Site of myocardial infarction. A determinant of the cardiovascular changes induced in the cat by coronary occlusion.
The influence of site of acute myocardial infarction on heart rate, blood pressure, cardiac output, total peripheral resistance (TPR), cardiac rhythm, and mortality was determined in 58 anesthetized cats by occlusion of either the left anterior descending (LAD), left circumflex or right coronary artery. LAD occlusion resulted in immediate decrease in cardiac output, heart rate, and blood pressure, an increase in TPR, and cardiac rhythm changes including premature ventricular beats, ventricular tachycardia, and occasionally ventricular fibrillation. The decrease in cardiac output and increase in TPR persisted in the cats surviving a ventricular arrhythmia. In contrast, right coronary occlusion resulted in a considerably smaller decrease in cardiac output. TPR did not increase, atrioventricular condition disturbances were common, and sinus bradycardia and hypotension persisted in the cats recovering from an arrhythmia. Left circumflex ligation resulted in cardiovascular changes intermediate between those produced by occlusion of the LAD or the right coronary artery. Mortality was similar in each of the three groups. We studied the coronary artery anatomy in 12 cats. In 10, the blood supply to the sinus node was from the right coronary artery and in 2, from the left circumflex coronary artery. The atrioventricular node artery arose from the right in 9 cats, and from the left circumflex in 3. The right coronary artery was dominant in 9 cats and the left in 3. In conclusion, the site of experimental coronary occlusion in cats is a major determinant of the hemodynamic and cardiac rhythm changes occurring after acute myocardial infarction. The cardiovascular responses evoked by ligation are related in part to the anatomical distribution of the occluded artery. (+info)
Control of ketogenesis from amino acids. IV. Tissue specificity in oxidation of leucine, tyrosine, and lysine.
In vitro and in vivo studies were made on the tissue specificity of oxidation of the ketogenic amino acids, leucine, tyrosine, and lysine. In in vitro studies the abilities of slices of various tissues of rats to form 14CO2 from 14C-amino acids were examined. With liver, but not kidney slices, addition of alpha-ketoglutarate was required for the maximum activities with these amino acids. Among the various tissues tested, kidney had the highest activity for lysine oxidation, followed by liver; other tissues showed very low activity. Kidney also had the highest activity for leucine oxidation, followed by diaphragm; liver and adipose tissue had lower activities. Liver had the highest activity for tyrosine oxidation, but kidney also showed considerable activity; other tissues had negligible activity. In in vivo studies the blood flow through the liver or kidney was stopped by ligation of the blood vessels. Then labeled amino acids were injected and recovery of radioactivity in respiratory 14CO2 was measured. In contrast to results with slices, no difference was found in the respiratory 14CO2 when the renal blood vessels were or were not ligated. On the contrary ligation of the hepatic vessels suppressed the oxidations of lysine and tyrosine completely and that of leucine partially. Thus in vivo, lysine and tyrosine seem to be metabolized mainly in the liver, whereas leucine is metabolized mostly in extrahepatic tissues and partly in liver. Use of tissue slices seems to be of only limited value in elucidating the metabolisms of these amino acids. (+info)
Pulsed Doppler ultrasonographic evaluation of portal blood flow in dogs with experimental portal vein branch ligation.
Portal blood flow was measured using pulsed Doppler ultrasound in 6 dogs before and after left portal vein branch ligation. Mean portal vein blood flow velocity and mean portal vein blood flow were significantly reduced after ligation and the congestion index was increased (p < 0.01). Pulsed Doppler ultrasound studies provide valuable physiological information which may assist the clinician with the diagnosis of canine hepatic circulatory disorders. (+info)
Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation.
Hepatic fibrosis or increased liver collagen contents drive functional abnormalities that, when extensive, may be life threatening. The purpose of this study was to assess the effects of the chronic stimulation or inhibition of nitric oxide synthesis in rats with hepatic fibrosis induced by permanent common bile duct ligation (3 weeks) and the role of expression of the different nitric oxide synthase isoforms. Bile duct ligation led to an important accumulation of collagen in the hepatic parenchyma, as shown both histologically and by the hydroxyproline contents of livers. Bilirubin and serum enzyme activities (measured as markers of cholestasis) increased several-fold after bile duct ligation. The area of fibrotic tissue, liver hydroxyproline content and serum markers of cholestasis were clearly related in obstructed rats. The absence of modifications in haemodynamic parameters excludes circulatory changes from being responsible for the development of liver alterations. In animals treated with NG-nitro-L-arginine methyl ester (L-NAME) the area of fibrosis was similar to that of untreated animals, the signs of cholestasis and cellular injury being more evident. In rats treated with L-arginine the area of fibrosis was almost three times larger than that found in bile duct ligated rats and in L-NAME-treated bile duct ligated rats, although the observed biochemical changes were similar to those seen in rats treated with L-NAME. Our results with inducible nitric oxide synthase, obtained by Western blots and immunohistochemistry, indicate a greater expression of the inducible enzyme in bile duct ligated and L-arginine-treated animals and a lower expression in the L-NAME and control groups. Constitutive nitric oxide synthase expression, obtained by Western blots, was very similar in all groups, except for the L-arginine-treated rats in which it was lower. These results suggest that nitric oxide production may be a key factor in the development of fibrosis in bile duct ligated rats. They also support the hypothesis of a dual role for nitric oxide; one beneficial, mediated by its circulatory effects, and the second negative, through its local toxic effects. (+info)
Uninjured C-fiber nociceptors develop spontaneous activity and alpha-adrenergic sensitivity following L6 spinal nerve ligation in monkey.
We investigated whether uninjured cutaneous C-fiber nociceptors in primates develop abnormal responses after partial denervation of the skin. Partial denervation was induced by tightly ligating spinal nerve L6 that innervates the dorsum of the foot. Using an in vitro skin-nerve preparation, we recorded from uninjured single afferent nerve fibers in the superficial peroneal nerve. Recordings were made from 32 C-fiber nociceptors 2-3 wk after ligation and from 29 C-fiber nociceptors in control animals. Phenylephrine, a selective alpha1-adrenergic agonist, and UK14304 (UK), a selective alpha2-adrenergic agonist, were applied to the receptive field for 5 min in increasing concentrations from 0.1 to 100 microM. Nociceptors from in vitro control experiments were not significantly different from nociceptors recorded by us previously in in vivo experiments. In comparison to in vitro control animals, the afferents found in lesioned animals had 1) a significantly higher incidence of spontaneous activity, 2) a significantly higher incidence of response to phenylephrine, and 3) a higher incidence of response to UK. In lesioned animals, the peak response to phenylephrine was significantly greater than to UK, and the mechanical threshold of phenylephrine-sensitive afferents was significantly lower than for phenylephrine-insensitive afferents. Staining with protein gene product 9.5 revealed an approximately 55% reduction in the number of unmyelinated terminals in the epidermis of the lesioned limb compared with the contralateral limb. Thus uninjured cutaneous C-fiber nociceptors that innervate skin partially denervated by ligation of a spinal nerve acquire two abnormal properties: spontaneous activity and alpha-adrenergic sensitivity. These abnormalities in nociceptor function may contribute to neuropathic pain. (+info)
Hypothermic neuroprotection of peripheral nerve of rats from ischaemia-reperfusion injury.
Although there is much information on experimental ischaemic neuropathy, there are only scant data on neuroprotection. We evaluated the effectiveness of hypothermia in protecting peripheral nerve from ischaemia-reperfusion injury using the model of experimental nerve ischaemia. Forty-eight male Sprague-Dawley rats were divided into six groups. We used a ligation-reperfusion model of nerve ischaemia where each of the supplying arteries to the sciatic-tibial nerves of the right hind limb was ligated and the ligatures were released after a predetermined period of ischaemia. The right hind limbs of one group (24 rats) were made ischaemic for 5 h and those of the other group (24 rats) for 3 h. Each group was further divided into three and the limbs were maintained at 37 degrees C (36 degrees C for 5 h of ischaemia) in one, 32 degrees C in the second and 28 degrees C in the third of these groups for the final 2 h of the ischaemic period and an additional 2 h of the reperfusion period. A behavioural score was recorded and nerve electrophysiology of motor and sensory nerves was undertaken 1 week after surgical procedures. At that time, entire sciatic-tibial nerves were harvested and fixed in situ. Four portions of each nerve were examined: proximal sciatic nerve, distal sciatic nerve, mid-tibial nerve and distal tibial nerve. To determine the degree of fibre degeneration, each section was studied by light microscopy, and we estimated an oedema index and a fibre degeneration index. The groups treated at 36-37 degrees C underwent marked fibre degeneration, associated with a reduction in action potential and impairment in behavioural score. The groups treated at 28 degrees C (for both 3 and 5 h) showed significantly less (P < 0.01; ANOVA, Bonferoni post hoc test) reperfusion injury for all indices (behavioural score, electrophysiology and neuropathology), and the groups treated at 32 degrees C had scores intermediate between the groups treated at 36-37 degrees C and 28 degrees C. Our results showed that cooling the limbs dramatically protects the peripheral nerve from ischaemia-reperfusion injury. (+info)
Mid-term results of endoscopic perforator vein interruption for chronic venous insufficiency: lessons learned from the North American subfascial endoscopic perforator surgery registry. The North American Study Group.
PURPOSE: The safety, feasibility, and early efficacy of subfascial endoscopic perforator surgery (SEPS) for the treatment of chronic venous insufficiency were established in a preliminary report. The long-term clinical outcome and the late complications after SEPS are as yet undetermined. METHODS: The North American Subfascial Endoscopic Perforator Surgery registry collected information on 148 SEPS procedures that were performed in 17 centers in the United States and Canada between August 1, 1993, and February 15, 1996. The data analysis in this study focused on mid-term outcome in 146 patients. RESULTS: One hundred forty-six patients (79 men and 67 women; mean age, 56 years; range, 27 to 87 years) underwent SEPS. One hundred and one patients (69%) had active ulcers (class 6), and 21 (14%) had healed ulcers (class 5). One hundred and three patients (71%) underwent concomitant venous procedures (stripping, 70; high ligation, 17; varicosity avulsion alone, 16). There were no deaths or pulmonary embolisms. One deep venous thrombosis occurred at 2 months. The follow-up periods averaged 24 months (range, 1 to 53 months). Cumulative ulcer healing at 1 year was 88% (median time to healing, 54 days). Concomitant ablation of superficial reflux and lack of deep venous obstruction predicted ulcer healing (P <.05). Clinical score improved from 8.93 to 3.98 at the last follow-up (P <. 0001). Cumulative ulcer recurrence at 1 year was 16% and at 2 years was 28% (standard error, < 10%). Post-thrombotic limbs had a higher 2-year cumulative recurrence rate (46%) than did those limbs with primary valvular incompetence (20%; P <.05). Twenty-eight of the 122 patients (23%) who had class 5 or class 6 ulcers before surgery had an active ulcer at the last follow-up examination. CONCLUSIONS: The interruption of perforators with ablation of superficial reflux is effective in decreasing the symptoms of chronic venous insufficiency and rapidly healing ulcers. Recurrence or new ulcer development, however, is still significant, particularly in post-thrombotic limbs. The reevaluation of the indications for SEPS is warranted because operations in patients without previous deep vein thrombosis are successful but operations in those patients with deep vein thrombosis are less successful. Operations on patients with deep vein occlusion have poor outcomes. (+info)
Contribution of extracranial lymphatics and arachnoid villi to the clearance of a CSF tracer in the rat.
The objective of this study was to determine the relative roles of arachnoid villi and cervical lymphatics in the clearance of a cerebrospinal fluid (CSF) tracer in rats. 125I-labeled human serum albumin (125I-HSA; 100 micrograms) was injected into one lateral ventricle, and an Evans blue dye-rat protein complex was injected intravenously. Arterial blood was sampled for 3 h. Immediately after this, multiple cervical vessels were ligated in the same animals, and plasma recoveries were monitored for a further 3 h after the intracerebroventricular injection of 100 micrograms 131I-HSA. Tracer recovery in plasma at 3 h averaged (%injected dose) 0.697 +/- 0.042 before lymphatic ligation and dropped significantly to 0.357 +/- 0. 060 after ligation. Estimates of the rate constant associated with the transport of the CSF tracer to plasma were also significantly lower after obstruction of cervical lymphatics (from 0.584 +/- 0. 072/h to 0.217 +/- 0.056/h). No significant changes were observed in sham-operated animals. Assuming that the movement of the CSF tracer to plasma in lymph-ligated animals was a result of arachnoid villi clearance, we conclude that arachnoid villi and extracranial lymphatic pathways contributed equally to the clearance of the CSF tracer from the cranial vault. (+info)