bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular regulation in canines during low-frequency acceleration
Authors: Knapp C. F. , Evans J. M. , Randall D. C. , Marquis J. A.
Published: December 2017

Integrated, reflex, cardiovascular regulation in unanesthetized (tranquilized), chronically-instrumented dogs was studied using sinusoidal whole-body spinal-axis acceleration (+/- 2 Gz) at frequencies below 0.25 Hz. The participation of neurally mediated cardiac and vascular control mechanisms was examined by comparing the responses of the same animal in a normal (reflexive) state and ina pharmacologically blockaded (nonreflexive) state. Integrated neural mechanisms were found to be the most effective in minimizing acceleration-induced, arterial pressure disturbances for frequencies below 0.012 Hz; became progressively out of phase with the disturbances between 0.012 and 0.052 Hz, resulting in decreased effectiveness; and failed to significantly participate in the regulatory process for frequencies between 0.052 and 0.25 Hz, where “protection” was provided by the hydraulic and intrinsic biomechanical characteristics of the circulatory system. An analysis of the relative contribution of peripheral vascular and cardiac mechanisms indicated that 1) neurally mediated, systemic vascular responses were largest for frequency; 2) heart rate oscillations were large for frequencies below 0.052 Hz (corner frequency) and then decreased rapidly with increasing frequency; and 3) neurally mediated stroke volume oscillations were the largest for the lowest frequencies and decreased with increasing frequency.
Role of angiotensin and vasopressin on blood pressure of ganglionic blocked dogs
Authors: Houck P. C. , Fiksen-Olsen M. J. , Britton S. L. , Romero J. C.
Published: December 2017

This study was designed to investigate the possible role of angiotensin and vasopressin in the maintenance of arterial blood pressure during acute blockade of the autonomic nervous system. Two groups of eight dogs each were anesthetized with pentobarbital sodium, and autonomic ganglia were blocked with hexamethonium (20 mg/kg). Thirty minutes later group 1 received the vasopressin antagonist 1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine arginine vasopressin (10 micrograms/kg) followed after a 30-min interval by captopril (1 mg/kg). Group 2 received the same drugs, except the order of administration of vasopressin antagonist and captopril was reversed. Vasopressin antagonist during ganglionic blockade (group 2) produced a greater fall in blood pressure than did captopril during ganglionic blockade (group 1). These data indicate that vasopressin plays a greater pressor role than angiotensin in the acute response to ganglionic blockade. Additional studies were performed to determine if the autonomic nervous system alone can support the resting blood pressure in the anesthetized dog. Combined blockade of angiotensin and vasopressin without autonomic blockade produced a significant decrease in blood pressure, suggesting that the autonomic nervous system alone is not able to support the control blood pressure in the anesthetized dog.
Transmural distribution of cardiac glucose uptake in rat during physical exercise
Authors: Takala T. E. , Ruskoaho H. J. , Hassinen I. E.
Published: December 2017

The transmural distribution of glucose uptake in the left ventricle of the heart in vivo was studied using the 2-deoxyglucose tracer method under conditions of resting and swimming. Intravenous tracer infusion and aortic blood sampling were performed through chronically implanted catheters. The ventricular glucose uptake of the resting rats averaged 1.5 mumol X min-1 X g protein-1 and was about 60% higher in the subendocardial layers than in the superficial layers (P less than 0.01). During a 20-min swimming period that increased the cardiac work load twofold, the glucose uptake rate was slower (P less than 0.001), about 1.0 mumol X min-1 X g protein-1, and evenly distributed across the left ventricular wall, whereas the reduction in glycogen stores, also evenly distributed through the ventricular wall, was 30 mumol glycosyl units/g protein. Blood lactate concentration increased from 1.8 to 10-13 mM and blood glucose from 6.1 to 12 mM during swimming, but plasma free fatty acid concentration decreased slightly. The inhibition of glucose uptake during swimming was probably caused by the increased use of other oxidizable substrates.
A mathematical model of the vagally driven primary pacemaker
Authors: Bristow D. G. , Clark J. W.
Published: December 2017

Information regarding the electrical behavior of cells in the sinoatrial (SA) node of the heart is by no means complete; yet sufficiently detailed information is available in the literature to allow the formulation of a reasonably quantitative model of the membrane of the primary pacemaker cell (P-cell) and its parasympathetic innervation. In a previous study [Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H207-H218, 1982], the well-known McAllister-Noble-Tsien model of the cardiac Purkinje fiber is modified to account for the electrical activity of the SA node. In the present study, the effects of vagal activity on sinus rhythm are considered by adding a special acetylcholine-sensitive "muscarinic channel" to the membrane model for the P-cell. The resulting model mimics published data quite well and is capable of characterizing the free-running SA node cell as well as its responses to electrotonic and vagal stimulation.
Crystal-controlled telemetry system for long-term acquisition of physiological data
Authors: Anderson R. M. , Livnat A. , Zehr J. E.
Published: December 2017

A crystal-controlled telemetry system was developed for long-term high-reliability recording of blood pressure in unrestrained animals. The miniaturized transducer-transmitter system is powered by two lithium batteries that allow for more than 200 h of continuous recording of blood pressure before battery replacement. The total system has a flat frequency response of 0-25 Hz and a time stability of +/- 1 mmHg/day. Linearity is better than 0.5%. The high degree of dependability of the system permits us to perform continuous, unattended, around-the-clock recordings of pressure and heart rate in unrestrained animals. Very high dependability is achieved by the use of a novel piezoresistive blood pressure transducer and by the inherent stability of the crystal-controlled radio-frequency oscillator of the transmitter. The receiver is also crystal tuned to the measured transmitter frequency. This transmitter-receiver frequency locking ensures very reliable reception of the telemetered signal.
Arterial baroreceptors have minimal physiological effects on adrenal medullary secretion
Authors: Fater D. C. , Sundet W. D. , Schultz H. D. , Goetz K. L.
Published: December 2017

The influence of arterial baroreceptors on secretion of catecholamines from the adrenal medulla was evaluated by several methods. Conscious mongrel dogs with surgically denervated hearts were hemorrhaged until an estimated 16% of their blood volume had been removed. On a separate day they were anesthetized and their blood pressure was lowered with intravenous nitroglycerin. Neither of these maneuvers produced appreciable increases in heart rate in these dogs. In contrast, in a group of sham-operated control dogs, hemorrhage induced a mean increase in heart rate of 20 beats/min (P less than 0.05), and nitroglycerin-induced hypotension induced an increase of 50 beats/min (P less than 0.05). In a separate group of conscious dogs with aortic arch denervation but intact cardiac nerves, occlusion of the common carotid arteries for 5 min increased blood pressure and heart rate significantly but elicited only small, insignificant increases in plasma epinephrine and norepinephrine; the peak concentration of epinephrine achieved was considerably less than the amount necessary to cause appreciable effects on blood pressure and heart rate as determined in another experiment by infusing varying amounts of epinephrine into conscious, cardiac-denervated dogs. We conclude that the arterial baroreceptor reflex, within the range of activity likely to occur during most physiological and pathophysiological adjustments in the conscious dog, exerts only minimal effects on the secretion of catecholamines from the adrenal medulla.
Hormonal and renal response to plasma volume expansion in the primate Macaca mulatta
Authors: Billman G. E. , Keyl M. J. , Dickey D. T. , Kem D. C. , Keil L. C. , Stone H. L.
Published: December 2017

The purpose of this study was to investigate the hormonal and renal response to plasma volume expansion in the ketamine-anesthetized rhesus monkey. The blood volume was determined in nine animals and found to be 6% of the body weight. Six monkeys received isoncotic isotonic fluid amounting to 25% of the blood volume. Plasma volume expansion led to significant decrease in the plasma concentrations of antidiuretic hormone (46.7%) and aldosterone (78.4%) as well as plasma renin activity (50.0%). The mean arterial pressure, plasma osmolality, and plasma concentrations of Na+ and K+ were unaffected by plasma volume expansion. However, renal plasma flow, glomerular filtration rate, the excretion of Na+ and K+, and urine flow increased. It was concluded that, in the ketamine-anesthetized rhesus monkey, circulating hormones contribute to blood volume homeostasis presumably through a neural mechanism similar to that observed in dogs and humans.
Rat brain interstitial fluid pressure measured with micropipettes
Authors: Wiig H. , Reed R. K.
Published: December 2017

Interstitial fluid pressure (IFP) in the rat brain has been measured with micropipettes, 2-4 microns in diameter, after trepanation and incision of dura. IFP was compared with cerebrospinal fluid pressure (CSFP) measured by a 0.3-mm (OD) cannula in the lateral ventricle. Control IFP averaged 3.43 +/- 0.65 (SD) mmHg (n = 83) with a corresponding CSFP of 3.53 +/- 0.71 (n = 83). Pretreatment with indomethacin to reduce inflammation during preparation did not affect IFP and CSFP. Infusion of a 20% mannitol solution amounting to 5% of body weight resulted in an average IFP of -5.66 mmHg and CSFP of -4.56 mmHg 20 min after start of the infusion, after which a gradual rise in both pressures was observed. Similar results were obtained after infusion of hypertonic urea. Inflation of a cuff around the rat neck resulted in an immediate and similar rise in IFP and CSFP. Increasing the arterial CO2 partial pressure to 80 mmHg increased IFP to 12-14 mmHg and pial venular pressure to 13-15 mmHg, while CSFP rose to about 10 mmHg. The micropuncture technique for measurement of brain IFP is rapid and practically atraumatic and may be used in a variety of animals.
Plasma vasopressin in rats: effect of sodium, angiotensin, and catecholamines
Authors: Brunner D. B. , Burnier M. , Brunner H. R.
Published: December 2017

A radioimmunoassay was set up to measure plasma arginine vasopressin levels (AVP). Characteristics of the assay include a sensitivity to 0.25 pg, high specificity of the antibody, mean recovery of added unlabeled arginine vasopressin of 80%, and an interassay coefficient of variation of 7.6%. This assay was used to investigate the influence of various factors on plasma vasopressin levels in a total of 121 awake male rats. Blood samples obtained in Wistar rats via an indwelling arterial catheter yielded results similar to those following decapitation, i.e., 1.27 +/- 0.26 vs. 1.68 +/- 0.39 pg/ml. Forty-eight hour dehydration markedly increased plasma AVP to 21.8 +/- 2.39 pg/ml. AVP was less than 0.5 pg/ml in Brattleboro rats. Low and high sodium intake, angiotensin II infusion (10 and 30 ng/min), and converting enzyme inhibition by captopril (100 mg/kg) did not alter plasma AVP. During norepinephrine infusion (250 ng/min) plasma AVP rose to 5.28 +/- 1.29 pg/ml, whereas it tended to fall with isoproterenol infusion (10 ng/min). Plasma AVP was slightly higher in spontaneously hypertensive rats than in Wistar-Kyoto controls.
Cardiopulmonary reflexes and arterial pressure during rest and exercise in dogs
Authors: Walgenbach S. C. , Donald D. E.
Published: December 2017

Mean arterial blood pressure, heart rate, and cardiac output were monitored at rest and during exercise of two grades of severity in conscious dogs under control conditions and after progressive interruption of the baroreflexes. Aortic arch denervation and vascular isolation and pressurization of the carotid sinuses were used to interrupt arterial baroreflexes. Subsequent interruption of cardiopulmonary afferents was produced by acute bilateral cervical vagotomy. The results indicate that 1) with the cardiopulmonary receptors alone operative, the arterial blood pressure response to exercise is abnormal, 2) cardiopulmonary receptors do not contribute to the moment-to-moment modulation of arterial pressure, and 3) the carotid sinuses, aortic arch, and cardiopulmonary receptors are all involved in determining the mean level of arterial blood pressure. It is concluded that vagally innervated cardiopulmonary receptors do not have a significant role in regulating arterial blood pressure during exercise but are involved in establishing the general level of arterial blood pressure.
Automated limb blood flow plethysmograph
Authors: Marcus R. R. , Horvath S. M.
Published: December 2017

An automated limb blood flow plethysmograph has been developed and interfaced to a PDP-11/60 computer. This system automatically inflates blood pressure cuffs, calibrates strain gauges, provides real-time display of limb circumference changes, and provides digital output of limb blood flow and real-time graphic display of cuff pressure. The system has been designed to require a minimum amount of user interaction by providing automatic calibration in situ, which is initiated by depressing a switch, and automatic venous cuff inflation, which initiates computer analysis of blood flow data. Digital and graphic display of blood flow is provided on a computer terminal 12 s after the start of venous occlusion. All raw data are stored on a disk for optional postexperiment analysis, which enables each blood flow curve to be graphically displayed and reanalyzed under user control. Calculated data are stored on a disk for output to a line printer at the conclusion of an experiment. A trend plot of all analyzed blood flows can be displayed on a computer terminal anytime during an experiment.
Blood volume and its measurement in the chronically catheterized sheep fetus
Authors: Brace R. A.
Published: December 2017

Single and double indicator-dilution measurements of the circulating blood volume were made in chronically catheterized sheep fetuses averaging 131 days gestation. Blood volume measured with 51Cr-labeled red blood cells averaged 110.3 +/- 10.7 (SD) ml/kg with a range of +/- 15% of the mean (n = 23). The 125I-albumin (n = 7) and 125I-fibrinogen (n = 5) blood volumes averaged 126.2 +/- 9.8 (SD) and 124.5 +/- 6.9 ml/kg, respectively. The double-indicator fetal blood volume averaged 120.6 +/- 8.3 ml/kg (n = 12); however, this value is too high due to the assumptions used when determining plasma volumes. In addition, after either a 15% fetal hemorrhage or intravenous epinephrine infusion, there was no statistically significant release of red blood cells into the circulation. Labeled maternal red blood cells were removed from the fetal circulation at an average rate of 18%/h, whereas there was no detectable loss of labeled autologous fetal cells from the circulation. Finally, there were spontaneous changes in fetal blood volume including an average decrease of 2.3 +/- 0.3% (SE) (n = 10) during low-level uterine contractions (i.e., contractures). In summary, it appears that labeled fetal red blood cells provide the most accurate estimate of circulating fetal blood volume because of unresolvable problems in extrapolating the plasma label back to zero time. In addition, changes in blood volume can be accurately calculated from either hematocrit or hemoglobin concentration because there appeared to be no red cell reservoirs in the fetuses.
Cerebral venous outflow and arterial microsphere flow with elevated venous pressure
Authors: Wagner E. M. , Traystman R. J.
Published: December 2017

The cerebral blood flow response to cerebral venous pressure elevation was studied in pentobarbital-anesthetized dogs using the cerebral venous outflow and radiolabeled microsphere techniques. Cerebral venous pressure elevation resulted in a significant reduction in cerebral venous outflow at a pressure of approximately 2.0 mmHg (referenced at the level of the external auditory meatus). At higher pressures, cerebral venous outflow decreased at a rate of 0.5 ml x min-1 x mmHg-1. Mean arterial pressure was 102.0 mmHg, and thus cerebral perfusion pressure (mean arterial pressure minus cerebral venous pressure) was well within the range for cerebral autoregulation. These results were obtained regardless of whether cerebrospinal fluid pressure was allowed to rise concomitantly with cerebral venous pressure (11 dogs) or was maintained at atmospheric pressure (7 dogs). However, simultaneous measurement of cerebral venous outflow and total and regional cerebral blood flow with the radiolabeled microsphere technique with venous pressure elevation (6 dogs) produced discrepant results. As cerebral venous pressure was elevated to approximately 16.0 mmHg, cerebral venous outflow decreased to 40% of control while total and regional cerebral blood flow values remained unchanged, so that regional and cerebral vascular resistances decreased. These results suggest that cerebral venous pressure elevation opens intracranial venous anastomotic channels and diverts blood flow from the measured venous drainage through other drainage sites. In addition, our results suggest that the dominant mechanism of cerebral autoregulation is metabolic, not myogenic.
Electrophysiological differentiation of alpha-receptors on arteriolar smooth muscle
Authors: Morgan K. G.
Published: December 2017

The effects of clonidine (a prototype of an alpha 2-agonist) and phenylephrine (a prototype of an alpha 1-agonist) on intracellularly recorded electrical activity and vessel size of feline submucosal arterioles were compared. Phenylephrine constricts the vessels and causes a depolarization and the initiation of oscillations of the membrane potential. These oscillations occasionally give rise to spike potentials. In contrast, clonidine produces no significant depolarization of the resting potential in spite of the simultaneous initiation of contraction. Neurally induced depolarizations (excitatory junction potentials) are not blocked and are sometimes augmented by the nonselective alpha-blocker phentolamine even though the depolarization induced by norepinephrine is blocked by phentolamine. Excitatory junction potentials are antagonized by the alpha 1-blocker prazosin. The contraction caused by clonidine is blocked to a greater degree by yohimbine (a relatively selective alpha 2-blocker) than by prazosin. The contraction caused by phenylephrine is blocked to a greater degree by prazosin than by yohimbine. These data indicate that phenylephrine and clonidine act by different mechanisms and, taken together with previous studies, suggest that alpha 1- and alpha 2-stimulation utilize different excitation-contraction coupling mechanisms.
Contribution of adenosine to arteriolar autoregulation in striated muscle
Authors: Morff R. J. , Granger H. J.
Published: December 2017

The contribution of adenosine to blood flow autoregulation in striated muscle was evaluated by direct in vivo visualization of arterioles in the rat cremaster muscle. Male Sprague-Dawley rats were anesthetized with pentobarbital sodium, and the cremaster muscle was surgically exposed and maintained in a controlled tissue bath environment with pH 7.40, CO2 tension (PCO2) congruent to 40 mmHg, and O2 tension (PO2) at either a high (congruent to 70 mmHg) or a low (congruent to 10 mmHg) value. Local adenosine activity was blocked in some animals by the addition of theophylline (3 X 10(-5) M) to the bath medium. Individual second (2A)- and third (3A)-order arterioles were observed via closed-circuit television microscopy, and blood flow in each arteriole was calculated from simultaneous measurements of arteriolar diameter and red blood cell velocity. Perfusion pressure to the animal's hindquarters was altered by varying the degree of occlusion of the sacral aorta; arteriolar diameter, velocity, and blood flow responses were plotted as a function of the varying pressure. Both 2A and 3A arterioles exhibited vasodilation and substantial superregulation of blood flow (increased blood flow with decreased perfusion pressure) when bath PO2 was low and adenosine activity was not blocked. Addition of theophylline to the cremaster bath medium significantly reduced the dilation and abolished superregulation, although substantial autoregulation remained. When bath PO2 was high, the degree of arteriolar dilation and autoregulation was reduced compared with the low bath PO2 responses, and blocking adenosine activity had no effect on the responses. These results support the concept that changes in local adenosine levels are involved in the autoregulatory responses observed in the rat cremaster muscle and that the magnitude of adenosine's contribution is directly related to the degree of tissue hypoxia. However, blocking adenosine activity did not totally abolish autoregulation, suggesting that other metabolic and/or myogenic factors may also be contributing to blood flow regulation in this tissue.
Clearance of rabbit plasma angiotensinogen and relationship to CSF angiotensinogen
Authors: Lewicki J. A. , Printz J. M. , Printz M. P.
Published: December 2017

Rabbit plasma angiotensinogen was purified 1,390-fold by classical purification procedures. Analytical polyacrylamide gel electrophoresis and direct activity assay revealed that the purified preparations were greater than 90% native angiotensinogen. The purified angiotensinogen was radiolabeled with 125I-Na using the immobilized lactoperoxidase-Sepharose method and injected into awake, conscious rabbits. Complex clearance kinetics were observed that were resolved by a three-component model; half of the protein was cleared rapidly (t1/2 = 6 and 54 min), presumably reflecting mixing and redistribution, whereas half exhibited slow clearance kinetics (t1/2 = 8.58 h). The clearance kinetics were independent of the method of iodination and the isoelectric-point microheterogeneity of the protein. With knowledge of clearance kinetics we tested whether cerebrospinal fluid angiotensinogen could derive from the plasma pool. After injection of approximately 100 microCi 125I-angiotensinogen into the rabbit circulation, little 125I-angiotensinogen was detected in cerebrospinal fluid. Further, the brain space of 125I-angiotensinogen was identical to that of 125I-albumin, a protein that does not partition from plasma into the central nervous system. We conclude that the brain prohormone does not appear to be derived from the plasma pool.
Cardiac function and myosin ATPase in diabetic rats treated with insulin, T3, and T4
Authors: Garber D. W. , Everett A. W. , Neely J. R.
Published: December 2017

The effects of insulin, T4, and T3 treatment on cardiac function, myosin ATPase activity, and myosin isozyme distribution were studied in alloxan diabetic rats. Diabetes resulted in depressed peak ventricular pressure development, heart rate, and left ventricular +dP/dt. Myocardial Ca2+-activated myosin ATPase activity was reduced in association with lower serum levels of T3 and T4. The V1 isozyme of myosin decreased, and both V2 and V3 isozymes increased. Insulin treatment totally reversed the changes in function, serum thyroid hormones, and myosin ATPase activity. Treatment of diabetic animals with T4 (5 or 10 micrograms/day) prevented the decrease in myosin ATPase but did not prevent the changes in cardiac function, myosin isozymes, or serum T3 levels. Pharmacological doses of T3 (3 micrograms/day) that were adequate to maintain higher than normal serum T3 corrected the decrease in Ca2+-activated myosin ATPase and heart rate but only partially corrected the changes in pressure development and myosin isozyme distribution. Only when serum T3 was increased to four times normal was cardiac function corrected.
Sodium-calcium exchange in dog heart mitochondria: effects of ischemia and verapamil
Authors: Wolkowicz P. E. , Michael L. H. , Lewis R. M. , McMillin-Wood J.
Published: December 2017

Na+ - Ca2+ exchange was studied in two preparations of dog heart mitochondria isolated from normal and ischemic muscle following occlusion of the circumflex (CFX) coronary artery with or without prior verapamil infusion. Na+ - Ca2+ exchange in mitochondria isolated using polytron homogenization showed sigmoidal kinetics with phosphate, whereas mitochondria isolated using gentle nagarse treatment showed hyperbolic kinetics and a Vmax 60% greater than the polytron preparation. Nagarse did not alter the sigmoidal kinetics or exchange velocities of the polytron mitochondria observed with phosphate. With acetate, both preparations exhibited hyperbolic kinetics, and the sodium required for half-maximum activity was increased. Verapamil inhibited Na+ - Ca2+ exchange in both preparations with phosphate, but not with acetate. Thirty or sixty minutes of acute ischemia following CFX occlusion produced significant epicardial surface S-T elevation in the ischemic area and a decrease in myocardial segment shortening. Na+ - Ca2+ exchange of both ischemic preparations was depressed, and the kinetics of the polytron preparation changed to hyperbolic. Pretreatment of the experimental animals with verapamil (0.3 mg/kg) before 60 min of ischemia protected the exchange rates in both preparations, and the sigmoidicity of the polytron mitochondria was retained.
Left ventricular oxygen consumption and function in hypoxemia in conscious lambs
Authors: Fisher D. J.
Published: December 2017

The effects of hypoxemia on left ventricular myocardial blood flow, myocardial oxygen consumption, and contractile function were studied in 12 conscious newborn lambs 4-24 days after birth. Through a left thoracotomy, we placed fluid-filled catheters in the ascending aorta, coronary sinus, and left atrium. An electromagnetic flow transducer was placed around the ascending aorta, and a solid-state pressure transducer was introduced into the left ventricle. Three to four days later we measured aortic and coronary sinus blood oxygen contents, left ventricular myocardial blood flow, heart rate, aortic and left ventricular blood pressures, ascending aortic blood flow velocity, and the first derivative of left ventricular pressure (dP/dt) and ascending aortic blood flow velocity (dV/dt) during a control period and during 50 and 75% reductions in ascending aortic oxygen content. Myocardial oxygen consumption was calculated. There was no significant change in aortic or coronary sinus blood pH or CO2 tension during the study. Coronary sinus blood oxygen content and the arteriovenous difference of oxygen across the left ventricle decreased as a linear function of the aortic blood oxygen content. Myocardial blood flow increased in proportion to the reduction in aortic blood oxygen content. Myocardial oxygen consumption increased during hypoxemia but not as a function of aortic blood oxygen content. There was no significant change in left ventricular end-diastolic pressure or aortic mean blood pressure. dP/dt and dV/dt doubled during hypoxemia, but the increases did not occur as a function of the aortic blood oxygen content. In conscious, unanesthetized newborn lambs, 50 and 75% reductions of aortic blood oxygen content were associated with significant increases of left ventricular myocardial blood flow, oxygen consumption, and contractile function.
Electrical stimulation causes endothelium-dependent relaxation in lung vessels
Authors: Frank G. W. , Bevan J. A.
Published: December 2017

Ring segments of blood vessels were isolated from the lungs of rabbits, cats, and monkeys. After constriction with norepinephrine, electrical field stimulation caused smooth muscle relaxation in these segments. Mechanical removal of the endothelial layer, verified by scanning electron microscopy, abolished or greatly attenuated the relaxation. The response could be restored in part by apposing the endothelial surface of another vessel segment and the denuded inner surface of the constricted vessel segment. Incubation with tetrodotoxin, procaine hydrochloride, guanethidine, propranolol, atropine, metiamide, indomethacin, quinacrine hydrochloride, 5,8,11,14-eicosatetraynoic acid, aminophylline, and verapamil failed to block or enhance the relaxation response to field stimulation. We conclude that the vascular endothelium in the larger pulmonary arteries and veins studied contains a diffusible substance that inhibits smooth muscle contraction. Its release by electrical field stimulation in vitro does not involve classic neuronal transmitter release or metabolism of arachidonic acid by cyclooxygenase or lipooxygenase.
Effect of ischemia, hypertrophy, hypoxia, acidosis, and alkalosis on canine defibrillation
Authors: Kerber R. E. , Pandian N. G. , Hoyt R. , Jensen S. R. , Koyanagi S. , Grayzel J. , Kieso R.
Published: December 2017

Our purpose was to assess the effect of myocardial ischemia, left ventricular hypertrophy, and systemic hypoxia and acid-base abnormalities on the energy requirements for defibrillation. We determined the defibrillation threshold (DFT), the minimum energy required to defibrillate. DFT was not significantly elevated after left anterior descending coronary occlusion, nor was there a relationship between the size of the occluded coronary distribution area (coronary risk area) and the change in DFT in individual animals. Renal hypertension and left ventricular hypertrophy were induced by unilateral nephrectomy and contralateral renal artery stenosis. DFT in left ventricular hypertrophy dogs was not significantly higher than in dogs without hypertrophy. Finally, we induced systemic hypoxia and acid-base abnormalities. Neither respiratory nor metabolic acid-base disturbances affected DFT, but during systemic hypoxia (O2 tension 45 +/- 2) DFT fell from 83 +/- 49 to 58 +/- 28 J (P less than 0.01). Thus in dogs, myocardial ischemia, left ventricular hypertrophy, and acid-base abnormalities do not elevate defibrillation energy requirements, whereas hypoxia reduces the energy needed to defibrillate.
Effect of experimental diabetes on rat cardiac cAMP, phosphorylase, and inotropy
Authors: Vadlamudi R. V. , McNeill J. H.
Published: December 2017

The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the effect of isoproterenol on adenosine 3',5'-cyclic monophosphate (cAMP) content, inotropy, and phosphorylase activity. Experimental diabetes was induced by intravenous injection of either alloxan (40 mg/kg) or streptozotocin (50 mg/kg). There were no changes in either basal cAMP levels or in isoproterenol-induced cAMP levels in hearts from diabetic rats at either 3 days or 100-120 days after induction of diabetes. Maximum changes produced by isoproterenol in positive and negative dP/dt developments of diabetic rat hearts were also not different from control at either time point. However, phosphorylase was activated to a significantly greater extent by isoproterenol in hearts obtained from acute as well as chronic diabetic rats. Chronic diabetic rat hearts exhibited significantly higher total phosphorylase activity. Diabetic rat hearts had slightly but not significantly higher basal phosphorylase a activity. Furthermore, prostaglandin E1 activated phosphorylase in diabetic rat hearts but not in control rat hearts. Acute metabolic derangements and alterations in Ca2+ homeostasis caused by diabetes could be the underlying causes for this phosphorylase response. Thyroid hormone levels were depressed in diabetic rats. However, hypothyroidism is probably not responsible for the alterations in phosphorylase activity.
Muscular blood flow distribution patterns as a function of running speed in rats
Authors: Laughlin M. Harold , Armstrong R. B.
Published: December 2017

Page H296: M. Harold Laughlin and R. B. Armstrong. “Muscular blood flow distribution patterns as a function of running speed in rats.” Page H299, Table 2: the value for leg soleus (S) muscle at a treadmill speed of 30 m/min should be 137 instead of 17.
Relationship between weight gain and lymph flow in dog lungs
Authors: Drake R. E. , Scott R. L. , Gabel J. C.
Published: December 2017

Lung weight is a useful indicator of increases in lung extravascular volume. In addition, the lung lymph flow rate (QL) is an important factor in lung fluid balance. We have studied the weight and QL responses to elevations in capillary pressure (Pc) in intact dog lung lower left lobes. We measured lobe weight continuously. We also measured QL from small lymph vessels from the same lobes. The base-line QL was 1.7 +/- 1.5 microliter/min, and the weight was constant. After we increased Pc by 8-20 cmH2O, both weight and QL increased transiently. In most lungs the weight reached a new steady state. When we increased Pc further, weight increased continuously; however, QL reached a plateau. The continuous weight gain was due to edema. These results show that weight and QL respond similarly in nonedematous lungs; however, the weight and QL responses in edematous lungs may be different.
Myocardial blood flow during exercise after gradual coronary occlusion in the dog
Authors: Bache R. J. , Schwartz J. S.
Published: December 2017

Myocardial blood flow was studied with radioactive microspheres in 14 dogs 1 mo after placement of an Ameroid constrictor on either the left circumflex or the left anterior descending coronary artery to result in total coronary occlusion without myocardial infarction, as well as in 7 normal control dogs. Measurements were performed during quiet resting conditions and during two levels of treadmill exercise to achieve heart rates of approximately 180 (light exercise) and 230 beats/min (heavy exercise). During resting conditions myocardial blood flow in the collateral-dependent area was normal in all dogs. Three different patterns of response occurred during treadmill exercise in the animals with coronary occlusion. In five dogs, both the volume and transmural distribution of myocardial blood flow behaved similarly to the normal dogs at both exercise levels. In five dogs, blood flow behaved normally during light exercise, but during heavy exercise a transmural redistribution of perfusion occurred in the collateralized area to result in subendocardial underperfusion. Finally, in four dogs even light exercise resulted in subendocardial underperfusion in the collateral-dependent area, whereas further increasing the exercise load resulted in an actual decrease of subendocardial blood flow below the resting level. These data demonstrated that although resting myocardial blood flow was normal in the collateral-dependent area 1 mo after Ameroid implantation, a markedly heterogeneous response occurred during exercise, ranging from a completely normal response to a severe degree of exercise-induced subendocardial underperfusion.
Effects of free radical generation on mouse pial arterioles: probable role of hydroxyl radicals
Authors: Rosenblum W. I.
Published: December 2017

Mouse pial arterioles were exposed to the free radical-generating reactants acetaldehyde and xanthine oxidase. Concentrations of 0.5 mM acetaldehyde and 0.1 U/ml xanthine oxidase caused reversible dilations, whereas higher concentrations produced initial constrictions followed by reversible dilations. The following free radical scavengers inhibited the dilation when added to the lower concentrations of reactants: superoxide dismutase, a superoxide scavenger; catalase, an H2O2 scavenger; and mannitol, a hydroxyl scavenger. In addition, pretreatment of the animal with dimethyl sulfoxide, a hydroxyl scavenger, also inhibited the response. The scavengers were also tested against either the dilation produced by increased inspired CO2 or against the dilation produced by local application of 10(-3) M papaverine. No significant effect was observed. The data support the hypothesis that hydroxyl radicals can dilate pial arterioles, since all the scavengers can ultimately reduce levels of hydroxyl generated by acetaldehyde plus xanthine oxidase.
Microphotometric determination of hematocrit in small vessels
Authors: Pries A. R. , Kanzow G. , Gaehtgens P.
Published: December 2017

Evaluation and calibration of a microphotometric method for hematocrit determination in microvessels of transilluminated tissues is described. This method is based on the relation of the optical density (OD) of a microvessel to its hematocrit (Hct). The following requirements of the microphotometric system appear essential: narrow-band monochromatic light source with efficient false light suppression, high numerical aperture of the objective and low numerical aperture of the condensor. We used a video system to measure the intensities of incident (Io) and transmitted (I) light. For converting of Io and I into OD values, correcting procedures were evaluated to eliminate the influence of glare, shading, and fading. The calibration procedure was performed with glass tubes of inner diameter (ID) between 13 and 68 microns perfused with red cell suspensions. A function was fitted to the data, correlating OD to ID and Hct. The standard deviation of the original data from this function is +/- 0.02 units of fractional hematocrit. The presented method allows the continuous determination of the hematocrit in a microvessel as well as the off-line evaluation of the hematocrit distribution within a microvessel network.
Effects of age on mechanical and electrical performance of rat myocardium
Authors: Capasso J. M. , Malhotra A. , Remily R. M. , Scheuer J. , Sonnenblick E. H.
Published: December 2017

Left ventricular papillary muscles were isolated from male Fischer rats at 3, 6, 12, and 24 mo of age. Mechanical performance and transmembrane action potential characteristics were recorded simultaneously. Contractile protein enzyme activity was determined in the same hearts from which papillary muscles were used for acquisition of mechanical and electrical information. There was an age-related increase in the isometric time to peak tension and time to half relaxation with no age-related change in peak isometric developed tension. Resting tension showed a significant increase at both 12 and 24 mo of age. Although no significant change was noted in peak rate of tension rise (+T') or fall (-T'), there was a significant age-related prolongation in the time to +T' and -T'. Isotonically, peak shortening decreased in 24-mo-old animals. Time to peak shortening increased, whereas peak velocity of muscle shortening decreased from 3 to 24 mo of age. A significant and progressive prolongation was noted in the duration of the transmembrane action potential at 50% and 75% repolarization. In addition an age-related progressive decline was seen in contractile protein enzyme activity. These biochemical and electrophysiological alterations may help to explain the contractile modifications during aging.
Cardiorenal hemodynamics and sodium excretion in rats with myocardial infarction
Authors: Hostetter T. H. , Pfeffer J. M. , Pfeffer M. A. , Dworkin L. D. , Braunwald E. , Brenner B. M.
Published: December 2017

The relation between left ventricular function and renal excretion of sodium (Na+) was studied in rats with myocardial infarction (MI) and varying degrees of left ventricular dysfunction. Three groups of rats were defined: 1) control sustained no infarct, 2) small to moderate infarcts involved 10-40% of the left ventricular circumference, and 3) large infarcts involved greater than 40%. In conscious rats, Na+ excretion was measured after administration of saline load by gavage. Four hours after the load, rats with large MI excreted less than one half the amount of Na+ excreted by control rats, whereas rats with small to moderate MI excreted an intermediate amount. In a second group of anesthetized rats, Na+ excretion, renal hemodynamics, and ventricular performance were determined before and after acute intravenous volume expansion with a balanced salt solution. Rats with small to moderate MI demonstrated minimal impairment in ventricular pumping ability but excreted less Na+ after volume expansion than did control rats. However, rats with large MI demonstrated marked impairment in left ventricular performance and exhibited the least natriuretic response to volume loading. Glomerular filtration rate and renal plasma flow failed to increase with volume expansion in both groups of rats with MI. Thus Na+ excretion in response to acute volume loading was diminished in rats with large MI and markedly impaired cardiac performance but was also reduced in rats with small to moderate MI and minimal changes in ventricular pumping capacity.
Endothelial albumin permeability measured with a new technique in perfused rabbit lung
Authors: Kern D. F. , Levitt D. , Wangensteen D.
Published: December 2017

This study describes two methods of measuring the albumin permeability-surface area product (PS) of the pulmonary microvascular endothelium in isolated, perfused rabbit lungs. Both involve direct sampling of lung tissue to measure how much labeled albumin has entered the extravascular space during a known exposure period. In one, the traditional "multiple-sample" method, extravascular albumin is measured for several different exposure times to determine the kinetics of transcapillary albumin movement, and PS is calculated from that data. We found single-exponential kinetics, with a half time of 77 min and a PS of 2.28 X 10(-3) cm3 . min-1 . g blood-free wet lung-1. The second, "single-sample" method, is a new modification that involves exposing the tissue to labeled albumin for only 3 min, followed by a 3-min vascular washout. Tissue is then analyzed for extravascular albumin and PS calculated assuming the interstitial albumin concentration is essentially zero. The PS obtained was 2.44 X 10(-3) cm3 . min-1 . g blood-free wet lung-1, not significantly different from the value obtained using the more accepted method. Possible sources of error in the new method are discussed, and we conclude that it is an easy, quick, reliable way of accurately measuring macromolecular PS in the lung and presumably other organs as well.
Kinetics of rouleaux formation using TV image analyzer. I. Human erythrocytes
Authors: Shiga T. , Imaizumi K. , Harada N. , Sekiya M.
Published: December 2017

An apparatus for determining the velocity of erythrocyte rouleaux formation was constructed, combining an inverted microscope, a transparent cone-plate viscometer, a TV image analyzer, and a computer. At lower shear rates, the overall process is the sedimentation and the rouleaux formation followed by the development of three-dimensional aggregates. The individual erythrocyte could be observed and the process was expressed by the time courses of the changes in the count and area of particles; taking the computed increment in the area/count, the rate of rouleaux formation could be estimated. The effects of shear rates, hematocrits, plasma proteins, and pH were quantified. The rate of rouleaux formation in autologous plasma increased by (1) lowering the shear rates (1.9 less than or equal to gamma less than or equal to 15 s-1),2) increasing the hematocrit (up to 0.6%), 3) adding human fibrinogen (up to 600 mg/dl) or gamma-globulin, and 4) increasing pH. The transformation to echinocytes or to stomatocytes decreased the rate of rouleaux formation. The pH effect was explained by the increase in mean corpuscular volume at lower pH rather than by the changes in the electrostatic repulsion or in the protein binding.
Partial isolation of an endogenous norepinephrine uptake inhibitor in canine plasma
Authors: Freas W. , Carrillo A. , DiMarzio L. , Haddy F. J. , Muldoon S. M.
Published: December 2017

We have previously reported that homologous plasma inhibits the accumulation of [3H]norepinephrine ( [3H]NE) by the canine saphenous vein. The purpose of this study was to extract the inhibitory substance(s) from plasma and to examine some of its properties. The net accumulation of tritium by saphenous vein strips following incubations in [3H]NE was inhibited 34.4 +/- 6.1% by a 60% plasma in Krebs solution. An acetone extract of this plasma reconstituted to 83% of its original unextracted volume also significantly inhibited net tritium accumulation by 24.5 +/- 4.7%. After lyophilization of this extract, the inhibitor was not readily solubilized in dilute acetic acid but was soluble in dilute sodium bicarbonate solutions. This extract solution, reconstituted to 66% of the original plasma volume, significantly inhibited the accumulation of [3H]NE by 35.0 +/- 9.8%. Kinetic analysis using this preparation suggests that the inhibition may be competitive in nature. The activity was not sensitive to heat but was abolished by the neuronal uptake blocker cocaine. Further purification with gel chromatography produced a small molecular weight fraction that inhibited tritium accumulation. When this sample was reconstituted in a volume equivalent to that of the unextracted plasma, the contractile response of the isolated canine saphenous vein to electrical stimulation was significantly enhanced. Thus the inhibitory activity of plasma on the uptake of [3H]NE by the canine saphenous vein is due in part to a heat-stable small molecule that inhibits the initial rate of [3H]NE uptake.
Capillarity and fiber types in the cremaster muscle of rat and hamster
Authors: Sarelius I. H. , Maxwell L. C. , Gray S. D. , Duling B. R.
Published: December 2017

We determined muscle fiber type and capillarity in cremaster muscle samples from rats and hamsters of different ages. Histochemical estimation of oxidative capacity was made from the activity of either nicotinamide dinucleotide tetrazolium reductase (NADH-TR) or succinic dehydrogenase (SDH), and fibers were termed fast or slow from myofibrillar ATPase activity. Fibers were classified as type I (low ATPase, high NADH-TR/SDH), type IIa (high ATPase, high SDH/NADH-TR), type IIb (high ATPase, low SDH/NADH-TR), or type IIc (no acid reversal of ATPase, high NADH-TR). Type IIb fibers accounted for 60-80% of the muscle area in both species at all ages. The principal change with maturation was muscle fiber hypertrophy. Mean cross-sectional fiber area increased from 488 +/- 70 (SE) and 453 +/- 19 micron2 in young hamsters and rats, respectively, to 1,255 +/- 99 and 1,540 +/- 101 micron2 in adults. Capillary density (no. of capillaries/mm2 tissue) paralleled fiber hypertrophy; it decreased significantly with maturation from 684 +/- 60 (SE) to 228 +/- 26/mm2 in hamsters and from 341 +/- 15 to 213 +/- 15/mm2 in rats. In vitro estimates of capillary density are compared with previously obtained in vivo data (31), and sources of error are identified. We conclude that reported differences in microvascular function in the cremaster muscle in vivo during maturation or between species cannot be ascribed to changes in muscle composition.
Vasopressin and renin responses to hemorrhage in conscious, cardiac-denervated dogs
Authors: Wang B. C. , Sundet W. D. , Hakumaki M. O. , Goetz K. L.
Published: December 2017

We measured plasma arginine vasopressin (AVP) and plasma renin activity (PRA) during continuous hemorrhage in cardiac-denervated and sham-operated conscious dogs. Hemorrhage produced comparable decreases in aortic pressure, cardiac output, stroke volume, pulmonary arterial pressure, and left and right atrial pressures in each group of dogs. After 10 ml blood/kg body wt had been removed, AVP was increased in sham-operated dogs (P less than 0.05) but not in cardiac-denervated dogs. After 20 and 30 ml blood/kg body wt had been removed, AVP was increased in all dogs, but the response was markedly attenuated in cardiac-denervated dogs. Hemorrhage at 10 and 20 ml/kg caused comparable increases in PRA in each group of dogs. However, at 30 ml/kg hemorrhage the increase in PRA was significantly higher in cardiac-denervated dogs than in sham-operated dogs. Our results suggest that cardiac receptors play a dominant role in mediating the release of AVP during hemorrhage in conscious dogs. In contrast, we found no evidence for a dominant role of cardiac receptors in mediating renin secretion during hemorrhage.