Systemic blood pressure response to the inhibition of two hyperpolarizing pathways: a comparison to NO-synthase inhibition.

The impact on blood pressure of two vasodilating mechanisms, underlied by vascular smooth muscle hyperpolarization, was studied and compared to that induced by nitric oxide NO mechanism. Systemic blood pressure, after inhibitory intervention in arachidonic acid metabolism cytochrome P-450 inhibition by miconazole 0.5 mg/100 g b.w. , one of the hyperpolarizing pathways, did not change. After the inhibition of the action voltage-dependent K(+) channels operator by 4-aminopyridine 0.1 mg/100 g b.w. , the other hyperpolarizing pathway, blood pressure declined slightly from 132.3+/-3.2 mm Hg to 116.5+/-5.0 mm Hg, P<0.05 . Inhibition of nitric oxide production L-NAME 5 mg/100 g b.w. increased blood pressure considerably 123.5+/-2.7 mm Hg to 155.4+/-3.1 mm Hg, P<0.001 . After inhibition of the hyperpolarizing pathway by miconazole, hypotension induced by acetylcholine (Ach, 10 microg represented 63.0+/-1.9 mm Hg vs control value 78.6+/-5.2 mm Hg P<0.001 , by bradykinin (BK) 100 microg 59.4+/-3.9 mm Hg vs control value 71.2+/-6.1 mm Hg P<0.05 . After inhibition of the hyperpolarizing pathway by 4-aminopyridine, hypotension induced by ACh 10 microg achieved 64.6+/-2.5 mm Hg vs control value 78.4+/-2.8 mm Hg P<0.001 and that induced by BK 100 microg 56.6+/-5.3 mm Hg vs control value 72.3+/-2.5 mm Hg P<0.001 . ACh or BK hypotension after the inhibition of the above hyperpolarizing pathways was significantly attenuated. On the contrary, after NO-synthase inhibition the hypotension to ACh was significantly enhanced. Blood pressure decrease after ACh 10 microg hypotension was 91.8+/-4.1 mm Hg vs control value 79.3+/-3.3 mm Hg P<0.01 , and after BK 100 microg it was 78.4+/-7.1 mm Hg vs control value 68.3+/-5.2 mm Hg. A different basal BP response, but equally attenuated hypotension to Ach and BK, was detected after the inhibition of two selected hyperpolarizing pathways. In cotrast, the inhibition of NO production elicited an increase in systemic BP and augmentation of ACh and BK hypotension. The effectiveness of further hyperpolarizing mechanisms in relation to systemic BP regulation and nitric oxide level remains open.

2,3-diphosphoglycerate and oxygen supply of tissues in cardiosurgical diabetics.

THE MAIN AIM OF THE STUDY: The oxygen supply of tissues was studied under haemodilution in cardiosurgical diabetic and non-diabetic patients. METHODS: There were 30 cardiosurgery patients examined, 9 were patients with diabetes mellitus.and 21 were non-diabetic patients. Venous blood samples were examined preoperatively, intraoperatively and for 10 days after operation. RESULTS: Haemodilution caused a decrease in haematocrit values in both groups, as well as in the erythrocyte count and haemoglobin concentration. Postoperatively, an increase was recorded in haematological values in both groups, the values had not reached the baseline even by 10th day. Increased values of blood oxygen saturation and partial oxygen pressure during the operation returned to baseline in both groups in the postoperative days. Values of p50 did not change in both groups for the period of observation. CONCLUSION: The obtained data suggest that sufficient oxygen supply to tissues was ensured under haemodilution in cardiosurgery patients in both groups. These results confirm multifactorial dependence of blood oxygen transport to tissues (Tab. 1, Fig. 3, Ref. 13).

The assessment of erythrocyte deformability by filtration rate.

The aim of the study was to monitor the erythrocyte deformability as one of important factors securing the appropriate tissues perfusion in healthy subjects and diabetic patients with insulin dependent diabetes mellitus. Erythrocyte deformability was determined by the method of filtration and centrifugation, and the erythrocyte filtrability was calculated as a percentage of filtered erythrocytes out of the number of erythrocytes counted before centrifugation. Diluted blood suspensions were filtered by centrifugation through membrane filters with pores of 5 microm in diameter. The speed and duration of centrifugation of 1400 rpm and 5 min respectively were selected as the best ones for filtration due to the lowest value of the coefficient of variance. The values of the arithmetic mean and standard deviation of erythrocyte filtrability were 72.2 +/- 7.9% in normal subjects. In the group of diabetic patients with the long history of insulin therapy the values amounted to 69.1 +/- 4.4%. In diabetic patients, the average value of blood glucose was 11.7 mmol x L(-1), and the glycated haemoglobin concentration reached 9.04%. From the viewpoint of reference values, these facts indicate good compensation of diabetes mellitus. Other haematological values, namely erythrocyte count, haematocrit value, haemoglobin concentration and mean cell volume were within normal reference ranges. No difference between the groups of healthy subjects and diabetic patients was found. (Fig. 4, Ref. 18.)

The effect of selected membrane active substances on erythrocyte deformability.

Aminoguanidine improved the erythrocyte filterability by 4%, pyridoxyliden-aminoguanidine by 11% and pyridoxal by 13% in healthy subjects. In diabetic patients the aminoguanidine effect on erythrocyte filterability was improved by 7%, PAG effect by 9% and pyridoxal effect by 15% in comparison to the control group. The other investigated haematological variables in both groups were within the range of the physiological standard. All of the tested substances demonstrated a mild protective influence on erythrocyte elasticity both in healthy subjects and diabetic patients. Significant elasticity improvement was obtained only by pyridoxal (p<0.01) in patients with diabetes mellitus. (Fig. 4, Ref. 18.).

[Oxygen transport values in patients with surgery performed under extracorporeal blood circulation]. / Hodnoty parametrov transportu kyslíka u pacientov operovaných v podmienkach mimotelového krvného obehu.

The aim of the work was to study the O2-transport changes to tissues in cardio-surgical patients suffering from CAD and operated during extra-corporeal blood circulation (ECC). The changes of selected haematologic variables, 2,3-diphosphoglycerate (2,3-DPG) and ATP concentration, acid-base balance parameters with p50 calculation were measured in the venous blood samples taken before the operation, during the operation and on the 1st, 2nd, 3d, 5th, 7th and 10th day after the operation. From the obtained results follows, that extreme haemodilution causes significant decrease of the haematocrit value (Htc) by 35%, the value of haemoglobin (Hb) by 37% and the count of erythrocytes (Er) by 37% from the initial values. The count of reticulocytes (Ret) was increased by 52%. In the days after operation the increase in Htc values, the values of Hb and count of erythrocytes was observed, whereby the initial values were not reach even on the 10th day after the operation. The increase of the reticulocytes count by 33% prevailed to the 10th day after the operation in comparison with the initial values. 2,3-DPG concentration was increased between 3d and 10th day after the operation by 30% and ATP concentration between 5th and 10th day was increased by 23% from the initial values. Hb-O2 saturation (SpO2) and pO2 were increased already during the operation, the increase prevailed until the 7th day by 27%, pO2 until the 3d day by 39% from the initial values. Calculated values p50 did not change in the course of this study--they fluctuated in range +/- 0.04 kPa from the initial value 3.55 kPa. Supposing multifactorial character of Hb oxygenation and deoxygenation process it is possible to conclude, that the determined changes of observed parameters did not significantly influence O2-transport to tissues during ECC. (Fig. 3, Ref. 12.)

NO concentration in the periendothelial area of the femoral artery of the dog measured in vivo.

.NO concentration was measured in the periendothelial area of the femoral artery by Malinski's porphyrinic .NO sensor in seven anaesthetized dogs. The basal concentration was 154.2 +/- 5.6 nM and two-minute intraarterial infusions of acetylcholine (3-4 micrograms/ml/min) or bradykinin (30-40 ng/ml/min) increased this value significantly to 204.3 +/- 16.4 and 266.5 +/- 16.4 nM (P < 0.01), respectively. Inhibition of .NO synthase by L-NAME (50 mg/kg) declined the basal .NO concentration only to 137.2 +/- 3.3 nM (P < 0.01). Subsequent administration of acetylcholine and bradykinin attenuated significantly the increase in .NO concentration. Surprisingly, both agonists still induced a significant increase of .NO concentration by 125.3 +/- 8.3 and 156.6 +/- 26.9 nM, respectively (P < 0.01). One of the possible explanations may be that besides arginine-citrulline plus the .NO pathway other sources of .NO could be involved in the high level of .NO after .NO synthase blockade by L-NAME.

Early changes of protein synthesis in myocardium and coronary arteries induced by NO synthase inhibition.

The question was addressed whether short-term (4 hour) NO deficiency, inducing an increase in blood pressure in anaesthetized dogs, does influence proteosynthesis in the myocardium and coronary arteries. A potentially positive answer was to be followed by the study of the supporting role of ornithine decarboxylase for the polyamines pathway. N(G)-nitro-L-arginine-methyl ester (L-NAME) (50 mg/kg per hour) was administered i.v. to inhibit NO synthase. After the first L-NAME dose diastolic blood pressure increased from 131.8+/-2.0 to 149.4+/-3.9 mm Hg (p<0.001) and was maintained at about this level till the end of the experiment. Systolic blood pressure only increased after the first dose (from 150.8+/-1.1 to 175.0+/-5.8 mm Hg, p<0.01), returning thereafter to the control level. Similarly, the heart rate declined only after the first dose (from 190.4+/-5.3 to 147.6+/-4.5 beats/min, p<0.01). Total RNA concentrations increased in the left cardiac ventricle (LV), the left anterior descending coronary artery (LADCA) and left circumflex coronary artery (LCCA) by 15.9+/-0.7, 29.7+/-1.3 and 17.6+/-1.0%, p<0.05, respectively. The same applied to [14C]leucine incorporation (by 86.5+/-5.0, 33.5+/-2.6, 29.3+/-4.1%, p<0.05, respectively). The above parameters indicated an increase of proteosynthesis in the LV myocardium and both coronary arteries LADCA and LCCA after short-term NO deficiency. Surprisingly, the ornithine decarboxylase activity in the LV myocardium decreased significantly by 40.2+/-1.6% (p<0.01) but the changes were not significant in the coronary arteries. This unexpected finding makes the role of polyamines in increasing proteosynthesis during a pressure overload due to NO deficiency questionable.

Early changes in protein synthesis in epicardial coronary artery of pressure-overloaded heart.

In anesthetized dogs, a 4-h, approximately 30% increase in blood pressure induced by constriction of the abdominal aorta brought about an increase in the total RNA content in the left anterior descending coronary artery (LADCA) and the left ventricular (LV) myocardium (9.05 +/- 1.72 and 11.06 +/- 4.68%, respectively) but not in the left circumflex coronary artery (LCCA). Under the same experimental conditions, [14C]leucine incorporation increased in LADCA and LV myocardium (45.34 +/- 13.54 and 58.07 +/- 11.91%, respectively), but not in LCCA. The data indicate an early shift in protein synthesis in LADCA and simultaneously in the myocardium during a short-term pressor event. The difference in the shift of protein synthesis in the two main branches of the left coronary artery was related to the quantitatively different deformation of the LADCA and LCCA due to different deformation of the underlying myocardium and/or of the annulus fibrosus atrioventricularis during changes in the left or right ventricle volume [M. Gerová, E. Barta, M. Stolárik, and J. Gero, Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H1049-H1053, 1992]. The results support the hypothesis that the deformation and/or rate of deformation of cells in the coronary wall may trigger an increase in protein synthesis. Changes in protein synthesis in the myocardium and LADCA were found to be reversible 2 h after releasing the aortic constriction.

Nitric oxide in the periendothelial area of femoral vein of the dog assessed in vivo by a porphyrinic sensor.

Nitric oxide concentration in the periendothelial are of the femoral vein in anaesthetized dogs was measured directly with a catheter- protected porphyrinic sensor. A 2- to 4-fold increase occurred in the basal NO concentration of 90 +/- 12 nM after acetylcholine injection (1-1.5 micrograms/kg). A linear correlation was found between femoral artery blood flow and NO concentration in the periendothelial area of the femoral vein. Noradrenaline decreased NO levels below the detection limit of the porphyrinic sensor (10 nM).

Biomechanical signals in the coronary artery triggering the metabolic processes during cardiac overload.

Peculiarities in structure and deformability of epicardial conduit coronary arteries are described. The thin wall of animal coronary artery contrasts the human coronary artery in which the remarkable wall thickness is due namely by the intima thickness. Deformation in length and diameter of conduit coronary arteries, due to the left and right ventricle volume increase, has been defined in non-beating canine heart. Ramus interventricularis anterior being firmly tethered to the myocardium undergoes about 3 times larger deformation than ramus circumflexus. In anaesthetized dogs a 30% increase in blood pressure, elicited by aortic constriction, induces an increase in diameter of coronary artery, in segment length, in blood flow and consequently in shear stress which represents a load for circumferentially running smooth muscle bundles, longitudinally running smooth muscle bundles, as well as for the endothelium. The above load lasting 4 h is already reflected by an increase in total RNA content and [14C] leucin incorporation in the left ventricle myocardium in the wall of ramus interventricularis anterior, not in ramus circumflexus. The findings fit completely with the different range of deformation of both the above coronary branches and indicates an increase in proteosynthesis not only in myocardium, but in ramus interventricularis anterior as well. An increase in ornithindecarboxylase activity in coronary wall leading to an increase in biogenic polyamines, is present in the case only, when blood pressure increase is induced by infusion of noradrenaline.

Protein metabolism in coronary wall affected by cardiac load.

The relation between biomechanics of conduit coronary artery and metabolic processes in its wall were studied in cardiac pressure overload, in anaesthetized dogs. Two sorts of forces and/or coronary deformations were followed: (1) radial and length deformation of ramus interventricularis anterior (RIA) due to ventricle volume changes, and (2) shear stress in ramus circumflexus (RC) ensuing the blood flow changes. Increase in aortic pressure (33.9 +/- 2.30%) accompanied an increase in RIA diameter (4.6 +/- 0.38%) and an increase in segment length (8.0 +/- 1.0%) indicating that both circumferential and longitudinal oriented muscle bundles were loaded. Increase in RC blood flow (55.6 +/- 4.0%) and diameter (3.8 +/- 0.3%) resulted in an increase of shear stress (35.15 +/- 11.16%) that affects particularly the endothelial cells. Two hours lasting cardiac load suggested a tendency, 4 h lasting load resulted in a significant increase both in RNA content (11.06 +/- 4.68% and 9.05 +/- 0.72%) and in [14C]leucine incorporation (53.59 +/- 13.75% and 48.41 +/- 16.16%) in the myocardium and RIA wall, respectively. No change was found in RC wall. The process was reversible, 2 h after the load had ceased. The heterogeneity of metabolic processes reflected closely the heterogeneity in coronary deformation.

Blood pressure and vasomotor responses to sympathetic stimuli in patients with chronic myocardial infarction.

The responses of resistance and capacitance vessels of skin and muscle, and of blood pressure to reflex influences mediated by the sympathetic system were investigated in a group of 63 male patients in a chronic phase of myocardial infarction. In the group of patients with MI, as compared to the controls: (1) the reactive increase of systolic BP and heart rate was significantly smaller but longer lasting after cessation of the stimuli; (2) the vasoconstrictory reactions in skin were significantly prolonged in resistance as well as in capacitance segments of vascular bed; and (3) the resting blood flow in muscle was significantly lower and the vasodilatation during an emotional reaction was less pronounced and shorter. Possible underlying mechanisms of this vasomotor pattern are discussed.