bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence against local neural mechanism for intestinal postprandial hyperemia
Authors: Nyhof R. A. , Chou C. C.
Published: December 2017

The role of local intestinal nerves in the nutrient-induced intestinal hyperemia was investigated in jejunal segments of anesthetized dogs by comparing the hyperemic effect of intraluminal glucose and oleic acid solutions before and after mucosal anesthesia and infusions of methysergide, hexamethonium, and tetrodotoxin. Methysergide, hexamethonium, and tetrodotoxin all failed to alter either the vascular or metabolic responses to luminal placement of glucose or oleic acid. The increases in blood flow and oxygen uptake produced by glucose or oleic acid, however, were blocked or attenuated after exposing the mucosa to dibucaine. The effect was norepinephrine due to an altered vascular response to vasoactive substances as dibucaine did not alter vascular responses to isoproterenol or norepinephrine. Dibucaine, however, inhibited active transport and increased passive transport of glucose across rat intestinal sacs in vitro. Oxygen consumption of the canine jejunal mucosa was also inhibited by dibucaine in vitro. It seems that inhibition of the nutrient-induced intestinal hyperemia by dibucaine is due, at least in part, to its effect on oxygen consumption and glucose transport of the mucosal epithelial cells. Nutrient-induced hyperemia appears not to be neurally mediated but more closely related to metabolism.
Adenosine reduces catecholamine contractile responses in oxygenated and hypoxic atria
Authors: Dobson J. G.
Published: December 2017

The properties of adenosine attenuation of catecholamine-elicited increases in peak contractile force, rate of force development, and rate of relaxation were studied in isolated rat atria. Adenosine, at a concentration that did not cause a direct depressant effect by itself, was capable of reducing by approximately 15% the increase in the contractile parameters elicited by isoproterenol. This reduction was not overcome by elevating the catecholamine concentration. The adenosine reduction was prevented by theophylline or the presence of adenosine deaminase. The reduction appears to be independent of the acetylcholine-mediated reduction of catecholamine responses. Adenosine reduced the positive inotropic responses elicited by norepinephrine and epinephrine but not phenylephrine. Adenosine deaminase in oxygenated atria potentiated the catecholamine-elicited contractile responses and reduced the progressive fall of the elevated contractile responses observed with continual catecholamine stimulation. In hypoxic atria adenosine deaminase potentiated the positive inotropic responses observed with catecholamine stimulation. The results suggest that an adenosine-specific mechanism is capable of attenuating the elevation in contractility elicited by beta-adrenergic stimulation. In addition, endogenous adenosine may be responsible, in part, for the reduction of catecholamine-mediated contractile responses in oxygenated and hypoxic myocardial tissue.
Modification of lymph during passage through the lymph node: effect of histamine
Authors: Maron M. B.
Published: December 2017

The possibility that histamine may cause the fluid and protein content of lymph to be altered during passage through the lymph node was evaluated using the canine perfused popliteal lymph node preparation. This preparation enables nodal perfusion via an afferent lymphatic (all other afferents are ligated) with artificial lymph of known composition and collection of the total efferent effluent for analysis of potential changes in volume and composition. In 11 dogs, the node was perfused at an average flow rate of 0.229 ml/min with artificial lymph containing 3.71 g/100 ml albumin. Under base-line conditions, there was no significant modification of the lymph as it passed through the node. The addition of histamine to the infusate (2-4 micrograms base/ml) caused the efferent lymph flow to increase to 0.295 ml/min (35.3% increases, P less than 0.05), the efferent protein concentration to increase to 4.32 g/100 ml (15.2% increases, P less than 0.05), and the efferent protein flux to increase from 8.40 to 12.86 mg/min (58.0% increases, P less than 0.05). The appearance of Evans blue dye-tagged protein and plasma protein fractions, not originally present in the lymph, in the efferent lymph at this time further indicated that the source of the added fluid and protein was the nodal vasculature. Mass balance calculations indicated that the addition of a fluid with a protein concentration of approximately 90% that of plasma to the lymph could account for the observed increases in efferent lymph flow and protein concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial adaptations to endurance exercise in aged rats
Authors: Starnes J. W. , Beyer R. E. , Edington D. W.
Published: December 2017

Isolated perfused working hearts of 25-mo-old male Sprague-Dawley rats trained to run for 16 wk were compared with hearts from 9- and 25-mo-old sedentary animals. Under low work load conditions, systolic and diastolic aortic pressures, aortic flow, and oxygen consumption of the three groups were similar. Under high work load, systolic pressure of trained old and 9-mo groups were higher than the 25-mo sedentary values, but diastolic pressures were similar. At a systolic pressure of 150 mmHg, coronary flow of the old trained heart was higher than that of the age-matched controls, although not equal to the 9-mo sedentary group. The oxygen consumption of the intact hearts under the latter conditions follows the same quantitative trend. Left ventricular cytochrome c concentrations and rates of oxidation of glutamate-malate, palmitoylcarnitine, and succinate were increased in the older rats by training but not to the level of the 9-mo old. These data indicate that appropriate exercise in aged animals improves myocardial function and aerobic energy metabolism.
Splanchnic and renal contributions to circulatory homeostasis in sodium depletion
Authors: Echtenkamp S. F. , Davis J. O. , Freeman R. H. , Dietz J. R. , Villarreal D.
Published: December 2017

Chronic sodium depletion is a state of reduced cardiac output in which the renin-angiotensin system is actively involved in maintenance of mean arterial blood pressure (MAP). Angiotensin II (ANG II) blockade with saralasin is known to produce renal vasodilation and a decrease in MAP in the sodium-deplete dog. In this study conscious trained dogs with chronic indwelling catheters were sodium depleted with diuretics plus a low sodium diet. Hepatic blood flow (HBF) and renal blood flow (RBF) were determined concurrently by the clearances of bromosulfophthalein and p-aminohippurate, respectively. When compared with the sodium-repleted state, the depleted dogs had reduced HBF with no change in MAP or RBF. In addition, the hepatic renin clearance and percent hepatic renin extraction were reduced. When saralasin was given intravenously to the depleted dogs, the response was a decrease in MAP with a concurrent decrease in both renal and splanchnic vascular resistances. The increased plasma renin activity during saralasin was accompanied by increased hepatic renin extraction but no significant rise in hepatic renin clearance. Saralasin also resulted in a large decrease in the urinary excretion of prostaglandin E2. This study provides evidence that increased plasma ANG II levels are responsible for the increased splanchnic vascular resistance during chronic sodium depletion.
Rabbit aortic medial thickness under relaxed and specified simulated in vivo conditions
Authors: Schneiderman G. , Pritchard W. F. , Ramirez C. A. , Colton C. K. , Smith K. A. , Stemerman M. B.
Published: December 2017

A method is presented for measuring the thickness of the intima-media layer of the normal rabbit descending thoracic aortic wall under both relaxed (excised) and specified simulated in vivo conditions. The in vivo conditions were simulated by maintaining the aorta in situ at its normal longitudinal extension while perfusing its lumen at the normal mean arterial pressure with a mixture of liquid silicone polymer and a catalyst, thus providing physiological radial distension. After the rubber cured, both relaxed and extended-distended tissue segments were obtained from adjacent sites on the same aorta. These tissue segments were fixed and further processed for measurement of their medial thicknesses by light microscopy. This data was used to estimate the ratio of the medial thickness of the relaxed, excised aorta to that under in vivo conditions, 1.72 +/- 0.15. This information is required for quantitative analysis of data obtained from previous studies of in vivo macromolecular transport across the rabbit thoracic aortic wall.
Thermodilution method overestimates low cardiac output in humans
Authors: van Grondelle A. , Ditchey R. V. , Groves B. M. , Wagner W. W. , Reeves J. T.
Published: December 2017

We compared 57 cardiac output measurements by the thermodilution and Fick methods in 26 patients and found that thermodilution values were higher in all 16 cases in which Fick outputs were less than 3.5 l/min. In 10 cases where Fick values were less than or equal to 2.5 l/min, thermodilution and Fick measurements differed by an average of 35%. When combined with the results of previous studies comparing the thermodilution, dye dilution, and Fick techniques, these findings suggest that the thermodilution method overestimates true cardiac output in the low output range. This overestimation probably is due to heat loss under conditions of low flow. Because the thermodilution method is used widely in patients with low output states, these findings have potentially important clinical implications.
Effects of catecholamines on cardiac chronotropic response to vagal stimulation in the dog
Authors: Chassaing C. , Duchene-Marullaz P. , Veyrac M. J.
Published: December 2017

The influence of isoproterenol, norepinephrine, and dopamine on the cardiomoderator effects of moderate vagal stimulation was studied in anesthetized dogs. The drugs were administered at increasing doses in successive perfusions. Stimulation of the vagus nerve, the parameters of which remained constant throughout each experiment, was performed immediately before each sequence of perfusion and after 10-min perfusion. Isoproterenol at 0.025, 0.05, 0.1, and 0.2 microgram X kg-1 X min-1 raised heart rate dose relatedly but did not alter heart rate under vagal stimulation. Thus the amplitude of vagal bradycardic effects increased dose relatedly. Norepinephrine at 0.125, 0.25, 0.5, and 1 microgram X kg-1 X min-1 lowered heart rate through reflex hypertension. Heart rate under vagal stimulation remained constant. Thus the effects of vagal stimulation decreased as dose increased, finally becoming null. Dopamine at 0.5, 1, 2.5, and 5 micrograms X kg-1 X min-1 did not significantly alter heart rate, but at 10 and 20 micrograms X kg-1 X min-1, like norepinephrine, it raised blood pressure, causing a reflex fall in heart rate. At all doses, heart rate under vagal stimulation remained stable. Consequently, at the highest doses, the net effects of vagal stimulation were slight. These results suggest the simultaneous involvement of sympathetic-parasympathetic interactions both post- and prejunctionally. In the latter case, different mechanisms of regulation of neurotransmitter release are involved during vagal stimulation according to the sympathomimetic used. With isoproterenol, norepinephrine release seems more particularly affected, whereas with norepinephrine and dopamine, acetylcholine release is apparently inhibited.
Regional circumferential lengthening patterns in canine left ventricle
Authors: Lew W. Y. , LeWinter M. M.
Published: December 2017

We employed sonomicrometers in open-chest dogs to study lengthening of short segments of circumferentially oriented myocardium located at the base, midportion, and apex of the anterior left ventricular free wall. Left ventricular pressure was varied by inferior vena caval occlusion and volume expansion. Diastole was divided into rapid and slow lengthening phases. Rapid lengthening was completed first at the basal site at each of three successive levels of left ventricular diastolic pressure (LVDP). At the base, significant further lengthening occurred during the slow lengthening phase while at the apex virtually all lengthening was completed during the rapid phase. At low LVDPs, peak lengthening rates (dl/dt) were greatest at the apex. As LVDP was increased, regional differences in dl/dt diminished. These results indicate that there is regional variation in the timing of the phases of diastole and in lengthening patterns of the left ventricle. The volume-dependent variation in lengthening rates that we observed is consistent with the concept of regional differences in elastic recoil, which may contribute to active ventricular filling.
Arteriolar responses to elevation of venous and arterial pressures in cat mesentery
Authors: Burrows M. E. , Johnson P. C.
Published: December 2017

These studies were undertaken to determine the importance of metabolic (flow-dependent) and myogenic (pressure-dependent) factors in the response of arterioles to changes in intravascular pressure. The response of 26 arterioles in the isolated cat mesentery to increased venous and arterial pressure was studied by measuring changes of arteriolar diameter, red blood cell velocity, and intravascular pressure. Circumferential wall tension and volume flow in the arterioles were calculated. The fraction of the arteriolar responses to intravascular pressure elevation that could be attributed only to a myogenic response in which wall tension is regulated varied from 20 to 56%, depending on the method of pressure elevation. The largest fraction of the response attributable to a myogenic mechanism (ignoring the contributions of flow) varied from 50 to 93%. The fraction of the responses attributable only to flow dependency varied from 0 to 23%, whereas the largest fraction attributable to this mechanism varied from 18 to 73%, depending on the method of pressure elevation. It is concluded that, in cat mesentery, both metabolic and myogenic mechanisms appear to contribute to local regulation of flow with elevation of intravascular pressure, but other factors cannot be excluded.
Enhanced sensitivity of diabetic hearts to alpha-adrenoceptor stimulation
Authors: Downing S. E. , Lee J. C. , Fripp R. R.
Published: December 2017

Inotropic responses to alpha-adrenergic stimulation with methoxamine were compared in 12 normal (N) and 12 diabetic (Db) lambs. Diabetes was produced by giving alloxan monohydrate (150 mg/kg iv). Measurements of maximal rate of rise of left ventricular pressure (dP/dtmax), left ventricular end-diastolic pressure (LVEDP), coronary flow, and myocardial O2 consumption were made simultaneously in hemodynamically controlled preparations. All animals were subjected to ganglionic blockade (tetraethylammonium chloride, 100 mg) and beta1-adrenergic blockade (practolol, 4 mg/kg). Methoxamine was given in incremental doses ranging from 0.4 to 6.0 mg/kg. dP/dtmax increased progressively to 126 +/- 4% of initial values in N. However, the increase was twice as large (150 +/- 4%) in the diabetics (P less than 0.005). LVEDP fell in both groups. These changes were abolished by phentolamine (2 mg/kg). Inotropic responses to methoxamine in lambs 2 and 3 wk after induction of diabetes did not differ from those with acute (2 days) diabetes. Dose-response curves obtained by infusing Ca2+ (2-8 mg X min-1 X kg-1) were identical in N and Db. It is concluded that lamb myocardium possesses an alpha-adrenergic receptor system that is stimulated by methoxamine in a dose-dependent manner and blocked by phentolamine. Db hearts are supersensitive to alpha-receptor activation. The mechanistic basis for this latter finding has not been examined but may relate to altered receptor density or nucleotide regulation.
Isolated myocytes from adult canine left ventricle: Ca2+ tolerance, electrophysiology, and ultrastructure
Authors: Hewett K. , Legato M. J. , Danilo P. , Robinson R. B.
Published: December 2017

We have developed a method for isolating single cardiac muscle cells in high yield (greater than 5 X 10(7) cells) from the canine left ventricle. Most of the myocytes are single cells with ultrastructural detail indistinguishable from intact ventricular myocardium, and more than 50% of the isolated cells remain elongated for at least 7 h in 0.5 mM calcium. Electrophysiological studies demonstrate that external potassium has a strong influence on repolarization in the isolated ventricular cells. Action potentials in [K+]o = 3.78 mM exhibit a positive over-shoot (greater than zero potential), but repolarization often arrests at congruent to -35 mV unless driven to more negative potentials by hyperpolarizing current. This phenomenon of two levels of resting potential is not observed at [K+]o = 5.78 mM. At the higher potassium concentration, values for maximum diastolic potential, amplitude, maximum rate of rise of phase 0, and action potential duration all are similar to those of intact ventricular muscle. However, the potential at the peak of the action potential plateau (phase 2) in the isolated myocyte is considerably more negative than that of intact myocardium. In addition, there is a conspicuous notch between phases 1 and 2 of the action potential in the isolated myocyte, whereas the notch is small or absent in intact myocardial action potentials. In summary, our method results in a preparation of stable, ultrastructurally and electrophysiologically intact cells, which should prove useful in studies requiring a large and homogeneous population of myocardial cells.
Physiological and metabolic characterization of a cardiomyopathy induced by chronic copper deficiency
Authors: Kopp S. J. , Klevay L. M. , Feliksik J. M.
Published: December 2017

Male weanling rats were made copper deficient with a purified diet containing all known essential dietary nutrients except copper. Copper deficiency was verified by indirect (anemia, growth retardation, hypercholesterolemia, gross pathology, and abnormal electrocardiograms) and direct (tissue copper analysis) criteria. His bundle electrographic and electrocardiographic changes detected in the copper-deficient group consisted most notably of depressed His-Purkinje system conductivity and S-T segment depression. Phosphorus-31 nuclear magnetic resonance spectroscopic analysis of cardiac, renal, and hepatic tissue perchloric acid extracts revealed significant metabolic changes associated with the dietary copper deficiency, including a generalized marked decrease in ATP and phosphocreatine levels and a corresponding increase in inorganic orthophosphate and ADP levels in the various tissues. Tissue-specific changes consisting of elevated ribose 5-phosphate (heart), phosphocholine (heart), and inosine monophosphate (kidney) and decreased glycerol 3-phosphorylethanolamine (liver) and glycerol 3-phosphorylcholine (liver) levels were detected in copper-deficient rats. Microscopic examination of heart tissue from copper-deficient rats revealed extensive disruption of mitochondrial fine structure, including fragmentation of cristae and inner and outer mitochondrial membranes, which resulted in pronounced vacuolization throughout the tissue. Although the physiological and metabolic disturbances manifested in hearts from copper-deficient animals generally mimic myocardial responses to chronic ischemia, the observed changes are interpreted in a broader context to represent the appearance of a copper-dependent cardiomyopathy.
Effects of ribose on cardiac metabolism and function in isoproterenol-treated rats
Authors: Zimmer H. G. , Ibel H.
Published: December 2017

Continuous iv infusion of ribose for 5 h in unanesthetized and unrestrained rats treated with isoproterenol (25 mg/kg sc) further enhanced the available pool of 5-phosphoribosyl-1-pyrophosphate and the biosynthesis of adenine nucleotides in the myocardium. The increase in adenine nucleotide biosynthesis was of such an extent that the isoproterenol-induced decline of the ATP level (mumol/g) was attenuated after 5 h (isoproterenol + ribose infusion 4.0 +/- 0.2, n = 10; isoproterenol + NaCl infusion 3.5 +/- 0.1, n = 23; control 4.5 + 0.1, n = 38) and prevented after 24 h (isoproterenol + ribose infusion 4.6 +/- 0.3, n = 5; isoproterenol + NaCl infusion 3.2 +/- 0.1, n = 9). Ribose, however, did not affect the isoproterenol-elicited elevation of the adenosine 3',5'-cyclic monophosphate (cAMP) and glucose 6-phosphate content nor did it influence the decline in glycogen. Thus ribose acts primarily via elevation of the cardiac 5-phosphoribosyl-1-pyrophosphate pool. Measurements of hemodynamic parameters with an ultraminiature catheter pressure transducer in intact rats anesthetized with thiobutabarbital sodium revealed that ribose infusion for at least 3 h further enhanced the isoproterenol-elicited increase in left ventricular dP/dtmax by about 20% but did not influence appreciably the rise in heart rate and the fall in left ventricular systolic pressure. Since ribose did not affect the immediate hemodynamic alterations induced by isoproterenol, it appears that it exerts its hemodynamic effects via the pronounced influence on cardiac adenine nucleotide metabolism.
Doppler measurement of myocardial thickening with a single epicardial transducer
Authors: Hartley C. J. , Latson L. A. , Michael L. H. , Seidel C. L. , Lewis R. M. , Entman M. L.
Published: December 2017

To eliminate the need for intramyocardial transducers in measuring regional left ventricular (LV) function we have developed a pulsed Doppler technique utilizing a single epicardial transducer. Wall thickening is evaluated by digitally integrating the velocity of myocardial layers passing through the sample volume located at a selected depth. Thickening fraction (TF) can then be estimated by dividing the systolic excursion by the sample volume depth. The Doppler method was compared with the transit-time method in three acute dogs by placing the 4-mm-diameter epicardial Doppler transducer over a 2-mm-diameter endocardial crystal tunneled through the LV wall. With the sample volume set to 1 mm less than the minimum LV thickness, simultaneous measurements of TF by the Doppler and transit-time methods showed good agreement (r = 0.95) during control, ischemia, volume overload, shock, and anoxia. In 28 chronically instrumented piglets signals were obtained for longer periods with Doppler transducers than with transit-time segment-length crystals. We conclude that the Doppler technique provides a high-fidelity wall thickening waveform and a good estimate of TF with minimal disturbance to the ventricle and that the technique is suitable for use in both acute and chronically instrumented animals.
5-Hydroxytryptamine can mediate endothelium-dependent relaxation of coronary arteries
Authors: Cohen R. A. , Shepherd J. T. , Vanhoutte P. M.
Published: December 2017

5-Hydroxytryptamine caused contractions of isolated canine coronary artery rings. These contractions were larger in the absence of the endothelium, whereas those caused by phenylephrine, potassium chloride, and prostaglandin F2 alpha were not. When coronary arteries were contracted with prostaglandin F2 alpha, 5-hydroxytryptamine caused relaxation in some rings with endothelium but only further contraction in all rings without endothelium. The inhibitory action of 5-hydroxytryptamine mediated by the endothelium was unaffected by blockade of monoamine oxidase or cyclooxygenase. In rings with endothelium, aggregating platelets, which released 5-hydroxytryptamine and thromboxane A2, caused relaxation. The relaxations caused by 5-hydroxytryptamine and aggregating platelets were antagonized by methysergide but not by ketanserin. These observations suggest that the response to 5-hydroxytryptamine is the net result of a direct contractile action on coronary smooth muscle and an inhibitory action mediated by the endothelium. In some vessels the endothelium-dependent inhibitory responses to aggregating platelets may be mediated in part by released 5-hydroxytryptamine. The serotonergic receptors on endothelial cells may be of a different subtype than those mediating contractions of the smooth muscle cells.
Heterogeneity in the response to dopamine of monkey cerebral and peripheral arteries
Authors: Toda N.
Published: December 2017

In helical strips of monkey cerebral and mesenteric arteries contracted with prostaglandin F2 alpha, dopamine in low concentrations produced a moderate relaxation but in high concentrations produced a contraction from the level of relaxation. On the other hand, coronary, renal, and femoral arterial strips responded to dopamine with only a concentration-dependent contraction. Treatment with phenoxybenzamine or phentolamine potentiated the dopamine-induced relaxation seen in cerebral and mesenteric arteries and reversed the contraction in the other arteries to a relaxation. After treatment with phenoxybenzamine, relaxant responses to dopamine of cerebral, mesenteric, and renal arteries were almost identical, and, compared with those, the responses of coronary and femoral arteries were appreciably less. Relaxations induced by dopamine were not influenced by propranolol, atropine, aminophylline, cimetidine, and aspirin but were markedly attenuated by droperidol. Adenosine-induced relaxations were not affected by droperidol. It is concluded that dopamine preferentially relaxes monkey cerebral and mesenteric arteries, possibly via dopaminergic receptors. It appears that the dopamine-induced contractions mediated by alpha-adrenoceptors predominate over the relaxation in coronary, renal, and femoral arteries, and dopaminergic receptor function is greater in cerebral, mesenteric, and renal arteries than in coronary and femoral arteries.
Effects of indomethacin in conscious dogs with experimental high-output heart failure
Authors: Villarreal D. , Davis J. O. , Freeman R. H. , Dietz J. R. , Echtenkamp S. F.
Published: December 2017

The role of renal prostaglandins in the control of renin release and renal hemodynamic function (RHF) was studied in conscious dogs with a surgically created infrarenal aortocaval fistula, a model of high-output heart failure (HOHF). In series 1 during acute cardiac failure, indomethacin administration produced striking reductions in RHF but failed to alter the high level of plasma renin activity (PRA). In series 2, administration of indomethacin to dogs with chronic HOHF also resulted in pronounced decrements in RHF in spite of normal levels of PRA. Studies of individual animals with meclofenamate in both series 1 and 2 confirmed the findings with indomethacin with one exception; in one dog with chronic severe HOHF a very high level of PRA was present initially and fell 44% after meclofenamate. These observations indicate that in the acute and chronic phases of HOHF prostaglandins are involved in the maintenance of renal blood flow and glomerular filtration rate but do not play an essential role in the control of renin release.
Effect of pressure and stirring on in vitro aortic transmural 125I-albumin transport
Authors: Fry D. L.
Published: December 2017

The in vitro transport of 125I-albumin across the endothelial-injured canine aortic preparation was studied as a function of pressure (P) at various locations (z) along the vessel from stirred and quiescent reagents [serum (S) and a comparable albumin (A) reagent] to study mechanisms of vascular protein accumulation. Uptake (M, nmol X cm-2) was calculated from tissue radioactivity and strain-corrected vessel specimen surface area. Corresponding transmural concentration distributions [c(x)] were measured by quantitative microautoradiography. The results showed that 1) M and c(x) increased with P, decreased with z, and were lower from S than from A; 2) changes in M with stirring failed to demonstrate significant concentration gradients in the liquid at the vessel interface even with large uptake rates; 3) the c(x) contours were consistent with simple diffusion and convection in a homogeneous slab; 4) c(x) in the media near the intima increased with P above the assumed equilibrium concentration, suggesting interstitial solute rejection or edema formation with P; and 5) lower c(x) with S than A was consistent with a decreased reagent albumin activity, tissue binding, or tissue hydration.
Vascular effects of arginine vasopressin, angiotensin II, and norepinephrine in adrenal insufficiency
Authors: Ishikawa S. , Schrier R. W.
Published: December 2017

Plasma arginine vasopressin (AVP) levels were 9.6 pg/ml in the mineralocorticoid-deficient rats, a value significantly greater than 4.8 pg/ml in the glucocorticoid-deficient rats (P less than 0.05), and 1.6 pg/ml in controls (P less than 0.001). The AVP antagonist of the vascular effect of AVP, [1(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine] AVP, [d(CH2)5Tyr(Me)AVP] (5 micrograms/kg), decreased mean arterial pressure (MAP) from 76.5 to 71.6 mmHg (P less than 0.01) in mineralocorticoid-deficient rats on day 10 but not in glucocorticoid deficient rats on day 14 (113.2-111.6 mmHg, NS) or in control rats (109.7-110.2 mmHg, NS). Plasma renin activity was 40.7 ng X ml-1 X h-1 in mineralocorticoid-deficient rats and 7.2 in glucocorticoid-deficient rats (P less than 0.001). The angiotensin II antagonist, [Sar1-Gly8]angiotensin II (5 micrograms X kg-1 X min-1), decreased MAP from 69.3 to 53.2 mmHg in mineralocorticoid-deficient rats (P less than 0.001) but not in glucocorticoid-deficient rats. Plasma norepinephrine was 1,138 pg/ml in mineralocorticoid-deficient rats and 251 pg/ml in glucocorticoid-deficient rats (P less than 0.001). The alpha-adrenergic blocker, phenoxybenzamine (3 mg/kg), reduced MAP from 82 to 51 mmHg in mineralocorticoid deficient rats (P less than 0.005), a decrease in MAP greater (P less than 0.05) than that observed in glucocorticoid-deficient rats (107.7-84.8 mmHg, P less than 0.02). In addition, the AVP antagonist caused a greater and more prolonged reduction in MAP in mineralocorticoid-deficient rats after the administration of either the angiotensin II antagonist or alpha-blocker. These results indicate that AVP, norepinephrine, and angiotensin II are involved in maintaining blood pressure in the mineralocorticoid-deficient state.
Mass of left ventricular myocardium estimated with dynamic spatial reconstructor
Authors: Iwasaki T. , Sinak L. J. , Hoffman E. A. , Robb R. A. , Harris L. D. , Bahn R. C. , Ritman E. L.
Published: December 2017

Using the Dynamic Spatial Reconstructor (DSR), a unique multiple X-ray source, high-repetition-rate CAT scanner, we estimated left ventricular (LV) myocardial volume and chamber volume of eight dogs ranging from 2.5 to 32.5 kg. Dogs were given subcutaneous morphine (3 mg/kg) and anesthetized with intravenous pentobarbital sodium (22 mg/kg). A bolus of 1 ml/kg body wt contrast medium was injected into the superior vena cava and 60/s scans repeated over 7 s were performed. Each 0.0167-s scan generated image data for 120 1.8-mm-thick transverse slices, in the dextro and levo phases of the angiograms. Retrospective reformatting of the scan data was used to generate images of thin slices perpendicular to the aortoapical axis of the LV. The LV muscle and chamber volumes were estimated from their outlines in each imaged slice using a manually operated trackball interfaced to a computer. Values of the LV muscle ranged from 18.0 to 146.8 cm3 by DSR and showed a good correlation with the postmortem values (r = 0.99, y = 0.94x + 4.1). Ratios of volume of the myocardium to chamber volume ranged from 1.19 to 3.10.
Enhanced ATP and GTP synthesis from hypoxanthine or inosine after myocardial ischemia
Authors: Harmsen E. , de Tombe P. P. , de Jong J. W. , Achterberg P. W.
Published: December 2017

Increasing therapeutic use is made of purines for the treatment of ischemic heart disease, but little is known about regulatory mechanisms involved. Therefore we perfused isolated rat hearts with 0.02 mmol/l [8-14C]hypoxanthine or inosine. Under normoxic conditions about 1% is taken up by the heart and partially used for synthesis of ATP and GTP at a rate of 0.4 and 0.1 nmol X min-1 X g dry wt-1, respectively. After relatively mild ischemia (coronary flow reduction of 70% for 20 min), no increase in myocardial purine uptake is observed, but ATP and GTP synthesis rates are doubled (P less than 0.001). D-Ribose stimulates the hypoxanthine incorporation rate in normoxic perfused rat hearts to 1.1 and 0.5 nmol X min-1 X g dry wt-1 for ATP and GTP, respectively, which is further increased during postischemic perfusion. About 80% of the [8-14C]inosine or [8-14C]hypoxanthine passes through the heart unchanged, while 15% is converted to (hypo)xanthine and uric acid. We conclude from these experiments that inosine and hypoxanthine incorporation into ATP and GTP is at least partly regulated by the availability of 5-phosphoribosyl-1-pyrophosphate.
Changes in regional blood flow and cardiac output after L-glutamate stimulation of A5 cell group
Authors: Stanek K. A. , Neil J. J. , Sawyer W. B. , Loewy A. D.
Published: December 2017

Changes in regional blood flow and cardiac output were measured by the reference organ method in pentobarbital-anesthetized rats with radioactive microspheres (15 microns) before and after chemical stimulation of the A5 cell group with the excitatory amino acid L-glutamate an agent that excites cell bodies but not fibers of passage. This stimulation caused a decrease in mean arterial pressure, heart rate, cardiac output, and calculated stroke volume. The limb skeletal muscles showed a large increase in blood flow and decrease in vascular resistance, whereas the trunk musculature showed no change in flow or resistance. The blood flow of the entire gastrointestinal tract decreased. Blood flow in the skin decreased with no change in resistance. The cardiac muscle of the ventricles showed a decrease in flow without a change in resistance. The ipsilateral half of the brain showed a decrease in blood flow, while the contralateral side showed no change. The kidneys exhibited no change in blood flow and a decrease in resistance. A5 stimulation in guanethidine-sympathectomized rats caused no change in regional blood flow. In contrast, an increase in cardiac output was observed, and the possible interpretations for this change are discussed. Rats treated with intraventricular injections of 6-hydroxydopamine showed no changes in regional blood flow or cardiac output, indicating that catecholamine neurons are involved in these responses.
Characteristics of reactive hyperemia in the cerebral circulation
Authors: Gourley J. K. , Heistad D. D.
Published: December 2017

Reactive hyperemia has been characterized in many vascular beds, but little is known about quantitative characteristics of reactive hyperemia in the cerebral circulation. We measured velocity of blood flow and pial artery diameter to characterize the time course of reactive hyperemia and used microspheres to study regional blood flow in the brain. Cerebral ischemia was produced by raising intracranial pressure or by arterial occlusion with a cuff around the neck. Five seconds of ischemia produced virtually maximal peak reactive hyperemia, and 30 s of ischemia produced maximal peak reactive hyperemia. During reactive hyperemia after 30 s of cerebral ischemia, there was a three- to fourfold increase in cerebral blood flow. The magnitude of reactive hyperemia was greater in gray matter than in white matter. Minimal resistance during reactive hyperemia, after ischemia produced by arterial occlusion, is similar to minimal resistance during seizures or hypercapnia, which suggests that reactive hyperemia produces maximal vasodilatation. Oxygen saturation of cerebral venous blood increased almost twofold during reactive hyperemia, which indicates that factors in addition to venous (and presumably tissue) oxygen are important determinants of reactive hyperemia. In summary, 1) we have characterized the time course of reactive hyperemia in the cerebral circulation; 2) reactive hyperemia after arterial occlusion produces maximal cerebral vasodilatation; and 3) there is marked heterogeneity of the response, with much larger increases in flow in cortical gray matter than white matter.
Effect of histamine and propranolol on extravascular lung water
Authors: Schwartz J. S. , Konopka R. G. , Spragg R. G.
Published: December 2017

The ability of an intravenous infusion of 21 micrograms X kg-1 X min-1 histamine diphosphate to cause pulmonary edema was studied in dogs in which beta-blockade either was or was not in effect, since current evidence suggests that beta-blockade can prevent catecholamines from antagonizing the vascular permeability effect of histamine in the systemic circulation. Mixed venous histamine levels ranging from 140 to 580 ng/ml were achieved; norepinephrine and epinephrine levels increased significantly, although in animals receiving propranolol, heart rate remained depressed. Neither lung wet weight-to dry weight ratio nor extravascular lung water increased in animals receiving histamine or histamine and propranolol. We conclude that the inability of histamine to produce substantial pulmonary edema cannot be explained on the basis of catecholamine stimulation of beta-adrenergic receptors within the lung.
Mechanical restitution of isolated perfused canine left ventricles
Authors: Burkhoff D. , Yue D. T. , Franz M. R. , Hunter W. C. , Sagawa K.
Published: December 2017

We measured cardiac mechanical restitution curves, which describe the time course of recovery of ventricular contractile strength following a steady-state beat. In the first series of experiments, we studied left ventricles that beat isovolumically throughout the experiment, allowing use of dP/dtmax as a reliable index of contractile strength independent of the influence of changing ventricular pre- and afterload. The commencement of mechanical restitution was found to be associated with the onset of electrical diastole; thereafter, contractile strength rose monoexponentially to a plateau that was maintained for test pulse intervals as long as 15 s. The time constant of restitution (typically 245 ms) was independent of priming frequency and ventricular volume. These findings were interpreted in terms of a model of intracellular calcium fluxes within the myocardial cells. In a second series of experiments, we measured mechanical restitution curves from isolated ventricles that ejected against a simulated arterial impedance system. Under this condition, we did not observe the monoexponential time course of mechanical restitution as was measured under isovolumic conditions. The differences between the mechanical restitution curves measured under isovolumic and ejecting conditions were attributed to the influences of changing hemodynamic conditions on dP/dtmax that caused it to be an unreliable index of contractile strength.
Angiotensin II attenuates baroreflex control of heart rate and sympathetic activity
Authors: Guo G. B. , Abboud F. M.
Published: December 2017

We determined whether angiotensin II (ANG II) modulates the arterial baroreflex control of lumbar sympathetic nerve activity (LSNA) in chloralose-anesthetized rabbits. Intravenous infusion (iv) of ANG II caused significantly less reflex bradycardia and less inhibition of LSNA than iv phenylephrine (PE) for equivalent increments in arterial pressure. During a background iv infusion of ANG II, which caused a small sustained increase in arterial pressure, the reflex inhibition of heart rate (HR) and LSNA in response to further increases in pressure with graded doses of PE was attenuated, but the reflex increase in HR and LSNA in response to hypotension with graded doses of nitroprusside was unchanged. This modulation of the baroreflex by ANG II is specific since a similar background infusion of PE did not alter baroreflex responses to further increases or to decreases in arterial pressure. The frequency of aortic baroreceptors was comparable for equivalent increases in pressure caused by iv ANG II or PE. When ANG II was confined to the isolated carotid sinuses, the reflex inhibition of HR and LSNA during distension of carotid sinuses was unchanged. An excitatory effect of ANG II on the efferent limb of the baroreflex that would oppose the reflex bradycardia or inhibition of LSNA is unlikely because when the pressor effect of ANG II was prevented by nitroprusside, there were no changes in HR and LSNA. We conclude that through an effect on the central nervous system iv ANG II has a selective effect on the arterial baroreflex; it impairs reflex decreases in HR and LSNA during hypertension but not reflex increases in HR and LSNA during hypotension.
Parallel baroreceptor control of sinoatrial rate and atrioventricular conduction
Authors: O'Toole M. F. , Wurster R. D. , Phillips J. G. , Randall W. C.
Published: December 2017

The vagal efferent limb of baroreceptor reflexes was studied in 10 anesthetized (alpha-chloralose) dogs to determine its differential regulatory significance on sinoatrial (SA) rate and antegrade atrioventricular (AV) conduction. The arterial pressure stimulus for these reflexes was produced by intra-aortic balloon inflation (increase) and hemorrhage (decrease); the efferent sympathetic reflex was blocked by spinal cord transection. The dromotropic response to arterial pressure changes was studied over a physiological range of arterial pressures (60-150 mmHg) with the chronotropic response intact, with atrial pacing to prevent the chronotropic response, and after atropine or bilateral vagotomy. In all animals, the chronotropic response to arterial pressure changes balanced the dromotropic response to preserve 1:1 AV conduction over most arterial pressures. If the chronotropic response was prevented with atrial pacing, an unbalanced and independent vagal regulation of AV conduction was "unmasked" with resultant high-grade second-degree AV block. The independent regulations of SA rate and AV conduction were further found to be finely matched to produce an equilibrium of chronotropic-dromotropic changes as arterial pressure varied. Clinical conditions arising from disruption of this equilibrium are discussed.
Depressed reticuloendothelial clearance of platelets in rats after trauma
Authors: Kaplan J. E. , Moon D. G. , Minnear F. L. , Saba T. M.
Published: December 2017

Platelet microembolization may contribute to microcirculatory and organ damage following trauma and shock. It is hypothesized that posttraumatic reticuloendothelial depression predisposes to such microembolization by failure to clear altered platelets from the circulation. The present study evaluated the short-term (1 h) clearance and organ localization of radiolabeled homologous damaged platelets in normal rats and in rats following sublethal Noble-Collip drum trauma. Platelets were collected in citrated platelet-rich plasma from normal rats and labeled with 51Cr in citrated saline. Platelets were altered by repeated centrifugation in protein-free medium. These platelets differed functionally and morphologically from normal platelets. Disappearance of iv injected damaged platelets conformed to a two-compartment exponential clearance. Velocity of clearance in the rapid compartment correlated with hepatic platelet localization, whereas velocity of clearance in the second compartment correlated with splenic platelet localization. Clearance rate of the rapid compartment was depressed at 1 h after trauma and elevated at 24 h. These changes were associated with a decrease in hepatic platelet localization at 1 h and an increase above normal at 24 h. Splenic platelet localization was decreased by 3 h following trauma. Pulmonary platelet localization was increased at all times following trauma. It is concluded that the posttrauma state is associated with a defect in the reticuloendothelial system clearance of altered platelets, which may augment embolization of platelets in the lung.
Effects of propranolol and epinephrine on density of capillaries in rat heart
Authors: Vetterlein F. , Schmidt G.
Published: December 2017

The influence of propranolol and epinephrine on the time course of capillary plasma filling and the maximal obtainable capillary density was studied in the hearts of anesthetized rats. The blood plasma was labeled in vivo with macromolecule-coupled fluorochromes (lissamine-rhodamine B 200 and fluorescein isothiocyanate) for different periods of time and the density of marked capillaries determined in frozen sections of the heart. In the propranolol-treated (1.0 mg/kg) rats complete filling was observed after 40 s (controls: 10 s). When epinephrine (5.0 micrograms X kg-1 X min-1) was infused, plasma filling was completed within 5 s. Maximal capillary densities were higher in the drug-treated groups than in the control group (controls 3,530 capillaries/mm2; propranolol 3,890 capillaries/mm2; epinephrine 3,930 capillaries/mm2, subepicardium). This increase was induced by a reduction in mean diameter of muscular fibers due to a higher distension of the left ventricular wall in the drug-treated rats. It is concluded that changes in plasma transit times and in intercapillary distances due to fiber lengthening were induced by high doses of propranolol or epinephrine.
Heart cyclic nucleotide responses to sustained aortic constriction in neonatal and adult rats
Authors: Dowell R. T. , Haithcoat J. L. , Thirkill H. M. , Palmer W. K.
Published: December 2017

The present studies examined adenosine and guanosine 3',5'-cyclic monophosphate (cAMP and cGMP) levels in left ventricular tissue of neonatal and adult rats subjected to 3-10 days of abdominal aortic constriction. Left ventricular cAMP levels were elevated after 3 days of pressure overloading in neonatal rats (2,274 +/- 430 pmol/g; mean +/- SE) compared with composite control values (1,280 +/- 124) obtained from sham-operated neonates, sham-operated adults, and aortic-constricted adult groups. cAMP levels declined progressively until, at 10 days after aortic constriction, values were lower (681 +/- 25 pmol/g) than control (1,621 +/- 107). Left ventricular cGMP level was higher in sham-operated neonatal (38 +/- 3 pmol/g) than in sham-operated adult rats (17 +/- 1) at 3 and 10 days postsurgery, but pressure overloading exerted no effect on cGMP measurements. Adenylate cyclase activity in left ventricular tissue homogenate was higher in 3-day sham-operated neonatal (58 +/- 3 pmol X mg protein-1 X min-1) compared with sham-operated adult (10 +/- 1) rats as the result of augmented nonmuscle cell activity. Elevated cAMP values in 3-day, pressure-overloaded neonates occurred despite lower adenylate cyclase activity (44 +/- 2), via degradative modulation (cAMP phosphodiesterase). Guanylate cyclase activity in left ventricular tissue was consistent with prevailing cGMP levels and was not influenced by aortic constriction. The present experiments show that neonatal cardiac enlargement is associated with biphasic alterations in cAMP level which are modulated, at least in part, via degradative reactions.