bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioassay of endothelium-derived relaxing factor(s): inactivation by catecholamines
Authors: Rubanyi G. M. , Lorenz R. R. , Vanhoutte P. M.
Published: December 2017

A bioassay technique was developed to analyze the effect of vasoactive substance(s) released from endothelial cells. Canine femoral arteries with or without endothelium were perfused with physiological salt solution at 37 degrees C. The perfusate was bioassayed with a ring of coronary artery without endothelium. A substance(s) released by the endothelial cells under basal conditions caused relaxation of unstimulated coronary arteries or relaxation of those contracted with prostaglandin F2 alpha. The release of the relaxing substance(s) was augmented by acetylcholine. The relaxation induced by acetylcholine was biphasic: an initial rapid phase followed by a partial recovery and a slowly developing prolonged relaxation; the half-life of the substance(s) causing the initial phase averaged 6.3 s. Norepinephrine, epinephrine, and ascorbic acid, given downstream of the femoral artery, reversibly prevented the second phase but only attenuated the initial relaxation. These observations indicate that an endothelium-derived relaxing substance(s) is released into the lumen of the femoral artery under basal conditions and during stimulation with acetylcholine. Catecholamines can inactivate the relaxing substance(s) but do not prevent either its production by endothelial cells or its action on vascular smooth muscle.
Cardiac mechanics and energetics: chemomechanical transduction in cardiac muscle
Authors: Gibbs C. L. , Chapman J. B.
Published: December 2017

When a heart is in a stable inotropic state, the end-systolic pressure-volume points of each work cycle fall on a straight line regardless of the magnitude of the afterload or the initial end-diastolic volume: cardiac O2 consumption (MVO2) per beat is linearly correlated with ventricular systolic pressure-volume area (PVA), defined in terms of stroke work and potential energy components. Moreover, if the basal and activation components of the cardiac energy cycle are subtracted, hearts operate at a constant PVA/MVO2 efficiency. The present review examines the energetic implications of these results for current muscle models, discussing the energetic background of earlier skeletal muscle viscoelastic models and examining differences between the vectorial outputs of ion transport ATPases and myofibrillar ATPases. The PVA data point to a unique stoichiometric relationship between myocardial energy flux and vectorial output, and it is shown that most existing myocardial O2 consumption data can be reconciled with the PVA concept. However, most muscle models would not predict a linear stoichiometric relation between energy flux and pressure-volume potential energy. We pose the question as to whether there is an undiscovered autoregulatory process at work in muscle.
Mechanisms of vasodilation induced by vasoactive intestinal polypeptide in rabbit mesenteric artery
Authors: Itoh T. , Sasaguri T. , Makita Y. , Kanmura Y. , Kuriyama H.
Published: December 2017

Vasoactive intestinal polypeptide (VIP; over 10(-13) M) inhibited the norepinephrine (NE)-induced contraction evoked from the rabbit mesenteric artery. Increased concentrations of VIP (over 10(-9) M) inhibited the contractions induced by caffeine and 39 mM [K]o. However, VIP (below 10(-7) M) had no effect on the membrane potential and resistance of muscle cells. In Ca-free solution, VIP (10(-10) M) inhibited the NE-induced contraction, but the second application of NE after removal of VIP enlarged the amplitude of contraction over that in the control. Yet when 10(-9) M VIP was applied, both the first and second contractions were consistently smaller than those observed by application of 10(-10) M VIP. In Na- and Ca-free solution, repetitive applications of NE generated contractions longer than those observed in Ca-free solution. When VIP (10(-10) M) was applied once (3 min), the contraction was inhibited only once during repetitive applications of NE. VIP (over 10(-9) M) dose dependently inhibited the NE-induced contraction and had a long-lasting inhibition after washout of the tissue. In saponin-treated skinned muscles, VIP (10(-7) M) had no effect on the Ca-induced contraction or on the Ca store sites. VIP (over 10(-8) M) was about 10 times more potent than equimolar concentrations of isoproterenol in increasing the content of adenosine 3', 5'-cyclic monophosphate (cAMP). These results indicate that VIP (10(-10) M) selectively inhibits the Ca release activated by NE, and high concentrations (over 10(-9) M) would expectedly increase the Ca extrusion from cells following increase in the levels of cAMP.
Crystalloid and perfluorochemical perfusates in an isolated working rabbit heart preparation
Authors: Chemnitius J. M. , Burger W. , Bing R. J.
Published: December 2017

Krebs-Henseleit buffer (KH) and a perfluorochemical (FC-43) were compared as perfusates in an isolated working rabbit heart preparation. Both perfusates were oxygenated in an identical manner using an infant bubble oxygenator. After 60 min of perfusion, no difference could be detected in the ratio of wet to dry heart weight between KH- and FC-43-perfused hearts (KH, 6.25 +/- 0.3; FC-43, 5.99 +/- 0.20). Left ventricular systolic pressure, maximal rate of left ventricular pressure rise, mean aortic systolic pressure, cardiac output, aortic flow, left ventricular power, and myocardial O2 consumption (MVO2) were significantly higher in FC-43-perfused hearts throughout the time of perfusion. However, there were no differences in resistance to cardiac output and heart rate. In KH- and FC-43-perfused hearts, MVO2 and left ventricular power were closely correlated (KH, r = 0.793; FC-43, r = 0.831). Significantly higher coronary flow of KH-perfused hearts could be attributed to the lower viscosity of KH (1.05 Pa . s) compared with FC-43 (1.91 Pa . s). Increased O2 extraction during KH perfusion could not compensate for low O2-carrying capacity of KH buffer (345 compared with 705 nmol O2 X ml-1 in FC-43 emulsion). A postischemic increase of coronary flow was observed only in FC-43-perfused hearts (28%). These results demonstrate a different response of perfused heart preparations to FC-43 and KH buffer.
Parasympathetic control of transmural coronary blood flow in dogs
Authors: Reid J. V. , Ito B. R. , Huang A. H. , Buffington C. W. , Feigl E. O.
Published: December 2017

The transmural distribution of coronary blood flow was studied during vagal stimulation in closed-chest, morphine- and alpha-chloralose-anesthetized dogs. The left main coronary artery was cannulated and perfused at constant pressure. Bradycardia during vagal stimulation was prevented by atrioventricular heart block and ventricular pacing. Beta-adrenergic receptors were blocked with propranolol (1 mg/kg iv), and aortic pressure was stabilized by means of a pressure reservoir. Regional myocardial blood flow was measured with 9-micron radioactive microspheres during vagal stimulation and during intracoronary acetylcholine infusion. Vagal stimulation increased coronary blood flow uniformly across the left ventricular wall. In contrast, intracoronary acetylcholine infusion, at a rate selected to increase total flow to the same degree, vasodilated the subendocardium more than the subepicardium, increasing the inner/outer blood flow ratio. It is concluded that both vagal activation and acetylcholine produce coronary vasodilation that is independent of left ventricular preload, afterload, and heart rate. Acetylcholine vasodilation preferentially vasodilates the subendocardium, increasing the inner/outer flow ratio, but vagal stimulation produces uniform vasodilation across the left ventricular wall.
Cerebrovascular hypoxic and autoregulatory responses during reduced brain metabolism
Authors: Donegan J. H. , Traystman R. J. , Koehler R. C. , Jones M. D. , Rogers M. C.
Published: December 2017

The effect of reducing cerebral oxygen consumption (CMRO2) on the cerebral blood flow (CBF) responses to isocapnic hypoxic hypoxia and hypotension was examined in sheep. Newborn and adult animals were studied because of their different base-line CMRO2. Microsphere-measured CBF responses during pentobarbital coma (i.e., electroencephalographic silence) were compared with responses in conscious or lightly sedated animals. Induction of barbiturate coma reduced both CMRO2 and CBF by 50% from the awake value and by 25% from the value obtained in animals sedated with pentobarbital. The CBF response to 30 and 50% reductions in arterial O2 content (CaO2) was attenuated during coma, but only in proportion to the decrease in CMRO2. Whether CMRO2 was normal or reduced, the normoxic cerebral O2 delivery (CaO2 X CBF) was maintained during hypoxia in both newborns and adults. The relative autoregulatory index (fractional change in CBF divided by fractional change in perfusion pressure) was determined during graded hemorrhage. The index was not significantly different from zero (which represents perfect autoregulation) in awake, lightly sedated, or comatose animals. The data demonstrate that both base-line CBF and responses to hypoxia are closely tied to CMRO2 and that 50% reduction of CMRO2 does not impair cerebrovascular autoregulation.
Hemodynamic and regional circulatory alterations in dog during anaphylactic challenge
Authors: Kapin M. A. , Ferguson J. L.
Published: December 2017

Microspheres were employed to measure the cardiac output (CO), percent distribution of CO (%CO), and blood flow (BF) to various tissues in the dog during anaphylactic shock. Five minutes after challenge there was a 66 and 83% drop from control for mean arterial pressure and CO, respectively. Arterial glucose and lactic acid rose 62 and 537%, respectively. Furthermore, there was a narrowing of the systemic arteriovenous difference for PO2 and a widening of the venoarterial difference for PCO2. Pressure compensation toward control values began 5 min postchallenge and continued through 180 min. Circulatory perturbations during severe hypotension (less than mmHg) included depressed %CO and BF to the pancreas and spleen and elevated %CO to the brain and adrenals. Cerebral and adrenal BF remained unchanged at this period. BF to the kidneys, liver (hepatic artery), and gastrointestinal tract dropped markedly as a function of increased peripheral resistance and decreased CO. As cardiac performance improved, blood flow to the pancreas, spleen, liver, diaphragm, and gastrointestinal tissues returned toward control but was elevated to the adrenals and decreased to the brain.
Myocardial perfusion in compensated and failing hypertrophied left ventricle
Authors: Parrish D. G. , Ring W. S. , Bache R. J.
Published: December 2017

This study examined blood flow in the hypertrophied left ventricle with and without failure. Left ventricular hypertrophy was produced in 20 dogs by banding the ascending aorta at 6-7 wk of age; studies were performed after animals reached adulthood. Sixteen dogs had compensated hypertrophy, while four dogs had cardiac failure manifested by left ventricular dilatation and end-diastolic pressures greater than 18 mmHg. The degree of hypertrophy, assessed by left ventricular-to-body weight ratio, was similar in animals with compensated hypertrophy (7.29 +/- 0.26 g/kg) and failure (8.45 +/- 0.15); both were greater than control (4.50 +/- 0.15, P less than 0.01). Left ventricular systolic pressure was similar in compensated hypertrophy (184 +/- 9 mmHg) and failure (226 +/- 29), as compared with control (130 +/- 4; P less than 0.01). Left ventricular blood flow measured with microspheres was 0.89 +/- 0.07 ml X min-1 X g-1 in control animals, was increased to 1.34 +/- 0.05 with compensated hypertrophy (P less than 0.001), and was further increased with failure to 1.86 +/- 0.40 (P less than 0.05). The left ventricular wall thickness-to-cavity diameter ratio was increased to 0.63 +/- 0.04 with compensated hypertrophy but was only 0.40 +/- 0.05 in dogs with failure (P less than 0.01), suggesting that wall stress was greater in hearts with failure. These data suggest that increased blood flow rates in dogs with failure resulted from increased myocardial O2 requirements due to increased systolic wall stress. Need for increased blood flow during resting conditions in dogs with failure would impair the ability for further coronary vasodilation during periods of cardiac stress.
Incomplete coronary vasodilation during myocardial ischemia in swine
Authors: Pantely G. A. , Bristow J. D. , Swenson L. J. , Ladley H. D. , Johnson W. B. , Anselone C. G.
Published: December 2017

To determine if endogenous (ENDG) vasodilation was maximum during myocardial ischemia, left anterior descending (LAD) mean pressure (P) was reduced for 20 min in 13 swine. At LAD P of 45 mmHg (LAD P45) flow fell during ENDG = 25 but rose to 44 ml/min during adenosine (AD) infusion (P less than 0.01). Flow increased to subendocardium (ENDG 0.65 vs. AD 1.04 ml X min-1 X g-1) and to subepicardium (ENDG 0.99 vs. AD 1.83 ml X min-1 X g-1; P less than 0.05). No significant change occurred in myocardial O2 consumption (MVO2; ENDG 2.91 vs. AD 3.18 ml X min-1 X g-1), lactate extraction (ENDG = -5 vs. AD-1%), and wall thickening (WTh; ENDG + 16 vs. AD + 17%). At LAD P35, flow during ENDG was 12 but rose to 19 ml/min during AD (P less than 0.01). Flow increased to subendocardium (ENDG 0.24 vs. AD 0.46 ml X min-1 X g-1; P less than 0.02) and subepicardium (ENDG 0.51 vs. AD 0.87 ml X min-1 X g-1; P less than 0.01). No significant change occurred in MVo2 (ENDG 1.38 vs. AD 1.59 ml/min), lactate extraction (ENDG -38 vs. AD -22%), WTh (ENDG -1 vs. AD + 1%). Thus endogenous vasodilation reserve was not used fully during ischemia. AD increased flow but did not improve abnormalities in myocardial function or metabolism.
Baroreceptor reflex cardiovascular control in mongrel dogs and racing greyhounds
Authors: Cox R. H. , Bagshaw R. J. , Detweiler D. K.
Published: December 2017

The open-loop carotid sinus baroreflex control of arterial pressure-flow relations were compared in mongrel dogs and racing greyhounds (GH) anesthetized with alpha-chloralose. The carotid sinuses were bilaterally isolated and perfused under controlled pressure. Pulsatile pressure and flow were simultaneously measured in the ascending aorta, the celiac, superior mesenteric, left renal, and right iliac arteries. Open-loop set point values of mean arterial pressure were higher in GH before and after vagotomy. Reflex gains were similar before vagotomy but lower in GH after vagotomy. The overall range of control of arterial pressure was the same before vagotomy but smaller in GH after vagotomy. The variation of mean arterial pressure with mean carotid sinus pressure in GH was shifted toward higher pressure levels similar to resetting. The overall effects of vagotomy on carotid sinus baroreceptor reflex responses were smaller in GH. Operating point values of regional resistance were generally smaller in GH. Operating point sensitivities of regional resistance were the same except for the iliac bed, which was more sensitive in GH. These results document significant regional differences in the baroreceptor control of regional hemodynamics between mongrels and greyhounds that could contribute to altered responses especially to "hypertensive" perturbations.
Sympathetic regulation of cerebral blood flow during reflex hypertension
Authors: Lacombe P. , Miller M. C. , Seylaz J.
Published: December 2017

The cerebral circulatory effects of physiological stimulation of the sympathetic nervous system have been examined in the present study. In lightly anesthetized rabbits, reflex sympathetic activation was provoked by bilateral sinus deafferentation and vagotomy. Regional cerebral blood flow (CBF) was measured by the [14C]-ethanol technique and compared in paired brain structures following unilateral superior cervical ganglionectomy. Two subgroups of hypertensive rabbits were statistically distinguished. In the first (19 of 28 rabbits), CBF in the innervated hemisphere was little modified by hypertension but there was a significant side-to-side difference in CBF between the hemispheres. In the second group (9 rabbits) CBF was markedly increased by the systemic hypertension, and little difference was noted between innervated and denervated hemispheres. We demonstrate that, during acute hypertension, the superior cervical system contributes to cerebrovascular autoregulation; this contribution varies according to the brain region studied. In a subgroup of animals, little sympathetic activity could be evidenced, and it is hypothesized that in these rabbits a vasodilatory system was activated that counteracted the myogenic, autoregulatory responses.
Prejunctional adrenergic inhibition by aggregating platelets in canine blood vessels
Authors: Lorenz R. R. , Vanhoutte P. M.
Published: December 2017

Experiments were performed to determine the effect of aggregating platelets on adrenergic neurotransmission. Rings of canine saphenous veins and left circumflex coronary arteries were incubated with [3H]norepinephrine and suspended for superfusion. Aggregating platelets and exogenous 5-hydroxytryptamine decreased the overflow of [3H]norepinephrine evoked by electrical stimulation of the adrenergic nerve endings. The reduction of transmitter overflow caused by 5-hydroxytryptamine was prevented by the serotonergic antagonist methiothepin in a concentration that did not significantly affect the release of 5-hydroxytryptamine or thromboxane B2 from the aggregating platelets. Methiothepin decreased but did not abolish the inhibitory effect of aggregating platelets on neurotransmitter overflow. These experiments demonstrate that 5-hydroxytryptamine and other substances released from aggregating platelets can exert prejunctional inhibition of adrenergic neurotransmission in isolated blood vessels.
Unique coronary vasodilator induction by leukotriene D4
Authors: Ezra D. , Feuerstein G. , Czaja J. F. , Laurindo F. R. , Finton C. K. , Yeh G. C. , Goldstein R. E.
Published: December 2017

Coronary blood flow (CBF) and myocardial contractility decrease markedly in response to intracoronary administration of leukotriene D4 (LTD4). With steady infusion, however, both CBF and contractility escape, approaching preinfusion values despite ongoing LTD4 administration. To clarify the mechanism of this escape, we reinfused plasma from the coronary vein draining the myocardial area receiving LTD4. Introducing this plasma into a coronary artery caused a marked rise in coronary flow for the duration of the plasma infusion. Coronary flow reduction with vasopressin or mechanical occlusion matching that caused by LTD4 failed to elicit vasodilator production. Thus a unique coronary vasodilator factor is induced by LTD4. Whole blood or platelet-rich plasma incubated with LTD4 in vitro produced the same pattern of coronary dilation on intracoronary infusion; LTD4 incubation with platelet-poor plasma failed to elicit a vasodilation. The vasodilator factor is stable and is not potassium, a prostaglandin, catecholamine, histamine, serotonin, adenosine, adenosine diphosphate, or platelet-activating factor. Production of this leukotriene-induced vasodilator factor may account for the escape from LTD4-induced coronary constriction.
Effects of barodenervation on cardiovascular responses to static muscular contraction
Authors: Waldrop T. G. , Mitchell J. H.
Published: December 2017

The purpose of this study was to measure blood flow to various tissues during static muscular contraction in anesthetized cats and to evaluate if the baroreflex modulates the cardiovascular responses to muscular contraction. Contraction of the hindlimb muscles induced by ventral root stimulation caused increases in arterial pressure (delta 37.8 +/- 5.5 mmHg) and heart rate (delta 13.9 +/- 3.1 beats/min). Increases in blood flow to the heart, working skeletal muscles, and selected areas of the central nervous system occurred during muscular contraction. Blood flow to visceral organs did not change during muscular contraction. Baroreceptor-denervated cats showed a greater rise in arterial pressure (delta 55.5 +/- 5.5 mmHg) during muscular contraction than did the baroreceptor-intact cats. However, blood flow responses were similar in both groups. Thus the baroreceptor reflex modulates the pressor response without changing the alteration in blood flow during induced muscular contraction in anesthetized cats.
Effect of fatty acid oxidation on efficiency of energy production in rat heart
Authors: Hutter J. F. , Piper H. M. , Spieckerman P. G.
Published: December 2017

Myocardial fatty acid oxidation has been reported to be accompanied by an elevated O2 consumption compared with carbohydrate oxidation. The exact amount of this additional O2 consumption is controversial. Different investigators have observed an O2 wasting effect that is too large to be explained by the different ATP-to-O2 ratios of these substrates. With the use of isolated perfused rat hearts, O2 consumption and hemodynamic measurements were computer analyzed to provide on-line estimates of the ratio between O2 consumption and demand (EQ). Increasing palmitate or octanoate concentrations decreased the respiratory quotient, which was accompanied by a disproportionate increase of EQ. Inhibition of fatty acid oxidation by an inhibitor of acylcarnitine transferase or a blockade of mitochondrial thiolase caused a drastic reduction of fatty acid oxidation. The fatty acid-induced enhancement of O2 consumption was decreased to a much smaller extent, indicating that there are two different mechanisms responsible for the O2-wasting effect, one that depends on mitochondrial fatty acid oxidation and another that is not affected by an inhibition of this pathway.
Modification of lymph by lymph nodes. III. Effect of increased lymph hydrostatic pressure
Authors: Adair T. H. , Guyton A. C.
Published: December 2017

Previous studies have shown that lymph nodes function as fluid exchange chambers in which the protein concentration of lymph is changed in the direction required to establish equilibrium of the Starling forces acting across the nodal blood-lymph barrier. We examined the effect of increased lymph hydrostatic pressure on efferent lymph by use of an isolated dog popliteal node preparation in which lymph having a protein concentration averaging 27.6 +/- 1.2% (SD) of that of plasma was infused into the node at a flow rate averaging 45.6 +/- 0.2 (SD) microliter/min. We compared steady-state values of prenodal and postnodal lymph flow and protein concentration following step increases in efferent lymph pressure from 0 to over 15 mmHg. Increasing efferent lymph pressure to values less than about 8 mmHg caused the efferent lymph protein concentration to increase; however, further increases in lymph pressure caused the lymph protein concentration to decrease to values approaching those attained at very low lymph pressures. We suggest that the failure of high lymph pressure to increase lymph protein concentration might be caused by blood vessel collapse within the node, a condition believed to increase nodal blood capillary pressure and to decrease blood-lymph barrier filtration coefficient. An important finding was that increasing efferent lymph pressure caused significant amounts of lymph proteins to be lost during nodal transit. Therefore, it appears that increasing efferent lymph pressure to very high values has little effect on lymph protein concentration but has great effect on postnodal lymph protein flux.
Effect of temperature on transcapillary water movement in isolated cat hindlimb
Authors: Wolf M. B. , Watson P. D.
Published: December 2017

Capillary filtration coefficient (CFC) was measured in the isolated cat hindlimb preparation, perfused at 20 ml X min-1 X 100 g muscle-1 with a perfusate containing 6 g/dl albumin and normal electrolyte concentrations, to which were added 50 ml of the cat's blood and 6 micrograms of the vasodilator isoproterenol. CFC was determined three to six times in an initial control period during which the tissue temperature (measured by a 5-mm disk thermistor implanted in a thigh muscle) was controlled near 37 degrees C. Tissue temperature was decreased to 5-10 degrees C by lowering perfusate and ambient air temperatures. About 50 min were required for tissue temperature equilibration. CFC was measured at low temperature and then again at 37 degrees C. For nine experiments, the ratio of CFC at low temperature to that in the 37 degrees C control periods averaged 87% of the ratio of water viscosity at 37 degrees C to that at low temperature. The activation energy for water calculated from these data was 5.0 kcal/mol. These results may be explained by all transcapillary water flow moving by diffusion through narrow pores or by about 90% moving by convection, with the remainder going through a lipid pathway. However, the results may be entirely due to a direct effect of temperature on the geometry of the transcapillary pathway for water movement.
Decreased auxotonic sarcomere shortening in hypertrophied rabbit myocardium
Authors: Hultgren P. B. , Hamrell B. B.
Published: December 2017

Auxotonic sarcomere length change occurs during isometric twitches of isolated cardiac muscle preparations. To assess the amount of internal work in hypertrophied myocardium, we measured auxotonic sarcomere length change during isometric tension development over a range of initial muscle and sarcomere lengths. Hypertrophy was produced by banding the pulmonary artery, which resulted in an increase in the ratio of right ventricular free wall weight to total ventricular weight (normal 0.19 +/- 0.004; hypertrophy 0.35 +/- 0.008; P less than 0.001). Right ventricular free wall trabeculae and papillary muscles were studied with optical and mechanical instrumentation, including a helium-neon laser, to measure sarcomere length and isometric twitch parameters. The resting sarcomere length-resting tension relationship was shifted to the left of normal in the hypertrophied preparations (P less than 0.001). The relationship of sarcomere length at the peak of the twitch with total tension at the same instant was shifted downward and to the right of normal in hypertrophy (P less than 0.01). For the same amount of total tension development there was less than normal sarcomere shortening in the hypertrophied preparations (P less than 0.001). Consequently, there is less than normal work per sarcomere during auxotonic sarcomere shortening in hypertrophied heart muscle. Less sarcomere work for a particular functional state is important to consider in the assessment of the basis of myocardial function in compensated pressure overload hypertrophy.
Increased arteriolar wall-to-lumen ratio in a normotensive vascular bed in coarctation hypertension
Authors: Plunkett W. C. , Overbeck H. W.
Published: December 2017

In rats with coarctation hypertension, resting resistance and resistance at maximal vasodilation are elevated in the hindquarters, although blood pressure in this vascular bed remains normal. To assess the nature of these non-pressure-related vascular abnormalities, we observed third- to fifth-order arterioles in the cremaster microcirculation using standard techniques and chloralose-urethan anesthesia in rats with coarctation or sham coarctation of the abdominal aorta. Four weeks after clipping, carotid pressure was significantly elevated in coarcted compared with sham-coarcted rats, but femoral pressure was not. The wall-to-lumen ratio and wall thickness in cremaster arterioles was elevated by 12-33% in coarcted compared with sham-coarcted rats in the resting state. After maximal arteriolar relaxation with topical nitroprusside, differences in wall-to-lumen ratio persisted. We also studied the microcirculation of one-kidney normotensive control and one-kidney, one-clip Goldblatt hypertensive rats. Femoral pressure in Goldblatt hypertensive rats was elevated, but changes in the microcirculation were similar to those observed in coarcted rats. These non-pressure-related changes in vascular structure in hypertension may result from systemic neural or humoral influences and/or growth factors local to vascular wall tissues.
A uniform enzymatic method for dissociation of myocytes from hearts and stomachs of vertebrates
Authors: Mitra R. , Morad M.
Published: December 2017

A method is presented that consistently yields a large number of calcium-tolerant myocytes from mammalian, amphibian, and elasmobranch hearts and from mammalian stomach. The use of incubating solutions or cell harvesting techniques was not required. The time needed to isolate cells was shorter than previously reported values. Action potentials recorded from each cell type appear similar in configuration to that of the intact multicellular tissue. The isolated myocytes appear to tolerate long periods of electrophysiological experimentation using the "giga-seal" suction electrode technique of Hamill et al. (Pfluegers Arch. 391: 85-100, 1981). This method is ideally suited for comparative electrophysiological studies, since the procedure for cell isolation was not seriously modified according to the preparation or species used.
Myogenic properties of cerebral blood vessels from normotensive and hypertensive rats
Authors: Osol G. , Halpern W.
Published: December 2017

Myogenic properties of posterior cerebral arteries from normotensive and hypertensive rats were analyzed in vitro and quantified in terms of both pressure range limits and degree of myogenic activity. Spontaneously hypertensive rat (SHR) vessels were significantly narrower in a fully relaxed state, and both wall thickness and wall-to-radius ratios were increased. After equilibration in 1.6 mM calcium physiological saline solution a substantial tone developed which resulted in average diameter decreases of 34 and 37% in Wistar-Kyoto (WKY) and SHR, respectively; average lumen diameters were approximately 125 micron. Rapid changes in transmural pressure (delta P 10-25 mmHg/s) were applied and diameter responses measured continuously. Myogenic responses began 1-3 s after a change in transmural pressure, and arteries regained their initial diameters after a pressure step in about 2 min; a final, steady-state diameter was achieved in 4-5 min. Myogenic pressure ranges were 49-145 mmHg in WKY and 64-181 in SHR; when responses were segregated according to positive and negative pressure steps, more myogenic responses were observed at lower pressures for pressure step decreases when compared with pressure step increases. Thus myogenic ranges for increasing pressure steps were 71-151 (WKY) and 72-188 mmHg (SHR) and for decreasing steps 45-117 (WKY) and 57-148 mmHg (SHR). Myogenic responses in SHR were weaker than in WKY rats: the former maintained essentially a constant diameter over a wide range of pressures, whereas arteries from the latter decreased diameter with increasing pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
Intracellular K+ and Na+ activities under hypoxia, acidosis, and no glucose in dog hearts
Authors: Nakaya H. , Kimura S. , Kanno M.
Published: December 2017

To gain a better understanding of the ionic mechanisms responsible for the electrophysiological disturbances occurring during myocardial ischemia, transmembrane potentials and intracellular potassium (aiK) and sodium (aiNa) ion activities were measured under individual and combined conditions of hypoxia (Po2 less than 50 mmHg), respiratory acidosis (pH 6.6), and no glucose in isolated epicardial ventricular muscle preparations of the canine heart using conventional and ion-selective microelectrode techniques. After 30 min superfusion with hypoxic, acidic, and glucose-free solution under 2-Hz stimulation, resting membrane potential (RMP) was significantly reduced from -85.5 +/- 0.6 to -69.5 +/- 1.0 mV, accompanied by decreases in action potential amplitude, maximum upstroke velocity of phase O, and action potential duration. aiK was significantly decreased from 101.0 +/- 5.6 to 79.5 +/- 5.8 mM, whereas aiNa was not significantly altered by the combined condition. RMP and aiK were moderately decreased by hypoxia alone, slightly decreased by acidosis, and hardly affected by the glucose-free condition. The extent of depolarization was well correlated with the decrease in aiK. These results suggest that Na+-K+ pump inhibition may not be a major cause of K+ efflux from myocardial cells under the hypoxic, acidic, and glucose-free condition and that hypoxia is the most important factor affecting aiK and RMP among these conditions.
Effect of chronic surgical denervation of dog heart on myocardial Na+-K+ pump
Authors: Wanless R. B. , Drake-Holland A. J. , Noble M. I.
Published: December 2017

The effect of chronic denervation of the myocardium on myocardial Na+-K+ pump activity and numbers of pump sites was studied in dogs. Right ventricular biopsies were taken immediately before and 4 wk after chronic surgical denervation, when depletion of norepinephrine is complete. Na+-K+ pump activity was assayed by ouabain-sensitive 86Rb uptake into ventricular tissue slices. The number of pump sites was measured by [3H]ouabain binding in ventricular tissue slices. Ouabain-sensitive Rb uptake was increased after denervation by an average of 147%. [3H]-ouabain binding at a concentration of 1.25 X 10(-6) M increased by an average of 27.6% after denervation. Acutely applied norepinephrine (2 X 10(-7) M) stimulated ouabain-sensitive Rb uptake both before and after denervation. The stimulation was greater after denervation, indicating supersensitivity. The cause of these changes is not known.
Distribution of lung vascular resistance after chronic systemic-to-pulmonary shunts
Authors: Michel R. P. , Hakim T. S. , Hanson R. E. , Dobell A. R. , Keith F. , Drinkwater D.
Published: December 2017

Congenital cardiac shunts produce pathological lesions on the arterial side of the lung vasculature. We examined the effects of chronic shunts (14.2 +/- 1.2 mo) in 10 young dogs, between the left subclavian and the left lower lobe (LLL) artery, on pulmonary vascular pressure and flow (P-Q) relationships, segmental resistance with arterial and venous occlusion (AVO), and sensitivity to drugs. At final thoracotomy, mean LLL pulmonary arterial pressure (Ppa) was 23.2 +/- 4.3 mmHg compared with 11.9 +/- 0.9 in the right lung (P less than 0.05); two animals had LLL Ppa of 41 and 48 mmHg. The LLL artery and vein were cannulated, and pressure-flow (P-Q) and AVO measurements were made and compared with previous control LLL (n = 11) and contralateral right lower lobe (RLL, n = 5). Responses to serotonin, histamine, and vasodilators (diltiazem and isoproterenol) were evaluated. Comparisons of morphometric measurements were made between LLL and RLL. We found a significant increase in arterial resistance as measured with AVO and a hypersensitivity to serotonin in the shunt LLL, without changes in total pulmonary vascular resistance or P-Q measurements; vasodilators had a small effect only in the hypertensive lobes. Our data suggest that chronic shunts to the pulmonary circulation increase arterial resistance and sensitivity to serotonin, even in the absence of discernible morphometric changes, and that vasoconstriction may be an important precursor to the development of morphological lesions.
Coronary blood flow and myocardial segment dimensions during simulated dives in seals
Authors: Elsner R. , Millard R. W. , Kjekshus J. K. , White F. , Blix A. S. , Kemper W. S.
Published: December 2017

Three harbor seals Phoca vitulina richardsi and five spotted seals Phoca vitulina largha were used in studies of acute episodes of local myocardial ischemia in open-chest, anesthetized animals and of coronary blood flow and regional function as indicated by left ventricular segment dimensions during experimentally simulated dives of conscious, instrumented animals. We observed that seal myocardium, in which there are few coronary anastomoses, responded to brief local occlusion with prompt local dysfunction and systolic bulging; coronary flow in the nondiving seal oscillated irregularly and declined with spontaneous apnea and related falling heart rate; flow continued to oscillate but was much reduced during dives, frequently ceasing entirely for periods as long as 45 s; ventricular segment dimension shortening was reduced intermittently during dives; and elevated heart rate induced during dives by cardiac pacing or by administration of atropine diminished or eliminated the reductions in coronary blood flow. Responses of seal heart reflect the reduction in cardiac metabolic demand during diving and the seal's myocardial adaptation for enhanced anaerobic glycolysis. The seal heart can maintain mechanical function during dives with minimal coronary perfusion, despite the progressive and ultimately profound hypoxia, hypercapnia, and acidosis. Reduced cardiac metabolism, copious glycolytic reserves, and metabolite washout by intermittent brief bursts of coronary blood flow are apparently sufficient to support continued cardiac function, even though the seal heart has little tolerance for acute localized ischemia.
Effects of octanol on canine subendocardial Purkinje-to-ventricular transmission
Authors: Joyner R. W. , Overholt E. D.
Published: December 2017

The effects of 0.2 mM octanol on action potential propagation were investigated using in vitro preparations of canine papillary muscles. In these preparations an action potential initiated in the superficial Purkinje (P) layer propagates across specific Purkinje-ventricular junction (PVJ) sites into the underlying ventricular (V) layer. The conduction delay at PVJ sites increased from 4.85 +/- 1.55 to 8.85 +/- 3.34 (mean +/- SD) ms (n = 10, P less than 0.005), an 82% increase. However, propagation within the V syncytium was much less affected, with a decrease of conduction velocity by only 10% and a decrease in the maximal rate of rise of the action potential of 23%. The results indicate that octanol, which has previously been shown to increase gap junctional resistance, has a preferential effect on PVJ sites, as predicted by the hypothesis that there is a restricted pathway for intracellular current flow from P cells to V cells at these sites.
Conditions for dipyridamole potentiation of skeletal muscle active hyperemia
Authors: Klabunde R. E.
Published: December 2017

The effects of dipyridamole on active hyperemia were evaluated in dog gracilis muscles undergoing sustained isometric contractions. Muscles were stimulated to contract for 5, 15, 25, and 50 s at 20% maximal tension (20% Tmax) or for 10 s at 100% Tmax during intra-arterial infusion of either saline or dipyridamole (1 microM). In two separate groups of dogs, muscles were stimulated to contract under free-flow or restricted-flow (ischemic) conditions. In the later group, blood flow was reduced to 50% of precontraction level during the period of contraction. Dipyridamole increased resting vascular conductance by about 45%; however, it did not affect the change in vascular conductance resulting from muscle contraction. The recovery time for active hyperemia following free-flow contractions at 20% Tmax was not altered by dipyridamole. However, dipyridamole increased the recovery time following 50 s of restricted-flow contraction (20% Tmax) and 10 s of 100% Tmax contractions by 46 and 169%, respectively. These results suggest that adenosine contributes to active hyperemia following sustained ischemic contractions at 20% Tmax and contractions at 100% Tmax but not from contractions at 20% Tmax where blood flow is allowed to increase freely.
Fluid and protein shifts after postural changes in humans
Authors: Hinghofer-Szalkay H. , Moser M.
Published: December 2017

With the use of a new mass density detection method, blood density (BD), plasma density (PD), and erythrocyte density (ED) were measured during different postures in euhydrated humans. ED remained stable under various head-up tilt (HUT) procedures. Changes of PD and BD mirrored the time course of hemodilution and hemoconcentration. The mass density of the shifted fluid (FD) was virtually identical for the outward filtrated fluid when upright and for the inward movement of fluid when supine; it averaged 1,008.3 g/l (37 degrees C), which is equivalent to a protein concentration of 30 g/l. PD and BD increased almost linearly with increasing angles of tilt. A stepwise increase from supine position to 90 degrees HUT within 2 h resulted in a mean plasma volume (PV) loss of 18%. Repeated sudden HUT to 70 degrees for 45 min, separated by 45-min supine (0 degree) periods, resulted in slightly reduced PV shifts which averaged -14% during 45 min of quiet HUT. The results indicate that erythrocyte volume remains constant after assuming different HUT positions in euhydrated subjects; a net loss of intravascular protein occurs during postural hemoconcentration, and protein gain occurs with postural hemodilution; the protein concentration of the shifted fluid resembles that of whole-body lymph; and microsample densitometry on blood and plasma is an accurate technique for measuring dynamic responses of rapid blood-volume changes in humans.
Cat carotid body oxygen metabolism and chemoreception described by a two-cytochrome model
Authors: Nair P. K. , Buerk D. G. , Whalen W. J.
Published: December 2017

We have analyzed O2 disappearance curves (DCs) in cat carotid bodies (CBs) measured with our O2 microelectrode, after stopping flow of either blood (108 DCs in 12 cats) or a hemoglobin-free (Locke) perfusion solution (35 DCs in 6 cats). Prior to occlusion, the mean tissue PO2 levels were 74.5 +/- 2.8 (SE) Torr in blood-perfused CBs and 103.4 +/- 2.6 in Locke-perfused CBs. The O2 consumption rates (VO2) determined from the initial 3 s of the DCs were 1.46 +/- 0.08 and 1.50 +/- 0.10 (SE) ml O2 . 100 g-1 . min-1, respectively, for the blood-perfused and Locke-perfused CBs. The change in total sinus nerve activity from the CB was also measured following stopped flow. The nerve activity began to increase immediately, providing further evidence that classic hypoxia is not the mechanism of chemoreceptor discharge. However, about two-thirds of the increased activity in blood-perfused CBs occurred after tissue PO2 levels fell below 20 Torr. As the CB tissue PO2 decreased, the O2 disappearance rate (-dPO2/dt) also decreased for both experimental conditions, indicating that the CB VO2 varies with O2 concentration. The increase in nerve discharge and O2 disappearance rate can be interpreted by a two-cytochrome model for O2 metabolism, with both high and low affinities.
Histamine-induced protein leakage in hypertensive rats: inhibition by verapamil
Authors: Miller F. N. , Joshua I. G. , Fleming J. T. , Parekh N.
Published: December 2017

Hypertension has been associated with an enhanced transport of macromolecules from the vasculature to the interstitium. The first objective of this study was to determine if, under control conditions, there is an enhanced leakage of macromolecules from the cremaster vasculature of the hypertensive rat. The second objective was to determine if the response to a mediator of macromolecular leakage (histamine) was altered in the renovascular hypertensive rat. A third objective was to determine if a calcium entry blocker, verapamil, could inhibit histamine-induced leakage and, if so, was the sensitivity to verapamil different in the renovascular hypertensive rat. Rats were anesthetized with pentobarbital, and the cremaster preparation was used for in vivo television microscopy studies. Fluorescein isothiocyanate was tagged to rat serum albumin (FITC-RSA), and the leakage of this albumin from the vasculature to the interstitium was quantitated by the use of fluorescent microscopy techniques. There was no difference during control conditions in macromolecular leakage between the normotensive and hypertensive rats. However, histamine induced a greater leakage in the renovascular hypertensive rat than in the normotensive controls. In addition, verapamil, in the presence of normal calcium levels, inhibited the histamine-induced leakage in the hypertensive rats but not in the normotensive controls. These data suggest that enhanced macromolecular leakage during hypertension may be due to an increased sensitivity to mediators of protein leakage. These agents may produce protein leakage by enhancing entry of extracellular calcium into endothelial cells.
Differential effect of thyroxine on atrial and ventricular isomyosins in rats
Authors: Samuel J. L. , Rappaport L. , Syrovy I. , Wisnewsky C. , Marotte F. , Whalen R. G. , Schwartz K.
Published: December 2017

Two myosin heavy chains (MHCs), alpha and beta, which exhibit different levels of ATPase activity related to the different velocities of muscle shortening, are differentially expressed in rat cardiac ventricles, depending on the developmental stage and the thyroid status of the animals. In contrast, no changes have been reported concerning the expression of atrial MHCs in the same physiological and pathological conditions. We have now performed studies with sensitive techniques to test the hypothesis that the expression of alpha- and beta-MHCs can also be modulated in the rat atria, although at a low level. Atrial and ventricular isomyosin patterns of various groups of rats were examined by two-dimensional peptide mapping, immunofluorescence with specific anti-alpha- and anti-beta-MHC immunoglobulins, and electrophoresis under nondenaturing conditions. Normal ontogenic development of the atria is characterized by the disappearance of a small amount of beta-MHC, present at 19 days in utero. At 3 wk of age, atria and ventricles both contain only alpha-MHC. Severe hypothyroidism, produced either by methylthiouracil (MTU) treatment of pregnant females and of their litters or by hypophysectomy of adult animals, did not significantly deinduce atrial alpha-MHC but was characterized by a significant although slight accumulation of beta-MHC (less than 5% of total myosin). This latter effect was abolished by L-thyroxine restoration. It is concluded that alpha- and beta-MHC are developmentally and hormonally regulated both in atria and ventricles, although the extent of regulation is very different for the two tissues.
Electrotonic interactions between aggregates of chick embryo cardiac pacemaker cells
Authors: Veenstra R. D. , DeHaan R. L.
Published: December 2017

Synchronization of spontaneously active heart cell aggregates occurs shortly after they are brought into contact. The synchronous rate is determined by pacemaker phase resetting and passive subthreshold electrotonic interactions. To further study the effects of passive electrical interactions, we have used 150-microns diameter aggregates prepared from cells of 4d (4-day ventricle + 1 day in vitro), 7d, and 14d embryonic chick ventricle as models of primary, latent, and nonpacemaker tissues, respectively. Coupling of 4d and 7d aggregates (4d/7d pairs) leads to intermediate synchronous rates. We show here that elevating external K+ from 1.3 to 2.8 mM, which has no effect on 4d/4d pairs but selectively reduces the beat rate of 7d/7d pairs by 42%, slows the synchronous beat rate of 4d/7d pairs by 23%. Increases in electrical coupling in newly joined 4d/14d pairs cause the 4d rate to slow to a minimum value (16 +/- 13 beats/min, n = 16) just prior to the onset of synchronous activity. The rate slowly recovers to a final value of 40 +/- 12 beat/min. We conclude that the spontaneous beat rate of a primary pacemaker is modulated by both active and passive interactions with latent or nonpacemaker tissues.