The protective effects of resveratrol and L-NAME on visceral organs following aortic clamping.

BACKGROUND: This study investigated the effect of temporary occlusion of the aorta on the development of ischemia-reperfusion (I/R) injury of the visceral organs, the optimal timing of administration of resveratrol, and its mechanism of protection via inhibiting nitric oxide (NO) release with an NO synthase inhibitor. METHODS: Rabbits were divided into seven groups according to the administration period of resveratrol and/or N(G)-nitro-L-arginine methyl ester (L-NAME): control group; group 1, resveratrol during ischemic period; group 2, resveratrol during reperfusion period; group 3, L-NAME during ischemic period; group 4, L-NAME during reperfusion period; group 5, resveratrol during ischemic period and L-NAME during reperfusion period; group 6, L-NAME during ischemic period and resveratrol during reperfusion period. The infrarenal aorta was clamped for 30 min. Blood samples were taken for the biochemical assessment, and organ specimens were taken for pathological assessment at 24hr of reperfusion. RESULTS: In groups 5 and 6, the renal I/R injury was comparatively milder (I/R injury score 1.04+/-0.29 in control group, 0.25+/-0.17 in group 5, and 0.33+/-0.13 in group 6 [p<0.05]). The I/R injury of bowel was milder in group 5 (I/R injury score 1.8+/-0.80 in control group vs. 0.0+/-0.0 in group 5 [p<0.05]). CONCLUSION: The protective effects of resveratrol on organs that have high metabolic rate like kidney and bowel was proven histopathologically. It may be beneficial to use different pharmacological medications in different periods of the I/R damage as they represent different characteristics with and without oxygen. The combination of resveratrol and L-NAME against I/R injury appears to be an effective option in the near future.

Collaborative therapy with nebivalol and L-NAME for spinal cord ischemia/reperfusion injury.

Postoperative neurologic deficit is the most devastating complication after thoracoabdominal aortic aneurysm repair. Our aim was to investigate whether nebivolol has protective effects during ischemia or reperfusion and the most effective mechanism of protection via inhibiting nitric oxide (NO) release with an NO synthase inhibitor in an experimental model of spinal cord ischemia/reperfusion injury. Spinal cord ischemia was induced by occlusion of the infrarenal aorta for 30 min. Thirty-one rabbits were divided into five groups according to the administration period of nebivolol and/or N(G)-nitro-L-arginine methyl ester (L-NAME): control group; group NI, nebivolol during ischemic period; group NR, nebivolol during reperfusion period; group NILR, nebivolol during ischemic period and L-NAME during reperfusion period; and group LINR, L-NAME during ischemic period and nebivolol during reperfusion period. Blood samples were taken at both ischemia and reperfusion periods to obtain nitrite/nitrate levels. After neurologic evaluation at 24 hr of reperfusion, malondialdehyde (MDA) levels were measured. Neurologic impairment was significantly lower in group LINR (Tarlov score 3.4 +/- 0.6, p < 0.05). MDA levels were lower in nebivolol-treated animals, but the lowest value was achieved in the NR group, 35.6 +/- 2.7 nmol/g (p < 0.001). Nitrite levels were decreased significantly in all nebivolol-treated animals in the reperfusion period, but the lowest value was measured in the LINR group (455 +/- 137 vs. 1,760 +/- 522 nmol/mL, p < 0.001). Prophylactic use of nebivolol reduced neurologic injury, and combining with L-NAME provided the best clinical improvement by attenuating the inflammatory mileu in this experimental model. Combination of nebivolol and L-NAME appears to be an effective option for spinal cord protection against ischemia/reperfusion injury.

Comparison of the Ovary and Kidney as Sites for Islet Transplantation in Diabetic Rats.

BACKGROUND: Currently, the most commonly used site for clinical islet transplantation is the liver although it is far from being an ideal site. Low oxygen tension and the induction of an inflammatory response impair islet implantation and lead to significant early loss of islet. The present study aimed to investigate and compare the efficacy of islet transplantation to the ovary and kidney subcapsule in diabetic rats. METHODS: The study was performed with 3 groups of rats (control, ovary, and kidney subcapsule) including 6 Sprague female rats each. Diabetes model was created with the use of streptozotocin, and blood glucose levels of the rats were measured after 72 hours. Thirty days after the transplantation, blood samples were obtained from the rats, and then pancreas, kidney, and ovary specimens were fixed in 10% formaldehyde and the experiment completed. After staining with hematoxylin and eosin, the tissue samples were morphologically evaluated by a specialist histopathologist. RESULTS: Changes in mean blood glucose and C-peptide levels were statistically significant in the ovary and kidney subcapsule groups. Histologic examination revealed that granulosus insulin-bearing cells were detected in the islet grafts of both ovary and kidney subcapsule groups. The renal subcapsule group had inflammation signs on histologic examination. The islet cells of both ovary and renal subcapsule groups had no vacuolization. CONCLUSIONS: We showed that the ovary might be a new site for islet transplantation. Further research should be done on whether the initial results of this study can be reproduced in larger numbers of animal models and eventually in humans.

Biomarkers of free radical injury during spinal cord ischemia.

Plasma and urinary levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) were analysed at baseline and during the ischemia-reperfusion period in experimental spinal cord ischemia. A significant and immediate increase of 8-iso-PGF(2alpha) in plasma at the start and up to 60 min, and in the urine at 90-150 min following ischemia indicate an association of oxidative injury. The inflammatory response indicator 15-keto-dihydro-PGF(2alpha) in plasma increased significantly at the start and up to 60 min after ischemia. No such increase was seen in animals with no spinal cord ischemia. Thus, free radical mediated and cyclooxygenase catalysed products of arachidonic acid are increased during spinal cord ischemia as a consequence of oxidative injury and inflammation.

Cardiopulmonary bypass as a cause of free radical-induced oxidative stress and enhanced blood-borne isoprostanes in humans.

Free radicals are believed to be involved in postsurgery-related complications. We studied whether cardiopulmonary bypass (CPB) operation has any immediate impact on the initiation of oxidative stress and inflammatory response by measuring isoprostanes and prostaglandin F2alpha during and 24 h following CPB. The levels of 8-iso-PGF2alpha (a major F2-isoprostane and biomarker of oxidative stress) and 15-keto-dihydro-PGF2alpha (a major metabolite of PGF2alpha and biomarker of inflammatory response) were measured in frequently collected plasma samples before, during, and up to 24 h postsurgery in 21 patients. 8-Iso-PGF2alpha levels significantly increased within 3 min (p <.0001) and continued until 50 min (p <.0001) during CPB. On the contrary, no significant increase of inflammatory response indicator, 15-keto-dihydro-PGF2alpha was found during and up to 24 h postoperatively. These findings establish an increased free radical-induced oxidative stress activity rather than inflammatory response after CPB.

Aspects of the spinal cord circulation as assessed by intrathecal oxygen tension monitoring during various arterial interruptions in the pig.

OBJECTIVE: We sought to study the effect of various modes of interruption of the spinal cord blood supply on intrathecal oxygenation. METHODS: In 24 pigs intrathecal PO (2), PCO (2), and pH were continuously monitored with a multiparameter catheter (Paratrend 7, Biomedical Sensors; Diametrics Medical, Inc, St Paul, Minn) during and after aortic crossclamping or selective interruption of segmental arteries and proximal collateral circulation. RESULTS: Proximal aortic clamping (n = 6) produced complete ischemia, whereas a second clamp close to the celiac trunk (n = 4) partly protected against spinal cord ischemia. This is explained by prevention of the steal phenomenon in the excluded part of the aorta. Adding clamps to the subclavian arteries (n = 6) created complete spinal ischemia as the collateral circulation was interrupted. In another group (n = 4) all segmental arteries below T5 were occluded with no reaction in the intrathecal variables. Additional selective clamping of supreme intercostal arteries (n = 4) showed the relative importance of the subclavian and vertebral collateral pathways. CONCLUSIONS: Continuous intrathecal PO (2) was monitored during various modes of interruption of the spinal cord blood supply. This provided insight into the ischemia mechanisms and relative importance of the segmental contribution and proximal collateral pathways of the spinal cord circulation in pigs. A short literature review is given, and aspects of comparative anatomy are discussed.

Monitoring of intrathecal oxygen tension during experimental aortic occlusion predicts ultrastructural changes in the spinal cord.

OBJECTIVE: To study the correlation between intrathecal PO2 and ultrastructural changes in the spinal cord during thoracic aortic occlusion in pigs. MATERIAL AND METHODS: In 18 pigs, online intrathecal oxygenation was monitored by a multiparameter Paratrend catheter (Biomedical Sensors, High Wycombe, United Kingdom) during 60 minutes' clamping of the proximal and distal descending thoracic aorta. The animals were randomly divided into 2 groups (A and B) depending on the level of distal aortic clamping. Distal aortic perfusion was restored through an aorto-iliac shunt, which also maintained low thoracic segmental perfusion of the spinal cord in group B. Perfusion-fixation technique was used before harvesting the spinal cord specimens, which later were evaluated with light and electron microscopy by an independent observer. Intrathecal parameters were interpreted as normal if PO2 was more than 0.8 kPa and PCO2 was less than 12 kPa, as intermediate ischemia if PO2 was 0.8 or less or PCO (2) was more than 12 kPa, and as absolute ischemia if PO2 was 0.8 or less and PCO2 was more than 12 kPa. RESULTS: Among 6 animals with ultrastructural changes of absolute spinal cord ischemia-reperfusion injury, 5 also had absolute ischemia according to variables derived by the Paratrend catheter. The 2 methods were in agreement in 3 of 5 animals with intermediate ischemia-reperfusion changes and in 5 of 6 animals with normal findings. The accuracy of cerebrospinal fluid PO2 and PCO2 to predict electron microscopy-verified intermediate or absolute ischemia-reperfusion injury was 94%. CONCLUSIONS: Monitoring of intrathecal PO2 after clamping of the descending aorta correlated with ultrastructural changes in the spinal cord in this pig model.

Oxidative stress and changes in alpha- and gamma-tocopherol levels during coronary artery bypass grafting.

We studied whether cardiopulmonary bypass (CPB) has any immediate impact on the initiation of antioxidative defenses in the body by measuring F(2)-isoprostanes and alpha- and gamma-tocopherol, respectively. 8-iso-PGF(2alpha) levels increased significantly within 3 minutes and until the end of CPB. alpha-Tocopherol levels increased gradually at 20 min during CPB and continued until 6 hours after CPB. gamma-Tocopherol levels followed a similar fashion at the end of CPB. 8-iso-PGF(2alpha) and tocopherol levels kept at basal level 12 and 24 hours post CPB. These findings suggest that an increased free radical-induced oxidative stress together with a gradual appearance of antioxidative defense system during and after CPB.

Preservation of myocardial metabolism in acute coronary artery occlusions with retrograde coronary sinus perfusion and iloprost.

A total of 12 healthy mongrel dogs were subjected to the study. The left anterior descending artery was occluded. The occlusion was done for 15 min. At the end of this period, without removing the occlusion, the heart was retroperfused for 3 h. Then, occlusion was removed and reperfusion was supplied. Animals were divided into two equal groups. Six animals received iloprost and the other six control did not receive any additional treatment. In the iloprost group, the drug was administered into the coronary sinus. After 15 min following occlusion, iloprost was infused at a rate of 50 microg/min continuously. Cardiac output (CO), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), heart rate (HR), pulmonary capillary wedge pressure (PCWP), right atrium pressure (RAP), myocardial oxygen extraction (MOE) and myocardial lactate extraction (MLE) parameters were examined in the two groups, before and during retroperfusion and during the reperfusion (1-4 h). Iloprost retroperfusion (50 microg/min) was started at the fifteenth minute of occlusion and continued till the end of the observation period (3 h). The measured hemodynamic data showed that the hearts treated with iloprost had satisfactory preservation of cardiac function. At the end of the reperfusion period cardiac output was 1.5 +/- 0.06 L/min in the control and 1.7 +/- 0.04 L/min in the iloprost group (P < 0.05). At the end of the reperfusion period, tumor necrosis factor level was raised significantly in the control group (P < 0.05). Myocardial lactate release was also high in the control group (P < 0.05). CPK-MB release was low in the iloprost group (P < 0.05). We conclude that retrogradely administered iloprost reduced the risk of myocardial injury and it is probable that this drug effectively distributes to the area of myocardium at risk.

Perinatal mitral valve interventions: a report of 10 cases.

BACKGROUND: Rheumatic mitral valve stenosis is still an endemic disease in some parts of the world and may complicate pregnancy and perinatal period. During the 10-year period between January 1988 and December 1997, 10 pregnant women with mitral stenosis were operated on. METHODS: Combined cesarean delivery and closed mitral valvulotomy (CMV) were performed on 6 patients, combined cesarean delivery and Mitral Valve Replacement (MVR) were performed on 1 patient, and 3 patients had CMV during their third trimester. RESULTS: There was 1 stillbirth. All other patients and delivered babies were healthy. MVR was necessary for mitral restenosis in one patient 5 years after her CMV. Three of the remaining patients had some degree of restenosis but did not require reoperation. CONCLUSION: CMV when indicated during pregnancy can be performed with low risk. For symptomatic patients responding to medical therapy, a combined approach of cesarean section and CMV will prevent possible complications that may arise on perinatal period due to hemodynamic fluctuation.

A clinical dilemma: cardiac and pericardiac echinococcosis.

BACKGROUND: Cardiac and pericardial echinococcosis as a life-threatening disease may present with a clear picture most of the time, however it may also become a clinical puzzle. METHODS: In the period between 1977 and 1998, 14 patients were operated on with the diagnosis of cardiac and pericardial echinococcosis. Nine patients were operated on with standard cardiopulmonary bypass (CPB) techniques, and the remaining 5 patients were operated on without CPB. Transesophageal echocardiography (TEE) or intraoperative surface echocardiography were used to plan and perform the operation for the late cases. RESULTS: One patient died during the postoperative period due to the rupture of interventricular septum. All other patients survived the perioperative period, received mebendazole treatment, and exhibited no recurrence during the follow-up. CONCLUSIONS: The definitive treatment is the surgical extraction of the cyst. Because the clinical picture may vary according to the number, size, and location of cysts, as well as complications, cardiac echinococcosis should be remembered and included in the differential diagnosis to achieve the treatment. Intraoperative surface echocardiography is of paramount value for diagnosis and planning the management of a successful surgery.

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.

Reduction of the infarcted area with the use of simplified coronary sinus retroperfusion during experimental coronary artery occlusion.

This study examined if the use of simplified coronary sinus retroperfusion would lead to any reduction in the infarcted area associated with improved right and left ventricular function. Twelve mongrel dogs were entered in this study. Following anesthesia, a fast response thermistor was placed on the pulmonary artery via the jugular vein and aorta via the left ventricular apex. The left anterior descending artery (LAD) was separated from the vein. A retrograde cardioplegia catheter was inserted into the coronary sinus. Following these procedures, LAD was occluded for a period of 3.5 h. After 30 min ischemia, the aorta-coronary sinus connection was established. The animals were divided into two equal groups. One group was not treated and was considered the control group (six animals). In the remaining group (six animals), retroperfusion was used and was considered the retroperfusion group. At the end of the study, the left ventricular ejection fraction was 65+/-15% in the retroperfusion group and 48+/-5% in the control group (P<0.05). The left ventricular stroke work index was 0.44+/-0.04 (g m/kg) in the retroperfusion group and 0.31+/-0.05 (g m/kg) in the control group (P<0.05). Cardiac output was 1650+/-75 ml/min in the retroperfusion group and 1250+/-125 ml/min in the control group. The ratio of the infarct size to the area at risk was 49+/-5% in the control group and 7+/-3% in the retroperfusion group. In light of these studies, we conclude that simplified coronary sinus retroperfusion appears to be an effective method that must be taken into consideration.

ATP-MgCl2 treatment after experimental acute myocardial ischemia and reperfusion.

BACKGROUND: The effect of ATP-MgCl2 on myocardial metabolism and hemodynamics was investigated in this study. METHODS: Twelve dogs were entered in this research. Six dogs received ATP-MgCl2 and the remaining dogs were considered as controls. The amount of ATP and MgCl2 concentration of this solution is 100 mumol/ml each. The volume administered to the animals during the aortic occlusion is 0.25 ml/kg/hour; in the solution are 100 mumol/ml dose each. The volume administered to the animals during reperfusion is 0.25 ml/kg/hour. The left anterior descending artery was occluded for a period of one hour and the drug was administered during reperfusion. RESULTS: Three hours after reperfusion, cardiac output was 1524 +/- 26 ml/min in the control group and 1638 +/- 47 ml/min in the ATP-MgCl2 group (p < 0.05), pulmonary capillary wedge pressure was 14 +/- 3 in the control group and 8 +/- 2 in the ATP-MgCl2 group. At the same time interval tissue ATP and lactate level was 7 +/- 3, 1.3 +/- 0.4 in the control group and 14 +/- 2, 0.0 +/- 0.2 in the ATP-MgCl2 group respectively (p < 0.05). CONCLUSIONS: In this study we demonstrated that ATP-MgCl2 usage after one hour of arterial occlusion protects the heart from the adverse effects of ischemia/reperfusion.

Effects of ATP-MgCl2 administration in hypovolemic dogs.

BACKGROUND: The aim of the study was to evaluate the efficacy of ATP-MgCl2 on myocardial insufficiency associated with hypovolemic shock in dogs. We designed the study as a controlled randomized study. METHODS: Six mixed-breed dogs weighing 22 +/- 3 kg were included in the control group and 20 +/- 3 kg in the ATP-MgCl2 group. After the animals were anesthetized 40 ml/kg of blood was withdrawn in 15 minutes. Animals were observed for 45 minutes after removal of blood. Six animals received 45 ml/kg of lactated Ringer's solution and the other animals were treated with 45 ml/kg of lactated Ringer's solution and ATP-MgCl2. All measurements were made before removal of blood, 45 min after exsanguination and at 1 hour intervals for 3 hours. The following parameters were measured; systemic and pulmonary arterial pressures, pulmonary capillary wedge pressure, central venous pressure, cardiac output, rectal temperature, arterial pH, PCO2 and PO2 and mixed venous hemoglobin oxygen saturation. In addition blood samples were collected for the analysis of lactate and tumor necrosis factor (TNF) concentrations. RESULTS: After hemorrhage, cardiac index (CI) decreased significantly from 122 +/- 9 to 52 +/- 9 ml/kg/min in the control group (p < 0.0001) and from 124 +/- 11 ml/kg/min to 50 +/- 6 ml/kg/min in the ATP-MgCl2 group, respectively (p < 0.0001). After volume replacement, Cl was 93 +/- 6 ml/kg/min in the control group and 111 +/- 4 ml/kg/min in the ATP-MgCl2 group 3 hours after the onset of reinfusion, respectively (p < 0.05). TNF was 36 +/- 5 pg/ml in the control group and 21 +/- 3 pg/ml in the ATP-MgCl2 group (p < 0.05). Three hours after the onset of hemorrhagic shock, oxygen consumption and delivery were 126 +/- 14 and 206 +/- 19 ml/min in the control group and 198 +/- 16 and 305 +/- 27 ml/min in the ATP-MgCl2 group, respectively. At the same time point the oxygen extraction ratio was 0.49 +/- 0.04 in the control group and 0.61 +/- 0.03 in the ATP-MgCl2 group (p < 0.01). CONCLUSIONS: Hemorrhagic shock causes TNF release which may cause multiple organ failure. Organ dysfunction still persists even after the appropriate treatment. ATP-MgCl2 attenuates the release of TNF which may improve the adverse effects of hemorrhagic shock.

Preservation of myocardial functions by pentoxyphylline cardioplegia during and after cardiopulmonary bypass.

BACKGROUND: The aim of the presented study was to evaluate the preservation effect of the pentoxyphylline-blood cardioplegia on myocardial functions during and after the cardiopulmonary bypass in an experimental dog model. METHODS: Central hemodynamics and metabolic variables such as creatine phosphokinase, myocardial oxygen extraction and myocardial lactate extraction were obtained during and following 4 hours after the cardiopulmonary bypass after the baseline scores were recorded. Twelve mongrel dogs were divided into two equal groups. The first group of animals served as controls. The second group of animals was treated with pentoxyphylline cardioplegia that was added to each blood cardioplegia as 15 mg/100 ml. RESULTS: After bypass, the hemodynamic parameters were better in the pentoxyphylline group. Cardiac index fell in all animals, but it was significantly less in the control group. Pulmonary capillary wedge pressure was lower in the pentoxyphylline group as an index of better preservation of ventricular filling pressure. CPK-MB was significantly higher in the control group both at 2 and 4 hours after the bypass. It was 79 +/- 13 iu/L in the control group and 41 +/- 9 iu/L in the pentoxyphylline group 4 hours after cardiopulmonary bypass. MLE was also higher both on bypass and following bypass in the control group. CONCLUSIONS: In conclusion, pentoxyphylline usage may reduce the risks of ischemic-reperfusion injury during and following cardiopulmonary bypass and aortic cross-clamping. It can be an administered drug during cardioplegia.

Protein C, S and antithrombin III levels in patients with acute mechanical valve thrombosis.

BACKGROUND: Mechanical prosthetic heart valve thrombosis is a serious complication with an incidence of 1-6%. The reduction in active vitamin-K dependent protein C and S levels caused by warfarin treatment also results in a prothrombotic state. This study was conducted to investigate the connection between protein C (PC), protein S (PS), antithrombin III (ATIII) deficiency and prosthetic mechanical valve thrombosis. METHODS: Twenty-nine of the 283 patients who underwent valve replacement with St. Jude medical prosthesis had mechanical valve thrombosis (group 2). The rest were considered as group 1. Twelve of the 29 patients (41.4%) had isolated aortic valve replacement, 12 had isolated mitral valve replacement (41.4%) and 5 patients had double valve replacement (17.2%). Most of the patients had rheumatic valve disease at their 1st operation. The mean time of occurrence for mechanical valve occlusion was 4.1+/-1.0 years following surgery. RESULTS: The values of PC, PS and ATIII were obtained when the mechanical valves stuck or at routine follow-up. PC, PS and ATIII levels were significantly lower in the mechanical valve thrombosis group. PC levels were 75.4+/-37.6% and 49.9+/-32.2% in group 1 and 2, respectively (p=0.001). PC, PS and ATIII values were mostly lower in the 2nd group but this difference only became significant after at least 2 years of warfarin usage. CONCLUSIONS: Natural anticoagulant levels can be low during the use of warfarin. In which case the dose can be increased in order to hold the international normalized ratio (INR) at 3-3.5. However, more frequent follow-up is required and patients should be investigated for hypercoagulation states or deficiency in anticoagulant proteins. Patients referred to hospital with any mechanical valve thrombosis or recurrent thromboembolism should be evaluated for hypercoagulant proteins.

Beneficial effects of iloprost during experimentally induced hemorrhagic shock.

BACKGROUND: The aim of the study was to evaluate the efficacy of iloprost on myocardial insufficiency associated with hypovolemic shock in dogs. We designed the study as a controlled randomized study. METHODS: Sixteen mixed-breed dogs were included into the study and divided into two equal groups as the control and iloprost groups. Mean arterial pressure was reduced to 45 mmHg by withdrawing the arterial blood into citrated bags. The control group did not receive any drug but the other group received iloprost at a rate of 20 ng/kg/min by an infusion pump. Iloprost infusion was started 30 min after the blood pressure was reduced to 45 mmHg. All measurements were made before removal of blood, 45 min after exsanguination and at 1 hour intervals for 3 hours. Left ventricular stroke work index was measured 72 hours after the study. The hemodynamic and biochemical parameters and blood gas analysis were obtained. RESULTS: After hemorrhage, cardiac index (CI) decreased significantly from 132 +/- 14 to 51 +/- 8 ml/kg/min in the control group and from 128 +/- 11 ml/kg/min to 47 +/- 13 ml/kg/min in the iloprost group, respectively but at the end of the third hour it was 81 +/- 8 ml/kg/min in the control group and 105 +/- 6 ml/kg/min in the iloprost group (p < 0.05). Tumor necrosis factor-alpha (TNF alpha) was 41 +/- 8 pg/ml in the control group and 18 +/- 6 in the iloprost group 3 hours after bleeding (p < 0.05). Tumor necrosis factor-alpha concentration was significantly higher in the control group than in the iloprost group. There was no significant difference in pH between the groups but actual bicarbonate concentrations were different between the groups (p < 0.05). At the end of the third hour total body oxygen consumption was 105 +/- 11 ml/min in the control group and 132 +/- 12 ml/min in the iloprost group (p < 0.05). Oxygen delivery 3 hours after hemorrhage was 201 +/- 19 ml/min in the control group and 252 +/- 24 ml/min in the iloprost group (p > 0.05). Left ventricular stroke work index was higher in the iloprost group (p < 0.05). CONCLUSIONS: Hemorrhagic shock causes tumor necrosis factor-alpha release which may lead to multiple organ failure. Organ dysfunction still persists even after the appropriate treatment. Iloprost attenuates the release of tumor necrosis factor-alpha which may improve the adverse effects of hemorrhagic shock.

Mg++SO4 treatment improves the hemodynamics following the acute myocardial ischemia and reperfusion.

BACKGROUND: The effect of Mg++SO4 on myocardial hemodynamics was investigated in this study. METHODS: Twelve dogs were entered in this research. Six dogs received Mg++SO4 and the remaining dogs were considered as controls. The amount of Mg++SO4 that was administered to the animals was 0.15 mmol/kg/hr each. The left anterior descending artery was occluded for a period of 1 hour and the drug was administered during reperfusion. RESULTS: Two hours after reperfusion, cardiac output was 1275+/-50 ml/min in the control group and 1475+/-25 ml/min in the Mg++SO4 group (p<0.05), pulmonary capillary wedge pressure was 18+/-3 mmHg in the control group and 12+/-2 mmHg in the Mg++SO4 group. CONCLUSIONS: In this study it was shown that Mg++SO4 usage after 1 hour arterial occlusion and 2 hours reperfusion protects the heart from the adverse effects of ischemia/reperfusion and had a better central hemodynamics.

Mitral valve replacement with St. Jude Medical prosthesis and low-dose anticoagulation in patients aged over 50 years.

BACKGROUND AND AIMS OF THE STUDY: These studies were designed to assess the effect of low-dose anticoagulation in elderly patients after mitral valve replacement. METHODS: Between 1986 and 1995, 250 patients aged > or = 50 years underwent isolated mitral valve replacement at the Cardiovascular Surgery Clinic of Turkiye Yuksek Ihtisas Hospital. The overall hospital mortality rate was 8%. Postoperatively, all patients received 2.5 mg/day warfarin, and 225 mg/day dypridamole and 250 mg/day aspirin following removal of mediastinal tubes. This regimen was continued indefinitely thereafter. RESULTS: Postoperatively, the mean International Normalized Ratio (INR) was 1.4 +/- 0.67 (range: 0.9 to 4.19) and mean prothrombin time 13.33 +/- 1.98 min (range: 11.7 to 21.3 min). Mean follow up was 1.42 +/- 1.2 years (range: 2 months to 8.3 years); total cumulative follow up was 322.75 patient-years (pt-yr). During follow up, six patients (1.85% per pt-yr) developed thromboembolic complications (including mechanical valve thrombosis), two (0.62% per pt-yr) developed oral anticoagulant-related bleeding, and two (0.62% per pt-yr) developed paravalvular leak. Five patients died during follow up (late mortality rate 1.2% per pt-yr). The nine-year actuarial survival rate was 93.9 +/- 4.8% for the entire group. CONCLUSIONS: Low-dose oral anticoagulation after mitral valve replacement with St. Jude Medical prosthesis in elderly patients provided satisfactory clinical results.