Danuta Zborowska-Sluis

Effect of acute sympathectomy by epidural anesthesia on the canine coronary circulation.

The effects of reversible sympathetic neural blockade of the canine myocardium under control conditions and in the presence of decreased coronary blood flow and after myocardial infarction were investigated in 17 dogs. A multiple-microsphere technique was used to measure distribution of blood flow in the myocardium. Epidural blockade was associated with the following changes in the ratio of endocardial to epicardial blood flow: under control conditions, no change; after 50 per cent decrease in coronary flow, 18 per cent increase in endocardial/epicardial ratio; after myocardial infarction at unrestricted coronary flow, 43 per cent ratio increase; after myocardial infarction and 50 per cent decrease in coronary flow, 76 per cent increase of endocardial/epicardial ratio. These effects appear to be independent of systemic factors, and may result from alterations in tone of transmural resistance vessels. In addition, cervicothoracic epidural blockade resulted in a decrease in systemic pressure and an increase in coronary vascular resistance as myocardial oxygen demand decreased. When systemic pressure was restored these effects were abolished. In the presence of myocardial infarction, epidural blockade had less effect on systemic pressure and left ventricular filling pressure was decreased. With decreased coronary flow, sympathetic blockade redistributed coronary blood flow, favoring the endocardium in both the normal and the infarcted heart.

Evidence of carbonic anhydrase activity in skeletal muscle: A role for facilitative carbon dioxide transport

Abstract Carbon dioxide, water and vascular space were measured in the hind limb of the dog, with blood and plasma perfusion, before and after the administration of acetazolamide. Inhibition of carbonic anhydrase by acetazolamide resulted in a decrease in carbon dioxide space from greater than water space to similar to vascular space. This observation is consistent with the presence of carbonic anhydrase in the extravascular compartment. Its presence in this location could act to facilitate carbon dioxide transport.

Acute effect of L-arginine on hemodynamics and vascular capacitance in the canine pacing model of heart failure

Summary: The effect of L-arginine, 250 mg/kg over 10 min, on hemodynamics and venous function was studied in nine splenectomized dogs under light pentobarbital anesthesia before and after 17 × 1 days of rapid right ventricular pacing (RRVP) at 250 beats/min. Chronic RRVP induced mild congestive heart failure with increased mean circulatory filling (Pmcf), right atrial (Pra) and pulmonary capillary wedge pressures (Ppcw), and reduced cardiac output (CO). During the development of heart failure, total vascular compliance assessed from Pmcfblood volume relationships during circulatory arrest was unchanged, but total vascular capacitance was markedly reduced, with an increase in stressed and reduction in unstressed blood volumes. At baseline but not after RRVP, L-arginine increased CO and reduced pulmonary vascular resistance. There were no significant changes in Pra, Ppcw, or total peripheral resistance. L-Arginine failed to alter total vascular compliance and capacitance or central blood volume in the baseline or failure state. These results do not support the hypothesis that increased Pmcf and reduced total vascular capacitance in the early stages of pacing-induced heart failure are caused by reduced substrate availability for or an endogenous competitive antagonist of NO synthase in venous endothelial cells.

Effects of nitroglycerin and nitroprusside on vascular capacitance of anesthetized ganglion-blocked dogs.

Summary: To determine whether changes in vascular capacitance induced by nitroglycerin (NTG) and nitroprusside were due to changes in compliance or unstressed vascular volume, doses producing similar reductions in arterial pressure (Psa) were studied on separate days in six dogs anesthetized and ventilated with pentobarbital after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline blood volumes and after in-creases of 5 and 10 ml/kg. Central blood volumes (CBVs, pulmonary artery to aortic root) were determined from transit times, and separately measured cardiac output (CO) was estimated by thermodilution (right atrium to pulmonary artery). NTG and nitroprusside produced similar reductions in Psa and Pmcf without significantly altering right atrial pressure (Pra), pressure gradient for venous return, or CO. Total vascular compliance was not altered, but total vascular capacitance was increased on an average of 4.0 × 1.4 ml/kg after NTG and 3.0 × 1.3 ml/kg after nitroprusside by increases in unstressed volume. Both drugs caused a variable reduction in CBV, averaging 2 ml/kg. Thus, both drugs produced a large increase in peripheral venous capacitance by increasing unstressed vascular volume without altering total vascular compliance.

The effect of acetazolamide on myocardial carbon dioxide space.

Carbon dioxide, water and vascular space were measured in the heart muscle of the dog before and after the administration of acetazolamide. In contrast to the skeletal muscle whose CO2 space was markedly reduced by acetazolamide, cardiac muscle CO2 space was only minimally reduced. This suggests that cardiac muscle does not have extravascular carbonic anhydrase. Its presence in skeletal muscle and absence in cardiac muscle probably relates to the differences in cell size between the two types of muscle and their differing degree of vascularity.

The effect of carbon dioxide and h+ on canine erythrocyte glycolysis

Incubation of canine erythrocytes in 0.5% CO2, in air or 5% CO2 has no significant effect on glucose utilization if pH is constant. Decreasing pH from 7.7 to 7.2 decreased glucose utilization at a given concentration of CO2. At a given pH decreasing CO2 from 5% to 0.5% increased lactate production. Decreasing pH from 7.7 to 7.3 reduced potassium uptake by erythrocytes and decreasing CO2 from 5% to 0.5% decreased uptake further, so that net output was observed at pH 7.2, CO2 0.5%. These findings are consistent with a pH effect upon glucose utilization probably at the phosphofructokinase step. These data are suggestive of a second control step responsive to CO2 which lies distal to the pH effect. The effect of CO2 on potassium flux probably represents an alteration in erythrocyte energy metabolism with decrease energy availability. Hydrogen ion and CO2 control of erythrocyte metabolism could act to alter haemoglobin affinity for oxygen and carbon dioxide and hence act as a physiologic signal system.

Reversal of hyperventilation induced hyperlactatemia by acetazolamide.

Abstract Acetazolamide administration to hyperventilating dogs was found to both reverse and to prevent the associated hyperlactatemia. This inhibition of glycolysis was associated with a reversal of the hyperventilation induced alkalosis, an increase in PCO2, and an increase in blood CO2 content. A unique effect of these three variables on the control of the glycolytic rate as measured by a rise in arterial lactate concentration could not be identified.

Effect of captopril treatment on total and central vascular capacitance in dogs with chronic heart failure

Summary Chronic rapid right ventricular pacing (RRVP) at 250 beats/min produces low cardiac output (CO) heart failure, marked reduction in total vascular capacitance, and a shift in volume centrally. The effect of converting enzyme inhibition with captopril on cardiac preload was investigated in this model of heart failure. Eight splenec-tomized dogs were treated with captopril (6.4 mg/kg daily) for 3 days before and 35 ± 3 days (mean ± SEM) after continuous RRVP was initiated and the outcome was compared with that of 5 untreated dogs subjected to RRVP for 32 ± 3 days. Similar reductions in systemic arterial pressure (Psa) and CO and increases in right atrial pressure (Pra) and total peripheral resistance (TPR) were noted in both groups, however, pulmonary capillary wedge pressure (Ppcw) was higher in the untreated group (18.4 ± 1.6 vs. 12.1 ± 2.0 mm Hg). Total vascular compliance and capacitance was estimated from mean circulatory filling pressures (Pmcf) at different blood volumes (TBV) during transitory cardiac arrests with acetylcholine (ACh). Pmcf after chronic RRVP was higher in untreated animals (12.6 ± 1.9 vs. 8.4 ± 0.7 mm Hg) and compliance was lower (1.9 ± 0.2 vs. 2.6 ± 0.2 ml/mm Hg/kg). Total vascular capacitance at a Pmcf of 6 mm Hg was lower in untreated animals (50 ± 6 vs. 68 ± 3 ml/kg). Central vascular capacitance was also lower in untreated animals because Ppcw was higher and central blood volume (CBV) as a proportion of TBV was higher (21 ± 3 vs. 15 ± 2%). Four of 5 untreated and 1 of 8 treated dogs had severe ascites. Captopril treatment attenuated the marked reduction in total and central vascular capacitance associated with heart failure during RRVP.

Carbon dioxide mediated glycolysis II

Abstract Prolonged incubation (5 hr) of canine erythrocyte at pH 7.2, or pH 7.7 and PCO2 3.5 or 35 were used to determine the effect of CO2 on glycolysis. The following was observed: 1) an inverse relationship exists between lactate production and CO2. 2) the inhibitory effect of H+ ion on glucose uptake is decreased by prolonged incubation (5 hr compared to 1 hr). 3) carbon dioxide becomes inhibitory for glucose uptake following prolonged incubation. 4) increasing external bicarbonate decreases erythrocyte 2–3 DPG. 5) iodoacetate inhibition of glycolysis reverses the inverse relationship of lactate (pyruvate) to CO2 suggesting that the CO2 sensitive enzyme lies proximal to 1–3 diphosphoglycerate.

The effect of carbonic anhydrase inhibition on the canine in vivo H+PCO2 relationship☆

Abstract The in vivo canine H + -P CO 2 relationship was measured in muscle venous, pulmonary arterial, and arterial blood, at a range of P CO 2 values during hyperventilation, before and following acetazolamide. An increase in slope of the straight line describing this relationship was detected from the muscle venous to the arterial sampling site. Following acetazolamide the muscle venous and pulmonary arterial lines had a similar slope to the unchanged arterial line. The response of the venous lines suggests that carbonic anhydrase plays a significant role in determining the effective in vivo buffering of the venous compartment.