bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of high doses of aspirin on pulmonary hemodynamics and lung water
Authors: Maron M. B.
Published: December 2017

The purpose of this study was to determine if aspirin, in doses that elevate plasma salicylate concentrations to values reported in patients with salicylate-induced pulmonary edema, produce pulmonary vasoconstriction in a canine, isolated perfused left lower lung lobe (LLL) preparation. In 10 LLL's, aspirin (avg 97.8 mg/dl plasma) caused LLL arterial pressure to rise from 9.1 +/- 0.3 to 23.0 +/- 1.8 (SE) Torr. In contrast, no vascular pressure changes were observed in placebo-treated control LLL's. Sodium meclofenamate and indomethacin, structurally dissimilar cyclooxygenase inhibitors, elicited similar responses to aspirin, suggesting that a mechanism involving products of prostaglandin cyclooxygenase was involved in producing the vasoconstriction. The double-occlusion technique was used to localize the sites of the vasoconstriction. The results suggested that all three drugs caused both lobar arterial and venous tone to increase. Although high doses of aspirin produced pulmonary vasoconstriction in the isolated, perfused LLL, the aspirin-treated LLL's gained less weight and extravascular water than the control lobes.
Albumin modulation of capillary permeability: test of an adsorption mechanism
Authors: Huxley V. H. , Curry F. E.
Published: December 2017

We investigated further the mechanism whereby albumin interacts with the walls of capillary blood vessels to maintain normal permeability properties. In individually perfused capillaries of frog mesentery, hydraulic conductivity was measured as the albumin perfusate concentration was first reduced in three steps from 0.1 to 0 g/dl (intermediate concns 0.01 and 0.001 g/dl), then increased in up to four steps to 1 g/dl (intermediate concns 0.001, 0.01, and 0.1 g/dl). The albumin concentration required to return hydraulic conductivity toward control values, following Ringer perfusion, was at least an order of magnitude larger than that required to maintain permeability close to control values prior to Ringer perfusion. The experiments indicate that the affinity of albumin for binding sites on the capillary wall following Ringer perfusion is less than the albumin affinity for binding sites after the capillary has been perfused with solutions containing 0.1 g/dl albumin. Before the hysteresis of hydraulic conductivity on albumin concentration can be understood, the factors determining the transport of albumin into the membrane must be investigated further.
A theoretical model of a compliant arterial stenosis
Authors: Santamore W. P. , Bove A. A.
Published: December 2017

Recent clinical and experimental evidence indicates that coronary artery stenoses may rapidly change their size and shape in response to alterations in vasomotor tone and intraluminal pressure. This theoretical study models a partially compliant arterial stenosis to examine the hemodynamic impact of these alterations. In rigid vessels, a 98% reduction in luminal area would predictably produce subendocardial ischemia in the resting state. In contrast, stenoses, with part of the arterial wall normal by the underlying plaque, responded to vasoconstriction and to changes in intraluminal pressure. With part of the arterial wall normal by the plaque, both vasoconstriction and decreases in intraluminal pressure could increase the hemodynamic severity of the stenosis. Further, the more eccentrically positioned the underlying plaque was, the greater the effects of vasoconstriction and intraluminal pressure on stenotic severity. Thus the morphological configuration of the plaque and the normal wall segment in the stenosis appear to be important determinants of the hemodynamic response of the stenosis to vasoconstriction and blood pressure changes. In turn, these changes in stenotic severity can greatly influence flow through the vessel.
Creatine kinase and phosphorylase in cardiac lymph: coronary occlusion and reperfusion
Authors: Michael L. H. , Hunt J. R. , Weilbaecher D. , Perryman M. B. , Roberts R. , Lewis R. M. , Entman M. L.
Published: December 2017

Cardiac lymph, collected from conscious dogs, was monitored for glycogen phosphorylase and creatine kinase (CK) enzymatic activity during control state, circumflex coronary artery (CFX) occlusion, and reperfusion. CFX occlusions, lasting for intervals as short as 10 min, initiated a release of phosphorylase and CK into the cardiac lymph, which was immediately observed during reperfusion of the ischemic tissue. Blood plasma levels did not appear for several hours. In the absence of reperfusion, the appearance of enzymes in cardiac lymph was delayed and peaked later. Glycogen phosphorylase and CK entered the lymph in greater quantities with reperfusion as the length of occlusion was increased. Histological examination of multiple sections of the reperfused hearts showed infarcts in hearts where CFX occlusions lasted 20 min or longer; occlusions of 10-15 min showed evidence of cell injury and death in two hearts and no definable infarct in the majority. Ischemic intervals of short duration release functionally active glycogen phosphorylase and CK, which reflect changes in myocardial cell egress of macromolecules and/or cell death.
Effect of controlled ventilation on renal and splanchnic blood flows during nicotine
Authors: Bedran de Castro M. T. , Downey H. F. , Crystal G. J. , Bashour F. A.
Published: December 2017

The present study was undertaken to evaluate the influence of respiratory condition [free breathing (FB) vs. controlled ventilation (CV)] and of anesthetic [pentobarbital (PA) vs. chloralose (CA)] on nicotine-induced vasomotor responses in the renal cortex and splanchnic beds. Nicotine (36 micrograms . kg-1 . min-1 iv) was infused in four groups of dogs: group I, PA and CV; group II, PA and FB; group III, CA and CV; group IV, CA and FB. Regional vascular conductances (VC) were calculated from regional blood flows measured with 15-microns radioactive microspheres. In group I, VC fell in renal cortex (-22%) and pancreas (-52%), increased in liver (hepatic arterial bed +130%), and did not change significantly in duodenum and spleen. In group III, VC fell to a greater extent in renal cortex, pancreas, duodenum, and spleen than in group I; VC in hepatic arterial bed did not change. In FB dogs (groups II and IV), nicotine caused marked hyperventilation, but decreases in VC in renal cortex, pancreas, and duodenum were similar to those in CV dogs. Results indicate that during intravenous infusion of nicotine 1) hyperventilation does not attenuate or reverse vasoconstriction in renal cortex, pancreas, or duodenum under either PA or CA, although it does in spleen under CA; 2) vasodilator mechanisms predominate over vasoconstrictor mechanisms in the hepatic arterial bed; and 3) vasoconstrictor responses in renal cortex, pancreas, duodenum, spleen, and liver are more pronounced under CA than under PA.
Local endogenous opiate activity in dog myocardium: receptor blockade with naloxone
Authors: Caffrey J. L. , Gaugl J. F. , Jones C. E.
Published: December 2017

The participation of endogenous opiates in myocardial performance and coronary blood flow was investigated. Heart rate, left ventricular contractile force (LVCF), left coronary blood flow (LCBF), and left ventricular oxygen extraction were monitored in anesthetized dogs before and after intracoronary opiate receptor blockade with naloxone. LVCF consistently increased in a dose-dependent fashion following intracoronary naloxone. The increasing LVCF was accompanied by significant increases in LCBF and myocardial oxygen consumption, without changes in heart rate. Rapid onset of responses suggested the presence of endogenous opiates operating locally within the myocardium. Similar effects did not follow right atrial injection of naloxone, ruling out a systemic mechanism. Furthermore, naloxone injected into the isolated left anterior descending artery selectively increased contractile force in that perfusion territory while the adjacent untreated circumflex territory showed no change. The administration of dynorphin into the coronaries produced a depression of LVCF qualitatively consistent with these effects. The effect of dynorphin was subsequently reversed with naloxone. These results support the concept that endogenous opiates participate in the regulation of myocardial function through local mechanisms at the myocardial level.
Adenine nucleotides, serotonin, and endothelium-dependent relaxations to platelets
Authors: Houston D. S. , Shepherd J. T. , Vanhoutte P. M.
Published: December 2017

Aggregating platelets cause an endothelium-dependent relaxation of isolated contracted canine coronary arteries. The role of adenine nucleotides and of 5-hydroxytryptamine in causing this relaxation was determined. Rings of these arteries were suspended in organ chambers filled with physiological salt solution and contracted with prostaglandin F2 alpha. Adenosine diphosphate relaxed rings with intact endothelium but had no effect on endothelium-denuded rings. The relaxation was attenuated by the enzyme, apyrase, which hydrolyzes adenosine tri- and diphosphate. 5-Hydroxytryptamine (5-HT) exerted a direct contractile effect mediated by the endothelium. The latter was prevented by the 5-HT1 serotonergic antagonist, methiothepin, but not by the 5-HT2 serotonergic antagonist, ketanserin. The endothelially mediated relaxation to aggregating platelets was prevented by apyrase but not by methiothepin or ketanserin. Responses to platelets were unaltered by the inhibitor of cyclooxygenase, meclofenamate. These experiments demonstrate the key role of adenine nucleotides in mediating the endothelium-dependent relaxation of canine coronary arteries to aggregating platelets.
Plasma vasopressin response to osmotic and hemodynamic stimuli in heart failure
Authors: Uretsky B. F. , Verbalis J. G. , Generalovich T. , Valdes A. , Reddy P. S.
Published: December 2017

Arginine vasopressin (AVP) regulation was studied in 42 patients with severe heart failure (CHF) and 10 patients without CHF during cardiac catheterization. Plasma AVP levels were elevated in CHF compared with non-CHF patients (2.98 +/- 2.48 vs. 1.01 +/- 0.44 pg/ml, P less than 0.01). In non-CHF patients, osmotic loading with angiographic contrast caused increases in plasma osmolality (283 +/- 4 to 290 +/- 5 mosmol/l, P less than 0.05) and AVP (1.01 +/- 0.44 to 1.79 +/- 0.20 pg/ml, P less than 0.001). In 10 CHF patients, similar osmotic loading produced an increase in plasma osmolality (275 +/- 13 to 288 +/- 17 mosmol/l, P less than 0.05) and an exaggerated rise in plasma AVP (3.61 +/- 3.17 to 16.30 +/- 12.17 pg/ml, P less than 0.001). The increase in plasma AVP per unit increase in osmolality was greater (P less than 0.01) in the CHF patients (1.36 +/- 1.25 pg . mosmol-1 . 1(-1)) than in non-CHF patients (0.18 +/- 0.17). To determine whether improved cardiac performance would lower AVP levels, 18 CHF patients received the experimental agent MDL 17,043, with improved cardiac index (1.9 +/- 0.4 to 3.3 +/- 0.7 1 . min-1 . m-2, P less than 0.001). Plasma AVP levels did not change significantly (1.99 +/- 0.74 to 2.81 +/- 2.06 pg/ml), but significant inverse correlations were found between changes in plasma AVP and changes in mean (r = -0.53) and systolic (r = -0.65) arterial pressure after MDL 17,043 infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Persistence of coronary vasodilator reserve despite functionally significant flow reduction
Authors: Aversano T. , Becker L. C.
Published: December 2017

This study was done to determine whether coronary vasodilator reserve is exhausted when coronary flow falls and regional function becomes abnormal during low-pressure perfusion. In 10 open-chest, anesthetized dogs the left circumflex coronary artery (LC) was cannulated and perfused via a blood-filled reservoir. At LC pressures of 35 and 50 mmHg, regional segment lengths were measured with sonomicrometer crystals and regional flow with radiolabeled microspheres before and after adenosine vasodilation. Control measurements were made at 80 mmHg perfusion pressure. Prior to adenosine, flow fell transmurally when LC pressure was reduced to 50 and 35 mmHg and rose significantly following adenosine. No change in function occurred at an LC pressure of 50 mmHg, but at 35 mmHg LC segmental shortening fell to 30 +/- 14% of control, and LC flow fell to 42 +/- 5% of control, with endocardial and epicardial flows of 0.40 +/- 0.04 and 0.70 +/- 0.09 ml . min-1 . g-1, respectively. After adenosine, endocardial and epicardial LC flow rose to 0.69 +/- 0.08 and 1.81 +/- 0.47 ml . min-1 . g-1, respectively (P less than 0.05). LC segment shortening improved modestly to 50 +/- 15% of control (P less than 0.02). We conclude that transmural vasodilator reserve is maintained in the face of functionally significant reductions of coronary flow at low perfusion pressure. Adenosine-induced flow increases are associated with a modest improvement in segmental function.
Endothelium-dependent contractions to arachidonic acid are mediated by products of cyclooxygenase
Authors: Miller V. M. , Vanhoutte P. M.
Published: December 2017

Arachidonic acid produces endothelium-dependent relaxation in canine arteries and endothelium-dependent contraction in veins. In canine femoral arteries, the relaxation is prevented by inhibitors of cyclooxygenase. To determine the role of cyclooxygenase in the contraction evoked by arachidonic acid in the veins, rings of canine femoral and intrapulmonary veins, with and without endothelium, were suspended in organ chambers and set at their optimum length for isometric tension measurements. In rings of femoral and pulmonary vein contracted with norepinephrine, arachidonic acid produced a concentration-dependent increase in tension that was eliminated by removal of the endothelium or by treatment with the inhibitors of cyclooxygenase (indomethacin, meclofenamate, or acetylsalicyclic acid). The contractions were not prevented by inhibitors of thromboxane synthetase or prostacyclin synthetase or lipoxygenase. Pulmonary and femoral veins with or without endothelium relaxed to low, but contracted to high concentrations of prostacyclin and prostaglandin E2. Prostaglandin F2 alpha caused endothelium-independent contractions in both blood vessels. The present study suggests that the endothelium-dependent contractions to arachidonic acid observed in canine veins are mediated by prostanoids other than thromboxane and prostacyclin.
Left ventricular function of the isolated, genetically obese rat's heart
Authors: Paradise N. F. , Pilati C. F. , Payne W. R. , Finkelstein J. A.
Published: December 2017

We sought to determine if left ventricular (LV) function of the heart from the adult, chronically obese animal is impaired. Hearts from 50 wk-old genetically obese female Zucker rats (624 +/- 13 g) and their lean littermate controls (275 +/- 5 g) were isolated during ether anesthesia, supported metabolically by retrograde aortic perfusion (6 ml/min, 35 degrees C) with physiological solution containing suspended canine erythrocytes (hematocrit, 20%), and the ventricles were paced at 180 beats/min. A distensible, fluid-filled balloon was placed in the LV, and pressure-volume (PV) relationships were obtained. The obese and lean end-diastolic PV curves were not different, and therefore the obese and lean LV chamber compliances were similar. Comparison of the systolic PV relationships demonstrated that the obese rat's heart had a greater pressure-generating capability, which probably was a reflection of its increased LV mass (0.96 +/- 0.03 vs. 0.72 +/- 0.02 g). The calculated average meridional (or circumferential) peak systolic wall stress in the LV of the obese rat's heart, however, was significantly reduced compared with control. This diminished ability to develop systolic stress from the same end-diastolic volumes suggests that the hypertrophied LV of the middle-aged obese rat's heart is dilated or that its contractility is depressed, or both.
Circulatory responses to onset of exercise: role of arterial and cardiac baroreflexes
Authors: Ludbrook J. , Graham W. F.
Published: December 2017

Six rabbits were exercised on a moving belt at 13 m/min for 60's. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), and systemic vascular resistance index (SVRI) were measured. Exercise was done under the following four permutations of input from baroreceptors (B) and cardiac receptors (C): BC, both inputs present; B, only baroreceptor input (intrapericardial procaine); C, only cardiac receptor input (surgical barodenervation); 0, both inputs deleted. The reflex effects on SVRI of the two inputs were calculated as (B - 0) and (C - 0) and their interaction as (BC - 0) - [(B - 0) + (C - 0)]. The effects of baroreceptor input plus interaction on all cardiovascular variables were also calculated, as (BC - C). At rest, (B - 0) and (C - 0) each tonically depressed SVRI without interacting, and (BC - C) tonically depressed SVRI, MAP, and HR. Within 10 s of the start of exercise these tonic effects were abolished, although a small, SVRI-lowering interaction appeared. Suppression of the tonic reflex effects of arterial baroreceptor and cardiac receptor input supported systemic vascular resistance at the onset of exercise and contributed to the rise of arterial pressure.
Norepinephrine on venous compliance and unstressed volume in cat liver
Authors: Greenway C. V. , Seaman K. L. , Innes I. R.
Published: December 2017

Hemodynamic relationships between flows, pressures, and blood volume have been examined in the denervated liver of cats anesthetized with pentobarbital. Portal and hepatic lobar venous pressures, portal and total hepatic flows, and hepatic blood volume were recorded when portal flow was varied from 0 to 240 ml X min-1 X 100 g liver-1 and when hepatic outflow pressure was varied from 0 to 9.5 mmHg, before, during, and after intravenous infusion of norepinephrine (2 micrograms X min-1 X kg body wt-1). Portal pressure was 1-2 mmHg higher than lobar venous pressure and 8-9 mmHg higher than inferior vena caval pressure, showing that the major site of resistance in the portal circuit was in the large hepatic veins. Intrahepatic pressure was linearly related to total hepatic flow, and norepinephrine increased the intercept but not the slope of this relationship. Hepatic blood volume was linearly related to intrahepatic pressure with a calculated compliance of 2.5-3.0 ml X mmHg-1 X 100 g liver-1 and a calculated unstressed volume at zero pressure of 10-15 ml/100 g liver. Norepinephrine did not significantly change vascular compliance but caused a marked reduction of 15-20 ml/100 g liver in calculated unstressed volume. Thus norepinephrine reduced hepatic blood volume by 15-20 ml/100 g liver at any given intrahepatic pressure. It is concluded that venoconstriction in the hepatic bed occurs by a decrease in unstressed volume with little change in compliance. Unstressed volume represents a true blood volume reserve, independent of passive influences, which can be mobilized by the central nervous system.
Effects of loading conditions and inotropic state on rapid filling phase of left ventricle
Authors: Bahler R. C. , Martin P.
Published: December 2017

Afterload, activation sequence, inotropism, and extent of shortening affect the time constant (T) of left ventricular (LV) isovolumic pressure decay, yet it is unknown if they modify peak lengthening velocity of the LV minor axis [(dD/dt)/D]. Accordingly, we studied their effects on (dD/dt)/D, measured by sonomicrometry, in nine anesthetized open-chest dogs during atrial pacing at 2 Hz. Afterload was increased 20-40 mmHg by 1) constricting the ascending aorta and 2) occluding the descending aorta for four beats. Activation was altered by right ventricular pacing. These interventions, plus constriction of venae cavae, were studied during four inotropic states. Aortic stenosis increased (dD/dt)/D (P less than 0.05), whereas occlusion of the descending aorta, vena caval constriction, and right ventricular pacing decreased (dD/dt)/D (P less than 0.05). Left atrial pressure was constant except during vena caval constriction. Alterations in inotropic state modified (dD/dt)/D (P less than 0.001). Extent of shortening and (dD/dt)/D were directly related (r = 0.80, P less than 0.001). Changes in (dD/dt)/D and T were inversely related (r = 0.70, P less than 0.001), and alterations in the interval from -dP/dtpeak to the end of rapid filling were directly related to changes in T (r = 0.75, P less than 0.001). We conclude that (dD/dt)/D can be modified by systolic and diastolic load perturbations, activation sequence, and inotropic interventions. These effects relate to changes in extent of shortening, time course of inactivation, or both.
Reduction in cerebral arteriolar oxygen consumption by arachidonate
Authors: Levasseur J. E. , Kontos H. A. , Ellis E. F.
Published: December 2017

The oxygen consumption of cerebral arterioles from anesthetized cats was measured using the Cartesian diver microrespirometer following in vitro incubation with 200 micrograms/ml of arachidonate or 50 micrograms/ml of 15-hydroperoxy-eicosatetraenoic acid (15-HPETE). Both agents depressed oxygen consumption severely. This effect was inhibited completely by a combination of superoxide dismutase (SOD) and catalase, indicating that it is mediated by oxygen radicals. Similar depression of oxygen consumption was observed during incubation of the vessels with xanthine oxidase and acetaldehyde as substrate. This enzymic system is known to generate superoxide and hydrogen peroxide. The effect of xanthine oxidase was also partially inhibited by SOD and catalase. The effect of arachidonate was partially inhibited by cyclooxygenase inhibitors. The effect of lipoxygenase inhibitors could not be adequately tested because they depressed oxygen consumption by themselves. Prostaglandins H2 and E2 had no effect on arteriolar oxygen consumption. The results show that arachidonate and 15-HPETE in high concentration depress cerebral arteriolar oxygen consumption via an oxygen radical-mediated mechanism. Furthermore, the radical is generated in the vessel wall and does not require either the brain parenchyma or the formed elements of the blood or the meninges for its production.
Superoxide dismutase enhances recovery following myocardial ischemia
Authors: Burton K. P.
Published: December 2017

Oxygen-derived free radicals, specifically superoxide (O-2) and the hydroxyl radical (OH.), have been implicated as possible mediators in the development of myocardial damage induced by ischemia and reflow. The purpose of this study was to examine the ability of superoxide dismutase (SOD), a O-2 scavenging enzyme, to protect the heart against functional and structural alterations due to ischemia and reflow. An isolated perfused rabbit interventricular septal preparation was used for these experiments. Septa were treated with SOD by adding either 10 or 20 micrograms/ml of the enzyme to the perfusion solution 15 min prior to ischemia and during reflow. Other septa were not treated. Septa were made ischemic for 1 h and reperfused for 1 h. The contractile performance of reperfused septa was found to be significantly improved in SOD-treated septa when compared with nontreated septa. After 60 min of reflow, values for nontreated, 10- and 20-micrograms/ml SOD-treated septa, respectively, were 48.5 +/- 5.2 (SE), 67.4 +/- 4.2, and 82.0 +/- 3.8% of control values for developed tension. The rise in resting tension observed with reflow was significantly decreased. SOD treatment also provided significant protection of myocardial ultrastructure. The percent of myocytes showing normal structure was increased approximately 40%, and the percentages of myocytes showing mild or severe damage were decreased approximately 30 and 15%, respectively, for SOD-treated septa. Vessel structure showed a similar trend. Thus SOD preserves myocardial function and structure in septa reperfused following ischemia. These results support the possibility that oxygen-derived free radicals may be involved in the damage resulting from ischemia and reflow.
Role of vasopressin and sympathetic nervous system during hypertonic NaCl infusion in conscious dog
Authors: Hasser E. M. , Haywood J. R. , Bishop V. S.
Published: December 2017

The contribution of arginine vasopressin (AVP) and the sympathetic nervous system to the pressor response elicited by hypertonic NaCl infusion was investigated in conscious dogs with intact carotid sinus baroreceptors or in dogs subjected to chronic sinoaortic baroreceptor denervation (SAD). Infusion of 6% NaCl at 0.05 ml X kg-1 X min-1 for 60 min increased plasma osmolality an average of 12 +/- 2 mosmol/kg in both intact and SAD dogs. Arterial pressure increased 6 +/- 2 mmHg in intact animals and was normalized by subsequent administration of a specific vascular AVP antagonist. Pretreatment with the AVP antagonist did not alter resting arterial pressure but prevented the increase due to the osmotic stimulus. Pretreatment with ganglionic blockade reduced resting arterial pressure (-17 +/- 2 mmHg). Subsequent infusion of hypertonic NaCl elevated arterial pressure (21 +/- 7 mmHg) to a significantly greater level than that observed with the autonomic nervous system intact. In SAD dogs, the osmotic stimulus increased arterial pressure (16 +/- 1 mmHg) to a significantly greater extent than in intact animals. Subsequent administration of AVP antagonist normalized arterial pressure, and pretreatment with the antagonist prevented any pressor response. Pretreatment with ganglionic blockade did not alter the pressor response (15 +/- 2 mmHg) to hypertonic NaCl. Data suggest that the increase in arterial pressure due to an osmotic stimulus is due to AVP release and does not require a functional sympathetic nervous system. The response is normally buffered by arterial baroreflexes, presumably due to sympathetic withdrawal.
Different effects of two types of ischemia on myocardial systolic and diastolic function
Authors: Paulus W. J. , Grossman W. , Serizawa T. , Bourdillon P. D. , Pasipoularides A. , Mirsky I.
Published: December 2017

Acute increases in left ventricular (LV) diastolic pressure relative to volume occur during angina in humans and after pacing tachycardia in dogs with coronary stenoses. In this study we assessed myocardial function following pacing tachycardia in dogs with coronary stenoses and compared it with function of the same myocardial segment during coronary occlusion. Also we calculated regional wall stiffness following pacing tachycardia in dogs with coronary stenoses. In anesthetized dogs with two-vessel critical (90%) coronary stenoses, ultrasonic crystals were implanted subendocardially to measure either anterior wall (AW) and lateral wall (LW) segment lengths (SL; n = 14) or LV wall thickness (h; n = 7). LV pressure was measured using a high-fidelity micromanometer catheter. After pacing tachycardia in dogs with two-vessel coronary stenoses, there was a substantial rise in LV end-diastolic pressure (from 6 +/- 1 to 15 +/- 1 mmHg; P less than 0.001), a slight increase in end-diastolic segment length (AWEDSL from 15.6 +/- 1.0 to 16.4 +/- 1.0 mm; p less than 0.01; and LWEDSL from 13.8 +/- 1.4 to 14.3 +/- 1.4 mm; P greater than 0.01) and a reduction of percent systolic shortening of the ischemic segments. An upward shift of the diastolic pressure-SL relation was observed in the postpacing period. During coronary occlusion the diastolic pressure-SL relation of the same segment shifted rightward, or rightward and downward, and systolic shortening became holosystolic bulging. Ischemia due to coronary stenoses plus increased O2 demand had substantially different effects on regional wall motion and segmental diastolic mechanics than did ischemia due to coronary occlusion. Over the same range of residual transmural LV diastolic pressure, the radial stiffness modulus was higher after pacing tachycardia in the presence of coronary stenoses.
Regulation of gap junctional conductance
Authors: Spray D. C. , White R. L. , Mazet F. , Bennett M. V.
Published: December 2017

Gap junctional conductance is regulated by the number of channels between coupled cells (the balance between formation and loss of these channels) and by the fraction of these channels that are open (gating mechanisms). A variety of treatments are known to affect junction formation. Adenosine 3',5'-cyclic monophosphate (cAMP) is involved in some cases, and protein synthesis may be required but precursor molecules can also exist. Junction removal occurs both by dispersion of particles and by internalization of junctional membrane. Factors promoting removal are not well understood. A variety of gating mechanisms exist. Coupling may be controlled by changes in conductance of nonjunctional membranes. Several kinds of voltage dependence of junctional conductance are known, but rat ventricular junctions at least are electrically linear. Cytoplasmic acidification decreases conductance of most gap junctions. Sensitivity in rat ventricular myocytes allows modulation of coupling by moderate changes near normal internal pH. Increasing intracellular Ca also decreases junctional conductance, but in the better studied cases sensitivity is much lower to Ca than H. A few data support low sensitivity to Ca in cardiac cells, but quantitative studies are lacking. Higher alcohols such as octanol block junctional conductance in a wide range of tissues including rat ventricular myocytes. An antibody to liver gap junctions blocks junctions between rat ventricular myocytes. Cross reactivity indicates at least partial homology between many gap junctions. Although differences among gap junctions are known, a general physiology is being developed, which may have considerable relevance to normal cardiac function and also to conduction disorders of that tissue.
Baroreflex control of sympathetic nerve activity after elevations of pressure in conscious rabbits
Authors: Undesser K. P. , Pan J. Y. , Lynn M. P. , Bishop V. S.
Published: December 2017

The purpose of this study was to assess the effect of rapid baroreceptor resetting on the baroreflex control of renal sympathetic nerve activity in conscious rabbits. Renal sympathetic nerve activity was recorded and used as an index of the efferent limb of the baroreflex. Heart rate and arterial pressure were also recorded. Arterial pressure was raised with either phenylephrine or angiotensin II to a level that eliminated renal sympathetic nerve activity and was maintained at this level for periods of time ranging from 1 to 60 min. On returning pressure to control levels, renal sympathetic nerve activity remained suppressed for up to 90 min, with the duration of the suppression dependent on the magnitude and duration of the pressure stimulus. During this period of suppressed nerve activity, baroreflex curves were generated. The curves produced at this time were also suppressed as compared with control baroreflex curves. With time, the suppressed baroreflex curves returned to control. Further studies were performed to show that the suppression of renal sympathetic nerve activity was mediated via the prolonged increase in baroreceptor afferent activity during the pressure stimulus and was not due to a central effect of phenylephrine. This study indicates that although baroreceptor afferent activity may reset rapidly, there does not appear to be an augmentation of renal sympathetic nerve activity as would be expected.
Autoregulation of capillary pressure and filtration rate in isolated rat hindquarters
Authors: Korthuis R. J. , Granger D. N. , Townsley M. I. , Taylor A. E.
Published: December 2017

The hypothesis that skeletal muscle capillary pressure and/or capillary filtration rate are autoregulated was tested in 10 isolated rat hindquarters. Capillary pressure was directly assessed with the venous occlusion technique as abdominal aortic pressure was reduced in 25-mmHg decrements from 125 to 25 mmHg. Capillary pressure was not altered by reduction of arterial pressure from 125 to 100 mmHg, but it decreased progressively when arterial pressure was reduced from 100 to 25 mmHg. As perfusion pressure was reduced, capillary filtration rate decreased progressively, while the capillary filtration coefficient increased. The progressive decrease in capillary pressures was less than that predicted for a totally passive system, implying that capillary pressure was autoregulated to some degree. However, analysis of pre- to postcapillary resistance ratios suggested that the degree of capillary pressure autoregulation was minimal when perfusion pressures varied over a range of 100–25 mmHg. Capillary filtration rate was maintained better than would be predicted from the measured fall in capillary pressure by readjustments of interstitial Starling forces. These results indicate that capillary pressure is poorly autoregulated in rat skeletal muscle but that compensatory readjustments in interstitial Starling forces help maintain fluid balance and prevent excess dehydration of the interstitium of skeletal muscle as arterial pressure is reduced.
Inhibition of rat ventricular automaticity by adenosine
Authors: Heller L. J. , Olsson R. A.
Published: December 2017

This study was designed to characterize adenosine's negative chronotropic effect on ventricular pacemakers. The spontaneous beating rate of isolated, isovolumic rat ventricular preparations perfused with Krebs-Henseleit solution decreased as the adenosine concentration was increased [log M effective concentration 50% (EC50) = -5.22 +/- 0.17]. The lack of effect of propranolol or atropine on this adenosine response eliminates the involvement of endogenous neurotransmitters. Support for the involvement of an external cell surface receptor was provided by findings that theophylline and 8-(4-sulfophenyl)theophylline, an analogue thought to act solely at the cell surface, significantly increased the adenosine log M EC50 to -3.94 +/- 0.22 and -3.61 +/- 0.22, respectively. An increase in spontaneous beating rate induced by theophylline, but not by its analogue, was blocked by the addition of propranolol. The relative chronotropic potency of the adenosine analogues R-PIA, S-PIA, and NECA suggests that the cell surface receptors may be of the Ri type. The negative chronotropic effects of adenosine and its analogues occurred at concentrations that had no effect on the developed pressure of the paced preparation. Electrocardiographic evaluations indicate that at high agonist concentrations, there was an abrupt alteration in electrical properties of the preparation, which could be blocked by theophylline and its analogue.
Oxygen transport in rest-work transition illustrates new functions for myoglobin
Authors: Gayeski T. E. , Connett R. J. , Honig C. R.
Published: December 2017

Myoglobin (Mb) saturation was measured spectroscopically in 1,950 randomly selected cells from dog gracilis muscles frozen in situ during the transition from rest to steady twitch contraction at approximately 70% maximum rate of O2 consumption (VO2max). Measurements were made at the center of muscle-cell profiles in cross section, with spatial resolution approximately 5 X 5 X 3 micron. PO2 was calculated from saturation by use of the oxymyoglobin dissociation curve. Flow increased more rapidly than VO2 (half-times 5 and 14 s, respectively). Mb saturation changed little through 15 s. Saturation was lowest at 30 s and rose somewhat between 30 s and steady state. The lowest intracellular PO2 at any time or location was 1.5 Torr, and only 5% of loci were below 2 Torr. Since 1.5 Torr is about 10 times the minimum PO2 required for the observed VO2 (Connett et al. An upper bound on the minimum PO2 for O2 consumption in red muscle in vivo. Adv. Exp. Med. Biol. In press.), neither anoxia nor hypoxia was present. The observed fall in saturation and intracellular PO2 during exercise permits Mb to 1) promote transcapillary O2 flux, 2) facilitate intracellular O2 diffusion, 3) minimize convective and diffusive shunting, and 4) buffer intracellular PO2 above the tension that limits cytochrome turnover.
Energy sources in fully aerobic rest-work transitions: a new role for glycolysis
Authors: Connett R. J. , Gayeski T. E. , Honig C. R.
Published: December 2017

Rate of O2 consumption (VO2), intracellular PO2, lactate extraction, and tissue contents of phosphocreatine, creatine, ATP, lactate, and pyruvate were measured during rest-work transitions in dog gracilis muscles. Samples were taken at rest and after 5, 10, 15, 30, 60, and 180 s of twitch contraction at 4/s. There was no anoxia at any time or location [companion paper, Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H914-H921, 1985]. Energy was supplied by a continuous utilization of phosphocreatine stores, a slow rise in VO2, and two distinct bursts of glycolysis. Glycolytic rate was independent of tissue PO2 and VO2 and was poorly correlated with phosphocreatine under the aerobic conditions of our experiments. The glycolytic bursts served as a source of ATP, and the bulk of the lactate formed remained in the tissue. Lactate efflux was a small fraction of tissue lactate; it depended on blood flow but not on tissue lactate content. At steady state a small glycolytic flux maintained the high tissue lactate mainly by matching rates of pyruvate production and oxidation. We propose that this flux and the high tissue lactate concentration buffer cytosolic redox and/or substrate supply in support of the aerobic functions of mitochondria during exercise.
Effect of cell turnover and leaky junctions on arterial macromolecular transport
Authors: Weinbaum S. , Tzeghai G. , Ganatos P. , Pfeffer R. , Chien S.
Published: December 2017

A new quantitative model is presented to explore the changes in vascular permeability that would result if the intercellular clefts around widely scattered endothelial cells were to become leaky to macromolecules in the range of roughly 4–10 nm during normal cell turnover. Although these open junctions occupy less than 10(-5) of the en face area of the endothelial surface, it is shown that the endothelial permeability can increase by 50–100% due to the experimentally observed regional variations in turnover in the larger arteries, whereas in the thinner walled veins and smaller arteries the subendothelial concentration is not significantly elevated. These results provide a very plausible explanation for the observed focal differences in the uptake of 125I-albumin and 131I-fibrinogen in blue and white areas and the nonselectivity of the local enhancement in uptake for these two molecules as a function of molecular size. The model has important implications for the localization of atherogenesis and the importance of endothelial cell turnover on the transport of proteins in vessels of all sizes.
Apamin, a highly specific Ca2+ blocking agent in heart muscle
Authors: Bkaily G. , Sperelakis N. , Renaud J. F. , Payet M. D.
Published: December 2017

Apamin, a bee venom polypeptide, was recently reported to block specifically the Ca2+-dependent K+ channels that are not blocked by tetraethylammonium chloride in muscle cells. We report here that apamin blocked the naturally occurring slow action potentials (APs) in cultured cell reaggregates from chick hearts. The effects of apamin were not reversible on washout with Tyrode solution only (up to 24 h), but quinidine (10(-8) M) reversed the apamin blockade of the slow channels. Apamin also blocked the isoproterenol-induced slow APs in freshly isolated chick ventricular cells depolarized by 22 mM extracellular K+ concentration ([K+]o) in a dose-dependent fashion (10(-12) to 10(-10) M). Apamin at 5 X 10(-11) M blocked the isoproterenol-induced slow APs without affecting the membrane potential. Washout (with Tyrode solution containing 22 mM [K+]o and 10(-6) M isoproterenol) did not recover the slow APs. However, recovery of the slow APs was possible only when quinidine (10(-8) M) was added to the superfusion medium. The fast APs were rapidly restored by washout with Tyrode solution only. The present data show that apamin is a highly specific compound that tightly binds to the Ca2+ slow channels, thus blocking the slow APs in heart muscle. In addition, quinidine antagonizes the apamin binding on the slow APs.
Mathematical models of arterial transmural transport
Authors: Fry Donald L.
Published: December 2017

H240: Donald L. Fry. “Mathematical models of arterial transmural transport.” Page H244: The denominator “t” on the left of Eq. 14a was omitted; Eq. 14a should read

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Page H261: Eq. A1Oa should read

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Page H262: Eq. C6 should read

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and Eq. C7 should read

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Page H263: Eq. C9 should read

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Thromboxane A2/prostaglandin H2 mobilizes calcium in human blood platelets
Authors: Brace L. D. , Venton D. L. , Le Breton G. C.
Published: December 2017

The present study investigated the mechanism by which thromboxane A2/prostaglandin H2 (TXA2/PGH2) stimulates platelet activation. Previous studies in isolated platelet vesicles have suggested that TXA2/PGH2 functions to release calcium from intraplatelet stores. On this basis, we investigated whether TXA2/PGH2 causes mobilization of calcium in intact platelets. Calcium redistribution was measured using the fluorescent probe, chlortetracycline (CTC), and a photon-counting microspectrofluorometer. Human platelet-rich plasma was incubated with CTC (50 microM) for 40 min at 25 degrees C. Shape change was induced with arachidonic acid (AA, 100 microM) or ADP (0.75-1.0 microM). It was found that AA addition resulted in a significant release of intraplatelet calcium. This release was blocked by inhibition of the cyclooxygenase with indomethacin (20 microM) or the specific TXA2/PGH2 antagonist, 13-azaprostanoic acid (13-APA, 100 microM). On the other hand, neither indomethacin nor 13-APA had any effect on calcium release stimulated by ADP. However, prostacyclin (13 nM) inhibited both AA- and ADP-induced calcium release. These findings provide evidence that cyclooxygenase products of AA, i.e., TXA2 and/or PGH2 directly caused the mobilization of intraplatelet calcium. Furthermore, this calcium mobilization appears to be mediated through a specific TXA2/PGH2 receptor interaction.
Endothelium-dependent vasodilation by melittin: are lipoxygenase products involved?
Authors: Forstermann U. , Neufang B.
Published: December 2017

Vascular relaxation in response to acetylcholine and other vasodilator compounds has been shown to depend on intact endothelial cells. These dilator compounds obviously induce the formation of an unstable endothelium-derived relaxing factor or factors (EDRF) from the intima which relax the subjacent smooth muscle cells. The chemical identity of this factor (these factors) is still unclear. In the present study we demonstrate that endothelium-dependent relaxation of rabbit aorta was induced by melittin, a polypeptide toxin that activates phospholipase A2 to liberate polyunsaturated fatty acids (especially arachidonic acid) from membrane phospholipids. The relaxation induced by melittin had several properties similar to the acetylcholine relaxation. It was inhibited by potential inhibitors of phospholipase (mepacrine and p-bromophenacylbromide), by inhibitors of lipoxygenase (nordi-hydroguaiaretic acid, compound BW 755C, and 5,8,11,14-eicosatetraynoic acid) but not by the cyclooxygenase inhibitor indomethacin. An exogenous preparation of phospholipase C also induced endothelium-dependent relaxations. These findings support the hypothesis that oxidized metabolites of polyunsaturated fatty acids (e.g., arachidonic acid) may be involved directly (as mediators) or indirectly in the process of endothelium-dependent relaxation. On the other hand, exogenous arachidonic acid was a comparatively weak endothelium-dependent relaxant. However, this does not exclude an important role of endogenous arachidonic acid since the exogenous acid may not sufficiently reach its site of metabolism.
Relationships among arteriolar, regional, and whole organ blood flow in cremaster muscle
Authors: Proctor K. G. , Busija D. W.
Published: December 2017

The relationship between microvessel and tissue blood flow (BF) was determined with two different techniques during changes in local vasomotor tone in the rat cremaster muscle. Whole organ and regional BF were measured with the radioactive microsphere technique (BFms) and compared with values calculated in individual arterioles (BFc) using the dual-slit cross-correlation technique. In the muscle prepared for microcirculatory observation (i.e., dissected, surgically divided into a flattened sheet, and covered with clear plastic), resting BFms was 43 +/- 3 ml X min-1 X 100 g-1, which was significantly higher than paired BFms in the contralateral undisturbed muscle (24 +/- 7 ml X min-1 X 100 g-1). Over a range in vasomotor tone, regional BFms to the edge of the tissue, which was exposed to the trauma of the surgery, was 56 +/- 7 ml X min-1 X 100 g-1 compared with 38 +/- 5 in the less traumatized center region, a significant difference of 79 +/- 31%. There was no linear relationship between arteriolar BFc and BFms. The correlation was not improved if the factors of vessel size, vasomotor tone, animal size, or muscle size were considered. Changes in arteriolar BFc (y) overestimated changes in total tissue BFms (x) by a factor of 2 (y = 2.01x - 0.6; r = 0.86), but changes in arteriolar BFc were proportional to changes in BFms if only the center region (x) of the tissue was considered (y = 1.08x - 0.1; r = 0.84). The general implication from these results is that factors that influence perfusion heterogeneity, such as surgical trauma, should be carefully considered when correlating macro- and microcirculatory measurements of BF.
Reversal of thromboxane A2/prostaglandin H2 and ADP-induced calcium release in intact platelets
Authors: Brace L. D. , Venton D. L. , Le Breton G. C.
Published: December 2017

We previously demonstrated that thromboxane A2 and/or prostaglandin H2 (TXA2/PGH2), ADP, and A23187 cause calcium mobilization in intact human platelets. Other studies have also shown that platelet shape change and aggregation induced by a variety of platelet agonists can be reversed by specific antagonists. In the present study, we used the fluorescent calcium probe chlortetracycline to evaluate whether the reversal of platelet activation involves a resequestration of intraplatelet calcium. It was found that the TXA2/PGH2 receptor antagonist 13-azaprostanoic acid (13-APA) reversed calcium mobilization and shape change induced by AA but not that induced by ADP. A similar specificity of action was observed using the specific ADP receptor antagonist, ATP, in that ATP only reversed ADP-induced calcium release and shape change. In contrast, prostacyclin reversed both AA and ADP-induced calcium redistribution and shape change. In the latter experiments, a net calcium sequestration was actually observed on prostacyclin addition. These findings indicate that the resequestration of released calcium leads to platelet deactivation. Furthermore, there appear to be at least two mechanisms by which a reduction in cytosolic calcium can be produced: specific interruption of the agonist-receptor interaction, for example, 13-APA antagonism of TXA2/PGH2; and stimulation of platelet adenosine 3',5'-cyclic monophosphate production by prostacyclin and consequent calcium sequestration.