Hemorheological changes caused by intermittent Pringle (Baron) maneuver in beagle canine model.

In liver resection operations the Pringle (Baron) maneuver can be used for temporary ischemia by clamping the hepatoduodenal ligament intermittently. In this beagle canine model we investigated whether hemorheological parameters may alter in systemic, portal and hepatic venous blood and in arterial samples during-after Pringle maneuvers. In Pringle Group unilateral femoral artery and external jugular vein were cannulated. From median laparotomy the hepatoduodenal ligament was exposed. The portal venous system was catheterized via a mesenteric vein and through the inferior caval vein a catheter was led to the hepatic veins. After stabilization, a 15-minute Pringle maneuver was carried out three times with 5-minute interpolated reperfusion periods. In Control Group Pringle maneuvers were not made. Before and after Pringle maneuvers parallel blood samples were taken from the cannulated vessels for determining hematological parameters and erythrocyte aggregation. Following Pringle maneuvers erythrocyte deformability, blood and plasma viscosity were also tested. The results showed that besides systemic hemorheological effects of the intermittent Pringle maneuver local leukocyte count, hematocrit and erythrocyte aggregation index altered mainly in portal venous blood, depending on the repeating number of the maneuvers. Thus, investigations of hemorheological parameters might be useful to determine the optimal duration of the Pringle maneuver.

The effects of renal ischemia-reperfusion on hemorheological factors: preventive role of allopurinol.

Changes in hemorheological parameters were studied in dogs following unilateral renal artery clamping (45-minute ischemia then reperfusion), with and without preoperative administration of allopurinol. Sham-operated animals were also evaluated. Blood samples were collected preoperatively, at beginning and at 30, 60 and 120 minutes of reperfusion, then on the 1st, 3rd, 5th and 7th days. Filtration properties of erythrocytes (relative cell transit time, RCTT), whole blood and plasma viscosity (WBV, PV), fibrinogen level and hematology parameter were determined. RCTT significantly increased for both ischemic groups at 30 minutes of reperfusion, and remained elevated on the 1st and 2nd postoperative days; these changes were abolished by allopurinol pretreatment. WBV and hematocrit increased on the 1st day, and PV and fibrinogen level showed elevation on 1st-5th postoperative days. We thus conclude that decreases of RBC deformability (i.e., higher RCTT) were characteristic and specific on early postoperative days after renal ischemia-reperfusion and that these alterations were prevented by pre-ischemia administration of allopurinol.

Antiulcer effect of the N- and O-beta-D-glucopyranosides of 5-aminosalicylic acid.

Starting from methyl 5-nitrosalicylate (20) the N- and O-beta-glucopyranosyl derivatives (24, 28) of 5-aminosalicylic acid were prepared. The LD50 values of these compounds were determined on mice, and the inhibitory effect of 24 (0.83 mmol/kg) and 28 (1.2 mmol/kg) on gastric ulcer on rats, induced by indomethacin was investigated.

Age-dependence of free radical-induced oxidative damage in ischemic-reperfused rat heart.

Oxygen free radical-induced oxidative damage is involved in both aging and ischemia-reperfusion. The purpose of this study was to determine the aging-induced oxidative alterations in rat heart as well as the age-dependence of heart injury following ischemia-reperfusion. A comparative study was performed on young and old ischemic-reperfused rat hearts. Protein oxidation and the ascorbyl radical level in heart tissue were determined in order to characterize the oxidative stress. Comparing the control conditions, old hearts have 31% more oxidized proteins as measured by protein carbonyl content, and 18% lower ascorbyl radical level as determined by ESR, than young ones. The extent of increase of protein oxidation and ascorbyl free radical depletion induced by ischemia-reperfusion is less pronounced in the old hearts (7 and 8% respectively), as compared to the young ones (55 and 21% respectively). Pre-treatment with a free radical scavenger, such as centrophenoxine, diminished the ischemia-reperfusion injury in both young and old rat hearts.

Study of the factors influencing cardiac growth. III. Digitoxin treatment and thyroxine-induced cardiac hypertrophy in the rat.

Thyroxine (T4) administered to rats in a dose of 1 mg/kg for 12 days induces cardiac hypertrophy. The purpose of the present study was to determine the effect of prophylactic + simultaneous digitoxin treatments on the development of T4-induced cardiac hypertrophy. Digitoxin (1 mg/kg body weight) was given per os, once daily for 6 days prior to T4 administration and continued simultaneously with T4 treatment. To determine myocardial enlargement, wet heart weight, myocardial nucleic acid and protein were measured. Digitoxin treatment induced a slight increase in wet ventricle weight and a significant elevation of myocardial RNA content (mg/ventricles) and concentration (mg/g). At the same time, the degree of T4-induced cardiac hypertrophy in digitoxin-treated and untreated animals was nearly the same. On the basis of these results it can be stated that--unlike the cardiac hypertrophy induced by pressure overload or hypoxia,--the T4-induced cardiac hypertrophy is not altered by digitoxin administration.

Alterations of contractility and sarcoplasmic reticulum function of rat heart in experimental hypo- and hyperthyroidism.

Myocardial contractility and Ca2+-pump function of sarcoplasmic reticulum (SR) were studied on hearts of untreated, thyroidectomized and thyroxine-treated rats. In hypothyroid rats the contractile force, the maximum velocity of tension development and relaxation significantly decreased (by 73.2%, 68.2%; and 67.8%, respectively), while the time to peak tension was prolonged (by 25.9%) as compared with the control group. In hyperthyroidism opposite changes were found. Since the transport of calcium opposite changes were found. Since the transport of calcium by SR plays an important role in controlling contraction and, first of all, relaxation of muscle, function of the sarcoplasmic reticulum was also investigated under the above experimental conditions. In thyroidectomized rats the rate of Ca2+-uptake and Ca2+-activated ATPase activity of SR significantly decreased (by 31.7% and 61.0%, respectively), while Ca2+-binding remained unchanged. After thyroxine treatment both the Ca2+-uptake and binding capacity of SR were even decreased (by 25.6% and 12.9%, respectively), in spite of an increase in Ca2+-activated ATPase activity (by 67.3%). These changes in Ca2+ transport function of cardiac SR may only partially be responsible for the abnormalities in contraction and relaxation observed in hearts from hypo- and hyperthyroid rats.

Study of the factors influencing cardiac growth. II. Digitoxin treatment and isoproterenol-induced cardiac hypertrophy in the rat.

Isoproterenol (IPR) administered to rats in a dose of 5 mg/kg for 4 days induces cardiac hypertrophy. The purpose of the present study was to determine the effect of prophylactic + simultaneous digitoxin treatment on the development of IPR-induced cardiac hypertrophy. Digitoxin (1 mg/kg body weight) was given per os, once daily for 6 days prior to IPR administration and continued simultaneously with IPR treatment. To determine myocardial enlargement, wet heart weight, myocardial nucleic acid and protein were measured. Digitoxin treatment induced slight but significant increase in wet ventricle weight and myocardial RNA content (mg/ventricle). At the same time the degree of IPR-induced cardiac hypertrophy in digitoxin-treated and untreated animals was nearly the same. On the basis of these results it can be stated that--unlike the cardiac hypertrophy induced by pressure overload or hypoxia,--the IPR-induced cardiac hypertrophy is not altered by digitoxin administration.

Study of the factors influencing cardiac growth. I. Comparison of cardiomegaly induced by isoproterenol in euthyroid and thyroidectomized rats.

The purpose of the present work was to study the cardiac growth-stimulating effect of IPR in hypothyroid animals, in which the in vitro sensitivity of the myocardium to beta-adrenergic agonists is significantly decreased. To determine the degree of myocardial enlargement, wet and dry ventricle weight and myocardial RNA, DNA and protein were measured. IPR administered to euthyroid rats in a dosage of 5 mg/kg/day for 4 days induced cardiomegaly. In thyroidectomized rats, a consistent depression of IPR-induced cardiomegaly was observed. This phenomenon appears to be in accordance with earlier observations showing a marked decrease in maximal beta-receptor level of ventricular membranes after thyroidectomy or PTU treatment.

Effect of induced hypothyroid state on the mechanical and electrical properties of the rat ventricular myocardium.

The effect of hypothyroid state on the transmembrane potential was studied in isolated cardiac ventricular trabeculae of rats. Hypothyroid state was induced by methimazole treatment or thyroidectomy and checked by determining serum thyroxine level. Hypothyroidism decreased the maximum rate of depolarization (Vmax) and the resting potential, increased the overshoot and the duration of action potential at 20, 50 and 90% repolarization. These changes were more pronounced after methimazole treatment than after thyroidectomy. The results strongly suggest that in hypothyroidism the significant alterations in the voltage-time course of the transmembrane action potential influencing Ca2+-movement across the sarcolemma may have an indirect role in the decreased myocardial contractility. On the other hand, methimazole has an aspecific cardiac effect which may modify the cardiac effect of hypothyroidism induced by the drug.

The effect of hypothyroidism on myocardial contractility and sarcoplasmic reticulum function in rats.

Changes in contractility and ATPase activity of SR from hearts of hypothyroid rats were investigated. Rats were made hypothyroid by daily injection of 100 mg/kg methimazole for 14 days. In methimazole-treated rats, the contractile force, the maximum velocity of tension development and relaxation were significantly decreased, however, the time to peak tension remained unchanged. Function of SR was studied by determining of Ca2+-activated ATPase activity, which was significantly decreased after methimazole treatment. This diminution may be partially responsible for a slower reduction of the free Ca2+ in the surroundings of contractile proteins and thus decrease the rate of relaxation.

Comparison of ATPase activity of cardiac sarcoplasmic reticulum fraction from rat and dog.

The purpose of the present study was to compare the ATPase activities of cardiac SR in two species in which the different intrinsic myocardial contractility can only partially be explained by the different properties of cardiac myosins. In cardiac SR isolated from rat heart, the total ATPase activity was 1512.5 +/- 23.3 nmol Pi/mg protein/min, nearly four times as high as in dog cardiac SR (408.8 +/- 28.9 nmol Pi/mg protein/min). The Ca2+-activated ATPase in rat cardiac SR represented only 23.8% of the total ATPase activity, while in dog cardiac SR it was approximately 50% of the total. Thus, the specific Ca2+-activated ATPase was nearly two times higher in the cardiac SR of the rat than in that of the dog. This higher rate of ATP hydrolysis in rat cardiac SR may be, at least in part, responsible for the increased intensity and shorter duration of the active state in the rat myocardium. Polyacrylamide gel electrophoresis of SR showed that the relative amount of Ca2+-pump protein was two times higher in dog heart, similar to the percentage of Ca2+-activated ATPase activity. At the same time, the specific Ca2+-activated ATPase activity and the relative amount of Ca2+ pump protein in both the rat and dog cardiac SR were inversely related.