bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional myocardial and ventricular shape: a surface representation
Authors: Janicki J. S. , Weber K. T. , Gochman R. F. , Shroff S. , Geheb F. J.
Published: December 2017

To date, a detailed three-dimensional (3D) analysis of cardiac shape and size has not been available. Accordingly, we developed a method for such an analysis using sectioned hearts and a computer-based 3D description of the epi- and endocardial surfaces of the left and right ventricles (LV and RV) and the interventricular septum. The accuracy of this analysis as a function of section thickness (hs) was evaluated and reference axes for the LV, RV, and myocardium determined in eight canine hearts. After diastolic arrest, the RV, LV, and their atria were fixed in formaldehyde solution at pressures of 6 and 12 cmH2O, respectively. The hearts were then cast (plastic or gelatin) and sectioned, and the surfaces were digitized. We found that 1) accurate 3D computer reconstructions and computed volumes of the LV, RV, and myocardium were obtained then hs less than or equal to 5 mm, 2) the apex-to-base circumference and cross-sectional area relations could be approximated provided hs less than 10 mm, and 3) the section centers of gravity for the LV, RV, and myocardium defined three distinct vertical lines. Thus, an accurate description of 3D configuration is obtainable by a 5-mm section thickness. The centers of gravity provide a set of geometrical references for the study of shape in normal and diseased hearts.
Sinoatrial node artery distribution and its relation to hierarchy of cardiac automaticity
Authors: Hardie E. L. , Jones S. B. , Euler D. E. , Fishman D. L. , Randall W. C.
Published: December 2017

The sinoatrial node (SAN) artery (SANA) was cannulated in dogs anesthetized with chloralose (7 dogs) or pentobarbital (1 dog). Intra-SANA injection of acetylcholine (ACh) with edrophonium (EPh) produced a transient junctional rhythm (JR) when the cannula tip lay near SANA origin. However, when ACh-EPh was injected while the cannula tip lay within SAN region, a slower P wave rhythm, rather than a JR, developed. To determine visually the injected ACh-EPh distribution, an equal volume of dye was injected under similar conditions. Dye-distribution patterns were consistent in all atria. These averaged 44 +/- 2% of the total endocardial surface, indicating that SANA distribution is not discrete, but widespread. Dye extended cranially, caudally, and laterally and included documented subsidiary pacemaker sites. Dye approached, but never trespassed, the coronary sinus ostium. Results suggest that cholinergic drug injection into the proximal SANA may suppress not only the SAN, but subsidiary atrial pacemakers as well. In this situation, junctional pacemakers probably emerge, not because of inherently greater automaticity, but after default of subsidiary atrial pacemakers.
Centrally mediated effect of phenytoin on digoxin-induced ventricular arrhythmias
Authors: Garan H. , Ruskin J. N. , Powell W. J.
Published: December 2017

Studies on the efficacy of phenytoin administered directly into the cerebrospinal fluid in protecting against digoxin-induced arrhythmias were carried out in 20 anesthetized dogs. Phenytoin was administered in an average dose of 10 mg directly into the cisterna magna of 10 dogs. The other control dogs received only the vehicle for phenytoin intrathecally. Both groups of dogs subsequently received a toxic dose of digoxin (0.2 mg/kg) intravenously. The time after intravenous digoxin to the onset of ventricular premature beats, ventricular tachycardia and ventricular fibrillation (VF) was significantly shorter in control animals compared to the phenytoin-treated dogs. In the control group, one dog survived the 3-h observation period without developing ventricular fibrillation, whereas 5 of the 10 phenytoin-treated dogs survived this period without VF (P less than 0.05). Phenytoin had a similar protective effect against digoxin-induced arrhythmias in 10 other dogs that received phenytoin intravenously. In the animals that received phenytoin intrathecally, plasma concentrations of phenytoin were undetectable. Thus, in this experimental model, phenytoin exerts a protective effect against digoxin-induced ventricular arrhythmias which is mediated via the central nervous system.
Effect of calcitonin, hydrocortisone, and parathyroid hormone on canine bone blood vessels
Authors: Driessens M. , Vanhoutte P. M.
Published: December 2017

Experiments were designed to determine whether or not calcitonin, parathormone, and glucocorticoids have direct effects on the vascular smooth muscle cells of bone blood vessels. Tibias of mongrel dogs were isolated. The arteria nutriens was cannulated and perfused at constant flow with aerated Krebs-Ringer solution (37 degrees C). The perfusion pressure was continuously recorded. In unstimulated preparations calcitonin caused dose-dependent increases in perfusion pressure, indicating that it causes constriction of bone blood vessels. Parathormone did not affect basal perfusion; it did not significantly alter vasoconstrictions caused by the injection of norepinephrine indicating that the hormone has no direct effect on the vascular smooth muscle of bone blood vessels. Hydrocortisone, at low concentrations, augmented the constrictions caused by exogenous norepinephrine and periarterial nerve stimulation; at higher concentrations, hydrocortisone caused a dose-dependent inhibition of the response to adrenergic activation. The depressant effect of hydrocortisone was antagonized by propranolol, suggesting that the glucocorticoid facilitates beta-adrenergic relaxation of the vascular smooth muscle cells by catecholamines.
Acute and chronic changes after aortic valve damage in the intact dog
Authors: Belenkie I. , Rademaker A.
Published: December 2017

Acute aortic regurgitation was produced under anesthesia in 11 closed-chest dogs previously instrumented with ultrasound transducers. The immediate responses included increases in end-diastolic diameter (EDD), fractional shortening (FS), heart rate, left ventricular end-diastolic pressure (LVEDP), and pulmonary capillary wedge pressure (PCWP), the latter being transient as was a decrease in left ventricular peak systolic pressure (LVSP). End-systolic diameter (ESD) did not change. The grouped data suggest that no further changes occurred following the initial responses except in PCWP and LVSP. The data from individual dogs showed that there was a tendency for EDP, LVEDP, and PCWP to return toward control values after the initial increases in those dogs in which the heart rate increased after valve damage. This suggests that there were ongoing compensatory adjustments after the initial responses in this subgroup. Twelve dogs were followed chronically in the intact conscious state with echocardiographic measurements after acute aortic valve damage. EDD and ESD increased rapidly for about 80 days after which EDD increased slowly, whereas ESD showed no further change. Wall thickness and FS did not change throughout the period of study, suggesting that increasing wall thickness may be a relatively late change and that it may be related to the level of myocardial compensation.
Effect of tetraethylammonium chloride on action potential in cardiac Purkinje fibers
Authors: Ito S. , Surawicz B.
Published: December 2017

Intracellular loading with 20 mM tetraethylammonium chloride (TEA) diffusing through the cut end of the preparations prolonged action potential duration (APD) in dog Purkinje fibers without changing maximum diastolic potential, overshoot, and dV/dtmax. The APD was prolonged at all rates of stimulation, but, contrary to the normal rules, APD increased more after longer than after shorter interstimulus intervals. TEA increased the number of beats required to achieve the new steady-state APD after an abrupt change in the rate of stimulation. The effect of varying extracellular potassium concentration on maximal diastolic potential suggested that intracellular loading with TEA had no effect on the time-independent "background" outward current (IK1). If we ascribe all observed TEA effects to the reduction of time dependent slow outward current Ix1, we can propose a hypothesis concerning the role of Ix1 in the regulation of APD at slow heart rates.
Renal blood flow changes in contralateral kidney of Goldblatt hypertensive dog
Authors: Zimmerman B. G. , Mommsen C.
Published: December 2017

Sequential changes in systemic arterial blood pressure (BP), renal blood flow (RBF) in the contralateral kidney, and plasma renin activity (PRA) were examined on conscious dogs with construction of a single renal artery (RAC). An increase of 24 mmHg in bP occurred within 2 days after RAC, and BP later plateaued at a lower level. RBF in the contralateral kidney transiently increased by 24% and then returned to the control level in 11-14 days. PRA also peaked early after RAC and then returned to control. The clamp was tightened and the renal artery was occluded (RAO) 3-20 days after RAC. BP, RBF, and PRA increased to an even greater degree than after RAC. BP peaked at 145 mmHg, and RBF increased 61.5% at 2-3 days after RAO. BP and RBF both decreased but remained above the control for the duration of the study, BP at 127 mmHg and RBF at 256 ml/min. RBF per gram for the hypertrophied contralateral kidney was calculated from the RBF before death and the weight at death. The final RBF per gram of the contralateral kidney (2.7 ml.min-1.g-1) decreased and renal vascular resistance increased compared with the estimated control RBF/g (3.7 ml.min-1.g-1) and renal vascular resistance. These results suggest that the final RBF of the contralateral kidney is not increased in proportion to its increase in weight and that it may be relatively hypoperfused in two-kidney one-clip Goldblatt hypertension.
Filling of microcirculation in skeletal muscles during timed India ink perfusion
Authors: Renkin E. M. , Gray S. D. , Dodd L. R.
Published: December 2017

Lower leg muscles of anesthetized rabbits were perfused in situ with heparinized India ink at flows and pressures comparable to normal resting levels of 4 ml.min-1.100 g-1). Paired cross sections were counterstained with eosin to show ink-containing microvessels and reacted for alkaline phosphate to show all vessels. The fraction of microvessels filled with ink (Fi) increased progressively with perfusion time. At 3.5 s, mean Fi for the muscles studied fell between 0.12 and 0.19. At 60-90 s, the following levels were reached: medial gastrocnemius 0.74, lateral gastrocnemius 0.76, tibialis anterior 0.59, and soleus 0.80. The number of open capillaries and their distribution of flow velocities can be inferred from such data only if the perfusion rate is known or by recourse to a specified anatomic model. The time course of ink appearance shows best agreement with 60-80% of the vessels open and accessible to ink, with microvascular transit times ranging from less than 3 to greater than 30 s. If microvascular path lengths are assumed to be uniform, the range of velocities must be four times to one-fourth the mean, with 15-30% of the microvessels perfused at velocities equal to or greater than the mean. Alternatively, if microvascular velocity is assumed uniform, flow path lengths must vary from one-fourth to four times the average. Anatomic measurements of other suggest that less than one-half the variability in ink transit is attributable to differences in microvascular length. Thus both length and velocity must vary among alternate arteriovenous pathways.
Isoproterenol-induced restoration of contraction in K+-depolarized hearts: relationship to cAMP
Authors: Ingebretsen W. R. , Friedman W. F. , Mayer S. E.
Published: December 2017

The action of isoproterenol on inotropic state, cAMP concentration, and phosphorylase b-to-a conversion was studied under conditions that are known to alter membrane properties in guinea pig papillary muscles. In accord with the results of other investigators, contractile events induced by electrical stimulation were abolished by tetrodotoxin (10 microM) or 22 mM K+ and were subsequently restored by the addition of isoproterenol (10 nM-100 microM). However, in the presence of 22 mM K+, but not tetrodotoxin, the dose-response and temporal relationships between isoproterenol and elevations in cAMP concentration were shifted to the right, whereas those for phosphorylase activation were shifted to the left. Thus the low concentrations (less than 10 nM) of isoproterenol that restored tension development did not produce a measurable increase in cAMP. Contractile responses induced by 10 nM isoproterenol were blocked by (--)-propranolol but not by (+)-propranolol or phentolamine. Methoxamine did not restore contractile events in 22 mM K+-treated muscles or induce changes in cAMP content or phosphorylase activation. These results show that conditions can be obtained (e.g., partial depolarization of cardiac cell membranes) in which beta-adrenergic receptor activation leads to restoration of inotropic state in guinea pig myocardium without an obligatory increase in tissue cAMP content. The restoration of contractile events and enhancement of phosphorylase response under these conditions suggest that beta-adrenergic receptor activation may lead to Ca2+-channel activation directly or by increasing a small pool of cAMP and thereby altering localized protein phosphorylation in the cell membrane.
Closed-chest electrode-catheter technique for His bundle ablation in dogs
Authors: Gonzalez R. , Scheinman M. , Margaretten W. , Rubinstein M.
Published: December 2017

A modified quadripolar electrode catheter that had two-thirds of the distal surface insulated with high-voltage plastic was inserted in 10 dogs. After a His bundle potential had been recorded, a synchronized direct-current electrical discharge was delivered between the electrodes showing the largest His bundle deflection using a standard direct-current defibrillator, and a metallic plate was positioned over the dog's back. Complete atrioventricular (AV) block was induced in 9 of 10 dogs, which were followed for 3 mo before being killed. During AV block, the QRS complex was broad and not preceded by a His bundle deflection. The mean control cycle length during AV block was 1,441 +/- 223 ms and decreased to 1,151 +/- 181 ms after exercise, a response that was usually abolished by beta-blockade. Overdrive pacing resulted in pacemaker suppression with gradual rate stabilization after 10-20 beats. There was no evidence of myocardial or valvular damage. This technique provides for a stable model of complete AV block and is suitable for experiments in which heart rate control is required. In addition, this technique may be of value for patients with tachycardia requiring His bundle section.
Tissue PO2 and arteriolar responses to metabolic stimuli during maturation of striated muscle
Authors: Proctor K. G. , Damon D. N. , Duling B. R.
Published: December 2017

Tissue O2 tension (PO2) and small arteriolar diameter were measured in hamsters aged 32, 60, and 80 days. The cremaster muscle was isolated and superfused with a solution equilibrated with 0, 5, or 10% O2 stimulated to contract at 1 Hz. Resting muscle tissue PO2 was proportional to superfusate PO2 and was not different between age groups. The decrease in tissue PO2 during contraction was greatest in adult animals when the superfusate PO2 was low but was equal in all groups when the superfusate PO2 was high. Elevated superfusate PO2 was correlated with a vasoconstriction, the magnitude of which varied inversely with age. Resting and contraction-induced vascular diameter were largest in the youngest animals, relative to maximum diameter, but absolute resting and contraction-induced diameters were similar in all groups. We suggest that tissue PO2 at rest was similar because of an age-associated decrease in fiber O2 consumption to maintain a constant proportionality between O2 supply and demand. The relative stability of tissue PO2 during contraction in young animals might have reflected superior regulation. However, a simple numerical analysis predicts smaller tissue PO2 decreases during contraction in young animals because of short intercapillary distances and other altered O2 supply parameters, even if regulation had been identical in all age groups.
Contamination of caudal mediastinal node efferent lymph in sheep
Authors: Drake R. , Adair T. , Traber D. , Gabel J.
Published: December 2017

Many investigators have used the chronic sheep lung lymph preparation to collect caudal mediastinal node (CMN) efferent lymph. These investigators have assumed that the lymph collected with the preparation is almost pure lung lymph. We examined 17 sheep for possible systemic contamination to the lymph, and in each sheep we found one to five lymph vessels that ran from the diaphragm to the CMN. Contamination from these vessels would not be eliminated in the chronic sheep preparation. We estimated the flow rate from these vessels to be 3.0 +/- 2.6 (SD) ml/h in anesthetized sheep. This represents 25-60% of the lymph flow rate in the chronic lymph preparation. In five sheep, we also located 1-4 esophageal lymph vessels that entered th CMN. These results show that lymph collected with the chronic sheep lung lymph preparation contains a significant nonpulmonary contamination.
Interaction between carotid and cardiopulmonary baroreflexes in control of plasma ADH
Authors: Thames M. D. , Schmid P. G.
Published: December 2017

The purpose of this study was to determine if there is an interaction between carotid baroreceptors (CBR) and cardiopulmonary receptors with vagal afferents (CPVA) in the control of plasma vasopressin (ADH). Changes in ADH (radioimmunoassay) in the superior vena cava were determined in 13 chloralose-anesthetized dogs with aortic nerves sectioned during concomitantly induced changes in CBR and CPVA input. CBR input was changed by altering pressure (CSP) in the isolated perfused sinuses. Carotid sinus pressure (CSP) was initially set at 50 mmHg. The CPVA input was reversibly interrupted by cooling the vagi to 0 degrees C while CSP was concomitantly increased to 135 or 200 mmHg or was held constant at 50 mmHg. Vagal cold block (VCB) with CSP held constant at 50 mmHg resulted in large increases in arterial pressure and plasma vasopressin. Increases in CSP to 200 mmHg resulted in significant decreases in arterial pressure and in plasma vasopressin despite concomitant VCB. VCB and concomitant increase in CSP to 135 mmHg resulted in a significant fall in arterial pressure, whereas plasma vasopressin tended to increase. Thus, the influence on arterial pressure of raising CSP to 135 mmHg exceeds that of VCB. In contrast, the influence of VCB on ADH equals or exceeds that of raising CSP to 135 mmHg. These differential responses of arterial pressure and plasma ADH suggest an interaction between CBR and CPVA in the control of ADH and arterial pressure.
Properties of intestinal and cutaneous arteries and veins in two-kidney one-clip Goldblatt hypertension
Authors: Greenberg S.
Published: December 2017

This study evaluates whether changes in arterial and venous smooth muscle contractility and extensibility precede or result from the elevated arterial pressure (MAP) and total peripheral resistance (TPR) of two-kidney one-clip Goldblatt hypertension (2-KGH). The experiments measure the contractile and extensibility properties of rings of canine mesenteric, cutaneous, gracilis, and pulmonary arteries and veins (0.4-1.0 mm OD) prior to and days 1 and 32 after the initiation of two-kidney one-clip Goldblatt hypertension (2-KGH), produced by unilateral constriction of the renal artery (URAC). The reactivity (ED50) and tension development to norepinephrine (NE), angiotensin II (ANG II), potassium chloride (KCl), serotonin (5-HT), 9 alpha, 11 alpha-epoxymethano prostaglandin H2 (EMP), prostaglandin B2 (PGB2), and CaCl2 were determined. Mean arterial pressure (MAP) and TPR were unchanged from pre-URAC values 24 h post-URAC but were significantly elevated 32 days post-URAC. The ED50's for 5-HT, ANG II, EMP, and PGB2 were decreased in each of the arteries and veins obtained from dogs with 2-KGH, within 24 h post-URAC, and either became more pronounced (PGB2, EMP, and 5-HT) or returned to pre-URAC values by day 32 post-URAC. The ED50's for NE, KCl, and CaCl2 were unchanged from pre-URAC values. Maximal tension development of the arteries and veins to each of the agonists increased within 24 h post-URAC, prior to an increase in MAP or TRP. Within 32 days post-URAC, maximal tension development of the veins obtained from 2-KGH was increased from pre-URAC values, whereas tension development by the arteries was decreased. Extensibility decreased in each of the arteries and veins obtained from dogs with 2-KGH 24 h post-URAC. The extensibility decreased further by day 32 post-URAC as the level of MAP and TPR increased. These data support the postulate that altered venous and arterial smooth muscle contractility and extensibility precede the elevated MAP and TPR of 2-KGH in dogs. Moreover, since these changes occur in both artery and vein, they must reflect the action of circulating humoral or intrinsic vascular or neural substances. Finally, the decrease in arterial contractility suggests that the enhanced vascular responses in vivo and in situ may reflect the greater mechanical advantage of the hypertrophied blood vessel and not an arterial vasculature with enhanced contractility.
Cardiac electrical resultant dipole moment of spontaneously hypertensive rats
Authors: Hodgkin B. C. , Nelson C. V. , Angelakos E. T.
Published: December 2017

The cardiac electrical resultant dipole moment (RDM) of 17 spontaneously hypertensive rats (SHR) was compared with that of 17 Wistar-Kyoto rats (WKY), 65-100 days of age. Relative to body weight, left ventricular weight was 23% greater and right ventricular weight was 18% greater for SHR than for WKY. Left ventricular wall thickness was 11% larger and myocyte diameter was 13% larger for SHR than for WKY. RDM orientation for SHR was more dorsal, leftward, and cranial from middle to end of qRS. The second spatial magnitude peak of QRS, M2, was significantly smaller for SHR than for WKY (P less than 0.001) whereas M3 for SHR was significantly greater than for WKY (P less than 0.001). The alterations in RDM of SHR are greater than can be accounted for simply on the basis of increased cell size. The excitation sequence for SHR might be different from that of WKY. Results show the necessity of considering the details of the spatial magnitude curve during QRS.
Lysophosphoglycerides in ischemic myocardium effluents and potentiation of their arrhythmogenic effects
Authors: Snyder D. W. , Crafford W. A. , Glashow J. L. , Rankin D. , Sobel B. E. , Corr P. B.
Published: December 2017

Lysophosphoglycerides accumulate in ischemic myocardium. To determine whether lysophosphatidylcholine (LPC) concentrations increase in extracellular fluid and may be arrhythmogenic, the anterior descending coronary artery of the open-chest cat (n = 12) was perfused with a Krebs-albumin solution after 10 min of ischemia and the effluent assayed for LPC. A twofold increase in LPC (0.097 +/- 0.02 to 0.170 +/- 0.03 mM) was observed. Microelectrode intracellular recordings from from normal feline endocardium at pH 7.4 in vitro revealed little change in action potentials when superfused with feline plasma despite augmented LPC to twice normal levels (0.74 mM). However, at pH 6.7, marked changes were elicited by LPC-enriched plasma including diminished resting membrane potential (-96 +/- 1 to -35 +/- 7 mV), amplitude (102 +/- 3 to 36 +/- 8 mV), maximum rate of rise (Vmax) of phase 0 (178 +/- 24 to 26 +/- 11 V/s), and conduction velocity with fractionation of the action potential. Acidified control plasma decreased only Vmax (from 161 to 57 V/s). Thus LPC increases twofold in effluents from cat myocardium in vivo after 10 min of ischemia and, coupled with ischemia-induced acidosis, is sufficient to induce marked electrophysiological derangements in vitro.
Cerebrovascular response to hypoxia in baroreceptor- and chemoreceptor-denervated dogs
Authors: Traystman R. J. , Fitzgerald R. S.
Published: December 2017

Cerebral hemodynamic responses to arterial hypoxemia were studied in anesthetized paralyzed dogs that were or that had undergone carotid baroreceptor denervation, carotid chemoreceptor denervation, vagotomy, or both vagotomy and carotid sinus nerve section. Arterial O2 content was lowered from control (19.0 vol%) to 9.6 vol% by either decreasing arterial O2 tension [hypoxic hypoxemia (HH)] or increasing carboxyhemoglobin saturation[carbon-monoxide hypoxemia (COH)] at normal O2 tension. In intact animals (composite control values from all groups) HH and COH resulted in similar increases in cerebral blood flow (to 205 and 197% of control, respectively). Cerebral vascular resistance decreased more with COH than with HH (to 42 vs. 60% of control). The response from carotid baroreceptor-denervated animals and from vagotomized animals did not differ from that of the intact animals. After carotid chemoreceptor denervation and combined carotid sinus nerve section and vagotomy, both HH and COH increased cerebral blood flow to 194% of control (same increase as in intact animals, carotid baroreceptor-denervated animals, and vagotomized animals) and produced equal reductions in cerebral vascular resistance (to 34% of control). These data show that the carotid and aortic chemoreceptors are not necessary for the increase in cerebral blood flow provoked by hypoxemia and that this response is not modified by the carotid and aortic baroreceptors.
Local cerebral glucose utilization and blood flow during metabolic acidosis
Authors: Kuschinsky W. , Suda S. , Sokoloff L.
Published: December 2017

The relationship between local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) was studied in two groups of normal conscious rats. LCGU was measured by the [14C]deoxyglucose technique and LCBF by the [14C]iodoantipyrine technique. When the LCGU of 39 brain structures was correlated with their respective values of LCBF an excellent correlation (r = 0.96) was obtained between LCGU and LCBF, demonstrating a tight coupling at a local level. Chronic metabolic acidosis was induced in two other groups of rats by adding 0.35 M NH4Cl to the drinking water for 5-6 days. This resulted in a significant (P less than 0.01) reduction in overall cerebral glucose utilization (-29%) and a nonsignificant reduction in overall cerebral blood flow (-8%). This dissociation between the overall cerebral glucose utilization and blood flow during metabolic acidosis cannot be taken as an indicator of uncoupling because the values for LCGU were still well correlated (r = 0.95) with the values for LCBF, indicating a resetting of the coupling mechanism to a new level.
Reversibility of abnormal arterial baroreflex control of heart rate in heart failure
Authors: White C. W.
Published: December 2017

The reversibility of the abnormalities in arterial baroreceptor control of heart rate in heart failure was examined in an experimental model of canine high-output biventricular failure produced by an arteriovenous fistula that could be later surgically corrected by ligation. Marked attenuation of arterial baroreceptor control of heart rate in response to both hypertensive and hypotensive stimuli was seen in this model of heart failure. After surgical correction the heart rate response to a hypertensive stimulus did not return to normal but remained severely blunted for up to 8 mo of follow-up. The lack of reversibility after surgical correction suggests that permanent structural changes in arterial baroreceptors may occur after heart failure of short duration.
Changes in vagal phasic chronotropic responses with sympathetic stimulation in the dog
Authors: Stuesse S. L. , Wallick D. W. , Zieske H. , Levy M. N.
Published: December 2017

Sympathetic stimulation both shortens the cardiac cycle and potentiates the cardiac response to vagal stimulation. In the present study the effects of sympathetic stimulation on the chronotropic responses of the heart to brief bursts of vagal stimulation were determined in open-chest anesthetized dogs. The sinoatrial nodal pacemaker cells demonstrate a paradoxical response to repetitive bursts of vagal stimuli over a certain portion of the cardiac cycle. That is, the cardiac cycle length does not increase but actually decreases as the vagal stimulation frequency is raised. Background levels of sympathetic stimulation do not significantly alter the range over which this “paradoxical” response occurs. Sympathetic stimulation decreases the cardiac chronotropic response to short bursts of vagal stimuli regardless of the time in the cardiac cycle that the stimulus is given; however, it does not decrease the time from the minimum vagal chronotropic response to the subsequent atrial depolarization although the total cardiac cycle is shortened. Since sympathetic stimulation shifts the overall temporal relationship between vagal stimulation and pacemaker response, small changes in sympathetic tone may greatly alter the cardiac response to phasic vagal stimulation if the vagal stimulus is given at certain times in the cardiac cycle.
Regulation of adrenal blood flow: response to hemorrhagic hypotension
Authors: Houck P. C. , Lutherer L. O.
Published: December 2017

Adrenal blood flow was measured during hemorrhagic hypotension in pentobarbital-anesthetized dogs using the radioactive-microsphere technique. A decrease in adrenal vascular resistance occurred during hemorrhage that was sufficient to maintain adrenal blood flow at prehemorrhage levels even with a decrease in mean arterial blood pressure (MABP) to as low as 50 mmHG. Blockade of alpha- and beta-adrenergic receptors, H1- and H2-histamine receptors, and prostaglandin synthesis all decreased resting adrenal blood flow. However, blood flow did not decrease further with hemorrhage subsequent to these interventions. Neither cholinergic blockade (muscarinic) alone nor ganglionic blockade subsequent to cholinergic blockade changed adrenal blood flow. However, ganglionic blockade alone increased adrenal blood flow. Hemorrhage subsequent to hypophysectomy also did not change blood flow to the adrenal. These data suggest that the maintenance of adrenal blood flow during hemorrhagic hypotension to 50 mmHg MABP is independent of the autonomic nervous system, prostaglandin synthesis, histamine receptors, or an intact pituitary-adrenal axis, even though all of these systems do influence adrenal blood flow.
Autonomic control of ventricular refractoriness
Authors: Nattel S. , Euler D. E. , Spear J. F. , Moore E. N.
Published: December 2017

The effects of vagal and sympathetic stimulation on canine ventricular refractoriness were studied in vivo. Sympathetic stimulation reduced the left ventricular refractory period to an extent linearly related to the logarithm of nerve stimulation frequency. Vagal stimulation had no effect in the absence of sympathetic stimulation but produced a frequency-dependent attenuation of sympathetic effects when the two systems were stimulated simultaneously. The effects of combined vagal and sympathetic stimulation were best described by a multilinear regression model using the logarithm of vagal and sympathetic frequency as covariates. The magnitude of vagal attenuation of sympathetic effects did not show any regional variation at the five widely spaced sites (2 right ventricular, 3 left ventricular) studied.
Comparative response of the developing canine myocardium to inotropic agents
Authors: Park I. S. , Michael L. H. , Driscoll D. J.
Published: December 2017

Developmental changes in cardiac muscle function were assessed in isolated dog ventricular muscle strips obtained from dogs of three age groups: 2 day, 4 wk, and adult. Active tension (AT) and maximum rate of contraction and relaxation (+dT/dt, -dT/dt) increased significantly with age. Total contraction time increased with age. Time to peak tension increased between 4 wk and adulthood, and relaxation time increased between 2 day and 4 wk (P less than 0.05). The degree of post-"extra stimulus" potentiation in response to a single premature extra stimulus (SPES) or to sustained paired stimulation (SPS) was similar in all age groups. However, a longer period of SPS was necessary to reach peak AT in young animals than in adults. AT, +dT/dt, -dT/dt, and (-dT/dt)/T increased significantly in all age groups in response to increasing concentrations of isoproterenol. However, while (+dT/dt)/T increased significantly in the 4-wk and adult groups, it remained unchanged from control in the 2-day group with increasing concentration of isoproterenol. The ED50 of isoproterenol was significantly greater in the 2-day and 4-wk groups than in the adult group. AT increased significantly in young muscles but not in adult muscles when additional calcium was added to the bath containing the highest concentration of isoproterenol. In adult muscles SPS produced the greatest AT but not in the 2-day group, which required increased calcium concentration as well as isoproterenol. Maturation of several membrane systems is implicated.
Adaptive changes of pyruvate oxidation in perfused heart during adrenergic stimulation
Authors: Bunger R. , Permanetter B. , Sommer O. , Yaffe S.
Published: December 2017

Pyruvate oxidation was studied in isolated guinea pig hearts perfused under various conditions of work and stimulated by norepinephrine. Hearts metabolized pyruvate alone or in combination with 3-hydroxybutyrate or acetate as substrate. [1-14C]-pyruvate-dependent 14CO2 release into the venous effluent (MVpyr) was, like myocardial oxygen consumption (MVO2), directly related to aortic pressure or filling pressure. At high aortic pressures, ventricular pressure development and not work performance was the major determinant of MVO2 and thus MVpyr. With 1 mM pyruvate as sole substrate, 0.08 microM norepinephrine produced parallel changes in hemodynamic performance, MVO2. MVpyr, and pyruvate dehydrogenase complex (PDC) activity (active form). Similar and dose-dependent effects of norepinephrine were observed during infusion of 5 mM DL-3-hydroxybutyrate as cosubstrate. When 1 mM acetate was applied, MVpyr was also dependent on work performance and norepinephrine stimulation. However, in perfusions with 25 mM potassium chloride, norepinephrine did not enhance hemodynamic function or MVO2 and hence PDC activity and MVpyr. Thus regulation of the PDC in catecholamine-stimulated heart appears to be linked predominantly to myocardial energy demand even when alternative energy-providing substrates are utilized.
Effects of inorganic phosphate on ion exchange, energy state, and contraction in mammalian heart
Authors: Ponce-Hornos J. E. , Langer G. A.
Published: December 2017

Effects of inorganic phosphate (Pi) on contractile function, ionic exchange, and cellular energetic state were investigated in isolated, arterially perfused, interventricular rabbit septa. The addition of 10 or 20 mM Pi to a N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffered perfusate showed 1) a decrease in developed tension due to a decrease in free Ca concentration; 2) an increase in diastolic tension; 3) a decrease in 42K uptake at the same time that 42K efflux was depressed; 4) an increase of 24Na activity; 5) an increase in tissue 47Ca activity; and 6) a decrease in tissue adenosine 5'-triphosphate (ATP) levels. If a 10-mM Pi intervention was applied without changing the free Ca concentration of the perfusate, the mechanical record showed a transient positive inotropic effect without changes in K efflux. These results are consistent with Pi-induced stimulated mitochondrial Ca uptake and Na-K pump inhibition that combine to increase cellular Ca uptake. The increase in cellular Ca and the decrease in cellular ATP would both tend to increase diastolic tension. In the presence of antimycin A, respiration-dependent Ca uptake is inhibited, and mitochondrial Ca uptake is then maintained at the expense of cellular ATP. This process of mitochondrial Ca uptake could account for the deficiency of ATP and the rigor type contracture that occurs with antimycin A. This energy-deficient state is modified if mitochondrial ATP consumption is blocked by oligomycin, and such treatment prevents the ATP-deficient rigor. Under these conditions, although mitochondrial Ca uptake is blocked by the presence of antimycin A and oligomycin, Ca uptake remains augmented secondary to Na-K pump inhibition by Pi.
Left ventricular performance in endotoxin shock in dogs
Authors: Guntheroth W. G. , Jacky J. P. , Kawabori I. , Stevenson J. G. , Moreno A. H.
Published: December 2017

Endotoxin shock, with maximal velocity of contraction (Vmax) as our index of contractility, showed no myocardial depression in an earlier 4-h study (Guntheroth, Proc. Soc. Exp. Biol. Med. 157: 610--614, 1978). Because of reports of late deterioration, we studied six dogs until spontaneous death (9--18 h). Heart rate nearly doubled and left ventricular filling pressure and aortic mean pressure fell, but Vmax did not change significantly. Because of concern that the marked increase in heart rate may have contributed to an artifactual maintenance of Vmax (due to its frequency dependence, inherent in dp/dt), we studied a final group of five dogs with three additional indicators of contractility. End-systolic pressure-diameter ratio (Emax), ejection fraction (sonar-determined from the minor axis of the left ventricle), and frequency-normalized average rate of generation of power density (FARPD) all fell early and remained low until death. We conclude that myocardial contractility is significantly reduced in endotoxin shock, early and sustained. Its presence is masked somewhat in the untreated subject by the reduced work load, secondary to hypovolemia.
Ventricular function in norepinephrine-induced cardiomyopathic rabbits
Authors: Lee J. C. , Downing S. E.
Published: December 2017

Catecholamine cardiomyopathy (CM) was produced in rabbits by a 90-min infusion of norepinephrine (NE, 2 micrograms . kg-1 . min-1). Left ventricular (LV) contractility and pump function (VF) were examined 2 days later and compared with control animals. The effects of hypercapnia [CO2 tension (PCO2) greater than 70 mmHg] and inotropic responsiveness to NE were also determined. VF was assessed by means of left ventricular function curves obtained with constant aortic pressure and heart rate and quantified by determining stroke volume at left ventricular end-diastolic pressure of 10 cmH2O (SV10). Mean SV10 was 1.16 +/- 0.06 ml in controls but averaged only 0.93 +/- 0.05 in CM (P less than 0.02). Hypercapnia caused significantly greater depression of VF in CM than in controls. NE dose-response curves demonstrated increases in both LV dP/dtmax and SV10 in each group. The percent increase in LV dP/dtmax was markedly attenuated n CM, but the increments in SV10 did not differ. The mean histological score in the CM animals was 1.6 +/- 0.1, indicating extensive myofiber injury. No histological abnormalities were observed in the controls. Thus functional defects correlated with the presence of histopathological changes. In addition, a dissociation of velocity (dP/dtmax) and force (SV10) responsiveness to inotropic stimulation was identified in the CM group.
Effects of blood volume changes on characteristic impedance of the pulmonary artery
Authors: Dujardin J. P. , Stone D. N. , Forcino C. D. , Paul L. T. , Pieper H. P.
Published: December 2017

Experiments were performed on eight anesthetized dogs to study the response of the characteristic impedance (Zc) of the main pulmonary artery to changes in circulating blood volume. Pressure and flow were measured in the proximal main pulmonary artery under control conditions, after hemorrhage (-15% of the estimated blood volume), again under control conditions, and finally after volume expansion (+30% of the estimated blood volume). Two different methods were used to determine Zc from these recordings. With the frequency-domain method values for Zc were obtained by averaging the input impedance moduli between 2 and 15 Hz. With the time-domain method Zc was derived as the slope of the early ejection pressure-flow relationship. The values for Zc obtained with the two methods were not statistically different. In the time-domain method the average increase in Zc with hemorrhage was 30.7 +/- 7.4 (SE) %, and the average decrease with volume expansion was -21.1 +/- 5.0 (SE) %. Because the time-domain method allowed the values of Zc during control conditions and after hemorrhage to be obtained in the same pressure range, it was concluded that the observed changes were caused by a change in the activity of the smooth muscle in the pulmonary arterial wall. Similarly, it was concluded that the decrease in Zc after volume expansion was active in nature.
Capillary network geometry and red cell distribution in hamster cremaster muscle
Authors: Klitzman B. , Johnson P. C.
Published: December 2017

Vascular geometry and red cell distribution were examined in 133 capillaries by means of intravital microscopy in the cremaster muscle of the pentobarbital-anesthetized hamster. Significant correlations (P less than 0.01) were found between diameter and flow, length and resistance, red cell transit time and flow, and red cell flux and hematocrit. Most unexpected was the lack of correlation (P greater than 0.2) between flow and resistance, length, or hematocrit. In addition, we analyzed the relation between blood flow and red cell flux at capillary bifurcations. The red blood cells had a slight (7%), but significant (P less than 0.025), tendency to enter the branch having either higher flow, red cell velocity, or pseudoshear rate (velocity/diameter). The net effect of the preferential red cell flow was to reduce mean capillary hematocrit from 13.7% prior to the bifurcation to 13.3% in the two branches. Finally, increasing the oxygen level of the superfusate above the muscle caused vasoconstriction and an increased heterogeneity of capillary red cell flux and hematocrit, decreasing the capacity for oxygen transport to the tissue.
Mass-balance approach for estimating transcapillary fluid and protein movement
Authors: Friedman J. J. , Szwed J. J. , Johns B. L.
Published: December 2017

This study assesses the applicability of a procedure based on mass conservation to estimate transcapillary protein transport (PT) in patients. In a tissue that exhibits net transcapillary protein transport, total transcapillary fluid movement (FMT) is defined according to the law of mass conservation as: FMT = FA (CV − CA)/CV + PT/CV where FA is arterial plasma flow and CV and CA are respectively venous and arterial protein concentration. The first term above (FMO) was estimated from changes in venous plasma oncotic pressure. The second term was estimated both from the rate of tissue accumulation of 125I-albumin and from the mass-balance relationship as (FMT − FMO). FMT was determined in a jejunal segment as the sum of the changes in tissue weight, fluid secretion, and lymph flow. Increasing venous pressure by 10 and 20 mmHg produced changes in FMT and PT which, as estimated by the two methods, were not significantly different. Thus PT can be estimated from the mass-balance relationship without employing either radioactive labels or noxious tissue manipulation; such an approach should be suitable for clinical application.

cat; jejunal segment; plasma oncotic pressure

Submitted on December 12, 1980

Accepted on September 16, 1981
Multiplexer displays two pressure signals on single oscilloscope channel
Authors: Battagin R. L. , Glantz S. A.
Published: December 2017

High-fidelity pressure transducers may drift during long experiments. To correct for this drift, many investigators periodically rebalance the high-fidelity transducer, comparing the results from the high-fidelity transducer with those from a fluid-filled catheter connected to an external transducer. This procedure is subject to error because the high-fidelity and reference signals have to be displayed on different oscilloscope channels; thus these channels can drift differently, being subject to parallax and other problems. This procedure also requires two display channels, which are often in short supply during two display channels, which are often in short supply during complex experiments. We present a design for a multiplexer that will display two pressure signals on one oscilloscope channel, thereby solving these problems and saving one channel to display other information.
Pulmonary and coronary endothelial effects of acute myocardial ischemia in dogs
Authors: Gee M. H. , Flynn J. T. , Spath J. A.
Published: December 2017

We measured pulmonary arterial (Ppa) and left atrial (Pla) pressures, lung lymph flow rate (QL), and protein clearance in 23 anesthetized dogs with ligation (MI) dogs or sham ligation (sham-MI dogs) of a coronary artery combined with either large transient increases in Pla or moderate steady-state increases in Pla. In steady-state experiments we also collected cardiac lymph. Plasma and lymph concentrations of several prostanoids including prostacyclin (PGI2) and thromboxane B2 (TXB2) were measured. Lung lymph flow rates and protein clearances were increased in MI dogs compared with those in sham-MI dogs in experiments with transient increases in Pla. Similarly in steady-state experiments lung QL and protein clearance were increased after MI. Cardiac QL increased after MI with no change in lymph protein clearance. Lung and cardiac lymph PGI2 and plasma TXB2 concentrations increased after MI. We suggest that acute MI results in increased lung vascular permeability and that activation of formed elements in blood may be involved in mediating MI-induced vascular injury.
Red blood cell and plasma distribution in SHR cremaster muscle microvessels
Authors: Baker C. H. , Wilmoth F. R. , Sutton E. T. , Takach K.
Published: December 2017

Distribution of blood in the cremaster muscle microvasculature of spontaneously hypertensive (SHR) and Wistar-Kyoto normotensive (WKY) rats was determined by fluorescence videomicroscopy and densitometry. Bolus intra-arterial injections of fluorescein isothiocyanate (FITC)-dextran or dichlorotriazenylaminofluorescein-treated red blood cells (DTAF-RBC) produced time-concentration curves in the series-coupled segments. WKY and SHR mean arterial pressure averaged 89 +/- 6 and 125 +/- 5 mmHg, respectively. Arteriolar diameters were not different between the two groups. The smallest SHR venules (V4) and larger diameters than those of WKY (P less than 0.05), whereas V3 and V2 were not different. WKY diameters for V1 were significantly greater than those of SHR. The mean transit (t) and appearance times (ta) of both indicators were equal at the largest arteriole (A1) in both groups. In A2, A3, and A4 the t for both indicators were generally lower in SHR than in WKY rats but not significantly. The venular t were significantly greater in SHR than in WKY rats with DTAF-RBC consistently less than FITC-dextran values. The greater cross-sectional area of V4 in SHR than WKY rats would reduce flow velocity and elevate t. Dispersion (ta/t = 1.0 indicates no dispersion) of both indicators was less in WKY than in SHR. The ratios for both groups increased at V4 because ta increased more than t. Shorter circuits for red blood cells than for plasma and less plasma skimming exists in WKY than in SHR.