Gerald A. Klassen

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.

Blood Flow and Tissue Space of the Left Coronary Artery in Man

Using a constant infusion of two indicators, T-1824 bound to albumin and tritiated water, flow and transit time were measured in the left coronary system of intact man. Indicators were infused for 6 minutes into the left coronary artery with sampling from the coronary sinus in a region that drained exclusively the inflow of the left coronary artery and from the brachial artery for recirculation. The degree of heterogeneity of myocardial perfusion could be defined by the time required for the curve to reach a plateau. A correlation coefficient of 0.966 was found between the two indicator-measured blood flows. The average myocardial hematocrit was calculated and found to be similar to the arterial. In the presence of myocardial disease, total flow of the left coronary artery was increased. When this was divided by tissue volume, the blood flow per unit volume of tissue was decreased in the presence of the idiopathic cardiomyopathy.

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.

Myocardial tissue recruitment in the dog as determined by double tracer dilution method.

The amount of tissue perfused, as determined from the difference in volume of distribution between a diffusible indicator (123I-antipyrine) and an intravascular indicator (121I-albumin) was measured at different values of coronary flow, perfusion pressure, and vasomotor tone in The working left rentride of an open-chest dog. Coronary pressure and flow were regulated independently from The systemic circulation and coronary vasomotor tone was reduced by dipyridamole. At each flow vasomotor tone was assessed by using as a reference The maximal vasodilatton induced by arrest of flow. Measured tissue space was considered to be related to The capillary surface area available for tracer diffusion and therefore to The number of perfused capillaries per volume of muscle. A relationship between coronary blood flow and tissue volume was observed. It was found to be independent of vasomotor tone. Vasodilation was found to increase available exchanging capillary surface at a constant perfusion pressure.

Myocardial Blood Flow

It is generally agreed that coronary inflow is mainly diastolic and coronary sinus outflow mainly systolic (Gregg, 1962). To locate this phase shift, phasic red cell velocity and diameters of coronary arterioles, capillaries, and venules were measured in the beating turtle and dog heart using high-speed cinematography (400 frames/s) with transillumination of the left ventricle. A 20-gauge needle, containing a small quartz rod and a mirror angled at 45°, was inserted underneath the superficial layer of the myocardium to transmit heat-filtered light from a pulsating xenon arc through the ventricular muscle toward the objective of an infinitycorrected microscope. In recent experiments, a floating, counterbalanced focus keeper was used to maintain the focal distance between the moving heart and the stationary objective of the microscope. Red cell velocity was determined by frame-to-frame analysis of red cell progression using a reference scale (Tillich et al., 1971; Bing et al., 1972)

The effects of partial chronic denervation on forearm metabolism.

Effects of chronic denervation upon in vivo forearm metabolism were studied in six patients and six controls. The diagnosis was amyotrophic lateral sclerosis in four patients, the neuronal form of Charcot-Marie Tooth disease in one patient, and an unclassified chronic disease of the lower motor neurons in one patient. In all cases the forearm muscles showed clinical weakness and electrical evidence of denervation, while muscle biopsy from a proximal muscle of the upper limb showed typical denervation atrophy. At rest there was increased oxygen utilization and lactate output as well as a tendency for increased uptake of glucose and long chain fatty acids from arterial blood per 100 ml of forearm tissue. During exercise the abnormally high lactate output increased further. An increased arterial lactate concentration was present during rest and exercise. Oxidation of fatty acids was not impaired. It is suggested that these abnormalities are consistent with an augmented utilization of blood borne fuels at rest by denervated muscles. A concurrent regional ischemia of muscles during rest and exercise, possibly due to defective autoregulation of skeletal muscle blood flow, may explain the abnormally high lactate generation.

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.

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.