摘要:

We systematically modified isoproterenol's chemical structure to reduce chronotropic, arrhythmogenic, and vascular side effects. Experiments on dogs showed that the resulting drug, dobutamine, had an inotropic efficacy as great as that of epinephrine due to a direct action on β1cardiac receptors. However, unlike epinephrine, dobutamine's effect on α and β2vascular receptors was slight. At equivalent inotropic doses, dobutamine had less than a fourth of the chronotropic effect of isoproterenol. Desmethyl-imipramine (DMI), which blocks the sympathetic nerve fiber uptake mechanism, had no effect on dobutamine's actions. In contrast, DMI antagonized dopamine's inotropic effect, and marked chronotropic and pressor responses occurred when we used doses of dopamine large enough to elicit a direct inotropic effect. Dobutamine increased the contractility of isolated cat papillary muscles more but the automaticity less than did isoproterenol. In ischemic dog hearts, dobutamine lacked significant arrhythmic activity, whereas dopamine, norepinephrine, and isoproterenol caused severe ectopic activity. In dogs with experimentally induced low cardiac contractility, low cardiac output, and hypotension, dobutamine produced dose-related increases in cardiac contractility and output, restored arterial blood pressure, and reduced total peripheral resistance slightly. In contrast, isoproterenol failed to restore blood pressure, had only a meager effect on cardiac contractility and output, caused extreme tachycardia, and lowered peripheral resistance more than did dobutamine. Norepinephrine, which did not increase cardiac contractility or output as much as dobutamine, excessively elevated peripheral resistance and arterial blood pressure.

ISSN:0009-7330    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

The changes in renal function produced by endogenous synthesis qf prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the precursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions of preformed prostaglandin (PG) E2and F2a.PGE2given at 0.01–0.3 μg/kg min−1produced dose-related increases in urine flow, sodium and potassium excretion, free water clearance, and renal blood flow. The glomerular filtration rate increased only at the lowest dose and the calculated filtration fraction fell. Arachidonic acid at 1.0–30.0 μg/kg min−1similarly produced dose-related increases in electrolyte excretion, but the increase in renal blood flow was much less than that produced by PGE2and there were no changes in glomerular filtration rate, filtration fraction, or free water clearances. PGF2αhad essentially no effects at infusion rates of 0.03-1.0 μg/kg min−1. All renal effects of arachidonic acid were inhibited by simultaneous infusions of an inhibitor of prostaglandin synthetase, 5, 8, 11, 14-eicosatetraynoic acid (20:4). None of the effects produced by PGE2were inhibited by 20:4. These results indicate that enhanced endogenous renal prostaglandin synthesis, which can be produced by arachidonate infusion, results in significant alterations of renal function. This finding strengthens the hypothesis that renal prostaglandins formed in vivo have physiological importance as regulators of renal function.

ISSN:0009-7330    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

The effects of enhanced endogenous production of prostaglandins by the kidney on the distribution of blood flow in the renal cortex were assessed by infusing sodium arachidonate, the precursor of the renal prostaglandins, into one renal artery of the dog. The changes produced with arachidonate (3 × 10−6g/kg min−1and 10−5g/kg min−1) were compared with those produced by infusions of prostaglandin (PG) E2(10−7g/kg min−1) and PGF2α(3 × 10−7g/kg min−1) into one renal artery. Distribution of renal blood flow was measured by the radioactive microsphere technique. Sodium arachidonate caused an increase in blood flow to the inner cortical zones with no change in flow to the nephrons in the outermost quarter of the cortex. PGE2increased flow to all cortical zones, and PGF2αproduced no change in flow. Since arterial blood pressure did not change, changes in vascular resistance were reciprocal to changes in flow. Thus, vascular resistance fell in the inner cortical regions but not in the outer regions, with arachidonate infusions and in all regions of the cortex with PGE2infusions; no changes were seen with PGF2αinfusions. These data indicate that prostaglandin formed endogenously in the kidney affects the vascular resistance of only the inner cortical nephrons; the data thus support the hypothesis that renal prostaglandins are one mediator of renal autoregulation of blood flow.

ISSN:0009-7330    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

The effect of thyroid state on the activity of myosin adenosinetriphosphatase (ATPase) was examined in the rat and the rabbit. Cardiac myosin from thyroxine-treated rabbits showed enzymatic properties characterized by high Ca2+-activated ATPase activity, low activating energy, lower rate of inactivation at alkaline pH, and no activation by Af-ethylmaleimide compared with the same properties in the normal rabbit; thyroidectomy did not affect the enzymatic properties of rabbit cardiac myosin. These findings suggest a difference in the myosin molecule at or near the active site, involving some sulfhydryl groups, between hyperthyroid and euthyroid rabbits. However, rat cardiac myosin showed a pattern of activity in the euthyroid state similar to that of the hyperthyroid rabbit and changed to the euthyroid type after thyroidectomy. These changes were specific for cardiac myosin, since no change was observed in skeletal myosin. It is unlikely that there are major differences in the myosin molecule associated with the two types of activity, since similar proportion and amino acid composition of the subunits of cardiac myosin were observed in the different thyroid states. Thus, we concluded that the administration of thyroxine to the rabbit stimulates the synthesis of new cardiac myosin with altered enzymatic properties and that synthesis of this type of cardiac myosin is maintained by the normal level of thyroid hormone in the rat.

ISSN:0009-7330    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

We studied the renal function and the intrarenal blood flow of nine dogs whose thoracic inferior vena cava had been previously ligated (caval dogs) and nine other dogs. Following preparative surgery which included placement of a left atrial catheter, a femoral artery catheter, and bilateral ureteral catheters, the caval dogs gained an average of 2.1 kg of fluid weight, whereas the normal dogs gained no weight. Although neither the caval dogs' blood pressure (114 ± 7 vs. 120 ± 4 mm Hg) nor their inulin clearance (0.64 ± 0.06 vs. 0.79 ± 0.06 ml/min g−1kidney weight) was significantly reduced, their estimated renal blood flow (CPAM/[1-hematocrit]) was considerably lower (2.30 ± 0.24 vs. 3.25 ± 0.15 ml/min g−1). During the clearance study, the caval dogs' excretion of sodium (79 ± 18 vs. 158 ± 17 μEq/min) and their fractional clearance of sodium (2.0 ± 0.4 vs. 3.4 ± 0.5%) were reduced. Studies with microspheres failed to demonstrate a selective decrease in blood flow. However, comparison studies of nine other dogs (five caval and four normal) demonstrated that microsphere results were less reproducible in caval dogs than they were in normal dogs. We have concluded that reduced blood flow is the only consistent alteration of renal function in this edematous animal model and that previous suggestions of altered distribution are not supported by these studies.

ISSN:0009-7330    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

Quantification of the permeability of connective tissue linings isolated from implanted capsules was achieved by two types of experiments. The objective of the first type was to determine the restriction offered by the lining to diffusion ofl25I-labeled human serum albumin. The restricted diffusion coefficient of albumin with respect to the connective tissue lining the luminal capsule surface (internal lining) averaged 3.0 × 10−7± 0.4 × 10−7cmVsec in ten experiments indicating that the rate of migration of albumin across the structure was 35% of its free diffusion rate in water. In contrast, the albumin diffusion coefficient obtained for the abluminal (external) lining suggested that diffusion of albumin through this structure was 73% of the free diffusion rate in water. The objective of the second type of experiment was to determine solute reflection coefficients for inulin, serum albumin, and γ-globulin with respect to the internal and external linings. For the internal lining, the reflection coefficients were: inulin 0.07, albumin 0.23, and γ-globulin 0.53. The external lining showed greater leakiness as evidenced by its lower reflection coefficient for a given molecule and its higher hydraulic conductivity. An equivalent pore calculation resulted in a calculated pore radius of 250–350 Å for the internal lining and a calculated pore radius of 500–600 Å for the external lining. The ineffectiveness of the leaky capsule lining in transmitting oncotic pressure suggests that under normal conditions the capsule measures interstitial hydrostatic pressure rather than oncotic pressure.

ISSN:0009-7330    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

We investigated the accuracy and the sensitivity of a modification of the acetylene inhalation technique for the determination of lung tissue volume (Vt) during various grades of hemodynamic pulmonary edema in 23 dogs. After base-line acetylene measurements were obtained, intravascular driving force (pulmonary wedge pressure minus intravascular colloid osmotic pressure) was varied between −8 and +17 mm Hg by the inflation of an intra-aortic balloon and the infusion of isotonic saline. After 30 minutes at this new driving force, four timed acetylene samples were again collected. Vt (when factored by alveolar volume, VA) increased from base line to 0.23 ± 0.07 ml/ml between a driving force of 0 and + 17 mm Hg. This same change in Vt/VAwas accompanied by an increase in the lung wet weight-dry weight ratio from 3.84 ± 0.31 to 5.2 ± 0.25. Vt was 271 ± 57 ml compared with an actual lung wet weight of 288 ± 57 g; Vt tended to overestimate lung wet weight in severe pulmonary edema. Alloxan-induced pulmonary edema (6 dogs) tended to parallel these data. We conclude that the acetylene method may be a relatively accurate noninvasive method for the determination of increasing lung water in pulmonary edema.

ISSN:0009-7330    

出版商:OVID    

年代:1975

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1975

数据来源: OVID