bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible vascular isolation of carotid sinuses in conscious dogs
Authors: Stephenson R. B. , Donald D. E.
Published: December 2017

A surgical technique has been developed that permits reversible vascular isolation of both carotid sinuses in the conscious dog. Seven dogs so prepared were studied over periods of 4-12 wk. Repeatable stimulus-response curves relating arterial blood pressure to carotid sinus pressure were obtained for sinus pressures of 40-240 mmHg. Two studies gave evidence that the ability of the carotid baroreceptors to influence arterial pressure was not or was minimally affected by the surgical dissection. In 10 dogs one sinus was surgically prepared; 3 wk later the dogs were anesthetized and vagotomized. The steady-state stimulus-response curves for the chronically prepared sinuses showed no consistent differences from the curves for the opposite, acutely prepared sinuses. In 8 other dogs the hypertensive responses to bilateral carotid occlusion were compared before and after surgical preparation of both sinuses. The responses to carotid occlusion tended to be decreased after surgery but the differences were small and were significant only in 3 dogs.
Effects of ventricular pacing on regional left ventricular performance in the dog
Authors: Badke F. R. , Boinay P. , Covell J. W.
Published: December 2017

Changes in regional left ventricular (LV) performance induced by ventricular pacing were studied in two groups of open-chest anesthetized dogs. In the first group of five dogs, local function at the LV anterior base, anterior apex, and posterior apex was assessed by ultrasonic crystal pairs with atrial, right ventricular, LV apical, and LV base pacing. Ventricular pacing produced asynchrony of contraction and marked changes in the shortening pattern at each site, as well as an average 27% reduction in peak systolic pressure and peak dP/dt compared to atrial pacing. Moreover, the extent of shortening during LV ejection was reduced or unchanged at all sites measured during ventricular pacing. In the second group of five dogs, function of the septum and opposing LV lateral wall was studied with atrial and LV lateral wall pacing. Lateral function was assessed with a crystal pair and septal function by cineradiography of a lead bead implanted in the septum. Ventricular pacing produced reciprocal interaction between the two walls, with early lateral shortening inducing septal bulging and late septal shortening inducing lateral wall systolic lengthening. We conclude that ventricular pacing produces significant changes in regional myocardial function, likely induced by reciprocal interaction of opposing myocardial regions. Furthermore, such interaction appears deleterious to global ventricular function, presumably because volume is sequestered and pressure is dissipated into relatively inactive segments that are out of phase with the bulk of contracting myocardium.
Development of two-kidney Goldblatt hypertension in rats under dietary sodium restriction
Authors: Munoz-Ramirez H. , Chatelain R. E. , Bumpus F. M. , Khairallah P. A.
Published: December 2017

In Sprague-Dawley rats with unilateral renal artery stenosis and an intact contralateral kidney, administration of a low-sodium diet did not prevent the development of hypertension. Despite an elevated blood pressure, hyponatremia, marked activation of the renin-angiotensin system, and increased hematocrit values, only 10% of the rats showed lesions of malignant hypertension. Systolic blood pressures of one- and two-kidney sham-operated rats fed a low-sodium diet were significantly higher than that of normotensive controls fed a normal diet. Uninephrectomy did not reduce plasma renin activity. The low-sodium diet increased plasma renin activity to about the same level in one- and two-kidney normotensive rats. However, the increase in plasma renin activity elicited by dietary sodium restriction was markedly less in one-kidney Goldblatt hypertension. Systolic blood pressure reached similar levels in one- and two-kidney Goldblatt hypertensive rats fed a low-sodium diet. These data indicate that a decrease in sodium intake does not prevent the development of two-kidney Goldblatt hypertension.
The area postrema plays no role in the pressor action of angiotensin in the rat
Authors: Haywood J. R. , Fink G. D. , Buggy J. , Phillips M. I. , Brody M. J.
Published: December 2017

The area postrema has been shown to have a major role in mediating the pressor effects of peripheral angiotensin in the dog, cat, and rabbit. The purpose of this study was to ascertain the function of the medullary circumventricular structure in the conscious rat. The pressor potency of angiotensin administered into the vertebral and carotid arteries was compared with intra-aortic infusions of angiotensin. Although no difference in pressor activity of angiotensin could be detected between intraaortic and intravertebral administration, greater sensitivity was observed during intracarotid infusion. No difference in the course of one-kidney renal hypertension was observed between sham-lesioned rats and animals with an area postrema lesion. In addition, lesioned and sham-lesioned animals showed equivalent responses to graded doses of angiotensin administered either intravenously or into the lateral ventricle. It was concluded that in the rat the area postrema plays no role in mediating the central nervous system actions of angiotensin whether the peptide reaches the brain via the blood or the cerebrospinal fluid.
A new method for quantification of aortic regurgitation during cardiac catheterization
Authors: Mendelsohn S. , Carlson C. J. , Rapaport E.
Published: December 2017

Clinical methods of estimating aortic insufficiency are unsatisfactory. We developed a radioisotope method of quantitating aortic regurgitant volume. The method is easily performed, convenient, and can be carried out repetitively. The mathematical derivation of the method is presented and a mechanical model is used to verify assumptions. The potential utility and possible difficulties of applying the method clinically are discussed.
Fetal cardiac output measured by four-way thermodilution
Authors: Gilbert R. D. , Power G. G. , Schroder H. , Longo L. D.
Published: December 2017

To measure fetal cardiac output by thermodilution, we injected 2.5 ml of iced 5% glucose rapidly into the superior vena cava and recorded areas of temperature-time curves in the brachiocephalic artery (AS) and descending aorta (BS). One minute later we repeated the injection into the inferior vena cava and recorded areas under two curves (AI and BI). Cardiac output was calculated as Qco = H (AS + BI - AI - BS) (ASBI - AIBS), where H is the change in caloric content of the blood. In a mechanical model we found thermal results correlated well with timed collections (r = 0.98) with a slope of 0.995. In 7 acutely prepared fetal lambs, electromagnetic flow probe measurements of total cardiac output (descending aorta + brachiocephalic artery) correlated well (0.90) with thermal measurements. The slope (1.16) was significantly greater than 1.0, reflecting the inclusion of coronary and pulmonary flows in thermal, but not in flow probe, measurements. In 11 acutely and chronically prepared fetal lambs, the correlation between microsphere and thermal measurements was 0.81 with a slope of 1.09, not significantly different from 1.0. Hence, thermodilution gives results comparable to other methods and is convenient, indefinitely repeatable, inexpensive, and nonradioactive.
Effect of acetylcholine and vasoactive intestinal peptide on cerebral blood flow
Authors: Heistad D. D. , Marcus M. L. , Said S. I. , Gross P. M.
Published: December 2017

These experiments were performed to determine whether the neurotransmitters acetylcholine (ACh) and vasoactive intestinal peptide (VIP) increase cerebral blood flow (CBF). In anesthetized dogs, infusion of very large doses of ACh (500 microgram/min) into the carotid artery increased CBF (measured with microspheres) 50%. Anatomical limitations prevented adequate testing of cerebrovascular responses in dogs. In anesthetized rabbits, infusion of ACh (10 microgram/min) into the carotid artery produced a twofold increase in CBF. Vessels in gray matter were more responsive than vessels in white matter. ACh did not alter cerebral oxygen consumption, which indicates that the dilator effect of the drug is not an indirect effect mediated through an increase in metabolism. The vasodilator response to ACh was attenuated by atropine (1 mg iv). Intracarotid infusion of VIP in rabbits increased blood flow to cerebral gray matter: infusion of VIP (10 microgram/min) incresed flow 33%. We conclude that 1) cerebral vasodilator responses to ACh and VIP are larger than previously recognized and 2) responses to these drugs occur primarily in cerebral gray matter. Because the neurotransmitters increase CBF significantly, these studies should encourage further studies concerning effects of cholinergic and peptidergic nerves on cerebral vessels.
Improvement in ischemic myocardial blood flow following a new calcium antagonist
Authors: Jolly S. R. , Gross G. J.
Published: December 2017

The effect of FR 7534, a new dihydropyridine CA2+ antagonist, nitroglycerin, and dipyridamole have been compared on coronary collateral function in pentobarbital-anesthetized open-chest dogs following acute ligation of the left anterior descending coronary artery. Measurements of tissue blood flow using radioactive microspheres were made 60 min postligation after low and high doses of each drug and at the higher dose with methoxamine added to to return mean aortic pressure. FR 7534 treatment increased subepicardial, subendocardial, and transmural tissue flow by 100% in the central ischemic zone when perfusion pressure was controlled by methoxamine. Nitroglycerin also increased ischemic tissue flow, but to a lesser degree, 18% transmurally. Dipyridamole produced no significant change. Tissue flow in normal myocardium was similarly increased by FR 7534 and dipyridamole but slightly reduced by nitroglycerin. FR 7534 and nitroglycerin also increased retrograde coronary pressure when aortic presure was maintained constant. FR 7534, but not nitroglycerin, increased ischemic contractile force. In this model, FR 7534 may produce greater effects than nitroglycerin in increasing blood supply to ischemic myocardium delivered by endogenous collaterals especially when aortic perfusion pressure was controlled.
Differences in automaticity between Purkinje strands from right and left dog ventricle
Authors: Reiser J. , Anderson G. J.
Published: December 2017

Previous in situ studies have implicated differences in the pacemaker rates between the left and right ventricular conduction system. Our studies were conducted to characterize automaticity in peripheral right and left canine Purkinje fibers in vitro. Standard microelectrode techniques were utilized. In paired right (RPF) and left (LPF) canine Purkinje fibers, control intrinsic rate (IR) was found to be higher in LPF (24.8 +/- 1.7 beats/min) than in RPF (11.5 +/- 1.5 beats/min, P less than 0.01). Following overdrive stimulation at various cycle lengths, LPF consistently showed earlier escape beats. In low K0+ (1.35 mM), IR increased comparably in both RPF and LPF. However, high K0+ (5.4 mM) resulted in a greater reducton of the IR in RPF (-78%) than in LPF (-58%). After epinephrine (10(-6) M) the IR of LPF > RPF although the chronotropic response was more pronounced in RPF. Adrenergic stimulation preceded by beta-adrenergic blockade did not produce significant differences in the intrinsic rate between RPF and LPF. These findings indicate that automaticity in right and left Purkinje strands is functionally dissimilar.
Prediction of regional myocardial blood flow in dogs
Authors: Munch D. F. , Downey J. M.
Published: December 2017

Three indices of regional coronary flow were tested to determine if a good correlation between calculated driving pressure and flow could be found. Four different myocardial depths were examined. All three indexes were based on subtraction of a backpressure to flow. The first assumed backpressure to be equal to ventricular pressure; the second assumed backpressure to be twice ventricular pressure; and the third index assumed backpressure to be zero and thus was simply coronary pressure. Only the index that used left ventricular pressure as the backpressure to flow exhibited proportionality for the subendocardial samples. Similarly, only coronary pressure yielded a good fit for the subepicardial samples. Although subendocardial flow was always in proportion to the index, the index was poor at predicting the absolute value of that flow. The usefulness of such a directional predictor of subendocardial perfusion was illustrated by examining the phase shift resulting from partial occlusion of a coronary artery. The index predicted that subendocardial flow would be lower when coronary pressure was reduced by partially occluding the coronary vessel than when it was presented with an equivalent steady pressure. Microsphere measurements confirmed this prediction. We conclude that an index that assumes ventricular pressure to be the backpressure to flow is an accurate predictor of relative changes in subendocardial perfusion.
Atrial inotropic responses to brief vagal stimuli: frequency-force interactions
Authors: Martin P.
Published: December 2017

The effect of brief vagal stimulus burst on atrial contractile force was assessed in paced- and unpaced-heart preparations by recording the changes in pressure (AP) generated in a balloon in the right atrial appendage or by a miniature strain gauge on the atrium. One and 3 stimuli per vagal burst depressed AP up to 62 and 90%, respectively. The response varied with the time in the cardiac cycle at which the stimulus was given. Identical stimuli produced a greater inotropic depression at longer cardiac cycle durations. The differences between the magnitudes of the AP responses at two different mean heart rates were relatively constant when the stimulus intensity was increased from 1 to 99 stimuli per burst. A low-level stimulus caused a greater depression in contractile force when the heart rate was allowed to change than with the identical stimulus when the heart was paced, although this difference in paced- and unpaced-heart responses tended to disappear when the stimulus intensity (burst width) was increased. The composite frequency-force relationship was relatively flat over normal heart periods, but fell off by 15-20% at the extremes. The present results show an unexpected interaction between the vagal inotropic effect and the frequency-force relationship such that a given vagal stimulus causes a greater depression of atrial contractile force at lower heart rates.
Left stellate stimulation: regional myocardial flows and ischemic injury in dogs
Authors: Giudicelli J. F. , Berdeaux A. , Tato F. , Garnier M.
Published: December 2017

The effects of left stellate ganglion stimulation (LSGS) on regional myocardial blood flow (RMBF) and epicardial S-T segment were investigated in the normal and ischemic myocardium of anesthetized dogs. In nonischemic myocardium LSGS decreased calculated coronary resistance, increased RMBF, and reduced the endocardial-to-epicardial (endo-to-epi) ratio. These effects were reversed after atenolol (1 mg/kg) and abolished after combined atenolol and phenoxybenzamine (3 mg/kg) treatments. In ischemic myocardium LSGS did not change RMBF but increased S-T segment. However, after atenolol, LSGS increased ischemic RMBF and the ischemic-to-nonischemic areas flow ratio (reverse coronary steal phenomenon), these effects being abolished by phenoxybenzamine. We conclude that 1) LSGS increases RMBF and decreases endo-to-epi ratio in nonischemic areas by beta 1-adrenergic stimulation through metabolic autoregulation, 2)beta 1-adrenergic blockade in nonischemic areas unmasks alpha-adrenergic vasoconstriction inducing a redistribution of flow towards ischemic areas, and 3) further elevation of S-T segment by LSGS is due to oxygen requirements enhancement by beta 1-adrenoceptors stimulation.
Experimental angiotensin II hypertension
Authors: Young D. B. , Murray R. H. , Bengis R. G. , Markov A. K.
Published: December 2017

The mechanisms by which angiotensin II (AII) produces hypertension was studied in a group of 13 large dogs maintained on a Na intake of 200 meq/day. AII was infused at 10 ng x kg-1 x min-1 iv for 8 days. Arterial pressure increased from the control level of 98 +/- 3 to 160 +/- 7 mmHg and cardiac output fell significantly from the control value of 3.4 +/- 0.2 to 2.4 +/- 0.2 and 2.6 +/- 0.1 l/min on the 5th and 8th days of AII infusion. Mean circulatory filling pressure (MCFP) rose from the control mean of 9.5 +/- 0.5 to 11.6 +/- 0.9 (P < 0.05) and 12.6 +/- 0.6 mmHg (P inverted question mark 0.05) on the 5th and 8th day of infusion. On the 1st day of AII infusion, approximately 70 meq Na was retained; this retention persisted until the 4th day, when a marked natriuresis returned the dogs to Na balance. 22Na space increased slightly (P < 0.05) during the early part of the study, but fell back to the control level by the 5th day of infusion. Blood volume was unchanged throughout the study. The marked increase observed in MCFP with unchanged blood volume indicates that the unstressed volume or compliance of the circulatory system must have decreased. In this form of hypertension, the increase in arterial pressure was achieved without volume expansion and cardiac output elevation, but with large initial increases in arterial and venous vascular tone.
Widespread distribution and rate differentiation of the atrial pacemaker complex
Authors: Boineau J. P. , Schuessler R. B. , Hackel D. B. , Miller C. B. , Brockus C. W. , Wylds A. C.
Published: December 2017

In a study to examine the basis of rate-related changes in the electrocardiographic P wave we found a multicentric rather than unifocal origin of the atrial depolarization wave in dogs. Three to five pacemakers, or origin points, were distributed over a 30- to 40-mm area compared to the 11-mm size of the sinus node. Two or three of the sites could excite simultaneously, or one specific site would dominate excitation. Each separate origin point dominated excitation within a specific range of heart rates, and on reaching either the upper or lower limits of this range, a new focus abruptly dominated and initiated the atrial wave front. We have obtained evidence to suggest that these findings may be explained by a widely distributed atrial pacemaker complex. The spatial distribution of this system exceeded the dimensions of the canine sinus node by a factor of three to four times. The pacemaker centers, although distributed, were consistently located at specific positions along the superior vena caval-right atrial junction. Also, each separate pacemaker site appeared functionally differentiated to generate a specific range of heart rates. We propose that in addition to the sinus node there are other specialized atrial pacemaker centers, and that this specialization, including the differentiated response and coordination, is conferred by focal receptor characteristics and their inputs.
Effect of pentobarbital anesthesia on vulnerability to ventricular fibrillation
Authors: Dawson A. K. , Leon A. S. , Taylor H. L.
Published: December 2017

Ventricular fibrillation threshold (VFT), frequently determined in dogs during pentobarbital sodium anesthesia, usually is replaced by a single repetitive extrasystole threshold (SRET) or a multiple repetitive extrasystole threshold (MRET) determination in conscious animals and in the human being. In the present study SRET, MRET, and VFT were determined initially in 39 pentobarbital sodium-anesthetized dogs. One week later these three thresholds were redetermined during anesthesia in 13 of the 39 dogs (control group). In the remaining 26 dogs (experimental group), thresholds were redetermined while the dogs were conscious. Significant changes in threshold values occurred only in the experimental group for VFT (P < 0.001) and MRET (P < 0.02). The square of the linear correlation coefficient showed conscious state MRET to be a good predictor of conscious state VFT (R2 = 0.90). Conscious state SRET and anesthetized state VFT showed less predictiveness for the conscious VFT (R2 = 0.72 and 0.51, respectively). These data indicate that MRET may be preferable to SRET as an index of VFT. The SRET, MRET, and VFT determined during pentobarbital anesthesia may not accurately reflect the value of these parameters in the conscious animal.
Reference sample microsphere method: cardiac output and blood flows in conscious rat
Authors: Ishise Shozo , Pegram Barbara L. , Yamamoto Jin , Kitamura Yoshio , Frohlich Edward D.
Published: December 2017

Validation of the reference sample method (RSM) in the rat was accomplished by: 1) simultaneous measurement of cardiac output (CO) by the RSM and electromagnetic flowmetry method in ether-anesthetized open-chest Wistar rats, and 2) determination of systemic and regional hemodynamic reproducibility in conscious rats following three serial injections of microspheres. The optimal sampling time and sampling rate were determined in several CO states. The results indicate that: 1) 200 or more microspheres contained in the reference sample result in an accurate determination of CO, 2) almost 100% of the microspheres are trapped by tissues with in 20 s of cessation of the microsphere injection, 3) the hemodynamic steady state is affected only under low cardiac output conditions at a high sampling rate (1.211 ml/min), 4) three repeated injections of microspheres in conscious animals do not alter systemic hemodynamis, and 5) the reproducibility of regional blood flow distribution is good in all organs except the liver, stomach, spleen, and skin (third application). These data indicate that the RSM is reliable, providing reasonable accuracy and reproducibility of systemic and regional hemodynamics in the rat.
Direct metabolic effects of isoproterenol and propranolol in ischemic myocardium of the dog
Authors: Goodlett Michael , Dowling Kyran , Eddy Lynne J. , Downey James M.
Published: December 2017

The effect of either isoproterenol or propranolol on the metabolism of ischemic myocardium was examined. To ensure that all changes were due to changes in metabolism and not drug-induced changes in residual flow to the ischemic regions, we devised a preparation in which two coronary branches on the same heart were simultaneously perfused at a low flow rate. Microsphere measurements verified that the two ischemic regions were receiving identical blood flow rates. One branch received an infusion of 0.9% NaCl and the other received the drug. After 1 h both regions were biopsied and the high-energy phosphate levels in each region were determined. ATP and phosphocreatine each fell to about 50% of their starting values in the 0.9% NaCl-treated regions, and isoproterenol did not further depress the high-energy phosphate concentrations. Propranolol, on the other hand, significantly preserved the high-energy phosphate concentrations. We conclude that although isoproterenol seemed incapable of accelerating energy utilization in ischemic myocardium, propranolol is apparently capable of reducing it.
An inexpensive pressure telemetry system
Authors: Barber Billy J. , Quillen Jr. E. W. , Cowley Jr. Allen W.
Published: December 2017

An inexpensive telemetry system using transducers and recorders commonly available, i.e., Statham and Grass, is described. The direct-current signal of a Statham transducer is applied to a voltage-controlled oscillator, thereby frequency encoding the pressure sensed by the transducer. This encoded signal frequency modulates a Colpitts oscillator, which acts as a radio-frequency oscillator-transmitter in the 88- to 108-MHz band. This transmitter and transducer, along with a rechargeable NiCd battery pack (total wt 0.5 kg), are mounted in a canvas jacket and worn by a dog previously prepared with a chronic indwelling arterial catheter. With a fully charged battery pack, a signal can be transmitted up to 250 ft for 50 h. A frequency-modulation automotive receiver, powered by and interfaced with a Grass 7B recorder, receives the signal and drives a tachometer circuit that reconverts the audio-frequency signal to a voltage proportional to pressure. This voltage is then applied to the driver amplifier of the Grass to produce a charted record. This system introduces no distortion as seen by comparison of direct and telemetered signals and is drift free for intervals exceeding 24 h.
Left ventricular asynergy during intracoronary isoproterenol infusion in dogs
Authors: Ilebekk A. , Lekven J. , Kiil F.
Published: December 2017

Myocardial contractions were examined in the left ventricle of anesthetized, open-chest dogs during infusion of a beta-adrenergic agent, isoproterenol (0.1-0.5 micrograms/min) into a shunt line to the left anterior descending coronary artery. Myocardial chord lengths were continuously monitored by pairs of ultrasonic elements inserted into the isoproterenol-infused and control regions. Heart rate remained constant, but isoproterenol altered contraction patterns in both control and infused regions. Contraction in the infused region started before ejection and stretched the control myocardium in early systole. Because of early relaxation, however, the infusion region was stretched at the end of ejection and in early diastole, while the control myocardium continued to shorten. Thus, isoproterenol infusion to a part of the left ventricle induces asynergic muscle contractions and despite localized inotropic stimulation stroke volume may not be significantly increased.
Brain adenosine production in rat during sustained alteration in systemic blood pressure
Authors: Winn H. R. , Welsh J. E. , Rubio R. , Berne R. M.
Published: December 2017

Brain production of adenosine and its metabolites, inosine and hypoxanthine was determined in 46 rats during sustained (5 min) reduction in mean arterial blood pressure (MABP) caused by hemorrhage. Also measured were ATP, ADP, AMP, phosphocreatine (PCr), and lactate. Brain tissue was obtained by the freeze-blowing technique. Ventilation was controlled to maintain constant arterial O2 tension, CO2 tension, and pH. When MABP was decreased from 135 + 3 (SE) mmHg to 72 +/- 2 mmHg, within the range of cerebral autoregulation, brain adenosine concentration doubled from 0.55 +/- 0.12 to 1.16 +/- 0.13 nmol/g (P < 0.015). Unlike the changes in adenosine concentrations, adenine nucleotides and PCr remained stable. Lactate varied inversely with MABP. With moderate to severe hypotension (MABP = 45 +/- 3 mmHg), adenosine levels increased almost sixfold. The increment in brain adenosine concentration within the autoregulatory range supports a role for this potent dilator of pial vessels in the regulation of cerebral blood flow.
Effect of aging on permeability of cockerel aorta to 125I-albumin
Authors: Ezekowitz M. D. , Parker K. H. , Salpidoru N. , Oxenham R. C.
Published: December 2017

The in vivo uptake of 125I-albumin (A), containing < 1% free iodide, by the cockerel aorta 10-243 min after intravenous injection was quantitatively studied in 22 normotensive normolipemic anesthetized cockerels, Uptake initially was rapid and linear with time (T) (10-37 min), thereafter slowing and approaching an equilibrium with the blood. The permeability of the wall (Pm) to A was defined as accumulated wall activity/mean blood activity X endothelium surface area X T from intravenous injection to death of animal for T in the range 10-37 min. Pm was determined in the young group, age 197 +/- 51 days (means +/- SD; n = 6), which represented cockerels close to puberty, and compared to a middle-aged group, age 591 +/- 15 days (n = 5). Pm in the older group, 1.5 X 10(-6) +/- 0.218 ml . cm-2 . s-1 (means +/- 1 SE) was twofold greater than the younger group, 0.813 X 10(-6) +/- 0.046 (P < 0.0001). Total cholesterol content, within the wall in 12 different animals, was unchanged over the period 130-320 days. It is concluded that Pm to A increases with age as part of a physiological process. This finding should be considered in any model of atherosclerosis.
Spontaneous mechanical alternans in papillary muscles from atherosclerotic rabbits
Authors: Peterson D. W. , Napolitano C. A. , Griffith D. W.
Published: December 2017

Mechanical alternans developed spontaneously in 5 of 17 right ventricular papillary muscles from atherosclerotic rabbits. The rabbits had eaten an atherogenic diet of 5% lard, 5% peanut oil, 0.5% cholesterol, and 89.5% rabbit pellets for 116-184 days. In one muscle mechanical alternans developed slowly and persisted. When the condition had developed fully, in the weaker contraction the muscle shortened only 20% as far when contracting isotonically and developed only 38% as much tension when contracting isometrically. Added to the superfusate, calcium (5.0 mM) or norepinephrine (1.5 X 10(-5) M) abolished the alternans. In four muscles mechanical alternans was only temporary. Compared with the 12 muscles that did not develop alternans, these 4, when contracting isometrically 12 times/min but not in alternans, had longer latency and required more time to develop tension at the maximum rate and to develop peak tension. Contracting isotonically, they required more time to accelerate to maximum velocity of shortening and to shorten maximally. Raising the contraction frequency to 24/min decreased the differences in performance between the two groups. Norepinephrine (1.5 X 10(-5) M) made the differences smaller still. We think that both the mechanical alternans and the differences in performance between the muscles that developed alteranans and those that did not resulted from a defect in the cardiac cell's handling of calcium. Diet-induced changes in the lipid composition of the sarcoplasmic reticulum or sarcolemma or both seem probable causes.
Peripheral muscarinic control of norepinephrine release in the cardiovascular system
Authors: Muscholl E.
Published: December 2017

Activation of muscarinic cholinergic receptors located at the terminal adrenergic nerve fiber inhibits the process of exocytotic norepinephrine (NE) release. This neuromodulatory effect of acetylcholine and related compounds has been discovered as a pharmacological phenomenon. Subsequently, evidence for a physiological role of the presynaptic muscarinic inhibition was obtained on organs known to be innervated by the autonomic ground plexus (Hillarp, Acta. Physiol. Scand. 46, Suppl. 157: 1-68, 1959) in which terminal adrenergic and cholinergic axons run side by side. Thus, in the heart electrical vagal stimulation inhibits the release of NE evoked by stimulation of sympathetic nerves, and this is reflected by a corresponding decrease in the postsynaptic adrenergic response. On the other hand, muscarinic antagonists such as atropine enhance the NE release evoked by field stimulation of tissues innervated by the autonomic ground plexus. The presynaptic muscarine receptor of adrenergic nerve terminals probably restricts the influx of calcium ions that triggers the release of NE. However, the sequence of events between recognition of the muscarinic compound by the receptor and the process of exocytosis still remains to be clarified.
Localization of purine and pyrimidine nucleoside phosphorylases in heart, kidney, and liver
Authors: Rubio R. , Berne R. M.
Published: December 2017

In isolated livers and kidneys perfused with Krebs-Henseleit solution, the relationship of the concentration of adenosine (Ado) to that of its degradation products inosine (Ino) and hypoxanthine (Hyp) in biliary, urinary, and venous effluents were determined. They revealed ratios of Hyp:Ado:Ino, 1.9:1:0.9, 0.7:1:0.6, and 1.3:1:0.5 for guinea pig biliary, guinea pig urinary, and rat urinary effluents, respectively, and their respective venous effluent were 58:1:29, 8.6:1:5.4, and 7.4:1:3.2. The greater proportion of Ino and Hyp in the venous effluents suggests active production in Ino and Hyp at the vessel wall. Purine nucleoside phosphorylase localization was determined histochemically and found most active in the cytoplasm of capillary endothelium and Kupffer cells. Thus, there is agreement between purine analysis and histochemical findings. The reliability of the histochemical technique was also tested by comparing activities of purine nucleoside phosphorylase (a cytoplasmic enzyme) and pyrmidine nucleoside phosphorylase (a nuclear enzyme) that catalyze similar reactions (nucleoside + inorganic phosphate in equilibrium base + ribose-1-phosphate) but with different base specificites and cellular localization, as indicated by cell fractionation studies. The histochemical results show that in contrast to the purine nucleoside phosphorylase, the pyrmidine specific enzyme was most active in the nuclei of endothelial and Kupffer cells. Thus, the technique discriminates between the two enzymes.
Stimulation of cardiac receptors with veratrum alkaloids inhibits ADH secretion
Authors: Thames M. D. , Peterson M. G. , Schmid P. G.
Published: December 2017

The purpose of this study was to determine whether cardiac receptors that are stimulated by veratrum alkaloids exert an inhibitory influence on the secretion of vasopressin (ADH). In six chloralose-anesthetized dogs, injection of cryptenamine (2 microgram/kg) into the circumflex coronary artery resulted in a significant (P < 0.05) fall in arterial pressure (-45 +/- 5 mmHg). Despite this hypotension and the presence of intact arterial baroreflexes, there was no change in plasma ADH (measured in the superior vena cava). In eight dogs with sinoaortic baroreceptor denervation, hemorrhage of 10 ml/kg decreased arterial pressure 20 +/- 5 mmHg (P < 0.05) and increased plasma ADH from 14 +/- 5 to 38 +/- 13 microU/ml (P < 0.05). Intracoronary injection of cryptenamine (1 microgram/kg) decreased plasma ADH to 23 +/- 7 microU/ml during the 5 min immediately after cryptenamine injection and to 16 +/- 4 microU/ml 20 min after injection. In eight dogs with sinoaortic denervation, hemorrhage and injection of vehicle resulted in a progressive increase in plasma ADH over the same time period. Vagotomy abolished the inhibitory response to cryptenamine injection. These data show that stimulation of cardiac receptors with vagal afferents by intracoronary injection of a veratrum alkaloid inhibits ADH secretion. Activation of these receptors can prevent arterial baroreflex-induced increases in ADH.
Heart rate response of fetal and adult sheep to hemorrhage stress
Authors: Macdonald A. A. , Rose J. , Heymann M. A. , Rudolph A. M.
Published: December 2017

The responses of heart rate and blood pressure to hemorrhage of 15% of estimated blood volume were studied in 24 chronically instrumented fetal lambs of gestational ages 81-144 days (0.55-0.98 gestation) and 6 conscious adult nonpregnant ewes. A transient tachycardia of 25 +/- 3 beats/min (+ 15 +/- 2%) was noted in the fetuses after removal of about 5% blood volume and reduction of mean arterial pressure of 2 +/- 1 mmHg (8 +/- 2%). With 15% reduction of blood volume fetal mean arterial pressure fell 12 +/- 1 mmHg (27 +/- 2%), venous pressure fell from 3.5 +/- 0.5 to 2.0 +/- 0.5 mmHg, and heart rate dropped by 39 +/- 8 beats/min (22 +/- 4%). The fetal bradycardia during the hemorrhage period was reversed by atropine administration. In adult ewes, mean arterial pressure decreased 12 +/- 3 mmHg, venous pressure was unchanged but heart rate increased by 25 +/- 6 beats/min (29 +/- 8%). These studies indicate the presence of a functional baroreflex by 81 days (0.55 gestation).
Hepatic capacitance responses to changes in flow and hepatic venous pressure in dogs
Authors: Bennett T. D. , Rothe C. F.
Published: December 2017

The effect of changes in inflow and hepatic venous pressure (Phv) on the hepatic vascular bed was studied in denervated, pump-perfused canine livers. Hepatic arterial, portal venous, and hepatic venous pressures and flows were continuously monitored as was the hepatic venous hematocrit (Hct). The hepatic venous outflow, which averaged 1179 +/- 356 (SD) ml x min-1 x kg tissue-1 at control conditions, was controlled by a servosystem set to keep Phv at the desired level. Hepatic volume changes (delta V) were determined by integration of the difference between hepatic inflow (Fin) and outflow (Fhv). Over the range of Phv of 0-15 mmHg, the delta V-to-delta Phv ratio (apparent compliance C) was linear; C = 19.8 ml x mmHg-1 x kg tissue-1. These increases in Phv caused transient and plateau increases in Hct of 1.26 and 0.42%/mmHg, respectively. Varying inflow over the range of 0-156% of control by changing hepatic arterial and/or portal venous flow(s) resulted in delta V of 0.066 ml/kg per ml x min-1 x kg tissue-1 change in flow. We conclude that changes in Fin as well as changes in Phv cause changes in liver volume; and that a significant fraction of the volume shift accompanying changes in Phv is due to transsinusoidal plasma movement.
Resting potential changes associated with Na-K pump in failing heart muscle
Authors: Houser S. R. , Freeman A. R. , Jaeger J. M. , Breisch E. A. , Coulson R. L. , Carey R. , Spann J. F.
Published: December 2017

Microelectrode and single sucrose gap techniques were used to measure transmembrane potentials in normal and failing papillary muscles. Six muscles from control animals and 10 from banded animals were cooled (2-4 degrees C) and subsequently rewarmed to 37 degrees C. Normal muscles demonstrated significantly greater increases in maximum diastolic potential (--Emax) on rewarming than those from failing animals. In muscles subjected to transient periods of rapid stimulation, --Emax depolarized initially on stimulation but eventually plateaued at a depolarized level and then hyperpolarized beyond prestimulation levels. These changes in --Emax were altered in failing muscles. The initial rate of depolarization (delta -- Emax/delta t) on stimulation and the magnitude of this depolarization (delta -- Emax) was decreased at all rates studied. The time necessary to arrive at the plateau (time to delta -- Emax) was significantly lengthened in failing muscles. The hyperpolarization seen on rewarming cooled preparations and the changes in --Emax during stimulation have both been related to an activation of an electrogenic Na-K pump suggesting that this ion-transport system is altered in failing heart muscle. The decrease in delta -- Emax/delta t and delta -- Emax seen in failing muscles indicates that K efflux may be lower or that the volume of confined intercellular spaces is greater in failing heart muscle.
Reflex cardiovascular response during injection of capsaicin into skeletal muscle
Authors: Crayton S. C. , Mitchell J. H. , Payne F. C.
Published: December 2017

In an anesthetized dog, injections of capsaicin, a potent stimulator of small myelinated and unmyelinated fibers that originate as free nerve endings, into a neurally intact donor-perfused hindlimb produced a significant (P less than 0.05) increase in mean aortic pressure (20%), heart rate (12%), cardiac output (28%), and respiratory minute volume (97%). Organ blood flows were measured with 25-micrometers radioactive microspheres. During the injection of capsaicin, there was a decrease in renal blood flow (-25%), but liver, spleen, brain, heart, and skeletal muscle flows remained near control values. After section of the afferent neural connection from the donor perfused hindlimb, the responses to the injection of capsaicin were abolished. These reflex cardiovascular and respiratory responses and changes in organ flow caused by stimulation of capsaicin-sensitive receptors in skeletal muscle are similar to those that occur during induced isometric exercise in the hindlimb.
Regression of cardiac oxygen consumption on ventricular pressure-volume area in dog
Authors: Suga H. , Hayashi T. , Shirahata M. , Suehiro S. , Hisano R.
Published: December 2017

Left ventricular systolic pressure-volume area (PVA) has been reported to be a reliable predictor of cardiac oxygen consumption rate per beat (VO2) in a given heart with a stable inotropic background. PVA is the specific area in the pressure-volume (PV) diagram, consisting of the area (EW) within the PV loop and the area (PE) bound by the end-systolic and end-diastolic PV lines and the relaxation segment of the PV loop. EW and PE correspond to the external mechanical work and the end-systolic elastic potential energy in the ventricular wall, respectively. We determined the optimal combination of EW and PE for the best prediction of VO2, using the linear multiple regression analysis. From EW, PE, and VO2, data of many isovolumic and ejecting contractions, the optimal coefficients of EW and PE were 1.67 +/- 0.43 (SD; 7 hearts) and 1.74 +/- 0.49 (10(-5) ml O2/mmHg . ml), virtually identical to each other, corroborating that PVA, i.e., a simple sum of EW and PE, can reliably predict VO2 of a given heart in a stable contractile state.
Relaxation of bovine mesenteric lymphatics in response to transmural stimulation
Authors: Ohhashi T. , Roddie I. C.
Published: December 2017

The responses of isolated quiescent segments of bovine mesenteric lymphatics to 10-s trains of pulses (50 V for 0.3 ms at 2 Hz) administered transmurally have been studied using various drugs. Each train of pulses consistently produced a brief contraction that was completely blocked by tetrodotoxin, alpha-adrenoceptor antagonists, bretylium, and guanethidine. Cocaine potentiated the contractions. Tyramine caused an increase in the basal tone, some spontaneous contractions, and an inhibition of contraction. The contraction was sometimes followed by a relaxation that could be of short duration or long lasting. Both types of relaxation were abolished by tetrodotoxin. Propranolol reduced both types of relaxation, causing more suppression of the short type. Bretylium completely blocked the short type of relaxation and slightly reduced the long-lasting type. Hexamethonium and atropine had no effect on any of the responses. These findings suggest that the contraction resulting from transmural stimulation is due to the action of excitatory postganglionic sympathetic nerves. It is concluded that both types of relaxation occur mainly in response to beta-adrenergic inhibitory stimulation. The possibility of nonadrenergic inhibitory innervation in bovine mesenteric lymphatics is also discussed.
Effects of hyperkalemia and glycoside on thallium exchange in rabbit ventricle
Authors: Krivokapich J. , Shine K. I.
Published: December 2017

The exchange characteristics of thallium-201 (201Tl) were studied using the isolated arterially perfused rabbit interventricular septum to gain insight into the mechanisms that govern its uptake and subsequent washout from myocardial tissue. The results were compared to potassium-42 (42K) exchange. Unlike 42K, the uptake and tissue washout exchange rates for 201Tl were not equal. The 201Tl washout exchange rate was slower than that for the uptake. Hyperkalemia increased the efflux of both 42K and 201Tl, but the increase in 201Tl efflux was not due to an increase in permeability, as was true for 42K, but to a hyperkalemia, induced increase in compartment size of exchangeable 201Tl. Acetylstrophanthidin (ACS) resulted in an increase in 201 Tl efflux similar to the increase in 42K efflux seen with ACS. However, ACS did not inhibit 201Tl influx, in contrast to the known inhibition of 42K influx. This indicated that influx of tracer amounts of 201Tl was not dependent on the sodium-potassium pump. A model of Tl exchange in rabbit ventricles is proposed.
Effects of high-frequency harmonics on cardiac relaxation indices
Authors: Martin G. , Gimeno J. V. , Ramirez A. , Cosin J. , Baguena J.
Published: December 2017

This study was designed to determine the degree to which the systematic distortions in the pressure curve due to recording and filtering systems influence the relaxation indices. The purposes are 1) to analyze the dependency on the high frequencies of the relaxation and contractility parameters, 2) to determine the degree to which the catheter recordings modify those parameters, and 3) to test the monoexponential hypothesis in which the T index is based (Weiss, Frederiksen, and Weisfeldt, J. Clin. Invest. 58: 751-760, 1976). In 17 open-chest dogs, the left ventricular pressure (LVP) was recorded in four different ways: 1) with a large-bored metal cannula, 2) with a catheter-tip manometer, 3) with a Cournand catheter, and 4) with a pigtail catheter. The ECG and LVP were digitized by a computer. A Fourier analysis was performed, and the LVP waves were resynthesized with different numbers of harmonics. We conclude that 1) the catheter recordings are not recommended to calculate relaxation indices, 2) relaxation parameters present more sources of errors than contractility parameters, 3) the monoexponential hypothesis of T is fulfilled if the isovolumic relaxation is considered to end at the time the LVP is 10 mmHg more than left ventricular end-diastolic pressure level, 4) the dependency on higher harmonics of T index and +dP/dtmax is similar, and 5) -dP/dtmax is much more high-frequency dependent than T index.
Dependency of myocardial reactive hyperemia on coronary artery pressure in the dog
Authors: Dole W. P. , Montville W. J. , Bishop V. S.
Published: December 2017

We studied the effects of coronary artery pressure on myocardial reactive hyperemia following brief flow arrests in 20 closed-chest anesthetized dogs. The circumflex artery was perfused from a pressurized arterial reservoir with a cannula inserted through the right carotid artery. Increasing coronary pressure from 60 to 160 mmHg did not alter heart rate, systemic pressure, or left ventricular dP/dtmax. For 10-s inflow occlusions, 20-mmHg increments in coronary pressure from 40 to 160 mmHg resulted in proportional increases in peak hyperemic flow [40 +/- 4 to 257 +/- 18 (SE) ml/min], total hyperemic flow (2 +/- 1 to 42 +/- 4 ml), and the duration of hyperemic flow (9 +/- 2 to 37 +/- 3 s). These results were unchanged when preocclusion pressure was held constant and postocclusion pressure varied. The influence of coronary artery pressure on hyperemic flow was progressively less pronounced after occlusions of shorter duration. These data indicate that coronary artery pressure has a major influence on the characteristics of myocardial reactive hyperemia after brief periods of arterial flow arrest. The observed pressure dependency suggests that coronary reactive hyperemia may be, in part, a passive flow response that could be explained by a transient depression of the normal vascular reactivity to postocclusion pressure. A passive component to reactive hyperemia could account for the overrepayment of bloow flow debt characteristically observed in the heart.
Inhibitory effect of anoxia on reperfusion- and digitalis-induced ventricular tachyarrhythmias
Authors: Carbonin P. , Di Gennaro M. , Valle R. , Weisz A. M.
Published: December 2017

In the isolated rat heart, anoxia or ischemia do not induce important ventricular tachyarrhythmias (VTAs). During the 1st min of reperfusion, VTAs are frequent. The frequency and severity of VTAs during reperfusion depend on the duration and the extent of the myocardial damage. Anoxia abolishes reperfusion-induced VTAs as did verapamil (2.5 X 10(-6) M). In isolated guinea pig hearts, beta-methyldigoxin (1.27 X 10(-6) M) provokes VTAs that are progressively increasing in severity. After 26 min of perfusion with an oxygenated beta-methyldigoxin-containing medium, all isolated guinea pig hearts develop ventricular fibrillation. By changing the abnormal rapid ventricular rhythms into progressively slower irregular idioventricular rhythm, anoxia counteracts all types of VTAs exhibited by the intoxicated guinea pig hearts. In conclusion, two conditions seem to be necessary for the development of VTAs during the reperfusion: 1) a sufficient degree of myocardial damage provoked by the preceding ischemic perfusion, and 2) the presence of oxygen during the reperfusion.