Zülfikar Saritas

Effect of Mg2SO4 usage on spinal cord ischemia-reperfusion injury: Electron microscopic and functional evaluation

Objectives: To evaluate the effects of intravenous magnesium sulfate (Mg2SO4) administration on ischemia-reperfusion injury of the spinal cord. Material and Methods: Sixteen rabbits were randomly assigned to the control (group I, 8 rabbits) and the study group (group II, 8 rabbits). The abdominal aorta was clamped for a period of 30 min followed by a reperfusion period of 60 min. The animals in group II received 0.25 ml/kg/h Mg2SO4 intravenous infusion (15% Mg2SO4) throughout this procedure. The animals were then observed for 24 h after which their neurological states were evaluated and tissue samples obtained from the spinal cord were examined with electron microscopy. Results: Aortic pressure distal to the cross-clamp during the occlusion period was 9 ± 3 mm Hg in group I and 19 ± 6 mm Hg in group II. All animals in group I were paraplegic at the end of the study. In group II the neurological outcome of 1 animal was poor while the other 7 animals were neurologically in a good condition. Electron microscopic examinations of the spinal cord tissues of group I revealed severe injury but the ultrastructure was well preserved in group II. Conclusions: Intravenous Mg2SO4 administration may have protective effects on the ischemia-reperfusion injury of the spinal cord. We propose that Mg2SO4 may be an additional protective pharmacological agent in thoracal and thoracoabdominal aortic surgery.

Experimental Inhibition of Protamine Cardiotoxicity by Prostacyclin

Twelve animals (26 ± 5 kg) were subjected to the study. In this experimental study, the authors used prostacyclin to inhibit the toxic metabolite release during protamine admin istration. Animals were divided into two equal groups. Six animals received prostacyclin (the prostacyclin group), and the other six animals did not receive any additional treatment (the control group). All cardiac output and biochemical measurements were evaluated at baseline; before cardiopulmonary bypass; and at 5, 30, and 60 minutes after protamine administration. The measured cardiac index showed that the hearts treated with prostacyclin had satis factory preservation of left ventricular function. Metabolic and biochemical data showed that the tumor necrosis factor level was raised significantly in the control group (20.75 ± 2.2 in the control group and 13.75 ± 2.5 pg/mL in the prostacyclin group). Also, E and P selectin levels were elevated in the control group, but this change was less marked in the prostacyclin group. In addition, the intracellular adhesion molecule-1 (ICAM-1) level was significantly higher in the control group than in the prostacyclin group (9.26 ±2.13 in the control group and 5.13 ± 1.66 ng/mL in the prostacyclin group). The authors observed that prostacyclin inhibited the toxic mediator release during heparin reversal with protamine. This inhibition is one way of protecting the myocardium reserves from protamine cardiotoxicity.

Iloprost added to the cardioplegic solutions improves myocardial performance.

A total of 12 mongrel dogs were divided into two equal groups. Six animals received IIoprost and the other 6 animals did not receive any additional treatment. In the Iloprost group, Iloprost was added to the cardioplegic solution (25 ng). Also, Iloprost was used (10 ng/kg/min.) 5 min. before and after cross-clamping. All cardiac output and biochemical measurements were evaluated before cross-clamp and 15 min., 1 h, and 4 h after cross-clamp. The measured dp/dt shows that the hearts treated with Iloprost preserved left ventricular function. Comparison of contractility indices between the groups revealed that contractile recovery was 59% in the control group and 71% in the Iloprost group (p < 0.05). Tumor necrosis factor (TNF) alpha level was significantly elevated in the control group (p < 0.001). Its level was 22.2 +/- 2.2 pg/mL in the control group and 13.8 +/- 1.0 pg/mL in the Iloprost group. E- and P-selectin levels were elevated in the control group (p < 0.001). ICAM-1 level was also elevated in the control group. ICAM-1 level was 17.7 +/- 1.8 ng/mL in the control group and 8.5 +/- 1.8 ng/mL in the Iloprost group. The Iloprost that was added to the cardioplegic solution and low dose administration during the pre- and post-ischemic period inhibits the toxic mediator release from endothelium-leukocyte interaction and reduces the severity of ischemia-reperfusion injury.

Implantation of Novel Small-Diameter Polyurethane Vascular Prostheses Interposed in Canine Femoral and Carotid Arteries

Objectives: The performance of small-diameter (3–5-mm) vascular grafts still poses a challenge in the field of vascular surgery. We present here our preliminary experience with implanting unique small-sized polycarbonate urethane vascular grafts in 7 dogs. Material and Methods: Each animal was implanted with 4 interposition grafts, 2 femoral and 2 carotid. No anti-thrombotic medication was administered. Doppler sonography was performed at 3-month intervals to examine for patency and flow characteristics. Animals were sacrificed electively at 3, 6 and 12 months. Results: At 3 months, all grafts were patent. After 6 months, 3 grafts occluded and at 1 year a further 6 grafts occluded. Hence 9 of 28 grafts occluded (67.9% patency). During the study, no correlation could be established between flow velocity or resistance index and occlusion. Histopathology showed intimal hyperplasia to be the cause of occlusion. Conclusions: Compared to literature data on small-diameter grafts in the same position, ADIAM’s Biomechanical grafts performed clearly better. Compliance data suggest a correlation between elastic compliance and patency.

Inhibition of Myointimal Proliferation by Octreotide in Canine Vein Interposition Grafts

Purpose: The aim of this study was to evaluate the efficacy of octreotide in modulating the progression of intimal hyperplasia in autogenous vein bypass grafts in a canine model. The effect of the drug on the progression of intimal hyperplasia was measured with the Gilman parameter, a measure used extensively as a wound-healing descriptor. Methods: 12 mongrel dogs were randomly and equally divided into two groups. The first group (octreotide group) was administered octreotide 20 µg/kg/day. The control group (group II) received saline solution by subcutaneous injection. Each dog had 8- to 10-cm segments of autogenous jugular vein bypassed to the femoral arteries. Quantitative data on luminel narrowing over time from intimal hyperplasia were compared from calculated Gilman parameters after image analysis of retrieved, histologically processed graft sections. Each vein graft was analyzed by computerized morphometric analysis. Results: The mean Gilman parameter for distal graft segments was 0.47 ± 0.17 mm in the control group and 0.25 ± 0.07 mm in the octreotide group 6 weeks after operation (p < 0.05). Distal graft segments between the control and octreotide groups were statistically significant. In proximal, medial and distal graft segments, the mean Gilman parameters were 0.51 ± 0.16 mm in the control group and 0.37 ± 0.18 mm in the octreotide group, the difference being statistically significant (p < 0.01). Conclusion: Octreotide significantly inhibits myointimal thickening, and these data support the efficacy of octreotide in reducing intimal hyperplasia in arterialized vein grafts during the short postoperative period. Further investigations are required to as certain whether this beneficial effect of octretide persists in the long term.

Effects of Carnitine on Preconditioned Latissimus Dorsi Muscle at Different Burst Frequencies

Abstract Exercise and electrical stimulation may result in a decrease in carnitine levels associated with preconditioned latissimus dorsi muscles. Therefore, the effects of exogenous carnitine were studied in a model of latissimus dorsi muscle contraction. Twelve dogs were studied. Under anesthesia, the latissimus dorsi was placed around an implantable mock circulation system. The muscle was made fatigue‐resistant with the aid of chronic low‐frequency electrical stimulation. Six animals received carnitine 0.15 mmol/kg; the other six served as control. The muscles were stimulated with 20, 43, and 85 Hz pulse training. During the 90‐minute stimulation period, the pressure that developed in the mock circulation was measured at 15 minute intervals. The changes in ATP and lactate levels were measured every 30 minutes. Stimulations at 20 and 43 Hz did not result in any change in pressure or metabolic data over the course of 90 minutes of stimulation. When the 85 Hz burst was applied, ATP levels decreased, while lactate levels increased, with an associated drop in pressure in the control group. ATP and lactate levels were, respectively, 13.8 ± 1.4 μmol/g and 15.0 ± 4.0 μmol/g in the carnitine group and 10.3 ± 1.1 μmol/g and 23.0 ± 3.0 μmol/g in the control group at the end of 90 minutes (p < 0.05). The pressure at the same time interval was 74 ± 4 mmHg in the control group, and 85 ± 3 mmHg in the carnitine group (p < 0.05). In this study, we demonstrated that carnitine administration enhances muscle performance in terms of metabolic and pressure changes during high‐frequency electrical stimulation at 85 Hz.

Investigation of effects of levobupivacaine injection to rabbit knee joint on histopathologic changes of joint cartilage tissue and changes of serum biochemical parameters.

The aim of this study is to evaluate the effects of intra‐articular levobupivacaine on rabbit knee articular cartilage and certain biochemical parameters in the blood. A total of 24 New Zealand rabbits were included to study. Blood sampling was carried out in all animals on the first day, then the subjects were randomly allocated either to the control group (Group C, n = 9) or to the levobupivacaine group (Group L, n = 15). Group C underwent each two intra‐articular injections of saline, 0.25 mL into the right knee and 0.50 mL into the left one. Group L was injected 0.25 mL (1.25 mg) of levobupivacaine into the right knee and 0.50 mL (2.5 mg) into the left one. The groups were divided randomly into three. Tissue and blood samples for histologic and biochemical examination were collected from Groups C1 and L1 on the first, C2 and L2 on the second, and C3 and L3 on the tenth day of the study. Interleukin‐1β (IL‐1 β), interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), and C‐reactive protein (CRP) levels were analyzed. No statistically significant differences could be detected when comparing either left or right joints within the same groups and with Group C and L (P > 0.05). Significant elevations of biochemical parameters were found in Group C. It is concluded that levobupivacaine does not lead to significant histologic changes in rabbit articular cartilage. Significant elevations of biochemical parameters being generally found in the C Group, it is thought that such elevations are not linked to levobupivacaine. Intra‐articular levobupivacaine may be a safe alternative for use in post‐operative analgesia.

Contractile response of different segments of the latissimus dorsi muscle to chronic stimulation

OBJECTIVE This study was planned to investigate if there is any difference in terms of the muscle force between the distal and proximal segments of the latissimus dorsi muscle. SUBJECTS AND METHODS An inplantable mock circulation system was placed around the latissimus dorsi muscle. The wrapping procedure around the implantable mock circulation was performed by using two different latissimus dorsi muscle segments. In group 1, the very proximal and in group 2, very distal part of the latissimus dorsi were wrapped. The main difference is the blood supply to the distal part of the latissimus dorsi that was interrupted during dissection. During the stimulation period which lasted 120 minutes, the pressure developed in this system and adenosine triphosphate (ATP) levels were measured. RESULTS The stimulation at 20 Hz did not result in any change in pressure and metabolic data. When it was switched to 43 and 85 Hz, ATP levels decreased with a resultant drop in pressure in group 2. However ATP levels were 15.9 +/- 2.2 micromol/gr and 14.8 +/- 2.5 micromol/gr in group 1, 12.0 +/- 1.4 micromol/gr and 6.1 +/- 1.2 micromol/gr in group 2 at 43 and 85 Hz respectively (p < 0.05) at the end of the 90 minutes. The pressures at the same time interval were 89 +/- 11 and 102 +/- 7 mmHg in group 1, 61 +/- 7 and 65 +/- 8 mmHg in group 2 (p < 0.05). CONCLUSION In this study, we demonstrated that changes in the distal segment of the latissimus dorsi muscle affects its performance in terms of metabolic and pressure changes during high frequency electrical stimulation at 43 and 85 Hz.

Comparison of metabolic responses to deep hypothermic total circulatory arrest and retrograde cerebral perfusion in an experimental model.

An experimental study was designed to search the effectiveness of retrograde cerebral perfusion which is presently used as cerebral protection method for the surgery of arcus aorta. Twelve dogs were subjected to the study. Six of them were remained in total circulatory arrest at 20 degrees C for 60 min. Retrograde cerebral perfusion was done again at 20 degrees C for 1 h for the other six dogs. Tumor necrosis factor (TNF), P-selectin, Intracellular Adhesion Molecule (ICAM), Creatine Phosphokinase (CPK-BB) and tissue Adenosine triphosphate (ATP) levels were measured, before the cardiopulmonary bypass at 37 degrees C and during perfusion period at 5, 60 min and 4 h. Tissue ATP level for retrograde cerebral perfusion group was 3.99+/-0.7 mcmol/g tissue and 2.86+/-0.1 mcmol/g tissue for total circulatory arrest group at fourth hour (p<0.05). TNF level was significantly higher in total circulatory arrest group than retrograde cerebral perfusion group (p<0.05). The samples taken at fourth hour of reperfusion showed the TNF level was, 162.55+/-13.1 pcg/ml for total circulatory arrest group and this value was 12.5+/-3.4 pcg/ml for retrograde cerebral perfusion group.ICAM (Intracellular Adhesion Molecule) level was higher in total circulatory arrest group (18.75+/-3.6 ng/ml) when compared to retrograde cerebral perfusion group (8.75+/-1.8 ng/ml) (p<0.05). All parameters showed that retrograde cerebral perfusion preserved the brain functions better comparing with total circulatory arrest. The time necessary for aortic surgery may be provided by the retrograde cerebral perfusion technique.

Effects of Prostacyclin on Hemodynamics after Intestinal Ischemia-Reperfusion

Ten rabbits underwent 30 minutes of superior mesenteric artery occlusion to assess the release of tumor necrosis factor, subcellular damage, and hemodynamic changes after intestinal ischemia-reperfusion injury. Five were treated with prostacyclin 5 ng/kg/min 5 minutes before the arterial occlusion. It was increased to 25 ng/kg/min during occlusion, decreased to 5 ng/kg/min for the first 5 minutes of reperfusion, and then discontinued. A control group of 5 rabbits did not receive any pharmacological agent. Specimens were obtained from the small intestine for electron microscopy after 10 minutes and after 60 minutes of reperfusion, while simultaneous blood samples were collected for measurement of tumor necrosis factor. Minimal changes were seen in tissue from the prostacyclin group but severe mitochondrial damage and vacuolation occurred in the control group. The tumor necrosis factor level was 11.97 ± 3.17 U/mL in the control group and 5.06 ± 2.19 U/mL in the prostacyclin group, one hour after the end of mesenteric occlusion (p < 0.05). Hemodynamic status, assessed by central venous and arterial pressures, was much more affected in the control group than in the prostacyclin group. Mean arterial pressure was 71 ± 5 mm Hg in the control group, and 91 ± 6 mm Hg in the prostacyclin group (p < 0.05). Central venous pressure was 5.3 ± 0.9 mm Hg in the control group and 2.3 ± 0.7 mm Hg in the prostacyclin group (p < 0.05). We conclude that intravenous prostacyclin reduced the severity of reperfusion injury occurring during the early period of reperfusion by inhibiting the release of the toxic mediator tumor necrosis factor, thus decreasing distant organ injury.