Prevention of paraplegia in pigs by selective segmental artery perfusion during aortic cross-clamping.
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PURPOSE: During thoracoabdominal aortic aneurysm repair, a prolonged interruption of the spinal cord blood supply can result in irreversible spinal cord damage. The aim of this study was to investigate whether selective segmental artery perfusion during aortic clamping could prevent paraplegia in pigs. METHODS: Specially designed segmental artery perfusion catheters, which could be attached to an extracorporeal bypass graft system, were used. In experiment I (n = 10), it was assessed whether selective segmental artery perfusion could reverse electrophysiologic evidence of spinal cord ischemia and maintain transcranial motor evoked potentials (tc-MEPs) during 60 minutes of aortic cross-clamping. The abdominal aorta, containing critical segmental arteries, was bypassed through use of an aortoaortic bypass graft system. After the disappearance of tc-MEPs, an aortotomy was followed by selective segmental artery perfusion. In experiment II (n = 10), the aim was to determine whether selective segmental artery perfusion could prevent paraplegia. In five animals (group A), aortic cross-clamping was followed by selective segmental artery perfusion; five control animals (group B) underwent segmental artery blockade only. Postoperative hind limb function and spinal cord histopathology were evaluated on the third postoperative day. RESULTS: In experiment I, tc-MEPs disappeared within 3.7 +/- 3.7 minutes after cross-clamping and returned in all animals in 8.5 +/- 5.3 minutes after selective perfusion. During the study period, tc-MEP amplitudes recovered to a median of 49% (range, 28%-113%) of baseline values. Total bypass graft flow was 880 +/- 294 mL/min, of which 184 +/- 54 mL/min was directed to the selective perfusion catheters. The flow in individual catheters was 52 +/- 13 mL/min. In experiment II, all perfused animals demonstrated normal hind limb function, whereas four of five control animals were paraplegic on day 3 (P =.04) In the perfused animals, histopathologic examination showed either no spinal cord damage or eosinophilic neurons only, whereas in paraplegic controls there was infarction in large areas of the cord (P <.0001). CONCLUSION: In pigs, selective segmental artery perfusion can provide sufficient spinal cord blood flow to prevent paraplegia resulting from 60 minutes of aortic clamping, as shown by clinical outcomes and histopathologic examination. (+info)
In 42 children with congenital heart disease coagulation factor levels were studied serially during the first 20 hours following cardiopulmonary bypass surgery. The acyanotic patients, and also cyanotic patients who survived the operation, showed a progressive improvement in their coagulation profile from initial low postoperative levels. In 12 cyanotic patients who died within 72 hours, however, the coagulation factor levels either remained low, or fell further, until death. Fresh frozen plasma was administered to eight of these patients without apparent benefit. The abnormal coagulation profile correlated significantly with low skin temperature and increased blood loss and was considered to represent excess intravascular coagulation secondary to low cardiac output and poor tissue perfusion. (+info)
Liver support by extracorporeal blood purification: a clinical observation.
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Liver failure associated with excretory insufficiency and jaundice results in an endogenous accumulation of toxins involved in the impairment of cardiovascular, kidney, and cerebral function. Moreover, these toxins have been shown to damage the liver itself by inducing hepatocellular apoptosis and necrosis, thus creating a vicious cycle of the disease. We report a retrospective cohort study of 26 patients with acute or chronic liver failure with intrahepatic cholestasis (bilirubin level > 20 mg/dL) who underwent a new extracorporeal blood purification treatment. A synthetic hydrophilic/hydrophobic domain-presenting semipermeable membrane (pore size < albumin size, 100-nm thick) was used for extracorporeal blood detoxification using dialysis equipment. The opposite side was rinsed with ligandin-like proteins as molecular adsorbents that were regenerated online using a chromatography-like recycling system (molecular adsorbent recirculating system [MARS]). Bile acid and bilirubin levels, representing the previously described toxins, were reduced by 16% to 53% and 10% to 90% of the initial concentration by a single treatment of 6 to 8 hours, respectively. Toxicity testing of patient plasma onto primary rat hepatocytes by live/dead fluorescence microscopy showed cell-damaging effects of jaundiced plasma that were not observed after treatment. Patients with a worsening of Child-Turcotte-Pugh (CTP) index before the treatments showed a significant improvement of this index during a period of 2 to 14 single treatments with an average of 14 days. After withdrawal of MARS treatment, this improvement was sustained in all long-term survivors. Ten patients represented a clinical status equivalent to the United Network for Organ Sharing (UNOS) status 2b (group A1), and all survived. Sixteen patients represented a clinical status equivalent to UNOS status 2a, and 7 of these patients survived (group A2), whereas 9 patients (group B) died. We conclude that in acute excretory failure caused by a chronic liver disease, this treatment provides a therapy option to remove toxins involved in multiorgan dysfunction secondary to liver failure. (+info)
Use of a dynamic method in calibration of dye-dilution curves during cardiac surgery.
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A simplified dynamic method of calibration for dye-dilution curves is described. The method involves appropriate matching of the fluid volume in the mixing chamber, the blood withdrawal rate, and the calibration dose of dye. It was used to compare the observed versus calibrated pump output of a heart-lung machine with individual dye-dilution curves obtained from 15 patients during total cardiopulmonary bypass. The results indicate that the difference (range+14% to-8%) between the two is statistically insignificant. The method is rapid and relatively simple. It is particularly useful for cardiac output determination during unsteady clinical conditions because of the ability to calibrate dye curves at the time they are recorded. (+info)
Correction of the transposition of the great arteries.
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Inversion of the atrial flow in transposition of the great arteries is achieved in the following way: the remaining atrial septum is detached from behind, leaving it as a flap between both AV-valves. The incision is continued into the coronary sinus and the Vena magna cordis to the base of the left atrial appendage along the mitral ring. The resulting flap from the split coronary sinus is sutured to the left atrial wall in front of the left side pulmonary veins, thus forming a septum dorsal to the caval veins, diverting the left pulmonary venous blood to the right side. The atrial septal flap is reattached in front of the caval vein orifices. In 50 cases a small Dacron patch was used to complete the midportion of the new septum. Six patients died and so far we have encountered one superior Vena cava stenosis and one pulmonary vein stenosis. In 16 patients completion of the midportion of the new atrial septum was done with a partially excised flap from the right atrial wall still attached to the Vena cava inferior. This method resulted in 3 operative deaths. In 42 of 58 survivors the ECG has been repeatedly controlled 3 months to 6 years postoperatively. Thirty-six of the 42 patients have sinus rhythm, 4 vary between nodal and sinus-rhythm and 2 have a total AV-dissociation. (+info)
Vascular endothelial growth factor release following coronary artery bypass surgery: extracorporeal circulation versus 'beating heart' surgery.
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AIMS: The aim of this study was to examine the circulating levels of vascular endothelial growth factor, following coronary artery bypass graft surgery performed using both standard cardiopulmonary bypass or the 'octopus technique' on the beating heart. BACKGROUND: Vascular endothelial growth factor has a number of effects that are beneficial in the setting of coronary artery bypass graft surgery including cardioprotection, potent angiogenic activity and amelioration of intimal hyperplasia. Hypoxia is a powerful stimulator of vascular endothelial growth factor expression yet the ability of ischaemia, occurring during coronary artery bypass graft surgery, to induce vascular endothelial growth factor production is unknown. METHODS AND RESULTS: Serum vascular endothelial growth factor levels were determined in patients undergoing coronary artery bypass graft surgery with standard cardiopulmonary bypass (CPB-CABG group; n=20), with off-pump coronary artery bypass; (OP-CABG; n=12) and in patients undergoing non-cardiac major surgery (n=6). The effect of hypoxia on vascular endothelial growth factor release by neonatal rat cardiac myocytes in vitro was studied. In the CPB-CABG group vascular endothelial growth factor levels were significantly increased to 78.5+/-39.3 and 110.5+/-16.3 pg. microl(-1)8 and 24 h post-operatively, declining to 14.9+/-9.9 pg. microl(-1)by 48 h to pre-operative values (14.4+/-8.6 pg. microl(-1)). Significantly higher vascular endothelial growth factor levels were also present in the OP-CABG group 3, 6 and 24 h post-operatively (levels 136. 6+/-29.3, 143+/-26.12 pg. microl(-1)and 93.5+/-20.1 pg. microl(-1), respectively). However, non-cardiac major surgery did not result in elevated vascular endothelial growth factor levels post-operatively (46.36+/-9.76 vs pre-surgery levels of 26.84+/-6.1 pg. microl(-1)). Either 15 min or 3 h of hypoxia stimulated vascular endothelial growth factor release from neonatal rat cardiac myocytes in vitro. Twenty-four and 48 h post hypoxia, levels of vascular endothelial growth factor were significantly elevated by approximately 17.5- and 48.5-fold respectively. CONCLUSIONS: These data demonstrate myocardial ischaemia secondary to CPB-CABG and OP-CABG to be a potent stimulator of vascular endothelial growth factor production, which may have implications for graft endothelialization and cardiovascular haemodynamics post-operatively. (+info)
Thrombolysis by thienopyridines and their congeners.
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We propose that anti-platelet thienopyridines, such as ticlopidine or clopidogrel, are thrombolytic owing to endothelial release of prostacyclin (PGI2) and tissue plasminogen activator (t-PA). In this study we used anaesthetised Wistar rats with extracorporal circulation in which arterial blood superfused thrombi which adhered to a strip of collagen. Weight of thrombi was continuously monitored. When administered intravenously, clopidogrel or its R enantiomer deprived of anti-platelet action, both at doses of 3 mg x kg(-1), produced lost in weight of thrombi by 14.1 +/- 1.3% or 16.0 +/- 1.4% (n = 9), and at doses 10 mg x kg(-1) by 28.3 +/- 2.3% or 30.4 +/- 1.9% (n = 8), respectively. Maximum of thrombolysis occurred 30-45 min following the drug administration. Ticlopidine at a dose of 30 mg x kg(-1) reduced weight of thrombi by 33.7 +/- 1.7% (n = 32). Thrombolytic action of ticlopidine was accompanied by a rise in 6!keto-PGF1alpha blood levels from 0.42 +/- 0.10 to 1.58 +/- 0.29 ng x ml(-1) and t-PA antigen plasma levels from 4.70 +/- 1.00 to 12.90 +/- 1.15 ng x ml(-1) (n = 7). Five out of eleven tested thienopyridine congeners with pyrimidine or pyrimidinone instead of pyridine rings had thrombolytic potencies similar to that of clopidogrel (ED30s at a range of 6.2-11.4 mg x kg(-1)). A substantial increase in thrombolytic potency (ED30s at a range of 0.3-2.1 mg x kg(-1)) was observed for congeners in which thienyl ring was condensed with an additional cyclopentyl, cyclohexyl or cycloheptyl structures or in which thienopyridine complex was replaced for a pyridopyrimidine one. We claim that thienopyridines, independently of their delayed anti-platelet action, do produce immediate thrombolysis in vivo. This new activity emulates capacity of their native, non-metabolised molecules to release prostacyclin and tissue plasminogen activator. We have also shown that structural changes in molecules of thienopyridines may intensify their thrombolytic potency. (+info)
Administration of clemastine--H1 histamine receptor blocker in the prevention of haemodynamic disorders after protamine sulfate administration in patients subjected to coronary artery bypass grafting in extracorporeal circulation.
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INTRODUCTION: Adverse effects of protamine administration after CPB: fall in arterial blood pressure and pulmonary hypertension are still a source of problems. CPB and protamine administration are both accompanied by increased histamine levels in blood. The aim of this study was to examine if clemastine can accelerate the normalisation of arterial blood pressure during the protamine administration after CPB during CABG operations. MATERIAL AND METHODS: Fifty three patients subjected to CABG operations were studied. Control group (n = 27) did not receive clemastine, Clemastine group (n = 26) received 2 mg i.v. clemastine, before CPB. After CPB were completed, patients were given protamine (heparin to protamine ratio--1:1.5) within 7 minutes, through peripheral vein. Changes in arterial blood pressure from the beginning of protamine administration to 2.5, 5, 7.5, 10, 15, and 30 minutes thereafter, as well as heart rate, CVP, doses of inotropic drugs and vasodilators were compared between the groups. RESULTS: No difference in heart rate, CVP, doses of inotropic drugs and vasodilators between the group was noted. An increase in arterial blood pressure 5, 7.5, 10, and 15 minutes after the beginning of the protamine administration were greater in clemastine group than in control group. Groups were comparable with regard to surgical procedures and doses of anaesthetic drugs. It is now known that protamine exerts a negative effect on cardiac contractility either through a decrease in coronary perfusion pressure (vasodilatation), or through a direct toxic effect on cardiac muscle. The administration of clemastine before CPB can reduce peripheral vasodilatation and capillary leak related to histamine release during CPB. In the clemastine group, faster increase in arterial blood pressure toward a physiologic range was observed. We conclude that administration of clemastine is connected with the normalization of ABP during and after protamine reversal of heparin coagulation during CABG operations. (+info)