rats, Inbred Strains; Reperfusion Injury; Serum Albumin, Radio-Iodinated; Technetium Tc 99m Pyrophosphate; Time Factors

Limiting the rate of reperfusion blood flow has been shown to be beneficial locally in models of ischemia-reperfusion injury. We investigated the effects of this on eicosanoids (thromboxane B2, 6-keto-PGF1 alpha, and leukotriene B4), white blood cell activation, and skeletal muscle injury as quantitated by triphenyltetrazolium chloride and technetium-99m pyrophosphate after ischemia-reperfusion injury in an isolated gracilis muscle model in 16 anesthetized dogs. One gracilis muscle in each dog was subjected to 6 hours of ischemia followed by 1 hour of limited reperfusion and then by a second hour of normal reperfusion. The other muscle was subjected to 6 hours of ischemia followed by 2 hours of normal reperfusion. Six dogs each were used as normal reperfusion controls (NR) and limited reperfusion controls (LR), with 5 dogs being treated with a thromboxane synthetase inhibitor (LR/TSI) and another five with a leukotriene inhibitor (LR/LI). LR in all three groups (LR, LR/TSI, and LR/LI) showed a benefit in skeletal muscle injury as measured by triphenyltetrazolim chloride and technetium-99m pyrophosphate when compared with NR. However, there was no significant difference between the groups with LR regarding eicosanoid levels and white blood cell activation when compared with NR. These results demonstrate that LR produces benefits by mechanisms other than those dependent upon thromboxane A2, prostacyclin, or white blood cell activation.

Topics: Animals; Blood Flow Velocity; Diphosphates; Disease Models, Animal; Dogs; Eicosanoids; Leukocytes; Muscles; Reperfusion Injury; Technetium; Technetium Tc 99m Pyrophosphate; Tetrazolium Salts; Time Factors

Limiting the rate of reperfusion blood flow following prolonged ischemia in skeletal muscle has been shown beneficial. However, the persistence of this benefit with reinstitution of normal blood flow remains undefined. We investigated the role of temporary limited reperfusion on ischemia-reperfusion injury in an isolated gracilis muscle model in six anesthetized dogs. Both gracilis muscles were subjected to 6 hr of ischemia followed by 2 hr of reperfusion. Reperfusion blood flow was limited for the first hour in one gracilis muscle to its preischemic rate followed by a second hour of normal reperfusion (LR/NR). The contralateral muscle underwent 2 hr of normal reperfusion (NR/NR). Muscle injury was quantified by technetium-99m pyrophosphate (TcPyp) uptake and by histochemical staining using triphenyltetrazolium chloride (TTC) with planimetry of the infarct size. Capillary permeability was evaluated by muscle weight gain. Results are reported as the mean +/- SEM: [table: see text] These data demonstrate a sustained benefit from temporary limited reperfusion. This methodology should be considered in the surgical management of the acutely ischemic limb.

Topics: Animals; Blood Flow Velocity; Blood Pressure; Diphosphates; Dogs; Female; Histocytochemistry; Ischemia; Kinetics; Male; Muscles; Organ Size; Reperfusion Injury; Technetium; Technetium Tc 99m Pyrophosphate; Tetrazolium Salts; Time Factors

Ischemia-reperfusion damage to skeletal muscle may cause serious local as well as systemic complications, its impact predominantly related to the quantity of ischemic muscle in the lower extremity. To date, there has been no noninvasive method of estimating that quantity. The authors used single photon emission computed tomography (SPECT) to quantify the volume of muscle that takes up technetium-99 pyrophosphate above a baseline threshold. Compared with the standard technique of staining slices of the muscle with nitroblue tetrazolium they found a close correlation using SPECT (r = 0.88, p less than 0.01, n = 19) in the canine model. In humans, this clinically applicable noninvasive technique may allow the surgeon to document accurately the extent of muscle necrosis in the lower extremity, to anticipate the impact of an ischemia-reperfusion injury and evaluate methods of reducing the extent of post-ischemic skeletal muscle necrosis.

Topics: Animals; Diphosphates; Dogs; Leg; Muscles; Necrosis; Nitroblue Tetrazolium; Reperfusion Injury; Technetium; Technetium Tc 99m Pyrophosphate; Tomography, Emission-Computed