bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in arterial wall properties during development and maintenance of renal hypertension
Authors: Cox R. H.
Published: December 2017

Segments of carotid and tail arteries were used to determine the effects of two-kidney Goldblatt hypertension on mechanical properties and chemical contents. Arteries were obtained after 4 and 12 wk of hypertension. Systolic pressures averaged 129 mmHg in control animals and 150 mmHg in hypertensive ones. Pressure-diameter data were recorded under conditions of active (145 mM K+) and passive (0 Ca2+ and 2 mM EGTA) smooth muscle. Small increases in passive stiffness were found after 4 and 12 wk in the carotid arteries of hypertensive animals, but no significant change occurred in the tail arteries. Small but significant decreases in total connective tissue content of these arteries were found after 12 wk of hypertension. Maximum values of active stress response were significantly larger in carotid arteries from hypertensive animals at both 4 and 12 wk of hypertension. No significant differences were found for the tail arteries. The K+ content of the carotid but not the tail artery was larger for the hypertensive animals. When corrected for differences in relative cell content most of the differences in active force development were eliminated. The differences in passive mechanics can not be explained on the basis of the changes in connective tissue content. The active smooth muscle responses and content changes suggest that they are directly related to the moderate elevation of arterial pressure.
Isolated working rat heart perfusion with perfluorochemical emulsion Fluosol-43
Authors: Segel L. D. , Rendig S. V.
Published: December 2017

Isolated working rat hearts were perfused with the perfluorochemical emulsion Fluosol-43 to determine whether it would support prolonged, stable cardiac function. The perfluorochemical emulsion provides a controlled perfusate composition, relatively high oxygen capacity, and a colloid osmotic pressure that is similar to that of plasma. Electrically paced (325 beats/min) hearts were perfused for 6 h at 35 degrees C in a recirculating system. Hemodynamic and mechanical function of seven Krebs-Henseleit-perfused hearts declined significantly more than that of seven Fluosol-43-perfused hearts over the 6-h period. The percent of initial function remaining at 6 h for Krebs-Henseleit-perfused vs. Fluosol-43-perfused hearts was 70.3 +/- 5.0 vs. 95.4 +/- 1.1% (P less than 0.001) for left ventricular peak systolic pressure; 55.6 +/- 7.7 vs. 97.5 +/- 2.4% (P less than 0.001) for dP/dtmax; 27.1 +/- 7.2 vs. 60.6 +/- 5.2% (P less than 0.005) for cardiac output; 11.0 +/- 6.3 vs. 67.2 +/- 3.4% (P less than 0.001) for external work efficiency; and 17.4 +/- 8.4 vs. 67.7 +/- 4.5% (P less than 0.001) for stroke rhythmic than Fluosol-43-perfused hearts during the last 3 h of perfusion. Perfusate lactate concentration was 4.5-fold higher in the Krebs-Henseleit perfusate than in the Fluosol-43 perfusate at 6 h, reflecting greater anaerobic metabolism in the Krebs-Henseleit-perfused hearts. Thus isolated rat hearts perfused with Fluosol-43 have greater maintenance of hemodynamic and mechanical function over a longer time period than hearts perfused with Krebs-Henseleit bicarbonate buffer.
Vasopressin in brain of spontaneously hypertensive rats
Authors: Rascher W. , Lang R. E. , Unger T. , Ganten D. , Gross F.
Published: December 2017

In stroke-prone spontaneously hypertensive rats (SHRSP) and in normotensive Wistar-Kyoto rats (WKY), arginine vasopressin (AVP) was measured by means of a radioimmunoassay in the plasma, the pituitary gland, the hypothalamus, and the brain stem. In 6- and 14-wk-old SHRSP, the plasma concentration of AVP was lower than in age-matched WKY (P less than 0.01), whereas it was elevated at 28 wk of age (P less than 0.01). In the pituitary of 6-wk-old SHRSP, AVP was higher than in WKY (P less than 0.05), but no such difference was found in older rats. In the hypothalamus and the brain stem, AVP content was reduced in all age groups of SHRSP. Plasma osmolality was diminished in 28-wk-old SHRSP only (P less than 0.01), whereas hematocrit in all age groups was higher in SHRSP than in WKY. It is concluded that the secretion of AVP and possibly its synthesis in the hypothalamus are reduced in SHRSP. Whether the reduced AVP content in the brain stem is related to the sustained elevation of blood pressure has to be studied further.
Colloid osmotic pressure changes in isolated isogravimetric cat hindlimb
Authors: Watson P. D.
Published: December 2017

The development of osmotic pressure, following the addition of bovine serum albumin (BSA) to the perfusate, was measured in an isogravimetric cat hindlimb fully dilated with papaverine. The changes in colloid osmotic pressure were followed by recording the changes in venous pressure (PVI) necessary to maintain constant weight. Capillary filtration coefficient (CFC) and vascular compliances were calculated from weight changes following steps in venous pressure. Venous BSA levels reached arterial within 1 min, and PVI reached a new steady state 13.1 +/- 0.9 (SE) min (n = 9 in 6 limbs) after adding BSA. This apparent delay in the development of the osmotic pressure agrees with earlier reports. However, when the BSA was added under constant venous pressure conditions, the fluid reabsorption reached its maximum rate within 1.5 min. The data suggest that the BSA is osmotically fully effective after the capillary washin. The slowness of the rise of PVI in the isogravimetric state is probably caused by the time necessary to absorb sufficient fluid from the interstitium to raise the capillary pressure to a level that balances the increased oncotic pressure. A mathematical model supports this explanation.
Dependence of 13NH3 myocardial extraction and clearance on flow and metabolism
Authors: Krivokapich J. , Huang S. C. , Phelps M. E. , MacDonald N. S. , Shine K. I.
Published: December 2017

The isolated arterially perfused rabbit interventricular septum was used to study the relationship between flow (F) and myocardial uptake and subsequent clearance of bolus injections of 13N-labeled ammonia (13NH3). Multiple 13NH3 injections were delivered to a total of 19 septa at perfusion rates (F/g) ranging from 0.2-4.0 ml.min-1.g-1. Ten septa were studied at 37 degrees C and nine were studied at 28 degrees C to obtain uptake and clearance data at different metabolic rates. The septa were perfused without recirculation with a modified Tyrode solution. Analysis of the time-activity curves generated by the injections of 13NH3 revealed that the data was best described by three components. The first two components exhibited short clearance times (t1/2s less than 7 min) in contrast to prolonged clearance times (30-500 min) for component 3. Component 1 was consistent with a freely diffusible 13NH3 compartment. Component 3 persists and permits myocardial imaging 15 min or more after 13NH3 injection. At each perfusion rate the extraction fraction of component 3 was twice as large, and the clearance time of component 3 was twice as fast at 37 as at 28 degrees C, implying that the extraction and washout of this third component are dependent on enzymatic reactions. The total myocardial extraction into component 3 from a systemic injection is determined by multiplying the extraction fraction by the perfusion rate (EF(3) X F/g) and was directly related to the perfusion rate at both 28 and 37 degrees C.
Lack of time-dependent augmentation of carotid sinus baroreflex system after vagotomy
Authors: Hosomi H. , Yokoyama K.
Published: December 2017

The purpose of this experiment was to study whether the carotid sinus baroreflex system (CS system) increases its gain with time after vagotomy in compensation for the loss of the vagally mediated arterial pressure control system (V system). In 7 dogs anesthetized with pentobarbital sodium we determined the responsiveness of the V system by repeatedly measuring the overall open-loop gain (G) of the negative feedback control system. G was assessed as (delta API/delta APS) -- 1, where delta API and delta APS are, respectively, the immediate and steady-state falls in arterial pressure at the aortic arch following a stepwise reduction in blood volume. delta API, delta APS, and G in intact condition were -12.0 +/- 1.8 mmHg, -1.1 +/- 0.2 mmHg, and 10.1 +/- 0.7 (SD), respectively. delta API, delta APS, and G after vagotomy, i.e., G of the CS system (GCS), were -15.6 +/- 3.6 mmHg, -6.4 +/- 1.9 mmHg, and 1.6 +/- 0.4 GCS did not change with time over 4 h after vagotomy. We conclude that the CS system cannot augment its ability to restore arterial pressure in compensation for the lost function of the V system within 4 h after vagotomy in the anesthetized dog.
Characterization of carnitine transport in isolated perfused adult rat hearts
Authors: Vary T. C. , Neely J. R.
Published: December 2017

Carnitine transport was characterized in isolated perfused adult rat hearts. Carnitine uptake consisted of both a saturable (carrier-mediated) and nonsaturable (diffusion) component. Perfusion with 0.05 mM mersalyl acid, a sulfhydryl binding agent, inhibited the carrier-mediated transport but did not inhibit diffusion. The saturable transport system exhibited Michaelis-Menten kinetics with a maximum velocity of 154 nmol . g dry wt-1 . h-1 and an apparent Michaelis constant of 24 microM. D-carnitine competitively inhibited L-carnitine transport with an apparent inhibitor dissociation constant of 500 microM. Anoxia and K+ arrest resulted in only a slight inhibition of the saturable transport, suggesting that transport is not adenosine 5'-triphosphate (ATP) dependent. At physiological concentrations of extracellular carnitine (44 microM), total carnitine uptake rate was about 100 nmol . g dry wt-1 . h-1, 80% of which was by carrier-mediated transport. This rate of uptake would require about 60 h to replace the total cellular carnitine. Loss of tissue carnitine also appeared to be a slow process. These results suggest that carnitine is transported across the sarcolemma by both diffusion and carrier-mediated transport.
Immunoreactive glandular kallikrein in rat plasma: a radioimmunoassay for its determination
Authors: Rabito S. F. , Scicli A. G. , Kher V. , Carretero O. A.
Published: December 2017

A radioimmunoassay (RIA) has been developed to measure immunoreactive glandular kallikrein in rat plasma. To prevent the binding of radioactive kallikrein to plasma inhibitors, 125I-kallikrein was inactivated with phenylmethylsulfonyl fluoride (PMSF), a procedure that maintained 125I-kallikrein immunoreactivity. Different volumes of plasma displaced 125I-PMSF-kallikrein in a parallel fashion to the kallikrein standard curve. The sensitivity of the RIA was 200 pg, and the recovery of nonradioactive active kallikrein added to plasma was 58.7%. The concentration of immunoreactive glandular kallikrein in normal rat plasma averaged 47.1 +/- 1.7 (SE) ng/ml. Bilateral nephrectomy caused a threefold increase in circulating glandular kallikrein (50 +/- 2.7 to 167 +/- 7 ng/ml; P less than 0.001). REmoval of the submandibular and sublingual glands significantly decreased its concentration from 52 +/- 2.3 to 34 +/- 1.6 ng/ml (P less than 0.001). Immunoreactive glandular kallikrein was higher in the submandibular gland vein than in arterial blood (venous: 94 +/- 10.5; arterial: 64 +/- 6.3 ng/ml; P less than 0.05) and was lower in the renal venous blood (venous: 44 +/- 2.2; arterial: 53 +/- 2.6 ng/ml; P less than 0.05). In conclusion, this study shows that the use of 125I-PMSF-kallikrein as tracer prevents the interference in the RIA caused by plasma protease inhibitors. It also indicates that the submandibular gland is an important source of the immunoreactive glandular kallikrein in rat plasma and that the kidney probably participates in its metabolism. Glandular kallikrein released by the submandibular gland into the circulation may participate in regulating local blood flow before it is inactivated by plasma inhibitors.
Effect of ADP-induced platelet aggregation on lung fluid balance in sheep
Authors: Minnear F. L. , Moon D. G. , Kaplan J. E. , Malik A. B.
Published: December 2017

The effects of platelet aggregation (PA), induced by an intravenous injection of adenosine 5'-diphosphate (ADP), on pulmonary fluid and protein exchange and on arterial blood gases were determined in artificially ventilated sheep prepared with lung lymph fistulas. ADP injection produced small increases (P less than 0.01) in pulmonary lymph flow (Qlym) and transvascular protein clearance (Qlym X lymph-to-plasma protein concentration ratio). These changes were not associated with significant increases in pulmonary arterial and left atrial pressures, pulmonary blood flow, or pulmonary vascular resistance. ADP-induced PA did not increase the pulmonary endothelial permeability to proteins, because an elevation of pulmonary microvascular pressure (Pmv), induced by inflation of a left atrial balloon catheter, produced the same increases in Qlym and protein clearance as in normal sheep after comparable increases in Pmv. The increases in Qlym and protein clearance can be explained by an increase in pulmonary vascular surface area. ADP-induced PA decreased the arterial oxygen tension, which was sustained for the 3 h duration of the study; the arterial carbon dioxide tension did not change and the arterial pH decreased (P less than 0.05) after PA. Chronic depletion of platelets with antiplatelet serum prevented the increases in Qlym and protein clearance and the arterial hypoxemia, indicating that these changes were the direct result of PA. Thus ADP-induced PA in sheep increased pulmonary fluid filtration and protein clearance by an increase in the vascular surface area. Also PA produced a rapid and prolonged arterial hypoxemia, which may result from the release of vasoactive and bronchoactive factors causing a maldistribution of ventilation and perfusion.
Hydrolysis of sarcolemma by lysosomal lipases and inhibition by chlorpromazine
Authors: Beckman J. K. , Owens K. , Knauer T. E. , Weglicki W. B.
Published: December 2017

The susceptibility of the lipids of canine cardiac sarcolemma to attack by soluble lysosomal lipases was studied to simulate in vitro the lipolytic injury that occurs during ischemia. The sarcolemmal fraction was incubated at 37 degrees C with the soluble portion of rat hepatic lysosomes (the lysosol) under conditions (pH 5.0, 5 mM ethylenediaminetetraacetic acid) appropriate for the activity of the major lysosomal lipases. Incubation of sarcolemma with lysosol resulted in a 78% lipolysis of sarcolemmal triacylglycerols, a lesser degradation of glycerophospholipids, and a parallel production of free fatty acids and lysophospholipids. The hydrolysis of sphingomyelin was negligible but was greatly stimulated (75%) by the addition of Triton X-100 (1 mg). Endogenous lipolytic activities of the sarcolemma did not contribute significantly to the observed lipid hydrolysis either in the presence or absence of detergent. The lipolysis of sarcolemmal triacylglycerols, glycerophospholipids, and sphingomyelin (Triton X-100 stimulated) were inhibited by varying concentrations of chlorpromazine. Thus cardiac sarcolemma is susceptible to hydrolysis of lysosomal lipases, and chlorpromazine inhibits this potentially injurious process.
Atropine does not attenuate cerebral vasodilatation during hypercapnia
Authors: Busija D. W. , Heistad D. D.
Published: December 2017

To study the contribution of cholinergic nerves to cerebral vasodilation during hypercapnia, we blocked muscarinic cholinergic receptors with atropine. We used two new approaches. First, total and regional cerebral blood flow (CBF) were measured with microspheres. Second, efficacy and specificity of muscarinic blockade by atropine were examined using the cranial window method. In anesthetized cats we measured CBF with 15-micrometers microspheres six times during each experiment: during normocapnia (PCO2 = 32-34 Torr), moderate hypercapnia (PCO2 = 48-50 Torr), and severe hypercapnia (PCO2 = 61-64 Torr), before and after intravenous administration of vehicle or atropine (0.5 mg/kg). Hypercapnia produced graded increases in blood flow in all areas of the brain. Atropine did not attenuate increases in CBF during hypercapnia. We examined efficacy and specificity of muscarinic blockade by atropine using the cranial window method. Acetylcholine (10(-7) and 10(-6) M) and adenosine (10(-7) and 10(-5) M), dissolved in artificial cerebrospinal fluid, dilated pial arteries in a dose-dependent fashion. Intravenous administration of atropine attenuated vasodilation produced by acetylcholine but did not affect the response to adenosine. Thus atropine, at a dose that effectively blocked muscarinic receptors, did not attenuate the increase in CBF during hypercapnia. The study suggests that cholinergic nerves are not involved in steady-state cerebral vasodilatation during hypercapnia.
Adenosine and free-flow functional hyperemia in striated muscle
Authors: Proctor K. G. , Duling B. R.
Published: December 2017

Striated muscle arteriolar responses to 1.5 min of 1-Hz contraction and/or increased tissue O2 partial pressure (PO2) were observed during exposure of the tissue interstitial space to adenosine deaminase (ADA) to evaluate the role of adenosine (ADO) as a regulator for blood flow. The microvasculature of the hamster cremaster muscle was continuously superfused with a bicarbonate buffer containing 11 micrograms ADA/ml and equilibrated with 5% CO2 and various O2 concentrations. Arterioles (resting diameter less than 30 micrometers) constricted a maximum of 55% when the superfusate gas tension was increased from 0 to 95% O2, but ADA had no effect on this behavior. Arterioles dilated during exercise, but the diameter change was decreased 20-25% during exercise with ADA treatment at both normal and elevated tissue PO2. As ADA had no effect on either the vasodilation to 2-chloroadenosine or resting arteriolar diameter, it was probably specific in its action. Assuming that all extracellular ADO was accessible to ADA and that ADA neutralized most newly formed ADO, we conclude that ADO is one component of a multifactor system mediating short periods of free-flow exercise hyperemia and that the release of ADO is not necessarily dependent on tissue hypoxia.
Exchange of potassium and strontium in adult bone
Authors: Maltby B. , Lemon G. J. , Bassingthwaighte J. B. , Kelly P. J.
Published: December 2017

The kinetics of exchange of strontium (85Sr) and potassium (42K) were studied in the mid-tibial cortical bone of 37 adult dogs. After injection of these two tracer cations and tracer-labeled albumin into the tibial nutrient artery, two types of observations were made: 1) collection of sequential venous samples to provide the outflow indicator-dilution curves and to calculate the extraction and retention at early times; and 2) detection of energy-selected gamma emissions via a detector over the tibia to give the time course of content of 42K and 85Sr in the tibia. Extractions of K+ and Sr2+ were 50 and 60% during a single transcapillary passage. More Sr2+ than K+ was retained in the first minutes. Their rates of washout over a 3-h period were similar. The interpretation is that the rate of uptake at extravascular sites is faster for Sr2+ than for K+, as is the rate of release, and that the extravascular volume of distribution for Sr2+ (adsorption sites in the interstitium or on bone) is much larger than that for K+ (intracellular).
alpha-Adrenergic control of oxygen delivery to myocardium during exercise in conscious dogs
Authors: Heyndrickx G. R. , Muylaert P. , Pannier J. L.
Published: December 2017

alpha-Adrenergic control of the oxygen delivery to the myocardium during exercise was investigated in eight conscious dogs instrumented for chronic measurements of coronary blood flow, left ventricular (LV) pressure, aortic blood pressure, and heart rate and sampling of arterial and coronary sinus blood. After alpha-adrenergic receptor blockade a standard exercise load elicited a significantly greater increase in heart rate, rate of change of LV pressure (LV dP/dt), LV dP/dt/P, and coronary blood flow than was elicited in the unblocked state. In contrast to the response pattern during control exercise, there was no significant change in coronary sinus oxygen tension (PO2), myocardial arteriovenous oxygen difference, and myocardial oxygen delivery-to-oxygen consumption ratio. It is concluded that the normal relationship between myocardial oxygen supply and oxygen demand is modified during exercise after alpha-adrenergic blockade, whereby oxygen delivery is better matched to oxygen consumption. These results indicate that the increase in coronary blood flow and oxygen delivery to the myocardium during normal exercise is limited by alpha-adrenergic vasoconstriction.
Regional myocardial radiotracer kinetics in dogs using miniature radiation detectors
Authors: Jacobs M. L. , Okada R. D. , Daggett W. M. , Fowler B. N. , Strauss H. W. , Geffin G. , Pohost G. M.
Published: December 2017

An implantable device for continuous measurement of regional myocardial radioisotope activity was designed and validated. The probe consists of a 2-mm3 cadmium telluride crystal surrounded by lead foil housed in a 4.5-mm outer diameter steel cylinder. Activity in serial dilutions of thallium-201 measured by this miniature gamma detector correlated well with activity measured in the well counter (r = 0.99). In vivo probe measurements of regional myocardial thallium-201 activity in a canine model were compared with activity in punch biopsies, again with excellent correlation (r = 0.90). The crystal was mounted on a modified arterial clamp, which was inserted into the left ventricle through, the apex and situated on the endocardial surface of the anterior or posterior wall. It was thus possible to measure regional isotope activity without excessive background from the blood pool and opposite heart wall. The probe was found best suited for monitoring activities of isotopes with energies between 60 and 250 keV. With a pair of these devices, dynamic studies of the myocardial kinetics of radioisotopes such as thallium-201 in normal and ischemic myocardium are now possible.
Response of cerebral blood flow to changes in PCO2 in fetal, newborn, and adult sheep
Authors: Rosenberg A. A. , Jones M. D. , Traystman R. J. , Simmons M. A. , Molteni R. A.
Published: December 2017

Developmental effects on the response of cerebral blood flow (Qc) and cerebral O2 consumption (CMRO2) to changes in CO2 tension were assessed in unanesthetized fetal, newborn, and adult sheep. Blood flow was measured using the radioactive microsphere technique. CMRO2 was calculated as the product of Qc and the difference in O2 content between arterial and sagittal sinus blood (CaO2 -- CVO2). The response of Qc to changes in arterial CO2 tension increased from fetus [3.53 +/- 0.56 ml.100 g-1.min-1.mmHg PaCO2(-1) (SE)] to newborn (5.16 +/- 0.59) to adult (6.20 +/- 0.63). Only the fetal-adult difference was significant (P less than 0.05). It has been suggested that developmental differences in CO2 responsiveness of cerebral blood flow are the result of differences in CMRO2. We corrected for differences in CMRO2 by looking at the response to CO2 of the variable 1/(CaO2--CVO2). According to the Fick principle 1/(CaO2--CVO2) = Qc/CMRO2, i.e., blood flow per unit O2 consumption. The fetal response was not significantly different from the newborn, but the adult was significantly different from both (P less than 0.05). Thus the difference in CO2 response of cerebral blood flow between fetus and adult cannot be explained by differences in CMRO2.
Membrane properties of smooth muscle cells in pulmonary hypertensive rats
Authors: Suzuki H. , Twarog B. M.
Published: December 2017

The membrane properties of smooth muscle cells in rat main pulmonary artery (MPA) and small pulmonary artery (SPA) were investigated during chronic normobaric hypoxia and after monocrotaline injection. As chronic pulmonary hypertension developed, pronounced differences between MPA and SPA were observed. These findings may shed light on mechanisms of smooth muscle hypertrophy. 1) The resting membrane potential of smooth muscle in MPA became less negative than the normal (depolarized), whereas the resting membrane potential of smooth muscle in SPA became more negative (hyperpolarized). 2) In MPA, both the length and time constants diminished. 3) In MPA, the maximum membrane depolarization produced by a 10-fold increase in extracellular [K+] decreased. 4) In SPA, the depolarization observed in K+-free solution was more rapid and greater in amplitude, and the transient hyperpolarization following restoration of K+-containing solution increased. 5) In SPA, initial and sustained depolarization evoked by Na+-deficient solutions were increased. 6) Depolarization in MPA was due to increased membrane permeability, perhaps to Cl-, whereas hyperpolarization in SPA could be attributed to increased activity of an electrogenic Na+-K+ pump.
Effects of increased venous pressure on albumin- and IgG-excluded volumes in skin
Authors: Bell D. R. , Mullins R. J.
Published: December 2017

The effect of increased venous pressure on the exclusion of plasma albumin and gamma-immunoglobulin G (IgG) in skin interstitium was studied in anesthetized rabbits. In eight rabbits, venous pressure in the left leg was increased from 7 to 26 mmHg, while the right leg served as a control. Samples of plasma and prenodal popliteal lymph were collected for 4 h before taking samples of heel skin. The extracellular and plasma spaces in the tissue samples were measured using 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and 125I-labeled human serum albumin, respectively. The protein spaces were calculated from measurements of endogenous albumin and IgG concentrations using rocket electroimmunoassay. For control skin, albumin and IgG were both excluded from 50% of the interstitial space. The interstitial space after venous congestion was increased 1.4 times control. There was a washout of interstitial albumin and no change in the albumin-excluded volume fraction. For IgG, there was no change in the extravascular mass and a decrease in the excluded volume fraction. Changes in the interstitial gel matrix of skin were different from those in visceral organs and consistent with a greater amount of collagen.
Response of large hindlimb veins of dog to aortic arch chemoreceptor stimulation
Authors: Britton S. L. , Donald D. E.
Published: December 2017

Experiments were performed in chloralose-anesthetized dogs to examine the reflex effects on tone in the saphenous vein of stimulating the aortic arch chemoreceptors. The saphenous vein was perfused with cooled (30 degrees C) aortic blood at constant flow, and perfusion pressure was measured. In 13 animals the aortic arch chemoreceptors were stimulated by injection of cyanide (0.1 mg/kg) into the root of the aorta. Cyanide caused a decrease (20 +/- 2 mmHg) in saphenous vein perfusion pressure and an increase (44 +/- 4) in aortic pressure. These changes that occurred subsequent to aortic root cyanide injections were abolished by vagotomy or section of the aortic nerves (afferent pathway); section of the lumbar sympathetic chain at L4 and L5 abolished the dilator response of the vein (efferent pathway) but did not alter the increase in aortic pressure. Four dogs were prepared for cardiopulmonary bypass and separate perfusion of the systemic circulation and the isolated aortic arch. Delivery of hypoxic-hypercapnic blood to the isolated aortic arch caused a dilation of the saphenous vein and an increase in systemic arterial perfusion pressure. From these results we conclude that cutaneous venomotor tone can be reflexly reduced through the aortic chemoreflex.
Reflexes elicited by acute stretch of atrial vs. pulmonary receptors in conscious dogs
Authors: Schultz H. D. , Fater D. C. , Sundet W. D. , Geer P. G. , Goetz K. L.
Published: December 2017

We measured hemodynamics and renal function in conscious dogs while partially obstructing blood flow at various sites within the thorax. Inflation of a balloon in the left atrium increased left atrial pressure (LAP) by 9 mmHg and caused a parallel increase in pulmonary arterial pressure (PAP); heart rate, arterial pressure, and total peripheral resistance increased; stroke volume and right atrial pressure decreased; and cardiac output remained unchanged. The increase in LAP was accompanied by a fourfold increase in urine flow and a threefold increase in sodium excretion. Plasma vasopressin (AVP) and renin activity (PRA) decreased. On the other hand, partial occlusion of the pulmonary veins or the main pulmonary artery produced similar increases in PAP without affecting LAP, systemic hemodynamics, renal function, or plasma AVP. Similarly, inflation of a balloon in the right atrium failed to alter renal function, plasma AVP, or PRA. Finally, constriction of the thoracic inferior vena cava decreased LAP and increased PRA. In summary, these data emphasize that inflation of a balloon in the left atrium of the conscious dog produces a composite response consisting of alterations in cardiovascular function, renal function, and circulating hormones. Moreover, our data indicate that the response is mediated by a reflex initiated from receptors located in the left atrium; we detected no evidence that receptors located in the pulmonary vasculature or right heart contribute to this response.
Effect of ischemia on mechanical function and high-energy phosphates in rabbit myocardium
Authors: Nishioka K. , Jarmakani J. M.
Published: December 2017

This study was designed to evaluate the effect of ischemia and reperfusion on myocardial mechanical function and high-energy phosphates in the neonate. All studies were performed utilizing the isolated arterially perfused septal preparation of newborn and adult rabbit hearts that were maintained at 27, 33, or 37 degrees C and paced at 90 beats/min. After mechanical function had been stabilized, 60 min of global ischemia was induced and was followed by 60 min of reperfusion. The muscle was kept in a humidified, warm, oxygen-poor atmosphere. During ischemia, developed tension (DT) and maximal rate of tension development (+dT/dtmax) declined at the same rate in the newborn and the adult, and the values at the end of ischemia were not significantly different from 0. The resting tension (RT) increased significantly in the two age groups during ischemia, but the increase in the newborn was significantly less than that in the adult. After 60 min of reperfusion, the recovery of +dT/dtmax in the newborn was significantly greater than that in the adult at each temperature. Tissue ATP content in the newborn was significantly greater than that in the adult, both at the end of ischemia and after reperfusion. Importantly, a significant correlation (r = 0.90) between the recovery of +dT/dtmax and tissue ATP content was found. These data indicate that 1) the newborn myocardium is more resistant to ischemia than the adult myocardium and 2) this resistance might be explained by less depletion of myocardial ATP levels during ischemia.
Myocardial aging: functional alterations and related cellular mechanisms
Authors: Lakatta E. G. , Yin F. C.
Published: December 2017

Studies that have examined the effect of age on the myocardium do not support the notion that a generalized decline in myocardial function occurs with adult aging but, rather, that certain specific changes in cardiac biochemistry and function occur. Although in many instances the molecular bases for these changes have not been precisely defined, sufficient clues regarding their nature are at hand to provide at least the first step toward an understanding of the dramatic effects of aging or time on the myocardium. A fundamental understanding of the effects of aging will provide an additional dimension to studies of myocardial biochemistry and function and may be useful in elucidating mechanisms of excitation-contraction coupling in the heart.
Lack of influence of potassium or osmolality on steady-state exercise hyperemia
Authors: Mohrman D. E.
Published: December 2017

Hyperkalemia, hyperosmolality, and hypoxia are known to have synergistic vasodilatory effects on resting skeletal muscle. The purpose of this study was to determine the importance of hyperkalemia and hyperosmolality in the hyperemia accompanying steady-state muscle exercise. Denervated dog gastrocnemius-plantaris muscles were perfused at constant pressure. Blood flow (Q), oxygen consumption (VO2), and venous potassium ion concentration ([K+]), osmolarity (OSM), and oxygen tension (PO2) were measured during steady-state exercise at rates between rest and 6 Hz. In control experiments the transition from rest to 6-Hz exercise resulted in large increases in VO2 and Q but modest increases in venous [K+] (+0.7 +/- 0.2 meq/l) and OSM (+6.1 +/- 1.2 mosmol/kg). Increasing venous [K+] by 2.3 meq/l by intra-arterial infusion of isotonic KCl had no steady-state effect on resting Q, nor did it alter the relationship of Q to VO2 or PO2 during exercise. Similarly, increasing venous OSM by 13 mosmol/kg by hypertonic saline infusion produced no alterations in steady-state exercise hyperemia. These findings indicate that neither local hyperkalemia nor hyperosmolality plays a significant role in sustaining the hyperemia of steady-state exercise.
Reflex cardiovascular depression induced by capsaicin injection into canine liver
Authors: Ashton J. H. , Iwamoto G. A. , Longhurst J. C. , Mitchell J. H.
Published: December 2017

Capsaicin was injected into the portal circulation of 29 dogs after a blood delay pathway was constructed between the liver and right heart, through which capsaicin-contaminated blood could be replaced while systemic hemodynamics were maintained constant. Capsaicin (500 micrograms) rapidly decreased left ventricular systolic pressure (-10%), mean arterial pressure (-12%), heart rate (-4%), renal vascular resistance (-7%), maximal rate of left ventricular pressure rise (dP/dtmax) (-12%), and dP/dt at 25 mmHg developed left ventricular pressure (-15%) in animals with paced hearts. Left ventricular end-diastolic pressure did not change. Vagus nerve interruption at the level of the diaphragm did not alter hemodynamic changes occurring during capsaicin injections, but anterior hepatic nerve interruption eliminated the changes, suggesting that the cardiovascular responses were reflex in origin and that the principal afferent pathway traverses the hepatic nerve. This study demonstrates that activation of afferent fiber receptors within the liver tissue can contribute to neural regulation of the cardiovascular system, but the natural stimulus for these receptors is not known.
Regional myocardial function and metabolism during acute coronary artery occlusion
Authors: Kanaide H. , Yoshimura R. , Makino N. , Nakamura M.
Published: December 2017

Regional changes in myocardial function and oxidative metabolism during acute coronary artery occlusion were recorded spectrophotometrically by incorporating fiber optics in the isolated rat heart perfused by Langendorff's procedure. Oxygen saturation of myoglobin, reduction of cytochrome aa3, and the dynamic wall thickness of the left ventricle were continuously and concurrently measured from absorbancy increments at 581-592 nm, 605-630 nm, and 568-592 nm, respectively. In contrast to a gradual decrease in the extent of systolic wall thickening in anoxia, observed decreases in both the extent and the duration of systolic wall thickening and the appearance of a late systolic bulge occurred within 5 s after the onset of regional ischemia. After 10 s of both anoxia and regional ischemia, oxygen saturation of myoglobin decreased by 50%, but fluorescence of nicotinamide adenine dinucleotide remained at aerobic level which indicated that mitochondrial oxidative energy production might still be maintained. Thus early and pronounced dysfunction of the ischemic region appeared to precede a substantial loss of ATP production.
Circulatory effects of chemical sympathectomy in fetal, neonatal, and adult sheep
Authors: Tabsh K. , Nuwayhid B. , Murad S. , Ushioda E. , Erkkola R. , Brinkman C. R. , Assali N. S.
Published: December 2017

Circulatory effects of chemical sympathectomy with 6-hydroxydopamine (6-HD), including changes in vascular sensitivity to neurotransmitters, were investigated in chronically instrumented unanesthetized fetal, neonatal, and adult sheep. In all animals acute response to 6-HD consisted of hypertension and tachycardia, which lasted 2-3 h. Chronic phase of sympathetic ablation then followed during which arterial pressure and heart rate of sympathectomized fetus and neonate returned to and remained at levels observed in intact animals, whereas adult sheep were slightly hypotensive throughout this period. In all animals supersensitivity of peripheral circulation to norepinephrine occurred, but only the fetus exhibited supersensitivity to acetylcholine and isoproterenol. Our conclusions are as follows: 1) acute phase of chemical sympathectomy in fetal, neonatal, and adult sheep simulates strong adrenergic stimulation; 2) absence of significant alteration in arterial pressure of fetus and neonate during the chronic phase of sympathectomy suggests a minor role for the adrenergic system in the maintenance of resting tone of peripheral circulation; and 3) on the basis of present and previous data, we postulate that the supersensitivity of fetal circulation to acetylcholine and isoproterenol may be secondary to changes occurring in pulmonary vascular bed.
Coronary blood flow changes following activation of adrenergic receptors in the conscious dog
Authors: Gwirtz P. A. , Stone H. L.
Published: December 2017

The role of coronary vascular adrenergic receptors in changing coronary flow was studied in dogs instrumented to measure left circumflex artery blood flow (CBF), mean coronary artery blood pressure (CBP), and heart rate (HR). Norepinephrine (NE), isoproterenol (IP), and phenylephrine (PH) were injected into the left circumflex artery before and after selective intracoronary alpha- and beta 1- or combined beta 1- and beta 2-receptor blockade. NE, IP, and PH did not alter CBP (112 +/- 6 mmHg). In addition, IP and PH did not affect HR (103 +/- 4 beats/min). NE increased HR to 150 +/- 6 beats/min, which was eliminated by blocking beta 1-receptors with atenolol and by removing the left stellate ganglion. IP increased CBF from 65 +/- 9 to 115 +/- 16 ml/min (mediated by both beta 1- and beta 2-receptors). PH caused an alpha-receptor-mediated coronary vasoconstriction (42 +/- 5 ml/min), which was potentiated by beta 1- and beta 2-receptor blockade. NE caused a biphasic flow response. CBF initially increased to 117 +/- 14 ml/min (mediated predominantly by beta 1-receptors) followed by a prolonged decrease to 54 +/- 7 ml/min (mediated by alpha-receptors). Removing the left stellate ganglion did not affect the CBF response to NE. These data indicate that PH directly stimulates coronary alpha-receptors and IP stimulates myocardial beta 1- and coronary beta 2-receptors. NE also stimulates myocardial cells causing a reflex that increases HR and indirectly increases CBF. The vasoconstriction to NE and PH was not evident after pentobarbital anesthesia, whereas the coronary vasodilation and increase in HR to NE was still present.
Functional significance of reduced cardiac sympathetic innervation in the newborn dog
Authors: Erath H. G. , Boerth R. C. , Graham T. P.
Published: December 2017

The functional significance of anatomically reduced cardiac sympathetic innervation in the newborn is not known. This problem was investigated by examining ventricular contractile responses to repeated maximal left stellate ganglion stimulation in adrenalectomized and sham-adrenalectomized newborn (4-12 days of age) and adult dogs. At the end of five periods (5 min/period) of stimulation, sham-adrenalectomized puppies were still able to augment left ventricular force 13.0 +/- 3.8% (mean +/- SE; P less than 0.05) above control values. However, adrenalectomized puppies did not maintain their ability to enhance left ventricular force after the first period of stimulation. Similar results were obtained with measurements of the first time derivative of left ventricular force (dF/dt), right ventricular force, right ventricular dF/dt, and peak left ventricular pressure. Adult dogs were able to augment these measurements of cardiac function significantly throughout five stimulation periods whether or not their adrenal glands were intact. After five stimulation periods, adrenalectomized newborn dogs responded to isoproterenol, indicating that their cardiac beta-adrenergic receptors remained functional. We conclude that the known sparse ventricular sympathetic innervation in the newborn dog is associated with inability to maintain significant cardiac functional responses after repeated sympathetic stimulation and that adrenal integrity is required in the newborn to maintain appropriate ventricular responses to sympathetic stimulation.
Bicarbonate ion modulation of cerebral blood flow during hypoxia and hypercapnia
Authors: Koehler R. C. , Traystman R. J.
Published: December 2017

The relative importance of changes in extracellular fluid (ECF) pH in mediating increases in cerebral blood flow (CBF) during hypoxia and hypercapnia was assessed by varying [HCO(-3)]ECF in pentobarbital-anesthetized dogs. Blood flow to one caudate nucleus (CNBF) that was bathed by cerebrospinal fluid (CSF) of varied [HCO(-3)] was compared with CNBF (measured by radiolabeled microspheres) on the contralateral side, which received a normal-[HCO(-3)]CSF perfusate. Raising [HCO(-3)]CSF from 25 to 60 meq/l for 150 min lowered CNBF by 16% and suppressed the slope of cNBF response to hypercapnia by 61% but suppressed the slope of CNBF response to hypoxia significantly less (22%). Lowering [HCO(-3)]CSF to 8 meq/l increased CNBF by 71% and augmented the response to hypercapnia by 126% but did not alter the slope of the response to hypoxia. These data indicate that changes in [H+]ECF can account for the increased CBF during hypercapnia but not for the entire hypoxic response. The increase in lactic acid production that would be necessary to solely account for the increase in CBF during hypoxia is much greater than what has been reported in the literature.
Enhanced renal vasoconstriction in rats fed essential fatty acid-deficient diet
Authors: Sakr H. M. , Dunham E. W.
Published: December 2017

The effects of angiotensin II (ANG II) and norepinephrine (NE) on total renal blood flow (RBF) were studied in rats fed an essential fatty acid (EFA)-deficient diet. EFA deficiency was employed, as an alternative to the use of cyclooxygenase inhibitors, to investigate the influence of arachidonic acid metabolites on rat RBF. Intrarenal arterial (ira) bolus doses of ANG II (2-16 ng) and NE (25-100 ng) elicited significantly greater decrements in RBF and increments in renal vascular resistance in anesthetized Sprague-Dawley rats fed EFA-deficient diets than in control rats, which were fed EFA-adequate diets. Indomethacin (5 mg/kg iv) enhanced the vasoconstrictor responses to ANG II and NE in rats fed the EFA-adequate diet but not in rats fed the EFA-deficient diet. In rats fed regular laboratory chow the renal vasoconstrictor response to ANG II was potentiated after the administration of either indomethacin or naproxen (5 mg/kg iv). Methacholine and prostaglandins E2 and I2 caused dose-related renal vasodilatation when injected (ira) over the dose range of 10-40 ng in rats fed either the EFA-deficient or -adequate diets. The increased responsiveness of the renal vascular bed to ANG II and NE in rats fed EFA-deficient diets was not attributable to reduced vasodilator efficacy. Collectively, these results suggest that the net effect of endoperoxide products of arachidonic acid metabolism attenuates the vasoconstrictor influences of exogenous ANG II and NE in the intact rat kidney.
Voltage and time dependence of restitution in heart
Authors: Lipsius S. L. , Fozzard H. A. , Gibbons W. R.
Published: December 2017

Between beats, cardiac muscle gradually recovers the ability to contract in response to a stimulus. We examined the time and voltage dependence of this "restitution" process using sheep cardiac Purkinje fibers that were voltage clamped by the two-micro-electrode technique. The rate and time course of restitution depended on the voltage and duration of preceding conditioning depolarizations. As the voltage of a conditioning depolarization was made less negative, the early rate of restitution increased, the process reached a greater peak value, and oscillations in the time course of restitution became more likely. When conditioning depolarizations were to voltages near or above the normal action potential plateau, increasing their duration had much the same effect as increasing voltage. However, with conditioning depolarizations to -40 or -50 mV, prolongation had little or no effect on the subsequent rate of restitution. The voltage during restitution affected both the time course and final extent of restitution. Steady-state restitution was an approximately sigmoid function of voltage. The early rate and peak value of restitution increased as the voltage during restitution was made more negative. Oscillations of restitution were dramatic at voltages between -70 and -50 mV. The behavior of restitution confirms that most of the calcium that activates contraction comes from intracellular stores. The complex time and voltage dependence of restitution suggests that the process reflects the time course of calcium reaccumulation in an internal store.
Reactive and exercise hyperemia during high levels of adenosine infusion
Authors: Hester R. L. , Guyton A. C. , Barber B. J.
Published: December 2017

In these experiments we tested the quantitative importance of adenosine as a mediator in the regulation of muscle with blood containing adenosine at concentrations more than 1,000 times the normal resting adenosine level (1, 7) so that the effect of any endogenously released adenosine would be miniscule in comparison with the effect of this perfused adenosine. Therefore, any major blood flow responses that should occur while the muscle remained continuously under the influence of the perfused adenosine could hardly be ascribed to endogenous adenosine. At the onset of the perfusion with the adenosine the blood flow increased approximately sevenfold. However, over 1-3 h of continued perfusion, the blood flow returned to or near to control despite the extreme amounts of adenosine. Then, while the muscle was still exposed to the adenosine, both reactive hyperemia and exercise hyperemia were elicited for varying time periods and varying degrees for a total of 96 separate measurements in 12 preparations. In all instances the increases in blood flow during hyperemia were almost exactly identical to those recorded prior to adenosine perfusion. Because it would have been almost impossible for the small amounts of endogenous adenosine to cause the large hyperemia responses in the face of the extreme amounts of perfused adenosine, it is concluded that both the reactive and exercise hyperemia responses are probably caused either entirely or almost entirely by factors other than adenosine.